zyxw zyx zyx zyxwvuts zyxwvutsrqponm zyxwvutsrqponm zyxwvutsrqpon Aust N Z J Obstei G y m 1 2001; 41: 1: 7 8 8 1 GYNAECOLOGICALONCOLOGY Primary Bartholin gland carcinoma: a report of seven cases Andreas Obermair,lJ Susanne Koller,l Alexander J Crandon,' Lewis Perrin.' and James L Nicklin' Queensland Centrefor Gynaecological Cancel; Royal Women'sHospital.' Herston, Quolensland,Austmlia. University Hospital Medical School Vienna, Department of Gynecology and Vienna. Austria SUMMARY This study reviews our experience with 7 patients with primary Bartholin gland cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and compares this with previously p u b lished data. A retrospective clinicopathologic review of all patients with primary BGC treated at QCGC from 1988 to 2OOO was performed. Of the 7 patients treated, all underwent primary surgery and 5 of the 7 patients received radiotherapy postoperatively All patients presented with a local swelling or a lump.Two had associated discharge and 2 had asso ciated pain. Of the 7 patients, 2.3 and 2 respectively were classified as having Stage IB, I1 or I11 disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had adenoid-cystic carcinoma and 1 had a small-cellneuroendocrine cancer of the Bartholin INTRODUCTION Primary carcinoma of the Bartholin gland is a rare malignant tumour comprising less than 1% of aU primary female genital tract tumours.l3 Because of the low incidence, knowledge of management and factors influencing the clinical outcome of patients with Bartholin gland carcinoma is limlted. Consequently. we reviewed our series of patients with primary Bartholin gland carcinoma and report our experience with this rive tumour in a Gynaecologfcal Cancer Centre. We also present the flrst recorded case of small cell carcinoma of the Bartholin gland. gland. None of the patients with SCC developed recurrent disease. The patient with adenoidcystic carcinoma experienced local recurrences at 4 years and again at 5 years and 3 months. Nine years after primary treatment she was diagnosed with pul. monary metastases. The patient with small-cellneuroendocrine cancer of the Bartholin @and was considered tumour-free after operat ion. Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no evidence of disease. She died 1 year and three months after diagnosis from disseminated pulmonary disease. We present the first report of small cell neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the management of vulva1 cancer at other sites appear to be appropriate for manage ment of BGC. MATERIALS A N D METHODS Patients The records of all pattents dhgn& with ~ r l v n ran l cer treated at the W<;C W e n Jnnimry izIlR nnd March #K10 were rrvicwnf Fmm thew WM-&P H'F idrn tUled all pntlents whose di-waw Pulnllcd the critrrln for Bartholln gland canwr (tUW (1) the turnour art.- at the site of the Hartholln gland. (ll)the tumoirr is m n ststen?histologically with R p r l m r y n m p k ~ n of t ths Bartholin gland: (ill) them is no Pvldcnm Crc n prm-tous. c o n m n t . or subsequent primary tumoirr d similar histological type el-whcrr. A total of t mtlents ful filled the crlterh for RCG and form the h i s td this report. Petient charastcrist im arc l b t d In Table I zyxwvuts zyx Treatment Address To? correspondence Andmas ObermaIr MD Queensland Centre for CynaecologlcalCancer Ned Hanlon Building. Royal Womens Hoapitai Herston Bueensland r10*,Australia Andreas Obermair MD. Susanne Koller MD. Alexander J Crandon MD. Lewis Perrin MD. James L Nicklin MD Local treatment consisted of 8 radical hemiv-uI~w tomy (n = 4) or of a wide local excision ( n :u Dissection of the inguinofemoral lymph ncwlcs w a s carried out in all but 2 of the pitrents Rea.sons for not performing the inguinofemoral lymphadrncctom) included medical masons (n 1) and ~pfii.~71 of the patient (n = 1). A single patient m n p d pvrincal zyxwvutsrq zyxwvut zyxwvut zyxwvuts zy zyxw zyxwvuts ANDREAS OBERMAIR ET AL radiotherapy (60 Gy) plus groin radiotherapy Three patients received groin and pelvic radiotherapy Radiotherapy was given as a direct perineal field (60 Gy) without a groin field (n = l), or with a groin field (n = 3), and chemoradiation of the vulva with groin fields was given in 1patient. Two patients did not have any radiotherapy The 1988 International Federation of Obstetrics and Gynaecology (FIGO) staging system for vulvar cancer was used to classify stage of disease. Treatment is listed in table 1. During the study period 370 patients were treated by the Queensland Centre for Gynaecological Cancer (QCGC) for vulva1 carcinoma. The diagnosis of primary Bartholin gland cancer (BGC) was established in 7 of these 370 patients (1.9%). All 7 patients fulfiled the criteria for a primary BGC and therefore none Case Age Tumoursize (mm) . . 1 63 2 66 mx4 3 49 35xmxm 4 71 22 5 44 65 x 40 x 30 6 45 30 7 55 45x35 14x13~4 were excluded from analysis? The mean age was 56.1 years (range 4p71 years). The main presenting symptoms were a local swelling or lump in all7 patients along with pain (n = 2) or vaginal discharge (n = 2). The delay of diagnosis ranged from 6 weeks to 2 years (Table 1). No patient was found to have a second pathology but 1 was found to have vulvar inlra-epithelial neoplasia 0 III on the vulva. Squamous cell carcinoma was noted in 5 of the 7 patients. Adenoid-cystic carcinoma was found in 1 patient and a small cell cancer of neuroendocrine origin also was noted in a single patient. One patient (Case 3) had a history of 5 months local swelling and underwent local excision of an encapsulated tumour with clear margins. She was diagnosed with a small cell neuroendocrine-type caner of the Bartholin gland on the right side with intact skin overlying the carcinoma.The histologicalfeatureswere typ zy zyxw zyxwvutsrq zyxwvut RESULTS Table 1 Patient characteristics 79 Duration of symptoms before diapsosis - Histology Stage SCC SCC small cell, neuroendocrine SCC Adenoidcystic m 6 weeks II II 2 months m 3 months II 2 Years IB 6 weeks 2 months SCC SCC m 5 months Follow-up NED 5 years, 6 months NED 6 years, 1month Died 15months, disseminated disease NED 3 years, 9 months Rec # 1:4 years, local Rec # 2: 5 years. 3 months, mom pubis Rec # 3: 9 years, pulmonary metastam. Alive with disease NED 2 years NED 5 months NED = No evidence of disease, SCC = Squamous cell earcinoma, Rec = Recurrence Table 2 Treatment details Initialtreatment surgicalmargins Radiotherapy Nod= postoperative 1 Excision biopsy, radical hemivulvectomy, bilateral inguinofemoral node dissection Clear but close (0.5mm) Perineal field Negative 2 Local radical excision, chemoradiation Involved Chemoradiotherapy and fields to perineum,both groins and pelvis Not done 3 Local excision Clear but close Nil Not done 4 Radical hemivulvectomy, bilateral inguinofemoral node dissection Clear but close (1.5 mm) Field to lefl groin and hemipelvis Left groin: 1 of 9 positive Right groin: negative 5 Radical local excision, bilateral inguinofemoral node dissection Clear Field to vulva Negative 6 Excision biopsy, radical hemivulvectomy, ipsilaterd inguinofemoral node dissection Clear Nil Negative 7 Excision biopsy, radical hemivulvectomy, bilateral inguinofemoral node dissection Clear but close (6 nun) Field to groins and pelvis Lfft g r o k 3 Of 10 positive Rightgroin: negative Case 80 zyxwvut zyxwvutsrqponm zyxwvutsr zyxwvutsrqp zyxw zyxwvutsr ANWOG Figure 1A Small cell neuroendocrine-typecancer of the Bartholin gland (40x). Figure 1B Small cell neuroendocrine-typecancer of the Bartholin gland (400~). zyxwv zyxwvutsrqp zyxwvuts ical of poorly differentiated small cell carcinoma with neuroendocrine differentiation. The tumour displayed sheets of poorly differentiated hyperchromatic malignant epithelial cells with scant cytoplasm and granular chromatin. Abundant apoptotic debris and mitotic figures were seen (Figure 1). Tumour cells stained positively with Cam 5.2, neurone specific enolase and synaptophysin, supporting the above diagnosis. Further staging investigations included a CT scan of the chest, the abdomen and the pelvis, as well as a bone scan. The CT scan of the chest and the pelvis showed some minor right inguinal lymphadenopathy which measured 1 cm in diameter with no other enlarged nodes and no soft tissue disease. The right inguinal lymphadenopathy only occurred following the operation on the Bartholin gland, and therefore we considered it a postoperative reactive change. The bone scan was normal. Full blood count and serum biochemistry and thyroid function tests were normal. She refused all further surgical therapy as well as adjuvant radiotherapy and chemotherapy. She died of disseminated pulmonary disease 15 months after diagnosis. One patient (Case 5) had a 2-year history of local swelling and had a simple excision of the Bartholin gland showing adenoid-cystic carcinoma. Five weeks later she underwent radical re-excision of the tumour bed with bilateral inguinofemoral lymph node dissection. Surgical margins were clear and all nodes examined were negative. She was given postoperative radiotherapy to the vulva consisting of 57.5 Gy in 23 fractions. The first recurrence ocurred 4 years later in the anterior vaginal wall and was treated by radical local excision only. The second recurrence ocurred 1 year and 3 months later on the mons pubis and was treated by radical local excision and radiotherapy Nine years after the primary treatment she presented with breathlessness and a chest x-ray revealed multiple pulmonary metastases. She was alive with disease at the time of preparation of this report. DISCUSSION This series reports our experience with BGC and presents the only known example of small cell neuroendocrine cancer of the Bartholin gland. There are fewer than 350 cases of BGC in the entire world literature. This series of 7 patients contributes to the body of understanding of this disease. In our series, BGC accounted for 1.90.0of all vulvar cancers treated at the Queensland Centre for Gynaecological Cancer between January 1988 and March 2000. This incidence is very similar to the 3 O t O noted by previous reports.”.“ In this series the first ever described case of a small cell primary carcinoma of the Bartholin gland is presented (Figure 1). Unlike earlier reports, the majority of patients were diagnosed with a squamous cell cancer (n = 5) with only a single case of adenoidcystic carcinoma. The diagnostic criteria described by Wilkinson were required for a diagnosis of BGC.3That is: (i) the tumour had to occur at the site of the Bartholin gland: (ii) the histological type had to be consistent with a primary Bartholin gland cancer: and (iii) it could not be a metastatic deposit. These criteria apply to all of the 7 patients reported in this analysis. We did not apply the diagnostic criteria espoused by Copeland’j and othet-~,’.~.~ which includes a ‘transition from normal gland or duct tissue to neoplastic tissue‘. This would have specifically excluded the patient with small cell neuroendocrine cancer. This type of malignancy is believed to arise from ubiquitous. solitary neuroendocrine-type cells scattered in the louer genital tract. Therefore. there can be no transition from normal to neoplastic. Similar to the treatment of patients with vulva1 cancer generally. most authors would recommend radical excision of the primary lesion (with a margin of at least 1 cm) plus inguinofemoral Iymphadenectomy.l With BCG, the deep surgical margin is potentially compromised by the proximity to the inferior pubic ramus. Despite the extent of our surgery. surgical zyxwvutsrq zyxwvutsrq zyxwv zyx zyxwvutsr zyxw margins of > 1 cm were achieved in only 2 patients. Four patients had clear surgical margins of < lcm, and a single patient had an involved margin. This would also explain the high rate of adjuvant radiotherapy used to treat the primary site. Inguinofemoral lymphadenectomy was performed in 5 of the 7 patients with a bilateral lymphadenectomy in 4 of the 5 patients. In 1 patient (Case 6 ) only the ipsilateral nodes were removed and proved to be negative. Pelvic lymphadenectomywas not done in any of the patients. In 3 patients the groin nodes were histologically negative and they received no adjuvant radiotherapy. In 2 patients the nodes were positive and both received postoperative radiation to the primary site as well as to both groins and the hemipelvis. Both patients had SCC of the Bartholin gland and were tumour-free at 3 years and 9 months and at 5 months, respectively. Interestingly,no patient with SCC of the Bartholin gland experienced any form of recurrence. The patient with small cell neuroendocrine cancer experienced early widespread systemic recurrence of disease, as is typical of this malignancy arising at other sites. The single patient with adenoid-cystic carcinoma of the Bartholin gland had widespread perineural invasion in the primary lesion. She developed 2 local recurrences despite radiotherapy. This clinical behaviour is well described for this cell type.6 She developed late distant disease 9 years after initial treatment. In summary, we have presented 7 patients with BGC, including the first report of small cell neuroen- docrine cancer of the Bartholin gland. Therapeutic principles in the management of vulval cancer at other sites appear to be appropriate for management of BGC. ACKNOWLEDGEMENT The authors would like to thank Jan Brady, QCGC for assistance in data management. REFERENCES Hacker NF. Vulva Cancer, in:Berek JS. Hacker NF Eds.Practical Gynecologic Oncology. 2nd ed. Baltimore, Williams and WiLkins 1994; 403439. Burke TM.Eifel P. McGuire W, Wilkinson W.Vulva, In:Haskins WJ, Perez CA, Young RC Eds. Principles and Practice of Gynecologic Oncology. 2nd ed. Philadelphia, Lippinmtt Raven 1996; 717-751. Wilkinson EJ. Premaligmnt and malignanttumorsof the vulva, in Kurman RJ Ed. Blaustein’s Pathology of the female genital tract. 4th ed. New York. Springer Verlag 1994.87-129. C m s e n RJ.primary carcinoma of Bartholin’s gland. Am J Surg zyx zyxwvu zy 1948; 75: 597-600. Leuchter RS, Hacker NF. 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