High Grade / Poorly Differentiated Neuroendocrine Carcinoma of the Gastrointestinal Tract
Definition
- High grade neoplasm of the GI tract demonstrating neuroendocrine differentiation
Alternate/Historical Names
- Adenocarcinoma with endocrine differentiation/features
- Atypical carcinoid
- High grade / poorly differentiated endocrine carcinoma
- Large cell neuroendocrine carcinoma
- Oat cell carcinoma
- Small cell carcinoma
Diagnostic Criteria
- Two basic patterns
- Small cell (undifferentiated) carcinoma
- Scant cytoplasm, very high nucleus/cytoplasm ratio
- Finely granular, stippled chromatin
- Nucleoli small to absent
- Nuclear molding
- Immunohistochemical demonstration of neuroendocrine differentiation not required
- Many are positive:
- CD56 90%
- Synaptophysin 72-100%
- Chromogranin 64-78%
- Many are positive:
- Large cell neuroendocrine carcinoma requires both morphologic and immunohistologic (or ultrastructural) evidence of neuroendocrine differentiation
- Morphologic features suggestive of neuroendocrine differentiation (not all are seen in each case)
- Generally uniform polygonal/cuboidal cells with slightly granular eosinophilic cytoplasm
- Densely cellular with solid growth pattern
- Nesting and/or broad trabeculae with nuclear palisading
- Rosettes and rosette like structures but limited true gland formation
- Focal gland formation or intracytoplasmic mucin is permitted
- Fine to coarsely granular (stippled) chromatin pattern with thin nuclear membranes
- Usually have vesicular nuclei with prominent nucleoli
- Necrosis
- Demonstration of neuroendocrine differentiation is required
- Percent of cells required to stain ranges from 20 to 50% in various studies
- Synaptophysin, chromogranin and CD56 are the most specific
- Reported reactivity:
- CD56 54%
- Synaptophysin 94-100%
- Chromogranin 71-78%
- Neuron specific enolase and PGP9.5 are less specific but accepted by many studies
- Specific endocrine secretory products less frequently seen
- Morphologic features suggestive of neuroendocrine differentiation (not all are seen in each case)
- Small cell (undifferentiated) carcinoma
- Frequently associated with adenoma and/or adenocarcinoma
- If >30% of both patterns, see mixed adenoneuroendocrine carcinoma (MANEC)
- May also show focal glandular or squamous differentiation within endocrine areas
- Not associated with low grade, well differentiated neuroendocrine neoplasm (carcinoid)
- Most frequent in esophagus, stomach, ampulla of Vater, colon, rectum and anus
- Very rare in small intestine, appendix
- (Rare throughout the GI tract compared to conventional adenocarcinomas)
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting/last update: 7/27/10, 1/25/15
