Impact of pericardial fluid glucose level and computed tomography attenuation values on diagnosis of malignancy-related pericardial effusion.

BACKGROUND: We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT). METHODS: This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups. RESULTS: All patients were diagnosed as having exudative PE by Light's criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light's criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4-26.0] vs 17.4 [IQR, 13.7-26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012). CONCLUSIONS: Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

What is the normal composition of pericardial fluid?

OBJECTIVE: Biochemical and cytological pericardial fluid (PF) analysis is essentially based on the knowledge of pleural fluid composition. The aim of the present study is to identify reference intervals (RIs) for PF according to state-of-art methodological standards. METHODS: We prospectively collected and analysed the PF and venous blood of consecutive subjects undergoing elective open-heart surgery from July 2017 to October 2018. Exclusion criteria for study enrolment were evidence of pericardial diseases at preoperatory workup or at intraoperatory assessment, or any other condition that could affect PF analysis. RESULTS: The final study sample included 120 patients (median age 69 years, 83 men, 69.1%). The main findings were (1) High levels of proteins, albumin and lactate dehydrogenase (LDH), but not of glucose and cholesterol (2) High cellularity, mainly represented by mesothelial cells. RIs for pericardial biochemistry were: protein content 1.7-4.6 g/dL PF/serum protein ratio 0.29-0.83, albumin 1.19-3.06 g/dL, pericardium-to-serum albumin gradient 0.18-2.37 g/dL, LDH 141-2613 U/L, PF/serum LDH ratio 0.40-2.99, glucose 80-134 mg/dL, total cholesterol 12-69 mg/dL, PF/serum cholesterol ratio 0.07-0.51. RIs for pericardial cells by optic microscopy were: 278-5608 × 106 nucleated cells/L, 40-3790 × 106 mesothelial cells/L, 35-2210 × 106 leucocytes/L, 19-1634 × 106 lymphocytes/L. CONCLUSIONS: PF is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Physicians should stop to interpret PF as exudate or transudate according to tools not validated for this setting.

Comparison between optical microscopy and automation for cytometric analysis of pericardial fluids in a cohort of adult subjects undergoing cardiac surgery.

AIMS: Limited information is available on number and type of cells present in the pericardial fluid (PF). Current evidence and has been garnered with inaccurate application of guidelines for analysis of body fluids. This study was aimed at investigating the performance of automate cytometric analysis of PF in adult subjects. METHODS: Seventy-four consecutive PF samples were analysed with Sysmex XN with a module for body fluid analysis (XN-BF) and optical microscopy (OM). The study also encompassed the assessment of limit of blank, limit of detection and limit of quantitation (LoQ), imprecision, carryover and linearity of XN-BF module. RESULTS: XN-BF parameters were compared with OM for the following cell classes: total cells (TC), leucocytes (white blood cell [WBC]), polymorphonuclear (PMN) and mononuclear (MN) cells. The relative bias were -4.5%, 71.2%, 108.2% and -47.7%, respectively. Passing and Bablok regression yielded slope comprised between 0.06 for MN and 5.8 for PMN, and intercept between 0.7 for PMN and 220.3 for MN. LoQ was comprised between 3.8×106 and 6.0×106 cells/L for WBC and PMN. Linearity was acceptable and carryover negligible. CONCLUSIONS: PF has a specific cellular composition. Overall, automated cell counting can only be suggested for total number of cells, whereas OM seems still the most reliable option for cell differentiation.

Cytological evaluation of pericardial fluids: A 5 years experience in tertiary care center.

BACKGROUND: Cytological examination of pericardial effusion fluids is important in diagnosing the etiology of underlying disease, staging, and prognosis of cancer. AIMS AND OBJECTIVES: (1) To study cytological evaluation of pericardial effusions in various pathological conditions in a tertiary care center. (2) To analyze their frequency and clincopathological correlation of the diagnosis. MATERIALS AND METHODS: Our study was a retrospective study performed in the Department of Pathology from 1st January 2012 to 31st December 2016. The study sample included all the pericardial effusions submitted in the pathology department for cytological evaluation. Clinical details and relevant parameters correlated with clinical findings. Each fluid underwent cytospin and cytocentrifuge along with preparation of conventional smears. RESULTS: Of 120 cases, 80% were of benign effusion and 20% were of malignant effusion. Male-to-female ratio was 1.44:1 with patient age ranging from 3 to 90 years. CONCLUSION: Benign effusions can been seen in younger age group and malignant ones in the older age group. The preliminary pericardial fluid analysis in resource-limited settings is the most convenient and cost-effective method for accurate diagnosis. It reduces the demand of invasive investigations and its complications. At times, it is the first test to point toward underlying malignant process thereby affecting the prognosis, survival, and treatment outcome of the patient.

SLE pericardial effusion clinically mimicking hypothyroidism and tuberculosis diagnosed on cytology with LE cells.

The occurrence of lupus erythematosus cells (LE cells) in serous body fluids is extremely uncommon but, when present, is highly specific for systemic lupus erythematosus (SLE). LE cells are commonly reported in pleural and peritoneal effusions but very rarely documented in pericardial effusion. Here, we report a case in which pericardial fluid examination clinched the diagnosis of SLE which was clinically suspected of tuberculosis/hypothyroid effusion by striking presence of LE cells on May-Grünwald Giemsa-stained and Papanicolaou stained smears. Subsequent serologic studies revealed high titers of anti-nuclear antibodies and anti-ds-DNA confirming the diagnosis of SLE. This case highlights the importance of careful examination of pericardial fluid or pleural or peritoneal fluid in the diagnosis of unsuspected cases of SLE in an era wherein "LE cell detection" is considered to be of historic interest.

Sarcomatoid carcinoma in cytology: Report of a rare entity presenting in pleural and pericardial fluid preparations.

Sarcomatoid carcinoma is rarely found in pleural or pericardial fluid, with very few cases published to date. Here, we describe a 59-year-old female who presented with cough persisting for 5 months. Chest CT scan revealed a 6.0 cm cavitary mass in the left lung base with bulky mediastinal and hilar lymphadenopathy. An additional 1.2 cm right adrenal mass was seen and was suspicious for metastatic disease. The patient developed dyspnea, tachycardia, pleuritic chest pain and generalized weakness and was admitted to the hospital. She was found to have pleural and pericardial effusions, which were drained and sent to cytology. The fluid revealed enlarged highly pleomorphic malignant cells, some displaying multinucleation with irregular nuclear borders, coarse chromatin and prominent nucleoli. Tumor cells were positive for CK7 and Vimentin and negative for MOC-31, Ber-EP4, B72.3, Sox10, Melan-A, TTF-1, Napsin-A and CK20. A concurrent surgical biopsy of the tumor mass displayed immunopositivity for AE1/AE3 and CAM5.2. The tumor was negative for p40, TTF-1, calretinin, D2-40 and STAT6. A diagnosis of sarcomatoid carcinoma with giant cells and spindle cells was rendered. Sarcomatoid carcinomas of the lung are very uncommon consisting of 1% of non-small-cell lung carcinomas and are even more unusual in cytology specimens. Despite its rarity, it is important to keep this entity in mind in the differential diagnosis of a fluid specimen with bizarre nuclear atypia and the above staining pattern.

Diagnostic role of cytology in serous effusions of patients with hematologic malignancies.

BACKGROUND: We investigated serous effusions occurring during the course of an already known hematologic neoplasia or as a first manifestation of it. We correlated cytology results with flow cytometry results, when available. In the absence of flow cytometry, our correlation was based on clinical follow up information obtained retrospectively. We evaluated our results in relation to the data of the literature and we considered some new suggestions for the improvement of cytology service. METHODS: Serous effusions in hematologic patients were retrieved from the files of the Department of Cytology, Laiko Hospital, for a period of 2 years. All patients had enrolled either a previous hematologic history, or a suspicious clinical and imaging status. Seventy-three serous effusions were included. Cytology reports consisting of morphology and immunocytochemistry assessment were correlated to flow cytometry results and, occasionally, to clinical follow-up. RESULTS: In the group of patients with previous history, sensitivity was 82.76%, positive predictive value was 100%, specificity 100%, and negative predictive value was 58.33%. In the group of patients without previous history, sensitivity and positive predictive value were both 91%, whereas specificity and negative predictive value could not be estimated. CONCLUSION: We provide evidence that the diagnostic accuracy of cytology with the adjunct of immunocytochemistry is high compared to flow cytometry for detecting hematologic malignancies. In order to improve clinical performance, it is suggested that a cytology triage of serous effusions in all patients with hematologic malignancy must be implemented.

Performance Characteristics of Body Fluid Cytology Analysis of 344 380 Responses From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

CONTEXT: - Body fluid cytology is an important diagnostic tool used to identify various conditions. However, an accurate diagnosis in this setting can sometimes be challenging. OBJECTIVE: - To identify the performance characteristics of body fluid cytology by analyzing participant responses from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. DESIGN: - Participant responses from 5102 slides were analyzed for concordance to the general category (GC) and to the reference diagnosis (RD). Nonlinear mixed models were used to analyze concordance. RESULTS: - The overall GC concordance was 95.2%. The GC type, participant type, and preparation type were significantly associated with GC concordance ( P < .001). Concordance for malignant cases was higher than it was for benign cases. Cytotechnologists had better GC concordance compared to pathologists. ThinPrep (Hologic, Marlborough, Massachusetts) slides had the highest GC concordance. Participant type, fluid type, preparation type, and participant interpretation were significantly associated with RD concordance ( P < .001). Pathologists performed better than cytotechnologists did for RD concordance. Pericardial fluid had the lowest RD concordance, especially for cases with normal or reactive findings. Modified Giemsa-stained slides performed best for lymphoma and hematopoietic malignancy. Small cell carcinoma had the highest GC concordance, and its RD concordance was higher in pleural than in peritoneal fluids. Adenocarcinoma showed the highest concordance rates for both GC and RD. CONCLUSIONS: - This study illustrates the challenges associated with interpreting body fluid cytology, particularly in pericardial fluid, and the factors that may affect accurate diagnoses. The results also highlight the value of using multiple preparation types in challenging cases.

Pericardial Effusion.

The normal pericardial sac contains up to 50 mL of fluid, which consists of a plasma ultrafiltrate. Anything greater constitutes a pathologic effusion. The curvilinear pressure-volume relationship of the pericardial sac dictates hemodynamic consequences of a pericardial effusion and is responsible for rapidly accumulating fluid that causes cardiac tamponade. A variety of diseases and complications cause pericardial effusion. The most common are idiopathic pericarditis, cancer, connective tissue disorders, and hemorrhage. Management of pericardial effusion is dictated by whether tamponade is present or threatened. If it is, urgent/emergent pericardiocentesis is indicated. If not, a systematic approach to diagnosis and management should be undertaken.

A cytologic diagnosis of BRAFV600E Erdheim-Chester disease on pericardial fluid.

We report the case of a 74-year-old woman admitted to the emergency unit for resting dyspnea. Clinical presentation, cardiac MRI and echocardiography were consistent with cardiac tamponade requiring emergency pericardiocentesis. Cytologic examination of the pericardial fluid revealed the presence of CD68pos CD1aneg S100neg foamy histiocytes (Fig. 1). Additional investigations complied with the diagnosis of Erdheim-Chester histiocytosis. Treatment with αIFN was initiated but the patient developed severe neutropenia that contraindicated further administration. The detection of BRAFV600E mutation on histiocytes isolated from the pericardial liquid and CNS involvement (cerebral masses) prompted the administration of vemurafenib, a selective BRAFV600E kinase inhibitor. Four months after the initiation of low-dose vemurafenib, pericarditis almost resolved and cerebral masses decreased by 50% (Fig. 2). To our knowledge, analysis of pericardial fluid allowing the diagnosis of Erdheim-Chester disease and the detection of the BRAFV600E mutation has in fact been rarely described in the literature. This case report and the successful evolution under vemurafenib also support the use of BRAFV600E inhibitors in αIFN-intolerant patients with BRAFV600E mutation, particularly in case of heart and central nervous system involvement.

External quality assurance in nongynecologic cytology: The Australasian experience.

BACKGROUND: The Royal College of Pathologists of Australasia Cytopathology Quality Assurance Program has operated an external quality assurance program in nongynecologic cytopathology since 1993. Glass slide preparations of a wide range of nongynecologic cases were circulated to approximately 200 cytopathology laboratories in 16 countries. METHODS: General nongynecologic cytology cases were manufactured from residual specimens after routine diagnosis. Fine-needle aspiration (FNA) cases were made by sampling fresh tissue and making direct specimens. The majority of cases consisted of both air-dried and fixed preparations. Results returned to laboratories included illustrated case discussions highlighting diagnostic features, key differential diagnoses, and useful adjunctive tests. RESULTS: The current study reviewed >22,000 results for 123 nongynecologic cases. Cases found to cause the most diagnostic difficulties included serous effusion cases with metastatic carcinoma in a dispersed pattern, well-differentiated carcinoma, and cellular reactive cases; urine specimens with sparse malignant cells; reactive pneumocytes in a bronchoalveolar lavage; breast FNA cases with papillary lesions; gestational specimens; and fibroadenoma. FNA specimens from the lung and thyroid, particularly papillary thyroid carcinoma, generally were well reported. CONCLUSIONS: The use of multiple preparations of the same specimen has allowed interlaboratory comparison, and the quality assurance program has played an educational role as well as informing the laboratory accreditation process. Cancer Cytopathol 2017;125:349-361. © 2017 American Cancer Society.

Contemporary management of pericardial effusion: practical aspects for clinical practice.

A pericardial effusion (PE) is a relatively common finding in clinical practice. It may be either isolated or associated with pericarditis with or without an underlying disease. The aetiology is varied and may be either infectious (especially tuberculosis as the most common cause in developing countries) or non-infectious (cancer, systemic inflammatory diseases). The management is essentially guided by the hemodynamic effect (presence or absence of cardiac tamponade), the presence of concomitant pericarditis or underlying disease, and its size and duration. The present paper reviews the current knowledge on the aetiology, classification, diagnosis, management, therapy, and prognosis of PE in clinical practice.

The Diagnostic Value of Pericardial Fluid and Pericardial Biopsy: Single Center Experiences.

BACKGROUND: Patients with recurrent pericardial effusion and pericardial tamponade are usually treated in thoracic surgery clinics by VATS (video-assisted thoracoscopic surgery) or open pericardial window operation. The diagnostic importance of pathological evaluation of the pericardial fluid and tissue in the same patients has been reported in few studies. We reviewed pathological examination of the pericardial tissue and fluid specimens and the effect on the clinical treatment in our clinic, and compared the results with the literature. METHODS: We retrospectively analyzed 174 patients who underwent pericardial window operation due to pericardial tamponade or recurrent pericardial effusion. For all patients both the results of the pericardial fluid and pericardial biopsy specimen were evaluated. Clinicopathological factors were analyzed by using descriptive analysis. RESULTS: Median age was 61 (range, 20-94 years). The most common benign diagnosis was chronic inflammation (94 patients) by pericardial biopsy. History of malignancy was present in 28 patients (16.1%) and the most common disease was lung cancer (14 patients). A total of 24 patients (13.8%) could be diagnosed as having malignancy by pericardial fluid or pericardial biopsy examination. The malignancy was recognized for 12 patients who had a history of cancer; 9 of 12 with pericardial biopsy, 7 diagnosed by pericardial fluid. Twelve of 156 patients were recognized as having underlying malignancy by pericardial biopsy (n = 9) or fluid examination (n = 10), without known malignancy previously. CONCLUSION: Recurrent pericardial effusion/pericardial tamponade are entities frequently diagnosed, and surgical interventions may be needed either for diagnosis and/or treatment, but specific etiology can rarely be obtained in spite of pathological examination of either pericardial tissue or fluid. For increasing the probability of a specific diagnosis both the pericardial fluid and the pericardial tissues have to be sent for pathologic examination.

Cytologic and Immunophenotypic Features of Malignant Cells in Pediatric Body Fluids.

OBJECTIVE: Cytospin preparations and immunocytochemistry are common methods in hospitals to evaluate malignancies in body fluids. Characteristics of malignant cells in pediatric body fluids have not been adequately evaluated. STUDY DESIGN: 183 pleural, peritoneal and pericardial pediatric fluid specimens were examined by cytospin preparations and immunocytochemistry from two hospitals using similar procedural techniques. Cytologic diagnoses were correlated with the results of clinical history, histology and ancillary studies. RESULTS: Forty cases with malignancy were identified (21.9%); the most common diagnoses were rhabdomyosarcoma and acute lymphoblastic lymphoma (9 and 8 cases, respectively). Small round cell tumors revealed similar morphology as clusters of small round cells with central nuclei and scant cytoplasm with frequent small vacuoles. Twenty-one cases were evaluated by immunocytochemistry, 12 by flow cytometry and 5 by cytogenetic analysis. CD3, CD20, TdT, CD10, desmin and myogenin were the most common markers. Staining artifacts causing interpretation difficulties were noted in 5 cases that were resolved by molecular studies and deferral for surgical specimens. CONCLUSIONS: Small round cell tumors are the most common malignancies encountered in pediatric body fluids and share a nonspecific morphology. Although immunocytochemistry is helpful to arrive at the correct diagnosis, other ancillary studies may be necessary, particularly in hematologic malignancies and other difficult cases.