HISTOPATHOLOGIC AND IMMUNOHISTOCHEMICAL DIAGNOSIS OF BENIGN AND MALIGNANT FIBROUS AND FIBROHISTIOCYTIC TUMORS OF THE SKIN

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HISTOPATHOLOGIC AND IMMUNOHISTOCHEMICAL DIAGNOSIS OF BENIGN AND MALIGNANT FIBROUS AND FIBROHISTIOCYTIC TUMORS OF THE SKIN Hideko Kamino, MD, and Eduardo Salcedo, MD

This article reviews criteria for the histopathologic diagnosis of benign and malignant fibrous and fibrohistiocytic proliferations of the skin. These lesions are composed of several of the following elements in variable proportions: fibroblasts, myofibroblasts, histiocytes, dermal dendrocytes, collagen, elastic fibers, and connective tissue m ~ c i n .9*~ , 47 The benign proliferations are very common tumors, and most of them are easily diagnosed on routine hematoxylin-and-eosinstained sections. There are variants of these lesions that show cytologic atypia or unusual features that could be mistaken for malignant neoplasms. Histopathologic criteria and immunohistochemical reactions that are helpful in distinguishing among these entities are listed in this article. Immunohistochemistry for vimentin, CD34, muscle-specific actin, factor XIIIa, and histiocytic markers KP-1, HAM 56, and a,-antichymotrypsin are very helpful in distinguishing among these entities, but there are some pitfalls in their interpretation. This is an expanded update of an article that appeared in Dermatologic Clinics in 1992. 327

DEEP DERMATOFIBROMA EXTENDING INTO THE SUBCUTANEOUS TISSUE

Dermatofibromas usually involve only the reticular dermis and do not pose a diagnostic problem. However, when dermatofibromas are composed predominantly of fibroblasts and myofibroblasts and extend to the subcutaneous tissue, it can be difficult to distinguish them from the early plaque stage of dermatofibrosarcoma protuberans. Clinical Features

Deep dermatofibromas are most often present on the trunk and proximal extremities of young to middle-aged patients. These lesions measure from 1 to 2 cm in diameter. The skin surface may be flat or slightly elevated. On palpation, the lesion is nodular and attached to the subcutaneous tissue. The clinical diagnosis usually includes cyst, dermatofibroma, and lipoma.

From the Dermatopathology Section, New York University Medical Center, New York, New York

DERMATOLOGIC CLINICS VOLUME 17 * NUMBER 3 * JULY1999

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Histopathologic Findings

A predominantly fibroblastic dermatofibroma is composed of plump fibroblasts arranged in short intersecting fascicles in a haphazard array, admixed with thick, polarizable (birefringent) collagen bundles? The fibroblasts have oval nuclei with small nucleoli. There are scattered mitotic figures but no evidence of atypical mitoses. The collagen bundles are thick, acellular, and straight. There is a perivascular inflammatory-cell infiltrate of lymphocytes and plasma cells at the periphery and base of the lesion. In the fibroblastic variant of dermatofibroma, a few mononuclear and multinucleated histiocytes with hemosiderin in their cytoplasm may be present. Epidermal hyperplasia with hyperpigmentation of the basal layer and flattened rete ridges is a common finding.47 In 1990, Kamino and Jacobson described two main patterns of extension of dermatofibromas into the subcutaneous tissue.** The most frequent pattern, seen in 72% of cases, consists of irregular extensions into the subcutaneous tissue in a vertical or radial fashion, predominantly along the septae, which have a wedge-shaped appearance (Fig. 1). The second pattern, seen in 28% of cases, consists of a smooth, well-circumscribed, deep margin that bulges into the subcutaneous tissue (Fig. 2). In both patterns, fat cells are admixed with fibroblasts and collagen bundles in a narrow band at the interface between the lesion and the subcutaneous tissue or in areas of pre-existing perifollicular

and perieccrine adipose tissue. There is an atrophic variant of dermatofibroma in which the dermal component is thin and the lesion usually extends into the subcutaneous tissue (Fig. 3).6,37, 53 The patterns of extension of dermatofibroma into the subcutaneous tissue can be differentiated from those of dermatofibrosarcoma protuberans, which are also described in this article. Familiarity with these patterns is helpful in distinguishing deep dermatofibromas that extend into the subcutaneous tissue from dermatofibrosarcoma protuberans, thereby avoiding excessive treatment for this benign condition. lmmunohistochemistry

Positive immunohistochemical reactions for vimentin, factor XIIIa (Fig. 4);. 9, 36 musclespecific actin (Fig. 5), and histiocytic markers, such as KP-1 and HAM 56, and negative reaction for CD34 support a diagnosis of deep dermatofibroma.', 53 However, sometimes at the periphery of dermatofibromas there is a relatively increased number of CD3Cpositive dermal dendritic cells. These appear to be the pre-existing dendritic cells that have been pushed by the expanding constituent cells of the dermatofibroma. DERMATOFIBROMA WITH ATYPICAL CELLS

Most dermatofibromas are easy to diagnose, both clinically and histopathologically.

Figure 1. Deep derrnatofibrorna extending into the subcutaneous tissue with the characteristic radial pattern with wedge-shaped septae.

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Figure 2. Derrnatofibrorna extending into the subcutaneous tissue with a smooth border.

However, there are some dermatofibromas in which the presence of atypical cells could be a pitfall in their histologic diagnosis, leading to confusion with atypical fibroxanthoma (superficial variant of malignant fibrous histiocytoma). In 1963, Levan et a1 described two cases of dermatofibromas with atypical cells as pseudosarcomatous dermatofibroma.28In more recent publications, additional cases have been described as atypical (pseudosarcomatous) cutaneous histiocytoma,14 atypical cutaneous fibrous histio~ytoma,’~ and derma-

tofibroma with monster cells.44The authors prefer the term dermatofibroma with atypical cells for this variant of dermatofibroma.

CIinical Features Dermatofibromas with atypical cells are most often present in middle-aged patients and are more commonly located on the extremities of women. Most lesions measure approximately 1 cm in greatest diameter; how-

Figure 3. Atrophic derrnatofibrorna with a thin dermal component extending into the subcutaneous tissue.

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Figure 4. Dermatofibroma extending into the subcutaneous tissue. Immunoreaction for Factor Xllla shows numerous positive dermal dendritic cells.

ever, some lesions may measure up to 2.5 cm. The clinical diagnosis usually includes dermatofibroma. Among the cases reported in three studies, there was no evidence of recurrence in any lesion.14,29, 44 Histopathologic Findings

Dermatofibromas with atypical cells, similar to more typical dermatofibromas, consist

of a dermal nodule composed of plump fibroblasts arranged as short intersecting fascicles and admixed with thick collagen fibers. The characteristic feature of this variant of dermatofibroma is the presence of large, atypical, mononuclear and multinucleated cells with large pleomorphic and hyperchromatic nuclei. Some of them have prominent nucleoli (Fig. 6). The atypical cells have abundant pale-staining vacuolated cytoplasm, fre-

Figure 5. Dermatofibroma. lmmunoreaction for muscle-specific actin shows positive fibroblastshnyofibroblasts between thick collagen bundles.

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Figure 6. Dermatofibroma with atypical cells. The cells have large, hyperchromatic nuclei with prominent nucleoli. Some cells have abundant vacuolated cytoplasm. A few cells are multinucleated.

quently with hemosiderin deposits. Nuclear atypia is more commonly present in the cells with histiocytic differentiation than in the fibroblastic cells. Mitotic figures are rare. The " overlying epidermis is usually hyperplastic.l4,29,44

lmmunohistochemistry

The fibroblasts and myofibroblasts react positively for vimentin and muscle-specific actin. Factor XIIIa highlights an increased number of dermal dendritic cells. The large atypical cells with abundant cytoplasm are positive for vimentin and the histiocytic markers KP-1, HAM 56, and a,-antichymotrypsin. The cells are CD34-negative.

support a diagnosis of dermatofibroma with atypical cells.

PLEOMORPHIC FIBROMA OF THE SKIN

Pleomorphic fibroma of the skin was described in 1989 by Kamino et al.23Pleomorphic fibroma is a variant of cutaneous fibromas or acrochordons in which cytologic atypia is present. The cytologic atypia seen in these lesions is similar to that present in other benign mesenchymal neoplasms such as pleomorphic l i p ~ m aand ~ ~variants of dermatofibroma with atypical cells.14,29, 44

Differential Diagnosis

Clinical Features

The differential diagnosis includes atypical fibroxanthoma (a superficial form of malignant fibrous histiocytoma) and pleomorphic fibroma. Dermatofibroma with atypical cells, in contrast to atypical fibroxanthoma, presents in younger patients, predominantly on extremities, as a smaller and well-circumscribed lesion. Histopathologically, the sparsity of mitotic figures, the absence of atypical mitotic figures, and the lack of solar elastosis

Pleomorphic fibromas are present in adults, with a slight preponderance in women. The lesions appear as solitary, skin-colored, domeshaped papules or polypoid lesions, measuring from 0.4 to 1.6 cm in greatest diameter. They are usually located on extremities. The lesions are asymptomatic and present for several years prior to the biopsy. On follow-up, pleomorphic fibromas have shown a benign clinical course.2,23

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Histopathologic Findings

Pleomorphic fibromas are dome-shaped or polypoid lesions characterized by low cellularity and a predominance of thick collagen bundles in a haphazard array (Fig. 7). The overlying epidermis is usually thin. Scattered between the collagen bundles, there are spindle- and irregularly shaped multinucleated cells with large, pleomorphic, and hyperchromatic nuclei (Fig. 8). Some cells show multilobed nuclei. Mitotic figures are rare. Most of the cells have scant cytoplasm and indistinct cytoplasmic borders. Moderate amounts of connective tissue mucin and scattered fat cells are seen in some cases. A variant involving the subcutaneous tissue with muscle and neural differentiation has been de~cribed.~' lmmunohistochemistry

The spindle-shaped cells and the irregularly shaped, multinucleated giant cells are positive for vimentin. The latter are also positive for CD34. The spindle-shaped cells react positively for muscle-specific actin.15

is characterized by a dermal proliferation of large epithelioid cells with angulated border~.~~ CIinical Features

The entity is more common in adults in the fifth decade of life, with a slight predominance in women. Most of the lesions are present on the extremities, predominantly on the thighs. Epitheloid cell histiocytomas present as polypoid lesions or as firm, sessile papules or nodules measuring from 0.5 to 1.5 cm. Because the lesions may have a vascular appearance, the most frequent clinical diagnosis is pyogenic granuloma, followed by histiocytoma (dermatofibroma). The lesions are usually present from a few months to several years prior to their biopsy. Clinical follow-up shows no evidence of recurrence after conservative excision. Wilson Jones et a1 described one lesion that persisted and recurred after biopsy, but after re-excision there was no evidence of recurrence.l', 52

EPlTHELlOlD CELL HISTIOCYTOMA

Histopathologic Findings

Epithelioid cell histiocytoma was described in 1989 by Wilson Jones and coworkers, and

Epithelioid cell histiocytoma is polypoid or dome-shaped in appearance. The overlying

Figure 7. Scanning magnification of a polypoid pleomorphic fibroma depicts the low cellularity

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Figure 8. Pleomorphic fibroma. There are scattered large cells with pleomorphic and hyperchromatic nuclei, a few of which are multinucleated.

epidermis is thin, and some lesions are focally crusted or ulcerated. At the periphery, there is a collarette of epithelium (Fig. 9). This lesion involves a thickened papillary dermis and the upper reticular dermis with a rounded appearance at their bases that is well demarcated from the underlying dermis. Occasionally there is a teardrop-shaped extension into the lower reticular dermis. Epithelioid cell

histiocytoma is very cellular and is characterized by a dermal proliferation of large, epithelioid stellated and triangular cells with angulated borders. The cells have a very uniform appearance, and the nuclei are oval with small nucleoli (Fig. 10). Some cells have two or more nuclei. Mitotic figures are rarely seen. The cells are partially separated by delicate collagen fibers and variable amounts of con-

Figure 9. Dome-shaped configuration of an epithelioid cell histiocytoma with the characteristic collarette of epithelium.

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Figure 10. Epithelioid cell histiocytorna with spindle-shaped and stellated cells with angulated borders and vesicular nuclei with small nucleoli.

nective tissue mucin. There is no evidence of nesting of cells or epidermal involvement. Adnexal structures are not present in the core of these lesions.”,52

described by Huge1 in the German literature in 1991 as plaqueformige dermale fibromatoseI9 and in 1992 by Kamino et a1 as dermatomyofibroma.24

lmmunohistochemistry

CIinical Features

The neoplastic cells react positively for vimentin, and most of the cells are also positive for factor XIIIa (Fig. ll),indicating a histogenesis towards dermal dendrocytes.”,52 Most of the epithelioid cells are negative for histiocytic markers such as HAM 56, KP-1, MAC 387, lysozyme, a,-antitrypsin and a,-antichymotrypsin.

Because of the presence of large epithelioid cells, the main histologic differential diagnosis of epithelioid histiocytoma is intradermal Spitz nevus. Negative immunohistochemical reactions for S-100 protein and HMB-45 antigen and positive reaction for factor XIIIa support a diagnosis of epithelioid cell histiocytoma.

Dermatomyofibroma presents as an asymptomatic oval or annular, firm, well-circumscribed, flat, superficial plaquelike lesion that, in most cases, is located in or around the shoulder region, including axilla, upper arm, and neck. This entity predominantly affects young women with a mean age of 29.8 years. The lesions measure from 1 to 2 cm in greatest diameter.24A case of a linear dermatomyofibroma measuring 8 cm in length has been d e ~ c r i b e d .The ~ ~ skin surface is flat and smooth, and the color ranges from tan or brown to erythematous. The lesions are usually present from 6 months to 2 years prior to biopsy. The clinical diagnosis often includes dermatofibroma and granuloma annulare, and, less frequently, pseudolymphoma, fibroma, lipoma, and cyst. After conservative excision, there has been no evidence of clinical recurrence in the cases reported.l0r19, 24

DERMATOMYOFIBROMA

Histopathologic Findings

Dermatomyofibroma, a distinct dermal fibroblastic and myofibroblastic entity, was

Dermatomyofibroma is characterized by a well-circumscribed, plaquelike, monomor-

Differential Diagnosis

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Figure 11. With immunoreaction for Factor Xllla, many of the cells react positively.

phous proliferation of spindle-shaped cells involving the reticular dermis (Fig. 12). In most cases, the upper portion of the subcutaneous septae are also involved. The fascicles of cells surround adnexal structures, which are preserved. The spindle-shaped cells are arranged as well-defined, elongated, intersecting fascicles predominantly parallel to the skin surface. The fascicles of spindle-shaped cells have a very uniform appearance (Fig. 13). The

spindle-shaped cells have scanty cytoplasm and elongated nuclei with rounded or pointed ends and one or two small nucleoli. There is no evidence of nuclear atypia or necrosis. Mitoses are occasionally present. The cells are separated by thin collagen fibers, and the elastic fibers are preserved. The fascicles, spindle-shaped cells, collagen fibers, and elastic fibers may have a wavy appearance. Masson’s trichrome stain high-

Figure 12. Dermatomyofibroma. Characteristic plaque-like configuration with fascicles of spindle-shaped cells oriented parallel to the skin surface. Adnexal structures are spared.

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Figure 13. Dermatomyofibroma. Fascicles of spindle-shaped cells with a parallel arrangement between thin collagen bundles. The cells have uniform oval nuclei with rounded or pointed ends.

lights the presence of thin collagen fibers between the spindle cells. With Verhoeff-van Gieson stain, the elastic fibers appear slightly increased in number compared with the surrounding uninvolved dermis. lmmunohistochemistry

The spindle-shaped cells react positively for vimentin and muscle-specific actin. The cells are negative for smooth-muscle actin, desmin, factor XIIIa, and CD34. These results support a fibroblastic-myofibroblastic differentiation and rule out smooth-muscle differentiation.’O,19, 24 Electron Microscopy Findings

Most of the spindle-shaped cells show characteristics of fibroblasts with prominent rough endoplasmic reticulum. Some cells have intracytoplasmic myofilaments, indicat24, 33 ing myofibroblastic differentiation.10, Differential Diagnosis

The differential diagnosis includes dermatofibroma, leiomyoma, and early plaque stage of dermatofibrosarcoma protuberans. Immunohistochemistry readily distinguishes dermatomyofibroma from these entities.

SCLEROTIC FIBROMA OF THE SKIN

Sclerotic fibroma of the skin is a distinct type of collagenous fibroma that was originally reported as a component of Cowden’s 7, disease or multiple hamartoma ~yndrome.~, 30,43, However, a sporadic solitary form without association with other hamartomas has been more recently described.31,35 This entity is included in this article because the constituent cells react positively for CD34 (H. Kamino, personal communication), and this positive reaction could lead to their misdiagnosis as early dermatofibrosarcoma protuberans. Clinical Features

In Cowden’s disease or multiple hamartoma syndrome, the sclerotic fibromas can be solitary or multiple and present in the skin and/or mucous membranes. Sclerotic fibromas are pearly papules or nodules and usually measure less than 1 cm in diameter. Cowden’s disease is characterized by a constellation of multiple epithelial and mesenchyma1 hamartomas located in the skin, mucous membranes, breast, thyroid, and gastrointestinal tract.4,48This is probably a genodermatosis inherited as an autosomal dominant trait.& The sporadic form of sclerotic fibroma is a solitary skin-colored or waxy papule or nod-

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Figure 14. Dome-shaped configuration of a sclerotic fibroma. Scanning magnification highlights the hypocellular and collagenous nature of this lesion.

ule that measures up to 1cm in diameter. The lesion is present predominantly in adults, in both men and women. There is no predilection for any particular anatomic site.31,35

Histopathologic Findings Sclerotic fibroma is characterized by a wellcircumscribed round or oval, dome-shaped dermal nodule (Fig. 14). The nodule is hypo-

cellular and composed predominantly of sclerotic thick collagen bundles in a parallel arrangement and separated by spaces containing deposits of connective tissue mucin. Between the collagen bundles there are thin spindle-shaped cells with scanty cytoplasm and a small nucleus. Aggregates of parallel collagen bundles intersect each other in a plywood-like or whorl-like pattern (Fig. 15).43 Blood vessels are small and inconspicuous. The overlying epidermis is usually thin.

Figure 15. Sclerotic fibroma. Thick collagen bundles arranged as intersecting fascicles in a “plywood-like” or “whorl-like” pattern.

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lmmunohistochemistry

The spindle-shaped cells react positively for vimentin and muscle-specific actin and to a lesser degree for CD34, which highlights the positive spindle-shaped cells between thick collagen bundles (Fig. 16).15,51 Positivity for CD34 may lead to a misdiagnosis as early dermatofibrosarcoma protuberans. The matrix shows variable staining for collagen IV, procollagen, and laminh4

Differential Diagnosis

The main differential diagnosis of sclerotic fibroma includes pleomorphic fibroma and keloid. Pleomorphic fibroma, described previously, is also hypocellular but is characterized by the presence of large, spindle-shaped and irregularly shaped multinucleated cells with large, pleomorphic, hyperchromatic nuclei scattered between thick collagen bundles in a haphazard array. Keloids are larger, illdemarcated, multinodular lesions characterized by heterogeneous foci of very thick, hypocellular, eosinophilic collagen bundles admixed with more cellular areas with plump fibroblasts, thinner collagen fibers, mucin deposits, and increased vascularity.

ATYPICAL FIBROXANTHOMA

Atypical fibroxanthoma is considered to be the superficial variant of malignant fibrous histiocytoma. Clinical Features

Atypical fibroxanthoma occurs more commonly on sun-exposed skin of the head and neck of elderly patients. The neoplasm measures from l to 2 cm in greatest diameter and usually displays a history of rapid growth. The skin surface can be ulcerated and crusted. Less often, lesions may be seen on the trunk or extremities of younger patients. Atypical fibroxanthoma is a low-grade sarcoma and usually is cured by conservative excision.13,49 This tumor has a very low incidence of local recurrence. Rare cases that developed metastases have been reported.18 Histopathologic Findings

The neoplasm presents as a dome-shaped nodule that lifts a thin epidermis, which may be focally eroded and crusted. At the periphery, a collarette of epithelium may be present. The neoplasm is usually composed of a mixture of atypical spindle-shaped cells and

Figure 16. Sclerotic fibroma. lmrnunoreaction for CD34 highlights the spindle-cell configuration of cells between thick collagen bundles.

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like multinucleated giant cells has been de-

lmmunohistochemistry

Both the spindle-shaped cells and the histiocyte-like cells react positively for vimentin. The spindle-shaped cells are positive for muscle-specific actin. The large histiocyte-like cells react positively for a,-antichymotrypsin (Fig. 19).27Both populations of cells are negative for CD34. Differential Diagnosis

Figure 17. Atypical fibroxanthoma. Low magnification highlights the large, pleomorphic, atypical cells between collagen bundles.

larger histiocyte-like cells with abundant pale-staining and vacuolated cytoplasm (Fig. 17). Both types of cells have large, pleomorphic, and hyperchromatic nuclei, and some of them are multinucleated. There are numerous typical and atypical mitotic figures (Fig. 18). At the periphery and base, there is solar elastosis. An unusual variant with osteoclast-

The differential diagnoses include spindlecell squamous-cell carcinoma, spindle-cell malignant melanoma, dermatofibroma with atypical cells, and pleomorphic fibroma. Immunochemistry is the most helpful tool to distinguish among these entities. PLAQUE STAGE OF DERMATOFIBROSARCOMA PROTUBERANS

The classic histopathologic descriptions of dermatofibrosarcoma protuberans have been based on the fully developed nodular lesions. However, in the early stages dermatofibrosarcoma protuberans may occur as slightly elevated or atrophic indurated plaques.l6.53

Figure 18. Spindle-shaped and large pleomorphic cells with hyperchromatic nuclei. An atypical mitotic figure is seen on the left.

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Figure 19. An enlarged histiocyte-like cell reacts positively for alpha1-antichymotrypsin.

When the lesions are biopsied at this stage, they may be confused with dermatofibromas or scars. CIinical Features

Plaque-stage dermatofibrosarcoma protuberans is characterized by a flat or depressed atrophic surface. On palpation, the plaque is indurated and may be bound down to the underlying subcutaneous tissue. It measures from one to a few centimeters in greatest diameter at the time of diagnosis.

form pattern.12,17, 45 The spindle-shaped cells also infiltrate the hair muscles, the stroma between eccrine coils, and sometimes the blood vessel walls. The epidermis is usually thin. At the periphery of the plaques, the preexisting collagen bundles are infiltrated by the neoplastic spindle-shaped cells and appear more cellular and wavy.2l Dermatofibrosarcoma protuberans exhibits

Histopathologic Findings

Plaque stage of dermatofibrosarcoma protuberans is characterized by a flat or depressed surface, hypocellularity, and a proliferation of slender spindle-shaped cells arranged as elongated fascicles which run parallel to the skin surface. In this stage, a storiform pattern is usually inconspicuous or absent. The cells have slender wavy nuclei, there is no evidence of cytologic atypia, and mitotic figures are rare. At the center of the lesion, the dermis may appear thinner, and the eccrine coils and subcutaneous tissue appear closer to the skin surface. The spindleshaped cells are usually admixed with thin, nonpolarizable collagen bundles and variable amounts Of connective tissue In a few Cellular foci, the spindle-shaped cells are arranged as short interlacing fascicles in a stori-

Figure 20. Early nodular area of dermatofibrosarcorna protuberanswith the characteristic “honeycomb’ or “lacelike” pattern of infiltration into the subcutaneous tissue.

HISTOPATHOLOGIC AND EMMUNOHISTOCHEMICAL DIAGNOSIS OF TUMORS OF THE SKIN

two main patterns of infiltration into the subcutaneous tissue. The first pattern is the wellknown and previously described honeycomb or lacelike pattern in which the neoplastic and spindle-shaped cells extend between fat cells (Fig. 20). This pattern is more commonly seen in early and well-developed nodular areas of dermatofibrosarcoma protuberans. The second pattern consists of bundles of spindleshaped cells oriented parallel to the skin surface and arranged in a multilayered pattern (Figs. 21, 22).21,22 This pattern is most commonly seen in plaque lesions of dermatofibrosarcoma protuberans smaller than 3 cm in diameter. In dermatofibrosarcoma protuberans, it is common to see fat cells scattered throughout the neoplasm including the dermal component. The plaque stage of dermatofibrosarcoma protuberans tends to be less cellular than the nodular lesions and is composed of a more uniform population of slender, spindle-shaped cells (Fig. 23). lmmunohistochemistry

In the plaque stage, the spindle-shaped cells react strongly positive for CD34 antibody (Fig. 24).', 3, 26, 53 The reaction is stronger in the plaque areas than in the nodular foci.2o Plaque and nodular areas are negative for factor XIIIa.', 53

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Differential Diagnosis

The differential diagnoses of plaque stage dermatofibrosarcoma protuberans include deep dermatofibroma extending to the subcutaneous tissuez2and dermatomyofibr~ma,~~ which have been described previously. FIBROSARCOMA CIinical Features

Fibrosarcoma is a neoplasm predominantly of deep soft tissues that may involve the overlying dermis and consists of a solitary tumor that measures from 3 to 10 cm in greatest diameter. The neoplasm grows slowly and usually is diagnosed when it becomes a palpable nodule, which may be painful. Fibrosarcoma is more common in young to middleaged adults in the fourth and fifth decades of life. It is most commonly located on the lower extremities, followed by the upper extremities, trunk, and head and neck.34,39 Fibrosarcoma may appear in old burn scars and in areas of chronic radiation d e r m a t i t i ~ .The ~~ tumor tends to recur. Metastases, which are usually hematogenous to the lung, occur in less-differentiated tum0rs.3~Rare cases of congenital or infantile fibrosarcomas have been reported. Fibrosarcomas in children tend to be less aggressive."

Figure 21. Plaque stage of dermatofibrosarcoma protuberans with infiltration into the subcutaneous tissue with a multilayer pattern.

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Figure 22. Dermatofibrosarcoma protuberans with a rnultilayer pattern with bundles of parallel spindle-shaped cells.

Histopathologic Findings

Fibrosarcomas usually secondarily involve the subcutaneous tissue and reticular dermis from the underlying soft tissues (Fig. 25). Fibrosarcoma is composed of a monomorphous population of atypical spindle-shaped cells arranged as intersecting fascicles. There are thin collagen fibers between the cells. In some foci, the intersecting fascicles have a characteristic herring-bone pattern (Fig. 26). The cells have scanty cytoplasm and elongated hyperchromatic nuclei. Mitotic figures are seen in variable numbers. Myxomatous foci may be present. High-grade or poorly differ-

entiated fibrosarcomas are more cellular and show cells with more oval or round nuclei, high mitotic rate, foci of necrosis, and less distinct herring-bone pattern.=*39 lmmunohistochemistry

In most of the cases, the constituent cells react only to vimentin and, to a lesser degree, to muscle-specific actin. Differential Diagnosis

The differential diagnoses of fibrosarcomas include nodular fasciitis, fibromatosis, derma-

Figure 23. Plaque stage of dermatofibrosarcorna protuberans with slender spindle-shaped cells infiltrating collagen bundles.

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Figure 24. Plaque stage derrnatofibrosarcorna protuberans with strong positive reaction of the spindle-shaped cells with CD34.

Figure 25. Scanning magnification of fibrosarcoma infiltrating the subcutaneous tissue and lower reticular dermis.

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Figure 26. Fibrosarcoma. Fascicles of atypical spindle-shaped cells in the characteristic “herring-bone’’ pattern. There are scattered mitotic figures.

tofibrosarcoma protuberans, predominantly fibroblastic atypical fibroxanthoma (malignant fibrous histiocytoma), and malignant peripheral nerve sheath tumor. ACKNOWLEDGEMENT The authors thank James Harter for his assistance in preparation of this manuscript.

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