Chimeric antigen receptor T-cell (CAR-T) therapy targeting for B-cell maturation antigen (BCMA) is used to treat patients with multiple myeloma (MM). To investigate gastrointestinal changes associated with CAR-T therapy, we performed a retrospective study. A total of 10 patients with 26 gastrointestinal biopsy specimens who underwent CAR-T therapy for MM were identified. Except for one patient with residual multiple myeloma, all specimens demonstrated markedly reduced or absent plasma cells. The most prominent biopsy findings occurred in the small intestine, primarily the duodenum, and included lamina propria lymphocytic infiltration, villous atrophy, foveolar metaplasia, an absence of plasma cells, and an increase in intraepithelial lymphocytes. There was an average of 7 apoptotic bodies per 10 high-power fields (hpf). The terminal ileum was also notable for increase in apoptotic bodies (average of 9.5 apoptotic bodies/10 hpf), villous atrophy, and lamina propria lymphocytic infiltration. The stomach biopsies overall typically showed mild inflammation with no increase in apoptotic bodies. A few colonic specimens demonstrated active colitis and prominent apoptotic bodies, while the majority of the colonic biopsies did not have significant findings other than melanosis coli, and an absence or reduction of plasma cells. The disproportionately greater injury in the duodenum versus the colon highlights the importance of upper endoscopic evaluation in symptomatic patients after CAR-T therapy. The mechanisms for these patterns of injury and differential anatomic findings are unknown; however, an immune-mediated injury associated with CAR-T therapy is suspected. Our study identifies a unique pattern of intestinal injury in patients with MM who received BCMA-targeted CAR-T therapy; this encompasses histologic findings more profound in the small intestine, which include absence of plasma cells, an increase in apoptotic bodies, lymphocytic infiltration, and villous atrophy.

Background & Aims: Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study identified histopathologic features of the TAC specimen associated with pouch failure and investigated the molecular mechanisms of this susceptibility using single-cell spatial transcriptomics. Methods: We analyzed a cohort of 417 patients who underwent IPAA between 2000 and 2010 at the University of Chicago Medical Center for up to 18 years. Histologic examination of TAC specimens focused on disease activity, depth of inflammation, and specific features, including granulomas and deep ulcers. A subset of patients was profiled using single-cell spatial transcriptomics to map gene expression and immune cell interactions in relation to the risk of pouch failure. Results: The 18-year pouch failure risk was 23%, with post-procedure clinical features of Crohn’s disease as a major risk factor (hazard ratio [HR], 4.3; 95% confidence interval [CI], 2.3–8.1) as well as high-risk histologic features, including deep chronic inflammation (HR, 21; 95% CI, 11–41) and severe disease activity (HR, 14; 95% CI, 5.7–32) in TAC specimens. Spatial transcriptomics showed immune infiltration of T and myeloid cells, reduced myocyte-glial interactions, and cytokine signaling pathways such as interleukin (IL)-10, IL-1β, and type I/II interferons, associated with an increased risk of pouch failure. CD68 immunohistochemistry confirmed that deep CD68+ macrophage infiltration is associated with increased risk of future pouch failure. Conclusion: Histologic features including CD68 immunohistochemisty and spatial molecular profiling are predictive of IPAA failure. These findings support the use of histologic evaluation and targeted molecular analysis of the TAC specimen to identify high-risk patients and improve IPAA outcomes.

Modern pathology requires precise data interpretation to enhance patient care and operational efficiency. We applied a Python-based informatics approach to analyze turnaround times, second opinion consultations, and diagnostic concordance. This investigation aimed to determine actionable insights and assess the feasibility of a subspecialty frozen section service. Monthly frozen section data from 2023 was gathered. A Python script was developed to transform the data into over 150 dynamic graphs. These visualizations detail turnaround times, second opinions, concordance rates, and overall performance metrics. Breakdowns by case complexity and specialty pairing (surgeon and pathologist subspeciality) further informed our analysis. The average turnaround time of 43.4 minutes for same-specialty pairs versus 46.9 minutes for different specialties. Cases requiring a second opinion extended turnaround time notably, and delays were most pronounced in breast, gastrointestinal, and renal cases. Diagnostic concordance remained high at 97.5% regardless of surgeon-pathologist speciality pairing. Our findings demonstrate that aligning surgeon and pathologist specialties modestly reduces turnaround times, yet complexity and second opinion requirements significantly extend them. Tailored second opinion protocols and subspecialty-specific strategies can optimize efficiency and maintain high diagnostic accuracy. Also, targeted interventions, such as refining second opinion protocols, can enhance both operational efficiency and diagnostic accuracy in modern pathology.

The development of postoperative recurrent tumors or metastasis following surgical resection of colorectal cancer remains a major obstacle to colon cancer cure. While a high-fat diet is a risk factor for the development of recurrence, studies that examine the molecular mechanism by which diet drives postoperative tumors have been lacking. Here, using a murine model that mimics postoperative tumor formation, we show that the tumorigenic influence of a high-fat diet strongly depends on the genetic backbone of the primary tumor cells. We identify deoxycholic acid as a major contributor to the promotion of tumor recurrence only when the primary cancer cell has an APC-driving mutation. We investigate the deoxycholic acid effect on the proliferation of organoids and identify the organoid response to deoxycholic acid treatment, including the transcriptome expression and transfer RNA abundance, modification, and charging. The integrated analysis of mRNA and tRNA sequencing results reveals enhanced decoding of codons in proliferation-promoting genes. Our results provide a new understanding of how both diet and tumor genetics together lead to postoperative colorectal cancer recurrence.

BACKGROUND:Thyroid nodules may be detected during the workup of thyroid hormone abnormalities and as incidental findings during unrelated imaging studies. The diagnosis of a thyroid nodule is mainly established by performing fine needle aspiration (FNA) under ultrasound guidance. Thyroid nodules are classified as nondiagnostic, defined in the Bethesda System for Reporting Thyroid Cytopathology as samples with excess blood, cyst fluid only, and lack of thyroid follicular cells. The current study evaluates a series of nondiagnostic FNAs to assess whether repeat sampling improves yield and what patient management, and outcomes are after a nondiagnostic FNA. METHODS:Thyroid FNAs from 2016 to 2023 were retrieved from our institution archives. All cases were performed under ultrasound guidance and with rapid on-site evaluation. Cases were assigned the Bethesda System Category. Nondiagnostic FNAs were further reviewed for repeat FNA procedures, potential molecular testing, or diagnostic resections. RESULTS:In total 3104 thyroid FNAs were reviewed, with 153 (4.9%) being nondiagnostic. Of the 154 FNAs, there were 129 patients with an average age of 60 and a male-to-female ratio of 1:3.2. Of the 130 patients, there were 50 patients who underwent 55 repeat FNAs. Thirty-seven (67%) of the repeats were benign, 13 (24%) were nondiagnostic again, and 5 (9%) were atypia of undetermined significance (AUS). Molecular testing was performed on repeat FNAs diagnosed AUS. Four cases showed no mutations and had a high likelihood of being benign. One case did have an NRAS Q61R mutation, and resection revealed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Seventeen (13% of all cases) with nondiagnostic FNA were resected. Twelve (71%) thyroidectomies showed benign adenomatous nodules. The remainder showed incidental papillary thyroid microcarcinoma (0.1 cm), an infarcted follicular adenoma, a noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and metastatic renal cell carcinoma (2×). CONCLUSION:Thyroid nodules with nondiagnostic cytology are reassuring of being highly likely a benign nodule. Only 5 of the 55 (9%) repeat FNAs yielded abnormalities, with only one of those being truly a follicular neoplasm (confirmed by molecular testing and resection). No primary thyroid malignancies have been identified in follow-up (repeat FNA or surgery). Clinical and ultrasound follow-up may be more appropriate management for nondiagnostic thyroid FNAs.