Section 4 -

FIBROHISTIOCYTIC TUMORS OF SKIN Jennifer M. McNiff, M.D. Yale University School of Medicine

Dermatofibroma (Fibrous Histiocytoma): Clinical features: Typically firm papule on extremities of young adults, may be pigmented Case 4-1: Classic dermatofibroma A 35-year-old woman presented with a firm papule on her thigh. Case 4-1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4-2: Atrophic dermatofibroma A 40-year-old man had a small papule on his shoulder. Case 4-2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4-3: Aneurysmal dermatofibroma (sclerosing hemangioma) A 42-year-old man had a discolored firm nodule on his proximal thigh. Case 4-3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4-4: Deep dermatofibroma A 36-year-old man had a firm nodule on his back, with a clinical impression of cyst. Case 4-4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4-5: Granular dermatofibroma A 30-year-old man had a nodule on his back, with a clinical impression of scar. Case 4-5 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4-6: Sclerotic fibroma A 50-year-old woman had a nodule on her abdomen with a clinical impression of nevus. Case 4-6 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Proliferation of fibroblasts centered in mid-dermis with storiform growth pattern Spindle cells trap dense collagen into balls Cells are plump with angular nuclei, mitoses may be present Epidermal hyperplasia common, sometimes with follicular or sebaceous induction Histologic variants presenting diagnostic challenges: Deep DF Granular cell DF Angiomatoid DF DF with atypical cells (Atypical cutaneous fibrous histiocytoma) Clinical features: Seen in Cowden's disease (multiple hamartoma syndrome) or sporadically Small pearly papules or nodules, any site Histologic features: Well-circumscribed hypocellular bundles of collagen Collagen lies in parallel arrays, separated by spaces containing mucin (plywood grain pattern) IP staining +CD34, actin, vimentin Epithelioid Cell Histiocytoma Clinical features: Typically polypoid lesions, most common on extremities of adults. Clinical impression often includes pyogenic granuloma, nevus, and basal cell carcinoma. Case 4-7: Epithelioid cell histiocytoma A 40-year-old man presented with an exophytic nodule on his foot, with a clinical impression of basal cell carcinoma. Case 4-7 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Polypoid and centered in papillary dermis, usually with epidermal collarette Epidermis flattened with effaced rete ridges Even distribution of large angular epithelioid cells which tend to interdigitate Abundant eosinophilic cytoplasm, large eccentrically placed nuclei Minor component of spindle cells, abundant small blood vessels IP staining positive for factor XIIIa, vimentin, negative for S100, HMB45, CD34 Differential diagnosis: Desmoplastic (dermal) Spitz nevus: nested, not interdigitating cells, S100 positive Malignant melanoma: cellular atypia, epidermal involvement, S100 positive Histiocytoid hemangioma: enlarged endothelial cells, CD31 positive Reticulohistiocytoma: more abundant cytoplasm, secondary elements Atypical fibroxanthoma: more atypia, abnormal mitoses, sun-damaged skin of elderly Comment: This unique variant of benign fibrous histiocytoma was first recognized in 1988, and represents approximately 0.5% of benign fibrous histiocytomas. Unlike classic dermatofibroma, however, most cases of epithelioid cell histiocytoma (ECH) are lesions of papillary dermis, with uniform epithelioid cells, sharp circumscription, and prominent vascularity. Intranuclear inclusions are frequently identified, so that the cells of ECH may easily be mistaken for spitzoid melanocytes. Focal clusters of S100 positive cells may also be seen in ECH, and represent a diagnostic pitfall. In addition, the clinical presentation and prominent vessels create the impression of a primary vascular neoplasm. ECH merits recognition because of its unusual and potentially confounding histologic features. Dermatomyofibroma Clinical features: Young adults with 1-2 cm asymptomatic plaques Favors shoulder area, axilla, upper arm, and neck Case 4-8: Dermatomyofibroma A 32-year-old woman presented with a plaque on her arm, with a clinical impression of dermatofibroma versus mastocytoma. Case 4-8 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Uniform spindle cells in mid to deep reticular dermis and subcutis Fascicles lie parallel to epidermis Distinctive sparing of adnexal structures IP MSA +, SMA -, desmin -, CD34 – Comment: This represents a unique fibrocytic lesion described first as plaque-like dermal fibromatosis in 1991 by Hugel, and subsequently as dermatomyofibroma by Kamino in 1992. Multinucleate Cell Angiohistiocytoma Clinical features: Multiple dome-shaped or flat papules 2-15 mm in diameter Tendency to be clustered on an anatomic area, but may be generalized Most often located on dorsal hand and thigh, also reported on face and chest Age range 35 to 74 years, mean 56 years Lesions usually present for years, occasional reports of spontaneous regression Case 4-9: Multinucleate cell angiohistiocytoma A 59-year-old woman presented with a flat papule on the extensor surface of her middle finger. Case 4-9 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Increased vessels in a diffuse pattern centered in the upper reticular dermis Scattered multinucleate cells with 3-10 nuclei and scalloped angular cytoplasm Slightly coarse collagen, vaguely parallel to epidermis Sparse perivascular lymphocytic infiltrate No "collagen balls" or trapping of collagen at the periphery Differential diagnosis: Dermatofibroma Angiofibroma Hemangioma Comment: Some observers view multinucleate cell angiohistiocytoma as a variant of dermatofibroma, but the consistent presence of multiple lesions, especially on hands, and the absence of follicular induction or "collagen balls" suggest these lesions represent a unique entity. Cellular Digital Fibroma Clinical features: Present as innocuous papules on fingers, toes Case 4-10: Cellular digital fibroma A 34-year-old woman developed a small firm round papule on her finger, with a clinical impression of wart. Case 4-10 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Dome-shaped papule covered by normal squamous epithelium Intersecting fascicles of delicate spindle cells fill the superficial reticular dermis Stroma is fibrotic or occasionally myxoid Inflammation is typically absent Spindle cells label strongly for CD34, with few scattered Factor XIIIa positive stromal cells, and no labelling for S100 protein or EMA May show a resemblance to dermatofibrosarcoma protuberans (DFSP) Comment: Cellular digital fibromas represent a recently described variant of benign acral fibromas with strong CD34 positivity. There is a growing list of CD34-positive tumors in the literature, including sclerotic fibroma, solitary fibrous tumor, pleomorphic fibroma, DFSP, and vascular lesions. The clinicopathologic features of cellular digital fibromas seem unique among this list, however. Importantly, superficial biopsies showing a high degree of cellularity and storiform growth may raise diagnostic concern regarding DFSP. DFSP is rare on the digits of adults, however, and cellular digital fibromas are typically small and clinically innocuous. Nonetheless, awareness of cellular digital fibroma is important to prevent misdiagnosis and over treatment of these small benign tumors. Nodular Fasciitis Clinical features: Rapidly growing self-limited nodules, range from 1-5 cm Sometimes tender; typically affect young to mid-age adults Histologic features: "Pseudosarcomatous" proliferation of spindle cells in myxoid stroma Tissue culture appearance Mitoses may be numerous, edema and extravasated RBCs common Differential Diagnosis: Fibrosarcoma and malignant fibrous histiocytoma Fibrous Hamartoma of Infancy Clinical features: Typically develops in first two years of life Small rapidly growing nodule of subcutis or deep dermis. About one quarter may be present at birth More common in boys than girls Axillae and inguinal regions often affected, uncommon on hands and feet Often several centimeters in diameter Case 4-11: Fibrous hamartoma of infancy A one-year-old girl presented with a 3-centimeter plaque on her lower abdomen, with a clinical impression of dermatofibrosarcoma protuberans. Case 4-11 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Three distinct components giving an "organoid appearance:" Trabeculae of spindle cells and collagen Loose round areas with basophilic mucoid matrix Variable amounts of mature fat, often abundant Fibrous spindle cell areas may stain for actin Loose myxoid areas stain for mucin Differential diagnosis: Infantile fibromatosis (usually more deeply situated, lacks "organoid pattern" Myofibromatosis (often multinodular, hemangiopericytoma-like pattern Calcifying aponeurotic fibroma (acral, older children) Giant cell fibroblastoma (more widespread myxoid areas, giant cells) Comment: Fibrous hamartoma of infancy has a very characteristic pattern when all three tissue components are present. In more fibrous examples, this lesion maybe confused with other fibrous tumors of childhood. Distinction is important because this is a benign lesion, cured by local excision. There is a low but definite rate of recurrence, estimated to be about 16%, but recurrences are indolent and cured by excision. The nature of the cells, in particular the myxoid organoid areas, remains obscure. Infantile Digital Fibroma Clinical presentation: Firm nontender nodule less than 2 cm in diameter Usually present within first year of life, one-third present at birth Fingers affected more frequently than toes, thumb and great toes spared Lesions may be multiple, affecting more than one digit on same hand/foot Local recurrence is common, seen in > 60% cases Case 4-12: Infatile digital fibroma A 9-month-old boy presented with two nodules on his right ring finger. Case 4-12 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Key histologic features: Nodular aggregates of spindle cells, sometimes trapping adnexa Characteristic small round perinuclear inclusions in cytoplasm of fibroblasts Inclusions are eosinophilic and resemble erythrocytes Inclusions are red by Masson Trichrome, purple by PTAH, and do not stain by PAS or Alcian blue Differential diagnosis: Acquired digital fibrokeratoma Palmar fibromatosis Infantile myofibromatosis Angiofibroma Comment: The inclusion bodies in this lesion are diagnostic, and have led to the alternate name "inclusion body fibromatosis." Although there is an initial period of growth in these tumors, many tend to regress spontaneously if followed over time. There is a recent report of treating infantile digital fibroma successfully with intralesional fluorouracil rather than with surgery. The lesions are thought to derive from myofibroblasts, and the inclusions are suspected to contain bundles of actin myofilaments. There may be a relationship to trauma in some cases, and histologically similar lesions have been reported in adults following trauma in other sites. Atypical Fibroxanthoma Clinical features: Nearly always on sun-exposed skin of elderly Rapid growth, ulcerated surface Subset may be seen on extremities of younger patients Case 4-13: Atypical fibroxanthoma A 79-year-old woman presented with an eroded papule on her cheek, with a clinical impression of squamous cell carcinoma. Case 4-13 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Dome-shaped nodule Pleomorphic cells, some spindled, some bizarre shapes Numerous mitoses, including atypical forms Prominent solar elastosis IP: Procollagen +, MSA +, CD34 -, S100 protein - Differential diagnosis: Spindle squamous cell carcinoma Malignant melanoma Pleomorphic fibroma Atypical dermatofibroma Dermatofibrosarcoma Protuberans Clinical features: Slow growing tumor, trunk proximal extremities, young and middle-aged adults Solitary or multiple nodules within indurated plaque, sometimes atrophic Usually greater than one cm in diameter Local recurrence common, distant metastasis rare Case 4-14: Dermatofibrosarcoma A 65-year-old woman presented with a 2-centimeter plaque on her left flank. Case 4-14 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Histologic features: Dermal and subcutaneous tumor Bland spindle cells form storiform patterns Honeycomb pattern of spindle cells in subcutaneous fat Minimal intermingled mature collagen Epidermis spared, usually not hyperplastic May show fibrosarcomatous areas Differential diagnosis: Deep dermatofibroma Malignant fibrous histiocytoma Diffuse neurofibroma Fibromatosis Comment: The distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) continues to pose diagnostic dilemmas for pathologists in daily practice. With routine histology, DFSP tends to be more deeply situated and invades the subcutis in a more diffuse manner. Although some DFs invade the subcutis, this is usually present as tapered aggregates of cells resembling the limbs of starfish. Also, DFs tend to contain abundant mature keloidal collagen and be associated with epidermal hyperplasia, features not typical of DFSP. By immunohistochemistry, most DFSP stain diffusely for CD34, while DF typically stain for Factor XIIIa and not CD34. However, some DF stain at least focally for CD34, and there are reports of "indeterminate fibrohistiocytic lesions" with overlapping features of DF and DFSP. DFSP is characterized by a specific cytogenetic translocation, t(17;22)(q22;q13) and a supernumerary ring chromosome derived from translocation of t(17;22). These translocations affect genes related to the formation of collagen type 1 and platelet-derived growth factor. Giant Cell Fibroblastoma Clinical Presentation: GCF presents as a slowly growing painless mass, most common in childhood Recent reports describe cases of DFSP with areas of GCF and vice versa, as well as GCF recurring as DFSP years after initial excision GCF is now generally regarded as a variant of DFSP Case 4-15: Giant cell fibroblastoma/DFSP A 13-year-old girl presented with a 3-centimeter multinodular tumor in her groin. Case 4-15 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Key histopathologic findings: GCF shows bland spindle cells and multinucleate giant cells in a myxoid stroma Sinusoidal spaces resembling vessels are characteristic of GCF GCF stain for CD34 and vimentin Differential diagnosis: Malignant fibrous histiocytoma Myxoid liposarcoma Comment: Despite the histologic differences between GCF and DFSP, a biologic similarity between the lesions is supported by the coexistence of both tumors in one site, the positive staining of both with CD34, and recent cytogenetic evidence of rearrangement of chromosomes 17 and 22 in both GCF and DFSP. References: Haycox CL et al. Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment. J Am Acad Dermatol 1997;37:438-444. Kamino H, Jacobson M. Dermatofibroma extending into the subcutaneous Tissue: Differential diagnosis with dermatofibrosarcoma protuberans. Am J Surg Pathol 1990;14:1156-1164. Kaddu S, McMenamin ME, Fletcher CDM. Atypical fibrous histiocytoma of the skin. Clinicopathologic analysis of 59 cases with evidence of infrequent metastasis. Am J Dermatopathol 2002;26:35-46. Glusac EJ, McNiff JM. Epithelioid cell histiocytoma: a simulant of vascular and melanocytic neoplasms. Am J Dermatopathol 1999;21:1-7. Kamino H, Reddy VB, Gero M, et al: Dermatomyofibroma: A cutaneous plaque-like proliferation of fibroblasts and myofibroblasts. J Cutan Pathol 1992;19:85-93. Shapiro PE, Nova MP, Rosmarin LA, Halperin AJ. Multinucleate cell angiohistiocytoma: A distinct entity diagnosable by clinical and histologic features. J Am Acad Dermatol 1994;30:417-422. McNiff JM, Subtil A, Cowper SE, Lazova R, Clusac EJ. Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans. J Cutan Pathol 2005:32:413-418. Dickey GE et al. Fibrous hamartoma of infancy: current review. Pediatr Dev Pathol 1999;2:236. Hayashi T et al. Infantile digital fibromatosis: a study of the development and regression of cytoplasmic inclusion bodies. Mod Pathol 1995;8:548. Cin PD et al. Cytogenetic and immunohistochemical evidence that giant cell fibroblastoma is related to dermatofibrosarcoma protuberans. Genes, Chromosomes, & Cancer 1996;15:73-75.