Human Pathology 2021 March 2 [Link]

Hiroe Itami, Tomomi Fujii, Tokiko Nakai, Maiko Takeda, Yohei Kishi, Fumiaki Taniguchi, Chiyoko Terada, Fumi Okada, Yuji Nitta, Minami Matsuoka, Shoh Sasaki, Sumire Sugimoto, Tomoko Uchiyama, Kohei Morita, Takahiko Kasai, Ryuji Kawaguchi, Chiho Ohbayashi


Adenomatoid tumors (ATs) are benign mesothelial tumors with good prognosis and usually occur in female and male genital tracts, including in the uterus. ATs are genetically defined by tumor necrosis factor receptor-associated factor (TRAF) 7 mutations and a high frequency of AT cases show immunosuppression. On the other hand, malignant mesotheliomas (MMs) are malignant mesothelial tumors with very poor prognosis. Genetic alterations in TRAF, MTAP, and BAP1 in ATs derived from the uterus and MMs of pleural or peritoneal origin were compared by gene sequence analysis or immunohistochemical approaches. Formalin-fixed paraffin-embedded tissues derived from patients were used for immunohistochemical staining of L1CAM, BAP1, MTAP, and HEG1 in 51 uterine AT cases, 34 pleural or peritoneal MM cases, and for next-generation sequencing of the TRAF7 gene in 44 AT cases and 21 MM cases. ATs had a significantly higher rate of L1CAM expression than MMs, while MMs had a significantly higher rate of loss of MTAP and BAP1 expression than ATs. There was no difference in the rate of HEG1 expression between the tumor types. Most of the ATs (37/44; 84%) had somatic mutations in TRAF7, none of the MMs did (0/21; 0%). Additionally, a low frequency of AT cases was associated with a history of immunosuppression (9/51; 17.6%). TRAF7 mutation is one of the major factors distinguishing the development of AT from MM, and immunosuppression might not be associated with most AT cases.