A 44-year-old woman, G3P1T1L1, was referred to gynaecology oncology services by her family physician (on the two-week wait pathway), for a suspected diagnosis of vulvar neoplasm. The woman presented at her local surgery with a large right labial mass that was causing persistent perineal discomfort. The mass measured approximately 30 × 40 mm in size and had been growing slowly over the past two years. When seen by the gynecology oncology team, a few weeks later, the woman denied local pain, itching, discharge or bleeding but she complained of increased discomfort with sitting and cycling. She reported no abdominal pain, urinary or bowel symptoms. She also had no symptoms of cachexia or infection.
The woman had a history of mild, seasonal, non-medicated asthma and depression, for which she was treated with Fluoxetine, 20 mg OD. She reported secondary amenorrhea, as a consequence of a Mirena IUS inserted 5 years previously for contraceptive purposes. Prior to the IUS insertion, she used oral contraceptives for almost 20 years. She was not sexually active at presentation. Her pregnancy and delivery were uneventful. Except for a Chlamydia infection in her early twenties, she had no other gynecologic history. Her Papanicolaou smear was normal, and her cervical screening was up to date. She did not smoke, drink alcohol, or used recreational drugs. She had no drug allergies. There was no history of gynecological cancer in her close family.
On examination, she was systemically well, and her vitals were stable. Her general physical examination was unremarkable. Local examination identified a 50 × 60 × 70 mm non-tender mass on the posterior aspect of the right labia majora. This was well delineated and has a moderately firm consistency. There were no signs of infection or inflammation or other suspicious features. There was no generalized lymphadenopathy or large inguinofemoral lymph nodes at bilateral palpation of the groins. The clinical impression was a large right Bartholin cyst, and the patient was counselled about management options, re-assured, and by mutual agreement was added to the surgical waiting list to be treated by the benign gynecology team.
While awaiting surgery, the patient noted enlargement and swelling of the vulvar mass that became painful. Referral and re-examination by the oncologic gynecologist four months later found an increased in size, now moderately tender labial mass of 80 × 80 × 70 mm. There was still no evidence of an inflammation or abscess. Except for accelerated growth, there were no other suspicious features of malignancy. Her surgery was planned in several weeks for excision of Bartholin gland cyst and replacement of Mirena coil.
Macroscopic examination of the surgical specimen showed a circumscribed mass, 80 × 70 × 40 mm, weighting 117 gm. The external surface of the mass was ragged and tan coloured. The cut surface was solid with a white “whorled” appearance. Histological examination revealed a well circumscribed tumor (Fig. 1 Panel A, B), composed of intersecting fascicles of uniform spindle-shaped cells with elongated ovoid nuclei and fairly abundant eosinophilic cytoplasm (Fig. 1 Panel C). There was no cytological atypia or coagulative tumor necrosis, and the mitotic count was less than 1 mitotic figure per 10 high powered fields. Immunohistochemistry showed that the cells were diffusely positive for smooth muscle actin (SMA), desmin, and h-caldesmon (Fig. 2, Panel A, B, and C, respectively). The morphological and immunohistochemical features were those of a benign vulvar leiomyoma.
The patient was informed on the report of vulvar fibroid and re-assured regarding the benign character of the vulvar growth. Two years post surgery, the patient remains well, and is completely asymptomatic, with no evidence of disease recurrence.
Discussion and Conclusions
Here we presented a case of vulvar smooth muscle neoplasm that mimicked a Bartholin gland cyst and was also suspected of possible malignant transformation. Although rare, vulvar leiomyomas may occur at the same location as Bartholin duct cysts or abscesses and, as illustrated by this case, the clinical diagnosis by physical examination is challenging. Most vulvar leiomyomas are initially clinically misdiagnosed as Bartholin cyst or abscess. In our case, the woman had no pain and inflammatory signs, which excluded the diagnosis of Bartholin’s abscess. Absence of signs of infection combined with the latency in tumor growth prompted the initial patient referral to oncology specialist. The tumor characteristics on examination pointing rather to a cystic than a solid structure led to the specialist diagnosis of Bartholin cyst, a more common clinical encounter than that of a Bartholin fibroma.
Vulvar leiomyomas are uncommon benign mesenchymal tumors which are usually asymptomatic but can cause swelling and local discomfort. Leiomyomas are benign soft tissue tumors of mesenchymal origin. Vulvar leiomyomas are rare benign monoclonal tumors, that occur most commonly in the fourth and fifth decades of life (3). A recent review found 41 years the average age of occurrence, with a range from 15 to 73 years (2). As with our case, the personal and family histories of patients with vulvar leiomyoma generally reveal no abnormal findings (2, 5–7). The genetics of vulvar leiomyoma remain undefined; several possible genes (high-mobility group AT-hook 2 gene (HMGA2), factor gene pleomorphic adenoma gene 1 (PLAG1), RBI-inducible coiled-coil 1 gene (RB1CC1)) might be involved but the mechanism through which any of these genes regulate the aberrant smooth muscle cell development and survival has not been identified (8, 9).
Three principal histological patterns of vulvar leiomyomas have been identified: spindled, epithelioid, and myxoid or myxohyaline, although combinations of these can also be present (10). The management is similar for all histological types. The spindled pattern, present in our case, is a relatively common type of vulvar leiomyoma, in which there is a fascicular proliferation of spindle-shaped cells with ovoid to elongated nuclei and richly eosinophilic cytoplasm (2, 5). The key to histologic differentiation between benign and malignant forms, respectively between leiomyoma, atypical leiomyoma, and leiomyosarcoma are a set of criteria defined by Tavassoli & Norris and later modified by Nielsen et al and Nucci & Fletcher (2, 5, 10, 11). The differentiation criteria between the three forms are presented in Table 1. Both leiomyomas and leiomyosarcomas are positive on immunohistochemistry for smooth muscle cell markers, including smooth muscle actin, desmin, and caldesmon. In addition, leiomyosarcomas are immunopositive for S-100 and cytokeratin. S100 is present in myoepithelial cells (12–14). A recent review shows their importance as markers in cancer (12). Some of these tumors may express oestrogen, progesterone, and androgen receptors (15–18), the significance of which for the development of these tumors is not fully understood (19). Therefore, for our case, we did the smooth muscle cell markers to aid in the differential with malignancy. A relationship between hormonal contraception and growth of such tumors has not been established to date, thus, potential involvement of the contraception used by our patient to the development and growth of the vulvar tumor, although possible, was not inferred. The hormonal receptors staining was not considered to have played a role in the diagnosis or management of our patient. However, the relationship between hormones and the growth of vulvar leiomyomas warrants further study.
Differential histologic diagnostic criteria between benign and malignant neoplasm of smooth muscle cells tumors of the vulva.
Tavassoli & Norris criteria (1979)26
1) ≥ 5 cm in the greatest dimension
2) Infiltrating margins
3) ≥ 5 mitotic figures per 10 high-power fields
Nielsen et al criteria (1996)21
4) moderate to severe cytological atypia
Nucci & Fletcher (2000)25
5) coagulative tumor necrosis
1 criteria: Leiomyoma
2 criteria: Atypical leiomyoma
≥ 3 criteria: Leiomyosarcoma
any 1 to 4 criteria & criteria 5: Leiomyosarcoma
The differential diagnosis of a solid growth the Bartholin’s gland include leiomyoma, primary carcinoma, and leiomyosarcoma and other vulvar mesenchymal lesions such as cellular angiofibroma, angiomyofibroblastoma and aggressive angiomyxoma. (22–24). Leiomyosarcomas of the vulva are very rare, thus frequently mistaken for benign Bartholin’s gland lesions, which delays the diagnosis and management. The treatment is complex, generally aiming for complete excision with a goal of pathologic confirmation of negative margins (6). Radical hemivulvectomy with inguinal lymphadenectomy has been reported for some cases (25). Multidisciplinary discussions between oncologists, gynecologist, and pathologists can provide guidance to ensure that adequate surgical excisions are performed and advise on the need for radiotherapy and chemotherapy, as these tumors are aggressive, with high rate of recurrence and distant metastases (25–27). The role of adjuvant therapy is not clear and comparisons between studies are rather difficult to reach a clear consensus.
Other vulvovaginal mesenchymal lesions, such as aggressive angiomyxoma and cellular angiofibroma can be distinguished from vulvar leiomyoma through histological evaluation and immunohistochemistry, specifically the absence of diffuse staining for smooth muscle markers (especially h-caldesmon). Bartholin gland carcinoma is another rare differential, presenting as a painless swelling, which may be clinically confused with a Bartholin gland cyst or abscess. Histologically, these tumors are a heterogeneous group; adenocarcinoma and squamous cell carcinoma each account for approximately 40%, adenoid cystic carcinoma for 15%, and adenosquamous carcinoma for 5%. Their treatment, which is not yet standardized, include either wide local excision or radical vulvectomy and lymphadenectomy followed or not by local radiation therapy, or radiotherapy alone. A study by Balat et al (20) showed no difference between the treatment employed in the rate of primary tumor control or 5-year disease-free survival rate, whereas others found that conventional therapy yielded a 5-year survival of 67%, with two thirds of the patients having a local recurrence in spite of local radiotherapy (21).
In contrast to solid tumors, which often present as gradually enlarging painless masses, the Bartholin ‘s abscess presents as a painful lump, that over time becomes fluctuant, and associates with fever and local inflammation. The Bartholin’s cyst is less painful but may cause local discomfort and often associates with history of recurrent Bartholin’s abscesses. A recent systematic review found that there is no current randomised trial evidence to support the use of any single surgical intervention for the treatment of a symptomatic cyst or abscess of the Bartholin’s gland (22–26).
As our case illustrates, histological evaluation is essential for diagnosis, especially if there are clinical features suggestive of malignancy such as accelerated growth. As such, we support the premise that a biopsy-excision or at least a biopsy should be performed before attempting other procedures such as cyst drainage in cases were the clinical context is not fully relevant of the presumed pathology. Establishment of a full differential diagnosis and correct final diagnosis are essential for optimal clinical management.
Various reports comment on the importance of imaging of vulvar neoplasms, which may confirm the presence, location, size of the tumor, and help with its characterization. Ultrasonography is the most widely used diagnostic tool because of easy access, low costs and being non-invasive. Pelvic computed tomography and pelvic MRI are more sparingly used and employed for rather difficult cases or were malignancy and/or local spread is suspected (2, 19, 27). As with many other reports, we have not employed any of the technologies above. As the tumor was solitary, well circumscribed, asymptomatic for a long time, and clinical evaluation did not find any suspicious features, a benign neoplasm was suspected with a high degree of certainty and thus no imaging investigations were deemed necessary. However, the place of different imaging methods in positive and differential diagnosis of vulvar tumors is not clear. No consensus exist regarding which method should be employed and criteria for positive diagnosis have not been defined.
There is limited reporting of secondary outcomes of vulvar leiomyoma, including hematoma, infectious morbidity, persistent pain, dyspareunia, and risk of recurrence. In spite of careful haemostasis with ligature and diathermy of the blood vessels from the tumor bed, a haematoma did form several days after the surgery in our patient. Non-obstetric vulvar haematomas are not common and there are no guidelines for their management. However, the principle of management in obstetric haematomas can be applied by analogy to the haematomas post gynecologic surgery (28, 29). Thus, due to size and discomfort symptoms reported by the patient, we opted for drainage in order to reduce the pain, accelerate the recovery, and prevent secondary infection and necrosis.
Regarding the recurrence risk of vulvar leiomyomas, the opinions are controversial. For instance, Nielsen et al. recommend close long-term follow-up because of the high risk of recurrence (5). From 25 smooth-muscle tumors of the vulva analysed in that study, 19 were followed up to an average of 5 years and four had local recurrence and one distant metastasis was found (5). Whereas in several other reports, the patients had one to two recurrences during a median follow up period of 25 months, others found no recurrence at one or two years, as was the case in our patient (2, 30, 31). Complete enucleation or excision of the tumor with surrounding normal tissue decreases the rate of recurrence and increases the five-year survival rate (5, 30). Considering the small number of cases and limited available follow-up data, the long-term clinical behavior of vulvar leiomyoma remains to be established.
Clinical experience with diagnosis and management of smooth muscle tumors of the vulva is scarce. More data is required to improve knowledge on the natural history, diagnostic criteria, optimal management, and prognostic factors of vulvar neoplasms. Because these lesions can present with late-relapse, long-term follow up is advised until more evidence is available.