Pseudoglandular (adenoid, acantholytic) squamous cell carcinoma of the penis. A case report
Pseudoglandulárny (adenoidný, akantolytický) dlaždicovobunkový karcinóm penisu. Popis prípadu
Prezentovaný je prípad pseudoglandulárneho (adenoidného, akantolytického) dlaždicovobunkového karcinómu penisu u 60-ročného pacienta. Tumor obsahoval okrem štruktúr konvenčného dlaždicovobunkového karcinómu komponent pseudoglandulárny, ktorý napodobňoval tubuly adenokarcinómu. V epidermis vedľa tumoru nebola nájdená prekurzorová dysplastická lézia. Imunohistochemicky exprimovali bunky nádoru pancytokeratín AE1/AE3, p53 a p63, a boli negatívne na endotelové markery, CEA a p16. Farbenia na mucín boli negatívne. Metastázy boli prítomné v regionálnych lymfatických uzlinách a vo funiculus spermaticus. Štyri týždne po operácii sa objavili početné kožné/podkožné metastázy v podbrušku, v oboch ingvinách a na prednej mediálnej strane stehien. Vyšetrenie CT zistilo pakety metastaticky postihnutých lymfatických uzlín v panve. Vysoké štádium pri prezentácii tumoru a ďalší priebeh potvrdzujú, že pseudoglandulárny dlaždicovobunkový karcinóm penisu je vysoko agresívny tumor.
Key words:
adenosquamous carcinoma - pseudoglandular (adenoid, acantholytic) squamous cell carcinoma - penis - p16 - p53
Authors:
M. Zámečník 1; P. Mukenšnabl 2; A. Chlumská 2,3
Authors place of work:
Medicyt, s. r. o., laboratory Trenčín, Slovak Republic
1; Šikl's Department of Pathology, Faculty Hospital, Charles University, Plzeň, Czech Republic
2; Laboratory of Surgical Pathology, Plzeň, Czech Republic
3
Published in the journal:
Čes.-slov. Patol., 47, 2011, No. 1, p. 15-18
Category:
Původní práce
Summary
A case of so-called pseudoglandular (adenoid, acantholytic) squamous cell carcinoma (SCC) of the penis occurring in a 60-year-old man is described. The tumor showed, in addition to the pattern of conventional moderately to poorly differentiated SCC, a component of tubular-appearing pseudoglandular SCC. No precancerous dysplastic lesion was found near the lesion. Immunohistochemically, the tumor cells expressed pancytokeratin, p53 and p63, and they were negative for endothelial markers, carcinoembryonic antigen and p16. Stains for mucin were negative. Metastases were found in the regional lymph nodes and spermatic cord. Four weeks after the penectomy, multiple cutaneous/subcutaneous metastases appeared and metastases in the pelvic lymph nodes were visualized through a CT scan. The advanced stage of the tumor seen in the present case further confirms that pseudoglandular SCC represents a highly aggressive tumor.
Key words:
adenosquamous carcinoma - pseudoglandular (adenoid, acantholytic) squamous cell carcinoma - penis - p16 - p53
So-called pseudoglandular (adenoid, acantholytic) squamous cell carcinoma is a rare type of squamous cell carcinoma (SCC) that was described in the skin (1-3), oral cavity (4), breast (1,5), lung (1,6), bladder (7), uterine cervix (8) and vulva (7,8). In the penile location, pseudoglandular SCC was described quite recently by Cunha et al. (9). The tumor represents a highly malignant type of penile squamous cell carcinoma (SCC) that contains a tubular-appearing acantholytic pattern strongly mimicking adenocarcinoma. After the first publication, two further cases were added by Colecchia and Insabato (10). Because no additional reports were published, we would like to present our recent case of this rare tumor.
MATERIALS AND METHODS
The tissue of the excised tumor was fixed in 4% formalin and processed routinely. The sections were stained with hematoxylin and eosin, PAS, PAS with diastase pretreatment, alcian blue at pH 2.5, and mucicarmine. Following primary antibodies were used for immunohistochemistry: p53 (clone DO-7), CD31 (JC70A), epithelial membrane antigen (EMA, E29), carcinoembryonic antigen (CEA, II-7) (all from Dako Cytomation), and p16 (JC8), pancytokeratin (AE1/AE3), CD34 (Qbend 10) (all from LabVision). Immunostaining was performed according to the standard protocols using avidin-biotin complex labeled with peroxidase or alkaline phosphatase. Microwave antigen pretreatment was performed prior to applying the primary antibodies with exception of CD34. Appropriate positive and negative controls were applied.
CASE REPORT
A 60-year-old man with arterial hypertension and type 2 diabetes mellitus presented with a large irregular white-gray tumor occupying right half of the glans penis. The tumor grew over several months. After the diagnostic excision confirming SCC, complete penectomy with bilateral inguinal node dissection was performed. Four weeks after the penectomy, multiple cutaneous/subcutaneous metastases in pubic, bilateral inguinal and bilateral anterior/medial femoral regions appeared. Three of the cutaneous/subcutaneous lesions were excised and histopathologically examined. In addition, a CT scan revealed multiple metastases in the pelvic lymph nodes. The patient was started on radiotherapy. However, this therapy was ineffective because new lenticular cutaneous metastases appeared. Therefore, the radiotherapy was discontinued and the patient was started on palliative chemotherapy (cisplatin, 5-fluorouracil). The possibility of additional radiotherapy will be considered later.
Grossly, the tumor was ulcerated and flat, invading 3 cm deep into the corpus cavernosum. Moreover, numerous satellite nodules were seen in the corpus cavernosum, some of them even near the proximal resection margin. Histologically, the tumor showed two intermingled components (Fig. 1). The first was conventional, moderately to poorly differentiated squamous cell carcinoma without koilocytic features (11,12), and the other showed a pseudoglandular pattern with cuboidal to cylindrical epithelium (Fig. 1A,B). The nuclei of the pseudoglandular epithelium were highly atypical and posessed frequent mitotic figures. The cells were arranged in pseudoglands toward the luminal space. Some of the spaces contained necrotic debris or non-specific eosinophilic material. Gradual transitions were seen between both components. In rare foci, isolated neoplastic cells or small groups of the cells diffusely infiltrated the penile stroma (Fig. 1C). The squamous cell nests showed focally, in addition to small adenoid spaces, early acantholysis with intercellular edema and dyscohesion of the cells. This indicated that formation of pseudoglandular spaces represents a result of acantholysis (Fig. 1D). The conventional SCC- and pseudoglandular components comprised 40% and 60% of the tumor volume, respectively. The tumor was deeply invasive, with infiltration of the corpus cavernosum. A few foci of vascular or perineural invasion were found. The tumor grew discontinuously with formation of satellite nodules. The cutaneous margin of the lesion showed epidermal hyperplasia without atypia, and non-specific dermatitis without features of lichen sclerosus (Fig. 1E). Features of penile squamous intraepithelial neoplasia or other known precursor lesions (bowenoid, pagetoid) (11,13,14) were not found. Small 4 mm sized tumor infiltrate was found in a connective tissue of the spermatic cord, with obvious peri- and intraneural tumor spread. There was a 2.5 cm large metastasis in one of the right-sided inguinal lymph nodes. The other three right inguinal lymph nodes and the ten left inguinal nodes lacked metastasis. The lymph node metastasis and all three excised 0.5-1cm sized cutaneous/subcutaneous metastases also showed microscopically both pseudoglandular and conventional SCC patterns. Stains for mucin were negative in the neoplastic cells as well as in the adenoid spaces. Immunohistochemically (Fig. 2), the tumor cells expressed strongly and diffusely pancytokeratin AE1/AE3, p63 (not shown) and p53, and they were negative for p16, CEA, EMA, CD31 and CD34.
DISCUSSION
The present case of pseudoglandular SCC shows morphologically all features described in previous studies of this rare entity (9,10). A high stage and grade appear to be typical for this tumor type according to previous reports (9,10). Our observation is similar, and thus it confirms that pseudoglandular SCC represents, along with sarcomatoid carcinoma, a tumor of the highest malignant potential in the group of penile carcinomas. All published cases together with the present case show that 6 of 10 (60%) patients had regional lymph node metastasis, and 4 of 10 patients (40%) died from the disease. At the histologic level, the poor prognosis of the tumor is indicated by high-grade nuclear features and frequent vascular and/or perineural invasion, which were seen also in our case.
Regarding the natural history of pseudoglandular SCC, Cunha et al. found near the tumor margin low-grade intraepithelial squamous lesion (intraepithelial penile neoplasia, differentiated) in 4 of 7 cases (9). Thus, it seems that the precursor lesion for penile pseudoglandular SCC is differentiated intraepithelial penile neoplasia which is not HPV-related (11). Although additional cases, including the present tumor, showed only a hyperplastic lesion without atypia near the tumor margin (9,10), it is quite possible that the precursor lesion was overgrown by the invasive tumor, because the tumors were large at their first presentation. Immunohistochemical negativity of p16 found in our case further suggests that the tumor is not HPV related (15). Ancillary studies of HPV in acantholytic SCCs (without regard to the location of the tumor) also showed negative results, although available data remain very scanty at present. In one case of penile acantholytic SCC, in situ hybridization showed no positivity for HPV (16). In another case of vulvar adenoid SCC, Horn et al. did not find the viral DNA (17).
In the differential diagnosis, the pseudoglandular morphology strongly mimics the tubular pattern of an adenocarcinoma or the vascular channels of an epitheloid angiosarcoma. Negative stains for mucin prevent misdiagnosis of an adenocarcinoma or adenosquamous carcinoma. Negativity of endothelial markers (versus positivity of cytokeratins and p63) and the presence of conventional squamous cell component are helpful for the differentiation from the epitheloid angiosarcoma.
In conclusion, we have described an additional case of a pseudoglandular SCC of the penis. Our findings indicate, similarly to those described in previous studies, that the tumor is a highly aggressive type of SCC, and that it is probably not HPV-related. Pathologists should be familiar with this entity because it shows distinct clinical features and prognosis, and, by histologic examination, it can mimic other penile tumors.
Correspondence
address:
M.
Zámečník, M.D.
Medicyt,
s.r.o.
Legionárska
28
91171
Trenčín
Slovak
Republic
Phone:
+421-32-3936956
E-mail:
zamecnikm@seznam.cz
Zdroje
1. Banerjee SS, Eyden BP, Wells S, et al. Pseudoangiosarcomatous carcinoma: a clinicopathological study of 7 cases. Histopathology 1992; 21: 13–23.
2. Conde-Taboada A, Florez A, De la Torre C, et al. Pseudoangiosarcomatous squamous cell carcinoma of the skin arising adjacent to decubitus ulcers. Am J Dermatopathol 2005; 27: 142–144.
3. Nappi O, Wick MR, Pettinato G, et al. Pseudovascular adenoid squamous cell carcinoma of the skin. A neoplasm that may be mistaken for angiosarcoma. Am J Surg Pathol 1992;16: 429–438.
4. Zidar N, Gale N, Zupevc A, et al. Pseudovascular adenoid squamous-cell carcinoma of the oral cavity - a report of two cases. J Clin Pathol 2006; 59: 1206-1208.
5. Eusebi V, Lamovec J, Cattani MG, et al. Acantholytic variant of squamous cell carcinoma of the breast. Am J Surg Pathol 1986; 10: 855–861.
6. Nappi O, Swanson PE, Wick MR. Pseudovascular adenoid squamous cell carcinoma of the lung: clinicopathologic study of three cases and comparison with true pleuropulmonary angiosarcoma. Hum Pathol 1994; 25: 373–378.
7. Pitt MA, Morphopoulos G, Bisset DL. Pseudoangiosarcomatous carcinoma of the genitourinary tract. J Clin Pathol 1995; 48: 1059–1061.
8. Horie Y, Kato M. Pseudovascular squamous cell carcinoma of the uterine cervix: a lesion that may simulate an angiosarcoma. Pathol Int 1999; 49: 170–174.
9. Cunha IW, Guimaraes GC, Soares F, et al. Pseudoglandular (adenoid, acantholytic) penile squamous cell carcinoma: a clinicopathologic and outcome study of 7 patients. Am J Surg Pathol 2009; 33: 551-555.
10. Colecchia M, Insabato L. Pseudoglandular (adenoid, acantholytic) penile squamous cell carcinoma. Am J Surg Pathol 2009; 33: 1421-1422.
11. Cubilla AL, Dillner E, Schelhammer PF. Tumours of the penis. Malignant epithelial tumours. In: Eble J et al. (eds). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARCPress; 2004: 281-290.
12. Velazquez EF, Ayala GE, Liu H, et al. Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10mm. Am J Surg Pathol 2008; 32: 974–979.
13. Cubilla AL, Meijer JLM, Young RH. Morphological features of epithelial abnormalities and precancerous lesions of the penis. Scand J Urol Nephrol Suppl 2000; 34: 215–219.
14. Cubilla AL, Velazquez EF, Young RH. Epithelial lesions associated with invasive penile squamous cell carcinoma: a pathologic study of 288 cases. Int J Surg Pathol 2004; 12: 351–364.
15. Benevolo M, Mottolese M, Marandino F, et al. Immunohistochemical expression of p16 (INK4a) is predictive of HR-HPV infection in cervical low-grade lesions. Mod Pathol 2006; 19: 384-391.
16. Qi XP, Lin GB, Zhu YL, et al. Pseudoangiosarcomatous squamous cell carcinoma of the penis: a case report with clinicopathological and human papilloma virus analyses. Zhonghua Nan Ke Xue 2009; 15: 134-139.
17. Horn LC, Liebert UG, Edelmann J, et al. Adenoid squamous carcinoma (pseudoangiosarcomatous carcinoma) of the vulva: a rare but highly aggressive variant of squamous cell carcinoma-report of a case and review of the literature. Int J Gynecol Pathol 2008; 27: 288-291.
Štítky
Patologie Soudní lékařství ToxikologieČlánek vyšel v časopise
Česko-slovenská patologie
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