Sarcomatoid mesothelioma originating from mesothelioma in situ: are methylthioadenosine phosphorylase loss and CDKN2A homozygous deletion poor prognostic factors for preinvasive mesothelioma?

Abstract

The diagnosis of mesothelioma in situ (MIS) is challenging with conventional diagnostic approaches.Although recent advances in genomic-based assays have made it possible to diagnose MIS, the prognosis, treatment indications, and prognostic factors remain unclear. Previous reports have shown that MIS progresses to invasive mesothelioma; however, to the best of our knowledge, progression to sarcomatoid mesothelioma has not yet been reported. A 73-year-old man was diagnosed with MIS associated with methylthioadenosine phosphorylase (MTAP) loss and a CDKN2A homozygous deletion. Strikingly, pathological examination revealed that the MIS lesion had progressed to sarcomatoid mesothelioma. In analyses of previously reported cases and our case, MIS with a CDKN2A homozygous deletion or MTAP loss progressed to invasive mesothelioma earlier than that without them, indicating that a CDKN2A homozygous deletion and MTAP loss could be poor prognostic factors. Genomic analyses might be useful for predicting the prognosis of MIS and contributing to an optimal treatment.

Progression of Sarcomatoid Mesothelioma from Mesothelioma In Situ: A Case Report on Morphologic Changes during a Nine-month Interval and Careful Observation of Cytology in Early- stage Mesothelioma

“…One of the signi cant points noted herein is that both lesions exhibited loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A). These abnormalities were the same as those found in the case of sarcomatoid mesothelioma arising from MIS previously reported by our group [4,5]. Another important nding reported herein is the prominent cell-in-cell engulfment evidenced in pleural effusion cytology.…”

“…To our knowledge, we have reported on the second case of sarcomatoid mesothelioma arising from MIS, following the rst report (which was also presented by our research group) [4,5]. Interestingly, both cases share the same genomic abnormalities (BAP1 retain, MTAP loss, and CDKN2A homozygous deletion).…”

Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report

“…We have presented a case of MIS that showed obviously malignant mesothelial cells based on cytology of pleural effusion. Based on our search of the literature, 17 cases of pleural MIS have been reported (Table I) (2,(5)(6)(7)(8)(9)(10)(11)(12). According to available data from previous reports, MIS was confirmed only in 8 cases before progression to mesothelioma (2,5,6,8,10,11).…”

“…Based on our search of the literature, 17 cases of pleural MIS have been reported (Table I) (2,(5)(6)(7)(8)(9)(10)(11)(12). According to available data from previous reports, MIS was confirmed only in 8 cases before progression to mesothelioma (2,5,6,8,10,11). It is difficult to suspect MIS at the time of sampling due to unremarkable clinical findings including symptoms, serum tumor markers, radiology, and even pathology.…”

“…Additionally, BAP-1 and MTAP may be used as prognostic markers in mesothelioma ( 16 ). Nishikubo et al ( 11 ) reported that, among 13 patients with MIS, the median progression-free survival for patients with CDKN2A homozygous deletion or MTAP loss was 18 months; in patients who had lost BAP-1 but retained CDKN2A and MTAP, the median progress-free survival was 60 months. Although the authors did not elucidate the mechanism, they hypothesized that BAP-1 loss occurs during the early phase of the disease and MTAP/CDKN2A deletion occurs at a later phase ( 6 , 17 ).…”