A Retroperitoneal Mass in an Elderly Woman

A 71-year-old nun living in a convent was seen by her primary physician because of persistent left abdominal flank discomfort during the previous 6 months. This was accompanied by a 15-lb weight loss and left lower extremity weakness, numbness, and pain on ambulation. Except for systemic hypertension, her past medical history was unremarkable. On physical examination, a tender mass was palpated in her left lower abdomen. The pain elicited by palpation radiated to the left hip and groin areas. There was also contracture of the left hip that was painful on straightening. Results of laboratory examinations were within normal limits. Computed tomographic scanning revealed a large enhancing left retroperitoneal soft tissue mass juxtaposed to the left iliac bone that involved the left iliopsoas and the inferior extent of the left psoas muscle (Figure 1). A subsequent computed tomography–guided fine-needle aspiration biopsy of the retroperitoneal mass was consistent with a malignant neoplasm. The patient was referred to Loyola University Medical Center for surgical management, and the radiologic survey for metastatic lesion was negative. Preoperative embolization of 2 lumbar vessels and a branch of the iliac artery that supplied the tumor was performed. During the surgical resection, the retroperitoneal mass was noted to be closely associated with the left iliacus and left psoas muscles and to be encasing a segment of the left femoral nerve. Except for extrinsic compression, the adjacent visceral organs, including the lumbosacral vertebrae, were not involved by the tumor.The specimen received for pathologic examination was a large, irregular, solid mass that measured 11.0 × 10.5 × 9.0 cm and weighed 480 g. Histologically, the tumor was highly cellular and was partly surrounded by a capsular rim of fibroconnective tissue and compressed skeletal muscles (Figure 2). The tumor cells were arranged in loose and solid sheets traversed by broad and delicate fibroconnective tissue septae. The tumor cells exhibited marked cellular pleomorphism with abundant bizarre cells. The cytoplasm of the tumor cells was copious and eosinophilic, with intermittent hyaline-like inclusions that displaced the nucleus eccentrically (Figure 3). No cytoplasmic cross-striation was appreciated. The nuclei were irregular and hyperchromatic. Mitotic activity was abundant. There were also numerous multinucleated giant cells with regular nuclear outline and vesicular chromatin admixed with the pleomorphic tumor cells (Figure 4). Scleroses and necrosis within the neoplasm were abundant. Occasional osteoid to hyaline-like material was also noted. The tumor was encasing several branches of peripheral nerves. Electron-microscopic study of the tumor cells demonstrated paranuclear cytoplasmic aggregates of intermediate filaments. No unequivocal ultrastructural evidence of skeletal muscle differentiation was identified. The tumor extended to one of the surgical resection margins.The patient had an unremarkable postoperative recovery, received radiation therapy, and was closely followed up with radiologic surveys. However, 11 months after surgical resection, local and multiple distant tumor recurrences involving the colon and the peritoneum occurred in the abdominal cavity. The largest mass measured 12.8 × 10.9 × 7.4 cm and was affixed to the large intestine. The patient underwent an en bloc resection with right hemicolectomy and resection of the peritoneal tumor nodule. Pathology showed histomorphology and immunohistochemical staining profile similar to the original tumor. The patient had an uneventful postoperative recovery and showed no radiologic evidence of tumor recurrence 3 months after surgery.What is your diagnosis?Based on the immunohistochemical findings, the differential diagnosis of the current tumor includes pleomorphic sarcomas with rhabdomyoblastic differentiation. These include pleomorphic rhabdomyosarcoma (RMS), sarcomas with heterologous rhabdomyoblastic differentiation, and possibly a juvenile-type RMS with anaplastic feature (anaplastic RMS) occurring in an adult patient.1–3 Heterologous rhabdomyoblastic differentiation can occur in a variety of sarcomas, including malignant mesenchymoma, malignant triton tumor, dedifferentiated liposarcoma, and dedifferentiated chondrosarcoma.3 Accurate identification of these sarcomas relies on searching for well-differentiated areas characteristic of the original tumor phenotype, which was not seen in our diffusely pleomorphic tumor. Juvenile-type RMSs can also occur, albeit very rarely in adults, and as seen in pediatric patients, these tumors may show marked anaplasia.12 However, the anaplasia in juvenile RMS is only focal, whereas in the current tumor anaplasia was diffuse.1 Furthermore, areas of obvious transition to well-differentiated juvenile-type RMS, which aids in its identification, were absent in this tumor.1Pleomorphic RMS is the most common RMS in adults, comprising about 7% of all the pleomorphic sarcomas.2 It accounts for 42% of RMSs in patients greater than 40 years of age.4 The tumor has a male predilection (2.8:1 male-to-female ratio).5 The site of involvement includes the lower extremity, abdomen/retroperitoneum, chest/abdominal wall, spermatic cord/testes, and upper extremity. The tumor size ranges from 1.5 to 15 cm (mean, 7.3 cm).5Grossly, the tumor is usually well circumscribed and typically involves large voluntary muscles.235 The current tumor was closely associated with the iliopsoas muscle. Histologically, the tumor is composed of large, bizarre neoplastic cells with eosinophilic cytoplasm and large polygonal or straplike cells with copious deeply eosinophilic cytoplasm or rhabdoid morphology.25 A diagnostic criteria for pleomorphic RMS was proposed by Gaffney et al3; this included (1) pleomorphic spindle cell sarcoma occurring in voluntary muscles, (2) presence of rhabdoid cells, (3) demonstration of desmin and myoglobin immunoreactivity by the tumor cells, and (4) unequivocal demonstration of skeletal muscle differentiation. More recently, Furlong et al5 proposed 3 variants for pleomorphic RMS: (1) classic pleomorphic RMS, which are composed of large, atypical, pleomorphic, polygonal rhabdomyoblasts with abundant eosinophilic cytoplasm; (2) round cell pleomorphic RMS, which are composed of clusters of atypical rhabdomyoblasts with background of slightly atypical medium-sized round blue rhabdomyoblasts; and (3) spindle cell pleomorphic RMS, which are composed of spindle rhabdomyoblasts arranged in storiform pattern. The current tumor is morphologically consistent with the classic variant of pleomorphic RMS.Although rhabdoid cells are seen in pleomorphic RMS, this cell morphology has also been reported, albeit very rarely, in leiomyosarcomas and malignant melanomas.67 In the current tumor, the presence of osteoclast-like giant cells also placed the giant cell variant of malignant fibrous histiocytoma into the differential diagnosis. The gradually diminishing entity of malignant fibrous histiocytoma used to constitute most of the pleomorphic sarcomas and was regarded as the most common soft tissue sarcoma of adulthood prior to the widespread utilization of immunohistochemistry and electron microscopy.24 Malignant fibrous histiocytoma remains the main differential diagnosis for pleomorphic mesenchymal malignancies, but it is now considered as a diagnosis of exclusion if specific lineage of differentiation is undefinable by morphology, immunohistochemistry, special stain, and electron microscopy.4 In contrast, the current tumor expressed desmin and myoglobin consistent with its rhabdomyoblastic lineage.By immunohistochemistry, pleomorphic RMS is positive for skeletal muscle markers myoglobin (97%), myogenin (56%), and MyoD1 (53%).5 Expression of at least 1 skeletal muscle–specific marker is required to make a diagnosis.5 The negativity to myogenin in our tumor therefore did not exclude the diagnosis of pleomorphic RMS. Electron microscopy of pleomorphic RMS may demonstrate rhabdomyoblastic differentiation, indicated by variance from alternating thick and thin filaments with Z-band material to well-defined sarcomeres.23 However, similar to the current tumor, ultrastructural rhabdomyoblastic features may not be detected in all the cases. In the series by Gaffney et al,3 ultrastructural evidence of skeletal muscle differentiation was seen in only 2 of 6 tumors examined. The minimum ultrastructural criteria for skeletal muscle differentiation is the presence of short parallel bundles of myosin filaments with attached ribosome arranged in single file (myosin-ribosome complex).3 Karyotypically, pleomorphic RMSs often demonstrate highly complex karyotypes that lack specific genetic abnormalities, unlike embryonal and alveolar RMSs, which do have specific genetic abnormalities.It has been shown that presence of anaplasia in RMS can portend a graver prognosis.1 In the follow-up of 30 cases by Furlong et al,5 70% of the patients with pleomorphic RMS had died of the disease by 20 months, 3% were alive with the disease at 12 months, and 27% had no evidence of the disease at 83 months. The most important predictors for the survival outcome are the patient age, tumor size, extent of the disease, and margin status after resection.4 Because of the relatively poorer prognosis of pleomorphic RMS compared with the other pleomorphic sarcomas, definitive pathologic identification of this entity is very important.