The story began one year before the patient’s admission, when he incidentally noticed a fist-sized mass on his right back. The mass enlarged significantly over the following six months and became mildly tender to the touch. An outside hospital had offered only a presumptive diagnosis of lipoma, and no treatment was given. By the time he reached the Grade-A tertiary hospital in Zhuhai in 2024, imaging told a more complicated story. A non-contrast magnetic resonance imaging scan of the chest and back soft tissues revealed a mass measuring approximately 176 by 99 by 202 millimeters in the subcutaneous area of the posterolateral right scapula. On T1-weighted imaging the lesion showed predominantly hyperintense signals, consistent with fat, which decreased on fat-suppressed sequences and showed no signal attenuation on opposed-phase images. Within the mass, multiple T1-hypointense nodules, patchy areas, and linearations were visible, appearing hyperintense on fat-suppressed T1- and T2-weighted imaging. The largest nodule measured about 28 by 13 millimeters with distinct boundaries, and the adjacent latissimus dorsi muscle showed abnormal morphology.

Before surgery, the team performed an ultrasound-guided core needle biopsy of the right shoulder and back region. Under the microscope, that biopsy revealed adipose tissue without obvious cellular atypia, suggesting an adipocytic tumor but leaving open the critical question of whether it was a simple lipoma or an atypical lipomatous tumor/well-differentiated liposarcoma, a distinction that needle biopsies alone often cannot resolve. The surgical team proceeded with an extended excision under general anesthesia, making a longitudinal fusiform incision of approximately 20 centimeters along the right posterior axillary line. The tumor was exposed by dissecting the planes of the tumor capsule, the latissimus dorsi, serratus anterior, teres major, and teres minor muscles layer by layer. Intraoperatively, the surgeons found the tumor had a broad base, indistinct boundaries, infiltration into surrounding tissues, and a tendency to extend toward the axilla. The extended excision removed the tumor completely along with portions of the latissimus dorsi and serratus anterior muscles.

The gross specimen was a grayish-yellow mass measuring 20 by 17 by 6 centimeters, sectioned in a book-like manner, with a fusiform strip of skin measuring 16 by 6.5 centimeters attached to one side. The tumor surface appeared encapsulated, but the cut surface was grayish-yellow and soft to locally medium in texture, with no apparent grayish-white areas, and its boundary with the striated muscle was ill-defined. Part of the tumor resembled yellow-white adipose tissue, while other areas presented a cord-like, multiloculated structure. Under the microscope, the tumor was composed of fibrous and myxoid stroma containing mildly to moderately atypical spindle cells, along with varying proportions of adipocytes, lipoblasts, and floret-like multinucleated giant cells, the characteristic cellular constellation of ASPLT.

Immunohistochemistry, the technique that uses antibodies to detect specific proteins in tissue sections, added crucial pieces to the puzzle. The tumor cells were positive for CD34, with focal positivity for S-100, MDM2, Desmin, P16, and a Ki67 proliferation index of approximately 1 percent. The cells were negative for CDK4, MyoD1, beta-Catenin, ALK, SMA, and HMB45, and demonstrated a loss of expression for the retinoblastoma protein, RB1. That RB1 loss is a molecular signature found in roughly 50 to 70 percent of ASPLT cases, according to the literature reviewed by the authors, and it drives the atypical cellular proliferation and pleomorphic morphology that give these tumors their worrisome appearance. It firmly places ASPLT within the RB1-deleted tumor family rather than a sarcomatous lineage.

The decisive test, however, was fluorescence in situ hybridization, or FISH, a molecular technique that uses fluorescently labeled DNA probes to detect specific genetic changes in cells. Based on a count of 100 cells, the number of red and green signals were 249 and 241 respectively, yielding an MDM2/CEP12 ratio of 1.03. That ratio indicated no amplification of the MDM2 gene, and this absence is the paramount diagnostic criterion separating ASPLT from atypical lipomatous tumor/well-differentiated liposarcoma, which is typically characterized by amplification of the MDM2 and CDK4 genes. While MDM2 or CDK4 may display focal weak positivity on immunohistochemistry in ASPLT, they are not co-expressed, and the definitive absence of MDM2 amplification clarifies the molecular basis of the diagnosis. Integrating histomorphology, immunohistochemistry, and FISH allowed the team to identify the lesion as an adipocytic tumor with no obvious local capsule and focal involvement of striated muscle, consistent with ASPLT.

The classification of this entity has evolved considerably. ASPLT was initially reported by Dei Tos and colleagues and was historically regarded as a morphological subtype of well-differentiated liposarcoma. The fifth edition of the World Health Organization Classification of Soft Tissue and Bone Tumours, published in 2020, explicitly defined it as a benign adipocytic tumor and confirmed that atypical spindle cell lipomatous tumor and atypical pleomorphic lipomatous tumor belong to the same disease spectrum. The age of onset ranges from 6 to 87 years, peaking between 50 and 60, with a slight male predominance. The tumor most frequently affects the extremities, thighs, shoulders, and back, and rarely the head and neck or retroperitoneum. Its defining hallmark is a consistently indolent biological behavior despite concerning morphological atypia, with poorly defined borders, an absence of a true capsule, and highly variable proportions of atypical spindle cells, adipocytes, lipoblasts, and multinucleated giant cells embedded within a fibrous or myxoid stroma.

Differential diagnosis remains the central clinical challenge. Beyond well-differentiated liposarcoma, ASPLT must be distinguished from spindle cell lipoma, a benign lesion composed of uniform spindle cells admixed with mature adipocytes that is diffusely positive for CD34; ASPLT presents with a more complex pleomorphic cellular morphology and an infiltrative growth pattern, although the two share RB1 loss as a common pathophysiological link. Diffuse neurofibroma generally demonstrates diffuse S100 positivity, whereas S100 expression in ASPLT can be negative or only weakly positive, and its cellular morphology features pleomorphic cells and lipoblasts rather than uniform spindle cells. Mammary-type myofibroblastoma, composed primarily of uniform myofibroblasts and collagenous stroma with desmin positivity, lacks the pleomorphic cells and distinctive adipocytic atypia seen in ASPLT. The authors also point to the tumor microenvironment as a biological context: factors such as progranulin, described as proangiogenic agents in visceral adipose tissue, participate in tissue remodeling, localized inflammation, and cellular proliferation, and similar proangiogenic and inflammatory remodeling factors likely mediate the fibrous changes, myxoid alterations, and infiltrative growth patterns observed in these adipocytic neoplasms.

Management of ASPLT centers on complete surgical excision, the cornerstone of treatment. Because of its infiltrative growth, the local recurrence rate is documented at approximately 10 to 15 percent, strongly correlated with positive or narrow surgical margins. Despite this tendency for local recurrence, the long-term prognosis remains excellent, with virtually no documented cases of distant metastasis. In this case, the patient was followed for 18 months postoperatively with no evidence of tumor recurrence or metastasis, though the authors acknowledge that an 18-month follow-up is relatively limited and that continued clinical surveillance remains of paramount importance given the tumor’s subtle infiltrative capability and clinicopathological heterogeneity. The case’s broader message is clear: when a fatty-appearing mass shows atypical spindle cells, lipoblasts, or floret-like giant cells, morphology alone can mislead clinicians into over-diagnosis, and only the combined weight of histology, immunohistochemistry, and FISH can reliably separate this benign entity from its malignant mimic, sparing patients the morbidity of unnecessarily aggressive interventions.

Subject of Research: Diagnosis of atypical spindle cell/pleomorphic lipomatous tumor using histology, immunohistochemistry, and FISH

Article Title: Clinicopathological features and differential diagnosis of a case report of atypical spindle cell/pleomorphic lipomatous tumor

Article References: Wang, C., Jiang, Y., Liu, Q., & Wang, Y. (2026). Clinicopathological features and differential diagnosis of a case report of atypical spindle cell/pleomorphic lipomatous tumor. Frontiers in Musculoskeletal Disorders, 4, Article 1922243. https://doi.org/10.3389/fmscd.2026.1922243

Image Credits: AI Generated

DOI: 10.3389/fmscd.2026.1922243

Keywords: atypical spindle cell/pleomorphic lipomatous tumor, ASPLT, well-differentiated liposarcoma, MDM2 amplification, FISH, RB1 loss, immunohistochemistry, soft tissue tumor, WHO classification, lipomatous neoplasm, case report, surgical excision