A Challenging Case of Pleomorphic Lipoma of the Shoulder Mimicking Liposarcoma

Introduction

Considered to be on the same morphological spectrum as spindle cell lipoma, pleomorphic lipoma is an uncommon benign adipocytic neoplasm characterized by pleomorphic and floret giant cells while otherwise resembling a variety of other soft tissue tumors [1–3]. It is a lesion predominantly occurring in older men in the subcutaneous tissue of the posterior neck, back, and shoulders [1,2]. Diagnosis of pleomorphic lipoma is determined by gross examination depicting a well-circumscribed adipocytic mass and is supported histopathologically by cluster of differentiation (CD) 34 positivity and loss of RB transcriptional corepressor 1 (RB1) expression [2,4]. Treatment, entailing complete surgical excision of the mass with clear margins, is generally curative, with a low recurrence rate [1,3]. Here we report a case of a 68-year-old man with a left upper extremity mass concerning for an atypical lipomatous tumor or low-grade liposarcoma, with subsequent analysis after resection showing benign pleomorphic lipoma.

Case Report

A 68-year-old man with a past medical history significant for hypertension, hyperlipidemia, well-controlled HIV, and a prior cerebrovascular accident presented to the general surgery clinic with a progressively enlarging and painful mass on the left upper extremity. The patient reported that the mass first appeared several years earlier, shortly after receiving a vaccination in the left upper arm. He noted a gradual increase in size over time and, more recently, the development of localized discomfort. He denied any constitutional symptoms, including fever, weight loss, or night sweats.

On physical examination, a firm, non-mobile, subcutaneous mass measuring 5×3 cm was palpated over the lateral aspect of the left upper arm. The lesion demonstrated overlying warmth and mild erythema but lacked fluctuance, drainage, or regional lymphadenopathy. A soft tissue ultrasound of the left upper extremity was performed, revealing a lobulated, subdermal soft tissue mass measuring 4.7×1.0×2.5 cm (Figures 1, 2), without significant internal hypervascularity. Within the lesion, an internal hypoechoic component measuring approximately 8×4 mm was identified (Figure 3). Given the lesion’s progressive growth and associated pain, surgical excision was recommended for both definitive diagnosis and symptom relief.

The patient underwent surgical excision of the left upper extremity mass with primary closure. Intraoperatively, a yellow, lobulated soft tissue mass was found within the subcutaneous layer, extending toward the muscular plane.

The specimen was submitted for pathological examination. Grossly, it demonstrated a well-circumscribed lesion. Microscopically, on low-power view (hematoxylin and eosin [H&E], 40×), the lipomatous lesion was composed of atypical spindle cells, with some showing marked pleomorphism and multinucleation (Figure 4; arrow), along with variably sized adipocytes (Figure 4; arrowhead) embedded within fibrotic and slightly myxoid stroma. On high-power view (H&E, 200×), the section highlighted atypical spindle tumor cells (Figure 5; asterisk) and multinucleated giant cells within an associated fibrotic stroma. These atypical and pleomorphic cells raised the possibility of an atypical lipoma or low-grade liposarcoma. To clarify the diagnosis, the case was reviewed by a soft tissue pathology specialist at a tertiary cancer center, where immunohistochemical stains were performed. The tumor cells showed strongly positivity for CD34 and loss of RB1 expression. Stains for MDM2 and CDK4 were negative. The Ki-67 proliferation index was low (<1%). These immunohistochemical findings (data not shown) were consistent with pleomorphic lipoma, rather than an atypical lipomatous tumor or well-differentiated liposarcoma.

The patient tolerated the procedure well and was discharged with routine postoperative care. At his follow-up, the surgical site was healing appropriately, and the patient reported complete resolution of the preoperative pain and discomfort.

Discussion

Pleomorphic lipoma is a rare benign adipocytic neoplasm that can closely mimic atypical lipomatous tumors or liposarcomas clinically and histologically. It was first described as a distinct entity by Shmookler and Enzinger in 1981 [1], and 2 years later, Azzopardi et al reported 9 similar cases [5]. Despite being benign, pleomorphic lipoma remains a diagnostic challenge due to its significant histologic overlap with malignant soft tissue tumors.

Pleomorphic lipoma predominantly affects men (approximately 83%) between the ages of 50 and 70, with a mean age of 57 years [1]. However, occurrences in younger individuals have also been reported [6]. This tumor most commonly arises in the posterior neck, shoulders, and upper back [1,2]. On physical examination, it typically presents as a painless, slow-growing, well-circumscribed subcutaneous mass [1]. However, as demonstrated in our case, pleomorphic lipomas can occasionally cause pain and extend toward deeper structures, including the muscular plane. Previous reports have noted cases in which the mass was attached to the superficial muscular fascia [1].

The average duration from symptom onset to diagnosis is approximately 3 years [7]. Ultrasonography is a useful, low-cost initial imaging modality that can assess lesion size, depth, echogenicity, and border definition. However, it lacks specificity in differentiating benign from malignant adipocytic tumors. Multiphase magnetic resonance imaging (MRI), particularly with contrast, is the gold standard for soft tissue mass evaluation. Typical lipomas show homogeneous hyperintensity on T1-weighted images and suppress on fat-saturated sequences. Features such as thick septations, nodular non-fatty components, or incomplete fat suppression suggest atypical lipomatous tumor or liposarcoma [8]. In contrast-enhanced computed tomography (more often used for retroperitoneal or intra-abdominal masses), lipomas appear as well-circumscribed, low-attenuation lesions. Atypical lipomatous tumor/liposarcomas may exhibit thick septations, nodularity, or calcifications. Positron emission tomography–computed tomography is not useful for distinguishing benign from low-grade malignant adipocytic tumors, as both can exhibit low-to-moderate fluorodeoxyglucose uptake [8].

Recent studies have explored the biomechanical and extracellular matrix (“oncomatrix”) characteristics that may distinguish benign from malignant soft tissue neoplasms [9]. These properties, which reflect the endogenous stiffness and organization of the tumor microenvironment, are emerging as potential biomarkers of malignancy. Advanced imaging techniques such as MRI-based elastography or ultrasound elastography may, in the future, allow noninvasive assessment of these biomechanical differences. However, current evidence suggests that such modalities can provide only indirect information about tissue composition and cannot yet replace histopathologic or immunohistochemical evaluation for definitive diagnosis.

Fine-needle aspiration can be helpful in some cases, particularly in the head and neck [10], but pleomorphic lipoma can mimic malignancy cytologically. Therefore, surgical excision followed by histopathologic examination remains the definitive diagnostic approach. In Shmookler and Enzinger’s study, no recurrences were reported up to 6.5 years after excision, highlighting the importance of complete resection [1,3].

Pleomorphic lipoma is characterized histologically by variably sized adipocytes intermixed with pleomorphic and floret-like multinucleated giant cells [1,11]. These are often embedded in a myxoid stroma with ropey collagen fibers [1,11]. In rare cases, pleomorphic lipomas lack a adipocytic component – so-called “fat-free variants” – which further complicates diagnosis [7,12]. Immunohistochemically, tumors show strong CD34 positivity and loss of nuclear RB1 expression [2,4]. Immunostainings for S-100 protein, desmin, and smooth muscle actin are typically negative [2]. Misdiagnosis as liposarcoma can lead to overtreatment, including unnecessarily aggressive surgical resections. Awareness of pleomorphic lipoma’s distinct histologic and clinical features can help avoid such outcomes.

Conclusions

In summary, pleomorphic lipoma is a rare benign adipocytic tumor that can closely mimic liposarcoma histologically, leading to potential diagnostic confusion. This case underscores the importance of histopathologic evaluation and immunohistochemical profiling in distinguishing pleomorphic lipoma from malignant soft tissue tumors, which can prevent unnecessary aggressive treatment.