Case of the Month: Posterior neck

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2015, case 13, and is a spindle cell/pleomorphic lipoma.

Histologic sections reveal bland spindle cells with occasional hyperchromatic rounded cells and rare “floret-like” multinucleated giant cells with variable amounts of admixed mature adipose tissue and ropey collagen. In some regions, tumor cells palisade and there are rare arrays of tumor cells creating random fascicles with “school of fish” pattern. No storiform pattern is present. There is no cytologic atypia, mitotic activity or necrosis present. In some sections there is a prominent vascular proliferation lined by benign endothelial cells devoid of erythrocytes. The endothelial cells express D2-40 supporting interpretation of lymphatics. Adult-like lipocytes are present in most sections, and no lipoblasts are present within the neoplasm.

The clinicopathologic findings in this case are characteristic of spindle cell/pleomorphic lipoma. For years spindle cell lipoma and pleomorphic lipoma were considered separate but related entities; however, given the significant overlapping clinical, histologic, immunohistochemical, and cytogenetic features, these two lesions are now considered a single entity representing a morphologic spectrum.

Spindle cell/pleomorphic lipoma shows a distinct male predominance with approximately 90% of cases occurring in men 45 to 60 years of age. About 80% of spindle cell/pleomorphic lipomas occur in the subcutaneous tissue of the posterior neck, shoulder, and back, with the remaining 20% arising in unusual locations including face, forehead, scalp, and buccal-perioral area. The differential diagnosis for subcutaneous adipocytic tumors, particularly atypical lipomatous tumor, a tumor that combines spindle cell lipoma and atypical lipoma with widened septa and hyperchromatic lipocytic atypia out of range for spindle cell/pleomorphic lipoma. Deeper seated lesions including in groin, retroperitoneum and skeletal muscle are considered well differentiated liposarcoma, when atypia is present. Most cases of spindle cell/pleomorphic lipoma are solitary; however, rare patients with multiple lesions have been reported, and a few familial cases have been seen. Spindle cell/pleomorphic lipomas exhibit benign behavior, and conservative local excision is considered appropriate treatment. Local recurrences are only rarely encountered following incomplete excision, and metastasis is not seen.

Grossly, spindle cell/pleomorphic lipoma forms a well-circumscribed oval to discoid mass with a yellowish to grayish-white cut surface that is oftentimes firmer in texture than classical lipoma due to lesser amounts of fat and more abundant collagen. Occasionally, spindle cell/pleomorphic lipoma may exhibit a more gelatinous texture due to an abundance of myxoid stroma. Most cases of spindle cell/pleomorphic lipoma are encapsulated; however, cases seen in unusual locations such as thigh, groin, buttock, face, forehead, scalp, hands, and the buccal-perioral area are less frequently encapsulated. Invasion into surrounding tissue is not a feature.

As the name of the lesion suggests, spindle cell/pleomorphic lipoma demonstrates a broad morphologic spectrum histologically. At one end of the spectrum, accounting for approximately 90% of cases, including the one presented here, is the classical spindle cell lipoma, which is composed of mature fat admixed with small bland spindle cells exhibiting elongated uniform wavy nuclei and scant pale eosinophilic cytoplasm. The spindle cells are usually arranged in short parallel arrays or fascicles between fat cells, oftentimes with a “school of fish” pattern that sometimes demonstrates prominent nuclear palisading; no storiform pattern is seen. The spindle cells are typically associated with bundles of thick rope-like collagen with variable numbers of admixed mast cells (which can be numerous), lymphocytes, and plasma cells. Lipoblasts are not present, and mitotic activity is virtually absent. The amount of fat in spindle cell lipomas can range from 10-90%; however, rare cases lacking fat (fat-free variant) have been reported. Some spindle cell lipomas exhibit abundant fibrous stroma (“fibrous spindle cell lipoma”), while others demonstrate prominent myxoid change. Still others contain numerous slit-like vascular spaces, a variant previously referred to as the “pseudoangiomatoid variant” of spindle cell lipoma; however, recent immunohistochemical studies have shown the vascular spaces to be lined by D2-40+ endothelial cells, consistent with true lymphatic vascular channels.

Although the majority of tumor cells in classical spindle cell lipoma exhibit bland spindle cell morphology, variable numbers of larger round cells with atypical hyperchromatic nuclei and occasional multinucleated giant cells with radially arranged “floret-like” nuclei can be seen. In approximately 10% of cases of spindle cell/pleomorphic lipoma, these hyperchromatic round cells and “floret-like” multinucleated giant cells account for the vast majority of cells in the lesion, and represent the pleomorphic end of the morphologic spectrum (so-called pleomorphic lipomas). As with classical spindle cell lipomas, the amount of fat present in pleomorphic lipomas is variable and mitoses and lipoblasts are not a feature. Some cases of spindle cell/pleomorphic lipoma have features encompassing the entire morphologic spectrum of the entity with areas exhibiting classical spindle cell morphology merging with other areas demonstrating classical pleomorphic features.

Immunohistochemical staining of spindle cell/pleomorphic lipomas typically show the spindle/pleomorphic cells to be strongly and diffusely positive for CD34 and vimentin and negative for keratin, S-100, CD68, desmin, and smooth muscle actin. BCL-2 and CD10 are also frequently positive. Although the spindle/pleomorphic cells are typically negative for S-100, rare instances of S-100 positivity have been reported. It should be remembered that any fat cells present in the lesion will stain for S-100. The spindle/pleomorphic cells in spindle cell/pleomorphic lipoma have also been shown to stain positive for androgen receptors, which might help explain the marked male predominance seen with this lesion.

Regardless of where on the morphologic spectrum a particular case of spindle cell/pleomorphic lipoma may lie, the cytogenetic abnormalities are similar. The karyotypes of spindle cell/pleomorphic lipoma are frequently hypodiploid with the majority of cases having monosomy or partial loss of chromosomes 13 and/or 16. In cases with abnormalities involving chromosome 16, a breakpoint in 16q13 is usually involved. In cases with abnormalities in chromosome 13, losses of 13q12 and 13q14-q22 are typically seen. Less common abnormalities have also been reported in chromosomes 6, 10, and 17.

The differential diagnosis for spindle cell/pleomorphic lipoma depends where on the morphologic spectrum a particular lesion lies, and which features predominate. Cases with classical spindle cell lipoma morphology can sometimes be confused with dermatofibrosarcoma protuberens (DFSP); however, DFSP typically originates in the dermis and extends into the subcutis, and usually occurs in younger patients. While both DFSP and spindle cell/pleomorphic lipoma demonstrate CD34+ spindle cells, the spindle cells in DFSP tend to be plumper and are arranged in a characteristic storiform pattern not seen in spindle cell/pleomorphic lipoma. Moreover, DFSP lacks the ropey collagen typically seen in spindle cell/pleomorphic lipoma, is located in trunk and proximal extremity, and has an infiltrative pattern.

In cases of spindle cell/pleomorphic lipomas with prominent myxoid stroma, intramuscular myxoma may enter into the differential. Both lesions commonly occur in the shoulder area, and both tend to occur in patients 40 to 70 years of age. Intramuscular myxomas, however, occur more commonly in females, and as the name of the lesion implies, intramuscular myxomas are usually more deep-seated than spindle cell/pleomorphic lipomas, typically arising within skeletal muscle. While some morphologic overlap exists between the tumor cells of the two lesions, the tumor cells of intramuscular myxoma are typically negative for CD34 with occasional positivity for actins. Intramuscular myxoma may at times be associated with a GNAS gene mutation, especially in Mazabraud syndrome.

Some cases of spindle cell/pleomorphic lipoma with prominent myxoid stroma can also exhibit a prominent plexiform vascular pattern similar to that seen in myxoid liposarcoma. Unlike myxoid liposarcoma, spindle cell/pleomorphic lipoma is more superficially located, better circumscribed, and lacks lipoblasts. In addition, the ropey collagen typically seen in spindle cell/pleomorphic lipoma is not a feature of myxoid liposarcoma, and while some CD34 reactivity can be seen in myxoid liposarcoma, it is not the diffuse strong CD34 positivity characteristic of spindle cell/pleomorphic lipoma. In difficult cases, FISH analysis for rearrangements in the DDIT3 and/or FUS genes can be helpful, as these are typical of myxoid liposarcoma.

Nodular fasciitis is another spindle cell lesion that can form a well-circumscribed spherical nodule fascial based in the subcutaneous tissue, but is more commonly forearm or forehead rather than posterior neck, shoulder, and back. Unlike spindle cell/pleomorphic lipoma, nodular fasciitis typically presents as a rapidly growing lesion, and is usually seen in younger patients, age 20 to 40 years. Microscopically, nodular fasciitis tends to have a more variable appearance than spindle cell/pleomorphic lipoma, and unlike spindle cell/pleomorphic lipoma, the tissue culture fibroblast-like tumor cells of nodular fasciitis exhibit frequent mitotic activity and are positive for smooth muscle actin and negative for CD34.

Other tumors that can be CD34 positive and in the differential diagnosis include solitary fibrous tumor (SFT), yet this would be less common in the neck and has staghorn vasculature with haphazard arrangement of spindled cells and perivascular and stromal fibrosis. Other neck tumors in the differential diagnosis include nuchal fibroma and Gardner fibroma, the latter beta-catenin positive; these are separated by their predominant fibrous tissue and entrapped fat rather than a lipoma (fatty tumor) variant.

Cases of spindle cell/pleomorphic lipoma exhibiting prominent nuclear palisading and numerous mast cells can sometimes be confused with schwannoma. While there is significant morphologic overlap between the spindle cells in spindle cell/pleomorphic lipoma and those in schwannoma, the cells in the latter lesion are usually more wavy and buckled in appearance. Moreover, while the spindle cells in schwannoma may occasionally express CD34, they invariably express strong and diffuse S-100, a marker negative in spindle cell/pleomorphic lipoma.

1. Which lesion arises in the dermis and is characterized by CD34+ tumor cells arranged in a monotonous storiform pattern?
   1. Dermatofibrosarcoma protuberans
   2. Intramuscular myxoma
   3. Myxoid liposarcoma
   4. Nodular fasciitis
   5. Schwannoma
   6. Spindle cell/pleomorphic lipoma
2. Which lesion classically forms a slow-growing, well-circumscribed mass in subcutaneous tissue of the posterior neck, shoulder, and back that is characterized by CD34+ tumor cells with variable amounts of admixed fat and ropey collagen?
   1. Dermatofibrosarcoma protuberans
   2. Intramuscular myxoma
   3. Myxoid liposarcoma
   4. Nodular fasciitis
   5. Schwannoma
   6. Spindle cell/pleomorphic lipoma
3. Which lesion forms a well-circumscribed subcutaneous mass characterized by rapid growth and frequent mitotic activity?
   1. Dermatofibrosarcoma protuberans
   2. Intramuscular myxoma
   3. Myxoid liposarcoma
   4. Nodular fasciitis
   5. Schwannoma
   6. Spindle cell/pleomorphic lipoma

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John J. Schmieg, MD, PhD
Assistant Professor of Pathology
Tulane University School of Medicine
New Orleans, LA

Byron E. Crawford, MD
Surgical Pathology Committee
Tulane University School of Medicine
New Orleans, LA

1. Dermatofibrosarcoma protuberans (a)
2. Spindle cell/pleomorphic lipoma (f)
3. Nodular fasciitis (d)