Cytologic presentation of malignant mesothelioma in pleural effusions

1,601 pleural effusions were found to be malignant between 1976 and 1987. Among these were 26 (1.6% of the malignant effusions) mesothelioma. Only 2 cases showed pronounced cytologic features that made a definite diagnosis possible on cytologic criteria alone. In 20 cases diagnosis of mesothelioma was strongly suggested by the patient's history and cytology of the effusion was compatible with mesothelioma. In the other 4 cases special examinations (histo- and immunohistochemistry, electron microscopy) led to the final diagnosis. The cytologic features of mesothelioma and other examination techniques, needed to resolve the differential diagnosis of mesothelioma versus other neoplasm in pleural effusions, are discussed.     

Cytologic diagnosis of a metastatic oligodendroglioma in a pleural effusion. A case report

BACKGROUND: Extraneural metastasis of oligodendroglioma is extremely rare and is diagnosed primarily by biopsy or autopsy and very occasionally by fine needle cytologic examination. We report a case of metastatic oligodendroglioma diagnosed by cytologic examination of a pleural effusion. Such a diagnosis has not been reported before. CASE: A 64-year-old woman developed anemia and bilateral pleural effusion 7 years after an operation for an oligodendroglioma over the left frontal lobe. Cytologic examination of the pleural effusion showed aggregates of atypical polygonal cells containing round, hyperchromatic nuclei and scanty, granular cytoplasm in Liu's and Papanicolaou stain and cell blocks. Immunohistochemical staining of the tumor cells revealed a positive reaction for antibodies to glial fibrillary acidic protein, S-100 and Olig2. Pleural biopsy confirmed the cytologic diagnosis of pleural effusion. A pathologic fracture of the right humeral and femoral bones was noted 1 month later, and the specimen also showed infiltrating oligodendroglioma cells in bone tissue. CONCLUSION: To the best of our knowledge, this is the first metastatic oligodendroglioma diagnosed by pleural cytology. Fine needle cytology can provide a reliable and rapid way to detect an extracranial metastatic oligodendroglioma in different organs.     

Amiodarone pulmonary toxicity. Clinical, cytologic and ultrastructural findings

Amiodarone, a new antiarrhythmic drug, may produce severe and potentially lethal pulmonary toxicity. A case is presented of a patient on amiodarone therapy who presented with recurrent pleural effusions and subsequently developed pulmonary infiltrates. The diagnosis of lung toxicity was documented by the cytologic examination of the pleural effusions and the bronchial washings. It was further supported by the ultrastructural demonstration of the characteristic cytoplasmic osmiophilic lamellar inclusions in the foamy macrophages. We conclude that cytologic and ultrastructural examinations of bronchial lavage cells are extremely helpful in the diagnosis of amiodarone-induced pulmonary toxicity.     

Cytologic finding of chyloascites in lymphangioleiomyomatosis. A case report

BACKGROUND: Lymphangioleiomyomatosis is a rare disease, histologically characterized by an abnormal proliferation of smooth muscle around the lymphatics. Lung is the most common site of involvement, and patients usually present with dyspnea, chest pain, and cough. Chylous pleural effusion and ascites occasionally appear during the course of the disease. There are only a few reports on the cytologic findings in this disease. To our knowledge, the cytologic findings of chylous pleural effusion and chyloascites have not been reported before. CASE: A 23-year-old female presented with chylothorax, chyloascites and a retroperitoneal mass. Cytologic examination of chylous pleural effusion and chyloascites revealed numerous cohesive and thick clusters of cells with a high nuclear/cytoplasmic ratio, oval nuclei and slightly increased chromatin content. Mitosis and necrosis were not observed. Exploratory laparotomy and transbronchial lung biopsy were performed, and the histologic diagnosis was lymphangioleiomyomatosis involving the retroperitoneal lymph nodes, uterine fundus and lungs. Immunohistochemistry showed that the characteristic clusters in chylous fluids were positive for alpha-smooth muscle actin. CONCLUSION: A diagnosis of lymphangioleiomyomatosis is possible from cytologic findings of effusions with the aid of clinical findings.     

DNA flow cytometry of pleural effusions. Comparison with pathology for the diagnosis of malignancy

A study was undertaken to determine the potential value of DNA flow cytometry (FCM) for the diagnosis of malignancy in pleural effusions and to compare its results with those of traditional cytomorphology. Forty-one pleural fluids from 37 patients were evaluated by DNA FCM and routine cytologic techniques. Of the 41 pleural fluids, 29 (70.7%) demonstrated an abnormal DNA content by FCM. Two of the 29 pleural fluids had been originally diagnosed as benign by cytology. Cytologic review of these two cases showed no abnormal cells; therefore, there were no false-negative cases based on cytology. In 12 (29.3%) of the 41 fluids, DNA FCM and cytologic evaluation both indicated benign processes. Our preliminary observations indicate that FCM is an accurate and reliable technique that may be of aid in the diagnosis of malignant effusions. The technique may prove to be of special value in the differential diagnosis of reactive mesothelial cells versus malignant mesothelioma as well as for following patients who receive chemotherapy for malignant pleural effusions. DNA FCM may also complement cytomorphologic diagnoses in other serous, exfoliative or aspiration material.     

Positive effusion cytology as the initial presentation of malignancy

During a period of four years (1981 to 1984), 641 ascitic, 860 pleural and 47 pericardial fluid specimens were examined cytologically. Of these, 154 ascitic samples, 174 pleural specimens and 10 pericardial effusions, obtained, respectively, from 108, 133 and 7 patients, were found to contain malignant cells. In 7 patients, ascites, and in 18 cases, pleural effusions were the first indication of cancer. None of the positive pericardial fluids was the initial presentation of malignancy. The cytologic findings and follow-up data on these 25 patients are the subject of this study. The most common type of neoplasm in these effusions was adenocarcinoma (86% of the ascitic and 78% of the pleural fluids). Most of the malignant neoplasms in ascitic fluids were derived from ovarian tumors (5 of 7) while those in pleural effusions came mainly from lung tumors (12 of 18). Mammary carcinoma, which was the most common malignant tumor found in cases of pleural effusions, did not present initially with an effusion in any of our cases. The cytologic diagnosis was confirmed in all cases by either biopsy or strong clinical evidence. The prognosis in patients who initially presented with an effusion was poor. All of the patients with an adequate follow-up died within 29 months in cases of ascites and within 19 months in cases of pleural effusions.     

Primary malignant pleural tumors (mesotheliomas) presenting as localized masses. Fine needle aspiration cytologic findings, clinical and radiologic features and review of the literature

The cytologic and histologic appearances of four localized primary malignant pleural tumors occurring in three patients subjected to fine needle aspiration are presented. In one case, the radiographic mass was the only manifestation of what was found to be a diffuse epithelial mesothelioma at surgery. Two other patients had localized primary sarcomatous mesotheliomas, of low grade and high grade, respectively. In the latter patient, a second metachronous but identical tumor appeared on the contralateral side during follow-up. The clinical findings, radiologic features and cytologic differential diagnosis of both the epithelial and the sarcomatous variants are discussed, together with a review of the literature pertinent to localized primary malignant pleural tumors.     

A case of Pneumocystis carinii in pleural fluid with cytologic, histologic and ultrastructural documentation

Pneumocystis carinii involvement of the pleural cavity in a patient with the acquired immune deficiency syndrome was documented by cytologic as well as scanning and transmission electron microscopic study of pleural fluids. Histologic examination of the pleura and the subpleural lung revealed vasculitis and infarctlike necrosis as well as P carinii in the tissue. Although a few cases of extrapulmonary P carinii infection have been reported, this appears to be the first time its presence in pleural fluid has been documented.     

Immunoglobulin crystal-storing histiocytosis in a pleural effusion from a woman with IgA kapa multiple myeloma: a case report

BACKGROUND: Crystal-storing histiocytosis (CSH) is a rare disorder occurring in patients with lymphoproliferative diseases, predominantly multiple myeloma and low grade B-cell lymphoma. This report presents the first case of CSH diagnosed on pleural fluid from a patient with multiple myeloma (MM). CASE: A 79-year-old women with IgA kappa MM underwent thoracocenthesis and thoracic drainage because of a pleural effusion. Cytologic and immunocytochemical examination of pleural fluid revealed abundant histiocytic, CD68-positive cells with prominent intracytoplasmic, needlelike, crystalloid inclusions showing strong immunopositivity for IgA heavy and kappa light chains. Identical crystals were observed on an extracellular background. No myeloma infiltration was detected. Two weeks later, examination of new pleural fluid from the patient showed a similar cytologic picture, but, in addition, isolated plasma cell features were identified. They were too few for a meaningful determination of clonality. The patient died I month after the CSH diagnosis. CONCLUSION: This case illustrates the value of cytologic examination of serous fluids from patients with plasma cell dyscrasias, not only to evaluate possible infectious or neoplastic causes but also to diagnose CSH.     

Diagnostic accuracy of toluidine blue-stained wet films in effusion cytology

OBJECTIVE: To evaluate the usefulness of toluidine blue-stained wet films in the preliminary cytologic evaluation of serous effusions by means of specificity, sensitivity, and positive and negative predictive value. STUDY DESIGN: One hundred seventy-six samples consisting of 122 pleural and pericardial effusions and 54 peritoneal effusions from 160 patients were included in the study. A toluidine blue-stained wet film of each sample was evaluated, and diagnoses were compared with the diagnoses by conventional smears and cell blocks on the same sample. RESULTS: The sensitivity of wet films was 69%, 68% in pleural and pericardial effusions and peritoneal effusions, respectively, and the specificity of wet films was 93%, 92% in pleural and pericardial effusions and peritoneal effusions, respectively. Positive predictive values of smears alone were 78% and 75%; negative predictive values of smears alone were 96% and 95% in pleural and pericardial effusions and peritoneal effusions, respectively. CONCLUSION: Preliminary cytologic evaluation of serous effusions with toluidine blue-stained wet films is simple and economical. It provides the opportunity to plan additional procedures for the samples.     

Survival of patients with malignancy-associated effusions

For a better understanding of the prognosis after the onset of a malignancy-associated effusion in patients known or subsequently shown to have cancer, survival time was compared with the findings and the date of the first cytologic diagnosis of an effusion. The number of patients studied was 254; 171 had a pleural and 83 a peritoneal effusion. The average survival time was 25.5 weeks, which was about equal for both sites of effusions. After two years, only 6% of all patients were alive. When the cytologic diagnosis of the effusion was "malignant," only 4% survived after two years; when the cytologic diagnosis was "suspicious for malignancy" and "nonmalignant," these figures were 5% and 7%, respectively. This indicates that a cytologic diagnosis of benign or nonmalignant is not a good indicator of a better prognosis in cancer patients for whom benign causes of the effusion have been excluded. There appeared to be a prognostic relationship between the length of the interval from the initial diagnosis of cancer to the time of examination of the first sample of the effusion: a longer interval was correlated with a better survival. When survival time was viewed in relation to therapy, patients whose pleural effusions were only treated by aspiration were found to have a particularly short average survival (13.9 weeks).     

Pneumocystis carinii in pleural fluid. The cytologic appearance

We describe the cytologic appearance of Pneumocystis carinii in pleural fluid of a patient with acquired immunodeficiency syndrome and a rapidly accumulating pleural effusion. The diagnosis of P carinii infection was made by examination of air-dried, Diff-Quik-stained Cytospin preparations of the pleural fluid. The diagnostic appearances of P carinii organisms stained by this method and by the Papanicolaou stain are reviewed. The unusual predominance of the trophozoite forms of the organism in this case made Diff-Quik an ideal special stain for identifying the organisms. Furthermore, this case illustrates a novel presentation of P carinii infection and suggests that P carinii should be considered an etiologic agent in the differential diagnosis of pleural effusion in an immunocompromised host.     

Potential use of loss of heterozygosity in pleural effusions of breast cancer metastases using the microsatellite marker of the 16q22.1 region of the CDH1 gene

OBJECTIVE: To evaluate the presence of allelic loss in 16q22.1, including the locus of E-cadherin, in pleural effusions in breast cancer patients. STUDY DESIGN: Molecular analysis of DNA was performed using a DNA extraction kit (NucleoSpin, Macherey-Nagel, Germany). Loss of heterozygosity (LOH) in primary tumors and pleural effusions was analyzed using a microsatellite marker of the CDH1 gene, D16S265, described in previous studies. LOH was evaluated by radioactive polymerase chain reaction assay in 17 samples of pleural effusions and breast tissues (primary tumors and nonneoplastic adjacent tissue) from breast cancer patients: 7 positive for neoplastic cells, 6 suspected and 4 cases without evidence of neoplastic cells in the effusions. RESULTS: Thirteen cases (76%) were informative. LOH was detected in 5 cases (38.5%). In 3 of them LOH was detected only in the cytologic sample, and in 2 of them LOH was detected in the primary tumor and cytologic sample. CONCLUSION: Results show that LOH in the CDH1 gene can identify tumor cells in pleural effusions when morphologic analysis is difficult.     

Pleural effusion cytology in a case of cytophagic histiocytic panniculitis (subcutaneous panniculitic T-cell lymphoma). A case report

BACKGROUND: Cytophagic histiocytic panniculitis (CHP) presents with subcutaneous panniculitis associated with hemophagocytic syndrome. Many cases of CHP are now being classified as a natural disease progression of subcutaneous panniculitic T-cell lymphoma (SPTL). There have been no cytologic reports dealing with pleural aspirates in cases of CHP or SPTL. CASE: A pleural aspirate obtained from a 19-year-old female revealed lymphoma cells and hemophagocytic histiocytes. A skin biopsy specimen showed the presence of CD8-positive lymphoma cells in fat lobules associated with cytologically benign histiocytes with erythrophagocytosis and lymphophagocytosis. CONCLUSION: Hemophagocytic histiocytes were seen in the pleural effusion from a patient with SPTL.     

Ultrastructure of pleural mesothelioma and pulmonary adenocarcinoma in malignant effusions as compared with reactive mesothelial cells.

OBJECTIVE: To determine the ultrastructural features of diffuse malignant pleural mesothelioma cells in cytologic specimens from pleural effusions. STUDY DESIGN: We retrospectively studied 35 pleural effusions: 12 diffuse malignant pleural mesotheliomas (8 epithelial type, 4 biphasic type), 12 pulmonary adenocarcinomas and 11 cases of reactive mesothelial cells. RESULTS: In the cytoplasm, reactive and malignant mesothelial cells had more-abundant intermediate filaments (P < .05, P < .01) and fewer free ribosomes (P < .001, P < .001) than adenocarcinoma cells. Reactive mesothelial cells had fewer mitochondria than mesothelioma cells (P < .05). Mesothelioma cells had longer, thinner microvilli on the cell surfaces (P < .001); length/diameter ratios of microvilli were 19.1 +/- 7.0 (mesothelioma) vs. 9.1 +/- 2.2 (adenocarcinoma) and 9.2 +/- 2.4 (mesothelial cells). Giant intercellular junctions (desmosomes or desmosomelike structures > 1 micron in length) were found in eight cases of mesothelioma. Core filaments or rootlets in microvilli were present in two cases of adenocarcinoma. CONCLUSION: Because cytologic specimens from pleural effusions were easy to obtain, we think ultrastructural cytology is useful in distinguishing mesothelioma from adenocarcinoma and benign effusions.     

The distinction of mesothelioma from adenocarcinoma in malignant effusions by electron microscopy

To determine the usefulness of the electron microscopic (EM) differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma in cytologic specimens of serous fluids, we undertook a prospective study of 17 pleural and peritoneal effusions from 14 patients. In the nine effusions identified as malignant by routine cytologic examination, EM correctly diagnosed three mesotheliomas and six adenocarcinomas. EM resolved the differential diagnosis of mesothelioma versus adenocarcinoma in three cases in which routine cytologic examination could not. As with tissue specimens, EM cannot be used to diagnose the malignancy of cytologic specimens; it can, however, reliably identify the origin of cells diagnosed as malignant by routine cytologic examination. We conclude that, when EM is used to evaluate cytologically malignant effusions, it can accurately distinguish mesothelioma from adenocarcinoma. This technique will be diagnostically useful in selected cases and may be helpful in avoiding more invasive procedures as well as delays in diagnosis and therapy.     

Polymerase chain reaction for Mycobacterium tuberculosis complex DNA. Use on negative archival Ziehl-Neelsen cytologic samples

OBJECTIVE: To evaluate the usefulness of a nested polymerase chain reaction (PCR) for Mycobacterium tuberculosis complex on routinely stained cytologic samples from patients with extrapulmonary tuberculosis. STUDY DESIGN: Nested PCR for the detection of a fragment of the IS6110 insertion sequence of M tuberculosis complex was applied to Ziehl-Neelsen-negative archival cytologic slides of serous effusions (pleural [n = 7], peritoneal [n = 1] and pericardial [n = 1]) and a lymph node fine needle aspirate (n = 1) from nine human immunodeficiency virus (HIV)-positive patients with autopsy-proven active extrapulmonary tuberculosis. Malignant effusions and aspirates from nine HIV-positive patients with non-Hodgkin's lymphoma and pleural effusions from seven HIV-negative patients with heart failure were used as controls. DNA was extracted after removing the coverslip and gently scraping the cytologic sample from the slides. RESULTS: In all cases, enough DNA was obtained for PCR without any significant loss of integrity, as demonstrated by PCR positive for HLA-Dq. PCR for M tuberculosis was positive in 8 of the 10 samples (80%) from patients with tuberculosis but also in three samples (30%) from HIV-positive patients in the control group. None of the samples from the HIV-negative patients was positive. CONCLUSION: PCR for M tuberculosis can be reliably performed on archival cytologic slides from extrapulmonary samples, but although it is highly sensitive, it may lead to positive results in immunocompromised patients without any sign of active tubercular disease.     

The Effect of Pleural Abrasion on the Treatment of Primary Spontaneous Pneumothorax: A Systematic Review of Randomized Controlled Trials

Background

Pleural abrasion has been widely used to control the recurrence of primary spontaneous pneumothorax (PSP). However, controversy still exists regarding the advantages and disadvantages of pleural abrasion compared with other interventions in preventing the recurrence of PSP.

Methods

The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 15, 2014 to identify randomized controlled trials (RCTs) that compared the effects of pleural abrasion with those of other interventions in the treatment of PSP. The study outcomes included the PSP recurrence rate and the occurrence rate of adverse effects.

Results

Mechanical pleural abrasion and apical pleurectomy after thoracoscopic stapled bullectomy exhibited similarly persistent postoperative air leak occurrence rates (p = 0.978) and 1-year PSP recurrence rates (p = 0.821), whereas pleural abrasion led to reduced residual chest pain and discomfort (p = 0.001) and a smaller rate of hemothorax (p = 0.036) than did apical pleurectomy. However, the addition of minocycline pleurodesis to pleural abrasion did not reduce the pneumothorax recurrence rate compared with apical pleurectomy (3.8% for both procedures) but was associated with fewer complications. There was no statistical difference in the pneumothorax recurrence rate between mechanical pleural abrasion and chemical pleurodesis with minocycline on either an intention-to-treat basis (4 of 42 versus 0 of 42, p = 0.12; Fisher exact test) or after exclusions (2 of 40 versus 0 of 42, p = 0.24; Fisher exact test). Pleural abrasion plus minocycline pleurodesis also did not reduce the pneumothorax recurrence rate compared with pleural abrasion alone (p = 0.055). Moreover, pleural abrasion plus minocycline pleurodesis was associated with more intense acute chest pain. The postoperative overall recurrence rate in patients who underwent staple line coverage with absorbable cellulose mesh and fibrin glue was similar to that with mechanical abrasion after thoracoscopic bullectomy (13.8% vs. 14.2%, respectively; p = 0.555), but staple line coverage resulted in less postoperative residual pain than mechanical abrasion (0.4% vs.3.2%; p<0.0001). Pleural abrasion after thoracoscopic wedge resection did not decrease the recurrence of pneumothorax compared with wedge resection alone (p = 0.791), but the intraoperative bleeding and postoperative pleural drainage rates were higher when pleural abrasion was performed.

Conclusions

In addition to resulting in the same pneumothorax recurrence rate, thoracoscopic pleural abrasion with or without minocycline pleurodesis is safer than apical pleurectomy in the treatment of PSP. However, minocycline pleurodesis with or without pleural abrasion is not any more effective than pleural abrasion alone. Moreover, additional mechanical abrasion is not safer than additional staple line coverage with absorbable cellulose mesh and fibrin glue after thoracoscopic bullectomy because of increased postoperative pain. Additionally, pleural abrasion after thoracoscopic wedge resection should not be recommended for routine application due to the greater incidence of adverse effects than wedge resection alone. However, further large-scale, well-designed RCTs are needed to confirm the best procedure.     

Mycobacterium kansasii infection diagnosed by pleural fluid cytology: a case report

BACKGROUND: Identification of disseminated nontuberculous Mycobacterium infection is a challenge, especially when it occurs in patients without a known cause of immunosuppression. Acid-fast organisms in the pleural fluid are rare and easily missed, especially when they occur in patients without a clinical suspicion of infection. The classical cytologic picture of tuberculous pleural fluid with lymphocytosis and paucity of mesothelial cells is not seen. CASE: A 57-year-old man presented with chronic neutrophilia of unknown etiology together with chest pain and bilateral pleural effusions. Pleural fluid cytology revealed organisms seen in the cytoplasm of numerous macrophages and neutrophils, creating a "negative image" on Diff-Quik smears. Acid-fast stains demonstrated intracellular acid-fast bacilli consistent with mycobacteria. Microbiologic studies with DNA probe technology resulted in identification of the mycobacterial organism as Mycobacterium kansasii. CONCLUSION: Nontuberculous Mycobacterium should be included in the differential diagnosis in patients with inflammatory, exudative pleural effusions.