Pleomorphic Soft Tissue Tumors



Pleomorphic Soft Tissue Tumors





INTRODUCTION

Many benign soft tissue tumors can occasionally show focal variation in size, shape, and staining properties of cells and particularly of nuclei. Nuclear pleomorphism, which relates to polyploidy, is not itself conclusive of malignancy and must be assessed in the overall clinical and morphologic context of individual cases. Thus, exclusion of malignancy in benign tumors with focal atypia is considered in the accounts of specific entities. These include pleomorphic fibroma (see Chapter 4), atypical cutaneous fibrous histiocytoma (see Chapter 4), symplastic leiomyoma (see Chapter 6), nerve sheath tumors (see Chapter 9), and atypical vascular proliferations (see Chapter 17). Another group of lesions consistently shows diffuse pleomorphism but does not metastasize. It includes pleomorphic hyalinizing angiectatic tumor (PHAT) and atypical fibroxanthoma (AFX) and is considered in this chapter.

Pleomorphic sarcomas account for up to 15% of adult soft tissue sarcomas, and although often grouped together as high-grade sarcomas for management purposes, it is increasingly clear that, in many instances, the specific lineage or differentiation is predictive of behavior. This can often be very focal or detectable only by immunohistochemistry or other techniques. These tumors, therefore, require wide sampling and ancillary investigation. There remain up to 10% of pleomorphic sarcomas that appear to show no differentiation after using all available diagnostic methods. These tumors have historically been called malignant fibrous histiocytomas (MFHs), but this designation was discouraged in the 2002 World Health Organization classification and abolished in the 2013 edition, and they are now termed undifferentiated pleomorphic sarcomas (UPSs). Undifferentiated carcinomas can also assume a pleomorphic sarcoma-like morphology, and many organ-based apparent sarcomas are really of epithelial origin. In the abdomen, most pleomorphic sarcomas are now considered to represent dedifferentiated liposarcoma (see Chapters 5 and 16). The differential diagnosis of pleomorphic tumors is summarized in Table 13.1.












TABLE 13.1 Differential Diagnosis of Pleomorphic Soft Tissue Tumors

Typical Clinical Features

Microscopic Features

Ancillary Investigations


Pleomorphic hyalinizing angiectatic tumor

Adults, solitary subcutaneous lesion, lower leg

Circumscribed, dilated vessels with fibrinoid or hyalinized walls, atypical spindle cells, nuclear inclusions, inflammation, hemosiderin, myxoid change


No mitoses or necrosis

CD34+ in many cases t(1;10) (p11;q24), TGFBR3-MGEA5 fusion, VGLL3, CHMP2B amplifications


Undifferentiated pleomorphic sarcoma (malignant fibrous histiocytoma)

Adults, deep soft tissue, proximal limbs


Intra-abdominal tumors are mostly dedifferentiated liposarcoma

Large tumor with hemorrhage and necrosis


Pleomorphic spindle, polygonal and multinucleated tumor cells, atypical mitoses


Variable inflammation and myxoid change


Residual myxofibrosarcomatous areas in some

Focal SMA or desmin in some cases, rare CK+ cells, CD34+ in some


MDM2+, CDK4+ in intra-abdominal examples


Undifferentiated pleomorphic sarcoma with giant cells (giant cell malignant fibrous histiocytoma)

Adults, deep soft tissue, proximal limbs

As undifferentiated pleomorphic sarcoma with admixture of osteoclast-like giant cells in variable numbers, often associated with hemorrhage

Focal SMA or desmin in some cases, rare CK+ cells. CD34+ in some


Osteoclast-like giant cells are CD68+


Undifferentiated pleomorphic sarcoma with inflammatory cells (inflammatory malignant fibrous histiocytoma)

Adults, retroperitoneum and deep soft tissue of proximal limbs

Areas of typical undifferentiated pleomorphic sarcoma, sheets of foamy cells, some atypical, heavy infiltrate predominantly of neutrophils

Focal SMA or desmin in some cases


CD68+, in retroperitoneum many are dedifferentiated liposarcoma & MDM2+, CDK4+


Inflammatory well-differentiated liposarcoma

Adults, retroperitoneum, groin

Scattered cells with large irregular hyperchromatic nuclei in dense lymphoid infiltrate.


Areas of typical well-differentiated liposarcoma sometimes found

MDM2+, CDK4+


Pleomorphic myofibrosarcoma

Adults, deep soft tissue, proximal limbs

Pleomorphic spindle, polygonal and multinucleated tumor cells, atypical mitoses


Variable inflammation and myxoid change

SMA+ multifocally in subplasmalemmal “tram-track” pattern, desmin+ occasionally, h-caldesmon−


Atypical fibroxanthoma

Adults, head and neck, shoulder, superficial dome-shaped lesion with overlying epidermal thinning or ulceration


Dermal infiltrate is storiform, fascicular, or patternless

Pleomorphic spindle and polygonal cells throughout, abnormal mitoses


Clear cell, spindle cell, and giant cell variants

SMA+ focally, CD10+


Myxofibrosarcoma

Subcutis, fascia, or deep soft tissue


Extremities, older adults


Recurrent

Multinodular, spindle cells in myxoid stroma, variable nuclear pleomorphism


Can merge with high-grade pleomorphic sarcomatous areas

CD34+ in many, SMA+ in pleomorphic areas


Myxoinflammatory fibroblastic sarcoma

Mostly extremities, adults


Cutaneous or subcutaneous, can involve tendons

Multinodular ill-defined myxoid foci with vacuolated fibroblasts, intervening cellular areas with Reed-Sternberg-like and atypical mononuclear cells, eosinophils, plasma cells, hemosiderin

CD34+ in some. t(1;10) (p11;q24), TGFBR3-MGEA5 fusion, VGLL3, CHMP2B amplifications


Pleomorphic liposarcoma

Adults, deep soft tissue, limbs, rarely skin or subcutis

Undifferentiated pleomorphic sarcoma with variable numbers of pleomorphic lipoblasts, sometimes forming sheets


Rare epithelioid variant focally

S100 protein+, CK+ (epithelioid variant), melan-A+, (epithelioid variant)


Dedifferentiated liposarcoma

Older adults, large retroperitoneal tumor, recurrences frequent

Low-grade dedifferentiation: cellular fascicles with mild pleomorphism


High-grade dedifferentiation: pleomorphic undifferentiated sarcoma, or myxofibrosarcoma-like


Heterologous osteochondroid or rhabdomyosarcomatous elements


Extensive sampling might show well-differentiated liposarcomatous component, but this can be absent especially in tumors in abdomen

MDM2+, CDK4+, P16+


Desmin, SMA, CD34 all variably focally positive


Fluorescence in situ hybridization shows MDM2 and CDK4 amplification


Dedifferentiated chondrosarcoma

Usually bony origin, can extend into soft tissue

Undifferentiated pleomorphic sarcoma with contiguous differentiated chondrosarcoma of varying grade

SMA+, S100 protein+ in chondroid area


Pleomorphic leiomyosarcoma

Older adults, limbs, abdomen, head and neck sites

At least two-thirds of tumor is pleomorphic, but focally typical smooth muscle cells in fascicles are present


Pleomorphic component is undifferentiated pleomorphic sarcoma

SMA+, desmin+, hcaldesmon+ variably in both components but less frequent in undifferentiated component


Pleomorphic rhabdomyosarcoma

Rare, older adults M > F, proximal limbs, retroperitoneum, pelvis

Sheets of polygonal, round, or spindle cells with abundant eosinophilic cytoplasm, atypical mitoses, necrosis

Desmin+, myogenin+ (nuclei), MyoD1+ (nuclei), CD56+


Pleomorphic mesothelioma

Sheet-like mass involving pleura, peritoneal surface, or omentum

Fascicles of pleomorphic spindle cells, tapered nuclei, scanty cytoplasm, mitoses, necrosis


Desmoplastic or hyalinized stroma

CK+ focally, calretinin+


Undifferentiated (sarcomatoid) carcinoma

Adults, visceral and soft tissue sites


History of primary carcinoma in some

Pleomorphic spindle or epithelioid tumor cells in sheets, sometimes areas of epithelial morphology or overlying dysplasia

CK+, EMA+, CD34 negative, SMA+ in some, desmin negative, h-caldesmon−


Metastatic melanoma

Any age, history of primary melanoma

Pleomorphic spindle and epithelioid tumor cells, sometimes rhabdoid appearance


Melanin pigment rare

S100 protein+ (diffuse), HMB45 and melan-A+ variably in epithelioid areas


Rare aberrant CK+ or desmin+


Anaplastic large cell lymphoma

Extranodal (soft tissue) involvement is usually associated with advanced nodal disease

Sheets of cells with prominent nucleoli, multinucleated forms

CD30+, ALK+, CD43+, CD45+, CD3+, TIA1+, t(2;5) (p23;q35), TMP3-ALK fusion




PLEOMORPHIC HYALINIZING ANGIECTATIC TUMOR


Clinical Features

This is a locally aggressive lesion that arises mainly in adults (median: 50 years) of either sex in the ankle, foot, or leg, and occasionally other sites, as a slowly growing, painless subcutaneous mass up to 19 cm in diameter (mean: 5 cm). Over a third of reported examples have recurred, so that adequate local excision with follow-up is indicated. Disease has sometimes persisted after resection, and in one example, the recurrence resembled myxofibrosarcoma,1 but none has metastasized.2,3


Pathologic Features

PHAT is circumscribed but nonencapsulated (e-Fig. 13.1), often with a hemorrhagic cut surface. The principal microscopic features (Fig. 13.1, e-Figs. 13.2 to 13.7) are (1) dilated blood vessels of varying size with subintimal and extravascular fibrinoid or collagenous material, extending into zones of stromal hyalinization, and (2) short spindle or ovoid cells, including many with hyperchromatic pleomorphic nuclei and often prominent nuclear pseudoinclusions (e-Figs. 13.6 and 13.7). Mitotic activity and necrosis are usually absent. Additional features include focal myxoid change, a variable component of fat, mast cells, foamy macrophages, and intracellular hemosiderin deposition.

Early lesions show an infiltrate of iron-laden spindle cells around vessels with myxoid change. This is followed by vascular ectasia and
fibrin exudation, and subsequently increased cellularity and atypia with loss of fat.3






FIGURE 13.1 Pleomorphic hyalinizing angiectatic tumor. Dilated and congested vessels with fibrinoid deposition in walls lie in a stroma containing cells with hyperchromatic pleomorphic nuclei and lymphocytes.


Ancillary Investigations

The lesional cells in the majority of PHAT display immunoreactivity for CD34 but are negative for S100 protein, which is helpful in the distinction from schwannoma.2,3 Electron microscopy does not reveal specific differentiation, but the cells are assumed to be fibroblastic.2 Two unbalanced translocations involving chromosomes 1 and 3 and chromosomes 1 and 10 have been described in a PHAT that also had features of hemosiderotic fibrolipomatous tumor (HFLT) (see below).4 The rearrangements of TGFBR3 and MGEA5 as seen in some HFLT and myxoinflammatory fibroblastic sarcoma (MIFS) were not initially found in cases of PHAT so studied.5,6 More recently, however, the presence of TGFBR3 and/or MGEA5 rearrangements has been shown using fluorescence in situ hybridization techniques in PHAT, in tumors showing mixed features of HFLT and PHAT,7 and in hybrid HFLT/MIFS. This suggests that PHAT is related to both HFLT and MIFS, and that PHAT and MIFS may represent morphologic variants of a single, genetically defined entity in which MIFS has metastasizing potential.


Variant

Hemosiderotic Fibrolipomatous Tumor Early PHATs are very similar to HFLTs, originally termed hemosiderotic fibrohistiocytic lipomatous lesions.8,9 These are considered in more detail in Chapter 15. They occur mainly in females in the fifth to seventh decades, in the ankle region with occasional examples at other sites. Most have a history of trauma and a correlation with venous stasis has been suggested.10 HFLTs are circumscribed and composed of plump fibrohistiocytic-like cells (sometimes with intranuclear inclusions) in a septal and perivascular distribution in subcutaneous fat (e-Figs. 13.8 and 13.9). Other features include a focally myxoid stroma, aggregates of small vessels, and marked hemosiderin deposition. The lesional cells, as in PHAT, are immunoreactive for CD34 and also for calponin. About 50% recur.


PLEOMORPHIC SARCOMAS

These are generally high-grade neoplasms in which the common and predominant component is a mixture of undifferentiated spindle, polygonal, or epithelioid, and multinucleated cells. Additional features include variable fibrosis, myxoid stroma, inflammatory infiltrate, hemorrhage, and necrosis. Many examples on detailed examination show foci of mesenchymal differentiation, such as lipoblastic or myoid cells, which allow specific categorization, and similar histologic appearances can also be found in some undifferentiated carcinomas, melanomas, and mesotheliomas.


Prognostic factors in general include tumor size, grade, and location. Additionally, there is evidence that the presence of myoid differentiation, whether manifest morphologically or by immunohistochemistry, is an adverse prognostic factor.11,12 Also, dedifferentiated liposarcoma in the abdomen has a better outcome than other pleomorphic sarcomas.13 The pathologist should therefore attempt to subtype a pleomorphic sarcoma as far as possible to give maximum information for clinician and patient.

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Jun 18, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Pleomorphic Soft Tissue Tumors

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