Antimyosin scintigraphy for diagnosis and follow-up of patients with clinically suspected myocarditis]

Antimyosin-scintigraphy is believed to have a high specificity but a low sensitivity for the diagnosis of myocarditis when histological analysis of endomyocardial biopsy is used as the reference method. However, the histological evaluation itself seems to have a low sensitivity for the diagnosis of myocarditis. Therefore, immunohistological techniques have been developed for the detection of lymphocytic infiltrates and increased expression of HLA antigens in the myocardium. The present study compares the results of antimyosin-scintigraphy with histological and immunohistological analysis of the endomyocardial biopsy. 65 patients with clinically suspected myocarditis underwent antimyosin-scintigraphy and histological and immunohistological analysis of the endomyocardial biopsy. Myocarditis could be diagnosed histologically in only 9/36 (25%) patients with a positive antimyosin scan but additional immunohistological analysis revealed lymphocytic infiltrates in 31 (86%) of these patients. In 29 patients with a normal antimyosin scan, histological analysis showed evidence of myocarditis in 3 (10%) patients; additional immunohistological evaluation disclosed lymphocytic infiltrates in 17 (59%) patients. With immunohistological analysis of the endomyocardial biopsy as the reference method, antimyosin-scintigraphy has a high sensitivity but a lower specificity for the diagnosis of myocarditis. Detection of autoantibodies against human cardiac myosin in patients with myocarditis is associated with a significantly lower incidence of positive antimyosin scans in these patients. Antimyosin-scintigraphy was repeated after six months in 14 patients with myocarditis. Histological and immunohistological evaluation of the endomyocardial biopsy now showed persistent myocarditis in 3/8 patients with a positive antimyosin scan and in 5/6 patients with a normal antimyosin scan.     

Correlations of C1q- and C3d-bearing circulating immune complexes with immunopathological disease activity in lupus nephritis patients

The serum levels of circulating immune complexes (CIC) measured by three different types of enzyme immunoassay (EIA) using monoclonal anti-C1q and antibodies and C1q as solid phase reagents were compared with clinical disease activity and immunohistological glomerular lesions in 29 SLE patients. Three types of CIC measured by these assays (anti-C1q CIC, anti-C3d CIC and C1q SP CIC) showed significantly higher levels in patients than in controls and were significantly associated with the clinical and serological disease activities. Anti-C1q CIC showed good correlation not only with mesangial IgG depositions (P < 0.01), but also with that of C1q (P < 0.05). C1q SP CIC also showed a weak correlation with mesangial C1q deposition (P < 0.05). Serum levels of anti-C3d CIC increased with the degree of mesangial IgG and complement depositions. Analysis of the clinical course of a patient with active SLE revealed a more rapid decrease of anti-C1q CIC and anti-C3d CIC along with the improvement of disease activity, including the mesangial lesion, than that of C1q SP CIC. According to these results, the CIC detected with assays using monoclonal antibodies against complement fragments, especially the anti-C1q assay, is likely to provide specific information regarding the clinical, serological and immunohistological disease activity in lupus nephritis.     

Temporal lobe epilepsy and ganglioglioma in children. Clinical aspects, imagery and neuropathology; nosological discussion of six cases

BACKGROUND: Gangliogliomas belong to debated nosological entity. They are classified as neuronal or neuroglial tumors. PATIENTS AND METHODS: Six children aged from 4 months to 15 years (mean age: 4 years and 6 months) were initially seen for partial seizures resistant to treatment. Tumoral resection was performed in all six. Diagnosis was made from immunohistological study of the tumor. DISCUSSION: Gangliogliomas are non-malignant, with a good prognosis, even if inaugural clinical manifestations are severe. Neuroradiological diagnosis with astrocytomas and cortical dysplasia is not easy, and pathological distinction from cortical dysplasia is difficult. CONCLUSION: The immunohistochemical confirmation of diagnosis permits a logical therapeutic attitude: complete resection of tumor is followed by an excellent outcome.     

Juvenile hyaline fibromatosis

BACKGROUND: Juvenile hyaline fibromatosis is a sporadic hereditary disease with autosomal recessive mode of inheritance, characterized by the presence of nodules and tumours in the skin and soft tissues and gingival hyperplasia. The majority of patients are growth retarded, suffer from joint disorders, contractures, osteolytic lesions and have a positive family history. The disease most frequently occurs in children, but may be diagnosed also in adults. Since 1873, when the disease was described by Murray, only a few cases were introduced in the literature. THE AIM AND THE BASIS OF THE STUDY: To present the clinical pattern of a patient diagnosed at the age of 28 and describe also the histopathological, immunohistological and electron-microscopic findings of excisions from the lesions. METHODS: The pathologist in cooperation with clinicians from several disciplines established the diagnosis on the basis of typical histopathological picture and additional immunohistological tests not yet introduced in the literature. RESULTS: Tumorous lesions contained hyaline structureless matrix often with chondroid or even osteoid metaplasia, calcium salts. The matrix contained numerous fibroblastoid-like cells with eosinophilic cytoplasm, oval nucleus and often pericytoplasmic halo. ELMI investigation revealed dilated cisternae of rough endoplasmic reticulum and hypertrophic Golgi apparatus. Sporadically were particles with calcium salts density detected. Immunohistochemical tests revealed the expression of vimentin, alfa1-antitrypsin and alfa1-antichymotripsin by the tumorous cells. CONCLUSION: The authors presented an extremely sporadic childhood disease in an adult. The results are in accordance with the data from the literature. Immunohistochemical picture of "cementicles" has not yet been introduced in the available literature. (Fig. 12, Ref. 25.)     

Angiosarcoma of the nasal septum

This is a report on a female patient, 37 years old, with a polypous, sessile tumor on the nasal septum covered by smooth mucous membrane. She was treated with local excision. The histological diagnosis was an angiosarcoma, confirmed by immunohistological stain with factor VIII-like antigen, thrombomodulin, and UEA. She currently remains free of the disease 12 months after diagnosis. Angiosarcoma in the head and neck area and especially the localization in the nasal septum are extremely rare. Prognosis, differential diagnosis, metastasis formation, and therapy of this tumor are presented.     

Treatment of poison ivy/oak allergic contact dermatitis with an extract of jewelweed

A case of precursor B-cell lymphoma of unusual location in the mandible is presented. Clinical features as well as technical examinations led to the misdiagnosis of chronic osteomyelitis. Only immunohistological examination of intraoperatively taken biopsies was able to reveal the true diagnosis. High-dose chemotherapy was started and full remission could be achieved.     

Primary plasmacytoma of the thyroid: a case report and comparative literature study between Western nations and Japan

A 52 year old man presented with primary thyroid plasmacytoma. The patient was initially followed up for thyroid dysfunction. The histological examination of the removed thyroid revealed a proliferation of mature and immature plasma cells indicative of plasmacytoma with Hashimoto's disease. After radiotherapy (40 Gy) to the neck following right hemi-thyroidectomy, the patient is currently alive and well 3 years after diagnosis without any evidence of tumor. The immunohistological examination of the removed thyroid showed monoclonality for immunoglobulin G-Kappa light chains. Sixty-six literature cases of primary thyroid plasmacytoma were reviewed and comparison of the clinical and histological characteristics between Japanese and Western cases noted. The incidence of the patients with antithyroid antibody was significantly lower (P < 0.01) in Western patients (42.9%) than in Japanese patients (87.5%). The higher incidence of thyroid dysfunction and Hashimoto's disease in Japan in comparison with Western nations was well reflected in the incidence of antithyroid antibody.     

Traumatic dislocations of the lesser toes

Meningiomas are common lesions in adults but unusual in infancy and meningiomas located in the posterior cranial fossa are even more rare. Metaplastic changes of meningothelial meningiomas can lead to the rarely observed xanthomatous form. We describe the case of a posterior pyramid xanthomatous meningioma in a 2-year-old girl. After detailed neuroradiological evaluation, the histological diagnosis was confirmed with the aid of immunohistochemical evaluation. A critical case evaluation in the light of the more recent literature, the surgical strategy and technique, and an immunohistological hypothesis are reported.     

Cathepsin D expression in skin metastasis of breast cancer

Cathepsin D, an aspartic proteinase, correlates with invasion and metastasis in breast cancer and with poor prognosis. In the present study, we examined the immunohistological expression of cathepsin D in both primary (5 cases) and skin-metastatic breast cancers (13 cases) and compared it to those in gastric (2 cases) and lung (4 cases), and primary eccrine cancers (3 cases). All breast and gastric cancers were adenocarcinomas. The 2 gastric cancers were poorly differentiated, while the 4 lung cancers consisted of 2 poorly differentiated adenocarcinomas, 1 poorly differentiated large cell carcinoma, and 1 moderately to poorly differentiated squamous cell carcinoma. We also surveyed the immunohistological distribution of cathepsin B, carcinoembryonic antigen, gross cystic disease fluid protein-15, c-erbB-2, and estrogen receptor. In almost all breast cancer samples, the cancer cells demonstrated strong expression of cathepsin D in the cytoplasm, but weak staining patterns with other antibodies. Gastric and lung cancer cells did not respond with cathepsin D (except one metastatic lung cancer) or the other immunohistological markers. Since cathepsin D is strongly expressed in primary and metastatic lesions of breast cancer, cathepsin D could be useful as an adjunct to a panel of immunohistochemical stains in determining the primary site of origin of metastatic cancer in the skin.     

Pulmonary cavernous hemangioma--identification of its endothelial cell origin by immunohistological staining

A 45-year-old woman was referred to our hospital because of a tumorous shadow in the S10 segment of the left lung. A chest computed tomography (CT) scan showed a nodular lesion with a slightly irregular margin and no contrast enhancement. CT-guided aspiration biopsy was tried but did not result in a histological diagnosis. The tumor was excised during video-assisted thoracoscopic surgery. Histological examination of the specimen revealed cavernous hemangioma. Most cells lining the lumen of the cavernous structure stained positively for von Willebrand factor antibody and negatively for anti-epithelial membrane antigen antibody, which suggests that the tumor was associated with endothelium. To the best of our knowledge, this is the first report of a case in which the diagnosis of pulmonary cavernous hemangioma was confirmed with an immunohistological study.     

Intrauterine growth and ultrasound findings in fetuses with Beckwith-Wiedemann syndrome

A 64-year-old man with a 5-year history of progressive systemic sclerosis (PSS) was hospitalized because of melena. Radiological and endoscopic examinations showed an ulcerative lesion with sharply demarcated and raised margins in the fornix of the stomach. Tumor markers--serum carcinoembryonic antigen (CEA, 11.3 mg/ml) and neuron-specific enolase (NSE, 38.9 ng/ml) were elevated. Histological examination of endoscopic biopsy specimens (and of necropsy specimens) showed proliferation of atypical small round cells. Immunohistological examination of these cells showed they were positive for epithelial membranous antigen (EMA), and neuron-specific enolase (NSE), but negative for UCHL1, leukocyte common antigen (LCA), anti-leukocyte B-cell (MB1), and anti-leukocyte T-cell (MT1) antigens. Based on these histological and immunohistological tests, a definite diagnosis of small cell carcinoma of the stomach with PSS was established. Our case is a rare combination of PSS and gastric small cell carcinoma. We also reviewed the literature for the association between PSS and gastric cancer in Japanese patients.     

Very low birthweight infants: outcome in a sub-Arctic population

We have previously described the cloning and sequencing of a gene portion coding for the terminal part of a 34-kDa protein of Mycobacterium avium subsp. paratuberculosis, the etiological agent of Johne's disease (P. Gilot, M. De Kesel, L. Machtelinckx, M. Coene, and C. Cocito, J. Bacteriol. 175:4930-4935, 1993). The recombinant polypeptide (a362) carries species-specific B-cell epitopes which do not cross-react with other mycobacterial pathogens (M. De Kesel, P. Gilot, M.-C. Misonne, M. Coene, and C. Cocito, J. Clin. Microbiol. 31:947-954, 1993). The present work describes the preparation of polyclonal and monoclonal antibodies directed against a362 and the use of these immunoglobulins for histopathological diagnosis of Johne's disease. The new immunohistological procedures herewith detailed proved to be able to identify M. avium subsp. paratuberculosis antigens in the intestinal tissues and lymph nodes of cattle affected by either the paucibacillary or pluribacillary form of the disease. They yielded negative responses not only with healthy animals but also with those affected by tuberculosis (Mycobacterium bovis). Both immunohistological procedures proved to be as sensitive as or more sensitive than Ziehl-Neelsen staining and, in addition, to be endowed with species specificity.     

Sarcomatoid carcinomas of the lung: a clinicopathologic review

Sarcomatoid carcinomas (SC) of the lung are the most common pulmonary neoplasms that exhibit a composition by spindled or pleomorphic tumor cells. As such, many of them may be confused easily with true sarcomas diagnostically unless special immunohistological or ultrastructural analyses are performed. Reactivity is expected for keratin, epithelial membrane antigen, or collagen type IV in the sarcomalike elements in SC, although it may be focal. Electron microscopy often shows the presence of junctional complexes between tumor cells, with or without pericellular basal lamina and cytoplasmic skeins of intermediate filaments. Current terminological preferences are such that several formerly used terms--including "spindle-cell carcinoma," "pulmonary blastoma," "squamous cell carcinoma with pseudosarcomatous stroma," "pseudosarcoma," and "carcinosarcoma"--are now encompassed by the more generic designation of "sarcomatoid carcinoma." The clinical course of patients with this neoplasm is aggressive, with an overall 5-year survival rate approximating 20%.     

Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease

BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. METHODS: We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. RESULTS: Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. CONCLUSIONS: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.     

Nosological comparisons of DSM-III-R and DSM-IV alcohol abuse and dependence in a clinical facility: comparison with the 1988 National Health Interview Survey results

The purpose of this study was to compare DSM-III-R and proposed formulations of DSM-IV diagnoses of alcohol use disorders in a clinical sample with the same assessment methods used in a large national survey previously reported. Issues included the number of symptoms required for abuse and dependence diagnoses, the effects of requiring evidence of physiological dependence to make the dependence diagnosis (Option 1 vs. Option 2), whether to require a duration criterion, and the concept of alcohol abuse. The diagnostic criteria proposed in the 1991 DSM-IV options book were the criteria investigated in this study. Concordance between DSM-III-R and DSM-IV was closest when the form of DSM-IV used was most similar to DSM-III-R. The duration criterion had much less effect on a dependence diagnosis in this clinical sample than in the general population. DSM-IV Option 2 for alcohol dependence excluded a number of cases from the dependence diagnosis who received such a diagnosis under DSM-III-R and DSM-IV Option 1. Abuse continued to function as a residual category, especially noticeable under increasingly restrictive definitions of dependence, and was rare in both the clinical and general population sample. Implications of the findings for research and other purposes are discussed.     

Expression of endothelin-1 in amniotic fluid embolism and possible pathophysiological mechanism

Since endothelin is a potent vasoconstrictor and bronchoconstrictor, endothelin-1 expression in the lung was investigated using immunohistological techniques in two cases of amniotic fluid embolism. Intense expression of endothelin-1 was observed in amniotic squames while weaker staining was seen in alveolar epithelium, bronchiolar epithelium and intraalveolar macrophages and focally in vascular endothelium. Endothelin-1 may play a role in the early and transient haemodynamic alteration of pulmonary hypertension in amniotic fluid embolism.     

Lattice corneal dystrophy type II associated with familial amyloid polyneuropathy type IV

BACKGROUND: Finnish-type familial amyloidosis (FAP-IV) is an autosomal, dominantly inherited disorder characterized by progressive polyneuropathy and lattice corneal dystrophy type II. The vast majority of families with this disorder originated from Finland. Only two families, in neighboring districts, have been reported in Japan previously. METHODS: The authors report two additional Japanese patients with FAF-IV. The proband, a 70-year-old man, had decreased perspiration and abnormal facial muscle movement. Results of neurologic examination showed bilateral facial and hypoglossal nerve palsies, and an autonomic disturbance, including orthostatic hypotension and dysfunction of perspiration. Histochemical, immunohistological, and DNA studies confirmed the diagnosis of FAP-IV. RESULTS: Results of ophthalmologic examination showed asymptomatic lattice corneal dystrophy of both eyes, but the appearance of the cornea was different from that described in the patients from Finland. Lattice lines in the authors' patient were very fine, short, and glassy and could be observed with indirect retroillumination, but might be missed with direct illumination by the slit-lamp microscope. The proband's younger half-sister, a 68-year-old woman, showed clinical findings and laboratory data similar to those of the proband. CONCLUSION: The authors report two Japanese patients with lattice corneal dystrophy type II related to FAP-IV. This is the third Japanese family with this disorder, and there is no familial relationship to the two previously reported families in Japan.     

Specificity of antibodies to nitric oxide synthase isoforms in human, guinea pig, rat, and mouse tissues

Ten commercially available rabbit polyclonal anti-NOS antibodies were tested for their immunohistological applicability in normal human, guinea pig, rat, and mouse organs. Most antibodies reacted as expected and described in the literature with various tissues of the investigated species. Several antibodies did not react with the expected cell populations in a certain species, or reacted in previously unknown patterns. In addition, different antibodies to the same isoform rarely detected identical cell populations, even within one species. Most of these unexpected immunoreactivities were observed in bronchial epithelial, glomerular epithelial, and vascular smooth muscle cells. These unexpected results usually occurred when the antibodies were tested in other organs or species than that to which they were originally raised. We therefore strongly recommend the use of anti-NOS antibodies only after careful immunohistological and biochemical analysis of their reactivity in the organ and species to be studied.