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Abnormal beta-catenin and reduced axin expression are associated with poor differentiation and progression in non-small cell lung cancer.

We studied the expression of axin and beta-catenin and their relation to clinicopathologic factors in 100 non-small cell lung cancers (NSCLCs) by immunohistochemical analysis. The mutation in exon 3 of the beta-catenin gene was examined by polymerase chain reaction and direct sequencing. Preserved axin expression was significantly higher in well- and moderately differentiated NSCLC samples than in poorly differentiated ones. Reduced membranous expression of beta-catenin was shown in 80 cases, whereas 26 cases had aberrant nuclear expression. Poor differentiation and lymph node metastasis were associated significantly with reduced beta-catenin expression. Lower axin expression was related significantly to higher nuclear beta-catenin expression. However, this study failed to detect any exon 3 mutation in the beta-catenin gene in the 100 NSCLC samples. We conclude that reduced beta-catenin and axin expression might predict poor differentiation in NSCLC. Reduced axin expression, but not mutation in exon 3, might be an important explanation for the abnormal beta-catenin expression in NSCLC.

Adult↗

Chromosome abnormalities in AIDS-associated lymphadenopathy.

Cytogenetic studies were performed on direct and 24-hour culture preparations of eight lymph node biopsies from seven patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC)-associated lymphadenopathy in whom histological evidence of lymphoma was not detected. Three of these seven had chromosomal abnormalities, including chromosome instability in one and clonal chromosomal abnormalities in two; one of the latter was a t(8;14)(q24;q32). The remaining five showed normal karyotypes. Epstein-Barr virus (EBV) titers were elevated in all three patients that exhibited chromosome abnormalities, two of whom later developed malignant lymphoma. A control group of five patients with reactive lymphadenopathy not associated with AIDS failed to reveal chromosomal aberrations, but elevated EBV titers were present in two. These data are consistent with current views on the role of EBV and chromosome change in the development of lymphoma in immunodeficient states and suggest that karyotypically abnormal AIDS-related lymphadenopathy represents a prelymphomatous proliferation.

Acquired Immunodeficiency Syndrome↗

Dilemmas in managing prostate carcinoma. (Part I): Localized disease.

Since we cannot predict which patients have biologically significant prostate carcinoma, except in the face of other known, significantly life-limiting disease, all palpable abnormalities should be considered for a diagnostic procedure. Negative core needle biopsy, fine needle aspiration, open perineal biopsy, transurethral biopsy, or urinary and prostatic fluid cytology results do not exclude cancer. If cancer is suspected, repeat biopsies and careful, frequent follow-up are mandatory.

Humans↗

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction].

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.

Brain Diseases↗

Applicability of tissue aspirate for quick parathyroid hormone assay to confirm parathyroid tissue identity during parathyroidectomy for primary hyperparathyroidism.

HYPOTHESIS: Intraoperative quick parathyroid hormone (PTH) assay for tissue aspirate facilitates the confirmation of parathyroid tissue identity and allows a more selective use of frozen section examination during parathyroidectomy for primary hyperparathyroidism. DESIGN: A retrospective review of a prospective protocol of the applicability and accuracy of quick PTH assay for tissue aspirate as a biochemical frozen section tool. SETTING: A university hospital department of surgery. PATIENTS: Quick PTH assay for aspirate obtained from suspected parathyroid gland excised during parathyroidectomy for primary hyperparathyroidism. MAIN OUTCOME MEASURES: The accuracy of this biochemical identification of parathyroid tissue identity was correlated with histological examination and outcome. RESULTS: Quick PTH assay was performed for aspirate from at least 1 excised parathyroid gland in 122 (98%) of 125 patients while 13 patients (10%) had PTH aspirate for nonparathyroid tissues including thyroid (n = 10), thymic (n = 2) and lymphatic (n = 1) tissues. Frozen section examination was performed for 15 patients (12%), including the 3 patients who did not undergo tissue aspirate for quick PTH assay. All except 3 patients had an aspirate assay value of greater than 1500 pg/mL (range, 625 to >1500 pg/mL) for parathyroid tissue while the value of PTH aspirate for nonparathyroid tissue ranged from 27 to 229 pg/mL (median, 72 pg/mL) in 13 patients. The median size of abnormal parathyroid gland was 70 to 15,000 mg (median, 775 mg). CONCLUSIONS: With the availability of quick PTH assay, tissue aspirate for PTH assay can be adopted as an alternative to traditional frozen section examination to confirm parathyroid gland identity. Frozen section examination can be employed more selectively.

Adenoma↗

The role of ICAM-1 molecule in the migration of Langerhans cells in the skin and regional lymph node.

ICAM-1 (CD54) plays an important role in the cell-cell interaction and migration of leukocytes. Previous studies have shown that ICAM-1 is involved in inflammatory reactions and that a defect in ICAM-1 gene inhibits allergic contact hypersensitivity. This study indicates that the migration of hapten presenting Langerhans cells into the regional lymph nodes was significantly reduced in ICAM-1-deficient mice compared to wild-type C57BL/6 mice. The reduced number of dendritic cells in regional lymph nodes did not result from abnormal migration of Langerhans cells into the skin of ICAM-1-deficient mice. The concentration and distribution of Langerhans cells in the naïve skin of ICAM-1-deficient mice was equal to that of wild-type mice. Following hapten sensitization, Langerhans cell migration out of the skin and recruitment of fresh Langerhans cells back to the epidermis was not affected in ICAM-1-deficient mice. Further experiments demonstrated that ICAM-1 deficiency on lymphatic endothelium rather than on dendritic cells was responsible for the reduced migration of Langerhans cells into draining lymph nodes. This study indicates that ICAM-1 regulates the migration of dendritic cells into regional lymph nodes but not into or out of the skin.

Animals↗

Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease categorized by an overgrowth of atypical smooth muscle cells (LAM cells) in the lungs and axial lymphatics, which is associated with the mesenchymal tumor angiomyolipoma. The disease occurs in women generally in their mid thirties with a prevalence approximately 1 per million in the general population but is much more frequent in women with tuberous sclerosis complex (TSC). LAM is categorized by airflow obstruction, lung cysts, recurrent pneumothorax, and pleural and abdominal chylous collections. The disease is progressive, generally resulting in respiratory failure and death. The TSC-2 gene is abnormal in LAM cells and may be responsible for their disordered growth. These cells are of an unusual phenotype, expressing smooth muscle proteins, melanoma proteins, estrogen and progesterone receptors. Although at present of unknown significance these are useful in diagnosis. Treatment is largely supportive, being directed at airflow obstruction, pneumothorax, chylous complications, and bleeding from angiomyolipomas. In patients with rapidly progressive disease, hormone manipulation is frequently tried in the form of progesterone or antiestrogen therapies although no firm evidence of their efficacy exists.

Journal Article↗

Malignant sex-cord stromal tumor of the testis: report of a case with special reference to its unusual intracytoplasmic substructures.

A case of malignant sex-cord stromal tumor (gonadal stromal tumor) in the left testis of a 42-year-old man with no sign of hormonal abnormality is reported. Histologically, a large portion of the tumor was composed of solid nests of round cells with a moderate amount of eosinophilic cytoplasm, but some areas contained small spaces somewhat resembling Call-Exner bodies and/or the follicular structures of granulosa cell tumors. In general, however, the tumor cells did not show a clear-cut differentiation into either Sertoli cells or granulosa cells. The tumor, because of its high mitotic rate, lymphatic, venous and capsular invasion, and metastasis to the para-aortic lymph nodes, was considered to be malignant. We simply designated this tumor, therefore, as a malignant sex-cord stromal tumor. An ultrastructural study revealed unique intracytoplasmic bodies composed of multiple stacks of tubular structures which superficially mimicked annulate lamellae. No lipid droplets, Reinke's crystalloids or Charcot-Böttcher filaments were seen. The rarity of the tumor and the presence of unusual substructures prompted us to report the case.

Adult↗

Myeloid antigen expression on common acute lymphatic leukaemia blasts after culture.

Blast cells from seven out of ten patients with common acute lymphoblastic leukaemia (cALL) developed the myeloid antigen MY7 (CD13) after culture, and one of these coexpressed the myeloid antigen MY9 (CD33). CD13 expression appeared to be independent of maturation since it could be induced more readily in cultures which did not contain the differentiation promoter 12-O-tetradecanoyl-phorbol 13 acetate (TPA). CD13 expression in culture was not seen on one null ALL, or 6 B-CLL investigated or on normal tonsillar B cells or PBMC under similar conditions. CD13 expression on cALL blasts probably represents evidence of abnormal gene expression in the leukaemic cells. However the absence of CD13 expression on the earlier B null ALL or the later B-CLL suggests we cannot exclude the possibility that CD13 expression is a feature of normal precursor B cells.

Adult↗

Fetal nuchal fluid--physiological or pathological?--In pregnancies less than 17 menstrual weeks.

For pregnancies less than 17 menstrual weeks, increasing amounts of nuchal fluid increase the risks of chromosome abnormalities with localized nuchal fluid, diffuse nuchal fluid, cystic hygroma, and fetal hydrops having chromosomal risks of 12, 23, 50, and 78 per cent, respectively. The ultrasound appearance of localized or diffuse nuchal fluid is not a specific discriminator, but a fluid depth of greater than or equal to 5 mm may be an indicator of increased risk of fetal chromosomal abnormalities. If the fluid depth is less than 5 mm, there is a stronger negative predictive value and negative likelihood risk of a fetal chromosome abnormality. Gestational age did not improve the fluid depth predictive value. Differentiation of physiological from pathological requires chromosome analysis, serial ultrasound evaluation, and good clinical examination as a newborn and possibly as a young child. Long-term follow-up of those cases identified with resolving nuchal fluid abnormalities is not available and is required for a complete understanding of physiological and pathological aetiologies. Genetic counselling for fetal nuchal fluid would be recommended.

Chromosome Aberrations↗

Facial infiltrative lipomatosis.

BACKGROUND: Although there are multiple case reports and small series concerning facial infiltrative lipomatosis, there is no composite radiological description of the condition. OBJECTIVE: Radiological evaluation of facial infiltrative lipomatosis using plain film, sonography, CT and MRI. MATERIALS AND METHODS: We radiologically evaluated four patients with facial infiltrative lipomatosis. Initial plain radiographs of the face were acquired in all patients. Three children had an initial sonographic examination to evaluate the condition, followed by MRI. One child had a CT and then MRI. RESULTS: One child had abnormalities on plain radiographs. Sonographically, the lesions were seen as ill-defined heterogeneously hypoechoic areas with indistinct margins. On CT images, the lesions did not have a homogeneous fat density but showed some relatively more dense areas in deeper parts of the lesions. MRI provided better delineation of the exact extent of the process and characterization of facial infiltrative lipomatosis. CONCLUSION: Facial infiltrative lipomatosis should be considered as a differential diagnosis of vascular or lymphatic malformation when a child presents with unilateral facial swelling. MRI is the most useful single imaging modality to evaluate the condition, as it provides the best delineation of the exact extent of the process.

Adipose Tissue↗

Cytogenetic findings in eleven gastric carcinomas.

We describe the results of the cytogenetic study of 10 primary adenocarcinomas of the stomach and one lymph node metastasis of a gastric adenocarcinoma after direct harvesting or short-term in vitro culture. All cases showed a variable number of numerical and/or structural clonal cytogenetic aberrations. Polysomy of chromosomes 2 and 20 were the most common numerical abnormalities. Rearrangements of chromosomes 1, 3, 7, and 13 were each observed in more than half the cases. Chromosomes 3 and 13 were the chromosomes more often exhibiting structural cytogenetic aberrations. In five tumors, rearrangements of chromosome 6 resulting in partial deletion of 6q were noted (common deleted region 6q21-22-->qter). The recurrent markers observed in our series were an i(8q) and an i(17q) in three and two cases, respectively. Double minutes (dmin) or homogeneously staining regions (hsr) were evident in three tumors. Contrary to the recent claim that structural abnormalities affecting 11p13-p15 were specifically involved in gastric cancer, we detected rearrangements of this region in only two cases.

Adenocarcinoma↗

A practical approach to ultrasound of cervical lymph nodes.

Although the role of high resolution ultrasound (US) in evaluating cervical nodes is well established, it is often combined with fine needle aspiration cytology (FNAC). As a result, US appearances that help in distinguishing the various causes of cervical adenopathy are often overlooked and not emphasized. The aim of this study is to re-emphasize to the sonologist the US clues that may help in differentiating the aetiology of abnormal cervical nodes. We, therefore, present the spectrum of US appearances of lymph nodes. One hundred and forty patients (702 abnormal nodes) with known pathology were compared with 100 normal subjects (1211 nodes). After identifying an abnormal nodes, US features that further help in distinguishing between the various pathologies are the distribution of lymphadenopathy, echogenicity, calcification, distal enhancement, intranodal cystic necrosis, matting and soft tissue oedema.

Adolescent↗

Histiocytosis X of the thymus in association with myasthenia gravis.

A patient with myasthenia gravis underwent thymectomy following the failure of medical treatment. The thymus was normal except for four nodules, which, on histologic and electron microscopic examination, were found to consist of proliferative clusters of Langerhans' cells characteristic of histiocytosis X. This patient therefore had two disease processes in which thymic abnormalities are frequently encountered, but their simultaneous occurrence in the same patient has not hitherto been documented. The case is briefly discussed in the context of current concepts of the pathogenesis of histiocytosis X and myasthenia gravis.

Adult↗

Sinus histiocytosis with massive lymphadenopathy: virological, immunological and morphological studies.

The histiocytes from a patient with sinus histiocytosis were tested for the presence of Epstein-Barr viral nuclear antigen (EBNA) before and after in vitro growth. On both occasions the histiocytes as well as the lymphocytes were EBNA negative. Likewise the profile of EBV viral capsid antibody (VCA) suggests that this virus is unlikely to be directly involved in the development of the disease. The maintenance of an unusually high level of antibodies to EBV and measles, both viruses which produce persistent infections, indicates that the humoral immune response is active. That a normal humoral response occurred in response to mumps virus during the same period suggests that a deficiency in the cell mediated immune response to the persistent viruses might be the reason for the abnormally high antibody levels. The fresh as well as the cultured histiocytes had only Fc receptors. The affected lymph node lymphocytes developed unusual large inclusion bodies following in vitro culture.

Adolescent↗

Pulmonary vascular changes associated with isolated mitral stenosis in India.

Pulmonary vascular changes were studied in 100 cases of isolated mitral stenosis; these included 90 patients in whom lung biopsies were obtained at valvotomy and 10 patients who came to necropsy. Medial thickness of the pulmonary arteries was measured in each case and in 12 cases was correlated with the haemodynamic data. Most patients were young, 78 being 30 years of age or less and 42 under 20 years or less. Males predominated 2:1. All patients with mitral stenosis showed varying degrees of vascular and other associated parenchymal changes. The most conspicuous were those observed in the muscular branches of the pulmonary artery in which the media was thickened in all cases, moderately in 44 and considerably in 28 cases. Dilation lesions representing grade 4 lesions of hypertensive pulmonary vascular disease (Heath and Edwards, 1958), hitherto not described in mitral stenosis, were observed in 4 cases. The intima was found to be frequently abnormal, showing oedema, fibrosis, and, more importantly, variable degrees of muscularization, often suggesting the incipient formation of a second media. Arteries and arterioles were often occluded by thrombi in various stages of organization, and the freshly formed channels tended to acquire a muscular lining. Arterioles were muscularized in all cases, and in many there was a pronounced intimal proliferation. Other changes included medial hypertrophy in the veins and and occasional muscularization and dilatation of the lymphatics. A notable feature was hypertrophy of the musculature of the bronchiolo-alvelar system seen in a majority of cases. The alveolar walls showed variable degrees of thickening and fibrosis, intimal proliferation of alveolar capillaries, and "epithelialization" of alveoli. Haemosiderosis was present in 70 cases. On the whole the more severe changes were observed more often in the younger subjects, further supporting the observation that rheumatic mitral stenosis in India commonly affects the juvenile age groups and is characterized by association with severe pulmonary hypertension. Medial hypertrophy was proportional to the level of pulmonary artery pressure.

Adolescent↗

Application of ultrastructural morphometry to lung biopsy specimens in pulmonary histiocytosis X.

Stereological techniques were applied to an electron microscopic study of biopsy samples from nine human lungs with diffuse pulmonary histiocytosis X, and the results were compared with values for normal lungs. This made possible a morphometric analysis of the tissue changes associated with the measurable abnormalities in gas transfer present in this disease. The small increases in arithmetic mean thickness of the alveolar-capillary membranes appeared insufficient to account for the reduction in gas transfer present. When compared with normal lung, a threefold increase in volumetric fraction of septal intercapillary tissue was found along with a corresponding decrease in septal capillaries. While uniformity of distribution cannot be determined by this method, it appears that abnormalities of blood gas transfer in this disease result primarily from a decrease in the available diffusing surface and the ventilation-perfusion distrubances with which these tissue changes are associated.

Adult↗