LAUSR

To the Editor, Skene gland adenocarcinoma is a very rare tumor with only 15 cases reported in the literature. Tregnago et al. presented the first series of four cases in 2018. Three of their cases were morphologically consistent with prostatic acinar adenocarcinoma, analogous to Gleason score 4 + 4 = 8. We present a case of a 77‐year‐old female with history of diverticulitis who presented with chronic constipation and intermittent abdominal pain. During workup (CT abdomen and pelvis), she was incidentally found to have a large periurethral mass. Magnetic resonance imaging showed a 4.3 × 3.8 × 2.8 cm enhancing mass adjacent to the posterior wall of the urethra. Cystoscopy showed no intraluminal urethral mass and urine cytology was negative. She underwent a needle core biopsy of this mass. Histopathological examination showed a high‐grade adenocarcinoma predominantly composed of sheets of cells with signet ring cell‐like features (Figure 1a), including foci of poorly formed and fused glands with focal glomeruloid architecture (Figure 1b), analogous to prostatic acinar adenocarcinoma, Gleason score 5 + 4 = 9 (Grade Group 5). No in‐situ or invasive urothelial carcinoma was identified. On immunohistochemical staining, the tumor cells were positive for pancytokeratin, NKX3.1 (Figure 1c), and prostate specific antigen (PSA) (Figure 1d); while negative for GATA3, mammaglobin, uroplakin, p63, p40, CK7, CK20, CDX2, PAX8, mucicarmine, CA‐IX, HNF‐1 beta, napsin, and p16. The overall morphologic and immunohistochemical profile was consistent with a high‐grade adenocarcinoma arising from the periurethral Skene glands. Further biomarker analysis by immunohistochemistry showed the tumor cells were positive for androgen receptor (AR) (Figure 1e), and negative for ETS‐related gene (ERG) and phosphatase and tensin homolog (PTEN) (Figure 1f). Primary urethral carcinoma is a rare tumor which is more common in women than in men. The most common histological type is squamous cell carcinoma followed by urothelial carcinoma and adenocarcinoma. Primary urethral adenocarcinoma has two main histological subtypes; columnar cell/mucinous adenocarcinoma and clear cell adenocarcinoma. A rare subtype is adenocarcinoma arising from the periurethral Skene glands, and only 15 cases have been reported in the literature. Skene glands are the female homolog of the male prostate gland and it has been shown in the literature that normal Skene glands are positive for PSA and prostate specific acid phosphatase (PSAP). In 2018, Tregnago et al. published a series of cases demonstrating immunoreactivity for other prostatic markers (i.e., NKX3.1 and P501S) in addition to PSA and PSAP and confirmed that Skene gland adenocarcinoma microscopically appears similar to high‐grade prostatic adenocarcinoma. In our patient, the tumor had sheets and single cells with signet ring cell‐like features (analogous to Gleason Grade 5), and foci of poorly formed and fused glands with focal glomeruloid architecture (analogous to Gleason Grade 4). This tumor was positive for prostatic markers (i.e., NKX3.1 and PSA) similar to what has been described in prior case reports and case series. However, novel to this case, we further analyzed the expression of other biomarkers including AR, ERG, and PTEN. The PTEN and ERG mutations are two of the most common mutations found in prostatic adenocarcinoma. The PTEN gene encodes for the PTEN protein, which has several anti‐oncogenic functions. Mutations in PTEN result in decreased expression of this protein, which contributes to tumorigenesis. The ERG gene encodes for the ERG protein, which disrupts AR signaling by inhibiting AR expression. Translocations of the ERG gene and the formation of the TMPRSS2‐ ERG fusion gene result in increased levels of ERG expression. The expression of these biomarkers in Skene gland adenocarcinoma has not been reported in the literature. Our case demonstrated loss of PTEN expression, but no overexpression of ERG was found.