Clinical, immunophenotypic and genomic findings of NK lymphoblastic leukemia: a study from the Bone Marrow Pathology Group.

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL patients were significantly younger (p = 0.021) and presented with higher white blood cell (WBC) (p = 0.037) and platelet counts (p = 0.041). Flow cytometry showed more frequent expression of cytoplasmic CD3 (cCD3, p = 0.064) and CD33, (p = 0.065), while HLA-DR was significantly absent from NK-LL (p = 0.035) compared to AUL. Compared to T-ALL, NK-LL cases showed less frequent cCD3 (p = 0.002), CD4 (p = 0.051), and CD10 expression (p = 0.06). The frequency of abnormal karyotypes was similar between NK-LL, AUL, and T-ALL. The mutational profile differed in four leukemia groups, with a significance enrichment of NOTCH1 (p = 0.002), ETV6 (p = 0.002) and JAK3 (p = 0.02) mutations in NK-LL as compared to AML. As compared to T-ALL, NK-LL cases showed a higher number of total mutations (p = 0.04) and significantly more frequent ETV6 mutations (p = 0.004). Clinical outcome data showed differences in overall survival between all four groups (p = 0.0175), but no difference in event free survival (p = 0.246). In this largest study to date, we find that that NK-LL shows clinical presentation, immunophenotypic and molecular characteristics distinct from AUL, T-ALL, and AML. Our findings suggest NK-LL is a distinct acute leukemia entity and should be considered in the clinical diagnosis of acute leukemias of ambiguous lineage.

CT angiographic evaluation of perforators in the lower limb and their reconstructive implication.

BACKGROUND: The perforator flaps evolved on the knowledge of the vascular tree from the main vascular trunk up to the subdermal plexus. Therefore, we thought that it's necessary to map the whole vascular arcade by CT angiography. The aim of this study is to evaluate the perforators and the whole vascular tree of the lower limb by peripheral CT angiography with 3D reconstruction and intraoperative evaluation. This study helps in designing flaps of different constituents based on the selected perforators. MATERIALS AND METHODS: Twenty patients having lower limb defects were selected. CT angiography was done using a non-ionic iodinated contrast media injected through the antecubital vein. The lower limbs were imaged using volume rendering CT scan machine. Three dimensional reconstructions were made. The whole arterial tree, along with the perforators, were mapped. Findings of the audio-Doppler were correlated with the CT angiographic observations. Further these evaluations were confirmed by intraoperative findings. RESULTS: The three dimensional CT angiographic reconstruction with bone and soft tissue provided advanced knowledge of this vascular network. It delineated the main vessel, the perforators, their caliber, distance from fixed bony landmarks and course up to the subdermal plexus. These findings were confirmed during dissection of the proposed flap. The perforators were mainly musculocutaneous in the proximal leg and septocutaneous distally. CONCLUSIONS: The vascular details visualized by this technique made advancement over the existing methods namely color Doppler, audio Doppler, two dimensional angiography etc. It improved the understanding of perforator flaps and their successful clinical application.

Molecular signatures linked with aggressive behavior in basal cell carcinoma: a report of 6 cases.

A small subset of basal cell carcinoma (BCC) characterized by rapid growth, recurrence, deep local invasiveness to dura, and/or bone is classified as extremely aggressive. Histologically, exclusive of invasive sites these tumors are similar to nonaggressive BCC. In the present study, we compare the molecular signatures of these 2 types of tumors. Twenty-one BCC specimens, 6 aggressive and 15 nonaggressive, were used in the study. DNA was extracted from formalin-fixed paraffin-embedded sections of 21 pairs of normal and tumor tissue. The specimens were subjected to loss of heterozygosity (LOH) analysis on chromosome 9q22 in the PATCHED gene. Regulatory single nucleotide polymorphisms (SNPs) at -308 in the tumor necrosis factor alpha and -1082 in the interleukin 10 genes were examined. LOH at one or more markers was observed in all 6 of the aggressive specimens compared with 2 of the 15 nonaggressive BCC specimens. A total of 63.6% of all heterozygous markers in the aggressive tumors showed LOH compared with 17.9% of the nonaggressive BCC. The tumor necrosis factor alpha -238 SNP and the interleukin 10 -1082 SNP were more prevalent in aggressive BCC. The results of this pilot study indicate that LOH at chromosome 9q22 is a potential marker for the identification of aggressive behavior in BCCs. Furthermore, our study suggests that cytokine SNPs may be used to stratify risk in the assessment of aggressiveness in BCC.