Atypical ductal adenocarcinoma of the prostate with endometrioid immunohistological features

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Atypical ductal adenocarcinoma of the prostate with endometrioid immunohistological features

M. Lucan, V. Lucan, V. Vasiliu, G. Iacob
Clinical case, no. 3, 2009
* Department of Endourology, CIURT, Cluj-Napoca, Romania
* Department of Endourology
* Service d'Anatomopathologie, Hôpital Necker, AP-HP, Paris, France
* Department of Anatomopathology

Malignancies of the prostate urethra are rare events. Most of them are urothelial neoplasm and only few are adeno-carcinoma. More frequently, a ductal adenocarcinoma of the prostate, formerly named endometrioid adenocarcinoma, protrude into the urethral lumen (1). Extremely rarely, a clear cell adenocarcinoma may arise in a malformed prostatic utricle (2), or from the peripheral prostate parenchyma (3).
Atypical ductal adenocarcinoma of the prostate with endometrioid immunohistological features is an unusual presentation of a prostate cancer.

Case report
Clinical history: A 52 year old male patient was admitted to our institution for total haematuria and dysuria with normal serum PSA.
A previous endoscopy, performed in another urologic clinic a month previously, had documented a tumor located at the verumontanum. The pathological examination described a tubulo-papillary adenocarcinoma with negative immunohistology for CK7, p63, 34bE12 and PSA.
Material and methods: The patient underwent extensive clinical and imaging assessment including abdominal and endorectal ultrasound, flexible urethrocystoscopy, whole body CT scan, standard and endorectal MRI.
The cystoscopy revealed an exophytic tumor located at the verumontanum and significant trabeculation of the bladder.
On transrectal MRI (Fig. 1) the tumor extended from the verumontanum to the whole left prostate lobe toward the seminal vesicle and to the rectal wall. CT scan of the thorax, abdomen and pelvis did not add other pathological findings.
The patient underwent radical retropubic prostatectomy with lymph node dissection. The surgery was uneventful with dissection performed in anatomic planes.
The specimen was submitted to pathology for gross and microscopic examination.
Results: Gross Features: The surgical specimen measured 72x63x35 mm, weighting 54 grams, and included prostate, seminal vesicles, and deferent ducts. At the verumontanum, above the ejaculatory duct orifices, an exophytic tumor was present (Fig. 2).
Histological features corresponded to a ductal adenocarcinoma (Fig. 3.), located at the verumontanum, with intra-urethral extension and ductal spread. The tumor had invaded the seminal vesicle, with extensive extraprostatic vein invasion, and lack of lymph node invasion (stage pT3b, pN0). The immunohistology positive for AE1/AE3, CD10, EMA, PR (Fig. 4) and negative for PSA, PSAP, AR favored the diagnostic of ductal adenocarcinoma of the prostate with immuno-histological endometrioid features.

Figure 1
Figure 2
Figure 3
Figure 4

In most cases, a tumor protruding at the verumontanum is a ductal adenocarcinoma, sharing the histological features of the endometrioid adenocarcinoma, a denomination not used at present. It was thought to have endometrioid origin, arising in the prostate utricle, a müllerian remnant located at the verumontanum (1). The prostatic epithelial origin is today well known (8, 9), and it is considered a specific entity (10). Typical clinical findings includes: obstructive symptoms and haematuria, lower increase serum PSA and PSAP, enlarged nodular prostate, presence of an exophytic papillary lesion in the prostatic urethra. Gross characteristics are unspecific and microscopic patterns are similar with endometrioid carcinoma but the cells may have clear cytoplasm. Practically, all cases are at least focally PSA and PSAP positive in immunohistology. At initial stages, the tumor is located central in the prostate and frequently associates acinar prostate carcinoma. When extended, both prostate lobes are more or les involved. Differential diagnosis includes other malignancies with urethral origin or secondary involvement of the prostate from other sites: lung, skin (melanoma), gastrointestinal tract, kidney, testis and endocrine glands (4). The prognosis remains poor.
In this case, the tumor architecture was characteristic for a ductal adenocarcinoma. Yet, the tumor spread was unusually located only on the left prostate lobe even if the pathologic stage was high. Moreover, the absence of the PSA or PSAP positive staining pose significant difficulties for a positive diagnostic.
Other prostatic urethra malignancies are rare events, encountered in less than 1% of the cases. Most of them are urothelial tumors (4) and only few are adenocarcinoma (5).
Urethral clear cell adenocarcinoma is extremely rare. It was formerly named mesonephric carcinoma because of the similarities with the müllerian counterpart in the female genital tract (2). Commonly, the patients present with dysuria and hematuria. Gross findings are unspecific. Microscopy is characteristic with one or more of the typical patterns: tubulo-cystic, papillary and/or diffuse. The tumor cells may be flat, cuboidal or columnar, with eosinophilic to clear cytoplasm. Typically the papillae are small, with hyalinized fibrovascular core and hobnail cells are present at least focally (2, 6). The clear cell adenocarcinoma, arising in the urothelial tract, may express CK7, CK20, CEA, CA125, LeuM-1 and lack PSA, PSAP, estrogen and progesterone receptors, with high MIB-1 activity (2, 4). With regard to immunohistological studies, most of the clear cell adenocarcinoma originate in urothelial neoplasms with particular glandular differentiation but some of them are associated with müllerian duct remnants. Clear cell adenocarcinoma may develop also from the müllerian duct cyst (3) or from the prostatic utricle, resembling the histological and immunohistological features seen in the müllerian system (6, 7).
In this case, the immunostaining was also negative for 34bE12, p63, CK7, CK20, CEA, CA125. Extended immunohistology was carried out for: EMA, C-kit, CD30, PLAP, CD10, synaptophysin, CD59, PR and ER.
The only positive immunostaining for AE1/AE3 (weak), EMA, PR, and CD10, were arguments to consider that the tumor express endometrioid features in the lack of other immunohistochemical features specific for prostate secretor cell origin.
This case was unusual due to multiple particularities. The tumor protrudes at the verumontanum and invades only the left prostate lobe with extensive vascular and seminal vesicle invasion only on the left side. The atypical immuno-histochemistry was negative for prostate markers, but with endometrioid features.

We thank to Dr. Martin Susani and Dr. Heinz Regele from Clinical Institute of Pathology, University of Vienna, Austria, for providing complementary immunohistochemistry.
Conflict of interest statement: We declare that we have no conflict of interest.

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