Section 8 -

Lipoblastoma Cheryl M. Coffin, M.D. David M. Parham, M.D.

Clinical History: A 2-year old boy presented with a tumor in the right buttock. The lesion had been present since birth and had been slowly growing. Examination revealed non-tender mass that appeared to be adherent to the underlying muscle and did not interfere with mobility. MRI studies indicated that the mass was infiltrative and had the density of fat. The lesion was excised with narrow margins. A recurrence was noted at seven months and was excised with no further problems. Discussion and Differential Diagnosis: This lesion represents a lipoblastoma, which is a tumor at least partially composed of immature fat. This particular example largely consists of mature-appearing fat, consonant with the tendency of these lesions to undergo maturation into lipomas. The tumor consists of lobules of fatty tissue delimited by thin fibrous septa. Although primarily composed of mature-appearing adipocytes, the lobules also contain variable amounts of a mucinous stroma. Close examination of cells within this myxoid stroma reveal that some are spindly to stellate and contain vacuoles. Occasional signet ring forms are present. There is no evidence of necrosis or atypia. Additional studies were not performed. Lipoblastomas usually arise in infants, although older children are sporadically affected. There are two manifestations of the disease: circumscribed lesions referred to as lipoblastoma and diffuse infiltrative tumors called lipoblastomatosis. The latter form has a greater tendency to recur, as with the present case. Most commonly, lipoblastomas arise in the extremities, but they may arise in other superficial locations as well as the mediastinum and retroperitoneum. Wide local excision is particularly recommended for diffuse lesions to prevent recurrence, which is not related to the degree of maturation or myxoid change. Malignant transformation is not reported. The distinguishing cell type in lipoblastoma is the lipoblast, which is a rounded cell containing multiple fat vacuoles, which fuse and marginalize the nucleus, forming a signet ring cell reminiscent of those in mucinous carcinoma. Differential diagnosis primarily centers around distinction from other adipocytic tumors, particularly myxoid liposarcoma, hibernoma, lipoma. Myxoid liposarcoma is a rare neoplasm in children, but it does occur. La Quaglia and colleague reported 13 cases occurring over a period of 40 years in the Memorial Sloan-Kettering Cancer Center series, and another 13 in the AFIP series were reported by Smookler and Enzinger. Out of 154 non-rhabdomyosarcomatous soft tissue sarcomas reported at St. Jude Children's Research Hospital in 1993, 5 were liposarcomas. Pediatric examples of liposarcoma are more common likely to occur in adolescents than young children, but reports of the latter indicate that a second age peak occurs in infancy. Both myxoid liposarcoma and lipoblastoma contain lobules of neoplastic fat, lipoblasts, and a richly-vascularized myxoid stroma. The most important features that suggest liposarcoma are areas of nuclear atypia and hypercellularity, and in older children this diagnosis should be strongly considered in cases of apparent lipoblastoma. Genetic studies to detect the TLS/CHOP fusion or the t(12;16)(q13;p11) translocation would confirm a diagnosis of myxoid liposarcoma in equivocal cases. On the other hand, lipoblastoma is genetically characterized by rearrangements of chromosome 8q11-13, affecting the PLAG1 gene. PLAG1 functions as a proto-oncogene in pleomorphic adenoma, hepatoblastoma, and AML. Among benign lipomatous tumors, hibernoma might be confused with lipoblastoma because the vacuolated appearance of brown fat. However, the cytoplasm of brown fat adipocytes has a granular eosinophilic quality not seen in lipoblasts. Also, these tumors are distinctly rare in young children, only one case being cited in the most recent Enzinger and Weiss textbook. Lipomas can be more of a challenge to separate from lipoblastomas, which undergo lipomatous maturation with time. Some examples of pediatric lipomas are doubtlessly represent terminally matured lipoblastomas. Basically, the only morphologic distinction is the presence of lipoblasts in the latter tumor, although lipomas tend to be less cellular than lipoblastomas. Other lesions to consider in the differential diagnosis of pediatric lipomatous tumors are fibrous hamartoma of infancy and lipofibromatosis. Fibrous hamartoma is usually easily recognized by its accompanying content of primitive mesenchyme and myofibroblasts, and the combination of these cell types gives the lesions an organoid quality. Lipofibromatosis lacks the organoid pattern and the primitive mesenchyme, but it contains an admixture of fibroblastic and adipocytic components. It is a locally invasive lesion that has been referred to as "infantile fibromatosis" (see Enzinger and Weiss), but it contains fat as an integral component. As with lipoblastomatosis, wide excision is advised to prevent recurrence. Finally, with unusual aggressive lesions containing signet ring cells, it may be wise to consider mucinous carcinoma, which is the most common manifestation of gastrointestinal cancer in children. These tumor may have unusual presentations, but their constituent cells are cytokeratin- and mucin-positive, distinguishing them from lipoblasts. References: Coffin CM, Dehner LP. Soft tissue tumors in first year of life: a report of 190 cases. Pediatr Pathol 1990; 10:509-26. Fetsch JF, Miettinen M, Laskin WB, Michal M, Enzinger FM. A clinicopathologic study of 45 pediatric soft tissue tumors with an admixture of adipose tissue and fibroblastic elements, and a proposal for classification as lipofibromatosis. Am J Surg Pathol 2000; 24:1491-500. 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