8246/3 Neuroendocrine carcinoma, NOS


Definitions

Stomach
ICD-O-3 topography code: C16
ICD10: C16
           

A neuroendocrine carcinoma (NEC) is a poorly differentiated, highgrade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling NET, diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine carcinoma 1
 
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



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Esophagus
ICD-O-3 topography code: C15
ICD10: C15
           

/span>euroendocrine carcinoma (NEC) is a poorly differentiated, high-grade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling NET, diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine carcinoma.

Neuroendocrine tumours of the oesophagus are exceedingly rare. Most of the reported cases are neuroendocrine carcinomas (NEC) or mixed adenoneuroendocrine carcinoma (MANEC), the latter with either an adenocarcinoma or a squamous cell carcinoma component
2
 
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



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Pancreas
ICD-O-3 topography code: C25
ICD10: C25
           

Pancreatic NETs (neuroendocrine tumours) and NECs (neuroendocrine carcinomas) are classified on the basis of criteria similar to those for other neuroendocrine neoplasms of the gastrointestinal tract as below:

A neuroendocrine carcinoma (NEC) is a poorly differentiated, highgrade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling NET, diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine carcinoma
3
 
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



.





Kidney
ICD-O-3 topography code: C64
ICD10: C64
           

Neuroendocrine carcinoma is a poorly-differentiated malignant epithelial neoplasm with signs of neuroendocrine differentiation
4
 
Ronald A. DeLellis, Ricardo V. Lloyd, Philipp U. Heitz, Charis Eng
World Health Organization Classification of Tumours. Pathology and Genetics of Tumors of Endocrine Organs
IARC Press: Lyon 2004



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In the kidney, these tumours are usually located close to the renal pelvis, often surrounding the pelvicaliceal cavities and/or extending into renal sinus adipose tissue. They are histologically composed of sheets, nests and trabeculae of small, round to fusiform cells separated by stroma. Mitotic activity is high, vascular tumour embolism common, and tumour necrosis often extensive and accompanied by perivascular DNA deposition (Azzopardi phenomenon). A concomitant urothelial carcinoma is frequently found.
Neuroendocrine carcinoma of the kidney occurs in adults (mean age 60 years, no sex predilection). The prognosis is poor and stage dependent. Regional lymph node as well as distant metastases are common. More than 75% of patients succumb within one year of diagnosis
5
 
Eble JE, Sauter G, Epstein JI, Sesterhenn IA (Eds.)
World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs.
3rd Edition
IARC Press: Lyon 2004



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Colon and rectum
ICD-O-3 topography code: C18-C20
ICD10: C18-C20
           

Neuroendocrine carcinoma (NEC) is a poorly differentiated, highgrade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling neuroendocrine tumour (NET), diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine carcinoma
6
 
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



.





Region of the ampulla of Vater
ICD-O-3 topography code: C24.1
ICD10: C24.1
           

Neuroendocrine carcinoma (NEC) is a poorly differentiated, high grade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling neuroendocrine tumour (NET), diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine carcinoma
7
 
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



.





Gallbladder and extrahepatic biliary tract
ICD-O-3 topography code: C23-C24.0
ICD10: C23-C24.0
           

/span> neuroendocrine carcinoma (NEC} is a poorly differentiated, highgrade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling NET, diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine carcinoma
8
 
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



.

>



Small intestine
ICD-O-3 topography code: C17
ICD10: C17
           

Neuroendocrine carcinoma (NEC) is a poorly differentiated, highgrade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling neuroendocrine tumour (NET), diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine
carcinoma
9
 
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



.





Breast
ICD-O-3 topography code: C50
ICD10: C50
           

These tumours consist of densely cellular, solid nests and trabeculae of cells that vary from spindle to plasmacytoid and large clear cells
10
Click to access Pubmed
Sapino A, Righi L, Cassoni P, Papotti M, Pietribiasi F, Bussolati G (2000)
Expression of the neuroendocrine phenotype in carcinomas of the breast.
Semin Diagn Pathol 17: 127-37



separated by delicate fibrovascular stroma. The classic features of carcinoid tumours of the gastrointestinal tract or lung, i.e. ribbons, cords and rosettes, are not features of neuroendocrine carcinomas of the breast. The majority are of low or intermediate grade 11
Click to access Pubmed
Sapino A, Righi L, Cassoni P, Papotti M, Gugliotta P, Bussolati G (2001)
Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women.
Mod Pathol 14: 768-76



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See Carcinoma with neuroendocrine features for images and detailed discussion.



Anus and anal canal
ICD-O-3 topography code: C21
ICD10: C21
           

Neuroendocrine carcinoma (NEC) is a poorly differentiated, highgrade malignant neoplasm composed of small cells or large to intermediate cells, sometimes with organoid features resembling neuroendocrine tumour (NET), diffusely expressing the general markers of neuroendocrine differentiation (diffuse expression of synaptophysin; faint or focal staining for chromogranin A), with marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF); high grade (G3) defined according to the proliferation fraction and histology. This definition refers to neoplasms previously classified as small cell carcinoma, large cell (neuro)endocrine carcinoma, or poorly differentiated (neuro)endocrine carcinoma.