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Fibrous histiocytoma (FH) or dermatofibroma is a common cutaneous lesion mostly seen in adults and rare in the first two years of life. Two hundred sixty-seven patients younger than 18 years with a diagnosis of FH or dermatomyofibroma, a lesion with morphologic overlap with FH, were identified from the files of a single institution, with only 13 (4.8%) occurring in patients younger than 5 years. Ten patients had either underlying neurologic, autoimmune, or metabolic disorders or a family history of autoimmune conditions. Histologic review of hematoxylin and eosin staining and immunostaining on 75 FHs and dermatomyofibroma in 70 patients showed the following results: 33 classic FHs, 8 classic FHs characterized by a peculiar retiform morphology with thin fascicles of elongated cells forming a network reminiscent of the eruptive variant of FH, 19 deep/cellular variants, 5 aneurysmal variants, 3 lipidized variants (including two lesions in a patient affected by mucopolysaccharidosis IV), 3 dermatomyofibromas, and 4 isolated cases of hemosiderotic, granular cell atypical, and epithelioid FH. Immunostaining for factor XIIIa highlighted a dense network of dendritic cells in FH, which was significantly reduced in the FH with retiform morphology. Smooth muscle actin staining was positive in a high percentage of FHs (85.3%). The current series demonstrates that FH in children may show unique clinical and morphologic features. The retiform pattern with decreased dendritic cells found in congenital lesions and in two older patients with lesions in two locations might have a different pathogenesis, probably related to an altered immune response in very young patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Langerhans cell (LC) histiocytoma is a neonatal tumor that often consists of a single, ulcerated nodule. Systemic involvement is rare, and LC histiocytoma is considered to be a variant of congenital, self-healing LC histiocytosis (also referred to as Hashimoto-Pritzker disease). In view of its low prevalence, LC histiocytoma is not always diagnosed in a clinical examination and requires histological confirmation. Furthermore, the histological and molecular features of LC histiocytoma have not been well characterized. Here, we report on 6 cases of this rare disease and review the corresponding literature. LC histiocytoma differs from classical self-healing LC histiocytosis with regard to the pathological features; we found that LC histiocytoma was associated with massive infiltration by histiocytes of various sizes and shapes (although often large) throughout the dermis and the superficial subcutis. Epidermotropism was rare, mitotic figures were not inconspicuous, and necrotic or calcified areas were often present. Immunohistochemical assessment revealed a mixture of different types of histiocytes (with CD1a CD207, CD1a CD207, and CD1a CD207 CD163 cells). Genetic testing was performed in 5 cases; it revealed a BRAF mutation (p.V600E and p.485_490delinsF) in 2 cases, a HRAS mutation (p.T58I) in 1 case, a combination of 2 PTEN mutations in another case (p.I224M and p. R234W), and no mutations in the fifth case. All the lesions regressed spontaneously, and none recurred during follow-up.

Alterations in dermal collagen are noted in dermatofibroma, dermatofibrosarcoma protuberans, morphea, lichen sclerosus et atrophicus, hypertrophic scars, and keloids. The authors sought to determine whether variations in birefringence of collagen by polarized microscopy could be of help in diagnosing such conditions. Representative hematoxylin and eosin sections of 400 cases, including dermatofibroma, dermatofibrosarcoma protuberans, hypertrophic scars, keloid, morphea, and lichen sclerosus, were examined under polarized microscopy. Distinct patterns of birefringence of collagen for each disease were noted under polarized microscopy. This study highlights the use of polarized microscopy as adjunctive tool in differentiating different diseases with collagen alteration.

Dermatofibroma is a common benign fibrohistiocytic tumor with many clinicopathological variants. Myxoid dermatofibroma is one of these variants, which is characterized by marked stromal mucin deposition. This report presents a case of myxoid dermatofibroma on a great toe that had been slowly growing for two years. Histopathologically, the relatively well-circumscribed dermal tumor was separated from the epidermis by a small grenz zone. The tumor tissue consisted of oval to spindle-shaped cells with well-defined cell borders and spindly condensed nuclei. No cytologic atypia or mitotic figures were found. Although most of the tumor cells were embedded in a prominently myxoid stroma, typical features of classic dermatofibroma including a storiform growth pattern and more densely packed collagen were observed at the periphery. Immunohistochemically, the tumor cells showed positive staining for CD68 and CD99, and negative staining for CD34 and S-100. Histopathological differential diagnoses of myxoid dermatofibroma include soft tissue neoplasms with myxoid tumor stroma, such as superficial acral fibromyxoma, cellular digital fibroma, superficial angiomyxoma, myxoid dermatofibrosarcoma protuberans and low-grade fibromyxoid sarcoma. Immunohistochemical staining can be useful in the differential diagnosis of these tumors. This case highlights the challenges encountered in the histopathological interpretation of myxoid dermatofibroma. Pathologists should keep in mind the diagnosis of myxoid dermatofibroma when dealing with myxoid neoplastic lesions arising on acral sites.

Multinucleate cell angiohistiocytoma (MCA) is a benign fibrohistiocytic and vascular proliferation usually located on the extremities. It may be underdiagnosed owing to lack of recognition by clinicians and pathologists. We report a 48-year-old man with asymptomatic grouped reddish papules on the dorsum of his right hand for 8 years. Histopathological and immunohistochemical examinations revealed features of MCA with a fibrohistiocytic cell infiltrate in the dermis and multinucleate cells in the stroma. Recently, the dermoscopy aspects of MCA have been described. We add another observation of this useful tool and correlate it with clinical evolution.

Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.

Purpose: Atypical fibroxanthoma is a cutaneous dermal malignancy that presents on the sun-damaged skin of elderly people. It requires a definitive diagnosis, from a high-grade sarcoma to a nonmesenchymal neoplasm. The recommended treatment protocol differs from similar histologically related tumors; thus, a diagnosis of atypical fibroxanthoma should fulfill strict histologic and immunohistochemical stain criteria. The use of these standards will exclude other skin malignancies, including malignant fibrous histiocytoma, angiosarcoma, malignant melanoma, and squamous cell carcinoma. This study was performed with the aim of identifying key immunostains to develop diagnostic criteria., Materials and Methods: Forty-two cases were studied retrospectively over a 10-year period using a panel of immunostains., Results: The average age at presentation was 78 years, with a male predominance. The scalp was found to be the most common site of occurrence, although other investigators have found the forehead, cheeks, nose, and ears as the prevailing sites of presentation., Conclusions: An extensive panel of immunohistochemical stains can be used to prove a diagnosis of atypical fibroxanthoma., (Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

A heterogeneous group of benign fibrohistiocytic lesions has been assembled under the umbrella term, dermatofibroma. These lesions share a morphology of bland spindled cells encompassed by and intercalating through thick dermal collagen; unique variants have been described based on secondary histologic features, some of which include aneurysmal, myxoid, lipidized, signet ring, angiomatous, and keloidal. Here, we present a distinct dermatofibroma variant henceforth known as collapsing angiokeloidal dermatofibroma identified in 2 patients with slowly growing nodules of the buttock and the arm. Microscopically, the lesions have a characteristic dermatofibroma appearance but are accompanied by unusual diffuse small caliber vessels whose walls are collapsed by a thick, eosinophilic, keloid-like substance. The eosinophilic material resembles the adjacent dermal collagen; however, it does not stain for type-4 collagen or type-1 procollagen, amyloid, or glycogen. Although the exact composition of the keloidal material remains ambiguous, the architectural novelty of collapsing angiokeloidal dermatofibroma serves to further expand the morphologic spectrum of benign fibrous histiocytomas, although highlighting the difficulty in distinguishing between it and similar lesions.

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.

Atypical fibroxanthoma (AFX) (dermal pleomorphic sarcoma) remains a somewhat controversial entity. Some authors have averred that AFX is a fiction, suggesting that such lesions merely represent misclassified examples of spindled squamous cell carcinoma. In addition, the immunoperoxidase confirmation of AFX has been less than straightforward and has historically been approached as a diagnosis of exclusion because of the lack of sensitivity and specificity of available "positive" reagents. Procollagen 1 (PC1) and CD10 represent recently developed immunoperoxidase reagents that have been forwarded as useful in this setting, and we sought to characterize our experience, both to confirm the utility of these antibodies and to compare them. Our investigation included 3 separate data sets. Group 1 consisted of a retrospective review of 98 consecutive cases in which PC1 was used in the evaluation of dermatopathology specimens in routine practice during a 13-month interval. Group 2 consisted of a direct comparison of 11 AFX, 11 dermatofibroma (DF), and 7 epithelioid dermatofibroma (EDF) using the CD10 reagent on cases identified by database search. Group 3 consisted of a retrospective review of 47 cases in which CD10 was used in routine practice during a 10-month interval. Group 1 included 47 AFX, 13 carcinomas, and 6 melanomas. PC1 expression was observed in 45 of 47 AFX (96%), with a strong reaction in 78% of cases. Among a comparison group of carcinomas, 13 of 13 displayed strong keratin immunopositivity and 11 of 13 (85%) lacked PC1 expression whereas 2 showed focal weak labeling. Six of six melanomas exhibited avid S100 expression and none labeled with PC1. In group 2, strong CD10 immunoreactivity was present in 11 of 11 AFX. Similarly, 11 of 11 DFs were also positive. In contrast, 6 of 7 cases of EDF lacked CD10 expression. Group 3 included 38 AFX and 9 miscellaneous spindle cell proliferations. Of the 38 AFX, 37 (97%) labeled with CD10 and in 34 (92%) the reaction was strong. PC1 immunostaining was also completed in 34 of 38 AFX from group 3 and 27 (79%) cases showed positive labeling. Our results confirm that both PC1 and CD10 can be used as positive markers of AFX. We believe that CD10 and PC1 immunostaining can be used as a useful adjunct to supplement the diagnosis of AFX, within the context of an immunoperoxidase panel. Not surprisingly, CD10 expression is also common in DF, a benign analog of AFX, with the exception of its epithelioid variant. In direct head-to-head comparison, our experience indicates that the staining of AFX with CD10 is more avid than that observed with PC1. Lastly, out data includes over 80 examples of AFX, <5% of which showed keratin labeling. Given a general lack of keratin expression, it seems unlikely that AFX merely represents poorly differentiated squamous carcinoma.

More recent techniques to characterize the genetic profile of soft-tissue tumors include the use of gene arrays. Using this technique, Apolipoprotein D (Apo D), a 33-kDa glycoprotein component of high-density lipoprotein, has been found to be highly expressed in dermatofibrosarcoma protuberans. To corroborate these results, we sought to ascertain the utility of Apo D by investigating its sensitivity and specificity in a variety of CD34-positive and CD34-negative cutaneous neoplasms including superficial acral fibromyxoma, sclerotic fibromas, and cellular dermatofibromas. Of interest, we found absence of Apo D expression in all four cases of superficial acral fibromyxoma. Of the remaining CD34-positive lesions, Apo D expression was noted in 35/36 (97%) cases of dermatofibrosarcoma protuberans, 3/5 (60%) giant-cell fibroblastomas, 4/4 (100%) sclerotic fibromas, 8/8 (100%) neurofibromas, and 1/1 (100%) solitary fibrous tumor. Of the CD34-negative lesions, Apo D expression was noted in 2/22 (9%) regular dermatofibroma, 23/45 (51%) cellular dermatofibroma, 10/10 (100%) malignant fibrous histiocytoma, 9/10 (90%) atypical fibroxanthoma, 7/8 (86%) cellular neurothekeoma, 9/9 (100%) malignant melanoma, 8/8 (100%) melanocytic nevi (100%), 0/2 superficial angiomyxoma, 0/15 fibromatosis, 0/1 nodular fasciitis, and 1/2 (50%) desmoplastic fibroblastomas. In summary, our findings indicate that Apo D expression is not specific to dermatofibrosarcoma protuberans. Its principal use as an immunohistochemical adjunct lies in its utility in differentiating superficial acral fibromyxoma from dermatofibrosarcoma protuberans. Although strong positive staining of Apo D in a markedly atypical fibrohistiocytic lesion is suggestive of atypical fibroxanthoma and/or malignant fibrous histiocytoma, further studies with the inclusion of other atypical spindled cell neoplasms are required to conclusively prove the same.

Multiple eruptive dermatofibromas are a rare presentation of dermatofibroma which are frequently associated with underlying diseases such as human immunodeficiency virus infection or lupus erythematosus. Eruptive dermatofibromas generally present a characteristic histology with a poorly circumscribed lesion showing hyperplasia of the epidermis, prominent bundles of collagen and a diffuse proliferation of fibrocytes. We report an unusual case of multiple eruptive dermatofibromas showing massive depositions of mucin within the dermis. A 20-year-old woman presented with nearly 100 red to yellowish papules and nodules distributed symmetrically all over the integument which developed over a period of 9 years. Comprehensive clinical and laboratory diagnostics showed no signs indicating any underlying disease. To our knowledge this is the first report of multiple eruptive myxoid dermatofibromas. We consider this case to be a unique presentation of multiple eruptive dermatofibroma showing massive deposition of mucin.

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.

Background: Basaloid epidermal proliferations (BEP), morphologically resembling basal cell carcinoma (BCC), have been described overlying dermatofibromas. Distinguishing the two is important because of non-aggressiveness of BEP and local aggressiveness of BCC. The aim of this study is to determine whether CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP from BCC., Methods: Ten cases of BEP overlying dermatofibromas were selected. Ten cases of BCC were used as control. The two groups were stained with CK20 antibody. Numerical density of CK20 stained Merkel cells in peri-lesional epidermis, BEP and BCC was determined by examining 300 cells at 400X in two separate areas by three independent pathologists. To determine statistical significance, the results were compared using t-test method., Results: Density of Merkel cells in peri-lesional epidermis was 0.2-0.3%. No merkel cells were detected in the BCC. BEP overlying dermatofibromas showed an obvious increase in CK 20 stained Merkel cells. The difference was statistically significant (P < 0.02) CONCLUSIONS: We report a significant increase in CK20 stained Merkel cells in BEP overlying dermatofibromas as compared to BCC. CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP overlying dermatofibromas from BCC. Mahmoodi M, Asad H, Salim S, Kantor G, Minimo C. Anti-CK20 staining of Merkel cells helps differentiate basaloid proliferations overlying dermatofibromas from basal cell carcinoma.

Myxofibrosarcoma or myxoid malignant fibrous histiocytoma is one of the most common fibroblastic sarcomas in older patients. It is characterized by a tendency for predominantly subcutaneous, multinodular, diffusely infiltrative growth, which may extend to the overlying dermis and present as a cutaneous lesion. Histologically, it comprises a spectrum ranging from hypocellular low-grade myxoid to high-grade pleomorphic sarcoma. Because the dermal presentation usually appears relatively banal, accurate diagnosis is sometimes challenging. In this report, we present two cases of myxofibrosarcoma with dermal involvement.

We report on two patients with granular cell atypical fibroxanthoma. Both neoplasms were solitary, light-tan, dome-shaped papules on sun-exposed areas of the head in two elderly white men. Microscopically, these neoplasms showed a dermal proliferation of pleomorphic granular cells with irregular hyperchromatic nuclei, multinucleated cells, and scattered mitoses. Immunohistochemical stains were positive for CD68 and vimentin and negative for Melan-A or human melanoma black (HMB)-45, S-100 protein, pancytokeratin, and actin, consistent with atypical fibroxanthoma. The differential diagnosis of granular cells in neoplasms containing cytological pleomorphism is challenging in view of the many different neoplasms that may present with granular cytoplasm. These include the conventional granular cell tumor and its malignant form, leiomyoma, leiomyosarcoma, dermatofibroma, dermatofibrosarcoma protuberans, and angiosarcoma.

Dermatofibromas are common cutaneous lesions. In most cases, they can be readily identified clinically and show a typical histology. In a small percentage of cases they show unusual clinical and more often histologic features that may cause differential diagnostic problems. In addition there are reactive fibrous lesions with neural or smooth muscle features that we speculate may represent dermatofibroma variants.

We have recently treated two Japanese with Bednar tumor, pigmented dermatofibrosarcoma protuberans. The tumors were multilobular with brown-pigmentation and an irregular surface. Firm nodules were growing into the deep subcutaneous tissue, but they were movable over the underlying tissue. Histopathological examination and immunohistochemical studies showed the typical features of Bednar tumor and positive staining for CD34, which is known to be expressed in dermatofibrosarcoma protuberans. Bednar tumor is thought to be a variant of dermatofibrosarcoma protuberans and to have intermediate malignancy.

This report describes the clinicopathologic, immunohistochemical, and ultrastructural features of a benign fibrous histiocytoma of 3 years' duration situated on the posterior right arm of a 17-year-old woman. To our knowledge, this is the first published description of an association between the histologic features of benign fibrous histiocytoma with proliferating dermal dendrocytes and solid clusters of indeterminate cells and inflammatory infiltrate containing numerous eosinophils. Cell type identification was confirmed by immunohistochemical demonstration of positivity of indeterminate cells for CD1a and S-100 protein, by absence of Birbeck granules in electron microscopy study, and by positivity of fibroblast-like cells for factor XIIIa and negativity for CD34. Mitosis or cytologically atypical cells were absent. The MIB1-measured proliferative index of the tumor cells was less than 5% in spindle cells and approximately 15% in indeterminate cells. Possible pathogenic pathways are discussed that could account for divergent differentiation or a combination of neoplasms of different lineages.

We report the case of a 6-year-old Japanese boy with a plexiform fibrohistiocytic tumor on the right perioral region. Clinically, the tumor, 5 mm in diameter, was a solitary, hard, erythematous, slowly growing, painless nodule. There was no preceding trauma. Histology revealed a well-circumscribed plexiform lesion with a biphasic appearance. Immuno-histochemistry demonstrated CD68 positivity in many of mononuclear macrophages. The lesion was negative for S-100 protein, lysozyme, CD57 and factor XIIIa. Interestingly, the tumor showed an intradermal location from superficial to deep dermis, and lacked osteoclast-like giant cells. During the follow-up for 9 months after the resection, there was no recurrence or metastasis., (Copyright John Libbey Eurotext 2003.)

Myxofibrosarcoma (myxoid malignant fibrous histiocytoma) is one of the most common fibroblastic sarcomas in the older patient, where it can sometimes present with anatomically deceptive boundaries. Myxofibrosarcoma is now fully characterized as a distinctive and definable pathologic entity. Clinically there is a tendency for predominantly subcutaneous, multinodular, diffusely infiltrative growth, which may extend to the overlying dermis and present as a cutaneous lesion. Histologically myxofibrosarcoma comprises a spectrum ranging from hypocellular low-grade myxoid to high-grade pleomorphic sarcoma. We report herein 6 cases of myxofibrosarcoma each with dermatological presentation as a cutaneous nodule. The dermal component in each of the lesions was low- to intermediate-grade and predominantly myxoid resulting in confusion with benign myxoid neoplasms in small biopsy specimens. The purpose of this series is to focus the attention of workers in dermatology on a subject rarely discussed in dermatopathology literature: the cutaneous presentation of myxofibrosarcoma and the potential for clinical and histologic misinterpretation, as benign dermal lesions.

Aims: Dermatomyofibroma (plaque-like dermal fibromatosis) represents a distinct clinicopathological entity in the spectrum of cutaneous mesenchymal neoplasms showing a myofibroblastic line of differentiation. These benign neoplasms occur frequently, but not exclusively, in young women, and the shoulder girdle as well as the upper trunk are common locations. Histologically, dermatomyofibroma is characterized by a plaque-like proliferation of cytologically bland spindle-shaped tumour cells containing an ill-defined, pale eosinophilic cytoplasm and elongated, neuroid nuclei. Neoplastic cells are arranged in bundles and fascicles orientated parallel to the skin surface, adnexal structures are spared and elastic fibres are increased and fragmented. Immunohistochemically, tumour cells express vimentin and variably muscle actin and alpha-smooth muscle actin, but are negative for desmin, CD34, S100, and epithelial markers. The main differential diagnosis includes hypertrophic scar, dermatofibroma (fibrous histiocytoma), pilar leiomyoma, neurofibroma, adult myofibromatosis, extra-abdominal fibromatosis and plaque-stage dermatofibrosarcoma protuberans., Methods and Results: We report three cases of dermatofibroma arising in male patients aged 31, 36, and 47 years on the thigh, chest wall and back, respectively. All lesions were completely excised and no local recurrence has been reported. Histologically, the neoplasms showed classical features of dermatomyofibroma; however, in addition abundant extravasated erythrocytes, scattered inflammatory cells, numerous capillaries, and sieve- and slit-like spaces, features resembling plaque-stage Kaposi's sarcoma, were noted. In none of the cases did spindled tumour cells stain positively for CD34, and HHV8 was not detected by polymerase chain reaction., Conclusions: The reported cases widen the clinicopathological spectrum of dermatomyofibroma and emphasize plaque-stage Kaposi's sarcoma as an additional differential diagnosis.

Background: Malignant cutaneous spindle cell lesions with marked sclerosis are uncommon. Only a few cases of cutaneous leiomyosarcoma and dermatofibrosarcoma protuberans with sclerosis have been published., Methods: We report a case of atypical fibroxanthoma (AFX) with prominent sclerosis and hyalinization occurring on the scalp of an 81-year-old male., Results: Histopathologic examination revealed an exophytic, well-delineated, focally ulcerated tumor arising in sun-damaged skin. The lesion was composed of atypical spindle cells arranged in a fascicled and vaguely storiform pattern. Occasional multinucleated giant cells were present. The tumor cells were strongly positive for CD99 (O13), vimentin, and smooth muscle actin, and focally positive for CD68. There was striking sclerosis with hyalinization throughout the lesion., Conclusions: Rarely, AFX may exhibit marked sclerosis with areas of complete replacement of tumor by hyalinized collagen. In a small biopsy, such hyalinization may be a diagnostic pitfall leading to an erroneous diagnosis.

Nine cases of an unusual presentation of atypical fibroxanthoma that we previously termed pigmented atypical fibroxanthoma are reported. Pigmented atypical fibroxanthoma can be easily mistaken for malignant melanoma both clinically and histopathologically. The resemblance of pigmented atypical fibroxanthoma to melanoma is secondary to the ability of neoplastic cells to ingest and degrade erythrocytes following intratumoral hemorrhage and to accumulate hemosiderin in their cytoplasm. The histopathologic diagnosis of pigmented atypical fibroxanthoma can be easily confirmed by immunohistochemistry and iron stain.

The ability of macrophages to produce reactive nitrogen species, particularly nitric oxide (NO) is correlated with an enhanced microbicidal or tumoricidal activity during pathogenic or tumoral invasion, respectively. NO reacts in water with oxygen and its reactive intermediates to yield, among others, nitrite and nitrate, which are relatively, stable anions. In this study, we show the varying concentrations of nitrite and nitrate present in different body fluids during AK-5 tumor growth and regression in Wistar rats. We have followed the tumor progression profile and the corresponding levels of nitrite and nitrate present in three major body compartments: the tumor mass; the serum which is the intermediary site; and the peritoneal compartment which is the priming ground for the macrophages. We are thus able to show that the status of the tumor has a direct correlation with macrophage activation and motility to different sites in the body. We also demonstrate after in vitro coculture, that the levels of nitrite and nitrate secreted by the macrophages correlate with their cytocidal capacity.

Plexiform fibrohistiocytic tumor (PFT) is a rare but distinctive soft tissue tumor of children and young adults characterized by a mixture of histiocyte-, myofibroblast-, and osteoclast-like giant cells arranged in a plexiform pattern. We report the clinicopathologic and immunohistochemical features of an apparently unique case of PFT without multinucleated giant cells presenting in a 3-year-old child. Light microscopy revealed a subcutaneous tumor composed of a plexiform proliferation of histiocyte- and myofibroblast-like cells. Multinucleated osteoclast-like giant cells, the third classic cellular component of this mesenchymal neoplasm, were not observed. The differential diagnosis is also discussed. Emphasis is placed on the importance of the recognition of PFT, because it may exhibit an aggressive behavior.

Introduction: The atypical fibroxanthoma (AFX) is considered by most authorities to represent a superficial or minimally invasive variant of malignant fibrous histiocytoma that most often presents as a solitary nodule on the sun-exposed skin of the elderly. Among the rarest variants is the clear cell AFX, a lesion which raises consideration to a differential diagnosis encompassing a variety of neoplastic and non-neoplastic clear cell proliferations., Methods: We describe three cases of a distinctive cutaneous neoplasm arising in the sun-exposed skin of elderly patients. In all cases, formalin-fixed, paraffin-embedded tissue was available for analysis. The histology in concert with the immunophenotype was held to be diagnostic of the clear cell variant of AFX., Results: All tumors comprised sheets of large cells with foamy cytoplasms and hyperchromatic, polyploid nuclei manifesting frequent and atypical mitoses. The critical cells in our cases expressed CD68 but none of CD3, CD20, CD34, S-100 protein, muscle-specific actin, factor XIIIa, Melan-A, carcinoembryonic antigen, or cytokeratin., Conclusion: Although typical examples of AFX provoke diagnostic consideration of spindle cell cancers of the skin (most often spindle cell melanoma, spindle cell squamous cell carcinoma, and leiomyosarcoma), the clear cell variant raises other differential diagnostic considerations instead. These include balloon cell melanoma, sebaceous carcinoma, pleomorphic liposarcoma, chordoma, parachordoma, tricholemmal carcinoma and clear cell squamous cell carcinoma. A diagnosis of AFX is one of exclusion; one must employ immunohistochemical markers to rule out the aforementioned differential diagnostic considerations. By reporting the fifth, sixth and seventh cases of clear cell AFX, we hope to alert dermatopathologists to this distinctive and unusual neoplasm, recognition of which is essential to avoid under- or over-diagnosis and inappropriate therapy.

Background: Multinucleate cell angiohistiocytoma (MCAH) is an uncommon lesion clinically characterized by multiple papules usually located on the face and acral regions of elderly women. Histopathologically, MCAH is characterized by dermal vascular hyperplasia associated with increased number of factor XIIIa-positive fibrohistiocytic cells and multinucleate cells with scalloped borders., Methods: We report the clinical, histopathological and immunohistochemical features of three cases of MCAH, with ulstrastructural study in one of them. The patients were a woman and two men of 56, 40 and 70 years of age, respectively. They all had multiple dull-red papules, which had appeared over several years and were located on the face, the trunk and the dorsa of the hands, respectively., Results: The reticular dermis presented a fibrohistiocytic proliferation of factor XIIIa-positive cells, with abundant bizarre multinucleate cells and vascular hyperplasia. Increased mast cell numbers were seen in all cases, often in apposition to multinucleate cells., Conclusion: Histopathological differential diagnosis of MCAH includes mainly angiofibromas and dermatofibromas, even though vascular hyperplasia can be prominent and has led to many authors to classify MCAH among vascular tumors. Bizarre multinucleate cells can be found in reactive, neoplastic and inflammatory lesions in many sites of the body, and mast cells can play a role in their morphogenesis.

Normal skin is composed in part of cells that express CD34. These include periadnexal spindle cells, vascular endothelial cells, and interstitial dendritic cells. We report on a tumor composed mainly of CD34-reactive spindle cells. A 66-year-old Japanese woman presented with a skin-colored, dome-shaped, cutaneous papule on her left palm that was 7 mm in diameter and had developed within the preceding 3 months. Light microscopic examination showed a well-circumscribed polypoid tumor consisting of spindle-shaped cells and thin collagen fibers arranged loosely in a fascicular pattern within a myxoid matrix. Immunohistochemically, most of the tumor cells stained strongly for CD34, but did not stain with antibodies to S-100 protein, smooth muscle actin, desmin, neuron-specific enolase, epithelial membrane antigen, or factor XIIIa. Staining for vimentin and CD68 was positive. We believe this lesion to be a CD34-reactive myxoid dermal dendrocytoma of a type that has not been described previously.

We report a case of a 64-year-old woman with a giant dermatofibroma on her back with the unusual histologic feature of monster cells. The firm, exophytic, 3-cm nodule had purple and yellow components with surface telangiectasia. Histologic examination demonstrated characteristic findings of a dermatofibroma, including rete ridge flattening and bridging; a stroma containing scattered, large, round, eosinophilic collagen bundles; and a polymorphous dermal infiltrate of spindle and xanthomatous cells with scattered siderophages. Some xanthomatous cells demonstrated features consistent with monster cells, including huge bizarre nuclei and one or more nucleoli. Immunohistochemical staining for factor XIIIa was positive. A diagnosis of giant dermatofibroma with monster cells (DFMC) was made. Giant dermatofibromas are rare, with monster cells being an uncommon finding in dermatofibroma. To our knowledge, this is the first report of DFMC.

Thirty-four cases of fibrous histiocytoma (dermatofibroma) arising on the face are reported. These neoplasms occurred frequently in females (24 female, 10 male) and showed a broad age range (12 to 85 years; mean: 43.6 years, median: 41 years). The neoplasms originated on the forehead (nine cases), the cheek (eight cases), the eyebrow (four cases), the temporal region (three cases), the nose (two cases), and the ear (one case); in seven cases the location face was given only. Five of 27 cases with follow-up information (median: 5 years) recurred locally; in one case four recurrences were excised within 8 years. The majority of cases extended into the subcutis and deep soft tissue including striated muscle (50% of cases). Histologically, only the minority of cases was composed entirely of histiocytoid and spindle-shaped tumor cells arranged in a storiform growth pattern. In many cases cellular fascicles and bundles of spindle-shaped tumor cells were noted in addition to classical morphological features of fibrous histiocytoma. A moderate mitotic rate (mean: 2.97 mitoses in 10 HPFs) was observed, and in few cases increased atypia was evident. Frank tumor necrosis and/or vascular invasion were not identified. Immunohistochemical studies revealed Factor XIIIa positivity in 13 out of 17, focal CD68 positivity in 6 out of 10, and alpha-smooth muscle actin positivity in 16 out of 19 cases tested. These lesions should be distinguished from dermatofibrosarcoma protuberans, including its fibrosarcomatous variant, leiomyosarcoma, and low-grade myofibroblastic sarcoma. Cases of fibrous histiocytoma of the face have to be excised with wider margins in comparison with examples of classical fibrous histiocytoma occurring on the extremities because of diffuse infiltration, involvement of deeper structures, and an increased rate of local recurrences.

Merkel cell carcinoma (MCC) is a rare, frequently lethal, primary neuroendocrine carcinoma of the skin. Histopathologically, it appears as a dermal nodule of small, undifferentiated malignant cells. Historically, MCC was considered to be an eccrine carcinoma. Recognition of its neuroendocrine features later led to the hypothesis that it arose from Merkel cells in the skin, although recent evidence revisits the question of an epithelial origin. We present a case of MCC arising on the temple of a 78-year-old male, in association with an actinic keratosis. Three years later, a local tumor recurrence showed a mixed malignancy comprising small cell neuroendocrine and large cell squamoid components. A further recurrence at the site two years later, after local radiotherapy, revealed a bizarre pleomorphic large cell morphology with retention of immunohistochemical features of a neuroendocrine carcinoma. Evolution to a bizarre pleomorphic large cell neoplasm has been recorded in malignant tumors treated by radiotherapy, but is unique for MCC. The association of this MCC with an actinic keratosis and the development of squamoid differentiation in a local recurrence support the link between MCC and epithelial neoplasia. In addition, its evolution to an atypical fibroxanthoma-like morphology is of interest, because some view atypical fibroxanthomas as bizarre variants of squamous cell carcinoma.

Background: There have been several reports in the literature of dermatofibromas with granular cells. Here we report a granular cell tumor with the architecture of a dermatofibroma. This is the first report of this histological variant of granular cell tumor. The lesion was a 2.5-cm oval, hyperpigmented plaque present for "years" on the back of a 60-year-old African-American woman., Methods: The specimen was processed using formalin fixation and paraffin embedding. Tissue sections were stained with hematoxylin and eosin. Immunohistochemical studies were performed with antibodies directed against S-100 protein, neuron-specific enolase, and factor XIIIa., Results: Histopathologic examination revealed granular cells, some of which were spindle shaped, distributed singly and in small groups between collagen bundles resembling a dermatofibroma. Immunohistochemical studies showed the tumor cells to be positive for S-100 and neuron-specific enolase and negative for factor XIIIa., Conclusion: The immunohistochemical findings support the diagnosis of a granular cell tumor with a dermatofibroma-like pattern.

A 55-year-old woman presented with an asymptomatic red plaque on the left upper back for 6 or 7 years. The lesion was depressed in response to finger pressure. The clinical diagnosis was anetoderma. Histopathologically, the characteristic cells of cellular dermatofibroma proliferated within the thinned dermis, which showed atrophy of about 60 or 70%. The proliferated cells were positive for factor XIIIa and negative for CD34. The involved dermis showed the loss of elastic fibers on elastica van Gieson stain. Electron microscopically, the proliferating cells phagocytized the elastic fibers. We report a typical case of atrophic dermatofibroma and show the possibility that the cause of this disease might be elastophagocytosis between the collagen fibers by the dermatofibroma cells.

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.