Sudden death in young competitive athletes: clinicopathologic correlations in 22 cases.

PURPOSE: To investigate the pathologic substrates of sudden death in young competitive athletes. PATIENTS AND METHODS: Twenty-two cases of sudden death in young competitive athletes occurring in the Veneto region (northern Italy) in the period January 1979 to December 1989 were studied by postmortem examination. The athletes included 19 males and three females, ranging in age from 11 to 35 years (mean, 23 years). RESULTS: In 18 cases, sudden death occurred during (16 cases) or immediately after (two cases) a competitive sport activity. In 10 subjects, sudden death was apparently the first sign of disease. Postmortem examination disclosed that this fatality was due to arrhythmic cardiac arrest in 17 cases; among these, right ventricular cardiomyopathy, also known as "right ventricular dysplasia," was the most frequently encountered cardiovascular disease (six cases), followed by atherosclerotic coronary artery disease (four cases), conduction system pathology (three cases), anomalous origin of right coronary artery from the wrong aortic sinus (two cases), and mitral valve prolapse (two cases). In two athletes, the abrupt lethal complication was "mechanical" and consisted of pulmonary embolism and rupture of the aorta; in three athletes, death was due to a cerebral cause. All athletes with right ventricular cardiomyopathy died during effort, and most had a history of palpitations and/or syncope. Whenever available, electrocardiographic (ECG) tracings showed inverted T waves in precordial leads and/or left bundle branch block ventricular arrhythmias. CONCLUSIONS: Clinicopathologic correlations indicate that in the Veneto region of Italy, right ventricular cardiomyopathy is not so rare among the cardiovascular diseases associated with the risk of arrhythmic cardiac arrest, and seems to account for the majority of cases of sudden death in young athletes; this disorder can be suspected during life on the basis of prodromal symptoms and ECG signs.

Simultaneous visualization of immunodetected antigens and tissue components revealed by non-enzymatic histochemical stains.

We explored the possibility of simultaneous application of histochemical and immunohistochemical staining techniques on the same paraffin-embedded human tissue section. Conventional histological stains (PAS, Alcian, Alcian-PAS, Van Gieson, Gomori silver impregnation, and Giemsa) were used in association with a battery of markers (keratins, leucocyte common antigen, S-100 protein, Factor VIII-related antigen) that are widely employed in diagnostic and experimental studies. We found that the best procedure was to perform immunostaining before the histochemical reaction, as this enables all the other possible combinations to be carried out. In addition, several detection systems, such as peroxidase-anti-peroxidase (PAP), alkaline phosphatase-anti-alkaline phosphatase (APAAP), and avidin-biotin complex (ABC), were tested and all gave consistent results. Some minor modifications of the histological staining methods were necessary, but the current immunohistochemical techniques could be used as established. Preliminary findings indicate that immunohistochemistry can be combined with histochemistry techniques by means of a relatively simple procedure whose only disadvantage is the time required to carry out the double staining.

Cardiac conduction system abnormalities as a possible cause of sudden death in young athletes.

Histologic examination of serial sections of the conduction system of the hearts of three young persons who died suddenly while engaged in active sports was performed. In no case were electrocardiogram tracings available. One patient, an 11-year-old girl, had micro-Ebstein's anomaly of the tricuspid valve associated with a septoseptal Kent fascicle through a wide gap of the central fibrous annulus and upper Mahaim fibers. Another patient, a 24-year-old football player, had a focal, 75 per cent obstructing atherosclerotic plaque in the proximal descending coronary artery, with scattered band necrosis and patchy myocardial fibrosis; upper and lower Mahaim fibers joined the atrioventricular node and the left bundle branch with the crest of the interventricular septum. The third patient, a 26-year-old cycling champion, had a conspicuous atrial fascicle of ordinary and transitional myocardium bypassing the atrioventricular node to anastomose with the His bundle (James accessory atrioventricular pathway). These findings indicate that atrioventricular conduction system abnormalities may play a fatal arrhythmogenic role in sudden death and raise questions regarding the prevention of electrical instability in young people engaged in active sports.

Cusp disruption by massive lipid infiltration. A rare cause of porcine valve dysfunction.

A 68-year-old man underwent reoperation because of severe incompetence of a mitral valve xenograft, 96 months following implantation. Gross examination of the device showed yellow spots on the cusps, suggesting lipid infiltration, and a torn commissure. Plasmatic cholesterol and lipiprotein levels were normal. X-ray examination of the explants showed no calcific deposits. Histologic and electron microscopic studies disclosed massive accumulation of lipid clefts and droplets, predominantly at the level of the tear; focal loss and detachment of the endothelial lining and scanty porcine fibroblasts and collagen bundles with preserved periodicity were also noted. Primary disruption of porcine valvular bioprostheses without significant calcifications or collagen breakdown is uncommon. In the present case, lipid accumulation was the main determinant of tissue failure.

Cardiac ultrastructure in primary restrictive cardiomyopathy.

A five-year clinical follow-up and the results of myocardial biopsies are described in a patient with primary restrictive cardiomyopathy. Histologic examination of a right ventricular endomyocardial biopsy taken early in the course of the illness was not contributory. Histologic examination of a left ventricular endomyocardial biopsy five years later showed hypertrophy and disarray of myocytes, thickening of the endocardium, and interstitial fibrosis. Connective tissue was compact and regularly oriented in the endocardium, but tangled and irregularly oriented in the interstitium. It is concluded that the irregular network of collagen fibrils and elastic fibers limits diastolic relaxation and prevents ventricular dilatation; that the coexisting hypertrophy results from an attempt to maintain normal pump function; and that the myocyte disarray is a consequence of abnormal mechanical forces generated under conditions of severe fibrosis.

Right ventricular myxoma: review of the literature and report of two patients.

The cases of 2 patients with right ventricular myxoma are reported, together with a review of the literature. In both patients the ultimate diagnosis was reached by means of angiocardiography, which revealed large filling defects in the right ventricle. In 1 patient, cardiac catheterization failed to record a transpulmonary gradient. Echocardiography, performed after hemodynamic investigation in both patients, revealed the usual pattern of abnormal echoes moving from the right ventricular cavity to the right outflow tract during the cardiac cycle. In both patients the tumor was successfully excised through a right atrial approach. This approach was preferred to the right ventriculotomy because it provides adequate surgical exposure, avoids undue trauma to the ventricular myocardium, and offers an easy way for inspection of the left heart.

Relationship between apoptosis, tumour necrosis factor, and cell proliferation in chronic cholestasis.

BACKGROUND: Target of the immune response in chronic autoimmune cholestasis, is the bile duct epithelium. Lymphocytic infiltration and apoptosis have both been suggested to mediate the destruction of hepatocytes and biliary epithelium in primary biliary cirrhosis. AIMS: To further address this issue in two cholestatic liver diseases characterized by an autoimmune pathogenesis and, furthermore, evaluate the relationship between apoptosis and both tumour necrosis factor alpha and cell proliferation. METHODS: Liver tissue specimens from 16 patients with primary biliary cirrhosis, 15 with primary sclerosing cholangitis, and 16 with chronic hepatitis C (controls) were evaluated. DNA-fragmentation of apoptotic cells was ascertained by the TdT-mediated deoxyuridine triphosphate nick-end labelling method. Tumour necrosis factor alpha expression and cell proliferation (Ki-67 antigen) were assayed by immunohistochemistry. RESULTS: Hepatocytes with DNA fragmentation were observed in 75% of patients with primary biliary cirrhosis, in 66.6% with primary sclerosing cholangitis, and in 43.7% with chronic hepatitis C. Biliocytes showed apoptosis in only 3 cases of primary biliary cirrhosis. Biliocytes showed a strong cytoplasmic expression in 4 cases (1 primary biliary cirrhosis, 2 primary sclerosing cholangitis and 1 chronic hepatitis C). A few intralobular and portal inflammatory mononuclear cells expressing tumour necrosis factor alpha were observed in 62.5% of patients with primary biliary cirrhosis, 46.1% with primary sclerosing cholangitis, and 56.2% with hepatitis C virus chronic hepatitis. The amount of intraportal mononuclear cells expressing Ki-67 antigen was significantly higher in primary biliary cirrhosis specimens than in primary sclerosing cholangitis (p<0.001) or hepatitis C virus-related chronic hepatitis (p<0.03). No correlation was found within the 3 groups of patients between the Ki-67 histological score and the severity of liver disease. Moreover, no relationship was found between TdT-mediated deoxyuridine triphosphate nick-end labelling and either tumour necrosis factor alpha or Ki-67 staining. CONCLUSIONS: Apoptosis is a phenomenon which frequently involves hepatocytes in chronic autoimmune cholestasis. This process is apparently parallel, but unrelated to cell proliferation. Cell proliferation mainly involves mononuclear cells in portal tracts of primary biliary cirrhosis specimens. The finding of tumour necrosis factor alpha expression in biliocytes deserves further study to establish whether this cytokine is involved in triggering bile duct lesions.

Descriptive epidemiology of non-Hodgkin's lymphoma in the province of Padova, 1970-1974.

The age-standardized incidence rates of non-Hodgkin's lymphoma in the province of Padova during the period 1970-1974 were 3.19/10(5)/year for males and 1.60/10(5)/year for females. These rates are similar to those found in other industrialized countries and slightly higher than in the province of Torino. An increasing trend with age is described, beginning in the age group 35-44, while low rates were found in younger ages in both sexes. No relevant pattern was shown in the geographical distribution of cases, and no observed/expected ratio was significant in any of the administrative districts considered. The influence of environmental factors and the limitations due to uncertain diagnostic criteria and the small size of the population considered are discussed.

[Histopathologic and ultrastructural study of tumors induced by murine sarcoma virus (msv) (author's transl)]. / Studio istopatologico e ultrastrutturale dei tumori indotti da virus del sarcoma murino (MSV)

Various growth phases of Moloney murine sarcoma virus (M-MSV) induced tumors in suckling and young adult BALB/c mice have been studied by light and electron microscopy. In the early phase (3-6 days following M-MSV), observations at the injection site of the thigh muscles consisted of endo- and perimysial edema "activated" muscle satellite, cells, endothelial cells and fibroblasts, scattered type C virus particles within the muscle fibers, muscle fibers and endomysial cells undergoing necrosis and macrophage and granulocyte infiltration. During the overt tumor phase (6-12 days following M-MSV), observation of neoplastic tissue disclosed proliferation of several cell type (endothelial, periosteal, fibroblasts, etc.), poorly differentiated myoblasts along with atypical rhabdomyoblast-like cells and sarcolytes, type C virus budding from muscle fiber and myoblast plasma membrane, and intense degenerative and regenerative changes in the muscle fibers together with more profuse granulocyte infiltration. The regressive phase (13-21 days following M-MSV) presented reduced cellularity of the neoplastic tissue, a decrease in blast cells, diminishing granulocyte infiltration with contemporaneous appearance of prominent lymphocyte foci and gradual disappearance of virus particles. Although many cell types of mesenchymal origin proliferate following M-MSV infection, the above morphological findings indicate that striated muscle is a preferential site for virus replication and transformation. Furthermore, the peculiar virus cell relationships leading to cell lysis and continuous recruitment of newly infected cells have been widely documented. In the light of these findings it is suggested that, besides the host immune control of virus spread and tumor cell multiplication, the non clonal growth pattern of M-MSV induced tumors is a crucial factor in determining the spontaneous regression which occurs with high frequency in this experimental system.

Chondromyxoid fibroma of the iliac bone: a case report with ultrastructural observations.

Ultrastructural findings in an unusual case of chondromyxoid fibroma are reported. The tumor was located in the iliac bone of a 42-year-old woman with left hip pain of 5 years duration.

The extent of surgery for thyroid medullary cancer.

AIMS: Evaluation of the impact of the extent of primary surgery and reintervention on the outcome of patients with medullary thyroid carcinoma. METHODS: Seventy-two patients with medullary thyroid carcinoma (MTC) were surgically treated between 1967 and 1992. RESULTS: Fifty-five cases were sporadic, 5 patients had MEN 2A, 4 MEN 2B syndrome and 8 familial non-MEN MTC; 1 patient had stage I disease, 30 patients stage II, 36 stage III and 5 stage IV. Sixty-four had their initial treatment at our center, and 8 came for subsequent treatment. At first treatment, 8 patients were subjected to partial thyroidectomy, 10 to total thyroidectomy, 53 to total thyroidectomy with neck dissection, and 1 to only radical neck dissection; postoperative serum calcitonin (Ct) levels returned to normal in 3, 6 and 27 patients, respectively. In the patient with only radical neck dissection, Ct levels remained elevated. No patient with Ct normalization after surgery became responsive to pentagastrin in the follow-up. Thirteen patients had a reoperation due to nodal relapse. At a mean follow-up of 5.7 years (6-252 months), the 10-year survival rate was 84.5% with a significant difference between patients under and over 40 years of age (96.4 vs 57%), between stage I-II (100%) and stage III, IV (83.8%, 0% respectively). At the last follow-up, 36 (50%) patients were alive and disease free and 26 were alive with disease (15 with distant metastases). Of the 10 deaths, 7 were due to tumor recurrence, 3 to 120 months after surgery. CONCLUSIONS: Data suggest that an earlier diagnosis rather than more extensive surgery could improve survival and reduce recurrences. However, the least treatment required is total thyroidectomy plus central neck and upper mediastinum clearance and in addition, according to the extent of nodal involvement, mono- or bilateral neck dissection. To avoid ineffective reoperation due to distant (mainly liver) micrometastases, persistent residual microscopic disease requires a more aggressive restaging.

Fine-needle aspiration cytology of malignant nerve sheath tumors.

Precise preoperative diagnosis of three malignant nerve sheath tumors (MNST) was based on their remarkably uniform and highly characteristic cytologic appearance. The differential diagnosis with benign nerve sheath tumors and other spindle cell sarcomas is addressed, and the possibility of achieving confident diagnosis on cytologic material from at least some soft-tissue sarcomas is confirmed.

Recurrent synovial cyst of deep soft tissues. A case report.

BACKGROUND: Cystic lesions of deep soft tissues are rare and usually are composed of a mesenchymal tumor undergoing necrosis or regressive changes. Benign cysts arising de novo are even more rare and may show features of different morphology, potentially leading to an inexact diagnosis. CASE: A 68-year-old male presented with a deep, firm mass in the upper part of the back from which a dense liquid was aspirated, with an inconclusive diagnosis. A second fine needle aspiration was performed, and the lesion was surgically biopsied. Immunohistochemical studies were also inconclusive, while ultrastructural studies suggested an origin in the synovia of the scapular bursa. CONCLUSION: The cytologic picture was suspicious for malignancy due to the presence of numerous pseudopapillary structures, reminding us of a secondary deposit from a renal or thyroid primary or mesenchymal neoplasm. However, the bland nuclear aspect suggested the benignity of the lesion, and the electron microscopic features confirmed the synovial origin.

Juvenile pilocytic astrocytoma of the optic nerve diagnosed by fine needle aspiration biopsy.

Fine needle aspiration biopsy of an orbital mass was performed under CT guidance in a nine-year-old boy presenting with rapidly increasing proptosis of the right eye with lateral displacement and no light perception. The cytologic findings consisted of bipolar astrocytes with cytoplasmic fibrillated processes intermingled with Rosenthal fibers. A cytologic diagnosis of juvenile pilocytic astrocytoma was advanced; this was confirmed by subsequent histologic study of the surgical specimen. The differential diagnosis among juvenile pilocytic astrocytoma, neurilemmoma and meningioma of the optic nerve are discussed.

Fibergastroscopic study of early and advanced gastric cancer in a series of 8,000 consecutive patients.

Eight cases of early gastric cancer (EGC) (histological diagnosis on the resected specimens) were detected Type III (excavated; seven out of eight cases). In three endoscopies. They constituted 3.3% of the gastric cancers observed (239 cases). The most frequent type of EGC was Type III (excavated: seven out of eight cases). In three patients the diagnosis was made only at a second examination, since the first had been negative for malignancy; at the follow-up examination in these cases, the lesion seemed to have healed. The operation was therefore carried out only on the basis of the histological interpretation of endoscopic biopsies.

Long-term survival in response to combined chemotherapy and radiotherapy in laryngeal small cell carcinoma.

Fourteen patients with small cell carcinoma of the larynx are studied. This represents the largest series, from a single institution, reported in the literature. This neoplasm is usually highly aggressive and the prognosis very poor, but, in our experience, combined chemo- and radiotherapy can significantly improve the clinical course of the disease. Three of six patients who received this combined modality treatment are still clinically disease-free more than six years after the initial diagnosis.

[Bilateral synovial chondromatosis of the first metatarsophalangeal joint: a case report. ]. / Su di un caso di condromatosi sinoviale bilaterale della prima metatarso-falangea.

Synovial chondromatosis is a rare pathology of unknown aetiology. It originates from the chondroid metaplasia of the connective tissue of the synovial membrane. Consequently, cartilaginous nodules develop in the affected joints, first calcifying and then ossifying. The bursae mucosae, the vaginae tendinis and the para-articular connective tissue are less frequently affected. The most common locations of this pathology are the knee, the hip, the shoulder, the elbow and the ankle. The small joints are rarely affected, even less the bilateral involving of joints, above all of hand or foot, is exceptional. In a clinical and radiological valuation, it is difficult to distinguish synovial chondromatosis from osteoarthritis and from degenerative arthopathies in general. A sure diagnosis can be obtained only by means of a histological examination. We here report a case of synovial chondromatosis bilaterally located on the first metatarsophalangeal joint. Clinical and radiological features were similar to those of hallux rigidus, a typical and peculiar metatarsophalangeal joint pathology. The diagnostic suspicion arose during surgery, and was subsequently confirmed by histological examination. During the following visits, the patient did not present any painful symptomatology.