INTRODUCTION: TROP2 antibody-drug conjugates have shown promising anti-tumour activity, but neither the activity of these agents nor TROP2 expression has been well studied in pulmonary large cell neuroendocrine carcinoma...INTRODUCTION: TROP2 antibody-drug conjugates have shown promising anti-tumour activity, but neither the activity of these agents nor TROP2 expression has been well studied in pulmonary large cell neuroendocrine carcinoma (LCNEC), a rare and aggressive cancer type. We aimed to (i) determine the prevalence of TROP2 immunoreactivity in LCNEC; (ii) assess whether TROP2 immunoreactivity in LCNEC is related to RB1 loss on IHC or to the presence of NSCLC or SCLC components and (iii) determine whether TROP2 immunoreactivity in LCNEC has prognostic significance. METHODS: TROP2 immunohistochemistry was performed on 58 pure LCNECs and 25 areas of LCNEC that were combined with other carcinomas, in tissue microarray format. TROP2 was scored for the percent of tumour cells staining, and with evaluation of cytoplasmic versus membranous staining, approximating a previously published predictive scoring method. RESULTS: TROP2 staining in ≥1% and ≥50% of LCNEC cells was present in 60% and 26% of pure LCNEC tumours, respectively. Cytoplasmic-type staining, previously implicated in greater antibody-drug conjugate response, was present in 48% of pure LCNEC cases. Positive TROP2 staining was less frequent in pure LCNEC than in the LCNEC component of tumours that also contained a NSCLC component (≥1%: P = 0.0087; ≥50%: P = 0.011), and ≥50% TROP2 staining in pure LCNEC was associated with retained RB1 staining on immunohistochemistry (P = 0.032). TROP2 staining was not associated with recurrence-free survival or disease-specific survival outcomes. CONCLUSION: Frequently positive TROP2 IHC suggests that TROP2 antibody-drug conjugates may be potential treatments for LCNEC.
Apornvirat S, Hadi EJ, Gudi M
… +13 more, Bae YK, Ng V, Xiu Y, Tan CS, Mok CW, Hong GS, Chan G, Ang P, Cheng S, Lim TH, Fox SB, Rakha E, Tan PH
Histopathology
· 2026 Jun · PMID 42365981
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BACKGROUND: Malignant adenomyoepithelioma (M-AME) is an extremely rare and morphologically diverse breast tumour, posing significant diagnostic and management challenges. We present seven cases of M-AME with different hi...BACKGROUND: Malignant adenomyoepithelioma (M-AME) is an extremely rare and morphologically diverse breast tumour, posing significant diagnostic and management challenges. We present seven cases of M-AME with different histological compositions to contribute additional data to the existing literature. Through these cases, we review and discuss potential pitfalls and classification challenges in diagnosing M-AME. METHODS AND RESULTS: We performed a retrospective clinicopathological review of seven cases of M-AME from women aged 45-74 years (median 53 years). Each case exhibited distinct architectural patterns and compositions of classic and malignant components: (1) Adenomyoepithelioma (AME) with metaplastic spindle and squamous cell carcinoma; (2) Invasive AME with an aberrant immunohistochemical profile; (3) Invasive AME with an adenomyoepithelial adenosis pattern; (4) Metaplastic spindle cell carcinoma arising from AME with suspicion of M-AME in situ; (5) Atypical AME with late lung metastasis harbouring HRAS p.G13R and in-frame PIK3R1 deletion; (6) and (7) M-AME in situ. CONCLUSION: M-AME encompasses heterogeneous patterns that overlap with the infiltrative-like pattern of classic AME (adenomyoepithelial adenosis form of tubular AME) and metaplastic breast carcinoma. Recognition of the underlying AME architecture, coupled with immunohistochemical and molecular correlation, supports pragmatic classification into in situ or invasive M-AME or conventional breast carcinoma arising in the context of AME. Together with clinical, radiological, and molecular correlations, this approach can help guide appropriate management.
Yaprak Bayrak B, Akgul M, Cheng M
… +3 more, Yıldırım NA, Sangoi AR, Cheng L
Histopathology
· 2026 Jun · PMID 42363647
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Perivascular epithelioid cell tumours (PEComas) comprise a distinctive and biologically heterogeneous family of mesenchymal neoplasms defined by perivascular epithelioid differentiation and dual melanocytic and smooth mu...Perivascular epithelioid cell tumours (PEComas) comprise a distinctive and biologically heterogeneous family of mesenchymal neoplasms defined by perivascular epithelioid differentiation and dual melanocytic and smooth muscle-like immunophenotypes. Within the genitourinary (GU) tract, renal tumours are historically designated as angiomyolipoma (AML) and represent the most common and biologically informative manifestation of PEComa, serving as the conceptual reference model for understanding PEComa across different organ sites. Extrarenal GU PEComas, on the other hand, are rare, morphologically diverse and frequently pose significant diagnostic challenges, particularly in limited biopsy material. This review synthesizes contemporary clinicopathological, immunohistochemical and molecular data on GU PEComas, with emphasis on diagnostic pathology, risk stratification and practical diagnostic interpretation. This also emphasizes classification based on shared molecular drivers rather than organ site or legacy terminology and provides a guide for accurate diagnosis, risk assessment and interpretation of PEComas in daily pathology practice.
Histopathology
· 2026 Jun · PMID 42363645
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AIMS: Low-grade spindle cell lesions of the breast (LGSCL-B) are uncommon, with malignant counterparts being particularly rare. Management recommendations for desmoid-type fibromatosis (DF), in particular, have evolved....AIMS: Low-grade spindle cell lesions of the breast (LGSCL-B) are uncommon, with malignant counterparts being particularly rare. Management recommendations for desmoid-type fibromatosis (DF), in particular, have evolved. METHODS AND RESULTS: A retrospective review of cases from 2000 to 2024 was conducted using LGSCL-B-related keyword searches. Clinical features were assessed, and when available, core needle biopsy (CNB) findings were correlated with excision specimens and imaging. Of 68 LGSCL-B samples, DF was the most frequent subtype (28 cases, 41%). A total of six resections were negative for β-catenin expression, including three resections from cases diagnosed as DF and three resections from cases categorized as undetermined on CNB and subsequently finalized as DF on resection. Myofibroblastoma occurred in 12 patients, more often in men (58%), with lipid-rich (n = 3) and myxoid (n = 2) variants. One lesion initially diagnosed as a solitary fibrous tumour was reclassified as a palisaded myofibroblastoma. Malignancy was identified in two biopsies: a spindle cell sarcoma and a fibromatosis-like metaplastic carcinoma; the latter was reclassified at resection as a malignant phyllodes tumour with heterologous bone formation. Thirteen CNB (19%) were indeterminate, including one described with ambiguous wording, a spindle cell sarcoma with a differential encompassing both benign and malignant entities. CONCLUSIONS: Most LGSCL-B can be classified on CNB, but approximately one-fifth yield indeterminate results. Diagnostic challenges include overlapping morphological features, immunohistochemical profiles and potential reclassification at resection. Awareness of these pitfalls, along with selective use of adjunct molecular testing, may enhance diagnostic accuracy and reduce overtreatment.
Ferreira IM, Simplício M, Vieira RJ
… +2 more, Morais R, Gullo I
Histopathology
· 2026 Jun · PMID 42363644
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This systematic review with meta-analysis aims to analyse the existing literature on clinicopathological features of sporadic gastric hyperplastic polyps (GHP), with special emphasis on risk factors associated with neopl...This systematic review with meta-analysis aims to analyse the existing literature on clinicopathological features of sporadic gastric hyperplastic polyps (GHP), with special emphasis on risk factors associated with neoplastic transformation, as well as available immunohistochemical and molecular data relevant to GHP carcinogenesis. We searched two electronic databases and included studies reporting the presence of dysplasia and adenocarcinoma arising in GHP. Meta-analysis of odds ratios (ORs) was performed using random-effects models. We included 58 studies, 11 of which were included in quantitative synthesis. The overall rate of neoplastic transformation in GHP was 6.0% and progression to adenocarcinoma was observed in 1.5%. Statistically significant risk factors for neoplastic transformation were age ≥65 years (OR 2.60; 95% confidence interval [CI] [1.88-3.59]), size ≥20 mm (OR 4.63; 95% CI [1.82; 11.77]) with increasing size thresholds, as well as intestinal metaplasia (OR 3.65; 95% CI [1.68; 7.97]). Although the evidence is limited, the available data suggest that GHP located in the cardia or arising in a dysplastic background gastric mucosa may represent higher-risk subsets. Immunohistochemical subtyping of dysplasia showed a progressive shift from a predominantly gastric phenotype in non-neoplastic GHP to a hybrid (gastric-intestinal) phenotype in dysplasia and adenocarcinoma. TP53 alterations and chromosomal instability were the most frequently reported molecular events. GHP present a significant neoplastic potential, particularly in the presence of additional clinicopathological risk factors. Lesion size, patient age and - above all - the status of the surrounding gastric mucosa should guide endoscopic management, pathological interpretation and surveillance strategies.
Marins LV, Murden R, Misdraji J
… +9 more, Reid MD, Tang L, Umetsu S, Wang HL, Wen KW, Yantiss RK, Nizam A, Gutman DA, Gonzalez RS
Histopathology
· 2026 Jun · PMID 42322148
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AIMS: Appendiceal goblet cell adenocarcinoma (GCA) is an uncommon malignancy that has been described under various names and grading schemes. The 5th Edition of the World Health Organization (WHO) Classification of Diges...AIMS: Appendiceal goblet cell adenocarcinoma (GCA) is an uncommon malignancy that has been described under various names and grading schemes. The 5th Edition of the World Health Organization (WHO) Classification of Digestive System Tumours provides a three-tiered system for grading these neoplasms, but the reproducibility of this classification scheme has not been studied. METHODS AND RESULTS: We scanned 58 H&E-stained slides from 20 GCA and circulated the whole-slide images among seven pathologists with interest in appendiceal pathology. They evaluated each slide for the presence of 15 histological patterns defined by the WHO as criteria for low-grade (n = 5) and high-grade (n = 10) GCA. Cases were also evaluated for the presence of extracellular mucin. Participants also reported the percentage of high-grade features in each whole slide image and each case. Interobserver variability was assessed statistically. All seven observers agreed on the WHO grade for four of the 20 cases (20%; one grade 1, three grade 3). Using Fleiss's kappa statistic, overall agreement for cases was fair at 0.29 (95% confidence interval [CI]: 0.14-0.44), and pairwise agreement between observers ranged from 0.00 to 0.82 (median = 0.13). Gwet's agreement coefficient ranged from 0.10 to 0.87 (median = 0.28), while overall agreement was 0.36 (95% CI: 0.17-0.54). There was significant variability with respect to assessing the presence of individual features. The best agreement was seen for extracellular mucin (neutral feature, κ = 0.43) and tumour sheets (high-grade feature, κ = 0.41), whereas the worst agreement was seen for mild architectural disarray/tubular fusion (low-grade feature, κ = 0.05) and necrosis (high-grade feature, κ = 0.07). CONCLUSIONS: We conclude that interobserver agreement for grading GCA using the three-tiered WHO 5th Edition classification system is fair at best. A validated two-tiered system (i.e. low- versus high-grade) may be more reproducible.
Shu Y, Zhang H, Lugli A
… +2 more, Simmer F, Nagtegaal ID
Histopathology
· 2026 Jun · PMID 42322147
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AIMS: Tumour budding (TB) has been recognized as an additional prognostic factor in the TNM (2017) and WHO (2019) classification systems. However, its prognostic impact in stages II and III colorectal cancer (CRC) remain...AIMS: Tumour budding (TB) has been recognized as an additional prognostic factor in the TNM (2017) and WHO (2019) classification systems. However, its prognostic impact in stages II and III colorectal cancer (CRC) remains inconsistently defined. This study aims to systematically evaluate the prognostic value of high-grade TB in stage II-III CRC. METHODS AND RESULTS: A systematic search of PubMed, Embase and Cochrane Library was conducted to identify studies reporting the association between high-grade TB and survival outcomes in stage II-III CRC. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were calculated using random-effects models. A total of 43 studies involving 17,831 patients were included. Univariable analysis showed that high-grade TB was significantly associated with worse DFS (HR 2.53, 95% CI 2.14-3.00), OS (HR 2.40, 95% CI 1.69-3.42) and CSS (HR 3.37, 95% CI 2.19-5.19). Multivariable analysis confirmed the independent prognostic value of high-grade TB for all three outcomes. Subgroup analysis stratified by TNM stage revealed that high-grade TB consistently predicted adverse outcomes in both stage II and stage III disease. CONCLUSIONS: This study confirms that high-grade TB is an independent prognostic factor in stage II-III CRC, consistently associated with worse DFS, OS and CSS. Incorporating TB into routine histopathological assessment may improve risk stratification and help identify high-risk patients, although its role in guiding therapeutic decisions requires further prospective validation.
Histopathology
· 2026 Jun · PMID 42318959
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AIMS: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), collectively termed PSC-IBD, have an increased risk of developing nonconventional and/or invisible colorectal dysplasia, part...AIMS: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), collectively termed PSC-IBD, have an increased risk of developing nonconventional and/or invisible colorectal dysplasia, particularly in the right/proximal colon, compared with patients with IBD alone. PSC-IBD patients are also more likely to exhibit abnormal DNA content (e.g. aneuploidy or an elevated 4N fraction) in the right/proximal colon, often preceding the detection of dysplasia. We therefore hypothesized that PSC-IBD patients who subsequently develop colorectal dysplasia may frequently demonstrate aberrant p53 immunohistochemical staining in histologically benign colon biopsies, particularly from the right/proximal colon, obtained prior to dysplasia detection. METHODS AND RESULTS: p53 immunohistochemistry was performed on 91 benign colon biopsies from 25 PSC-IBD patients obtained during the surveillance colonoscopy immediately preceding the procedure at which dysplasia was detected (mean interval: 20 months) (dysplasia group). As controls, p53 staining was performed on 76 benign colon biopsies from 20 IBD patients (10 PSC-IBD and 10 IBD-only) without a history of colorectal neoplasia. Nuclear staining intensity was graded as weak (1+), moderate (2+) or strong (3+), and staining extent was categorized as negative (<10%), patchy (10%-50%) or diffuse (>50%). Aberrant p53 overexpression was defined as strong nuclear staining in ≥10% of epithelial cells (patchy or diffuse). These results were compared with previously reported DNA flow cytometric findings from the same samples. Aberrant p53 overexpression was significantly more frequent in the dysplasia group than in controls (20% vs. 3% per biopsy, P < 0.001; 36% vs. 5% per patient, P = 0.027). Conversely, weak p53 staining was more common in controls (79% vs. 44% per biopsy, P < 0.001; 65% vs. 28% per patient, P = 0.013). Concordance between abnormal DNA content and aberrant p53 overexpression was 19% at the biopsy level and 42% at the patient level. Both aberrant p53 overexpression (72%) and abnormal DNA content (67%) were more frequently localized to the right/proximal colon. For predicting subsequent dysplasia, aberrant p53 overexpression demonstrated a sensitivity of 36%, specificity of 95%, positive predictive value (PPV) of 90% and negative predictive value (NPV) of 54%. Abnormal DNA content showed a sensitivity of 48%, specificity of 95%, PPV of 92% and NPV of 59%. When both markers were used together, sensitivity increased to 64%, with a specificity of 90%, PPV of 89% and NPV of 67%. CONCLUSIONS: PSC-IBD patients who subsequently develop colorectal dysplasia exhibit a significantly higher frequency of aberrant p53 overexpression in benign colon biopsies, particularly from the right/proximal colon, obtained prior to dysplasia detection compared with IBD patients who do not develop dysplasia. These findings suggest that aberrant p53 overexpression in benign colon biopsies may help identify PSC-IBD patients at increased risk for colorectal dysplasia.
Weeda YA, Issa SM, Halfwerk H
… +15 more, Botros M, de Boer OJ, Brosens LA, Doukas M, Kats-Ugurlu G, Ten Kate F, van der Laan J, van Lijnschoten I, Ooms AHAG, Oudijk L, van der Post RS, Raicu MG, Timmer B, van der Wel MJ, Meijer SL
Histopathology
· 2026 Jun · PMID 42318944
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INTRODUCTION: Evidence supporting the use of p53 immunohistochemistry (p53-IHC) in Barrett's oesophagus (BE) is largely based on selected series, limiting generalizability. This study evaluates p53-IHC in a nationwide, r...INTRODUCTION: Evidence supporting the use of p53 immunohistochemistry (p53-IHC) in Barrett's oesophagus (BE) is largely based on selected series, limiting generalizability. This study evaluates p53-IHC in a nationwide, real-world BE-cohort within a universal healthcare system, assessing concordance with referring hospitals, interobserver agreement (IOA) and its impact on routine diagnostic decisions. METHODS: Revision cases submitted to the Dutch Esophageal Pathology Panel (DEPP) were assessed by trained and experienced pathologists for haematoxylin and eosin (H&E)-based classification (Vienna classification), p53-IHC patterns (wild-type, overexpression, double clone, null mutation and equivocal) and combined H&E/p53-IHC review. Concordance between referring hospitals and the expert panel (Cohen's kappa) and IOA among panel pathologists (Fleiss' kappa) were assessed, along with the impact of p53-IHC on diagnostic reclassification. RESULTS: A total of 1,146 consecutive patient consultation cases (1,704 biopsy levels) were included, with a median of 12 DEPP pathologist assessments per biopsy. Overall concordance of p53 assessment between referring hospitals and the expert panel was moderate-to-substantial (κ = 0.61, 95% CI 0.58-0.64), with 24.2% of p53-IHC assessments reclassified. IOA among 13 pathologists assessing 316 endoscopic biopsies was substantial (κ = 0.65, 95% CI 0.61-0.69). Ancillary p53-IHC influenced pathologists' decisions across biopsy levels. For non-dysplastic (NDBE) biopsies, aberrant p53-IHC prompted reclassification to indefinite for dysplasia (IND, 9.2%) or low-grade dysplasia (LGD, 4.8%). For IND biopsies, p53-IHC shifted diagnoses toward NDBE (17.0%) or LGD (37.1%). CONCLUSION/DISCUSSION: p53-IHC interpretation is reliable, reproducible and clinically meaningful in BE diagnostics when standardized criteria are applied. These findings support broader use of p53-IHC in routine practice and incorporation of assessment criteria into guidelines.
Grosse C, Grosse A, Noack P
… +6 more, Preuss CI, Schwarz HK, Schneeweiss B, Gitter T, Schrenk P, Langer R
Histopathology
· 2026 Jun · PMID 42315983
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AIMS: Short-term preoperative endocrine therapy (ET) is increasingly used in oestrogen receptor (ER)-positive, HER2-negative breast cancer as a functional test of endocrine sensitivity. We aimed to characterise histomorp...AIMS: Short-term preoperative endocrine therapy (ET) is increasingly used in oestrogen receptor (ER)-positive, HER2-negative breast cancer as a functional test of endocrine sensitivity. We aimed to characterise histomorphological and immunophenotypic changes following preoperative ET and to identify predictors of endocrine response, defined as post-treatment Ki67 ≤ 10%. METHODS AND RESULTS: In this retrospective single-centre study, 180 patients treated with short-course preoperative ET (median duration 29 days) were compared with 151 patients undergoing primary surgery without ET. Paired biopsy and resection specimens were assessed for histological features, stromal proportion, stromal tumour-infiltrating lymphocytes (strTILs) and expression of ER, progesterone receptor (PR), HER2 and Ki67. Genomic risk was determined using the MammaPrint assay. Preoperative ET was associated with a significant reduction in tumour proliferation, with 73.9% of cases showing post-treatment Ki67 ≤ 10% compared with none in controls (P < 0.001). Histological grade decreased in 36.7% of ET-treated tumours versus 7.9% of controls (P < 0.001), predominantly reflecting reduced mitotic activity. ER expression remained stable, whereas PR expression decreased more frequently following ET (P < 0.001) and was independently associated with Ki67-defined response. HER2-low status was more frequently observed after ET (P < 0.001), but HER2 expression and microenvironmental parameters, including strTILs, were not associated with response. High genomic risk was independently associated with a lower likelihood of achieving post-treatment Ki67 ≤ 10% (P < 0.001). CONCLUSIONS: Short-course preoperative ET induces rapid and reproducible morphological and immunophenotypic changes in ER-positive, HER2-negative breast cancer. Ki67-defined response is associated with genomic risk and PR expression, whereas microenvironmental features appear to have limited predictive value.
Zhang Y, Zheng K, Tang Y
… +9 more, Yang K, Chen Z, Li Y, Zhang Y, Zhang G, Qiu L, Peng R, Liu X, Jiang L
Histopathology
· 2026 Jun · PMID 42315496
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OBJECTIVES: TP53 mutations, prevalent in 50%-70% of lung adenocarcinoma (LUAD), are associated with poor prognosis and therapeutic resistance. This study aimed to evaluate the diagnostic accuracy of p53 immunohistochemis...OBJECTIVES: TP53 mutations, prevalent in 50%-70% of lung adenocarcinoma (LUAD), are associated with poor prognosis and therapeutic resistance. This study aimed to evaluate the diagnostic accuracy of p53 immunohistochemistry (IHC) as a rapid and cost-effective alternative to next-generation sequencing (NGS) for TP53 mutation detection in LUAD patients. MATERIALS AND METHODS: A multicentre cohort of 221 LUAD patients was analysed. TP53 mutation status was determined via NGS and compared with p53 IHC staining patterns. A multiparametric p53 IHC assessment system was established, integrating staining intensity, spatial distribution and subcellular localization data. RESULTS: p53 IHC demonstrated high concordance with TP53 mutation status, achieving an overall accuracy of 91.40% (κ = 0.83). A novel ≥40% cut-off for 3+ nuclear staining predicted TP53 mutations with 94.81% accuracy (κ = 0.91). Complete p53 absence or cytoplasmic expression strongly correlated with truncating mutations (92.31% concordance), while missense mutations were linked to nuclear overexpression. TP53-mutant tumours exhibited distinct molecular profiles, including increased frequencies of RB1, MET, ERBB2, MYC and PTCH1 mutations, alongside reduced STK11 comutations. Kaplan-Meier survival analysis demonstrated that p53 IHC serves as a reliable surrogate marker for TP53 mutation status, offering significant prognostic value in LUAD patients. CONCLUSION: p53 IHC, particularly using a ≥40% cut-off at 3+ intensity, is an accurate and accessible surrogate for TP53 mutation detection in LUAD patients. This method facilitates rapid molecular stratification, optimal resource utilization and informed prognostic and therapeutic decision-making in routine pathology practice.
Lin LH, Odintsov I, Towery EA
… +4 more, Quade BJ, Nucci MR, Ordulu Z, Kolin DL
Histopathology
· 2026 Jun · PMID 42312930
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AIMS: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome characterized by germline TP53 mutations and increased risk of various malignancies. While rare uterine leiomyosarcomas (LMS) have been reported, other...AIMS: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome characterized by germline TP53 mutations and increased risk of various malignancies. While rare uterine leiomyosarcomas (LMS) have been reported, other uterine smooth muscle tumours (uSMT) have not been studied in this context. METHODS AND RESULTS: We describe clinicopathological features of uSMT from 10 LFS patients (four uSMT of uncertain malignant potential (STUMP), two leiomyomas with bizarre nuclei [LMBN] and four with only conventional leiomyomas [LM]) and next-generation sequencing results of eight tumours. Among six p53-aberrant tumours (four STUMPs, one LMBN, one LM) by immunohistochemistry (IHC), three STUMPs had biallelic TP53 inactivation and three uSMT (two STUMPs, one LMBN) had loss of fumarate hydratase (FH) by IHC with inactivating FH variants. One patient with a p53-aberrant, FH-deficient LMBN had a concurrent p53-wild-type, FH-proficient LM with a novel ACTG2::BRAF fusion. Two STUMPs with TP53 biallelic inactivation and intact FH had additional alterations, one with LMS features, including chromosome instability, ATRX, and RB1 alterations; the other with del(22q), CYLD, and ELOC mutations. The remaining two sequenced LM showed MED12 alterations, one with del(22q). No recurrences were seen in nine patients with follow-up and no LMS were diagnosed. CONCLUSION: uSMTs exhibit a broad morphologic spectrum in LFS, and multiple molecular alterations may drive tumorigenesis, including MED12, FH, TP53, RB1, ATRX, and a novel ACTG2::BRAF fusion. Although some may be incidental, uSMT in this setting appears enriched for atypical morphology, FH deficiency, and aberrant p53 expression, suggesting an interplay between p53 and FH pathways in tumorigenesis.
Cheng A, Barnes P, Rayson D
… +2 more, Liwski C, Bethune G
Histopathology
· 2026 Jun · PMID 42266109
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AIMS: The pathological assessment of breast cancer resection specimens with neoadjuvant therapy (NAT) offers invaluable information for prognosis and further management. At times, these cases are difficult to pathologica...AIMS: The pathological assessment of breast cancer resection specimens with neoadjuvant therapy (NAT) offers invaluable information for prognosis and further management. At times, these cases are difficult to pathologically evaluate, at least partly due to tumour bed obscuration after NAT. This study aimed to compare time and resource utilization by surgical pathology laboratories when handling breast specimens treated with NAT against those without NAT. We secondarily aimed to identify features associated with tumour bed identifiability at gross assessment. METHODS AND RESULTS: In this retrospective, single-institution study, we identified 241 breast resection specimens with systemic NAT between 2019 and 2025. A 1:1 non-NAT control group was randomly selected. The NAT cohort had a higher median number of tissue blocks (20.0 versus 13.0, P < 0.001), as well as larger proportions requiring gross resampling (23.7% versus 7.1%, P < 0.001) and pathologist review (16.2% versus 4.6%, P < 0.001) compared with the control. The NAT cohort had a longer median pathology report turnaround time (17.0 days versus 15.0 days, P < 0.001). In NAT cases, pretreatment clinical stage was associated with macroscopic identifiability of the tumour bed. CONCLUSIONS: Breast cancer resection specimens with NAT required significantly more time and laboratory resources than similar specimens without NAT. As NAT becomes more frequent across breast and other cancer types, pathological assessment of the excisional specimens from these patients is expected to become more challenging and time-consuming. By recognizing these trends early, healthcare systems can plan and allocate resources accordingly.
Histopathology
· 2026 Jun · PMID 42266100
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OBJECTIVE: This study aimed to develop a reproducible immunohistochemistry method for formalin-fixed, paraffin-embedded (FFPE) muscle sections and to assess its diagnostic utility for idiopathic inflammatory myopathies (...OBJECTIVE: This study aimed to develop a reproducible immunohistochemistry method for formalin-fixed, paraffin-embedded (FFPE) muscle sections and to assess its diagnostic utility for idiopathic inflammatory myopathies (IIM) in settings where snap-frozen muscle biopsy is unavailable. METHODS: Twenty cases were analysed: dermatomyositis (n = 5), inclusion body myositis (n = 2), immune-mediated necrotizing myopathy (n = 5), overlap myositis (n = 1), unspecified myopathy (n = 3), mitochondrial myopathy (n = 1), LGMD R2 dysferlin-related muscular dystrophy (n = 1), facioscapulohumeral muscular dystrophy (n = 1), and neurogenic muscle change (n = 1). Immunohistochemistry was performed on 3-μm FFPE muscle sections using heat-induced antigen retrieval with citrate/EDTA buffer and overnight incubation at 4°C with antibodies against MHC-I, MHC-II, MAC, MxA, and p62. Frozen sections were analysed in parallel for comparison. RESULTS: Comparable staining intensities and patterns for MHC-II, MxA, and p62 were achieved in FFPE muscle sections. Although discrepancies between frozen and FFPE sections occurred in eight cases, each involving a single marker, no statistically significant differences in immunohistochemical results were observed for MHC-II (P = 0.4795), MxA (P = 0.4795), and p62 (P = 0.6171). Concordance between methods was high, reaching 90% for MHC-II and MxA and 80% for p62. These isolated discrepancies may reflect variability in antigen expression associated with the segmental and patchy involvement characteristic of IIM. However, MHC-I and MAC staining were unsuccessful in FFPE sections. CONCLUSIONS: Successful immunolabelling of MHC-II, MxA, and p62 was achieved in FFPE muscle sections. These findings indicate that several diagnostically informative markers for IIM can be reliably assessed in FFPE muscle, providing a practical diagnostic option in resource-constrained settings.