Review

Malignant mesothelioma 1982: Review of 4710 published cases

Mesothelioma is a rare but highly aggressive malignancy with poor prognosis that frequently present with recurrent effusions. Establishing the diagnosis by cytology can lead to early diagnosis and treatment and consequently improve prognosis.

This review examines the cytological diagnosis of mesothelioma in the context of its historical and morphologic evolution and provides an update of the current reporting systems. Clues to identify the mesothelial and malignant nature of the sample are detailed as well as the supporting ancillary tests.

Cytologically, the samples are overwhelmingly cellular and malignancy is recognized by both architectural and cytological atypia. Numerous variably sized clusters and enlarged cells are easily identified, some with papillary architecture and collagen cores. Recognizing the mesothelial nature of the cells and supportive immunostains are essential to rule out the differential diagnosis of metastatic carcinomas and reactive mesothelium. Current ancillary tests such as homozygous deletion of CDKN2A, loss of BRCA1-associated protein, and methylthioadenosine phosphorylase expression can provide further support of malignancy.

At this time with the aid of current ancillary tests and in the hands of cytopathologists with adequate experience with the interpretation of effusions, the diagnosis of mesothelioma can be established with accuracy in most cases.

We report a case of malignant pericardial mesothelioma (MPcM) with epithelioid and sarcomatous features in a 28-year-old female. She presented with new onset orthopnea and dyspnea on exertion. Chest imaging revealed a large soft tissue mass in the left atrium. The patient underwent surgical resection with septal reconstruction, and initial preliminary pathology review indicated undifferentiated sarcoma with positive margin. She subsequently received 1 cycle of cyclophosphamide and adriamycin, however, outside additional pathology review revealed a diagnosis of pericardial malignant mesothelioma with epithelioid and sarcomatoid features. Her chemotherapy regimen was altered to carboplatin and pemetrexed, after which she completed 5 cycles. Heart imaging at one month post completion of chemotherapy demonstrated rapid local tumor recurrence. She was not a candidate for further surgical resection, and instead underwent definitive radiation therapy (RT) treating the entire left atrium with 54 Gy in 30 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions to the recurrent gross disease. Follow-up imaging at one month after completion of RT demonstrated a local progression and the patient resumed further systemic therapy. Further imaging with a PET/CT at 3 months after completion of radiation therapy revealed resolution of hypermetabolic uptake at the left atrium and she was actively being evaluated for possible further resection.

Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.

Malignant mesothelioma most commonly arises in the pleura and peritoneum but also occurs rarely at other anatomical sites with mesothelial tissue, namely, the pericardium and tunica vaginalis testis (TVT). This review provides a better understanding of the epidemiology of mesothelioma of these extrapleural sites.

We conducted a systematic review of the epidemiologic and clinical literature on pericardial mesothelioma and mesothelioma of the TVT. We also analyzed U.S. Surveillance, Epidemiology, and End Results cancer registry data to describe incidence patterns of these malignancies.

An etiologic role of asbestos exposure has been hypothesized for pericardial and TVT mesotheliomas, but no analytical case-control epidemiologic studies exist to test this relationship. A substantial proportion of cases with these malignancies report no known asbestos exposure. In large occupational cohorts with heavy asbestos exposures, no cases of pericardial or TVT mesothelioma have been reported. Trends in the incidence of these malignancies do not match those of pleural mesothelioma, which correspond to historical trends of commercial asbestos use. A male preponderance of pericardial mesothelioma is not evident.

In the absence of analytic epidemiologic studies, the etiologic role of environmental risk factors for mesothelioma of the pericardium and TVT remains elusive.

Macroscopic complete surgical resection with adjuvant chemotherapy can provide a survival advantage in patients with malignant pleural mesothelioma (MPM). Patients with nonepithelioid histology are largely excluded from such radical operations even though they might benefit. The degree of epithelioid differentiation varies in biphasic histology. We report the outcomes of pleurectomy and decortication and the effect of epithelioid differentiation on overall survival of patients with MPM.

This report is based on the outcomes of 144 patients who underwent pleurectomy and decortication at a single institution between 2008 and 2015. The variables assessed were age, gender, histology, and pathologic T and N stage. No patients with pure sarcomatoid histology were included. Two independent pathologists estimated the percentage of epithelioid histology. A Cox regression model was used to identify significant predictors of survival. The Kaplan-Meier method was used to summarize overall and subgroup survival.

Included were 116 men and 28 women with a median age of 69 years (range, 43 to 88 years). The 2-year survival from pleurectomy and decortication was 20%. Median survival overall was 13.34 months and was 20.1 months for the 100% epithelioid subgroup (n = 77), 11.8 months for the 51% to 99% epithelioid subgroup (n = 39), and 6.62 months for the less than 50% epithelioid subgroup (n = 28). The amount of epithelioid differentiation was a significant predictor of survival (p < 0.001). Differences in survival based on the T, but N stage, were not statistically significant.

The percentage of epithelioid differentiation is an independent predictor of survival in MPM and should be taken into careful consideration when recommending surgical treatment for patients with biphasic MPM.

A 58-year-old woman presented with an 8-month history of shortness of breath on exertion. Previous chest imaging had shown pleural thickening and peripheral nodules in the upper lung zones, without lymphadenopathy. A diagnostic procedure was performed.

Presentation of Case

Dr. Christopher J. Mutrie (Thoracic Surgery): A 58-year-old woman was seen in the outpatient pulmonary clinic of this hospital because of shortness of breath on exertion.

The patient had been well until approximately 8 months before this presentation, when she noted shortness of breath while jogging her usual 4 miles daily. During the next 7 months, her symptoms gradually worsened until she became winded within 7 minutes after starting to jog or after climbing stairs, with associated leg fatigue. Approximately 1 month before this evaluation, she was seen at an outpatient clinic of another hospital. On examination, …