Case Presentation. Gordon Callender M.D. Surgical Resident
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1 Case Presentation Gordon Callender M.D. Surgical Resident
2 Retroperitoneal Sarcomas
3 Sarcomas Heterogeneous group of rare tumors that arise predominantly from the embryonic mesoderm. Expected incidence for 2004: 8,680 in the US (.63% of all cancers) Expected sarcoma related deaths: 3,660 (1.15% of all cancers) Soft tissue sarcomas can occur anywhere in the body, however: 1. Extremity (59%) 2. Trunk (19%) 3. Retroperitoneum (15%) 4. Head & Neck (9%) Cormier JN et al CA Cancer J Clin 2004; 54:94-109
4 General Characteristics >50 histologic subtypes: Most common Malignant fibrous histiocytoma (28%) 2. Liposarcoma (15%) 3. Synovial (10%) 4. Malignant peripheral nerve sheath tumors (6%) 5. Rhabdomyosarcoma is the most common in pediatric patients. Most exhibit similar clinical behavior, and staging is defined by depth, grade, and size of the tumor. Dominant pattern of metastasis is hematogenous. Lymph node involvement is rare (<5% of cases) except for certain histologic subtypes (epithelioid, synovial, rhabdomyosarcoma, clear-cell, angiosarcoma.)
5 TABLE 1 Sarcoma Histologic Subtypes of Soft Tissue Histologic Subtypes n % Malignant Fibrous Histiocytoma Liposarcoma Leiomyosarcoma Unclassified Sarcoma Synovial Sarcoma Malignant Peripheral Nerve Sheath Tumor 72 6 Rhabdomyosarcoma 60 5 Fibrosarcoma 38 3 Ewing s Sarcoma 25 2 Angiosarcoma 25 2 Osteosarcoma 14 1 Epithelioid Sarcoma 14 1 Chondrosarcoma 13 1 Clear cell Sarcoma 12 1 Alveolar Soft Part Sarcoma 7 1 Malignant Hemangiopericytoma Modified from Coindre et al. 1
6 General Characteristics Risk factors: 1. External beam RT 8x-50x increase chance of developing sarcomas in pt. treated for breast, cervical, ovarian, or testicular cancer (latency of 10 years). 2. Exposure to herbicides (phenoxyacetic acid) and wood preservatives (with chlorophenols). 3. Chronic lymphedema following ALND: may develop lymphangiosarcoma of the involved extremity (Stewart-Treves syndrome).
7 Histology of Retroperitoneal Sarcomas Most frequently encountered are liposarcoma (~20%) and leiomyosarcoma (~20%) followed by fibrosarcoma, schwannoma, and malignant fibrous histiocytoma in adults. Tumor grading: atypia number of mitotic figures presence of necrosis
8 Extrarenal Rhabdoid Tumor Described in Initially found after a review of Wilms tumors.1 A rare, highly aggressive malignancy seen almost exclusively in infancy or early childhood.2 1. Beckwith JB et al. Histopathology and prognosis of Wilms tumor from the first National Wilms Tumor Study. Cancer 1978; 41: Lowe L et al. Radiographics 2000; 20:
9 Two general types of malignant rhabdoid tumor:1 intrinsic renal disease. extrarenal disease: most common: CNS other locations: retroperitoneum, paravertebral, esophagus, liver, musculoskeletal, bladder, heart, lungs, orbit, breast, placenta.2,3 One case report involved the mesentery.4 Considered a very rare tumor with extremely poor prognosis. 18-month survival rate of ~20% Sajedi M. et al. J Ped Hem Onc. May 2002;24(4) Chang et al. Journal of Urology. 171(2): , Feb Ng W et al. J Clin Pathol 2003;56: Ohgaki M, et al. Surg Today. 2003; 33(7): Chung C et al. AJR 1995;164: Figures 14, 15. (14) Rhabdoid tumor. Photograph of a gross specimen shows a round, lobulated mass with a nonspecific appearance. A small amount of normal kidney (K) is noted at the edge of the specimen. (Reprinted, with permission, from reference 7.) (15) Rhabdoid tumor in an 8-month-old boy with hematuria. C T scan shows a left renal mass with heterogeneous enhancement (arrow). (Courtesy of T im Booth, MD, Children s Medical Center, Dallas, T ex.)
10 Typically occur in infancy, but median patient age ranges from 3 weeks to 50 years of life. Death occurs on average 6 months after diagnosis, although a handful of case reports of patients living for years after diagnosis. One was of a patient with bladder involvement s/p partial cystectomy and chemotherapy who lived for 9 years. 5 year survival rates are not available. 1. Parham D et al. Am J Surg Pathol 1994; 18: Chang J et al. J Urol 2004; 171(2):
11 Pathological/ Immunohistochemistry Features of Rhabdoid Tumors Histologically characterized by sheets of large polygonal cells with prominent nucleoli & cytoplasmic inclusions of hyaline material. They lack myogenous characteristics unlike rhabdomyosarcomas. Positive for cytokeratin, +/- epithelial membrane antigen (EMA), vimentin, and CAM5.2. 1,2 Similarity has been found between rhabdoid tumor and epithelioid sarcomas histologically.3 1. Zhou Y et al. Arch Pathol Lab Med. Sept Ohgaki M, et al. Surg Today. 2003; 33(7): Guillou L Am J Surg Pathol. 1997;21:
12 Genetics of Rhabdoid Tumors Genetically appears to be a chromosomal translocation of 11 and 22 (t(11;22)(p15.5;q11.23). This abnormality is located in close proximity to genes involved in Beckwith-Wiedermann syndrome, rhabdomyosarcoma and Wilms tumor. Newsham I et al. Genomics Feb;19(3):433-40
13 Clinical Presentation of Retroperitoneal Sarcomas Often present with mild non-specific symptoms, or lack there of due to their location, unless they become large and cause obstruction. Most frequent symptoms are abdominal pain, discomfort, or a non-tender palpable mass. Neurological signs, or ascites are less often seen. Local invasion of retroperitoneal structures have been described in the literature. Some patients may have moderate fever, mild leukocytosis: secondary to central necrosis of large tumors. Herman K, Surg Onc 7(1999):
14 Diagnosis History & Physical CBC, Electrolytes, LDH? Radiology: CT Scan: may differentiate between lymphoma, or GU tumors. MRI: can be useful in identifying invasion of nearby organs or major vascular structures including the aorta, IVC. FNA biopsy or open biopsy for tissue diagnosis
15 Treatment Patients with resectable disease should undergo laparotomy. Goal of a curative operation is a complete resection of tumor with adjacent or infiltrated organs and structures. En bloc resections with contiguous organs is seen in up to 83%.1 Most advocate attaining control of large vessels prior to excising the mass. Overall resectability rates have appeared to improve during the 1990s (50-95%) compared to historical rates of 38-74%. A case report has described a laparoscopic resection of a primary RS tumor Jaques D et al, Ann Surg 1990;212: Horiguchi A et al. J Urol 1998;159:
16 Survival Data Survival data from combined series, collected by Storm [8] Tumour grading and survival in retroperitoneal sarcoma studies Group of patients Number of patients 5-year survival rate 10-year survival rate Author/year Number of patients 5-year survival Grade I 5-year survival Grade II, III All % 18% Complete % 45% resection Incomplete % 8% resection Partial resection 59 26% 12% Biopsy only 54 9% 0% GI 49 74% 42% GII,GIII 80 24% 11% Zorig [6] % 16% Singer [22] % 46% Karakousis [10] 87 88% 48% 1996 Herman [19] % (GI,II) 30% (GIII) K. Herman, T. Kusy / Surgical Oncology 7 (1999) 77} 81 Local recurrence rates after a complete resection has been described as 40% after 2 years, 72% after 5 years, and 91% after 10 years
17 Prognostic Factors Unresectable primary tumor Positive gross margins High grade histology Dr. Brennan s experience: Median survival: 103 months vs 18 months (gross negative vs incomplete resection). (MSKCC Ann Surg 1998). Local relapse is the most common cause of cancer related death Studies have also found improved survival from radical resections vs. incomplete resections +/- chemotherapy or RT. Malerba M et al World J. Surg. 23, , 1999
18 Chemotherapy Overall discouraging. Most studies have demonstrated no difference in survival. May be useful in combined modality therapy.
19 One study examined the use of autologous peripheral blood stem cell transplantation (PBCST) + high dose chemotherapy using ICE protocol (ifosfamide, carboplatin and etoposide) for patients with recurrent refractory sarcomas. The data suggested a possible delay in relapse of disease. Hyperthermic intraperitoneal intraoperative chemotherapy following debulking surgery for abdominal sarcomatosis has been performed using doxorubicin and cisplatin (Phase I) has been performed and suggested an therapeutic potential in improving locoregional control. Anticancer Res Sep-Oct;22(5): Cancer (9)
20 Radiation Therapy Less effective than treating sarcomas of the extremity. May be due to limitation of toxic effects (ex. radiation enteritis or delayed wound healing > 50 Gy) or selection bias, in that more aggressive tumors are referred to RT. Some evidence that local control may be achieved with intraoperative brachytherapy vs. external beam RT. However no improvement in survival was demonstrated. McGinn C. Surgical Oncology 9 (2000) 61-65
21 Surveillance & Recurrence Recurrence patterns are related to the histopathology:1 Liposarcomas tend to recur with local disease (rarely have distant mets.) All other types of retroperitoneal sarcomas are more likely to recur with distant metastasis. Some have recommended follow-up CT scans authors2 every 6 months and surgical resection when feasible. 1. Gronchi A et al, Cancer Jun1;100(11): Eillber FC et al, Curr Treat Options Oncol Aug;1(3):274-8.
22 Summary Retroperitoneal sarcomas represent aggressive tumors that often present late. Surgery remains the main modality of therapy. When feasible, contiguous organs should be excised in addition to the primary tumor. At present little evidence of effective chemotherapy or radiotherapy to treat these tumors.
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