Predictive value of histopathologic parameters in early squamous cell carcinoma of oral tongue

The clinical course of early squamous cell carcinoma of oral tongue (OTSCC) is unpredictable and various histopathologic parameters of the primary tumour have been suggested as prognostic factors to be used in clinical decision-making. We reviewed clinicopathologic data of 73 patients diagnosed with Stage I–II OTSCC. Predictive value of pathological T-stage, depth of infiltration, grade, and mode of invasion with respect to local recurrences, occult cervical metastases, and disease specific survival (DSS) was analysed. Depth of infiltration and pT-stage significantly predicted occult nodal disease, while only pT-stage predicted local recurrence. Specific cut-off value for depth of infiltration separating high-risk and low-risk patients was not found. Significant correlations between the histopathologic parameters and DSS were not found. We conclude that depth of infiltration predicted occult nodal disease but its value in clinical decision-making is limited because of poor specificity when using a cut-off value that offers reasonable sensitivity for finding the patients with occult nodal disease. The risk for occult metastases and local recurrence was high in patients with pT2 tumours.     

Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease

The most common monogenic cause of small-vessel disease leading to ischemic stroke and vascular dementia is the neurodegenerative syndrome cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is associated with mutations in the Notch 3 receptor. CADASIL pathology is characterized by vascular smooth muscle cell degeneration and accumulation of diagnostic granular osmiophilic material (GOM) in vessels. The functional nature of the Notch 3 mutations causing CADASIL and their mechanistic connection to small-vessel disease and GOM accumulation remain enigmatic. To gain insight into how Notch 3 function is linked to CADASIL pathophysiology, we studied two phenotypically distinct mutations, C455R and R1031C, respectively associated with early and late onset of stroke, by using hemodynamic analyses in transgenic mouse models, receptor activity assays in cell culture, and proteomic examination of postmortem human tissue. We demonstrate that the C455R and R1031C mutations define different hypomorphic activity states of Notch 3, a property linked to ischemic stroke susceptibility in mouse models we generated. Importantly, these mice develop osmiophilic deposits and other age-dependent phenotypes that parallel remarkably the human condition. Proteomic analysis of human brain vessels, carrying the same CADASIL mutations, identified clusterin and collagen 18 α1/endostatin as GOM components. Our findings link loss of Notch signaling with ischemic cerebral small-vessel disease, a prevalent human condition. We determine that CADASIL pathophysiology is associated with hypomorphic Notch 3 function in vascular smooth muscle cells and implicate the accumulation of clusterin and collagen 18 α1/endostatin in brain vessel pathology.     

Mycobacterium abscessus Complex Identification with Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

We determined that the Vitek MS Plus matrix-assisted laser desorption ionization–time of flight mass spectrometry using research-use-only (RUO) v.4.12 and in vitro-diagnostic (IVD) v.3.0 databases accurately identified 41 Mycobacterium abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates identified by whole-genome sequencing to the species but not the subspecies level, from Middlebrook 7H11 and Burkholderia cepacia selective agars. Peak analysis revealed three peaks potentially able to differentiate between subspecies.