Prognostic significance of histologic parameters of soft tissue sarcomas.

BACKGROUND AND METHODS. A univariate and multivariate analysis for the correlation between histomorphologic factors and prognosis was made using data from 1116 patients with soft tissue sarcoma, including 1005 cases available with complete histologic and follow-up data. RESULTS. The overall 5-year survival rate was 43.6%. The univariate analysis using Kaplan-Meier survival curves showed that tumor differentiation, cellularity, nuclear atypia, cellular pleomorphism, mitotic activity, amount of fibrous stroma, extent of myxoid areas, extent of tumor necrosis, and histologic grading (determined by the estimated range of malignancy for each type of sarcoma using a reported guideline) were all significant prognostic factors in the overall soft tissue sarcoma group. By a multivariate analysis using a procedure based on the Weibull model to failure data, the histologic grading and extent of tumor necrosis were proved to be prognostically significant in the overall sarcoma group. However, after additional analysis on each histologic type of sarcoma, it was determined that both tumor necrosis and histologic grading were applicable in only two types: malignant fibrous histiocytoma and leiomyosarcoma. Liposarcoma, synovial sarcoma, and malignant schwannoma each also showed some determinable factor of prognostic significance. CONCLUSIONS. It was concluded that there seemed to be no single universal prognostic parameter that could be applied to each soft tissue sarcoma type. These results suggest that the predictive significance of the various histologic parameters should be based on each specific type of sarcoma.     

Tubular adenoma of the gallbladder with squamoid spindle cell metaplasia. Report of three cases with immunohistochemical study.

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells.     

Ovarian sarcoma with histologic features of telangiectatic osteosarcoma of the bone

A primary osteosarcoma occurred in the left ovary of a 47-year-old Japanese woman. The preoperative diagnosis, based on computerized tomography, was cystic teratoma. The excised tumor was composed of large multilocular cysts containing blood and associated with an area of solid tissue. Histologically, the tumor was a "pure" osteosarcoma that showed prominent cellular anaplasia and blood-filled spaces lined with tumor cells. The lesion resembled a telangiectatic osteosarcoma of bone. Serum alkaline phosphatase levels reflected progression of the disease. Despite aggressive adjuvant chemotherapy, the patient died 8 months later of a local recurrence and intra-abdominal spread of the tumor.     

Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver dysfunction, and its prevalence has markedly increased; however, the mechanisms involved in the pathogenesis of NAFLD have not been thoroughly investigated in humans. In this study, we evaluated the expression of fatty acid metabolism-related genes in NAFLD. Real-time RT-PCR was performed using liver biopsy samples from 12 NAFLD patients. The target genes studied were: acetyl-CoA carboxylase (ACC) 1, ACC2, and fatty acid synthase (FAS) for the evaluation of de novo fatty acid synthesis; carnitine palmitoyltransferase 1a (CPT1a), long-chain acyl-CoA dehydrogenase (LCAD), and long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase alpha (HADHalpha) for beta-oxidation in the mitochondria; peroxisome proliferator-activated receptor- (PPAR-) alpha and cytochrome P450 2E1 (CYP2E1) for oxidation in peroxisomes and microsomes (endoplasmic reticulum) respectively; and diacylglycerol O-acyltransferase 1 (DGAT1), PPAR-gamma, and hormone sensitive lipase (HSL) for triglyceride synthesis and catalysis. In NAFLD, expression of ACC1 and ACC2, but not FAS was increased, indicating that de novo fatty acid synthesis is enhanced in NAFLD. In contrast, expression of CTP1a, a rate-limiting enzyme, was remarkably decreased, indicating that beta-oxidation in the mitochondria was decreased, although the expression of LCAD and HADHalpha was increased. Expression of PPAR-alpha was increased, whereas that of CYP2E1 was reduced. The expression of DGAT1, PPAR-gamma, and HSL was enhanced. These data suggest that in NAFLD, increased de novo synthesis and decreased beta-oxidation in the mitochondria lead to accumulation of fatty acids in hepatocytes, although the extent of oxidation in peroxisomes and microsomes remains unclear.     

Plexiform neurilemoma: A clinicopathological and immunohistochemical analysis of 23 tumours from 20 patients

Summary A clinicopathological and immunohistochemical study was done on 23 plexiform (multinodular) neurilemomas excised from 20 Japanese. Ages of the subjects ranged from 2 years to 69 years with a mean age of 30 years. The tumours occurred most often on the trunk (14), and were located commonly in the dermis and subcutis (19). Three lesions apparently originated from the peripheral nerve trunks. Multiple tumours were observed in six instances, and two were associated with von Recklinghausen's disease. Microscopically, they appeared as multinodular growths, most nodules were moderately cellular, and both Antoni A and B patterns were distinct in 10 tumours. Obvious Verocay bodies were noted in seven tumours and abortive ones in five. Immunohistochemical reactivity to S-100 protein was demonstrated in both nuclei and cytoplasm of almost all tumour cells of all lesions examined. Recurrences are nil among the 4 patients who could be followed. Correlations with trauma and with von Recklinghausen's disease are briefly discussed.     

Infantile and adult fibrosarcomas of the soft tissues.

Histologic sections of 68 soft-tissue sarcomas initially diagnosed as fibrosarcoma were reviewed, and 36 were excluded because of revised diagnosis. The tumors from the remaining 32 patients were analyzed clinicopathologically, and were classifed into two types; the adult type (22 cases) and the infantile type (10 cases). The adult type fibrosarcoma occurred in adults aged 25 to 67 years and consisted of spindle-shaped fibroblastic cells which formed interlacing bundles accompanied by variable amounts of collagen or reticulin fibers. The infantile fibrosarcoma affected children below the age of seven years in this series and was characterized by proliferation of immature fibroblasts forming indistinct bundles, frequently exhibiting areas of an angiosarcoma-like pattern and cavernous blood vessels. The authors expressed the view that infantile fibrosarcoma should be separated from adult fibrosarcoma, because between these two types of fibrosarcoma there were marked differences in the histologic feature as well as in the age, sex and anatomical distributions.     

The PPARgamma ligand, 15-Deoxy-Delta12,14-PGJ2, regulates apoptosis-related protein expression in cholangio cell carcinoma cells

PPARgamma is known to induce apoptosis in malignant tumor cells, but the mechanism of this induction is not well understood. We investigated induction of apoptosis with 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a PPARgamma ligand, in cholangio cell carcinoma (CCC) cells (RBE, ETK-1 or HuCCT-1). Apoptosis was induced in RBE and ETK-1 cells with 15d-PGJ2, but not in HuCCT-1 cells, although PPARgamma was expressed in all CCC cells. Apoptosis-related proteins were also expressed, including FLIP, bclx, Apaf-1 and XIAP, but expression levels differed among the three cell lines. RBE cells treated with 15d-PGJ2 showed caspase activation, and it appeared that PPARgamma-induced apoptosis was dependent on caspase activation. However, neither ETK-1 nor HuCCT-1 cells showed significant activation of caspase-8 or -3 with 15d-PGJ2 treatment, raising the possibility of a caspase-independent apoptosis induction pathway. XIAP was down-regulated by 15d-PGJ2 in all three CCC cell lines. Therefore, 15d-PGJ2 induces apoptosis in CCC cells via caspase-dependent or independent pathways. 15d-PGJ2 may also induce down-regulation of XIAP and may promote caspase cascade activation through TNF-family receptor signaling pathways.     

Bednar tumor (pigmented dermatofibrosarcoma protuberans). An analysis of six cases

Six cases of Bednar tumor were analyzed clinicopathologically along with a review of 39 published cases. The findings were then compared with data on 44 cases of ordinary dermatofibrosarcoma protuberans (DFSP) obtained from our files. The clinical manifestations of the patients and the anatomic locations of the tumors were similar between the two categories, but the rate of recurrence was lower in cases of Bednar tumor. The histologic pattern of Bednar tumor was indistinguishable from ordinary DFSP except for scattered melanosome-containing cells. Ultrastructural and immunohistochemical examinations showed no evidence of neuroectodermal differentiation of dominant spindle-shaped cells in Bednar tumor, supporting a fibroblastic line of differentiation. The origin and pathogenesis of the melanosome-containing cells were considered. These cells failed to react with HMB-45, a melanoma-specific antibody, and the large majority of melanosomes present were mature or at Stage IV, plus a few immature ones at Stage II. These pigmented cells do not appear to be neoplastic, and cannot be used as proof to indicate that Bednar tumor is a neuroectodermal neoplasm.     

Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity

Liver cirrhosis is caused by a relative imbalance between synthesis and degradation of collagens. Arg-Gly-Asp (RGD) peptide is a major adhesive domain of several extracellular matrix (ECM) components, such as that involved in the binding of fibronectin to the alpha5beta1 integrin receptor. We previously reported that RGD peptide increased the expression of matrix metalloproteinase in hepatic stellate cells (HSCs) which play a major role in hepatic fibrosis. We evaluated whether RGD-peptides inhibit the progression of liver fibrosis in an animal model of carbon tetrachloride-induced hepatotoxicity. RGD peptide (GRGDS) (1 mg/kg body weight) was injected intraperitoneally (i.p.) 3 times a week for one month. The group treated with control peptide (GRGES) showed pathologically typical hepatic fibrosis, while the RGD-treated group showed minimal fibrotic changes. The liver contents of collagen and hydroxyproline in the RGD-treated group was significantly lower than that of the control group. Collagenase activity measured in liver homogenates was significantly higher in the treated group than in the control group. In an in vitro study using TWNT-4 cells derived from human HSCs, RGD peptide (100 mug/ml) reduced the expression of type I collagen and tissue inhibitor of matrix metalloproteinase-1, and increased that of matrix metalloproteinase-1. These results indicated that RGD peptides inhibited liver fibrosis associated with both decreased collagen production and increased collagenase acitivity, and suggested that RGD peptide might be useful for the therapy of hepatic fibrosis.     

INFANTILE DIGITAL FIBROMATOSIS HISTOPATHOLOGICAL and ELECTRON MICROSCOPIC STUDY WITH A REVIEW OF THE LITERATURE

Five cases of Infantile digital fibromatosis were described. Three were male and two were female. Multiple lesions were noted in two cases. The lesions were Intradermal and had a peculiar histologic pattern with intracytoplasmic inclusions. By electron microscopy, the inclusions were composed of a meshwork of both fibrils and fine granules and have no limiting membrane. No virus-like particle could be identified in the proliferating cells. Follow-up information was available in all five cases; one had recurring tumors.