FIBROHISTIOCYTIC TUMORS OF INTERMEDIATE MALIGNANCY

1.Dermatofibrosarcoma protuberans 2.Sarcoma arising in dermatofibrosarcoma protuberans 3.Bednar tumor 4.Giant cell fibroblastoma 5.Angiomatoid fibrous histiocytoma 6.Plexiform fibrohistiocytic tumor 7.Soft tissue giant cell tumor of low malignant potential

->All are characterized by a significant risk of local recurrence but a limited risk of regional and distant metastasis->in the younger population->dermatofibrosarcoma and its juvenile counterpart, giant cell fibroblastoma, seem to be most closely related to a fibroblast; and indeed the discovery of CD34 immunoreactivity in these two lesions provides a linkage to the CD34+ dendritic cells that populate the dermis->“fibrohistiocytic.” It has a bimodal population of cells, one of which has the histologic and immunophenotypic properties of a histiocyte and the other resembling a myofibroblast.=> +/- cd68; = myoid markers!!

1.DERMATOFIBROSARCOMA PROTUBERANS • firm, plaque-like lesion of the skin, often with surrounding red to blue discoloration.[5]

These lesions have been compared with the morphea of scleroderma or morphea-like basal cell carcinoma. Rarely-atrophy or multiple small subcutaneous nodules.

• The skin overlying these tumors is taut or even ulcerated. Occasionally, areas of the tumor have a translucent or gelatinous appearance corresponding microscopically to myxoid change. Hemorrhage and cystic change are sometimes seen in the tumors, but necrosis, a common feature of malignant fibrous histiocytoma, is rare.

• Micro:• the overlying epidermis does not usual ly display the hyperplasia that characterizes some

cutaneous fibrous histiocytomas (dermatofibromas).• In deep regions, the tumor spreads along connective tissue septa and between adnexae or it intricately interdigitates with lobules of subcutaneous fat, creating a lace-l ike or honeycomb

effect

Superficial (A) and deep (B) extensions of dermatofibrosarcoma protuberans. Spread of the tumor between preexisting col lagen of the dermis may simulate the appearance of a cutaneous fibrous histiocytoma (A). At the deep margin the tumor intricately interdigitates with normal fat (B).

Dermatofibrosarcoma protuberans infi ltrating between adnexal structures /\

uniform population of slender fibroblasts arranged in a distinct, often monotonous, storiform pattern around aninconspicuous vasculature; giantcel ls, xanthoma cel ls, and inflammatory elements are few in number or absent; occasional tumors containmyxoid areas - the storiform pattern becomes less distinct and the vascular pattern more apparent-such tumors can resemble myxoid l iposarcoma

(A) Myxoid change in dermatofibrosarcoma protuberans. (B) When the myxoid change is prominent, the storiform pattern may be lacking and the tumor may resemble a myxoid liposarcoma.

An unusual feature of dermatofibrosarcoma protuberans is the myoid nodule. It may represent an unusual nonneoplastic vascular response to the tumor . Fibrosarcomas have more than 5 mitotic figures/10 high-power fields(HPF), in contrast to areas of conventional dermatofibrosarcoma protuberans,which usual ly have fewer than 5 mit/10 HPF.

(A) Dermatofibrosarcoma protuberans showing the transition to fibrosarcoma (lower left). (B) CD34 in dermatofibrosarcoma(upper right) with fibrosarcomatous areas. marked diminution of CD34 immunostain in the fibrosarcomatous portion of the tumor (lower left).

Fibrosarcomatous areas within dermatofibrosarcoma protuberans

•Dermatofibrosarcoma protuberans is characterized by the nearly consistent presence of CD34; its presence in dermatofibrosarcoma protuberanssuggests a close l inkage to the normal CD34+ dendritic cel ls of the dermis, including those that ensheath the adnexae, nerves, and vessels.•Apolipoprotein D ~

CD34 immunoreactivity within a conventional dermatofibrosarcoma (A) and markedly reduced immunoreactivity within a fibrosarcomatous area of dermatofibrosarcoma protuberans (B).

Differential diagnosis: benign fibrous histiocytoma ; Malignant fibrous histiocytoma (pleomorphic undifferentiated sarcoma); neurofibroma; myxoid liposarcoma

1b. SARCOMA ARISING IN DERMATOFIBROSARCOMA PROTUBERANS (FIBROSARCOMATOUS VARIANT OF DERMATOFIBROSARCOMA PROTUBERANS)• the “sarcomatous” foci should constitute at least 5–10% of the tumor , in contrast to simply a rare to occasional microscopic focus. These zones are characterized by a fascicular (rather than storiform) architectural pattern and are composed of plump spindle cel ls of high nuclear grade. Mitotic activity is increased in these areas, whereas CD34 immunoreactivity is often diminished(Fig. 13-19B), compared to the surrounding dermatofibrosarcoma. In addition, fibrosarcomatous areas are also characterized by a higher MIB-1 label ing index and increased p53 immunostaining than the classic areas. Although we have never required an absolute level of mitotic activity to diagnose sarcomatous change, mitotic activity within these sarcomatous areas averages 7–15/10 HP F[10,] [41] compared to 1-3/10 HP F in dermatofibrosarcoma.

1c. BEDNAR TUMOR (PIGMENTED DERMATOFIBROSARCOMA PROTUBERANS, STORIFORM NEUROFIBROMA)

Bednar tumor . Gross appearance of the tumor is identical to conventional dermatofibrosarcoma protuberans, but the substance of the tumor is fleckedwith melanin pigment.

Pigmented dermatofibrosarcoma protuberans (Bednar tumor)(A).dendritic pigmented cells (B).

2. GIANT CELL FIBROBLASTOMAGrossly, the lesions consist of gray to yellow mucoid masses that are poorly circumscribed and measure 1–8 cm. Micro: loosely arranged, wavy spindle cells with a moderate degree of nuclear pleomorphism that infiltrate the deep dermis and subcutis and encircle adnexal structures in a fashion similar to dermatofibrosarcoma protuberans; The tumors vary in cellularity from those approximating the cellularity of dermatofibrosarcoma protuberans to those that are hypocellular with a myxoid or hyaline stroma ;-Large and irregular in shape, the pseudovascular spaces are lined by a discontinuous row of multinucleated cells that represent variants of the basic proliferating tumor cell. Although these cells appear to contain multiple overlapping nuclei, as seen by light microscopy, they actually represent multiple sausage-like lobations of a single nucleus-ultrastructurally .-Vimentin+-CD34 +/-

-S100-

3.ANGIOMATOID FIBROUS HISTIOCYTOMA•Previously termed angiomatoid malignant fibrous histiocytoma;• relative rarity of metastasis and the overall excellent clinical course;• slowly growing nodular , multinodular , or cystic mass of the hypodermis or subcutis;• One of the most characteristic features is the presence of irregular blood-fi l led cystic spaces best appreciated on cross section.This feature may be so striking as to give the impression of a hematoma, hemangioma, or a thrombosed vessel

Gross specimen of an angiomatoid fibrous histiocytoma illustrating cystic change and a hemosiderin-stained tumor . Normal fat is present at the periphery.

=three features: irregular sol id masses of histiocyte-like cells, cystic areas of hemorrhage, and chronic inflammation. In general, the solid masses of histiocyte-like cells interspersed with areas of hemorrhage occupy the central portion of the tumor , and the inflammatory cells form a dense peripheralcuff that blends with the surrounding pseudocapsule.

Angiomatoid fibrous histiocytoma. Histiocyte-like cells are arranged in solid sheets. Lymphoid infiltrate surrounds the tumor nodule.

4.PLEXIFORM FIBROHISTIOCYTIC TUMOR• in children and young adults and is rarely encountered after the age of 30 years;• small (1–3 cm), ill-defined masses with a gray-white trabecular appearance;•mixture of two components: a differentiated fibroblastic component and a round cell histiocytic component containing multinucleated giant cells;• numerous tiny cellular nodules that occupy the dermis and subcutaneous tissue ;• histiocytic cells that often contain multinucleated, osteoclast-like giant cells and occasionally undergo focal hemorrhage;• The nodules are circumscribed by short fascicles of fibroblastic cells that intersect slightly or ramify in the soft tissue, creating a plexiform growth pattern;• the cells in the 2 zones appear to be in an intermediate stage between fibroblasts &histiocytes.

Immunohistochemical ly, the multinucleated giant cel ls and many of the mononuclear cells express CD68, suggesting true histiocytic differentiation, whereas the spindle cells express smooth muscle actin, as one would expect of myofibroblasts (Fig. 13-51). The cells do not contain other histiocytic markers such as HLA-DR, lysozyme, or L-2; nor are S-100 protein, keratin, desmin, and Factor XIIIa present.

5. SOFT TISSUE GIANT CELL TUMOR OF LOW MALIGNANT POTENTIAL

• the term “soft tissue giant cel l tumors of low mal ignant potential” was proposed for a group of lesions that represents the benign end of the spectrum of malignant giant cell tumor of soft parts (malignant fibrous histiocytoma, giant cell type) and that seem to be the soft tissue analogue of giant cell tumor of bone;•at any age; may develop in superficial or deep soft tissue, most commonly on the arm or hand;•bland mononuclear cells, short spindle cells, and osteoclasts;•lack the strikin atypia that is the hallmark of giant cell forms of malignant fibrous histiocytoma;•often have brisk mitotic activity; about one-half display vascular invasion (as may be seen with giant cell tumor of bone), although necrosis is not seen;•they express CD68 and smooth muscle actin, and the osteoclastic giant cells express the osteoclast-specific marker tartrate-resistant acid phosphatase (TRAP ) !!!!!!!•Ihc neg: CD45, S-100 protein, desmin, and lysozyme.

Giant cell tumor of low malignant potential with mild (A) and moderate (B) atypia of the mononuclear tumor cells. This contrasts with the marked atypia of classic malignant fibrous histiocytoma, giant cel l type.

Differential diagnosis: tenosynovial giant cell tumor , plexiform fibrohistiocytic tumor, epithelioid sarcomas and nodular fasciitis with giant cells.