8020/3 Carcinoma, undifferentiated, NOS


Definitions

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

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.

Undifferentiated carcinoma of the pancreas
This is a malignant epithelial neoplasm in which a significant component of the neoplasm does not show a definitive direction of differentiation. These neoplasms usually occur in elderly people, and males and females are equally affected.
Three histological variants have been described. Anaplastic giant cell carcinomas are composed of pleomorphic mononuclear cells admixed with bizarre-appearing giant cells with eosinophilic cytoplasm. Cells with spindle-cell morphology predominate in the sarcomatoid carcinoma, and carcinosarcomas have cells recognizable as adenocarcinoma as well as a high-grade spindle-cell component. In contrast to ductal adenocarcinoma, undifferentiated carcinomas are poorly cohesive, cellular and often have only scant stroma 1
 
Cubilla AL, Fitzgerald PJ (eds)
Tumours of the Exocrine Pancreas.
Armed Forces Institute of Pathology: Washington, DC 1984



2
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Klöppel G, Adsay NV (2009)
Chronic pancreatitis and the differential diagnosis versus pancreatic cancer.
Arch Pathol Lab Med 133: 382-7



3
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Tschang TP, Garza-Garza R, Kissane JM (1977)
Pleomorphic carcinoma of the pancreas: an analysis of 15 cases.
Cancer 39: 2114-26



. Nuclear pleomorphism, mitoses as well as perineural, lymphatic, and vascular invasion are easily identified.
Immunohistochemically, most of these carcinomas express keratin and vimentin but not E-cadherin
4
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Hoorens A, Prenzel K, Lemoine NR, Klöppel G (1998)
Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki-ras mutations provides evidence of a ductal origin.
J Pathol 185: 53-60



5
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Paal E, Thompson LD, Frommelt RA, Przygodzki RM, Heffess CS (2001)
A clinicopathologic and immunohistochemical study of 35 anaplastic carcinomas of the pancreas with a review of the literature.
Ann Diagn Pathol 5: 129-40



6
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Winter JM, Ting AH, Vilardell F, Gallmeier E, Baylin SB, Hruban RH, Kern SE, Iacobuzio-Donahue CA (2008)
Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer.
Clin Cancer Res 14: 412-8



.
Electron microscopy reveals epithelial differentiation, microvilli and occasional mucin in some cases
7
 
Cubilla AL, Fitzgerald PJ (eds)
Tumours of the Exocrine Pancreas.
Armed Forces Institute of Pathology: Washington, DC 1984



.
The prognosis is extremely poor, and average survival is just 5 months
8
Click to access Pubmed
Hoorens A, Prenzel K, Lemoine NR, Klöppel G (1998)
Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki-ras mutations provides evidence of a ductal origin.
J Pathol 185: 53-60



9
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Paal E, Thompson LD, Frommelt RA, Przygodzki RM, Heffess CS (2001)
A clinicopathologic and immunohistochemical study of 35 anaplastic carcinomas of the pancreas with a review of the literature.
Ann Diagn Pathol 5: 129-40



10
Click to access Pubmed
Tschang TP, Garza-Garza R, Kissane JM (1977)
Pleomorphic carcinoma of the pancreas: an analysis of 15 cases.
Cancer 39: 2114-26



11
 
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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Colon and rectum
ICD-O-3 topography code: C18-C20
ICD10: C18-C20
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.

Undifferentiated carcinoma of the colon and rectum
These rare tumours lack morphological, immunohistochemical, and molecular biological evidence of differentiation beyond that of an epithelial tumour and have variable histological features. Some of these tumours have MSI-H
12
 
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
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.

Undifferentiation or poorly differentiated carcinoma of the gallbladder and extrahepatic biliary tract
This neoplasm is more common in the gallbladder than in the extrahepatic bile ducts. Characteristically, glandular structures are few or absent. There are several histological variants: spindle cell, giant cell (including those with osteoclast- like giant cells), small cell (nonneuroendocrine), and a nodular/lobular type that superficially resembles breast carcinoma
13
 
Albores-Saavedra J, Henson DE, and Klimstra DS eds.
Tumors of the Gallbladder, Extrahepatic Bile Ducts, and Ampulla of Vater
Armed Forces Institute of Pathology: Washington, DC 2000



14
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Albores-Saavedra J, Molberg K, Henson DE (1996)
Unusual malignant epithelial tumors of the gallbladder.
Semin Diagn Pathol 13: 326-38



15
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Diebold-Berger S, Vaiton JC, Pache JC, d'Amore ES (1995)
Undifferentiated carcinoma of the gallbladder. Report of a case with immunohistochemical findings.
Arch Pathol Lab Med 119: 279-82



16
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Guo KJ, Yamaguchi K, Enjoji M (1988)
Undifferentiated carcinoma of the gallbladder. A clinicopathologic, histochemical, and immunohistochemical study of 21 patients with a poor prognosis.
Cancer 61: 1872-9



17
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Haratake J, Yamada H, Horie A, Inokuma T (1992)
Giant cell tumor-like cholangiocarcinoma associated with systemic cholelithiasis.
Cancer 69: 2444-8



18
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Nakanishi Y, Ito T, Kubota K, Takeda H, Yonemori A, Kawakami H, Zen Y, Kondo S (2007)
Spindle cell-type undifferentiated carcinoma of the common bile duct of the hepatic hilus: report of a case.
Surg Today 37: 708-12



19
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Nishihara K, Tsuneyoshi M (1993)
Undifferentiated spindle cell carcinoma of the gallbladder: a clinicopathologic, immunohistochemical, and flow cytometric study of 11 cases.
Hum Pathol 24: 1298-305



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The recently described benign giant cell tumour of the biliary tree, a true histiocytic neoplasm, can be distinguished from carcinoma with osteoclast-like giant cells by immunohistochemical assessment of CD163, CD68, HAM56, and keratins
20
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Albores-Saavedra J, Grider DJ, Wu J, Henson DE, Goodman ZD (2006)
Giant cell tumor of the extrahepatic biliary tree: a clinicopathologic study of 4 cases and comparison with anaplastic spindle and giant cell carcinoma with osteoclast-like giant cells.
Am J Surg Pathol 30: 495-500



21
 
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



.



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

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.

Undifferentiated carcinoma of the esophagus lacks definite microscopic features of squamous differentiation. The tumour cells form nestsand sheet-like arrangements. Immunohistochemically, tumours express squamous epithelial markers. Such neoplasms must be distinguished from neuroendocrine/small cell neuroendocrine carcinoma (NEC). Undifferentiated carcinoma is negative for neuroendocrine
markers
22
 
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
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.

Undifferentiated / poorly differentiated carcinoma of the ampulla of Vater
There are two types of undifferentiated carcinoma of the ampulla:

(1) The first is composed of small (non-neuroendocrine) cells while in the second type spindle cells predominate and resemble a sarcoma (sarcomatoid carcinoma). The first type is highly cellular with minimal stroma and is composed of relatively small cells with scant cytoplasm, vesicular nuclei and prominent nucleoli arranged in solid sheets or nests
23
 
Albores-Saavedra J, Henson DE, and Klimstra DS eds.
Tumors of the Gallbladder, Extrahepatic Bile Ducts, and Ampulla of Vater
Armed Forces Institute of Pathology: Washington, DC 2000



24
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Molberg KH, Heffess C, Delgado R, Albores-Saavedra J (1998)
Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and periampullary region.
Cancer 82: 1279-87



. There are no glands or signet-ring cells. Numerous mitotic figures and necrosis of variable extent are common. Immunohistochemical stains for neuroendocrine markers are negative.

(2) The second type of undifferentiated carcinoma consists predominantly of fascicles of spindle cells, some of which are keratinpositive, supporting their epithelial phenotype. When extensively sampled, these tumours often contain glandular structures or nests of frank epithelial cells. Considerable cytological atypia including the presence of pleomorphic and anaplastic giant cells may be present in the spindle cell component. When heterologous elements such as cartilage, bone and skeletal muscle are present, the term ?carcinosarcoma? is justified
25
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Kijima H, Takeshita T, Suzuki H, Tanahashi T, Suto A, Izumika H, Miki H, Terasaki Y, Nakamura M, Watanabe H, Tamaoki N, Omiya H (1999)
Carcinosarcoma of the ampulla of Vater: a case report with immunohistochemical and ultrastructural studies.
Am J Gastroenterol 94: 3055-9



26
 
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



.



Liver and intrahepatic bile ducts
ICD-O-3 topography code: C22
ICD10: C22
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.

Undifferentiated hepatic carcinomas are tumours that are primary to the liver and can be diagnosed as carcinomas based on immunohistochemistry, but cannot be further classified. Undifferentiated carcinoma is rare, accounting for < 2% of epithelial liver tumours. There is a male preponderance, but data on geographical distribution are not available. Localization, clinical features, symptoms and signs, and diagnostic procedures display no differences compared with hepatocellular carcinoma. Undifferentiated carcinomas are postulated to have a worse prognosis (compared with HCC), although greater case numbers to support this are not available
27
 
Craig JR, Peters RL, and Edmondson HA
Tumours of the Liver and Intrahepatic Bile Ducts
Armed Forces Institute of Pathology
Washington, DC. 1989



28
 
Ishak KG, Anthony PP, and Sobin LH
Histological Typing of Tumours of the Liver
Springer: Berlin, Heidelberg, New York, Tokyo 1999



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

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.

Poorly differentiated carcinoma of the stomach is rare
29
 
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



.



Thyroid gland
ICD-O-3 topography code: C73
ICD10: C73
           

Poorly differentiated carcinoma of the thyroid is a follicular-cell neoplasm that shows limited evidence of structural follicular cell differentiation and occupies both morphologically and behaviourally an intermediate position between differentiated (follicular and papillary carcinomas) and undifferentiated (anaplastic) carcinoma
30
 
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



.
Poorly differentiated carcinoma remains a controversial entity. The disease is more common in women and in patients older than 50
31
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Carcangiu ML, Zampi G, Rosai J (1984)
Poorly differentiated ("insular") thyroid carcinoma. A reinterpretation of Langhans' "wuchernde Struma".
Am J Surg Pathol 8: 655-68



32
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Sobrinho-Simões M, Sambade C, Fonseca E, Soares P (2002)
Poorly differentiated carcinomas of the thyroid gland: a review of the clinicopathologic features of a series of 28 cases of a heterogeneous, clinically aggressive group of thyroid tumors.
Int J Surg Pathol 10: 123-31



. The prognosis depends primarily on TNM staging, completeness of surgery and responsiveness to radioactive iodine therapy. The mean five-year survival rate is about 50% 33
Click to access Pubmed
Carcangiu ML, Zampi G, Rosai J (1984)
Poorly differentiated ("insular") thyroid carcinoma. A reinterpretation of Langhans' "wuchernde Struma".
Am J Surg Pathol 8: 655-68



34
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Nishida T, Katayama S, Tsujimoto M, Nakamura J, Matsuda H (1999)
Clinicopathological significance of poorly differentiated thyroid carcinoma.
Am J Surg Pathol 23: 205-11



35
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Papotti M, Botto Micca F, Favero A, Palestini N, Bussolati G (1993)
Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular, trabecular, and solid patterns.
Am J Surg Pathol 17: 291-301



36
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Sobrinho-Simões M, Sambade C, Fonseca E, Soares P (2002)
Poorly differentiated carcinomas of the thyroid gland: a review of the clinicopathologic features of a series of 28 cases of a heterogeneous, clinically aggressive group of thyroid tumors.
Int J Surg Pathol 10: 123-31



. Death is caused by regional and distant metastases rather than by local invasion 37
 
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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Fallopian tube and Uterine ligaments
ICD-O-3 topography code: C57
ICD10: C57
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.



Nasal cavity and Sinuses
ICD-O-3 topography code: C30-C31
ICD10: C30-C31
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.



Thymus
ICD-O-3 topography code: C37
ICD10: C37
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.



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

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.





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

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.



Ovary
ICD-O-3 topography code: C56
ICD10: C56
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.



Corpus uteri
ICD-O-3 topography code: C54
ICD10: C54
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation
38
 
Tavassoli FA, Devilee P (Eds.)
World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs.
3rd Edition
IARC Press: Lyon 2003



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Urinary system: Renal pelvis, ureter, bladder, urethra
ICD-O-3 topography code: C65-C68
ICD10: C65-C68
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.



Cervix uteri
ICD-O-3 topography code: C53
ICD10: C53
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation
39
 
Tavassoli FA, Devilee P (Eds.)
World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs.
3rd Edition
IARC Press: Lyon 2003



.



Vagina
ICD-O-3 topography code: C52
ICD10: C52
           

Undifferentiated carcinoma is a usually aggressive, malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or urothelial cell differentiation.