Unusual case of ovarian basosquamous carcinoma metastatic disease from cutaneous primary malignancy

Metastases to the ovary most commonly originate from gastrointestinal adenocarcinomas, while primary cutaneous tumors are rare and typically melanoma.1 Basosquamous carcinoma (BSC), or metatypical basal cell carcinoma, is an uncommon variant of basal cell carcinoma (BCC) with squamous differentiation, representing approximately 2% of non-melanoma skin cancers.2 Histologically, BSC demonstrates a transition zone between basaloid and squamoid cells, and typically expresses Ber-EP4 and cytokeratin 5/6 on immunohistochemistry.2, 3 Compared to other non-melanoma skin cancers, BSC has a greater propensity for local recurrence and distant metastases, frequently involving the brain, bone, lung, and liver.3 Here, we describe a case report of BSC with ovarian metastasis in a 38-year-old woman, 15 years after initial diagnosis of the disease. Case studies are not subject to institutional review board (IRB) review. The patient provided written informed consent as required by IRB policy. A PubMed literature search from its inception through August 1, 2025 using terms related to BSC and gynecologic disease identified no prior reports of ovarian metastasis, returning only one publication describing vulvar BSC.1 A 37-year-old Caucasian female presented to the gynecologic oncology clinic with enlarging bilateral adnexal masses on magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) in the setting of known metastatic BSC. She reported mild dysmenorrhea without other gynecologic symptoms. Her history included mid-back BCC diagnosed in 2010 and treated with Mohs surgery, that recurred in 2019 as BSC, with peripheral palisading and squamous differentiation and diffuse Ber-EP4 positivity. In January 2024, she presented with severe abdominal pain and vomiting. Imaging showed bilateral ovarian lesions, peritoneal nodularity concerning for carcinomatosis, and a liver mass with biliary obstruction. Liver biopsy confirmed metastatic BSC. Cancer-antigen 125 testing was negative, and 70-gene Invitae pan-hereditary cancer panel was negative for germline pathogenic variants. Immunohistochemistry studies of liver biopsy showed strong, diffuse positivity for cytokeratin 5/6, p63, cytokeratin 7 and Bcl2 and weak positivity for GATA-3 and PAX8. Focal staining for CD56, CD10, and chromogranin-A was noted, while EMA, CEA, p16, synaptophysin, WT-1, CK20, CDX2, and S100 were negative. Tumor sequencing revealed high tumor mutational burden (91 mu/Mb), TP53 and TERT promoter mutations, and CDKN2A/B deletions. The patient was treated with PD-1 inhibitor immunotherapy, cemiplimab, for 18 cycles. Post-treatment imaging showed improvement of hepatic and peritoneal lesions but progression of ovarian masses (Figure 1a,b). A PET-CT correlated with MRI findings showing (fluorodeoxyglucose) FDG-avid bilateral ovarian masses (Figure 1c). Given the presence of residual disease, resection was recommended. Gross examination following hysterectomy and bilateral salpingo-oophorectomy revealed right (8 × 5 cm) and left (6 × 4 cm) ovarian masses, with normal uterus, cervix, and bilateral fallopian tubes. The tumor focally extended to the ovarian surface with necrosis (Figure 1d). Final pathologic diagnosis of ovarian masses was reported as metastatic carcinoma with similar morphology to the patient's established recurrent cutaneous basal cell carcinoma (Figure 1e). No evidence of carcinoma was found on cytology of pelvic washings, tubes, or uterus. Postoperative PET/CT showed no residual or recurrent radiotracer uptake in the pelvis (Figure 1f). Gynecologic involvement of BSC has been reported as primary cutaneous BSC arising in the vulva, vagina, cervix, and breast.1, 4 Non-melanoma skin cancers rarely metastasize to the ovary, and most reported ovarian metastases from cutaneous primaries involve melanoma or Merkle cell carcinoma.2, 5 In contrast, BSC metastasis to the ovaries has not previously been described in the literature. The diagnosis in this case was supported by diffuse Ber-EP4 positivity and squamous marker expression (cytokeratin5/6, p53), consistent with BSC, and absence of neuroendocrine marker staining characteristics of Merkel cell carcinoma. Furthermore, the tumor exhibited somatic Hedgehog pathway mutations (e.g., PTCH1), a common characteristic of BSC tumors.3 Optimal management and treatment of metastatic BSC remains challenging without specific guidelines from the National Comprehensive Cancer Network (NCCN), and current practice follows recommendations for advanced cutaneous squamous cell carcinoma (SCC) or BCC. Immune checkpoint inhibitors, particularly anti–PD-1 agents such as cemiplimab, have demonstrated efficacy in advanced non-melanoma skin cancers.3 However, in this case, there was mixed response to systemic therapy, with ovarian tumor progression, yet favorable tumor response in the liver and peritoneal implants. This discrepancy may reflect the unique ovarian tumor microenvironment, known to confer complex immune evasion mechanisms across subtypes of primary and metastatic ovarian cancer.6 The patient's demographic profile as a young female with a truncal primary lesion differs from the typical presentation of BSC in older men with head and neck primaries.3, 7 Despite aggressive local treatment and systemic immunotherapy, prognosis for metastatic BSC remains variable, with reported 5-year survival rates from 17.5% to 54%.8 This case reinforces the importance of maintaining a broad differential when assessing adnexal masses, especially in patients with a history of malignancy. Consideration of oophorectomy in cases with residual metastatic disease to the ovary is reasonable for diagnostic and therapeutic purposes, and further documentation of similar cases is warranted in the future. As the incidence of skin cancers rises globally, previously undocumented metastatic patterns may become more relevant in gynecology. Julia Shuford: Conceptualization, data acquisition, literature review, writing and editing. Zoe Roecker: Conceptualization, literature review, supervision, writing and editing. Brannan Brooks Griffin: Conceptualization, data acquisition and interpretation. Namita Khanna: Conceptualization, supervision, and data acquisition. The authors have nothing to report. The authors report no conflict of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.