Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Divya Sharma, MD, associate professor, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center; Paula Toro, MD, assistant professor of pathology, Emory University/Grady Memorial Hospital, Atlanta; and Kristen Brao, MD, PhD, cytopathology fellow, Mass General Brigham, Boston.
Histopathologic progression of autoimmune atrophic gastritis
September 2026—Autoimmune atrophic gastritis is chronic, immune-mediated inflammation restricted to the gastric body. Despite well-defined histologic features, its pathologic progression is still not fully understood. Therefore, the authors conducted a study to evaluate the pathologic progression of autoimmune atrophic gastritis. They reviewed cases with at least two follow-up biopsies. Clinical data, including anemia and autoimmune antibody status, were collected. Gastric samples were analyzed to assess inflammation, atrophy, enterochromaffin-like cell hyperplasia, and the development of neuroendocrine tumors (NET) or carcinoma. The cohort included 180 cases from 32 patients (21 female, 11 male), with an average follow-up of 6.8 years and 5.7 biopsies per patient. Inflammation, atrophy, and intestinal metaplasia remained stable in 59.4 percent (19 of 32), 78.1 percent (25 of 32), and 50 percent (16 of 32) of patients who had follow-up biopsies, respectively. Among the autoimmune atrophic gastritis index cases, six patients had NET, with five experiencing recurrence after endoscopic excision. During follow-up, six additional patients developed NET, half of whom had recurrence following endoscopic excision. The NET were well differentiated, with a Ki-67 index of less than three percent. Two patients were initially diagnosed with adenocarcinoma in the background of autoimmune atrophic gastritis, and two more developed adenocarcinoma during follow-up. No significant changes were observed in the antrum during follow-up, and the antrum consistently showed minimal to mild inflammation and reactive gastropathy. Long-term follow-up indicated that autoimmune atrophic gastritis is linked to the pathologic progression of NET and gastric adenocarcinoma. NET arising in the background of autoimmune atrophic gastritis are well differentiated and show no evidence of metastasis. These findings may provide guidance on optimal endoscopic surveillance intervals for patients with the disease.
Wang X, Jiao J, Huh WJ, et al. Histopathologic progression of autoimmune atrophic gastritis: A retrospective review of 180 specimens from 32 patients. Arch Pathol Lab Med. 2026;150(1):81–87.
Correspondence: Dr. Xuchen Zhang at xuchen.zhang@yale.edu
Aggressiveness of intraductal carcinoma of the prostate with a solid nest pattern
The grading of intraductal carcinoma of the prostate associated with conventional prostatic adenocarcinoma remains controversial, particularly regarding whether intraductal carcinoma of the prostate exhibiting a solid nest pattern is prognostically equivalent to Gleason grade 5 conventional prostatic adenocarcinoma. The authors conducted a study to evaluate the differences and similarities in prognostic impact between intraductal carcinoma of the prostate (IDC-P) and conventional prostatic adenocarcinoma (CPA). They retrospectively analyzed consecutive radical prostatectomy patients with grade 5 CPA as a primary, secondary, or tertiary pattern, as well as cribriform IDC-P, and excluded cases exhibiting comedonecrosis within IDC-P. They then compared clinicopathologic features and long-term oncologic outcomes between those with (n = 28, 24.3 percent) and without (n = 87, 75.7 percent) solid-pattern IDC-P. Solid IDC-P cases were significantly associated with a higher incidence of lymph node metastasis, larger estimated tumor volume, and more frequent administration of adjuvant therapy immediately after prostatectomy. No significant differences were observed between the two groups relative to preoperative prostate-specific antigen, grade group, pT stage, or surgical margin status. Univariate analysis revealed significantly worse biochemical recurrence-free survival (P = .010) and cancer-specific survival (P = .003) for patients with solid IDC-P. In multivariable Cox regression analyses, solid IDC-P remained significantly predictive of postoperative recurrence when adjusting for prognostic factors, including grade group (hazard ratio, 1.902; P = .039) and percentage of pattern five (hazard ratio, 1.986; P = .028). Solid-pattern IDC-P was found to represent an independent adverse prognostic indicator in men undergoing radical prostatectomy, further suggesting that the clinical impact of solid IDC-P and Gleason grade 5 CPA, or cribriform IDC-P, are not comparable. Therefore, assigning grade 5 to solid IDC-P may be inadequate.
Shi H, Wang Y, Miyamoto H. Intraductal carcinoma of the prostate with a solid nest pattern may be more aggressive than Gleason grade 5 conventional prostatic adenocarcinoma. Am J Surg Pathol. 2026;50(2):156–162.
Correspondence: Dr. Hiroshi Miyamoto at hiroshi_miyamoto@urmc.rochester.edu
Clinical impact of AI-augmented lymph node evaluation in various metastatic cancers
Lymph node assessment plays a critical role in cancer staging and prognosis but remains a time-consuming and labor-intensive task in pathology. While artificial-intelligence tools have shown promise in improving diagnostic accuracy, their real-world clinical utility for detecting lymph node metastases across multiple cancer types remains underexplored. The authors conducted a study to evaluate the diagnostic performance and efficiency of an AI module in detecting lymph node metastases from gastric, colorectal, and breast cancers and to assess its impact on pathologist workflow. For the retrospective study, the authors used 314 whole slide images from 95 patients who underwent resection for gastric, colorectal, or breast cancer. Three board-certified pathologists reviewed the slides with and without AI assistance. They recorded and compared diagnostic accuracy, review time, and number of mouse clicks required to detect metastases. AI assistance increased sensitivity, which had ranged from 91.8 to 93.9 percent, to 95.9 percent for all pathologists, while specificity remained high, at 97.0 to 98.9 percent. The time required to detect lymph node metastases decreased by up to 78 percent for some cancer types. The AI-guided click-based review required an average of 1.4 to 5.2 clicks, depending on tissue type, with colorectal metastases detected most efficiently. Challenging subtypes, such as breast carcinoma with apocrine differentiation, required more extensive click-based interaction. The AI module identified micrometastases across all three cancer types. The authors concluded that the AI module improved pathologists’ sensitivity in detecting lymph node metastases and significantly reduced review time, particularly for positive nodes. These findings support the integration of AI tools into routine pathology practice to enhance diagnostic efficiency and accuracy.
Lami K, Munkhdelger J, Ando S, et al. Clinical impact of artificial intelligence-augmented lymph node evaluation in metastatic gastric, colorectal, and breast cancer. Arch Pathol Lab Med. 2026;150:533–541.
Correspondence: Dr. Kris Lami at krislami@nagasaki-u.ac.jp
Prognostic impact of blood vessel invasion in infiltrative papillary thyroid carcinoma
Papillary thyroid carcinoma with blood vessel invasion is classified as intermediate risk by the American Thyroid Association. However, no publications have adequately distinguished between encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and infiltrative PTC with regard to blood vessel invasion (BVI). The World Health Organization recently reclassified invasive EFVPTC, a RAS-like tumor, as a distinct prognostic entity separate from conventional PTC. The authors conducted a study to investigate the prognostic impact of BVI in infiltrative PTC. Their retrospective matched case-control study included 134 cases of infiltrative PTC with BVI and at least one year of patient follow-up. A one-to-one matched control group of 134 infiltrative PTC without BVI, matched for PTC subtype and American Joint Committee on Cancer stage, was also included. CD31 and D2-40 IHC were performed on 195 blocks to distinguish BVI from lymphatic vessel invasion. Blood vessel invasion was defined as a CD31–positive/D2-40–negative endothelium-lined tumor embolus within a vessel wall, whereas lymphatic vessel invasion was defined as a free-floating tumor plug lacking an endothelial lining within a CD31/D2-40–positive vessel. The median follow-up period for the study was 5.3 years. Extensive BVI was the only independent adverse prognostic factor for disease-free survival (hazard ratio, 3.531) on multivariate survival analysis. On univariate analysis, infiltrative PTC with extensive BVI was associated with significantly decreased distant metastasis-free patient survival when compared with tumors without BVI or with focal BVI. Using CD31 and D2-40 as gold standard ancillary tools, the authors established reliable histologic criteria to differentiate BVI from lymphatic vessel invasion. Extensive BVI is an independent adverse prognostic factor in infiltrative BRAF V600E-like PTC and should therefore be considered in initial risk stratification for infiltrative PTC.
Ghossein RA, Roy D, Shaha A, et al. The prognostic impact of blood vessel invasion in infiltrative papillary thyroid carcinoma: a retrospective case–control study. Histopathology. 2026;88(3):673–682.
Correspondence: Dr. Bin Xu at xub@mskcc.org
Creation of a diagnostic scoring system for neuroendocrine neoplasms of the pancreas
Accurately distinguishing between well-differentiated pancreatic neuroendocrine tumors, grade 3 (PanNET G3) and pancreatic neuroendocrine carcinomas (PanNEC), both of which are forms of high-grade neuroendocrine neoplasms of the pancreas, is crucial as they differ in prognosis, molecular profile, and response to treatment. The authors aimed to integrate the assessment of morphologic, IHC, and molecular features into a reproducible, point-based scoring system that improves diagnostic accuracy for differentiating PanNET G3 from PanNEC. They identified 58 cases (29 PanNET G3, 29 PanNEC), after applying inclusion and exclusion criteria, which were analyzed. Lasso logistic regression identified predictive features of PanNEC, and multivariable logistic regression was used to assign weights to each factor. Positive predictors of PanNEC included p53 alterations (+4 points), Rb1 loss (+3 points), interstitial reaction (+3 points), coexisting non-neuroendocrine carcinoma (+3 points), abundant mitoses (+2 points), and a Ki67 proliferation index greater than 40 percent (+1 point). Negative predictors included coexisting PanNET G1/2 (−2 points), plasmacytoid cells (−1 point), DAXX/ATRX loss (−1 point), and somatostatin receptor subtype 2A score three expression (−1 point). In validation testing, the average score for PanNEC was 9.52 (median, 10.0), and the average score for PanNET G3 was −1.31 (median, −1.0). Using a cutoff of 5.0, the model achieved an area under the curve of 0.989 for distinguishing PanNEC from PanNET G3. The authors concluded that this novel scoring system demonstrated excellent diagnostic performance in differentiating PanNEC from PanNET by integrating the assessment of morphologic and IHC features. They proposed that prospective studies with larger cohorts are warranted to validate its clinical utility.
Kinowaki Y, Wang C, Fukumura Y, et al. Building a diagnostic scoring system for high-grade neuroendocrine neoplasms of the pancreas. Am J Clin Pathol. 2026. doi.org/10.1093/ajcp/aqaf154
Correspondence: Dr. Mari Mino-Kenudson at mminokenudson@mgb.org
Clinical significance of relative location of perineural cancer invasion on prostate biopsy
Perineural invasion detected on prostate biopsy is an indicator of aggressive prostate cancer, including extraprostatic extension. However, the clinical relevance of its relative location within the biopsy core remains poorly understood. Therefore, the authors conducted a study to assess radical prostatectomy findings relative to long-term oncologic outcomes in prostate cancer patients with a single focus of perineural invasion on biopsy. They assessed corresponding radical prostatectomy findings and long-term oncologic outcomes in 180 prostate cancer patients exhibiting only a single focus of perineural invasion on the entire systematic biopsy. To assess the prognostic impact of the location of perineural invasion, the authors created subgroups based on the distance from the perineural invasion to the closest tip of the core. The subgroups were less than 1 mm (n = 26, 14.4 percent), 1 to less than 2 mm (n = 43, 23.9 percent), 2 to less than 3 mm (n = 36, 20.0 percent), 3 to less than 4 mm (n = 27, 15.0 percent), 4 to less than 5 mm (n = 28, 15.6 percent), and 5 mm or more (n = 20, 11.1 percent). Univariate survival analysis in a dichotomized distance-based cohort (less than 1 mm versus 1 mm or more) revealed significantly higher risks of biochemical recurrence (P< .001) and cancer-specific mortality (P = .042) in patients with perineural invasion less than 1 mm from the core tip than in those with perineural invasion 1 mm or more from the tip. No significant differences were noted between the two groups regarding clinicopathologic features, including total tumor length on biopsy or estimated tumor volume on prostatectomy, tumor grade on biopsy or prostatectomy, pT or pN category, and surgical margin status. In multivariable Cox regression analysis, those with perineural invasion of less than 1 mm from the core tip had significantly worse recurrence-free survival before (hazard ratio, 3.435; P< .001) and after (hazard ratio, 3.228; P = .002) adjusting for prostatectomy factors than those with perineural invasion of 1 mm or more from the core tip. Perineural invasion detected within 1 mm of the biopsy core tip was, therefore, found to independently predict a worse postoperative prognosis. The authors concluded that the spatial characteristics of perineural invasion on needle core biopsy may enhance the risk stratification of prostate cancer.
Lanipekun OK, Wang, Y, Miyamoto H. Clinical significance of the relative location of perineural cancer invasion on prostate biopsy: Detection within 1-mm of the core tip as an independent prognosticator. Hum Pathol. 2026. doi.org/10.1016/j.humpath.2025.106015
Correspondence: Dr. Hiroshi Miyamoto at hiroshi_miyamoto@urmc.rochester.edu