Villous Adenoma Arising in the Urethra of a Female with Bladder Augmentation History: A Case Report and Review of the Literature.

Villous adenomas (VAs) in the female urethra are rare with only seven cases in the English literature to our knowledge. In patients with bladder augmentation cystoplasty, the neoplasia development risk increases and most of these develop in the neobladder or anastomosis line. Only two cases of VA developing from the native bladder mucosa have been reported. Physical examination of a 76-year-old female who had a history of augmentation cystoplasty revealed a caruncula-like structure protruding from the urethral meatus. The urinary USG showed that the lesion had no relation with the bladder. The lesion was excised. Microscopically, it consisted of villous structures covered with pseudostratified intestinal type epithelium. Low-grade dysplasia was present in the epithelium but high-grade dysplasia or in-situ/invasive carcinoma was not observed. Immunohistochemical study showed positivity for CK7, CK20, EMA, CEA and CDX2. The case was reported as VA of the urethra. We presented the first VA case arising in the urethra of a female patient with intestinal bladder augmentation. Excision is curative for pure VAs. Transformation to carcinoma or recurrence has not been reported. However, in one third of the cases, a malignant tumor may accompany the lesion. Therefore, all excision material should be examined carefully. Routine endoscopic follow-up should be performed in cases with bladder augmentation.

Mesonephric (Wolffian-derived) Adenocarcinoma of the Female Urethra.

The current World Health Organization (WHO) classification of adenocarcinoma of the urinary tract including the urethra includes uncommon Müllerian-derived carcinomas such as clear cell and endometrioid adenocarcinomas. The concept of primary mesonephric (Wolffian-derived) adenocarcinoma (MA) in the urethra (and urinary tract in general) is currently regarded as controversial as the term "mesonephric" had been also inaccurately applied in the past to label Müllerian-derived carcinomas, particularly clear cell adenocarcinoma. Further, pathologically well-documented or bona fide urethral MAs have not yet to be reported. Herein, we describe 2 examples of MA in elderly females that primarily presented in the urethra and manifested clinically with obstructive lower urinary tract symptoms. Both tumors exhibited histology similar to those in MAs of the female genital tract including the distinctive tubular proliferations with luminal eosinophilic materials. The first case, in addition, showed a variety of patterns including ductal (glandular), solid, fused/sieve-like tubules, dilated tubules, and spindled cells. The second case also showed a transition to the more irregular and poorly formed tubular proliferation of cells with greater nuclear atypia and with a desmoplastic response. Both tumors showed positivity for PAX8, GATA3, and luminal CD10, and 1 tumor analyzed harbored KRAS and ARID1A mutations. One patient received neoadjuvant chemotherapy and underwent resection but had local tumor recurrence and metastasis to the lungs and lumbar spine 12 months after presentation. In conclusion, MA, similar to those occurring in the female genital tract and distinct from the recognized Müllerian-derived carcinomas, may present primarily as urethral tumors. MA in the urethra probably shares a common pathogenesis with vaginal MA as both may originate from the same caudal loci of mesonephric remnants along the closely apposed anterior vaginal and posterior urethral walls. MA should be considered in future classifications for urethral tumors and we recommend that the confusing term "mesonephroid adenocarcinoma" should no longer be used.

Skene's Glands Adenocarcinoma: A Series of 4 Cases.

Skene's (periurethral) gland adenocarcinoma is very rare, with only 7 cases reported in the literature. This is the first series of cases on this entity. We describe the histologic, immunohistochemical, and clinical findings of 4 patients with Skene's gland adenocarcinoma retrieved from the Johns Hopkins Urologic Pathology Consult Service from 1984 to 2017. The average age at diagnosis of the 4 women was 74.5 years (range, 61 to 87 y). Tumors were treated by limited resections with negative margins. Tumor size ranged from 1.0 to 2.0 cm (mean, 1.5 cm). Average follow-up time was 40.7 months (range, 4 to 132 mo). Three of our cases were morphologically consistent with prostatic acinar adenocarcinoma with variable cribriform, fused, and poorly formed glands, analogous to Gleason score 4+4=8. Of these, one had mixed ductal features with neoplastic cells showing papillary carcinoma with columnar cytology. These 3 lesions were positive for PSA, P501S, NKX3.1, and AMACR. Focal goblet cells positive for CK20 and negative for prostatic markers were seen in one of these cases, suggesting intestinal differentiation (although negative for CDX2 and SATB2). A fourth case had glandular and papillary formations with pseudostratified columnar epithelium and mucin secretion, showing positivity for CK7, ER, and P16, and negativity for prostatic markers, suggesting serous differentiation (although negative for PAX8 and WT1). PIN4 cocktail confirmed the origin in preexisting paraurethral glands in 3 of the cases. All patients were alive and free of recurrence or metastatic disease at the time of last follow-up. Because of the rarity of Skene's gland adenocarcinomas, there is no consensus regarding their treatment. Our findings demonstrate that Skene's gland adenocarcinomas recapitulate morphologies and immunohistochemical markers seen in prostatic adenocarcinoma. However, it is unknown whether applying the same grading criteria for prostatic adenocarcinomas to Skene's gland adenocarcinoma is valid given the small number of cases with variable treatment and limited follow-up.

Adenoid cystic carcinoma of the urethra/Cowper's gland with concurrent high-grade prostatic adenocarcinoma: a detailed clinicopathologic case report and review of the literature.

Primary adenoid cystic carcinoma of the urethra is uncommon with only 9 cases reported in the medical literature; all tumors arose from Cowper's glands. Herein, we report the histological features and immunohistochemical characteristics of 1 patient with primary adenoid cystic carcinoma involving the entire posterior urethra, prostate gland, corpus spongiosum, corpora cavernosa, urogenital diaphragm, perianal soft tissue, and muscularis propria layer of rectum. We also review other published cases to evaluate the prognosis and treatment.

Primary mucinous adenocarcinoma of the female urethra: a contemporary clinicopathologic analysis.

Primary mucinous adenocarcinoma of the female urethra is very rare and may lead to both diagnostic and therapeutic challenges. Although primary mucinous adenocarcinoma of the prostate and prostatic urethra has been well characterized in men, this is the largest clinicopathologic study to date of primary mucinous adenocarcinoma of the female urethra. A search was made through the files of 2 major academic institutions for cases of confirmed primary mucinous adenocarcinoma arising from the female urethra. Tumors arising from adjacent organs were excluded both clinically and pathologically in all cases. Five cases were identified. The mean patient age was 67 years (range, 54-74 years). All patients presented with a polypoid/papillary mass arising from the urethra. Pathologic stages were as follows: pT4 3 (60%) of 5 cases; pT3 1 (20%) of 5 cases, and pT2 1 (20%) of 5 cases. Immunohistochemical stains for GATA3, p63, CK7, CK20, CDX2, ER, PAX8, and ß-catenin were performed on all cases. Immunohistochemical stains were positive in the tumor cells for CDX2 in 4/5 (80%) cases; focally positive for CK20 in 4/5 (80%) cases; focally positive for CK7 in 4/5 cases (80%); and negative for p63, GATA3, ER, PAX8 and ß-catenin in all cases. In the 4 patients with available follow-up data, mean follow-up was 25 months (range, 4-54 months). It is critical for pathologists to be aware of this entity in light of potential diagnostic pitfalls and therapeutic implications.

Prostate type epithelial polyps of urogenital tract: a series of 3 cases and literature review.

OBJECTIVE: To present clinicopathologic and immunohistochemical features of 3 cases of rare and unusual condition of urogenital tract, prostatic epithelial polyps situated in various parts of the urinary tract, with a heterogeneous presentation and a benign behavior. METHODS: Detailed data on 3 patients with polyps in the urinary tract presented from January 2008 to December 2012 were reviewed, and the clinicopathologic characteristics of the patients and disease along with various diagnostic and treatment modalities were recorded. RESULTS: All the 3 patients were aged older than 45 years. The presenting symptom hematuria was common to each patient. One patient had polypoidal growth in preprostatic (intramural) urethra; the other 2 had polyps in bladder. Each patient had other urogenital tract disease, 2 were known case of benign prostatic hyperplasia, and 1 had past history of urinary bladder carcinoma. Clinically, each of the case was misdiagnosed as aggressive lesions; however, after histopathologic diagnosis, management was undertaken according to benign result. No recurrence or metastasis was observed to date. Immunohistochemical stain prostate-specific antigen was positive in the epithelium. All 3 patients were recurrence-free on follow-up. CONCLUSION: The prostate type epithelial polyps are rare in urinary bladder and bladder urethra and are frequently associated with concurrent pathologies of urogenital tract. These are benign conditions with differential of other benign and malignant disorders.

Cytological significance of abnormal squamous cells in urinary cytology.

The aim of this study was to evaluate the significance of abnormal squamous cells (ASCs) in urinary cytology to clarify whether finding of ASCs could improve diagnostic accuracy. A total of 3,812 urine specimens were reviewed. We focused on three parameters of ASCs, necrotic debris, and ASC clusters, and linked them to histological diagnosis and clinical information. ASCs were identified in 34 (0.9%) specimens from 21 different patients. The incidence of ASCs was higher in females than in males. The 34 urine specimens were categorized as voided urine (16 cases), bladder-catheterized urine (17 cases), and bladder-washed fluid (1 case). Six (28.6%) of 21 patients were histologically diagnosed as having combined urothelial carcinoma and squamous cell carcinoma (SCC). Eight patients (38.1%) were histologically diagnosed as having SCC originating from sites other than the urinary tract; those urine specimens showed ASCs that were likely to have been exfoliated from malignant lesions. Necrotic debris and ASC clusters were identified in 12 specimens (35.3%) from 11 patients and 4 specimens (11.8%) from 4 patients, respectively, from a total of 34 specimens. Our results indicate that a great amount of care is needed for cytological diagnosis when attempting to recognize ASCs in urine specimens because ASCs were identified in not only SCC of the bladder but also in carcinoma or nonmalignant lesions of nonurinary tracts. Necrotic debris was found not only in patients who had malignant bladder tumors but also in those who had malignant lesions in locations other than the bladder.

Small cell carcinoma arising from the bulbar urethra: a case report and literature review.

Primary neuroendocrine carcinomas of the genitourinary tract are rare and aggressive tumors carrying a bad prognosis. With squamous cell and transitional cell carcinoma being the most commonly reported urethral malignancies, primary small cell carcinoma (SCC) of the urethra is extremely rare. To date, only 5 cases have been reported in the literature. We present the first case of primary SCC occurring in the bulbar urethra in an 89-year-old male. We discuss the clinical, histological and immunohistochemical features of SCC of the urethra. Furthermore, we summarize the available literature and discuss the possible treatment options for this rare yet aggressive neoplasm.

Carcinosarcoma of female urethra with melanocytic differentiation.

Carcinosarcoma arising from the female urethra is rare. We report an unusual case of urethral carcinosarcoma from a female patient with melanocytic differentiation. The tumor consists of a high-grade papillary serous carcinoma with psammoma bodies and a mesenchymal component with area of heterologous (cartilaginous) element. More interestingly, there are epithelioid tumor cells containing melanin pigment. On immunohistochemical stains, the epithelioid tumor cells are positive for S100, HMB45 and Mart-1, but negative for cytokeratin. This case represents an unusual carcinosarcoma with areas of melanocytic differentiation. Such rare tumors have been occasionally reported in the breast, uterus, kidney, and lung. These cases demonstrate the capacity of tumor cells to differentiate into divergent elements, supporting the concept of pluripotent tumor stem cells.

Urethral stromal tumor with pacemaker cell phenotype.

Penile malignancies are rare in developed countries. The authors present a case of a penile urethral mesenchymal tumor occurring in a 51-year-old Caucasian male and displaying light microscopic, immunohistochemical, and ultrastructural features suggestive of a pacemaker cell type, combined with a lack of diagnostic features of any other established tumor category. The immunohistochemical profile was intensely positive for vimentin, PKC theta, and NSE and weakly positive to nonreactive for CD34 and smooth muscle actin, and entirely negative for CD117 (c-kit), S-100, and other markers. C-kit and PDGFRA gene analysis showed no mutations. Electron microscopy revealed tumor cells with plentiful cytoplasm and cytoplasmic processes/filopodia, both filled with intermediate filaments and occasional solitary focal densities. There were also prominent smooth endoplasmic reticulum cisternae, caveolae, neurosecretory granules, particularly concentrated in cytoplasmic processes, and synaptic-type structures. Poorly formed basal lamina, gap junctions, and intercellular collagen aggregates, consistent with skeinoid-type fibers, were also noted. Interstitial cells with potential pacemaker function have been recently described in the lower urinary tract, including the urethra, and this tumor may be related to this cellular phenotype.

Female urethral adenocarcinoma with a heterogeneous phenotype.

We here report a very rare case of female urethral adenocarcinoma. A 77-year-old woman presented with urinary retention. Cystoscopy showed a urethral tumor and the biopsy material showed adenocarcinoma. Macroscopically, the tumor measuring 3.0 x 3.0 x 2.4 cm was predominantly observed around the periurethral area on the proximal side. Histologically, patterns of columnar/mucinous adenocarcinoma, clear cell adenocarcinoma and papillary/micropapillary carcinoma were observed, but there was no evidence of a cribriform pattern. Immunohistochemically, neoplastic cells of at least one of three components were positive for CK7 and CK20 or CA125. We suggest that female urethral adenocarcinoma with a histologically and immunohistochemically heterogeneous phenotype may originate from cells within urethral or paraurethral tissue, such as urethritis glandularis or intestinal metaplastic epithelium and Mullerian tissue.

Carcinoid tumor in the female urethral orifice: rare case report and a review of the literature.

We experienced an extremely rare tumor in the female urethral orifice in a 57-year-old Japanese woman. To our knowledge, only two cases of primary urethral carcinoid tumor have been reported. The previous reports of urethral carcinoid tumor were recognized in the male middle urethra and penile urethra. The present case was resected, and diagnosed as a carcinoid tumor by histological, immunohistochemical and ultrastructural findings. The tumor cells were stained by chromogranin A, synaptophsin and neuron-specific enolase, and neurosecretory granules were confirmed with electron microscopy. The patient did not complain of any symptoms until 5 years after the resection of the tumor. Therefore, the case we describe here is the first known report of carcinoid tumor in the Japanese female urethra.

Adenocarcinoma of female paraurethral duct showing neuroendocrine differentiation.

Two cases are presented in which a female urethral adenocarcinoma took the form of a diverticular cancer. The pathologic examination of each tumor revealed a columnar/mucinous type of adenocarcinoma with evidence of abundant mucous secretion. Some of the cancer cells were positive on immunohistochemical staining with the conventional neuroendocrine marker chromogranin A, indicating focal neuroendocrine differentiation. The present cases may indicate a possible site of origin for female paraurethral adenocarcinomas.

Myxoid invasive papillary urothelial carcinoma of the bladder and urethra.

An unusual case of myxoid transitional cell (urothelial) carcinoma occurring in a 75-year-old man is presented. The primary tumour in the bladder, which was treated by partial cystectomy, consisted of areas of conventional high grade invasive (into the lamina propria) papillary urothelial carcinoma with separate myxoid areas. The latter component accounted for 25% of the tumour. Nine months later, the patient presented with haematuria once again, and a tumour was detected in the urethra. This was excised and histological examination showed only myxoid tumour without any overlying dysplasia or obvious epithelial differentiation. The myxoid areas were positive for epithelial markers and negative for all mesenchymal markers. This case highlights an uncommon variety of papillary urothelial carcinoma that invokes a wide differential diagnosis. Immunohistochemistry is essential in making the correct diagnosis.

Leiomyoma of the male urethra: a case report and review of the literature.

We describe the case of a 48-year-old quadriplegic black man with history of C4-C5 cervical spine and cord injury secondary to a fall, who presented to the University of Cincinnati Medical Center Urology Service with obstructive symptoms at urination. A bulbous urethral stricture was diagnosed and subsequently resected with primary urethral reanastomosis. On pathologic examination, the surgical specimen contained an epithelioid leiomyoma at the site of the urethral stricture. Although leiomyomas of the female urethra are relatively common, we identified only 2 previously reported cases of leiomyomas of the male urethra in the English-language medical literature. To the best of our knowledge, we describe the third case of leiomyoma of the male urethra, the first of the epithelioid type.

Intraductal carcinoma of the prostate metastatic to the penile urethra: a rare demonstration of two morphologic patterns of tumor growth.

Penile metastases from prostate cancer are rare and are usually a manifestation of wide-spread cancer dissemination. Isolated urethral metastases form a small fraction of these cases, have a longer survival rate and may represent spread by implantation following instrumentation. We report a case of prostatic carcinoma presenting with an isolated metastasis to the penile urethra after catheterisation and transurethral prostatectomy. The primary tumor had a prominent intraductal component whose architectural features were mimicked in the metastasis. The possible mechanisms of spread and the diverse appearances of cancer associated with an intraductal component are discussed.

Small cell carcinoma arising from the outer urethral orifice: a case report examined by histologic, ultrastructural and immunohistochemical methods.

A case of small cell carcinoma arising in the outer urethral orifice is presented. The resected tumor showed a proliferation of small round or fusiform neoplastic cells in the submucosa. Tumor cells were arranged in sheets or a trabecular manner and possessed markedly hyperchromatic nuclei with a high N:C ratio, closely resembling small cell carcinoma of the lung. Characteristically, pagetoid intraepithelial spreading could be identified. However, there was no evidence of in situ transitional cell carcinoma and adeno- or squamous cell carcinoma components anywhere. Ultrastructurally, each tumor cell contained only a few membrane-bound cored granules measuring 60-100 nm, which were compatible with neurosecretory granules, and desmosome-like intercellular attachments, but lacked aggregated microfilaments. By immunohistochemical examination, tumor cells were positive for epithelial markers, such as cytokeratin and epithelial membrane antigen, and neuron specific enolase, but negative for any other neuro-endocrine markers. Extensive systemic examination failed to show the primary site to be other than the outer urethral orifice. These findings indicate that the current tumor is a small cell carcinoma with neuro-endocrine differentiation arising from the outer urethral orifice.