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

Introduction

In recent years, the understanding and classification of atypical spindle cell/pleomorphic lipomatous tumor (ASLT/APLT) have undergone a significant evolution (1, 2). With advancing research, the 5th edition of the World Health Organization (WHO) Classification of Soft Tissue and Bone Tumours (2020) explicitly defined it as a benign adipocytic tumor and confirmed that ASLT and APLT belong to the same disease spectrum (3). This entity is increasingly recognized for its broad clinicopathological heterogeneity and variable anatomical distribution. While it commonly occurs in the subcutaneous tissues of the extremities and trunk, its diverse morphological manifestations often mimic more aggressive malignancies. However, despite its sometimes concerning cellular atypia, ASPLT consistently demonstrates a remarkably indolent biological behavior. Although associated with a relatively high local recurrence rate if incompletely resected, the risk of distant metastasis is extremely low (4, 5). This article reports a case of ASPLT to explore its clinicopathological features, diverse biological contexts, and essential differential diagnostic criteria.

Case description

Clinical data

The case originated from a Grade-A tertiary hospital in South China in 2024, involving a 44-year-old male patient. Preoperatively, an ultrasound-guided core needle biopsy was performed, which was later followed by an extended surgical excision. During the procedure, the tumor was observed to have a tendency to extend toward the axilla. The evaluated specimens included the needle biopsy tissue from the right shoulder and back, as well as the completely excised tumor tissue.

One year prior to admission, the patient incidentally discovered a fist-sized mass on his right back. The mass significantly enlarged after 6 months and was accompanied by mild tenderness (Figure 1A). An external hospital had previously given a presumptive diagnosis of “lipoma?” and no treatment was administered. The patient had no significant past medical history or previous relevant treatments.

Ancillary examinations

A non-contrast magnetic resonance imaging (MRI) of the chest and back soft tissues revealed a mass measuring approximately 176 mm × 99 mm × 202 mm in the subcutaneous area of the posterolateral right scapula. The T1-weighted imaging (T1WI) showed predominantly hyperintense signals, with decreased signals on fat-suppressed sequences, and no signal attenuation on opposed-phase images (Figure 1B). Multiple T1WI hypointense nodules, patchy areas, and lineartations were visible within the lesion, which appeared hyperintense on fat-suppressed T1WI and T2WI (Figure 1C). The largest nodule measured approximately 28 mm × 13 mm with distinct boundaries, and the adjacent latissimus dorsi muscle demonstrated abnormal morphology.

Treatment methods

Following the completion of preoperative evaluations, the patient underwent tumor excision under general anesthesia. A longitudinal fusiform incision of approximately 20 cm was made along the right posterior axillary line. The tumor was exposed by dissecting the planes of the tumor capsule, latissimus dorsi, serratus anterior, teres major, and teres minor muscles layer by layer. Intraoperatively, the tumor was found to have a broad base, indistinct boundaries (Figure 1D), infiltration into surrounding tissues, and extension toward the axilla. An extended excision was performed, resecting the tumor completely along with portions of the latissimus dorsi and serratus anterior muscles (Figures 1E–H). Upon cross-sectioning, part of the tumor resembled yellow-white adipose tissue (Figure 1F), while other areas presented a cord-like, multiloculartated structure (Figure 1G). The specimen was subsequently sent for pathological examination.

Pathological data

• Microscopically, the preoperative needle biopsy revealed adipose tissue without obvious cellular atypia (Figures 2A, B), suggesting an adipocytic tumor and necessitating differentiation between a lipoma and an atypical lipomatous tumor/well-differentiated liposarcoma.
• Macroscopic examination of the postoperative specimen: The gross specimen was a grayish-yellow mass measuring 20 × 17 × 6 cm, which had been sectioned clinically in a book-like manner. A fusiform strip of skin, measuring 16 × 6.5 cm, was attached to one side of the surface. The tumor surface appeared to be encapsulated; 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.
• Microscopic findings (Figures 2C–F): The tumor was composed of fibrous and myxoid stroma, mildly to moderately atypical spindle cells, and varying proportions of adipocytes, lipoblasts, and floret-like multinucleated giant cells.
• Immunohistochemistry: The tumor cells were positive for CD34 (Figure 2H), S-100 (focal+), MDM2 (focal+), Desmin (focal+), P16 (focal+), and Ki67 (approximately 1%+). The cells were negative for CDK4, MyoD1, β-Catenin, ALK, SMA, HMB45, and demonstrated a loss of expression for Rb (Figure 2G).
• FISH testing: Based on a count of 100 cells, the number of red and green signals were 249 and 241, respectively, resulting in an MDM2/CEP12 ratio of 1.03 (Figure 2G). This indicated no amplification of the MDM2 gene.
• Diagnostic opinion: Based on the histological morphology, immunohistochemical profile, and FISH results, the lesion was identified as an adipocytic tumor with no obvious local capsule and focal involvement of the striated muscle, consistent with the diagnosis of an atypical spindle cell/pleomorphic lipomatous tumor.

Follow-up

The patient was followed up for 18 months postoperatively, with no evidence of tumor recurrence or metastasis observed.

Discussion

Broader spectrum and heterogeneity

ASPLT was initially reported by Dei Tos et al. (6) and was historically regarded as a morphological subtype of well-differentiated liposarcoma (7). Today, it is recognized as part of a broader spectrum of recently described atypical spindle cell/pleomorphic lipomatous tumors characterized by significant clinicopathological heterogeneity. The age of onset ranges from 6 to 87 years, peaking between 50 and 60 years, with a slight male predominance (8). While it exhibits a variable anatomical distribution-most frequently affecting 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 (3). The tumor typically exhibits 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 (8, 9).

Molecular characteristics and diagnostic significance

The molecular foundation of ASPLT is crucial for its precise diagnosis. Immunohistochemically, a loss of RB1 expression is observed in approximately 50%–70% of cases (4, 10). Expanding on the significance of this, RB1 loss drives atypical cellular proliferation and the pleomorphic morphology seen in these tumors, firmly placing ASPLT within the RB1-deleted tumor family rather than a sarcomatous lineage. Furthermore, while MDM2 or CDK4 may display focal weak positivity on immunohistochemistry, they are not co-expressed. The definitive absence of MDM2 amplification is a paramount diagnostic criterion. Together, the loss of RB1 and the absence of MDM2 amplification clarify the molecular basis of the diagnosis, distinguishing it definitively from aggressive liposarcomas. These specific molecular nuances reinforce why FISH remains an essential, non-negotiable adjunct in diagnostically ambiguous cases where morphology alone might mislead the clinician into over-diagnosis.

Tumor microenvironment and adipose tissue biology

Beyond its morphological and molecular definitions, understanding the microenvironment of ASPLT provides a stronger biological context regarding adipose tissue behavior. The local stromal and vascular milieu significantly contribute to the distinct histopathological features observed in these neoplasms. As highlighted by Binișor et al. (11), factors such as progranulin act as proangiogenic agents in visceral adipose tissue, actively participating in tissue remodeling, localized inflammation, and cellular proliferation. Incorporating these biological concepts helps explain the complex tumor microenvironment that supports the development and sustenance of adipocytic neoplasms. Even though ASPLT itself is benign and indolent, localized alterations in adipose tissue biology, driven by similar proangiogenic and inflammatory remodeling factors, likely mediate the fibroustations, myxoid changes, and infiltrative growth patterns frequently observed in clinical specimens, thereby broadening our understanding of its tumorigenesis beyond mere structural morphology.

Differential diagnosis

• Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma (ALT/WDL): ALT/WDL is typically characterized by the amplification of the MDM2 and CDK4 genes, a molecular alteration absent in ASLT/APLT (12, 13). The contrasting frequent loss of RB1 in ASPLT clearly distinguishes the molecular profiles of these two entities (14).
• Spindle Cell Lipoma: This benign lesion is composed of uniform spindle cells admixed with mature adipocytes and is diffusely positive for CD34. In contrast, ASLT/APLT presents with a more complex pleomorphic cellular morphology and an infiltrative growth pattern, although they share RB1 loss as a common pathophysiological link (2, 15).
• Diffuse Neurofibroma: Neurofibromas generally demonstrate diffuse S100 positivity. In ASLT/APLT, S100 expression can be negative or only weakly positive (4), and the cellular morphology features pleomorphic cells and lipoblasts rather than uniform spindle cells (10).
• Mammary-Type Myofibroblastoma: Primarily composed of uniform myofibroblasts and collagenous stroma with desmin positivity, this tumor lacks the pleomorphic cells and distinctive adipocytic atypia seen in ASPLT (4, 16).

Management, prognosis, and surveillance

Currently, clinical evidence dictates that the primary management of ASPLT is complete surgical excision. Because of its infiltrativegins, the local recurrence rate is documented at approximately 10%–15%, which is strongly correlated with positive or narrow surgicalgins (4, 17). Despite this tendency for local recurrence, the long-term prognosis remains excellent due to the tumor's benign, indolent nature, with virtually no documented cases of distant metastasis. Although the present case demonstrates a favorable outcome with no recurrence, we acknowledge that an 18-month follow-up is relatively limited. Given the tumor's subtle infiltrative capability and clinicopathological heterogeneity, continued clinical surveillance remains of paramount importance.

Clinical lessons

ASPLT is a refined, benign entity within the 5th edition of the WHO classification, belonging to a distinct diagnostic spectrumarate from ALT/WDL. Its core histological hallmarks include spindle cells, adipocytes, lipoblasts, and floret-like pleomorphic multinucleated giant cells, driven by distinct microenvironmental factors and RB1 loss. Complete surgical excision remains the cornerstone of treatment, offering a highly favorable prognosis, provided that morphology, immunohistochemistry, and FISH are correctly integrated to avoid unnecessarily aggressive interventions.

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Footnotes

Edited by: Silvia Vanni, IRST, Italy

Reviewed by: Elena Niculet, Dunarea de Jos University, Romania

Mikiko Aoki, Fukuoka University, Japan