Management of Bartholin’s Gland Carcinoma in a Perimenopausal Woman: A Case Report

Introduction

Bartholin’s gland carcinoma (BGC) is an extremely rare malignancy, representing less than 5% of vulvar cancers and under 0.001% of all gynecologic cancers [1–4]. It is typically detected in postmenopausal women but has also been reported in younger patients [5,6]. Because of nonspecific symptoms such as vulvar discomfort or a palpable nodule, BGC is often initially misdiagnosed as a benign condition, which contributes to delays in diagnosis.

There is no consensus regarding optimal management of BGC due to the small number of reported cases. Most patients undergo radical treatment, often combining surgery, chemotherapy, and radiotherapy, directed by a multidisciplinary team of gynecologic, medical, and radiation oncologists [1,7–9]. Recent reports have indicated that human papillomavirus (HPV) infection and tumor markers such as carcinoembryonic antigen (CEA) and cancer antigen 19–9 (CA 19–9) may be relevant to the biology and monitoring of BGC [10]. However, the molecular characterization of this cancer remains poorly understood despite advances in molecular biology methods [11].

This case report describes a 53-year-old woman with BGC who underwent surgery, chemotherapy, and radiotherapy, accompanied by molecular and tumor marker analysis. The case is noteworthy because of the patient’s perimenopausal age, the integration of multimodal oncologic therapy, the longitudinal assessment of CEA and CA 19–9, and the long-term clinical outcome.

Case Report

LABORATORY INVESTIGATIONS:

HPV testing of the tumor tissue using polymerase chain reaction–based genotyping did not detect high-risk types (ie, HPV 16 and 18; Table 1). The patient also had no history of HPV-related disease.

Serum CEA and CA 19–9 levels were measured at multiple time points. Both markers were elevated at diagnosis but significantly decreased after chemotherapy and radiotherapy, indicating an association with remission (Table 2).

Histologic sections demonstrated features indicative of adenoid cystic carcinoma, including cribriform and tubular patterns with small hyperchromatic nuclei and mucicarmine-positive cyst-like spaces (Figure 1).

Discussion

BGC comprises less than 5% of all vulvar cancers and less than 0.001% of all gynecologic cancers. It is typically detected in postmenopausal women [2–4] but has also been described in premenopausal women [5,6]. Because symptoms are often nonspecific, such as discomfort or a vulvar mass, misidentification as benign Bartholin’s cyst is common, similar to the initial diagnosis for our patient. This issue emphasizes the importance of excising or biopsying any atypical Bartholin’s lesion in women age 40 and older.

There is no universally accepted treatment protocol for BGC, but most reports describe surgery with or without adjuvant chemotherapy and radiotherapy [1,7–9]. Some authors support extended lymphadenectomy, whereas others recommend more conservative nodal management with adjuvant radiotherapy in selected cases [12–17]. Although radiotherapy is associated with side effects, a few studies have confirmed its benefit in reducing local recurrence rates [18,19]. In advanced or inoperable cases, chemotherapy has been used as neoadjuvant or palliative therapy [2,4]. In our patient, radical excision with lymphadenectomy followed by paclitaxel–carboplatin chemotherapy and postoperative radiotherapy resulted in long-term remission. The absence of lymph node involvement and the moderately differentiated histology (G2) may partly explain this favorable outcome. This finding supports the notion that multimodal treatment can be effective in carefully selected cases.

Molecular characterization of BGC remains poorly defined despite advances in genomic methods. Most available data are derived from studies of vulvar carcinoma, which have identified mutations in tumor protein p53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), phosphatase and tensin homolog (PTEN), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and other genes [11,12]. In the present case, HPV tests revealed negativity for high-risk types, including HPV 16 and 18, and the patient had no history of HPV-related disease. These observations suggest an HPV-independent pathogenesis, further underscoring the heterogeneity of BGC.

We also assessed CEA and CA 19–9 as potential biomarkers. Both were elevated at diagnosis and significantly decreased after chemotherapy and radiotherapy, indicating an association with remission. Whereas Ohno et al reported CEA in both tissue and serum but CA 19–9 only in tissue [20], we observed reductions in both markers in serum, suggesting that these markers can be used to monitor treatment response. However, this observation is limited to a single case, and larger studies are needed to confirm the clinical relevance of these markers.

Although the tumor was located near a remote episiotomy scar, we do not propose any causal relationship. The scar was considered incidental because the patient had no history of infection or abnormal wound healing, and such scars are usually barely detectable decades after childbirth.

In summary, this case highlights the diagnostic challenges associated with BGC, demonstrates that multimodal therapy can achieve long-term remission, and provides additional evidence that CEA and CA 19–9 may have a role in monitoring disease activity. The patient’s negative HPV status further supports the existence of HPV-independent subtypes of BGC.

Conclusions

Approximately 300 cases of BGC have been reported in the literature, including ~200 cases documented in a single review by Zhan et al [21], underscoring its rarity. Our findings showed that paclitaxel–carboplatin therapy with radiotherapy produced the expected results. CEA and CA 19–9 also appear to be useful markers of treatment response and cancer remission. Given the absence of a precise molecular profile of BGC, genomic and RNA sequencing of tumor samples, as well as HPV genotyping of both archived and newly collected specimens, would be advisable. The deposition of these data in a publicly accessible database would support future research and improve understanding of this rare malignancy.