Angiomatoid Fibrous Histiocytoma in a Six-Year-Old Child

Abstract:   We report a case of AFH presenting as an asymptomatic subcutaneous nodule on the arm of a 6-year-old boy. AFH is a fibrohistiocytic tumor of intermediate malignancy. Predominantly seen in children and young adults, AFH presents as a deep dermal or subcutaneous nodule usually on the extremities. The histology is characterized by a fibrous capsule, surrounding lymphocytic infiltrate and blood-filled cystic spaces lined by flattened tumor cells. AFH cells express desmin, epithelial membrane antigen, and CD 68 in over 60% of cases; they are negative for myogenin, MYOD1, and endothelial markers. Rate of local recurrence is 2% to 20%. The metastatic rate is 1%. Management is with wide surgical excision and careful follow-up.     

Pleomorphic angiomatoid fibrous histiocytoma: a case confirmed by fluorescence in situ hybridization analysis for EWSR1 rearrangement

Angiomatoid fibrous histiocytoma (AFH) is a neoplasm of uncertain histogenesis with intermediate malignant potential. It occurs in superficial soft tissues in any age group and at any body site, although the typical example occurs on extremities in children/young adults. The neoplasm is usually composed of a bland histiocytoid proliferation of cells with eosinophilic cytoplasm forming a syncytium, often surrounded by a dense fibrous pseudocapsule and lymphoid infiltrate, with abundant intralesional hemorrhage forming blood-filled spaces. AFH may show striking pleomorphism and mitotic activity, and such cases can lead to confusion with other atypical mesenchymal lesions, including pleomorphic sarcomas. Recent findings have shown that a majority of cases of AFH have translocations involving the EWSR1 or FUS genes. We present a diagnostically challenging case of AFH with pleomorphic features and minimal lymphoid and angiomatoid changes involving the superficial subcutis and deep dermis on the scalp of an 8-year-old boy. "Areas with typical AFH morphology were identified and the diagnosis confirmed with identification of an EWSR1…" rearrangement detected by fluorescence in situ hybridization. Pleomorphic AFH should be included in the differential diagnosis of atypical mesenchymal tumors of skin and superficial subcutis and molecular testing may prove helpful in this regard.     

Dermal dendrocytes participate in the cellular pathology of experimental acute graft-versus-host disease

In a well established murine model relevant to human disease, graft-versus-host disease results from recognition of recipient minor histocompatibility antigens by donor bone marrow-derived T lymphocytes. Previous studies suggest that factor XIIIa-positive dermal dondrocytes may be involved in the pathogenesis of disorders involving antigen presentation to T cells and dermal fibrosis. This study was undertaken to determine (i) whether normal murine skin contains factor XIIIa-positive dermal dendrocytes, and (ii) whether such cells participate in the pathophysiology of acute graft-versus-host disease. Graft-versus-host disease was produced using B10.BR CD8+ donor T cells administered to CBA recipients. Skin samples were collected weekly for a 5-week period and evaluated by immunohistochemistry and electron microscopy. Our data indicate that normal murine dermis contains factor XIIIa-positive cells localized primarily around deep dermal microvessels. Ultrastructural analyses reveal these cells to have long processes, pinocytotic vesicles, fibronexuses, and intimate associations with mast cells. During graft-versus-host disease, factor XIIIa-positive dendrocytes appeared within the superficial dermis. By ultrastructure, the dendrocytes were hypertrophic and highly branched, and demonstrated an intimate relationship with neighboring cells. In conclusion, factor XIIIa-positive dendrocytes comprise a normal component of the murine dermis and undergo alterations in experimental acute graft-versus-host disease consistent with participation in disease pathophysiology.     

Dermoscopic findings of haemosiderotic and aneurysmal dermatofibroma: report of six patients

BACKGROUND: The clinical diagnosis of dermatofibroma is commonly easy. However, the differentiation of dermatofibroma from other cutaneous tumours is difficult in some instances, primarily in atypical cases and rare variants. Haemosiderotic dermatofibroma is a variant composed of numerous small vessels, extravasated erythrocytes and intra- and extracellular haemosiderin deposits. Aneurysmal dermatofibroma is a variant composed of large, blood-filled spaces without endothelial lining. Some authors consider that haemosiderotic dermatofibroma is an early stage in the development of aneurysmal dermatofibroma. The clinical differential diagnosis of haemosiderotic or aneurysmal dermatofibroma must include melanoma and other melanocytic tumours, vascular neoplasms, adnexal tumours and nonspecific cysts. Dermoscopy improves the diagnostic accuracy in pigmented and nonpigmented skin lesions. OBJECTIVES: To evaluate specific dermoscopic criteria. METHODS: Dermoscopic examination (using the DermLite Foto; 3Gen, LLC, Dana Point, CA, U.S.A.) of six patients with haemosiderotic or aneurysmal dermatofibromas was performed to evaluate specific dermoscopic criteria. RESULTS: A multicomponent pattern with a central bluish or reddish homogeneous area in combination with white structures and a peripheral delicate pigment network along with vascular structures was noted in five of six lesions. CONCLUSIONS: This dermoscopic pattern yielded the diagnosis of haemosiderotic or aneurysmal dermatofibroma in most cases. However, this multicomponent pattern may present in some melanomas and although it is useful in determining a clinical diagnosis of aneurysmal dermatofibroma, it may not be specific to this entity.     

Immunohistochemical studies of the histogenesis of dermatofibrosarcoma protuberans

Paraffin-embedded tissue sections taken from 16 patients with dermatofibrosarcoma protuberans were stained by means of the peroxidase-antiperoxidase technique using antibodies against S 100 protein, NSE, Leu 7, lysozyme, alpha-1 antitrypsin, alpha-1 antichymotrypsin, cytokeratin, desmin, vimentin, and factor VIII. Most of the tumor cells showed positive reactions to vimentin. Only 1-3% of the cells within the tumor area answered to the histiocytic markers lysozyme, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. The remaining antibodies investigated did not react with the tumor cells. Our results support a fibroblastic, and contradict a neural or histiocytic, histogenesis of dermatofibrosarcoma protuberans.     

Cutaneous malignant fibrous histiocytoma with the characteristics of different variants

We report the case of a 50-year-old woman with cutaneous malignant fibrous histiocytoma (MFH) on the right hypogastric region. A purplish-red blood-filled tumor, approximately 40 mm in diameter, was detected on the region. A histopathologic analysis of the excised tumor showed that it extended from the upper dermis to the subcutaneous tissue over the fascia and, furthermore, that a variety of cells, from highly atypical spindle shaped to histiocytelike, were embedded in the collagenous stroma without forming a capsule. The storiform pattern was not significant. In addition, an area occupied primarily by multinucleated giant cells and rich in vascular components was observed in the deep portion of the tumor that came into contact with the bloody contents. Based on these findings, the patient was diagnosed as having a cutaneous MFH exhibiting the characteristics of different variants.     

Epithelioid sarcoma with angiomatoid features: report of an unusual case arising in an elderly patient within a burn scar

Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor with a characteristic predilection for adolescents and young adults, and a tendency to occur on distal extremities. We report a case of ES arising in an 80-year-old woman within a burn scar that histopathologically showed unusual 'angiomatoid' features. The patient presented initially with a solitary nodule on her right wrist arising at the site of a burn scar. Histopathologically, the tumor was composed of a proliferation of relatively bland, epithelioid and spindle cells focally arranged in a nodular pattern around areas of 'geographic' necrosis. In addition, there were prominent foci of hemorrhage and blood-filled spaces as well as tumor cells with intracytoplasmic vacuoles, features suggestive of an angiomatous process. Immunohistochemistry showed positivity of tumor cells for cytokeratins and epithelial membrane antigen (EMA) whereas all vascular markers tested were negative. The overall histopathologic features were consistent with a diagnosis of ES. Follow up showed multiple recurrences arising proximally along the right upper extremity. Our case underlines the clinical and histopathological heterogeneity of ES, emphasizing the unusual occurrence of ES with 'angiomatoid' features in the elderly. In this uncommon setting, this tumor should be especially distinguished from epithelioid hemangioendothelioma and epithelioid angiosarcoma. The significance of development of ES on a healed burn scar is uncertain, but may suggest a possible causal relationship.     

Factor XIIIa in nodular malignant melanoma and Spitz naevi

The distribution of factor XIIIa-positive dermal dendritic cells was studied in a series of nodular malignant melanomas and compared with that seen in Spitz naevi. Two patterns of distribution were recognizable: (a) diffusely spread through the tumour and (b) located mainly at the periphery of the tumour. These did not correlate with the diagnosis of melanoma or Spitz naevus and the distribution appeared to be a function of growth pattern of the tumour. The diffuse pattern was the most common regardless of diagnosis and the distribution of factor XIIIa-positive cells is the same in malignant melanoma and Spitz naevi.     

An immunohistochemical study of dermatofibrosarcoma protuberans supports its fibroblastic character and contradicts neuroectodermal or histiocytic components

Paraffin-embedded material from 26 cases of dermatofibrosarcoma protuberans (DFSP) was investigated by the peroxidase-antiperoxidase technique. Antibodies to S-100 protein, Leu-7 antigen, and neuron-specific enolase (neural markers); to lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin (histiocytic markers); and to cytokeratin, desmin, vimentin, and factor VIII were used. The tumor cells reacted only for vimentin. In addition, 12 cases showed positive reactions with histiocytic markers (1-3% of the cells; in two cases, up to 10%). These results support a fibroblastic and contradict a neural or histiocytic histogenesis of DFSP.     

Congenital angiomatoid malignant fibrous histiocytoma. A light-microscopic, immunopathologic, and electron-microscopic study

We present a case of a congenital angiomatoid malignant fibrous histiocytoma. This rapidly growing lesion, which was located in the subcutis of the left upper arm, was excised at the age of 8 1/2 months. The patient, a girl, was well and free of disease 10 months after surgical removal of the tumor. The tumor appeared grossly encapsulated. The gray-tan tissue contained cystic spaces filled with recent and organizing hemorrhages. Microscopically, the tumor was composed of solid masses of histiocyte- and fibroblast-like cells, inflammatory infiltrate, and multifocal irregular blood-filled spaces, which were predominantly devoid of endothelial cells. The tumor was studied immunohistochemically with antibodies specific for FVIII-related antigen, S-100 protein, epithelial membrane antigen, vimentin, desmin, alpha-1-antitrypsin, muramidase, laminin, and collagen type IV. Ulex europaeus lectin-I was also utilized. These studies, along with our ultrastructural findings, suggest that: (a) the tumor is composed of a mixture of mesenchymal cells; (b) an imperfect angiogenesis may be taking place, resulting in a wide spectrum of vascular structures; and (c) the cell of origin may be a pluripotent mesenchymal cell.     

Atypical fibrous histiocytoma of the skin and subcutis in childhood and adolescence

The authors have observed 15 examples of a distinctive fibrohistiocytic lesion in children and adolescents which they chose to designate as "atypical fibrous histiocytoma" (AFH). Patient ages ranged from 1 to 19 years (mean 9.3 yr.). Only two cases were encountered in the first year of life, but 7 were seen in children under the age of 10 yr. The anatomic distribution of AFH showed a tendency for a truncal origin (66%), and none was located in the skin of the face, neck, or scalp. Tumor sizes ranged from 1 to 3 cm, and one-third were 2 cm or greater in maximum dimension. Histologically, AFH was characterized by a multinodular, dermal or dermal-subcuticular proliferation of spindle cells, with tapered, cytologically bland nuclei. However, nucleocytoplasmic ratios were increased when compared with those of normal fibroblasts. Nuclear chromatin was dispersed or vesicular; nucleoli were seen in a minority of cases, but mitotic activity was regularly present. Admixed giant cells were present but infrequent, cellularity was dense, and a storiform growth pattern was consistently seen. Mean followup in this group of cases averaged 75 mo. Seven patients (47%) had tumor recurrences after initial excision; in two of these, tissue margins had been free of involvement. The authors conclude that AFH of childhood is analogous to a lesion that has previously been reported as "benign fibrous histiocytoma" in adults. Complete excision and regular postoperative surveillance are recommended for these tumors.     

Somatostatin- and factor XIIIa-immunoreactive cells in psoriasis during clobetasol propionate and calciprotriol treatment

This study describes the changes in number and distribution of somatostatin- and factor XIIIa-immunoreactive dendritic cells in the epidermis and dermis of psoriatic lesional skin during topical treatment with clobetasol propionate or calcipotriol. Immunohistochemical analysis showed that the number of each cell type was increased in lesional skin as compared to normal skin. Investigation of serial biopsies from psoriasis lesions revealed a significant reduction in the number of somatostatin- and factor XIIIa-positive dendritic cells during the treatments. The reduction rate of the somatostatin-positive cells differed between the two groups and closely paralleled the healing process induced by the two treatments. These findings and the fact that somatostatin has been used in several studies as treatment for psoriasis may indicate that the somatostatin-positive cells are specifically involved in the healing process of psoriasis. The reduction of the factor XIIIa-positive cells was associated with the healing process as a whole, but showed no relation to either treatment.     

Recurrent malignant fibrous histiocytoma with expression of cytokeratin.

A case of locally recurrent malignant fibrous histiocytoma was documented in a 70-year-old man. He first noticed a subcutaneous nodule forty years previously. The tumor was surgically removed four times during the last four years with local recurrence on every occasion. In the recurrent tumors, the tumor cells almost completely replaced the whole dermis and invaded skeletal muscles. They were composed of pleomorphic spindle cells arranged in a storiform pattern and bizarre histiocytic cells, which were present principally in the deeper portions of the tumor. Both types of tumor cells showed marked nuclear atypicality. In the primary tumor, surrounding a large necrotic area, spindle-shaped cells were arranged in a storiform pattern. These tumor cells exhibited only mild nuclear atypia. The recurrent tumor was strongly positive for vimentin and alpha-1-antichymotrypsin. Most tumor cells were also weakly positive for KL1, a monoclonal antibody for keratin. A Western-blot analysis revealed the presence of two bands (62 and 69 Kd) reacting with KL1 in the fractions which were obtained from the tumor according to the method for keratin extraction.     

Vascular eccrine giant spiradenoma--a case report with histology and immunohistology of a rare variant of benign sweat gland tumors

Giant vascular eccrine spiradenoma (GVES) is a rare variant of benign tumors of the sweat glands, which differs from common eccrine spiradenoma in both its size and vascularity. Clinically as well as macroscopically, this intradermal or subcutaneous encapsulated tumor might be mistaken for an angiomatous lesion or thrombosis. Histological examination reveals clearly delimited "cords" showing two types of cells, prominent blood-filled cavities and extensive hemorrhages. According to immunohistochemical findings, the epithelial cells contain cytokeratin, protein S-100 and carcino-embryonal antigen (CEA). Like the endothelial cells of vessels, some of the luminal epithelial cells also bind Ulex europaeus lectin; however, they do not show factor VIII-associated antigen.     

动脉瘤样纤维组织细胞瘤1例

患者女,42岁。背部出现结节1年,伴瘙痒。皮肤科情况:背部可见一个豌豆大蓝褐色结节,皮损组织病理示纤维组织细胞瘤结构中出现出血性腔隙。手术切除结节,随访至今无复发。     

Atypical fibrous histiocytoma of the skin with CD30 and p80/ALK1 positivity and ALK gene rearrangement

We report the case of a two patients who presented with a solitary, asymptomatic, angiomatoid nodule on the right thigh. Histopathological finding showed a poorly circumscribed lesion, located in the dermis. The morphological aspect strongly suggested the diagnosis of atypical fibrous histiocytoma (AFH), but surprisingly, the neoplastic cells were diffusely CD30+, with a membrane staining devoid of paranuclear dot. The lesions were tested for p80/ALK1 expression. Surprisingly, we found a diffuse cytoplasmic positivity. Interestingly, using break‐apart fluorescent in situ hybridization (FISH), we evidenced an ALK rearrangement in nearly 50% of the neoplastic cells. The expression of CD30 and ALK1 with ALK gene rearrangement raised the possibility of three diagnoses: a primary cutaneous anaplastic large cell lymphoma (ALCL), a cutaneous inflammatory myofibroblastic tumor (IMT), an AFH of the skin associated with ALK gene rearrangement and CD30 positivity. The three hypotheses were discussed and finally, although p80/ALK1 expression and cytogenetic abnormalities in fibrous histiocytoma (FH) are not yet reported to the best of our knowledge, we favored the diagnosis of AFH.     

Solitary form of infantile myofibromatosis: a histologic, immunohistochemical, and electronmicroscopic study of a regressing tumor over a 20-month period.

We present the repeated clinical, histologic, immunohistochemical, and ultrastructural observations on a cutaneous myofibromatous tumor over a 20-month period. A 6-day-old Japanese female had a solitary tumor on her left wrist at birth. A biopsy was first performed at 16 days of age, when the tumor was likely fully developed. Thereafter, the tumor gradually regressed. A second biopsy was performed at 58 days of age, when the tumor was already in a phase of early regression. Finally, the tumor was resected at 20 months of age, when it was in a phase of late regression. Our study demonstrated that undifferentiated immature histiocytic cells predominated over spindle cells in the first biopsy specimen, but thereafter the former cells decreased or disappeared in parallel with the increase in the latter cells, which showed characteristics similar to myofibroblasts, in regressing lesions. This evidence suggests that the undifferentiated immature histiocytic cells are precursors of the spindle cells. Spindle cells in the phase of early regression also showed many vacuoles and lipid-like droplets in the cytoplasm, even though they actively produced massive amounts of glycogen. These findings also suggest that tumor regression results from cytoplasmic vacuolation and disruption of spindle cells. Our results are considered to demonstrate, for the first time, the clinical and histologic features of the different developmental or regressive phases of infantile myofibromatosis.     

Ultrastructural aspects of normolipidemic xanthomatosis

Summary Electron microscopic aspects in ten cases of normolipidemic cutaneous xanthomatosis have been investigated. Two additional types IV and V hyperlipoproteinaemic xanthomatosis have also been included.Ultrastructural findings in all cases were similar. Abundant histiocytic cells with numerous intracytoplasmic lipid vacuoles, lysosomes, and myelin-figures, were the striking features. Moreover, in older lesions microfilaments and lipid vacuoles were found in some fibroblastic cells, as well as long space collagen around them. In some specimens we observed: giant multinucleated histiocytic cells, crystalline cleft-like spaces in histiocytes and some mastocytes with lipidic crystals in the extracellular space, as well as lipid vacuoles in Schwann cells, endothelial cells and pericytes. Rod-shaped tubulated bodies were found in some endothelial cells, with multiple basal vascular laminae. In xantelasma palpebrarum and in disseminate plane xanthoma the histiocytary foamy cells adopted a perivascular arrangement, as in hyperlipoproteinemic xanthomatosis.We concluded that ultrastructural aspects of different xanthomatosis are fairly similar as a consequence of the large amount of intracytoplasmic lipids accumulated in xanthomatous cells. In xanthelasma palpebrarum and in disseminated plane xanthoma this cell phase is reached by similar pathways to those for hyperlipoproteinemic xanthomatosis, whilst in xanthoma disseminatum and juvenile xanthogranuloma the pathways seem to be different.A classification of normolipidemic xanthomatosis is also provided.     

The fibroblastic nature of dermatofibrosarcoma protuberans: Morphological investigations in vivo and in vitro

Summary Six cases of dermatofibrosarcoma protuberans were studied ultrastructurally. Biopsy material from all six cases as well as cell cultures derived from four cases were examined. In all cases, the tumor cells in vivo and in vitro were related to fibroblasts. The two cases with histiocytoid features and a small spiral pattern exhibited numerous lipid vacuoles but no histiocytic cell markers. In these two cases, cultured cells contained a higher number of intracytoplasmic vacuoles than the control fibroblasts. Two other cases exhibited some basement-membrane-like material surrounding tumor cells. All of the investigated cell strains obtained from the tumors showed synthesis of collagenous proteins similar to that found in fibroblasts. However, the level of total collagen was reduced, and type-III collagen was absent.The morphological variations in these cases of dermatofibrosarcoma protuberans appeared to be related to the histological pattern and may reflect the heterogeneity of normal fibroblasts.     

A light and electron microscopic study of a case of radiation induced malignant giant cell tumor of the soft tissue.

A case of malignant giant cell tumor of the soft tissue in a 59-year-old female is presented. Total hysterectomy was performed for uterine carcinoma (histologically squamous cell carcinoma) in 1963, followed by radiation treatment for 6 months. Chronic radiodermatitis developed thereafter on the skin of the hip joint region, buttocks and lower abdominal region. A tumor developed in the lesion of chronic radiodermatitis of the left hip joint region in August 1976 and this was excised on February 23, 1977. Two recurrent tumors and a metastatic lesion in the inguinal lymph node developed, which were surgically removed. The main tumor, measuring 7.5 cm in maximum diameter, was found chiefly in the subcutaneous adipose tissue. Histologically, it was composed of a mixture of fibroblastic spindle-shaped cells, histiocytic mononuclear cells, bizarre giant cells and osteoclast-like multinucleated giant cells. Occasionally osteoid tissues were seen. Electron microscopically, undifferentiated cells, fibroblastic cells, monohistiocytic cells, osteoclast like multinucleated giant cells and macrophages were observed, and these cells were considered to be divided into three cell lines, that is an undifferentiated cell line, fibroblastic cell line and histiocytic cell line. The histogenesis of malignant giant cell tumor in this case, is considered to have been from undifferentiated cells to both fibroblastic and histiocytic differentiation through the neoplastic stimulus of radiation.