Management of high-grade pleomorphic sarcoma with colon metastasis

Soft tissue sarcomas (STS) are a heterogeneous group of tumors of mesenchymal origin that represent a rare form of adult malignancy. According to the World Health Organization classification system, there are more than 100 histologic subtypes of sarcoma based on tissue of origin. Staging criteria most commonly use the American Joint Committee on Cancer’s TNM Classification of Malignant Tumours. About 50% of soft tissue sarcomas originate in the lower extremity.¹ Advancements in the use of multimodal therapy have reduced the need for amputation and allowed for equally effective treatment strategies that use limb-sparing surgical resections.

Although most sarcoma metastases spread in a hematogenous fashion, nodal spread is underestimated. Certain histologic subtypes carry a higher predilection for nodal involvement: these include rhabdomyosarcoma, synovial sarcoma, epithelioid sarcoma, vascular sarcoma, and clear-cell sarcoma.^2-4 Fong and colleagues have reported that 2.6% of sarcomas have lymphatic spread.³ In the current report, we describe a rare observation of locoregional pelvic nodal metastases from a large undifferentiated pleomorphic sarcoma of the right thigh.

Case presentation and summary

A 63-year-old white woman had a 1-year history of a right thigh mass and an unintentional weight loss of 40 lb. After a year of chiropractic care, she was referred to a physician because of palpable inguinal adenopathy and a 20-cm mass in the medial compartment of the right thigh, with heterogeneous appearance on a magnetic-resonance imaging scan (Figure 1). The patient was referred to the sarcoma transdisciplinary team for evaluation. She was diagnosed by core needle biopsy with a high-grade malignant epithelioid and spindle-cell neoplasm, favoring pleomorphic sarcoma. The metastatic work-up confirmed locoregional right inguinal and retroperitoneal lymph node disease, with 2 lung nodules that were too small to characterize. She also had a paraneoplastic leukocytosis with a white blood cell count of 45,500 cells/ml (normal 10,500 cells/ml).

The patient was discussed in the sarcoma-specific multidisciplinary conference, and chemotherapy was recommended. She received 8 cycles of the combination of gemcitabine 1,500 mg/m² and docetaxel 50 mg/m² on day 1 and every other week. She had a partial remission, and the lung nodules disappeared. Because of the good remission, a wide resection of the primary soft tissue tumor with inguinal and bilateral retroperitoneal lymph node dissection was performed. A total of 16 nodes were recovered during surgery, 8 from the right inguinal excision, 1 infrarenal aortocaval node, 3 right iliac nodes, and 4 left iliac nodes. All were negative for malignancy, with 1 necrotic right inguinal node. The right thigh soft tissue specimen contained extensive hyalinization (26.0 cm in dimension) with nodular necrosis and no residual tumor (Figure 2). Final pathologic staging was ypT0, ypN0 with focally positive alpha-smooth muscle actin. The patient then received postoperative chemotherapy with the same regimen of gemcitabine and docetaxel, for a total of 16 cycles.

About 8 months after surgery, she presented to the emergency room with a 3-day history of blood per rectum, anemia, and fatigue. She also reported a weight loss of 10 lb in the previous month. She was admitted for hydration and monitoring. Although computed-tomography (CT) scans of the abdomen and chest done during the previous month and had been interpreted as having no evidence of recurrence or any lymph node disease, the results of an inpatient colonoscopy revealed 2 colonic masses, 1 in the ascending colon and another in the transverse colon. The biopsy findings were consistent with undifferentiated pleomorphic sarcoma, favoring epithelioid histology. The CT scans were re-evaluated in light of these colonoscopic findings. These masses were visible retrospectively on imaging but had been interpreted as stool given the lack of abnormality on imaging 3 months before.

Adequate re-staging was complete, and without other evidence of disease, an extended right hemicolectomy was performed. The postoperative pathology report described geographically 2 distinct masses: a 7-cm mass in the ascending colon, about 3 cm from the ileocecal valve; and a 4-cm mass in the transverse colon, about 7.5 cm from the distal margin of resection. Both masses were identified as high-grade pleomorphic sarcoma. Again, all nodes recovered were negative for malignancy (0/5). Of note is that the background colonic mucosa showed active multifocal colitis with deep inflammatory activity likely consistent with a paraneoplastic syndrome.

Discussion

Surgery remains the primary treatment modality for localized soft tissue sarcoma. Obtaining a margin-free resection, while maintaining optimal function, is the objective with extremity sarcoma. In addition to surgical resection, doxorubicin-based adjuvant chemotherapy remains the standard of care with modest improvement in overall survival and disease-free survival, especially in sarcomas of the extremities.^5,6 Gemcitabine also has activity in soft tissue sarcomas⁷ and might synergize with docetaxel. High response rates of 53% with fixed dose infusion rates of these agents in uterine leiomyosarcoma led the Sarcoma Alliance for Research through Collaboration investigators to consider this regimen for other STS.⁸ An overall response rate of 16% was noted across all sarcoma subtypes, and undifferentiated pleomorphic sarcoma had a response rate of 32%.