Unbalanced t(1;16) as the sole karyotypic abnormality in a breast carcinoma and its lymph node metastasis.
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The case of a 57-year-old man with lymphadenopathy fever, splenomegaly, and polyclonal gammopathy is described. The difficult clinical course, the short lived response to cytotoxic treatment, the frequent infections, the immunologic abnormality, and the histologic findings in lymph node biopsy and postmortem material justified our diagnosis of angioimmunoblastic lymphadenopathy with dysproteinemia, a new entity described recently.
Prenatal molecular genetic diagnosis for Noonan syndrome I is reported. Noonan syndrome was suspected because of large cystic hygroma colli, massive pleural effusion and ascites at 23 weeks of gestation and normal karyotype (46,XX). DNA was prepared from amnion cells and screened for mutations in the PTPN11 gene. In exon 8, a missense mutation (S285F) was found. Delivery was induced at 33 weeks of gestation because of silent cardiotocography (CTG). Despite immediate drainage of the hydrothorax, mechanical ventilation was insufficient and the child died 9 h after birth due to severe pulmonary hypoplasia. Pleural punctate was enriched for small lymphocytes and thus was characterized as chylus. Prenatal ultrasound findings in Noonan syndrome usually are unspecific and rarely lead to a diagnosis. However, with the combination of cystic hygroma, pleural effusion, ascites and normal karyotype Noonan syndrome should be considered and DNA testing for PTPN11 mutations may be appropriate. Malformations of lymphatic vessels and/or chylothorax in Noonan syndrome seem to be more frequent than usually anticipated.
The possibility that cyclooxygenase products of arachidonic acid might contribute to the defective T lymphocyte function of homosexual men with the reactive lymph node syndrome was examined in vitro. T lymphocyte proliferation, assessed by the uptake of [3H]thymidine after the addition of phytohemagglutin, was 72,870 +/- 66,816 counts per minute (mean +/- SD) for eight patients and 119,589 +/- 64,913 counts per minute for 30 controls (P less than 0.05, Student's t test). Treatment with the cyclooxygenase inhibitor indomethacin increased the phytohemagglutin-induced proliferation of the T lymphocytes from five of eight patients, but none of 12 healthy homosexual and heterosexual control subjects. The production of prostaglandin E2 by T lymphocytes from six patients was 16.1 +/- 10.5 pg/5 X 10(6) cells/hr, as contrasted with that of 4.9 +/- 1.3 and 4.3 +/- 2.1 pg/5 X 10(6) cells for four healthy homosexual and six healthy heterosexual control subjects, respectively (P less than 0.01, Student's t test). The production of prostaglandin E2 by the patients' monocytes was normal. Abnormalities of the cyclooxygenase pathway of T lymphocytes of patients with the reactive lymph node syndrome may reflect an immunoregulatory defect, which predisposes to infections and may evolve into the more severe abnormalities of the acquired immune deficiency syndrome.
A case of metastatic small cell carcinoma of the lung is reported; initially, on the basis of morphology, phenotyping with monoclonal antibodies, and cytochemistry, the carcinoma was interpreted as a hematopoietic neoplasm. Noncohesive blast-like cells observed in bone marrow and lymph node biopsy specimens stained with the monoclonal antibodies Leu-M1 and OKIa1 and were also positive for nonspecific esterase and acid phosphatase. Although these findings suggested a monocytic origin for the neoplastic cells, further analysis, including ultrastructural examination, disclosed metastatic small cell carcinoma. This case illustrates the need for caution in the interpretation of staining with monoclonal antibodies because of the potentially wide range of normal and abnormal cells and tissues that may react with monoclonal reagents.
Since a large variety of disorders may lead to lymph node enlargement determining the cause of peripheral lymphadenopathy (LAP) in children can be difficult. This retrospective study evaluated 200 children who were admitted to an Oncology-Hematology department because of lymphadenopathy and aimed to determine the clinical and laboratory findings that were valuable for differential diagnosis. A specific cause for lymphadenopathy was documented in 93 (46.5%) cases. One hundred forty (70%) children were classified as having a benign cause for lymph node enlargements. Fourteen (10%) of these cases underwent an excisional lymph node biopsy, and histopathological examination showed a reactive hyperplasia. Sixty (30%) cases were classified as having a malignant disease-causing lymphadenopathy. In terms of differential diagnosis, some associated systemic symptoms, physical findings, and laboratory investigations showed significant difference between benign and malignant lymphadenopathy groups. The following findings were determined as being important to alert the physician about the probability of a malignant disorder: location of the lymphadenapathy (supraclavicular and posterior auricular), duration of the lymph node enlargement (>4 weeks), size of the lymph node (>3 cm), abnormal complete blood cell findings, abnormalities in chest X-ray, and abdominal ultrasonography.
Steroid receptor status, cellular kinetics, abnormal proto-oncogene presence, and lymph node metastases all have been shown to provide prognostic information in breast cancer. The factors guide the choice of therapy and predict the course of the disease. Both disease-free survival and overall survival are predicted by these variables. Steroid receptors are the most reliable predictor of hormonal responsiveness. Lymph node involvement is crucial in determining the extent of the disease and the need for adjuvant therapy. Cellular kinetics and abnormal proto-oncogene presence predict tumor aggressiveness. Together these prognostic factors provide considerable information to the clinician.
Lymphoblastoid (LB) cells interact in vitro with human fibroblasts. Cell complexes can be dissociated by trypsin treatment. Binding on fibroblasts is higher for Epstein-Barr virus-producer LB cells than for nonproducers, and depends on the origin of the fibroblastic cells. Stromal fibroblasts isolated from a metastatic lymph node tumor exhibited a highly increased potency of binding LB cells in comparison with fibroblasts isolated from normal breast epidermis or the primary breast tumor from the same patient. After a 10-hour interaction period, LB cells undergo abnormal divisions giving rise to the formation of 'mini cells'.
A 30-year-old female underwent surgical removal of a primary cutaneous peripheral primitive neuroectodermal tumour (PNET) of the left thigh. A subsequent 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) scan showed abnormal accumulation of FDG in the left upper pelvic region, consistent with metastasis to a left common iliac node. A series of follow-up imaging studies revealed that a cyst of the corpus luteum of ovary was responsible for the abnormal FDG accumulation.
OBJECTIVE: The purpose of this study was to evaluate the role of MR imaging in the preoperative assessment of candidates for pelvic exenteration. Specifically, we sought to determine if MR imaging was reliable in selecting patients with pelvic cancer for surgical exenteration. MATERIALS AND METHODS: MR images of the pelvis were retrospectively evaluated in 23 patients with proved pelvic cancer. These images were analyzed for (1) presence and location of the primary or recurrent tumor; (2) tumor extension to the bladder, rectum, or pelvic sidewall; and (3) presence and location of lymphadenopathy. On the basis of the MR findings, we determined suitability for pelvic exenteration by using generally accepted contraindications to surgery (involvement of the pelvic sidewall muscles or metastatic lymphadenopathy). In addition, tumor involvement of the bladder or rectum was evaluated to help determine the type of exenteration indicated. Surgical and/or histologic confirmation was available in all 23 cases. RESULTS: The accuracy of MR imaging in selecting patients was 83% (19 of 23), with a positive predictive value of 56% and a negative predictive value of 100%. In evaluating tumor involvement of the pelvic sidewall and lymph nodes, the negative predictive values were 100% and 95%, respectively. Tumor extension into the pelvic sidewall was overestimated in four patients, in three of whom it was not possible to distinguish radiation changes from tumor on MR images. For assessing extension of these pelvic tumors into the bladder and rectum, MR imaging had an accuracy of 81% and 85%, respectively. CONCLUSION: MR imaging may provide an accurate means of selecting patients considered for pelvic exenteration. MR accurately determined which patients should undergo the surgery, by demonstrating absence of sidewall abnormalities or adenopathy. Radiation changes could not be reliably distinguished from tumor involvement in those patients with sidewall abnormalities, however, especially in the first 6 to 12 months after treatment.
Bilateral hilar and mediastinal lymphadenopathy was observed in a 32-year-old man who had been engaged in asbestos spraying for 16 years. Lymph nodes obtained from Daniel's biopsy revealed tissue reaction compatible with sarcoidosis. On the other hand, a large number of asbestos particles were detected in the lung tissue from transbronchial lung biopsy and in bronchoalveolar lavage fluid, but no epithelioid granuloma was observed in the lung tissue. Various immunoserological findings such as PPD skin test, serum angiotensin converting enzyme activity, serum beta-glucuronidase and lysozyme level, serum antinuclear antibody, lymphocyte subset of blood and bronchoalveolar lavage fluid were inconsistent with sarcoidosis. However, lymph node enlargement and immunological abnormalities in this patient may be related to asbestos exposure and may not have occurred merely by chance.
OBJECTIVE: To study the abnormal amplification and role of Myc gene family in the development of laryngeal cancer. METHOD: A PCR-PAGE-Laser scanning technique was applied. RESULTS: There was no Myc gene amplification in the normal laryngeal tissues. The abnormal L-myc and C-myc gene were positive in 47% (15/32) of laryngeal cancers and 41% (13/32) of the cancers shown the N-myc gene amplification. Myc gene amplification was not related to age, sex and differentiation (P > 0.05), but the N-myc amplification was higher in patients with lymph node metastasis (P < 0.05). CONCLUSION: The N-myc amplification may play a role of positive regulation in the lymph metastasis of laryngeal cancer. The abnormal amplification of Myc gene family is one of the causes in development of laryngeal cancer.
OBJECTIVE: To investigate mRNA expression and mutation of MTA1 and nm23H1 genes in ovarian carcinoma (OC) in relation to lymph node (LN) metastasis. METHODS: A panel of eight normal ovarian tissues, twenty primary OC specimens and twenty corresponding LNs was examined for mRNA expression and mutation of MTA1 and nm23H1 genes by using RT-PCR and RT-PCR-SSCP. The level of expression was determined by the relative optic density (ROD) of the PCR products. RESULTS: The frequency of MTA1 overexpression was 100% (7/7) in primary OC with metastasis but only 38.5% (5/13) in those without metastasis (P = 0.0103). Overexpression of MTA1 was observed in 87.5% (6/7) of LNs with metastasis but in only 23% (3/13) of LNs without metastasis (P = 0.0118). In contrast with MTA1, low expression of nm23H1 mRNA was seen in 7 of 7 OC with metastasis but only in 4 of 13 (30%) of those without metastasis (P = 0.0043). Low nm23H1 expression was also seen in 7 of 7 LNs with metastasis but only in 5 of 13 (38.5%) nonmetastatic LNs (P = 0.0102). The ROD ratio of MTA1 to nm23H1 increased with the development of metastasis. No mutation of MTA1 and nm23H1 was found by SSCP analysis. CONCLUSION: The mRNA expression of MTA1 and nm23H1 is positively and negatively correlated with LN metastasis, respectively. Expression abnormalities but not mutation of the two genes are frequent events related to LN metastasis of ovarian cancer.
Ataxia-telangiectasia (AT) is a complex multiparametric disease associating oculocutaneous telangiectasias, cerebellar ataxia, elevated chromosomal aberration frequency and varied degrees of immunodeficiency. Recently a wasted mutant mouse (wst) has been described as an animal model of AT. We have looked in the wasted mutants for the presence of immune and endocrine abnormalities characteristic of AT. In contrast to the T cell immunodeficiency in AT, wasted mutants had a marked hypoplasia of all lymphoid organs, which affected both T and B lymphocyte subsets. The marked thymic atrophy appearing at the final stage of their disease did not modify the endocrine function of the thymic epithelium which produced normal levels of the thymic hormone thymulin. Although in vitro interleukin 2 (IL-2) production by splenic T cells in response to Con A was markedly diminished, these mice presented normal T and B cell proliferative responses to mitogens. Finally, no significant increase in serum alpha-fetoprotein level (a typical marker of AT) was found throughout the course of the disease. Although by many aspects, i.e. neurological disorder, chromosomal aberrations and early death, wasted mice presented similarities with human AT, major discrepancies in the typical features of immune abnormalities were found between the mouse model and the human disease.
A focus of increased uptake on a 201Tl minus 99mTc subtraction scintigram of the parathyroid glands was found in a patient with persistent hypercalcemia. This area was not caused by an abnormal parathyroid gland but by an enlarged lymph node containing metastatic tissue from an adenocarcinoma of the ovary.
Thoracic and abdominal radiographs from 100 dogs with lymphosarcoma were reviewed to determine the type and frequency of radiographic abnormalities associated with the disease. Sternal lymphadenopathy was the most frequent (60%) thoracic radiographic abnormality. Hepatomegaly (47%), splenomegaly (55%), and sublumbar lymphadenopathy (49.5%) were the most frequent abdominal radiographic abnormalities; these were most often seen in combination. A single radiographic abnormality or combination of abnormalities was not observed frequently enough to suggest that a diagnosis could be made only on the basis of radiographic findings.
The presentation to the Department of Pediatric Otolaryngology at the Children's Hospital of Michigan of a series of patients with sensorineural hearing loss and enlargement of the vestibular aqueduct prompted exploratory tympanotomy in three patients (two unilateral and one bilateral), for a total of four ears. These explorations were prompted by progression and/or fluctuation of hearing levels. The discovery of abnormal round windows in all four ears with a post-traumatic fistula present in one ear suggested the presence of a new association. A previously undescribed association of an enlarged vestibular aqueduct, sensorineural hearing loss and round window abnormality with potential fistula formation was identified. A review of the anatomy and physiology, literature review, and a prospective analysis with discussion of eight patients with enlarged vestibular aqueduct syndrome evaluated and treated at Children's Hospital of Michigan, is presented. We conclude that all children with sensorineural hearing loss should undergo extensive evaluation to determine etiology, including radiographic studies of the temporal bone. Further, the presence of an enlarged vestibular aqueduct should prompt the otolaryngologist to consider the presence of a round window abnormality and the potential for predisposition to perilymph fistula.
A new xenograft model for human epithelial ovarian carcinoma, with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR-5 cell line were injected i.p. into 6- to 8-week-old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site-dependent and tumor cell survival was dose-dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor-bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated.