PPMM is a rare malignancy that is more frequent in males in their fifth to seventh decades .4 As outlined in our 2 cases, the combination of an aggressive malignancy, non-specific presenting symptoms, diagnostic complexities, and ineffective treatment options results in a poor prognosis with high mortality. Once the diagnosis is established, one-year survival is 22%, with a median survival rate of two months.4,5 The most common cause of death is cardiac tamponade, heart failure, or pulmonary embolism. One of our patients died two months after diagnosis due to progressive disease.6 The other patient also died two months after diagnosis due to pulmonary embolism, most likely due to the hypercoagulable state caused by the underlying malignancy.
The presenting symptoms are largely insidious and include dry cough, dyspnea, fatigue, and low-grade fevers. A review of 103 cases published in 2018 reported that 92% of all patients were symptomatic upon presentation.7 The reported median time for a diagnosis was three months.7 The frequent delay in diagnosis is due to the non-specific constellation of symptoms and the challenges of tissue sampling in this anatomic site.
PPMM may arise as a localized or diffuse mass. The three histological types are epithelioid (60%), sarcomatoid (20%), and biphasic (20%), with epithelioid tumours conferring a better prognosis.8 While one of our patient’s had an epithelioid subtype and the other had a sarcomatoid subtype, both died around the same duration after diagnosis was established. As opposed to pleural and peritoneal mesotheliomas which are generally associated with asbestos exposure, PPMM has not been directly associated with asbestos exposure. Instead, genetics, infection, recurrent serosal inflammation, radiation, and chemical exposure have been proposed to play a part. None of our patients had exposure to asbestos.1,2,4
A recent review of PPMM cases identified that 12.6% of patients were diagnosed through autopsy, which is a significant improvement from the 75% postmortem diagnosis cited in prior studies.7 While cytological analysis from pericardiocentesis may be performed, the procedure yields malignant cells in only 20% of cases.9 Imaging modalities may help identify functional cardiac evaluation, involvement of adjacent structures, degree of constriction, extent of metastasis, and involvement of neoplasm of the pleura. Evidence from the literature confirms that the most accurate diagnostic procedure is the histopathological analysis of tissue obtained through biopsy or surgical resection.3 Fluorescence in situ hybridization (FISH) of our patients showed that both had 9p21 deletions. Several studies have stated that homozygous deletion of the 9p21 gene locus is linked to a poor prognosis and higher mortality rate.10 Given the diagnostic challenges, perhaps genomic profiling may facilitate early detection, and there may be avenues for targeted gene therapy in the future.
There is no consensus on treatment strategies for patients with PPMM. In the early stages of malignancy, where the tumor is localized, surgical resection confers a survival benefit. McGehee et al. reported that mass resection resulted in median survival of 27 months compared to a median survival of 3 months in patients who did not undergo resection.7 However, surgery is challenging as there is a risk of damage to local neurovascular structures, epicardium, and myocardium. With palliative intent, surgical drainage of large pericardial effusions may improve their quality of life2.
As the response to radiotherapy is poor, chemotherapy has been utilized as an adjuvant to surgery or used solely in extensive malignancy. Both of our patients received chemotherapy, as surgical resection was deemed not to be beneficial to their prognosis. However, they died soon after the commencement of chemotherapy. Studies have shown that a combination of doxorubicin, vincristine, and cyclophosphamide reduces tumour progression prolonging survival up to 17.5 months.11 Similarly, a study conducted by Kim et al. reported that combining cisplatin, gemcitabine, and vinorelbine in 4 cycles enabled the patient to remain disease-free for 24 months after completion of chemotherapy.2
Newer therapies for PPMM including anti-angiogenesis drugs, photodynamic therapy, gene therapy, biologic response modifiers, and more targeted chemotherapy regimens are currently undergoing clinical trials. These therapies provide hope for better treatment options in the future.2,6,11 Presently it appears multimodal therapy confers the most notable median survival rate in patients diagnosed with PPMM.