bims-mesote 2021-09-05 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2021–09–05
eight papers selected by
Laura Mannarino, Humanitas Research

Loss of Methylthioadenosine Phosphorylase by Immunohistochemistry Is Common in Pulmonary Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.
Relationship Between Physical Function and Health Utility in Patients Undergoing Surgical Treatment for Malignant Pleural Mesothelioma.
Evidence-based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology.
Pleural mesothelioma classification-update and challenges.
Examining the impact of physical function performance in predicting patient outcomes after lung-sparing surgery for malignant pleural mesothelioma.
FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma.
State of the art cytology of pleural fluid, focusing on the diagnosis of mesothelioma.
Solid papillary mesothelial tumor.

Am J Clin Pathol. 2021 Aug 31. pii: aqab091. [Epub ahead of print]

Loss of Methylthioadenosine Phosphorylase by Immunohistochemistry Is Common in Pulmonary Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

Simone Terra, Anja C Roden, Eunhee S Yi, Marie Christine Aubry, Jennifer M Boland.

   OBJECTIVES: Differentiating malignant pleural mesothelioma from benign reactive mesothelial processes can be quite challenging. Ancillary tests such as BRCA1-associated protein 1 (BAP1) immunohistochemistry and p16 fluorescence in situ hybridization (FISH) are helpful tools to aid in this distinction. Immunohistochemistry for methylthioadenosine phosphorylase (MTAP) has recently been proposed as an effective surrogate marker for p16 FISH and is an attractive alternative test due to shorter turnaround time. There are little data regarding the specificity of MTAP loss for mesothelioma or whether it may be useful to distinguish mesothelioma from the most common entity in the differential diagnosis, sarcomatoid carcinoma.
METHODS: We studied well-characterized cases of sarcomatoid carcinoma (n = 34) and sarcomatoid mesothelioma (n = 62), which were stained for MTAP (clone 2G4) and BAP1 (clone C-4).
RESULTS: Loss of MTAP expression was observed in 17 (50%) of 34 pulmonary sarcomatoid carcinomas; BAP1 expression was retained in all of the cases in which it was performed (n = 31). MTAP expression was lost in 38 (61%) of 62 sarcomatoid mesotheliomas; BAP1 was lost in 6 (10%) of 62. In the six cases with BAP1 loss, five also had loss of MTAP, while MTAP expression was retained in one.
CONCLUSIONS: Loss of MTAP expression by immunohistochemistry is common in pulmonary sarcomatoid carcinoma, as it is present in half of cases. This rate is similar to what is observed in sarcomatoid mesothelioma (61%). Therefore, this stain is not useful to distinguish between these two malignancies. MTAP loss is more common than BAP1 loss in the setting of sarcomatoid mesothelioma (61% vs 10%, respectively).

Keywords:  BAP1; MTAP; Sarcomatoid carcinoma; Sarcomatoid mesothelioma

DOI:  https://doi.org/10.1093/ajcp/aqab091
Integr Cancer Ther. 2021 Jan-Dec;20:20 15347354211043508

Relationship Between Physical Function and Health Utility in Patients Undergoing Surgical Treatment for Malignant Pleural Mesothelioma.

Takashi Tanaka, Shinichiro Morishita, Masaki Hashimoto, Toru Nakamichi, Yuki Uchiyama, Seiki Hasegawa, Kazuhisa Domen.

   PURPOSE: Health utility, which is a measure of patient-reported outcome (PRO), has recently been used in health-related quality of life for patients with various cancers. However, the relationship between health utility and the physical function and of patients undergoing pleurectomy/decortication (P/D) as surgical treatment for malignant pleural mesothelioma (MPM) has not been reported in the perioperative and convalescent phases. This study aimed to evaluate the perioperative and postoperative health utility of patients undergoing P/D for MPM at one year postoperatively and to examine the relationship with physical function.
METHODS: We included patients underwent P/D. Grip strength, knee extension strength, 6-minute walk distance (6MWD), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were measured to assess physical function, and the Short-Form Six-Dimension (SF-6D) was completed to assess health utility. These assessments were performed preoperatively, postoperatively, and one year postoperatively. Statistical analysis was performed using one-way analysis of variance for comparison of pre and postoperative and one year mean values.
RESULTS: There were 24 subjects (23 males, 65.5±8.3 year). SF-6D, 6MWD, FVC, and FEV1 values one year operatively improved significantly compared with postoperative. Additionally, SF-6D was correlated with 6MWD.
CONCLUSION: Health utility were also correlated with exercise capacity.

Keywords:  convalescent phase; health utility; malignant pleural mesothelioma; patient-reported outcome; physical function; pleurectomy/decortication; quality of life; rehabilitation

DOI:  https://doi.org/10.1177/15347354211043508
Cancer Cytopathol. 2021 Sep 03.

Evidence-based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology.

Ilaria Girolami, Ersilia Lucenteforte, Albino Eccher, Stefano Marletta, Matteo Brunelli, Paolo Graziano, Pasquale Pisapia, Umberto Malapelle, Giancarlo Troncone, Aldo Scarpa, Tao Huang, Liron Pantanowitz.

  Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta-analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy-one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59-0.71) and a specificity of 0.99 (CI, 0.93-1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38-0.57) and 0.62 (CI, 0.53-0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78-0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70-0.90) and 0.65 (CI, 0.41-0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68-0.77) and a specificity of 0.90 (CI, 0.84-0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.

Keywords:  biomarker; cytology; diagnostic specificity and sensitivity; effusion; immunohistochemistry; mesothelioma; meta-analysis; pleura; systematic review

DOI:  https://doi.org/10.1002/cncy.22509
Mod Pathol. 2021 Aug 31.

Pleural mesothelioma classification-update and challenges.

Sanja Dacic.

Mesothelial tumors are classified into benign or preinvasive tumors, and mesotheliomas. The benign or preinvasive group includes adenomatoid tumors, well-differentiated papillary mesothelial tumors, and mesothelioma in situ. Malignant tumors are mesotheliomas and can be localized or diffuse. Histological classification of invasive mesotheliomas into three major subtypes-epithelioid, sarcomatoid, and biphasic is prognostically important. It also plays a significant role in the treatment decisions of patients diagnosed with this deadly disease. Grading and subtyping of epithelioid mesotheliomas have been one of the major changes in the recent WHO classification of pleural tumors. Mesothelioma in situ has emerged as a precisely defined clinico-pathologic entity that for diagnosis requires demonstration of loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH. The use of these two biomarkers improves the diagnostic sensitivity of effusion specimens and limited tissue samples and is valuable in establishing the diagnosis of epithelioid mesothelioma. In this review, recent changes in the histologic classification of pleural mesothelioma, importance of ancillary diagnostic studies, and molecular characteristics of mesotheliomas are discussed.

DOI: https://doi.org/10.1038/s41379-021-00895-7
Disabil Rehabil. 2021 Aug 29. 1-8

Examining the impact of physical function performance in predicting patient outcomes after lung-sparing surgery for malignant pleural mesothelioma.

Simon Ho, Melissa Culligan, Joseph Friedberg, Olga Goloubeva, Victoria Marchese.

   PURPOSE: The purpose of this study was to examine the impact of physical function performance and pulmonary function on patient outcomes after lung-sparing surgery for malignant pleural mesothelioma (MPM).
MATERIALS AND METHODS: A retrospective review of 54 patients with MPM from 2015 to 2020 was performed. The primary objective was to assess whether physical function, as measured by the Eastern Cooperative Oncology Group Performance Status (ECOG), and pulmonary function tests were predictive of postoperative patient outcomes (ventilator days, chest tube days, hospital length of stay). A secondary objective was to explore demographic and preoperative variables that best predict postoperative physical function and patient outcomes.
RESULTS: Data include 54 patients who underwent extended pleurectomy-decortication. Preoperative ECOG was a significant predictor of postoperative patient outcomes while preoperative lung function lacked predictive ability. Preoperative ECOG was also predictive of preoperative lung function. Age on the day of surgery was the best predictor of postoperative physical function, which was significantly reduced postoperatively.
CONCLUSIONS: Preoperative physical function performance was a significant predictor of postoperative outcomes. The results of our study highlight the importance of physical function in patients with MPM and support the need for early rehabilitation and further research to determine optimal rehabilitation interventions.IMPLICATIONS FOR REHABILITATIONPreoperative physical function can predict outcomes after lung-sparing surgery for malignant pleural mesothelioma (MPM).Physical function in patients with MPM should be carefully examined.To accurately reflect patients' abilities, patient assessment should include both patient-reported outcomes and performance-based measures.Patients with MPM should receive rehabilitation early after diagnosis and throughout the continuum of care.

Keywords:  Physical function; disability; extended pleurectomy-decortication; lung-sparing surgery; mesothelioma; rehabilitation

DOI:  https://doi.org/10.1080/09638288.2021.1970256
Clin Cancer Res. 2021 Aug 30. pii: clincanres.1466.2021. [Epub ahead of print]

FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma.

Erica C Nakajima, Paz J Vellanki, Erin Larkins, Somak Chatterjee, Pallavi S Mishra-Kalyani, Youwei Bi, Hisham Qosa, Jiang Liu, Hong Zhao, Missiratch Biable, Lauren Tesh Hotaki, Yuan Li Shen, Richard Pazdur, Julia A Beaver, Harpreet Singh, Martha Donoghue.

On October 2, 2020, the U.S. Food and Drug Administration (FDA) approved nivolumab with ipilimumab as first-line treatment for adult patients with unresectable malignant pleural mesothelioma (MPM). The approval was based on results from Study CA209743 (CHECKMATE-743), an open-label trial of patients with MPM randomized to receive nivolumab and ipilimumab for up to two years (n=303) or six cycles of chemotherapy with cisplatin or carboplatin plus pemetrexed (n=302). Overall survival (OS) was improved for patients who received nivolumab and ipilimumab, with a median OS of 18.1 months (95% CI: 16.8, 21.5) compared to 14.1 months (95% CI: 12.5, 16.2) (HR 0.74; 95% CI: 0.61, 0.89; p = 0.002), for patients who received chemotherapy. The magnitude of benefit was larger for patients with non-epithelioid versus epithelioid histology. Additional clinical pharmacology data supports an alternative dosing regimen of nivolumab than evaluated in the trial, which will reduce the number of required treatment visits. This application was reviewed under FDA's Project Orbis, in collaboration with Australia's Therapeutic Goods Administration, Switzerland's Swissmedic, Health Canada, and Brazil's National Health Surveillance Agency or ANVISA (Agência Nacional de Vigilância Sanitária). Nivolumab and ipilimumab is the first drug regimen approved by the FDA for MPM since 2004.

DOI: https://doi.org/10.1158/1078-0432.CCR-21-1466
Cytopathology. 2021 Sep 01.

State of the art cytology of pleural fluid, focusing on the diagnosis of mesothelioma.

Sara E Monaco, Luka Brcic, Sanja Dacic.

   OBJECTIVE: Mesothelioma has always been a challenging diagnosis to render in body cavity cytology samples. This review is a timely update on pleural fluid cytology and ancillary studies that should be considered in the diagnosis of mesothelial proliferations, specifically mesotheliomas.
METHODS: Information about new diagnostic approaches and ancillary studies in mesothelioma was obtained from the peer-review literature and the author's experiences.
RESULTS: Although the morphological diagnosis of mesothelioma is fraught with numerous challenges given the overlap with other diagnostic entities, there are a variety of immunohistochemical and FISH studies available to help in determining mesothelial origin and in distinguishing malignant proliferations from the more common benign or reactive mesothelial proliferations.
CONCLUSIONS: Although the ancillary studies can be helpful, there are important pitfalls to be aware of when interpreting these cases, and this review highlights some of the challenges to be aware of.

Keywords:  immunohistochemistry-FISH; mesothelioma; pleural fluid

DOI:  https://doi.org/10.1111/cyt.13055
Mod Pathol. 2021 Sep 03.

Solid papillary mesothelial tumor.

Andrew Churg, Nolwenn Le Stang, Sanja Dacic, Daniel Pissaloux, Hugues Begueret, Peggy Dartigues, Sophie Giusiano-Courcambeck, Ruth Sequeiros, Jean-Claude Pairon, Franck Tirode, Francoise Galateau-Sallé.

We report nine examples of a previously undescribed type of peritoneal circumscribed nodular mesothelial tumor characterized by nests or sheets of mesothelial cells with sharp cell borders and extremely bland, sometimes grooved, nuclei. In some cases, nests were separated by fibrous bands. All patients were women, age range 30-72 years (median 52 years). All tumors were incidental findings during surgery and grossly were either solitary nodules or a few small nodules on the peritoneal surface. Referring pathologic diagnoses included diffuse malignant mesothelioma, localized malignant mesothelioma, well-differentiated papillary mesothelioma, and adenomatoid tumor. No tumor showed BAP1 loss by immunohistochemistry nor deletion of CDKN2A by FISH. RNA-seq revealed that these tumors clustered together and were distinct from peritoneal diffuse malignant mesotheliomas. Very few mutations or translocations were found, none of them recurrent from tumor to tumor, and no tumor showed an abnormality in any of the genes typically mutated/deleted in diffuse malignant mesothelioma. Array CGH on three cases revealed two with a completely flat profile and one with a small deletion at 3q26-3q28. On follow-up (range 5-60, median 34 months), there were no deaths, no recurrences, and no evidence of metastatic disease nor local spread; one case that initially had scattered nodules on the pelvic peritoneum had the same pattern of nodules at a second look operation 2 years later. We propose the name solid papillary mesothelial tumor for these lesions. These appear to be either benign or very low-grade tumors that need to be separated from malignant mesotheliomas.

DOI: https://doi.org/10.1038/s41379-021-00899-3