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.

Department of Biopathology Institut Bergonié Comprehensive Cancer Center Bordeaux France; Bordeaux Institute of Oncology Université de Bordeaux Institut Bergonié Bordeaux France

Department of Biopathology Institut Bergonié Comprehensive Cancer Center Bordeaux France; Bordeaux Institute of Oncology Université de Bordeaux Institut Bergonié Bordeaux France; University of Bordeaux Talence France

Department of Laboratory Medicine and Pathology Mayo Clinic Jacksonville Florida

Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota

Department of Pathology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Pathology Johns Hopkins School of Medicine Baltimore Maryland

Department of Quantitative Health Sciences Division of Computational Biology Mayo Clinic Rochester Minnesota

Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy

Laboratory of Pathology National Cancer Institute National Institutes of Health Bethesda Maryland

Zobrazit více v PubMed

Lae ME, Pereira PF, Keeney GL & Nascimento AG Lipoblastoma-like tumour of the vulva: report of three cases of a distinctive mesenchymal neoplasm of adipocytic differentiation. Histopathology 40, 505–509 (2002). PubMed

Droop E, Orosz Z, Michal M. & Melegh Z. A lipoblastoma-like tumour of the paratesticular region - male counterpart of lipoblastoma-like tumour of the vulva. Histopathology 76, 628–630 (2020). PubMed

Gambarotti M, Erdogan KE, Righi A. et al. Lipoblastoma-like tumor of the spermatic cord: case report and review of the literature. Virchows Arch 478, 1013–1017 (2021). PubMed

Mirkovic J. & Fletcher CD Lipoblastoma-like tumor of the vulva: further characterization in 8 new cases. Am J Surg Pathol 39, 1290–1295 (2015). PubMed

Schoolmeester JK, Michal M, Steiner P. et al. Lipoblastoma-like tumor of the vulva: a clinicopathologic, immunohistochemical, fluorescence in situ hybridization and genomic copy number profiling study of seven cases. Mod Pathol 31, 1862–1868 (2018). PubMed

Deyrup AT, Chibon F, Guillou L. et al. Fibrosarcoma-like lipomatous neoplasm: a reappraisal of so-called spindle cell liposarcoma defining a unique lipomatous tumor unrelated to other liposarcomas. Am. J. Surg. Pathol 37, 1373–1378 (2013). PubMed

Mariño-Enriquez A, Nascimento AF, Ligon AH, Liang C. & Fletcher CDM Atypical Spindle Cell Lipomatous Tumor: Clinicopathologic Characterization of 232 Cases Demonstrating a Morphologic Spectrum. Am. J. Surg. Pathol 41, 234–244 (2017). PubMed

Soft Tissue and Bone Tumours. 5th edn, (International Agency for Research on Cancer, 2020).

Martinez AP, Fritchie KJ, Weiss SW et al. Histiocyte-rich rhabdomyoblastic tumor: rhabdomyosarcoma, rhabdomyoma, or rhabdomyoblastic tumor of uncertain malignant potential? A histologically distinctive rhabdomyoblastic tumor in search of a place in the classification of skeletal muscle neoplasms. Mod Pathol 32, 446–457 (2019). PubMed

Kalari KR, Nair AA, Bhavsar JD et al. MAP-RSeq: Mayo Analysis Pipeline for RNA sequencing. BMC Bioinformatics 15, 224 (2014). PubMed PMC

Winters JL, Davila JI, McDonald AM et al. Development and Verification of an RNA Sequencing (RNA-Seq) Assay for the Detection of Gene Fusions in Tumors. J Mol Diagn 20, 495–511 (2018). PubMed

Zhang Y, Parmigiani G. & Johnson WE ComBat-seq: batch effect adjustment for RNA-seq count data. NAR Genom Bioinform 2, lqaa078 (2020). PubMed PMC

Robinson MD, McCarthy DJ & Smyth GK edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139140 (2010). PubMed PMC

Perret R, Tallegas M, Velasco V. et al. Recurrent YAP1::MAML2 fusions in “nodular necrotizing” variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases. Mod Pathol 35, 1398–1404 (2022). PubMed

Freitag CE, Sukov WR, Bryce AH et al. Assessment of isochromosome 12p and 12p abnormalities in germ cell tumors using fluorescence in situ hybridization, singlenucleotide polymorphism arrays, and next-generation sequencing/mate-pair sequencing. Hum Pathol 112, 20–34 (2021). PubMed

Wang Y, Cottman M. & Schiffman JD Molecular inversion probes: a novel microarray technology and its application in cancer research. Cancer Genet 205, 341–355 (2012). PubMed

Gleeson FC, Kipp BR, Voss JS et al. Endoscopic ultrasound fine-needle aspiration cytology mutation profiling using targeted next-generation sequencing: personalized care for rectal cancer. Am J Clin Pathol 143, 879–888 (2015). PubMed

Kutasovic JR, Nones K, Lakis V. et al. Comprehensive histopathologic and genomic analysis of a novel case of lipoblastoma-like tumour of the vulva demonstrating malignant behaviour. Human Pathology Reports 30, 300678 (2022).

Coffin CM, Lowichik A. & Putnam A. Lipoblastoma (LPB): a clinicopathologic and immunohistochemical analysis of 59 cases. Am J Surg Pathol 33, 1705–1712 (2009). PubMed

Brandal P, Bjerkehagen B. & Heim S. Rearrangement of chromosomal region 8q11–13 in lipomatous tumours: correlation with lipoblastoma morphology. J Pathol 208, 388–394 (2006). PubMed

ten Heuvel SE, Hoekstra HJ, van Ginkel RJ, Bastiaannet E. & Suurmeijer AJ Clinicopathologic prognostic factors in myxoid liposarcoma: a retrospective study of 49 patients with long-term follow-up. Ann Surg Oncol 14, 222–229 (2007). PubMed

Kuroda M, Ishida T, Horiuchi H. et al. Chimeric TLS/FUS-CHOP gene expression and the heterogeneity of its junction in human myxoid and round cell liposarcoma. Am J Pathol 147, 1221–1227 (1995). PubMed PMC

Ud Din N, Zhang P, Sukov WR et al. Spindle Cell Lipomas Arising at Atypical Locations. Am J Clin Pathol 146, 487–495 (2016). PubMed

Enzinger FM & Harvey DA Spindle cell lipoma. Cancer 36, 1852–1859 (1975). PubMed

Dal Cin P, Sciot R, Polito P. et al. Lesions of 13q may occur independently of deletion of 16q in spindle cell/pleomorphic lipomas. Histopathology 31, 222–225 (1997). PubMed

Chen BJ, Marino-Enriquez A, Fletcher CD & Hornick JL Loss of retinoblastoma protein expression in spindle cell/pleomorphic lipomas and cytogenetically related tumors: an immunohistochemical study with diagnostic implications. Am J Surg Pathol 36, 1119–1128 (2012). PubMed

Anderson WJ, Fletcher CDM & Jo VY Atypical Pleomorphic Lipomatous Tumor: Expanding Our Current Understanding in a Clinicopathologic Analysis of 64 Cases. Am J Surg Pathol 45, 1282–1292 (2021). PubMed

Marino-Enriquez A, Nascimento AF, Ligon AH, Liang C. & Fletcher CD Atypical Spindle Cell Lipomatous Tumor: Clinicopathologic Characterization of 232 Cases Demonstrating a Morphologic Spectrum. Am J Surg Pathol 41, 234–244 (2017). PubMed

Lecoutere E. & Creytens D. Atypical spindle cell/pleomorphic lipomatous tumor. Histol Histopathol 35, 769–778 (2020). PubMed

Creytens D, Mentzel T, Ferdinande L. et al. “Atypical” Pleomorphic Lipomatous Tumor: A Clinicopathologic, Immunohistochemical and Molecular Study of 21 Cases, Emphasizing its Relationship to Atypical Spindle Cell Lipomatous Tumor and Suggesting a Morphologic Spectrum (Atypical Spindle Cell/Pleomorphic Lipomatous Tumor). Am J Surg Pathol 41, 1443–1455 (2017). PubMed

Ossifying fibromyxoid tumours with lipomatous and cartilaginous differentiation: A diagnostic pitfall

Non-cutaneous syncytial myoepitheliomas are identical to cutaneous counterparts: a clinicopathologic study of 24 tumors occurring at diverse locations