Splenic angiomatoid nodular transformation in a child with increased erythrocyte sedimentation rate.

An 11-year-old girl was referred to the authors' hospital with a complaint of growth retardation. Physical examination revealed splenomegaly. Laboratory examination revealed increased sedimentation rate. Her imaging studies showed a splenic mass. Splenectomy was performed and histopathological examination revealed sclerosing angiomatoid nodular transformation (SANT) of the spleen. The disease rarely affects children but it could cause growth retardation and increased sedimentation rate, mimicking the chronic inflammatory diseases.

Lipidized dermatofibromas and their relationship to serum lipids.

BACKGROUND: Lipidized dermatofibromas represent a rare variant of dermatofibroma that has been regarded as an incidental finding with no particular clinical significance. OBJECTIVE: The goal of this study was to investigate the relationship between lipidized dermatofibromas and patient age, anatomic location, and serum total cholesterol. METHODS: A retrospective case control format was used with an experimental group containing patients with biopsy-proven lipidized dermatofibromas and a control group containing patients with nonlipidized dermatofibromas. RESULTS: Ages in the experimental group ranged from 35 to 75 years with a mean value of 53 years whereas ages in the control group ranged from 27 to 72 years with a mean value of 48 years. A comparison between the mean of the ages between the two groups using the t test method showed no statistically significant difference (P = .09). Lesion location on the body was grouped into 4 sites: leg, thigh, trunk, and upper extremity. Of the 23 patients in the experimental group, 10 had lesions on the legs, 5 had lesions on the thighs, 2 had lesions on the trunk, and 5 had lesions on the upper extremities. Of the 41 patients in the control group, 15 had lesions on the legs, 7 had lesions on the thighs, 9 had lesions on the trunk, and 10 had lesions on the upper extremities. A comparison between the two groups showed no statistically significant difference (P = .60). In all, 16 of the 23 patients in the experimental group and 24 of the 41 patients in the control group were considered to have high cholesterol. A comparison showed no statistically significant difference between the cholesterol levels of the two groups (P = .38). LIMITATIONS: Limitations that we encountered during the study included the relative infrequency of lipidized dermatofibromas, limiting the number of patients in the study. In addition, medication histories and lipid levels on patients were not always available. In addition, we formed a control group from people who had their cholesterol checked often, which may cause them to have a higher average cholesterol than that of the general population. CONCLUSIONS: Our data show that lipidized dermatofibromas do not differ clinically from nonlipidized dermatofibromas in age distribution of patients, tumor location, or underlying serum lipid levels.

Clinical implications of serum C-reactive protein levels in malignant fibrous histiocytoma.

Paraneoplastic syndromes (PNSs) associated with mesenchymal tumors are uncommon. Previous reports sporadically described inflammatory PNSs with elevated serum C-reactive protein (CRP) levels and leukocytosis in patients with inflammatory malignant fibrous histiocytoma (MFH) of soft tissue; however, the relationship between other subtypes of MFH and PNS has not been extensively investigated. Forty-six patients with primary MFH of soft tissues who underwent radical surgery were retrospectively analyzed. These patients were divided into 2 groups according to preoperative serum CRP level: normal (<1.0 mg/dl) and elevated (> or = 1.0 mg/dl). The correlation between serum CRP level and several clinicopathologic factors was analyzed. Correlation between preoperative serum CRP level and metastasis-free and overall survival was also investigated by univariate and multivariate analyses. Elevated preoperative serum CRP levels were found in 65% of patients with a mean of 3.7 mg/dl. There were statistically significant relationships regarding tumor size, depth, histologic subtypes, grade, stage and metastatic rate among normal and elevated CRP groups (p < 0.001, p < 0.02, p < 0.005, p < 0.001, p < 0.001 and p < 0.05, respectively). When the tumor was removed, the elevated CRP level subsided into the normal range and other abnormal laboratory findings diminished in all cases. In 11/14 relapsed cases that showed elevated CRP preoperatively, the serum CRP level re-elevated with tumor relapse. The normal CRP group showed significantly more favorable prognosis than the elevated CRP group in metastasis-free and overall survival on univariate analysis (p < 0.02, p < 0.05, respectively). Patients with MFH frequently present with an inflammatory PNS, such as elevated serum CRP level, which can be a useful marker of disease activity and a valuable prognostic indicator.

[Determination and significance of nitric oxide and tumor necrosis factor-alpha induced by peripheral blood monocyte in vitro in patients with malignant bone tumors].

Peripheral blood monocytes from 15 cases of malignant bone tumors and 12 cases of health volunteers were seperated and induced by lipopolysaccharide(LPS) for 48-hour culture. The supernatant was collected for determining the content of nitrite and tumor necrosis factor-alpha(TNF-alpha) (by Griess and ELISA methods, respectively). The results were as follows: The content of nitrite and TNF-alpha in patients with malignant bone tumors was significantly higher than that in normal control; the content of nitrite and TNF-alpha in the malignant bone tumor group presented the positive correlation (r = 0.8909, P < 0.01). The results suggest that NO and TNF-alpha produced by activated macrophages may be related to the pathogenesis of malignant bone tumors.

High intratumoural level of cytokines mediates efficient regression of a rat histiocytoma.

We have studied the role of cytokines in the spontaneous regression of AK-5 histiocytoma in syngeneic rats. Animals in which the tumour regresses show high levels of cytokines in the serum compared with animals which succumb to the tumour, and levels of IL-2, IL-4, IL-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are significantly higher in tumour tissue of the former. Thus there is an association between rejection of the tumour and the levels of cytokines present in the tumour mass. Our results also suggest a predominant Th1-type of response in those rats that display early tumour rejection.

Soft tissues sarcoma with acute paraneoplastic hepatic dysfunction: case report.

A case of malignant fibrous histiocytoma of soft tissues of the right scapula associated with transitory hepatic dysfunction in the absence of liver metastases is reported. After primary radiation therapy, the patient manifested fever, anemia, thrombocytosis and hepatic dysfunction. All the abnormalities disappeared immediately after complete removal of the tumor. The patient was well, with no evidence of distant metastases, at more than 12 months later. It is concluded that the abnormalities of laboratory data were indirectly induced by the tumor, although the exact mechanism of this paraneoplastic syndrome was not clarified.

Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan.

PURPOSE: Isolated limb perfusion (ILP) with tumor necrosis factor (TNF), interferon gamma, and melphalan (M) has been reported to result in high response rates for extremity melanoma and sarcoma. We have evaluated the relationship of systemic TNF exposure to induction of several secondary mediators and incidence of systemic toxicity. PATIENTS AND METHODS: Nineteen patients with extremity melanoma (n = 16) or sarcoma (n = 3), underwent 90-minute ILP with TNF-alpha, interferon gamma (0.2 mg), and M (10 to 13 mg/L of limb volume) (TNF/IFN/M) (n = 12), or M alone (n = 7). Continuous intraoperative monitoring (CIM) for systemic leak from the perfusion circuit was performed using radioactive iodine-131 albumin. Cytokine levels in the perfusate and systemic circulation during and after ILP were measured by enzyme-linked immunosorbent assay. RESULTS: Systemic leaks > or = 1% from the perfusion circuit occurred in six patients who received TNF/IFN/M and in four who received M alone. Hypotension that required vasopressor support occurred in six of six patients with evidence of a leak (> or = 1%) and zero of six patients without a leak (< 1%). These six patients had significantly higher peak systemic TNF levels during and after perfusion than patients without a leak (2.8 and 8.2 ng/mL v 0.7 and 2.0 ng/mL, respectively; P < .05). All patients who received TNF/IFN/M had significantly greater increases in systemic interleukin-6 (IL-6) levels than in patients with M alone (12,395 +/- 10,374 pg/mL v 79.4 +/- 7.2 pg/mL, respectively; P < .001). Intracellular adhesion molecule (ICAM), IL-8, and TNF-R levels were also increased after ILP with TNF/IFN/M. CONCLUSION: ILP with TNF/IFN/M can be safely performed, as I131 albumin provides a sensitive measure of systemic leakage from the perfusion circuit. Patients with a measured leak of > or = 1% develop mild and transient postoperative hypotension with significantly higher systemic TNF levels and lower perfusate TNF levels than in patients without leaks.

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.

Cytokines in inflammatory malignant fibrous histiocytoma presenting with leukemoid reaction.

Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN-gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL-3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.

[A case of pulmonary malignant fibrous histiocytoma in which cytokines exhibited high value by subculture].

A case of pulmonary malignant fibrous histiocytoma (PMFH) was experienced, and the tumor was subcultured in nude mice. Tumor cells were resected and cultured in medium containing RPMI 1640 and 10% FCS. As a result, in both the nude mice and in the cytokines, as supernatant in the tumorous cells, cultured using ELISA method or RIA method. IL-1 alpha, beta, TNF-alpha, GM-CSF, and in particular IL-6 and G-CSF, exhibited markedly raised values. Clinically, the leukocyte and platelet counts on admission showed markedly elevated values of 27,500/mm3 and 48.3 x 10(4)/mm3, respectively, and the erythrocyte sedimentation rate was increased of 67 mm in 1 hour. These findings corresponded to the physiological findings of elevated IL-6 and G-CSF levels. We have experienced two further patients with PMFH, in whom serum levels of IL-6 and G-CSF were markedly elevated. Some reports have been published on cytokine-generating tumors, but there is no report about cytokine generation in PMFH. We report this patient's very interesting clinical course, together with elevation of cytokine generation.

[Malignant fibrous histiocytoma arising from the renal capsule: report of a case].

Malignant fibrous histiocytoma (MFH) is now considered the most common soft tissue sarcoma in adults, but MFH arising from the renal capsule is very rare. A 77-year-old woman was admitted with a painful mass in the left flank region on September 10, 1986. Preoperative diagnosis was hypovascular retroperitoneal tumor in contact with the upper pole of the right kidney. The tumor was removed together with the right kidney on December 18, 1986, and the specimen weighted 640 gm. Histological examination revealed storiform-pleomorphic malignant fibrous histiocytoma. No postoperative adjuvant therapy was carried out. Local recurrence of the disease was found about 9 months after the operation, and the patient died on February 23, 1988. Fifteen cases with MFH arising from the kidney reported in the Japanese literatures are reviewed, and the diagnosis, treatment, prognosis and tumor marker are discussed.

Serum alpha-1-antitrypsin in patients with malignant tumors occurring in the oral region.

In the present study, we have examined the immunoreactive levels of alpha-1-antitrypsin (AAT) and trypsin-inhibitory capacity (TIC) in the serum of patients with malignant tumors occurring in the oral region. AAT in the MFH group showed significantly high (468 +/- 129 mg/dl, mean +/- SD (n = 4)) as compared to those of other types of sarcoma groups (236 +/- 28 mg/dl, (n = 5)) and healthy controls (226 +/- 36 mg/dl, (n = 75)) (p less than 0.05). Patients with squamous cell carcinoma (SCC) also had increased levels of AAT (269 +/- 35 mg/dl, (n = 18)), but there was no significant difference among other groups including healthy controls. TIC of patients with MFH was higher (2.29 +/- 0.42 IU/ml, (n = 4)) than in the SCC group (1.44 +/- 0.25 IU/ml, (n = 18)), other sarcoma groups 1.21 +/- 0.16 IU/ml, (n = 5)) and controls (1.55 +/- 0.15 IU/ml, (n = 75)). These data suggest that the elevation of AAT and TIC would be helpful in the diagnosis of MFH.

Oncogenous osteomalacia: a new case secondary to a malignant tumor.

A case of oncogenous osteomalacia secondary to a fibrous malignant histiocytoma in a 31-year-old male is described. The patient also demonstrated a lupuslike anticoagulant. Clinical signs of osteomalacia preceded by 9 years those of the tumor, a feature occurring in only 8% of these malignancies. Surgical resection of the tumor and surrounding tissues was followed by a clinical improvement and a return to normal of serum phosphorus and tubular reabsorption of phosphate, though the lupuslike anticoagulant persisted. This first description of a fibrous malignant histiocytoma with associated osteomalacia and lupuslike anticoagulant makes compulsory the inclusion of these syndromes among those already described that may appear with this tumor.

Malignant fibrous histiocytoma associated with peripheral blood eosinophilia. In vitro studies demonstrating tumor-derived eosinophilopoietic activity.

Peripheral blood eosinophilia is a well-recognized paraneoplasia in many kinds of hematological and nonhematological malignancies. We report the case of a patient with a malignant fibrous histiocytoma. With increasing tumor burden, the patient developed a marked peripheral blood eosinophilia. Using an in vitro assay for growth of eosinophilic colonies, both the serum and the tumor of the patient proved to contain an eosinophilopoietic activity.

Serum B2-microglobulin determinations in patients bearing soft tissue sarcomas.

To determine whether serum beta 2-microglobulin values could be useful as a tumor marker in patients with soft tissue sarcomas, 31 preoperative sera stored in our serum bank were assayed by radioimmunoassay for beta 2-microglobulin levels. Sera were selected from patients known to have large bulky tumors, but no evidence of other major systemic disorders. Thirty-one sera of sex and age matched controls were assayed for comparison. The laboratory range for normal serum beta 2-microglobulin values was 1.1-2.4 mg/l. Our control patients had values ranging from 0.7-1.7 mg/l. Values in tumor patients ranged from 0.7-2.5 mg/l. No markedly elevated values were observed in any single patient. Four age groups, 20-29, 30-39, 40-49, and 50-59 years, revealed no significant differences. This observation differs from previously reported data. Serum beta 2-microglobulin appears to have no value as a tumor marker in patients with soft tissue sarcomas. We were unable to substantiate findings by others that there is a significant increase in values of normal subjects corresponding to advancing age.

[Hypophosphoremic osteomalacia of connective tissue tumors]. / L'ostéomalacie hypophosphorémique des tumeurs du tissu conjonctif.

The authors undertake a general review of the association between hypophosphoraemia and connective tissue tumour, based upon three personal cases and 27 cases of benign connective tissue tumours, as well as cases of hypophosphoraemia related to malignant tumours or to diffuse dysplasia of connective tissue origin, collected from the literature. This syndrome is distinguished from hypophosphoraemia induced by other tumours (myeloma, carcinoma of the prostate) which are based upon different mechanisms. Hypophosphoraemia, associated with a fall in plasma levels of 1-25 (OH)2 D3 by inhibition of renal 1 alpha hydroxylase, suggests the existence of a complex tubular deficit. Removal of the tumour, most often vascular and intra- or para-osseous, results in rapid normalisation of laboratory then radiological and clinical abnormalities. The physiopathology of the syndrome remains very mysterious. It may be likened to certain tubulotoxic syndromes due to cadmium and in particular to maleic acid. However no precise data yet exists regarding any possible abnormal tumour secretion. In practice, any case of hypophosphoraemic osteomalacia requires investigation to locate a possible tumour of connective tissue, and this all the more so when it is accompanied by very low plasma levels of 1-25(OH)2 D2.