Cutaneous soft tissue tumors: how do we make sense of fibrous and "fibrohistiocytic" tumors with confusing names and similar appearances?

In the 2018 World Health Organization Classification of Skin Tumors, a wide range of predominantly benign mesenchymal neoplasms are included in the fibroblastic, myofibroblastic, and "fibrohistiocytic" categories. By far the most common of these tumors is dermatofibroma (fibrous histiocytoma). There are many histologic variants of dermatofibroma, some of which (cellular, aneurysmal, and atypical) are associated with a higher risk of local recurrence; these variants may be mistaken for more aggressive tumor types, including sarcomas. Furthermore, distinguishing among the fibrous and "fibrohistiocytic" tumors can be a diagnostic challenge, given their sometimes-similar histologic appearances and confusing nomenclature. Immunohistochemistry and molecular genetic assays play a relatively limited role in the diagnosis of these tumor types, with notable exceptions (i.e., epithelioid fibrous histiocytoma and dermatofibrosarcoma protuberans). Proper recognition of dermatofibrosarcoma protuberans is critical, since this tumor type is associated with locally aggressive behavior; transformation to the fibrosarcomatous variant brings metastatic potential. In recent years, understanding of the molecular pathogenetic basis for cutaneous mesenchymal neoplasms has increased dramatically, with the discovery of gene rearrangements in some of these tumor types. In this review, the histologic features of the most common fibrous and "fibrohistiocytic" cutaneous mesenchymal neoplasms will be discussed, as well as recently identified molecular genetic alterations.

Subcutaneous dermatofibrosarcoma protuberans, a rare subtype with predilection for the head: A retrospective series of 18 cases.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) typically affects the dermis and subcutaneous tissue. The subcutaneous variant is rare. OBJECTIVE: We sought to characterize the subcutaneous DFSP (SC-DFSP) variant and compare it with cutaneous DFSP (C-DFSP). METHODS: This work was a retrospective study of DFSP treated in our institution. RESULTS: Of 124 cases of DFSP, 18 were SC-DFSP (14.5%). Except for the deep location, the pathologic and genetic features were indistinguishable from the C-DFSP variant. Histologically, of 18 SC-DFSP cases, 13 were classic DFSP, 3 fibrosarcomatous DFSP (FS-DFSP), 1 Bednar tumor, and 1 giant-cell fibroblastoma. All tumors expressed CD34 and the COL1A1-PDGFB fusion transcripts. In our series, higher proportions of SC-DFSP tumors (61%) than C-DFSP tumors (8.5%) were located on the head (P < .001). Of the 20 DFSP tumors on the head (16.1%), 11 were SC-DFSP and 9 were C-DFSP. In addition, half the SC-DFSP tumors affected muscle or periosteum, compared with a quarter of the C-DFSP tumors (P = .009). SC-DFSP needed a higher number of Mohs stages than did C-DFSP (P = .009). Median follow-up time was 63 months, and 2 FS-DFSP tumors recurred (1 SC-DFSP, 1 C-DFSP). LIMITATIONS: Limitations include the retrospective aspect of the study. CONCLUSIONS: Most DFSP tumors involving the head were subcutaneous and required more complex surgery. Dermatologists should be aware of this atypical presentation, especially in lesions involving the head.

[Fibrohistiocytic tumors of the skin: a heterogeneous group of superficially located mesenchymal neoplasms]. / Fibrohistiozytäre Tumoren der Haut: Eine heterogene Gruppe oberflächlich lokalisierter mesenchymaler Neoplasien.

So-called fibrohistiocytic tumors of the skin comprise a heterogeneous spectrum of superficially located neoplasms that often show fibroblastic and/or myofibroblastic differentiation. In this review clinicopathologically important variants of dermatofibroma and dermatofibrosarcoma protuberans and their differential diagnoses are discussed in detail. In addition, the clinicopathological features of atypical fibroxanthoma, angiomatoid fibrous histiocytoma, plexiform fibrohistiocytic tumors and pleomorphic dermal sarcoma are presented. Entities that have to be considered in the differential diagnosis are also mentioned.

A review of morphological aspects in dermatofibrosarcoma protuberans with clinicopathological correlations.

Dermatofibrosarcoma protuberans represents a rare malignant neoplasm involving the skin affecting all ages, frequently young adults. It is characterized by high rates of local recurrences after surgery and rare distant metastasis. Clinically it may present as a non-protuberant or a protuberant lesion, having a relative non-specific aspect mimicking a scar, morphea, a benign cyst or other skin tumor. Several clinicopathologic subtypes of dermatofibrosarcoma protuberans have been described: fibrosarcomatous, pigmented, juvenile, myxoid, atrophic, sclerosing and myoid. Among these, the fibrosarcomatous variant stands out as the most aggressive subtype with higher risk of local recurrences and metastasis. All clinicopathologic variants have in common a characteristic microscopic pattern of infiltration into subcutaneous fat. However, this may be present on small areas or unavailable for examination on biopsy fragments. For this reason, the awareness of this variable morphology is essential for establishing a correct diagnosis and performing an optimal treatment.

Vascular congenital dermatofibrosarcoma protuberans: a new histological variant of dermatofibrosarcoma protuberans.

We describe a case of congenital dermatofibrosarcoma protuberans (DFSP) that masqueraded as a vascular tumor both clinically and histologically. Based on the infiltrative growth pattern, presence of capillary-sized vessels, and spindle cell areas with slit-like vascular spaces and numerous thin-walled vessels at the periphery of the tumor, a kaposiform hemangioendothelioma was initially diagnosed. Strong diffuse CD34 positivity and the extension into the subcutaneous fat with a sieve-like effect prompted the fluorescence in situ hybridization analysis, which demonstrated a reciprocal t(17;22) translocation. According to our knowledge, this is the first report of a vascular histological variant of DFSP. This unique variant represents a potential pitfall for dermatopathologists and underlines the importance of cytogenetic diagnostics in unusual cases of DFSP.

[Dermatofibrosarcoma protuberans]. / Dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate malignancy that is initially localized to the skin from where it can invade deep structures (fat, fascia, muscle and bone). It is the most frequent fibrohistiocytic tumor, comprising approximately 1.8 % of all soft tissue sarcomas and 0.1 % of all cancers. It has an estimated incidence of 0.8-5 cases per one million persons per year. Treatment of localized disease consists in complete surgical excision of the lesion by conventional surgery with wide margins (>3 cm) or by micrographic Mohs surgery. Although the cases of metastatic DFSP do not reach 5 % of the total, almost all of them appear after previous local relapses. The prognosis for metastatic cases is very poor with a survival of less than 2 years following detection of metastatic disease. Patients with locally advanced DFSP are not candidates for an initial radical surgical therapy therefore neoadyuvant treatment is required prior to surgery in order to reduce tumor burden. In this regard, chemotherapy and radiotherapy have not been highly efficacious so it is necessary to consider new alternatives. The demonstration of the oncogenic power of the translocation COL1A1-PDGFB in DFSP has allowed the successful introduction of drug therapy with antagonists of the PDGFB receptor for metastatic or locally advanced cases.

Dermatofibrosarcoma protuberans: a clinicopathological study of 20 cases.

AIM: To review the dinical and histological data of 20 cases of dermatofibrosarcoma protuberans presenting at two dermatology centres in Lisbon from 1978 to 1998. PATIENTS AND METHODS: The 20 subjects comprised nine males and 11 females ranging in age from 25 to 79 years, with highest frequency of subjects in the 30-50 year olds. We reviewed the clinical features, histopathological aspects, including morphologic variants and immunohistochemical studies. RESULTS: Median age at diagnosis was 51 years and the trunk was the most frequent location. The characteristic histologic storiform pattern was seen in all cases. Three subjects presented fibrosarcomatous areas, one with myoid differentiation and another with multinucleated giant cells. Immunohistochemical stains revealed CD34 expression in the 18 specimens tested, FXIIIa was negative, and these two antigens proved important for the differential diagnosis of this neoplasm. Local wide excision was performed in 13 cases and seven patients underwent Moh's micrographic surgery. Follow-up ranged from 2 months to 17 years and three recurrences were recorded, two following classical surgery and one after Moh's surgery; there was no difference in the rate of local recurrence (15%) for the two kinds of treatment in our series.

Bednar tumor of the foot: a case report.

Pigmented dermatofibrosarcoma protuberans (Bednar tumor) is a rare neoplasm accounting for approximately 1-5% of all cases of dermatofibrosarcoma protuberans. The majority occurs on the trunk, and the remainders are more or less equally distributed in the upper and lower extremities and the head and neck. Microscopically it is characterized by spindled cells arranged in a tight storiform pattern and admixed with a small population of melanin-containing dendritic cells. The dendritic cells are the primary feature that distinguish this lesion from conventional dermatofibrosarcoma protuberans. We report here a case of Bednar tumor occurring on the dorsal aspect of the foot in a young female.

Indeterminate fibrohistiocytic lesions of the skin: is there a spectrum between dermatofibroma and dermatofibrosarcoma protuberans?

Routine histology and immunohistochemistry can usually distinguish dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP). DF generally expresses factor XIIIa whereas DFSP generally expresses CD34. The authors report 10 cutaneous fibrohistiocytic lesions combining clinical, histologic, and immunohistochemical features of both DF and DFSP. The lesions had an average size of 1.2 cm (range, 0.4-2.7 cm), and occurred on the trunk (n = 6), extremities (n = 3), and face (n = 1) of four men and six women (average age, 30.6 yrs; age range, 15-50 yrs). Eight lesions exhibited acanthosis and densely cellular fascicles with focal storiform areas. All had keloidal collagen, infiltrated the subcutis in a honeycomb pattern, and had low mitotic counts (0 to 4 mitoses per square millimeter). All were diffusely immunoreactive for factor XIIIa (30%-60% of the neoplastic cells) as well as CD34 (20%-70%). This series raises the possibility of a biologic spectrum between DF and DFSP; however, double-immunolabeling studies showed no notable coexpression of factor XIIIa and CD34 by individual cells, suggesting coexistence of two different cellular populations. After an average follow up of 22.3 months (range, 10-46 mos) in six cases, a single recurrence was documented. The ambiguous histologic features and the potential for local recurrence suggest that performing a complete excision may be prudent in these diagnostically indeterminate lesions.

A morphologic study of dermatofibrosarcoma protuberans: expansion of a histologic profile.

UNLABELLED: Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy characterized by a distinctive storiform growth pattern and frequent local recurrences. In this study, we retrospectively reviewed 48 cases of DFSP diagnosed at the Cleveland Clinic Foundation between 1970 and 1999 to determine the prevalence of morphologic variations including the presence of giant cell fibroblastoma (GCF)-like areas, multinucleated giant cells, hypercellular zones and fibrosarcomatous change. RESULTS: The cohort consisted of 42 patients (20 males, 22 females) with a median age at diagnosis of 40 years (range: 10-73 years). Forty-one primary tumors and seven recurrences were evaluated from these 42 patients. Tumor sites included the trunk (22 cases), head and neck (8 cases), upper extremities (7 cases) and lower extremities (6 cases). GCF-like areas were identified in seven (14.6%), multinucleated giant cells in ten (20.8%), hypercellular zones in 12 (25%) and fibrosarcomatous change in six (12.5%) cases, respectively. Combinations included giant cells and GCF-like areas (two cases), giant cells and hypercellular zone (two cases), and GCF-like areas and hypercellular zones (one case). Our findings suggest that DFSP has a wider range of morphologic features, including GCF-like areas, multinucleated giant cells, hypercellular zones and fibrosarcomatous change, than has been previously recognized in the literature.

[Pigmented fibrosarcomatous dermatofibrosarcoma protuberans (Bednar tumor). 3 case reports, analogy with the "conventional" type and review of the literature]. / Il dermatofibrosarcoma protuberans "pigmentato" (tumore di Bednar) fibrosarcomatoso. Osservazione di tre casi, analogie con la forma "convenzionale" e revisione della letteratura.

BACKGROUND: The so-called Bednar tumor represents a pigmented variant of dermatofibrosarcoma protuberans (DFSP) and is characterized by a usually scant (1-5% of cells) population of dendritic melanocytes within an otherwise typical DFSP. This pigmented variant accounts for up to 5% of all DFSPs. Other variants of DFSP include cases showing features (in the primary or recurrence) of either giant cell fibroblastoma or fibrosarcoma. Less than 5% of DFSPs are associated with metastases and many of these show either a fibrosarcomatous component or, much more rarely, an "MFH"-like appearance. Only one previous case has been reported which showed combined features of the pigmented and fibrosarcomatous variants. MATERIALS: We present herein 3 cases of fibrosarcomatous Bednar tumor, all occurring in males, 2 aged 75 and 1 aged 23; two patients were white and one black. The tumors were located on the trunk or shoulder and two had been present for many years with recent rapid growth. One patient developed local recurrence and metastases to bone and lung and died within 1 year. The other two patients are disease free at 3 and 5 years follow-up respectively. All three cases showed typical histological features and in two tumors the pigment was evident macroscopically. CONCLUSIONS: A through literature review, including all cases of fibrosarcomatous DFSP and metastasizing fibrosarcomatous DFSP (whether or not pigmented), confirms that the fibrosarcomatous variant of DFSP (including its pigmented counterpart) is significantly more aggressive than usual DFSP, thus underlining the importance of its accurate recognition.