Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients.

AIMS: Metaplastic spindle cell carcinomas may be difficult to distinguish histologically from other spindle cell lesions in the breast. Variable staining with cytokeratin immunomarkers has been reported for metaplastic carcinomas. We evaluated the diagnostic utility of anti-cytokeratin polyclonal antibody, wide spectrum screening keratin, to assess spindle cell breast lesions. METHODS AND RESULTS: Twenty-four patients with spindle cell breast carcinoma and 31 patients with benign or malignant spindle cell tumours were studied using a panel of antibodies directed against multiple cytokeratins (AE1/AE3, CAM5.2, wide spectrum screening keratin), epithelial membrane antigen (EMA), and vimentin. Sites of origin for the 31 controls included breast, bone, and soft tissue. All but one (95.8%) metaplastic carcinomas stained positively with wide spectrum screening keratin. Only rare or focal immunoreactivity was observed with AE1/AE3 in four cases; however, sensitivity of AE1/AE3 was improved in 13 cases using steam EDTA as an antigen retrieval technique. Three cases were immunoreactive with CAM5.2 and eight cases were immunoreactive with EMA. All control cases lacked immunoreactivity with the cytokeratin panel and EMA. The spindle cells in the metaplastic breast tumours (88%) and in the controls (97%) stained with vimentin. CONCLUSIONS: Wide spectrum screening keratin may be the most useful and convenient antibody in differentiating metaplastic spindle cell carcinoma from other spindle cell lesions in the breast.

Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type.

We reviewed pathologic, phenotypic, and clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type primarily involving lung to address unresolved questions regarding behavior and pathologic features of unambiguously diagnosed pulmonary MALT lymphoma. Lung specimens from 50 patients were reviewed. Forty-one had low-grade MALT lymphoma. Nine had low-grade MALT lymphoma and diffuse large B-cell lymphoma. The patients included 32 women and 18 men with a median age of 68 years (range 34-88 years). Half of the patients were asymptomatic at the time lymphoma was diagnosed. Radiographic abnormalities were more commonly unilateral (37 patients) than bilateral (12 patients). Localized masses or nodules occurred in 39 patients. Associated autoimmune disorders (29%) and monoclonal gammopathies (43%) were common. Low-grade lymphomas formed intraparenchymal masses composed of centrocyte-like cells, plasmacytoid lymphocytes, and plasma cells that formed lymphoepithelial lesions and exhibited a lymphangitic growth pattern. Mediastinal lymph nodes were involved histologically in 44% of cases. Lymphoma-specific survival was 71.7% at 10 years, and overall survival was significantly worse than age-and gender-matched control patients. None of the following features predicted those patients who had an adverse outcome: systemic symptoms, presence of autoimmune disorders or paraproteinemia, anatomic distribution and number of pulmonary lesions, lymph node involvement, or presence of anthracycline-treated large B-cell lymphoma.

Primary non-Hodgkin's lymphoma of the lung.

BACKGROUND: Primary non-Hodgkin's lymphoma of the lung is a rare entity. Although the prognosis is favorable, clinical features, prognostic factors, and patient management have not been clearly defined. METHODS: We reviewed retrospectively the records of 48 patients operated on for primary pulmonary non-Hodgkin's lymphoma. The study group consisted of 21 male (44%) and 27 female (56%) patients with a mean age of 61.8 years. Thirty-seven and a half percent of patients were asymptomatic, and 62.5% were seen with pulmonary symptoms, systemic symptoms, or both. A definitive diagnosis was obtained by thoracotomy in 90% of patients, thoracoscopy in 8%, and anterior mediastinotomy in 2%. RESULTS: Complete surgical resection was possible in 19 patients (40%). A mucosa-associated lymphoid tissue lymphoma (MALT) was found in 35 patients and lymphoma that was not of this type, in 13. The 1-year, 5-year, and 10-year survival rates were 91%, 68%, and 53%, respectively in the group with mucosa-associated lymphoid tissue lymphoma and 85%, 65%, and 64% in the group with lymphoma that was not of the mucosa-associated lymphoid tissue type. None of the prognostic factors studied (mode of presentation, smoking history, bilateral disease, postoperative stage, complete resection, adjuvant chemotherapy, histology) significantly influenced patient survival. CONCLUSIONS: Primary non-Hodgkin's lymphoma of the lung occurs with nonspecific clinical features. Although patient survival is good, prognostic factors could not be identified.

Meningioma metastatic to the lung.

Meningiomas constitute 15% to 18% of all primary intracranial and intraspinal tumors. Distant extracranial metastases are reported to occur in fewer than 1 in 1000 cases. Of 1992 primary intracranial meningiomas seen at Mayo Clinic Rochester from 1972 through 1994, we identified 3 (0.15%) with documented extracranial metastasis. A review of the literature suggests that previous craniotomy, venous sinus invasion, local recurrences, histological malignancy, and papillary morphology may be risk factors for systemic spread, as demonstrated in our cases. Although rare, metastatic meningioma should be considered in the differential diagnosis of abnormal findings on chest radiography in patients with known or suspected intracranial meningioma.

Paneth cell-like change in prostatic adenocarcinoma represents neuroendocrine differentiation: report of 30 cases.

Paneth cell-like change (PCLC) of the prostatic epithelium is considered to be a distinct form of neuroendocrine differentiation characterized by isolated cells or small groups of cells with prominent eosinophilic cytoplasmic granules. We evaluated 300 serially sectioned radical prostatectomy specimens from patients with prostatic adenocarcinoma who had not received prior adjuvant therapy (pathologic stages T2NOMO [177 patients], T3NOMO [100 patients], and TxN1MO [23 patients]). Paneth cell-like change was identified in 30 cases (10%), ranging from 1 to 20 high-power fields/positive case (mean, 4.1 high-power fields/case). There was no correlation of PCLC with prostate volume, prostate weight, Gleason grade, nuclear grade, lymph node metastases, serum prostate-specific antigen levels, cancer volume, area or presence of capsular perforation, seminal vesicle invasion, or glandular mucin (all P > .05), although a positive correlation was seen with cribriform pattern (r = 0.50, P = .0015). Immunohistochemistry revealed cytoplasmic immunoreactivity within cells of PCLC for chromogranin (seven of seven cases), neuron-specific enolase (seven of seven cases), serotonin (six of seven cases), prostate-specific antigen (five of seven cases), and prostatic acid phosphatase (four of seven cases); lysozyme was negative (seven cases). Our findings indicate that PCLC is more common than previously reported, but that it is not associated with tumor grade, serum PSA levels, or pathologic stage. This study also shows that PCLC represents neuroendocrine differentiation, suggesting that the term "Paneth cell-like change" be deleted from the pathologist's lexicon in relation to prostatic adenocarcinoma; a more appropriate term might be "neuroendocrine cells with large eosinophilic granules."

Effect of carcinogen dose and age at administration on induction of mammary carcinogenesis by 1-methyl-1-nitrosourea.

The objective of the work reported in this paper was to determine if the tumorigenic response to 1-methyl-1-nitrosourea (MNU) in the mammary gland varied with age of administration and was dose dependent when the carcinogen was injected prior to 50 days of age. Using a recently developed method for mammary tumor induction, MNU was injected i.p. at doses ranging from 25 to 75 mg/kg at 35 days of age or 50 mg/kg at 28, 35 or 42 days of age. Treatment with MNU resulted in induction of both benign and malignant mammary tumors. The incidence of mammary gland adenocarcinomas was 100% at and above the 50 mg/kg dose of MNU, irrespective of the age at which carcinogen was administered. The number of cancers increased in proportion to carcinogen dose, whereas cancer latency decreased as the MNU dose increased. In rats injected with 50 mg MNU/kg body weight at 28, 35 or 42 days of age, differences among groups in cancer incidence, number or latency were not statistically significant. Metastases of mammary neoplasms to lung, liver and spleen were observed in rats injected with MNU at 35 or 42 days of age. These data indicate (i) the dose responsiveness of MNU-induced mammary carcinogenesis in rats initiated prior to 50 days of age; (ii) the lack of effect of age at initiation if prior to 50 days on final tumor outcome; and (iii) that the age at which MNU is injected may affect the metastatic potential of the mammary carcinomas that are induced.

Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1-methyl-1-nitrosourea.

Dose-response relationships for the induction of mammary tumors by a single i.p. injection of 1-methyl-1-nitrosourea (MNU) were studied. Groups of 30 female Sprague-Dawley rats were given i.p. injections of 50, 37.5, 25, 12.5, or 0 mg MNU/kg body weight at 50 days of age. Animals were palpated for tumor detection twice weekly throughout a 28-week observation period. Administration of MNU i.p. caused no acute toxicity. Both benign and malignant mammary tumors were induced by MNU, but malignant tumors appeared earlier and at a faster rate than benign tumors. The incidence and numbers of mammary carcinomas increased whereas median cancer-free time decreased with increasing dose of MNU. Approximately twice as many mammary cancers were observed in the cervical-thoracic as in the abdominal-inguinal mammary gland chains irrespective of carcinogen dose, while the frequency of tumor occurrence in the left versus right chains was similar. Tumor latency decreased with increasing dose of MNU, but the quartiles for time to detection of all tumors within each carcinogen dose group were similar irrespective of anatomical region in which the tumors occurred. The mammary tumor response attained via i.p. injection was similar but the coefficient of variation for tumor multiplicity within a carcinogen dose group was lower in comparison to that observed when MNU was administered i.v. or s.c. Among these techniques for carcinogen injection, the i.p. route is the most rapid method and offers an added advantage of ease of administration with quantitative, reproducible delivery of the desired amount of carcinogen and a decrease in variability of tumor response among animals within a treatment group. This method is well suited for the technically less experienced investigator and for those in need for a rapid method of injecting MNU to large numbers of animals.

Diagnostic value of the maximal ST segment/heart rate slope in asymptomatic factory populations.

In Leeds in hospital populations of patients with angina the maximal ST/HR slope was found to be a reliable index of myocardial ischemia as assessed by coronary angiography. Subsequent studies in Leeds and elsewhere in populations of patients with cardiac enlargement or following myocardial infarction have shown that the slope is affected by myocardial scarring, ventricular enlargement and aneurysm. These findings implied that the slope had features in common with other usual exercise tests; studies in Leeds and elsewhere, however, have shown a superior diagnostic reliability using the maximal ST/HR slope in patients with angina. The present report involves the use of the slope in asymptomatic populations. Trials are being undertaken in two factory populations, which respectively comprised all volunteers or asymptomatic men over the age of 30 who were randomly chosen by computer. Subjects with slope values indicating, according to previous experience, myocardial ischemia equivalent to coronary heart disease were referred for cardiological investigations which included angiocardiography; blind comparisons were performed between results of investigations and the slope. So far 1194 subjects have been examined. In 68 subjects the maximal ST/HR slope indicated myocardial ischemia, and in 24 of these cardiological investigations were completed. In nine of the 24 subjects the slope corresponded to the number of significantly narrowed coronary arteries (greater than 75% reduction in luminal diameter); in 12 of the remaining 15 subjects who had no coronary narrowing, there were cardiac lesions which included cardiac enlargement, aortic valve disease, myocarditis, pericarditis, myocardial bridging and conduction defects.(ABSTRACT TRUNCATED AT 250 WORDS)