Pseudoglandular (Adenoid, Acantholytic) Penile Squamous Cell Carcinoma: A Clinicopathologic and Outcome Study of 7 Patients

Hospital do Cancer AC Camargo, Sao Paulo, Brazil.
American Journal of Surgical Pathology (Impact Factor: 5.15). 03/2009; 33(4):551-555. DOI: 10.1097/PAS.0b013e31818a01d8


Almost half of penile squamous cell carcinomas (SCCs) are of the usual type but there is a variegated spectrum of morphologically distinctive subtypes. In a pathologic review of 375 uniformly diagnosed and treated patients with penile SCC, we found 7 tumors with predominant pseudoglandular or adenoid features. The aim of the study was to delineate clinicopathologic features and outcome of an unusual variant of penile SCC. Clinical charts and pathologic materials were reviewed. The following informations were obtained: patient's age, tumor site, size, histologic grade (1, 2, and 3), thickness in millimeters, anatomic level of invasion [corpus spongiosum, corpus cavernosum (CC)], vascular and perineural invasion, groin nodal status, and follow-up in months. These features were compared with those of 224 cases of usual SCCs. Median age of the patients was 54 years. Tumors were large (average 4.6 cm) and involved multiple sites in 4 cases; exclusively the glans in 2 and site was unknown in 1. Microscopically, tumors were SCC with acantholytic areas ranging from solid nests with early necrosis or empty pseudoluminal spaces lined by 1 layer of squamous cells or cylindrical cells strikingly simulating glands. Tumors were deeply infiltrating (4 invaded CC, 2 corpus spongiosum, and 1 invaded preputial dermis) and were of high histologic grade (6 cases). Vascular invasion was present in 4 cases and perineural invasion in 2. The differential diagnosis was with gland forming penile tumors (surface adenosquamous, mucoepidermoid, and urethral adenocarcinomas) and the angiosarcomatoid variant of sarcomatoid carcinomas. There was regional nodal metastasis in 3 patients, 2 of which died from disease. The other 5 were either alive with no evidence of disease (12 and 21 y after diagnosis) or died from causes other than penile cancer (3, 4, and 7 y after diagnosis). Comparing with usual SCCs, pseudoglandular SCCs were of higher grade (88% vs. 44%), invaded deeper into CC (71% vs. 52%), and showed a higher incidence of regional metastasis (42% vs. 25%) and higher mortality (29% vs. 19%).

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    • "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 [6,10,12]. 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. "
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    ABSTRACT: Acantholytic squamous cell carcinoma (ASCC) is an uncommon histopathologic variant of SCC, characterized by marked acantholysis, wherein the tumor cells demonstrate defective cohesion to one another in the cancer nest leading to a pseudoglandular or pseudovascular appearance. The most common site of ASCC is the sun-exposed areas of the skin. Sporadic cases of ASCC have also been reported in various mucosal membranes and organs but to our knowledge this is the first case of primary ASCC of the large bowel. A 59-year-old woman underwent right hemicolectomy due to large tumor in cecum and initial part of the ascending colon. Microscopically, the tumor consisted of nests of focally keratinizing large, atypical, squamous epithelial cells. Approximately 70% of the tumor showed acantholytic changes and acantholysis was equally distributed through the entire tumor. Immunohistochemically tumor cells were diffusely positive for cytokeratin (CK) AE1/AE3 and focally positive for epithelial membrane antigen and syndecan 1. All other tested antibodies (CK7, CK 20, CK MNF116, E-cadherin, beta-catenin, p63, p16, CD31, CD34, CEA, estrogen, progesterone) showed negative reaction. Periodic acid Schiff and alcian blue staining showed no intracellular or extracellular mucinous material in the tumor. The diagnosis of acantholytic squamous cell carcinoma of the cecum was suspected and additional examination was recommended to exclude possibility of metastatic carcinoma. Extensive clinical examination which also included whole-body PET/CT scan showed no additional tumors. After the exclusion of possible metastatic disease the diagnosis of primary acantholytic squamous cell carcinoma of the cecum was confirmed. Six months after surgery the metastasis in small intestine and recurrence in the abdominal cavity at the site of surgery appeared and had the same morphological characteristic as the primary tumor in the cecum. We report a unique case of ASCC arising in cecum and on this way expands the range of tumors originating in colon. Reports of more cases of colonic ASCC would possibly help to elucidate origin, clinical behavior and therapy of these tumors.
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    ABSTRACT: We evaluated clinicopathological features and outcomes in patients with penile squamous cell carcinoma. We studied 333 patients with homogeneous surgical treatment, including circumcision in 4, local excision in 2, partial penectomy in 194 and total penectomy in 133. Of the patients 153 also underwent bilateral groin dissection. Followup was 8 to 453 months (average 100). The usual type of squamous cell carcinoma was noted in 65% of cases. Higher histological grade, deeper anatomical infiltration, and vascular and perineural invasion were common findings in sarcomatoid, basaloid and adenosquamous carcinoma cases, correlating with a higher rate of nodal metastasis and mortality. These features were unusual in verrucous, papillary and warty carcinoma cases. Recurrence in 22% of cases was common for the sarcomatoid, basaloid and adenosquamous types but was not noted for verrucous carcinoma. Locoregional relapse was more common in cases of usual, mixed, papillary and warty carcinoma, and systemic relapse was typical in sarcomatoid and basaloid carcinoma cases. The overall metastasis rate was 24% and the 10-year survival rate was 82%. The highest mortality rate was observed within the first 3 years of followup. High grade tumors were more common in penectomy cases and carcinoma exclusive of the foreskin had a better prognosis. The nodal metastasis risk groups were low--verrucous, papillary and warty, intermediate--usual and mixed, and high risk--sarcomatoid, basaloid and adenosquamous. Mortality risk groups were low--mixed, papillary and warty, intermediate--usual and basaloid, and high risk--sarcomatoid. These data should help clinicians to design therapeutic strategies and followup protocols.
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