Intra-abdominal Embryonal Rhabdomyosarcoma in an Adult

Gynecologic Oncology 74, 282–285 (1999) Article ID gyno.1999.5416, available online at http://www.idealibrary.com on

CASE REPORT Intra-abdominal Embryonal Rhabdomyosarcoma in an Adult Andrew M. Kaplan, M.D.,* Andrew J. Creager, M.D.,* Chad A. Livasy, M.D.,* Georgette A. Dent, M.D.,* and John F. Boggess, M.D.† *Department of Pathology and Laboratory Medicine and †Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, North Carolina 27514 Received November 30, 1998

not uncommon; however, primary intra-abdominal rhabdomyosarcoma has rarely been reported, and the vast majority present in the pediatric population [10]. We present a case of non-hepatobiliary, intra-abdominal embryonal rhabdomyosarcoma arising in an adult patient over 50 years of age.

Rhabdomyosarcoma is an uncommon neoplasm in the adult population. Sporadic cases of primary rhabdomyosarcoma arising in the abdomen have been reported, but these cases are limited almost exclusively to the pediatric population. We report a welldocumented case of primary intra-abdominal rhabdomyosarcoma in a 57-year-old woman. The patient presented with a pelvic mass and an elevated serum CA 125 and was referred to gynecologic oncologists at our institution for a presumed primary gynecologic malignancy. Intraoperatively, amorphous gelatinous tumor comprised a large portion of the peritoneal cavity. Surgical exploration of the abdomen failed to implicate any specific organ as the site of origin of the tumor. The overall histologic pattern of the resected tumor was most consistent with embryonal type rhabdomyosarcoma. To our knowledge this is the first well-documented case report of non-hepatobiliary, adult, intra-abdominal embryonal rhabdomyosarcoma in the English language literature. The presentation of a rare adult sarcoma mimicking a gynecologic malignancy was an unusual feature that complicated the diagnosis in this case. © 1999 Academic Press Key Words: embryonal rhabdomyosarcoma; intra-abdominal; sarcoma.

REPORT OF A CASE

INTRODUCTION

A 57-year-old woman with a history of bipolar affective disorder and cholecystectomy presented to an outside hospital with a 1-month history of progressive abdominal bloating. She reported a 3-year history of feeling constipated with intermittent bloating that recently had been accompanied by early satiety, shortness of breath, and dry heaves. Physical examination revealed an obese woman with decreased breath sounds at both lung bases, mild tachypnea, a markedly distended abdomen, and tense fullness on pelvic examination. Abnormal laboratory findings included a platelet count of 538 3 10 9/L and a CA 125 of 239 U/ml. CT scans demonstrated a large intra-abdominal and pelvic mass (Fig. 1), ascites, and a right pleural effusion. No retroperitoneal involvement by tumor was evident. The patient was transferred on oxygen to the gynecologic oncology service at our institution for further evaluation of the mass. Shortly after admission, she experienced increased shortness of breath and respiratory failure necessitating intubation and mechanical ventilation. Following chest tube drainage of a significant right pleural effusion which was negative for malignant cells by cytopathologic examination, surgical exploration of the abdomen was undertaken. Abdominal exploration at surgery revealed no ascites; instead, large amounts of amorphous, gelatinous tumor were invested within all compartments of the intraperitoneal spaces. The mass extended from the pelvic cul-de-sac to the left hemidiaphragm and a portion of the right hemidiaphragm. The uterus, ovaries, liver, spleen, intestines, and kidneys appeared unremarkable. The tumor was

Rhabdomyosarcoma is the most frequent soft tissue sarcoma in the pediatric population, occurring with an incidence equal to or greater than that of all other forms of soft tissue sarcoma combined [1, 2]. Historically, embryonal, botryoid, and alveolar subtypes have been considered juvenile varieties of rhabdomyosarcoma, while pleomorphic rhabdomyosarcoma is the subtype most frequently found in the adult population [2–5]. Juvenile subtypes of rhabdomyosarcoma are rare in adults [4, 6 – 8]. While rhabdomyosarcoma can arise in virtually any anatomic location, these tumors are typically located in the head and neck, genitourinary organs, retroperitoneum, and extremities [1, 9]. Secondary extension into the abdomen from a primary rhabdomyosarcoma of the retroperitoneum or pelvis is 0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.

282

283

CASE REPORT

tumor and ascites obstructing her ureters bilaterally. She was admitted and underwent paracentesis of approximately 3.5 L of ascites, which was negative for malignant cells by cytopathologic examination. Her hospital condition worsened acutely and she developed acute renal failure, aspiration pneumonia, and small bowel obstruction. Repeat CT scan after 2 weeks of hospitalization revealed rapid growth of her disease, and after discussion with her family, a DNR order was initiated. She suffered an acute myocardial infarction and died 13 months after her original diagnosis. METHODS AND MATERIALS Light Microscopy Tissue was fixed in 10% Formalin, embedded in paraffin, processed in the standard manner, and stained with hematoxylin and eosin. Periodic acid–Schiff stain with and without diastase digestion was used on a selected section. The tumor specimen was evaluated with respect to cellular morphology, cellularity, necrosis, nuclear pleomorphism, and mitotic count. FIG. 1. Abdominal and pelvic computed tomography. Note the clear demarcation between the retroperitoneum and a tumor mass, which essentially fills the entire peritoneal cavity.

intimately associated with the intestines, liver, and reproductive organs, but no clear site of origin was recognized. A frozen section was obtained intraoperatively which suggested that the tumor was a poorly differentiated malignant neoplasm and the differential diagnosis included carcinoma and sarcoma. Optimal debulking of the tumor was performed. Given the uncertainty of tumor origin and cell type at the time of surgery, it was felt to be essential to remove the ovaries and uterus to rule out a gynecologic source. Hysterectomy with bilateral salpingo-oophorectomy and omentectomy were performed. Postoperatively the patient’s respiratory status improved and she had a complete recovery of gastrointestinal function. Chemotherapy with ifosfamide and doxorubicin was initiated prior to discharge from the hospital. One month following her discharge a baseline CT scan revealed several tumor masses in the bowel mesentery as well as the pelvis. The patient completed a total of four courses of ifosfamide/doxorubicin/mesna over 5 months, resulting in marked decrease in tumor size, with near complete radiographic resolution of the tumor. Treatment was tolerated with only mild–moderate nausea and alopecia. The patient requested a change to an outpatient regimen following her fourth course and was switched to dacarbazine (DTIC) chemotherapy. She completed six total courses over the next 6 months, with essentially no toxicity. One month following her sixth course of DTIC, the patient presented to the hospital with increasing abdominal girth and early satiety. Evaluation with CT scan revealed a large pelvic

Immunohistochemical Analysis Formalin-fixed, paraffin-embedded sections of tumor from the patient were deparaffinized and rehydrated. The slides were stained with the direct avidin– biotin–peroxidase method (Dako, Carpinteria, CA), in which 3,39-diaminobenzidine was used as the chromogen, and counterstained with hematoxylin. The following antibodies were used: muscle-specific actin (Enzo Diagnostics, Farmingdale, NY), desmin (Dako), S100 (Dako), Cam 5.2 (Dako), biotinylated mouse antihuman IgG (Dako), and CA 125 (Signet Laboratories Inc., Dedham, MA). Pathology Examination of the uterus, ovaries, and fallopian tubes revealed these organs to be free of tumor. A portion of the intra-abdominal tumor was adherent focally to the serosa on the posterior aspect of the left fallopian tube. The resected tumor was received in the pathology laboratory in several containers as multiple fragments of largely unencapsulated tan– beige and maroon gelatinous tissue that in aggregate measured approximately 54 3 49 3 39 cm (Fig. 2). Portions of the tissue resembled a capsule wall consisting of tan– beige membranous fragments with fine surface vascularity. The cut surface of the tumor was variegated with slick mucoid gelatinous areas alternating with geographic areas of firmer maroon tissue separated by white fibrous septa. Foci of hemorrhage and necrosis were present. The tumor was extensively sampled for light microscopy, including one microscopic section for approximately every 2.5 cm of tumor in the greatest tumor dimension. Sections included any and all grossly heterogeneous areas of the tumor. Histologic sections of the mass showed a predominantly spindle cell neoplasm in a largely myxomatous, well-vascular-

284

KAPLAN ET AL.

FIG. 2. Representative portion of resected tumor with glistening surface and gelatinous consistency.

ized background. Most of the tumor was composed of a uniform moderately cellular and haphazard arrangement of cells (Fig. 3A). Rare areas of dense cellularity as well as focal storiform and fascicular patterns were identified. The neoplastic cells were largely undifferentiated, showing fusiform, stellate, and polygonal morphology with round to oval nuclei and varying amounts of eosinophilic cytoplasm. Interspersed among the undifferentiated cells were strap, tadpole, and polygonal cells with abundant eosinophilic, sometimes fibrillar, and occasionally vacuolated cytoplasm. Some of the malignant cells contained cytoplasmic cross-striations coupled with high-grade nuclear features, confirming rhabdomyoblastic differentiation (Fig. 3B). Occasional “spiderweb-like” and multinucleated giant tumor cells were identified (Figs. 3A and 3C). Many typical and atypical mitotic figures were appreciated, as were apoptotic cells. No calcification, osteoid, new bone formation, or epithelial elements were discerned. A periodic acid–Schiff stain with and without diastase revealed glycogen in the cytoplasm of many of the tumor cells. Immunohistochemical stains showed uniform strong cytoplasmic

FIG. 3. (A) Intermediate-power photomicrograph of tumor demonstrating a poorly differentiated spindle cell neoplasm with haphazard arrangement of cells in a moderately myxoid background. A spiderweb-like cell is highlighted by the dark arrow. (B) High-power photomicrograph demonstrating strap cells with anaplastic nuclei and cross-striations (inset, black arrow), confirming skeletal muscle differentiation. (C) High-power view of tumor reveals anaplastic multinucleated cells (white arrow). (D) Immunoperoxidase staining of tumor with desmin-specific antibodies (brown staining) supports muscle differentiation of the anaplastic cells.

285

CASE REPORT

reactivity of the tumor cells for desmin (Fig. 3D) and slightly less uniform staining for muscle-specific actin, supporting muscle origin. No reactivity for S100 protein, cytokeratins, or CA 125 was demonstrated in the tumor cells. DISCUSSION This case documents a very rare intra-abdominal rhabdomyosarcoma in an adult patient. Because this neoplasm presented as a pelvic mass in a middle-aged female with an elevated CA 125, the clinical and radiologic differential diagnosis strongly favored a gynecologic origin. Surgical exploration revealed a large tumor, which was initially interpreted as ascites radiographically, involving the majority of the peritoneal cavity. Intraoperative examination of the abdomen and pelvis failed to implicate any specific organ as the site of origin of the tumor and the retroperitoneum was found to be free of tumor. Clinical workup of the patient, which included physical examination and laboratory and radiographic studies, demonstrated no evidence of tumor involvement in any site besides the abdomen. Immunohistochemical staining of the tumor cells revealed that they did not express CA 125. The elevation of serum CA 125 in this case represents a nonspecific finding that can be seen in many nongynecologic malignant neoplasms as well as various benign conditions [11]. Because the histopathology of the neoplasm demonstrated focal marked pleomorphism of cells in a myxomatous background, the initial differential diagnosis included rhabdomyosarcoma, liposarcoma, myxoid leiomyosarcoma, malignant fibrous histiocytoma, and mesenchymoma. Rhabdomyosarcoma was strongly suggested by cells with rhabdomyoblastic differentiation, including cytoplasmic cross-striations. No lipoblasts were identified and immunohistochemical staining for S100 protein was negative. Strong, diffuse tumor cell positivity for actin and desmin confirmed the morphologic diagnosis of rhabdomyosarcoma. As no epithelial elements, areas of dedifferentiated sarcoma, or areas of other types of sarcomatous differentiation were observed, this rhabdomyosarcoma is best considered pure, rather than representing a heterologous element of a different neoplasm. The subtype of the tumor in this case was determined to be most consistent with embryonal rhabdomyosarcoma, although focal pleomorphic areas of the tumor were identified. Current considerations of embryonal rhabdomyosarcoma with focal pleomorphic areas favor a designation of embryonal rhabdomyosarcoma, especially with the existence of cells with crossstriations [3, 4, 12–14]. There was no evidence of an alveolar pattern or cambium layer within the tumor and only focal storiform areas were noted. The absence of these features militates against the diagnosis of the alveolar, botryoid, and spindled subtypes of rhabdomyosarcoma. The pleomorphic subtype of rhabdomyosarcoma occurs more commonly in adult patients than the juvenile subtypes [4,

12, 15]. It appears that rhabdomyosarcoma presents in adult patients as either juvenile or pleomorphic subtypes in locations typically seen in children or more commonly as pleomorphic rhabdomyosarcoma involving the extremities [4, 7, 16, 17]. The unique features of this case include the presentation of a juvenile subtype of rhabdomyosarcoma in an adult patient in a location not usually reported for this tumor. Furthermore, the nonspecific elevation in serum CA 125, which can be seen particularly in intraperitoneal processes, affected the clinical management of this patient due to the tumor mimicking a primary gynecologic malignancy. It should be reiterated, however, in summary that diagnosis of embryonal rhabdomyosarcoma in an adult is uncommon, and its intra-abdominal origin and occurrence in a pure form is extraordinarily infrequent. REFERENCES 1. Hays DM: Rhabdomyosarcoma. Clin Orthop 289:36 – 49, 1993 2. Molenaar WM, Oosterhuis AM, Ramaekers FCS: The rarity of rhabdomyosarcomas in the adult: A morphologic and immunohistochemical study. Pathol Res Pract 180:400 – 404, 1985 3. Newton WA, Gehan EA, Webber BL, et al: Classification of rhabdomyosarcomas and related sarcomas. Cancer 76:1073–1085, 1995 4. Hollowood K, Fletcher CDM: Rhabdomyosarcoma in adults. Semin Diagn Pathol 11(1):47–57, 1994 5. Miettinen M. Rhabdomyosarcoma in patients older than 40 years of age. Cancer 62:2060 –2065, 1988 6. Al-Jaberi TM, Al-Masri N, Tbukhi A: Adult rhabdomyosarcoma of the gallbladder: Case report and review of published works. Gut 35:854 – 856, 1994 7. Taylor RE, Busittil A: Case report: Adult rhabdomyosarcoma of Bladder: Complete response to radiation therapy. J Urol 142:1321–1322, 1989 8. Lloyd RV, Hajdu SI, Knapper WH: Embryonal rhabdomyosarcoma in adults. Cancer 51:557–565, 1983 9. Maurer HM, Mohan B, Gehan EA, et al: The intergroup rhabdomyosarcoma study—I. A final report. Cancer 61:209 –220, 1988 10. Bove KE: Pathology of selected abdominal masses in children. Semin Roentgenol 23(3):147–160, 1988 11. Ravel R: Clinical Laboratory Medicine, 6th ed. St. Louis, MO, Mosby, 1995, p. 580 12. Enzinger FM, Weiss SW (Eds.): Soft Tissue Tumors, 3rd ed. St. Louis, MO, Mosby, 1995, pp. 537–577 13. Newton WA, Soule EH, Hamoudi AB, et al: Histopathology of childhood sarcomas, intergroup rhabdomyosarcoma studies I and II: Clinicopathologic correlation. J Clin Urol 6(1):67–75, 1988 14. DeJong ASH, Van Kessel-Van Vark M, Albus-Lutter E: Pleomorphic rhabdomyosarcoma in adults: Immunohistochemistry as a tool for its diagnosis. Hum Pathol 18:298 –303, 1987 15. Gaffney EF, Dervan PA, Fletcher CDM: Pleomorphic rhabdomyosarcoma in adulthood: Analysis of 11 cases with definition of diagnostic criteria. Am J Surg Pathol 17(6):601– 609, 1993 16. Krumerman MS, Katatikarn V: Rhabdomyosarcoma of the urinary bladder with intraepithelial spread in an adult. Arch Pathol Lab Med 100:395–397, 1976 17. Jaworski RC: Pleomorphic rhabdomyosarcoma of the uterus: Case report with a review of the literature. Br J Obstet Gynaecol 91:1269 –1273, 1984