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Gynecologic Oncology 95 (2004) 243 246 www.elsevier.

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Case Report

Embryonal rhabdomyosarcoma (sarcoma botryoides) of the cervix presenting as a cervical polyp treated with fertility-sparing surgery and adjuvant chemotherapy
Kerry L. Bernala,*, Lylia Fahmyb, Steven Remmengab, Julia Bridgea,c,d, John Baker a
b a Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha, Nebraska Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, Nebraska c Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska d Department of Orthopedic Surgery, University of Nebraska Medical Center, Omaha, Nebraska

Received 23 December 2003

Abstract Background. Embryonal rhabdomyosarcoma (sarcoma botryoides) of the female genital tract is rare in the cervix. It tends to occur in children and young women, and appears to have a better prognosis than sarcoma botryoides of the vagina and uterus. Case. We report a case of embryonal rhabdomyosarcoma (sarcoma botryoides) presenting as a cervical polyp in a 19-year-old female. The tumor was composed of rhabdomyoblasts of varying differentiation dispersed within a loose, myxoid stroma, and formed a distinct dcambiumT layer beneath the epithelium. The patient was successfully treated with fertility-sparing surgery and adjuvant chemotherapy. Conclusions. Awareness of this uncommon lesion in this site and its clinical implications is important to avoid misdiagnosis. Therapy has recently inclined towards conservative treatment. D 2004 Elsevier Inc. All rights reserved.
Keywords: Embryonal rhabdomyosarcoma; Sarcoma botryoides; Cervix

Introduction Rhabdomyosarcoma is a tumor of skeletal muscle that is classified into three types: embryonal, alveolar, and undifferentiated. Sarcoma botryoides refers to a variant of the embryonal type that occurs beneath a mucosal surface. In the female genital tract, sarcoma botryoides typically occurs a vaginal tumor in infants. However, sarcoma botryoides is also known to rarely occur in the cervix or uterine fundus. The treatment for sarcoma botyroides of the female genital tract, whether it occurred in the vagina, cervix, or uterine fundus, has traditionally included

* Corresponding author. Department of Pathology/Microbiology, 987549 Nebraska Medical Center, Omaha, NE 68198-7549. Fax: +402 552 3625. E-mail address: kbernal@unmc.edu (K.L. Bernal). 0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2004.06.049

radical, fertility-compromising surgery. However, the recent literature suggests that sarcoma botryoides of the cervix behaves less aggressively than sarcoma botryoides of the vagina and uterus, and the treatment has inclined toward conservative surgery combined with adjuvant chemotherapy. Histologically, sarcoma botryoides is composed of malignant rhabdomyoblasts within a loose, myxoid stroma. The pathologic differential diagnosis includes benign entities such as rhabdomyoma and an edematous mesodermal cervical polyp (pseudosarcoma botryoides), and malignant entities such as adenosarcoma and other small, round, blue cell tumors. Although the alveolar type of embryonal rhabdomyosarcoma demonstrates a unique genetic translocation, sarcoma botyroides does not carry a unique genetic abnormalitiy, and only one case of cervical sarcoma botyroides has been cytogenetically analyzed [1].

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We report a case of sarcoma botryoides of the cervix presenting as a cervical polyp in a 19-year-old female, treated with conservative surgery and chemotherapy, with a favorable outcome.

Case report A 19-year-old nulligravid female presented with vaginal spotting for several weeks and the feeling of a mass protruding from the introitus. Examination in the clinic revealed a polyp within the vagina, thought to be arising from the endometrium. The patient was taken to the operating room, at which time the polyp was noted to actually arise from the posterior lip of the cervix. A polypectomy and endocervical curettage was performed. The specimen received for pathologic examination was a 3.5 2.0 1.2 cm lobulated mass covered by pink, smooth, and glistening mucosa. No distinct stalk was identified. The cut surfaces of the mass revealed soft, edematous, partially hemorrhagic parenchyma with focal white-tan areas. Microscopically, the polyp was covered by squamous and endocervical mucosa. Beneath the epithelium, a zone of increased cellularity composed of undifferentiated rhabdomyoblasts (dcambium layerT) was present (Fig. 1). Deep to the surface, many rhabdomyoblasts in varying degrees of differentiation were present, dispersed in a edematous and myxomatous stroma (Fig. 2). Immunohistochemical analysis revealed the rhabdomyoblasts to stain with desmin, muscle specific actin, and focally, myoglobin and vimentin. The tumor was negative for CD31. A few areas of metaplastic cartilaginous differentiation were also present (Fig. 3). These findings are consistent with an embryonal rhabdomyosarcoma (sarcoma botryoides). In the endocervical curettage specimen, a small focus of the tumor was also identified.

Fig. 2. Rhabdomyoblasts, some with distinct cross-striations, are present within the edematous stroma.

After the results of the pathologic examination were communicated to the patient, a chest X-ray and CT scan of the abdomen and pelvis were performed and revealed no evidence of metastatic or residual disease. Based on discussions with the radiologists, a pelvic MRI was not thought to be superior than a CT scan in detecting residual disease. Because of the small focus of tumor identified in the endocervical curettage specimen at the time of the polypectomy, the patient was taken back to the operating room for a cervical conization. No residual tumor was identified in the cervical conization specimen. According to the Intergroup Rhabdomyosarcoma Study Group (IRS) criteria, the patient was classified as a group IA. The patient was subsequently treated with chemotherapy. Her regimen consisted of 1. 5mg/m2 of Vincristine on Day 1, at a maximum dose of 2 mg. Actinomycin was given every 4 weeks for 6 cycles at a dose of 0.015 mg/kg for 5 days, at a maximum of 0.5 mg/day. She tolerated the treatment

Fig. 1. Characteristic of sarcoma botyroides is the cellular cambium layer underneath the cervical epithelium, and the deeper, edematous stroma.

Fig. 3. Metaplastic cartilage differentiation was also present.

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well, without adverse side effects. During therapy, she was treated with oral contraceptives. At the completion of therapy, the patient resumed normal ovarian function. She remains without evidence of disease 11 months following her original diagnosis.

Discussion The WHO classification of soft tissue tumors defines the botryoid type of rhabdomyosarcoma as a tumor of skeletal muscle differentiation arising beneath a mucosal epithelial surface [2]. It is known to occur in almost any mucosal-lined organ. In the female genital tract, the most common site is a vaginal lesion occurring in infants or young children. Sarcoma botyroides in the cervix is rare, and most of our information is based on individual case reports. The largest series consisting of original cases included 13 patients [3]. Furthermore, information regarding sarcoma botryoides of the cervix is difficult to obtain from the literature because the primary site of origin is not always described or known. Although sarcoma botryoides of the cervix has been reported in females as young as 5 months of age [4], it tends to occur in an older age group (children and young adults) than those that occur in the vagina. Most patients present with vaginal bleeding or a feeling of a mass in the introitus. Like sarcoma botyroides occurring at other mucosal sites, the tumor may form soft, grape-like clusters, present as single or multiple polyps [5]. The microscopic findings are similar to sarcoma botyroides occurring in the other organs, consisting of rhabdomyoblasts of varying differentiation dispersed within a loose, myxoid stroma. A distinct dcambiumT layer beneath the epithelium is characteristic. Several cases, including ours, have shown metaplastic cartilaginous differentiation [1,3,6,7]. Histopathologic factors that appear to correlate with an adverse prognosis include deep myometrial invasion [3], lymphatic invasion [7], and a focal alveolar pattern [7]. Several other lesions enter into the pathologic differential diagnosis, including adenosarcoma, edematous cervical mesodermal polyps (pseudosarcoma botryoides), rhabdomyoma, and other bsmall, round, blue cellQ tumors. Adenosarcomas can also be found in young women [5], but histologically can be distinguished from sarcoma botryoides by their fibrous stroma and leaf-like pattern of glands. Edematous cervical mesodermal polyps (pseudosarcoma botryoides) may resemble sarcoma botryoides due to their edematous stroma, but tend to occur in older women, are usually small, and lack a cambium layer or rhabdomyoblasts [5]. Rhabdomyoma is a benign tumor that displays skeletal muscle differentiation, but lacks a cambium layer and has uniformly distinct skeletal muscle differentiation of the tumor cells. It also tends to occur in an older age group [8]. Other bsmall, round, blue cell tumorsQ, such as small cell carcinoma and lymphoma, can also have similarity to sarcoma botryoides of the cervix.

The lack of a cambium layer and immunohistochemical markers can greatly aid in this distinction. Unlike alveolar rhabdomyosarcoma, which demonstrates a recurrent genetic translocation t(2;13)(q35;q14), molecular studies of embryonal rhabdomyosarcoma have not found a recurrent genetic abnormality that may aid in the diagnosis. Some authors have found allelic loss of 11p15 and complex structural and numerical changes, often including extra copies of chromosomes 2, 8, and 13 [2]. However, only one case of sarcoma botryoides of the cervix has been studied cytogenetically, showing the deletion of the short arm of chromosome 1, and trisomies 13 and 18 [1]. The first comprehensive review of cervical sarcoma botryoides was published by Brand et al. [4] (17 cases from the literature and 4 new cases). The authors found that after 68 months of follow-up, 80% of the patients were alive [4]. Among the five patients (24%) with recurrent disease, three of them died of their disease [4]. At that time, these authors suggested that the prognosis of sarcoma botryoides of the cervix is similar to that of other embryonal rhabdomyosarcomas of the female genital tract, and that primary therapy should consist of chemotherapy followed by responsedependent surgery [4]. However, in that same year, Daya and Scully [3] published a clinicopathologic study consisting of the largest series to date of original cases. This study found that 3 of the 13 patients treated with fertility-sparing surgery (polypectomy or cervicectomy) followed by chemotherapy had comparable results to those treated with more radical surgery with or without chemotherapy [3]. This group suggested that, in contrast to sarcoma botyroides occurring in the vagina, cervical sarcoma botryoides has a favorable outlook [3]. This conclusion is supported by the most recent review of cervical sarcoma botryoides published in 1998 which suggests that clinical group I RMS patients can effectively be treated by organ-preserving surgery [9]. Because the peak incidence of this tumor occurs in young females, patients often desire to retain their fertility potential, and therapy has evolved to include less radical surgical procedures and chemotherapy to meet this goal. Since Zeislers study in 1998, case reports have emerged of sarcoma botryoides that were confined to the cervix, treated with local excision (polypectomy or cervicectomy), and followed by chemotherapy, with favorable outcomes [3,9 14]. In one reported case in which adjuvant chemotherapy was not used after adequate surgical excision, the patient died of her disease 4 months after surgery [15]. This case emphasizes the importance of adjuvant chemotherapy in the treatment of this tumor. However, there are case reports of unfavorable outcomes despite adequate surgical excision and chemotherapy [7], interjecting a note of caution and emphasizing the need for close clinical follow-up. Embryonal rhabdomyosarcoma (sarcoma botryoides) of the cervix is a rare malignancy that tends to occur in women of reproductive age. It is important to distinguish from other

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K.L. Bernal et al. / Gynecologic Oncology 95 (2004) 243246 [5] Kurman RJ, Norris HJ, Wilkinson EJ, editors. Atlas of tumor pathology. Washington (DC)7 American Registry of Pathology, Armed Forces Institute of Pathology; 1992. p. 108 10. [6] Mainguene C, Hugol D, Caulet S, Ayel S, de Saint-Maur PP, Poitout P, et al. Botryoid rhabdomyosarcoma of the cervix. Clinico-pathologic study of a case. Ann Pathol 1993;13(1):40 4. [7] Perrone T, Carson LF, Dehner LP. Rhabdomyosarcoma with heterologous cartilage of the uterine cervix: a clinicopathologic and immunohistochemical study of an aggressive neoplasm in a young female. Med Pediatr Oncol 1990;18(1):72 6. [8] Robboy SJ, Anderson MC, Russell P, editors. Pathology of the female reproductive tract. London7 Churchill Livingstone; 2002. p. 231. [9] Zeisler H, Mayerhofer K, Joura EA, Bancher-Todesca D, Kainz C, Breitenecker G, et al. Embryonal rhabdomyosarcoma of the uterine cervix: case report and review of the literature. Gynecol Oncol 1998;69(1):78 83. [10] Gordon AN, Montag TW. Sarcoma botryoides of the cervix: excision followed by adjuvant chemotherapy for preservation of reproductive function. Gynecol Oncol 1990;36(1):119 24. [11] Lin J, Lam SK, Cheung TH. Sarcoma botryoides of the cervix treated with limited surgery and chemotherapy to preserve fertility. Gynecol Oncol 1995;58(2):270 3. [12] Marana HR, Andrade JM, Llorach-Velludo MA, Marana RR, Cunha SP, Tone AG, et al. Sarcoma botryoides of the female genital tract: long-term results of conservative treatment followed by pregnancy. A case report. Eur J Gynaecol Oncol 1999;20(2):122 3. [13] Porzio G, Toro G, Paris I, Ricevuto E, Ficorella C, Marchetti P. Cervical sarcoma botryoides treated with conservative surgery and adjuvant chemotherapy: a case report. Eur J Gynaecol Oncol 2000;21(5):499 500. [14] Zanetta G, Rota SM, Lissoni A, Chiari S, Bratina G, Mangioni C. Conservative treatment followed by chemotherapy with doxorubicin and ifosfamide for cervical sarcoma botryoides in young females. Br J Cancer 1999;80(34):403 6. [15] Vlahos NP, Matthews R, Veridiano NP. Cervical sarcoma botryoides. A case report. J Reprod Med 1999;44(3):306 8. [16] Arndt CA, Donaldson SS, Anderson JR, Andrassy RJ, Laurie F, Link MP, et al. What constitutes optimal therapy for patients with rhabdomyosarcoma of the female genital tract? Cancer 2001;91(12): 2454 68.

benign and malignant lesions that can occur in the cervix. In the past two decades, a dramatic improvement in survival rates has resulted from treatment with a combination of surgery and adjuvant chemotherapy. This case represents another example of successful, fertility-sparing surgery followed by chemotherapy for the treatment of this tumor. However, the extent of surgical therapy and subsequent adjuvant therapy should be balanced between the patients desire to maintain fertility and the presence of adverse prognostic variables. According to the IRS, fertility-sparing surgery followed by chemotherapy is appropriate treatment for patients with local disease [9,16]. Fertility-sparing surgery should not be considered with the presence of extensive uterine involvement and/or metastasis. In addition, the impact of other variables, such as deep myometrial invasion, lymphatic invasion, and foci of alveolar subtype, have not been well studied, but have been associated with adverse outcomes [3,7]. Their presence should prompt discussion with the patient regarding more aggressive surgical treatment.

References
[1] Palazzo JP, Gibas Z, Dunton CJ, Talerman A. Cytogenetic study of botryoid rhabdomyosarcoma of the uterine cervix. Virchows Arch A Pathol Anat Histopathol 1993;422(1):87 91. [2] Fletcher CD, Unni KK, Mertens F, editors. World Health Organization classification of tumors. Lyon France7 IARC Press; 2002. p. 146 9. [3] Daya DA, Scully RE. Sarcoma botryoides of the uterine cervix in young women: a clinicopathological study of 13 cases. Gynecol Oncol 1988;29(3):290 304. [4] Brand E, Berek JS, Nieberg RK, Hacker NF. Rhabdomyosarcoma of the uterine cervix. Sarcoma botryoides. Cancer 1987;60(7): 1552 60.