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Stains

Cytokeratin 7 (CK7, K7)


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 25 December 2011, last major update December 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

Definition
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● Type II keratin of simple nonkeratinizing epithelia (OMIM 148059); molecular weight 54 kDa
● Found in breast, lung, ovary and urothelium, but usually NOT in GI or stratified squamous epithelium

Uses by pathologists
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General patterns (specificity varies):
CK7+ / CK20+: carcinomas of bile duct (extrahepatic / gallbladder, often, Pathol Res Pract 2003;199:65), lung-mucinous bronchioloalveolar (Am J Clin Pathol 2004;122:421), pancreas (Cancer 2006;106:693, but see Arch Pathol Lab Med 2000;124:1196), urothelium (often, Arch Pathol Lab Med 2001;125:921, Hum Pathol 2002;33:1136); also primary mucinous tumors of ovary (74%), upper GI tract (78%) and endocervix (88%, Am J Surg Pathol 2006;30:1130)
CK7+ / CK20-: carcinomas of bile duct (intrahepatic, Pathol Res Pract 2003;199:65), breast (Ann Diagn Pathol 1999;3:350), endocervical and endometrial adenocarcinoma (Int J Gynecol Pathol 2002;21:4), esophagus (distal, Am J Surg Pathol 2002;26:1213), lung (not mucinous bronchioloalveolar, BMC Cancer 2006;6:31), salivary gland (Pathol Int 2005;55:386), thyroid (Appl Immunohistochem Mol Morphol 2000;8:189); mesothelioma (Cancer 2001;92:2727)
CK7- / CK20+: carcinoma of colon (particularly early stage, Hum Pathol 2005;36:275); primary mucinous tumors of lower GI tract (79%, Am J Surg Pathol 2006;30:1130), primary bladder adenocarcinoma (29%, Am J Surg Pathol 2001;25:1380)
CK7- / CK20-: carcinoma of adrenal cortex, prostate (Mod Pathol 2000;13:962)
● To distinguish primary lung carcinoma (CK7+ / CK20-) from metastatic colonic carcinoma to lung (CK7- / CK20+, BMC Cancer 2006;6:31)
● To distinguish adenocarcinoma of distal esophagus (CK7+ / CK19+: 90%, CK7+ / CK20-: 74%) from proximal stomach (CK7+ / CK19+: 44%, CK7+ / CK20-: 24%, Am J Surg Pathol 2002;26:1213)
● To distinguish chromophobe carcinoma (diffuse CK7+ staining) from oncocytoma (usually CK7-, Anal Quant Cytol Histol 2006;28:228)
● To help distinguish papillary renal cell carcinoma (CK7+) from metanephric adenoma (CK7-, Mod Pathol 2006;19:218)
● To distinguish endometrioid and clear cell carcinoma (CK7+) from yolk sac tumors (CK7-, Am J Surg Pathol 2004;28:1499)

Micro images
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Ampullary adenocarcinoma

   
Anal glands (left-fig e) and transitional zone (right, fig 1b) are CK7+


Anal gland carcinoma is CK7+ (fig c)


Barrett’s esophagus (fig B)


Bladder: intestinal meteaplasia and cystitis glandularis (typical staining)


Bladder: carcinoid and urothelium are CK7+ (fig f)

       
Bladder (left to right): plasmacytoid carcinoma, urachal mucinous cystadenocarcinoma, lymphoepithelioma-like carcinoma


Bladder/urethra: clear cell adenocarcinoma

   
Breast: Left-cylindroma; right-Paget’s disease


Breast-metaplastic carcinoma


Cardiac myxoma with glandular differentiation

   
Cervical adenocarcinoma: Left-intestinal type (fig C); right-signet ring type (fig C)

   
Cholangiocarcinoma: Left-intrahepatic (fig a); right-extrahepatic (fig c) and gallbladder (fig a)


Choroid plexus papilloma


Colonic and lung carcinoma (fig D-F)


Endolymphatic sac tumor (fig A)


Endometrioid adenocarcinoma (fig C)


Heart: myxoma


Kidney: metanephric adenoma, papillary carcinoma, Wilm's tumor

   
Kidney: left - chromophobe carcinoma-eosinophilic variant is CK7+ (fig 2C); right - oncocytoma has scattered CK7+ cells (fig 6)


Liver: hepatocellular carcinoma, fibrolamellar variant

           
Lung adenocarcinoma (left to right): non-mucinous bronchioloalveolar (fig C); mucinous bronchioloalveolar (fig C); metastatic to eye (choroid); metastatic to ovary


Melanoma (uterus)


Meningioma of middle ear / temporal bone


Mesothelioma with rhabdoid features (fig c)


Middle ear adenoma

       
Nasal cavity (left to right): respiratory epithelial adenomatoid hamartoma, seromucinous hamartoma, inverted papilloma


Ovarian mucinous cystadenoma is CK7+ (5b), but testicular mucinous cystadenoma (fig 3b) and colonic epithelium (fig 4b) are negative


Pancreas: lymphoepithelial cyst


Pancreas: ductal adenocarcinoma (fig e)


Penis/scrotum: mucoid cyst

   
Prostate: left-nephrogenic adenoma; right-adenocarcinoma (occasional CK7+ cells)

           
Renal cell carcinomas (left to right): papillary (fig 3b); papillary-solid variant; chromophobe, tubulocystic

       
Salivary gland carcinomas (left to right): mucoepidermoid are CK7+ (fig b, e); adenoid cystic (fig b, e); salivary duct (fig b, e)


Seminal vesicle adenocarcinoma

   
Skin: left-Mercel cell carcinoma; right-various tumors


Ureter (normal)-Cytokeratin 7 (RN7) with intense cytoplasmic staining (contributed by Leica Microsystems, Biosystems Division)


Urethra: clear cell adenocarcinoma


Urothelial carcinoma: with glandular differentiation (fig 4)

       
Various carcinomas (left to right): pancreatic-fig 1A, cholangiocarcinoma-fig 1C, urothelial-fig 1E; breast-fig 3A, ovary-fig 3C, lung-fig 3E, endometrium-fig 3G; colon-fig 4A, Merkel cell-fig 4C

Positive staining - normal
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● Anal glands and anal transition zone (Arch Pathol Lab Med 2001;125:1074)
● Bile ducts (Exp Cell Res 1987;170:235)
● Breast
● Cervical glands
● Endometrium
● Fallopian tube
● Fetal cells in transcervical mucus (J Obstet Gynaecol Res 2005;31:500)
● Gallbladder
● Kidney collecting ducts
● Lung
● Mesothelium
● Ovarian epithelium (Am J Pathol 1991;138:455)
● Pancreatic ducts (J Pathol 1998;184:234)
● Salivary gland acini (Mod Pathol 2004;17:803), intercalated ducts and intercalated duct lesions (Am J Surg Pathol 2009;33:1322)
● Thyroid epithelium
● Toker cells (Am J Dermatopathol 2005;27:185)
● Trophoblast (J Immunol Methods 2004;286:21)
● Urothelium (Eur J Cell Biol 2004;83:27)

Positive staining - non malignant
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● Cystitis glandularis (bladder) of usual type (intestinal type is CK7-)
● Colonic serrated adenoma (Dig Dis Sci 2005;50:1741)
● Ependymoma: extra-axial (80%) versus CNS (10%, Am J Surg Pathol 2008;32:710)
● Esophagus-Barrett’s: strong diffuse CK7+ surface and crypt epithelium, strong CK20+ surface and superficial crypt staining; interpretation is affected by fixative (Hum Pathol 2005;36:58, but see Mod Pathol 2002;15:611); pattern may help distinguish short segment Barrett’s from cardiac intestinal metaplasia (World J Gastroenterol 2005;11:6360)
● Eye: Fuchs endothelial dystrophy (Cornea 2006;25:956)
● Liver: bile duct adenoma, mesenchymal hamartoma, chronic allograft rejection (Am J Clin Pathol 2011;135:238). perivenular hepatocytes associated with cholestatic chemistry profile and heart failure (Mod Pathol 2010;23:1650)
● Lymph nodes: individual / clusters of neuroendocrine cells (Am J Surg Pathol 2010;34:1701)
● Nephrogenic adenoma of GU tract (Am J Surg Pathol 2009;33:1654)
● Pancreas: lymphoepithelial cyst (Mod Pathol 2010;23:1467)
● Salivary gland oncocytoma (Laryngoscope 2005;115:1097)

Positive staining - malignant
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● Adenocarcinomas-mucinous from ampulla, biliary tree, esophagus, pancreas, stomach (93%, Am J Surg Pathol 2011;35:1830)
● Adenocarcinoma-mucinous from colon / rectum / anus (only 19% are CK7+, most from rectum/anus, Am J Surg Pathol 2011;35:1830)
● Anal duct carcinoma (Hum Pathol 2011 Aug 3 [Epub ahead of print])
● Appendiceal epithelial neoplasms (benign and malignant-33%, Hum Pathol 2005;36:1217)
● Basaloid squamous cell carcinoma of Waldeyer’s ring (Hum Pathol 2000;31:1096)
● Bile duct carcinoma (90%, Hum Pathol 2005;36:1226)
● Bladder adenocarcinoma (63%, Appl Immunohistochem Mol Morphol 2005;13:358)
● Breast carcinoma (Ann Diagn Pathol 1999;3:350)
● Carcinoid (GI, 11%, Hum Pathol 2001;32:1087)
● Cervical adenocarcinoma (Am J Clin Pathol 2009;132:531)
● Colon adenocarcinoma related to ulcerative colitis (59%, Virchows Arch 2006;448:756)
● Germ cell tumors at various sites (variable, but usually negative)
● Kidney: renal cell carcinoma (chromophobe-Am J Clin Pathol 2007;127:225, clear cell tubulopapillary-Am J Surg Pathol 2010;34:1608, collecting duct, papillary-Am J Surg Pathol 2011;35:949)
● Liver: hepatocellular carcinoma (10-34% positive, Mod Pathol 2006;19:460, particularly scirrhous / fibrolamellar type, Histopathology 2005;47:382 or age 30 or younger, Am J Clin Pathol 2005;124:512)
● Lung: adenocarcinoma-94% vs. squamous cell-60% (Hum Pathol 2006;37:542, Am J Surg Pathol 2011;35:15)
● Merkel cell (50%, J Eur Acad Dermatol Venereol 2005;19:546)
● Mesothelioma, including with rhabdoid features (Mod Pathol 2006;19:373)
● Ovarian carcinoma (Mod Pathol 2006;19:1421), but mucinous carcinoma with pseudomyxoma ovarii (suggesting teratomatous derivation) are CK7- (Am J Surg Pathol 2007;31:854); ovarian carcinoids (24%), Sertoli cell tumors (13%, Am J Surg Pathol 2007;31:255)
● Paget’s cells (breast, anal, vulvar, esophageal, but not vulvar secondary to anorectal carcinoma, Am J Surg Pathol 1998;22:170-perianal, Hum Pathol 2002;33:545-vulvar, Am J Surg Pathol 2008;32:1068-esphageal)
● Pancreatic carcinoma including intestinal type (Ann Diagn Pathol 2007;11:3)
● Pseudomyxoma peritonei (almost all cases have variable positivity, Histopathology 2006;49:381)
● Salivary gland: carcinoma (100%, Pathol Int 2005;55:386), lymphadenoma (Mod Pathol 2011 Sep 2 [Epub ahead of print])
● Sinonasal adenocarcinoma (most, Ann Otol Rhinol Laryngol 2006;115:59)
● Small intestinal adenocarcinoma (Am J Surg Pathol 2004;28:1499)
● Synovial sarcoma (many, Mod Pathol 2006;19:659)
● Urothelial carcinoma (87%), urothelial carcinoma in situ of the bladder with glandular differentiation (Hum Pathol 2011;42:1653)
● Uterus: endometrioid adenocarcinoma (100%), endocervical (50%, Int J Gynecol Pathol 2012;31:57); most mucinous tumors (Appl Immunohistochem Mol Morphol 2009;17:8)

Negative staining
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● Adrenocortical carcinoma
● Cervical squamous epithelium
● Endometrial stromal sarcoma (Hum Pathol 2008;39:1459)
● GI epithelium (normal)
● GI carcinomas-nonmucinous (but see exceptions above)
● Hepatocytes; hepatoid adenocarcinoma
● Kidney: normal tubules, carcinoid (may have focal staining, Am J Surg Pathol 2007;31:1539), clear cell carcinoma (usually), oncocytoma
● Nasal cavity: nonkeratinizing nasopharyngeal carcinoma-differentiated and undifferentiated
● Pituitary adenomas (usually, Endocr Pathol 2005;16:201)
● Prostate adenocarcinoma (Mod Pathol 2000;13:962), but prostatic mucin producing urothelial-type carcinoma is usually CK7+ (83%, Am J Surg Pathol 2007;31:1323)
● Skin (squamous epithelium)
● Tongue
● Yolk sac tumor (Am J Surg Pathol 2004;28:1499)

End of Stains > Cytokeratin 7 (CK7, K7)


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