Lipoblastoma-Like Tumor and Fibrosarcoma-Like Lipomatous Neoplasm Represent the Same Entity: A Clinicopathologic and Molecular Genetic Study of 23 Cases Occurring in Both Men and Women at Diverse Locations

Abstract

Lipoblastoma-like tumor (LLT) is a benign soft tissue tumor demonstrating mixed morphologic features of lipoblastoma, myxoid liposarcoma, and spindle cell lipoma but lacking genetic alterations associated with those tumors. LLT was originally thought to be specific to the vulva but has since been reported in the paratesticular region. The morphologic features of LLT overlap with those of "fibrosarcoma-like lipomatous neoplasm" (FLLN), a rare, indolent adipocytic neoplasm considered by some to form part of the spectrum of atypical spindle cell and pleomorphic lipomatous tumor. We compared the morphologic, immunohistochemical, and genetic features of 23 tumors previously classified as LLT (n = 17) and FLLN (n = 6). The 23 tumors occurred in 13 women and 10 men (mean age, 42 years; range, 17 to 80 years). Eighteen (78%) cases arose in the inguinogenital region, whereas 5 tumors (22%) involved noninguinogenital soft tissue, including the flank (n = 1), shoulder (n = 1), foot (n = 1), forearm (n = 1), and chest wall (n = 1). Microscopically, the tumors were lobulated and septated, with variably collagenized fibromyxoid stroma, prominent thin-walled vessels, scattered univacuolated or bivacuolated lipoblasts, and a minor component of mature adipose tissue. Using immunohistochemistry, 5 tumors (42%) showed complete RB1 loss, with partial loss in 7 cases (58%). RNA sequencing, chromosomal microarray, and DNA next-generation sequencing study results were negative for significant alterations. There were no clinical, morphologic, immunohistochemical, or molecular genetic differences between cases previously classified as LLT or FLLN. Clinical follow-up (11 patients [48%]; range, 2-276 months; mean, 48.2 months) showed all patients were alive without disease, and only one patient had experienced a single local recurrence. We conclude that LLT and FLLN represent the same entity, for which "LLT" seems most appropriate. LLT may occur in either sex and any superficial soft tissue location. Careful morphologic study and appropriate ancillary testing should allow for the distinction of LLT from its potential mimics.

Keywords: fibrosarcoma-like lipomatous neoplasm; lipoblastoma-like tumor; lipomatous tumor; myxoid sarcoma.

Figure 1.

Macroscopic image of a paratesticular LLT demonstrating a well-defined, fibrofatty to myxo-gelatinous cut surface without necrosis.

Figure 2.

LLT often had multilobulated architecture separated by fibrous septa (A, B). A varying degree of fibromyxoid stroma was present, with accentuated delicate “chicken-wire” vasculature (C). Mature fat is often intermixed but can be more prominent at the periphery of lobules (D). All tumors were composed of bland eosinophilic spindle cells and at least focal uni- or bivacuolated lipoblasts (E, F). Erythrocyte extravasation and mild chronic inflammatory infiltrate were present in a subset (F).

Figure 3.

Tumors classified as FLLN were multinodular with dividing fibrous septa (A, B). Variable fibromyxoid matrix was present with prominent thin-walled capillary vessels (C). Mature adipocytes were interspersed but some tumors had clusters of mature fat concentrated at the periphery of lobules (D). All tumors were composed of bland spindle cells and uni- or bivacoulated lipoblasts (E, F). Some tumors had mild chronic inflammation (F).

Figure 4.

RB1 immunohistochemistry in tumors classified as LLT or FLLN showed either deficient (entirely negative) expression (A) or a mosaic pattern (heterogeneous, weak to moderate nuclear positivity) (B).

Figure 5.

Unsupervised clustering of 2,813 differentially expressed genes shows similar clustering among the 8 LLTs from 5 women and 3 men, and distinction from the 10 non-neoplastic adipose tissue controls, represented as a heat map.