|Year : 2014 | Volume
| Issue : 2 | Page : 374-376
Vimentin positive acantholytic penile squamous cell carcinoma with rhabdoid features
Ramesh Y Chavan, Akshay Bali, KS Savita, JV Chethan
Department of Pathology and Surgery, KLE University's Jawaharlal Nehru Medical College, Belgaum, Karnataka, India
|Date of Web Publication||14-Jul-2014|
Bali Clinic, Baldev Nagar, Ambala City, Haryana - 134 007
Source of Support: None, Conflict of Interest: None
Acantholytic variant of penile squamous cell carcinoma (SCC) is an exceedingly rare and associated with bad prognosis. Histologically it mimics angiosarcoma due to pseudovascular spaces. Vimentin immunopositivity in such cases represent epithelial to mesenchymal transition manifested by cellular discohesion. We describe a case of vimentin positive acantholytic penile SCC in a 55-year-old patient.
Keywords: Acantholytic, penis, rhabdoid, squamous cell carcinoma, vimentin
|How to cite this article:|
Chavan RY, Bali A, Savita K S, Chethan J V. Vimentin positive acantholytic penile squamous cell carcinoma with rhabdoid features. J Can Res Ther 2014;10:374-6
| > Introduction|| |
The age-adjusted incidence of penile cancer in urban India ranges from 0.7 to 2.3 cases per 100,000 men.  Squamous cell carcinoma (SCC) is the commonest type of malignancy arising from the epithelium of inner prepuce and glans penis. Penile SCC bears histological and behavioral resemblance to SCC of oropharynx, female genitalia, and anus. SCC of the penis is commonly divided into the usual, basaloid, verruciform, warty, verrucous, and papillary subtype.  Acantholytic SCC is an unusual variant. The prominent acantholysis results in formation of pseudoglandular and pseudovascular spaces, creating diagnostic confusion with angiosarcoma.  These tumors are also poorly differentiated, further complicating the exact histological characterization of the tumor. Immunohistochemistry (IHC) is often required for arriving at the exact diagnosis. We report a case of vimentin positive acantholytic variant of penile SCC in a 55-year-old patient.
| > Case report|| |
A 55-year-old male presented with a growth over the penis for four months duration [Figure 1]a. He complained of urinary obstruction and foul smelling discharge from the growth. Local examination revealed a fungating growth measuring 3 × 2 cm arising from the glans. There was no inguinal lymphadenopathy. Systemic examination and investigations including complete blood count, fasting blood sugar level, liver function test, and renal function test were within normal limits. Hepatitis B virus surface antigen and human immunodeficiency virus enzyme-linked immunosorbent assay were non-reactive. Partial penectomy was done and submitted for histopathological examination. Gross inspection revealed a growth projecting outside the prepuce measuring 2 cm in length. Cut section showed an irregular growth measuring 5.5 × 3 × 2 cm, gray white with few blackish areas. Growth was attached to the glans penis and urethra was free from growth.
|Figure 1: (a) Clinical photograph of the tumor arising from the glans penis, (b) microscopy of the tumor showing neoplasm arising from the overlying epidermis (H and E, ×40), (c) higher magnification depicting pseudovascular channels (H and E, ×100), (d) photomicrograph showing the acantholytic nature of the neoplastic cells (H and E, ×400)|
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Microscopy revealed a diffusely infiltrative tumor enveloped in an intense inflammatory infiltrate [Figure 1]b. The tumor cells showed extensive dyscohesion with formation of pseudoglandular, pseudopapillary and pseudovascular pattern [Figure 1]c. Tumor cells predominantly appeared as ovoid to rounded cells with deep pink cytoplasm and eccentric nuclei with nucleoli reminiscing of a rhabdoid phenotype [Figure 1]d. Differential diagnosis of epithelioid sarcoma, epithelioid angiosarcoma and malignant melanoma was considered and IHC was advised for exact characterization of the tumor.
The IHC staining protocol was performed by using the Super Sensitive one step PolymerHRP system (QD-600, BIOGENEX). Antigen retrieval was standardized by using citrate buffer in EZ-retrieval microwave at 96°C for three cycles. Primary antibodies included pancytokeratin (clone Lu-5), CK 5/6 (clones EPR1600Y and EPR1602Y), CK 8/18 (clone 5D3), CK 19 (clone RCK108), vimentin (clone SP20), p63 (clone 4B1E12), CD31 (clone 9G11), CD34 (clone QBend/10), S-100 (clone 15E2E2), desmin (clone D33), muscle specific actin (MSA) (clone HHF35) and smooth muscle actin (SMA) (clone 1A4) from BIOGENEX, India.
The tumor cells exhibited strong immunoreactivity for pancytokeratin, CK 5/6, vimentin, p63 and were immunonegative for CK 8/18, CK 19, S-100, CD31, CD34, SMA, desmin and MSA. CK 5/6 and p63 positivity suggested a squamous differentiation [Figure 2]. However, vimentin was also positive which hinted towards a possible epithelial to mesenchymal transition. Although pancytokeratin and p63 can occasionally be expressed in epithelioid angiosarcomas,  immunonegativity for the vascular markers, CD31 and CD34, ruled out angiosarcoma. Immunonegativity for CD34 also went against epithelioid sarcoma. Malignant melanoma can exhibit pseudopapillary pattern and very rarely pseudoangiosarcomatous change but S-100 negativity ruled it out.  Epithelioid leiomyosarcoma and rhabdomyosarcoma were eliminated by the negative staining for SMA and desmin, respectively. The final diagnosis concluded was invasive acantholytic SCC with rhabdoid phenotype.
|Figure 2: (a) Immunohistochemical staining exhibiting, diffuse cytoplasmic positivity for pancytokeratin (Pan CK, ×400), (b) strong cytoplasmic positivity for cytokeratin 5/6 (CK 5/6, ×400), (c) cytoplasmic vimentin positivity (Vimentin, ×400), (d) nuclear positivity for p63 (p63, ×400)|
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| > Discussion|| |
Acantholytic variant of penile SCC (also known as pseudoglandular or adenoid variant) primarily displays pseudoluminal spaces lined by a single layer of squamous cells.  Primary skin acantholytic SCC, however, shows anastomosing cordlike arrays of polygonal tumor cells containing detached tumor cells.  This variant can, therefore, be misdiagnosed morphologically as angiosarcoma as was in our case. IHC was instrumental in establishing the diagnosis.
The co-expression of p63 and CK5/6 is highly specific for SCC.  Glandular CK 8/18 and 19 is usually not expressed in SCC. However, a study by Fillies et al. on 308 cases of oral SCC observed that when CK 8/18 is expressed in SCC, it serves as an independent poor prognostic marker.  Immunonegativity for vascular markers, CD31 and CD34, ruled out epithelioid angiosarcoma. Furthermore, expression of Fli-1 in angiosarcoma and g2-chain of laminin-5 in acantholytic SCCs has recently been demonstrated as helpful in differentiating the two entities especially in cases showing overlap of cytokeratin and vascular markers expression.  Sarcomatoid carcinomas of penis can also exhibit focal pseudoangiomatous pattern and epithelioid cells. The tumor cells diffusely express vimentin, but co-expression of high molecular weight keratin and p63 usually establishes the epithelial origin. 
Intermediate filament proteins (IFP), namely keratins, vimentin, desmin, neurofilament protein, GFAP and lamins, are basic structural components of all human cells. They measure 7-10 nm in diameter and are arranged in bundles inside the cytoplasm. Among all the IFP, keratins exhibits the highest specificity and sensitivity for epithelial cells. Vimentin is a 57 kd protein specific for mesenchymal tissues. 
Epithelial to mesenchymal transition can occur in advanced stage of epithelial tumor spread, evidenced by decreased cell-to-cell adhesion, increased cell motility and positivity for mesenchymal markers like vimentin. Hence vimentin can serve as a useful marker for predicting tumor progression and metastasis. This phenomenon is further supported by the fact that metastatic tumors of epithelial origin show increased expression of mesenchymal cellular markers.  A study done by Jin et al. on esophageal SCCs found vimentin positivity as an independent predictor of metastasis.  Another study by Cheng et al. on cervical SCCs concluded that increased expression of vimentin was negative prognostic indicator for overall survival.  Thus, vimentin positive SCC may represent a highly malignant subset of SCC.
Cunha et al. in their study of seven cases of acantholytic SCC of penis concluded that acantholytic SCC behaves in more malignant fashion than the usual type with deeper invasion, more chances of regional lymph node metastasis and higher mortality rates.  Watanabe et al. reported a case of adenoid SCC of the penis manifesting with rapid lung metastasis.  However, Garcia et al. analyzed the published literature on acantholytic SCC of the penis and found contradictory findings suggesting it behaves no more aggressive than the usual type and prognosis primarily depends on the location, size, depth, differentiation, and previous treatment. 
| > References|| |
|1.||Barnholtz-Sloan JS, Maldonado JL, Pow-sang J, Giuliano AR. Incidence trends in primary malignant penile cancer. Urol Oncol 2007;25:361-7. |
|2.||Pizzocaro G, Algaba F, Horenblas S, Solsona E, Tana S, Van Der Poel H, et al. EAU penile cancer guidelines 2009. Eur Urol 2010;57:1002-12. |
|3.||Cunha IW, Guimaraes GC, Soares F, Velazquez E, Torres JJ, Chaux A, et al. Pseudoglandular (adenoid, acantholytic) penile squamous cell carcinoma: A clinicopathologic and outcome study of 7 patients. Am J Surg Pathol 2009;33:551-5. |
|4.||Lin XY, Liu Y, Zhang Y, Yu JH, Wang EH. The co-expression of cytokeratin and p63 in epithelioid angiosarcoma of the parotid gland: A diagnostic pitfall. Diagn Pathol 2012;7:118. |
|5.||Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology 2000;36:387-402. |
|6.||Nappi O, Wick MR, Pettinato G, Ghiselli RW, Swanson PE. Pseudovascular adenoid squamous cell carcinoma of the skin. A neoplasm that may be mistaken for angiosarcoma. Am J Surg Pathol 1992;16:429-38. |
|7.||Kaufmann O, Fietze E, Mengs J, Dietel M. Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol 2001;116:823-30. |
|8.||Fillies T, Werkmeister R, Packeisen J, Brandt B, Morin P, Weingart D, et al. Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity. BMC Cancer 2006;6:10. |
|9.||Velazquez EF, Melamed J, Barreto JE, Aguero F, Cubilla AL. Sarcomatoid carcinoma of the penis: A clinicopathologic study of 15 cases. Am J Surg Pathol 2005;29:1152-8. |
|10.||Driemel O, Müller-Richter UD, Hakim SG, Bauer R, Berndt A, Kleinheinz J, et al. Oral acantholytic squamous cell carcinoma shares clinical and histological features with angiosarcoma. Head Face Med 2008;4:17. |
|11.||Ikegawa S, Saida T, Takizawa Y, Tokuda Y, Ito T, Fujioka F, et al. Vimentin-positive squamous cell carcinoma arising in a burn scar. A highly malignant neoplasm composed of acantholytic round keratinocytes. Arch Dermatol 1989;125:1672-6. |
|12.||Paccione RJ, Miyazaki H, Patel V, Waseem A, Gutkind JS, Zehner ZE, et al. Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility. Mol Cancer Ther 2008;7:2894-903. |
|13.||Jin H, Morohashi S, Sato F, Kudo Y, Akasaka H, Tsutsumi S, et al. Vimentin expression of esophageal squamous cell carcinoma and its aggressive potential for lymph node metastasis. Biomed Res 2010;31:105-12. |
|14.||Cheng Y, Zhou Y, Jiang W, Yang X, Zhu J, Feng D, et al. Significance of E-cadherin, β-catenin, and vimentin expression as postoperative prognosis indicators in cervical squamous cell carcinoma. Hum Pathol 2012;43:1213-20. |
|15.||Watanabe K, Mukawa A, Miyazaki K, Tsukahara K. Adenoid squamous cell carcinoma of the penis. Report of a surgical case clinically manifested with rapid lung metastasis. Acta Pathol Jpn 1983;33:1243-50. |
|16.||Garcia C, Crowson AN. Acantholytic squamous cell carcinoma: Is it really a more-aggressive tumor? Dermatol Surg 2011;37:353-6. |
[Figure 1], [Figure 2]