ARTICLE
Auteur(s) : Derya Özçelik1,
Toygar Ünveren1, Nil Üstündağ Çomunoğlu2,
Ümran Yildirim3, Yeşim Gürol4, Cemal
Şenyuva1
1Department of Plastic, Reconstructive
and Esthetic Surgery, Düzce University, Düzce Medical Faculty,
Düzce, Turkey
2Department of Pathology, Yeditepe University,
Yeditepe Medical Faculty, İstanbul, Turkey
3Department of Pathology, Düzce University, Düzce
Medical Faculty, Düzce, Turkey
4Department of Microbiology, Yeditepe University,
Yeditepe Medical Faculty, İstanbul, Turkey
Verrucous carcinoma (VC) is the most differentiated variant of
squamous cell carcinoma with distinct features including slow
locally invasive growth, verrucous appearance and rare metastatic
activity. Scrotal VC is extremely rare [1, 2]. We report a
HPV-related advanced scrotal VC and anal condyloma acuminatum. To
our knowledge, no such case has been published previously.
A 48-year-old male presented with 10 × 8 cm
cauliflower-like, ulcerative lesion in the right scrotal skin (figure 1A). The tumor
had been present for 10 years and arose initially as a wart on the
right scrotum. His past history was negative for radiation
exposure, immunosupressant usage and the presence of occupational
predisposing factors for scrotal VC. Concomitant multiple
condylomatous lesions on the peri-anal region were present for 10
years (figure
1B).
The blood tests were normal. HIV, HCV and HBV tests were
negative. Computed tomography of the chest, abdomen, and pelvis
revealed no signs of metastasis. Only enlarged right inguinal lymph
nodes were detected. Incisional biopsies of the scrotal lesion
revealed well-differentiated VC. Then, excision of the entire tumor
and inguinal lymph node sampling were performed.
Histopathologically; diagnosis was well-differentiated VC.
Resection margins and deep tissue were free of infiltration.
Papillomatosis, hyperkeratosis, parakeratosis, acanthosis, and an
inflammatory cell infiltrate with an overall appearance consistent
with that of VC (figures
1C, D) were detected. The most conspicuous microscopic
findings were striking nuclear atypia of koilocytotic type and
clear cytoplasm. The anal lesions showed condyloma accuminata (figure 1E). No lymph
node metastasis was recognized. One-year postoperatively no
recurrence was observed.
HPV genotyping
DNA isolated from paraffin blocks of the tumoral tissue was
examined for HPV DNA by multiplex-polymerase chain reaction (PCR)
and reverse hybridization technique. We used a novel sensitive
SPF10 HPV PCR assay and genotyping line probe assay, allowing
simultaneous identification of 19 different HPV types. For this,
GenID (GmbH) HPV genotyping kit was used [3]. A 140 base pair
band was amplified with spesific biotin-labeled primers and finally
determined by dot-blot hybridization with sequence specific
oligonucleotide probes which represented particular HPV genotypes
and were already immobilized on nitrocellular membrane. During
hybridization, the denaturated amplified DNA binds to these probes.
Following a highly specific washing procedure, the surviving
hybrids are detected by a color reaction. The band pattern was
analysed using the template supplied. High-risk HPV types are known
as 31, 33, 35, 39 and 51, 52, 53, 56, 58, 59; low-risk HPV types
are 6, 11, 40, 42, 43, 44. The GenID-detection kit provides
nitrocellulose strips with HPV specific probes [3]. There are two
bands labeled HPV-3X and HPV-5X, which are representative for HPV
31, 33, 35, 39, and 51, 52, 53, 56, 58, 59, respectively. In our
genotypic study of HPV, these bands were positive with DNA from the
verrucous carcinoma. It would be incorrect, however, to conclude
from this that there were positive findings for all these types. It
only means that at least one type out of 31, 33, 35, 39, and at
least one type out of 51, 52, 53, 56, 58, 59, was present in the
excised tissue of VC. The same is true for the low-risk HPV types
6, 11, 40, 42, 43, 44 of which the related band was also positive
in the excised tissue of VC. It could be that only three types are
present in the VC and the detection test applied does not show
which of the 16 pooled types are really present. HPV 16, 18, 45
were negative. Immunohistochemical staining for HPV common antigen
was negative. HPV 6 and 11 were positive in condyloma lesion.
Immunohistochemistry
Samples were deparaffinized and steamed for 40 min in citrate
buffer, at pH 7 and at 95 °C. The primary antibody tested was
p53 (DO-7; Dako, USA, ready to use: 7 mL). Duration of
incubation with the primary antibody tested was 60 min.
Sections were immunostained by standard avidin-streptavidin
methods. Diaminobenzidine was used as a chromogen.
Immunohistochemistry showed 25% nuclear positivity of p53 (figure 1F).
Verrucous carcinoma of the scrotum is very rare. Pott [4], in
1775, noted a high incidence of this lesion in chimney sweeps and
linked it to soot embedded in the scrotal rugae. In 1940, Graves
and Flo [5] reported squamous cell carcinoma as an
occupation-related cancer. In addition to chimney sweeps, paraffin
or shale oil workers, mule spinners, machine operators, and lathe
workers were reported in historical series to be at risk of scrotal
malignancy.
Presently, scrotal carcinoma is not only occupation related, but
can also be secondary to nonspecific factors such as poor hygiene,
chronic irritation. Condyloma acuminatum has been reported to
progress to VC [6]. HPV has been associated with squamous cell
carcinoma arising in the scrotum [7].In the literature, scrotal VC
and HPV were reported in only one case having concomitant condyloma
acuminatum and scrotal VC with peripheral T-cell lymphoma [1]. HPV
16 and 18 were positive in the excised tissue. High-risk HPVs
detected in scrotal tumors can be the reason for carcinomatous
transformation from a possible condyloma to VC in our case. E6/E7
oncoproteins or p53 tumor suppressor gene mutation play a role in
the HPV-associated transition to carcinoma [8]. 25% overexpression
of p53 in tumoral tissue of our case supports the role of HPV in
the pathogenesis of scrotal VC.
Acknowledgements
Conflict of interest: none. Financial support: none.
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