Matthew L. Anderson, MD, PhD, Department of Obstetrics and Gynecology, Baylor College of Medicine, 1709 Dryden Road, Suite 1141, Houston, TX 77030, USA. Email: email@example.com
Vaginal leiomyosarcoma is a rare malignancy for which little data exists to guide treatment decisions. We describe a patient diagnosed with primary vaginal leiomyosarcoma who underwent hysterectomy and upper vaginectomy followed by whole pelvic radiation. Approximately 3 months after her initial treatment, she presented with an isolated pulmonary recurrence, which resolved after 12 cycles of chemotherapy. Nineteen months later, a second recurrence was found at the same site. This metastasis was resected and she has remained without evidence of further disease for more than 24 months. Similar to patients diagnosed with uterine sarcomas, resection of pulmonary metastases may offer women with recurrent vaginal leiomyosarcoma improved survival with good quality of life. Thoracotomy should be considered for women diagnosed with pulmonary recurrences of this disease.
Primary malignancies of the vagina are rare entities, comprising no more than 2% of all gynecological malignancies. Leiomyosarcoma accounts for only a small proportion of vaginal cancers, and no more than 70 cases have been reported in the literature. As a result, treatment decisions for women affected by this disease are based on insight gleaned from the experience of physicians with leiomyosarcoma arising at other anatomic sites. Initial treatment typically consists of surgical resection. Adjuvant chemotherapy appears to have little role for early-stage disease, and it is doubtful that adjuvant radiation therapy benefits long-term patient survival(1,2).
Several retrospective studies have suggested that the resection of pulmonary recurrences of uterine sarcomas significantly extends overall patient survival with limited morbidity(3,4). These observations suggest that the resection of pulmonary metastases from recurrent vaginal leiomyosarcoma offers a similar survival benefit. Here, we report a patient whose clinical experience is consistent with this hypothesis.
A 43-year-old Caucasian woman was first noted to have a small (<1 cm) cyst on her anterior vagina during routine examination. Past medical history was significant for low-grade cervical dysplasia, which was successfully treated by cryotherapy 7 years earlier. All subsequent Pap smears had been normal. Within 3 months, this cyst had enlarged dramatically, at which time a biopsy was performed. Microscopic examination revealed a neoplasm composed of spindle-shaped cells with 52 mitoses per ten high power fields. Imaging studies of the patient’s chest, abdomen, and pelvis were otherwise normal. The patient was taken to the operating room, where examination revealed a friable, 9-cm pedunculated mass arising from the anterior vaginal wall, distinct from the cervix. It was initially transected at its base, after which a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and upper vaginectomy were performed. No other metastatic disease or bulky lymphadenopathy was noted intraoperatively, although a hepatic wedge biopsy was performed to excise several suspicious cysts in the patient’s liver. No other staging procedures, such as sampling of the inguinal or pelvic lymph nodes, were performed.
Subsequent immunohistochemical analysis of the tumor revealed expression of vimentin, smooth muscle actin and keratins, as well as caldesmin and calponin. No evidence of S-100, HMB-45, cytokeratin 5, cytokeratin 6, CD31, CD34, or low molecular weight keratins was found. Rare cells were positive for myogenin. The patient’s liver biopsy revealed evidence of only benign hepatic cysts. There was no evidence of malignancy found in the patient’s uterus, cervix, ovaries, or fallopian tubes.
Approximately 3 months after her surgery, a small (1 cm) solitary nodule was discovered in the lower lobe of her right lung by computed tomography. This nodule was presumed to be recurrent leiomyosarcoma and initially treated with eight cycles of gemcitabine and docetaxel followed by an additional five cycles of gemcitabine alone. Although this treatment resulted in a complete clinical remission, a 1 cm pulmonary nodule was observed in a very similar position in the lower lobe of the patient’s right lung 19 months later (Fig. 1). As a result, the patient underwent thoracotomy with successful en bloc resection. Microscopic inspection of the second surgical specimen revealed a tumor with similar histologic features as the original vaginal sarcoma. The patient recovered from this surgery without complications and has remained free of disease for more than 24 months without further treatment.
Smooth muscle is a component of many tissues and organs. As a result, leiomyosarcoma can arise at almost any anatomic site in the human body. In women, approximately one-third of leiomyosarcomas originate in the gastrointestinal tract, particularly the small bowel and colon. Another one-third of leiomyosarcomas in women are found in the uterus. Because leiomyosarcomas occur only rarely at any anatomic site, their management presents a particular challenge, given the paucity of objective information to guide treatment. The clinical management of vaginal leiomyosarcoma is particularly challenging in that the rarity of this malignancy prevents physicians from directly comparing treatment alternatives. As a result, clinicians rely on their experience with leiomyosarcomas arising at other anatomic sites, such as the uterus. This approach is not unreasonable as vaginal and uterine leiomyosarcomas appear to have very similar natural histories, and smooth muscle cells in both the uterus and vagina are rich in estrogen receptors(5).
Resection of recurrent leiomyosarcoma was first found to benefit patient outcome in a retrospective study of 45 patients with pulmonary recurrences of different uterine sarcomas(3). Although leiomyosarcoma accounted for less than half of the cases in this study, thoracotomy resulted in long-term survival for a significant number of patients. A subsequent retrospective study from the same institution also concluded that optimal debulking of recurrent uterine leiomyosarcoma significantly improves patient survival, regardless of anatomic location of the recurrent disease(4). However, only 18 of the 41 patients in this second study had pulmonary recurrences. Similar results have been observed following the resection of pulmonary metastases from other soft tissue sarcomas(6).
In the present report, we describe a patient who experienced two pulmonary recurrences of vaginal leiomyosarcoma. The first recurrence was treated with a prolonged course of gemcitabine and docetaxel, a regimen with recently documented activity in uterine leiomyosarcoma(7). Although the use of these agents ultimately achieved a complete clinical response, a second recurrence was noted 19 months later, at a site very close to the prior metastasis. The location of this recurrence suggests that a very small volume of disease may have persisted, despite a prolonged course of chemotherapy. An optimal debulking was performed with her second recurrence, which has resulted in a much longer lasting clinical remission. An improved outcome may have been achieved by removing a population of chemotherapy-resistant cells that might have subsequently been responsible for tumor regrowth. Perhaps most importantly, this surgery resulted in no significant functional impairment in the daily activities of this very active patient. Using the search words “leiomyosarcoma,”“vagina,”“thoracotomy,” and “resection” to electronically search the medical literature from 1950 until the present, we could find no evidence that the resection of pulmonary metastases has been previously reported for patients with recurrent vaginal leiomyosarcoma. This case suggests that optimal debulking of recurrent pulmonary disease may offer a significant survival benefit for women with pulmonary recurrences of their vaginal disease, similar to other sarcomas that arise in the uterus. Until further data is available to more definitely address this question, we would suggest that thoracotomy be considered for women with vaginal leiomyosarcoma who experience a pulmonary recurrence and are fit to undergo surgical resection of their disease.