Lipoblastomas are benign neoplasms of the soft tissue that occur primarily in boys younger than 3 years.1 Although lipoblastomas have been noted to occur all over the body, most occur in the extremities.1 The term lipoblastomatosis refers to the same tumor with a diffuse rather than well-circumscribed growth pattern.2 Histologically lipoblastomas are characteristically composed of variably sized lobules of adipose tissue separated by fibrous septa. The range of cellular maturity found in the adipocytic component can cause diagnostic confusion because of overlapping histologic features with lipoma, fibrolipoma, myxoid soft tissue tumors including myxoid liposarcoma, and other lesions such as those termed lipofibromatosis. Cytogenetic analysis has begun to play a pivotal role in helping to diagnose lipoblastomas because the majority possess a genetic defect involving chromosome bands 8q11- 13.3,4 This region on chromosome 8 is the location of PLAG1, an oncogene that is believed to be responsible for the tumorigenesis of lipoblastomas.5 This characteristic genetic finding has broadened the clinicopathologic spectrum of lipoblastoma/lipoblastomatosis, as we illustrate in the patient presented herein.
REPORT OF A CASE
The patient was a 16-month-old, otherwise healthy boy who presented with an enlarging right hypothenar mass. His parents first appreciated the mass 4 months earlier and believed it to have nearly doubled in size. There was no recollection of trauma or infection. Physical examination revealed a healthy-appearing boy with an approximately 4 × 2-cm soft mass apparently based in the right hypothenar region and distorting the whole ulnar aspect of the hand; there was no discoloration, infection, or ulceration (Figure 1, A).
RADIOLOGIC FINDINGS
Ultrasound examination showed a heterogeneous mass with multiple echotextures. It was well defined and encapsulated with no demonstrable increased Doppler signal. Magnetic resonance imaging demonstrated a fairly well-defined enhancing mass lateral to the fifth metacarpal (Figure 1, B). It was heterogeneous with some central vacuolated areas. The mass was 3 cm in greatest diameter and involved the entire hypothenar region, extending through Guyon canal along the flexor retinaculum, as well as into the carpal canal along the flexor tendons.
PATHOLOGIC FINDINGS
Gross examination of an incisional biopsy specimen revealed 3 fragments of yellow-tan fibroadipose tissue admixed with firmer white tissue. Histologic examination revealed a fibrofatty lesion consisting of variably sized lobules of adipose tissue separated by fibrous septa (Figure 2, A through D). The lobular tissue consisted of variably sized adipocytes in a moderately myxoid background. Within myxoid areas the nuclei took on a stellate to slightly spindled configuration. Occasional cells showed cytoplasmic vacuolization causing indentation of the nucleus. The septa were moderately cellular, containing fibroblasts with narrow to stellate nuclei and abundant collagen. In several locations the boundary between the septa and the adipose tissue was difficult to discern, as the adipocytes appeared to be intermixed with the septa. Blood vessels varied in size with the largest vessels restricted to septa. Immunohistochemical staining was performed on paraf- fin-embedded sections; the stellate to spindled cells within the myxoid matrix were positive for S100, CD10, desmin, fascin, vimentin, glial fibrillary acidic protein, CD34, and bcl-2 and negative for glut-1, CD68, CD99, smooth-muscle and muscle-specific actins, and myogenin. NKIC3 was positive in fibroblasts only. Of note, a consultant with expertise in soft tissue pathology offered a diagnosis of lipofibromatosis.
CYTOGENETIC FINDINGS
Cytogenetic analysis of the biopsy specimen revealed 9 of 20 cells with the following karyotype: 46,XY, add(4)(q31),add(8)(q11.2),add 17(q21) (Figure 3). Fluorescence in situ hybridization with whole chromosome paint for chromosome 8 and a centromeric probe for chromosome 17 showed that the additional material on 17q21 was not derived from chromosome 8; an additional unexpected finding was small amounts of chromosome 8 material inserted into 2 different regions of the long arm of chromosome 4 (Figure 4), which was not readily apparent in the metaphase chromosome analysis.
COMMENT
We have described a 16-month-old boy with a large hypothenar lesion histologically and cytogenetically consistent with lipoblastoma/lipoblastomatosis. Lipoblastomas are benign pediatric soft tissue masses characterized by genetic alterations involving the PLAG1 oncogene located on chromosome 8.3,5 These lesions, seen mostly in boys younger than 3 years, tend to occur primarily on the extremities.3
The diagnosis or exclusion of lipoblastoma by histologic examination alone is difficult given the diverse histologic patterns seen in this lesion. Lipoblastomas may show a range of maturation, with immature lipoblasts easily distinguishing a lesion as lipoblastoma, whereas more mature lesions may have histologic overlap with lipoma, fibrolipoma, and lesions of fibrofatty overgrowth syndromes (eg, macrodactyly or Proteus syndrome). Myxoid soft tissue tumors such as neurothekeoma, myxoid liposarcoma, or low-grade fibromyxoid sarcoma may also enter the differential diagnosis, particularly with more myxoid variants of lipoblastoma. The small nature of some incisional biopsies may add to the diagnostic difficulty. A further diagnostic problem is the recent innovation of the term lipofibromatosis6 as a diagnosis for a range of pediatric fibrofatty lesions (including some overgrowth syndromes) most often occurring in the hands. Histologically, lipofibromatosis has been described as consisting of a high proportion of adipose tissue with a fibromatosis-like growth of fibroblasts partitioning lobules of fat. A few of the reported cases have had lobules with a myxoid appearance as may be seen in lipoblastoma. Proponents of the category of lipofibromatosis note that the degree of cellularity in the fibroblastic component is generally greater in lipofibromatosis than in lipoblastoma.6 Emerging data show that desmin immunostaining, highlighting septal and paraseptal spindle cells in lipoblastoma, is a sensitive marker and appears helpful diagnostically in separating lipoblastoma from its mimics.7
The diagnosis of lipoblastoma can be confirmed with cytogenetic testing because these tumors are cytogenetically unique, for the most part containing clonal chromosomal rearrangements involving the 8q11-13 region.5 Some lipoblastomas have been reported that contain a polysomy for chromosome 8 but lack a specific translocation. 3 In recent studies of lipomatous tumors, 8q11-13 rearrangement was found in a broader spectrum of adipose lesions than would have been predicted by histologic examination alone.3,4
The case presented herein illustrates the evolution of diagnostic surgical pathology, which has recognized ''signature'' genetic alterations in many tumors. Identification of cytogenetic abnormalities has been incorporated into diagnostic practice, yielding an appreciation of a broader histologic spectrum of individual tumors. The case also illustrates how a diffuse lesion of the hand that might have been labeled by some as a lipofibromatosis clearly falls within the category of lipoblastoma.
© 2008 College of American Pathologists Provided by ProQuest LLC. All Rights Reserved.
Copyright 2008 Archives of Pathology & Laboratory Medicine
