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Dermatofibroma, also known as “fibrous histiocytoma”, is one of the most common cutaneous soft-tissue tumors. Many variants of dermatofibromas have been described, and knowledge of these variations is important to avoid misdiagnosis of a possibly more aggressive tumor. Histological features of different variants can coexist in the same lesion, but typical common fibrous histiocytoma features are generally found, at least focally, in all cases. However, when cellular changes make up the majority of the lesion, the histopathological diagnosis can become more complex and requires immunohistochemical investigations for correct nosographic classification. We present the case of a cutaneous fibrous histiocytoma, “granular cell” variant, found on the left leg of a 74-year-old woman.

Aneurysmal fibrous histiocytoma (AFH) is a rare variant of benign fibrous histiocytoma. This tumor accounts for less than 2% of all fibrous histiocytomas, 1.7% of all cutaneous fibrous histiocytoma and it is typically known to occur in the extremities of middle-aged patients. A 23 year old male presented with slow growing, pigmented, nodular lesion on the left leg for the past 2 years. The swelling was initially non-tender, but there was a sudden increase in size associated with pain for the past 2 months. With a clinical suspicion of malignant melanoma an excision biopsy was performed and further evaluated by histopathology. The skin covered pigment lesion measuring 1.5x0.8x0.5cm showed fibrohistiocytic cellular proliferations containing blood filled spaces lacking endothelium on microscopy. Ancillary testing with bleaching, perls prussion blue reaction demonstrated the pigment as hemosiderin. Subsequently the lesion was negative for CD34 and positive for Factor XIIIA. Based on the histomorphology, ancillary testing and IHC, the diagnosis of Aneurysmal fibrous histiocytoma was made. Aneurysmal fibrous histiocytoma can be a challenging diagnostic entity due to its close clinical resemblance to melanoma and hemngioma. Although the pathogenesis is unclear, it is believed to be caused by extravasation of erythrocytes from capillaries leading to formation of the cystic blood spaces.

Cutaneous fibrous histiocytoma (cFH) is a common benign mesenchymal neoplasm. Although most cases of cFH behave indolently, rare cases have been reported that show aggressive behavior. At least 41 cases of metastatic fibrous histiocytoma (metFH) have been previously reported, with only eleven cases of fibrous histiocytomas that eventually metastasized analyzed with aCGH thus far. These limited studies have proposed that the number of chromosomal aberrations increases along a spectrum in cutaneous fibrous histiocytomas, making array-based comparative genomic hybridization (aCGH) a potential tool for recognizing aggressive cFHs and metastatic disease, especially when the time interval from the primary diagnosis is prolonged. Herein, we report a case of metastasizing cellular fibrous histiocytoma in which aCGH analysis of the primary and metastatic tumors demonstrated multiple shared chromosomal aberrations, helping support metastatic disease (nine years out from the initial diagnosis) and briefly review the current literature on aCGH and its role in predicting aggressive behavior in such neoplasms. Keywords: Cutaneous fibrous histiocytoma, Array-based comparative genomic hybridization, Cellular fibrous histiocytoma, Metastasizing fibrous histiocytoma

Objectives: While useful in diagnosing angiosarcomas, CD31 can also highlight histiocytes within soft tissue tumors and lead to errors in diagnosis. We sought to determine how often CD31 highlights cutaneous histiocytomas and histiocytoma mimics. Methods: We examined eight epithelioid cell histiocytomas (ECHs), 12 xanthogranulomas (XGs), nine cases of Langerhans cell histiocytosis (LCH), eight reticulohistiocytomas, 11 xanthomas, 29 atypical fibroxanthomas, nine granular cell tumors, four cases of angiolymphoid hyperplasia with eosinophilia, nine intradermal Spitz nevi, and nine angiosarcomas with antibodies directed against CD31, CD34, CD163, and factor VIII. Results: CD31 marked cells in three of 12 XGs, four of nine cases of LCH, one of eight reticulohistiocytomas, one of 11 xanthomas, 10 of 29 atypical fibroxanthomas, four of four cases of angiolymphoid hyperplasia with eosinophilia, nine of nine angiosarcomas, zero of nine granular cell tumors, and zero of eight ECHs. CD34 and factor VIII were negative in all nonvascular cases. Conclusions: Our results indicate that CD31 can mark lesional cells and imitate vascular tumors in cutaneous histiocytomas and histiocytoma mimics, an error that can be avoided by using a panel of antibodies.

Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners. A retrospective archival review was performed to identify cases of epithelioid fibrous histiocytoma (2012-2016). Immunohistochemistry was performed to confirm ALK expression. Targeted next-generation sequencing was applied on RNA extracted from formalin-fixed paraffin-embedded tissue to identify the fusion partners. Twenty-three cases fulfilled inclusion criteria. The mean patient age was 39 years (range, 8-74), there was no sex predilection, and >75% of cases involved the lower extremities. The most common gene fusions were SQSTM1-ALK (N=12; 52%) and VCL-ALK (N=7; 30%); the other four cases harbored novel fusion partners (DCTN1, ETV6, PPFIBP1, and SPECC1L). The pattern of ALK immunoreactivity was usually granular cytoplasmic (N=12; 52%) or granular cytoplasmic and nuclear (N=10; 43%); the case containing an ETV6 fusion partner showed nuclear staining alone. There was no apparent relationship between tumor morphology and the ALK fusion partner. In summary, SQSTM1 and VCL are the most common ALK fusion partners in epithelioid fibrous histiocytoma; DCTN1, ETV6, PPFIBP1, and SPECC1L represent rare fusion partners. The proteins encoded by these genes play diverse roles in scaffolding, cell adhesion, signaling, and transcription (among others) without clear commonalities. These findings expand the oncogenic promiscuity of many of these ALK fusion genes, which drive neoplasia in tumors of diverse lineages with widely varied clinical behavior. This is the first documented account of ETV6-ALK and SPECC1L-ALK translocations in neoplasms.

Aneurysmal Fibrous Histiocytoma (AFH) is a distinct and a rare clinicopathological variant of Cutaneous Fibrous Histiocytoma (CFH). It differs from the usual benign fibrous histiocytoma clinically and morphologically with high rate of recurrence. Here, we report a case of AFH with history of recurrence which presented as a polypoid swelling and showed vascular spaces with no endothelial lining which was proved negative by CD34 immunostaining. The spaces were bordered by tumour cells.

Background Cutaneous fibrous histiocytoma (FH) is a common mesenchymal neoplasm. Metastasis is rare, disproportionately occurring among the aneurysmal, cellular, atypical, and deep variants. Objective We determined whether DNA copy number changes occurred in atypical FH (AFH), and whether they were similar to those in metastasizing FH (MetFH) and benign cellular FH (CFH). Methods Five primary tumors of MetFH were evaluated by array-based comparative genomic hybridization analysis, with tissue from local recurrences and lung metastases in 2 and 2 patients, respectively. Seven indolent AFH and 5 CFH were identified for comparison. Results Substantial differences between the groups were found both in the frequency of chromosomal aberrations (higher among MetFH and absent or solitary in CFH) and array-based comparative genomic hybridization profiles (frequent gains of 7 and 8q and losses of Xq in MetFH; recurrent losses of chromosomes 9 and 22 in AFH; isolated loss of 5q and gain in chromosome 20 in 2 CFH). Fatal MetFH cases (2 of 5 cases) exhibited the highest rate of chromosomal aberrations. Limitations This study included a small sample size with a short-term follow-up. Conclusions Benign CFH, indolent AFH, and MetFH represent distinct biological entities within the spectrum of FH; array-based comparative genomic hybridization may be a tool in recognizing FH cases with metastatic potential and increasingly aggressive behavior.

Background: Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH. Methods: One hundred consecutive cases of morphologically typical CBFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: SMA positivity was found in tumor cells in 93 of 100 cases (93%). Desmin positivity was found in 32 of 100 cases (32%). CD34 was positive in 6 of 100 cases (6%). There was no evident correlation between immunophenotype and anatomic site or other clinical variables. Conclusion: Frequent desmin (32%) and occasional CD34 (6%) expression are encountered in CBFH. Desmin positivity can be explained on the basis of myofibroblastic differentiation. The occasional CD34 positivity in a subset of CBFH should not be a deterrent from making the correct pathologic diagnosis, based on characteristic morphologic features.

Atypical fibrous histiocytoma is a rare and a distinct variant of cutaneous fibrous histiocytoma which can be misdiagnosed as sarcoma. It is mainly composed of a mixture of fibroblastic and histiocytic cells, especially found in the skin (dermatofibroma), particularly in the limbs. It is quite uncommon and is difficult to distinguish from a malignant lesion. Due to the lack of clear cut predictive morphological patterns and due to the suspicion of malignancy, complete surgical excision is recommended. Provided that atypical fibrous histiocytoma is treated by complete excision, a benign outcome is to be expected in most cases. However, like the cellular and aneurysmal variants of fibrous histiocytoma, atypical fibrous histiocytoma shows a higher tendency to recur locally than ordinary fibrous histiocytoma and may rarely metastasize. Lesions with floridly atypical features represent potential pitfalls for overinterpretation as pleomorphic sarcoma, which would appear to be inappropriate in most cases. Due to its rarity and uncertainty, we report a case of atypical fibrous histiocytoma and discuss its presentation, nature, types and treatment with reference to a brief review of literature.

Reactive epithelial hyperplasia is a well-known phenomenon which occurs adjacent to certain neoplasms such as cutaneous fibrous histiocytoma, granular cell tumor, Spitz nevus, and melanoma. We report 46 cases of paratumoral follicular and epidermal hyperplasia associated with basal cell carcinoma (BCC). This reactive process associated with BCC has certain characteristic features. It is focal, superficial, and predominantly folliculocentric. It may resemble other tumors such as squamous cell carcinoma and may appear in sections where BCC is absent. The recognition of this entity may help dermatopathologists avoid misdiagnosing this process as a tumor and can suggest further search (section through the block or rebiopsy) when this reactive phenomenon is seen in sections without the associated BCC.

Background: Ulceration and osteoclast-like giant cells are two pathological features uncommonly seen in dermatofibromas. To our knowledge, the presence of these features has not been previously described within the same lesion. Methods: We report the clinical, histopathological and immunohistochemical findings of a 38-year-old man with an ulcerated dermatofibroma (DF) on the sole containing OLGC. Comments: DF, or cutaneous fibrous histiocytoma, is a frequent dermatological lesion with many clinicopathological variants. Therefore, a correct diagnosis is not always straightforward, especially when two rare features co-exist in the same lesion. Differential diagnosis was performed with cutaneous and even non-cutaneous lesions. An explanation for the clinicopathological findings is also described.

This is a report of a previously undescribed type of histiocytoma distinguished clinically by its occurrence as a solitary elevated nodule often with a vascular appearance and cytologically by the presence of large angulated epithelioid cells. Nineteen lesions from 11 women and eight men have been studied. The lower limb was the commonest site for the nodules. The mean age at presentation was 42 years (range 23-63). Only one lesion recurred after attempted removal. This lesion in the past may, have been mistaken for a Spitz naevus. Immunohistochemical findings mirror those of ordinary histiocytomas. In particular approximately 50% of the constituent cells label with a polyclonal antibody directed against factor XIIIa--an antibody that labels dermal fixed connective tissue cells (fibrocytes) and cells in ordinary histiocytoma, but not the cells of Spitz or common melanocytic naevi.

Atypical cutaneous fibrous histiocytoma is a rare variant of dermatofibroma/fibrous histiocytoma characterized by striking atypia, thus resembling atypical fibroxanthoma. We studied 9 examples of ACFH histopathologically and immunohistochemically to investigate the nature of these atypical cells. Histology revealed ill-defined skin nodules, which were polypoid in 6 cases. A minority of mononuclear and giant cells (< 5%) revealed striking pleomorphism and showed large nuclei with prominent nucleoli. Immunohistologically, the atypical cells expressed vimentin, but were negative for S-100 protein, the keratin marker MNF116, alpha smooth muscle actin, CD34, factor XIIIa, and monocyte/macrophage markers Ki-M1p, KP1 (CD68), and MAC387. Positivity for MiB1 was very modest (< 1%) and limited to small- and medium-sized, inconspicuous cells. Multinucleate giant cells proved to be heterogenous, on one hand cells with differentiation toward macrophages with positivity for Ki-M1p and KP1, on the other toward fibroblasts positive for vimentin only. These immuno-histochemical results for differentiation markers in atypical cutaneous fibrous histiocytoma are similar to our previous findings and data in atypical fibroxanthoma; MiB1 helps to separate these entities from each other as the latter shows a very high proportion of proliferative atypical cells corresponding to the numerous mitoses seen in routine sections.

Benign fibrous histiocytoma is a common soft tissue tumor that can be deep or superficially located. Although the deep type of fibrous histiocytoma has a predilection for the orbit, the eyelids are an unusual location for the cutaneous type. A 42-year-old woman had bilateral yellowish nodular masses of the eyelids for two years. Pathological examination after excision revealed benign fibrous histiocytoma. Our case is an unusual clinical presentation of cutaneous fibrous histiocytoma as well as a rare location such as the eyelids.

Epithelioid benign fibrous histiocytoma, also known as 'epithelioid cell histiocytoma,' has traditionally been considered a morphologic variant of cutaneous fibrous histiocytoma (dermatofibroma). In addition to its characteristic epithelioid cytomorphology, several phenotypic differences suggest that epithelioid fibrous histiocytoma may differ biologically from other variants. Recently, ALK rearrangement was described in two cases of epithelioid fibrous histiocytoma and separately in two cases reported as 'atypical' fibrous histiocytoma (with epithelioid features), with corresponding ALK expression detectable by immunohistochemistry. The goals of this study were to determine the frequency of ALK expression by immunohistochemistry in epithelioid fibrous histiocytoma, to determine its value for the diagnosis of epithelioid fibrous histiocytoma among variants and other histologic mimics, and to evaluate ALK gene rearrangement in epithelioid fibrous histiocytoma. ALK protein expression was evaluated in whole tissue sections from 33 epithelioid fibrous histiocytomas, 41 other cases of fibrous histiocytoma (11 conventional and 10 each cellular, atypical, and aneurysmal types), 10 cutaneous syncytial myoepitheliomas, and 5 atypical fibroxanthomas, using a mouse anti-ALK monoclonal antibody. Fluorescence in situ hybridization (FISH) was performed using break-apart probes. In total, 29/33 (88%) cases of epithelioid fibrous histiocytoma showed diffuse cytoplasmic ALK expression. Staining was moderate to strong in intensity in all cases except one, which showed diffuse weak expression. All other tumor types were negative for ALK expression. FISH demonstrated ALK rearrangement in all ALK-immunoreactive cases evaluated (n=13), and not in one ALK expression-negative epithelioid fibrous histiocytoma successfully examined. In conclusion, the majority of epithelioid fibrous histiocytomas demonstrate ALK expression and ALK gene rearrangement. ALK expression is not seen in other variants of fibrous histiocytoma, providing a useful diagnostic tool to distinguish epithelioid fibrous histiocytoma from most histologic mimics. The expression of ALK suggests that epithelioid fibrous histiocytoma is a biologically distinct tumor type, unrelated to conventional fibrous histiocytoma and histologic variants.

Background: Dermatofibroma (DF) or cutaneous fibrous histiocytoma is a common benign fibrohistiocytic lesion involving the dermis and subcutis. Histologically, it is subclassified into fibroblastic and histiocytoid forms. Its histogenesis is controversial. While often referred to as a neoplastic process, definite evidence of neoplasia in DF has been lacking. Alternatively, some authorities have suggested that DF is a fibrosing inflammatory process. Diagnostically, the most important question faced is the distinction from dermatofibrosarcoma protuberans (DFSP). Misdiagnosis can occur, as the early phase of DFSP can simulate DF, particularly the deep and cellular forms of DF. Methods: To address this issue, and to investigate whether DF is in fact a neoplasm, we evaluated 31 examples of DF of various histological types in female patients and assessed clonality by analyzing X-chromosome inactivation as indicated by the methylation status of the androgen receptor gene (HUMARA). Representative cases of DFSP were analyzed for comparison. Results: Among the selected 31 cases of DF, 24 cases provided intact DNA and informative polymorphism at the AR alleles, including one case of recurrent deep fibrous histiocytoma. Among these 24 cases, randomly inactivated AR alleles were observed in 17 cases including a deep, recurrent fibroblastic DF. A non-random inactivation at AR alleles was observed in seven cases, of which six cases showed either typical histiocytoid form of DF (four cases) or mixed cell types with predominant histiocytoid cell type (two cases). One fibroblastic DF also showed a monoclonal pattern. HUMARA analysis of DFSP revealed non-random inactivation of polymorphic AR alleles. Conclusions: These findings suggest that DF is a heterogeneous process. Monoclonal genotype was found in DFs with histiocytoid or mixed type with predominant histiocytoid features, suggesting that histiocytoid cells probably represent the neoplastic component. The fibroblastic form of DF may represent a reactive fibroblastic proliferation. Alternatively, it may represent a true neoplasm whose neoplastic cell type has been obscured by prominent reactive fibroblastic component.

We report on eight cases of a distinct variant of cutaneous schwannoma characterized by prominent Verocay body formation (75-100% of the tumor bulk) that may cause considerable diagnostic difficulties. Like ordinary cutaneous schwannomas, these lesions preferred the head and neck region of young adults without sexual predilection and were clinically interpreted as cyst, basal cell carcinoma, or nevus. Histological examination revealed well-circumscribed nodules. Three of them consisted exclusively of nodular or ribbon-like Verocay bodies. A variable admixture of Antoni A or B type of differentiation (< 25%) was seen in five other cases. The following patterns were seen: fascicular spindle-shaped, onion-like epithelioid, myxoid-hypocellular, and degenerated ("ancient") with prominent fibrosis/hyalinosis and occasional bizarre giant cells. Immunohistochemically, the lesions were positive for S-100 protein (and vimentin) but negative for a broad panel of neurogenic and intermediate filament markers. The capsule showed focal labeling for EMA and--when it was markedly thickened--also for SMA. Labeling with E9, an anti-metallothionein marker indicative of cell activity, was negative, underscoring the slow growth potential of these lesions. No recurrence was seen in the six patients with follow-up information. The differential diagnosis includes other lesions with prominent palisading. (Amianthoid) myofibroblastoma and palisading leiomyoma are consistently positive for SMA and desmin, respectively. Palisading cutaneous fibrous histiocytoma and myofibroblastic dermatofibroma are variably positive for Factor XIIIa, SMA, and E9 and/or NK1C3 (CD57). Palisaded encapsulated neuromas are primarilly differentiated by the presence of nerve fibers with myelin sheaths.

Recently, a distinct variant of cutaneous fibrous histiocytoma (FH) has been histologically characterized as a "cellular" subtype. This variant is often mistaken for sarcoma, including dermatofibrosarcoma protuberans. We report a case of cellular FH of the skin in which the cytogenetic analysis demonstrated a novel chromosome pattern, possibly allowing distinction from its histologic simulants.

Atypical fibrous histiocytoma (AFH) is an uncommon variant of cutaneous fibrous histiocytoma that can display histologic features associated with malignancy. Fewer than 150 cases have been reported in the literature. The majority of these lesions present on the trunk and extremities of middle-aged women. Genital lesions are rare, with one documented case of vulvar AFH and another case of scrotal AFH in the literature. We report an additional case of a 68-year-old woman who was diagnosed with an AFH in an unusual location, the perianal area. Histologically, the lesion was characterized by a nodular fairly well-circumscribed proliferation of large epithelioid macrophages with scattered lymphocytes and mast cells in the background. The atypical macrophages contained enlarged markedly pleomorphic nuclei with prominent nucleoli. Scattered multinucleated "monster cells" and atypical mitoses were observed throughout the lesion. Immunologically, the lesional cells were focally positive when stained with antibodies against CD163 and Factor XIIIa. They were negative for CD34, CD31, desmin, smooth muscle actin, CAM 5.2, keratin 5/6, S100, CD3, CD20, and CD30. The constellation of histologic and immunologic features was most consistent with an AFH. To our knowledge, this case is the first perianal presentation of AFH to date.

Cutaneous fibrous histiocytoma (FH) is considered a benign tumor; however, certain types of FH have been shown to have a tendency for local recurrence, and there are rare reported cases of metastasis. In this study, 16 cases of morphologically benign FH with locoregional or distant metastasis were identified in consult files. Pathologic features of primary, recurrent, and metastatic tumors, as well as clinical outcome, were evaluated. Nine were male and 7 were female patients; mean age was 42 years (range, 3 to 68 y). Primary tumors arose on the leg in 5 patients, buttock in 1, trunk in 3, shoulder in 3, neck in 2, and finger in 1. The primary site in 1 case was unknown. Fifteen primary tumors available for review involved the dermis; 6 extended into the superficial subcutis. Tumor size ranged from 1 to 5 cm (median 3.2 cm). Histologically, primary tumors showed characteristic features of FH, being composed in most cases of a polymorphous population of bland spindle and histiocytoid cells in a mixed storiform and fascicular growth pattern with admixed foam cells, multinucleate cells, and inflammatory cells in varying proportions. Histologic variants included 11 cellular (2 with mixed atypical and cellular features), 2 aneurysmal, 1 atypical, and 1 epithelioid type. All tumors showed entrapment of hyalinized collagen bundles. Mitotic activity ranged from

Dermatofibroma (cutaneous fibrous histiocytoma) represents a common benign mesenchymal tumor, and numerous morphological variants have been described. Some variants of dermatofibroma are characterized by an increased risk of local recurrences, and there are a few reported metastasizing cases. Unfortunately, an aggressive behavior cannot be predicted reliably by morphology at the moment, and we evaluated the value of array-comparative genomic hybridization (CGH) in this setting. Seven cases of clinically aggressive dermatofibromas were identified, and pathological and molecular features were evaluated. The neoplasms occurred in four female and in three male patients (mean age was 33 years, range 2–65 years), and arose on the shoulder, buttock, temple, lateral neck, thigh, ankle, and cheek. The size of the neoplasms ranged from 1 to 9 cm (mean: 3 cm). An infiltration of the subcutis was seen in five cases. Two neoplasms were completely excised, whereas an incomplete or marginal excision was reported in the remaining cases. Local recurrences were seen in six cases (time to the first recurrence ranged from 8 months to 9 years). Metastases were noted between 3 months and 8 years after diagnosis in six patients. Two patients died of disease, and two patients are alive with disease. Histologically, the primary tumors showed features of cellular dermatofibroma (four cases), cellular/aneurysmal dermatofibroma (one case), atypical/cellular dermatofibroma (one case), and classical dermatofibroma (one case). Mitotic figures ranged from 3 to 25 per 10 high-power fields, and focal necrosis was present in five cases. Interestingly, malignant transformation from cellular dermatofibroma to an obvious spindle cell/pleomorphic sarcoma was seen in one primary and in one recurrent neoplasm. Five neoplasms showed chromosomal aberrations by array-CGH, suggesting that these changes may represent an additional diagnostic tool in the recognition of cases of dermatofibroma with a metastatic potential.

Dermatofibroma, also called cutaneous fibrous histiocytoma or sclerosing hemangioma, is a fairly common, benign cutaneous tumor. Polypoid dermatofibroma is an unusual and poorly recognized form of this entity. We describe a peculiar case of this variant presenting with a unique morphology characterized by a round flat shape with a slim pedicle, although its histopathological picture was rather typical of that of ordinary dermatofibroma.

We report seventy-four cases of a distinctive variant of cutaneous fibrous histiocytoma, which is often mistaken histologically for sarcoma and which carries a high local recurrence rate. These tumors appeared most commonly in young or middle-aged adults, with a predominance in men (male/female ratio 1.9:1). Anatomic distribution was wide, with cases occurring mainly in the upper limb/limb girdle (34%), lower limb/limb girdle (27%), and head and neck region (20%). Most lesions had been present for only a few months, and their sizes ranged from 0.5 cm to 2.5 cm in maximum diameter. Twelve (26%) of 46 cases with follow-up (mean duration 3 years) recurred locally, in one case twice. Distinctive histologic features were a commonly fascicular growth pattern, predominance of eosinophilic spindle cells with tapering nuclei, a moderate mitotic rate (mean three per 10 high-power fields), and frequent extension into the subcutaneous fat (33% of cases). In addition, all cases showed at least focal cytologic polymorphism (inflammatory cells, foam cells, giant cells), and 58% showed associated epidermal alterations in common with usual cutaneous fibrous histiocytomas. Nine cases (12%) showed foci of central necrosis. Immunohistochemical studies (ABC method) found only vimentin and very focal smooth muscle actin positivity. Tests for CD34, desmin, S-100, keratin, and Factor XIIIa were negative in all cases. These lesions should be distinguished from dermatofibrosarcoma protuberans and leiomyosarcoma, with which many of these cases were initially confused.

Background: Epithelioid fibrous histiocytoma (EFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH) but can lack many characteristic features. The presence of epithelioid cytomorphology may mimic other dermal neoplasms. Our anecdotal experience of epithelial membrane antigen (EMA) expression in some examples of EFH has caused diagnostic difficulty. Our aim was to examine the immunohistochemical profile and incidence of EMA expression in EFH. Methods: Forty-four cases of EFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: Membranous EMA positivity was found in tumor cells in 27/42 cases (64%). Focal positivity for factor XIIIa was found in 10/14 (71%) and D2-40 in 14/27 (52%). Scattered smooth muscle actin (SMA)-positive tumor cells were seen in 11/43 (25%). Focal positivity for claudin-1 was found in 3/42 (7%). CD163 staining highlighted stromal macrophages; however, in five cases it was difficult to exclude focal staining of tumor cells. Tumor cells were consistently negative for pan-keratin, AE1/AE3, S100, CD31, CD34, CD68, desmin, p63, GFAP and CD45/LCA. Conclusion: Frequent EMA expression in EFH represents an unexpected finding and constitutes a potential diagnostic pitfall. Although of uncertain significance, this finding, when combined with established morphologic differences, raises the possibility that EFH is unrelated to classic FH. Doyle LA, Fletcher CDM. EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall.

CD163, a hemoglobin scavenger receptor, is expressed in monocytes and macrophages. Recent work has shown that this marker is specific for neoplasms of histiocytic differentiation. Our aim was to test the ability of CD163 to separate cutaneous histiocytomas from their morphologic mimics. We tested the expression of CD163 in 78 cases, including 19 xanthogranulomas, 16 atypical fibroxanthomas, 6 reticulohistiocytomas, 8 epithelioid cell histiocytomas, 9 cases of Langerhans cell histiocytosis, 10 xanthomas, and 10 intradermal Spitz nevi. CD163 expression was seen in all xanthogranulomas and reticulohistiocytomas, 4 epithelioid cell histiocytomas, 2 cases of Langerhans cell histiocytosis, and 8 xanthomas but was absent in atypical fibroxanthomas and Spitz nevi. CD163 is an excellent marker for confirming histiocytic differentiation and is useful in eliminating morphologic mimics such as Spitz nevi from the differential diagnosis. The lack of CD163 in atypical fibroxanthomas argues against a histiocytic origin for this tumor.

Dermatofibroma (DF), or cutaneous fibrous histiocytoma, is a common cutaneous tumor with many variants that may arise from alterations in the morphology and composition of its various components. One type that has not received much attention is DF with osteoclast-like giant cells. Two cases of this rare tumor are described. The importance of this tumor lies in the possible histologic confusion with a variety of benign and malignant neoplasms, including giant cell tumor of tendon sheath, giant cell tumor of bone, and giant cell reparative granuloma.

Dermatofibroma or cutaneous fibrous histiocytoma is a common benign skin lesion with multiple, distinct histologic variants, including cellular, aneurismal, epithelioid, atypical, lipidized "ankle-type," palisading, and cholesterotic. Although dermatofibromas are considered benign neoplasms, certain variants including cellular and aneurismal ones have shown to have a notable tendency to locally recur after excision. Indeed, although extremely rarely, metastases have been associated with the cellular and aneurysmal/atypical variants. Signet-ring cells are formed by cytoplasmic accumulations of various substances that push the nucleus toward the cellular border. The finding of signet-ring cells in a skin neoplasm always raises the suspicion of metastatic adenocarcinoma, although a number of reports have shown their occurrence in primitive cutaneous neoplasms as well. Signet-ring cell formation, however, has never been described in dermatofibroma. We present, for the first time, a new, distinctive variant of dermatofibroma, so-called signet-ring cell dermatofibroma, in a 16-year-old man with a slowly growing skin tumor on the lateral side of his right leg. Histologic examination demonstrated a striking signet-ring cell appearance of most of the cells in an otherwise fibrohistiocytic looking proliferation. Histochemical and immunohistochemical stainings confirmed the diagnosis of dermatofibroma. The phenomenon described in this case enlarges the histologic spectrum of cutaneous fibrous histiocytoma and may cause substantial differential diagnostic problems.

Aneurysmal fibrous histiocytoma (AFH) (Santa-Cruz DJ, Kyriakos M. Aneurysmal (‘Angiomatoid’) fibrous histiocytoma of the skin. Cancer 1981;47:2053–2061) is a distinct but poorly recognized clinicopathological variant of cutaneous fibrous histiocytoma (CFH) that may result from the slow extravasation of blood into the tumour. The resulting lesion can have a very different clinicopathological appearance resulting in diagnostic confusion. We describe a patient with an AFH that presented as a pigmented nodule on the foot and discuss clinical recognition and histological differentiation from other tumours.

Dermatofibroma (DF) or cutaneous fibrous histiocytoma is a common benign skin tumor that exhibits multiple, distinct histologic variants. Although clear cell DF has been described in the literature, balloon cell degeneration causing a clear cell DF phenotype has been not been reported to date. Herein, we describe the clinicopathologic findings of balloon cell DF arising on the heel of a 43-year-old man. Clinically, it presented as enlarging tan-white, ulcerated, firm 1.5 cm nodule, clinically suspected to be pyogenic granuloma. Excisional biopsy revealed a circumscribed fibrous tumor populated by mostly clear and spindle cells. A zonal arrangement separated the varied tumor cells where the most superficial, polypoid area showed large, clear polygonal balloon cells; the mid-dermal zone demonstrated a transition between balloon cells, epithelioid cells, and spindle cells; and the deep dermal zone had storiform arrangement of spindle cells, with the fascicles separated by coarse collagen bundles. A CD10+ > CD68+ > Factor XIIIa+ immunophenotype was identified with negative immunolabeling for S-100 protein, HMB-45, cytokeratin AE1/AE3, desmin, smooth muscle actin, lysozyme, and leukocyte common antigen (LCA). Ultrastructurally, the clear tumor cells were filled with multiple, empty, nonmembrane bound vacuoles of varying size. No recurrence has been described after complete excision and 7 months of follow up. DF with balloon cell change, likely secondary to persistent irritation, should be added to the differential diagnosis of cutaneous primary and metastatic neoplasms showing balloon cell degeneration such as balloon cell melanocytic nevi and renal cell carcinoma, respectively.

Cutaneous fibrous histiocytomas are usually regarded as superficial lesions and commonly known as dermatofibromas; however, unusual cases histologically showing fibrohistiocytic proliferation extending into the deeper dermis or subcutaneous tissues are occasionally experienced. Some authors propose this type as benign fibrous histiocytoma of the skin, distinct from dermatofibroma. We describe herein a case of systemic lupus erythematosus (SLE) who developed multiple nodules on the face, trunk and extremities. The nodule on the forehead did not present a typical clinical appearance of dermatofibroma, and histopathological examination showed fibrohistiocytic proliferation with a storiform pattern extending into the deep dermis and subcutaneous tissues. By contrast, histology of the nodule on the abdomen showed fibrohistiocytic proliferation confined to the dermis and compatible with dermatofibroma. Although multiple dermatofibromas are occasionally seen in patients with SLE, benign fibrous histiocytoma of the skin showing deeper invasion than dermatofibroma is rarely associated with SLE.

Aneurysmal fibrous histiocytoma is a rare variant of cutaneous fibrous histiocytoma that results from blood vessel proliferation and haemorrhage into a fibrous histiocytoma. The resulting lesion has a very different clinical appearance, hence the potential confusion with other skin lesions. This report describes the case of a 48 year old woman with a recurrent fibrous histiocytoma with prominent vasculature, which over a three year period recurred on two occasions, showing more progressive features of the aneurysmal variant. In addition, squamous lined cysts were present within this tumour, a finding that has not been described previously. The histological features of this rare lesion and the importance of the differential diagnosis from other similar appearing malignant lesions will be discussed.

Atypical fibrous histiocytoma is an uncommon, poorly documented variant of cutaneous fibrous histiocytoma. We studied 59 cases of atypical fibrous histiocytoma to better characterize the clinicopathologic spectrum. There were 33 males and 26 females (median age 38 years; range 5-79 years) with solitary lesions arising on lower (25 cases) and upper (17 cases) extremities, trunk (6 cases), head and neck (4 cases), and vulva (1 case); anatomic location was not stated in six cases. Lesions measured 0.4-8 cm in diameter (median 1.5 cm) and clinically were nodules (40 cases), polypoid tumors (18 cases), or a slightly elevated plaque (1 case). Histologically, the lesions were primarily dermal with superficial involvement of the subcutis in one third of the cases. Salient features included a proliferation of pleomorphic, plump, spindle, and/or polyhedral cells with mainly large, hyperchromatic, irregular, or bizarre nuclei, set in a background of classic features of fibrous histiocytoma, including spindle cell areas showing a storiform pattern and entrapped thickened, hyaline collagen bundles, especially at the periphery. Multinucleated giant cells, often with bizarre nuclei and foamy, sometimes hemosiderin-rich, cytoplasm were also variably present. The degree of pleomorphism varied from only focal and minimal (14 cases) or moderate (24 cases) to marked (21 cases). Mitotic activity was observed in 55 lesions, and the number of mitotic figures ranged from 1 to 15 per 10 high power fields. Atypical mitoses were noted in 20 lesions. Furthermore, some cases of atypical fibrous histiocytoma displayed other worrisome features less often observed in ordinary FH, including unusually large size (diameter >2 cm, 8 cases), involvement of the superficial subcutis (19 cases), and geographic necrosis (7 cases). Immunohistochemical studies performed in 42 cases showed only focal smooth muscle actin (10 cases) and CD34 (4 cases) positivity, whereas CD68, S-100 protein, desmin, pan-keratin, and epithelial membrane antigen were negative. Clinical follow-up data available in 21 patients (mean duration of follow-up 50.6 months, median 43 months) revealed local recurrences in three patients (one repeated); two patients developed distant metastases, one of whom died after 96 months. These two cases were not histologically distinct from the group as a whole. We conclude that atypical fibrous histiocytoma has a broader clinicopathologic spectrum than previously realized. Lesions with floridly atypical features represent potential pitfalls for overinterpretation as pleomorphic sarcoma, which would appear to be inappropriate in most cases. Provided that atypical fibrous histiocytoma is treated by complete excision, a benign outcome is to be expected in most cases. However, similar to the cellular and aneurysmal variants of fibrous histiocytoma, atypical fibrous histiocytoma shows a higher tendency to recur locally than ordinary fibrous histiocytoma and may rarely metastasize.

The palisading cutaneous fibrous histiocytoma is a unique benign spindle cell tumor that often occurs in an acral location. Histologic findings feature nuclear palisading reminiscent of a schwannoma. Previous studies have suggested that this tumor may be a variant of a dermatofibroma. We performed immunohistochemical staining with a panel of antibodies including neurofilament, S100 protein, factor XIIIa, epithelial membrane antigen, Leu-7, desmin, and vimentin. We found positive staining with factor XIIIa and vimentin, suggesting connective tissue differentiation for this tumor.

We herein describe the histopathologic findings of an otherwise stereotypical dermatofibroma replete with granular cells. The histopathologic diagnosis of dermatofibroma was underlined by immunohistochemical findings and ultrastructural examination. Cellular granularity is the result of cytoplasmic accumulation of lysosomal structures and can be observed not only in conventional granular cell tumor but in a variety of benign and malignant cutaneous neoplasms. Granular cell dermatofibroma represents a hitherto undescribed variant of dermatofibroma that can be added to the broad histopathologic spectrum of this benign fibrohistiocytic proliferation.

Two cases of metastasizing cellular dermatofibroma (cutaneous fibrous histiocytoma) are presented. The first patient, an 18-year-old man, had a nodule excised from his right upper thigh. He developed three local recurrences at 1.5, 2, and 2.5 years and metastasis to inguinal lymph nodes. He underwent lung segmentectomies for metastases 1.5 and 4 years later and was alive with no evidence of tumor at latest follow-up, which was 15 months after the last surgery. The second patient, a 33-year-old man, had a nodule removed from his right posterior neck. The tumor recurred 3 months later and was reexcised. Right cervical lymph node metastases were excised at 7 and 8 years. A year later, a right cervical lymph node dissection yielded one positive node of 35, and multiple metastases were excised from the right lung. The patient was alive with lung metastases 6 years later, which was the latest follow-up. Grossly, both tumors were single 2 cm nonulcerated dermal-subcutaneous nodules. Histologically, they were characteristic of cellular dermatofibroma; they were composed of plump to spindled "fibrohistiocytic" cells arranged in a storiform pattern and had areas of hemorrhage, hemosiderin, and infiltration between dermal collagen bundles peripherally. Recurrences and metastases were histologically similar except that lung metastases were cystic. The alternative diagnosis of angiomatoid malignant fibrous histiocytoma was considered for these two cases but was excluded because the tumors were partly dermal, had a well-defined storiform pattern, and lacked large blood lakes, multinodularity, a fibrous pseudocapsule, and surrounding chronic inflammation. We conclude that dermatofibromas can rarely metastasize. Risk factors for metastasis may include relatively large size, high cellularity, and local recurrence. Judging from these two cases, metastasizing dermatofibromas behave in an indolent manner.

We report a case of a rare variant of benign fibrous histiocytoma composed of abundant, multinucleated, osteoclast-like giant cells. Local excision with negative margins is the treatment of choice.

Forty cases of the distinctive but poorly recognized aneurysmal variant of cutaneous fibrous histiocytoma are described. These tumours presented most commonly in middle-age adults, with a slight predilection for females. Anatomical distribution was wide with most cases occurring in the lower limb/limb girdle (50%), upper limb/limb girdle (20%) and trunk (17%). Lesional size ranged from 0.5 cm to 4 cm. Haemorrhage accounted for the rapid clinical growth of some lesions and the frequent clinical confusion with a cyst, a melanocytic lesion or a haemangioma. Five (19%) of the twenty-six cases with follow-up (mean duration 2.5 years) recurred locally, twice in two cases. One of these cases had involvement of a regional lymph node in the second recurrence, most likely as a result of direct local extension. Distinctive histological features were prominent blood-filled spaces, varying from artefact-like clefts to cystic areas mimicking cavernous vascular channels but devoid of an endothelial lining, prominent haemosiderin deposition, numerous siderophages and giant cells, and a moderate mitotic rate. Despite the presence of prominent secondary changes due to haemorrhage, all cases showed cellular polymorphism, hyalinized collagen bundles surrounded by tumour cells in the periphery of the lesion and 88% showed some degree of epidermal hyperplasia, as seen in common fibrous histiocytoma. Immunohistochemistry (ABC method) revealed only vimentin and, rarely, focal smooth muscle actin positivity. CD68 was positive in some reactive macrophages only. Stains for CD31, CD34, desmin and factor XIIIa were negative in all cases tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatofibroma or cutaneous fibrous histiocytoma is a common cutaneous tumor. Rare histologic variants have been described. We report another variant of dermatofibroma characterized by osteoclast-like giant cells with metaplastic bone formation. Clinically the lesion was a small, brown, hard papule of several months' duration on the left anterior leg of a 58-year-old woman.

A Chinese woman had bilateral coin lesions of the lung, which grew slowly. At pathologic examination, the lesions were considered to be multiple sclerosing hemangiomas. Multiplicity is rare, and bilaterality has not been previously reported.

Eight cases of benign cutaneous fibrous histiocytoma containing scattered, bizarre, pleomorphic cells of multinucleate or histiocyte-like type are described. All arose in adults and four had originally been diagnosed as sarcomas. Lesions of this type are not well-known and merit wider recognition in order to avoid inappropriate treatment. Differential diagnosis principally includes atypical fibroxanthoma and pleomorphic malignant fibrous histiocytoma.

Seventeen cases are reported of a variety of cutaneous fibrous histiocytoma, which we have designated as aneurysmal ("angiomatoid") fibrous histiocytoma. These lesions differ from the classical cutaneous fibrous histiocytoma in both their clinical presentation and pathologic features. Clinically, they may be larger than the usual cutaneous fibrous histiocytoma, are blue, black, or dark red, and have a cystic consistency. They are most commonly located on the extremities and may be associated with symptoms of pain and rapid growth. The clinical diagnosis of fibrous histiocytoma is seldom considered in the differential diagnosis, which may include malignant melanoma, hemangioma, neurofibroma, and nonspecific cyst. Histologically, the lesions are characterized by the presence of large, blood-filled tissue spaces, which, at times, account for up to one half their size. These spaces lack an endothelial lining, being surrounded and lined by histiocytes, many of which contain hemosiderin pigment, fibroblasts, and foam cells. The solid portions of the tumor have the usual features of a cutaneous fibrous histiocytoma. This "angiomatoid" lesion is closely allied to what has been termed "hemosiderin histiocytoma," which appears to be a precursor stage in its formation. The presence of extravasated erythrocytes in combination with a spindle-cell stroma may lead to an erroneous diagnosis of Kaposi's sarcoma. This cutaneous tumor has architectural and cytologic similarities to its malignant soft tissue counterpart recently described as angiomatoid malignant fibrous histiocytoma. However, unlike the latter, the cutaneous lesion is benign and lacks the prominent inflammatory infiltrate, pleomorphic appearance, and systemic manifestations of its soft tissue counterpart. The distinctive clinical and pathologic features of the cutaneous lesion serve to separate it as a specific variant of the cutaneous fibrous histiocytomas.

We report 6 cases of an unusual variant of cutaneous fibrous histiocytoma in which nuclear palisading is a prominent feature. The lesions were equally distributed between males and females with a widely variable age range. Half of the cases occurred on the digits. Histopathologically, the lesions were characterized by areas of nuclear palisading with formation of Verocay-like bodies in addition to the more typical features of the "fibrous" variant of cutaneous fibrous histiocytoma. The differential diagnostic features between these lesions and those of other tumors in which nuclear palisading is seen are discussed.

We report 65 cases of a hitherto undescribed neoplasm that occurs chiefly in children and young adults, and has morphologic features reminiscent of both a fibrous histiocytoma and fibromatosis. The median age of the 65 patients was 14.5 years; two-thirds (67.7%) of the patients were younger than 20 years. The lesion was more common in female patients (46 cases) than in male patients (19 cases). It usually presented as a slow-growing, poorly demarcated dermal or subcutaneous mass that rarely exceeded 3 cm in greatest diameter. Its most common location was the upper extremity (63.1%), especially the regions of shoulder and forearm. Under the microscope, the lesions were characterized by a multinodular or plexiform proliferation of histiocyte- and fibroblast-like cells associated with multinuclear giant cells. Differential diagnosis chiefly includes cutaneous fibrous histiocytoma, plexiform neurofibroma, fibromatosis, and benign and malignant giant cell tumor. Twenty of the 32 cases (62.5%) with follow-up information were alive and well after local excision, but the tumor recurred in 12 cases (37.5%). In two patients with recurrence, the disease metastasized to regional lymph nodes 9 and 36 months after the initial excision, respectively. Metastasis to the lung or other organs was not observed. We were unable to demonstrate a close correlation between biologic behavior and any specific clinical or morphologic parameter.