Bartholin's gland carcinoma: Epidemiology and therapeutic management

doi:10.1016/j.suronc.2013.02.004

Surgical Oncology

Volume 22, Issue 2, June 2013, Pages 117-122

https://doi.org/10.1016/j.suronc.2013.02.004 Get rights and content

Abstract

Primary carcinoma of the Bartholin's gland is a very rare malignancy of the vulva. Of the utmost importance in the management of these tumors is the management by specialized gynecological oncologist at referral centres. Gynecologists should always consider these unusual neoplasms as a differential diagnosis of potentially benigns lesions of Bartholin's gland.

Treatment modality must be tailored to each patient: each histological type of these unusual neoplasms has their natural history and may require a different level of operative aggressiveness to obtain the optimal outcome. Given the rarity of this disease, there have been no prospective randomized trials to evaluate optimal treatment.

Therapeutic principles in the management of median vulvar cancer are applicable for Bartholin's gland carcinoma.

In this review, we aim to update the current knowledge on the treatment of Bartholin's gland carcinoma.

Introduction

Bartholin's gland was first described by Duverney who identified this gland in cows. It was subsequently identified in the human female in 1675 by Caspar Bartholin a Danish anatomist [1]. These paired glands, also called greater vestibular glands, are 0.5 cm in diameter and are found in the labia minora in the 4- and 8-o’clock positions. Typically they are nonpalpable and their function is to maintain the moisture of the vaginal mucosa's vestibular surface.

Documentation of Bartholin gland carcinoma was firstly reported in 1864 by Klob [2].

There is a minimal awarness of the possibility of Bartholin gland carcinoma (BGC) which is often misdiagnosed as a cyst or an abscess. Because suspicion is low, diagnosis is then delayed untill discovered at later stages.

There is no consensus on the treatment of Bartholin's gland carcinoma due to the lack of prospective and randomized controlled trials and large series in the literature. Recommendations for treatment, such as extensive vulvar surgery and inguinal and pelvic lymphadenectomy are based on limited clinical experience. BGC is a type of vulvar carcinoma and treated similarly to primary squamous cell carcinoma of the vulva. Most studies available in the recent literature are largely retrospective in nature. This article review the literature to discuss the management of BGC.

Section snippets

Definition

The diagnostic criteria of primary Bartholin's gland carcinoma were first established by Honan in 1897 : Correct anatomic location of the tumor, with a primary location deep in the labia, connection of tumor with the gland duct with the presence of adjacent intact gland tissue [3]. But these criteria having been too restrictive, they were widened by Chamlian and Taylor in 1971 [1], [4] : The tumor is accepted being a primary tumor of the Bartholin gland when (1) The tumor involving the area of

Epidemiology

Primary neoplasms of the Bartholin gland are rare and account for approximately 2–7% of vulvar cancer and less than 1% of all gynecologic malignancies [1], [4], [5], [6], [7]. The mean age at diagnosis is 50–60 years with a range 33–93 years [8], [9], [10], [11].

The utmost leading symptom is a painless visible mass in the posterior part of the labium majus which frequently leads to delay in obtaining the correct diagnosis, as many lesions are initially thought to be Bartholin gland cysts. Most

Histological types

Bartholin's neoplasm may arise from the gland itself or from its duct: Histologically, the duct of Bartholin gland near its orifice is composed of squamous epithelium many layers thick, which become transitional in character as the duct nears the gland. The secondary ducts are lined by a thinner transitional epithelium, and the terminal ducts and glands by a single layer of transitional or cylindrical epithelium.

Squamous cell carcinoma and adenocarcinomas are the predominating malignancy at

Pretreatment evaluation

A diagnosis of primary BGC cannot be established unless metastase from another source is eliminated. A careful complete history and physical examination should be performed including a thorough pelvic examination, cervical examination with Papanicoalou smear in women with no history of hysterectomy. Careful bimanual examination with palpation of the entire vagina can detect small nodules not visualized during the examination.

As patient comfort is essential to a succesful examination, the

Surgical management of the primary tumor

Therapeutic principles in the management of median vulvar cancer appear to be appropriate for management of BGC. The standard treatment for early stage (clinical T1 or T2 N0M0 tumors) is primary surgery with radical excision (hemivulvectomy for lesions <2 cm or radical total vulvectomy for lesions more than 2 cm diameter) with bilateral inguinofemoral lymph node dissection (ILND) followed by radiotherapy if indicated [17], [24].

It is common for the primary tumor to be excised by a general

Pronosis

The size and stage of the disease at the time of diagnosis are the most important indicators. Five year survival of patients treated with radical surgery range from 70% to 93%, when the nodes are negative, to 71% 5-year survival rate with a single positive inguinal node, and to less than 20% 5-year survival rate in patients with multiples inguinal nodes. These percentages underline the prognostic role of lymph nodes metastasis. The overall 5-year survival rate of approximately 70% is below the

Conclusion

Primary carcinoma of the bartholin's gland is a very rare malignancy of the vulva. Of the utmost importance in the management of these tumors is the management by specialized gynecological oncologist at referral centres as soon as possible.

The absence of specific symptoms explains the frequent delay to diagnosis and its discovery in later stages needing a more aggressive management.

Nowadays, with the SLN technique and neoadjuvant treatments, the inherent morbidity of BGC surgical treatment

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Authorship statement

Guarantor of the integrity of the study: [G. Body, L. Ouldamer]

Study concepts: [L. Ouldamer]

Definition of intellectual content: [L. Ouldamer]

Literature research: [L. Ouldamer, Z. Chraibi]

Data acquisition: [Z. Chraibi, F.Arbion]

Data analysis: [L. Ouldamer]

Manuscript preparation: [L. Ouldamer]

Manuscript editing: [I. Barillot]

Manuscript review: [I. Barillot, G. Body]

References (41)

P. Rosenberg et al.
Adenoid cystic carcinoma of Bartholin’s gland: a report of five new cases treated with surgery and radiotherapy
Gynecol Oncol
(1989)
M.G. Dodson et al.
Establishment and characterization of a squamous cell carcinoma of the vulva in tissue culture and immunologic evaluation of the host
Am J Obstet Gynecol
(1978 Jul 15)
J.G. Masterson et al.
Carcinoma of Bartholin gland; review of the literature and report of a new case in an elderly patient treated by radical operation
Am J Obstet Gynecol
(1955)
R.J. Cardosi et al.
Bartholin’s gland carcinoma: a 15-year experience
Gynecol Oncol
(2001)
M.A. Finan et al.
Bartholin’s gland carcinoma, malignant melanoma and other rare tumours of the vulva
Best Pract Res Clin Obstet Gynaecol
(2003)
S.-Y.V. Yang et al.
Adenoid cystic carcinoma of the Bartholin’s gland: report of two cases and review of the literature
Gynecol Oncol
(2006)
B. Kraemer et al.
Stage I carcinoma of the Bartholin’s gland managed with the detection of inguinal and pelvic sentinel lymph node
Gynecol Oncol
(2009)
L.S. Massad et al.
Multimodality therapy for carcinoma of the Bartholin gland
Gynecol Oncol
(1999)
L.R. Nycum et al.
Recurrent squamous cell carcinoma of the Bartholin’s duct treated with en bloc resection
Gynecol Oncol
(1999)
S. Pecorelli
Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium
Int J Gynaecol Obstet
(2009)

L.S. Downs et al.

Stage IV carcinoma of the Bartholin gland managed with primary chemoradiation

Gynecol Oncol

(2002)

G. Ferrandina et al.

Skull metastasis in primary vulvar adenocarcinoma of the Bartholin’s gland: a case report

Gynecol Oncol

(2005)

L. Balepa et al.

First detection of sentinel node in adenocarcinoma of Bartholin’s gland

J Gynecol Obstet Biol Reprod (Paris)

(2004)

J.A. de Hullu et al.

Management of vulvar cancers

Eur J Surg Oncol

(2006)

J.F. Magrina et al.

Squamous cell carcinoma of the vulva stage IA: long-term results

Gynecol Oncol

(2000)

M. Origoni et al.

Prognostic value of pathological patterns of lymph node positivity in squamous cell carcinoma of the vulva stage III and IVA FIGO

Gynecol Oncol

(1992)

M. Hampl et al.

Validation of the accuracy of the sentinel lymph node procedure in patients with vulvar cancer: results of a multicenter study in Germany

Gynecol Oncol

(2008)

C. Louis-Sylvestre et al.

Sentinel node localization should be interpreted with caution in midline vulvar cancer

Gynecol Oncol

(2005)

V. Anaf et al.

Adenoid cystic carcinoma of Bartholin’s gland: what is the optimal approach?

Eur J Surg Oncol

(1999)

M.J. Cunningham et al.

Primary radiation, cisplatin, and 5-fluorouracil for advanced squamous carcinoma of the vulva

Gynecol Oncol

(1997)

Cited by (38)

Adenoid cystic carcinoma of the Bartholin's gland is underpinned by MYB- and MYBL1- rearrangements
2024, Gynecologic Oncology
Adenoid cystic carcinoma (AdCC) of the Bartholin's gland (AdCC-BG) is a very rare gynecologic vulvar malignancy. AdCC-BGs are slow-growing but locally aggressive and are associated with high recurrence rates. Here we sought to characterize the molecular underpinning of AdCC-BGs.
AdCC-BGs (n = 6) were subjected to a combination of RNA-sequencing, targeted DNA-sequencing, reverse-transcription PCR, fluorescence in situ hybridization (FISH) and MYB immunohistochemistry (IHC). Clinicopathologic variables, somatic mutations, copy number alterations and chimeric transcripts were assessed.
All six AdCC-BGs were biphasic, composed of ductal and myoepithelial cells. Akin to salivary gland and breast AdCCs, three AdCC-BGs had the MYB::NFIB fusion gene with varying breakpoints, all of which were associated with MYB overexpression by IHC. Two AdCC-BGs were underpinned by MYBL1 fusion genes with different gene partners, including MYBL1::RAD51B and MYBL1::EWSR1 gene fusions, and showed MYB protein expression. Although the final AdCC-BG studied had MYB protein overexpression, no gene fusion was identified. AdCC-BGs harbored few additional somatic genetic alterations, and only few mutations in cancer-related genes were identified, including GNAQ, GNAS, KDM6A, AKT1 and BCL2, none of which were recurrent. Two AdCC-BGs, both with a MYB::NFIB fusion gene, developed metastatic disease.
AdCC-BGs constitute a convergent phenotype, whereby activation of MYB or MYBL1 can be driven by the MYB::NFIB fusion gene or MYBL1 rearrangements. Our observations further support the notion that AdCCs, irrespective of organ site, constitute a genotypic–phenotypic correlation. Assessment of MYB or MYBL1 rearrangements may be used as an ancillary marker for the diagnosis of AdCC-BGs.
Adenoid cystic carcinoma of Bartholin's gland, a case report with genomic data and literature review
2023, Cancer/Radiotherapie
Adenoid cystic carcinoma of the Bartholin's gland (ACCBG) is a rare, slowly but aggressive malignancy. We reported the case of a 31-year-old woman who was treated by local excision and then hemi-vulvectomy, with positive margins and perineural invasion. Radiation therapy (RT) was then performed delivering 45 Gy in 25 fractions in bilateral inguinal lymph nodes and 64.8 Gy in 36 fractions on the vulvar area. After 30 months, there was no local relapse (LR) but the patient presented a histologically documented lung recurrence. Genomic profiling of the tumor showed a MYB-NFIB fusion transcript and a somatic mutation of PLCG1. A treatment by Lenvatinib was started. We conducted a literature review of 100 published cases. Patients were mainly treated by radical vulvectomy (30%), hemi-vulvectomy (17%), wide or local excision (21% and 24%, respectively) or other. Forty-four percent of patients received postoperative RT, more frequently in case of positive margin (71.9% versus 29.5%). RT may reduce the risk of LR regardless of margin status, with 15.4% vs. 41.9% of LR with or without RT, respectively, in patients with negative margins, and 13% vs. 33.3% of LR with or without RT, respectively, in patients with positive margins. The risk of relapse of any type was 40.9% in patients who received adjuvant RT vs. 48.2% in patients who did not. Median time to relapse was 24 months (range 6–156 months). The most frequent metastatic sites were lung (76.7%) and bone (26.7%). Optimal treatment for ACCBG is still not clearly defined but pooling the data from published case report help us better understand this rare disease and help in the therapeutic decision.
Le carcinome adénoïde kystique de la glande de Bartholin est une maladie rare, lentement évolutive, mais agressive. Nous présentons le cas d’une patiente de 31 ans traitée pour un carcinome adénoïde kystique de la glande de Bartholin par excision locale puis hémi-vulvectomie avec berges chirurgicales atteintes et invasion périnerveuse. La patiente a reçu une radiothérapie adjuvante délivrant 45 et 64,8 Gy, en 25 et 36 fractions, respectivement, dans les aires ganglionnaires inguinales bilatérales et la région vulvaire. À 30 mois, il n’y avait pas de récidive locale, mais une récidive pulmonaire prouvée histologiquement. L’analyse génomique a retrouvé un transcrit de fusion MYB-NFIB et une mutation somatique de PLCG1 (phospholipase C, gamma 1). Ce cas a servi de point de départ à une revue de la littérature rassemblant 100 cas publiés. Les types de chirurgie les plus fréquemment réalisés étaient la vulvectomie radicale (30 %), l’hémi-vulvectomie (17 %), l’excision large (21 %) et l’excision locale (24 %). Quarante-quatre pour cent des patientes ont reçu une radiothérapie, plus fréquemment en cas d’atteinte des tranches de section (71,9 contre 29,5 %). La radiothérapie pourrait réduire le risque de récidive locale indépendamment de l’atteinte des berges chirurgicales, avec 15,4 % contre 41,9 % de récidives locales avec ou sans radiothérapie, respectivement, en cas de marges saines et 13 % contre 33,3 % de récidives locales avec ou sans radiothérapie en cas d’atteinte des tranches de section. Le risque de rechute tous types confondus était de 40,9 % chez les patientes après radiothérapie contre 48,2 % chez les patientes n’en ayant pas reçu. Le délai médian de la rechute était de 24 mois (6–156 mois). Les sites de récidives métastatiques les plus fréquents étaient les poumons (76,7 %) suivis des os (16,7 %). Le traitement optimal des carcinomes adénoïdes kystiques de la glande de Bartholin reste à définir, mais sa connaissance augmente grâce aux cas cliniques publiés.
Bartholin gland adenocarcinoma with micropapillary features: a case report with molecular evaluation
2023, Pathology
Bartholin gland carcinomas
2023, Diagnosis and Treatment of Rare Gynecologic Cancers
Approximately 6000 women are diagnosed with vulvar cancer annually. Vulvar cancer is a rare disease accounting for 5% of all gynecologic malignancies. Among vulvar cancers, Bartholin gland carcinomas are rarer still, accounting for 1%–7% of all vulvar tumors and less than 1% of all gynecologic cancers. The Bartholin gland (also known as Bartholin’s gland, or greater vestibular gland) was first described by the Danish anatomist Caspar Bartholin in 1675 and has the normal function of providing vulvovaginal lubrication. The Bartholin glands and ducts are located bilaterally at approximately the 4 and 8 o’clock positions in the labia minora, with duct openings just proximal to the introitus, and with an approximate size of 0.5–1 cm. Bartholin gland carcinomas occur in women with a median age of 53 years. The average tumor size at diagnosis is 39 mm. Approximately 17% of all patients are diagnosed with stage I disease, and 28% are diagnosed with stage II disease. Approximately 32% of patients are found to have stage III disease, in which disease has reached the inguinofemoral lymph nodes. Approximately 23% of patients are diagnosed with stage IV disease. Among patients who undergo primary surgical treatment, 5-year survival ranges from 70% to 93%. Here, we present a clinical case of Bartholin gland carcinoma. We address the epidemiology, pathology, diagnosis, work-up, staging, prognostic factors, treatment of primary disease (including lymph node sampling, treatment of stage III or IV disease, postsurgical treatment, and surveillance for recurrence), survival, and patterns of failure for this rare gynecologic malignancy.
Characteristics and outcomes of women with adenocarcinoma versus squamous cell carcinoma of the vulva: A Japanese Gynecologic Oncology Group study
2021, European Journal of Surgical Oncology
Citation Excerpt :
Hence, vulvar adenocarcinoma has been understudied. The few available studies were either limited in sample size or lacking in active comparison with SCC, making the results difficult to interpret [4–7]. In our prior analysis of an unselected population of patients with invasive vulvar cancer, the survival outcomes of women with vulvar adenocarcinoma were similar to those of women with SCC [8].
Studies on vulvar adenocarcinoma are lacking. Thus, we aimed to compare the characteristics and survival outcomes between vulvar adenocarcinoma and squamous cell carcinoma (SCC).
This was a preplanned sub-analysis of a previously organized nationwide retrospective observational study in Japan conducted between 2001 and 2010 (JGOG-1075S). Surgically treated women with stage I-IV vulvar invasive adenocarcinoma were compared to those with SCC. Multivariable analysis was performed to identify patient and tumor characteristics related to adenocarcinoma. Inverse probability of treatment weighting was used to balance the background differences, and a Cox proportional hazards regression model was fitted to estimate the effect of the histological type on survival.
Forty-eight women with adenocarcinoma were compared with 537 women with SCC. On multivariable analysis, women with adenocarcinoma were younger (median age, 64.5 vs. 70 years, adjusted odds ratio [OR] per age 0.975, 95% confidence interval [CI] 0.955–0.995, P = 0.016) and had higher positive surgical margin rates (31.2% vs. 18.4%, adjusted OR 2.376, 95% CI 1.188–4.754, P = 0.014) than those with SCC. However, according to the weighted model, the survival outcomes were comparable (hazard ratio for progression-free survival, 1.088, 95% CI 0.740–1.601, P = 0.667 and hazard ratio for overall survival, 1.008, 95% CI 0.646–1.573, P = 0.973). Similar associations were observed when the cohort was stratified by age (≤70 or >70 years), stage (I-II or III-IV), and surgical margin (negative or positive) (all, P > 0.05).
Vulvar adenocarcinoma is characterized by a younger age at diagnosis and higher positive surgical margin rates than SCC, but the survival outcomes are comparable.
Brain Metastasis From Bartholin Gland Carcinoma
2020, World Neurosurgery
Citation Excerpt :
SCNC of the Bartholin gland (BG) is a rare vulvar tumor of the female genital tract and one of the rarest subtypes of BG malignancies.14 Classically, neuroendocrine tumors metastasize to the liver, bones, and surrounding lymphnodes.6,14,15 Various radiographic methods can be utilized during staging.
Small cell neuroendocrine carcinoma of the Bartholin gland is an extremely uncommon gynecologic tumor. Brain metastasis from a malignant gynecologic lesion is rarely encountered and the prognosis for this type of metastasis is quite poor.
We report a case of a brain metastasis from a small cell neuroendocrine carcinoma of the Bartholin gland that was treated by surgical resection followed by whole-brain radiation therapy and review the literature.
Different treatment options, including resection, stereotactic radiosurgery, and whole-brain radiation therapy, as well as chemotherapy, are available and should each be considered on an individual basis.

View all citing articles on Scopus

View full text

ReviewBartholin's gland carcinoma: Epidemiology and therapeutic management

Abstract

Introduction

Section snippets

Definition

Epidemiology

Histological types

Pretreatment evaluation

Surgical management of the primary tumor

Pronosis

Conclusion

Conflict of interest statement

Authorship statement

Gynecol Oncol

Am J Obstet Gynecol

Am J Obstet Gynecol

Gynecol Oncol

Best Pract Res Clin Obstet Gynaecol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Int J Gynaecol Obstet

Gynecol Oncol

Gynecol Oncol

J Gynecol Obstet Biol Reprod (Paris)

Eur J Surg Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Eur J Surg Oncol

Gynecol Oncol

Review
Bartholin's gland carcinoma: Epidemiology and therapeutic management