Poorly Differentiated Neuroendocrine Carcinoma, Pancreas

 Mitoses > 20 in 10 HPF (based on count of at least 50 HPF; 1 HPF = 2 mm²), or


image Ki-67 labeling index > 20% based on at least 500 tumor cells (2,000 if possible)





Clinical Issues




• Very aggressive neoplasms

• Platinum-based chemotherapy (cisplatin or carboplatin) with etoposide

• Large cell morphology, positivity for both synaptophysin and chromogranin, and Ki-67 index < 55% have been reported as favorable parameters


Microscopic




• Small cell variant
image Resembles small cell carcinomas of lung

image Scant cytoplasm, hyperchromatic nuclei, prominent nuclear moulding

• Large cell variant
image Resembles large cell neuroendocrine carcinoma of lung


Ancillary Tests




• Neuroendocrine markers, keratin (+)

• Ki-67 proliferation index: Often necessary to determine grade and guide choice of therapy

• Mitoses and Ki-67 index should be counted in areas with highest proliferation (“hot spots”)

image
Small Cell Neuroendocrine Carcinoma
Small to medium-sized tumor cells with scant cytoplasm, indistinct nucleoli, molding, brisk mitoses and karyorrhectic debris are present.


image
Metastatic Small Cell Neuroendocrine Carcinoma
Pancreatic primary tumor metastatic to liver shows typical cytologic features of small cell neuroendocrine carcinoma, including prominent nuclear molding image. Absence of significant cytoplasm or prominent nucleoli distinguishes it from large cell neuroendocrine carcinoma.

image
Focal Squamous Differentiation
Squamous cells with keratin pearls indicating focal squamous differentiation in an otherwise typical small cell neuroendocrine carcinoma are shown.

image
Large Cell Neuroendocrine Carcinoma
The presence of abundant cytoplasm, prominent nucleoli, and brisk mitoses image (30 mitoses/10 HPF) are typical features of large cell neuroendocrine carcinoma.


TERMINOLOGY


Synonyms




• High-grade neuroendocrine carcinoma

• Poorly differentiated neuroendocrine carcinoma


Definitions




• Morphological and immunohistochemical features suggestive of neuroendocrine differentiation
• High proliferation

image Mitoses > 20 in 10 HPF (based on count of at least 50 HPF), or

image Ki-67 labeling index > 20% based on at least 500 tumor cells


ETIOLOGY/PATHOGENESIS


Unknown




• Do not arise from low-grade neuroendocrine tumors in most cases
• Genetic changes in small and large cell neuroendocrine carcinoma are similar, both are distinct from well-differentiated neuroendocrine tumor

image Immunohistochemical abnormalities in p53 (> 90%) and Rb (> 70%) common in small cell and large cell neuroendocrine carcinomas

image Genes typically involved in well-differentiated neuroendocrine tumor like SMAD4 (DPC4), DAXX, and ATRX are normal

image Bcl-2 overexpression common in neuroendocrine carcinomas, especially small cell


CLINICAL ISSUES


Epidemiology




• Incidence
image Rare, constituting 2-3% of all pancreatic neuroendocrine neoplasms


Presentation




• Jaundice
• Back pain

• Some patients present with hormonal symptoms

image Cushing syndrome

image Hypercalcemia


Treatment




• Surgical approaches
image Radical pancreatic surgery

image Many patients unresectable at diagnosis

• Drugs
image Platinum-based chemotherapy (cisplatin or carboplatin) with etoposide

image Alkylating agent temozolomide-based regimen often used as 2nd-line therapy


Prognosis




• Aggressive neoplasms
image Survival typically few months, less than ductal adenocarcinoma of pancreas

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Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Poorly Differentiated Neuroendocrine Carcinoma, Pancreas

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