Adenoid cystic carcinoma of the Bartholin's gland: Report of two cases and review of the literature

Gynecologic Oncology 100 (2006) 422 – 425 www.elsevier.com/locate/ygyno

Case Report

Adenoid cystic carcinoma of the Bartholin’s gland: Report of two cases and review of the literature Sook-Young Vivian Yang, Jeong-Won Lee, Woo-Sun Kim, Kyoung-Lan Jung, Sun-Joo Lee, Je-Ho Lee, Duk-Soo Bae, Byoung-Gie Kim * Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Republic of Korea Received 11 February 2005 Available online 27 September 2005

Abstract Background. Adenoid cystic carcinoma (ACC) of the Bartholin’s gland is a rare malignancy of the female genital tract and there have been 62 cases of ACC of the Bartholin’s gland in the literature. Cases. Two cases of ACC of the Bartholin’s gland are reported. Conclusion. There is no consensus on optimal treatment of ACC of the Bartholin’s gland. Most commonly, wide local excision and radical vulvectomy with or without lymph node dissection, are performed. More long-term follow up is recommended to evaluate optimal primary treatment and roles of radiotherapy and chemotherapy because ACC of the Bartholin’s gland recurs and metastasizes long after primary treatment. D 2005 Elsevier Inc. All rights reserved. Keywords: Adenoid cystic carcinoma; Bartholin’s gland; Vulvar carcinoma

Introduction Primary carcinoma of the Bartholin’s gland, first documented by Klob in 1864, is a rare malignancy tumor comprising less than 1% of all female genital malignancies and 2 –7% of all vulvar carcinoma [1]. The diagnostic criteria of primary Bartholin’s gland carcinoma were established by Honan in 1897: correct anatomic location of the tumor, with a primary location deep in the labia, with the overlying skin intact and the histologic presence of some elements of glandular epithelium [2]. Adenocarcinomas and squamous cell carcinomas comprise 90% of these tumors, but sarcomas, melanomas and undifferentiated tumors have been reported [3]. Adenoid cystic carcinoma (ACC) is a rare variant of Bartholin’s gland carcinoma, accounting 10 – 15% of all Bartholin’s gland malignancies [4,5]. ACC of the Bartholin’s gland is a slow growing tumor characterized by perineural infiltration, with marked tendency for local recurrences proceeding distant metastasis by months or many years. There have been 62

* Corresponding author. Fax: +82 2 3410 0630. E-mail address: [email protected] (B.-G. Kim). 0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.08.030

reported cases of ACC of the Bartholin’s gland in the literature. We present our experience of two patients with ACC of the Bartholin’s gland and review of the literature. Case reports Case 1 A 43-year-old woman presented with bean-sized palpable nodular mass in left vulvar area that had appeared 9 months earlier and was increasingly becoming painful. Mass was excised and the pathology showed ACC of the Bartholin’s gland with perineural and muscle invasion. No safe margin was achieved. She was then referred to our department. On physical examination, a 2  2 cm sized nodular mass was palpable in the left vulvar area. Abdomino-pelvic MRI showed no residual mass or abnormal inguinal lymph node enlargement. Radical hemivulvectomy with 2 cm resection margins and left inguinofemoral lymph node dissection were performed. Pathology confirmed ACC with extensive invasion into fibroadipose tissues. The size of tumor was 1.7  1.4  1.6 cm and there was also multifocal perineural invasion. The resection margins were all free of tumor and

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Fig. 1. Abdomino-pelvic MRI shows soft tissue mass in right vulva area measuring 7  5  3 cm and involving right clitoris, urethra and ano-rectal junction.

there was no inguinal lymph node metastasis. She received the adjuvant external beam radiation of total 6600 cGy to perineum and both groin areas over 33 fractions. It has been 17 months since the surgery and she is currently free of recurrence. Case 2 A 50-year-old woman underwent elective total abdominal hysterectomy with right salpingo-oophorectomy for leiomyoma and mass excision for right Bartholin’s gland mass. The pathology showed ACC of the Bartholin’s gland and no further treatment was done. A year later, she presented with the recurred right vulvar mass, but refused further evaluation and treatment. She returned 11 months later with vaginal wall mass as well as the right vulvar mass. A wide local excision with temporary colostomy was done. Pathology showed recurrent ACC of the Bartholin’s gland with frequent neural involvement and the resection margins were free of tumor. Two years later, the patient redeveloped the right vulvar mass and, on physical examination, a hard and elongated right vulvar mass of 4.5 cm was palpable with rectal wall invasion. She was then referred to our department. Abdomino-pelvic MRI showed soft tissue mass in the right vulvar area measuring 7  5  3 cm and involving right clitoris, urethra and ano-rectal junction (Fig. 1). There were no abnormally enlarged lymph nodes. She subsequently had total pelvic exenteration with radical vulvectomy with left salpingo-oophorectomy and both pelvic and inguinal lymph nodes dissection, ileal conduit and lower

anterior resection with Hartman’s colostomy. A patch of omentum was mobilized to fill the pelvic defect. The resection margins on pathology were free of tumor and there were no metastatic pelvic and inguinal lymph nodes. A year later, follow up abdomino-pelvic MRI showed multiple metastatic lung nodules, which were confirmed by chest CT. But there was no evidence of local recurrence. Multiple wedge resection and isolated thoracotomy were performed for lung metastasis. Pathology confirmed metastatic ACC (Fig. 2). However, she redeveloped metastatic lung nodules 4 months following the surgery and chemotherapy was commenced. She received 6 cycles of combination chemotherapy consisting cyclophosphamide (400 mg/m2), adriamycin (40 mg/m2) and cisplatin (60 mg/m2). It has been 10 months since the completion of chemotherapy. She has stable disease of lung metastasis with no local recurrence. Discussion ACC, first recognized in 1853, is a specific variant of adenocarcinoma of the salivary and mucous gland. It is found in various locations such as salivary glands, breast, skin and lung. In the female genital tract, ACC is more commonly found in the cervix. Most frequently, the cells are small and darkly stained with scanty cytoplasm. The cells are arranged in nests or sheets that are fenestrated by round and oval spaces, creating the characteristic ‘‘cribriform’’ pattern. Milchgrub et al. found that the type of histologic variant, whether classical, tubular or mixed variant, did not predict the survival from their study of

Fig. 2. Microscopic section of lung metastasis showing the cribriform pattern of tumor (A, low power view; B, high power view).

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Table 1 Adenoid cystic carcinoma of the Bartholin’s gland, primary treatments: resection margins and recurrences Treatment

Positive resection margin

Recurrence

Local recurrence

Distant, metastasis

Primary treatment Simple excisiona (n = 33) Radical vulvectomy (n = 30)

12 (48.0%), NS, 8 6 (30.0%), NS, 10

20 (68.9%), NS, 4 12 (42.8%), NS, 2

16 (55.1%) 4 (32.1%)

9 (31.0%) (3 lung, 3 bone) 9 (32.1%) (6 lung, 4 bone, 1 skull)

9 (64.3%), NS, 1

5 (35.7%), NS, 1

Adjuvant treatment Radiotherapy (n = 15)

0 (0%)

5 (35.7%) (5 lung, 2 bone, 1 liver)

NS, not specified. This table is a compilation of data from Refs. [1 – 10,13 – 16,19 – 25]. a This includes local excision (n = 26), partial vulvectomy (n = 1) and simple vulvectomy (n = 6).

17 patients whose histologic and survival data were available [6]. ACC of the Bartholin’s gland is a slow growing tumor, with a tendency for perineural invasion. The perineural invasion is characteristic and a possible cause for the pruritus and pain. The average age of patient was 47 years old and the most common symptom was painful nodule, from reviewing 64 cases reported so far. It has been suggested that the possibility of cancer should be considered when women over the age of 40 present with a Bartholin’s gland mass [7]. Often the lesion is overlooked as a cyst or inflammation and treated by drainage or marsupialization resulting in a delay in diagnosis and even being hazardous as local infiltration can disseminate the tumor in the path of needle [5]. However, Frable and Goplerud [8] demonstrated the usefulness of thinneedle aspiration biopsy in providing a definitive preoperative diagnosis, so that cancer therapy may be planned and carried out in a rational manner. There is currently no consensus regarding the optimal treatment when ACC of the Bartholin’s gland is diagnosed. Two types of procedures have been mostly performed: simple excision and radical vulvectomy with or without lymph node dissection. Table 1 summarizes the data from the literature review. Of 64 cases, one was a postmortem case with widespread metastasis and it was not included on the table. After reviewing the literatures, we found that 68.9% of patients who had simple excision had more than one reported recurrences compared to 42.9% of patients who had radical vulvectomy. Although there is no complete information on the status of the margins at the initial surgery, the positivity of resection margin was 48% in the simple excision group and 30% in the radical vulvectomy group. It has been pointed out that the most important aspect of treatment is to obtain clear surgical margins to lower the recurrence and reintervention rates [3,5,9]. This is in contrast to the findings of Lelle et al. from their experience with 11 patients. They found that all 4 patients who had negative margins developed the local recurrences and suggested that more conservative approach should be employed [10]. Table 2 summarizes the recurrence rate according to the resection margin status. The resection margin status was known in 45 patients and the recurrence rates were 52.9% in the margin positive group and 52.1% in the margin negative group (Table 2). From these results, we can conclude that the status of margin may not be as important as previously thought. For ACC of the salivary gland, there is an

agreement that the negative surgical margin is associated with significantly lower local recurrences and the surgical resection aimed at complete extirpation of the disease with adjuvant radiotherapy is advocated [11]. However, there is still a debate whether it influences the final outcome or distant metastasis [12]. The recurrence rates were not different with margin status according to our review of the cases. But half of the patients with positive resection margin had adjuvant radiotherapy and this could explain the result in part. There is also a limitation in evaluating the importance of resection margin status and primary treatment because ACC of the Bartholin’s gland often recurs and metastasizes after a long period and many of the patients were not followed up long enough. We believe that the surgery should be tailored to the extent and location of the tumor, small and unilateral tumor may be treated with simple excision and radical vulvectomy may be warranted for extensive or midline involvement of the tumor. Including this case, there have been 4 cases of pelvic exenteration [5,7,13]. There have been 31 lymph node dissections (27 inguinofemoral; 4 inguinal; 4 inguinofemoral and deep pelvic lymph node) reported so far and only two showed positive nodes [4,14]. Both were located on the ipsilateral side of the primary tumor and one patient had suspicious lymph node on preoperative abdomino-pelvic CT. One of our patients had no metastatic lymph node despite large tumor size and such short interval to the development of the lung metastasis. This confirms that the tumor may metastasize to distant organs before regional lymph nodes. From these results, need for inguinofemoral and pelvic lymph node dissection should be questioned unless the nodes are clinically and radiologically involved [5,10,15,16]. If performed, it should at least be limited to the ipsilateral side of the tumor [9]. Adjuvant radiotherapy has been recommended for patients with positive surgical margin or perineural involvement. Rosenberg et al. and Copeland et al. have reported benefits of postoperative external beam radiation for patients with Table 2 Adenoid cystic carcinoma of the Bartholin’s gland: resection margins and recurrences Resection margin

Recurrence

Positive (n = 18) Negative (n = 27)

9 (52.9%), NS, 1 12 (52.1%), NS, 4

NS, not specified. This table is a compilation of data from Refs. [1 – 10,13 – 16,19 – 25].

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positive margins [2,9]. Adjuvant radiotherapy was used in 15 patients, 9 with positive resection margins. There was no local recurrence. However, five patients, all with positive resection margins, developed distant metastasis. It seems that the adjuvant radiotherapy does lower the incidence of local recurrence in patients with positive resection margins. Bone and lung are the most common sites of metastasis for ACC of the Bartholin’s gland. Liver, kidney and brain metastasis occur less often [6]. There is limited evidence concerning the role of chemotherapy due to small number of cases. Budd et al. reported complete remission of metastatic ACC of the salivary gland using a combination of 5fluorouracil, adriamycin and mitomycin [17,18]. Several chemotherapeutic treatments for metastatic ACC of the Bartholin’s gland have been reported including combination of methotrexate, dactinomycin and chlormbucil, adriamycin [19] and cyclophosphamide [10]. Abrao et al. reported using combination of cyclophosphamide and adriamycin for two patients with lung metastasis, but it is too early to evaluate the results [15]. We used 6 cycles of cyclophosphamide, adriamycin and cisplatin for one of our patients with lung metastasis, achieving only stable disease status. ACC of the Bartholin’s gland is a slow growing tumor with late clinical presentation of recurrence and distant metastasis. According to Copeland et al., 5-year progress free interval is 47% and the 5-year survival rate is 71%. They are 38% and 50% respectively in 10 years and 13% and 51% at 15 years. From these results, it has been suggested to use 10- to 15-year survival rates rather than 5-year survival rates for ACC of the Bartholin’s gland [2,7]. In conclusion, ACC of the Bartholin’s gland is a rare malignancy of the vulva. Due to small number of the patients and lack of data, there is no consensus regarding optimal treatment. From reviewing cases, we believe that the resection margin may not be important for the recurrences. Although the radical vulvectomy group has lower resection margin positivity and recurrences, it is associated with higher operative complications and it seems best to tailor the surgery to the patients. The inguinofemoral and pelvic lymph node dissection should be reserved for the patients with clinically and radiologically suspicious lymph nodes. There is no standard adjuvant therapy for ACC of the Bartholin’s gland, but adjuvant radiotherapy lowers the local recurrence in patients with positive resection margins. Although chemotherapy has been used for distant metastasis of ACC of the Bartholin’s gland, its role is still unclear. The additional information gained during follow up of the patients presented here should be valuable to help understand this rare tumor and its treatment. References [1] Cardosi RJ, Speights A, Fiorica JV, Grendys Jr EC, Hakam A, Hoffman MS. Bartholin’s gland carcinoma: a 15-year experience. Gynecol Oncol 2001;82(2):247 – 51. [2] Rosenberg P, Simonsen E, Risberg B. Adenoid cystic carcinoma of Bartholin’s gland: a report of five new cases treated with surgery and radiotherapy. Gynecol Oncol 1989;34(2):145 – 7.

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