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Rare Case of Skene’s Gland Malignancy Raises Awareness About Treatment Options

Case report and literature review provide new insights into the management of rare malignancy

Skene’s Gland Malignancy: A Case Report and Systematic Review

Androgen deprivation therapy (ADT) and other mainstays of therapy for men with castration-resistant prostate cancer may be effective in the management of Skene’s gland malignancy, a rare paraurethral adenocarcinoma.

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The malignancy is exceedingly rare: only 15 cases have been reported in the literature. This is according to recent findings reported by a multidisciplinary team that have led the most comprehensive review of the disease to date.

“Paraurethral and urethra masses are typically unfamiliar even to specialists,” says Emily Slopnick, MD, a female pelvic medicine and reconstructive surgeon at Cleveland Clinic and part of the care team treating a patient with this rare malignancy. “And in this case, the patient didn’t even present with either of these masses; it was an enlarged lymph node,” she explains.

This clinical encounter led Dr. Slopnick and her colleagues to report details from the case and conduct a literature review. They published their findings in Urology.

Presentation, diagnosis – and why PSA evaluation is warranted

A 76-year-old female presented with a left inguinal mass. An excisional biopsy and pathological workup revealed malignant cells consistent with metastatic carcinoma. The patient was referred to gynecologic oncology with suspicion for ovarian germ cell tumor.

Upon physical examination, the gynecological oncology team found a 2 cm mass on the patient’s Skene’s gland, bordering the left distal urethra. The patient was immediately taken to the operating room to undergo bilateral salpingo-oophorectomy, a left obturator lymph node dissection, and a biopsy of the paraurethral mass.

Pathological evaluation confirmed that adenocarcinoma had infiltrated the lymph node and was extending into the surrounding tissue. Interestingly, the cellular composition was similar to that of a Gleason pattern 4 + 4 prostatic adenocarcinoma and even showed expression of NKX3.1 and prostate specific-membrane antigen.

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Because the Skene’s glands are the embryologic homologue of the prostate, this is a rare scenario when evaluating PSA levels in a female is helpful in confirming the diagnosis. Laboratory testing revealed significantly elevated PSA levels: 7.91 ng/mL (normal levels are < 0.2 ng/mL in a postmenopausal female).

A true multidisciplinary effort among urology, gynecology, and oncology

“Even getting to the diagnosis was a true multidisciplinary effort,” says Dr. Slopnick. “At a glance, those of us trained in urology may have assume it’s a urethral cancer or from the gynecological perspective, a vaginal cancer; and in this case, she presented with an enlarged lymph node, which can be the result of many things,” Dr. Slopnick explains.

The team moved forward with plans to excise the primary mass, but during the surgery they realized it extended more proximally then was apparent during the physical exam. Complete resection of the tumor would necessitate a total urethrectomy with urinary diversion. The team halted the surgery to allow for additional patient counseling and decision-making.

Her case was presented at a multidisciplinary tumor board conference, which led to a new plan. She was offered a regimen that has demonstrated success in treating men with advanced prostate cancer: androgen deprivation therapy (ADT) with the novel adrenal biosynthesis inhibitor abiraterone acetate and prednisone (AA/P).

The patient opted to stay on the hormonal therapy regimen and declined radiation therapy and surgical treatment. Her results have continued to be positive since beginning treatment. At 24 months, her PSA levels were undetectable; she had no evidence of metastases; and she had a RECIST-defined partial response.

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The authors recommend indefinite ADT treatment with ongoing PSA evaluation and imaging, according to the case report.

What is known about Skene’s gland malignancy?

This patient’s outcomes are generally consistent with those reported in the literature, asserts Dr. Slopnick. In the 15 cases identified as true Skene’s gland malignancy, the median patient age was 71 years old, and the most common presentation (N = 5) was an asymptomatic periurethral or urethral lesion. Other symptoms included hematuria or vaginal bleeding, vulvovaginal pain and lower urinary tract symptoms.

In eight cases, PSA levels were measured, and all were found to be elevated. In all eight of these cases, PSA levels regulated in tandem with treatment.

Treatment approaches did vary from patient-to-patient: eight included local excision (with or without pelvic lymphadenectomy), two underwent radical surgical resection, two received radiation therapy, and one, a more recent case, also utilized neoadjuvant ADT along with extensive radical surgery.

There was no incidence of recurrence or disease-related mortality in any of the 15 cases.

Considerations for ADT as a primary modality

In this case, the patient was offered adjuvant radical surgery or whole pelvis radiation therapy, but opted for the ADT treatment alone. This is the first reported case of treatment for this type of malignancy with an antiandrogen.

“Historically, surgical excision has been the preferred approach for managing this rare malignancy; however, hormonal therapy modalities, as in this case, and other regimens that are effective in treating castration-resistant prostate cancer should be considered in the management of Skene’s gland malignancies,” concludes Dr. Slopnick.

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Featured image: MRI shows a 2.4 x 2.2 x 2.6 cm enhancing mass in the distal urethra tethered to the anterior vaginal wall.

Image reproduced with permission from Elsevier. Slopnick EA, Bagby C, Mahran A, Nagel C, Garcia J, El-Nashar S, Hijaz AK. Skene’s Gland Malignancy: A Case Report and Systematic Review. Urology. 2022 Feb 19:S0090-4295(22)00149-2. doi: 10.1016/j.urology.2022.02.004. Epub ahead of print. PMID: 35192863.

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