2010— January Case of the Month

Updated January 11, 2010

CLINICAL SUMMARY: SOFT TISSUE

After reading the summary, try answering the three related multiple-choice questions below.

A 48-year-old woman presented with a large painless thigh mass, which was excised. Grossly, the mass was a well circumscribed,lobulated 17.7 x 15.2 x 11.8 cm unencapsulated tumor with a slightly yellow and gelatinous cut surface and focal areas of hemorrhage.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2007, Case 1 and is a myxoid liposarcoma.

Criteria for Diagnosis and Comments: This is an example of myxoid liposarcoma, which is the most common subtype of liposarcoma. It is a variably cellular neoplasm that shows three characteristic microscopic features: lipoblasts in various stages of differentiation, a delicate capillary network, and an abundant myxoid matrix. Mast cells are also commonly observed.

The proliferating cells of myxoid liposarcoma are relatively uniform lipoblasts that are most easily identified at the tumor periphery. In their earliest forms, they may appear as primitive mesenchymal cells but when mature they most often have a signet-ring morphology. They are occasionally multinucleate and are often S-100 positive. Although the tumor may grow rather aggressively, mitoses range from absent to very few. The main predictive factor for metastatic potential of this tumor is instead overall cellularity. Cellular areas consist of closely spaced primitive appearing round cells with a high N:C ratio and conspicuous nucleoli. Cytoplasm may be scant or relatively abundant. Myxoid stroma is typically absent in these areas. Such areas were previously termed "round cell liposarcoma" but it is now recognized that myxoid and round cell liposarcomas represent a histologic continuum with both patterns sharing a t(12;16)(q13;p11) translocation. The cellular/round cell areas are thought to represent the poorly differentiated end of the histologic spectrum. The presence of a significant round cell component, defined as greater than 5% in the current WHO classification, has been associated with an unfavorable outcome.

The vascular component of this tumor is quite characteristic. It is a delicate plexiform network composed of narrow thin walled vessels. It is more prominent in neoplasms that retain their primitive characteristics and is less notable in those with a preponderance of maturing lipoblasts. Another unique vessel-related finding is the presence of hypocellular zones around small veins and arteries.

The myxoid component contains glycosaminoglycans or mucopolysaccharides, which may be both extra and intracellular, and varies in both its amount and distribution. A colloidal iron stain will highlight hyaluronidase-sensitive myxoid material. There may be pooling of this material, imparting an almost cribriform or lacelike architectural pattern to the tumor. When this matrix is abundant it may also form cystic spaces filled with granular material. These "microcysts" can become quite large and architecturally complex. Their low power pattern is quite distinctive and has been described as pulmonary-edema like.

Clinically, myxoid liposarcoma presents as a large painless mass arising in muscle or deep soft tissue. The peak incidence is in the fifth decades; this tumor rarely develops in individuals less than 20 years of age. Myxoid liposarcoma has a very strong predilection for the thigh but may also be found in the popliteal fossa, groin, and buttock region. Other locations are extremely uncommon. The standard of care is surgical excision with wide margins. Post-surgical recurrence is uncommon and is usually local. However, these low-grade tumors may metastasize, most commonly to the lung, retroperitoneum or bone. Intramuscular myxoma is another neoplasm comprised of uniform cells in a myxoid stroma but lacking the characteristic vascular network and lipoblasts of myxoid liposarcoma. Intramuscular myxoma is also paucicellular, substantially less cellular than the least cellular myxoid liposarcomas.

Lipoblastoma is another tumor with delicate plexiform vasculature, a myxoid matrix, and small immature fat cells, a pattern that makes it almost histologically indistinguishable from myxoid liposarcoma. This tumor can also contain microcystic spaces, as found in myxoid liposarcoma. However lipoblastoma occurs almost exclusively in infants making this a very important clue in their distinction. Myxoid liposarcoma only rarely occurs prior to the age of twenty. Other distinguishing factors include the lobular architecture, lack of more cellular areas, and superficial location of lipoblastoma. Lipoblastomatosis, like lipoblastoma, also occurs within the first three years of life and twice as often in boys than girls. Lipoblastomatosis refers to more diffuse and deeper or infiltrative lesions that meet the histologic criteria for lipoblastoma. For this reason, this entity offers the same diagnostic dilemma as its subcutaneous and circumscribed counterpart, lipoblastoma and the same factors are used to distinguish this entity from myxoid liposarcoma.

Myxoid chondrosarcoma is in the differential diagnosis of myxoid liposarcoma in that it also is a tumor comprised of uniform cells with a myxoid stroma. Rarely myxoid liposarcoma may also have chondroid differentiation. However myxoid chondrosarcoma has a lobulated architecture, with intervening fibrous septa, in which the tumor cells are typically at the periphery of the lobules. The characteristic lipoblasts and capillary network of the myxoid liposarcoma are not found in the myxoid chondrosarcoma.

Myxoid dermatofibrosarcoma protuberans (DFSP), a locally aggressive tumor believed to be of fibroblastic origin, may have a myxoid background, as seen in myxoid liposarcoma; however, its cutaneous location helps distinguish this diagnostic entity. DFSP possesses a very characteristic storiform architectural pattern that is not present in myxoid liposarcoma. The storiform architecture may be lost in myxoid areas, but strong CD34 staining in DFSP differentiates it from myxoid liposarcoma.

Myxoid malignant fibrous histiocytoma (myxofibrosarcoma/MFH), another aggressive tumor which may be associated with previous radiation exposure, also has a myxoid stroma and rich capillary network which may present a diagnostic challenge in distinguishing it from myxoid liposarcoma. The mucopolysaccharide containing cells of myxoid MFH may also be confused with the primitive lipoblasts of myxoid liposarcoma. To distinguish these entities it is important to note that the mucopolysaccharide vacuoles in myxoid MFH do not distort the nucleus and that the material within these vacuoles is of the same color and density as the background myxoid stroma. In myxoid liposarcoma the cytoplasmic vacuoles are clear and usually of the signet ring type pushing the nucleus eccentrically and indenting it. Myxoid MFH typically arises in subcutaneous tissue, a very uncommon site of myxoid liposarcoma and is also pleomorphic in contrast to the more uniform cells of myxoid liposarcoma. Finally, although the arborizing vascular network of myxoid MFH may be reminiscent of myxoid liposarcoma, it does not possess the characteristic hypocellular zones found around small vessels in myxoid liposarcoma. Myxoid MFH is immunoreactive for factor XIIIa and CD68 and negative for S-100 protein.

Spindle cell lipoma is a benign circumscribed tumor characterized by an admixture of mature fat and collagen-forming spindle cells. This histologic variant of the common lipoma primarily occurs in middle-aged to elderly men with a male to female predominance of 9:1.
It may possess adipocytes that resemble signet ring cells and a myxoid stroma, which could be confused with those features of myxoid liposarcoma. However the rich vascular network of myxoid liposarcoma is not a feature of spindle cell lipoma, which additionally has coarse collagen and spindled cells with elongate nuclei. Finally the anatomic sites of these tumors are very different with the spindle cell lipoma favoring superficial locations of the back, neck, and shoulder.

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Supplementary Questions For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question

Diagnostic Set

Which tumor occurs almost exclusively before 3 years of age?

A. Intramuscular myxoma
B. Lipoblastoma / Lipoblastomatosis
C. Myxoid chondrosarcoma
D. Myxoid dermatofibrosarcoma protuberans (DFSP)
E. Myxoid malignant fibrous histiocytoma
    (myxofibrosarcoma/MFH)
F. Myxoid liposarcoma
G. Spindle cell lipoma

Which tumor exhibits CD34 immunoreactivity and a characteristic storiform architecture?

A. Intramuscular myxoma
B. Lipoblastoma / Lipoblastomatosis
C. Myxoid chondrosarcoma
D. Myxoid dermatofibrosarcoma protuberans (DFSP)
E. Myxoid malignant fibrous histiocytoma
    (myxofibrosarcoma/MFH)
F. Myxoid liposarcoma
G. Spindle cell lipoma

Which tumor occurs nine times more often in males than females and typically involves the neck or upper back?

A. Intramuscular myxoma
B. Lipoblastoma / Lipoblastomatosis
C. Myxoid chondrosarcoma
D. Myxoid dermatofibrosarcoma protuberans (DFSP)
E. Myxoid malignant fibrous histiocytoma
    (myxofibrosarcoma/MFH)
F. Myxoid liposarcoma
G. Spindle cell lipoma