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Breast malignant, males, children

Carcinoma subtypes

Neuroendocrine carcinoma - general


Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 3 November 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Definition
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● Carcinoma with neuroendocrine features in at least 50% of cells
● Terminology usually restricted to low grade tumors (high grade tumors are often called small cell carcinoma)
● May arise from neuroendocrine cell hyperplasia (Pathol Int 2012;62:331, J Clin Pathol 2012;65:699)

Terminology
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● Often (although not consistently) refers to cases lacking another specific histologic type, such as solid papillary, mucinous / colloid or micropapillary
● Also called endocrine carcinoma or solid cohesive neuroendocrine carcinoma
● Some cases were formerly called carcinoid tumor (Eur J Surg Oncol 1995;21:609)

Clinical features
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● Up to 5% of all breast carcinomas, depending on how defined
● Frequency increases with age
● Similar clinical presentation as ductal NOS; i.e. no carcinoid syndrome is present
● Similar prognosis as ductal NOS
● Apocrine phenotype (androgen receptor positive in 50% of cells) is present in elderly women (Mod Pathol 2001;14:768)

Case reports
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● 60 year woman presenting with kidney and adrenal metastases (Pathol Res Pract 2008;204:851)
● 63 year old woman presenting with perianal mass (Clin Breast Cancer 2007;7:892)
● 63 year old woman with local recurrence and metastatic progression one month after surgery (Ann Ital Chir 2012 May 31 [Epub ahead of print])
● 76 year old woman with metastases to skin (Am J Clin Dermatol 2007;8:379)
● 77 year old woman with HER2+ tumor (Breast Cancer 2012 Jun 19 [Epub ahead of print])

Treatment
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● Similar to ductal carcinoma NOS, but possibly add somatostatin for nuclear scanning and treatment of metastatic disease (G Chir 2008;29:203, Breast 2008;17:111)

Clinical images
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10 cm mass

Gross description
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● No distinctive gross features

Micro description
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● Small, low grade tumor cells in nests separated by fibrous tissue
● Rarely ribbons, rosettes or mitotic figures
● Usually no mucin, no DCIS
● No specific histologic patterns, such as solid papillary, small cell or mucinous / colloid

Micro images
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AFIP images:
           
Ribbon type growth pattern with  Tumor cells often have argyrophilic Grimelius+
some spindled cells        granules, tumor is immunoreactive for chromogranin

Contributed by Dr. Semir Vranic, Sarajevo:
           
Focal mucin production

           
Chromogranin expression     Synaptophysin expression

           
Estrogen receptor         HER2 protein


Distinct nests of cells with salt and pepper chromatin


Fig 2: H&E, chromogranin and synaptophysin

           
Various markers (Fig G, H, I)    (Fig A-D, H-I)

Well differentiated tumor with alveolar growth pattern: #1;   #2;   #3-with carcinomatous lymphangitis;  #4-synaptophysin+

Cytology description
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● Markedly cellular with mostly dispersed tumor cells, also some loose clusters, acinus-like formations, small sheets, rosette like formations and ribbons
● Cells are small and regular with moderate cytoplasm, fairly uniform and round / oval nuclei, often plasmacytoid with eccentric nuclei (Acta Cytol 1994;38:73, Indian J Pathol Microbiol 2007;50:65)

Positive stains
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● ER, PR (usually, Med Oncol 2012;29:2613)
● Also chromogranin, synaptophysin, neuron-specific enolase, GCDFP-15 (50%), TTF1 (20%)

Electron microscopy description
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● Dense core secretory granules

Electron microscopy images
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Dense core granules throughout the cytoplasm, but increased at cell membrane


Dense core granules measure 270-430 nm cluster near cell membrane

Differential diagnosis
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Lobular carcinoma: linear and targetoid patterns, nuclear features not neuroendocrine
● Metastatic carcinoid tumor (Am J Surg 2006;199:799, Diagn Cytopathol 2007;35:306)
Neuroendocrine DCIS: not invasive
● Other breast tumors with neuroendocrine features include small cell carcinoma, colloid carcinoma and invasive ductal carcinoma NOS with < 50% neuroendocrine tumor cells

Additional references
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Stanford University, Zhonghua Bing Li Xue Za Zhi 2011;40:604

End of Breast malignant, males, children > Carcinoma subtypes > Neuroendocrine carcinoma - general


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