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PubMed1999

Presence of RON receptor tyrosine kinase and its splicing variant in malignant and non-malignant human colonic mucosa.

The presence of RON and its variant isoform in malignant and non-malignant human colonic tissues was examined by immunohistochemistry using paraffin-embedded sections and RT-PCR analysis followed by direct sequencing of PCR product using RNAs isolated from frozen tissues. In normal colonic mucosa, RON was uniformly expressed in crypt cells, especially in the bottom of crypta. On the other hand, the expression was distributed heterogeneously in adenomas and in colon cancer. The expression of RON was significantly related to the degree of differentiation of colon cancer and the deletion of the expression was observed in colon cancer specimens with high incidence. The RT-PCR analysis of RNA isolated from non-malignant and malignant colonic tissue revealed the presence of two RON mRNA isoforms with 432-bp and 286-bp. Direct sequencing of major product of 432-bp was revealed to be identical to that of human wild-type RON. On the other hand, major product of 286-bp was revealed to be almost identical to that of a splicing variant of RON transcript which has been found in human gastric cancer cell line, KATO-III. The results obtained in this study may indicate that both wild-type RON and its variant isoform play an important role in regulating the normal function of colonic mucosa such as differentiation and motile activity and the expression of both wild-type RON and its variant isoform could be considered to be reduced during malignancy of human colonic mucosa.

Adenocarcinoma↗

PubMed2000

Malignant adenomyoepithelioma of the breast with malignant proliferation of epithelial and myoepithelial elements: a case report and review of the literature.

Malignant adenomyoepithelioma of the breast is a rare lesion characterized by malignant proliferation of epithelial and myoepithelial cells that show characteristic histologic and immunohistochemical features. Eleven cases have been reported, 4 of which showed evidence of distant metastasis. The authors report a case of malignant adenomyoepithelioma in the axillary tail of a 71-year-old woman, one of the oldest patients described so far, and review the literature. Malignancy in the current case was evidenced by the presence of local invasion, high mitotic rate, and severe cytologic atypia. The tumor was associated with adenosis and lobular adenomyoepithelial hyperplasia. Malignant adenomyoepithelioma is a rare neoplasm, diagnosable by light microscopy and immunohistochemistry. To date, it has only been reported in women, who ranged in age from 26 to 76 years. Metastases have only been documented in tumors 2.0 cm in diameter or larger.

Aged↗

PubMed1999

Soft tissue giant cell tumor of low malignant potential: a proposal for the reclassification of malignant giant cell tumor of soft parts.

Although "giant cell tumor of soft parts" has traditionally been considered a single entity as reflected in the original term "malignant giant cell tumor of soft parts (MGCT)" and later by the term "malignant fibrous histiocytoma, giant cell type" the degree of atypia and mitotic activity varies in this group, suggesting biologic heterogeneity. The clinicopathologic features of 31 tumors meeting the traditional criteria of MGCT but having only mild to moderate nuclear atypia are presented. Patients with these tumors (19 females; 12 males) ranged in age from 14 to 84 years (mean, 40 years) and presented with masses of involving either superficial (n = 16) or deep (n = 13) soft tissue. Most occurred on the arm or hand (n = 16) and ranged in size from 0.7 to 6.5 cm (mean, 2.1 cm). The tumors consisted of sheets and nodules of rounded mononuclear cells that blended with spindled cells and benign osteoclastic giant cells. Pleomorphic giant cells were absent. Osteoid was noted in 10 cases, but features typically associated with tenosynovial giant cell tumors (such as dense stromal hyaline, siderophages, and xanthoma cells) were nearly always absent. Mitotic figures ranged from 1-10/10 HPF (mean, 2-3/10 high-powered field), and angiolymphatic invasion was present in 10 cases. Necrosis was absent, however. The mononuclear cells expressed CD68, tartrate-resistant acid phosphatase, and smooth muscle actin, but lacked CD45, S100 protein, desmin, and lysozyme, an immunophenotypic profile identical to that of giant cell tumor of bone. Follow-up information in 19 patients (mean, 3 yrs; median, 1-7 yrs) indicated recurrences in four patients, but none developed metastasis. This behavior contrasts significantly with the high-grade behavior traditionally associated with MGCT of soft parts. These giant cell tumors can be consistently recognized by the lack of cytologic atypia even in the face of mitotic activity and vascular invasion. Although their long term metastatic risk is not fully defined, we propose they be termed "giant cell tumors of low malignant potential" and regarded as the soft tissue analogue of giant cell tumor of bone. The term "malignant giant cell tumor of soft parts" or giant cell malignant fibrous histiocytoma should be restricted to histologically high-grade lesions.

Acid Phosphatase↗

PubMed1979

[Correlation between differentiation and malignancy in human malignant melanocytes "in vivo" and "in vitro" (author's transl)].

The relationships between differentiation and malignant transformation were studied in human malignant melanomas in vivo and in vitro. Melanocyte differentiation was assessed by ultrastructural morphological characteristis (the appearance of the melanosomes and related structures) localization of dopa-oxidase and assay of 5-S-cysteinyldopa, a specific metabolite. The transformed characteristic of the cells in vitro was evaluated by their ability to give rise to established cell lines, karyological modifications and heterotransplantation in Nude mice and Syrian hamsters. Morphological variability of the cells in malignant melanomas is accompanied by variability in the localization of dopa-oxidase, the level of 5-S-cysteinyldopa, chromosome pattern and their heterotransplantibility. The lack of pigmentation in some malignant melanoma lines can result from either an irreversible loss of some functions which give rise in melanization and the malignancy in maintained, or by phenomenon of regulation determined by intra or extra-cellular factors with the loss of heterotransplantability. Modulation phenomena affecting tumorigenicity and pigmentation although sometimes concomitant are not identical.

Animals↗

PubMed2002

Malignant by name or malignant by nature: a case of Wegener's granulomatosis diagnosed as adenocarcinoma of unknown primary.

Most malignancies are characterised by malignant behaviour at some point in the disease trajectory. However, non-malignant diseases may exhibit malignant behaviour. A diagnosis of malignancy based on fine needle aspiration cytology (FNAC) can be misleading. We report a case of Wegener's granulomatosis initially diagnosed by FNAC as adenocarcinoma of unknown primary. The limitations of FNAC, the disparate prognoses of the two diagnoses despite a compatible clinical picture and the need for clinical vigilance in monitoring a disease course are highlighted.

Adenocarcinoma↗

PubMed1992

[67Ga scintigram and MRI in malignant bone tumors and malignant soft tissue tumors].

We have analyzed the characteristics of 67Ga scintigram and MRI in 11 malignant bone tumors and 11 malignant soft tissue tumors. Osteosarcoma showed a high accumulation in 67Ga scintigram and low signal intensity in T1 weighted image. T2 weighted image were not characteristic. Chondrosarcoma showed medium 67Ga accumulation and low signal in T1 weighted image and high signal in T2 weighted image. Ewing sarcoma showed low accumulation in 67Ga scan and medium intensity in MRI. Malignant soft tissue tumors showed rather low 67Ga accumulation compared with malignant bone tumors. Malignant fibrous histiocytoma showed medium accumulation of 67Ga, low signal in T1 weighted image and high signal in T2 weighted image. Liposarcoma showed low 67Ga accumulation and medium signal in T1 weighted image and high signal in T2 weighted image. To summarize these characteristics, three dimensional display is demonstrated.

Bone Neoplasms↗

PubMed2003

Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence.

The standardized incidence ratios (SIR) and cumulative incidence rates were determined for developing second malignant neoplasms (SMNs) after primary central nervous system (CNS) malignancies occurring during childhood using registry data. A total of 4553 cases of primary CNS malignancies were identified. Forty-six cases developed SMNs, 19 occurring in a previously radiated field. The SIRs of developing second malignant neoplasms were 6.3 and 3.1 for those cases receiving and not receiving radiation therapy, respectively. The 20-year cumulative incidences for developing SMNs were 3.3 and 1.2% for cases receiving and not receiving radiation therapy, respectively. Children surviving CNS malignancies have an increased susceptibility for SMNs.

Adolescent↗

PubMed1989

Induction of proliferation and blast transformation by interferon in human malignant and non-malignant lymph node B cells.

The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compared with effects on mononuclear blood cells from chronic lymphocytic leukemia (CLL) patients and healthy donors. Natural IFN-alpha (nIFN-alpha) induced a proliferative response in cells from seven of 17 of the B-cell lymphomas, in two of eight of the non-malignant lymph nodes, and in lymphoid blood cells from two of 32 CLL patients. With few exceptions, the proliferating cells were B cells and the data suggest that IFN acts directly on the B cells. Proliferation was not induced with IFN in cells from the T-cell lymphoma or in mononuclear blood cells from 13 healthy donors. nIFN-alpha induced blast transformation in cells from ten of 14 of the B-cell lymphomas and in four of seven of the non-malignant lymph nodes. Also beta- and gamma-IFN were shown to induce proliferation and blast transformation in lymph node cells from some patients. No major effect on the expression of various differentiation markers could be observed following culture in the presence of nIFN-alpha. We conclude that IFNs can induce proliferation and blast transformation in malignant and non-malignant B cells from lymph nodes.

Adult↗

PubMed1985

Statistical analyses of clinico-pathological, virological and epidemiological data on lymphoid malignancies with special reference to adult T-cell leukemia/lymphoma: a report of the second nationwide study of Japan. The T- and B-Cell Malignancy Study Group.

In the present nationwide survey, 1,040 new cases of lymphoid malignancy, in most of which expression of cell surface markers had been determined, and 243 controls for a case-control study on adult T-cell leukemia/lymphoma (ATL) and other types of lymphoid malignancies were enrolled during the two years (1982-84) from 24 institutions throughout Japan. Among the 1,040 cases, 197 cases of ATL, 183 cases of T-cell lymphoma and 236 cases of non T-cell lymphoma were used in the detailed analysis of the clinico-pathological and epidemiological findings. Furthermore, 66 cases of ATL and 174 cases of other lymphoid malignancies were used for case-control analysis. In order to standardize the clinico-pathological classification throughout Japan, 20 hematologists and 12 pathologists met once a year and made the final consensus diagnosis in each case of lymphoid malignancy. Five hundred cases of non-Hodgkin's lymphoma were examined for antibody to ATL-associated antigen (ATLA). Clinico-pathological and epidemiological features for these cases were compared according to their anti-ATLA antibody status. The new results obtained from this survey are as follows: All of the patients with ATL in Kyushu had anti-ATLA antibody, but several patients with ATL in other districts had no anti-ATLA antibody, suggesting that there was no association with ATL virus (ATLV) infection in these cases. There was a difference in the histopathological patterns in non-Hodgkin's lymphoma between Kyushu and the other districts, which was due to the difference in distribution of the ATLV-associated lymphoid malignancies, namely ATL, in each area. The histopathological distribution in anti-ATLA negative cases in the Kyushu district was almost the same as that in the other districts.

Adolescent↗

PubMed1986

[Secondary malignancies associated with hematological malignancies following anticancer treatment].

We have investigated the present status of secondary malignancies throughout the country following anticancer treatment for the initial cancers. We recorded by questionnaire 272 patients with multiple primary cancers associated with hematological malignancies from 64 among 1487 main institutes. Of them, we analyzed 131 patients who developed hematological malignancies from carcinomas metachronously and 101 patients who developed metachronous malignancies from hematological malignancies. Comparison of patients with a history of chemotherapy or radiotherapy for the initial cancer (treated group) and patients without (untreated group) showed that the incidence of secondary acute leukemias seemed to be higher than expected in the treated group. The characteristics of secondary acute leukemias were similar to those from the untreated group in age, types of leukemia, and hematological findings at diagnosis. However, patients from the treated group with secondary acute leukemias showed a tendency to have a higher frequency of antecedent hematological abnormalities and a poorer prognosis than those from the untreated group.

Acute Disease↗

PubMed1976

[Probability of malignant degeneration of ovarian tumors. Clinical study on the probability of malignant degeneration].

More than 600 cases of ovarian tumors were analyzed for histological type, age of patient, bilateral occurrence, mobility and malignant degeneration in restant ovaries. Tumors of germinal epithelial origin show the highest incidence (24%) of malignant degeneration, tumors of germ cells the lowest (3,5%). Incidence of malignant degeneration increases in relation to the age of the patient from 2% (and under 30 years) to 36,5% (60-70 years). Each form of tumor has its typical age peak, which is about 20 years higher for carcinomas than for their benign counterpart. Bilateral ovarian tumors are malignant in 29%, one-sided only in 13%. Among freely movable ovarian tumors, only 6% enclose a malignant tumor, among adhaerent ones 34%. The examination of the prognosis of granulosacell-tumors, dysgerminomas and teratoblastomas is based on a larger material.

Adolescent↗

PubMed1996

No association between the neuroleptic malignant syndrome and mutations in the RYR1 gene associated malignant hyperthermia.

The neuroleptic malignant syndrome (NMS) is a drug-induced disease caused by neuroleptics, but the pathogenesis of NMS is unknown. Since NMS is similar to malignant hyperthermia (MH) in clinical features and treatment, 6 mutations in the skeletal muscle ryanodine receptor (RYR1) gene, which were associated with MH, were investigated in unrelated NMS patients by single-strand conformation polymorphism analysis (SSCP). As a result, MH-susceptible RYR1 mutations were not detected in our NMS patients. A single base substitution, C7278T, was detected in one patient whose serum CPK level was repetitively elevated, but his other major symptoms did not fulfil the clinical criteria for NMS. Our results do not support the association between the neuroleptic malignant syndrome and mutations in the RYR1 gene associated with malignant hyperthermia.

Adult↗

PubMed1999

Malignant hyperthermia and neuroleptic malignant syndrome in a patient during treatment for acute asthma.

Acute asthma is well known to provoke complications. We report the case of a patient who needed intubation and mechanical ventilation for acute asthma. Despite a treatment with corticosteroids, bronchodilators, neuromuscular blocking drugs and magnesium sulfate, the situation remained uncontrolled and as a last resort, halothane became necessary. The patient then developed an episode of malignant hyperthermia with fever at 40 degrees C and rhabdomyolysis. At this time, halothane could be stopped and all the symptoms disappeared without modifying the rest of the treatment. Eight days later, he presented with a neuroleptic malignant syndrome following an injection of droperidol. Temperature rose to 42 degrees C, associated with muscle rigidity, sweating, tachycardia and severe circulatory collapse. The use of dantrolene in association with a symptomatic treatment of the collapse led to a favourable outcome in. Unfortunately, in vitro contracture test could not be performed in this case. The links between malignant hyperthermia and neuroleptic malignant syndrome remain unclear. Although these two pathologies share the same physiopathology, symptomatology and treatment, they are clearly individualized. This case seems to be the first description of their occurrence in the same patient.

Acute Disease↗

PubMed1976

Malignant hypertension in blacks. Malignant intrarenal arterial disease as observed by light and electron microscopy.

Volhard and Fahr recognized that hypertensive intrarenal vascular disease could be divided into two groups corresponding to the clinical states of benign and malignant hypertension. Since that time, numerous papers on malignant hypertension, primarily dealing with European derived populations, have emphasized fibrinoid necrosis of small arteries and arterioles as the lesion of malignant hypertension, although some have also recognized a myxoid intimal lesion as characteristic. Today in the United States, however, a significant proportion of malignant hypertension occurs in blacks. In the present study, patients have lacked fibrinoid necrosis of arterioles and only rarely have had some atypical necrosis of small arteries. The prominent, but not pathognomonic, lesion in this series is a myxoid intimal thickening of small arteries consisting of smooth muscle cells, acid mucopolysaccharides, basement membrane-like materal, collagen, and other amorphous and unidentified material, probably plasma derived.

Adult↗

PubMed1992

Prediction of malignant hyperthermia susceptibility in low-risk subjects. An epidemiologic investigation of caffeine halothane contracture responses. The North American Malignant Hyperthermia Registry.

The most commonly used laboratory test for predicting malignant hyperthermia susceptibility is the caffeine halothane contracture test. However, the specificity and sensitivity of proposed North American diagnostic guidelines for this test have never been evaluated in a large, human study population. Therefore, the authors conducted a multiinstitutional, prospective study of skeletal muscle contracture responses in a subject population at low risk for malignant hyperthermia susceptibility to help determine the specificity of the proposed guidelines. Subjects were selected arbitrarily from a population of patients undergoing surgery unrelated to performance of a diagnostic muscle biopsy. Subjects were admitted to this study and were presumed nonsusceptible if there was no evidence of any of the following malignant hyperthermia risk factors: prior abnormal response to triggering anesthetic agents, myopathy, or family history of malignant hyperthermia susceptibility. The authors suggested rejection of the proposed diagnostic guidelines if an 85% specificity estimate among subjects could not be obtained. The authors analyzed the responses of 1,022 muscle fascicles, derived from 176 subjects, to the following: 1) separate administration of 3% halothane or incremental caffeine concentrations, or 2) the joint administration of 1% halothane and incremental caffeine concentrations. The following contracture results were obtained. First, for individual fascicles, 9.2% exceeded a greater than 0.7 g threshold for 3% halothane, 15.2% exceeded a greater than or equal to 0.2 g threshold for 2 mM caffeine, 32.4% exceeded a 1-g increase for less than 4 mM caffeine, 2.6% had a greater than 7% maximal increase in tension at 2 mM caffeine, and 63.5% had a "halothane caffeine-specific concentration" at less than or equal to 1 mM caffeine. Second, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold were as follows: 45.8% for the four-component, 28.8% for the three-component, and 32.7% for the two-component contracture test. Third, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold for both halothane and caffeine were as follows: 9.5% for 3% halothane and 2 mM caffeine, 2.0% for 3% halothane and 7% maximal increase in tension at 2 mM caffeine, and 11.0% for 1% halothane and 2 mM caffeine. Fourth, center-to-center differences were the major source of variation in the rate that subjects exceeded proposed thresholds. These data demonstrate that proposed diagnostic guidelines must be modified to improve specificity estimates before adoption by diagnostic centers.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed2005

Differentiation between malignant and benign pleural effusion in patients with extra-pleural primary malignancies: assessment with positron emission tomography-computed tomography.

OBJECTIVES: We sought to define an accurate diagnostic approach for differentiating benign from malignant pleural effusion on positron emission tomography-computed tomography (PET-CT). MATERIAL AND METHODS: PET-CT studies of 31 patients with primary extrapleural malignancy and pleural effusion were reviewed retrospectively. CT parameters assessed were size and density (Hounsfield units, or HU) of the effusion and density (HU) and morphology of any solid pleural abnormality. Interpretation of PET data included review of the attenuation-corrected and nonattenuation-corrected images. RESULTS: PET-CT parameters that were found to be significant in identifying malignant pleural effusion included focal increased uptake of 18-fluorodeoxyglucose in the pleura (P<0.0001) and the presence of solid pleural abnormalities on CT (P<0.002): the sensitivity was 86% and 71%, respectively, and the specificity was 90% for each of the 2 parameters. A PET-CT pattern composed of pleural uptake and increased effusion activity on nonattenuation-corrected images was associated with sensitivity of 95%, specificity of 80%, positive predictive value of 91%, negative predictive value of 89%, and accuracy of 90%. CONCLUSIONS: On PET-CT, the presence of concomitant pleural abnormalities is the most accurate criterion in determining the malignant nature of pleural effusion.

Adult↗

PubMed1987

Malignant arterial hypertension. Relationship between blood pressure control and renal function during long-term observation of patients with malignant nephrosclerosis.

Eleven patients with malignant arterial hypertension and malignant nephrosclerosis, verified by percutaneous renal biopsy, were examined during an observation period of 47 months (median). All patients received antihypertensive therapy. Patients were divided into three groups with regard to development of renal function during the observation period. In two patients (group I), the integrated average blood pressure (IA-BP) was 134/95 mmHg (median) and the calculated creatinine clearance (Ccr) increased from 19 to 56 ml/min (medians). In four patients (group II), IA-BP was 154/102 mmHg and Ccr remained stable-at approximately 60 ml/min. In five patients, (group III), IA-BP was 189/114 mmHg, owing to lack of patient compliance and absence from regular control, and Ccr was reduced from 26 ml/min to less than 5 ml/min. During the first 2 months of antihypertensive therapy, renal function was temporarily reduced in 7 of the 11 patients. It is concluded that effective blood pressure control in patients with malignant arterial hypertension and malignant nephrosclerosis can be accompanied by a considerable improvement, or at least a preservation of renal function.

Adult↗

PubMed1994

Malignant mixed tumor (carcinosarcoma) of the pancreas: a case report supporting organ-induced differentiation of malignancy.

BACKGROUND: We present an unusual case of a malignant mixed tumor (carcinosarcoma) of the head of the pancreas that was surgically resected and whose tissue pathologic condition supported the concept of organ-induced differentiation of malignancy. METHODS: After a pancreaticoduodenectomy, tissue sections from various anatomic regions of the tumor were studied by routine histologic examination and immunocytochemistry. Genomic DNA from various regions of the tumor was extracted and digested with Hpa II, and a 511 bp region of the hypoxanthine phosphoribosyltransferase gene was amplified with the polymerase chain reaction to assess clonality. RESULTS: The pathologic findings revealed areas of both adenocarcinoma and leiomyosarcoma, but these disparate areas were not randomly distributed but rather were polar in nature. The adenocarcinomatous areas localized to the tumor within the head of the pancreas, an area of normal ontogenetic glandular development, whereas the leiomyosarcomatous areas localized to regions of the tumor infiltrating the duodenal wall, an area of normal ontogenetic smooth muscle development. Both the adenocarcinomatous and the leiomyosarcomatous areas showed evidence of monoclonality and clonal identity. CONCLUSIONS: This interesting polar distribution of histologic patterns illustrated by this malignant mixed tumor (carcinosarcoma) supports the hypothesis of organ-induced differentiation of malignancy.

Adenocarcinoma↗