胸腹水细胞端粒酶活性定性和定量检测

目的探讨端粒酶活性定量检测在诊断良恶性胸腹水中的应用价值。方法采用TRAP-银染定性方法和rrRAP-PicoGreen定量方法,对102例已确诊患者的胸腹水细胞进行端粒酶活性分析。结果恶性胸腹水细胞端粒酶活性明显高于良性胸腹水细胞,其定性检测诊断率明显高于细胞病理学。乳腺癌患者胸腹水细胞的端粒酶活性明显高于卵巢癌、肝癌患者胸腹水细胞的端粒酶活性;肺癌患者胸腹水细胞端粒酶活性明显高于肝癌。在良性胸腹水中,感染性胸腹水细胞端粒酶活性高于非感染性胸腹水。结论恶性胸腹水细胞端粒酶活性明显升高。端粒酶活性定量检测较定性检测更敏感、简便,对良恶性胸腹水的诊断和鉴别诊断有一定应用价值。     

Association of primary pleural effusion lymphoma of T-cell origin and human herpesvirus 8 in a human immunodeficiency virus-seronegative man

We describe a case of an 87-year-old human immunodeficiency virus (HIV)-negative man who developed a primary pleural lymphoma without any identifiable tumor mass associated with human herpesvirus 8 (HHV-8) infection. A large T-cell lymphoma was diagnosed based on morphologic, immunophenotypic, and molecular findings. The HHV-8 DNA sequences were detected using specific polymerase chain reaction amplification in the lymphomatous effusion. Study of the patient's serum confirmed the HHV-8 infection. This case report displays the characteristic features of HHV-8-related body cavity-based lymphoma/primary effusion lymphoma previously reported in HIV-seronegative patients, except that it is of T-cell origin. Whether this case may be included or not within the primary effusion lymphoma entity, the association of a pleural T-cell non-Hodgkin lymphoma with HHV-8 infection raises the question of the possible occurrence of T cells as the target of malignant transformation associated with HHV-8 infection.     

Cytology of small-cell carcinoma of the uterine cervix in serous effusion: a report on two cases

Cytologic features of 2 cases of small-cell carcinoma of the uterine cervix in the body fluid are described. Case 1 was a 34-yr-old woman with a stage IIA cervical tumor. Pleural effusion developed 6 mo after initial diagnosis. Case 2 was a 38-yr-old woman with a stage IB tumor. Ascites was detected 11 mo after hysterectomy. Histologically, both cervical tumors were indistinguishable from small-cell carcinoma of oat-cell type in the lungs or other sites. Cytologically, the tumor cells in the pleural effusion of case 1 had characteristic features of small-cell carcinoma, including nuclear molding. However, almost all tumor cells in the ascites of case 2 showed a single-cell pattern mimicking malignant lymphoma. Mitotic figures and karyorrhetic bodies were occasionally seen. Nuclear molding was rarely identified. Small-cell carcinoma should be included in the differential diagnosis of malignant effusions containing lymphoma-like cells.     

NON-AFRICAN BURKITT'S LYMPHOMA IN A YOUNG WOMAN

Non-African Burkitt's lymphoma is presented in a 29-year-old, unmarried woman, who developed tumors in both breasts and ovaries, ascites and pleural effusion. Assessment of B cells in the tumor cells, derived from ascites, pleural effusion and tumor tissue is 90%, surface IgM being consisted of 86%, in an average. Histologically, the tumor tissue demonstrates prominent, so-called starry-sky effect, and cytologically, tumor cells are poorly-differentiated lymphocytoid ceUs in their features.     

Miliary pulmonary metastases from a clinically occult pleural mesothelioma

Mesothelioma is a rare neoplasm of the serosal membranes. Signs and symptoms of a pleural effusion typically herald discovery of the tumor. We report a case of miliary metastatic mesothelioma involving both lungs in a 54-year-old man who presented with right-sided chest discomfort, numerous pulmonary nodules detected by computed tomography of the chest, and absent pleural effusion. Immunohistochemical and electron microscopy studies performed on wedge biopsies of parenchymal pulmonary nodules led to the diagnosis of metastatic mesothelioma. Subsequent pleural evaluation and biopsy of pleural thickening noted at a site of prior chest wall trauma identified the primary neoplasm and confirmed the diagnosis as malignant epithelioid mesothelioma. The histologic appearance of discohesive epithelioid cells in a distinctly myxoid background was the clue in this case leading to the consideration of metastatic mesothelioma and a thorough immunohistochemical evaluation of the tumor. This case shows that mesothelioma may metastasize throughout the lungs in a miliary pattern and the metastases may be clinically detected before the primary pleural tumor. Metastatic mesothelioma is a consideration for metastatic pulmonary tumors of unknown origin.     

De novo CD5‐positive primary cardiac diffuse large B‐cell lymphoma diagnosed by pleural fluid cytology

Primary cardiac lymphomas are exceedingly rare. The presence and extent of the intracardiac mass is determined by echocardiography, computed tomography (CT), or magnetic resonance imaging (MRI); however, the diagnosis is established by endomyocardial biopsy or by pericardial or pleural effusion cytology. We describe the pleural effusion cytologic features of a primary cardiac lymphoma in a 55‐year‐old woman who presented with progressive shortness of breath, fatigue, mild dizziness, dull chest ache, and lower extremity edema. Transthoracic echocardiography, CT, and MRI showed a large mass centered in the right atrium and extending into the right ventricle, associated with pericardial effusion and bilateral pleural effusions. Cytologic examination of the pleural fluid showed very large pleomorphic malignant cell, some of which were binucleated and multinucleated and had anaplastic features. Flow cytometry showed a kappa monotypic population of large cells coexpressing CD5, CD19, and CD20; and immunoperoxidase stains performed on the cell block sections showed that the large neoplastic cells were positive for CD20, PAX5, CD5, and MUM1 and showed a very high proliferation rate (over 90%) by Ki67 staining. The cytologic, flow cytometry, and immunohistochemistry findings established the diagnosis of de novo CD5‐positive primary cardiac diffuse large B‐cell lymphoma (DLBCL), anaplastic variant, which was confirmed by the subsequent endomyocardial biopsy. This is, to the best of our knowledge, the first report of de novo CD5‐positive primary cardiac diffuse large B‐cell lymphoma, and the first report of the anaplastic variant of DLBCL diagnosed by effusion cytology. Diagn. Cytopathol. 2014;42:259–267. © 2012 Wiley Periodicals, Inc.     

Clinical evaluation and tissue distribution of CA125 in patients with pleural effusion

CA125 in serum and pleural effusion was measured in 51 patients with malignant effusion and 38 patients with benign effusion, and the tissue distribution of CA125 was investigated by immunohistochemical technique. The 51 malignant effusions were secondary to primary lung cancer. The 38 benign effusions were taken from 23 patients with tuberculous pleurisy, 9 patients with empyema, 5 patients with congestive heart failure and one patient with nephrosis. In the mean level and the positive rate of serum CA125, no significant difference was shown between primary lung cancer and tuberculosis or the other benign diseases. The mean level of CA125 in pleural effusion of primary lung cancer was significantly higher than that in pleural effusion of tuberculosis (p less than 0.01), and showed a tendency to increase compared to that in pleural effusion of the other benign diseases (p less than 0.1). The mean level of CA125 in pleural effusion of tuberculosis was significantly lower than that in the other benign diseases (p less than 0.02). The positive rate of CA125 in malignant effusion was 43.1% and the diagnostic specificity of it was 86.7%. CA125 was detected in carcinoma cells and activated mesothelial cells in pleural effusion and mesothelial cells of normal pleural tissue by immunohistochemical staining. These results suggest that the measurement of CA125 in pleural effusion is useful for differential diagnosis of the malignant effusion from the benign effusion and that CA125 in pleural effusion of pleuritis carcinomatosa is produced by not only carcinoma cells but also activated mesothelial cells.     

Pseudomesotheliomatous carcinoma of the pleura: an autopsy case of metastasis from a G‐CSF‐producing anaplastic carcinoma of the pancreas

Pseudomesotheliomatous carcinoma is a malignant tumor that extends along the pleura mimicking malignant mesothelioma. An 81‐year‐old male patient presented to our hospital with epigastralgia, and abdominal computed tomography (CT) showed a 36‐mm tumor in the pancreatic tail. The laboratory data revealed a high leukocyte count (>44 000/μL). Chest CT showed left pleural thickening with pleural effusion. The cancer showed a poor response to chemotherapy, and the patient died of respiratory failure at 5 months after the onset of disease. Autopsy showed solid tumor with hemorrhage, measuring 6 cm in diameter, in the pancreatic tail, with wide invasion to the stomach, left adrenal gland, spleen, and diaphragm. The left pleura, which was circumferentially thickened by the involved tumor, macroscopically resembled pleural mesothelioma. Histologically, the primary pancreatic tumor was diagnosed as anaplastic carcinoma, due to the absence of glandular structures or other features that would indicate a definite direction of differentiation. The primary lesion and carcinoma involving the left pleura were all positive for G‐CSF. We recently experienced an autopsy case of G‐CSF‐producing anaplastic carcinoma with pseudomesotheliomatous spread.     

Anti-CD20 monoclonal antibody treatment of human herpesvirus 8-associated, body cavity-based lymphoma with an unusual phenotype in a human immunodeficiency virus-negative patient

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus first detected in Kaposi's sarcoma tumor cells and subsequently in primary effusion lymphoma (PEL) tumor cells and peripheral blood mononuclear cells from PEL patients. PEL has been recognized as an individual nosologic entity based on its distinctive features and consistent association with HHV-8 infection. PEL is an unusual form of body cavity-based B-cell lymphoma (BCBL). It occurs predominantly in human immunodeficiency virus (HIV)-positive patients but occasionally also in elderly HIV-negative patients. We describe a case of PEL, with ascites, bilateral pleural effusions, and a small axillary lymphadenopathy, in a 72-year-old HIV-negative man. PCR performed on a lymph node specimen and in liquid effusion was positive for HHV-8 and negative for Epstein-Barr virus. The immunophenotype of the neoplastic cells was B CD19+ CD20+ CD22+ with coexpression of CD10 and CD23 and with clonal kappa light chain rearrangement. The patient was treated with Rituximab, a chimeric (human-mouse) anti-CD20 monoclonal antibody. Thirteen months later, the patient continued in clinical remission. This is the first report of an HHV-8-associated BCBL in an HIV-negative patient in Argentina.     

Primary Effusion Lymphoma: An Untrivial Differential Diagnosis for Ascites

A primary effusion lymphoma is a rare type of non-Hodgkin''s lymphoma where serous cavities are involved. That-cause peritoneal, pleural and pericardial effusions without any lymphadenopathy. They affect immunosuppressive patients with human herpes virus-8 being the suspected etiological agent. The prognosis is usually poor despite treatment. Herein, the case of an immunocompetent patient with ascites and pleural effusion diagnosed as primary effusion lymphoma is presented and discuss the case in the light of the current literature.     

Early peripheral lymph node involvement of human herpesvirus 8-associated, body cavity-based lymphoma in a human immunodeficiency virus-negative patient

Human herpesvirus 8 (HHV-8), or Kaposi sarcoma-associated herpesvirus, is a gamma herpesvirus first detected in a specimen of Kaposi sarcoma from a human immunodeficiency virus (HIV)-positive patient. Human herpesvirus 8 is also found in an unusual clinicopathologic form of body cavity-based B-cell lymphoma, which has been named primary effusion lymphoma (PEL) and occurs primarily in HIV-positive patients. PEL is characterized by the formation of lymphomatous effusions, without obvious lymphadenopathy, tumor masses, or bone marrow involvement. Only a few cases of PEL in HIV-seronegative patients have been reported. We describe a case of an HHV-8-associated lymphoma, with ascites, pleural effusion, and axillary lymphadenopathy in an HIV-negative patient. The patient was a 68-year-old Jewish man of North African extraction, with a previous history of coronary bypass surgery and multiple blood transfusions. The pleural fluid contained large atypical lymphoid cells and was suggestive of lymphoma but could not provide a conclusive diagnosis of PEL. The lymph node contained groups of large anaplastic lymphoid cells. Polymerase chain reaction for HHV-8 performed on the lymph node specimen was positive, establishing the diagnosis of PEL. Polymerase chain reaction for Epstein-Barr virus was negative. Results of a gallium scan were normal. The patient did not respond to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone and progressively developed, massive intra-abdominal solid tumor formation. To our knowledge, this is the first report of a case of PEL that demonstrates peripheral lymph node involvement at diagnosis and the first report of PEL in an Israeli patient.     

肿瘤患者胸/腹水和外周血中TCR Vβ亚家族表达及调节性T细胞亚群的研究

目的:探讨肿瘤患者胸/腹水中肿瘤浸润性淋巴细胞(TIL)和外周血T细胞中T细胞受体(TCR)Vβ亚家族的表达变化情况、CD4/CD8细胞比例变化和Treg细胞的分布情况,分析肿瘤患者的免疫状态。方法:分离11例肿瘤患者胸/腹水和外周血以及4例健康人外周血的T细胞,采用流式方法检测Vβ24个亚家族及CD3、CD4、CD8、CD25、CD127的表达情况,统计分析T细胞中Vβ24个亚家族、Treg细胞的特点。结果:TCR Vβ亚家族的表达在肿瘤患者胸/腹水TIL中与血液淋巴细胞中存在着显著差异,其中肺癌患者(4/5)TIL中TCR Vβ8,结肠癌患者(3/4)TIL中TCR Vβ2等亚家族显著高表达;11例肿瘤患者胸/腹水样本中Treg的比例均比外周血高(P<0.05),其中5例肺癌患者胸腹水中CD8+T细胞比例降低。结论:肿瘤患者胸/腹水中的淋巴细胞TCR Vβ亚家族表达与外周血存在差异,表明肿瘤患者体内淋巴细胞发生了明显的优势取用和定向趋化。此外肿瘤微环境可能影响了TIL中CD4+细胞的分化导致胸腹水中Treg细胞的比例升高,同时伴随着CD8+T比例的下降,并可能因此影响到TIL中TCR Vβ亚家族的优势取用情况,且导致免疫耐受。     

血管内大B细胞淋巴瘤尸体解剖临床病理分析

目的 探讨血管内大B细胞淋巴瘤(IVLBCL)的临床病理特征及病理诊断.方法 对2例IVLBCL的尸体解剖检查(简称尸检)病例进行了临床病理、免疫表型(SP法染色)及抗原受体基因(TCRγ、IgH)重排检测.结果 (1)一般情况:2例尸检分别于2005年和1979年进行,均为男性患者,年龄为70岁和50岁.2人均以神经系统功能障碍(双下肢麻木或无力)为首发表现,起病急,病程短(分别为30 d和20 d),病情进展迅速,并在短期内出现多器官功能衰竭而死亡,生存期分别为85 d和44 d.(2)尸检主要发现:除例1患者有多发性皮肤和左心外膜下结节(直径0.5～2.5 cm)外,全身均未见明显占位性病变,但双肺、肾脏、脑、脾脏等脏器有不同程度地均匀肿大和重量增加.例1患者还有多浆膜腔积液.组织学观察见多脏器、组织(脑、垂体、脊髓和脊神经根、心、肺、肾、肝、脾、消化管、淋巴结、胰、肾上腺、甲状腺、睾丸等)的小血管内见数量不等的异形淋巴样细胞存在,且各处之肿瘤细胞形态相似.瘤细胞中等偏大,呈圆形或卵圆形,细胞质丰富,核质比高.细胞核为圆形或卵圆形,核膜较厚,核染色质呈斑块状散在分布,可见1～3个嗜碱性的小核仁.(3)免疫表型及抗原受体基因重排检测:肿瘤细胞均表达B淋巴细胞分化抗原CD20和CD79a;部分瘤细胞表达bcl-2蛋白和CD5抗原;2例之肿瘤细胞均不表达T细胞及髓系分化抗原等[CD3、髓过氧化物酶(MPO)、bcl-6、CD30、CD10和PCK等];Ki-67阳性率均为80%.PCR检测均检出免疫球蛋白重链基因(IgH)克隆性重排,而TCRγ基因呈胚系构型.结论 2例IVLBCL均以神经系统功能障碍为首发表现,有相似的病理形态学特征,免疫表型及基因型,预后差.     

Anaplastic plasmacytoma with malignant pleural effusion lacking evidence of monoclonal gammopathy

A case of plasmacytoma of the pleural cavity is reported with massive malignant pleural effusion, which, most unusually, lacked monoclonal gammopathy, thereby making it difficult to distinguish from lymphoma. The pleural tumor and pleural effusion contained large mononuclear lymphoma-like cells with distinct nucleoli. Immunohistochemistry revealed neither lymphoma markers nor clonal cytoplasmic nor cell surface immunoglobulins. Tumor cells were stained with vimentin and the plasma cell markers, VS38c, CD138 (syndecan-1), and MUM1 antibodies. Bone marrow contained small amounts of tumor consisting of similar cells. Electron microscopy showed well developed rough endoplasmic reticulum and peripherally positioned nuclei with euchromatin. Flow cytometry of bone marrow revealed a minimal involvement of CD38-positive cells. Chromosomal analysis of marrow cells revealed a complex abnormal karyotype. A polymerase chain reaction demonstrated clonal re-arrangement of the immunoglobulin heavy-chain gene. The overall results indicate a clonal expansion of tumor cells with primitive plasma cell differentiation with the highly unusual feature of absent monotypic immunoglobulin. The study illustrates the need for a comprehensive array of techniques to distinguish such rare non-synthesizing and non-secretory plasmacytomas from lymphoma.     

Fine‐needle aspiration biopsy of pleural metastases from a carcinosarcoma or true malignant mixed tumor of the parotid gland mimicking a mesothelioma

Malignant mixed tumor of the parotid is known to have odd sites for metastases. We describe the fine‐needle aspiration cytology (FNAC) findings of pleural metastasis from a malignant mixed tumor misdiagnosed as a mesothelioma on cytology at the onset. A 47‐year‐old man presented to us with breathlessness and a massive pleural effusion with pleural‐based nodules. He had been operated 2 years before for a pleomorphic adenoma of the parotid and had a healthy scar at that site. FNAC from the pleural lesions showed myxoid background substance with entrapped cuboidal epithelial cells with atypical nuclei, which were interpreted as mesothelial cells. These cells in contrast to the usual mesothelial cells were not arranged in sheets but rather were huddled in places and formed a pseudoacinar pattern and blended with the myxoid substance. After the diagnosis of a mesothelioma, patient received pemetrexed and cisplatin based chemotherapy with partial response. While on chemotherapy tumor recurred at the primary site in parotid and was confirmed to be a carcinosarcoma on a FNAC and biopsy. To conclude, pleural metastases from a true malignant mixed tumor of the parotid gland can be misdiagnosed as mesothelioma and could occur in the absence of uncontrolled disease at primary site. Both mesotheliomas and pleomorphic adenomas metastatic to the pleura are biphasic tumors, but in a patient with history of pleomorphic adenoma, the latter should be kept as a foremost possibility. Attention to the cytomorphology of tumor cells will also assist in confirming the diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

EBV‐associated but HHV8‐unrelated double‐hit effusion‐based lymphoma

Effusion‐based lymphoma is a rare and unique type of large B‐cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B‐cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6 . DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61‐year‐old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion. He has no HIV, HBV or HCV infection and no mass lesion by CT scans. Cytology of both pleural effusion and ascites show large lymphoma cells with plasmablastic morphology characterized by pleomorphic and eccentric nuclei, prominent nucleoli and frequent mitoses. Immunohistochemical study with cell block shows that the lymphoma cells express plasma cell‐related markers (CD138, MUM‐1 and EMA), but not CD3, CD30, CD45, B‐cell markers (CD19, CD20, CD79a, and PAX5), HHV8, ALK or cytokeratin. EBER is positive in most lymphoma cells. Fluorescence in situ hybridization reveals rearrangement at the IGH, BCL2, and MYC loci, but not at BCL6 . It is diagnosed as an EBV‐associated but HHV8‐unrelated double hit effusion‐based lymphoma with plasmablastic features. The patient passed away soon after diagnosis without chemotherapy. This is the first reported case of double‐hit effusion‐based lymphoma with MYC and BCL2 rearrangement. This case illustrates the importance of integrating clinical, cytological, immunophenotypical, and molecular findings to reach a correct diagnosis. Diagn. Cytopathol. 2017;45:257–261. © 2016 Wiley Periodicals, Inc.     

Cytologic features of ovarian granulosa cell tumors in pleural and ascitic fluids

Adult granulosa cell tumor (AGCT) is an uncommon neoplasm of the ovary with potential for aggressive behavior and late recurrence. The most important prognostic factor for AGCT is tumor stage. Thus, cytological assessment of pleural or ascitic fluids is crucial for initial staging and subsequent patient management. We report herein two cases of ovarian AGCT presenting with exfoliated tumor cells in pleural and ascitic fluid. The first case involved a 61‐year‐old woman who presented with stage Ic (a) AGCT. Seven years after initial diagnosis, pleural effusion and pleural dissemination were identified. The second case involved a 50‐year‐old woman who presented with stage IV AGCT with massive ascites and right pleural effusion. Fluid cytology from both cases showed cohesive or loose clusters of small uniform neoplastic cells with round‐to‐oval nuclei, coffee‐bean‐shaped nuclear grooves, small nucleoli, and scant cytoplasm. Call‐Exner bodies were also observed in these cytologic specimens. In the differential diagnosis of small monomorphic tumor cells in pleural effusion or ascites, coffee‐bean‐shaped nuclear grooves and cell clusters forming Call‐Exner bodies are diagnostic clues of AGCT. Diagn. Cytopathol. 2015;43:581–584. © 2015 Wiley Periodicals, Inc.     

胸水多项肿瘤标志物检测的临床价值

目的:通过对胸水中多项肿瘤标志物的联合检测来鉴别癌性、结核性胸水,以提高癌性胸水诊断的阳性率。方法:采用多肿瘤标志物蛋白芯片诊断系统,检测60例癌性胸水和30例结核性胸水中的12种常见肿瘤标志物。结果:癌性胸水组中CEA、NSE、SF、CA125四项肿瘤标志物均值数、阳性率均显著高于结核性胸水组。四种指标联检对癌性胸水的诊断阳性率可达96 7%。结论:胸水CEA、NSE、SF、CA125联检对鉴别良恶性胸水有重要价值,且可显著提高癌性胸水的阳性诊断率。     

Malignant mesothelioma with osteoblastic heterologous elements

A 59 year-old man with a history of asbestos exposure presented with a right pleural effusion and a diffuse pleural thickening with focal calcifications on chest X-ray. Cytological examination of pleural fluid indicated malignant mesothelioma. A biopsy specimen showed malignant mesothelioma surrounding a fragment of mature bone. The patient was treated with intrapleural interferon, but relapsed 3 years later. A fresh biopsy specimen showed round tumor cells surrounding osteoid substance. Only ten cases of this rare variant of malignant mesothelioma with osteoblastic heterologous elements have been reported in the literature. The most difficult differential diagnosis is primary pleural osteosarcoma.