Neuroendocrine neoplasms comprise a large family of proliferative lesions that involve almost every part of the body. Our understanding of their cells of origin as well as the pathology, pathophysiology and genetics of these neoplasms has made tremendous advances in the last few decades. While they are often discussed as separate entities in textbooks of gastroenteropancreatic pathology and pulmonary pathology, their scope is much broader. The book conveys the similarities and differences of these fascinating tumors that may be found from the hypothalamus and pituitary to the rectum, and in soft tissue as well as in many organs. Written by experts in the field, the authors emphasize their structural, functional, predictive and prognostic features and attempt to provide the clinical context that allows improved diagnosis and therapy while building on the genetics that clarifies patterns of inheritance and predisposition to tumor development through precursor lesions.
The Spectrum of Neuroendocrine Neoplasia provides a broad overview of neuroendocrine neoplasms using a practical approach to diagnosis, histological classification and therapy, and presents the most important and significant developments of the technologies used to diagnose, classify and treat them.
Author(s): Sylvia L. Asa, Stefano La Rosa, Ozgur Mete
Publisher: Springer
Year: 2020
Language: English
Pages: 478
City: Cham
Preface
Contents
Contributors
1: Neuroendocrine Neoplasms: Historical Background and Terminologies
Introduction
Neuroendocrine Tumors in the Ancient World
The Scientific Revolution
The Progress of Modern Science
The Evolution of Definitions and Terminologies
The Genetics of Neuroendocrine Neoplasia
The Modern Approach to Neuroendocrine Tumors
References
2: The Diagnosis of Neuroendocrine Neoplasms
Introduction
Gastroenteropancreatic and Lung Neuroendocrine Neoplasms
Carcinoid Syndrome
Hypoglycemia
Zollinger-Ellison Syndrome
Glucagonoma Syndrome
Verner-Morrison Syndrome
Somatostatinoma Syndrome
Pheochromocytomas and Paragangliomas
Medullary Thyroid Cancer
Pituitary Neuroendocrine Tumors
Hyperprolactinemia
Cushing Syndrome
Acromegaly
Hyperthyroidism
Parathyroid Adenoma and Carcinoma
Summary
References
3: Functional and Radiological Imaging of Neuroendocrine Neoplasms
Introduction
Lung Neuroendocrine Neoplasms
Bronchial NEN
General Considerations
Radiological Imaging
Nuclear Medicine Imaging
Digestive NEN
General Considerations
Radiological Imaging
Nuclear Medicine Imaging
Pancreatic NEN
General Considerations
Radiological Imaging
Nuclear Medicine Imaging
Colorectal NEN
General Considerations
Radiological Imaging
Nuclear Medicine Imaging
Appendix NEN
General Considerations
Radiological and Nuclear Medicine Imaging
Imaging of Rare Neuroendocrine Neoplasms
General Considerations
Characterization and Pre-therapeutic Staging
General Considerations
Radiological Imaging
Nuclear Medicine and Theranostic Imaging
References
4: Pituitary Neuroendocrine Neoplasms
Historical Background
Epidemiology
Tumor Classification and Morphology
Molecular Pathogenesis
Prognosis
References
5: Hypothalamic Neuroendocrine Neoplasms
Historical Background
Epidemiology
Tumor Classification and Morphology
Molecular Pathogenesis
Prognosis
References
6: Neuroendocrine Neoplasms of the Upper Aerodigestive Tract, Ear, and Salivary Glands
Background
Neoplasms of the Nasal Cavity and Paranasal Sinus
Neuroendocrine Neoplasms of the Nasal Cavity
Neuroendocrine Tumors (Carcinoids)
Neuroendocrine Carcinoma
Mixed Neuroendocrine-Nonneuroendocrine Neoplasm (MiNEN)
Olfactory Neuroblastoma
Neuroendocrine Neoplasms of the Larynx
Neuroendocrine Tumors (NETs, Carcinoids)
NET G1 (Typical Carcinoid)
NET G2 (Atypical Carcinoid)
Neuroendocrine Carcinoma
Mixed Neuroendocrine-Nonneuroendocrine Neoplasm (MiNEN)
Neuroendocrine Tumor of the Middle Ear
Neuroendocrine Neoplasms of the Salivary Glands
Neuroendocrine Tumors (NETs, Carcinoids)
Neuroendocrine Carcinoma
References
7: Thyroid Neuroendocrine Neoplasms
Historical Background
Epidemiology
Tumor Classification and Morphology
Molecular Pathogenesis
Prognosis
References
8: Parathyroid Neuroendocrine Neoplasms
Historical Background
Epidemiology
Tumor Classification and Morphology
Molecular Pathogenesis
Prognosis
References
9: Thoracic (Lung/Thymus) Neuroendocrine Neoplasms
Foreword
Classification of Thoracic NENs
Lung Neuroendocrine Neoplasms
Nonneoplastic Conditions and Preinvasive Lesions
Neuroendocrine Cell Hyperplasia
Clinical Features
Pathology
Tumorlets
Clinical Features
Pathology
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)
Clinical Features
Pathology
Neuroendorine Tumors (Carcinoids)
Epidemiology
Gross, Clinical Presentation and Imaging
Histopathology
Carcinoid Variants
Immunohistochemical Profile
Evidence-Based Grading Proposals
Large Cell Neuroendocrine Carcinoma
Epidemiology
Gross, Clinical Presentation and Imaging
Histopathology
Immunohistochemical Profile
Small Cell Carcinoma
Epidemiology
Gross, Clinical Presentation and Imaging
Histopathology
Immunohistochemical Profile
Combined Neuroendocrine-Non-neuroendocrine Carcinoma
Thymic Neuroendocrine Neoplasms (T-NENs)
Epidemiology
Gross, Clinical Presentation and Imaging
Histopathology
Immunohistochemical Profile
Origin of T-NENs and Combined Tumors
Molecular Pathology
Inheritance
Molecular Classification
Novel Insights on the Molecular Pathways of Progression
References
10: Neuroendocrine Neoplasms of the Gut
Background
Neuroendocrine Neoplasms of the Esophagus
Esophageal Neuroendocrine Tumor (NET)
Esophageal Neuroendocrine Carcinoma (NEC)
Esophageal Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN)
Neuroendocrine Neoplasms of the Stomach
Gastric Neuroendocrine Tumors (NETs)
ECL-Cell NETs
Type 1 ECL-Cell NET
Type 2 ECL-Cell NET
Type 3 NET
Type 4 ECL-Cell NET
G-Cell and D-Cell NETs
EC-Cell NET
Gastric Neuroendocrine Carcinoma (NEC)
Gastric Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN)
Neuroendocrine Neoplasms of the Duodenum
Duodenal Neuroendocrine Tumors (NETs)
Duodenal Gastrinoma
Somatostatin-Producing D-Cell NETs
Nonfunctioning NETs
Gangliocytic Paraganglioma
Duodenal Neuroendocrine Carcinoma (NEC)
Duodenal Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN)
Neuroendocrine Neoplasms of the Lower Jejunum, Ileum, and Right Colon
Ileal and Lower Jejunal Neuroendocrine Tumors (NETs)
Ileal and Lower Jejunal NEC and MiNEN
Neuroendocrine Neoplasms of the Appendix
Appendiceal Neuroendocrine Tumors (NETs)
Appendiceal NECs and MiNENs
Neuroendocrine Neoplasms of the Rectum
Rectal Neuroendocrine Tumors (NETs)
Rectal NECs and MiNENs
References
11: Pancreatic Neuroendocrine Neoplasms
Historical Background
Epidemiology
Tumor Classification and Morphology
Molecular Pathogenesis
Prognosis
References
12: Paragangliomas and Pheochromocytomas
Historical Background
Anatomy and Embryology
Epidemiology
Tumor Classification and Morphology
Molecular Pathogenesis
Prognosis
References
13: Neuroendocrine Neoplasms of the Breast
Background
The History of Br-NEN Concept: An Unclosed Circle
Br-NENs: Who’s Who?
Neuroendocrine Carcinoma of the Breast (Br-NEC)
Neuroendocrine Tumor of the Breast (Br-NET)
Other NENs and NEN-Like Neoplasms of the Breast
Metastatic NENs
Carcinomas of the Breast with Expression of General Neuroendocrine Markers
Br-NENs: Just Concepts or Real Entities?
References
14: Genitourinary Neuroendocrine Neoplasms
Background
Renal NENs
Renal NET
Renal NEC and MiNEN
NENs of the Urinary Bladder
NET of the Urinary Bladder
NEC and MiNEN of the Urinary Bladder
Prostatic NENs
Prostatic Adenocarcinoma with Neuroendocrine Differentiation
Immunoreactivity for General Neuroendocrine Markers in Otherwise Morphologically Typical Prostatic Adenocarcinoma
Adenocarcinoma with Well-Differentiated Neuroendocrine Cells
Prostatic Carcinoma with Amphicrine Features
Prostatic NETs
Prostatic NECs
Testicular NENs
Testicular NET
Neuroendocrine Neoplasms of the Uterus
NENs of the Uterine Cervix
NETs of the Uterine Cervix
NECs of the Uterine Cervix
NENs of the Endometrium
NETs of the Endometrium
NECs of the Endometrium
Neuroendocrine Neoplasms of the Ovary
Ovarian NETs
Ovarian NECs
References
15: Skin Neuroendocrine Neoplasms
Introduction
Skin NEN Included in the 2019 Who Classification of Skin Tumors
Merkel Cell Carcinoma
Molecular Prognostic and Therapeutic Targets
P53 and RB1 Pathway Genes
KIT Receptor Tyrosine Kinase
TERT Promoter
PI3K/AKT
MAP Kinase
β-catenin
Tissue Inhibitors of Metalloproteinases (TIMPs)
PD1/PDL-1
BRAF
Pathology Report
Surgery and Systemic Therapy
Conclusions
Endocrine Mucin-Producing Sweat Gland Carcinoma
Skin NEN Not Recorded in New Who Classification of Skin Tumors
Neuroendocrine Tumor (NET) of the Skin
Carcinoma with Neuroendocrine Differentiation
Take Home Message
References
16: Metastatic Neuroendocrine Neoplasms of Unknown Primary Site
Morphological Clues to the Primary Site
Immunohistochemical Markers Useful in the Detection of the Occult Primary Site
Transcription Factors in NENs
Caudal Type Homeobox 2 (CDX2)
Thyroid Transcription Factor 1 (TTF1)
Orthopedia Homeobox (OTP)
Paired Box Genes (PAX5, PAX6, and PAX8)
Insulin Gene Enhancer Binding Protein Isl-1 (Islet 1)
Pancreatic and Duodenal Homeobox 1 (PDX1)
Human Homeobox Proteins NK (Nkx)
GATA Transcription Factors
Estrogen and Progesterone Receptors (ER and PR)
Pituitary Transcription Factors
T Box Transcription Factor (TPIT)
Pituitary-Specific Transcription Factor 1 (PIT1)
Steroidogenic Factor 1 (SF1)
Hormonal Markers
Other Markers
Cytokeratins
Carcinoembryonic Antigen (CEA)
Prostate-Specific Acid Phosphatase (PSAP; Also Known as Prostatic Acid Phosphatase, PAP or PRAP)
Tyrosine Hydroxylase (TH)
Somatostatin Receptors (SSTRs)
Metastatic NENs in Specific Sites: Differential Diagnosis with Primary Neuroendocrine Neoplasms
Specific Diagnostic Issues in the Lung, Thymus, and Thyroid
Specific Diagnostic Issues in the Mammary Gland
Specific Diagnostic Issues in the Gonads
Specific Diagnostic Issues in the Sellar Region
Conclusion
References
17: Cytology of Neuroendocrine Neoplasms
General Cytomorphology
General Immunohistochemical and Immunocytochemical Profile
Pancreas and Biliary Tract
Morphology
Ancillary Techniques
Standardized Reporting
Differential Diagnosis
Skin
Upper Respiratory Tract and Lung
Pituitary
Thyroid
Morphology
Ancillary Techniques
Differential Diagnosis
Standardized Reporting
Parathyroid
Extra-Adrenal Paraganglia and Adrenal Medulla
Breast
Genitourinary
Tubular Gut
Retinoblastoma
References
18: Inherited Neuroendocrine Neoplasms
Introduction
Pituitary Neuroendocrine Neoplasms
Thyroid Neuroendocrine Neoplasms
Parathyroid Neuroendocrine Neoplasms
Lung and Thymic Neuroendocrine Neoplasms
Gastric Neuroendocrine Neoplasms
Intestinal Neuroendocrine Neoplasms
Pancreatic Neuroendocrine Neoplasms
Paraganglial Neuroendocrine Neoplasms (Pheochromocytoma and Paraganglioma, PPGL)
Role of Medical Geneticist in the Workup of Inherited Neuroendocrine Neoplasia Syndromes
Neuroendocrine Neoplasia Inheritance and Genetic Testing Approach
Nomenclature on Genetic Testing Results
References
19: The Management of Neuro-Endocrine Neoplasms
Introduction
Surgery
Surgically Resectable Disease
Surgical Treatment for Advanced Disease
Medical Therapy
Targeted Radiation Therapy
Symptom-Directed Therapies
Additional Treatment Options
Future Directions
References
Index
