Metastatic adenoid cystic carcinoma of the Bartholin Gland: Institutional cases and literature review of a rare gynecologic malignancy.

Cameron M. Liss: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Kaitlyn H. Pyrz: Writing – review & editing, Investigation, Data curation. Natasha Savage: Writing – review & editing, Validation. Sharad A. Ghamande: Writing – review & editing, Validation, Supervision, Resources, Methodology, Conceptualization.

A comprehensive literature review was conducted to identify all published cases of adenoid cystic carcinoma of the Bartholin gland with documented distant metastases. PubMed and Embase were searched from inception through September 2025 using combinations of the keywords “Bartholin gland,” “adenoid cystic carcinoma,” “metastasis,” “lung,” “liver,” “brain,” and “bone.” Reference lists of retrieved articles and relevant reviews were also screened for additional reports. Inclusion criteria were English-language publications describing histologically confirmed Bartholin gland adenoid cystic carcinoma with biopsy-confirmed distant metastasis and sufficient case-level clinical data for analysis. Exclusion criteria included review articles without individual patient data, conference abstracts lacking primary clinical detail, and reports of non-Bartholin vulvar adenoid cystic carcinoma. For each eligible case, extracted variables included study type, number of cases, patient age, presenting features, pathologic findings (including perineural invasion, margin status, and lymph node involvement), metastatic sites, interval to distant metastasis, treatment modalities, molecular findings, and reported outcomes. Extracted data were summarized descriptively and organized in tabular form. Institutional cases were identified through a retrospective case series review of patients treated at the Georgia Cancer Center, Augusta University Medical Center between January 2010 and September 2025. Inclusion criteria were histologically confirmed Bartholin gland adenoid cystic carcinoma with biopsy-confirmed distant metastasis and available clinical follow-up data. Clinical information, operative reports, pathology findings, imaging studies, and treatment histories were extracted from the electronic medical record. Histopathologic diagnoses were confirmed by board-certified gynecologic pathologists. Representative histopathologic images of pulmonary metastasis were reviewed and selected for illustration. Given the descriptive design and heterogeneity of published cases, analyses were limited to descriptive summary reporting of clinical characteristics and outcomes. Continuous variables were reported as ranges, and categorical variables were summarized as frequencies. This study was approved by the Augusta University Institutional Review Board (reference number 2377743–2). Informed consent was waived by the Institutional Review Board due to the retrospective nature of the study and use of coded data. No identifiable patient information is included in this report. All procedures were conducted in accordance with institutional ethical standards and the Declaration of Helsinki.

A total of 17 patients were identified, including two institutional cases and 15 cases from the literature. A 47-year-old woman initially presented in June 2018 with a vulvar mass. She underwent simple partial vulvectomy, and pathology demonstrated poorly differentiated adenoid cystic carcinoma of the Bartholin gland with extensive perineural invasion and positive surgical margins. Postoperative magnetic resonance imaging (MRI) of the pelvis demonstrated no residual disease. Adjuvant radiotherapy was not administered following initial surgery, and the patient was managed with close surveillance in the absence of radiographic residual disease. In August 2019, pelvic MRI revealed a 6.0 × 2.8 × 1.4 cm enhancing mass centered at the left vulva and vaginal introitus, abutting the urethra and involving the obturator internus muscle and ischial tuberosity. Examination under anesthesia with partial vaginectomy in September 2019 confirmed recurrent adenoid cystic carcinoma, without evidence of distant disease. Pelvic radiotherapy was subsequently administered and completed in December 2019. The patient subsequently experienced additional local recurrences requiring repeat vulvectomy in July 2022 and excision of a periurethral lesion in May 2023. In late 2024, surveillance imaging demonstrated innumerable pulmonary nodules. Computed tomography–guided biopsy of a right lower lobe nodule in November 2024 confirmed metastatic adenoid cystic carcinoma. Molecular profiling of the lung specimen demonstrated a MYB–NFIB gene fusion with KIT, PDGFRA, and VEGFR2 amplifications. Tumor mutational burden was low, and testing for programmed death-ligand 1 expression, microsatellite instability, BRAF, RET, and ERBB2 alterations was negative. Systemic therapy with carboplatin, paclitaxel, and bevacizumab was initiated in December 2024. After nine cycles, follow-up imaging demonstrated stable pulmonary disease with interval reduction in several nodules. As of August 2025, the patient remained clinically stable on maintenance bevacizumab. A 62-year-old woman presented in September 2009 with right labial pain and a vulvar mass. Imaging demonstrated a 2.3 × 1.9 cm lesion centered in the right Bartholin gland. Local excision revealed adenoid cystic carcinoma measuring 2.7 cm with lymphovascular invasion, perineural invasion, and positive margins. Definitive management with radical vulvectomy and groin lymph node dissection was performed in October 2009. Final pathology demonstrated no residual carcinoma and no lymph node metastasis. Postoperative positron emission tomography–computed tomography showed no evidence of distant disease. Adjuvant radiotherapy was not administered following definitive surgery given complete resection with negative margins and node-negative disease. In July 2010, surveillance imaging identified multiple bilateral pulmonary nodules measuring 3–7 mm. Wedge resections confirmed metastatic adenoid cystic carcinoma consistent with Bartholin gland origin. Representative histopathologic features of pulmonary metastasis are shown in Fig. 1 , Fig. 2 , Fig. 3 . Fig. 1 Pulmonary metastasis of adenoid cystic carcinoma demonstrating a well-circumscribed nodular lesion with tubular, cribriform, and focal solid architectural patterns. Hematoxylin and eosin stain; original magnification × 20. Fig. 2 High-power view demonstrating mitotic figures, apoptotic bodies, and nuclear atypia within metastatic adenoid cystic carcinoma. Hematoxylin and eosin stain; original magnification × 1000. Fig. 3 Intermediate-power view highlighting predominant cribriform architecture with associated myoepithelial differentiation and myxoid to hyalinized stromal globules. Hematoxylin and eosin stain; original magnification × 200. Pulmonary metastasis of adenoid cystic carcinoma demonstrating a well-circumscribed nodular lesion with tubular, cribriform, and focal solid architectural patterns. Hematoxylin and eosin stain; original magnification × 20. High-power view demonstrating mitotic figures, apoptotic bodies, and nuclear atypia within metastatic adenoid cystic carcinoma. Hematoxylin and eosin stain; original magnification × 1000. Intermediate-power view highlighting predominant cribriform architecture with associated myoepithelial differentiation and myxoid to hyalinized stromal globules. Hematoxylin and eosin stain; original magnification × 200. Molecular analysis demonstrated a MYB rearrangement by fluorescence in situ hybridization, strong c-KIT and platelet-derived growth factor receptor expression, microsatellite stability, and low tumor mutational burden. Immunohistochemistry was negative for estrogen receptor, progesterone receptor, and androgen receptor. The patient was treated with carboplatin, paclitaxel, and bevacizumab, achieving stable pulmonary disease. Six years after initiation of chemotherapy, she developed therapy-related acute promyelocytic leukemia characterized by t(15;17)(q24;q21)/PML–RARA fusion. The clinicopathologic features of previously reported cases are summarized in Table 1 . Eleven publications describing 15 patients with biopsy-confirmed distant metastases met inclusion criteria. Across reported cases, the lung was the most common metastatic site, followed by liver, brain, and bone. The interval to distant metastasis ranged from synchronous presentation to more than 15 years after initial diagnosis. Table 1 Clinicopathologic characteristics of published cases of metastatic adenoid cystic carcinoma of the Bartholin gland, summarizing reported cases with biopsy-confirmed distant metastases, including clinical presentation, pathologic features, metastatic sites, treatments, and outcomes. Author (Year) Study Type Metastatic Cases Included Age Presentation Pathology (Perineural invasion, Margins, Nodes) Metastatic Site(s) Interval to Metastasis Treatment(s) Outcome Aker (2020) Case report + literature review 1 58 Left vulvar pain with palpable Bartholin mass, initially misdiagnosed as Bartholin cyst; Adenoid cystic carcinoma Perineural invasion present; positive margins; nodes negative. Lung (right upper lobe, 1.2 cm) 49 months Local excision → hemivulvectomy; later lung wedge resection Alive and disease-free at 56 months; classic delayed pulmonary metastasis. Evin (2023) Case report + literature review 1 31 Right vulvar mass with several years of pain; Adenoid cystic carcinoma Perineural invasion present; positive margins; nodes not assessed. Lung (biopsy-proven nodules) 30 months Surgery → adjuvant radiotherapy → lenvatinib for lung disease Alive with progressive lung disease; MYB–NFIB fusion confirmed hallmark mutation. Feinberg (2024) Molecular case series (subset with 2 metastatic cases) 2 Cohort range 44 –79 Vulvar swelling or mass typical of Bartholin gland Adenoid cystic carcinoma; biphasic (ductal + myoepithelial) cribriform/tubular patterns common Perineural invasion common; margins variable; nodes not reported. Lung (most common), bone (occasional). Case-level details not provided Up to 16 years Surgery ± Radiotherapy; chemotherapy not detailed or standardized Long-term survival despite metastasis; All tumors showed MYB or MYBL1 rearrangements; study emphasizes diagnostic utility, not outcomes. Gray (2024) Case report 1 56 Remote Bartholin gland adenoid cystic carcinoma (diagnosed 8 years earlier) presenting with shortness of breath and hypoxemia; Adenoid cystic carcinoma Perineural invasion not specified; positive margins. Lung + mediastinal/hilar nodes 8 years Radical vulvectomy → chemo-radiation → systemic therapy (carboplatin/paclitaxel vs doxorubicin/bevacizumab) Alive with pulmonary and nodal metastases; emphasizes need for long-term surveillance. Hatiboglu (2005) Case report 1 59 Burning vulvar pain with hard right vaginal wall mass (3 × 2 cm); Adenoid cystic carcinoma (cribriform pattern) Perineural invasion present; margins close. Brain (cerebellar vermis, later cortex) 16 months Vulvectomy + brachytherapy → craniectomy + whole-brain radiotherapy Alive at short-term follow-up; first reported brain metastasis. Hsu (2013) Case series (2 cases) 2 37; 48 Postpartum vulvar mass (4 × 3 cm) and labial pain after prior marsupialization; adenoid cystic carcinoma (cribriform pattern) Case 1: extensive perineural invasion, positive margins, nodes positive. Case 2: Perineural invasion not stated, margins negative. Bone + lung (Case 1); bilateral lung (Case 2) 42 months (Case 1); 59 months (Case 2) Radical hemivulvectomy ± inguinofemoral lymph node dissection; radiotherapy; platinum/taxane chemotherapy; tamoxifen (1 case) Case 1: died of progression; Case 2: prolonged stability on tamoxifen- possible antiestrogen benefit. Nieuwenhuyzen- de Boer (2020) Case report + literature review 1 61 Right vulvovaginal pain with mobile Bartholin swelling initially presumed cyst; Adenoid cystic carcinoma (cribriform pattern) Perineural invasion present; incomplete excision; nodes not assessed. Lung (bilateral nodules) Synchronous with diagnosis Simple excision; no systemic therapy Persistent pulmonary disease at diagnosis; HPV-independent tumor. Ramanah (2013) Case report 1 48 Right vulvar mass, painful, initially treated as benign; Adenoid cystic carcinoma Perineural invasion not specified; margins positive → negative after re-excision. Brain + lung 24 months Local excision → re-excision + Radiotherapy → whole-brain Radiotherapy → chemotherapy (cyclophosphamide, doxorubicin, and cisplatin) Died 5 months after chemotherapy; first reported dual brain and lung metastases. Shahabi (2009) Case report 1 48 Enlarging right vulvar mass (3.5 × 4 cm); Adenoid cystic carcinoma Perineural invasion not reported; margins positive. Liver (bilateral lesions) Synchronous with diagnosis Radical hemivulvectomy with partial rectal resection; declined chemotherapy Persistent pelvic and hepatic disease; first reported liver metastasis. Yang (2006) Case series (2 cases) 2 43; 50 Case 1: painful left vulvar nodule (9-month history). Case 2: Bartholin mass found at hysterectomy, later recurrent and invasive; Adenoid cystic carcinoma Perineural invasion in both; margins negative after resection. Lung (multiple nodules) 4 years Surgery + Radiotherapy (Case 1); multiple resections + chemotherapy (cyclophosphamide, doxorubicin, and cisplatin) (Case 2) Case 1: No evidence of disease at 17 months; Case 2: stable disease at 10 months; delayed pulmonary recurrence typical. Yoon (2015) Retrospective series (subset with 2 metastatic cases) 2 Cohort range 50–67 Palpable Bartholin mass with pain common Perineural invasion in both; margins positive; nodes negative. Lung; liver 7–132 months Surgery ± Radiotherapy; cisplatin-based chemotherapy All alive; stable or progressive disease; long survival despite metastasis. Clinicopathologic characteristics of published cases of metastatic adenoid cystic carcinoma of the Bartholin gland, summarizing reported cases with biopsy-confirmed distant metastases, including clinical presentation, pathologic features, metastatic sites, treatments, and outcomes. Perineural invasion and positive surgical margins were frequently reported. Treatments were heterogeneous and included surgery with or without radiotherapy, which was most used in the setting of high-risk features such as positive margins or perineural invasion, as well as platinum-based chemotherapy. Outcomes ranged from prolonged disease stability to progression and death.

Although adenoid cystic carcinoma of the Bartholin gland is often indolent at diagnosis, it demonstrates a pattern of frequent local recurrence with the potential for delayed distant metastasis. Among several hundred reported cases in the literature, approximately 15 describe confirmed distant spread, representing roughly 5% of published cases. ( Ramanah et al., 2013 , Aker et al., 2020 , Gray et al., 2024 , Hatiboglu et al., 2005 , Shahabi et al., 2009 , Yang et al., 2006 , Yoon et al., 2015 ) Pooled analyses have reported 5-, 10-, and 15-year survival rates of 71%, 50%, and 51%, respectively. ( Di Donato et al., 2017 ) These data are consistent with characterization of this malignancy as persistent with potential for late recurrence despite initially localized presentation. The two institutional cases described here reflect this natural history, with initial localized disease followed by biopsy-confirmed pulmonary metastases several years later. Both cases exhibited perineural invasion and positive surgical margins at initial diagnosis, factors previously associated with an increased risk of local recurrence. ( Yoon et al., 2015 ) While perineural invasion may reflect more aggressive tumor biology, its association with distant metastasis is less clearly established. These findings reinforce that node-negative status does not preclude later hematogenous dissemination. Management of advanced adenoid cystic carcinoma remains challenging. Surgical resection remains the cornerstone of treatment for localized disease, with adjuvant radiotherapy frequently employed in the setting of positive margins or perineural invasion. Some reports suggest that radiotherapy may reduce local recurrence even when margins are negative. Systemic therapy has demonstrated limited durable benefit. Cisplatin- and carboplatin-based regimens have most commonly been used, typically resulting in temporary disease stabilization rather than sustained remission. ( Evin et al., 2023 , Feinberg et al., 2024 ) Consistent with salivary gland adenoid cystic carcinoma, which shares a common MYB-driven molecular profile across sites, targeted approaches, including tyrosine kinase inhibitors such as lenvatinib, have demonstrated modest activity with limited durability. ( Evin et al., 2023 , Feinberg et al., 2024 ) Reports describing cyclophosphamide-, adriamycin-, and cisplatin-based combinations for brain and lung metastases have shown similarly limited durability of response. ( Ramanah et al., 2013 ) The outcomes observed in our institutional cases are consistent with these patterns, with both patients achieving transient stability following treatment with carboplatin, paclitaxel, and bevacizumab. Molecular analyses have identified MYB or MYBL1 rearrangements as a characteristic feature of adenoid cystic carcinoma, with reported frequencies varying across studies. ( Evin et al., 2023 , Feinberg et al., 2024 ) These findings align the molecular profile of Bartholin gland adenoid cystic carcinoma with that of salivary gland adenoid cystic carcinoma. This shared molecular signature supports the biological similarity between these entities and provides a rationale for applying systemic strategies used in salivary gland disease. ( Feinberg et al., 2024 ). This study integrates two detailed institutional cases with all previously reported biopsy-confirmed metastatic cases, providing a comprehensive synthesis of clinical, pathologic, and molecular features. Molecular profiling in both institutional cases demonstrated MYB rearrangement, strong c-KIT and platelet-derived growth factor receptor expression, low tumor mutational burden, and microsatellite stability, consistent with previously described genomic patterns. Limitations include the rarity of the disease and reliance on retrospective case-level data, which limit the ability to draw definitive conclusions regarding optimal management. Heterogeneity in reporting across published cases further restricts comparative analysis. The molecular findings observed in these cases underscore the importance of routine molecular characterization and support continued investigation into biomarker-directed therapeutic strategies. Although therapies targeting KIT, platelet-derived growth factor receptor, or vascular endothelial growth factor receptor remain investigational, their consistent expression suggests potential avenues for future study. The development of therapy-related acute promyelocytic leukemia in one patient represents a rare but clinically significant treatment-related complication and highlights the importance of long-term monitoring in patients receiving systemic therapy.

Bartholin gland adenoid cystic carcinoma is a rare malignancy that may follow an indolent course yet demonstrate late distant metastasis. Published data indicate that distant spread occurs in a small but clinically meaningful proportion of cases and may arise years after initial treatment. The cases presented here highlight the potential for delayed pulmonary metastasis despite appropriate local management. Long-term surveillance should be considered given the risk of delayed distant metastases. Based on the observed patterns of recurrence, close imaging surveillance with cross-sectional imaging, such as MRI or CT, may be performed as frequently as every 3–4 months during the first two years following treatment, with decreasing frequency thereafter. These findings support extended surveillance beyond traditional follow-up intervals in patients with Bartholin gland adenoid cystic carcinoma. The data underlying this study are available from the corresponding author upon reasonable request. Patient Consent. Written informed consent was obtained from the patient for publication of this case report and accompanying images. Funding. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Bartholin gland carcinomas are exceedingly uncommon, accounting for only 3–4% of vulvar malignancies worldwide.( Bhalwal et al., 2016 ) Within this rare subset, adenoid cystic carcinoma represents fewer than 5% of Bartholin gland carcinomas. ( Di Donato et al., 2017 ) Fewer than 350 cases of Bartholin gland adenoid cystic carcinoma have been reported in the literature to date, and among these, only a small minority describe distant metastatic disease. Multiple reviews have described the epidemiology and management of Bartholin gland carcinoma; therefore, the present study focuses specifically on biopsy-confirmed metastatic disease. Despite its rarity, adenoid cystic carcinoma of the Bartholin gland represents a clinically important entity due to its distinctive biology and diagnostic challenges. Patients often present with nonspecific symptoms such as pain, burning, or a vulvar mass, findings frequently mistaken for benign conditions like Bartholin cysts, abscesses, or endometriosis.( Addley et al., 2023 ) This tendency toward misdiagnosis contributes to delayed recognition and disease progression. Histologically, adenoid cystic carcinoma demonstrates a cribriform growth pattern composed of small basaloid cells with scant cytoplasm and a pronounced propensity for perineural invasion, a feature that explains the hallmark pain of the disease and its high rate of local recurrence, even when surgical margins are negative. ( Woida and Ribeiro-Silva, 2007 ) Clinically, the course is typically indolent yet persistent, characterized by repeated local relapses and, less commonly, late-onset distant metastases. Metastatic spread, though rare, has been documented, most frequently to the lungs and less often to bone, liver, kidney, and brain. ( Aker et al., 2020 , Gray et al., 2024 , Hatiboglu et al., 2005 , Shahabi et al., 2009 , Yang et al., 2006 ) Several institutional series have shown that distant disease may arise even in node-negative patients, suggesting a predominantly hematogenous route of spread. ( Yoon et al., 2015 , Hsu et al., 2013 ) Larger pooled analyses confirm both the rarity of metastatic cases and the incomplete understanding of their natural history. ( Nieuwenhuyzen-de Boer et al., 2020 , Evin et al., 2023 ) Genomic profiling has identified recurrent MYB and MYBL1 rearrangements in most tumors, aligning Bartholin gland adenoid cystic carcinoma with the genomic profile of the more extensively studied salivary gland variant, and highlighting potential relevance for biomarker-driven therapeutic investigation. ( Evin et al., 2023 , Feinberg et al., 2024 ) Although systemic chemotherapy remains the mainstay for advanced disease, responses are typically limited and transient. ( Evin et al., 2023 ). Here, we present two detailed institutional cases of biopsy-confirmed distant spread of Bartholin gland adenoid cystic carcinoma and a comprehensive review of the published literature. Our objective is to contextualize institutional experience within the broader record, synthesize patterns of recurrence and metastatic dissemination, and explore implications for long-term management of this rare and biologically distinct gynecologic malignancy. Collectively, these cases illustrate the indolent yet persistent natural history of adenoid cystic carcinoma and represent, to our knowledge, the most comprehensive synthesis of biopsy-confirmed metastatic cases to date.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.