Abstract Background : Epithelioid leiomyosarcoma arising from the uterine cervix is extremely rare, with only few cases reported in the world literature.
J. Afr. Cancer (2012) 4:53-56 DOI 10.1007/s12558-011-0164-y
CASE REPORT / CAS CLINIQUE
Epithelioid leiomyosarcoma of the uterine cervix: a case report and review of the literature Léiomyosarcome épithélioïde du col utérin : à propos d’un cas et revue de la littérature O. Masbah · N. Mellas · I. Bekkouch · S. Mellas · N. Ismaili · M. Kamouni · K. Hassouni · T. Kebdani · N. Benjaafar · B.K. El Gueddari Reçu le 21 juillet 2010 ; accepté le 30 novembre 2010 © Springer-Verlag France 2011
Abstract Background : Epithelioid leiomyosarcoma arising from the uterine cervix is extremely rare, with only few cases reported in the world literature Case presentation : The case concerns a 41-year-old female patient who was admitted to our hospital, with worsening menorrhagia during the past 6 months. Pelvic examination revealed a large tumour of the uterine cervix extended into the upper vagina. Pelvic magnetic resonance imaging confirmed the presence of a cervical uterine tumour. Cervical biopsy and immunohistological study concluded leiomyosarcoma (grade 2). Radiological workup revealed the presence of pulmonary metastasis. A bilateral nephrostomy was performed before treatment because of obstructive renal failure. The treatment of this case consisted of ifosfamide and doxorubicin-based chemotherapy. After three cycles, the assessment of the disease showed partial response. The treatment was continued for three other cycles. But, the second evaluation of the patient revealed tumour progression. The treatment was then stopped, and best supportive care was provided. The patient is still alive. Conclusion : Although exceedingly rare, leiomyosarcoma can arise on the uterine cervix. Management of cervical leiomyosarcoma is extrapolated from the currently accepted
O. Masbah · I. Bekkouch · K. Hassouni · T. Kebdani · N. Benjaafar · B.K. El Gueddari Department of Radiotherapy, National Institute of Oncology, Rabat, Morocco N. Mellas · N. Ismaili Department of Medical Oncology, National Institute of Oncology, 10100, Rabat, Morocco S. Mellas Department of urology, Hassan II University Hospital, 30012, Fes, Morocco M. Kamouni Department of Pathology, National Institute of Oncology, Rabat, Morocco
management of uterine leiomyosarcoma. It is difficult to develop optimal management strategies and to predict prognosis of the disease. Pour citer cette revue : J. Afr. Cancer 4 (2012). Keywords Leiomyosarcoma · Uterine cervix · Chemotherapy · Cervical biopsy Résumé Introduction: Le léiomyosarcome épithélioïde du col utérin est une tumeur extrêmement rare, avec seulement quelques cas rapportés dans la littérature mondiale. Cas clinique: Il s’agit d’une patiente de 41 ans admise dans notre hôpital pour métrorragies datant de six mois. L’examen gynécologique a retrouvé une grosse tumeur du col utérin étendue à la partie supérieure du vagin. L’imagerie par résonance magnétique a confirmé la présence d’une tumeur du col utérin. La biopsie cervicale avec étude immunohistochimique a conclu : un léiomyosarcome (grade 2). Le bilan d’extension radiologique a révélé la présence de métastases pulmonaires. Une néphrostomie bilatérale a été réalisée avant le traitement en raison d’une insuffisance rénale obstructive. Le traitement de ce cas consistait en une chimiothérapie à base d’ifosfamide et de doxorubicine. Après trois cycles, l’évaluation de la maladie a montré une réponse partielle. Le traitement a été poursuivi pendant trois autres cycles. Mais, la seconde évaluation de la patiente a révélé une progression tumorale. Le traitement a été arrêté et la malade a été confiée aux soins palliatifs. La patiente est actuellement toujours en vie. Conclusion: Bien que très rare, un léiomyosarcome peut survenir au niveau du col utérin. Le traitement du léiomyosarcome du col utérin est extrapolé sur le traitement du léiomyosarcome du corps utérin. Il est difficile d’élaborer des stratégies thérapeutiques optimales et de prédire le pronostic de la maladie. To cite this journal: J. Afr. Cancer 4 (2012). Mots clés Léiomyosarcome · Col utérin · Chimiothérapie · Biopsie cervicale
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Introduction Epithelioid leiomyosarcoma is a rare variant of smooth muscle cell tumour. The disease is histologically characterized by a proliferation of predominantly round and polygonal epithelioid cells with eosinophilic cytoplasm [1] Although leiomyosarcoma is one of the most common non-epithelial malignant neoplasms arising in soft tissue and somatic organs, cases arising from the uterine cervix are extremely rare. Most epithelioid leiomyosarcomas occur in the uterine body. Only five cases of this tumour affecting the uterine cervix have been reported in the English literature [1–5] Our objective is to report the clinical and pathological findings, treatment and outcome of Epithelioid leiomyosarcoma of the cervix case of our case and to review the related literature.
Fig. 1 Light microscopy examination: uterine cervix biopsy: sheets and nets of rounded to polygonal cells with abundant eosinophilic cytoplasm
Case presentation A 41 year old women (gravida 8, para 7) was admitted to the National Institute of Oncology at Rabat with worsening menorrhagia for 6 months period. Pelvic examination showed a large tumour of the uterine cervix. The upper third of the vagina was involved by the tumoural process. Biologic tests showed a renal failure. Pelvic magnetic resonance imaging (MRI) showed a solid uterine mass measuring 5cm X 6cm X 8cm associated with iliac lymph nodes and ureterohydronephrosis; so the patient was addressed to the urologist for bilateral nephrostomy. Computed tomography (CT) scan of the lung showed multiples pulmonary metastasis. The histological study of cervical biopsy showed a predominantly epithelioid neoplasm. The connective tissue is infiltrated by a sarcomatoid proliferation of low cellular density. The cells were small to moderately large with eosinophilic cytoplasm. Marked nuclear pleomorphism as well as abundant mitotic activity, including numerous atypical mitotic figures was noted. The mitotic rate averaged 4 mitoses per 10 high power fields. The stroma is fibroinflammatory with a rare necrotic remaniements (Fig. 1). Immunohistochemical studies showed that the tumour was strongly positive for Ki67 (Fig. 2), smooth muscle actin (Fig. 3), and muscle specific actin, focally and weakly positive for desmin. The tumour was negative for S-100 and HMB-45. The immunohistochemical staining pattern, in conjunction with the morphologic features, suggested the diagnosis of an epithelioid leiomyosarcoma. Morphologically the tumour was grade 2. The patient was given three courses of ifosfamide 6g/m2, doxorubicine 60mg/m2. Evaluation after three courses of chemotherapy showed a partial response of the pulmonary
Fig. 2 Immunochemistry: anti-actin antibody positive
Fig. 3 Immunochimestry: anti-Ki67 antibody positive
metastasis and cervical tumour; and complete response of iliac lymph nodes. We have continued the treatment up to 6 courses of chemotherapy. Evaluation after 6 courses by
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pelvic (MRI) and thoracic scanner showed the progress of the cervical tumour size and pulmonary metastasis. Because the decrease of performance status (PS) of the patient (3.0), no further second line chemotherapy was possible. The patient is currently managed with best supportive care, and still alive six months since the beginning of the first cycle of chemotherapy.
Discussion Approximately 30 cervical leiomyosarcomas have been reported in the literature [6–8]. The proportional distribution of all previously reported cases of cervical sarcoma are summarized in Figure 4 [9] Epithelioid leiomyosarcoma arising from the uterine cervix is an exceedingly rare tumor, with only five cases reported in the world literature. All cases were treated by total abdominal hysterectomy and bilateral salpingooophorectomy (TAH + BSO). One of them received neoadjuvant chemotherapy and adjuvant local radiation. Three receive adjuvant chemotherapy. One receives adjuvant high-dose vaginal brachytherapy. Our patient was the first to be metastatic at first time of diagnosis. All the six cases developed lung metastasis, as it the case of those seen in leiomyosarcomas of the uterine corpus [10]. These findings support the fact that this type of neoplasm is a variant of leiomyosarcoma, even if it is extremely rare [4]. Patients with cervical leiomyosarcomas most commonly suffer from abnormal vaginal bleeding and/ or abdominopelvic pain. The tumours are typically large (up to 12 cm in one series) [10], poorly circumscribed masses that either protrude from the cervical canal or thicken and expand circumferentially [10]. Morphologically, epithelioid leiomyosarcoma is characterized by sheets and nets of rounded to polygonal cells with abundant eosinophilic cytoplasm and marked cytoplasmic
Fig. 4 Proportional distribution (estimated) of all previously reported cases of cervical sarcoma [9]
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vacuolization [1]. The current approach is to simply extrapolate diagnostic criteria from the corpus tumours and apply them to their cervical counterparts, incorporating various combinations of cytologic atypia, coagulative necrosis and mitotic activity to predict their malignant potential [11]. However, it is unclear if this is entirely appropriate in all cases [12]. The differential diagnosis for epithelioidleiomyosarcoma in hematoxylin–eosin (H&E) staining, therefore, includes malignant melanoma, metastatic carcinoma, and epithelioid sarcoma. To avoid misdiagnosis of such neoplasms, immunohistochemical features are necessary to support the diagnosis of epithelioid leiomyosarcoma [11]. Typically, melanomas are positive for S-100 protein, HMB-45, Melan-A, and tyrosinase but negative for cytokeratins, desmin, smooth muscle actin, epithelial membrane antigen, and CD68 [13]. Malignant melanoma, and metastatic carcinoma are generally excluded due to the immunohistochemical absence of HMB-45 and cytokeratin expression [11]. In contrast to epithelioid leiomyosarcoma, epithelioid sarcoma shows strong and diffuse expression of keratin markers [14]. In addition, desmin positivity is the most specific indicator of smooth muscle differentiation. Since therapeutic measures have been widely discordant amongest the reported cases, their true natural history and any variations in their malignant potential are not readily evaluable [9]. In a 1983 review [15], the outcomes of 12 previously reported patients for whom follow-up information was available were as follows: Death from the disease (n = 8), alive with recurrences within 2 years (n = 2), and alive after 5 years, disease status unstated (n = 2). In the largest series of 8 patients reported by Abell and Ramirez [10], 4 of the 6 patients died did of distant, hematogeneous metastases. Because of the rarity of the disease, no optimal treatment has been proposed for epithelioid leiomyosarcoma of the cervix. In Table 1 we report clinical and therapeutic characteristics and outcome of all published leiomyosarcomas of the cervix. In general, in theses published cases, treatment algorithm was extrapolated from treatment of uterine leiomyosarcoma [3]. The standard therapy for uterine leiomyosarcoma is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Random biopsies or retroperitoneal lymph node sampling of normal appearing structures rarely yield clinically useful information. With regard to adjuvant radiation therapy, there is no firm evidence from prospective studies that adjuvant radiation therapy is of benefit for patients with uterine sarcomas. Several studies show a trend for improved local control in patients receiving pelvic radiation therapy. In general, the adjuvant use of postoperative radiation therapy reduces pelvic relapse rate by approximately 50%; it is therefore prudent to consider its use in patients at high risk for local failure (tumors _5 cm, high
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Table 1 Clinical and therapeutic characteristics and outcome of all published Leiomyosarcomas of the cervix Authors
Age
Initial management
Adjuvant therapy
Neoadjuvant therapy
Sites of metastasis at first diagnosis
Sites of recurrence after initial management
Status, follow-up, months
Fujiwaki et al [1] Gotoh et al [2] Irvin et al [3] Toyoshima et al [4] Sahu et al [5] Present case
61 72 47 53 25 41
TAH + BSO TAH + BSO TAH + BSO TAH + BSO TAH + BSO CT
CT None RT CT RT None
None None None None CT None
– – – – – Lung metastasis
Lung metastasis None None Lung metastasis Lung metastasis
DOD, 5 NED, 10 NED, 4 NED, 20 NED, 6 NED, 6
TAH + BSO: total abdominal hysterectomy with salpingo-oophorectomy; DOD: died of disease, NED: no evidence of disease, M: months of follow-up.
mitotic count, high grade) [16]. However, radiotherapy treatment doesent shows benefit in survival. Similarly, adjuvant chemotherapy doesn’t significantly improve survival for patients with uterine leiomyosarcoma. Metastatic LMS of the cervix is managed in analogy to uterine leiomyosarcoma. Chemotapeutic regimen widely used in uterine LMS in the first line is doxorubicin plus ifosfamide. This regimen induced the higher reported response rate (30%) [17] For patients with recurrent disease, paclitaxel was tested in mono-therapy for leiomyosarcoma and in combination with carboplatin with good outcome [18,19]. Docetaxel plus Gemcitabine regimen was tested in phase II study and showed promising results [20].
Conclusion Epithelioid Leiomyosarcomas arising in the uterine cervix are exceedingly rare tumors. Because the number of reported cases in the literature is so small, the optimum means of managing cervical leiomyosarcoma has to be established. The ultimate prognosis of this disease is unclear. It seems appropriate that when faced with this disease process, the clinician therefore looks to the current accepted standards for the management of uterine leiomyosarcoma for guidance. Thus, more cases of this unusual morphologic variant and longer follow-up of existing and future cases are needed to determine the clinical behaviour of this neoplasm.
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