Recent developments in uterine mesenchymal neoplasms

Abstract

Smooth muscle and endometrial stromal tumours represent the two most common uterine mesenchymal neoplasms that may present diagnostic dilemmas for the practising surgical pathologist. Recent changes in morphological and staging criteria, as well as the discovery of new immunohistochemical markers, have improved the diagnosis and classification of these tumours. We highlight the difficulty in distinguishing tumour cell necrosis from infarct-type necrosis and the limited utility of p16 immunohistochemical expression in the diagnosis of leiomyosarcoma. We also discuss the controversial use of mitotic activity and necrosis as prognostic factors in endometrial stromal sarcomas. Emerging genetic information has also greatly expanded our understanding of 'sarcomagenesis' in both tumour types and may provide insight into potential therapeutic targets for the treatment of leiomyosarcoma and endometrial stromal sarcomas, harboring MED12 (mediator complex subunit 12) mutations and recurrent gene rearrangements, respectively. In this review, we discuss the core updates in the diagnosis and classification of uterine leiomyosarcomas and endometrial stromal sarcomas, highlighting new and important molecular genetic findings that may drive pathogenesis.

Practical issues related to uterine pathology: endometrial stromal tumors

“…[9][10][11][12]30,31 The reported frequency of JAZF1-JJAZ1 fusion has been detected in~48% of low-grade ESS. 32 The second most frequent abnormality is t(6;7)(p21;p15), a so-called variant translocation of the t(7;17), because of the involvement of 7p15 and 6p21 instead of 17q21 resulting in a JAZF1-PHF1 fusion gene. 31,33 The PHF1 gene at 6p21 can also fuse with EPC1 at 10p11 and MEAF6 at 1p34.…”

“…37 Surgical stage appears to be the most important prognostic factor. 38 Patients with low-grade ESS 32 have an excellent prognosis with a 90% 5-year disease-free survival if low stage (I/II); 5-year survival drops to 50% if high stage (III/IV). 39 …”

Uterus: Low-grade endometrial stromal sarcoma with t(X;17)(p11.2;q21.33) MBTD1/CXorf6

“…Mitotic figures are rare. By immunohistochemistry, the tumour components are diffusely and strongly positive for CD10 antigen and for oestrogen and progesterone receptors (Oliva et al, 2013).…”

“…Low-and high-grade endometrial stromal sarcomas are genetically heterogeneous group of tumours, frequently harbouring recurrent chromosomal translocations. The chimeric transcripts reorted so far are JAZF1/SUZ12, YWHAE/FAM22, ZCH7/BCOR, and recombination of PFH1 with JAZF1, EPC1, or MEAF6 (Koontz et al, 2001;Micci et al, 2006;Lee et al, 2012;Panagopoulos et al2012;Panagopoulos et al, 2013;Oliva et al, 2013).…”

“…Classical cases of LGESS are composed of cells that morphologically resemble non-neoplastic proliferative-phase or hyperplastic endometrial stromal cells (Chiang and Oliva, 2013).…”