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Diagn Pathol [JOURNAL]

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Intrapulmonary solitary fibrous tumor: clinicopathological analysis of 29 cases with emphasis on morphological spectrum and immunohistochemical profile.

Zeng X, Lin X, Ye L … +3 more , Wu Z, Lin Z, Li S

Diagn Pathol · 2026 Jul · PMID 42387616 · Full text

BACKGROUND: Intrapulmonary solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can mimic pulmonary adenofibroma (PAF) when respiratory epithelium is entrapped. METHODS: We retrospectively analyzed 29 intrapu... BACKGROUND: Intrapulmonary solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can mimic pulmonary adenofibroma (PAF) when respiratory epithelium is entrapped. METHODS: We retrospectively analyzed 29 intrapulmonary SFTs, reviewing clinical, histopathological, and immunohistochemical features. STAT6, CD34, ER, and PR were evaluated. RESULTS: The cohort included 18 males and 11 females (mean age 55.3 years); 69.0% were asymptomatic. Mean tumor size was 4.11 cm, with pleural attachment in 62.1%. Histologically, 79.3% showed biphasic cellularity, 86.2% had staghorn vessels, and 44.8% exhibited entrapped epithelium. Stromal changes included collagenization (89.7%), hemorrhage (24.1%), myxoid change (20.7%), cystic change (6.9%), and multinucleated giant cells (3.4%). Risk stratification identified 25 low-risk, three intermediate-risk, and one high-risk case. STAT6 was positive in all tested cases (28/28, 100%), and CD34 in 96.3%. Among 22 evaluable cases, 19 (86.4%) showed ER < PR. During a mean follow-up of 36.7 months, one high-risk patient (3.4%) developed local recurrence. CONCLUSION: Intrapulmonary SFT has a broad morphological spectrum with frequent epithelial entrapment as a key diagnostic pitfall. STAT6 is a reliable diagnostic marker, while ER < PR is common but of uncertain significance.

Evaluation of squamous cell carcinoma antigen as a diagnostic biomarker in pulmonary diseases: a male cohort study.

Lirong L, Kangying W

Diagn Pathol · 2026 Jun · PMID 42374516 · Full text

BACKGROUND: Early pulmonary disease recognition in men is often hindered by nonspecific clinical features and overlapping laboratory parameters. Squamous Cell Carcinoma Antigen (SCCA), a glycoprotein traditionally associ... BACKGROUND: Early pulmonary disease recognition in men is often hindered by nonspecific clinical features and overlapping laboratory parameters. Squamous Cell Carcinoma Antigen (SCCA), a glycoprotein traditionally associated with malignancy, has been proposed as a potential biomarker in a wider spectrum of pulmonary disorders. This study evaluated the diagnostic performance of serum SCCA in pulmonary diseases among the male cohort and determined its relationship with inflammatory markers. METHODS: We analyzed serum SCCA levels in 533 male patients diagnosed with squamous cell carcinoma (SCC), pneumonia, pulmonary nodules, or chronic obstructive pulmonary disease (COPD) at the Affiliated Hospital of Putian University (January 2017-November 2021), and compared them to 80 healthy male controls. Intergroup differences were assessed, correlations between SCCA and inflammatory markers were analyzed, and receiver operating characteristic (ROC) curves were used to determine disease-specific diagnostic performance. RESULTS: Serum SCCA levels differed significantly across disease groups. SCC patients had markedly higher concentrations (7.14 ± 3.64 ng/ml) than all other groups, whereas pulmonary nodules showed the lowest levels (1.45 ± 0.81 ng/ml). SCCA achieved its highest diagnostic accuracy in SCC (AUC = 0.792), outperforming its ability to differentiate other pulmonary conditions. CONCLUSION: Serum SCCA expression shows a promising and supportive biomarker in the diagnostic evaluation of pulmonary diseases among the male patients, meriting further validation in larger, multi-centre studies.

Biosensors for oral cancer detection: a scoping review.

Syawqie A, Sovira GDJ, Amaliya-Amaliya … +1 more , Ichwan SJA

Diagn Pathol · 2026 Jun · PMID 42332789 · Full text

This scoping review summarizes recent advances in biosensor technologies for the early, non-invasive detection of oral cancer, with a focus on salivary biomarkers and point-of-care platforms. Five databases (PubMed, Scop... This scoping review summarizes recent advances in biosensor technologies for the early, non-invasive detection of oral cancer, with a focus on salivary biomarkers and point-of-care platforms. Five databases (PubMed, Scopus, Web of Science, ProQuest, and EBSCO) were searched for studies published from 2019 to 2025. After duplicate removal and screening, nine eligible original studies were charted. The included platforms were primarily electrochemical, optical, and transistor-based biosensors targeting biomarkers such as interleukin-8 (IL-8), cytokeratin fragment 21.1 (Cyfra 21.1), cancerous inhibitor of PP2A (CIP2A/P90), and high-risk HPV genotypes. Reported limits of detection were frequently in the femtomolar range, although reporting of assay time, sample volume, and clinical diagnostic accuracy was inconsistent. Overall, biosensors show strong analytical potential for oral cancer screening; however, translation to routine clinical use will require standardized analytical validation, careful control of pre-analytical saliva variables, and well-designed multicenter clinical studies reporting sensitivity and specificity against appropriate reference standards.

Clinicopathological characteristics across the HER2 expression spectrum in invasive breast carcinoma of no special type: a single-centre retrospective study.

Tiwary A, Francis SS, Sharma S … +1 more , Pai A

Diagn Pathol · 2026 May · PMID 42169015 · Full text

BACKGROUND: The efficacy of trastuzumab deruxtecan in HER2-low metastatic breast cancer has shifted HER2 classification from a binary framework toward a continuous expression spectrum that now includes HER2-low and HER2-... BACKGROUND: The efficacy of trastuzumab deruxtecan in HER2-low metastatic breast cancer has shifted HER2 classification from a binary framework toward a continuous expression spectrum that now includes HER2-low and HER2-ultralow categories. Accurate characterization of these subgroups is essential for therapeutic stratification, yet their clinicopathological profiles remain incompletely defined, particularly in the Indian population. This study compared the clinicopathological features and short-term outcomes of invasive breast carcinoma of no special type across four HER2-defined subgroups. METHODS: Three hundred cases of invasive breast carcinoma of no special type diagnosed on core needle biopsy at a tertiary centre in southern India (2022-2023) were classified into HER2-positive, HER2-low, HER2-ultralow, and HER2-negative subgroups using immunohistochemistry with fluorescence in situ hybridisation confirmation. Associations were evaluated using chi-square tests, Kruskal-Wallis tests, binary logistic regression, correspondence analysis, and Kaplan-Meier survival analysis. RESULTS: HER2-low constituted the largest subgroup at 51.7%, followed by HER2-positive (32.3%), HER2-ultralow (9.0%), and HER2-negative (7.0%). HER2-low tumours demonstrated significantly higher oestrogen receptor (74.8%) and progesterone receptor (61.3%) positivity, lower Nottingham grade, and a greater proportion of low Ki-67 proliferation index compared to the other subgroups. Age, menopausal status, clinical stage, tumour size, lymphovascular invasion, perineural invasion, and stromal tumour-infiltrating lymphocyte density did not differ significantly across the four subgroups. On multivariate logistic regression, progesterone receptor positivity was the sole independent predictor of HER2-low status (odds ratio 1.92, 95% confidence interval 1.05-3.50, p = 0.034). The triple-negative phenotype increased progressively from HER2-low (25.2%) through HER2-ultralow (40.7%) to HER2-negative (57.1%). Correspondence analysis placed HER2-ultralow in an intermediate position between HER2-low and HER2-negative. No significant survival differences were observed over a median follow-up of 23 months. CONCLUSIONS: HER2-low tumours represent the majority of invasive breast carcinomas in this Indian cohort and exhibit a distinct profile defined by hormone receptor enrichment, lower grade, and reduced proliferative activity. The intermediate phenotype of HER2-ultralow supports its recognition as a biologically separate category. These findings highlight the importance of standardised HER2 reporting across the full expression spectrum to guide antibody-drug conjugate therapy eligibility.

Rapid slide-level assessment of glomerular yield using virtual staining of unstained renal biopsy sections.

Cai X, Chen X, Liu J … +3 more , Yang X, Xie L, Tang L

Diagn Pathol · 2026 May · PMID 42157065 · Full text

BACKGROUND: Renal biopsy remains the gold standard for the diagnosis of kidney diseases, and specimen adequacy is essential for reliable histopathological evaluation. However, confirmation of glomerular yield in routine... BACKGROUND: Renal biopsy remains the gold standard for the diagnosis of kidney diseases, and specimen adequacy is essential for reliable histopathological evaluation. However, confirmation of glomerular yield in routine pathology workflows often relies on histological sections after staining, which may delay feedback when deeper sectioning is required. METHODS: In this study, we investigated whether virtual staining applied to unstained renal biopsy sections could enable early assessment of glomerular adequacy. Unstained sections prepared under different mounting conditions were virtually transformed into H&E and special stains. The visibility of glomerular structures and the reliability of glomerular assessment were evaluated across multiple scanners. RESULTS: Optimized preparation of unstained sections enabled stable virtual staining with preserved morphological features. Virtual special stains enhanced the visualization of glomerular basement membranes and mesangial regions, allowing reliable identification of glomeruli on unstained tissue sections. This approach demonstrated robustness across different scanning systems, outperforming direct assessment on raw unstained images. CONCLUSIONS: Virtual staining of unstained renal biopsy sections provides a rapid and reagent-free strategy for early slide-level assessment of glomerular yield. By enabling feedback at the sectioning stage before routine staining, this method may improve efficiency and quality control in routine renal pathology workflows.

Expression differences and clinical significance of PD-L1 in lung cancer patients with different histological types and differentiation degrees.

Zhou X, Ao S, Guo Y … +1 more , Jin J

Diagn Pathol · 2026 May · PMID 42141444 · Full text

OBJECTIVE: To investigate the expression differences of PD-L1 in non-small cell lung cancer (NSCLC) patients with different histological types and differentiation degrees. METHODS: A retrospective analysis was conducted... OBJECTIVE: To investigate the expression differences of PD-L1 in non-small cell lung cancer (NSCLC) patients with different histological types and differentiation degrees. METHODS: A retrospective analysis was conducted on the clinical data of 538 NSCLC patients diagnosed at Ningbo Pathological Diagnosis Center (6 small cell lung cancer cases were excluded due to limited sample size). PD-L1 expression was detected by immunohistochemistry (clone 22C3) and evaluated by tumor proportion score (TPS). Univariate chi-square test and multivariate Logistic regression analysis were used to analyze the associations between PD-L1 expression and clinical pathological factors (gender, age, histological type, differentiation degree). RESULTS: PD-L1 expression showed significant gender-based differences (P = 0.000), with a higher positivity rate in male patients. No significant difference was found in PD-L1 expression among different age groups (P = 0.708). Multivariate Logistic regression analysis confirmed that histological type (OR = 2.135, 95%CI:1.526-2.990, P = 0.000) and differentiation degree (OR = 0.412, 95%CI:0.298-0.569, P = 0.000) were independent influencing factors of PD-L1 high expression in NSCLC patients. The proportion of adenocarcinoma (ADC) patients with negative PD-L1 expression was significantly higher than that of squamous cell carcinoma (SCC) patients (32.45% vs. 19.92%, P = 0.000), while the high expression rate of SCC was significantly higher than that of ADC (30.08% vs. 19.21%, P = 0.000). The negative expression rate of PD-L1 in well-differentiated tumors was the highest (45.71%, P = 0.000), and the high expression rate in poorly differentiated tumors was the highest (35.98%, P = 0.000). Among well-differentiated patients with negative PD-L1 expression, the proportion of ADC was significantly higher than that of SCC (61.11% vs. 29.41%, P = 0.023); among well-differentiated patients with low PD-L1 expression, the proportion of SCC was higher than that of ADC (52.94% vs. 38.89%, P = 0.037). CONCLUSION: PD-L1 expression in NSCLC is significantly correlated with histological type and differentiation degree, which are independent influencing factors of PD-L1 high expression. SCC and poorly differentiated tumors have higher PD-L1 expression levels, suggesting that these patients may have better responsiveness to PD-1/PD-L1 inhibitor immunotherapy. The study provides more precise pathological evidence for personalized immunotherapy strategies in NSCLC patients.

Mobile device smartphones for intraoperative diagnosis at the University Hospital Trust of Modena/UNIMORE: from validation process to costs analysis.

Fabbri VP, Reggiani Bonetti L, Pagni F … +7 more , Mazzini A, L'Imperio V, Caramaschi S, Parwani A, Dei Tos AP, Marletta S, Eccher A

Diagn Pathol · 2026 May · PMID 42129876 · Full text

BACKGROUND: Telepathology enables remote diagnostic consultation through digital image transmission and is particularly valuable in settings where subspecialty expertise is not immediately available. This study evaluated... BACKGROUND: Telepathology enables remote diagnostic consultation through digital image transmission and is particularly valuable in settings where subspecialty expertise is not immediately available. This study evaluated the diagnostic accuracy of PathoZoom, a web-based platform that allows real-time remote review of microscope images via mobile devices during intraoperative frozen section examination in a high-complexity academic hospital. METHODS: Seventy-five consecutive frozen section cases, processed between January and April 2024 at the University Hospital Trust of Modena/UNIMORE, were included. All cases were first diagnosed using conventional light microscopy (LM) and then, after a washout period, the same slides were reviewed remotely using the PathoZoom system and mobile smartphones. Diagnostic concordance between LM and telepathology was assessed, classifying discrepancies as major or minor, depending on their clinical impact in accordance with the current guidelines of the College of American Pathologists guidelines. RESULTS: Overall concordance was 96% (72/75 cases). One major discordance occurred in a basal cell carcinoma margin assessment, interpreted as negative by telepathology and positive by LM. Two minor discrepancies involved polymorphonuclear cell counts in orthopedic specimens. No differences in performance were observed between mobile devices. CONCLUSIONS: Thanks to the technological setting and results, PathoZoom and Smartphones are proposed as a diagnostic option for intraoperative consultation. Results support safety, feasibility and cost effectiveness of mobile-based telepathology in complex surgical settings and geographically extended healthcare networks.

Schwannoma of tongue: a clinicopathologic study of 34 cases and review of published literature.

Ud Din N, Khan M, Abdul-Ghafar J … +2 more , Safdar F, Ahmad Z

Diagn Pathol · 2026 Apr · PMID 42063167 · Full text

BACKGROUND: Schwannomas are exceedingly rare in the tongue. Here, we report clinicopathological features of tongue schwannomas diagnosed at the section of Histopathology, Department of Pathology and Laboratory Medicine,... BACKGROUND: Schwannomas are exceedingly rare in the tongue. Here, we report clinicopathological features of tongue schwannomas diagnosed at the section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital (AKUH), Karachi, Pakistan and reviewed the published literature. METHODS: Retrospective study of 34 tongue schwannomas diagnosed between 2011 and 2024. Hematoxylin and Eosin (H&E) and immunohistochemical (IHC) slides were reviewed. Demographic and clinical data were obtained. RESULTS: There was a slight female preponderance. Mean age was 30 years. Commonest sites were lateral borders and base of tongue. All tumors were surgically excised. Average tumor size was 2 cm. Histologically, 30 tumors exhibited classical features of schwannoma, while 4 were cellular. On IHC, strong and diffuse positivity of S100 protein and SOX10 was seen. No recurrences were reported in the cases where follow-up was available. None of the 34 cases had clinical features suggestive of Neurofibromatosis. CONCLUSIONS: Schwannomas although rare, should be included in the differential diagnosis of tongue masses. Early recognition and surgical excision result in excellent outcomes.

Monocytoid dendritic cells might be a specific marker for lung involvement in dermatomyositis.

Knirsch J, Al-Effah M, Popper H

Diagn Pathol · 2026 Apr · PMID 42057091 · Full text

Dermatomyositis (DM) is a rare autoimmune disease leading to inflammatory and degenerative changes affecting skin and muscles. Interstitial lung disease is a major risk factor for morbidity and mortality in DM. The preci... Dermatomyositis (DM) is a rare autoimmune disease leading to inflammatory and degenerative changes affecting skin and muscles. Interstitial lung disease is a major risk factor for morbidity and mortality in DM. The precise immune mechanism underlying DM, particularly in the context of lung involvement, remains poorly understood. This research focuses on the significance of dendritic cell subsets and Langerhans cells in the immune irregularities observed in DM.The study analyzed 12 cases of DM with lung involvement, and compared the findings to 12 cases with skin involvement. All subjects were untreated at the time of diagnosis, with ages ranging from the 20 to 80 years. Immunohistochemistry was utilized to characterize dendritic cell subsets and to assess cells expressing MDA5. Six cases of rheumatoid arthritis (RA) with fibrosing pneumonia were investigated for comparison.We identified dendritic cells and lymphocytes expressing the melanoma differentiation gene 5 (MDA5) protein. Monocytoid dendritic cells predominated in DM, and were absent in RA, therefore might serve as a diagnostic marker, separating DM from other autoimmune diseases. Our findings suggest that DCs and lymphocytes are constantly attacked by autoantibodies for MDA5, as these cells express the antigen. Furthermore, mature DC in skin and lung and Langerhans in the skin are replaced by immature DC. This might explain prolonged activation of the immune system resulting in fibrosis in both skin and lung tissues. The loss of Langerhans cells might be responsible for an increased penetrance of antigens through the epidermis.

Virtual assistants based on artificial intelligence for oral diagnosis: help for clinicians AI oral diagnosis helper.

de Araújo EGO, de Medeiros Carvalho LI, de de Souza BES … +9 more , de Santana IHG, Martins HDD, de Pontes Santos HB, Mélo CB, Dos Reis LA, Dias LMRP, Batista AUD, de Lucena EHG, Bonan PRF

Diagn Pathol · 2026 Apr · PMID 42032752 · Full text

BACKGROUND: Oral cancer is one of the most aggressive malignancies in the head and neck region, with high potential for and a poor prognosis. Despite advancements in diagnostic methods, early detection remains a challeng... BACKGROUND: Oral cancer is one of the most aggressive malignancies in the head and neck region, with high potential for and a poor prognosis. Despite advancements in diagnostic methods, early detection remains a challenge owing to the lack of specific symptoms in the initial stages and socioeconomic barriers limiting access to health care. Artificial intelligence has emerged as a promising tool for improving diagnostic accuracy in various medical fields, including oral pathology. This study aimed to evaluate the performance of the AI Oral Diagnosis Helper (AODH), developed using ChatGPT™ (versions 4 and 4o), in the diagnosis and management of oral diseases. METHODS: Thirty clinical cases were evaluated by two specialists for oral diagnosis and AODH. Diagnosis and treatment suggestions were compared with those of a gold standard specialist. Agreement and accuracy rates were calculated via Fleiss’ generalized kappa coefficient with a 95% confidence interval via RStudio. RESULTS: AODH via ChatGPT™ 4 (AODH4) correctly identified 22 out of 30 cases (73.3%), whereas AODH via version 4° (AODH4°) correctly identified 24 cases (80%). Expert 1 and Expert 2 correctly diagnosed 27 (90%) and 26 (86.7%) cases, respectively. Fleiss’s kappa indicated substantial reliability among AODHs and experts (K = 0.79). The AODH4 recommended appropriate diagnostic tests in 21 cases (70%), whereas the AODH4o did so in 26 cases (86.7%). For biopsy recommendations, Specialist 1 was accurate in 27 cases (90%), Specialist 2 was accurate in 26 cases (86.7%), AODH4 was accurate in 17 cases (56.7%), and AODH4o was accurate in 26 cases (86.7%). CONCLUSION: AODH demonstrated high diagnostic accuracy comparable to that of human specialists and can assist in oral diagnosis, especially where access to specialists is limited. The performance of AODH4o was superior to that of AODH4. Further research is needed to define the role of AI in enhancing clinical decision-making.

Clinical pathological characteristics and prognostic analysis of 140 cases of medullary thyroid carcinoma: validation of the international medullary thyroid carcinoma grading system in a chinese cohort.

Zhang Z, Yang Y, Dou Y … +4 more , Liu W, Dong L, Zhu Y, Lu H

Diagn Pathol · 2026 Apr · PMID 42021330 · Full text

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor with variable clinical behavior. The International Medullary Thyroid Carcinoma Grading System (IMTCGS) was developed to refine prognostic strat... BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor with variable clinical behavior. The International Medullary Thyroid Carcinoma Grading System (IMTCGS) was developed to refine prognostic stratification, but its validation in Chinese populations remains limited. This study aimed to validate the IMTCGS and evaluate the prognostic significance of Ki-67, preoperative calcitonin levels, and molecular alterations in a Chinese MTC cohort. METHODS: We conducted a retrospective analysis of 140 MTC patients who underwent initial surgery at a single center between May 2017 and June 2025. Tumors were graded using the IMTCGS criteria. Associations among clinicopathological variables, Ki-67 index, preoperative calcitonin levels, molecular characteristics (assessed by next-generation sequencing), and progression-free survival (PFS) were analyzed using Kaplan-Meier analysis, Cox proportional hazards models, and receiver operating characteristic (ROC) curves. RESULTS: High-grade MTC (47.9%) and Ki-67 index ≥ 5% (46.4%) were significantly associated with larger tumor size, higher T/N stage, greater lymph node metastasis burden, and vascular invasion (all p < 0.05). Preoperative calcitonin levels showed strong correlations with both tumor diameter (ρ = 0.623, p < 0.001) and lymph node metastasis count (ρ = 0.530, p < 0.001). RET mutations were predominant (89.5%), with exon 16 being the most frequently involved. High-grade disease, Ki-67 ≥ 5%, tumor diameter ≥ 2 cm, ≥ 5 metastatic lymph nodes, and male sex were all associated with significantly shorter PFS (all p < 0.05). Among all predictors, lymph node metastasis count showed the highest discriminatory accuracy for PFS (AUC = 0.793). CONCLUSIONS: The IMTCGS appears to effectively stratify tumor aggressiveness in Chinese MTC patients, with Ki-67 emerging as a critical component of risk assessment. Preoperative calcitonin level serves as a robust quantitative indicator of tumor burden, while the predominance of RET mutations reinforces their central pathogenic role. These findings support the clinical utility of integrating histological grading, proliferative markers, and biomarker profiling to enhance risk stratification and guide personalized management in MTC.

Comparison of immunohistochemistry, PCR, and NGS for the evaluation of mismatch repair deficiency and microsatellite instability in colorectal cancer: a retrospective study.

Wang L, Hu Y, Yuan H … +3 more , Yu N, Xiao L, Jin J

Diagn Pathol · 2026 Apr · PMID 42010682 · Full text

BACKGROUND: Microsatellite instability (MSI) and mismatch repair (MMR) deficiency serves as a critical predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC). However, dis... BACKGROUND: Microsatellite instability (MSI) and mismatch repair (MMR) deficiency serves as a critical predictive biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC). However, discrepancies among detection methods may lead to inconsistent results, which may contribute to ICIs resistance. This study aimed to evaluate the concordance of MMR status and MSI assessment across three commonly used methods and to explore factors underlying discordant cases. METHODS: We retrospectively analyzed MSI status in 534 CRC patients using three detection methods: immunohistochemistry (IHC) for MMR protein expression, and polymerase chain reaction (PCR) and next-generation sequencing (NGS) for MSI status assessment. Concordance between methods was measured using Kappa statistics, and discordant cases were further investigated. RESULTS: Among the 534 cases, 7.3% (39/534) were classified as deficient mismatch repair (dMMR) by IHC, 7.5% (40/534) as MSI-H by PCR, and 7.3% (39/534) as MSI-H by NGS. The highest concordance was observed between PCR and NGS (Kappa = 0.986), followed by NGS and IHC (Kappa = 0.943), and PCR and IHC (Kappa = 0.930). Discordant results occurred in five cases (0.9%), primarily attributable to assay-specific limitations, tumor heterogeneity, technical or pre-analytical issues, and biological variability. CONCLUSION: IHC, PCR, and NGS showed high overall concordance in MSI and MMR assessment. The small number of discordant cases highlights the inherent limitations of individual methods. While single-method testing is generally reliable, multi-platform evaluation may provide additional insights in diagnostically challenging or borderline cases.

Combined assessment of stromal tumor infiltrating lymphocytes and tumor peroxiredoxin 4 expression improved prognostic stratification in postoperative pancreatic cancer patients.

Liu Y, Han J, Shioya A … +4 more , Jiao W, Okuro M, Ito T, Yamada S

Diagn Pathol · 2026 Apr · PMID 41992245 · Full text

BACKGROUND: Pancreatic cancer (PC) is characterized by profound immunosuppression and marked biological heterogeneity. Stromal tumor-infiltrating lymphocytes (TILs) reflect host antitumor immunity, whereas peroxiredoxin... BACKGROUND: Pancreatic cancer (PC) is characterized by profound immunosuppression and marked biological heterogeneity. Stromal tumor-infiltrating lymphocytes (TILs) reflect host antitumor immunity, whereas peroxiredoxin 4 (PRDX4) represents tumor redox adaptation. However, their combined prognostic value remains unclear. METHODS: We retrospectively analyzed 138 resected cases of PC. Stromal TIL density was assessed on hematoxylin-eosin (H&E) sections, and tumor PRDX4 expression was evaluated by immunohistochemistry. Both markers were dichotomized into high and low groups using ROC-derived thresholds. Patients were further classified into four integrated subgroups: TIL-high/PRDX4-low (TH-PL), TIL-high/PRDX4-high (TH-PH), TIL-low/PRDX4-low (TL-PL), and TIL-low/PRDX4-high (TL-PH). Associations with clinicopathological features and disease-specific survival (DSS) were analyzed. RESULTS: High TIL density was associated with less advanced pathological stage and significantly improved DSS, whereas high PRDX4 expression correlated with lymphovascular and perineural invasion as well as advanced stage. An inverse association between TILs and PRDX4 was observed. Integrated subgroup analysis revealed distinct prognostic patterns: the TL-PH subgroup showed the poorest DSS, whereas the TH-PL subgroup demonstrated the most favorable outcomes. In multivariable Cox models, the TL-PH subgroup remained an independent adverse prognostic factor for both 3- and 5-year DSS, while the TH-PL subgroup showed a protective effect, particularly at 3 years. CONCLUSIONS: Stromal TILs and PRDX4 appear to capture complementary immune and redox features of PC. Their combined assessment may improve prognostic stratification and help to identify a potential redox-associated, immune-excluded subgroup with particularly poor outcomes.

Construction of an integrated diagnostic-therapeutic model for prostate cancer using rapid multiplex immunohistochemistry.

Luan Y, Geng YS, Gao YQ … +3 more , Lu SM, Xiao Q, Ding XF

Diagn Pathol · 2026 Apr · PMID 41975430 · Full text

OBJECTIVE: To explore the feasibility and clinical application value of constructing an integrated model for the diagnosis and treatment of prostate cancer based on rapid multiplex immunohistochemistry (RMI) combined wit... OBJECTIVE: To explore the feasibility and clinical application value of constructing an integrated model for the diagnosis and treatment of prostate cancer based on rapid multiplex immunohistochemistry (RMI) combined with intraoperative frozen section examination (IFSE). METHODS: A total of 50 patients with high suspicion of localized prostate cancer were prospectively enrolled at our hospital between January and November 2025. All patients underwent mpMRI/TRUS fusion‑guided transperineal targeted biopsy. Tissue specimens obtained during biopsy were processed for both IFSE and RMI. The RMI panel included antibodies against P504S, P63, 34βE12, and CK5/6. Patients with an intraoperative pathological diagnosis of prostate cancer proceeded directly to robot‑assisted laparoscopic radical prostatectomy (RARP). Those with negative intraoperative findings underwent systematic biopsy. The diagnostic performance of this model was evaluated using postoperative whole- mount histopathology or conventional pathology from systematic biopsy as the reference standard. RESULTS: The overall pathological positivity rate in this study was 86.00% (43/50). Of these, 39 patients were intraoperatively diagnosed with prostate cancer by rapid pathology and subsequently underwent immediate RARP. IFSE alone diagnosed prostate cancer in 37 cases, with a diagnostic sensitivity of 94.87% (37/39). The concordance rate of Gleason score with postoperative pathology was 81.08%. IFSE combined with RMI diagnosed prostate cancer in all 39 cases, each later confirmed by postoperative pathology following RARP, yielding a diagnostic sensitivity of 100%. The Gleason score concordance rate improved to 97.44%. The false-negative rate was 5.13% for IFSE alone, compared to 0% for the combined IFSE and RMI approach. The mean time to obtain pathological results was 29.80 ± 3.92 minutes for IFSE alone, and 29.93 ± 2.35 minutes for IFSE combined with RMI, indicating no significant prolongation. All 39 patients who underwent immediate RARP had a mean hospital stay of 7.31 ± 1.41 days, with only one hospitalization episode per patient. CONCLUSION: RMI effectively compensates for the limitations of IFSE alone. The combined application of IFSE and RMI within an integrated diagnostic–therapeutic model for prostate cancer significantly improves intraoperative diagnostic sensitivity and Gleason score accuracy without substantially extending waiting time.

Case report: a case of primary cutaneous diffuse large B-cell lymphoma, leg type with TdT positive in an elderly woman.

Zheng J, Li X, Chen H

Diagn Pathol · 2026 Apr · PMID 41923111 · Full text

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma, leg type(PCDLBCL-LT) is a rare form of lymphoma that originates from the post-germinal center and typically does not express terminal deoxynucleotidyl transfer... BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma, leg type(PCDLBCL-LT) is a rare form of lymphoma that originates from the post-germinal center and typically does not express terminal deoxynucleotidyl transferase(TdT), a marker of immunophenotypic immaturity. CASE DESCRIPTION: A 73-year-old female presented to our hospital with recurrent nodules on her lower limbs, which had persisted for over five years without systemic involvement, accompanied by a gradual increase in TdT expression. Histology revealed diffuse infiltration of centroblasts and/or immunoblasts within the dermis and subcutis, with CD20, CD10, BCL2 and c-MYC expression. Fluorescence in situ hybridization (FISH) showed MYC rearrangement without BCL2/BCL6 alterations, corroborating the diagnosis of TdT-positive PCDLBCL-LT. Following six cycle of R-CHOP chemotherapy, the patient achieved complete remission. A follow-up conducted one year showed no tumor recurrence. CONCLUSION: Our case showed that TdT can be expressed in PCDLBCL-LT, and highlight the importance of a comprehensive analysis of clinicopathology and ancillary testing to avoid misdiagnosis. Additionally, the clinical course of TdT-positive PCDLBCL-LT seems remain relatively favorable. However, further research is still needed on this relationship.

Detection of collagen band-associated regions in H&E-stained colonic biopsies of collagenous colitis patients using superpixel-based feature extraction and neural network classification.

Kiudelis V, Petrolis R, Ramonaitė R … +7 more , Jančiauskas D, Poškienė L, Kupčinskas J, Šabanas P, Čerapaitė-Trušinskienė R, Meilutytė-Lukauskienė D, Kriščiukaitis A

Diagn Pathol · 2026 Mar · PMID 41896924 · Full text

BACKGROUND: Collagenous colitis (CC) is diagnosed histologically and is characterised by a thickened subepithelial collagen band together with inflammatory and epithelial changes. Although routine haematoxylin and eosin... BACKGROUND: Collagenous colitis (CC) is diagnosed histologically and is characterised by a thickened subepithelial collagen band together with inflammatory and epithelial changes. Although routine haematoxylin and eosin (H&E) staining is sufficient for diagnosis in most cases, visual assessment of the collagen band can be challenging in borderline or heterogeneous specimens. Additional stains may be required in diagnostically difficult situations. THE AIM: To develop a machine-learning–based algorithm for detecting subepithelial collagen band-associated regions in routine H&E-stained colonic biopsy images as a decision-support tool for histopathological assessment. METHODS: H&E-stained colonic biopsy specimens from 36 patients with histologically confirmed CC were imaged at 20 × magnification (1392 × 1040 pixels). Images were segmented into 1,000 superpixels using the Simple Linear Iterative Clustering (SLIC) algorithm. Superpixels overlapping with expert-provided rough annotations of the collagen band were labelled and characterised using normalised RGB histograms. A feed-forward neural network classifier (three hidden layers, 10 neurons per layer) was trained to distinguish collagen band–associated from non-collagen regions. Class imbalance was addressed by data augmentation of minority-class superpixels. Post-processing with connected-component size filtering was applied to enforce spatial continuity. Superpixel-level performance was evaluated quantitatively, and image-level outputs were assessed using expert acceptability scoring. RESULTS: The classifier achieved a superpixel-wise accuracy of 0.928 (sensitivity 0.898, specificity 0.953). Size-based post-processing substantially reduced isolated false-positive detections. At the image level, the final algorithm achieved an acceptability accuracy of 0.846 according to expert evaluation. The model successfully highlighted subepithelial collagen band–associated regions consistent with expert annotations but did not model additional diagnostic features required for complete CC diagnosis. CONCLUSION: Our superpixel-based neural network highlights collagen-rich regions in H&E-stained colonic biopsies, offering decision support for pathologists. As diagnosis of collagenous colitis requires broader histopathological and clinical context, this method is intended as a decision-support tool rather than a stand-alone diagnostic solution.

Adenocarcinoma admixed with neuroendocrine carcinoma of the cervix: a clinicopathological diagnostic study and molecular features.

Yu M, Jiang M, Zhang X … +2 more , Chen H, Ye X

Diagn Pathol · 2026 Mar · PMID 41888927 · Full text

BACKGROUND: Cervical adenocarcinoma admixed with neuroendocrine carcinoma (A-NEC) is a rare and aggressive tumor with limited molecular characterization and no standardized treatment. This study aims to delineate its cli... BACKGROUND: Cervical adenocarcinoma admixed with neuroendocrine carcinoma (A-NEC) is a rare and aggressive tumor with limited molecular characterization and no standardized treatment. This study aims to delineate its clinicopathological and molecular features to improve diagnostic accuracy and identify potential therapeutic targets. METHODS: Fourteen rigorously diagnosed cervical A-NEC cases (2016–2024) were retrospectively analyzed according to the WHO 2020 criteria. Comprehensive evaluation included cytology, histomorphology, HPV genotyping, and immunohistochemical profiling of neuroendocrine markers, Ki-67, p53, PTEN, PI3K, and PD-L1. RESULTS: All patients presented with abnormal bleeding or discharge. While cytology detected abnormalities in all evaluable cases (10/10), it did not identify neuroendocrine components. Histology revealed interdigitated HPV-associated adenocarcinoma and neuroendocrine carcinoma (predominantly small cell type). Molecular analysis showed component-specific heterogeneity: although TP53 and PD-L1 expression were concordant, the neuroendocrine component exhibited PTEN loss in all 8 evaluable cases (8/8) and PI3K overexpression in 5/8 cases-a pattern not observed in adenocarcinoma components. NEC demonstrated high proliferative activity (median Ki-67 80%). Survival events were concentrated within the first 24 months. CONCLUSION: This clinicopathological analysis of 14 cervical A‑NEC cases highlights the diagnostic limitations of cytology and the need for histopathological confirmation in surgical specimens. The neuroendocrine component exhibits distinct molecular features (PTEN loss, PI3K overexpression), indicating dysregulation of the PI3K‑AKT‑mTOR pathway as a potential research target. Most events occur within 24 months, underscoring the importance of early monitoring. These findings improve the understanding of this rare malignancy and support future multicenter studies.

Calcifying fibrous tumors of the thoracic cavity: a clinicopathological series of seven solitary cases.

Lou G, Xing C, Zhang Y … +2 more , Yu S, Han G

Diagn Pathol · 2026 Mar · PMID 41872938 · Full text

BACKGROUND: This study aims to characterize the clinicopathological and immunophenotypic profile of calcifying fibrous tumor (CFT) occurring in the thoracic cavity, and to elucidate its key diagnostic features for accura... BACKGROUND: This study aims to characterize the clinicopathological and immunophenotypic profile of calcifying fibrous tumor (CFT) occurring in the thoracic cavity, and to elucidate its key diagnostic features for accurate pathological recognition and differential diagnosis. METHODS: A retrospective analysis was conducted on 7 cases of thoracic CFT (3 in the mediastinum, 2 in the diaphragm, 2 in the lung). Clinical, imaging, histopathological, and immunohistochemical data were reviewed, and patient outcomes were assessed. RESULTS: All patients underwent complete surgical excision. The mean patient age was 39 years, with a female predominance (5/7, 71.4%). Most patients were asymptomatic. The tumors presented as solitary, well-circumscribed masses. Histologically, they were characterized by abundant hyalinized collagen fibers, scattered bland spindle cells, variable lymphoplasmacytic infiltrates, and psammomatous/dystrophic calcifications. Immunohistochemically, tumor cells were diffusely and strongly positive for vimentin, with focal weak positivity for SMA and CD34. Markers including STAT6, ALK, and pan-CK were negative. During a mean follow-up period of 31 months, no recurrence or metastasis was observed. CONCLUSION: This study underscores the importance of including CFT in the differential diagnosis of well-circumscribed thoracic masses. Recognition of its pleural origin, classic histologic triad (hyalinized collagen, chronic inflammation, and calcification) along with a characteristic but nonspecific immunoprofile is crucial to avoid misdiagnosis as more aggressive entities and to guide appropriate conservative surgical management.

Clinicopathological analysis of 19 cases of mixed gangliocytoma-pituitary neuroendocrine tumors.

Du H, Hu X, Mei N … +4 more , Wang Y, Tang F, Du Z, Xiong J

Diagn Pathol · 2026 Mar · PMID 41872867 · Full text

Mixed gangliocytoma-pituitary neuroendocrine tumors (PitNETs) occurring in the sellar region are extremely rare neoplasms. To improve the understanding of these tumors and guide clinical diagnosis, a comprehensive retros... Mixed gangliocytoma-pituitary neuroendocrine tumors (PitNETs) occurring in the sellar region are extremely rare neoplasms. To improve the understanding of these tumors and guide clinical diagnosis, a comprehensive retrospective study analyzing clinical manifestations and pathological morphology in 19 cases of sellar mixed gangliocytoma-PitNETs was conducted. A total of 19 mixed gangliocytoma-PitNETs patients from Huashan Hospital, Fudan University (January 2013 – September 2025) were enrolled. Clinical manifestations, radiological characteristics, histological features, immunohistochemical and molecular analyses were systematically evaluated. This tumor is more common in women, and the cohort comprised 17 females and 2 males, aged 28–70 years (mean 45.3 ± 12.1). Acromegaly was the most common clinical presentation (6/19, 31.59%). Preoperative endocrine testing revealed elevated Insulin-like Growth Factor-1 (IGF-1) levels in the majority of patients (12/19, 63.16%). MRI demonstrated round or oval-shaped mass lesions with marked contrast enhancement. Histologically, PitNETs components exhibited diffuse sheets of small, uniform round-to-ovoid cells, accompanied by focal large gangliocyte-like cells. Immunohistochemistry revealed Pit-1 positive in all 19 cases and CAM5.2 highlights fibrous bodies in 18 cases while 1 case perinuclear positive. According to the 2022 WHO criteria, 18 cases (18/19, 94.74%) diagnosed as high-risk sparse granular somatotroph PitNETs and 1 case (1/19, 5.26%) diagnosed as dense granular somatotroph PitNETs. Molecular analyses of GNAS R201 and BRAF V600E mutations in 19 cases showed wild-type. All patients underwent transsphenoidal surgery (TSS). Postoperative follow-up (mean 67.2 ± 36.0 months, range 3–129) revealed no tumor recurrence. For PitNETs with gangliocytic components, histopathological evaluation must rigorously assess adenoma lineages, given their frequent association with high-risk Pit-1-lineage tumors.

Development and validation of a computer program for histoanatomical morphometric analysis of the bowel wall in children with Hirschsprung's disease.

Hawez T, Erlöv T, Granéli C … +6 more , Andersson G, Lundberg T, Fransson E, Evertsson M, Cinthio M, Stenström P

Diagn Pathol · 2026 Mar · PMID 41864910 · Full text

BACKGROUND: Developing new diagnostic imaging methods that provide detailed visualization of the histoanatomy of tissues and organs requires precise histomorphometric evaluation. With a particular focus on bowel, this st... BACKGROUND: Developing new diagnostic imaging methods that provide detailed visualization of the histoanatomy of tissues and organs requires precise histomorphometric evaluation. With a particular focus on bowel, this study aimed to develop and validate a computer program for reliable and efficient assessment of bowel wall histomorphometry. METHODS: A MATLAB-based computer program was developed in-house to manually delineate and automatically calculate mean layer thickness of the muscularis propria layers, submucosa and mucosa in histopathology images of bowel wall specimens from patients operated on for Hirschsprung’s disease. Validation included assessment of inter- and intra-observer reliability and agreement for generated mean thicknesses, as well as comparison with manual measurements (mean of 10 thickness measurement points). Reliability was assessed through intraclass correlation coefficient (ICC) (good > 0.75) and agreement through Bland-Altman analysis (good= mean close to zero and spread within 2 standard deviations). RESULTS: The program allowed for import of histopathology images for bowel wall layer analysis. After manual layer delineation, the program automatically calculated mean layer thickness (mm) ± standard deviation based on approximately 3000 measurement points. For the inter-observer analyses the reliability was moderate to good in the majority of the histoanatomic layers (ICC range 0.6–0.9) and agreement was similarly good based on the Bland-Altman analyses. Also, the intra-observer reliability ranged between good and excellent in the majority of histoanatomic layers (ICC range 0.7-1.0). The high-precision layer delineation and mean thickness extraction per image took 15 min, compared to 60 min for manual measurement. CONCLUSIONS: The developed computer program enables precise and time-efficient measurements of histoanatomic layer thicknesses in histopathology images of bowel wall, with good reliabilities and agreements between examinators. The program’s application is useful in histomorphometric evaluations for advancing diagnostic imaging techniques.
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