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.
M. Zámečník1; P. Mukenšnabl2; A. Chlumská2,3
Authors place of work:
Medicyt, s. r. o., laboratory Trenčín, Slovak Republic1; Šikl's Department of Pathology, Faculty Hospital, Charles University, Plzeň, Czech Republic2; Laboratory of Surgical Pathology, Plzeň, Czech Republic3
Published in the journal:
Čes.-slov. Patol., 47, 2011, No. 1, p. 15-18
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.
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.
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.
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.
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
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.
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