Age-related schwannomatosis with potential exosome-mediated contribution to prostate hyperplasia: a case report and mini-review

Abstract

A 72-year-old Caucasian man incurring a prostate hypertrophy presented with a right forearm nodule, the growth of which appeared to parallel the rise in his blood prostate-specific antigen (PSA) level. Echographic examination was consistent with a median-nerve schwannoma, and was confirmed upon magnetic resonance imaging (MRI). Excision of the nodule was readily performed without significant neural damage, and its schwannoma nature was confirmed upon immunohistochemistry analysis. Importantly, blood PSA dropped abruptly from ≈13 to ≈5 ng/ml within 2 months postschwannoma resection, a swift drastic reduction unachievable with oral dutasteride alone. However, 6 weeks later, a new nodule became apparent on the back of the left knee and was identified as a second schwannoma, thereby suggesting that its growth could have been stimulated by the resection of the first schwannoma, as previously described for vestibular schwannomas. The second schwannoma was in fact two: the bigger one was in the common fibular nerve and the smaller one in the tibial nerve. Both echography and MRI results were confirmed upon surgical resection of the bigger knee schwannoma. Although the third schwannoma has not yet been resected and formally characterized, we face a schwannomatosis case with an unexpected potential exosome-mediated stimulating effect on PSA secretion (PSA immunohistochemistry was negative on both schwannomas). On the other hand, preliminary genomic analysis showed a deficient balance for chromosome 22, the very chromosome carrying the three main genes involved in schwannomatosis. This age-related schwannomatosis case is thus discussed in light of the following: age-related DNA repair deficiency culminating in loss of chromosome/heterozygosity; CpG methylation/demethylation-based epigenetic aging; age-related functional decline of the immune system responsible for inefficient elimination of abnormal cells and subsequent tumorigenic cell turn-over; exosome-mediated pathologic intercellular communications; and prostate-invading brain neural progenitors as pathologic peripheral nervous system (PNS) cells.

Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication

“…SDEVs from high glucose-stimulated SCs have been reported to involve in mediating the development of diabetic peripheral neuropathy in a diabetic mouse model ( Jia et al, 2018 ). SDEVs are also reported to be involved in the development of age-related schwannomatosis (a rare genetic disorder that results in tumors that grow on the peripheral nerves throughout the body) ( Chignon-Sicard et al, 2019 ). These compelling findings elucidate the importance of SDEVs in glia-neuron cross talk both in health and in pathological conditions.…”

Schwann cell‐derived exosomes: Janus‐faced mediators of regeneration and disease

“…Apart from peripheral neuropathy, the involvement of SC-derived exosomes in schwannomatosis has also been reported (Chignon-Sicard et al, 2019). A case study of schwannomatosis displayed two important unusual characteristics: a potential stimulating effect on prostate-specific antigen secretion and a potential growth-stimulation effect on a cognate schwannoma tumor when a large schwannoma tumor was resected (Chignon-Sicard et al, 2019). It was reasoned that the interactions between distant cells through blood and other bodily fluids could contribute to both of the unusual features above (Chignon-Sicard et al, 2019).…”

“…A case study of schwannomatosis displayed two important unusual characteristics: a potential stimulating effect on prostate‐specific antigen secretion and a potential growth‐stimulation effect on a cognate schwannoma tumor when a large schwannoma tumor was resected (Chignon‐Sicard et al, 2019). It was reasoned that the interactions between distant cells through blood and other bodily fluids could contribute to both of the unusual features above (Chignon‐Sicard et al, 2019). Since exosomes are well‐known as the intercellular mediators found in most body fluids, it was suggested that exosome‐mediated cell communications were responsible for this case because the schwannoma tumor cells and tumor‐adjacent resident SCs could secrete exosomes targeting at prostate cells and distant schwannoma cells, resulting in an unexpected potential stimulating effect that led to prostate hyperplasia and cognate schwannoma (Chignon‐Sicard et al, 2019).…”

“…It was reasoned that the interactions between distant cells through blood and other bodily fluids could contribute to both of the unusual features above (Chignon‐Sicard et al, 2019). Since exosomes are well‐known as the intercellular mediators found in most body fluids, it was suggested that exosome‐mediated cell communications were responsible for this case because the schwannoma tumor cells and tumor‐adjacent resident SCs could secrete exosomes targeting at prostate cells and distant schwannoma cells, resulting in an unexpected potential stimulating effect that led to prostate hyperplasia and cognate schwannoma (Chignon‐Sicard et al, 2019). As the formation of schwannomatosis occurs over a prolonged period, it might be possible that healthy mature SCs are converted to repair SCs in the first response to any pathological insult from the tumors to attempt for nerve repair, and eventually these repair SCs become dysfunctional due to the chronic damage to the repair SCs.…”

Schwann cells in the normal and pathological lung microenvironment

“…Interestingly, apart from different neuropathies, the potential contribution of SC-derived exosomes in carcinogenesis has also been suggested ( Wong et al, 2022 ). A case study of schwannomatosis revealed a promoting effect on prostate-specific antigen secretion and a growth-accelerating outcome on a cognate schwannoma after resection of a prominent schwannoma ( Chignon-Sicard et al, 2019 ). This was explained by exosomes secreted from schwannoma cells and tumor-adjacent resident SCs that targeted prostate cells and distant schwannoma cells.…”