Soft Tissue Tumors in Children and Adolescents:
A Morphologic Pattern Oriented Approach with Molecular and Genetic Correlations
Section 8 -
Cheryl M. Coffin, M.D.
David M. Parham, M.D.
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
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
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.
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