Odze and Goldblum Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas

Odze and Goldblum Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas
Contributors
1 Gastrointestinal Tract Endoscopic and Tissue Processing Techniques and Normal Histology
Chapter Outline
Introduction
Bowel Preparation
Methods for Obtaining Tissue Specimens
Endoscopic Pinch Biopsy
Endoscopic Snare Polypectomy
Endoscopic Mucosal Resection
Methods of Processing Tissue for Pathologic Evaluation
Formalin
Orientation of Formalin-Fixed Tissue Obtained at Endoscopy
Flow Cytometry
Electron Microscopy
Endoscopy-Induced Artifacts
Pathologic Features of a Healing Biopsy Site
Methods for Obtaining Cytology Specimens
Brush Cytology
Fine-Needle Aspiration
Optical Techniques
Normal Histology of the Tubal Gut
Esophagus
Stomach
The Gastric Cardia
Small Intestine
Endocrine Cells
The Intestinal Mucosal Immune System
Colon
Appendix
Rectum and Anus
Lymph Node Drainage and Lymphatics of the Tubal Gut
Esophagus
Stomach
Small Intestine
Colon
Lymph Nodes
References
2 Screening and Surveillance Guidelines in Gastroenterology
Chapter Outline
Introduction
Surveillance in Patients with Barrett Esophagus
Surveillance in Patients with Chronic Gastritis and Intestinal Metaplasia or Dysplasia
Surveillance for Colorectal Neoplasia in Patients with Inflammatory Bowel Disease
Screening and Surveillance Guidelines for Colon Polyps
Definition and Clinical Considerations
Initial Management of Polyps
Management of Small Polyps
Management of Sessile Serrated Adenomas/Polyps
Hyperplastic Polyposis Syndromes
Management of Large Pedunculated Polyps
Management of Large Sessile Polyps
Postpolypectomy Surveillance
Management of Malignant Polyps
Colonoscopic Surveillance after Colon Cancer Resection
Interaction of Gastrointestinal Endoscopists and Pathologists
References
3 Diagnostic Cytology of the Gastrointestinal Tract
Chapter Outline
Introduction
Specimen Types
Specimen Preparations
Value and Accuracy of Specimens
Normal Morphology
Esophagus
Stomach
Small Intestine
Large Intestine
Infections
Candida
Herpes Simplex Virus
Cytomegalovirus
Helicobacter pylori
Giardia
Atypical Mycobacteria
Cryptosporidia
Microsporidia
Inflammatory, Reactive, and Metaplastic Changes
Nonspecific Changes
Pemphigus
Barrett Esophagus
Neoplastic Lesions
Squamous Dysplasia or Carcinoma
Glandular Dysplasia or Carcinoma
Endocrine Tumors
Mesenchymal Tumors
Lymphoid Tumors
References
4 Infectious Disorders of the Gastrointestinal Tract
Chapter Outline
Introduction
Viral Infections of the GI Tract
Cytomegalovirus
Clinical Features
Pathologic Features
Differential Diagnosis
Herpesvirus
Clinical Features
Pathologic Features
Differential Diagnosis
Adenovirus
Other Enteric Viruses
Human Papillomaviruses
Human Immunodeficiency Virus
Bacterial Infections of the Gastrointestinal Tract
Acute Self-Limited Colitis
Major Causes of Bacterial Enterocolitis
Vibrio cholerae and Related Species
Aeromonas and Related Species
Escherichia coli
Enterotoxigenic and Enteropathogenic E. coli
Enteroinvasive E. coli
Enteroadherent E. coli
Enterohemorrhagic E. coli
Salmonella
Typhoid (Enteric) Fever
Nontyphoid Salmonella Species
Shigella
Campylobacter
Yersinia
Clostridial Diseases of the Gut
Clostridium difficile–Related Colitis
Mycobacterial Infections of the GI Tract
Mycobacterium tuberculosis
Mycobacterium avium-intracellulare Complex
Spirochetal Infections of the GI Tract
Syphilis
Intestinal Spirochetosis
Other Causes of Sexually Transmitted Bacterial Proctocolitis
Miscellaneous Bacterial Infections
Bacterial Esophagitis
Phlegmonous Gastritis and Enteritis
Actinomycosis
Whipple Disease
Rhodococcus equi
Rocky Mountain Spotted Fever
Malakoplakia
Bacillary Angiomatosis
Helicobacter pylori and Helicobacter heilmannii
Fungal Infections of the GI Tract
Candida Species
Aspergillus Species
Mucormycosis
Histoplasmosis
Cryptococcus neoformans
Pneumocystis jiroveci
Parasitic Infections of the GI Tract
Protozoal Infections
Entamoeba histolytica
Flagellates
Giardia lamblia
Leishmania donovani and Related Species
Chagas Disease
Ciliates
Balantidium coli
Coccidians
Cryptosporidium parvum
Cyclospora cayetanensis
Isospora belli and Related Species
Microsporidia
Toxoplasma gondii
Miscellaneous Protozoal Infections
Helminthic Infections
Nematodes
Enterobius vermicularis
Ascaris lumbricoides (Roundworm)
Ancylostomiasis (Hookworm)
Trichuris trichiura (Whipworm)
Strongyloides stercoralis
Anisakis simplex and Related Species
Capillaria Species (Intestinal Capillariasis)
Trematodes
Schistosomiasis
Fasciolopsis buski and Related Species
Cestodes
Other Helminthic Infections
References
5 Manifestations of Immunodeficiency in the Gastrointestinal Tract
Chapter Outline
Primary Disorders of Immune Deficiency
Humoral Immunodeficiencies
Selective Immunoglobulin A Deficiency
X-Linked Agammaglobulinemia
X-Linked Hyperimmunoglobuin M Syndrome
Hyperimmunoglobulin E Syndrome
Common Variable Immunodeficiency
Infections in CVID
Inflammatory Disorders and Malignancy in CVID
Stomach
Small Bowel
Large Bowel
Combined Cellular/Humoral Immunodeficiencies
Severe Combined Immunodeficiency
Omenn Syndrome
Other Primary Immunodeficiencies
DiGeorge Syndrome
Chronic Mucocutaneous Candidiasis
Wiscott-Aldrich Syndrome
Chronic Granulomatous Disease
Miscellaneous Immune Deficiency Syndromes
Graft-versus-Host Disease
Acute GVHD
Chronic GVHD
Neutropenic Enterocolitis
The Gastrointestinal Tract in HIV Infection
Infections
HIV Enteropathy
Malignancy
References
6 Systemic Illnesses Involving the Gastrointestinal Tract
Chapter Outline
Introduction
Cardiovascular Disorders
Cardiac Surgery and Heart Transplantation
Ischemic Disease
Dermatologic Disorders
Bullous Diseases
Epidermolysis Bullosa
Pemphigus Vulgaris
Bullous Pemphigoid
Erythema Multiforme
Hailey-Hailey and Darier Diseases
Dermatitis Herpetiformis
Dermatogenic Enteropathy
Dermatologic Disorders Associated with Malignancies of the GI Tract
Acanthosis Nigricans
Tylosis
Miscellaneous Disorders
Endocrine Disorders
Adrenal Gland
Hypothalamus and Pituitary
Pancreas
Parathyroid
Thyroid
Multiple Endocrine Neoplasia
Hematologic Disorders
Hemorrhagic Disorders
Thrombotic Disorders
Megaloblastic Anemia
Leukemia and Lymphoma
Metabolic Disorders
Acrodermatitis Enteropathica
Plummer-Vinson Syndrome (Paterson–Brown Kelly Syndrome)
Vitamin Disorders
Pellagra
Lipoprotein Disorders
Abetalipoproteinemia
Tangier Disease
Lysosomal Storage Disorders
Fabry Disease
Common Mimics of Lysosomal Storage Diseases
Pigmented Lesions
Melanosis.
Pseudomelanosis.
Brown Bowel Syndrome.
Hemosiderosis/Hemochromatosis.
Barium Granuloma.
Nonpigmented Lesions
Xanthoma.
Muciphages.
Pseudolipomatosis.
Whipple Disease.
Mycobacterium avium-intracellulare Complex Infection.
Malakoplakia.
Granular Cell Tumor.
Signet Ring Cell Adenocarcinoma.
Clear Cell Carcinoid Tumor.
Malignant Histiocytosis.
Amyloidosis
Classification
Clinical Features
Pathologic Features
Familial Mediterranean Fever (Familial Paroxysmal Polyserositis, Recurring Polyserositis)
Pulmonary Disorders
Reproductive Disorders
Effects of Pregnancy and Exogenous Hormones
Decidualization of the Peritoneum
Endometriosis
Clinical Features
Pathologic Features
Differential Diagnosis
Rheumatologic Disorders
Scleroderma
Dermatomyositis and Polymyositis
Systemic Lupus Erythematosus
Mixed Connective Tissue Disease
Rheumatoid Arthritis
Reactive Arthritis
Sjögren Syndrome
Hereditary Connective Tissue Disorders
Urologic Disorders
Acute Renal Failure
Hemolytic-Uremic Syndrome
Chronic Renal Failure
Uremia
Long-Term Hemodialysis
Kidney Transplantation
Urinary Conduits
Miscellaneous Disorders
Chronic Granulomatous Disease
Sarcoidosis
Mastocytosis
Neoplastic Disease
References
7 Neuromuscular Disorders of the Gastrointestinal Tract
Chapter Outline
Introduction
Muscle Coats of the Bowel Wall
Neural Network of the Bowel
Esophagus
Primary Achalasia
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Secondary Achalasia
Idiopathic Muscular Hypertrophy
Differential Diagnosis
Stomach
Idiopathic Hypertrophic Pyloric Stenosis
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Gastroparesis
Small and Large Intestine
Hirschsprung Disease
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Treatment and Follow-Up
Other Developmental Disorders of the Enteric Nervous System
Hypoganglionosis
Hyperganglionosis
Intestinal Pseudo-obstruction
Acute Intestinal Pseudo-obstruction
Paralytic Ileus
Acute Idiopathic Intestinal Pseudo-obstruction (Ogilvie Syndrome)
Chronic Intestinal Pseudo-obstruction
Primary Chronic Intestinal Pseudo-obstruction
Myopathic Forms.
Pathologic Features.
Neuropathic Forms.
Pathologic Features.
ICC Abnormalities.
Pathologic Features.
Neurohormonal Peptide Abnormalities.
Differential Diagnosis.
Treatment and Prognosis.
Secondary Chronic Intestinal Pseudo-obstruction
Systemic Disorders.
Drugs and Toxins.
Infections.
Treatment and Prognosis.
Miscellaneous Conditions
Ceroidosis (Brown Bowel Syndrome)
Irritable Bowel Syndrome
Small Bowel Diverticulosis
Severe Idiopathic Constipation (Slow-Transit Constipation, Arbuthnot Lane Disease)
Differential Diagnosis and Workup of Patients with Intestinal Dysmotility
Suction Mucosal Biopsies
Full-Thickness/Seromuscular Biopsies
Resection Specimens
Microscopy
Histochemical Stains
Immunohistochemical Stains
Electron Microscopy
Future Outlook
References
8 Congenital and Developmental Disorders of the Gastrointestinal Tract
Chapter Outline
Molecular Mechanisms of Gastrointestinal Development
Embryology and Anatomic Development of the GI tract
Esophagus
Stomach
Small and Large Intestine
Congenital Anomalies of the GI Tract
General Aspects
Esophagus
Short Esophagus
Esophageal Atresia and Tracheoesophageal Fistula
Esophageal Cysts and Duplications
Neurenteric Remnants
Stomach
Gastric Atresia and Stenosis
Gastric Duplication
Neonatal Gastric Perforation
Small and Large Intestine
Hernias and Abdominal Wall Defects
Omphalocele (Exomphalos)
Gastroschisis (Laparoschisis)
Cloacal Exstrophy
Congenital Atresias and Stenoses
Malrotation
Duplications
Congenital Diverticula, Including Omphalomesenteric Remnants and Meckel Diverticulum
Heterotopias
Anorectal Malformations
References
9 Enteropathies Associated with Chronic Diarrhea and Malabsorption in Childhood
Chapter Outline
Introduction
Biopsy Sampling and Indications In Children
Intestinal Development in Children
Congenital Disorders of Intestinal Digestion, Absorption, and Transport
Carbohydrate Malabsorption and Disaccharidase Deficiencies
Pathogenesis
Lipid Trafficking Disorders
Abetalipoproteinemia
Hypobetalipoproteinemia
Chylomicron Retention Disease
Amino Acid Transport Disorders
Electrolytes and Trace Elements
Vitamins
Bile Acids
Congenital Defects of Intestinal Epithelial Differentiation
Microvillus Inclusion Disease
Clinical Features
Pathology
Treatment
Congenital Tufting Enteropathy (Epithelial Dysplasia)
Clinical Features
Pathology
Treatment
Enteroendocrine Cell Dysgenesis (Enteric Anendocrinosis)
Clinical Features
Pathology
Syndromatic Diarrhea (Trichohepatoenteric Syndrome)
Clinical Features
Pathology
Disorders of Immunomodulation
Autoimmune Enteropathy
Clinical Features
Pathogenesis
Pathology
Treatment
Autoimmune Polyendocrine Syndrome (APS 1)
Necrotizing Enterocolitis
Clinical Features
Pathogenesis
Pathology
Treatment
Lymphangiectasia
Clinical Features
Pathology
Metabolic Diseases
Neoplastic Disorders
References
10 Vascular Disorders of the Gastrointestinal Tract
Chapter Outline
Introduction
Anatomy of the GI Vascular System
Upper GI Bleeding
General Comments
Esophagus
Esophageal Varices
Mallory-Weiss Lacerations
Esophagitis and Esophageal Ulcers
Esophageal Diverticula
Stomach
Gastric Varices
Gastritis and Gastric Ulcers
Clinical Features and Etiology
Pathologic Features
Portal Hypertensive Gastropathy
Gastric Antral Vascular Ectasia
Hereditary Hemorrhagic Telangiectasia (Rendu-Osler-Weber Disease)
Lower GI Bleeding
Diverticulosis
Angiodysplasia
Arteriovenous Malformation
Hemorrhoids
Diaphragm Disease
Ehlers-Danlos Syndrome, Vascular Type (Type IV)
Miscellaneous Entities
Upper GI Ischemia
Esophagus
Stomach
Lower GI Ischemia
Arterial Insufficiency
Nonocclusive Arterial Insufficiency
Occlusive Arterial Insufficiency
Pathologic Features of Arterial Insufficiency
Venous Insufficiency
External Mesenteric Venous Compression
Mesenteric Venous Thrombosis
Intramural Disorders
Portal Pylephlebitis
Mesenteric Phlebitis
Idiopathic Myointimal Hyperplasia of Mesenteric Veins
Enterocolic (Lymphocytic, Granulomatous, or Necrotizing) Phlebitis
Mesenteric Phlebosclerosis
Microvascular Insufficiency
Vasculitis
Medium-Vessel Disease
Polyarteritis Nodosa
Kawasaki Disease
Small-Vessel Disease
Wegener Granulomatosis
Churg-Strauss Syndrome
Henoch-Schönlein Purpura
Leukocytoclastic Vasculitis
Cryoglobulinemic Vasculitis
Systemic Lupus Erythematosus and Other Immune Complex Diseases
Behçet Disease
Buerger Disease
Malignant Atrophic Papulosis (Kohlmeier-Degos Disease)
Segmental Arterial Mediolysis
Localized Vasculitis of the GI Tract
Differential Diagnosis of Ischemia in Lower GI Biopsies
References
11 Autoimmune Disorders of the Gastrointestinal Tract
Chapter Outline
Introduction
Autoimmune Enteropathy
Overview of Autoimmune Enteropathy
Syndromic Associations
IPEX Syndrome
APECED Syndrome
Clinical Features
Gut Epithelial Cell Antibodies
Pathogenesis
Pathologic Features
Small Intestine
Other Sites in the Tubular Gut
Liver and Pancreas
Differential Diagnosis
Treatment and Prognosis
Immunoglobulin G4 (IgG4)–Related Disease of the Gastrointestinal Tract
Overview of IgG4-Related Disease
Elevated Serum IgG4 Level
Other Organ Involvement
Response to Immunosuppressive Therapy
Histologic Diagnosis
IgG4-Related Disease of the Tubular Gut
Stomach
Ampulla
Small Bowel and Colon
IgG4-Related Cholecystitis
Non–IgG4-Related Diseases
Diseases of the Stomach
Diseases of the Colon
IgG4-Related Disease of the Retroperitoneum and Mesentery
Nodal Manifestation of IgG4-Related Disease
References
12 Drug-Induced Disorders of the Gastrointestinal Tract
Chapter Outline
Introduction
Nonspecific Injury Patterns
Organ-Specific
Esophagus
Pill Esophagitis
Stomach
Reactive Gastropathy
Small and Large Intestine
Colitis
Microscopic Colitis
Ischemic Enteritis/Colitis
Focal Active Colitis
Pseudo-obstruction (Ileus)
Non–Organ-Specific
Ulcers (Solitary and Multiple)
Perforation
Strictures
Apoptosis (Apoptotic Colopathy)
Vasculitis
Indirect Injury
Infectious Colitis
Specific Agents
Nonsteroidal Antiinflammatory Drugs
Pathogenesis
Risk Factors
Pathology
Esophagitis and Esophageal Strictures
Reactive Gastropathy
Erosions and Ulcers
NSAID Colitis
Miscellaneous Forms of NSAID-induced Colitis
Diaphragm Disease
Perforation
Exacerbation of Diverticular Disease or Inflammatory Bowel Disease
Differential Diagnosis
Proton Pump Inhibitors
Exacerbation of Corpus Gastritis and Atrophy
Endocrine Hyperplasia
Parietal Cell Hyperplasia and Fundic Gland Polyps
Microscopic Colitis
Differential Diagnosis
Sodium Polystyrene Sulfonate (Kayexalate)
Differential Diagnosis
Iron Therapy
Differential Diagnosis
Antacids, Sucralfate, and Gastric Mucosal Calcinosis
Colchicine
Chemotherapy
Selective Internal Radiation
Anti-CTLA4 Antibody–Induced Colitis
Neutropenic Colitis
Differential Diagnosis
Cathartics
Bulk Laxatives
Osmotic or Saline Laxatives
Stimulant or Irritant Laxatives
Mycophenolate Mofetil
Chemical Colitis (Glutaraldehyde)
References
13 Algorithmic Approach to Diagnosis of Inflammatory Disorders of the Gastrointestinal Tract
Chapter Outline
Introduction
Esophagus
Eosinophil-Predominant Esophagitis
Neutrophil-Predominant Esophagitis
Lymphocyte-Predominant Esophagitis
Granulomas
Pauciinflammatory Esophagitis
Ulcers
Gastroesophageal Junction
Stomach
General Comments
Gastritis
Focal Gastritis
Diffuse Gastritis
Lymphoplasmacytic
Intraepithelial Lymphocytes
Thick Subepithelial Collagen
Increased Eosinophils
Increased Neutrophils
Pauciinflammatory Gastritis (“Reactive Gastritis”)
Infiltrates
Small Intestine
General Comments
Complete Villous Atrophy
Partial Villous Atrophy
Lymphoplasmacytic
Eosinophils
Lamina Propria Infiltrates
Normal Villous Architecture
Colon
General Comments
Normal versus Abnormal
Inflammatory Disorders
Chronic Colitis
Chronic Colitis with Well-Preserved Architecture
Chronic Colitis with Abnormal Crypt Architecture
Acute Colitis
Acute Hemorrhagic Colitis
Acute (Nonhemorrhagic) Colitis
Eosinophil-Predominant Colitis
Paucicellular Colitis
Lamina Propria Infiltrates
Neoplasia
14 Inflammatory Disorders of the Esophagus
Chapter Outline
Introduction
Esophagitis
Gastroesophageal Reflux Disease
Clinical Features
Pathogenesis
Pathology
Squamous Hyperplasia
Inflammation
Neutrophils.
Eosinophils.
Lymphocytes.
Other Microscopic Features of GERD
Differential Diagnosis of GERD
Reactive Squamous Hyperplasia versus Dysplasia
Reactive Changes in Ulcers versus Dysplasia or Carcinoma
Natural History and Treatment of GERD
Infectious Esophagitis
Viral Esophagitis—Herpes
Clinical Features
Pathology
Differential Diagnosis
Treatment
Viral Esophagitis—Cytomegalovirus
Clinical Features
Pathology
Treatment
Other Viruses
Fungal Esophagitis—Candida
Clinical Features
Pathology
Differential Diagnosis
Treatment
Bacterial Esophagitis
Parasitic Esophagitis—Chagas Disease
Clinical Features and Pathogenesis
Pathology
Treatment
Pill-, Drug,- and Toxin-Related Esophagitis
Pill Esophagitis
Clinical Features
Pathology
Differential Diagnosis
Corrosive Esophagitis
Clinical Features
Pathology
Esophagitis Dissecans Superficialis
Clinical Features and Pathogenesis
Pathology
Differential Diagnosis
Treatment
Primary Eosinophilic Esophagitis
Clinical Features
Pathogenesis
Pathology
Gross (Endoscopic) Features
Microscopic Features
Differential Diagnosis
Natural History
Treatment
Lymphocytic Esophagitis
Mechanical Causes of Esophagitis
Achalasia
Clinical Features
Pathogenesis
Pathology
Treatment
Muscular Dystrophy
Mallory-Weiss Tears and Other Traumatic Esophageal Disorders
Congenital and Acquired Deformations
Esophageal Rings and Webs
Esophageal Diverticula
Esophageal Pseudodiverticulosis
Esophageal Involvement in Systemic Disease
Eosinophilic Gastroenteritis
Esophageal Involvement in Collagen Vascular Disorders (Including Scleroderma)
Esophageal Manifestations of Dermatologic Diseases
Graft-versus-Host Disease Involving the Esophagus
Chemotherapy- and Radiation-Induced Esophageal Injury
Crohn’s Disease
Esophageal Amyloidosis
Barrett’s Esophagus
Definition and Classification of Barrett’s Esophagus
Definition
Classification
Endoscopic Landmarks of Barrett’s Esophagus
Clinical Features
Pathogenesis
Pathology
Endoscopic Features
Microscopic Features
Goblet Cells versus Pseudogoblet Cells
Differential Diagnosis
Barrett’s Esophagus without Goblet Cells
Neoplastic Complications in Barrett’s Esophagus
Definition and Classification
Risk Factors and Pathogenesis
Pathology
Endoscopic Features
Microscopic Features
Negative for Dysplasia.
Indefinite for Dysplasia.
Positive for Dysplasia.
Crypt Dysplasia.
Nonintestinal (Nonadenomatous) Dysplasia.
Intramucosal Adenocarcinoma.
Adenocarcinoma with Submucosal Invasion.
Diagnostic Problems Related to Dysplasia
Sampling Error
Intraobserver and Interobserver Variability
Low-Grade Dysplasia versus High-Grade Dysplasia
High-Grade Dysplasia versus Intramucosal Adenocarcinoma
Intramucosal versus Submucosal Adenocarcinoma
Squamous Overgrowth (“Buried Barrett’s Esophagus”)
Adjunctive Diagnostic Tests of Dysplasia
Risk Assessment and Predictive Markers in Barrett’s Esophagus
Natural History and Risk of Malignancy
Treatment
Endoscopic Ablation and Resection
Endoscopic Mucosal Resection
Diagnostic Procedure.
Therapeutic Procedure.
References
15 Inflammatory Disorders of the Stomach
Chapter Outline
Historical Perspective
General Pathologic Features of Gastritis
Neutrophil Infiltration
Mononuclear Infiltration
Lymphoid Aggregates and Follicles
Eosinophil Infiltration
Mucosal Hyperemia and Edema
Surface Epithelium Degeneration
Surface Erosion
Foveolar Hyperplasia
Intestinal Metaplasia
Atrophy
Endocrine Cell Proliferation
Parietal Cell Alterations
Interfoveolar Smooth Muscle Hyperplasia
Updated Sydney System
Biopsy Protocol
Evaluation of Histologic Variables
Determination of Gradient of Inflammation
Diagnosis
Reporting Gastritis in the Absence of a Complete Biopsy Set
OLGA System
Acute Gastritis
Acute Hemorrhagic Gastritis
Clinical Features
Pathologic Features
Chronic Gastritis
Helicobacter pylori Gastritis
Clinical Features
Epidemiology
Pathologic Features
Subtypes of Helicobacter pylori Gastritis
Nonatrophic Antrum-Predominant Gastritis
Nonatrophic Corpus-Predominant Gastritis
Nonatrophic Pangastritis
Antrum-Restricted Atrophic Gastritis
Multifocal Atrophic Gastritis
Differential Diagnosis
Methods of Detecting Helicobacter pylori
Helicobacter heilmannii Infection
Natural History and Complications
Gastric Ulcers
Etiology
Pathologic Features
Complications
Dieulafoy Lesion
Helicobacter pylori–Negative Chronic Gastritis
Proton Pump Inhibitor Use
Recent Antibiotic Treatment
Causes of Chronic Active Gastritis Unrelated to Helicobacter Infection
Focally Active Gastritis
Other Infections
Reported Conclusions
Autoimmune Gastritis
Clinical Features
Epidemiology
Pathogenesis
Pathologic Features
Special Forms of Gastritis
Lymphocytic Gastritis
Clinical Features
Pathologic Features
Collagenous Gastritis
Eosinophilic Gastritis
Normal Eosinophil Counts in the Gastric Mucosa
Causes of Gastric Mucosal Eosinophilia
Idiopathic Eosinophilic Gastritis
Practical Suggestions for Diagnosis
Granulomatous Gastritis
Mycobacterial and Fungal Infections
Helicobacter pylori Infection
Parasites
Foreign Bodies
Tumors
Other Unusual Causes
Gastric Involvement in Systemic Granulomatous Diseases
Idiopathic Granulomatous Gastritis
Gastropathies
Reactive (Chemical) Gastropathy
Types of Chemical Injury to the Stomach
Acid, Alkali, and Large Quantities of Ethanol
Duodenopancreatic (Bile) Reflux
Medications
Pathogenesis of Reactive Gastropathy
Pathology
Morphologic Effects of Proton Pump Inhibitor Therapy
Clinical Relevance of a Diagnosis of Chemical Gastropathy
Other Drugs
Iron
Colchicine and Taxol
Kayexalate
Chemotherapy- and Radiation-Induced Gastropathy
Vascular Gastropathies
Gastric Antral Vascular Ectasia
Clinical Features
Pathologic Features
Portal Hypertensive Gastropathy
Clinical Features
Pathologic Features
Gastric Cardia, Carditis, and Gastroesophageal Junction
Histology of the Gastroesophageal Junction Region
Intestinal Metaplasia of the Gastroesophageal Junction
Gastroesophageal Junction Biopsies to Differentiate Carditis from Ultrashort Barrett’s Esophagus
Helicobacter pylori
Reporting a Biopsy from the Gastroesophageal Junction
Stomach in the Young and Elderly
Lymphoid Hyperplasia
Eosinophils
Atrophy
Gastric Epithelial Dysplasia
Dysplasia Precursor Lesions
Clinical Features and Incidence
Pathologic Features
Unusual Variants
Precursor Lesion of Poorly Cohesive Carcinomas
Polypoid Dysplasia in Familial Adenomatous Polyposis
Differential Diagnosis
Natural History and Treatment
References
16 Inflammatory Disorders of the Small Intestine
Chapter Outline
Disorders of Malabsorption
Gluten-Sensitive Enteropathy (Celiac Disease)
Epidemiology and Clinical Features
Pathogenesis
Pathologic Features
Background
Gross Pathology
Microscopic Pathology: Biopsy Strategy
Histology of Untreated Disease
Biopsies without Villous Blunting
Counting Intraepithelial Lymphocytes
Biopsies with Blunted Villi
Histology of Treated Disease (Response to a Gluten-Free Diet)
Refractory (Unclassified) Sprue
Malignancy in Gluten-Sensitive Enteropathy
Other Complications in Gluten- Sensitive Enteropathy
Differential Diagnosis
Other Disorders of Protein (Cow’s Milk and Soy Protein) Intolerance
Tropical Sprue
Epidemiology and Clinical Features
Pathologic Features
Gross Pathology
Microscopic Pathology
Differential Diagnosis
Bacterial Overgrowth Syndrome (Blind-Loop Syndrome, Stasis Syndrome)
Pathogenesis
Clinical Features
Pathologic Features
Eosinophilic Gastroenteritis
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Nutritional Deficiencies
Vitamin B12 Deficiency
Protein Deficiency
Acrodermatitis Enteropathica (Zinc Deficiency)
Iron Deficiency
Peptic Duodenitis and Duodenal Ulcer
Pathologic Features
Differential Diagnosis
Drug Injury of the Small Bowel
Nonsteroidal Antiinflammatory Drug–Induced Enteropathy
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Radiation- and Chemotherapy- Induced Enteritis
Radiation Injury
Acute Radiation Injury
Chronic Radiation Injury
Chemotherapy Injury
Immunomodulatory Drugs
Miscellaneous Drugs
Colchicine
Kayexalate
Inflammatory Bowel Disease
Crohn’s Disease
Epidemiology and Pathogenesis
Pathologic Features
Gross Pathology
Microscopic Pathology
Risk Factors for Anastomotic Recurrence after Surgery
Special Considerations for Biopsy Specimens
Terminal Ileum
Duodenal Crohn’s Disease
Differential Diagnosis
Duodenal Involvement by Ulcerative Colitis
Ileal–Anal Pouch Inflammation (Pouchitis)
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Treatment
Ischemic Disorders of the Small Intestine
Acute Mesenteric Insufficiency
Causes
Pathologic Features
Gross Pathology
Microscopic Pathology
Focal Segmental Ischemia
Neonatal Necrotizing Enterocolitis
Cryptogenic Multifocal Ulcerating Stenosing Enteritis
Graft-versus-Host Disease
Intestinal Lymphangiectasia
Primary Lymphangiectasia
Secondary Lymphangiectasia
Pathologic Features
Differential Diagnosis
Waldenström Macroglobulinemia
Pneumatosis Cystoides Intestinalis
References
17 Inflammatory Disorders of the Large Intestine
Chapter Outline
Approach to Evaluating Colitis
Normal Versus Abnormal
Acute Versus Chronic Colitis
Ulcerative Colitis
Epidemiology
Clinical Features
Risk Factors and Pathogenesis
Genetic Factors
Environmental Factors
Immune Factors
Pathologic Features
Gross Features
Microscopic Findings
Chronic Active Colitis.
Chronic Inactive (Quiescent) Colitis.
Effects of Prior Treatment on the Histology of Ulcerative Colitis.
Unusual Morphologic Variants of Ulcerative Colitis
Ascending Colon, Cecum, and Appendiceal Involvement as Skip Lesions in Ulcerative Colitis
Initial Presentation of Ulcerative Colitis in Pediatric Patients
Ileitis in Ulcerative Colitis
Upper GI Involvement in Ulcerative Colitis
Crohn’s-Like Aphthous Ulcers in Ulcerative Colitis
Granulomas in Ulcerative Colitis
Natural History and Treatment
Crohn’s Colitis
Clinical Features
Risk Factors and Pathogenesis
Genetic Factors
Environmental Factors
Immune Factors
Pathologic Features
Gross Features
Microscopic Features
General Comments.
Mucosal Changes.
Mural Changes.
Superficial (Ulcerative Colitis-Like) Crohn’s Colitis
Natural History and Treatment
Chronic Inflammatory Bowel Disease, Unknown Type (Indeterminate Colitis)
Historical Perspective
Pathologic Features
Natural History and Treatment
Ancillary (Serologic) Diagnostic Tests for IBD
Differential Diagnosis of Ulcerative Colitis versus Crohn’s Disease
Resection Specimens
Biopsy Specimens—Untreated
Biopsy Specimens—Treated
Dysplasia in Inflammatory Bowel Disease
Ulcerative Colitis: Incidence and Risk Factors of Dysplasia/Cancer
Crohn’s Disease: Incidence and Risk Factors of Dysplasia/Cancer
Pathologic Features of IBD Dysplasia
Gross Features and Anatomic Distribution
Microscopic Features
Morphologic Types of Dysplasia
Grading of Dysplasia
Nonintestinal Types of Dysplasia
Mucinous Dysplasia.
Serrated Dysplasia and Other Serrated Lesions.
Crypt Dysplasia.
Natural History and Treatment of Elevated (Raised) Dysplasia (DALMs)
Natural History and Treatment of Flat Dysplasia
Surveillance of Dysplasia
Sampling Error and Adjunctive Markers
Molecular Features of IBD Neoplasia
Other Colitides
Acute Self-Limited (Infectious) Colitis
Clinical Features
Specific Infectious Organisms
Campylobacter jenuni
Salmonella Species
Shigella Species
Escherichia coli
Yersinia enterocolitica
Pathogenesis
Tissue-Invasive Organisms
Toxigenic Organisms
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
Focal Active Colitis
Clinical Features
Pathologic Features
Natural History and Treatment
Ischemic Colitis
Pathogenesis
Acute Ischemic Colitis
Clinical Features
Specific Etiologic Factors
Pathologic Features
Gross Findings
Microscopic Findings
Natural History and Treatment
Chronic Ischemic Colitis
Clinical Features
Specific Etiologic Factors
Pathologic Features
Gross Findings
Microscopic Findings
Natural History and Treatment
Differential Diagnosis
Acute Ischemic Colitis
Chronic Ischemic Colitis
Radiation Colitis
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
Neonatal Necrotizing Enterocolitis
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
Allergic Proctocolitis
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Microscopic Colitis
Historical Perspective
Collagenous Colitis
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
Lymphocytic Colitis
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Other Types of Microscopic Colitis
Mastocytic Disorders
Mastocytic Enterocolitis
Systemic Mastocytosis
Irritable Bowel Syndrome
Apoptotic Colopathy
Diverticular Disease
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Crohn’s-Like Diverticulitis
Differential Diagnosis
Coexistent Crohn’s Disease and Diverticulitis versus Crohn’s-Like Diverticulitis
Natural History and Treatment
Diverticular Disease–Associated (Segmental) Colitis
Clinical Features
Pathogenesis and Association with IBD
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Diverticular Disease–Associated Colitis versus Ulcerative Colitis
Natural History and Treatment
Diversion Colitis
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Diversion Colitis versus Recurrent Ulcerative Colitis of Hartmann Pouch
Diversion Colitis versus Recurrent Crohn’s Disease of Hartmann Pouch
Natural History and Treatment
Drug-Induced Colitis
Nonsteroidal Antiinflammatory Drug–Associated Colitis
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
Mycophenolate Mofetil–Associated Colitis
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Cord Colitis Syndrome
Fibrosing Colonopathy
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
Chemotherapy-Associated Colonic Injury
Effects of Bowel Preparation Agents
Mucosal Prolapse Syndrome
Solitary Rectal Ulcer Syndrome
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
Colitis Cystica Polyposa/Profunda
Historical Perspective
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Behçet Syndrome
Clinical Features
Pathogenesis
Pathologic Features
Gross Findings
Microscopic Findings
Differential Diagnosis
Natural History and Treatment
References
18 Inflammatory Disorders of the Appendix
Chapter Outline
Normal Histology
Congenital, Developmental, and Acquired Anatomic Abnormalities
Abnormal Location
Duplication
Absence and Atresia
Appendiceal Septa
Diverticular Disease of the Appendix
Fibrous Obliteration of the Appendiceal Lumen
Acute Appendicitis and Associated Disorders
Clinical Features and Pathogenesis
Pathologic Features
Natural History and Outcomes
Stump Appendicitis
Periappendicitis
Chronic Appendicitis
Ulcerative Colitis
Crohn’s Disease
Granulomatous Appendicitis
Idiopathic Granulomatous Appendicitis
Differentiation of Crohn’s Disease from Idiopathic Granulomatous Appendicitis
Sarcoidosis
Interval (Delayed) Appendicitis
Cystic Fibrosis
Eosinophilic Appendicitis
Infectious Causes of Acute and Chronic Appendicitis
Bacterial Infections
Yersinia
Mycobacterium tuberculosis
Actinomyces
Campylobacter
Clostridium difficile and Shigella
Malakoplakia
Spirochetosis
Helicobacter pylori
Parasitic Infections
Enterobius vermicularis
Strongyloides stercoralis and Eosinophilic Appendicitis
Other Parasitic Infections
Viral Infections
Adenovirus
Cytomegalovirus
Epstein-Barr Virus
Measles Virus
Varicella-Zoster Virus
Fungal Infections
Miscellaneous Disorders of the Appendix
Intussusception of the Appendix
Endometriosis and Deciduosis
Endometriosis
Deciduosis
Gliomatosis and Heterotopias
Pigments, Foreign Material, and Processing Artifacts
Melanosis
Barium
Foreign Body Appendicitis
Rosai-Dorfman Disease
Acute Necrotizing Arteritis of Appendiceal Vessels
References
19 Polyps of the Esophagus
Chapter Outline
Introduction
Epithelial Polyps
Inflammatory and Hyperplastic Polyps
Squamous Papilloma
Heterotopia
Glycogenic Acanthosis
Adenomas
Polypoid Dysplasia in Barrett’s Esophagus
Spindle Cell Carcinoma
Squamous Cell Carcinoma and Adenocarcinoma
Melanoma
Mesenchymal Polyps
Granular Cell Tumors
Leiomyomas
Giant Fibrovascular Polyps
Rare Benign Polyps
Gastrointestinal Stromal Tumors
Cystic and Diverticular Lesions
References
20 Polyps of the Stomach
Chapter Outline
Introduction
Hyperplastic Polyps
Clinical Features and Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Dysplasia and Cancer in Hyperplastic Polyps
Morphologic Variants
Polypoid Foveolar Hyperplasia
Gastric Foveolar Polyps
Gastritis Cystica Polyposa or Profunda
Ménétrier Disease
Clinical Features
Pathogenesis
Pathologic Features
Treatment
Inflammatory Polyps
Inflammatory Retention Polyp
Polypoid Gastritis
Hamartomatous Polyps
Fundic Gland Polyp
Clinical Features and Pathogenesis
Pathologic Features
Natural History and Treatment
Peutz-Jeghers Polyp
Clinical Features and Pathogenesis
Pathologic Features
Juvenile Polyp
Clinical Features and Pathogenesis
Pathologic Features
Cronkhite-Canada Syndrome– Associated Polyps
Clinical Features
Pathologic Features
Embryonic Rests and Heterotopia
Pancreatic Heterotopia
Clinical Features
Pathologic Features
Differential Diagnosis
Pancreatic Acinar Metaplasia
Clinical Features
Pathologic Features
Differential Diagnosis
Brunner Gland Nodules
Epithelial Polyps
Adenoma
Clinical Features
Pathogenesis
Pathologic Features
Gross Features
Microscopic Features
Differential Diagnosis
Natural History and Treatment
Polypoid Carcinoma
Pyloric Gland Adenoma
Oxyntic Gland Polyp or Adenoma
Neuroendocrine (Carcinoid) Tumor
Metastatic Lesions
Nonepithelial Polyps
Inflammatory Fibroid Polyp
Clinical Features and Pathogenesis
Pathologic Features
Natural History and Treatment
Inflammatory Myofibroblastic Tumor
Clinical Features and Pathogenesis
Pathologic Features
Natural History and Treatment
Gastrointestinal Stromal Tumors
Differential Diagnosis of Gastric Stromal Polyps
Vascular Tumors
Lymphoid Polyps
Lymphoid Hyperplasia
Lymphoma
Miscellaneous Rare Polyps and Polyp-like Lesions
Xanthoma
Histiocytosis X
Pseudo–Signet Ring Cell Carcinoma In Situ
Granuloma
Amyloidosis
Calcium Deposits
Siderosis
References
21 Polyps of the Small Intestine
Chapter Outline
Introduction
Inflammatory Lesions
Hyperplasia and Heterotopia
Brunner Gland Hyperplasia/Hamartoma
Clinical and Endoscopic Features
Pathologic Features
Differential Diagnosis
Gastric Heterotopia
Clinical and Endoscopic Features
Pathologic Features
Differential Diagnosis
Pancreatic Heterotopia
Clinical and Endoscopic Features
Pathologic Features
Differential Diagnosis
Hamartomatous Polyps
Peutz-Jeghers Polyps
Clinical and Endoscopic Features
Pathologic Features
Juvenile Polyps
Clinical and Endoscopic Features
Pathologic Features
Benign Epithelial Neoplasms
Adenomas of the Small Intestine
Clinical and Endoscopic Features
Pathologic Features
Ampullary and Peraampullary Adenomas
Clinical and Endoscopic Features
Pathologic Features
Immunohistochemical and Molecular Features
Familial Adenomatous Polyposis
Clinical and Endoscopic Features
Risk of Malignancy
Pyloric Gland Adenoma
Hyperplastic Polyp
Neuroendocrine Tumors
NETs of the Duodenum, Ampulla, and Proximal Jejunum
Gastrin-Producing NETs
Clinical Features
Pathologic Features
Natural History
Somatostatin-Producing NETs
Clinical Features
Pathologic Features
Natural History
Gangliocytic Paraganglioma
Clinical Features
Pathologic Features
Natural History
NETs of the Distal Jejunum and Ileum
Clinical Features
Pathologic Features
Natural History
Neuroendocrine Carcinoma of the Small Intestine and Ampulla
Clinical Features
Pathologic Features
Natural History
Mesenchymal Lesions
Lymphatic Lesions
Primary Lymphangiectasia
Secondary Lymphangiectasia
Lymphoid Lesions
Benign Lymphoid Hyperplasia
Malignant Lymphoma
Multiple Lymphomatous Polyposis
Metastases
References
22 Polyps of the Large Intestine
Chapter Outline
Introduction
Inflammatory Polyps
Inflammatory Pseudopolyp
Pathologic Features
Natural History and Treatment
Prolapse-Type Inflammatory Polyp
Inflammatory Cap Polyp (and Cap Polyposis)
Colitis Cystica Profunda/Polyposa
Clinical Features
Pathologic Features
Diverticular Disease–Associated Polyp
Inflammatory Myoglandular Polyp
Hamartomatous Polyps
Juvenile Polyps and Juvenile Polyposis
Clinical Features
Pathologic Features
Natural History and Treatment
Peutz-Jeghers Syndrome
Clinical Features
Pathologic Features
Natural History and Treatment
Cowden Syndrome
Clinical Features
Pathologic Features
Natural History and Treatment
Cronkhite-Canada Syndrome
Clinical Features
Pathologic Features
Natural History and Treatment
Epithelial Polyps
Hyperplastic and Serrated Polyps
Nondysplastic Serrated Polyps
Hyperplastic Polyp
Clinical Features.
Classification and Pathogenesis.
Pathologic Features.
Differential Diagnosis.
Natural History and Treatment.
Sessile Serrated Adenoma/Polyp
Clinical Features and Synonyms.
Pathologic Features.
Dysplastic Serrated Polyps
Sessile Serrated Adenoma/Polyp with Dysplasia
Natural History and Treatment.
Traditional Serrated Adenoma
Pathologic Features.
Natural History and Treatment.
Conventional Adenoma with Serrated Architecture
Unclassifiable Serrated Polyps
Serrated Polyposis Syndrome
Natural History and Molecular Pathogenesis
Conventional Adenoma
Clinical Features
Pathologic Features
Natural History
Treatment and Surveillance Issues
Key Reporting Issues
Adenoma with Epithelial Misplacement (Pseudocarcinoma)
Clinical Features
Pathologic Features and Differential Diagnosis
Treatment
Flat Adenomas
Adenomatous Polyposis Syndromes
Familial Adenomatous Polyposis
Gardner Syndrome
Turcot Syndrome
Attenuated Familial Adenomatous Polyposis
MUTYH-Associated Polyposis
Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer Syndrome)
Adenomas and Adenoma-Like Dysplasia-Associated Lesions or Masses in Inflammatory Bowel Disease
Pathologic Features and Differential Diagnosis
Malignant Epithelial Polyps
Definition and Clinical Features
Treatment
Polypoid Endocrine Tumor
Metastasis to the Colon
Lymphoid Polyp
Mesenchymal Polyps
Ganglioneuroma
Clinical Features
Pathologic Features
Neurofibroma
Clinical Features
Pathologic Features
Granular Cell Tumor
Mucosal Perineurioma
Mucosal Schwann Cell Hamartoma
Leiomyoma of the Muscularis Mucosae
Leiomyosarcoma
Gastrointestinal Stromal Tumor
Lipoma
Lipomatous Ileocecal Valve
Inflammatory Fibroid Polyp
Miscellaneous Polypoid Lesions
Pneumatosis Coli
Clinical Features
Pathologic Features
Mucosal Pseudolipomatosis
Endometriosis
Clinical Features
Pathologic Features
Benign Infiltrative Processes
Muciphages
Xanthomas and Xanthogranulomas
Differential Diagnosis of Histiocytic Infiltrates
Systemic Mastocytosis
Inverted Appendix
Mucosal Tag
Atheroembolus-Associated Polyp
References
23 Molecular Diagnostics of Tubal Gut Neoplasms
Chapter Outline
Introduction
Methodologies
Sample Collection and Processing
Tissue
Microdissection
Circulating DNA
Nucleic Acid Extraction and Purification
Detection of Sequence Variants
Sanger Sequencing
Next-Generation Sequencing
Template Generation
Sequencing Reaction
Data Analysis
Sequencing Coverage
Clinical Applications
Targeted Sequencing
Whole-Exome Sequencing
Whole-Genome Sequencing
Rare Variant Detection
Rare Mutation Detection
BEAMing Technology
Detection of Minimal Residual Disease
Detection of Translocations and Genomic Copy-Number Alterations
Fluorescence and Chromogenic In Situ Hybridization
Polymerase Chain Reaction Detection of Translocations
Molecular Detection of Copy Number Aberrations
Microarray-Based Platforms
Array Technologies
Expression Arrays
Comparative Genomic Hybridization
Multimarker Assays
Molecular Diagnostics of Hereditary Gastrointestinal Cancer
Lynch Syndrome
Universal Molecular Screening for Lynch Syndrome
Microsatellite Instability Testing
Mismatch Repair Immunohistochemistry
Characterization of MLH1-Deficient Colorectal Cancers
BRAF Testing
MLH1 Methylation Testing
Germline Testing
Hereditary Diffuse Gastric Cancer
Molecular Diagnostics in Targeted Therapy
Principles of Targeted Therapy
Driver Mutations and Oncogene Addiction
Tyrosine Kinase Inhibitors
Monoclonal Antibody Therapies
Tumor Heterogeneity and Acquired Resistance to Targeted Therapy
HER2 Testing in Gastric and Gastroesophageal Cancer
Immunohistochemical Analysis of HER2 Expression
Fluorescence In Situ Hybridization Analysis of HER2 Copy Number
HER2 Testing in Other Cancers
Sensitivity to Anti-EGFR Therapy in Colorectal Cancer
KRAS Mutation Testing
Other Predictors of Resistance to Anti-EGFR Therapy
NRAS Mutation
BRAF Mutation
PIK3CA Mutation
PTEN Inactivation
HER2 Amplification
Acquired Resistance to Anti-EGFR Therapy
HER2 Amplification
EGFR Mutation
Gastrointestinal Stromal Tumor
KIT and PDGFRA Mutations
Imatinib Therapy
Sunitinib Therapy
Other Targeted Therapies
Resistance Monitoring during Therapy
Molecular Diagnostics and Predictive Factors for Chemotherapy
DNA Mismatch Repair Status
Proprietary Recurrence Risk Tests
Molecular Diagnostics of Hematologic Malignancies
Detection of Clonality
Light-Chain Restriction
Southern Blot
Polymerase Chain Reaction
Detection of Diagnostic Translocations and Other Cytogenetic Abnormalities
Detection of Mutations
Infectious Disease
References
24 Epithelial Neoplasms of the Esophagus
Chapter Outline
Introduction
Benign Neoplasms and Tumor-Like Lesions
Squamous Papilloma
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Prognosis
Adenoma
Submucosal Gland/Duct Adenoma
Polypoid Dysplasia in Barrett’s Esophagus
Tumor-Like Lesions
Developmental Cysts and Duplications
Heterotopias
Pseudoepitheliomatous Hyperplasia
Malignant Neoplasms
Squamous Cell Carcinoma
Clinical Features
Pathogenesis
Molecular Features
Squamous Dysplasia
Clinical Features
Pathologic Features
Gross Pathology
Microscopic Pathology
Differential Diagnosis (Reactive versus Neoplastic)
Prognosis and Treatment
Invasive Squamous Cell Carcinoma (Box 24.2)
Pathologic Features
Gross Pathology
Microscopic Pathology
Differential Diagnosis
Prognosis and Treatment
Variants of Squamous Cell Carcinoma
Basaloid Squamous Cell Carcinoma
Clinical Features
Pathologic Features
Special Studies
Differential Diagnosis
Prognosis
Carcinosarcoma
Clinical Features
Pathologic Features
Differential Diagnosis
Prognosis
Verrucous Squamous Cell Carcinoma
Clinical Features
Pathologic Features
Differential Diagnosis
Prognosis
Lymphoepithelioma-Like Carcinoma
Esophageal Carcinoma Cuniculatum
Adenocarcinoma
Clinical Features
Pathogenesis and Risk Factors
Intestinal (Goblet Cell) versus Nonintestinal (Nongoblet) Columnar Metaplasia
Molecular Features
Pathologic Features
Gross Pathology
Microscopic Pathology
Special Studies
Differential Diagnosis
Prognosis and Treatment
Dysplasia in Barrett’s Esophagus
Variants of Adenocarcinoma
Non–Barrett’s-Associated Adenocarcinoma
Adenoid Cystic Carcinoma
Carcinoma with Mixed Squamous and Glandular Elements
Neuroendocrine Neoplasms
Well-Differentiated Neuroendocrine Tumor (Grades 1 and 2)
Large Cell Neuroendocrine Carcinoma (Grade 3)
Small Cell Neuroendocrine Carcinoma (Grade 3)
Mixed Adenocarcinoma/Neuroendocrine Carcinoma (Grade 3)
Choriocarcinoma
Melanoma
Pleomorphic Giant Cell Carcinoma
Metastases
References
25 Epithelial Neoplasms of the Stomach
Chapter Outline
Introduction
Pathogenesis
Histologic Precursors of Gastric Cancer
Anatomic Distribution: Cardia Cancer
Early Gastric Cancer
Clinical and Pathologic Features
Natural History and Treatment
Advanced Gastric Carcinoma
Pathologic Features
Gross Features
Microscopic Features
Morphologic Subtypes of Gastric Adenocarcinoma
Gastric Carcinoma with Lymphoid Stroma
AFP Producing Carcinomas
Adenosquamous and Squamous Cell Carcinoma
Choriocarcinoma
Carcinosarcoma
Small Cell Carcinoma
Parietal Cell Carcinoma and Oncocytic Carcinoma
Paneth Cell Carcinomas
Malignant Rhabdoid Tumor
Metastatic Carcinomas
Gastric Carcinoma in Special Clinical Circumstances
Gastric Stump Carcinoma
Gastric Carcinoma in Young Patients
Genetic Predisposition and Hereditary Tumor Syndromes
Familial Diffuse Gastric Carcinoma
Hereditary Nonpolyposis Colorectal Cancer Syndrome
Familial Adenomatous Polyposis Coli
Li-Fraumeni Syndrome
Peutz-Jeghers Syndrome
Gastric Hyperplastic Polyposis
Natural History and Prognosis of Gastric Adenocarcinoma
Molecular Pathology of Gastric Cancer
Tumor Suppressor Genes
Oncogenes
References
26 Epithelial Neoplasms of the Small Intestine
Chapter Outline
Introduction
Small-Intestinal Neoplasia in Polyposis and Hereditary Cancer Syndromes
Familial Adenomatous Polyposis
Peutz-Jeghers Syndrome
Lynch Syndrome
Adenomatous Polyps
Preinvasive Ampullary Neoplasia
Small-Intestinal Adenocarcinoma
Clinical Features and Associations
Pathologic Features
Immunohistochemical Features
Ampullary Adenocarcinomas
Histologic Features
Immunohistochemical Features
Staging
Molecular Features
KRAS Mutations
TP53 Alterations
APC and β-Catenin Mutations
Mismatch Repair Genes
Epigenetic Alterations
SMAD4 Mutations
Prognosis
Crohn’s Disease–Associated Adenocarcinoma
Clinical Features
Pathologic Features of Dysplasia
Pathologic Features of Adenocarcinoma
Differential Diagnosis
Celiac Disease–Associated Adenocarcinoma
Other Types of Carcinoma
Hepatoid Carcinoma
Choriocarcinoma
Small Cell Carcinoma
Adenosquamous Carcinoma
Squamous Cell Carcinoma
Sarcomatoid Carcinoma
Carcinoma in Ileostomies
Carcinoma in Meckel Diverticula
Carcinoma in Heterotopic Pancreas
Metastatic Carcinoma
Gangliocytic Paraganglioma
References
27 Epithelial Neoplasms of the Large Intestine
Chapter Outline
Introduction
Clinical Features
Incidence
Epidemiology
Pathogenesis
Progression from Adenoma to Carcinoma
Genetic Model of Colorectal Cancer Progression
Chromosomal Instability.
Microsatellite Instability.
CpG Island Methylator Phenotype.
Implications of Progression Pathways for Screening and Prevention.
Molecular Pathway Classification of Colorectal Cancer.
WNT Signaling Abnormalities.
Other Genetic Alterations.
Molecular Profiles of Colorectal Cancer.
Gross Features and Specimen Handling
Pathologic Features
Criteria for Malignancy and Biopsy Diagnosis
Classification of Histologic Subtypes
Adenocarcinoma, Usual Type
Mucinous Adenocarcinoma
Signet Ring Cell Adenocarcinoma
Undifferentiated Carcinoma
Medullary Carcinoma
Serrated Adenocarcinoma
Carcinoma with Squamous Metaplasia (Adenoacanthoma)
Adenosquamous Carcinoma
Squamous Cell Carcinoma
Sarcomatoid Carcinoma (Spindle Cell Carcinoma, Carcinosarcoma)
Choriocarcinoma
Poorly Differentiated Neuroendocrine Carcinoma
Mixed Adenoneuroendocrine Carcinoma
Diffuse Carcinoma
Other Rare Subtypes of Colon Carcinoma
Carcinomas with DNA Mismatch Repair Deficiency
Villous Adenocarcinoma
Tumor Grading
Special Studies
Techniques to Facilitate Lymph Node Detection
Sentinel Lymph Nodes
Immunophenotype
Differential Diagnosis
Metastasis versus Multiple Synchronous Primary Carcinoma
Recurrent or Metastatic Carcinoma versus Metachronous Carcinoma
Colorectal Adenocarcinoma versus Endometrial or Ovarian Adenocarcinoma
Colorectal Adenocarcinoma versus Primary Small-Intestinal Adenocarcinoma
Natural History
Treatment
Surgical Therapy
Chemotherapy
Targeted Therapy
Investigational Agents
Role of Stage and Pathologic Factors in Management
Colon Cancer.
Rectal Cancer.
Prognostic Factors
Pathologic Staging
Depth of Tumor Invasion and Peritoneal Involvement
Lymph Node Involvement
Histologic Grade
Histologic Subtype
Proximal and Distal Resection Margins
Radial Resection Margin and Total Mesorectal Excision
Invasion of Endothelium-Lined Spaces
Host Immune Response
Invasive Margin (Leading Edge) of Tumor
Tumor Budding
Neoadjuvant Therapy for Rectal Carcinoma
Liver Metastases
Molecular Genetic Markers
Treatment Response Predictive Factors
Pathologic Predictive Factors
Molecular Genetic Predictive Markers
Predictors of Response to Fluoruracil
Predictors of Response to Irinotecan
Other Predictors of Response to Chemotherapy
Predictors of Response to Anti-EGFR Therapy
Predictors of Response to Anti-VEGF Therapy
Hereditary Nonpolyposis Colorectal Cancer and Lynch Syndrome
Clinical Features
Pathogenesis
Pathologic Features
Ancillary Studies Used by Pathologists for Lynch Syndrome Evaluation
Microsatellite Instability Testing
Mismatch Repair Immunohistochemistry
BRAF Mutation Testing
MLH1 Methylation Testing
Germline Testing
Differential Diagnosis
Role of the Pathologist
Universal Testing for Lynch Syndrome
Natural History and Treatment
Colorectal Cancer in Serrated Polyposis Syndrome
Colitis-Associated Neoplasia
Pathogenesis
Pathologic Features
References
28 Epithelial Neoplasms of the Appendix
Chapter Outline
Mucinous Epithelial Tumors
Nomenclature
Adenoma
Clinical Features
Pathogenesis
Pathology
Differential Diagnosis
Retention Cyst
Low-Grade Appendiceal Mucinous Neoplasm
Serrated Polyp of the Appendix
Natural History
Treatment
Low-Grade Appendiceal Mucinous Neoplasm
Clinical Features
Pathogenesis
Pathology
Differential Diagnosis
Retention Cyst
Ruptured Appendiceal Diverticulum
Natural History
Treatment
Adenocarcinoma
Clinical Features
Pathogenesis
Pathology
Differential Diagnosis
Low-Grade Appendiceal Mucinous Neoplasm versus Mucinous Adenocarcinoma
Natural History
Treatment
Pseudomyxoma Peritonei
Clinical Features
Pathology, Nomenclature, and Outcome
Treatment
Serrated Tumors of the Appendix
Clinical Features
Pathogenesis
Pathology
Hyperplastic Polyp/Diffuse Mucosal Hyperplasia
Sessile Serrated Adenoma/Polyp
Traditional Serrated Adenoma
Differential Diagnosis
Appendiceal Adenoma and LAMN
Neuroendocrine Tumors
Well-Differentiated Neuroendocrine Tumor (Carcinoid Tumor)
Clinical Features
Pathogenesis
Pathology
Differential Diagnosis
Goblet Cell Carcinoid
Metastatic Carcinoma
Natural History
Treatment
Tubular Carcinoid
Differential Diagnosis
Goblet Cell Carcinoid
Metastatic Adenocarcinoma
Natural History
Treatment
Neuroendocrine Carcinoma
Mixed Glandular and Endocrine Neoplasms
Nomenclature
Goblet Cell Tumors
Clinical Features
Pathogenesis
Pathology
Goblet Cell Carcinoid
Mixed Adenoneuroendocrine Carcinoma (MANEC)
Differential Diagnosis
Signet Ring Cell Adenocarcinoma versus Pure Goblet Cell Carcinoid Tumor
Conventional Adenocarcinoma versus Pure Goblet Cell Carcinoid Tumor
Metastatic Adenocarcinoma versus Pure Goblet Cell Carcinoid Tumor
Natural History
Treatment
Other Mixed Glandular and Endocrine Tumors
Secondary Tumors (Other Than Lymphoma)
References
29 Neuroendocrine Tumors of the Gastrointestinal and Pancreatobiliary Tracts
Chapter Outline
Neuroendocrine Cell System of the Gastrointestinal Tract
Terminology and Classification
Neuroendocrine Tumor Differentiation
True Neuroendocrine Tumors
Well-Differentiated Neuroendocrine Tumors
Clinical Features and Epidemiology
Pathologic Features
Morphologic Variants
Immunohistochemistry and Electron Microscopy
Molecular Biology
Differential Diagnosis
Pathologic Prognosticators and Clinical Outcomes
Treatment
Site-Specific Features
Esophagus
Stomach
Duodenum
Jejunum and Ileum
Appendix
Colon
Rectum
Pancreas
Gallbladder and Biliary Tract
Poorly Differentiated Neuroendocrine Carcinomas
Mixed Tumors
Mixed Adenoneuroendocrine Carcinomas
Mixed Neuroendocrine Tumor with Non-neuroendocrine Carcinomas
Duodenal Gangliocytic Paraganglioma
Incidental Neuroendocrine Cell Proliferations in Other Epithelial Tumors
Chimeric Tumors with Incomplete Neuroendocrine Differentiation
Conventional-Type Goblet Cell Carcinoids
High-Grade Goblet Cell Carcinoids
Other Tumors with Neuroendocrine Differentiation
Nonepithelial Tumors with Neuroendocrine Differentiation
Induced Neuroendocrine Differentiation
Focal Neuroendocrine Differentiation in Other Tumors
Metastatic Tumors of Neuroendocrine Origin
Neuroendocrine Tumor Mimics
Acknowledgment
References
30 Mesenchymal Tumors of the Gastrointestinal Tract
Chapter Outline
Introduction
Gastrointestinal Stromal Tumors (GISTs)
Clinical Features
Pathologic Features
Gross and Microscopic Features
Immunohistochemical Features
Molecular Findings
Differential Diagnosis
Prognosis and Treatment
GIST Syndromes and Succinate Dehydrogenase–Deficient GISTs
Tumors of Neural Origin
Schwannoma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Gangliocytic Paraganglioma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Ganglioneuroma and Ganglioneuromatosis
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Mucosal Perineurioma
Clinical Features and Background
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Mucosal Schwann Cell Hamartoma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry
Treatment and Prognosis
Granular Cell Tumor
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Tumors of Smooth Muscle Origin
Leiomyoma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Leiomyosarcoma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Smooth Muscle Tumors of Uncertain Malignant Potential
Fibroblastic Tumors
Mesenteric Fibromatosis
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Inflammatory Myofibroblastic Tumor
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Vascular Tumors
Hemangiomas and Other Benign Vascular Proliferations
Glomus Tumors
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Angiosarcoma and Kaposi Sarcoma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Tumors of Adipose Tissue
Lipomas and Liposarcomas
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Rare but Noteworthy Entities
Perivascular Epithelioid Cell Tumor
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Plexiform Fibromyxoma (Plexiform Angiomyxoid Myofibroblastic Tumor)
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Gastrointestinal Clear Cell Sarcoma–Like Tumor
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Synovial Sarcoma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
Gastroblastoma and Duodenoblastoma
Clinical Features
Pathologic Features
Gross and Microscopic Findings
Immunohistochemistry and Molecular Findings
Treatment and Prognosis
References
31 Hematolymphoid Tumors of the Gastrointestinal Tract, Hepatobiliary Tract, and Pancreas
Chapter Outline
Introduction
Gastric MALT Lymphoma
Clinical Features
Pathologic Features
Immunohistochemistry
Molecular Features
Staging, Treatment, and Outcome
Pathogenesis
Differential Diagnosis
Marginal-Zone Lymphoma versus Gastritis
Marginal-Zone Lymphoma versus Other Low-Grade Lymphomas
Transformation to Large B-Cell Lymphoma versus Marginal-Zone Lymphoma with Increased Large Cells
Poorly Preserved High-Grade Lymphoma versus Marginal-Zone Lymphoma
Plasmacytoma versus Marginal-Zone Lymphoma
Intestinal MALT Lymphoma
Clinical Features
Pathologic Features
Immunoproliferative Small-Intestinal Disease
Clinical Features
Pathologic Features
Stage A
Stage B
Stage C
Differential Diagnosis
Gastric Diffuse Large B-Cell Lymphoma
Clinical Features
Pathologic Features
Molecular Features
Staging and Outcome
Differential Diagnosis
Intestinal Diffuse Large B-Cell Lymphoma
Clinical Features
Pathologic Features
Differential Diagnosis
Mantle Cell Lymphoma
Clinical Features
Pathologic Features
Differential Diagnosis
Follicular Lymphoma
Burkitt Lymphoma
Clinical Features
Pathologic Features
Differential Diagnosis
Enteropathy-Associated T-Cell Lymphoma
Type I
Clinical Features
Pathologic Features
Immunohistochemical Features
Type II
Clinical Features
Pathologic Features
Molecular Features
Lymph Node Changes
Complicated Celiac Disease: Refractory Sprue and Ulcerative Jejunitis
Differential Diagnosis
Extranodal NK/T-Cell Lymphoma, Nasal Type
Other Gastrointestinal (GI) T-Cell Lymphomas
Appendiceal Lymphomas
Clinical Features
Pathologic Features
Differential Diagnosis
Hodgkin Lymphoma of the GI Tract
Clinical Features
Pathologic Features
Differential Diagnosis
GI Lymphoproliferative Disorders in Abnormal Immune States
Human Immunodeficiency Virus Infection
Lymphomas Associated with Iatrogenic Immunosuppression in Transplant Recipients
Inflammatory Bowel Disease–Associated Lymphoma
X-Linked Lymphoproliferative Disorder
Common Variable Immunodeficiency
Wiskott-Aldrich Syndrome
EBV-Positive Mucocutaneous Ulcer
Hepatic Lymphomas
Primary Hepatic Lymphoma
Clinical Features
Associated Disorders
Prognosis
Pathologic Features
Differential Diagnosis
Hepatosplenic T-Cell Lymphoma
Clinical Features
Pathologic Features
Hepatic Involvement in Widespread Lymphoma
Lymphomas of the Gallbladder
Clinical Features
Pathologic Features
Lymphomas of the Extrahepatic Bile Ducts
Pancreatic Lymphomas
Clinical Features
Pathologic Features
Differential Diagnosis
Proliferations of Histiocytes and Dendritic Cells in the GI Tract and Liver
Hemophagocytic Lymphohistiocytosis
Rosai-Dorfman Disease of the GI Tract and Liver
Differential Diagnosis
Histiocytic Sarcoma of the GI Tract
Differential Diagnosis
ALK-Positive Histiocytosis
Follicular Dendritic Cell Sarcoma
Clinical Features
Pathologic Features
Differential Diagnosis
Langerhans Cell Histiocytosis of the GI Tract and Liver
Differential Diagnosis
Mastocytosis: Manifestations in the GI Tract and Liver
Differential Diagnosis
References
32 Inflammatory and Neoplastic Disorders of the Anal Canal
Chapter Outline
Embryology and Anatomy of the Anal Canal
Embryologic Abnormalities of the Anus and Anal Canal
Clinical Features
Pathogenesis
Pathology
Prognosis and Treatment
Benign Tumors and Tumor-like Lesions of the Anus and Anal Canal
Hemorrhoids
Clinical Features
Pathogenesis
Pathology
Prognosis and Treatment
Hypertrophied Anal Papillae or Fibroepithelial Polyps
Clinical Features and Pathogenesis
Pathology
Prognosis and Therapy
Inflammatory Cloacogenic Polyps and Mucosal Prolapse
Clinical Features
Pathology
Differential Diagnosis
Inflammatory Disorders of the Anal Canal
Anal Tears, Fissures, and Ulcers
Clinical Features
Pathogenesis
Pathology
Prognosis and Treatment
Anal Abscesses and Fistulas
Common Infections of the Anal Canal
Clinical Features and Pathogenesis
Pathology
Differential Diagnosis
Inflammatory Bowel Disease
Clinical Features and Pathogenesis
Pathology
Differential Diagnosis
Prognosis
Treatment
Benign Tumors of the Anal Canal
Adnexal Tumors
Clinical Features
Pathology
Differential Diagnosis
Granular Cell Tumor
Clinical Features and Pathogenesis
Pathology
Squamous Neoplasms of the Anal Canal
Risk Factors and Pathogenesis
Nomenclature of Preinvasive Anal Squamous Neoplasia
Condyloma Acuminatum
Clinical Features
Pathology
Differential Diagnosis
Prognosis
Treatment
Anal Squamous Intraepithelial Neoplasia
Clinical Features
Pathology
Differential Diagnosis
Differentiating Reactive Changes or Immature Squamous Metaplasia from High-Grade Squamous Intraepithelial Lesions
Distinguishing Low-Grade and High-Grade Squamous Intraepithelial Lesions
Differentiating High-Grade Squamous Intraepithelial Lesions from Superficially Invasive Squamous Cell Carcinoma
Natural History and Treatment
Perianal Squamous Intraepithelial Neoplasia
Anal Canal Squamous Cell Carcinoma
Clinical Features
Pathology
Special Subtypes
Differential Diagnosis
Prognosis
Treatment
Verrucous Carcinoma and Giant Condyloma Acuminatum of Buschke-Löwenstein
Anal Adenocarcinoma
Clinical Features and Pathogenesis
Pathology
Differential Diagnosis
Prognosis and Treatment
Paget Disease of the Anus
Clinical Features
Pathogenesis
Pathology
Differential Diagnosis
Prognosis and Treatment
Anal Melanoma
Clinical Features and Pathogenesis
Pathology
Differential Diagnosis
Prognosis and Treatment
Other Rare Neoplasms of the Anal Canal
References
34 Molecular Genetics of Pancreatobiliary Neoplasms
Chapter Outline
Introduction
Pancreatic Neoplasms
Ductal Adenocarcinoma
Germline Alterations
Somatic Alterations
Implications for Pathology
Variants of Ductal Adenocarcinoma
Intraductal Papillary Mucinous Neoplasm
Germline Alterations
Somatic Alterations
Implications for Pathology
Mucinous Cystic Neoplasm
Germline Alterations
Somatic Alterations
Implications for Pathology
Serous Cystadenoma
Germline Alterations
Somatic Alterations
Implications for Pathology
Pancreatic Neuroendocrine Tumor
Germline Alterations
Somatic Alterations
Implications for Pathology
Solid-Pseudopapillary Neoplasm
Germline Alterations
Somatic Alterations
Implications for Pathology
Acinar Cell Carcinoma
Germline Alterations
Somatic Alterations
Implications for Pathology
Pancreatoblastoma
Germline Alterations
Somatic Alterations
Implications for Pathology
Biliary Neoplasms
Cholangiocarcinoma
Germline Alterations
Somatic Alterations
Implications for Pathology
Gallbladder Carcinoma
Germline Alterations
Somatic Alterations
Implications for Pathology
Conclusion
References
33 Gallbladder, Extrahepatic Biliary Tract, and Pancreas Tissue Processing Techniques and Normal Histology
Chapter Outline
Introduction
Normal Anatomy and Histology
Gallbladder and Extrahepatic Biliary Tract
Pancreas
Gallbladder
Gallstones
Cholesterol Stones
Pigment Stones
Processing Gallbladder Specimens
Cholecystitis
Carcinoma of the Gallbladder
Specimen Appearance
Specimen Dissection
Specimen Sectioning
Extrahepatic Biliary Tract
Processing Biliary Tract Specimens
Biliary Tract Cancer
Choledochal Cyst
Extrahepatic Biliary Atresia
Hepatectomy Specimens
Pancreas
Processing Pancreaticoduodenectomy Specimens
Intraductal Papillary Mucinous Neoplasms
Distal Pancreatectomy for Tumor
Distal Pancreatectomy for Pancreatitis
Frozen Sections and Intraoperative Consultation
Bile Duct Margins
Hilar Resections or Partial Hepatectomy
Distal Bile Duct Margin
Proximal Bile Duct Margin
Prognostic Considerations
Pancreaticoduodenectomy (Whipple) Procedure
Pancreatic Margins
Intraductal Papillary Mucinous Neoplasms
Intraoperative Pancreatic Biopsy
Gallbladder
References
35 Diagnostic Cytology of the Biliary Tract and Pancreas
Chapter Outline
Introduction
Cytologic Sampling of the Pancreatobiliary Tract
Indications
Contraindications
Rapid On-Site Evaluation
Sensitivity and Specificity
Biliary Brushing Cytology
FNAB Cytology
Specimen Preparation
Preparation of Pancreatobiliary Tract Brushing Specimens
Preparation of FNAB Specimens
Samples from Cystic Lesions.
Samples from Solid Masses.
Contaminants
Mesothelial Cells.
Hepatocytes.
Gastrointestinal Epithelium.
Gastric Epithelium.
Small-Intestinal Epithelium.
Cytology of the Biliary Tract
Normal Biliary Tract
Reactive Changes
Dysplasia
Adenoma of the Biliary Tract and Ampulla
Intraductal Neoplasms of the Biliary Tract
Adenocarcinoma
Differential Diagnosis
Reactive Processes versus Adenocarcinoma in the Biliary Tract
Ancillary Studies
Molecular Investigations
Aneuploidy and Chromosomal Analyses
Protein Analysis
Cytology of the Pancreas
Normal Pancreas and Contaminants
Ductal Cells
Acinar Cells
Islet Cells
Solid Masses
Cytologic Approach to Aspirates of Solid Masses: Ductal Pattern versus Solid Cellular Pattern
Reactive Processes
Acute Pancreatitis
Chronic Pancreatitis
Autoimmune Pancreatitis
Reactive Atypia
Ductal Adenocarcinoma
Diagnostic Criteria
Cellular Composition
Cellularity
Architectural Features
Background
Cytoplasmic Features
Nuclear Features
Nuclear Enlargement.
Anisonucleosis.
Mitoses.
Undifferentiated (Anaplastic) Adenocarcinoma
Undifferentiated Carcinoma with Osteoclast-Like Giant Cells
Variants of Ductal Adenocarcinoma
Adenosquamous Carcinoma
Colloid (Mucinous Noncystic) Carcinoma
Signet Ring Cell Carcinoma
Medullary Carcinoma
Differential Diagnosis and Pitfalls
Ancillary Studies
Cytologic Diagnosis of Nonductal Pancreatic Neoplasms
Well-Differentiated Pancreatic Neuroendocrine Tumors
Poorly Differentiated Pancreatic Neuroendocrine Carcinoma
Acinar Cell Carcinoma
Solid-Pseudopapillary Neoplasm
Pancreatoblastoma
Differential Diagnosis of PanNET, ACC, SPN, and PB
Pancreatic Cysts
Ancillary Studies
Mucin Stains
Cyst Fluid Viscosity
Tumor Markers
Enzymes
Mutations
Non-neoplastic Cysts
Pseudocysts
Ciliated Foregut Cyst
Lymphoepithelial Cyst of the Pancreas
Squamoid Cyst of the Pancreatic Ducts
Cystic Neoplasms
Serous Cystic Neoplasm (Serous Cystadenoma/Serous Cystadenocarcinoma)
Mucinous Cystic Neoplasm
Acinar Cell Cystadenocarcinoma
Intraductal Papillary Mucinous Neoplasm
Cytology for Mucinous Cysts
Invasive Carcinoma Associated with MCN or IPMN
Intraductal Oncocytic Papillary Neoplasms and Invasive Oncocytic Carcinomas
Role of Cytology in the Management of Mucinous Cysts
Cystic Pancreatic Neuroendocrine Tumors
Differential Diagnosis and Pitfalls: Neoplastic Mucinous Epithelium versus Gastrointestinal Contaminant
Rare Pancreatic and Extrapancreatic Cysts and Neoplasms
Pancreatic Metastases
References
36 Developmental Disorders of the Gallbladder, Extrahepatic Biliary Tract, and Pancreas
Chapter Outline
Introduction
Structural Development of the Gallbladder, Extrahepatic Biliary Tract, and Pancreas
Structural and Developmental Anomalies of the Gallbladder
Agenesis
Hypoplasia
Gallbladder Duplication
Septation
Phrygian Cap
Diverticulum
Anomalous Location
Heterotopias of the Gallbladder and Biliary Tree
Structural and Developmental Anomalies of the Extrahepatic Biliary Tract
Choledochal Cyst
Etiology
Classification
Pathology
Complications and Treatment
Biliary Atresia
Structural and Developmental Anomalies of the Pancreas
Complete and Partial Pancreatic Agenesis
Duct Abnormalities
Pancreas Divisum
Annular Pancreas
Heterotopic Pancreas
Congenital Cyst of the Pancreas
Cystic Fibrosis
Congenital Pancreatic Exocrine Deficiencies
Diabetes Mellitus
Neonatal Islet Cell Hypertrophy and Hyperplasia
Persistent Hyperinsulinemic Hypoglycemia of Infancy
Acknowledgment
References
37 Infectious and Inflammatory Disorders of the Gallbladder and Extrahepatic Biliary Tract
Chapter Outline
Introduction
Gallstones
Historical Perspective
Gallstone Classification
Cholesterol Gallstones
Pathogenesis
Epidemiology and Risk Factors
Pigment Gallstones
Pathogenesis
Epidemiology
Cholecystitis
Acute Cholecystitis
Acute Calculous Cholecystitis
Clinical Features
Pathogenesis
Pathologic Features
Natural History and Treatment
Acute Acalculous Cholecystitis
Clinical Features and Pathogenesis
Pathologic Features
Acute Emphysematous Cholecystitis
Clinical Features and Pathogenesis
Pathologic Features
Chronic Cholecystitis
Chronic Calculous Cholecystitis
Clinical Features and Pathogenesis
Pathologic Features
Treatment
Chronic Acalculous Cholecystitis
Lymphoeosinophilic and Eosinophilic Cholecystitis
Diffuse Lymphoplasmacytic Acalculous Cholecystitis
Lymphocytic Cholecystitis
Xanthogranulomatous Cholecystitis
Cholecystitis in Patients with Acquired Immunodeficiency Syndrome
Parasitic Infestation
Polyarteritis Nodosa and Other Types of Vasculitis
Cholesterolosis
Hydrops and Mucocele
Diverticular Disease
Ischemic Diseases
Traumatic Conditions and Chemical Cholecystitis
Biliary Fistulas
Metachromatic Leukodystrophy
Inflammatory Disorders of the Extrahepatic Bile Ducts
Simple Obstructive Cholangitis
Clinical Features
Risk Factors and Pathogenesis
Pathologic Features
Treatment
Primary Hepatolithiasis
Clinical Features
Epidemiology and Pathogenesis
Pathologic Features
Treatment
Primary Sclerosing Cholangitis
Clinical Features
Risk Factors and Pathogenesis
Pathologic Features
Natural History
Treatment
Immunoglobulin G4–Associated Cholangitis and Cholecystitis
Clinical Features
Pathologic Features
Treatment
Eosinophilic Cholangitis
Clinical Features
Pathologic Features
Treatment
Follicular Cholangitis and Pancreatitis
Clinical Features
Pathologic Features
Parasitic Infections of the Biliary Tract
Clonorchis sinensis
Ascaris lumbricoides
Fasciola hepatica
AIDS-Related Lesions
Cholangiopathy
Ischemic Cholangitis
Other Non-neoplastic Biliary Strictures
References
38 Benign and Malignant Tumors of the Gallbladder and Extrahepatic Biliary Tract
Chapter Outline
Introduction
Sampling Gallbladder Specimens
Gallbladder
Tumoral Intraepithelial Neoplasms
Intracholecystic Papillary- Tubular Neoplasms
Terminology
Clinical Features
Pathologic Features
Molecular Aspects
Differential Diagnosis
Natural History and Prognosis
Mucinous Cystic Neoplasms
Nontumoral Preinvasive Lesions: Dysplasia and Carcinoma In Situ
Clinical Features
Pathologic Features
Differential Diagnosis
Dysplasia versus Reactive Atypia
Cancerization of Mucosa versus Dysplasia
High-Grade Dysplasia versus Early Invasive Carcinoma
Molecular Aspects
Natural History and Prognosis
Adenocarcinoma
Clinical Features
Pathologic Features
Histochemical, Immunohistochemical, and Molecular Aspects
Differential Diagnosis
Natural History and Prognosis
Papillary Carcinomas
Mucinous Carcinoma
Adenosquamous and Squamous Cell Carcinomas
Carcinomas with Neuroendocrine Differentiation
Intestinal-Type Adenocarcinoma
Clear Cell Carcinoma
Signet Ring Carcinoma
Undifferentiated Carcinomas
Tubulocystic Carcinoma
Adenocarcinomas Arising in Specific Settings
Well-Differentiated Neuroendocrine Tumors
Pseudoneoplastic Lesions
Epithelial Alterations Mimicking Intraepithelial Neoplasia
Pseudotumors Clinically Mimicking Neoplasia
Extrahepatic Bile Ducts
Tumoral Intraepithelial Neoplasms
Intraductal Papillary Neoplasms of the Bile Ducts
Clinical Features
Pathologic Features
Molecular Aspects
Differential Diagnosis
Natural History
Intraductal Tubular and Tubulopapillary Neoplasms
Mucinous Cystic Neoplasms
Clinical Features
Pathologic Features
Molecular Aspects
Differential Diagnosis
Natural History
Nontumoral Dysplasia (Biliary Intraepithelial Neoplasia)
Clinical Features
Pathologic Features
Differential Diagnosis
Molecular Aspects
Natural History
Malignant Epithelial Tumors
Clinical Features
Pathologic Features
Molecular Aspects
Staging
Natural History and Prognosis
Other Tumor Types
Nonepithelial Tumors of the Gallbladder and Extrahepatic Bile Ducts
Mesenchymal Tumors
Paragangliomas
Secondary Tumors of the Gallbladder and Extrahepatic Bile Ducts
Acknowledgment
References
39 Inflammatory and Other Nonneoplastic Disorders of the Pancreas
Chapter Outline
Introduction
Acute Pancreatitis
Clinical Features
Etiology and Pathogenesis
Pathologic Features
Therapy
Chronic Pancreatitis
Confirming a Diagnosis
Alcoholic Pancreatitis
Clinical Features
Pathogenesis
Ductal Obstruction Theory
Toxic Metabolic Theory
Necrosis-Fibrosis Theory
Pathologic Features
Differential Diagnosis
Chronic Pancreatitis versus Pancreatic Adenocarcinoma
Location of Ducts and Glands.
Desmoplastic Stroma.
Cytoplasmic Features.
Nuclear Features.
Chronic Alcoholic Pancreatitis versus Autoimmune Pancreatitis
Chronic Pancreatitis and the Risk of Pancreatic Cancer
Therapy
Genetics of Pancreatitis
Trypsinogen Mutations
SPINK1 Mutations
CFTR Mutations
Hereditary Pancreatitis
Clinical Features
Pathologic Features
Pancreatic Divisum
Autoimmune Pancreatitis
Definition and Historical Aspects
Subtypes
Clinical Features
Serum Markers
Radiology
Pathogenesis
Etiology: Potential Initiating Mechanisms
Genetic Factors.
Bacterial Infection.
Autoimmunity.
Pathogenesis: Immunologic Alterations in Autoimmune Pancreatitis
Pathologic Features
Type 1 Autoimmune Pancreatitis
Type 2 Autoimmune Pancreatitis
Unclassified Autoimmune Pancreatitis
Immunohistochemistry
Differential Diagnosis
Autoimmune Pancreatitis versus Pancreatic Carcinoma
Autoimmune Pancreatitis versus Other Forms of Chronic Pancreatitis
Other Diseases That May Mimic Autoimmune Pancreatitis
Diagnostic Criteria
Diagnostic Value of an Ampullary or Bile Duct Biopsy
Therapy
Risk of Malignancy
Paraduodenal Pancreatitis (“Groove” Pancreatitis)
Definitions and Terminology
Clinical Features
Radiologic Features
Pathogenesis
Pathologic Findings
Differential Diagnosis
Therapy
Eosinophilic Pancreatitis
Clinical Features
Pathologic Findings
Differential Diagnosis
Tropical Pancreatitis
Etiology and Pathogenesis
Pathologic Features
Obstructive Pancreatitis
Infectious Causes of Pancreatitis
Tuberculous Pancreatitis
Clinical Features
Pathologic Findings
Other Infections
Solid Non-neoplastic Lesions That Mimic Pancreatic Neoplasms
Intrapancreatic Accessory Spleen
Clinical Features
Pathologic Features
Lipomatous Pseudohypertrophy
Clinical Features
Pathogenesis
Pathologic Features
Therapy
Pancreatic Hamartoma
Pathologic Features
Adenomyomatous Hyperplasia of the Vaterian System
Clinical Features
Pathologic Features
Non-neoplastic Cystic Lesions of the Pancreas
Pseudocyst
Clinical Features
Diagnosis of Pseudocyst
Pathologic Features
Differential Diagnosis
Therapy
Lymphoepithelial Cyst of the Pancreas
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Therapy
Squamoid Cyst of the Pancreas
Pathologic Features
Differential Diagnosis
Acinar Cell Cystadenoma (Cystic Acinar Transformation)
Clinical Features
Etiopathogenesis
Pathologic Findings
Enteric Duplication Cyst
Congenital and Hereditary Abnormalities of the Exocrine Pancreas
References
40 Tumors of the Pancreas
Chapter Outline
Introduction
Classification
Ductal Adenocarcinoma and Variants
Invasive Ductal Adenocarcinoma
Clinical Features
Pathologic Features
Ancillary Diagnostic Tests and Molecular Properties
Differential Diagnosis
Natural History
Morphologic Patterns of Ductal Adenocarcinoma
Foamy Gland Pattern
Large Duct Pattern
Vacuolated Pattern
Lobular Carcinoma–like Pattern
Solid Nested Pattern
Micropapillary Pattern
Other Pancreatic Carcinomas of Ductal Origin
Colloid Carcinoma
Medullary Carcinoma
Squamous Cell Carcinoma and Adenosquamous Carcinoma
Hepatoid Carcinoma
Undifferentiated Carcinoma
Undifferentiated Carcinoma with Osteoclast-like Giant Cells
Pancreatic Intraepithelial Neoplasia
Cystic Tumors
Serous Cystic Neoplasm
Clinical Features
Pathologic Features
Differential Diagnosis
Natural History
Mucinous Cystic Neoplasm
Clinical Features
Pathologic Features
Differential Diagnosis
Cystic Change in Typically Solid Tumors
Cystic Change in Ductal Adenocarcinoma
Cystic Pancreatic Neuroendocrine Tumor
Cystic Acinar Neoplasms
Lymphoepithelial Cyst
Miscellaneous Epithelial Cysts
Squamous Cysts of Pancreatic Duct
Dermoid Cysts
Epidermoid Cysts in the Intrapancreatic Accessory Spleen
Paraampullary Duodenal Wall Cysts
Retention Cysts
Other Cysts
Intraductal Neoplasms
Intraductal Papillary Mucinous Neoplasm
Clinical Features
Pathologic Features
Special Studies and Molecular Features
Differential Diagnosis
Natural History and Treatment
Intraductal Oncocytic Papillary Neoplasm
Intraductal Tubulopapillary Neoplasm
Differential Diagnosis of Cystic and Intraductal Lesions
Acinar Cell Carcinoma, Pancreatoblastoma, and Related Neoplasms
Acinar Cell Carcinoma
Clinical Features
Pathologic Features
Cystic Acinar Cell Neoplasms
Pancreatoblastoma
Mixed Acinar Cell Neoplasms
Pancreatic Neuroendocrine Neoplasms
Well-Differentiated Pancreatic Neuroendocrine Tumor
Clinical Features
Prognosis
Pathologic Features
Pancreatic Neuroendocrine Microadenomas
Well-Differentiated Pancreatic Neuroendocrine Tumors
Poorly Differentiated Neuroendocrine Carcinoma
Mixed Neuroendocrine Carcinomas
Solid Pseudopapillary Neoplasms
Clinical Features
Pathologic Features
Natural History
Differential Diagnosis of Solid Cellular Tumors
Mesenchymal and Lymphoid Neoplasms
Tumor-like Lesions
Secondary Tumors
References
41 Tumors of Major and Minor Ampulla
Chapter Outline
Introduction
Anatomic and Histologic Considerations
Classification of Ampullary Tumors
Preinvasive Neoplasms
Adenomas of the Ampullary Duodenum
Clinical Features
Pathologic Features
Differential Diagnosis
Intraampullary Papillary-Tubular Neoplasms
Clinical Features
Pathologic Features
Differential Diagnosis
Natural History and Prognosis
Flat Dysplasia
Invasive Adenocarcinomas
Classification
Clinical Features
Pathologic Features
Ancillary Diagnostic Tests and Molecular Properties
Molecular Features
Differential Diagnosis
Natural History and Treatment
Uncommon Carcinomas
Staging of Ampullary Carcinomas
Neuroendocrine Neoplasms and Related Tumors
Well-Differentiated Neuroendocrine Tumors
Clinical Features
Pathologic Features
Differential Diagnosis
Poorly Differentiated Neuroendocrine Carcinoma
Gangliocytic Paraganglioma
Mesenchymal Neoplasms
Tumor-like Lesions
Paraduodenal Pancreatitis
Adenomyomatous Hyperplasia
Other Tumor-Like Conditions
Gross Evaluation and the Surgical Pathology Report
Acknowledgment
References
44 Molecular Pathogenesis and Diagnostics of Hepatocellular Tumors
Chapter Outline
Introduction
Benign Hepatocellular Tumors
Focal Nodular Hyperplasia
Molecular Changes
Molecular Diagnostics
Hepatocellular Adenoma
Hepatocellular Adenoma with Inactivating Mutations of the HNF1A Gene
Molecular Changes
Molecular Diagnostics
Hepatocellular Adenoma with Activating Mutations of the CTNNB1 Gene
Molecular Changes
Molecular Diagnostics
Inflammatory Hepatocellular Adenoma
Molecular Changes
Molecular Diagnostics
Unclassified Hepatocellular Adenoma
Use of Molecular Diagnostics
Hepatocellular Carcinoma and Its Precursors
Molecular Changes in Hepatocarcinogenesis
Precancerous Lesions in Hepatocarcinogenesis
Dysplastic Foci
Large Cell Change in Hepatocytes
Dysplastic Nodules
Prognostic and Therapeutic Implications
Early Hepatocellular Carcinoma
Molecular Diagnostics
References
43 Liver Tissue Processing and Normal Histology
Chapter Outline
Liver Biopsy Specimens
Specimen Handling
Normal Microanatomy of the Liver
Interpretation of Liver Biopsies
Liver Resection Specimens
Partial Hepatectomies
Liver Explants
Routine and Special Stains
Immunohistochemistry
Electron Microscopy
Molecular Studies
In Situ Hybridization
Polymerase Chain Reaction
Laser Capture Microdissection
Gene Array Analysis
Prognostic and Therapeutic Information from Liver Biopsies
References
42 Algorithmic Approach to Diagnosis of Liver Disorders
Chapter Outline
Introduction
Helpful Diagnostic Tips
Identification of Major Pattern of Injury
Predominantly Portal Inflammation
Predominantly Lymphocytic Inflammation in Portal Tracts
Chronic Hepatitis C
Chronic Hepatitis B
Autoimmune Hepatitis
Acute Hepatitis
Chronic Biliary Diseases
Miscellaneous Conditions
Predominantly Plasma Cell Inflammation in Portal Tracts
Predominantly Mixed Portal Inflammation in Portal Tracts
Predominantly Eosinophilic Inflammation in Portal Tracts
Predominantly Granulomatous Inflammation in Portal Tracts
Atypical Lymphoid Infiltrate in Portal Tracts
Evaluation of Clinical and Serologic Information
Chronic Hepatitis C
Chronic Hepatitis B
Autoimmune Hepatitis
Ductular Reaction
Acute Bile Duct Obstruction
Ascending Cholangitis
Cholangitis Lenta (Ductular Cholestasis)
Acute Hepatitis with Submassive or Massive Hepatic Necrosis
Chronic Bile Duct Obstruction
Primary Biliary Cirrhosis
Primary Sclerosing Cholangitis
Mass Lesions
Focal Nodular Hyperplasia
Inflammatory Hepatocellular Adenoma
Space-Occupying Lesion
Cholangiocarcinoma
Other Chronic Liver Diseases
Steatosis
Steatosis with Ballooned Hepatocytes or Mallory-Denk Hyalin
Nonalcoholic Fatty Liver Disease
Alcohol-Induced Liver Disease
Chronic Hepatitis C
Wilson Disease
Steatosis without Mallory-Denk Hyalin or Ballooned Hepatocytes
Diffuse Microvesicular (Small Droplet) Steatosis
Steatosis Associated with Tumors
Prominent Lobular Inflammation
Nonsinusoidal Pattern of Lymphocytic Infiltration
Acute Hepatitis
Features of Recent Acute or Subacute Resolving Hepatitis
Nonhepatotropic Virus Hepatitis
Cytomegalovirus.
Herpes Simplex.
Adenovirus.
Sinusoidal Pattern of Lymphocytic Infiltration
Celiac Disease
Epstein-Barr Virus
Lymphoma and Leukemia
Extramedullary Hematopoiesis
Stellate Cell Lipidosis Associated with Hypervitaminosis A
Pigments in the Liver
Lipofuscin
Iron
Copper
Fibrosis (and Cirrhosis)
Fragmented Biopsy Specimen
Portal-Based Fibrosis
Perivenular and Perisinusoidal Fibrosis
Diagnosis of Solid and Cystic Masses
Tumor with Eosinophilic Cells
Cystic Tumors
References
45 Diagnostic Cytology of the Liver
Chapter Outline
Introduction
Use of Fine-Needle Aspiration Biopsy
Guidance Systems
Indications and Contraindications
Complications
Clinical Considerations
Specimen Preparation
Diagnostic Accuracy
Diagnostic Issues
Integrative Approach to the Evaluation of Liver Aspirates
Cytohistology of the Liver
Normal Morphology
Pigments
Steatosis
Infections
Cystic Lesions of the Liver
Cystic Lesions with an Epithelial Lining
Bile Duct Cyst, Simple Hepatic Cyst, and Fibropolycystic Disease
Ciliated Foregut Cyst
Mucinous Cystic Neoplasm and Intraductal Papillary Neoplasm
Metastases
Cystic Lesions without an Epithelial Lining
Non-neoplastic Cysts
Neoplastic Cysts and Tumor-like Lesions
Cavernous Hemangioma
Mesenchymal Hamartoma
Cystic Degeneration in a Benign or Malignant Tumor
Undifferentiated Embryonal Sarcoma
Solid Lesions of the Liver
Hepatocellular Appearance
Benign Hepatocellular Nodules
Primary Malignant Hepatocellular Neoplasms
Hepatocellular Carcinoma
Cellularity
Epithelial Cohesiveness
Vascular Patterns
Cellular Characteristics
Pigments
Cellular Inclusions
Background Elements
Cell Blocks and Microbiopsies
Variants of Hepatocellular Carcinoma
Hepatocellular Carcinoma with Fatty Changes
Hepatocellular Carcinoma with Clear Cell Changes
Hepatocellular Carcinoma with Small Cell Changes
Hepatocellular Carcinoma with Pleomorphic Features
Hepatocellular Carcinoma with Spindle Cell Features
Hepatocellular Carcinoma with Giant Cell Features
Special Types of Hepatocellular Carcinoma
Fibrolamellar Variant of Hepatocellular Carcinoma
Scirrhous Type of Hepatocellular Carcinoma
Undifferentiated Hepatocellular Carcinoma
Lymphoepithelioma-like Carcinoma
Sarcomatoid Hepatocellular Carcinoma
Very-Well-Differentiated Hepatocellular Carcinoma
Immunohistochemistry
Hepatoblastoma
Combined Hepatocellular-Glandular Appearance
Combined Hepatocellular Carcinoma and Cholangiocarcinoma
Nonhepatocellular Appearance
Benign Nonhepatocellular Lesions
Bile Duct Hamartoma, Bile Duct Adenoma (Peribiliary Gland Hamartoma)
Angiomyolipoma
Primary Malignant Nonhepatocellular Lesions
Intrahepatic Cholangiocarcinoma
Epithelioid Hemangioendothelioma
Angiosarcoma
Metastatic Malignant Nonhepatocellular Lesions
References
46 Acute and Chronic Infectious Hepatitis
Chapter Outline
Introduction
Viral Hepatitis
Clinical Features
Acute Viral Hepatitis
Chronic Viral Hepatitis
Hepatitis Viruses
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Other Hepatitis Viruses
Acute Hepatitis
Pathologic Features
Massive and Submassive Necrosis
Prognostic Factors
Differential Diagnosis
Chronic Hepatitis
Pathologic Features
Portal Inflammation
Lobular Necroinflammatory Activity
Fibrosis
Nomenclature and Scoring
Pathology of Specific Types of Chronic Viral Hepatitis
Chronic Hepatitis B
Delta Virus Infection
Hepatitis C
Combined Viral Infections
Prognostic Factors
Differential Diagnosis
Treatment of Chronic Hepatitis C
Cirrhosis and Regression of Fibrosis
Other Viral Infections of the Liver
Epstein-Barr Virus
Cytomegalovirus
Cytomegalovirus Infection in Otherwise Healthy Patients
Cytomegalovirus Infection in Immunocompromised Patients
Cytomegalovirus Infection in Neonates
Herpes Simplex Virus
Human Herpesvirus 6
Enteric Viruses
Viral Hemorrhagic Fever
Bacterial Infections of the Liver
Suppurative Bacterial Infections
Pyogenic Bacterial Abscess
Tularemia
Listeriosis
Liver in Sepsis
Granulomatous Bacterial Infections
Tuberculosis
Mycobacterium Avium-Intracellulare
Leprosy
Bartonella Species
Brucellosis
Rickettsia and Similar Species
Spirochete Infections
Syphilis
Miscellaneous Bacterial Infections
Salmonella Species
Whipple Disease
Fungal Infections of the Liver
Candidiasis
Aspergillosis
Histoplasmosis
Cryptococcosis
Parasitic Infections of the Liver
Protozoa
Malaria
Amebiasis
Flagellates
Visceral Leishmaniasis (Kala-Azar)
Miscellaneous Flagellates
Coccidians
Helminths
Nematodes
Ascaris lumbricoides
Toxocara canis
Enterobius vermicularis (Pinworms)
Strongyloides stercoralis
Trematodes
Schistosomiasis
Cestodes
Echinococcus granulosus and Related Species
References
47 Autoimmune and Chronic Cholestatic Disorders of the Liver
Chapter Outline
Introduction
Autoimmune Hepatitis
Clinical Features and Epidemiology
Pathogenesis
Pathology
Differential Diagnosis
Acute-Onset Autoimmune Hepatitis
Chronic Autoimmune Hepatitis
Grading and Staging
Natural History and Treatment
Primary Biliary Cirrhosis
Clinical Features and Epidemiology
Pathogenesis
Pathology
Differential Diagnosis
Autoimmune Cholangitis
Natural History
Treatment
Primary Sclerosing Cholangitis
Clinical Features and Epidemiology
Pathogenesis
Natural History
Pathology
Large Ducts
Liver
Differential Diagnosis
Treatment
Overlap Syndromes
Immunoglobulin G4–Associated Sclerosing Cholangitis
Secondary Sclerosing Cholangitis
Ischemic Cholangitis
Miscellaneous Ductopenic Syndromes
Obstructive Cholangitis
Clinical Features
Pathology
Differential Diagnosis
References
48 Toxin- and Drug-Induced Disorders of the Liver
Chapter Outline
Introduction
Epidemiology
Clinical Assessment and Prediction of Hepatotoxicity
Prevention of Drug Hepatotoxicity
Treatment and Prognosis
Pathologic Patterns of Toxic Liver Injury
Hepatocellular Injury
Acute Hepatocellular Injury
Predominantly Cytolytic Injury
Hepatitis with Spotty Necrosis/Apoptosis.
Hepatitis with Submassive Necrosis.
Massive Necrosis.
Predominantly Cholestatic Injury
Bland Cholestasis.
Cholestatic Hepatitis.
Chronic Hepatocellular Injury
Drug-Induced Liver Injury with Features of Autoimmune Hepatitis
Steatosis/Steatohepatitis and Phospholipidosis
Drug-Induced Steatosis and Steatohepatitis
Microvesicular Steatosis.
Macrovesicular Steatosis.
Steatofibrosis
Nonalcoholic Steatohepatitis and Chemotherapy-Associated Steatohepatitis
Phospholipidosis
Miscellaneous Patterns of Hepatocellular Injury
Pigment Accumulation
Adaptive Changes and Ground-Glass Hepatocytes
Anisonucleosis and Increased Mitoses
Bile Duct Injury
Acute Cholangitis
Chronic Cholangitis
Ductopenia
Vascular Injury
Portal Vein Lesions
Hepatoportal Sclerosis
Hepatic Artery Lesions
Hepatic Vein Lesions
Sinusoids
Sinusoidal Dilation
Peliosis
Sinusoidal Cells
Changes in Hepatic Stellate Cells.
Changes in Kupffer Cells and Macrophages.
Granulomatous Reactions
Hepatic Tumors
Examples of Common Offending Drugs
Analgesics
Acetaminophen
Acetylsalicylic Acid
Nonsteroidal Antiinflammatory Drugs
Sulindac
Ibuprofen
Antiinfectious Agents
Isoniazid and Antituberculosis Agents
Amoxicillin/Clavulanic Acid
Immunosuppressive and Antineoplastic Drugs
Oxaliplatin
Methotrexate
Drugs Used in Cardiovascular Diseases
Amiodarone
Statins
Drugs Used in Transplantation
Cyclosporine
Tacrolimus
Anabolic and Contraceptive Steroids and Estrogen Receptor Modulators
Contraceptive Pills
C17-Alkylated Anabolic Steroids
Danazol
Tamoxifen
Flutamide
Psychotropic Drugs
Carbamazepine
References
49 Fatty Liver Disease
Contents
Introduction
Definitions
Nomenclature
Alcohol-Induced Liver Disease
Clinical Features
Epidemiology and Prevalence
Familial Associations
Risk Factors
Pathogenesis
Pathology
Steatosis
Steatohepatitis
Alcoholic Hepatitis
Alcoholic Foamy Degeneration
Fibrosis and Cirrhosis
Other Pathologic Features of Alcohol-Induced Liver Disease
Megamitochondria.
Iron Deposition.
Acute and Chronic Cholestasis.
Vascular Lesions.
Treatment Effects.
Prognostic Lesions.
Lesions in the Allograft Liver.
Natural History and Treatment
Nonalcoholic Fatty Liver Disease
Clinical Features
Epidemiology and Prevalence
Familial Associations and Risk Factors
Pathogenesis
Pathology
Steatosis
Steatohepatitis
Fibrosis and Cirrhosis
Other Pathologic Features of Nonalcoholic Fatty Liver Disease
Mallory-Denk Bodies.
Megamitochondria.
Iron Deposition.
Glycogenated Nuclei.
Ductular Reaction.
Hepatocellular Glycogen.
Vascular Alterations.
Treatment Effects.
Prognostic Lesions.
Natural History and Treatment
Fatty Liver Disease in Various Patient Groups
Concurrent Alcoholic and Nonalcoholic Fatty Liver Disease
Fatty Liver Disease in Patients with Other Liver Disorders
Fatty Liver Disease in Children
Differentiating Alcohol-Induced from Nonalcoholic Fatty Liver Disease
Features That Occur More Frequently in Alcoholic Liver Disease
Features That Occur More Frequently In Nonalcoholic Fatty Liver Disease
Grading and Staging of Fatty Liver Disease
Other Forms of Fatty Liver Disease
Drug- and Toxin-Induced Fatty Liver Disease
Fatty Liver Disease after Transplantation
Protein-Energy Malnutrition
Total Parenteral Nutrition
Celiac Disease
Viral Hepatitides
Miscellaneous Causes of Fatty Liver Disease
References
50 Cirrhosis
Chapter Outline
Introduction
Definition
Pathogenesis
Collagen in the Liver
Hepatic Arterialization and Capillarization
Parenchymal Extinction
Shunt Formation
Congestive Hepatopathy
Vascular Thrombosis
Regeneration
Natural History and Reversibility of Cirrhosis
Anatomic Classification and Pathology
Macroscopic Features
Micronodular Cirrhosis
Macronodular Cirrhosis
Mixed Cirrhosis
Microscopic Features
Evolution of Cirrhosis
Micronodular Cirrhosis
Macronodular Cirrhosis
Unusual Variants
Incomplete Septal Cirrhosis
Postnecrotic Cirrhosis
Differential Diagnostic Considerations
Lobar Hypertrophy and Atrophy
Large Nodules in the Cirrhotic Liver
Nodular Regenerative Hyperplasia
Hepar Lobatum
Congenital Hepatic Fibrosis
Infarction of Nodules versus Congestive Necrosis of Nodules
Portal Vein Thrombosis
Patent Paraumbilical Veins
Capsular Fibrosis
Etiology
Chronic Hepatitis
Fatty Liver Disease
Chronic Biliary Diseases in Adults
Biliary Diseases in Pediatric Patients
Biliary Atresia
Cystic Fibrosis
Metal Overload States
Iron
Copper
Wilson Disease
Non-Wilsonian Copper Toxicosis
Congestive Cirrhosis
Drug-Induced Cirrhosis
Diagnosis
Types of Biopsy and Technical Issues
Role of Biopsy
Staging Systems
Diagnostic Pitfalls
Pitfalls in Assessing Fibrosis
Pitfalls in Diagnosing Cirrhosis
Acknowledgment
References
51 Vascular Disorders of the Liver
Chapter Outline
Introduction
Portal Vein Disease (Portal Vein Obstruction)
Clinical Features
Pathogenesis
Large Portal Veins
Small Portal Veins
Pathologic Features
Differential Diagnosis
Exclusion of Cirrhosis and Regressed Cirrhosis
Exclusion of Portal Vein Thrombosis
Exclusion of Parasitic Disease
Arterial Disease
Liver Injury Resulting from Ischemia and Shock
Pathologic Features
Differential Diagnosis
Arteritis
Hepatic Artery Obstruction
Arterioportal and Arteriovenous Shunts
Sinusoidal Disease
Sinusoidal Dilatation
Peliosis Hepatis
Clinical Features
Pathologic Features
Bacillary Angiomatosis
Sinusoidal Injury, Fibrosis, and Arterialization
Sinusoidal Obstruction Syndrome (Veno-occlusive Disease)
Clinical Features
Pathologic Features
Differential Diagnosis
Sinusoidal Cellular Infiltration
Amyloidosis and Light Chain Deposition Disease
Clinical Features
Pathologic Features
Hepatic Vein Disease
Thrombosis of Large Hepatic Veins (Budd-Chiari Syndrome)
Clinical Features
Pathogenesis
Membranous Obstruction of the Vena Cava
Pathologic Features
Differential Diagnosis
Congestive Heart Failure
Small Hepatic Vein Disease (Obliterative Hepatic Venopathy)
Nodular Hyperplasia and Other Tumor-Like Conditions
Large Regenerative Nodules
Pathologic Features
Focal Nodular Hyperplasia
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Nodular Regenerative Hyperplasia
Hepar Lobatum
Fibrotic Conditions with Vascular Pathophysiology
Congenital Hepatic Fibrosis
Hepatoportal Sclerosis
Definition
Clinical Features
Pathologic Features
Differential Diagnosis
Acknowledgment
References
52 Pathology of Liver and Hematopoietic Stem Cell Transplantation
Chapter Outline
Introduction
Donor Evaluation
Cadavers
Living Donors
Sources of Graft Dysfunction
Graft Dysfunction After Transplantation
Operative Timing and Methods
Posttransplantation Needle Biopsies of Allografts
Evaluation of the Failed Allograft
Reduced-Size and Living Related Allografts
Preservation/Reperfusion Injury
Clinical Features
Pathologic Features
Differential Diagnosis
Small-for-Size Syndrome
Pathophysiology
Clinical Features
Pathologic Features
Differential Diagnosis
Complications of Transplantation
Vascular Complications
Hepatic Artery Thrombosis
Pathophysiology
Clinical Features
Pathologic Features
Differential Diagnosis
Portal Vein Thrombosis
Pathophysiology
Clinical Features
Pathologic Features
Differential Diagnosis
Hepatic Vein and Vena Cava Complications
Pathophysiology
Clinical Features
Pathologic Features
Differential Diagnosis
Bile Duct Reconstruction
Pathophysiology
Clinical Features
Pathologic Features
Differential Diagnosis
Allograft Rejection
Antibody-Mediated Rejection
Pathophysiology
Clinical Presentation
Pathologic Features
Differential Diagnosis
Acute Cellular Rejection
Clinical Features
Pathologic Features and Grading
Differential Diagnosis
Chronic Rejection
Pathophysiology
Clinical Features
Pathologic Features and Staging
Differential Diagnosis
Posttransplantation Infections
Cytomegalovirus Hepatitis
Clinical Features
Pathologic Features
Differential Diagnosis
Herpes Simplex and Varicella-Zoster Viral Hepatitis
Pathologic Features
Human Herpesvirus 6
Human Herpesvirus 8
Epstein-Barr Virus
Clinical Features
Pathologic Features
Differential Diagnosis
Adenovirus Hepatitis
Pathophysiology
Pathologic Features
Differential Diagnosis
Late Liver Allograft Dysfunction
Recurrent Hepatitis Virus Infections
Hepatitis A Virus
Hepatitis B and D Viruses
Clinical Features
Pathologic Features
Differential Diagnosis
Hepatitis C Virus
Clinical Features
Pathologic Features
Usual Variant
Plasma Cell–Rich Autoimmune Variant
Fibrosing Cholestatic Hepatitis
Overlap of Recurrent Hepatitis C with Acute and Chronic Rejection
Differential Diagnosis
Hepatitis E Virus
Pathophysiology and Clinical Features
Pathologic Features and Differential Diagnosis
Disorders of Dysregulated Immunity
Primary Biliary Cirrhosis
Pathophysiology
Clinical Features
Pathologic Features
Differential Diagnosis
Plasma Cell–Rich, Recurrent, and New-Onset Autoimmune Hepatitis
Clinical Features and Pathophysiology
Pathologic Features and Differential Diagnosis
Recurrent Primary Sclerosing Cholangitis
Clinical Features
Pathologic Features
Differential Diagnosis
Metabolic Diseases and Toxic Injury
Recurrent Alcohol-Induced Liver Disease
Clinical Features
Pathologic Features
Recurrent Nonalcoholic Steatohepatitis
Clinical Features
Histopathologic Features
Differential Diagnosis
Idiopathic Posttransplantation Hepatitis
Clinical Features and Pathophysiology
Pathologic Features and Differential Diagnosis
Immunosuppression Optimization
Pathologic Features and Differential Diagnosis
Long-Term Changes Not Caused by Recurrent Disease
Adverse Drug Reactions and Toxic Injury
Hematopoietic Stem Cell Transplantation
Sinusoidal Obstruction Syndrome
Pathologic Features
Differential Diagnosis
Other Transplantation Effects
Graft-versus-Host Disease
Acute Graft-versus-Host Disease
Chronic Graft-versus-Host Disease
Pathogenesis of Graft-versus-Host Disease
Acute Graft-versus-Host Disease
Chronic Graft-versus-Host Disease
Nodular Regenerative Hyperplasia
Systemic Infection After Stem Cell Transplantation
Liver Pathology After Transplantation of Other Solid Organs
Acknowledgement
References
53 Liver Pathology in Pregnancy
Chapter Outline
Introduction
Laboratory and Histologic Changes of the Liver in Pregnancy
Intrahepatic Cholestasis of Pregnancy
Clinical Features
Pathologic Features
Pathogenesis
Acute Fatty Liver of Pregnancy
Clinical Features
Pathologic Features
Pathogenesis
Preeclampsia and Eclampsia
Clinical Features
Pathologic Features
Pathogenesis
HELLP Syndrome
Clinical Features
Pathologic Features and Pathogenesis
Hepatic Rupture
Clinical Features
Pathologic Features and Pathogenesis
Hyperemesis Gravidarum
Clinical Features
Pathologic Features and Pathogenesis
Hepatitis E Infection
Clinical Features
Pathologic Features and Pathogenesis
Herpesvirus Infection
Clinical Features
Pathologic Features and Pathogenesis
Budd-Chiari Syndrome
Clinical Features
Pathologic Features and Pathogenesis
Conclusions
References
54 Inherited Metabolic and Developmental Disorders of the Pediatric and Adult Liver
Chapter Outline
Introduction
Pediatric Liver Biopsies
Indications for Liver Biopsy in Children
Pediatric Liver Biopsy Specimen
Normal and Potentially Misleading Features of the Liver in Infants and Children
Architecture
Cell Populations
Hepatocyte Content
Response to Injury
Approach to the Diagnosis of Pediatric Liver Disorders in Liver Biopsies
Cholestatic Pattern
Steatotic Pattern
Storage Pattern
Hepatitic Pattern
Cirrhotic Pattern
Neoplastic Pattern
Liver Diseases of Infancy
Sudden Death
Neonatal Hemochromatosis
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Neonatal Jaundice
Extrahepatic Biliary Atresia
Clinical Features
Pathogenesis
Pathologic Features
Natural History and Treatment
Neonatal Sclerosing Cholangitis
Neonatal Hepatitis Syndrome
Clinical Features
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Syncytial Giant Cell Hepatitis
Paucity of Intrahepatic Bile Ducts
α1-Antitrypsin Deficiency
Syndromic Paucity of Bile Ducts: Alagille Syndrome
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History
Hereditary Disorders of Bilirubin Metabolism
Crigler-Najjar Syndrome and Gilbert Syndrome
Classification and Pathogenesis
Clinical and Pathologic Features
Dubin-Johnson Syndrome
Rotor Syndrome
Hereditary Disorders of Bile Acid Metabolism
Inborn Errors of Bile Acid Synthesis
3β-Hydroxy-Δ-C27-Steroid Oxidoreductase Deficiency
Δ-3-Oxosteroid 5β-Reductase Deficiency
Other Bile Acid Biosynthetic Disorders
Defects in Bile Secretion or Transport
Progressive Familial Intrahepatic Cholestasis
Progressive Familial Intrahepatic Cholestasis 1
Progressive Familial Intrahepatic Cholestasis 2
Progressive Familial Intrahepatic Cholestasis 3
Differential Diagnosis
Natural History
Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome
Familial Hypercholanemia
Cystic Fibrosis
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Aagenaes Syndrome
Disorders of Carbohydrate Metabolism
Glycogen Storage Diseases
Classification and Clinical Features
Pathogenesis
Pathologic Features
Natural History
Mauriac Syndrome
Galactosemia
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Hereditary Fructose Intolerance
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Congenital Disorders of Glycosylation
Mucopolysaccharidoses
Disorders of Amino Acid Metabolism
Hereditary Tyrosinemia
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Disorders of Lipid Metabolism
Gaucher Disease
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History
Niemann-Pick Disease Types A and B
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Niemann-Pick Disease Type C
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Farber Disease
GM1 Gangliosidosis
Lysosomal Acid Lipase Deficiency
Peroxisomal Disorders
Zellweger Syndrome
Mitochondrial Cytopathies
Clinical Features
Pathologic Features
Urea Cycle Disorders
Argininosuccinic Aciduria
Ornithine Transcarbamylase Deficiency
Citrin Deficiency (Citrullinemia Type II)
Inherited and Metabolic Diseases of Adolescents and Adults
Hereditary Hemochromatosis
Pathogenesis
Clinical Patients and Specific Types of Diseases
HFE-Associated Hereditary Hemochromatosis
Juvenile Hereditary Hemochromatosis
TFR2-Associated Hereditary Hemochromatosis
Ferroportin Disease
Pathologic Features
Differential Diagnosis
Natural History and Treatment
Wilson Disease
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Natural History and Treatment
α1-Antitrypsin Deficiency Liver Disease
Clinical Features
Pathogenesis
Pathologic Features
Natural History and Treatment
Abnormal Development of Liver Anatomy
Agenesis and Hypogenesis
Anomalies of Position
Situs Inversus
Accessory Lobe
Ectopic Liver
Pancreatic Heterotopia
Ciliated Hepatic Foregut Cyst
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)
Abnormal Development of the Biliary Tract
Von Meyenburg Complex (Biliary Hamartoma)
Autosomal Recessive Polycystic Kidney Disease
Clinical Features
Pathologic Features
Natural History
Congenital Hepatic Fibrosis
Clinical Features
Pathogenesis
Pathologic Features
Natural History
“Adult” Polycystic Liver Disease
Clinical Features
Pathogenesis
Pathologic Features
Natural History
Caroli Disease and Caroli Syndrome
References
55 Benign and Malignant Tumors of the Liver
Chapter Outline
Introduction
Specimen Analysis
Documentation
Biopsy Methods
Hepatocellular Tumors
Hepatocellular Adenoma
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Treatment
Focal Nodular Hyperplasia
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Treatment
Benign and Dysplastic Lesions in the Cirrhotic Liver
Macroregenerative Nodules and Low-Grade Dysplastic Nodules
Nomenclature
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Treatment
High-Grade Dysplastic Nodules
Clinical Features
Pathogenesis
Pathologic Features
Differential Diagnosis
Treatment
Hepatocellular Carcinoma and Its Variants
Clinical Features
Pathogenesis
Pathologic Features
Histologic Grading of Hepatocellular Carcinoma
Early or Small Hepatocellular Carcinoma
Rare Variants of Hepatocellular Carcinoma
Differential Diagnosis
Hepatocellular Carcinoma versus Adenocarcinoma
Hepatocellular Carcinoma versus Neuroendocrine Tumor
Hepatocellular Carcinoma versus Other Tumor Types
Prognosis and Treatment
Fibrolamellar Variant of Hepatocellular Carcinoma
Clinical Features
Pathologic Features
Differential Diagnosis
Prognosis and Treatment
Combined Hepatocellular Carcinoma and Cholangiocarcinoma
Bile Duct Tumors
Bile Duct Hamartoma
Bile Duct Adenoma
Clinical Features
Pathologic Features
Differential Diagnosis
Mucinous Cystic Neoplasms
Clinical Features
Pathologic Features
Differential Diagnosis
Simple (Biliary) Cyst
Other Benign Biliary Tumors or Lesions
Cholangiocarcinoma
Clinical Features
Pathologic Features
Differential Diagnosis
Prognosis and Treatment
Mesenchymal Tumors
Hemangioma
Clinical Features
Pathologic Features
Angiomyolipoma
Clinical Features
Pathologic Features
Differential Diagnosis
Inflammatory Pseudotumor
Clinical Features
Pathologic Features
Differential Diagnosis
Angiosarcoma
Clinical Features
Pathologic Features
Differential Diagnosis
Epithelioid Hemangioendothelioma
Clinical Features
Pathologic Features
Differential Diagnosis
Prognosis and Treatment
Kaposi Sarcoma
Clinical Features
Pathologic Features
Pediatric Neoplasms
Mesenchymal Hamartoma
Clinical Features
Pathologic Features
Infantile Hemangioma
Clinical Features
Pathologic Findings
Prognosis and Treatment
Hepatoblastoma
Clinical Features
Pathologic Features
Differential Diagnosis
Prognosis and Treatment
Embryonal (Undifferentiated) Sarcoma
Clinical Features
Pathologic Features
Hematopoietic Malignancies
Other Lesions Involving the Liver
Benign Neoplasms
Malignant Tumors
Metastatic Neoplasms
General Diagnostic Approach
Frozen Section Technique
References
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z