Atypical histologic features in melanocytic nevi.
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Biomedical subjects
Publications and source records attributed to S F Cramer.
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Although most published epidemiological studies have found little evidence of systemic autoimmune disease associated with silicone breast implants, there still remains a question of whether silicones can cause local and/or systemic immune dysfunction. This study further investigates the effects of silicones on autoantibody and immunoglobulin production and macrophage activation in female A.SW mice. Sixty mice were divided among four treatment groups receiving a 0.5-ml intraperitoneal injection of either phosphate-buffered saline (PBS), pristane, silicone gel, or silicone oil. Test bleeds were taken periodically for 6 months. In contrast to pristane, neither silicone gel nor silicone oil induced lupus-associated antinuclear autoantibodies (immunoglobulin G [IgG] anti-nRNP/Sm, Su, and ribosomal P) or lupus nephritis. However, serum IgM became elevated persistently within 1 month of silicone gel or silicone oil administration. Also, the level of IgG3 was clearly elevated in silicone oil-treated mice. In contrast, IgG1, IgG2a, and IgG2b levels were not affected greatly by either silicone gel or oil. Furthermore, peritoneal macrophages from silicone- and pristane-treated mice produced higher levels of interleukin-1beta (IL-1beta) and IL-6 than those from PBS-treated mice after lipopolysaccharide stimulation. These results suggest that silicone gels and oils are capable of inducing hypergammaglobulinemia and activating macrophages in female A.SW mice.
CONTEXT: Although myomas shrink after menopause, the cellular mechanism for this phenomenon has received little attention. It was recently demonstrated that fibrous degeneration is significantly associated with postmenopausal status in both small and large myomas. OBJECTIVE: The purpose of the present study was to evaluate whether reduction in myoma cell size is also associated with postmenopausal status in small myomas. DESIGN: Tumor size and patient age have also been related to fibrous degeneration in small (<1 cm) myomas. Therefore, in the present study, 10 pairs of premenopausal and postmenopausal small myomas were matched within 3 years for patient age, within 1 mm for size, and within 1 grade for degree of fibrous degeneration. Most of the women were in their 50s, the decade during which postmenopausal fibrous degeneration in small myomas is most prevalent. Myoma cell size was derived by morphometric evaluation of relative myoma cell area (correcting for percentage of stroma, as measured by point counting) and by direct counting of the number of myoma cells per unit area in trichrome-stained sections. RESULTS: Small myomas from postmenopausal women had significantly (P <.05) smaller cell sizes than did size-matched myomas from age-matched premenopausal women. Myoma cell sizes and nucleus-cell (N/C) ratios were highly variable, especially in premenopausal myomas. CONCLUSIONS: Reduction in myoma cell size is significantly associated with postmenopausal status in small uterine leiomyomas and may be an important mechanism for postmenopausal shrinkage of myomas. In addition, the high variability of myoma cell size and N/C ratio may further support the somatic mutation theory (ie, the theory that diverse mutations may account not only for variations in the growth potential of uterine myomas, but also for variations in their cellular details).
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The nature of Spitz nevi is poorly understood, and their distinction from malignant melanoma can be difficult. Although there is general agreement on the diagnostic criteria, experts continue to have some differences, and controversial cases are not rare. A major obstacle to progress in this area is the lack of basic knowledge about melanocyte differentiation in Spitz nevi, as compared with ordinary nevi and malignant melanomas. Based on the hypothesis that normal melanocytes may have a differentiation pathway with discrete stages, it is suggested that the features of Spitz nevi may reflect homeostatic mechanisms governing maturation in the melanocyte differentiation pathway, whereas those of malignant melanomas may reflect carcinogen-induced aberrations. This perspective may be helpful in the continuing effort to develop optimal criteria for the differential diagnosis of Spitz nevi from malignant melanomas.
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It is well known that uterine leiomyomas shrink after the menopause. Fibrosis is the most common type of myomatous degeneration, but its relationship to menopause has not been studied. We evaluated fibrosis in 237 small myomas (< 1 cm) in relation to menopause, tumor size, intrauterine location, and patient age. Substantial fibrosis was seen in 33 (21%) of 159 small premenopausal myomas versus 39 (50%) of 78 small postmenopausal myomas (P < 0.001). This relationship was even stronger for women between 40 and 60 years of age: 27 (21%) of 126 premenopausal women versus 12 (71%) of 17 postmenopausal women (P < 0.001). Only 23 (23%) of 101 2- to 4-mm myomas had substantial fibrosis versus 45 (40%) of 112 5- to 9-mm myomas (P < 0.01). Small postmenopausal myomas that were inframucosal had less frequent fibrosis (3 [27%] of 11) than their intramural and subserosal counterparts (36 [54%] of 67) (P = 0.05). There was a significant increase in seedling myomas (fully cellular myomas < 1 cm) from postmenopausal women aged 60 to 70 years (13 [35%] of 37) compared with younger postmenopausal women (1 [6%] of 17) (P < 0.01). We conclude that fibrosis is strongly associated with menopausal status in small uterine myomas, that size and location are also related to fibrosis in small myomas, and that seedling myomas may arise after the menopause. Our interpretation of these findings is that the most likely cause of fibrosis in small myomas is senescence and that there may be heterogeneity in the molecular basis of senescence.
A 44-year-old women was treated for hyperparathyroidism resulting from parathyroid hyperplasia. Several months later, following a flu-like episode, she developed fever, confusion, abdominal pain, and diffuse petechiae, with severe thrombocytopenia and hemolytic anemia. She died on the 11th day of hospitalization. At autopsy she had multiple endocrine neoplasia type I, with two islet cell tumors, adrenal adenoma, pituitary adenoma, and bronchial carcinoid with liver metastasis. Florid visceral microthrombi involved arterioles and capillaries of the heart, including the conduction system. Brain, kidney, pancreas, adrenal, and portal areas of the liver were also heavily involved, but thrombi were rare in the liver sinusoids and the lungs. PAS-positive subendothelial deposits were demonstrated. In spite of the disseminated malignancy, the morphologic and laboratory findings were inconsistent with disseminated intravascular coagulation (DIC), and supported the clinical diagnosis of TTP. To the best of our knowledge this is the first report association of TTP with MEN and raises the question of a genetic linkage and/or hormonal interaction.
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Nontraumatic aneurysms of the internal thoracic artery are rare. We report a case where multiple aneurysms of the right internal thoracic artery presented as an asymptomatic density on the chest radiograph. Operative findings and pathology are reviewed.
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A 60-year-old woman who was previously in good health presented with a sore throat, fever, and a flu-like syndrome. Treated initially with acetaminophen and fluids for a presumed viral infection, she had a syncopal episode 4 days later, was admitted to the hospital, and died 3 hours after admission. Laboratory test results suggested sepsis with disseminated intravascular coagulation (DIC), whereas blood cultures grew group A beta-hemolytic streptococci. A postmortem diagnosis of streptococcal toxic shock syndrome was established. It was of particular interest that the pulmonary microcirculation was filled with thrombi that contained numerous gram-positive cocci. Although death from sepsis with DIC is not uncommon, septic pulmonary thrombosis has not been previously described. We speculate that this paradox may reflect unique properties of the virulent strains of Streptococcus pyogenes that are associated with streptococcal toxic shock syndrome.
OBJECTIVE: The few previous epidemiologic studies of uterine myomas have relied on clinical evaluation to select controls, but we previously showed that myomas may be present in more than 75% of such uteri. STUDY DESIGN: We therefore attempted to evaluate risk factors using age-matched controls whose uteri were serially sectioned to exclude the presence of myomas. RESULTS: The small study size precluded a meaningful evaluation of most parameters but tended to confirm the negative association of myomas with cigarette smoking (P = .07). CONCLUSION: Using monoclonal smooth muscle proliferation in human atherosclerotic plaques as a model, we suggest that excessive injury to and repair of the endometrial lining of the uterus may promote monoclonal expansion of smooth muscle cell populations in the uterine wall (i.e., myomas). This theory is largely compatible with the estrogen hypothesis, but fundamental principles of tumorigenesis and previous epidemiologic data on myomas suggest that nutritional factors should be scrutinized as possible initiators (DNA-damaging substances) in the pathogenesis of uterine myomas.