Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.

OBJECTIVES: Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST (imPERCIST), shown by [18F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and modified RECIST (mRECIST), shown by CT, were compared for response evaluation and prognosis prediction. RESULTS: imPERCIST indicated nine progressive metabolic disease (PMD), eight stable metabolic disease (SMD), four partial metabolic response (PMR), and five complete metabolic response (CMR) cases. mRECIST showed nine with progressive disease (PD), nine stable disease (SD), seven partial response (PR), and one complete response (CR). Although high concordance was noted (κ = 0.827), imPERCIST correctly judged a greater percentage with CMR (15.4%). Following a median 10.0 months, 15 patients showed progression and eight died from MPM. With both, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients without progression (CMR/PMR/SMD, CR/PR/SD, respectively) as compared to PMD/PD patients (imPERCIST p < 0.0001 and p = 0.015, respectively; mRECIST p < 0.0001 and p = 0.015, respectively). METHODS: Twenty-six patients (23 males, 3 females; median 73.5 years) with histologically proven MPM and no curative surgery received nivolumab plus ipilimumab combination therapy. FDG-PET/CT and diagnostic CT scanning at the baseline, and after 2-4 cycles (2 in three, 3 in 17, 4 in six patients) were performed. Therapeutic response findings evaluated using imPERCIST and mRECIST were compared. PFS and OS analyses were done using log-rank and Cox methods. CONCLUSION: For unresectable MPM patient examinations, FDG-PET and CT provide accurate findings for evaluating tumor response and also prognosis prediction following first-line nivolumab plus ipilimumab immunotherapy (approximately three cycles).

Predictive potential of MRI in differentiating the predominant component in biphasic pleural mesothelioma.

PURPOSE: To assess the potential of apparent diffusion coefficient (ADC) values derived from diffusion weighted (DW) MRI preoperatively to predict the predominant histologic component among biphasic pleural mesothelioma (PM) tumors. METHODS: ADC maps were generated from DW MRI scans. Histology and predominant component of biphasic PM were confirmed following surgical resection. Statistical analyses were done with R (R Foundation for Statistical Computing, Vienna, Austria). Average ADC values corresponding to epithelioid- and sarcomatoid-predominant tumors were compared. ADC thresholding was accomplished by recursive partitioning and confirmed with ROC analysis. RESULTS: Eighty-four patients with biphasic PM's, 69 (82 %) epithelioid-predominant (BE) and 15(18 %) sarcomatoid-predominant (BS) tumors were evaluated. Thirty-eight (45 %) patients underwent extrapleural pneumonectomy (EPP), 39 (46 %) had extended pleural decortication (ePDC) and 7 (8 %) had pleural decortication (PDC). ADC values ranged between 0.696 x 10-3 to 1.921 x 10-3 mm2/s. BE tumors demonstrated significantly higher ADC values than BS tumors (p = 0.026). ADC values above 0.94 x 10-3 mm2/s were associated with a significant increase of relative risk of being in group BE over group BS (relative risk: 1.47, 95 %CI: 1.05-2.06, p = 0.027) CONCLUSION: Average ADC values of BE tumors were higher than BS tumors and the two groups can be separated by a cut off value of 0.94 X 10-3 mm2/s.

Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.

BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography. MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis. RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%. CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.

18F-FDG and 68Ga-PSMA PET/CT in Paratesticular Mesothelioma.

ABSTRACT: A 66-year-old man with local prostate adenocarcinoma underwent radical prostatectomy (Gleason score 3 + 4 = 7, pT2c) in 2016. Four years later, he presented with a hydrocele and cystic atypical change in the left scrotum and soft tissue in the left groin. Final histopathology revealed spermatic cord mesothelioma and left hemangiosis carcinomatosa. A bone biopsy of the sacrum revealed infiltrates of a prostatic adenocarcinoma with small cell neuroendocrine differentiation. Dual-tracer PET/CT imaging using 18F-FDG and 68Ga-PSMA was able to identify local recurrence of scrotal mesothelioma and differentiate metastases of prostate cancer from malignant mesothelioma.

Testicular mesothelioma disguised as hydrocele: a case report.

BACKGROUND: Testicular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis. CASE PRESENTATION: We present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1 month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up. CONCLUSION: Although hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants.

Epithelial Malignant Pleural Mesothelioma Mimics Lymphoma on 18 F-FDG PET/MRI : A Case Report.

ABSTRACT: Malignant pleural mesothelioma is a rare tumor with a poor prognosis. We describe a case of 55-year-old man without asbestos exposure history presenting with extensive lymph nodes with high 18 F-FDG uptake in PET/MRI but atypical pleural manifestations thereby being misdiagnosed for lymphoma. Pathological examination concludes for an epithelioid mesothelioma-associated lymph node metastasis. This case emphasizes that with the extensive lymph node abnormalities shown in PET imaging, in addition to the general consideration of lymphoma, it is still necessary to be vigilant about the possibility of mesothelioma and emphasizes the necessity of pathological examination.

Malignant Peritoneal Mesothelioma Complicating Familial Mediterranean Fever on 18 F-FDG PET/CT.

ABSTRACT: A 77-year-old man with a personal history of familial Mediterranean fever presented with a slowly enlarging tumefaction of the left abdominal wall and persistent inflammatory syndrome despite good adherence to colchicine. 18 F-FDG PET/CT showed a hypermetabolic muscular mass of the abdominal wall along with other hypermetabolic lesions including a peritoneal mass and several subcutaneous soft tissue nodules. CT-guided needle biopsy led to the diagnosis of a muscular localization of a malignant peritoneal mesothelioma, which is an extremely rare complication of familial Mediterranean fever. Six courses of chemotherapy with carboplatin and pemetrexed allowed an almost complete response.

Clinical Response of Primary Malignant Pericardial Mesothelioma with Peritoneal Dissemination to Nivolumab.

Malignant pericardial mesothelioma (MPM) is extremely rare, and peritoneal dissemination has not yet been reported. There is no consensus regarding appropriate pharmacological treatment for MPM, including immune checkpoint inhibitors (ICIs). We herein report a 36-year-old man with MPM diagnosed by peritoneal dissemination and treated with an ICI. Cytology of the ascites revealed malignant peritonitis, and a re-evaluation of a pericardial biopsy performed at the previous hospital led to a diagnosis of MPM. The patient was treated with nivolumab and showed a clinical response despite several complications, such as renal dysfunction and performance status deterioration. This case report provides suggestive information for the diagnosis and ICI therapy of a rare type of mesothelioma.

An overview on multimodal imaging for the diagnostic workup of pleural mesothelioma.

Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic and therapeutic viewpoint. Despite recent improvements in patient care, PM typically carries a poor outcome, especially in advanced stages. Therefore, a timely and effective diagnosis taking advantage of currently available imaging techniques is essential to perform an accurate staging and dictate the most appropriate treatment strategy. Our aim is to provide a brief, but exhaustive and up-to-date overview of the role of multimodal medical imaging in the management of PM.

The prognostic value of F18 Fluorothymidine positron emission tomography for assessing the response of malignant pleural mesothelioma to chemotherapy - A prospective cohort study.

INTRODUCTION: Malignant pleural mesothelioma is difficult to prognosticate. F18-Fluorodeoxyglucose positron emission tomography (FDG PET) shows promise for response assessment but is confounded by talc pleurodesis. F18-Fluorothymidine (FLT) PET is an alternative tracer specific for proliferation. We compared the prognostic value of FDG and FLT PET and determined the influence of talc pleurodesis on these parameters. METHODS: Overall, 29 prospectively recruited patients had FLT PET, FDG PET and CT-scans performed prior to and post one chemotherapy cycle; 10 had prior talc pleurodesis. Patients were followed for overall survival. CT response was assessed using mRECIST. Radiomic features were extracted using the MiM software platform. Changes in maximum SUV (SUVmax), mean SUV (SUVmean), FDG total lesion glycolysis (TLG), FLT total lesion proliferation (TLP) and metabolic tumour volume (MTV) after one chemotherapy cycle. RESULTS: Cox univariate analysis demonstrated FDG PET radiomics were confounded by talc pleurodesis, and that percentage change in FLT MTV was predictive of overall survival. Cox multivariate analysis showed a 10% increase in FLT tumour volume corresponded with 9.5% worsened odds for overall survival (P = 0.028, HR = 1.095, 95% CI [1.010, 1.187]). No other variables were significant on multivariate analysis. CONCLUSION: This is the first prospective study showing the statistical significance of FLT PET tumour volumes for measuring mesothelioma treatment response. FLT may be better than FDG for monitoring mesothelioma treatment response, which could help optimise mesothelioma treatment regimes.

Fluoro-edenite non-neoplastic diseases in Biancavilla (Sicily, Italy): pleural plaques and/or pneumoconiosis?

BACKGROUND: A mesothelioma cluster in Biancavilla (Sicily, Italy), drew attention to fluoro-edenite, a fibre classified by International Agency for Research on Cancer as carcinogenic to humans. Significant excesses in mortality and morbidity were observed for respiratory diseases and a significant excess of pneumoconiosis hospitalizations was reported. OBJECTIVE: Aim of this study is to assess the characters of the lung damage in Biancavilla residents hospitalized with pneumoconiosis or asbestosis diagnoses. METHODOLOGY: Medical records, available radiographs and computed tomography scans were collected. The obtained imaging was reviewed by a panel of three specialists and focused on pleural and parenchymal abnormalities. Cases with an ILO-BIT or ICOERD score equal or greater than 2 were considered positive for a pneumoconiosis-like damage, cases with a score lower than 2 or insufficient quality of imaging were considered inconclusive. If no pneumoconiotic aspects were present the cases were classified as negative. RESULTS: Out of 38 cases, diagnostic imaging for 25 cases were found. Ten cases out of 25 showed asbestosis-like features, nine subjects were considered negative. In six patients' results were inconclusive. CONCLUSIONS: Asbestosis-like features were substantiated in Biancavilla residents without known occupational exposure to asbestos. Further studies to estimate population respiratory health are required. Experimental studies on the fibrogenic potential of fluoro-edenite are needed.

Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results.

Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).

Ovarian Metastasis From Diffuse Epithelioid Malignant Mesothelioma Revealed by 18 F-FDG PET/CT.

ABSTRACT: Diffuse epithelioid malignant mesothelioma (MM) with metastasis to the ovary is rare. We reported FDG PET/CT findings in a 39-year-old woman with ovarian metastasis from diffuse epithelioid MM. The ultrasound findings at the external hospital revealed multiple masses in the hepatic hilus. FDG PET/CT examination was recommended to evaluate the nature of the lesions. It showed that 2 hypodense lesions in the perihepatic space had intense activity, and there was an additional FDG lesion in the right ovary, which was later confirmed as diffuse epithelioid MM with ovarian metastasis by pathological examination.

Primary pericardial mesothelioma complicated by pericardial calcification.

BACKGROUND: Pericardial calcification is usually a marker of chronic diseases, and its occurrence in rapidly progressing malignant primary pericardial mesothelioma (PPM) is extremely rare. Therefore, this atypical imaging appearance contributes to more frequent misdiagnosis of PPM. However, no systematic summary currently exists of the imaging characteristics of malignant pericardial calcification in PPM. In our report, its clinical characteristics are discussed in detail, to provide a reference to reduce the misdiagnosis rates of PPM. CASE PRESENTATION: A 50-year-old female patient was admitted to our hospital, presenting primarily with features suggestive of cardiac insufficiency. Chest computed tomography revealed significant pericardial thickening and localized calcification, suspicious of constrictive pericarditis. A chest examination performed through a midline incision showed a chronically inflamed and easily-ruptured pericardium that was closely adherent to the myocardium. Post-operative pathological examination confirmed a diagnosis of primary pericardial mesothelioma. Six weeks postoperatively, the patient experienced symptom recurrence and abandoned chemotherapy and radiation therapy. Nine months postoperatively, the patient died of heart failure. CONCLUSION: We report this case to highlight the rare finding of pericardial calcification in patients with primary pericardial mesothelioma. This case illustrated that confirmation of pericardial calcification cannot completely rule out rapidly developing PPM. Therefore, understanding the different radiological features of PPM can help to reduce its rate of early misdiagnosis.

Tumor thickness in mesothelioma predicts differential response to neoadjuvant therapy and survival.

OBJECTIVE: Neoadjuvant systemic therapy in resectable malignant pleural mesothelioma remains controversial and demonstrates variable responses. We sought to evaluate tumor thickness as a predictor of response to neoadjuvant therapy and as a prognostic marker for overall survival. METHODS: Data from patients who underwent neoadjuvant therapy followed by cytoreductive surgery from 2002 to 2019 were reviewed. Baseline and postneoadjuvant therapy tumor thickness were measured on computed tomography. Radiological tumor response was categorized as progressive disease (≥20% increase), partial response (≥30% decrease), or stable disease (in between). Tumor response outcomes were modeled using logistic regression and multinomial regression models. Overall survival was evaluated based on tumor thickness and tumor response. RESULTS: Of the 143 patients reviewed, 36 (25%) had progressive disease, 54 (38%) had stable disease, and 56 (39%) had partial response. The baseline tumor thickness of the progressive disease group (36 mm) was lower than in both stable disease and partial response groups (both 63 mm; P < .001). Both logistic regression and multinomial regression analyses demonstrated that thicker baseline tumor thickness was associated with decreased probability of progressive disease and increased probability of partial response. In a multivariable Cox model, thicker postneoadjuvant therapy tumor thickness was associated with worse overall survival (hazard ratio, 1.01, 95% confidence interval, 1.00-1.01, P = .008). The same trend was observed for thicker baseline tumor thickness (hazard ratio, 1.02, 95% confidence interval, 1.01-1.04, P = .008), and the risk was decreased in tumors with partial response (hazard ratio, 0.98, 95% confidence interval, 0.96-0.100, P = .014). CONCLUSIONS: We present the first study demonstrating the relationship between baseline tumor thickness and differential radiographic response to neoadjuvant therapy and survival. Further studies are needed to validate tumor thickness as both a prognostic and predictive biomarker.

A case of malignant peritoneal mesothelioma with a Fitz-Hugh-Curtis syndrome-like imaging finding.

Malignant peritoneal mesothelioma (MPeM) is a rare disease with a poor prognosis that develops in the mesothelial cells of the peritoneum. We encountered a 48-year-old man with no prior asbestos exposure who visited our hospital with abdominal pain. Laboratory findings showed elevated C-reactive protein of 15.5 mg/dL. Contrast-enhanced computed tomography (CT) detected a Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface and thickening of the peritoneum. Blood culture, Mycobacterium tuberculosis-specific IFN-γ release assay, Chlamydia trachomatis and Neisseria gonorrhoeae DNA testing, and antinuclear antibody were all negative. CA125 was high at 124.8 U/mL. The laparoscopy for diagnostic purposes revealed adhesions between the liver surface and peritoneum in addition to numerous small and large white nodules on the peritoneum. Biopsy of the nodules confirmed the diagnosis of epithelial-type MPeM. Treatment was initiated with combined cisplatin and pemetrexed, and CT 6 months later showed a reduced contrast effect on the liver surface and improved peritoneal thickening. A Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface on contrast-enhanced CT may help identify MPeM.

Mesotheliomas and Benign Mesothelial Tumors: Update on Pathologic and Imaging Findings.

A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics. While malignant mesotheliomas are biologically aggressive malignancies that occur primarily in patients exposed to asbestos with attendant poor survival rates, well-differentiated papillary mesothelial tumors and adenomatoid tumors charter a benign clinical course with an excellent prognosis. Mesothelioma in situ is a newly characterized entity represented by recurrent unexplained pleural effusions without any identifiable mass at imaging or thoracoscopy. Immunohistochemical markers based on BAP1, MTAP, CDKN2A, and TRAF7 gene mutations help differentiate diffuse mesotheliomas from benign mesothelial proliferations and localized mesotheliomas. Cross-sectional imaging modalities, including US, CT, MRI, and fluorine 18-fluorodeoxyglucose (FDG) PET/CT, permit diagnosis and play a major role in staging and assessing surgical resectability. Imaging studies are invaluable in providing noninvasive and quantitative assessment of tumor response in patients with unresectable disease. Owing to significant overlap in patient characteristics and pathomorphology, accurate diagnosis based on advanced histopathology techniques and genetic abnormalities is imperative for optimal management and prognostication. While patients with nonepithelioid pleural mesotheliomas benefit from immunotherapy, novel targeted therapies for CDKN2A-, NF2-, and BAP1-altered mesotheliomas are under consideration. © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.