Astrocytoma (CNS WHO grade 4), IDH-mutant with co-occurrence of BRAF p.V600E mutation, and homozygous loss of CDKN2A.

Molecular alterations nowadays play a crucial role in the diagnosis of brain tumors. Some of these alterations are associated with outcome and/or response to treatment, including sequence variants of isocitrate dehydrogenase (IDH) at position p.R132 or p.R172. Such IDH variants have so far been described in histone H3-wildtype primary brain tumors only in adult-type diffuse gliomas and are associated with a better outcome compared to their IDH-wildtype counterpart, the glioblastoma. Moreover, homozygous loss of CDKN2A and/or CDKN2B in IDH-mutant astrocytomas shortens the median overall survival regardless of histological features of malignancy. Such tumors are therefore considered to be aggressive and graded as WHO central nervous system (CNS) grade 4 lesions. The coexistence of an IDH-sequence variation and a BRAF p.V600E alteration has only rarely been described in diffuse astrocytomas. Due to the small number of cases, little is known about such neoplasms in terms of clinical behavior and response to treatment. Herein we describe the first case, to our knowledge, of an astrocytoma (CNS WHO grade 4), IDH-mutant, and BRAF p.V600E-mutant with homozygous deletion of CDKN2A. Pathologists should be aware that such an expression profile does exist even in WHO CNS grade 4 astrocytomas, IDH-mutant, and are encouraged to test for the BRAF p.V600E sequence variant as such an alteration may provide additional treatment options.

In Vivo Adenomyosis Tissue Sampling Using a Transvaginal Ultrasound-guided Core Biopsy Technique for Research Purposes: Safety, Feasibility, and Effectiveness.

STUDY OBJECTIVE: To determine if it is possible and safe to obtain adenomyosis tissue in vivo without removing the uterus in order to use it for further molecular investigations of adenomyosis, which would allow investigating the pathogenesis of the disease. DESIGN: A prospective cohort study. SETTING: A university hospital. PATIENTS: Eighty-one premenopausal women scheduled for a hysterectomy because of various benign indications were included. INTERVENTIONS: Ultrasound-guided, transvaginal uterine core biopsy samples were obtained, and the required time was registered. Any trauma to the pelvic organs, blood loss, and other complications were documented during the subsequent hysterectomy. Two biopsy samples were analyzed histopathologically to confirm the presence of adenomyosis, and another 2 were snap frozen using liquid nitrogen for use in further research. Laser microscopic dissection and RNA extraction were performed on the collected samples. MEASUREMENTS AND MAIN RESULTS: Biopsy specimens could be obtained in 80 (99%) of the 81 cases. There was no visible trace of the biopsy retrieval in 20 women (25%), perforation of uterine serosa or peritoneum was present in 56 (70%), and ongoing minor bleeding occurred in 4 (5%). The median amount of bleeding was 2 mL (range, 0-200 mL). No serious complications were observed. The procedure took 6.1 ± 1.9 minutes (mean ± standard deviation). Adenomyosis tissue was obtained in 10 (22%) of the 45 cases with adenomyosis. The inner myometrium with the junctional zone was accessible in all cases. It was possible to produce frozen sections, extract RNA, and dissect single adenomyosis glands with laser microscopic dissection. CONCLUSIONS: No serious complications caused by the uterine biopsies were observed. This technique opens up the possibility of investigating early stages of adenomyosis and the inner myometrium containing the junctional zone independent of hysterectomy specimens.