Pathologic Quiz Case: An 86-Year-Old Man With a Painless Right Tongue Mass

Archives of Pathology & Laboratory Medicine, Feb 2005 by Angeles, Ronald M, Vasquez, Jonathan, Kim, Oliver

An 86-year-old man with a significant history of smoking and alcohol intake presented with a painless right tongue mass that had been present for an unknown period of time. Physical examination revealed a pedunculated polypoid mass measuring 0.5 cm in greatest dimension involving the midanterior two thirds of the right tongue blade. The rest of the physical examination and the laboratory studies were unremarkable. The patient subsequently underwent an outpatient excisional biopsy of the tongue mass.

Grossly, the specimen consisted of an irregular, round fragment of tan to light yellow rubbery soft tissue measuring 0.3 � 0.2 � 0.2 cm. Histologically, the specimen was a well-circumscribed mass lined by squamous epithelium with mild parakeratosis (Figure 1). The submucosa was expanded by variably sized adipocytes interspersed within a fibrous stroma supported by a fibrovascular stalk. There were monovacuolated and multivacuolated lipoblast-like cells that showed scalloped nuclei (Figures 2 and 3). Immunohistochemical stains were positive for S100 protein (lipocytes and lipoblast-like cells) and CD34 (spindle cells, focal). The CD31 stain highlighted the blood vessels. Cytokeratin stains (AE1/AE3 and MAK-6) were negative.

What is your diagnosis?

Pathologic Diagnosis: Atypical Lipomatous Tumor of the Tongue

Liposarcoma is the most common soft tissue sarcoma, accounting for approximately 20% of all mesenchymal malignancies encountered by practicing surgical pathologists.1 The World Health Organization classification currently recognizes 5 types of malignant adipocytic tumors, including atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS).2 ALT/WDLPS represents 40% to 45% of all liposarcomas and tends to occur in the retroperitoneum and the limbs.1 It is very rare in the head and neck region and even rarer in the oral cavity. Fewer than 50 cases appear to have been described in the literature.1 The most commonly reported histologic subtype in this location has been myxoid liposarcoma, followed by ALT/WDLPS. Some authors believe that reports of the former cases likely represent examples of the well-differentiated subtype, with pronounced stromal myxoid changes as a consequence of chronic local trauma to the area.1 The most commonly reported site in the oral cavity is the cheek, followed by the tongue. It can occur in the floor of the mouth, soft palate, lip, and gingiva.3,4

In the study by Nascimento and colleagues,3 the median age at time of presentation was 49.5 years. There was a slightly greater frequency in men. The most common symptom was a slowly growing, painless mass or swelling. The initial impressions were mostly benign lesions, including lipoma or fibroma. Treatment consisted of excisional biopsy, followed by wider re-excision because of positive margins.

Grossly, these tumors are usually well-circumscribed, lobulated masses. Encapsulation is uncommon. The appearance can vary from white-tan to yellow depending on the proportion of adipocytic, fibrous, and myxoid areas. Necrosis and hemorrhage are common in larger specimens.

Microscopically, infiltration to the surrounding muscle is typically seen. Some cases may show diffusely infiltrative lesions with entrapment of muscle, nerves, or both.

All tumors show variation in adipocyte size, which is sometimes the most striking feature. There are hyperchromatic, atypical stromal cells present in the fibrous septa. A varying number of monovacuolated or multivacuolated lipoblasts may be seen.1-3,5 Lipoblasts are defined by the presence of single or multiple sharply marginated cytoplasmic vacuoles scalloping an enlarged hyperchromatic nucleus.1,2,5 It should be emphasized that the presence of lipoblasts does not confirm a diagnosis of liposarcoma, because some benign lesions, such as lipoblastoma, chondroid lipoma, spindle cell lipoma, and pleomorphic lipoma, contain lipoblasts.1,3,5 Additionally, the presence of lipoblasts is not required for the diagnosis of liposarcoma if atypical stromal cells are present.1,5 Immunohistochemical stains such as S100 play little or no role in the diagnosis.3

The major differential diagnoses are mostly benign lesions such as lipoma, fat necrosis, and spindle cell lipoma. Lipomas are lobulated and are composed of mature fat cells, with minimal variability in adipocyte size and no cytologie atypia. Trauma and ischemia can lead to fat necrosis. A thin fibrous capsule surrounds most of these tumors. Spindle cell lipomas are characterized by varying admixtures of adipose tissue, multinucleated giant cells, and bland spindle cells associated with bands of ropy collagen, often within a fibromyxoid matrix containing mast cells. Fibrous septa with atypical stromal cells and numerous lipoblasts should not be seen.2,3

ALT/WDLPS is characterized by the presence of supernumerary ring and giant chromosomes composed of amplified sequences from the 12q14-15 chromosome region. Several genes are present in this region, including MDM2 and CDK4. These oncogenes act as positive regulators of cell cycle progression at the G1-S checkpoint.1,5 Hostein and colleagues6 used real-time polymerase chain reaction to detect MDM2 and CDK4 gene amplification in 36 cases of lipomas and 48 cases of ALT/WDLPS and dedifferentiated liposarcomas. They found that MDM2 and CDK4 gene amplifications were seen in 98.2% and 82.4%, respectively, of liposarcomas and in only 2.8% and 5.6%, respectively, of lipomas. Co-amplification of the 2 genes was observed more in dedifferentiated liposarcomas than in ALT/WDLPS. This is a fast and reliable method that can be used with paraffin-embedded tissues when distinguishing between lipoma and liposarcoma proves to be difficult histologically. Amplification of chromosome 1 sequences is also seen in liposarcomas. Nilsson and colleagues7 showed that candidate oncogenes COAS1, COAS2, and COAS3 (ie, chromosome one amplified sequence) originating in lq21-23 were amplified in 13 of 21 cases (2 lipomas and 11 liposarcomas). The most common location of extra COAS signals was in supernumerary ring and giant marker chromosomes.