Identifying malignant mesothelioma by a pathological survey using the São Paulo state hospital cancer registry, Brazil.

OBJECTIVE: To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil. METHODS: Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM. RESULTS: Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review. CONCLUSIONS: Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.

Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis.

Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.

Mesothelioma in a developing country: a retrospective analysis of the diagnostic process.

OBJECTIVE: To evaluate the process of diagnosing patients with malignant pleural mesothelioma (MPM) at a tertiary care hospital. METHODS: This was a retrospective study involving patients referred to a tertiary-care cancer center in Brazil between 2009 and 2020. The diagnostic process was divided into four steps: onset of symptoms, referral to a specialist visit, histopathological diagnosis, and beginning of treatment. The intervals between each phase and the factors for delays were evaluated. Data including clinical status, radiological examinations, staging, treatment modalities, and survival outcomes were collected. RESULTS: During the study period, 66 patients (mean age = 64 years) were diagnosed with MPM and underwent treatment. Only 27 (41%) of the patients had knowledge of prior exposure to asbestos. The median number of months (IQR) between the onset of symptoms and the first specialist visit, between the specialist visit and histopathological characterization, and between definite diagnosis and beginning of treatment was, respectively, 6.5 (2.0-11.4), 1.5 (0.6-2.1), and 1.7 (1.2-3.4). The knowledge of prior asbestos exposure was associated with a shorter time to referral to a specialist (median: 214 vs. 120 days; p = 0.04). A substantial number of nondiagnostic procedures and false-negative biopsy results (the majority of which involved the use of Cope needle biopsy) were found to be decisive factors for the length of waiting time. The mean overall survival was 11.9 months. CONCLUSIONS: The unfamiliarity of health professionals with MPM and the patient's lack of knowledge of prior asbestos exposure were the major factors to cause a long time interval between the onset of symptoms and beginning of treatment. An overall survival shorter than 1 year is likely to have been due to the aforementioned delays.

Multicenter study of diffuse pleural mesothelioma. Histopathological and immunohistochemical features.

The pathological diagnosis of diffuse pleural mesothelioma (DPM) contributes to treatment selection and clinical trials interpretation. To know its characteristics and evaluate the viability of comprehensive pathological diagnosis of DPM in Argentina we did a retrospective descriptive study of DPM cases reported from 2009 to 2018. We analyzed 398 cases corresponding to 238 (60%) men and 160 (40%) women, median age 66 years, from surgical biopsies (78%), small biopsies (16.5%) and surgical resections (5.5%). The 77% were epithelioid (E-DPM), 12% biphasic, 10% sarcomatoid, and 4 cases transitional variant. In E-DPM the main pattern was tubular in 36% and solid in 33%. There was a second pattern in 179 cases. Considering the main pattern and the second together, 48% presented tubular subtype and 48% solid subtype. Stroma, necrosis, and nuclear score showed significant differences between E-DPM and non-epithelioid mesotheliomas. Overall tumor grade was predominantly low in E-DPM, except for 42% of the solid main pattern. We recognized the transitional variant extensively in 4 cases and focally in 8. The immunohistochemical antibody panel used included pan-cytokeratin, calretinin, WT-1, cytokeratin 5, CEA and TTF-1. The expression of cytokeratin 5, calretinin and WT-1 was lower in the sarcomatoid type (43%, 87 and 37%) than in the epithelioid type (92%, 98% and 93%). This study highlights the tumor heterogeneity of DPM that shows the diagnostic difficulty, and the feasibility of evaluating histological aggressiveness in E-DPM, B-DPM and S-DPM in our country.

El diagnóstico patológico del mesotelioma pleural difuso (MPD) contribuye a la selección del tratamiento y a la interpretación de los ensayos clínicos. Para conocer sus características y evaluar la viabilidad del diagnóstico patológico de MPD en Argentina se realizó un estudio descriptivo retrospectivo de los casos de MPD informados de 2009 a 2018. Se analizaron 398 casos correspondientes a 238 (60%) hombres y 160 (40%) mujeres, mediana de edad de 66 años, a partir de biopsias quirúrgicas (78%), biopsias pequeñas (16.5%) y resecciones quirúrgicas (5.5%). El 77% fue epitelioide (E-MPD), 12% bifásicos, 10% sarcomatoides y 4 casos variante transicional. En E-MPD se encontró como patrón principal el tubular en 36% y el sólido en 33%. Hubo un segundo patrón en 179 casos. Considerando el principal y el segundo patrón en conjunto, el 48% presentó subtipo tubular y el 48% subtipo sólido. El estroma, la necrosis y el score nuclear mostraron diferencias significativas entre E-MPD y mesoteliomas no epitelioides. El grado general del tumor fue predominantemente bajo en E-MPD, a excepción del 42% del patrón principal sólido. Reconocimos la variante transicional en forma extensa en 4 casos y focalmente en 8. La expresión de citoqueratina 5, calretinina y WT-1 fue menor en el tipo sarcomatoide (43%, 87 y 37%) que en el tipo epitelioide (92%, 98% y 93%). Este estudio destaca la heterogeneidad tumoral de MPD que evidencia la dificu ltad en el diagnóstico y la viabilidad de evaluar la agresividad histológica en E-MPD, B-MPD y S-MPD en nuestro país.

Mesotelioma peritoneal em onça-pintada (Panthera onca Linnaeus, 1758) / Peritoneal mesothelioma in jaguar (Panthera onca Linnaeus, 1758) / Mesotelioma peritoneal en jaguar (Panthera onca Linnaeus, 1758)

Mesoteliomas são neoplasias malignas que causam lesões graves e extensas em peritônio, pleura, pericárdio e órgãos adjacentes. O presente estudo de caso discorre sobre o óbito de uma onça-pintada (Panthera onca) mantida sob cuidados humanos em um zoológico do estado de São Paulo, com idade estimada de 19 anos, que apresentou aumento de volume abdominal, ascite, diminuição de deslocamento pelo recinto, inapetência e polidipsia. O paciente foi submetido a exames clínicos, laboratoriais e de diagnósticos por imagem, e em curto espaço de tempo foi a óbito. Os resultados anatomopatológicos e imuno-histoquímicos indicaram o diagnóstico conclusivo de mesotelioma peritoneal, com metástase em linfonodo mesenterico.(AU)

Mesotheliomas are malignant neoplasms and cause severe and extensive lesions in the peritoneum, pleura, pericardium and adjacent organs. The present case study discusses the death of a jaguar (Panthera onca) kept under human care in a zoo in the state of São Paulo, Brazil, with an estimated age of 19-years-old. He presented increased abdominal volume, ascites, decreased displacement by the enclosure, inappetence and polydipsia. The patient underwent clinical, laboratory and diagnostic imaging tests and died after a short period of time. The anatomopathological results indicated the diagnosis of peritoneal mesothelioma, with metastasis in the mesenteric lymph node.(AU)

Los mesoteliomas son neoplasias malignas y provocan lesiones graves y extensas en el peritoneo, pleura, pericardio y órganos adyacentes. El presente estudio de caso presenta la muerte de un jaguar (Panthera onca) mantenido bajo cuidado humano en un zoológico en el estado de São Paulo, Brasil, con una edad estimada de 19 años. El animal presentó aumento de volumen abdominal, ascitis, disminución del desplazamiento por el recinto, inapetencia y polidipsia. Al paciente se le realizaron pruebas clínicas, de laboratorio y de diagnóstico por imágenes, pero en poco tiempo falleció. Los resultados anatomopatológicos indicaron el diagnóstico de mesotelioma peritoneal, con metástasis en el ganglio mesenterico.(AU)

Mesotelioma peritoneal epitelioide papilar maligno em bovino gir – Relato de caso / Malignant papillary epitelioid mesothelioma in the peritoneal cavity of a gir cattle – Case report

O objetivo deste trabalho foi relatar um caso de mesotelioma peritoneal epitelioide papilar em um bovino. Foi atendida uma vaca Gir, com dez anos de idade, apresentando taquicardia, taquipneia, 8% de desidratação, hipomotilidade ruminal, edema de barbela e aumento da circunferência abdominal bilateral ventral. Os achados de palpação consistiram na presença de múltiplos nódulos abdominais firmes, de tamanhos variados, localizados na parede abdominal e presença de grande quantidade de líquido intra-abdominal, confirmados pela ultrassonografia transretal. O líquido peritoneal coletado foi classificado como transudato modificado. Foi realizada laparotomia exploratória pelo flanco, identificando-se aproximadamente 150 litros de líquido peritoneal e múltiplos nódulos de coloração esbranquiçada, firmes, irregulares e difusos no peritônio e na superfície serosa de diferentes órgãos. O exame histopatológico dos fragmentos coletados por biopsia confirmou o diagnóstico de mesotelioma peritoneal classificado como sendo do tipo epitelioide papilar. A maioria dos casos de mesotelioma ocorre de forma incidiosa e sua manifestação clínica ocorre em quadros mais avançados, quando o prognóstico se torna desfavorável ao animal. A partir das condições encontradas no presente relato, foi indicada eutanásia do animal em razão do comprometimento do bem-estar.

The aim of this paper was to report a case of papillary epithelial mesothelioma of the peritoneal surface in a cattle. A ten-yearold Gir cow was examined on a rural property, presenting tachycardia, tachypnea, 8% dehydration, ruminal hypomotility submandibular edema and bilateral ventral abdominal enlargement. Rectal palpation showed multiple firm abdominal nodules, of varying sizes, located in the abdominal wall and the presence of large amounts of intra-abdominal fluid, confirmed by transrectal ultrasonography. The peritoneal fluid collected was classified as modified transudate. Exploratory laparotomy was performed along the flank, identifying approximately 150 liters of peritoneal fluid and multiple whitish-colored nodules, firm, irregular and diffuse on the peritoneum and on the serous surface of different organs. Histopathological examination of the biopsy pieces confirmed the diagnosis of peritoneal mesothelioma classified as papillary epithelioid type. Most cases of mesothelioma occur insidious, and its clinical manifestation occurs in more advanced cases, when the prognosis becomes unfavorable for the animal. Based on the conditions found in this report, euthanasia of the animal was indicated due to compromised well-being.

Mesotelioma peritoneal epitelioide papilar maligno em bovino gir Relato de caso / Malignant papillary epitelioid mesothelioma in the peritoneal cavity of a gir cattle Case report

O objetivo deste trabalho foi relatar um caso de mesotelioma peritoneal epitelioide papilar em um bovino. Foi atendida uma vaca Gir, com dez anos de idade, apresentando taquicardia, taquipneia, 8% de desidratação, hipomotilidade ruminal, edema de barbela e aumento da circunferência abdominal bilateral ventral. Os achados de palpação consistiram na presença de múltiplos nódulos abdominais firmes, de tamanhos variados, localizados na parede abdominal e presença de grande quantidade de líquido intra-abdominal, confirmados pela ultrassonografia transretal. O líquido peritoneal coletado foi classificado como transudato modificado. Foi realizada laparotomia exploratória pelo flanco, identificando-se aproximadamente 150 litros de líquido peritoneal e múltiplos nódulos de coloração esbranquiçada, firmes, irregulares e difusos no peritônio e na superfície serosa de diferentes órgãos. O exame histopatológico dos fragmentos coletados por biopsia confirmou o diagnóstico de mesotelioma peritoneal classificado como sendo do tipo epitelioide papilar. A maioria dos casos de mesotelioma ocorre de forma incidiosa e sua manifestação clínica ocorre em quadros mais avançados, quando o prognóstico se torna desfavorável ao animal. A partir das condições encontradas no presente relato, foi indicada eutanásia do animal em razão do comprometimento do bem-estar.(AU)

The aim of this paper was to report a case of papillary epithelial mesothelioma of the peritoneal surface in a cattle. A ten-yearold Gir cow was examined on a rural property, presenting tachycardia, tachypnea, 8% dehydration, ruminal hypomotility submandibular edema and bilateral ventral abdominal enlargement. Rectal palpation showed multiple firm abdominal nodules, of varying sizes, located in the abdominal wall and the presence of large amounts of intra-abdominal fluid, confirmed by transrectal ultrasonography. The peritoneal fluid collected was classified as modified transudate. Exploratory laparotomy was performed along the flank, identifying approximately 150 liters of peritoneal fluid and multiple whitish-colored nodules, firm, irregular and diffuse on the peritoneum and on the serous surface of different organs. Histopathological examination of the biopsy pieces confirmed the diagnosis of peritoneal mesothelioma classified as papillary epithelioid type. Most cases of mesothelioma occur insidious, and its clinical manifestation occurs in more advanced cases, when the prognosis becomes unfavorable for the animal. Based on the conditions found in this report, euthanasia of the animal was indicated due to compromised well-being.(AU)

Mesotelioma pleural maligno. Actualización sobre diagnóstico y tratamiento / Malignant pleural mesothelioma. Update on diagnosis and treatment

RESUMEN Introducción: El mesotelioma pleural maligno es un tumor maligno primario de la pleura, comúnmente asociado con la exposición al asbesto. Se considera una patología rara y muy agresiva. Objetivo: Realizar una revisión sobre los criterios de diagnóstico y tratamiento actualizados en torno al mesotelioma pleural maligno. Métodos: Se realizó una revisión bibliográfica en fuentes de información disponibles en la Biblioteca Virtual de Salud, de la red telemática Infomed, entre ellas, las bases de datos SciELO, Pubmed/Medline, Cumed, Lilacs, así como el Google Académico. Se seleccionaron un total de 39 referencias. Conclusiones: Existen pocas referencias en la literatura nacional relacionadas con el diagnóstico, tratamiento y seguimiento de los pacientes con mesotelioma pleural maligno. El diagnóstico combina el uso del método clínico, los estudio imagenológicos e histoquímicos. No existe un tratamiento estándar, siendo recomendable un enfoque individualizado que combine según cada caso, cirugía, quimio y radioterapia. Los desafíos futuros incluyen el desarrollo de nuevas alternativas terapéuticas(AU)

ABSTRACT Introduction: Malignant Pleural Mesothelioma is a primary malignant tumor of the pleura, commonly associated with exposure to asbestos. It is considered a rare and very aggressive pathology. Objective: Conduct a review of updated diagnostic and treatment criteria for malignant pleural mesothelioma. Material and Methods: A bibliographic review was made through the search of information in sources available from the Cuban National Health Care Network and Portal (INFOMED), among them, databases such as SciELO, Pubmed / Medline, Cumed, Lilacs, as well as Google Scholar. Finally, a total of 39 references were selected for our study. Conclusions: There are few references in the national literature related to the diagnosis, treatment and follow-up of patients with malignant pleural mesothelioma. The diagnosis combines the use of the clinical method, the imaging and histochemical studies. There is no standard treatment, being recommended an individualized approach that combines according to each case, surgery, chemo and radiotherapy. Future challenges include the development of new therapeutic alternatives(AU)

Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively. CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

High frequency and severity of pleural changes in former workers exposed to anthophyllite associated with other contaminating amphibole asbestos in Brazil.

OBJECTIVE: To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, São Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995. METHODS: Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS). RESULTS: XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum = 1; maximum = 18; interquartile interval = 1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6 ± 7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85 mL and 150 mL, respectively. CONCLUSION: This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.

Chemotherapy Versus Supportive Care for Unresected Malignant Pleural Mesothelioma.

BACKGROUND: Management options for unresected malignant pleural mesothelioma (MPM) are largely limited to palliative chemotherapy and best supportive care. This study sought to delineate subgroups most likely to benefit from chemotherapy. PATIENTS AND METHODS: The National Cancer Database was queried for newly-diagnosed unresected sarcomatoid, biphasic, and/or metastatic (M1) MPM. Statistics included Kaplan-Meier overall survival (OS) analysis with and without propensity matching, landmark Kaplan-Meier analysis to address immortal time bias, and multivariable Cox proportional hazards modeling in all patients as well as within histologic/M-classification-based subcohorts. RESULTS: Of 4655 patients (48% chemotherapy, 52% best supportive care), 15%, 27%, and 40% had epithelioid, biphasic, and sarcomatoid disease, respectively; 41% had M1 disease. The median OS in the chemotherapy and BSC cohorts was 10.4 versus 4.8 months (P < .001). OS differences persisted following landmark analysis (P = .038) and propensity matching (P < .001). Chemotherapy was associated with higher OS in M1 cases with unknown histology and M1 epithelioid patients (P < .001 for both). For non-epithelioid cases, chemotherapy was associated with higher OS for M0 (P < .001 for sarcomatoid and biphasic) but not M1 (P > .05 for both) disease. CONCLUSIONS: Chemotherapy may benefit metastatic epithelioid and non-metastatic non-epithelioid MPM to a greater degree than metastatic non-epithelioid disease. Causation, however, is not implied, and careful patient selection in this population cannot be understated.

Aberrant Cytokeratin 20 Reactivity in Epithelioid Malignant Mesothelioma: A Case Report.

Malignant mesothelioma is an uncommon neoplasm that should be distinguished from the more common pulmonary adenocarcinomas and other metastatic lesions. Although diagnosis is based on morphologic features, immunohistochemical stains such as Calretinin, WT-1, CK-5/6, D2-40, Ber-Ep4, and MOC-31 are routinely used. Other organ-specific immunohistochemical markers are used when metastases from unknown primary lesion is suspected clinically. Here, we report a case of pleural epithelioid malignant mesothelioma expressing CK20. A 68-year-old male presented to the Emergency Department with nonproductive cough and progressive shortness of breath. Chest x-ray showed a large left-sided pleural effusion. Metastasis from a gastrointestinal primary was clinically suspected. Cytopathologic examination of the pleural fluid demonstrated atypical cells singly and in clusters with round nuclei, prominent nucleoli, and dense cytoplasm. The cell block demonstrated single and clusters of atypical cells positive for calretinin, D2-40, WT-1, CK-5/6, and CK7. Ber-EP4, MOC-31, TTF-1, Napsin-A, and CDX-2 were negative. CK20 was diffusely positive. A diagnosis of atypical mesothelial proliferation with aberrant CK20 expression was made. A subsequent pleural biopsy demonstrated sheets of highly atypical cells that were diffusely and strongly positive for the mesothelial markers and CK20. Multiple studies have shown malignant mesotheliomas to lack CK20 reactivity. To our knowledge, this is the first case report of a diffuse and strong CK20-positive mesothelioma. Such aberrant expressions should be kept in mind when cases are histologically atypical or lack reactivity for multiple mesothelial markers, especially when a gastrointestinal primary malignancy is suspected.

Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.

Mesotelioma pleural con síndrome de osteólisis / Pleural mesothelioma with osteolysis syndrome

Introducción: el mesotelioma es un tipo de tumor raro caracterizado por la invasión del mesotelio por células malignas. Es más frecuente en hombres que en mujeres. En 80 porciento de los casos su aparición se relaciona con la exposición a fibras de amianto o asbesto.Objetivo: presentar un caso de mesotelioma maligno con osteólisis grave generalizada, de interés debido a su poca frecuencia en Cuba, su escaso reporte estadístico y las características clínicas singulares de este paciente.Presentación del caso: paciente masculino, blanco, de 54 años, fumador y alcohólico. Acudió a consulta por tos, expectoración amarillenta con sangre y dolor punzante, poco intenso, en la región posteroinferior del hemitórax izquierdo, dolores en la columna cervical, costillas y extremidades, decaimiento marcado, apetito reducido y pérdida de peso. En el examen físico se constató dolor a la palpación y movilización de las extremidades, submatidez y estertores secos localizados en la región posterolateral izquierda baja del tórax. El estudio radiográfico mostró una imagen radiopaca definida que interesaba la pleura parietal izquierda e imágenes osteolíticas en el cráneo, la pelvis y los huesos largos. Mediante tomografía axial computarizada (simple y contrastada) de pulmón y los estudios histológicos se confirmó el diagnóstico de mesotelioma pleural maligno con ostéolisis grave generalizada.Conclusiones: dadas las características clínicas e imagenológicas del caso presentando es necesario profundizar en el estudio de esta enfermedad que, por su poca frecuencia de presentación y su polimorfismo, requiere de la correcta aplicación del método clínico para ser diagnosticada y tratada oportunamente(AU)

Introduction: mesothelioma is a rare tumor characterized by the invasion of the mesothelium by malignant cells. It is more common in men than in women. In 80 percent of cases, its appearance is related to exposure to amianthus or asbestos fibers.Objective: to present a case of malignant mesothelioma with severe generalized osteolysis, of interest due to its low frequency in Cuba, its scarce statistical report and the unique clinical characteristics of this patient.Case presentation: male patient, white, 54 years old, smoker and alcoholic. He came to consultation for cough, yellowish expectoration with blood and stabbing pain, not very intense, in the posteroinferior region of the left hemithorax, pain in the cervical spine, ribs and limbs, marked decay, reduced appetite and weight loss. Physical examination revealed palpation pain and mobilization of the extremities, submaturity and dry respiratory sounds located in the lower left posterolateral region of the thorax. The radiographic study showed a defined radiopaque image that interested the left parietal pleura and osteolytic images in the skull, pelvis and long bones. Through lung computerized tomography (simple and contrasted) and histological studies confirmed the diagnosis of malignant pleural mesothelioma with severe generalized osteolysis.Conclusions: given the clinical and imaging characteristics of the case presented, it is necessary to deepen the study of this disease that, due to its infrequent presentation and its polymorphism, requires the correct application of the clinical method to be diagnosed and treated in a timely manner(AU)

Secreted and Tissue miRNAs as Diagnosis Biomarkers of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates in the pleura, is diagnosed in advanced stages and has a poor prognosis. Accurate diagnosis of MPM is often difficult and complex, and the gold standard diagnosis test is based on qualitative analysis of markers in pleural tissue by immunohistochemical staining. Therefore, it is necessary to develop quantitative and non-subjective alternative diagnostic tools. MicroRNAs are non-coding RNAs that regulate essential cellular mechanisms at the post-transcriptional level. Recent evidence indicates that miRNA expression in tissue and body fluids is aberrant in various tumors, revealing miRNAs as promising diagnostic biomarkers. This review summarizes evidence regarding secreted and tissue miRNAs as biomarkers of MPM and the biological characteristics associated with their potential diagnostic value. In addition to studies regarding miRNAs with potential diagnostic value for MPM, studies that aimed to identify the miRNAs involved in molecular mechanisms associated with MPM development are described with an emphasis on relevant aspects of the experimental designs that may influence the accuracy, consistency and real diagnostic value of currently reported data.

Recent Advances in the Diagnosis of Malignant Mesothelioma: Focus on Approach in Challenging Cases and in Limited Tissue and Cytologic Samples.

Mesothelial proliferations can be diagnostically challenging in small specimens, such as body fluid cytology and small tissue biopsies. A great morphologic challenge for pathologists is the separation of benign reactive mesothelial proliferations from malignant mesotheliomas. Reactive mesothelial proliferations may have histologic features that resemble malignancy including increased cellularity, cytologic atypia, and mitoses. Recent advances in mesothelioma genetics resulted in identification of BAP1 mutations and p16 deletions as features of malignant mesotheliomas. Hence, BAP1 immunohistochemistry and fluorescence in situ hybridization for p16 emerged as 2 most common diagnostically helpful ancillary studies used on limited samples when the question is whether the proliferation is malignant or benign. In contrast, separation of mesothelioma from other malignancies is relatively straight forward using morphology and immunohistochemical stains. The choice of antibody panel to be applied in an individual case is driven by morphology, either epithelioid or sarcomatoid. This brief review will focus on morphology and ancillary testing of mainly pleural mesothelial proliferations.

Real-time PCR assay for the diagnosis of pleural tuberculosis.

INTRODUCTION: The diagnosis of pleural tuberculosis requires an invasive and time-consuming reference method. Polymerase chain reaction (PCR) is rapid, but validation in pleural tuberculosis is still weak. OBJECTIVE: To establish the operating characteristics of real-time polymerase chain reaction (RT-PCR) hybridization probes for the diagnosis of pleural tuberculosis. METHODS: The validity of the RT-PCR hybridization probes was evaluated compared to a composite reference method by a cross-sectional study at the Hospital Universitario de la Samaritana. 40 adults with lymphocytic pleural effusion were included. Pleural tuberculosis was confirmed (in 9 patients) if the patient had at least one of three tests using the positive reference method: Ziehl-Neelsen or Mycobacterium tuberculosis culture in fluid or pleural tissue, or pleural biopsy with granulomas. Pleural tuberculosis was ruled out (in 31 patients) if all three tests were negative. The operating characteristics of the RT-PCR, using the Mid-P Exact Test, were determined using the OpenEpi 2.3 Software (2009). RESULTS: The RT-PCR hybridization probes showed a sensitivity of 66.7% (95% CI: 33.2%-90.7%) and a specificity of 93.5% (95% CI: 80.3%-98.9%). The PPV was 75.0% (95% CI: 38.8%-95.6%) and a NPV of 90.6% (95% CI: 76.6%-97.6%). Two false positives were found for the test, one with pleural mesothelioma and the other with chronic pleuritis with mesothelial hyperplasia. CONCLUSIONS: The RT-PCR hybridization probes had good specificity and acceptable sensitivity, but a negative value cannot rule out pleural tuberculosis.

INTRODUCCIÓN: El diagnóstico de tuberculosis pleural requiere un método de referencia invasivo y demorado. La reacción en cadena de la polimerasa es rápida, pero su validación en tuberculosis pleural aún es débil. OBJETIVO: Establecer las características operativas de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) sondas de hibridación para el diagnóstico de tuberculosis pleural. MÉTODOS: Se evaluó la validez de la RT-PCR sondas de hibridación comparada con un método de referencia compuesto mediante un estudio transversal en el Hospital Universitario de la Samaritana. Se incluyeron 40 adultos con derrame pleural linfocitario. Tuberculosis pleural fue confirmada (en 9 pacientes) si el paciente tenía mínimo una de tres pruebas del método de referencia positiva: Ziehl-Neelsen o cultivo para Mycobacterium tuberculosis en líquido o tejido pleural, o biopsia pleural con granulomas; se descartó tuberculosis pleural (en 31 pacientes) si las tres pruebas eran negativas. Se determinaron las características operativas de la RT-PCR, mediante la Prueba Mid-P Exact, con el Software OpenEpi 2.3 (2009). RESULTADOS: La RT-PCR sondas de hibridación mostró una sensibilidad del 66.7% (IC 95%: 33.2%-90.7%) y una especificidad del 93.5% (IC 95%: 80.3%-98.9%). El VPP fue de 75.0% (IC 95%: 38.8%-95.6%) y un VPN de 90.6% (IC 95%: 76.6%-97.6%). Se encontraron dos falsos positivos para la prueba, uno con mesotelioma pleural y otro con pleuritis crónica con hiperplasia mesotelial. CONCLUSIONES: La RT-PCR sondas de hibridación tuvo una buena especificidad y una aceptable sensibilidad, pero un valor negativo no puede descartar tuberculosis pleural.