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Background: Plexiform fibrohistiocytic tumor is a soft-tissue tumor of intermediate malignancy occurring in children and young adults but is only rarely found in infants. The tumor usually involves the upper limbs and is slow growing and painless. Recurrence rate is high. Lymph node and systemic metastases can occur, but have never been reported in infants. Clinical behavior in infancy is not known. Histologically, the tumor is characterized by nodules of histiocyte-like and multinucleated cells and fascicles of spindle cells arranged in a plexiform pattern. Mitosis, atypia, and nuclear pleomorphism are common but not pronounced., Methods and Results: We report three cases in infants, one of which is congenital, having an unusual topography and a broad histological spectrum., Conclusion: In infants, wide excision with large safety margins should be performed as the behaviour of this tumor remains uncertain. Leclerc S, Hamel-Teillac D, Oger P, Brousse N, Fraitag S. Plexiform fibrohistiocytic tumor: three unusual cases occurring in infancy.

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.

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.

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.

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.

The list of entities comprising a proliferation of CD34 (+) spindle cells continues to grow. Described, herein, is a patient who had an indolent eruption of scattered papules composed of CD34 (+) spindle cells, beginning in adolescence. An 18-year-old female patient presented with asymptomatic, tan/brown papules over the neck, chest, and proximal extremities. They appeared 6 years previously and had slowly increased in number. Biopsy from the neck showed a proliferation of plump spindle cells, associated with delicate collagen, in the upper reticular dermis. No atypia nor mitotic figures were present. The spindle cells were negative for S-100, muscle actins, and Factor XIIIa, but stained intensely with CD34. This unusual mesenchymal proliferation of CD34 (+) apparent dermal dendrocytes did not have the storiform pattern, short fascicles, nor mitotic figures of DFSP. The completely negative muscle markers helped to exclude dermatomyofibroma, and no morphological evidence of vasoformative differentiation was seen. The clinical picture militated against solitary fibrous tumor. These eruptive tumors are benign and thought to represent a distinctive fibroma produced by proliferated CD34 (+) stromal cells.

We report immunomorphologic observations on a pleomorphic hyalinizing angiectatic tumor of soft parts (PHAT), a rare tumor recently described by Smith, Fisher, and Weiss. A 2 cm skin-covered, grossly lobulated, firm, yellow-tan, focally hemorrhagic tumor was excised from the dorsum of a 59-year-old woman's right foot. It infiltrated dermis and subcutis and entrapped skin adnexae. The tumor microscopically resembled both a pleomorphic malignant fibrous histiocytoma and a neurilemoma with fascicular spindle cell pattern, pleomorphic tumor giant cells, and focal congeries of ectatic, fibrinous, and slightly hyalinized vessels. Tumour cells produced abundant reticulin but collagenous sclerosis was minimal. Mast cells were numerous. Pleomorphic cells, some phagocytic, had intranuclear vacuolar inclusions and many cells had large pale cytoplasmic globular inclusions. Most tumor cells expressed vimentin and CD34, including pleomorphic cells. Factor XIIIa stained focally 20-40% of the spindle cells. S-100 and cytokeratin were negative and actin and desmin stained only vessel myopericytes. The Ki 67 index was 3% with mostly large CD34+ cells and a few smaller FXIIIa+ cells in the cycling fraction. We conclude that PHAT is a fibrohistiocytic tumor probably derived from proliferating microvascular CD34+ dendritic cells and FXIIIa+ dendrophage cell subsets. Possible interactions between these cell types deserve further study in PHAT and other fibrohistiocytic tumors.

Dermatofibromas (DF) are common, benign skin tumors composed predominantly of cells having elongated nuclei and very scant cytoplasm (i.e., fibroblasts) and capillaries in a collagenous stroma. Some authors distinguish DF from benign fibrous histiocytomas (BFH), which are composed of cells with round to oval nuclei and abundant cytoplasm (i.e., histiocytes). In general, this group of tumors expresses factor XIIIa but not the antigen recognized by MAC 387. However, immunohistochemical differences specifically between DF and BFH have not been reported. We have studied the immunophenotype of 23 lesions having morphologic features predominantly either of DF (17 cases) or BFH (6 cases) using antibodies against desmin (muscle marker), alpha-smooth-muscle actin (muscle and myofibroblast marker), CD68 and HAM56 antigen (markers commonly expressed by macrophages, so called "histiocytic" markers), CD34 (a marker present in hematopoietic, vascular, and occasional dermal dendritic cells), and factor XIIIa (a transglutaminase present in many cells including dermal dendrocytes). Many spindle-shaped cells expressed alpha-smooth-muscle actin while many large, round cells expressed the histiocytic markers. However, most lesions expressed at least focally both alpha-smooth-muscle actin and "histiocytic" markers. Thus a clear-cut distinction between DF and BFH could not be made based on immunophenotype alone. Additionally, the prominent alpha-smooth-muscle actin immunoreactivity and desmin non-reactivity suggests myofibroblastic differentiation in the spindle-cell regions of these tumors, and indicates that expression of alpha-smooth-muscle actin cannot be used as definitive proof of muscle differentiation in spindle-cell tumors. We conclude that DF and BFH are not discrete entities, but represent polar expressions of one nosologic entity exhibiting both myofibroblastic and "histiocytic" differentiation.

p53 protein plays an important role in control of cell proliferation by suppressing proliferation of cells with DNA damage. Mutations of the p53 gene increase the stability of the encoded nonfunctional protein which accumulates in the nuclei, allowing it to be detectable by immunohistochemistry. Mutant p53 protein has been observed in preneoplastic and neoplastic conditions supporting its role in the development of some human cancers. In this immunohistochemical study, we examined p53 expression in 12 Dermatofibrosarcoma Protuberans (DFSP) and 10 Dermatofibromas (DF). Results were compared with the cellular proliferation rate by using the monoclonal antibody Mib-1 which detects Ki-67 antigen expression. Nuclear accumulation of the p53 protein was observed in 11 DFSP. All DF were negative for p53. No statistical correlation could be established between p53 and Mib-1 staining in our cases. We conclude that mutations of the p53 gene may be involved in the molecular pathogenesis of DFSP but not of DF. Mib-1 index can not be successfully used to distinguish DFSP from DF.

Hysterectomy was performed in a 64-year-old woman because of a uterine malignant tumor which extensively involved both the endometrium and the myometrium. Histological examination revealed a malignant fibrous histiocytoma (MFH) of the pleomorphic-storiform type. The presence of epithelial or heterologous mesenchymal tumor components or cells of smooth muscle derivation was ruled out by immunohistochemistry and electron microscopy. The patient developed pulmonary metastases and died six months after surgery. MFH is a rare primary tumor of the uterus, but it should be considered in cases of malignant mesenchymal tumors without heterologous elements or signs of smooth muscle derivation.

Background: Bone morphogenetic proteins (BMPs) are potent inducers of bone formation. Functional and immunohistochemical studies have identified BMPs in a subset of osteosarcomas. In the present study, the authors extend the analysis of BMP expression to other bone and soft tissue sarcomas., Methods: Monoclonal antibody AbH3b2/17 against human BMP-2 and BMP-4 was used in avidin-biotin-immunoperoxidase assays with frozen sections of bone tumors (71 specimens), soft tissue sarcomas (69 specimens), and normal tissues., Results: Among bone tumors, BMP was detected in osteosarcomas (17 of 29 samples), malignant fibrous histiocytomas (MFHs) (6 of 6), and the spindle cell sarcomatous components of spindle cell (dedifferentiated) chondrosarcomas (4 of 4), but not in conventional chondrosarcomas (0 of 10) or Ewing's sarcomas (0 of 14). Histologic subtypes of osteosarcoma differed for BMP expression, with 8 of 9 fibrohistiocytic, 9 of 13 osteoblastic, and 0 of 5 chondroblastic lesions showing immunostaining. In all BMP-positive bone tumors, immunostaining was localized in the cytoplasm of primitive mesenchymal cells, with little or no staining in tumor matrix and more mature osteoblastic/chondrocytic cells. Among soft tissue sarcomas, MFHs (11 of 12), liposarcomas (5 of 11), leiomyosarcomas (3 of 9), and malignant schwannomas (3 of 8) showed cytoplasmic BMP immunostaining. Synovial sarcomas (0 of 9), rhabdomyosarcomas (0 of 8), and fibrosarcomas (0 of 7) were BMP-negative. All normal human tissues tested, including the tissues of a 16-week-old fetus, lacked BMP immunoreactivity., Conclusions: Bone morphogenetic protein is expressed in a subset of osteosarcomas, a high proportion of MFHs of bone and soft tissue, and in spindle cell chondrosarcomas. In these tumors, BMP is localized predominantly to the cytoplasm of malignant cells with primitive mesenchymal features; no or little BMP is detected in the more differentiated elements of bone and soft tissue sarcomas. Different histologic types of bone and soft tissue sarcomas may mimic discrete stages of mesenchymal differentiation as defined by BMP expression and histologic criteria.

Background: Dermatofibroma (DF) is a superficial form of benign fibrous histiocytoma, composed of a mixture of fibroblastic cells and histiocytic cells. The histogenesis of this lesion is a matter of controversy., Methods: Forty-five cases of DF were investigated by single and multiple immunostaining techniques, using panel of 12 antibodies including proliferating cell nuclear antigen (PCNA), vimentin, and macrophage/histiocyte markers (HAM56 and CD68)., Results: Double immunostaining demonstrated that 58% of the DF cells simultaneously expressed PCNA and vimentin, whereas only 5% were PCNA+/HAM56+, and 2% were PCNA+/CD68+. By triple-stain for PCNA, vimentin, and HAM56, 56% of the DF cells were PCNA+/vimentin+/HAM56-, but only a few cells were PCNA+/HAM56+/vimentin+/-. Of the PCNA positive cells, 88% were vimentin+HAM56- and 10% were HAM56+ vimentin-/+. The cells positive for CD68 showed similar distribution to that of HAM56+ cells, though there were fewer of the former than the latter in most cases. These results suggest that the majority of the proliferating cells in DF express vimentin but not histiocytic markers. Morphologically, the PCNA+/vimentin+/HAM56- (or CD68-) cells exhibited a spindle-shaped configuration resembling fibroblasts, whereas most of the HAM56+/CD68+ cells possessed abundant rounded cytoplasm and were similar to normal histiocytes., Conclusions: The present study suggests that the proliferative compartment of DF cells is composed chiefly of mesenchymal/fibroblastic lineage, accompanied by varying numbers of normal reactive histiocytes.

Thin sections of dermatofibromas, of a basal cell epithelioma, a patch stage lesion of Kaposi's sarcoma, a case of angiolymphoid hyperplasia with eosinophilia, and one case of malignant mastocytosis were incubated with antibody to factor XIIIa (FXIIIa). Regardless whether the tissue had been embedded in Lowicryl K4M, Epon, or Araldite, labeling was found in dermal dendrocytes, mast cells, and endothelial cells. In dermal dendrocytes, the reaction product was seen in dilated cisternae of the rough endoplasmic reticulum as well as free within the cytoplasm. In endothelial cells, FXIIIa was localized within Weibel Palade bodies, free within the cytoplasm, and in villous projections into the vasucular lumen. In mast cells, the reaction was found in mast cell granules exclusively. Mast cells, dermal dendrocytes, and endothelial cells have in common that all three express FXIIIa, belong to the microvascular unit, and are increased in number during angiogenesis and in fibrovascular processes. It thus seems that these cells are functionally related.

Methods: The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex., Results: As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed., Conclusion: These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.

The histogenesis of malignant fibrous histiocytoma (MFH) is controversial. To elucidate the cellular origin and characteristics of this neoplasm, the authors analyzed cell lines grown from 17 patients (15 soft tissue MFH and 2 bone MFH) by using light and electron microscopy, immunocytochemistry, enzyme cytochemistry, and functional tests for receptors for the Fc portion of immunoglobulin (Fc receptors) and immunophagocytosis. Each culture exhibited a storiform/pleomorphic pattern with mixed cellular populations consisting of spindle cells, polygonal cells, and bizarre giant cells; these morphologic features corresponded to the histologic characteristics of the primary tumors. The cells in each MFH line displayed histiocytic functional markers such as lysosomal enzymes, Fc receptors and immunophagocytosis. However, these cells differed from monocyte-derived macrophages (histiocytes) in immunoreactivity; the MFH cells expressed a mesenchymal antigen (FU3) distributed among perivascular cells and fibroblasts but demonstrated no positive reactions with Leu-M1 (CD15) and Leu-M3 (CD14), which recognize the cells of the monocyte-macrophage lineage. In conclusion, these findings suggest that MFH is not a tumor of true histiocytes but of facultative histiocytes showing mesenchymal differentiation in vitro. Chromosomal analysis performed in one MFH line demonstrated abnormal karyotypes; the modal chromosome number was 58, with 5 marker chromosomes.

Two malignant fibrous histiocytoma (MFH) cell lines were established: one from a storiform-pleomorph subtype and the other from a myxoid one (codes, MFH-3 and MFH-4). Light microscopic examination revealed large rounded cells, growing mostly separately, in both cell lines. Their ultrastructure was different in various aspects. The MFH-3 cells showed abundant lysosomal activity, a well-developed Golgi apparatus, and a few desmosome-like cell contacts. The MFH-4 cells had a well-developed rough endoplasmic reticulum, delicate bundles of tonofilaments, the formation of pseudoacini, and the presence of small completely developed desmosomes. Based on immunostaining and immunoblotting assays of cultured cells, both cell lines expressed immunoreactivity for vimentin; cytokeratins 7, 8, and 18; desmin; and laminin, but they lacked reactivity for cytokeratins 10 and 19, neurofilament, alpha-smooth muscle actin, S-100 protein, collagen type IV, carcinoembryonic antigen, and antigens specific for macrophages. Fibronectin and, to a variable extent, glial fibrillary acid protein and epithelial membrane antigen (EMA) were detectable in MFH-3 cells only. Furthermore, a 60-kilodalton band was present in both cell lines which was reactive for cytokeratins 8 and 18. The MFH-3 cells had the capacity to grow as xenografts with a carcinoma-like pattern. The cells retained their immunoreactivity for vimentin and cytokeratin 8 and showed the presence of desmosomes. Several of these immunophenotypic features also were noticed in established sarcoma cell lines and in short-term cultures of fibroblasts, smooth muscle cells, and endothelial cells. However, experimental data on the two MFH cell lines show that the MFH cell line may express some immunophenotypic and ultrastructural features considered to be specific for epithelial cells. The MFH cells may originate from multipotential mesenchymal cells with a capacity to differentiate to fibroblast-like cells, and less frequently, to epithelial cells, smooth muscle cells, and Schwannian cells. Such a differentiation became evident when these cells were adapted to culture conditions or grew in nude mice.