Soft Tissue Tumors With Giant Cells



Soft Tissue Tumors With Giant Cells





INTRODUCTION

Many soft tissue lesions have a variable component of benign multinucleated cells of various types. They include cutaneous fibrous histiocytoma (Touton-type giant cells) (see Chapter 4), giant cell fibroblastoma (closely packed small dark nuclei in horseshoe arrangement) (see Chapter 4), juvenile xanthogranuloma (small wreath-like giant cells) (see Chapter 23), pleomorphic lipoma (floret cells) (see Chapter 15), plexiform fibrohistiocytic tumor (small osteoclast-like cells) (see Chapter 22), and soft tissue chondroma (foreign-body type giant cells) (see Chapter 19). Some variants of tumors that normally lack giant cells can have such a component on occasion. These include nodular fasciitis (see Chapter 3), fibromatosis (see Chapter 2), atypical fibroxanthoma (see Chapter 13), leiomyosarcoma (see Chapter 6), epithelioid sarcoma (see Chapter 11), clear cell sarcoma (see Chapter 12), and undifferentiated pleomorphic sarcoma with giant cells (see Chapter 13). This chapter includes those entities in which giant cells are a prominent and consistent feature. The differential diagnosis is summarized in Table 23.1.


RETICULOHISTIOCYTOMA


Clinical Features

Reticulohistiocytoma is a rare cutaneous lesion that occurs in adults, and can be solitary or multicentric (reticulohistiocytosis). Solitary reticulohistiocytoma occurs in adults with a male predilection and can occur at any site. Multiple lesions are noted in fewer than one-fifth of patients.1 The lesions are circumscribed yellow-tan dermal nodules. They are benign or self-limiting lesions, and etiologically the lesions are thought to be immunologically driven rather than true neoplasms. Multicentric reticulohistiocytosis is a systemic disease with a spectrum of symptoms, including symmetric arthritis, fever, and weight loss. It is sometimes paraneoplastic, with concomitant malignancies reported in 15% to 28% of cases,2 and can




also be associated with autoimmune disorders. Patients develop multiple cutaneous and mucosal papules and nodules along with destructive arthropathy and visceral symptoms.








TABLE 23.1 Differential Diagnosis of Giant Cell Tumors

Typical Clinical Features

Microscopic Features

Ancillary Investigations


Reticulohistiocytoma

Solitary cutaneous or multicentric reticulohistiocytosis affecting skin and synovium of joints

Multinucleated giant cells with ground glass cytoplasm, plump histiocytes, and mixed inflammatory cells

PAS+ (diastase resistant) CD68+, CD163+, MiTF+ (nuclear) in some


Juvenile xanthogranuloma, cutaneous

Infants, head and neck, trunk, proximal limbs


Yellow-brown plaque or nodule

Infiltrative dermal lesion


Sheets of histiocytes


Older lesions have more foamy cells and more Touton giant cells

S100 protein−, CD163+


Juvenile xanthogranuloma, deep

Infants or young children, trunk, intramuscular

Monotonous sheets of macrophages

CD68+, S100 protein−, CD1a−


Regenerating skeletal muscle

Damage due to trauma or infiltrating neoplasm

Atrophy of muscle fibers bringing nuclei into close proximity, mimicking giant cells


No cytologic atypia

Desmin+


Localized tenosynovial giant cell tumor

Any age, F > M


Usually in digits, particularly hand, but may involve larger joints


Nodular, circumscribed mass closely related to the synovium of the tendon sheath or joint

Circumscribed


Sheets of small, histiocyte-like rounded or polygonal mononuclear cells, with varying numbers of osteoclast-like giant cells, foamy histiocytes, siderophages, and other inflammatory cells


Hemosiderin deposition

Osteoclast-like giant cells and proportion of mononuclear cells CD68+


Desmin+ dendritic cells in up to 50% of cases


Diffuse tenosynovial giant cell tumor

Young adults


Papilliform lesion within the synovium; can spread into surrounding soft tissue


Extra-articular form has no connection to adjacent joint; usually in periarticular soft tissue but sometimes muscle

Infiltrative margins, sheet-like patterns of mixture of mononuclear cells, osteoclast-like giant cells along with foamy cells, siderophages, and other inflammatory cells


Variable cellularity with looser zones


Cleft-like spaces

Immunophenotype similar to that in localized giant cell tumor


Giant cell tumor of soft parts (low grade)

Typically middle-aged adults


Extremities, trunk, abdomen and pelvis, and head and neck


More common in superficial than deep soft tissue

Multinodular, cellular nodules of multinucleated osteoclast-like giant cells distributed among mononuclear cells


Divided by collagenous septa with hemosiderinladen macrophages


Mononuclear and giant cells show vesicular, round to oval nuclei lacking atypia


Mitoses


Vascular invasion in some tumors

CD68+ (diffuse and strong in osteoclast-like giant cells, focal in mononuclear cells)


Variable SMA+ in mononuclear cells. CK and S100 protein+ (focally in occasional tumors)


Phosphaturic mesenchymal tumor

Frequently associated with oncogenic osteomalacia


Soft tissue, particularly limbs


Symptoms abate with removal of tumor

Low to focally moderate cellularity


Sheets of spindle to stellate cells with small, bland nuclei, within calcified smudgy myxoid to myxochondroid matrix


Mitotic activity absent to very low


Thin-walled branching hemangiopericytic vessels


Osteoclast-like giant cells

FGF23+ in most tumors


Tumoral calcinosis

Painless subcutaneous mass near joints or in extremities

Multilocular cyst


Fibrosing granulomatous giant cell reaction around crystalline amorphous or calcified material


Nodular fasciitis

Young adults, short history, sometimes previous trauma, size <5 cm

Loose fascicles of spindle and stellate cells in myxoid stroma, extravasated erythrocytes, lymphocytes


Small multinucleated cells in later stages

SMA+


Dermatofibroma

Dermal lesions

Epidermal hyperplasia


Storiform pattern of bland spindle cells with foamy histiocytes


Trapping of peripheral collagen bundles


Hemosiderin and mixed chronic inflammation


Touton-type giant cells

Factor XIIIa+, variable calponin and SMA+


Plexiform fibrohistiocytic tumor

Children to young adults. F > M


Most often in upper extremities


Small dermal or subcutaneous lesions

Multinodular or plexiform arrangements of histiocyte-like cells, spindle fibroblast-like cells and multinucleated, often osteoclast-like giant cells

Giant cells and histiocyte-like cells CD68+, fibroblast-like cells SMA+


Giant cell malignant fibrous histiocytoma

Older adults


Deep soft tissue of limbs or trunk

Sheets and fascicles of markedly anaplastic spindle to ovoid cells


Giant cells are predominantly osteoclast-like, but atypical tumor giant cells can also be present

Osteoclast-like giant cells CD68+


Giant cell fibroblastoma

Children in first decade


Dermis and subcutis

Loose fascicles of spindle cells in abundant collagenous to myxoid stroma


Variable numbers of scattered multinucleate stromal cells with central closely packed small dark nuclei arranged in wreath-like formations


Pseudovascular spaces rimmed by spindle and giant cells

CD34+


COL1A1-PDGFRB fusion transcripts


Pleomorphic lipoma

Neck and back


M > F


Subcutis

Admixture of mature adipocytes, bland spindle to ovoid cells, floret cells, and rope-like collagen bundles


Floret cells are multinucleate giant cells with hyperchromatic, radially arranged wreath-like nuclei

CD34+ (strong in spindle cells)


Variable S100 protein+


Leiomyosarcoma with osteoclast-like giant cells

Older adults


Retroperitoneum, extremities


Also in skin and subcutis and large blood vessels

Intersecting fascicles of spindle cells with bluntended nuclei, paranuclear vacuolations, and eosinophilic cytoplasm

SMA, desmin, and h-caldesmon+


Carcinoma with osteoclast-like giant cells

Primary site may be evident

Nested architecture, epithelioid cells

CK+, EMA+



Pathologic Features

Reticulohistiocytoma is a dermal nodular lesion (e-Fig. 23.1) comprising a mixture of mono- and multinucleated histiocytes and fibroblasts, xanthoma cells, and chronic inflammatory cells (Fig. 23.1).3 The histiocytes are plump with abundant granular eosinophilic cytoplasm. Multinucleate forms are frequent. These are often several times larger than the mononuclear histiocytes and have cytoplasm with a ground glass appearance (Fig. 23.2, e-Fig. 23.2). Nuclear atypia of varying degrees may be present as well as occasional mitoses. There may be focal nuclear spindling of the histiocytes, but this is rarely extensive, and necrosis is absent.

Multicentric reticulohistiocytosis shows similar features, with nodules in the dermis that may extend into epidermis or subcutis, and can also be present at other sites such as synovium. Typically, there are multinucleated histiocytes of irregular size and shape with prominent nucleoli, with ground glass or foamy cytoplasm, although these tend to be smaller with fewer nuclei than those in solitary reticulohistiocytoma. Earlier lesions contain a numerous mixed chronic inflammatory cell infiltrate with lymphocytes, plasma cells, eosinophils, mast cells, and histiocytes, while later lesions show larger numbers of giant cells and fewer lymphocytes.4 As lesions progress, the inflammatory component including giant cells diminishes and fibrosis occurs.4






FIGURE 23.1 Reticulohistiocytoma. The lesion is nodular and comprises a mixture of mono- and multinucleated histiocytes and fibroblasts, xanthoma cells, and chronic inflammatory cells.







FIGURE 23.2 Reticulohistiocytoma. The histiocytes are plump with abundant granular eosinophilic cytoplasm, and there are frequent multinucleated forms.


Ancillary Investigations

The mono- and multinucleated histiocytes express some monocyte/macrophage markers such as CD68, HAM56, and lysozyme but are negative for MAC387 and CD13.5 The plump epithelioid cells express CD163, and in some cases, there is focal nuclear immunoreactivity for microphthalmia-associated transcription factor.3 S100 protein is occasionally positive but desmin, SMA, and CD34 are negative.3,5


JUVENILE XANTHOGRANULOMA, SUPERFICIAL AND DEEP

Juvenile xanthogranuloma is a benign, stable, or self-limiting non-Langerhans cell histiocytic lesion of unknown etiology. This lesion also has giant cells, but this is not as prominent a feature. A detailed account is given in Chapter 12 (see e-Figs. 12.55 to 12.61). Superficial lesions extend to, although do not infiltrate, the epidermis, and also extend into the subcutis. Deep lesions can involve skeletal muscle. Early lesions show a monotonous infiltrate of macrophages with abundant eosinophilic cytoplasm. The cytoplasm accumulates lipid with time and becomes foamy. Older lesions in addition contain variable numbers of mixed inflammatory cells, including eosinophils, and giant cells of both Touton and foreign body type. They are usually located at the edges of the infiltrate or within the superficial dermis. Nuclear atypia, pleomorphism, and mitoses are rare. Deep lesions appear more monomorphic and less lipidized than superficial ones, and longstanding lesions become fibrotic.



TENOSYNOVIAL GIANT CELL TUMORS

Tenosynovial giant cell tumors can occur as localized or diffuse disease, and arise within (from the synovium of joints, bursae, or tendon sheaths) or outside joints. The clinical subtypes have similar immunohistochemical and genetic features.


LOCALIZED TENOSYNOVIAL GIANT CELL TUMOR (GIANT CELL TUMOR OF TENDON SHEATH)


Clinical Features

This relatively common tumor can occur at any age but is seen more often in adult females. It usually occur in the digits, particularly of the hand, but may rarely involve other sites including larger joints such as the ankle and knee.6 It presents as a slowly enlarging, painless, nodular, circumscribed mass closely related to the synovium of the tendon sheath or joint. Tumors may erode into adjacent bone.7 The tumor is benign and can usually be cured by surgical excision, although it can recur locally.

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

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