Once sarcomas become high grade, they may take on any number of appearances, regardless of line of differentiation. Some classic visual patterns are described in Table 29.2. The herringbone pattern is classically ascribed to fibrosarcoma, but in truth, fibrosarcoma is exceedingly rare, and most things that look like fibrosarcoma are not. A similar pattern is the leiomyosarcomatous pattern, which also has long bundles of tumor cells. A high-grade tumor with a myxoid stroma is usually a myxofibrosarcoma (once called “myxoid MFH ”). A tumor with large pink cells with eccentric nuclei may be called rhabdoid (when used as an adjective, this means resembling a rhabdomyosarcoma), and in fact sarcomas of all types may develop foci of true rhabdomyosarcoma. If, however, the sarcoma has none of these patterns, and no differentiation can be identified through immunostains, history, or the low-grade remnants of another tumor found at the periphery, the diagnosis of exclusion is an undifferentiated pleomorphic sarcoma (UPS ).

A reliable clue to a high-grade sarcoma is the presence of malignant nuclei. A pleomorphic sarcoma nucleus has some reproducible features across many tumor types. The nucleus has an irregularly shaped border and has dark, dense, granular chromatin that is fairly evenly distributed throughout the nucleus (Figure 29.2). Unlike carcinoma nuclei, prominent nucleoli and nuclear membranes are not a usual feature. Learning to recognize this sort of atypia is critical in identifying some of the sarcomas.

Throughout this chapter, you will find tables listing some of the more common entities, grouped by clinical behavior. Table 29.3 lists some of the common tumors of fat. There are no specific immunostains for fatty tumors, although MDM2 is a marker that is often expressed in well-differentiated liposarcomas (and negative in lipomas).

The most common soft tissue tumor is the lipoma. A lipoma is defined as a neoplasm of mature fat. It is histologically indistinguishable from ordinary fat; to tell the difference, you must know it appeared clinically as a discrete lobular mass. There are many histologic variants of lipoma, classified based on what additional soft tissue component is present, such as angiolipoma, myolipoma, myelolipoma, etc. A hibernoma is a lipoma of brown fat, in which the fat cells are full of innumerable tiny vacuoles. The lipoblastoma, despite the alarming name, is a benign pediatric tumor of mature fat and benign lipoblasts.

There is a lot of fuss about lipoblasts. They are immature fat cells in which the nucleus is star shaped or scalloped, due to being indented on multiple sides by small bubbles of fat (Figure 29.3). They are often associated with liposarcomas, but they can also appear in the benign lipoblastoma, and they are not necessary for a diagnosis of liposarcoma. Note that normal adipocytes are not mitotically active cells, so mitoses are generally seen only in high-grade liposarcomas.

One type of lipoma is notable for unusual cytologic features. Spindle-cell/pleomorphic lipom a is usually found on the back or neck of elderly men and may be fibrous and nonfatty on low power. Pleomorphic lipoma and spindle-cell lipoma represent two ends of a morphologic spectrum . Spindle-cell lipoma has areas of nondescript spindle cells and collagen and may remind you of a nerve sheath tumor if there is not much fat in the lesion. Pleomorphic lipoma is similar but with the addition of giant cells and floret cells (hyperchromatic wreath-shaped nuclei). These giant cells (Figure 29.4) are an example of a benign lesion simulating malignant atypia; clinical information is helpful in not mistaking these for liposarcomas.

Well-differentiated liposarcoma (WDLS ) is a tumor of adults. It looks similar to a lipoma on low power except for an increase in fibrous “interstitium” between fat cells and fibrous bands (Figure 29.5). A close examination of the fibrous areas reveals hyperchromatic, irregularly shaped nuclei; these are usually large and dark enough to be visible at 4×. Finding a lipoblast is a bonus. A softer feature is an assortment of differently sized fat cells, unlike the monomorphic benign lipoma, but this feature can be unreliable as it is seen in benign entities as well. WDLS is so named when it occurs in a nonresectable location, such as the retroperitoneum. By definition, when it occurs on an extremity, it is called an atypical lipomatous tumor (ALT), as the prognosis in these sites is excellent with simple resection.

When WDLS has been around for a while, especially in a recurrent or occult retroperitoneal lesion, there is a risk of the tumor transforming into a high-grade pleomorphic sarcoma. When this happens, you will see a tumor with WDLS areas and an abrupt transition to a high-grade tumor (storiform, spindled, pleomorphic, or even rhabdoid or leiomyosarcomatous). Regardless of morphology, this is called a dedifferentiated liposarcoma, and the key to diagnosis is recognizing adjacent WDLS . Because a retroperitoneal sarcoma is a dedifferentiated liposarcoma until proven otherwise, if you are grossing such a tumor, be sure to sample anything near the tumor that looks like normal fat: it may be the well-differentiated component.

Myxoid liposarcoma is unrelated to the WDLS ; it is actually a translocation tumor. It is not clearly fatty on gross examination, but may have a myxoid or gelatinous cut surface. The low-power impression is that of a gelatinous tumor with scattered fat cells and a stereotypical capillary network that has been compared to chicken wire (Figure 29.6). These vessels are very delicate , and, unlike normal capillaries, they have little substance to their walls; they appear as a naked sleeve of endothelium stretched through the tumor. The vessels are arborizing or branching and often take on Y-shapes. The tumor cells themselves are small regular rounded cells and single-vacuole lipoblasts, without the large atypical cells of WDLS . (This, remember, is in keeping with the translocation tumors.) Correct identification of myxoid liposarcoma on biopsy is essential, as it can be treated presurgically with radiation.

Myxoid liposarcoma can also transform into a higher-grade lesion. When the small uniform cells become very densely packed and obscure the vascular pattern, it is indicative of round cell morphology, a poor prognostic sign. Remember to always give the estimated round cell component when signing out this type of tumor.

The rare pleomorphic liposarcoma describes a high-grade tumor with extremely bizarre pleomorphic lipoblasts. It does not arise from WDLS or from a pleomorphic lipoma; conceptually you may think of it as a high-grade sarcoma that happens to have lipoblastic differentiation .

The fibroblast and the myofibroblast are ubiquitous cells in charge of the reparative changes that take place in every part of the body. In resting state, they are fusiform-to-stellate cells with oblong pale nuclei, and they lay down a collagen matrix. Their job is to proliferate, and therefore mitotic activity is not unusual in fibroblastic tumors. Although myofibroblasts may stain for actin (and are occasionally mistaken for smooth muscle), in general immunostains are not helpful in this tumor family (Table 29.4).