Journal of Pathology and Translational Medicine

Case Studies

Malignant Pleural Effusion from Metastatic Prostate Cancer: A Case Report with Unusual Cytologic Findings: Jinyoung Jeon, Tae-Jung Kim, Hong Sik Park, Kyo-Young Lee; J Pathol Transl Med. 2018;52(4):257-261. Published online June 7, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.08

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We present a case of 55-year-old man who complained of dyspnea and sputum for a month. He was an ex-smoker with a history of prostate cancer and pulmonary tuberculosis. Chest radiographs revealed bilateral pleural effusions of a small to moderate amount. Pigtail catheters were inserted for drainage. The pleural fluid consisted of large clusters and tightly cohesive groups of malignant cells, which however could not be ascribed to prostate cancer with certainty. We performed immunocytochemical panel studies to determine the origin of cancer metastasis. The immunostaining results were positive for prostate-specific antigen, alpha-methylacyl-coenzyme A racemase, and Nkx 3.1, consistent with prostate cancer. Pleural effusion associated with prostate cancer is rare. To our knowledge, this is the first case report in Korea to describe cytologic features of malignant pleural effusion associated with prostate cancer.

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EBUS-TBNA pleural biopsy reveals prostate cancer metastasis: A rare case report and review of the literature
Fotios Sampsonas, Dimitrios Komninos, Vasilina Sotiropoulou, Matthaios Katsaras, Dimitra Gkanetsou, Ourania Papaioannou, Panagiota Tsiri, Vasiliki Tzelepi, Argyrios Tzouvelekis
Pneumon.2024; 37(2): 1. CrossRef
Cytopathological Features of Extensive Bilateral Pleural Effusions in Metastatic Prostate Cancer: Report of a Rare Case
Hehua Huang, Caroline Yap
Cureus.2024;[Epub] CrossRef
Bilateral pleural effusion: etiology, diagnostics
N. A. Stogova
PULMONOLOGIYA.2022; 32(6): 885. CrossRef
Rare Metastatic Prostate Cancer Mimicking Lymphoma with Malignant Pleural Effusion
Tung Liu, En Meng, Yu-Chun Lin, Tai-Kuang Chao, Yi-Ming Chang
Journal of Medical Sciences.2021; 42(1): 46. CrossRef

Human Herpesvirus 8-Negative and Epstein-Barr Virus-Positive Effusion-Based Lymphoma in a Patient with Human Immunodeficiency Virus: Jung-Woo Choi, Younghye Kim, Ju-Han Lee, Young-Sik Kim; J Pathol Transl Med. 2015;49(5):409-412. Published online June 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.06.03

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Abstract PDF

A 39-year-old man infected with human immunodeficiency virus (HIV) was admitted to our hospital because of sudden onset of chest pain. Chest radiography revealed pneumothorax of the right lung. Computed tomographic scans disclosed a 5.8-cm-sized emphysematous bulla in the right middle lobe of the lung. Histologically, the wedge-resected lung showed medium to large atypical cells within the bullous cavity of the Pneumocystis jirovecii pneumonia, without solid mass formation. These atypical cells were confirmed to be large B-cell lymphoma, Epstein-Barr virus–positive and human herpesvirus 8–negative. Therefore, this case was not diagnosed as primary effusion lymphoma, but effusion-based lymphoma arising in an emphysematous cavity of an HIV-infected patient. This type of effusion-based lymphoma has never been reported, and, although rare, it should be noted in order to clinically diagnose this lymphoma.

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Primary Effusion Lymphoma: A Timely Review on the Association with HIV, HHV8, and EBV
Chih-Yi Liu, Bo-Jung Chen, Shih-Sung Chuang
Diagnostics.2022; 12(3): 713. CrossRef
Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics
Savanah D. Gisriel, Ji Yuan, Ryan C. Braunberger, Danielle L.V. Maracaja, Xueyan Chen, Xiaojun Wu, Jenna McCracken, Mingyi Chen, Yi Xie, Laura E. Brown, Peng Li, Yi Zhou, Tarsheen Sethi, Austin McHenry, Ronald G. Hauser, Nathan Paulson, Haiming Tang, Eric
Modern Pathology.2022; 35(10): 1411. CrossRef
Age and CD20 Expression Are Significant Prognostic Factors in Human Herpes Virus-8-negative Effusion-based Lymphoma
Tomomi Kubota, Yosuke Sasaki, Eisuke Shiozawa, Masafumi Takimoto, Tsunekazu Hishima, Ja-Mun Chong
American Journal of Surgical Pathology.2018; 42(12): 1607. CrossRef

Review

Current Concepts in Primary Effusion Lymphoma and Other Effusion-Based Lymphomas: Yoonjung Kim, Chan Jeong Park, Jin Roh, Jooryung Huh; Korean J Pathol. 2014;48(2):81-90. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.81

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Abstract PDF

Primary effusion lymphoma (PEL) is a human herpes virus 8 (HHV8)-positive large B-cell neoplasm that presents as an effusion with no detectable tumor in individuals with human immunodeficiency virus infection or other immune deficiencies. PEL is an aggressive neoplasm with a poor prognosis. PEL cells show diverse morphologies, ranging from immunoblastic or plasmablastic to anaplastic. The immunophenotype of PEL is distinct, but its lineage can be misdiagnosed if not assessed thoroughly. PEL cells usually express CD45, lack B- and T-cell-associated antigens, and characteristically express lymphocyte activation antigens and plasma cell-associated antigens. Diagnosis of PEL often requires the demonstration of a B-cell genotype. HHV8 must be detected in cells to diagnose PEL. In most cases, PEL cells also harbor the Epstein-Barr virus (EBV) genome. Similar conditions associated with HHV8 but not effusion-based are called "extracavitary PELs." PELs should be differentiated from HHV8-negative, EBV-positive, body cavity-based lymphomas in patients with long-standing chronic inflammation; the latter can occur in tuberculous pleuritis, artificial pneumothorax, chronic liver disease and various other conditions. Despite their morphological similarity, these various lymphomas require different therapeutic strategies and have different prognostic implications. Correct diagnosis is essential to manage and predict the outcome of patients with PEL and related disorders.

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Jose D. Sandoval-Sus, Amanda Brahim, Alina Khan, Barbara Raphael, Ali Ansari-Lari, Marco Ruiz
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High-dose Therapy and Autologous Hematopoietic Cell Transplantation as Consolidation Treatment for Primary Effusion Lymphoma
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Remission of an HHV8-related extracavitary primary effusion lymphoma in an HIV-positive patient during antiretroviral treatment containing dolutegravir
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Case Reports

Cytologic Diagnosis of Malignant Pleural Effusion in Multiple Myeloma: Two Case Reports.: Yoo Duk Choi, Sung Sun Kim, Chang Woo Han, Ji Shin Lee, Jong Hee Nam, Sang Woo Juhng, Chan Choi; Korean J Pathol. 2009;43(4):382-385.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.382

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Abstract PDF

Malignant pleural effusion in multiple myeloma (MM) is extremely rare and is associated with poor prognosis. We experienced two cases of MM IgA type with malignant pleural effusion. The diagnoses were based on characteristic cytology and CD138 immunocytochemistry. The patients received several cycles of combination chemotherapy, since symptoms were more aggressive with an uncontrolled pleural effusion. We review the clinical features of these cases and literature concerning myelomatous pleural effusion.

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Características de los pacientes con derrame pleural mielomatoso. Revisión sistemática
V. Riveiro, L. Ferreiro, M.E. Toubes, A. Lama, J.M. Álvarez-Dobaño, L. Valdés
Revista Clínica Española.2018; 218(2): 89. CrossRef
Characteristics of patients with myelomatous pleural effusion. A systematic review
V. Riveiro, L. Ferreiro, M.E. Toubes, A. Lama, J.M. Álvarez-Dobaño, L. Valdés
Revista Clínica Española (English Edition).2018; 218(2): 89. CrossRef
A 76-Year-Old Man With Anemia, Bone Pain, and Progressive Dyspnea
Thitiporn Suwatanapongched, Prapaporn Pornsuriyasak, Wasana Kanoksil, Thotsaporn Morasert, Warapat Virayavanich
Chest.2014; 145(4): 913. CrossRef

The Cytology of Metastatic Angiosarcoma in Pleural Fluid : A Case Report.: Na Rae Kim, Dong Hae Chung, Hyun Yee Cho; Korean J Pathol. 2009;43(3):285-259.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.285

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Abstract PDF

A 74-year-old woman presented with an abrupt onset of dyspnea that she had experienced for a week. She had been suffering from cutaneous nodules in the scalp for a year. Thoracentesis of the pleural fluid was performed. The Papanicolaou-stained smears, Thin prep and cell block preparations revealed clusters of oval-shaped cells concentrically layered about amorphous acellular cores, i.e., there was microacinar lumen formation as well as singly scattered atypical cells. The cells occasionally demonstrated intracytoplasmic vacuoles and hemosiderin deposits. Those cells stained for CD31 and they were negative for pancytokeratin. Punch biopsy from the scalp nodules revealed angiosarcoma. There are currently few reported cases of angiosarcoma in an exfoliative pleural effusion. Angiosarcoma has diverse, heterogeneous cytologic features. Making the cytologic diagnosis of metastatic angiosarcoma in pleural fluid is a challenge for pathologists. Knowledge of the clinical history is of great help for diagnosing this tumor when it appears in rare sites. Immunopanels with CD31, pancytokeratin and TTF-1 are helpful for making the differential diagnosis. The pathologists should look for clues suggesting the presence of vascular differentiation in the exfoliative cytologic materials when a diagnosis of angiosarcoma is suspected.

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Intranasal delivery of biologics to the central nervous system
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The Korean Journal of Pathology.2011; 45(2): 217. CrossRef

Original Article

Cytologic Analysis of Malignant Effusion.: Sang Pyo Kim, Ji Yeon Bae, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Chung Sook Kim; Korean J Cytopathol. 1995;6(2):116-124.

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Abstract PDF: Eighty cases of malignant effusion were cytologically studied to elucidate the incidence of primary tumor site and cytologic characteristics of each tumor types. Eighty fluid specimens were composed of 43 ascitic, 35 pleural, and 2 pericardial effusion and primary tumor site had been confirmed by histology. The frequent primary sites were stomach (22 cases, 28%), lung (21 cases, 26%), ovary (11 cases, 14%), liver (7 cases, 9%), and breast (4 cases, 5%). The principal malignant tumors were adenocarcinoma (56 cases, 70%), squamous cell carcinoma (7 cases, 9%), liver cell carcinoma (7 cases, 9%), small cell carcinoma (4 cases, 5%), and non-Hodgkin}s lymphoma (4 cases, 5%). The distinctive cytologic findings according to primary tumor types were as follows ; the gastric adenocarcinomas were mainly characterized by isolated cells and irregular clusters sometimes with signet ring cells. Papillary serous cystadenocarcinoma of ovary showed frequently papillary clusters and occasional psammoma bodies. Breast carcinoma of ductal type showed cell balls with smooth margins. Colonic adenocarcinoma showed rather irregular clusters or palisading pattern of cylindrical cells. Metastatic squamous cell carcinoma, liver cell carcinoma, small cell carcinoma, and non-Hodgkin}s lymphoma showed also characteristic features. These findings indicate that the cytological features observed in the great majority of malignant effusion are similar to those of primary tumor types, which are very helpful to indentify the primary tumor site.

Case Report

Effusion Cytology of Ki - 1 Positive Anaplastic Large Cell Lymphoma: A Case Report.: Mi Sook Lee, Mi Ja Lee, Yu Kyung Jeong, Sung Chul Lim, Keun Hong Kee, Ho Jong Jeon; Korean J Cytopathol. 1995;6(2):163-168.

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Abstract PDF: Ki-1 positive anaplastic large cell lymphoma is a newly described high-grade lymphoma and is defined by histopathological and immunologic criteria. We experienced a case of systemically involving Ki-1 positive anaplastic large cell lymphoma in a 44 year-old female which initially manifested as pleural effusion. Abdominopelvic CT scan showed the evidence of marked lymphadenopathy in retroperitoneal and both external and inguinal lymph nodes. On cytologic examination of pleural fluid tumor cells revealed pleomorphic large isolated cells with prominent nucleoli and abundant cytoplasms. The nuclei were large with irregular profiles including some deep invaginations. Also. occasional multilobed/multinucleated and binucleated nuclei were seen. Immunohistochemical examination was performed to differentiate from the undifferentiated adenocarcinoma. Hodgkin's disease, non-Hodgkin's lymphoma and malignant histiocytosis. The neoplastic cells were positive for leukocyte common antigen. CD3 CD30(ki-1) but negative for cytokeratin. epithelial membrane antigen. and CD15. A histologic diagnosis of Ki-1 positive anaplastic lymphoma was made by biopsies of the inguinal lymph node, polypoid lesion of the stomach and cecum.

Original Articles

Diagnostic Value of p53 Expression in the Evaluation of Effusions.: Jin Shin Lee, Chang Soo Park; Korean J Cytopathol. 1996;7(2):138-143.

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Abstract PDF: The diagnostic accuracy of routine cytological preparations from effusions ranges from 60% to 70%. Immunohistochemical markers, especially tumor-associated antigens, have been successfully employed to increase diagnostic sensitivity in effusion cytology. However, more than two different antibodies in diagnosis of effusions are needed. In the view of prevalence of abnormalities of p53 gene in human malignancies, we investigated the diagnostic usefulness of demonstration of p53 protein immunoreactivity in distinguishing benign changes versus malignant processes in effusions. p53 protein expression was studied immunohistochemically in 76 effusions(28 malignant and 48 benign) using anti-human p53 antibody. p53 immunoreactivity was identified in 19 of 28(67.9%) malignant effusions. In contrast, no p53 immunoreactivity was!, observed in all benign effusions. A specificity of 100% and a sensitivity of 67.9% Were observed. These results suggest that immunohistochemical detection of p53 protein seems to be helpful in distinguishing benign changes versus malignant processes in effusions, although its principal limitation is-its relatively low sensitivity.

Diagnostic Value of Flow Cytometric DNA Analysis in the Evaluation of Effusions .: Ji Shin Lee, Sang Woo Juhng; Korean J Cytopathol. 1997;8(1):20-26.

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Abstract PDF: The specificity of cytologic examination in effusions is high but the sensitivity is low. Therefore, various ancillary methods for the detection of malignant cells in effusions have been proposed. The presence of an aneuploid cell population is generally considered diagnostic of malignancy. The purpose of this study is to determine whether the routine use of flow cytometry adds to standard cytologic evaluation in effusions. We did flow cytometric DNA analysis in 76 effusions(28 malignant and 48 benign fluids). All the 48 benign effusions were diploid. There were 12(42.9%) aneuploid and 16(67.1%) diploid malignant effusions. Based on these results flow cytometric DNA analysis had a sensitivity of 42.9% and a specificity of 100%. These results suggest that flow cytometric DNA analysis may be a useful adjunct to conventional cytology, but its principal limitation is its relatively low sensitivity.

Cytologic Features and Distribution of Primary Sites of Malignant Cells in Body Cavity Fluids .: Kang Suek Suh, Chang Hun Lee, Hyun Ok Kim; Korean J Cytopathol. 1997;8(1):35-46.

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Abstract PDF: The authors reviewed 167 malignant effusions from 110 patients, of which the primary site was established on the basis of either biopsy or surgical resection of the primary neoplasm. Main factors analysed were the distribution of primary organs and the cytohistologic correlation of body cavity effusions. The 167 fluid specimens from 110 patients consisted of 90 cases(53.9%) of pleural, 68(40.7%) of peritoneal, and 9(5.4%) of pericardial origins. Histologically they consisted of 82 cases(74.5%) of adenocarcinoma, 8(7.3%) of malignant lymphoma, 6(5.5%) of squamous cell carcinoma, and 3(2.7%) of small cell carcinoma. The most common site among the primary lesions was the stomach in 25 cases(22.7%) followed by the lung in 21 (19.1%), ovary in 17(15.5%), and breast in 7(6.4%). As for the distribution of primary tumors in adenocarcinoma, the most common site was lung in 16 cases (48.5%) in pleural fluid and stomach in 22(48.9%) in peritoneal fluid. In pericardial effusions, all 5 cases were from the lung. As a whole, the cytologic findings of malignant effusion were fairly representative of histologic characteristics of primary lesions. Thus, when the primary lesion is unknown, careful evaluation of effusion cytology is presumed to be a helpful tool for tracing the primary tumor.

Case Report

Cytologic Findings of Rheumatoid Pleuritis in Pleural Effusion: A Case Report .: Hee Jeung Cha, Soo Kee Min, Joon Mee Kim, Young Chae Chu; Korean J Cytopathol. 1997;8(1):47-51.

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Abstract PDF: Patients with rheumatoid arthritis of any degree of severity or duration may develop necrotizing granulomatous pleuritis, a morphologic replica of the inflammatory reaction characteristic of rheumatoid synovitis and rheumatoid nodules. The principal feature is the background composed of granular, amorphous, particulate material or debris of various hues. The material is sometimes eosinophilic, sometimes more cyanophilic, or even green in the Papanicolaou stain. Within this background are elongated, fibroblast-like epithelioid cells, numerous multinucleated giant cells and degenerating leukocytes. The combination of the debris, spindle epithelioid cells, and multinucleated giant cells in fluid is pathognomonic for rheumatoid pleuritis. We experienced a hcase of rheumatoid pleuritis showing these characteristic cytologic findings. The patient was a 63 year-old man with positive rheumatoid factor. The pleual fluid specimen revealed elongated epithelioid cells and multinucleated giant cells in a background of amorphous granular material.

Original Articles

PLC-gamma1 for Differentiating Adenocarcinoma from Reactive Mesothelial Cells in Effusions.: Woo Yeong Ju, Sung Sook Kim; Korean J Cytopathol. 1997;8(2):115-119.

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Abstract PDF: Cytologic diagnosis of reactive or malignant effusion is sometimes difficult. Espe- cially, differentiation of benign reactive mesothelial cells from malignant cells in body effusion is more difficult. Recently, immunohistochemistry has been used to diagnose difficult cases. Phospholipase C(PLC)-gamma 1 is one of the isoenzyme of the PLC which plays central role in signal transduction involving cellular growth, differentiation and transformation by phosphorylating many protein component. Increased expression of PLC-gamma 1 in human breast carcinoma, colorectal carcinoma and stomach cancers are reported. To evaluate the efficacy of positive PLC-gamma 1 immunostaining in the diagnosis of malignancy in effusions, paraffin-embedded cell blocks of pleural fluid and ascites from 10 patients(5 metastatic adenocarcinomas, and 5 reactive mesothelial cells) were immunostained with a monoclonal antibody to PLC-gamma 1. PLC-gamma 1 immuostained all the adenocarcinomas in cell block(5/5) with intense membrane pattern, however, none of the reactive mesothelial proliferations stained with the diagnostic membrane pattern. Thus, our study strongly supports the conclusion that PLC-gamma 1 immunopositivity is likely to become a useful adjunct for the diagnosis of malignancy in effusions.

Distinction between Reactive Mesothelial and Carcinoma Cells in Serous Effusions by Mucin- and Immuno-cytochemical Panel .: Byung Heon Kim; Korean J Cytopathol. 1998;9(1):1-14.

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Abstract PDF: The cytologic distinction of carcinoma cells from reactive mesothelial cells can be difficult, especially in specimens containing abundant reactive mesothelial cells and inflammatory cells with scant carcinoma cells. This study evaluates the usefulness of mucin and immunocytochemistry for discrimination between reactive mesothelial cells and carcinoma cells, and sensitivity and specificity of these stains for the detection of metastatic carcinoma in serous effusions. Immunocytochemical panel including mucin cytochemistry with the periodic acid-Schiff(PAS) reaction after or without diastase digestion was undertaken on 127 serous effusion specimens with histologically confirmed diagnoses. The specimens including cell smears and cell blocks were stained with PAS and antibodies to carcinoembryonic antigen(CEA), epithelial membrane antigen(EMA), cytokeratin(CK), and vimentin. The sensitivities of these stains for metastatic carcinoma(127 cases) were 49%(46/94) in PAS, 48%(60/124) in CEA, 89%(97/109) in EMA, 88%(93/106) in CK, and 25%(20/81) in vimentin. The sensitivities of stains for reactive mesothelial cells(36 cases) were 19%(7/36) in EMA, 78%(28/36) in CK, and 75%(27/36) in vimentin. The PAS and CEA stains were not reacted with all cases of benign reactive serous effusions containing abundant reactive mesothelial cells. The specificities of stains for metastatic carcinoma(127 cases) were 100% in PAS, 100% in CEA, 81% in EMA, 22% in CK, and 25% in vimentin. The optimal combination of stains for use in a panel was PAS and CEA. Combined results from these two stains yielded an advanced sensitivity of 8% in PAS and 4% in CEA for metastatic carcinoma. EMA wasalso cosiderably useful for identification of carcinoma cells. CK and vimentin were not suitable for distinguishing between reactive mesothelial cells and carcinoma cells.

Immunocytochemical Expression of E-cadherin in Cell Blocks of Serous Effusions.: Byung Heon Kim, O Jun Kwon; Korean J Cytopathol. 2001;12(2):81-88.

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Abstract PDF: The differentiation between reactive mesothelial and carcinoma cells in serous effusion cytology can be a diagnostic challenge based on morphology alone. The expression of some cell adhesion molecules may be helpful in the differential diagnosis. This study evaluated the usefulness of E-cadherin immunocytochemistry for discrimination of carcinoma cells from reactive mesothelial cells. Alcohol fixed, paraffin embedded cell blocks taken from 42 reactive and 102 malignant serous effusions with histologically confirmed diagnoses were immunostained with monoclonal antibody to E-cadherin by LSAB method. E-cadherin expression was identified in only 2 benign reactive serous effusions(5%) whereas 91 malignant serous effusions(89%) expressed E-cadherin. The differences in immunostaining for E-cadherin between reactive and malignant serous effusions were statistically significant(p<0.001). The sensitivity and specificity of the E-cadherin immunostaining for carcinoma cells were 89% and 95%, respectively. In conclusion, E-cadherin is a useful diagnostic adjunct for differentiation between reactive mesothelial and carcinoma cells in serous effusions.

Utility of Calretinin in Distinction between Benign Reactive Mesothelial and Carcinoma Cells in Serous Effusions.: Byung Heon Kim; Korean J Cytopathol. 2001;12(2):89-96.

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Abstract PDF: The cytological distinction of carcinoma cells from reactive mesothelial cells in serous effusions may be difficult or impossible based on morphology alone, especially in specimens containing reactive mesothelial cells which form glandular or ball- or papillary-shaped conglomerates or which mimic malignant nuclear features. Calretinin is a newly reported immunocytochemical marker for mesothelial cells, which can potentially be utilized for facilitating this distinction. This study evaluated the usefulness of calretinin for the discrimination between reactive mesothelial and metastatic carcinoma cells in serous effusion. Immunocytochemical staining was undertaken on 33 benign reactive and 87 malignant serous effusion specimens with histologically confirmed diagnoses. The specimens including smears and cell blocks were stained with polyclonal antibody to calretinin by labelled streptavidin-biotin method. The positive expression of calretinin was noted in 32(97.0%) of 33 benign reactive effusions and 9(10.3%) of 87 malignant effusions. The sensitivity and specificity of the calretinin immunostaining for reactive mesothelial cells was 97.0% and 89.7%, respectively. In conclusion, calretinin is a useful marker for distinguishing between reactive mesothelial cells and carcinoma cells in serous effusions.

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