Bartholin gland carcinoma in a young female: a rare disease in an unusual age group

Abstract

Primary Bartholin gland carcinoma (BGC) is an extremely rare disease. It typically presents in elderly women. It can be confused with Bartholin gland cyst, which is a benign condition leading to a delay in diagnosis and treatment. We are presenting a case report of BGC in a 35-year-old woman, which has created a diagnostic as well as therapeutic dilemma.

Background

Primary Bartholin gland carcinoma (BGC) accounts for less than 5% of all vulvar carcinomas and less than 1% of all female genital tract malignancies.¹ It usually occurs in women of postmenopausal age with a median age of 50 years. The cause or pathogenesis is yet unknown but it is thought to be in association with vulvar infections or Bartholin gland infection. Moreover, it has also been seen through previous studies that the aetiological association is with human papilloma virus (HPV) infection specifically with HPV 16.

BGC is a slow growing tumour. The metastasis is mainly through local invasion although lymph node and haematogenous spread is seen as well. The diagnosis of this carcinoma is based on the criteria as described by Chamlian and Taylor. It comprises of evidence of transition to neoplastic elements as depicted histologically and there should be no evidence of primary tumour elsewhere.²

The carcinomas arising from Bartholin duct are usually squamous cell, and those arising from the gland are adenocarcinoma. Occasionally transitional cell, adeno squamous and adenoid cystic carcinomas may develop as well.^{3 4}

BGC can be confused with Bartholin gland cyst, which is a benign condition leading to a delay in diagnosis and treatment.⁵ The treatment modalities for BGC range from surgery to multimodal treatment with chemotherapy and radiotherapy, as suitable and in line with the advancement or stage of the disease. Prognosis for this has been reported to be poor due to late or misdiagnosis that ultimately leads to a delay in treatment.⁶

Case presentation

Here we are presenting a case report of BGC in a 35-year-old woman with the history of unilateral painless perineal swelling for 8 years. This increased gradually in size and became painful and tender in last 6 months. There were no associated symptoms. She had three live born by Lower Segment Caesarean Section (LSCS) and had no known medical comorbid.

Clinical examination revealed, a large left-sided perineal swelling 7×8 cm which was tender to touch and soft in consistency. It was mobile, neither fixed to underlying structures, vaginal mucosa nor to overlying skin. Cervix and vagina appeared normal. No inguinal or femoral lymph nodes were palpable. Pap smear was taken which was reported as normal.

Investigations

The baseline investigations were done which were all normal. Though clinically it looked like a benign Bartholin cyst but the size of the cyst and the duration of 8 years was unusual for the Bartholin cyst. It was therefore decided to go for further imaging before embarking on surgery.

MRI pelvis was done which revealed, a well-defined cystic lesion measuring 50×30×50 mm in Anteroposterior (AP), Transverse (TS) and Craniocaudal (CC) dimensions noted arising from the left posterolateral wall of lower vagina. This lesion was extending into the ischioanal fossa as well as inferiorly into the perineal soft tissues. The left puborectalis muscle was not separately visualised. It was abutting the left wall of the anal canal. This was hyperintense on T2-weighted images and hypointense on T1-weighted images. On post contrast enhancement there was focal thickened enhancing anterior wall up to 10 mm in maximum thickness. Remaining walls were thin. The surrounding fat was clean. No significant pelvic lymphadenopathy. Normal pelvic musculature and skeleton. Normal pelvic bowel loops. Normal urinary bladder. Normal flow-voids identified in major pelvic vessels.

This appearance was suggestive of Bartholin gland cyst.

Differential diagnosis

In view of clinical presentation, examination findings and MRI report the differential diagnosis of Bartholin gland cyst, lipoma, vulvar neoplasm and hidradenoma was made.

Treatment

Considering her age, clinical and MRI findings (Bartholin gland cyst without any local infiltration and any lymph node enlargement in pelvic and inguinal region), she was planned for complete enucleation of left Bartholin gland cyst.

During examination under anaesthesia, there was an enlarged left-sided Bartholin gland 8×8 cm. Incision was given at mucocutaneous junction on left side. Wide local dissection was done and the cystic swelling was completely enucleated. Surgical specimen was sent for histopathology.

Postoperative course was unremarkable.

Outcome and follow-up

The histopathological diagnosis was a surprise to all of us. The histopathologist contacted the primary consultant regarding the confirmation of detailed clinical history and intraoperative findings as they saw malignancy in the surgical specimen. Clusters and nests of tumour cells exhibiting squamoid differentiation were seen invading into the underlying stroma. The tumour was composed of nests of atypical squamous cells with moderate degree of nuclear pleomorphism and hyperchromasia. Mitotic figures and keratin pearls were also seen (see figures 1,2). Thus the final histology of the specimen reported as moderately differentiated squamous cell carcinoma most likely arising in a background of Bartholin cyst.

Figure 1.

Section of cyst wall showing lining of stratified squamous epithelium along with underlying squamous cell carcinoma.

Figure 2.

High magnification showing cluster of tumour cells and keratin pearls.

The case was presented in multidisciplinary tumour (MDT) board meeting. In view of rarity of disease in a very young patient, tumour board decided to review the literature before planning for adjuvant therapy. The final decision of MDT after extensive literature review and discussion was to keep her in close follow-up 3 monthly for clinical examination. The MDT did not recommend any adjuvant treatment in view of her long history (8 years of persistent swelling) and MRI findings which showed well defined cystic lesion with normal pelvic musculature, bones, pelvic bowel loops and normal large pelvic vasculature without significant lymphadenopathy. At her last follow-up, 1 year after surgery she was asymptomatic with no evidence of any recurrence.

Discussion

BGC is a slow growing tumour mostly seen in postmenopausal women. It commonly presents as a painless mass over the vulva. The histology may vary and the aetiology is still not well known. Most of the squamous cell carcinoma of the gland has been linked to HPV.¹

There is currently no consensus on treatment recommendations due to rarity of disease and lack of prospective trials.⁷ Surgery is the most recommended modality of treatment as evident by literature. This includes radical excision with inguino-femoral lymphadenectomy.⁸ Lymphadenectomy can be unilateral or bilateral, though the preference of one over the other is still controversial. In a series of 33 patients from MD Anderson, 42% of patients with BGC had nodal involvement and one-third of these patients developed recurrence.⁵ In our patient inguino-femoral lymph node dissection was not done which is probably not based on current standard guidelines. There are studies suggesting that some women undergoing inguinal lymphadenectomy would have negative lymph nodes on histology. It was presumed that in young women there are less benefit to drive from this procedure at the cost of significant morbidity.⁹ These surgical procedures of vulva are notorious to heal slowly and prone for infections, thus affecting the quality of life of patient.¹⁰

Radiotherapy is the other treatment modality. The main aim of this is to reduce morbidity and to some extent preservence of the normal function. The outcome of both treatment modalities is similar.¹¹ Lopez-varela et al concluded that primary radiation or chemoradiation was equally therapeutic as the surgical outcomes stated by Leuchter et al (71%) and by Cardosi et al (67%).

In addition to surgery and radiation, chemotherapy is also a treatment modality for BGC. It is used in association with radiation. Chemotherapeutic agents like cisplastin and 5-fluorouracil enhance the effects of radiation through radio sensitisation and helps destroy the tumour but harms the gland as well.¹²

Due to sparse data availability over the treatment options of BGC, it is largely based on what is already available for the treatment of vulvar and anal carcinomas. Moore et al published a study on the usefulness of preoperative chemoradiotherapy to preclude the need for radical resection.¹³ In addition to this, Han et al reported for locally advanced vulvar cancers, concurrent chemoradiotherapy reduces local relapse and improves survival when compared with radiotherapy alone.¹⁴

With varied data and discussions in different studies, the treatment for BGC is still not standardised. The need for the development of an optimal treatment option can only be bridged by more extensive studies in the future.

Learning points.

• The index of suspicion should always be high if there is any unusual clinical findings. In our case the size and duration of the swelling was quite unusual for Bartholin gland cyst which prompted us to do MRI pelvis before surgery.

• Any suspicious Bartholin gland swelling should prompt biopsy before planning any definite treatment. In our case, it was a cystic swelling in a 35-year-old woman so biopsy was not considered.

• The awareness of patient as well as the healthcare providers regarding the rare diseases is of utmost importance.