Universal screening for Lynch syndrome in colorectal cancer is recommended, and immunohistochemistry for the mismatch repair proteins is commonly used. To reduce cost, some screen using only MSH6 and PMS2, with reflex to the partner stain if either are absent (two-stain method). An expression pattern revealing absent MSH2 and intact MSH6 is not expected, but could result in failed Lynch syndrome detection. We analyzed tumors with absent MSH2 but any degree of MSH6 expression to determine if the two-stain method could miss MSH2 mutations. One-thousand seven-hundred thirty colorectal cancer patients from the Ohio Colorectal Cancer Prevention Initiative underwent tumor screening using microsatellite instability and immunohistochemistry. The two-stain method was used for 1235 cases; staining for all four proteins was completed for 495 cases. The proportion of positive cells and staining intensity were reviewed for MSH6, as well as MSH2 when available. Patients with mismatch repair deficiency underwent next-generation sequencing of germline DNA for mismatch repair genes. If negative, tumor next-generation sequencing was performed to assess for somatic mutations. Overall, thirty-three (1.9%, 33/1730) MSH2-absent cases were identified. Of those, fourteen had no MSH6 expression but eight (0.5%, 8/1730) had ambiguous and eleven (0.6%, 11/1730) had convincing MSH6 expression that could have been interpreted as intact. Germline next-generation sequencing identified MSH2 mutations in 11/14 cases with absence of both stains, 7/8 cases with ambiguous MSH6 expression, and 9/11 cases with convincing MSH6 expression. All remaining cases, except one, had double somatic mutations. The two-stain method fails to detect some patients with Lynch syndrome: (1) significant staining weaker than the control may be incorrectly interpreted as intact MSH6, or (2) Weak or focal/patchy MSH6 can be retained with the absence of MSH2. Accordingly, we recommend the four-stain method be used for optimal Lynch syndrome screening detection.
Nonalcoholic fatty liver disease (NAFLD) is prevalent in obese patients. We sought to determine the effects of bariatric surgery on the histological features of NAFLD. Two blinded pathologists graded liver biopsies done during bariatric procedures and subsequent operations in 160 patients using the Brunt classification. Data are mean ± SD. Interval between biopsies was 31 ± 26 months. Initial biopsies demonstrated steatosis 77 %, lobular inflammation 39 %, and chronic portal inflammation 56 %. Steatohepatitis was present in 27 %. Grade 2-3 fibrosis was present in 27 %, and cirrhosis was present in one patient. On post-bariatric biopsy, steatosis resolved in 75 %, lobular inflammation resolved in 75 %, chronic portal inflammation resolved in 49 %, and steatohepatitis resolved in 90 %. Fibrosis of any grade resolved in 53 % and improved in another 3 % of patients. Grade 2 fibrosis resolved in 58 %, improved in 3 %, and did not worsen in 11 %. Bridging fibrosis resolved in 29 %, improved in 29 %, and did not worsen in 29 %. Bariatric surgery is associated with resolution of steatosis or steatohepatitis in the majority of patients. More importantly, grade 2 or 3 (bridging) fibrosis is resolved or improved in 60 % of patients. Bariatric surgery should be considered as a treatment of NAFLD in severely obese patients.
Background:The quality and limitations of digital slides are not fully known. We aimed to estimate intrapathologist discrepancy in detecting specific microscopic features on glass slides and digital slides created by scanning at ×20.Methods:Hematoxylin and eosin and periodic acid–Schiff glass slides were digitized using the Mirax Scan (Carl Zeiss Inc., Germany). Six pathologists assessed 50–71 digital slides. We recorded objective magnification, total time, and detection of the following: Mast cells; eosinophils; plasma cells; pigmented macrophages; melanin in the epidermis; fungal bodies; neutrophils; civatte bodies; parakeratosis; and sebocytes. This process was repeated using the corresponding glass slides after 3 weeks. The diagnosis was not required.Results:The mean time to assess digital slides was 176.77 s and 137.61 s for glass slides (P < 0.001, 99% confidence interval [CI]). The mean objective magnification used to detect features using digital slides was 18.28 and 14.07 for glass slides (P < 0.001, 99.99% CI). Parakeratosis, civatte bodies, pigmented macrophages, melanin in the epidermis, mast cells, eosinophils, plasma cells, and neutrophils, were identified at lower objectives on glass slides (P = 0.023–0.001, 95% CI). Average intraobserver concordance ranged from κ = 0.30 to κ = 0.78. Features with poor to fair average concordance were: Melanin in the epidermis (κ = 0.15–0.58); plasma cells (κ = 0.15–0.49); and neutrophils (κ = 0.12–0.48). Features with moderate average intrapathologist concordance were: parakeratosis (κ = 0.21–0.61); civatte bodies (κ = 0.21–0.71); pigment-laden macrophages (κ = 0.34–0.66); mast cells (κ = 0.29–0.78); and eosinophils (κ = 0.31–0.79). The average intrapathologist concordance was good for sebocytes (κ = 0.51–1.00) and fungal bodies (κ = 0.47–0.76).Conclusions:Telepathology using digital slides scanned at ×20 is sufficient for detection of histopathologic features routinely encountered in dermatitis cases, though less efficient than glass slides.
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