Predictors of large cell transformation in patients with Sezary Syndrome-A retrospective analysis.

BACKGROUND: Large cell transformation (LCT) of Sezary Syndrome (SS) is a rare phenomenon. To date, there are no rigorous studies identifying risk factors for its development. OBJECTIVES: Here, we seek to characterize the clinicopathologic risk factors that predispose patients with SS to develop LCT. METHODS: We retrospectively evaluated all SS patient records available in the Michigan Medicine Cancer Registry from 2010-2021. Clinical and pathologic variables were compared between groups. The Kaplan-Meier method and log-rank test were used to assess overall survival. RESULTS: Of 28 SS patients identified, eight patients experienced LCT, and 20 did not (NLCT). Peak lactate dehydrogenase (LDH) before LCT (p = 0.0012), maximum total body surface area (TBSA) involvement before LCT (p = 0.0114), absolute CD8+ cell count measured on flow cytometry at diagnosis of SS (p = 0.0455) and at the most recent blood draw (p = 0.00736), and ulceration on biopsy (p = 0.0034) were significant clinicopathologic variables identified between the SS patients that developed LCT versus those that did not. CONCLUSIONS: Maximum TBSA involvement, peak LDH, presence of ulceration, and decreased levels of CD8+ cells in the peripheral blood may predict the development of LCT in patients with SS.

Functional and topographic effects on DNA methylation in IDH1/2 mutant cancers.

IDH1/2 mutations are early drivers present in diverse human cancer types arising in various tissue sites. IDH1/2 mutation is known to induce a global hypermethylator phenotype. However, the effects on DNA methylation across IDH mutant cancers and functionally different genome regions, remain unknown. We analyzed DNA methylation data from IDH1/2 mutant acute myeloid leukemia, oligodendroglioma, astrocytoma, solid papillary breast carcinoma with reverse polarity, sinonasal undifferentiated carcinoma and cholangiocarcinoma, which clustered by their embryonal origin. Hypermethylated common probes affect predominantly gene bodies while promoters in IDH1/2 mutant cancers remain unmethylated. Enhancers showed global hypermethylation, however commonly hypomethylated enhancers were associated with tissue differentiation and cell fate determination. We demonstrate that some chromosomes, chromosomal arms and chromosomal regions are more affected by IDH1/2 mutations while others remain resistant to IDH1/2 mutation induced methylation changes. Therefore IDH1/2 mutations have different methylation effect on different parts of the genome, which may be regulated by different mechanisms.

Time to Resolution of Symptoms After Suboccipital Decompression with Duraplasty in Children with Chiari Malformation Type I.

BACKGROUND: Duraplasty is a technique successfully used to treat Chiari malformation type I (CM-I). This study describes the timely manner of clinical outcomes and the postoperative course after craniectomy and duraplasty for the treatment of symptomatic CM-I in children. METHODS: A retrospective chart review was performed in 105 consecutive children who underwent surgical decompression of symptomatic CM-I with dural opening by a single surgeon between 1999 and 2015. RESULTS: In 16 of 28 children (57%) with typical Valsalva-related/tussive and mixed headaches, the symptoms resolved before discharge; by 6 months, all children were headache-free. Two of 28 children (7%) had recurrent headaches 9 months after surgery. Among the 78 children with syrinx, syrinx resolved or decreased in 68 (87%), recurred in 8 (10%), and was stable in 2 children (3%). Syrinx was resolved or decreased by 3 months in 51 children (65%) and by 6 months in 62 children (79%). Complications included aseptic meningitis requiring reoperation in 3 children (3%) and infection in one child (1%). Twelve children underwent reoperation, none within the first 30 days. No child had a major morbidity or mortality. CONCLUSIONS: In carefully selected children with CM-I, a high success rate can be achieved with suboccipital decompression and duraplasty. Valsalva-related/tussive headaches resolved by the time of discharge from the hospital in the majority of children, and syrinx resolved or decreased in two-thirds of the children by 3 months. By 6 months, headaches were resolved in all cases, and syrinx was resolved or decreased in 79% of cases.