A huge benign fibrous histiocytoma arising from the renal capsule: report of a case.

BACKGROUND: Neoplasms originating in the renal capsule are very rare. Benign fibrous histiocytoma(BFH) most commonly occurs in the dermis and subcutis, few cases of this tumor appear in the renal capsule. In particular, BFH larger than 20 cm are scarce. Here we report a rare huge one measuring 23 × 13 × 7 cm. CASE PRESENTATION: We report a 64-year-old man who presented with a few-months history of dull pain in the right groin. The tumor had its point of origin in the renal capsule which is a rare condition. Histologically, the tumor was composed of intersecting fascicles of fibroblastic cells forming a "storiform" pattern. Immunohistochemical studies were also performed, ultimately leading to the diagnosis of BFH. The patient was treated with radical nephrectomy. No recurrence was detected 4 months after surgery. CONCLUSIONS: BFH arising from the renal capsule was very rare. In particular, the case of more than twenty centimeters is extremely rare. The clinical presentation of renal BFH might be only a mass. However, differential diagnosis from renal cell carcinoma proved to be impossible before surgical intervention. It is difficult to diagnose only by means of histopathology, but the immunohistochemical method can provide a clear and definite diagnosis.

Rheb/mTOR/p70s6k Cascade and TFE3 Expression in Conventional and Sclerosing PEComas of the Urinary Tract.

Perivascular epithelioid cell tumors (PEComas) are rarely found in the urinary tract. The clinicopathologic characteristics of 10 cases, retrospectively collected from 5 medical institutions in 3 different European countries, are presented in this study. Male/female ratio was 3:7 and the average age at diagnosis was 62.7 years. Nine cases were sporadic and 1 showed germline mutation of the TSC2 gene. Eight cases were located in the kidney, 1 in the left adrenal and 1 in the right ureter. All of the patients were alive and free of disease at the time of last contact (mean follow-up, 14.1 mo). Four cases displayed a conventional morphology and 6 showed a prominent sclerotic stroma. By immunohistochemistry, melanocytic markers were consistently expressed, especially HMB-45 (10 cases), MiTF (9 cases), and Melan-A (6 cases). Desmin was expressed in 6 cases; 2 cases were positive for CD117; a single case showed TFE3 expression. pMAPK, mTOR, and pAKT demonstrated variable immunostaining with focal positivity in 7, 4, and 2 cases, respectively. Cytokeratins were repeatedly negative in all cases. PEComas in the urinary tract, especially in the renal region, may show a relatively high frequency of the sclerosing histologic subtype. Knowledge of the distinct histology and immunohistochemical profile is vital to correctly diagnose this rare entity.

Benign fibrous histiocytoma of the skull with increased intracranial pressure caused by cerebral venous sinus occlusion.

The authors present a very rare case of benign fibrous histiocytoma of the skull with increased intracranial pressure caused by sinus occlusion. A 33-year-old woman was referred for investigation of a right occipital protrusion with tenderness and double vision. She had only mild divergence insufficiency and bilateral papilledema neurologically. Imaging findings showed that the skull tumor was located at the right occipital bone with bone disruption and a compressed right sigmoid sinus. When planning the resection, caution was required to spare the collateral flow so as to manage the intracranial pressure. Immunohistochemical analysis showed that the tumor was positive for CD68, alpha1-antichymotrypsin, and alpha1-antitrypsin. From these findings, the tumor was diagnosed as a primary benign fibrous histiocytoma of the skull.

Fine-needle aspiration cytology of angiomatoid malignant fibrous histiocytoma.

Angiomatoid malignant fibrous histiocytoma (AMFH) is a rare, low-grade malignant mesenchymal neoplasm that affects mostly the extremities of children and young adults. Excisional surgery is the adequate treatment. The cytologic, immunocytologic, and histologic features noted in two patients having AMFH are presented. Cytologic smears showed histiocyte-like cells dispersed and in clusters, in close relation with eosinophilic mesenchymal fragments in a bloody background with lymphocytes. The tumor cells showed mild to moderate anisocariosis, often with nucleolus and vast, fragile cytoplasm. A fibroblastic-like spindle to ovoid cell population was also present in one patient. Immunohistochemical results are most consistent with myofibroblastic cell differentiation. When accompanied by adequate clinical information and ancillary techniques, a specific preoperative cytologic diagnosis is possible.

Role of mast cells in dermatofibroma: recent viewpoints into the pathogenesis.

Mast cells are often discussed to play an important role in the tissue fibrotic process, because increased numbers of mast cells are found in the fibrous lesions. Recent evidence has revealed that mast cells are a rich source of cytokines or mediators, which are supposed to play a crucial role in altering the environmental extracellular matrix, leading to fibrosis. Dermatofibromas (DFs) are benign tumors histologically characterized by local fibroblast proliferation. It has been demonstrated that multiple DFs occur in patients with autoimmune diseases or under immunosuppressive therapy, implying that DFs are reactive tumors, rather than true neoplasms, at least in one aspect. Increased numbers of mast cells are also found in both solitary and multiple DFs, in particular in the layers between the DF lesion and the overlying epidermis. The presence of mast cells could be significant in the induction of several histopathologic changes, including acanthosis of the overlying epidermis, basal melanosis, and possibly mononuclear cell recruitment, in DF. Further elucidation of the role of mast cells may lend support to the understanding of the mechanism of DF.

The mechanism of epidermal hyperpigmentation in dermatofibroma is associated with stem cell factor and hepatocyte growth factor expression.

Dermatofibromas have an increased brownish color due to hyperpigmentation of the overlying skin. To determine paracrine factors involved in the epidermal hyperpigmentation, we have studied the expression of cytokines in lesional and nonlesional dermatofibroma skin at the transcriptional and protein levels using reverse transcription polymerase chain reaction and immunohistochemistry, respectively. The number of tyrosinase immuno-positive melanocytes in the pigmented dermatofibroma epidermis is significantly increased (2-fold) compared with nonlesional normal epidermis. Reverse transcription polymerase chain reaction analysis of mRNAs encoding stem cell factor and hepatocyte growth factor demonstrated that there is an accentuated expression of stem cell factor and hepatocyte growth factor transcripts in the lesional dermatofibroma dermis compared with the nonlesional dermis, although there is no difference in their expression between the lesional and nonlesional epidermis. In contrast, mRNA transcripts encoding endothelin-1, growth-related oncogene alpha, and basic fibroblast growth factor are not increased in lesional epidermis or in dermis relative to nonlesional skin. In parallel, immunohistochemical analysis using antibodies to stem cell factor and hepatocyte growth factor reveal a marked immunostaining in growing fibroblastic tumor cells in the dermatofibroma lesions with no detectable staining in the nonlesional dermis, but there is no difference in their immunostaining between the lesional and nonlesional epidermis. Interestingly, and consistent with the increased expression of stem cell factor in lesional dermatofibroma dermis, toluidine blue staining in the dermis revealed a 5-fold increase in the number of mast cells, an indication of their longevity or accumulation induced by stem cell factor. These findings suggest an important role of fibroblastic tumor cell-derived stem cell factor in the mechanism involved in the hyperpigmentation of the dermatofibroma epidermis.

Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma.

Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and the development of pathological scarring. In this study, we demonstrate that keloid fibroblasts can be identified as apoptotic cells because of their highly condensed chromatin and discrete nuclear fragments. To further reveal the phenomenon of apoptosis, we quantified the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in surgically resected tissues of keloids (N = 10), hypertrophic scars (N = 10), normal healed flat scars (N = 10), and dermatofibroma (N = 10). The number of TUNEL-positive cells was relatively low, but was significantly higher for the keloid group compared with the normally healed flat scar group (p = 0.004), suggesting reduced cell survival and increased apoptotic cell death in a subpopulation of keloid fibroblasts. Furthermore, the number of TUNEL-positive cells was significantly higher for the keloid group compared with the dermatofibroma group (p = 0.044), suggesting that a subpopulation of keloid fibroblasts may suppress tumorgenicity at a greater rate than dermatofibroma by undergoing cell death. Hypertrophic scars had significantly higher levels of apoptosis than normally healed flat scars (p = 0.033). Therefore, these results suggest that selected fibroblasts in keloids and hypertrophic scars undergo apoptosis, which may play a role in the process of pathological scarring.

Cytotoxic effects of sphingolipids as single or multi-modality agents on human melanoma and soft tissue sarcoma in vitro.

We evaluated the cytotoxic effects of a cell-permeable ceramide (Cer), N-hexanoyl-D-sphingosine (C6-Cer) and of two related sphingoid bases, sphingosine (So) and dihydrosphingosine (sphinganine; Sa) on human melanoma cell lines and on soft tissue sarcoma lines recently established from fresh surgical biopsy specimens. These cell lines ranged from high susceptibility (939 melanoma) to strong resistance (A2058 melanoma and all three sarcomas) to tumour necrosis factor (TNF), an inducer of elevated intracellular Cer levels. However, all the cell lines demonstrated a dose-dependent susceptibility to C6-Cer with protracted cytotoxic kinetics, with the C8161 melanoma being the most sensitive and A2058 the least. Protein kinase C (PKC) antagonizes Cer-dependent apoptosis, and chelerythrine chloride, So and Sa, which inhibit PKC, caused extremely rapid cytotoxicity of melanoma cell lines, irrespective of their relative sensitivity to C6-Cer. So-mediated cytotoxicity was extensive even after only 90 min of treatment, within the time frame of limb perfusion. So and Sa only slightly potentiated the cytotoxic responses to TNF, C6-Cer or melphalan. Sphingolipid-driven intracellular pathways may offer opportunities for therapy of these tumours.

Phorbol 12-myristate 13-acetate can transform monocyte-derived dendritic cells to different cell types similar to those found in dermatofibroma. A possible in vitro model of the histogenesis of dermatofibroma.

Dermatofibroma is composed largely of interlacing fascicles of slender spindle cells set within a loose collagenous stroma and of scattered foamy histiocytes and multinucleated giant cells. There is clear evidence indicating that factor XIIIa+ dermal dendritic cells (DDCs) are the cells constituting dermatofibromas. However, it is still unknown what stimulation is responsible for transforming DDCs into different cell types, producing different subtypes of dermatofibromas. Recently, it has become possible to obtain dendritic cells (DCs), that are identical with DDCs in their phenotypic and functional characteristics, from the culture of CD14+ peripheral blood monocytes to which IL-4 and GM-CSF were added. Using these monocyte-derived DCs, we examined the ability of various cytokines, such as IL-1beta , IL-3, IL-5, IL-6, IL-7, IL-8, IL-10, TNFalpha, TGFbeta, M-CSF, IFNalpha, and IFNgamma, and phorbol 12-myristate 13-acetate (PMA), to induce different cell types observed in DFs. Among them, only PMA could induce a variety of cell types such as histiocytic cells, fibroblastic spindle-shaped cells, and even multinucleated giant cells of Touton or foreign body type. Phenotypically, all the induced cell types expressed CD1a, CD80, CD86, HLA-DR, and CD68 in a magnitude similar to that of non-treated monocyte-derived DCs. The expression of factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells, and weakest or negative in giant cells. These data suggest that dermatofibromas are a kind of neoplastic disease which is induced only by the effect of some tumor promoter on DDCs.

Epithelial induction in dermatofibroma: a role for the epidermal growth factor (EGF) receptor.

Dermatofibroma (DF) refers to a spectrum of firm, nodular, nonencapsulated lesions that occur commonly on the extremities. Histologically, DF is composed of spindle cells with variable differentiation toward histiocytic and vascular elements, often associated with epithelial hyperplasia and basilar keratinocyte pigmentation that histologically may simulate basal cell carcinoma (BCC). The characteristic epithelial changes are likely to be mesenchyma-mediated and probably represent a host reparative response otherwise known as the inductive phenomenon. Epidermal-mesenchymal cellular interactions, including induction, occur in various stages of embryonic skin development and in response to injury with tissue repair. Cellular interaction is mediated by direct apposition of cells or by soluble protein hormones produced directly by the cell (autocrine effect) or adjacent cells (paracrine effect). Among the important soluble mediators are epidermal growth factor (EGF), which is known to stimulate the proliferation and differentiation of a variety of transformed and benign tissues. We investigated the possible etiologic association between EGF receptor (EGF-R) expression and epithelial induction in a prospective series of 20 cases of DF compared to entities such as granular cell tumor, scar tissue, and nevus sebaceus similarly showing epithelial hyperplasia. Immunohistochemical staining for EGF-R showed strong dermal staining of dendritic spindle cells and overlying hyperplastic keratinocytes in each of the DF cases. Immunohistochemical staining for EGF-R was absent within all dermal loci of granular cell tumor (n = 3), nevus sebaceus (n = 6), and scar tissue (n = 12).

Primary malignant fibrous histiocytoma of the lung in a child: a case report and review of literature.

Malignant fibrous histiocytoma (MFH), an aggressive high-grade soft tissue sarcoma, usually occurs in the elderly during the fifth to seventh decade of life. It commonly arises in the retroperitoneum, extremities, and head and neck region. Primary pulmonary MFH is extremely rare and is frequently fatal. We present the youngest known case, a 9-year-old boy with a primary left lung grade II inflammatory MFH, stage II. He underwent a left upper lobectomy for tumor resection. After completing radiation therapy, he was started on vincristine, actinomycin D, and cyclophosphamide alternating with vincristine, doxorubicin, and cyclophosphamide every 3 weeks. After five such cycles, he had a histologically proven local recurrence. He then received chemotherapy consisting of ifosfamide (2 g/m2) and etoposide (VP-16) (100 mg/m2) given daily for 3 days every 3 weeks. The patient attained complete remission (CR) after five such cycles and completed treatment without any major complications. He received a total of 16 courses and is continuing in CR 36 months off treatment. Ifosfamide and etoposide (VP-16), known for their usefulness in treatment of adult soft tissue sarcomas, can be used as salvage chemotherapy for patients with MFH who fail the front-line conventional chemotherapy.

Radiation-induced malignant fibrous histiocytoma of the brachial plexus.

Brachial plexopathy is a common and disabling complication in cancer patients most often attributed to metastasis or radiation-induced fibrosis. Occasionally, other rare but potentially treatable causes are found. A 73 year old woman had a left radical mastectomy followed by radiation to the chest wall and axilla 24 years ago. She recently presented with left arm pain, chronic, nonprogressive lymphedema, profound distal arm sensory loss and progressive severe hand weakness. There was moderate atrophy of all intrinsic hand muscles, anesthesia of the hypothenar eminence and 4th and 5th digits, and no adenopathy or palpable mass in the axilla. EMG confirmed a brachial plexopathy. MRI showed loss of tissue planes consistent with radiation fibrosis, but CT showed a discrete mass in the brachial plexus. Open biopsy showed pleomorphic spindle shaped cells with immunoperoxidase stains consistent with malignant fibrous histiocytoma. Radiation-induced malignant fibrous histiocytoma may present with a brachial plexopathy in the absence of a palpable mass and should be considered in the differential diagnosis of brachial plexus lesions in cancer patients. CT scanning through the plexus may be useful when MRI is normal or equivocal.

Tumor necrosis factor accounts for the neutrophil emigration activity released by cultured malignant fibrous histiocytoma cells

Cultured malignant fibrous histiocytoma (MFH) cells obtained from a spontaneous and transplantable rat tumor were studied for their ability to release tumor necrosis factor (TNF) and a factor which induces neutrophil migration in vivo. MFH cells obtained from 7-day cultures spontaneously released both activities into the supernatant (TNF: 36 ñ 9 iu tnf/ml supernatant, N = 3; neutrophil chemoattractant factor: control, Medium ip: 6 ñ 1 x 10**6; MFH supernatant: 18 ñ 1 x 106 neutrophils/cavity, H = 5). these releases were enhanced by treating MFH cells with LPS (TNF; 61 percent; neutrophil chemoattractant factor: 46 percent) and were abolished by the glucocorticoid dexamethasone (TNF: 68 percent; neutrophil chemoattractant factor: 100 percent). Anti-TNF antiserum abolished the neutrophil chemoattractant activity of the supernatants (95 percent). The release of TNF or neutrophil chemoattractant activity was reduced in cells obtained from older cultures (14 and 21 days) (TNF: 7-day culture, 36 ñ 9;14-day culture, 19ñ2;21-day culture, 19ñ 1 IU of TNF/ml; neutrophil chemoattractant activity: 7-day culture, 18 ñ 1.6; 14-day culture, 13 ñ 3;28-day culture, 8 ñ 1 x 10**6 neutrophils/cavity). The predominant cells present in 7-day cultures of MFH were histiocyte-like cells as determined by nonspecific esterase methods. The number of these cells decreased as the cultures aged (7-day culture, 71 percent; 14-day culture, 5 percent; 21-day culture, 0 percent)...

Involvement of basic fibroblast growth factor in fibroblast-stimulatory serum activity of a patient with systemic lupus erythematosus and multiple dermatofibromas.

BACKGROUND: Multiple dermatofibromas (DFs) are often associated with systemic lupus erythematosus (SLE). An increased number of mast cells is observed in the upper portion or over the lesion of DF. OBJECTIVE: To investigate the role of the serum of a patient with multiple DFs, we examined its growth effects on fibroblasts. METHOD: 3H-Thymidine incorporation was used to examine the effects of the serum of an SLE patient with multiple DFs on fibroblasts derived from DF and normal skin. RESULTS: The serum of the SLE patient with multiple DFs exhibited a stronger growth-stimulatory activity on normal and DF-derived fibroblasts in a dose-dependent manner, compared to that of SLE without DFs or normal sera. The growth effects were inhibited in 40% by antiplatelet-derived-growth-factor antibody and almost completely inhibited by antibody against basic fibroblast growth factor. Cultured fibroblasts derived from the upper portion of the DF lesion, which included most of the numerous mast cells, demonstrated a higher level of 3H-thymidine uptake after stimulation of autologous serum compared to that from the mid and lower portions of DF. CONCLUSION: These results suggested the existence of various fibroblast growth factors derived from the mast cells in SLE patients with multiple DFs.