Pulmonary mycobacterial spindle cell pseudotumor in a lung transplant patient: progression without therapy and response to therapy.

Mycobacterial spindle cell pseudotumor (MSP) represents a rare, non-malignant, mass-forming reaction to various mycobacterial infections, typically occurring in immunocompromised patients. It is characterized by the proliferation of spindle-shaped fibrohistiocytic cells without the formation of epithelioid granulomas. Without staining for acid-fast bacilli, histological distinction from other spindle cell lesions, including malignancy, can be difficult. Most of the MSP cases reported in the literature have involved lymph nodes, skin, spleen, or bone marrow, but rarely involve the lung. MSP predominately occurs in patients who are immunosuppressed. We present a patient with MSP of the transplanted lung caused by non-tuberculous mycobacteria, in whom both the natural course of the untreated pseudotumor as well as the response to antimycobacterial treatments were observed.

Replication of HIV-1 in dendritic cell-derived syncytia at the mucosal surface of the adenoid.

Human immunodeficiency virus-type 1 (HIV-1) replicates actively in infected individuals, yet cells with intracellular depots of viral protein are observed only infrequently. Many cells expressing the HIV-1 Gag protein were detected at the surface of the nasopharyngeal tonsil or adenoid. This infected mucosal surface contained T cells and dendritic cells, two cell types that together support HIV-1 replication in culture. The infected cells were multinucleated syncytia and expressed the S100 and p55 dendritic cell markers. Eleven of the 13 specimens analyzed were from donors who did not have symptoms of acquired immunodeficiency syndrome (AIDS). The interaction of dendritic cells and T cells in mucosa may support HIV-1 replication, even in subclinical stages of infection.

The impact of calcification on the biomechanical stability of atherosclerotic plaques.

BACKGROUND: Increased biomechanical stresses in the fibrous cap of atherosclerotic plaques contribute to plaque rupture and, consequently, to thrombosis and myocardial infarction. Thin fibrous caps and large lipid pools are important determinants of increased plaque stresses. Although coronary calcification is associated with worse cardiovascular prognosis, the relationship between atheroma calcification and stresses is incompletely described. METHODS AND RESULTS: To test the hypothesis that calcification impacts biomechanical stresses in human atherosclerotic lesions, we studied 20 human coronary lesions with techniques that have previously been shown to predict plaque rupture locations accurately. Ten ruptured and 10 stable lesions derived from post mortem coronary arteries were studied using large-strain finite element analysis. Maximum stress was not correlated with percentage of calcification, but it was positively correlated with the percentage of lipid (P:=0.024). When calcification was eliminated and replaced with fibrous plaque, stress changed insignificantly; the median increase in stress for all specimens was 0.1% (range, 0% to 8%; P:=0.85). In contrast, stress decreased by a median of 26% (range, 1% to 78%; P:=0.02) when lipid was replaced with fibrous plaque. CONCLUSIONS: Calcification does not increase fibrous cap stress in typical ruptured or stable human coronary atherosclerotic lesions. In contrast to lipid pools, which dramatically increase stresses, calcification does not seem to decrease the mechanical stability of the coronary atheroma.

A comparison of the Framingham risk index, coronary artery calcification, and culprit plaque morphology in sudden cardiac death.

BACKGROUND: Neither clinical prediction models nor noninvasive imaging tests that detect coronary artery calcification identify all patients who experience acute coronary events. Variations in culprit plaque morphology may account for these inaccuracies. METHODS AND RESULTS: We compared the 10-year Framingham risk index, histologic coronary calcification, and culprit plaque morphology in 79 consecutive adults with sudden cardiac death. There was a modest relationship between the Framingham risk index and the extent of histologic coronary calcification (r=0.35, P=0.002). Agreement in risk classification between the histologic calcification score and the Framingham risk index occurred in 50 of 79 cases (63.3%, P=0. 039). Either a focus of coronary artery calcification >/=40 micromol/L (62% of cases) or a Framingham risk index score >/= average risk for age (62% of cases) were present in 66 of 79 (83.5%) cases. Cases with plaque erosion (n=22) had significantly less coronary calcification (P=0.003) and lower Framingham risk index (P=0.001) scores than stable (n=27) or ruptured (n=30) plaques. Fourteen of 22 (63.6%) cases of plaque erosion were classified as low risk by both the Framingham risk index and the histologic calcification score. CONCLUSIONS: The prediction of sudden cardiac death using the Framingham risk index and the measurement of coronary calcification are distinct methods of assessing risk for sudden cardiac death. Excessive reliance on either method alone will produce errors in risk classification, particularly for patients at risk of plaque erosion, but their combination may be complementary.

Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression.

BACKGROUND: Subclinical episodes of plaque disruption followed by healing are considered a mechanism of increased plaque burden. Detailed pathological studies of healed ruptures, however, are lacking. METHODS AND RESULTS: We identified acute and healed ruptures from 142 men who died of sudden coronary death and performed morphometric measurements of plaque burden, luminal stenosis, and smooth muscle cell phenotype. Healed ruptures were found in 61% of hearts and were associated with healed myocardial infarction, increased heart weight, dyslipidemia, and diabetes. Multiple healed rupture sites with layering were frequently found in segments with acute and healed rupture; the percent area luminal narrowing increased with increased numbers of healed sites of previous rupture. The underlying percent luminal narrowing for acute ruptures (mean 79+/-15%) exceeded that for healed ruptures (mean 66+/-14%, P:=0.0001), and the area within the internal elastic lamina was significantly less in healed ruptures than in acute ruptures, when segments were grouped by distance from the ostium. Healed ruptures favored the accumulation of immature smooth muscle cells at repair sites, with a cellular proliferation index of 0.40+/-0.09%, significantly higher than the index at the sites of rupture (P:=0.008). CONCLUSIONS: These data provide evidence that silent plaque rupture is a form of wound healing that results in increased percent stenosis. Healed ruptures occur in arteries with less cross-sectional area luminal narrowing than acute ruptures and are a frequent finding in men who die suddenly with severe coronary atherosclerosis.

Nonatherosclerotic narrowing of the atrioventricular node artery and sudden death.

OBJECTIVES: This study was undertaken to determine whether thickening of the atrioventricular (AV) node artery is a cause of sudden cardiac death. BACKGROUND: Thickening of the AV node artery has been implicated as a cause of sudden death primarily on the basis of case reports. Few pathologic studies have compared subjects who died of sudden cardiac death with normal control subjects who died traumatically. METHODS: The AV node artery in 27 patients with unexplained sudden cardiac death (mean age 24.8 +/- 7.4 years) was compared with that in 17 control subjects who died traumatically (mean age 25.6 +/- 7.0 years). No anatomic cause of death was found at autopsy in the subjects with sudden death, all of whom died of presumed cardiac arrhythmias. The conduction system of all hearts was studied by semiserial sections and Movat pentachrome stains. At the point of greatest narrowing of the AV node artery, the outer circumference and lumen outline were traced by computerized morphometry, the ratio of outer vessel area to lumen area was calculated and the histopathologic changes were noted. RESULTS: The rank-sum of ratios was significantly greater in the sudden death group than in the control group (p = 0.031, Wilcoxon rank-sum/Mann-Whitney statistic). A dysplastic AV node artery with significant acid mucopolysaccharide deposition was seen almost exclusively in the sudden death group (12 of 27 vs. 1 of 17, p = 0.006). In 10 subjects with sudden death a dysplastic AV node artery was narrowed > 2 SD over the control value; half of this subgroup died during exercise and one third had a family history of sudden unexplained cardiac death. CONCLUSIONS: Dysplasia of the AV node artery may contribute to death in a substantial portion of patients with unexplained sudden death, and such death is often associated with exercise and a family history of unexplained sudden death.

Arterial remodeling in the left coronary system: the role of high-density lipoprotein cholesterol.

OBJECTIVES: We sought to evaluate the plaque and patient variables related to arterial remodeling responses of early, de novo atherosclerotic lesions involving the left coronary artery. BACKGROUND: Coronary artery remodeling is a lesion-specific process involving either enlargement or shrinkage of atherosclerotic coronary arteries. There are little histologic data available correlating plaque morphologic and patient clinical characteristics with the degree and type of arterial remodeling in early atherosclerosis. METHODS: We studied 736 serial arterial sections from the left coronary system of 97 autopsy cases (mean age 33 +/- 11 years) by correlating the arterial remodeling response to plaque with demographic, serologic and histologic variables. Using the most proximal section as a reference, and considering the expected degree of internal elastic lamina tapering, remodeling was classified as positive (including neutral remodeling or compensatory enlargement) or negative. RESULTS: Remodeling was classified as positive in 84.3% (compensatory in 30.6%) and negative in 15.7% of sections with an overall mean luminal stenosis of 10.4 +/- 9.9%. In the lesions with the greatest arterial cross-sectional narrowing from each case, compensatory enlargement was associated with higher high-density lipoprotein (HDL) cholesterol (59.4 +/- 27.2 mg/dl) compared with either neutral (49.3 +/- 15.5 mg/dl) or negative remodeling (30.4 +/- 5.2 mg/dl; p = 0.019). In subjects with advanced atherosclerosis (maximum American Heart Association histologic grade 5 atherosclerosis), there was a modest linear relationship between higher HDL cholesterol and the propensity for positive remodeling (r2 = 0.37; p = 0.025). On multivariate analysis, only HDL cholesterol was related to the arterial remodeling response. CONCLUSIONS: Negative arterial remodeling occurs in early atherosclerosis. Higher HDL cholesterol may favor positive remodeling.

Coronary atherosclerosis in unheralded sudden coronary death under age 50: histo-pathologic comparison with 'healthy' subjects dying out of hospital.

AIM: sudden coronary death (SCD) in older individuals is generally associated with extensive coronary atherosclerosis, although it may be the first manifestation of ischaemic heart disease. In younger age-groups, SCD may occur in the presence of less severe disease. We sought to (1) examine the extent of coronary atherosclerosis in young victims of SCD compared with age- and sex-matched controls, (2) analyse the composition of atherosclerotic plaques in these patients, (3) identify the predominant mechanism of SCD, and (4) evaluate the possibility of detecting this mechanism on the basis of morphologic plaque features, in particular presence and amount of lipid accumulation and calcific deposits. METHODS AND RESULTS: coronary arteries were obtained at autopsy from 28 victims of SCD under age 50 with no prior clinical manifestation of ischaemic heart disease (IHD) and no myocardial scar formation and from 16 age- and sex-matched subjects dying of noncardiac causes out of hospital. Sections of all available major coronary arteries were cut in 5-mm intervals to yield a total of 1357 histologic sections, which were analysed using digitised planimetry. Victims of SCD had significantly more major coronary arteries per subject with luminal area narrowing > or = 75% than controls (on average, 2.1 vs. 0.2). Plaque area per histologic section was 5.1 +/- 2.1 mm(2) in SCD cases and 2.0 +/- 0.9 mm(2) in controls (P < 0.001). The major constituent of all plaques was fibrous tissue. Lipid core area per section was 0.49 +/- 0.59 mm(2) in SCD cases and 0.004 +/- 0.01 mm(2) in controls (P < 0.001), and calcified plaque area was 0.18 +/- 0.19 mm(2) in SCD cases and 0.02 +/- 0.05 mm(2) in controls (P < 0.001), both defining significant differences between SCD cases and controls. Arterial thrombosis, most often with underlying plaque rupture was the mechanism of SCD in > 80% of the cases. Considering histologic sections with > or = 50 and with > or = 75% area stenosis, plaque rupture was independently predicted by lipid core area. Calcific deposits were a frequent feature of plaque rupture but were only associated with it in univariate analysis. CONCLUSIONS: the extent and severity of coronary atherosclerosis in young victims of SCD as the first manifestation of IHD was substantially greater than in age-and sex-matched controls and comparable with that previously reported in SCD cases with a broader age range. Lipid core and calcified plaque areas provided for excellent separation between the two groups, which may have implications for identifying persons at increased risk for SCD by non invasive visualisation and assessment of the coronary arteries.

Effect of age, race, body surface area, heart weight and atherosclerosis on coronary artery dimensions in young males.

Compensatory arterial enlargement in response to atherosclerosis has been demonstrated for the left main coronary artery. Only limited data is available on the interaction of patient characteristics and atherosclerosis with coronary artery dimensions. The purpose of the present study was to evaluate the influence of age, race, body habitus, heart weight and atherosclerosis on coronary artery dimensions of young males. Hearts from 137 young men (age 32 +/- 8 years; 78 black, 59 white) with unnatural deaths (homicide, suicide, accident, drug overdose) were perfusion-fixed, and histologic sections were obtained from the left main, proximal left anterior descending and left circumflex coronary arteries. Computerized planimetry was performed on Movat stained sections. Multiple regression analysis was used to evaluate the relative contribution of plaque size, age, race, heart weight and body surface area on coronary dimensions and compensatory enlargement in response to atherosclerosis. In the left anterior descending and left main coronary arteries, black race, body surface area and age were independent predictors of increased lumen area. In the left circumflex, age was a predictor of lumen area. Plaque area, black race and body surface area independently predicted increased area enclosed by the internal elastic lamina area. There was compensatory enlargement of internal elastic lamina with increasing plaque size in both races in the three arteries, but the percent luminal stenosis was greater in whites due to smaller artery size. Luminal narrowing did not develop until plaques occupied 30% of internal elastic lamina area. Among a population of young men with non-cardiac deaths, blacks have larger lumen and area enclosed by internal elastic lamina than whites. Age and body surface area are major determinants of lumen areas, and compensatory arterial enlargement was seen in all examined arteries in the present study.

The pathology of Cronkhite-Canada polyps. A comparison to juvenile polyposis.

We studied Cronkhite-Canada (CC) polyps from nine patients, and compared them to gastric and colonic juvenile and gastric hyperplastic polyps. The CC polyp is characterized by its broad sessile base, expanded edematous lamina propria, and cystic glands. Similar features are found in the lesions of juvenile polyposis and gastric hyperplastic polyps. The only reliable distinction between CC and colonic juvenile polyposis was the pedunculated growth of the latter; however, this feature did not hold for gastric lesions. Unlike CC polyps, juvenile polyps sometimes have areas of dysplasia, but this is not typical. Therefore the diagnosis of CC polps, especially when located in the stomach, requires the presence of the ectodermal changes characteristic of this syndrome.

Osteosarcomas of the heart.

We reviewed nine primary cardiac sarcomas with osteosarcomatous differentiation. The patients' ages ranged from 24 to 67 (mean 38 years). All tumors were surgical specimens from the left atrium; many were clinically diagnosed as atypical myxomas. In eight cases complete excisions were attempted, one requiring reconstruction with grafting; one tumor was biopsied only. Two tumors extended into the pulmonary veins. Three patients died within 2 weeks after the initial surgery from postoperative complications; five patients had metastatic disease or died from disease; and one patient was lost to follow-up. Metastatic sites included lungs, thyroid, and skin. In addition to osteosarcoma, four tumors showed chondroid differentiation, three had osteoclastic cells, four had a prominent spindle cell component, and one had myxoid areas. All tumors showed immunohistochemical positivity for vimentin; stains for cytokeratin and desmin were negative. S-100 positivity was demonstrated in chondrosarcomatous areas of one tumor. We conclude that most cardiac osteosarcomas are clinically mistaken for myxomas because of location in the left atrium. They are larger, tend to infiltrate, and are very aggressive neoplasms. Histologically a variety of patterns may be encountered in addition to the osteosarcoma.

Localized vasculitis of the gastrointestinal tract.

We studied the clinical and pathologic findings of 63 patients with localized vasculitis of the gastrointestinal tract, including 35 partial bowel resections, 14 cholecystectomies, five partial pancreatectomies, six appendectomies, one omentectomy, one gastrectomy, and one esophagectomy. Vasculitis was classified histologically as polyarteritis (n = 33), phlebitis (n = 12), Churg-Strauss angiitis (n = 8), small-vessel vasculitis (n = 6), Buerger's disease (n = 2), and giant-cell arteritis (n = 1). Nineteen of 33 cases of polyarteritis affected the small bowel or gallbladder, and nine patients with polyarteritis had elevated serum antinuclear antibodies or rheumatoid factor. Eight of 12 cases of phlebitis affected the right colon; there were giant cells in four of these 12 cases, a history of medication use in seven of eight cases, and no evidence of serum autoantibodies. Short-term follow-up (mean, 5 years) demonstrated that systemic disease developed in six of 23 patients with polyarteritis (four of whom had elevated serum rheumatoid factor or antinuclear antibodies), the patient with giant-cell arteritis, and one of two patients with Buerger's disease. Systemic vasculitis did not develop in patients with other types of vasculitis. We conclude that patients with gastrointestinal phlebitis, polyarteritis without serum autoantibodies, and small-vessel vasculitis have a low short-term risk for the development of systemic disease.

Lipomatous hypertrophy of the atrial septum presenting as a right atrial mass.

Lipomatous hypertrophy of the atrial septum (LHAS) has been associated with cardiac arrhythmias and is defined as fatty infiltration > 2 cm thick in the atrial septum. The clinical and histologic features of surgically excised LHAS have not been previously studied. We studied 11 surgical resections of LHAS and compared them with 13 autopsy cases of LHAS and 24 control autopsy hearts. Of 11 surgical patients, eight were women: patients' mean age was 63 years, and six were described as mildly to overtly obese. Symptoms included congestive heart failure, atrial fibrillation, supraventricular tachycardia, palpitations, syncope, and incidental mass found at surgery. Imagining studies typically revealed a right atrial mass with a mean size of 6 cm (range, 2.5-10 cm). Multivacuolated fat was more extensive in surgical (p = 0.005) and autopsy (p = 0.009) cases of LHAS than in control hearts. Atypical, hypertrophied myocytes were presented in 72% of cases of LHAS compared with 8% of controls (p = 0.0003). In autopsy hearts, histologically abundant multivacuolated fat, heart weight, and body size were independently associated with increased atrial septal thickness. LHAS can be surgically excised, it has a distinctive histologic appearance marked by the presence of abundant multivacuolated fat and hypertrophied myocytes, and it is associated with increased body and cardiac mass.

Intra-abdominal fibromatosis. A pathologic analysis of 130 tumors with comparison of clinical subgroups.

We studied the clinical, gross, and histologic findings of 130 fibromatoses of the mesentery and other peritoneal sites. Seventeen patients had Gardner syndrome, 12 had prior abdominal surgery, and six had apparent estrogen elevation, including five pregnant or postpartum women and an alcoholic male with gynecomastia. The tumors were usually large and grossly circumscribed. Most often, they were located in the mesentery of the small bowel. They were multiple in 18 cases. Typical histologic features included a dense, collagenous stroma; prominent, dilated, thin-walled vessels; muscular hyperplasia of small arteries; keloidal change; myxoid change; and fibrous tissue insinuation into the muscularis propria of the bowel. Although mitoses were noted in many tumors, they were usually few in number. The gross and histologic features were similar in the clinical subgroups; however, keloidal change was seen less often in female patients. Less than half of the cases were initially correctly diagnosed. Most patients without Gardner syndrome were without recurrence at follow-up, even when the lesions had been incompletely excised.

Carcinoids of the duodenum. A histologic and immunohistochemical study of 65 tumors.

The light-microscopic and immunohistochemical characteristics of 65 duodenal carcinoids are presented. Most tumors showed a mixture of cribriform, insular, glandular, solid, and trabecular growth patterns. Eighty-five percent of the tumors were argyrophil and 15% argentaffin. The nonspecific neuroendocrine markers chromogranin, Leu-7, and neuron-specific enolase were positive in 97, 91, and 83% of tumors, respectively. Immunoreactivity for specific hormones/amines were as follows (percent positive tumors): somatostatin, 47%; N-gastrin, 56%; serotonin, 39%; calcitonin, 19%; insulin, 5%; pancreatic polypeptide, 3%; adrenal corticotropic hormone, 0%; glucagon, 0%. Sixty-eight percent had gastrin/cholecystokinin-like reactivity. Ten psammomatous tumors were located near the ampulla; eight were somatostatin positive, including two in patients with neurofibromatosis. One additional tumor in a patient with neurofibromatosis lacked psammoma bodies but elaborated somatostatin. Eight additional tumors in nonneurofibromatosis patients produced solely somatostatin. Duodenal carcinoids often elaborate more than one polypeptide hormone; those in the ampulla often elaborate somatostatin and have psammoma bodies.

Lymphoid changes of the nasopharyngeal and palatine tonsils that are indicative of human immunodeficiency virus infection. A clinicopathologic study of 12 cases.

We report 12 cases in which the histomorphologic changes of the nasopharyngeal tonsils (adenoids) or palatine tonsils suggest infection with the human immunodeficiency virus (HIV). The patients included 10 men and two women, aged 20 to 42 years (median, 33 years). The clinical presentation included airway obstruction, pharyngitis, fever, and a tonsillar or adenoidal mass lesion. Histologic evaluation of the excised adenoids or tonsils in 10 of the cases demonstrated a spectrum of changes including florid follicular hyperplasia, follicle lysis, attenuated mantle zone, and the presence of multinucleated giant cells (MGC). The latter characteristically localized adjacent to the surface or tonsillar crypt epithelium. Two of the 12 cases showed marked lymphoid depletion with absent germinal centers, plasmacytosis, and stromal vascular proliferation. Immunohistochemical evaluation for HIV p24 core protein showed reactivity in 10 of 12 cases localized to follicular dendritic cell network (FDC), the MGC, scattered interfollicular lymphoid cells, and cells identified within the surface or crypt epithelium. Localization of viral RNA by in situ hybridization paralleled the HIV p24 immunohistochemical findings. Additional significant findings included the presence of both CD-68 and S-100 protein in the MGC and the presence of S-100 protein in dendritic cells. Other than HIV, no microorganisms were identified. At the time of presentation, eight patients were not known to be a risk for HIV infection, nor were they known to be HIV infected or suffering from AIDS. In these patients, HIV infection was suspected on the basis of the histologic changes seen in the resected tonsillar and adenoidal tissue. Serologic evaluation (by enzyme-linked immunosorbent assay), confirmed the presence of HIV infection. Our findings suggest the possibility of HIV dissemination through the upper aero-digestive tract mucosa via target cells, such as intraepithelial dendritic cells, submucosal macrophages, and T-lymphocytes. Subsequent presentation of viral antigens to the tonsillar and adenoidal lymphoid tissues results in enlargement of these structures that clinically may simulate a neoplastic proliferation but causes histomorphologic changes that are highly suspicious for HIV infection even in asymptomatic HIV-positive patients.

Plaque rupture and plaque erosion.

There are multiple substrates for coronary thrombosis overlying an atherosclerotic plaque. The most common, plaque rupture, consists of an interruption of a thin fibrous cap overlying a lipid rich core. Plaque rupture is a result of macrophage infiltration and matrix degradation, is often seen in calcified plaques, and is highly associated with hypercholesterolemia. A less common substrate, plaque erosion, is not associated with elevated cholesterol and is the prime cause of coronary thrombosis in premenopausal women. The characteristic histologic features are abundant surface smooth muscle cells and proteoglycans, and a small or absent lipid rich core. The mechanisms of plaque erosion are unclear, and there are no consistent risk factors, although patients are often smokers.

Placental alkaline phosphatase immunohistochemistry of intratubular malignant germ cells and associated testicular germ cell tumors.

Two hundred three testicular germ cell tumors were studied immunohistochemically for the presence of placental alkaline phosphatase (PLAP). Special emphasis was placed on the pattern and incidence of positive staining of intratubular malignant germ cells (ITMGCs) adjacent to tumors. 99% of cases with adjacent ITMGCs showed a positive staining reaction in some or all IT-MGCs present. Other germ cell elements showed at least a focal positive staining reaction in the following proportions: seminomas, 96%; embryonal carcinomas, 96%; yolk sac tumors, 25%; mature teratomas, 5%; immature teratomas, 4%; choriocarcinomas, 45%; and syncytiotrophoblasts, 43%. The staining pattern for seminomas tended to be diffuse, whereas for embryonal carcinomas the staining pattern was more focal. Yolk sac tumors stained inconsistently for PLAP and a positive reaction was limited to a small percentage of cells. Syncytiotrophoblasts, singly or in choriocarcinomas, also showed variable positivity. These results corroborate the fact that PLAP is a sensitive marker for ITMGC, seminoma, and embryonal carcinoma.

Intramural coronary artery dysplasia of the ventricular septum and sudden death.

We report four cases of sudden unexpected death in three males and one female aged 12 to 31 years. Death occurred during exercise in three of four cases, and there was no history of sudden death or previous cardiac history in any patient. At autopsy, there was marked intramural coronary artery dysplasia of the ventricular septum, accompanied in three of the four cases by myocardial fibrosis. The arterial dysplasia was characterized by severe medial thickening with smooth muscle cell disorganization and marked luminal narrowing. There was no evidence of myofiber disarray or asymmetric septal hypertrophy to suggest hypertrophic cardiomyopathy. Other than an ostium secundum type atrial septal defect in one case, there were no associated cardiac or extracardiac lesions found at complete autopsy of these individuals. We conclude that small vessel disease of intramural coronary arteries of the ventricular septum may be an isolated finding leading to sudden cardiac death in young adults.

Hamartoma of mature cardiac myocytes.

The clinical and pathological findings of three patients with hamartomas of mature cardiac myocytes resembling localized hypertrophic cardiomyopathy are presented. Hypertrophic cardiomyopathy is manifest by a poorly demarcated area of cardiac hypertrophy, microscopically demonstrating myofiber disarray and intramural coronary thickening. Localized, nonencapsulated masses of hypertrophied cardiac myocytes in locations other than the left ventricle or ventricular septum have not been reported. The clinical and pathological data of three patients with localized hamartomas were retrospectively retrieved. The patients were 9, 22, and 28 years old, respectively; none had a known family history of heart disease or cardiomyopathy. Two patients had cardiac arrhythmias: one patient died suddenly, and one patient had the Wolff-Parkinson-White syndrome. The third patient was asymptomatic. Two patients treated surgically had single masses in the right atrium and right ventricle, respectively. The patient who died suddenly had multiple discrete masses throughout the atrial and ventricular myocardium, including the left ventricular free wall. None of the three patients had septal asymmetry suggestive of hypertrophic cardiomyopathy. Histologically, there were discrete but unencapsulated nodules of marked myocyte hypertrophy with disorganization, focal scarring, and thickened intramural arteries. There was no myocyte vacuolization suggestive of cardiac rhabdomyoma. Ultrastructurally, the myocytes showed abundant and disorganized myofilaments and normal intercellular junctions. Hamartoma of mature cardiac myocytes is a previously undescribed cardiac tumor that shares some features of hypertrophic cardiomyopathy and rhabdomyoma, but is currently best considered a separate entity.