Pleural Biopsy Specimens Research Articles

Immunohistochemical analysis of the p16INK4 cyclin-dependent kinase inhibitor in malignant mesothelioma.

The identification in 1994 of the CDKN2 gene as a target for mutations in a wide range of human cancers, including malignant mesothelioma, has been controversial because subsequent studies have detected a lower frequency of CDKN2 gene mutations in primary tumors than in cultured cell lines. These reports raised the hypothesis that another gene, distinct from CDKN2, might be the target of the chromosome 9p21 deletions frequently observed in these tumors. To address whether inactivation of CDKN2 function is an essential event in the etiology of malignant mesothelioma, we examined p16INK4 protein expression in primary thoracic mesotheliomas, in nonmalignant pleural tissues, and in independent mesothelioma cell lines. We also studied the growth rate of tumor cell lines following stable transfection of CDKN2 gene. Retinoblastoma (Rb) and p16INK4 protein expression was determined by immunohistochemical analysis from archival paraffin specimens of 12 primary thoracic mesotheliomas and a nonmalignant pleural biopsy specimen. In addition, protein immunoblot analysis for Rb and p16INK4 expression was conducted on 15 independent mesothelioma cell lines, and the ability of a transfected CDKN2 gene to suppress the growth of the mesothelioma cell lines H2373 and H2461 in vitro was examined. We demonstrated abnormal p16INK4 expression in 12 of 12 primary mesothelioma specimens and in 15 of 15 mesothelioma cell lines. All tumor specimens and the tumor cell lines showed expression of wild-type Rb protein. In addition, we have confirmed the ability of a transfected CDKN2 gene to suppress growth of two independent mesothelioma cell lines. Immunohistochemical analysis of the p16INK4 gene product is feasible in archival biopsy samples. With this analysis, CDKN2 gene inactivation can be determined in tumors that are contaminated with nonmalignant cells. Furthermore, since loss of p16INK4 protein expression can result from both genetic (gene mutations) and epigenetic (abnormal DNA hypermethylation) mechanisms, as we and others have shown recently, examination of protein expression is a highly sensitive method for analyzing the CDKN2 status in large numbers of tumor samples. This study suggests that inactivation of the CDKN2 gene is an essential step in the etiology of malignant mesotheliomas. Defining the role of the p16INK4:Rb tumor suppressor pathway and its immediate downstream substrates will be an important goal in designing future therapeutic strategies.

The value of immunohistochemistry of pleural biopsy specimens in the differential diagnosis between malignant mesothelioma and metastatic carcinoma: Grove A, Paulsen SM, Gregersen M. Institute of Pathology, Holstebro Central Hospital, DK-7500 Holstebro. Pathol Res Pract 1994; 190:1044–1055

The value of immunohistochemistry of pleural biopsy specimens in the differential diagnosis between malignant mesothelioma and metastatic carcinoma: Grove A, Paulsen SM, Gregersen M. Institute of Pathology, Holstebro Central Hospital, DK-7500 Holstebro. Pathol Res Pract 1994; 190:1044–1055

The Value of Immunohistochemistry of Pleural Biopsy Specimens in the Differential Diagnosis between Malignant Mesothelioma and Metastatic Carcinoma

The aim of the present study was to evaluate the aid of immunohistochemistry in the differential diagnosis between pleural malignant mesothelioma (MM) and secondary pleural carcinoma in pleural biopsy specimens. A series of MM (epithelial or biphasic type) (n = 39), and a series of secondary pleural carcinomas (n = 25) were studied with a panel of monoclonal antibodies against Ber-EP4, CEA, and Leu-MI (CD-15). Considering the markers one, two or three at a time, computer analysis was conducted to identify the immunophenotype with the highest sensitivity and specificity for both MM (n = 39) and adenocarcinoma (n = 19). The CEA/CD-15 marker combination had the highest specificity (MM = 100%; adenocarcinoma = 82.1%), and sensitivity (MM = 82.1%; adenocarcinoma = 100%) considering both categories of tumours. Positive reaction for CEA and/or CD-15 was the best indicator of metastatic adenocarcinoma. Negative reaction for CEA/CD-15 and Ber-EP4/CD-15 showed up to be 100% specific for MM. Positive reaction for one, two or even all these antigens, however, occurred in nine tumours predetermined as MM according to their gross appearance, and absence of other primary malignancies at autopsy. Ultrastructural examination (n = 7) of these tumours strongly supported the diagnosis in one case, and did by no means exclude the diagnosis MM in the other six cases. Neither did any of the tumours reveal ultrastructural signs of adenomatous differentiation, and they did not express PAS/diastase resistant globules, amylase or surfactant. Anti -Ber-EP4 was the antibody most frequently expressed in MM (n = 8). Until antibodies specific for MM are available, the limitation of immunohistochemistry to solve the diagnosis in all cases of pleural malignant tumours has to be considered.

Environmental Airborne Tremolite Asbestos Pollution and Pleural Plaques in Afghanistan

A 51-year-old man underwent pleuroscopy for radiologic pleural abnormalities. Pathologic examination of pleural and lung biopsy specimens concluded on hyalinized pleural plaques associated with mild asbestosis. Transmission electron microscopy analysis showed significant retention of tremolite asbestos fibers. The absence of any occupational exposure to asbestos and the existence of geologic deposits of tremolite in the Kabul area of Afghanistan suggest an environmental exposure during the patient's childhood spent in this region.

Mycobacterial Infection in Renal Transplant Recipients: A Delphi Survey

Study objective: To determine the prevalence and presentation of mycobacterial infection as well as the influence on outcome in graft function and patient survival in renal transplant recipients at our institution. Design: A retrospective review of case records of all renal transplant recipients from 1980 to 1992. Setting: Groote Schuur Hospital, a large teaching hospital and regional tertiary referral center in Cape Town, South Africa. Patients: During the period reviewed, 857 transplants were performed. The records of 487 patients who had remained in Cape Town were examined. Results: There were 22 cases of mycobacterial infection (21 confirmed or presumed Mycobacterium tuberculosis and 1 unidentified Mycobacterium other than tuberculosis). In seven cases, immunosuppression had been intensified within 3 months of diagnosis. The median time from transplantation to diagnosis was 14 months (range, 2 to 74). Chest radiograph findings included consolidation (14), miliary pattern (4), pleural effusion (3), tuberculoma (2), cavitation (2), and hilar lymphadenopathy (1). Diagnosis of tuberculosis was made on sputum smears (eight), pleural biopsy specimen (two), fine-needle aspiration (one), and fiberoptic bronchoscopy in ten cases (brushings, eight; transbronchial biopsy specimen, three). Extrapulmonary tuberculosis (in addition to pulmonary tuberculosis) occurred in five patients (tuberculous meningitis, one; renal tuberculosis, one; and dissemminated infection, four). Five of the seven patients in whom immunosuppression had been intensified had concurrent infections; two of these died and the remainder returned to dialysis within 6 months. All but one patient received three antituberculosis drugs, including rifampin and isoniazid, for between 6 and 18 months. At the end of the period of review, 12 (59 percent) patients were alive, 10 with functioning grafts and 2 receiving dialysis. Four patients died while receiving antituberculosis treatment, but death was only directly related to tuberculosis in one case. Conclusions: Tuberculosis is an important infection in renal transplant recipients in Cape Town, but disseminated disease is less common than reported elsewhere.

P53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens

To determine the utility of positive p53 protein immunostaining as an adjunct in the diagnosis of malignancy in pleural biopsy specimens, we reviewed 73 recently obtained pleural biopsy specimens that represented the typical range of diagnoses encountered in the evaluation of a proliferative pleural process. Immunohistochemistry was performed on paraffin sections of each biopsy specimen using a monoclonal antibody to the p53 suppressor gene product clone BP53-12 (BioGenex, San Ramon, CA) and a standard capillary gap (Microprobe, Fischer Scientific, Pittsburgh, PA) avidin-biotin complex technique with a citrate buffer antigen retrieval solution. Of the pleural biopsy specimens with unequivocal malignancy, 19 of 40 mesotheliomas and nine of 18 metastatic adenocarcinomas were immunopositive for p53 protein. All 13 of the biopsy specimens with reactive mesothelial hyperplasia or organizing pleuritis were negative. Two pleural biopsy specimens, which were interpreted as suspicious but inconclusive for malignancy, were positive for p53 protein and subsequent pathology specimens confirmed the presence of metastatic carcinoma in both of these biopsy specimens. Our findings suggest that p53 protein immunostaining is relatively sensitive and highly specific in differentiating reactive processes from primary or metastatic malignancies in histopathologically equivocal pleural biopsy specimens.

P53 immunostaining in the distinction between benign and malignant mesothelial proliferations using formalin-fixed paraffin sections.

The distinction between reactive mesothelium and mesothelioma in pleural biopsy specimens is notoriously difficult, and conventional immunohistochemical markers have provided no relief. The object of this study was to examine the frequency of immunohistochemically detectable p53 overexpression in routinely processed, paraffin-embedded tissue from pleural mesotheliomas and from pleura showing reactive mesothelial hyperplasia, using a polyclonal antibody to formalin-resistant p53 epitopes, and to consider the diagnostic utility of this antibody in the distinction between mesothelioma and reactive mesothelium in pleural biopsy specimens. Immunostaining was enhanced by pepsin predigestion prior to the application of the primary antibody. Positivity occurred in 10/16 epithelial mesotheliomas, 9/19 biphasic mesotheliomas, 2/12 sarcomatous mesotheliomas but in none of 20 reactive pleura. Immunostaining was particularly intense in some of the biopsy specimens, which may be due to the rapidity with which these small pieces of tissue were fixed. In conclusion, this study suggests that p53 immunostaining can help to distinguish epithelial or biphasic mesothelioma from reactive mesothelial hyperplasia in formalin-fixed, paraffin-embedded pleural biopsy specimens.

Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin

A 33-year-old white man with a history of allergic rhinitis and chronic sinusitis presented with asthma, pleuritic chest pain, marked peripheral eosinophilia, basilar pulmonary infiltrates, and pleural effusions. The patient had accelerating symptoms of asthma for 6 months. Results of a physical examination were within normal limits except for the chest examination that revealed dullness at both bases and diffuse expiratory wheezes. The complete blood cell count was normal except for a white blood cell count of 34,000 cells per microliter with 66% EOSs. The serum rheumatoid factor was 1: 5120, and the serum total IgE was 644 (IUlml). All other laboratory studies, including antinuclear antibodies, total hemolytic complement, and C3 levels, allergy skin tests to Aspergillus, purified protein derivative skin test, stool for ova and parasites, and serologies for filaria and paragonimiasis were within normal limits. The chest x-ray film revealed bilateral patchy basilar infiltrates and pleural effusions. Sinus x-ray films revealed extensive sinusitis. Pleural fluid (obtained by thoracentesis) revealed an exudate with a glucose of 6, a C3 of 25.5 (concomitant serum C3 of 113 mg/dl), a rheumatoid factor titer of 1: 10,240, and a total EOS count of 2394 cells per microliter. The pleural biopsy specimen revealed chronic pleuritis with eosinophilic infiltrate. Cultures were negative for bacterial, fungal, and tuberculous organisms. An open-lung biopsy specimen of the right lower lobe revealed patchy interstitial and intra-alveolar inflammatory infiltrates. Marked perivascular infiltration and prominent eosinophilic vasculitis were clearly observed. Subpleural and interlobular connective tissue was also heavily involved with EOS-rich inflammation. The pathologic findings were interpreted as most consistent with CSS vasculitis. The patient was initially treated with oral prednisone (60 mg/day or 1 mglkglday). During the ensuing 2 months, there was a prompt diminution of the CEC and complete resolution of the patchy basilar infiltrates and pleural effusions. As the prednisone dose was tapered, the peripheral

Atypical mesothelial hyperplasia associated with bronchogenic carcinoma

Atypical mesothelial hyperplasia encountered in pleural fluid or in a pleural biopsy specimen raises the suspicion that one may be dealing with a diffuse malignant mesothelioma of the pleura. We studied eight cases with cytologic or histologic changes of mesothelial atypia thought to be suspicious for diffuse malignant mesothelioma. In each case, the hyperplasia was associated with a bronchogenic carcinoma in the lung subjacent to the mesothelial hyperplasia. Bronchogenic carcinoma should be added to the list of causes of atypical mesothelial hyperplasia. This combination of reactive and malignant processes should be appreciated, since pleural carcinomatosis and diffuse malignant mesothelioma must be separated for clinical and epidemiologic reasons.

Subpleural Mononuclear Cell Infiltration: Significance in the Differential Diagnosis of Pleuritis Showing Nonspecific Histologic Findings

To determine if patients who had lymphocyte-rich pleural effusion and a pleural biopsy without any specific findings could be histopathologically differentiated between those with tuberculous and nontuberculous pleuritis, we histologically re-evaluated the pleural biopsies of all patients whose pleural effusion was predominant with lymphocytes and contained no malignant cells. A total of 40 patients with a nonspecific histologic findings of pleural biopsy specimen were categorized based on their ultimate diagnosis as having tuberculous (n = 15), carcinomatous (n = 10) or nontuberculous, benign pleuritis (n = 15). The pleural biopsy specimen of patients with nontuberculous, benign pleuritis frequently showed a band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate (10 out of 15 patients), while the same finding was infrequent in those with tuberculous pleuritis (0 out of 15, p = 0.0001) and pleuritis associated with carcinoma (three out of 10, p = 0.082). Based on these results, the presence of band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate in pleural biopsy specimens of patients with lymphocyte-rich pleural effusion suggests that the pleuritis is nontuberculous in its nature.

Case 36-1990

Presentation of CaseA 42-year-old woman was admitted to the hospital because of chylous ascites, lymphadenopathy, and weight loss.The patient was well until three years earlier, when she was evaluated elsewhere because of a right pleural effusion. A thoracentesis yielded fluid that was believed to be consistent with an exudate; no malignant-tumor cells or acid-fast bacilli were seen; microscopical examination of a pleural-biopsy specimen was reported to show nonspecific findings. Bronchoscopic examination was said to be negative. A test for antinuclear antibodies was positive in a titer of 1:1280; the results of tests of renal function were normal. A . . .

Cytologic and bacteriologic analysis of fluid and pleural biopsy specimens with Cope's needle. Study of 414 patients

This article describes the results of a dual diagnostic procedure, thoracentesis and pleural biopsy with a Cope's needle, in 414 patients with pleural effusion of unknown origin. A diagnosis of neoplasia or pleural tuberculosis was obtained in 241 subjects (149 with neoplasias and 92 with pleural tuberculosis). In an additional 55 patients, a diagnosis of tuberculosis or neoplasia was obtained using other procedures (15 with tuberculosis and 40 with neoplasias). In 105 subjects, the effusion was neither tuberculosis nor neoplasia. Thirteen patients were excluded from this study due to the impossibility of follow-up. The diagnostic process was repeated in 64 patients. Complications occurred in 46 patients (11%), of which 42 were pneumothorax. The dual diagnostic sensitivity in our series of thoracenteses and pleural biopsies made with a Cope's needle was 86% in tuberculosis and 79% in neoplasia with 100% specificity. The probability of a case being neither tuberculosis nor pleural neoplasia (negative predictive value) when the liquid and the pleural biopsy specimen are nonspecific (each procedure having been applied only once on each patient) is 56%, although a negative result does not exclude these diagnoses. In our opinion, the repetition of the dual procedure is indicated considering the scant morbidity and zero mortality.

Cytologic and Bacteriologic Analysis of Fluid and Pleural Biopsy Specimens With Cope's Needle

Cytologic and Bacteriologic Analysis of Fluid and Pleural Biopsy Specimens With Cope's Needle

Ewing's sarcoma cells in pleural fluid.

A 17-year-old male with effusion in the pleural cavity and a tumor on the left 7th rib was diagnosed by exfoliative cytological and histological examination of pleural fluid and biopsy specimen from the chest wall tumor.In the pleural effusion, small round cells with nuclear atypia were demonstrated as a mixture of monolayered clusters and single cells, with scanty and indistinct cytoplasm. The nucleus was round, supported by thin and smooth nuclear membrane, and hyperchromatic, showing finely granular chromatin pattern with one or two small but distinct nucleoli. PAS stain demonstrated intracellular glycogen. Histologically, biopsy specimen from the chest wall tumor yielded a diagnosis of round cell tumor, compatible with Ewing's sarcoma.Differential diagnosis of small round cell tumors was discussed from a morphological point of view.

Intrathoracic manifestations of disseminated prostatic adenocarcinoma

Four cases of disseminated adenocarcinoma of the prostate illustrating the clinical spectrum of intrathoracic involvement in this disease are presented. In two cases the presenting features of prostatic cancer were with lymphangitis carcinomatosa and an isolated pleural effusion, whereas two other cases developed intrathoracic metastases in the setting of previously known locally advanced prostatic cancer. In one this took the form of hilar and mediastinal lymphadenopathy and in the other that of pulmonary nodules. An immuno-cytochemical marker for prostatic specific antigen, a highly sensitive and specific tool for identifying prostatic epithelium, identified the prostate as the primary site of malignancy in the first two cases. Symptomatic and radiological responses were noted in all four cases after bilateral orchidectomy. Pulmonary metastases are common in the advanced stages of prostatic cancer but may also be present at the initial presentation with the disease even when the primary tumour is not clinically apparent. We recommend that (i) immuno-cytochemical stains for prostatic specific antigen are applied to all lung, pleural and mediastinal biopsy specimens showing adenocarcinoma in male patients, and (ii) all males with intrathoracic adenocarcinoma have prostatic aspiration cytology performed if the prostatic specific antigen stain is positive.

Diagnostic Significance of Mesothelial Hyperplasia in Pleural Biopsy Specimen

Diagnostic Significance of Mesothelial Hyperplasia in Pleural Biopsy Specimen

ＩＴＰが先行し，娘に同一の組織型，マーカーを持つ悪性リンパ腫の発症をみた節外性悪性リンパ腫の１例

Increasing attention has been payed to the development of lymphoma in patients with autoimmune diseases. However, reports of such cases are rare. Although familial aggregations of Adult T cell leukemia-lymphoma (ATLL) which have been frequently observed in Kyushu are pointed out, familial lymphomas other than ATLL are few in Japan.We reported a case of extranodal lymphoma with transient monoclonal gammopathy via hypogammaglobulinemia occurred subsequent to idiopathic thrombocytopenic purpura after unsuccessive treatment of corticosteroids for 3 years. A 76 years old man developed left pleural effusion in November, 1985. Diagnosis of lymphoma (diffuse large cell, B cell type) was obtained by the examination of pleural biopsy specimens using immunohistochemical techniques. Chemotherapy was started. Chest X-P examined in March, 1986 revealed multiple nodules in the left lung and central nervous system involvement of lymphoma was documented in July, 1986. Patient died in October, 1986. Autopsy revealed neither lymph node swelling nor lymph node involvement of lymphoma.His daughter who was 41 years old developed gastric pain in August, 1985. Biopsy specimen of gastric mass revealed lymphoma which was the same quality as father. In spite of gastrectomy and chemotherapy, she died in June, 1986

Malignant Pleural Effusions

From 1978 to 1982, 620 pleural fluid cytology specimens were examined, of which 80 were positive in 64 patients. Of these 64, three (0.5%) specimens had false-positive results. Adenocarcinoma of the lung was the most frequent (25 of 61) primary site, followed by breast (12 of 61), ovary (six of 61), and pancreas (five of 61). Comparing cytology with pleural core needle biopsy specimens in 26 patients, the cytology results were positive in 96%, while the needle biopsy specimens alone were positive in only 69%. Following the diagnoses of malignant pleural effusions, the patients receiving combined chemotherapy and radiotherapy had a mean survival of 328 days, compared with only 79 days for those who received no therapy. In conclusion, cytologic examination of Papanicolaou-stained smears yielded a greater percentage of positive diagnoses than either cell block preparations or pleural needle biopsy specimens. Over the past 25 years, the mean survival after the diagnosis of malignant pleural effusions has shown no improvement.

Malignant pleural effusions.

Pleural effusions are common in cancer patients, developing either from the malignant condition or from unrelated causes, such as congestive heart failure, pulmonary infarction, or infection. Diagnosis of malignant pleural effusion rests on demonstration of the presence of malignant cells in the pleural fluid or pleural biopsy specimen. Treatment is usually aimed at relief of symptoms rather than at the underlying malignancy. Specific therapeutic measures include thoracentesis, chest tube drainage, pleurodesis with chemicals or biologic agents, radiation and systemic chemotherapy, surgical pleurodesis, and pleuroperitoneal shunt. These should be supplemented by ancillary measures to maintain fluid and nutritional balance and prevent complications.

Sensitivity, Specificity, and Predictive Values of Closed Pleural Biopsy

To determine the clinical value of a nonspecific pleural biopsy specimen and fluid in malignant neoplasm and tuberculosis, we retrospectively reviewed records of all patients with pleural effusions undergoing the procedure at three community hospitals over six years. Two hundred eleven patients underwent biopsies. Adequate tissue was obtained in 207. The results were compared with the ultimate clinical and pathologic outcome by follow-up for 12 to 72 months. The initial procedure was diagnostic of malignant neoplasm in 54 patients and granulomatous disease in ten. A nonspecific or normal result was found in 143 (68%). Malignant neoplasms or tuberculosis was eventually established in 30 and excluded in 101 of the 143 patients. In 12 patients, no diagnosis was made. The procedure's sensitivities were 65% (malignant neoplasm) and 90% (tuberculosis). One false-positive result occurred in a patient with nontuberculous granulomatous pleuritis. The specificity and positive predictive value were 99% and 98%, respectively. The negative predictive value was 77%. Closed pleural biopsy with simultaneous fluid analysis is a valuable diagnostic procedure in community hospital patients, but a nonspecific result does not exclude malignant disease.