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A 45-year-old woman presents with a two-month history of vague abdominal discomfort. She underwent a hysterectomy with bilateral salpingo-oophorectomy three years ago. On physical exam, a large non-tender mass was palpable in the mid-abdomen. Imaging studies disclosed a heterogeneous 15.0 cm retroperitoneal soft tissue mass.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 4, and is a myxoid/round cell liposarcoma.
Criteria for Diagnosis and Comments:
The correct diagnosis in this case is myxoid liposarcoma with a round cell component (myxoid/round cell liposarcoma). Myxoid liposarcoma and round cell liposarcoma were historically considered separate subtypes of liposarcoma. The frequent transition areas between myxoid liposarcoma and round cell areas in the same tumor, along with the shared t(12;16)(q13;p11) chromosomal translocation, support a single classification as myxoid/round cell liposarcoma. The translocation results in fusion of the FUS (TLS) and CHOP genes on chromosomes 12 and 16, respectively. Myxoid/round cell liposarcoma is the most common type of liposarcoma, accounting for approximately 30–35% of liposarcomas. These tumors occur almost exclusively in adults, usually in the third to eighth decade with a male preponderance (male: female ratio of 3:1). Myxoid/round cell liposarcoma is somewhat unusual among soft tissue tumors in that it often metastasizes to unusual sites such as the soft tissue of the trunk or axilla before metastasizing to the lung. Lymph node metastases are also more common in myxoid liposarcoma than many other soft tissue malignancies. Liposarcomas are often located in the retroperitoneum or extremities, and the association with the colon in this case is unusual. Other types of liposarcoma include well-differentiated liposarcoma (lipoma-like [or “atypical lipomatous tumor”], sclerosing, inflammatory, and spindle cell), dedifferentiated liposarcoma and pleomorphic liposarcoma.
In the retroperitoneum, the three most common sarcomas are liposarcoma, leiomyosarcoma, and pleomorphic sarcoma (malignant fibrous histiocytoma) with well-differentiated liposarcoma being the most common type of liposarcoma in that location. The majority of dedifferentiated liposarcomas are also found in the retroperitoneum. The typical appearance of these tumors includes a low grade lipogenic component similar to well-differentiated liposarcoma and a spindled component that may include a heterologous element. Pleomorphic liposarcomas occur in the retroperitoneum and extremities with equal frequency and are the least common subtype, accounting for approximately 5% of liposarcomas. These tumors are characterized by marked cytologic pleomorphism, multi vacuolated lipoblasts, and intracytoplasmic eosinophilic material (globules or droplets) that may be lysosomal in origin. In the extremities, the differential diagnosis for a myxoid soft tissue neoplasm could include intramuscular myxoma, myxofibrosarcoma (myxoid malignant fibrous histiocytoma), and extraskeletal myxoid chondrosarcoma.
The diagnosis of myxoid/round cell liposarcoma relies upon careful and thorough gross evaluation of the gross specimen with sampling of any areas that appear more firm or solid than the surrounding myxoid tumor. Examination of H&E slides that show the typical myxoid appearance vascular pattern and lipoblasts (with or without a round cell component) is often sufficient for a definitive diagnosis. At low power, pure myxoid liposarcomas are multinodular with increased cellularity at the periphery of the nodules. Cytologically bland oval cells are seen in a myxoid matrix (hyaluronic acid) with a delicate capillary vascular pattern. Some cells contain one or more vacuoles typical for lipoblasts. Tumors with a round cell component may contain discrete nodules of the undifferentiated round cell component. However, in most cases, there is a gradual transition from myxoid liposarcoma to areas with larger, rounded cells and increased cellularity. Histologic findings with prognostic significance in myxoid liposarcoma include the proportion of round cell component, tumor necrosis, and p53 mutations. Most studies have shown decreased disease-free and overall survival in tumors with greater than 5% round cell component. However, other studies have shown a worse prognosis only for cases with 25% or more round cell component. Despite these differences, the 5% cutoff is generally accepted. In many studies, tumor necrosis is associated with a worse outcome, and the presence of p53 mutations may also portend a poor prognosis. In an otherwise typical myxoid liposarcoma, focal heterologous elements (cartilaginous, leiomyomatous, osseous) are not known to have an adverse effect on prognosis.
In small biopsy specimens or cases with few, if any, lipoblasts, the detection of the t(12;16) translocation may be extremely helpful in the differential diagnosis. Fresh tissue placed in RPMI may be used for complete karyotyping. Fluorescence in situ hybridization (FISH) for chromosome 12 (CHOP, 12q13) and reverse transcriptase polymerase chain reaction (RT-PCR) for the FUS-CHOP fusion transcripts may be performed on formalin-fixed paraffin-embedded tissue. Immunohistochemistry is of limited utility. The undifferentiated round cells and some of the spindle cells in myxoid/round cell liposarcoma may show cytoplasmic and nuclear immunoreactivity for S-100. Approximately 20% of extraskeletal myxoid chondrosarcomas also are positive for S-100. However, these tumors show the characteristic t(9;22) chromosomal translocation. The translocation in extraskeletal myxoid chondrosarcoma is often detected by FISH using a break apart probe for chromosome 22. FISH and/or immunohistochemistry for MDM2 (12q15) may be particularly helpful in the evaluation of small biopsy specimens. Well-differentiated liposarcomas show MDM2 amplification, whereas benign lesions containing adipose tissue (sclerosing mesenteritis and idiopathic retroperitoneal fibrosis) do not. The majority of high grade sarcomas, other than de-differentiated liposarcomas, are also usually negative for MDM2 amplification.
As mentioned above, this case is somewhat unusual in that myxoid/round cell liposarcomas are typically found in the extremities, especially the deep soft tissues of the thigh or buttock. Myxoid round cell liposarcomas have more vascularity than intramuscular myxomas and also contain lipoblasts. Myxofibrosarcomas typically show greater nuclear pleomorphism and tend to have curvilinear vessels invested with pericytic cells as opposed to the thin delicate â€œchicken-wireâ€� vascular pattern in myxoid liposarcoma. Extraskeletal myxoid chondrosarcomas are comprised of cords or nests of small uniform cells in a myxoid matrix. In some cases, these cells contain cytoplasmic hyaline inclusions suggestive of rhabdoid inclusions.