Review and hypothesis: the eosinophil and peripartum heart disease (myocarditis and coronary artery dissection)--coincidence or pathogenetic significance?

OBJECTIVES: To examine a possible relationship between peripartum heart disease (myocarditis and spontaneous coronary dissection) and the presence of eosinophils. BACKGROUND: Eosinophils have been shown to have potential collagenolytic and cytotoxic activity. Eosinophils may play a role in postpartum uterine involution. The presence of eosinophils in spontaneous coronary dissection and myocarditis in the postpartum period raises the possibility of a role for eosinophils in these diseases. METHODS: We reviewed the files of one of us (S.M.F.) for cases of peripartum myocarditis and spontaneous coronary dissection and assessed the frequency of eosinophilic inflammation. Seventeen postpartum myocarditis and/or cardiomyopathy cases were found and two spontaneous coronary dissections. Fifteen sex- and age-matched controls on non-postpartum myocarditis and borderline myocarditis were evaluated and eosinophil counts per unit area compared. Also, a Medline search of all previously published cases of spontaneous coronary dissection was performed back to 1966. RESULTS: Of the 16 heart biopsies and one autopsy in the peripartum period, 10 were shown to contain easily identified eosinophils (6 myocarditis, 1 borderline, 3 cardiomyopathy). When presence of eosinophils was compared with the control group, a statistically significant difference was obtained (P = 0.036). The two new spontaneous coronary dissection cases had eosinophils along the dissection plane; the literature search produced 13 of 24 autopsied peripartum spontaneous coronary dissections with eosinophils for a total of 15 of 26 with our cases. CONCLUSIONS: An association exists between eosinophils and peripartum cardiac disease (myocarditis and spontaneous coronary dissection). The role of eosinophils in labor, uterine involution and collagenolysis and the possible relation to cardiac disease are discussed.

Visceral myogenic tumors. A manifestation of HIV infection in children.

We report a primary smooth-muscle tumor of undetermined malignant potential of the liver in a child with acquired immune deficiency syndrome (AIDS). This patient represents the eighth child infected with the human immunodeficiency virus who developed a mesenchymal tumor other than Kaposi's sarcoma. All these children were younger than 10 years of age. These tumors often were histologically or clinically malignant and all but one were smooth-muscle tumors. These tumors arose exclusively in visceral organs, and the hepatobiliary, gastrointestinal, and tracheopulmonary systems were involved. Transmission of the virus occurred both vertically (in six children) and via blood transfusion (in two). Given the rarity of smooth-muscle tumors in uninfected children, the unusual frequency of these tumors suggests that immunosuppression induced by the virus permits the unregulated proliferation of a primitive mesenchymal cell disposed to myogenous differentiation, a situation not unlike that observed in the development of AIDS-related Kaposi's sarcoma in adults.

Low-grade adenosquamous carcinoma of the breast. A clinocopathologic study of 32 cases with ultrastructural analysis.

Low-grade adenosquamous carcinoma of the breast is an uncommon neoplasm of uncertain pathogenesis, clinical behavior, and malignant potential. This report describes the clinical and pathologic features of 32 cases of low-grade adenosquamous carcinoma. All patients presented with palpable tumors ranging from 0.6 to 8.6 cm (mean, 2.8 cm). Origin from an intraductal papillary tumor was found in 12 cases, including three with adenomyoepitheliomatous features. Electron microscopy disclosed glandular and squamous differentiation; the squamous cells often lined ducts that were structurally analogous to the acrosyringium of the eccrine sweat gland. Treatment consisted of mastectomy (13 patients) or excisional biopsy (19 patients). A single lymph node in one patient with a 3.5-cm primary carcinoma harbored metastatic adenocarcinoma. Axillary dissection revealed no metastases in 11 other patients. Another patient with an 8.0-cm breast tumor had metastatic adenosquamous carcinoma in the lung at initial diagnosis. After follow-up of 12 to 124 months, 20 of 25 patients had no recurrence. Five women treated by excisional biopsy had local recurrences in the breast. In one patient, the local recurrence was ultimately fatal due to invasion of the hemithorax. Estrogen and progesterone receptor studies were negative in 13 of 15 cases studied by biochemical analysis. The two tumors that were hormone-receptor positive were histologically associated with a papilloma and an adenomyoepithelioma, respectively. In the latter case, immunohistochemical studies showed the carcinoma to be hormone-receptor negative. Hormone receptor activity was limited to the adenomyoepitheliomatous component. This study confirms the largely indolent, but locally aggressive, clinical course of low-grade adenosquamous carcinoma of the breast. Although complete limited excision of small lesions may be curative, tumors greater than 3.0 cm may require more aggressive therapy.

Estrogen and progesterone receptor content in human thyroid disease.

Recent studies have confirmed the presence of estrogen and progesterone receptors in many benign and malignant thyroid tumors, but their clinical significance is unclear. The estrogen and progesterone receptor content of 135 thyroid lesions was assayed prospectively from 1980 through 1986 using the dextran-coated charcoal method. The cases included 30 papillary, 13 follicular, 6 medullary, and 2 Hürthle cell carcinomas. Thirty-two follicular adenomas, 45 goiters, and 7 cases of thyroiditis also were studied. Estrogen receptor protein was positive (> or = 2 fmol/mg) in 46% of the cases, with no clear statistical predilection related to the type or size of the thyroid lesion, age, or sex. Progesterone receptor protein was positive (> or = 10 fmol/mg) in 51% of the cases, with the highest median values obtained in papillary carcinomas, particularly in male patients and women older than 50 years. Metastases at presentation, noted in 28 of 51 carcinomas, were unrelated to receptor content. Mean follow-up of 55 months in 48 patients with various carcinomas yielded 12 cases with late metastases, which were similarly unrelated to receptor content. Although estrogen receptors are commonly detectable in thyroid lesions, they have no clear relationship to presenting clinical or pathologic features or, in cases of carcinoma, to subsequent metastatic potential. The role of progesterone activity in papillary carcinoma and in goiter merits more investigation.

Myocardial alterations in diabetes and hypertension.

Diabetes mellitus is a complex group of diseases that has hyperglycemia as a common metabolic abnormality. Although it is well-known that diabetic patients are susceptible to the effects of large vessel atherosclerosis with specific cardiac and cerebral complications, the association of diabetes mellitus with cardiac dysfunction caused by cardiomyopathy in the absence of significant coronary artery disease has been recognized for many years. However, the pathogenesis of diabetic cardiomyopathy remains unknown and has been somewhat controversial. Specifically, whether diabetes mellitus with its metabolic effects is sufficient to account for cardiomyopathy remains to be proven. This paper reviews the evidence for and against a metabolic etiology. In addition, we review the clinical and experimental evidence that supports the view that diabetes mellitus acts together with hypertension to produce structural damage in the heart that manifests as ventricular dysfunction and ultimately congestive heart failure. The concomitant effects of the metabolic derangements of diabetes and the vascular abnormalities associated with hypertension may lead to microvascular-induced tissue injury. Findings supporting this hypothesis are presented, along with observations suggesting that treatment with vasodilating calcium channel blockers or angiotensin converting enzyme inhibitors may be beneficial in regard to tissue pathology and mortality in experimental models. Recent clinical studies also support a role for the microcirculation in diabetics. Finally, it is suggested that if the microcirculation is pathogenetically involved in diabetic cardiomyopathy, then agents that improve microcirculatory flow along with tight control of hypertension may be as beneficial in the treatment or prevention of diabetic cardiomyopathy as strict metabolic control of hyperglycemia.

Endomyocardial biopsy diagnosis of small vessel disease: a clinicopathologic study.

We reviewed the clinical history of 191 patients undergoing endomyocardial biopsy and correlated signs and symptoms of heart disease with the presence or absence of small vessel disease. Idiopathic congestive heart failure (78%), arrhythmia (35%), and chest pain (25%) were the most frequent indications for biopsy. Small vessel disease was noted in 61% of the biopsies (67% female, 56% male): 10% severe, 36% moderate, and 15% mild small vessel disease. Patients with hypertension were twice as likely to have small vessel disease than those without hypertension. Of the 27 females with hypertension, 85% had small vessel disease, 67% with either severe or moderate small vessel disease. Small vessel disease was almost twice as frequent in patients with chest pain compared to patients without chest pain. Chest pain was significantly more common in patients with severe small vessel disease than in those with normal small vessels. Of all patients with chest pain, 18% had severe small vessel disease; however, of 20 patients with severe small vessel disease, 45% had chest pain. This analysis suggests that small vessel disease seen in endomyocardial biopsy is more common in women and is related to hypertension. When severe, it is likely to be associated with atypical chest pain.

AIDS cardiomyopathy: first rule out other myocardial risk factors.

Consecutive autopsies of 59 male AIDS patients revealed that 21 had other myocardial risk factors: 17 were alcohol abusers and 6 had hypertension or coronary artery disease. AIDS patients with these myocardial risk factors were older (mean age 45 versus 35 years, P less than 0.01), and were more likely to have cardiomegaly (mean heart weight 397 grams versus 350 grams, P = 0.06) than patients with AIDS alone. When evaluating patients for AIDS cardiomyopathy, other myocardial risk factors must be considered.

Peripartum versus idiopathic dilated cardiomyopathy in young women--a comparison of clinical, pathologic and prognostic features.

Clinicopathologic features of 13 women with peripartum cardiomyopathy were compared to 13 women aged 19 through 38 with idiopathic dilated cardiomyopathy. No presenting clinical or pathologic variable distinguished either group. However, the clinical course differed between the groups. Eleven of 13 patients with idiopathic dilated cardiomyopathy had a poor clinical outcome, defined as persistent heart failure or death. Patients in this group succumbed one year or more after disease onset. Five of 13 patients with peripartum cardiomyopathy had poor outcome, with death occurring 9 months or less after disease onset. The clinical course of peripartum cardiomyopathy appears distinct from that of idiopathic dilated cardiomyopathy in young women.

Effects of oxygen free radicals and scavengers on the cardiac extracellular collagen matrix during ischemia-reperfusion.

OBJECTIVE: Collagen is lysed early during ischemia-reperfusion, but whether this is due to ischemia or reperfusion injury is not known. The effect of oxygen free radicals and free radical scavengers on left ventricular hemodynamics, myocardial morphology and collagen content were studied in an isolated, Langendorff-perfused rat heart model of regional ischemia-reperfusion. METHODS: All hearts received left anterior descending coronary artery ischemia for 20 mins. Group 1 had ischemia only; group 2 had ischemia followed by reperfusion with oxygenated Krebs-Henseleit buffer for 20 mins; group 3 had oxygen free radicals generated by hypoxanthine and xanthine oxidase during reperfusion; group 4 had free radical scavengers with superoxide dismutase plus catalase; group 5 had both oxygen free radicals and free radical scavengers during reperfusion. RESULTS: Left ventricular developed pressure decreased significantly in group 3 during ischemia followed by reperfusion (58 +/- 3.1 mmHg versus 42 +/- 2.4 mmHg, P = 0.004), but did not change significantly in any of the other groups. Necrosis score on pathology was highest in group 3; this score also was higher than that in group 5 with free radical scavengers added (3.0 +/- 0.3 versus 2.0 +/- 0.4, P = 0.07) and higher than that of group 2 with reperfusion with buffer only (3.0 +/- 0.3 versus 1.4 +/- 0.5, P < 0.05). Collagen content decreased significantly compared with control in group 3 only with ischemia followed by reperfusion with the addition of oxygen free radicals (18.4 +/- 1.5 versus 11.9 +/- 1.7 g/mg protein, P < 0.05). The addition of free radical scavengers in group 5 mainly attenuated the collagen loss. Scanning electron microscopy revealed profound structural changes of the extracellular collagen matrix in numerous regions of 'stunning' independent of tissue necrosis. CONCLUSIONS: We conclude that: first, oxygen free radicals trigger significant collagen damage and left ventricular dysfunction during reperfusion; second, these changes extend beyond the ischemic damage alone; and third, free radical scavengers can effectively limit oxygen free radical-induced collagen loss and left ventricular dysfunction.

Lipothymoadenoma of the parathyroid.

We describe the clinical and morphological features of a most unusual functional mediastinal tumor that combines features of thymolipoma and lipoadenoma of the parathyroid gland. The lesion was unique in that microscopic elements of benign thymic, adipose, and parathyroid tissue were admixed intimately in one partially encapsulated mass. To the best of our knowledge, there has not been a previous description of this tumor. It was excised from a 54-year-old woman with a 10-year history of persistent hyperparathyroidism. The controversial relationship of embryological malformation, hamartoma, and neoplasm is exemplified by this entity.

Diabetic heart disease: the clinical and pathological spectrum--Part I.

Diabetes mellitus is a significant condition affecting major segments of all population groups studied. With the introduction of insulin and oral hypoglycemic therapy, and with better understanding of diet and weight control over the past half century, the primary causes of diabetic morbidity and mortality have shifted in varying proportions from metabolic derangements, infection, and renal insufficiency to different types of cardiovascular disease. Despite extensive clinical and laboratory research on the etiology, pathogenesis, and even the existence of cardiovascular disease associated with diabetes mellitus, however, considerable debate is still apparent in this field. Our purpose is to present an overview of the subject of diabetic heart disease, with a critical analysis of epidemiologic, clinical, and pathological data. Some of this material will be addressed from the perspective of research in this area over the past decade by one of us (SMF), particularly in experimental hypertensive and diabetic cardiomyopathy. However, overall, an attempt will be made to provide an objective and balanced analysis, in order to answer the question: does diabetic heart disease exist?

Diabetic heart disease--Part II: The clinical and pathological spectrum.

Diabetes mellitus is a significant condition, affecting major segments of all population groups studied. With the introduction of insulin and oral hypoglycemic therapy, together with better understanding of diet and weight control gained over the past half century, the primary causes of diabetic morbidity and mortality have shifted in varying proportions from metabolic derangements, infection, and renal insufficiency to different types of cardiovascular disease. Despite extensive clinical and laboratory research on the etiology, pathogenesis, and even the existence of cardiovascular disease associated with diabetes mellitus, however, considerable debate is still apparent in this field. Our purpose is to present an overview of the subject of diabetic heart disease, with a critical analysis of epidemiologic, clinical, and pathological data. Some of this material will be addressed from the perspective of research in this area over the past decade by one of us (SMF), particularly in experimental hypertensive and diabetic cardiomyopathy. However, overall, an attempt will be made to provide an objective and balanced analysis in order to answer the question: does diabetic heart disease exist?

Cytology of small cell carcinoma of the urinary bladder.

To characterize the cytologic spectrum of small cell carcinoma of the urinary bladder, a review of 42 urinary cytology specimens from 13 patients with histologically proven tumors was conducted. Patients ages ranged from 45 to 81 yr (mean 68.9). In four tumors, small cell carcinoma was the sole malignant cellular component: all 11 urinary specimens in these patients harbored cells with features of an undifferentiated small cell carcinoma. In the remaining nine tumors, small cell carcinoma appeared with transitional, squamous cell or adenocarcinoma, but in four, small cell carcinoma was the sole invasive component. Almost one third of urinary specimens in this group lacked a small cell component. Neuroendocrine differentiation was confirmed by immunopathology in eleven cases (neuron specific enolase positive in 11 of 12, synaptophysin in 2/11, chromogranin in 2/13, Leu 7 in 2/7), and by ultrastructural analysis in two. Small cell carcinoma is a cytologically recognizable variant of bladder cancer, but admixture with other malignant components may mask its appearance in urinary specimens.

Cytology of the thyroid gland: pitfalls in aspiration of the fibrotic nodule.

Fibrotic changes can be found in a variety of pathologic processes that affect the thyroid gland, and yet fine-needle aspiration (FNA) correlation of these lesions is not well-known. Cytologic findings are described from three different lesions, all with extensive fibrosis, that occurred in thyroid gland FNA. In each case, fibrotic changes resulted in cytologic changes potentially representing pitfalls in aspiration diagnosis. FNA revealed, solely or predominantly, fibroblasts in 2 patients whose subsequent thyroidectomies disclosed diffusely sclerotic papillary carcinoma and multinodular goiter. In the third case, an initially suspicious FNA was followed by multiple unsuccessful attempts at a second FNA. At thyroidectomy, a follicular adenoma with post-FNA fibrosis and infarction was identified. The differential diagnoses in thyroid FNA of fibrotic nodules can be broad, and this is discussed. Awareness of potential pitfalls may improve diagnostic accuracy.

Cytologic diagnosis of fat emboli in peripheral blood during sickle cell infarctive crisis.

A diagnosis of fat emboli can be suspected in a patient presenting with the typical symptoms of the fat embolism syndrome, but is rarely proved pathologically, except at autopsy. We described a 25-yr-old man with sickle cell anemia who developed an infarctive crisis complicated by unexplained fever, neurologic change, and respiratory abnormalities. Blood drawn from the femoral vein and examined cytopathologically yielded necrotic bone marrow elements admixed with fat. The cytologic finding of fat emboli from necrotic bone marrow provided the diagnosis and helped guide subsequent medical intervention. This sample test is recommended for patients at risk for fat emboli to aid in the clinical diagnosis.

Immunocytochemical evaluation of HBME-1, CA 19-9, and CD-15 (Leu-M1) in fine-needle aspirates of thyroid nodules.

Overlapping morphologic patterns that may be observed in goiter, follicular adenoma, and papillary carcinoma can limit the cytologic evaluation of the thyroid gland. In an attempt to develop a useful adjunctive test, the immunocytochemical reactivity of HBME-1, carcinoma antigen 19-9 (CA 19-9), and CD-15 (Leu-M1) was tested on 59 cell block preparations from fine-needle aspirations of the thyroid gland. HBME-1 monoclonal antibody was reactive in all 21 papillary carcinomas, in 4 of 18 adenomas, and in 5 of 20 goiters. CA 19-9 was identified in 13 of 21 carcinomas, 1 goiter, but none of the adenomas. CD-15 was present in 15 of 21 carcinomas, 1 goiter, and 1 adenoma. We conclude that HBME-1 is a sensitive marker of papillary thyroid carcinoma. CD-15 and CA 19-9 are less sensitive but more specific. This panel can be useful to help classify morphologically equivocal lesions. As with all immunocytochemical testing, caution must be exercised in the interpretation of results, and correlation made with morphologic and clinical data.

Cytologic features of pulmonary malakoplakia related to Rhodococcus equi in an immunocompromised host.

Cytologic features are described in bronchial brushings of a large cavitary lung mass from an immunosuppressed patient who had undergone liver transplantation. Scattered histiocytes with abundant eosinophilic, vacuolated cytoplasm were noted in a background of bronchial cells. Within approximately one fourth of the histiocytes, targetoid intracytoplasmic inclusions were present, consistent with Michaelis-Gutmann bodies. They were diffusely positive by histo-chemical staining with von Kossa, Gomori methenamine silver, and periodic acid-Schiff stains, and focally positive with Prussian blue stain. Cultures of the abscess yielded Rhodococcus equi. The characteristic microscopic features of pulmonary malakoplakia can be discerned in bronchial brushings, and should be sought, particularly in immunocompromised patients.

Diagnosis of metastatic appendiceal adenocarcinoid in liver by fine-needle aspiration cytology.

A 70-yr-old woman presented with symptoms clinically attributed to acute appendicitis. An adenocarcinoid tumor of the appendix was resected, followed by right hemicolectomy with negative lymph nodes. Seven years later, a fine-needle aspiration biopsy was performed on one of multiple hepatic nodules, revealing metastatic adenocarcinoid. The cytopathologic features of the metastatic tumor are described.

Distinction between bronchioloalveolar carcinoma and hyperplastic pulmonary proliferations: a cytologic and morphometric analysis.

The objectives of this study were to identify key cytologic features for the morphologic differentiation of bronchioloalveolar carcinoma from reactive pulmonary proliferations, and to determine if morphometry of the cytologic specimens could provide additional data to distinguish the two processes. We analyzed 15 morphologic criteria in pulmonary cytologic specimens from 17 histologically proven cases of bronchioloalveolar carcinoma and 13 cases with reactive cellular changes and compared the findings using univariate analysis. This revealed four statistically significant features more commonly associated with bronchioloalveolar carcinoma: (i) predominance of two- and three-dimensional tissue fragments, (ii) tenacious intercytoplasmic connections between cells, (iii) intranuclear cytoplasmic inclusions, and (iv) paucity of multinucleated cellular forms. Morphometric measurement revealed significant differences between the mean of the nuclear area of benign reactive cells and that of the malignant cells. The utilization of these criteria is helpful to diagnose bronchioloalveolar carcinoma and to distinguish it from reactive pulmonary processes.

Association between a shift in vaginal flora on Papanicolaou smear and acute chorioamnionitis and preterm delivery.

Bacterial vaginosis has been implicated as a cause of acute chorioamnionitis and preterm delivery. This study was designed to determine any association between the detection of bacterial vaginosis on a prenatal Papanicolaou (Pap) smear, defined as a shift in vaginal flora, and the subsequent occurrence of acute chorioamnionitis or preterm labor. A 47-mo retrospective case-control analysis comparing 186 patients with histologically-proven acute chorioamnionitis (cases) and 186 controls was performed. Initial prenatal Pap smears were evaluated for the presence of altered vaginal flora. Pap smears from women with acute chorioamnionitis were more likely to have altered vaginal flora than those without chorioamnionitis (P < 0.01). Preterm delivery was also more common among women with a shift in vaginal flora (P < 0.01). In conclusion, women at risk for chorioamnionitis and/or preterm delivery may be able to be identified by the results of their prenatal Pap smear.