In ASCC of the skin and breast different molecular alterations have been associated with loss of cellular adhesion, including loss of E-cadherin or syndecan-1 [12
]. In our case tumor cell showed loss of E-cadherin and beta-catenin while syndecan-1 expression was reduced and confined on small group of detached malignant cell. Loss of E-cadherin, beta-catenin and altered syndecan-1 expression suggest an impaired cellular adhesion, which may explain the peculiar histological appearance of these tumors and contribute to the observed aggressive clinical behavior in skin, penile and breast ASCC [6
]. In our case tumor had also aggressive course but making conclusions about clinical behavior of this type tumor in colon are difficult because this is a first case described with limited follow-up.
Before regarding such a case as primary SCC of the colon, especially when tumor is located 7 cm proximal to the dentate line, exclusion of possibilities of metastatic deposit from a source elsewhere or direct extension from other site is necessary [1
]. In addition, the affected segment of bowel could not be in continuity with squamous lined fistula or the anal squamous epithelium, mucin should be absent, intercellular bridges should be visible and keratin may or may not be present [1
]. Some predisposing conditions are thought to play a role in the development of primary colonic SCC such as inflammatory bowel disease (especially ulcerative colitis), schistostomiasis, pelvic irradiation, villous adenoma and duplication of the intestine [1
]. Our patient had no any mentioned predisposing conditions but her family history could suggest some genetic alterations that may have role in tumor formation and especially suspected was Lynch syndrome. Lynch syndrome or hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant genetic condition which is characterized with a high risk of colon cancer as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. Patients with Lynch syndrome usually present with adenocarcinoma of the proximal colon (cecum), with or without synchronous or metachronous colorectal cancer or other malignancy typical of the syndrome. The majority of colorectal carcinomas arising in Lynch syndrome are generally similar to sporadic colorectal cancer but mucinous, signet-ring and medullary types are identified with increased frequency in Lynch syndrome patients [15
]. In addition, the presence of tumor-infiltrating lymphocytes and especially presence of intraepithelial T-lymphocytes could identify the majority of colorectal cancers with this mutation [16
]. Despite patient denied additional cancers in family and did not know type and localization of colorectal cancer in relatives we recommended additional genetic testing to exclude possibility of Lynch syndrome.
We also considered HPV as potential carcinogen but immunostaining for p16 was negative and therefore additional investigations were not performed.
It is important for pathologist to discriminate between primary colonic ASCC and metastasis of any SCC or ASCC from elsewhere. Likewise, metastasis of endometroid carcinoma with squamous differentiation or transitional cell carcinoma with gland formation and squamous differentiation should be taken into consideration. Endometroid carcinomas are immunohistochemically positive for CK7, progesterone and estrogen receptors while transitional cell carcinomas are positive for CK7 and CK20. In our case these markers were negative and CK AE1/AE3 was strongly and diffusely positive in whole tumor including pseudoglandular and acantholytic areas. Recommended additional extensive clinical examination and immunohistochemical analysis excluded possible metastatic disease and patient fulfils all criteria for diagnosis of primary ASCC carcinoma.
There are four main proposed pathogenic theories trying to explain the origin of SCC of the colon [1
]. Squamous cells which are the source for SCC could originate from proliferation of uncommitted reserve or basal cells following mucosal injury, from squamous metaplasia of glandular epithelium resulting from chronic irritation, from embryonal nests of ectodermal cells or from stem cells [1
Colonic ASCC should be also differentiated from adenosquamous carcinoma and angiosarcoma. Adenosquamous carcinoma is defined as a tumor with malignant glandular and squamous component and the potential for metastases [17
]. In the colon and rectum, this tumor is extremely rare and accounts for 0.1% to 0.2% of all colon cancers. Histogenesis of adenosquamous carcinoma is unclear and several theories, that are similar to theories of origin of colonic SCC, have been proposed to try to explain squamous differentiation in colonic mucosa [17
]. Malignant glandular component in adenosquamous colonic carcinoma retain immunohistochemical characteristic of conventional colonic adenocarcinoma (positivity for CK20 and CEA) and contain mucinous material in the lumen or cells cytoplasms [17
Another rare tumor to be distinguished from ASCC is the angiosarcoma, especially in the variant of ASCC termed pseudovascular or angiosarcoma-like SCC where anastomosing spaces and channels that are mimicking neoplastic vessels of angiosarcoma are formed and keratin formation is absent [8
]. Angiosarcoma occurs very rarely in the intestinal tract as either primary or metastatic malignancy and can present great diagnostic difficulty, especially when it displays epithelioid cytomorphology [18
]. An incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognosis. Immunohistochemical examination is a useful tool in making the distinction but cytokeratins and epithelial membrane antigen should not be considered to be a distinct discriminating criterion, because malignant endothelial cells may be positive [18
]. Allison et al. [18
] immunohistochemically analyzed a series of 8 primary and metastatic angiosarcoma involving the gastrointestinal tract and found that tumor cells were immunoreactive for cytokeratins AE1/AE3 (7/8), cytokeratin 7 (2/8), Cam5.2/cytokeratin 8 (5/8), and cytokeratin 19 (5/8). In one case weakly and focal positivity for epithelial membrane antigen was also observed [18
]. In contrast to an angiosarcoma, the cells of ASCC are negative for endothelial markers such as CD31, CD34 and von Willebrand factor and these markers must be included in differentiating ASCC from angiosarcoma [8
The immunohistochemical and histochemical findings of the present tumor were compatible with the previous data of ASCC and exclude possibility of adenosquamous carcinoma or angiosarcoma [8