Histopathology最新文献

Testicular biopsies are often performed in men with unexplained infertility and azoospermia to ascertain the status of spermatogenesis. Testicular pathology is one of the primary causes of male infertility. However, infrequent exposure among pathologists and a lack of uniform reporting terminology pose diagnostic challenges and variability in interpretation. These issues may lead to inaccurate evaluations, potentially impacting clinical management. The goal of this review is to offer a straightforward, practical approach to interpreting testicular biopsies, thereby assisting pathologists who handle such rare samples. Accurate interpretation of testicular biopsy for infertility plays a crucial role in management of infertile men. In this review, we present a practical guide for reporting testicular biopsies.

Background and aims: Lobular carcinoma (LC) of the breast exhibits diverse morphology and clinical behaviour. The pleomorphic variant (pLC) displays distinct cytonuclear features and aggressiveness compared to the classic variant (cLC). However, diagnosing pLC remains subjective. This study aims to refine LC's cytonuclear features, focusing on pLC.

Methods: Whole slide images of 59 LCs, including both in situ (LCIS) and invasive (ILC) lesions, were analysed. Nuclear measurements, including nuclear size and variability, were scored using QuPath image analysis software. For comparison, selected features were scored in normal cells (n = 10) and pleomorphism score-matched invasive breast carcinoma (IBC) of NST type (n = 33). Additional visual assessment of the pleomorphic ILC (pILC) cohort (n = 90) was conducted for cytomorphological features characterisation.

Results: pILC demonstrated larger nuclear area and higher nuclear variability with abundance of cytoplasm than cILC. Compared to lymphocytes, pILC demonstrated a median area ranging from 2.7 to 4.7 times larger. Cut-off values for differentiating pILC from other ILC subtypes included median nuclear area > 48.2 μm² and interquartile range (IQR) > 19.4, nuclear perimeter median > 25.2 μm and IQR > 5.3 and maximum diameter > 9.1 μm and IQR > 2.2. Multivariable logistic regression confirmed these parameters as independent predictors of pILC, with the maximum diameter being the most significant (P < 0.001). Visual assessment recognised two pILC subtypes: apocrine and non-apocrine. Apocrine variant showed nuclear roundness, pale vesicular chromatin patterns and prominent nucleoli, while non-apocrine variant exhibited greater nuclear size and shape variation.

Conclusions: Objective nuclear measurements, combined with cytoplasmic and architectural features, provide a robust framework for diagnosing LC subtypes, improving diagnostic accuracy and reproducibility.

Aim: The term 'intramucosal carcinoma' in the colorectum is controversial when used as a synonym for high-grade dysplasia. However, setting clear definitions for this diagnosis (i.e. unequivocal infiltrative growth in the lamina propria, which might be most easily recognized in cases with overt poor differentiation or formation of signet ring cells or tumour budding) allow us to investigate its relevance.

Methods and results: We reviewed cases from our archive (1990-2024) and selected 14 true intramucosal carcinomas using our strict histological criteria, excluding high-grade dysplasia and invasive carcinomas. These occur primarily in conventional adenomas and are frequently associated with microsatellite instability (50%). Our study shows a low estimated incidence of intramucosal carcinoma (0.01%) in population screening and highlights the low lymph node risk and the good outcome of patients with intramucosal carcinoma.

Conclusion: The rare diagnosis of intramucosal colorectal carcinoma aids in identifying patients at increased colorectal cancer risk, notably those with hereditary syndromes. Standardizing this diagnosis is critical to prevent overdiagnosis and unnecessary treatment.

The classification and understanding of vascular anomalies have significantly evolved since the initial framework by Mulliken and Glowacki, distinguishing between vascular tumours and malformations. Recent advancements in molecular diagnostics have enhanced the accuracy of identifying and managing these complex lesions. This review provides an updated analysis of select vascular anomalies, focusing on Kaposiform hemangioendothelioma (KHE), Kaposiform lymphangiomatosis (KLA), and intramuscular fast-flow vascular anomalies. It highlights the similarities and differences between these lesions, their histopathological features, and molecular underpinnings, including key genetic mutations in the RAS/PI3K/mTOR signalling pathways. Moreover, the role of PIK3CA mutations in vascular overgrowth syndromes is explored, alongside emerging targeted therapies, such as PI3K and MEK inhibitors, that promise improved outcomes for patients with these challenging conditions. The integration of histology, molecular diagnostics, and multidisciplinary care remains critical for the accurate diagnosis and optimal treatment of vascular anomalies in the era of precision medicine.

Aims: Metaplastic breast carcinoma (MBC) is a heterogeneous group of invasive breast carcinoma with squamous, spindle cell, or mesenchymal elements. It may be monophasic or biphasic, and often coexists with invasive breast carcinoma of no special type (IBC-NST). Currently, there are no standardized guidelines for reporting MBC, and a diagnostic threshold for the metaplastic component is not established by the WHO classification.

Methods and results: A survey conducted from April-July 2023 gathered responses from 44 pathologists worldwide. Most respondents were academic breast pathologists, and attended weekly breast tumour boards. The criteria for diagnosing MBC were highly varied, with cutoffs ranging from any/<10% to >90% metaplastic component. Although 90% was the most common threshold used, only 25% of respondents applied it. Pathologists generally preferred diagnosing invasive carcinoma with mixed features when the metaplastic component was ≤50% and MBC when the metaplastic component >50%. Most pathologists reported both the type and percentage of metaplastic component. In all, 43% reported core biopsy and resection specimen with different approaches. Diagnostic guidelines reportedly used (if any) were highly varied.

Conclusion: The study underscores the need for standardized guidelines for MBC. Without clear and established diagnostic criteria, current data on MBC remains inconsistent and hinders further research into the clinical significance and prognostic implications of the metaplastic component.

Aims: Primary cutaneous marginal zone lymphoma (PCMZL) is considered a lymphoproliferative disorder (International Consensus Classification, ICC) or an overt lymphoma (WHO-HAEM5). Seeking evidence for a reactive process or true lymphoma, we retrieved recurrent PCMZLs from the French Study Group of Cutaneous Lymphoma (GFELC) database.

Methods: Histology, phenotype (light-chain restriction, immunoglobulin, and immune-receptor translocation-associated protein-1 [IRTA1] expression) and B-cell clonality at diagnosis and recurrence were compared according to recurrence site (local, locoregional, or distant) and outcomes.

Results: Initial lesions of the 61 patients (mean age 52) were mostly isolated on the trunk (48%) and classified T1 (70%). Times to first recurrence for local, locoregional, and distant recurrences, were 20, 29, and 37 months, respectively. Light-chain restriction type did not differ significantly between local/locoregional recurrences and distal recurrences (P = 0.06; n = 60). The same B-cell clones were identified for 23/42 local/locoregional recurrences, while 5/19 distant recurrences showed different clonal profiles (P = 0.0003). No tumour expressed IRTA1. Fifty-eight tumours were heavy-chain (IgG/IgG4) class-switched PCMZLs and 3 IgM+/IgD- PCMZLs. All IgM+ tumours underwent either transformation (skin or brain) into diffuse large B-cell lymphomas (DLBCLs) and extracutaneous spreading.

Conclusion: As suggested by WHO-HAEM5, immunoglobulin phenotype assessment (IgM alongside IgD) appears to be a possible valuable tool in the initial diagnosis of PCMZL to differentiate between the indolent class-switched PCMZL (IgM-negative) and IgM+ (IgD-) PCMZL, which has an uncertain prognosis. The variation in B-cell rearrangements and light chain restriction observed in distant recurrences of PCMZL may suggest different antigen-driven stimulation processes.

Aims: Esophageal submucosal gland duct adenoma is an extremely rare benign tumour, with only a few reported cases. We conducted the largest single-centre clinical study of esophageal submucosal gland duct adenoma, examining its molecular mechanisms and clinicopathological features.

Methods and results: Between 2018 and 2023, seven cases of esophageal submucosal gland duct adenoma were identified at a tertiary medical centre; two were female and five were male, aged between 51 and 75 years (mean = 63.8 years). Comprehensive evaluations of clinicopathological, immunohistochemical and molecular characteristics were conducted. Histologically, tumours showed papillotubular and cystic patterns lined with double layers of cells arranged in ducts, papillary folds and microcysts. The inner luminal tall columnar cells had eosinophilic cytoplasm and did not show mucin production and the basal cells showed myoepithelial differentiation. Immunohistochemically, inner luminal  layer cells were positive for CK7, CK19 and CK5/6 and outer basal layer cells were positive for SMA and P40. Both layers were negative for CK20, CDX2, MUC5AC, MUC6, MUC2, GCDFP15 and Alcian blue-periodic acid-Schiff (AB-PAS). Genomic analyses revealed the presence of BRAF V600E mutations in five of seven tumours (71.43%).

Conclusions: This study delineates a distinct subtype of benign adenoma arising from the esophageal submucosal gland duct, characterised by multiple lobulated cystic proliferation of benign epithelial layers within the submucosa. BRAF V600E mutations were present, similar to in sialadenoma papilliferum. We determined the genetic mutation present in esophageal submucosal gland duct adenoma, providing further evidence that it is an esophageal counterpart of minor salivary gland tumours.

Aims: Although molecular tests developed for a growing list of oncogenic alterations have significantly aided in the classification of head and neck carcinomas, tumours in which prototypical histologic and immunophenotypic features are lacking or only partially developed continue to pose diagnostic challenges. Searching for known diagnostic and therapeutic targets by clinical next-generation sequencing (NGS) assays can often lead to new discoveries.

Methods and results: We present our institutional experience in applying targeted RNA NGS in 36 head and neck carcinomas that were morphologically difficult to classify between 2016 and 2023. The patients ranged in age from 5 to 83 years (median, 64), with the majority of tumors occurring in the major salivary glands and the sinonasal tract. Overall, seven (19%) cases showed unusual gene rearrangements, including five novel alterations: MON2::STAT6 in a hard palate adenocarcinoma with mucinous features, POC5::RAF1 in apocrine intraductal carcinoma of the lacrimal gland, EWSR1::CDADC1 fusion in a basaloid carcinoma of the submandibular gland, NFATC2::NUTM2B in myoepithelial carcinoma, and NSD3::NCOA2 fusion in a peculiar high-grade carcinoma with a peritheliomatous growth pattern, and focal myogenic differentiation. Potential therapeutic actionability was identified in three cases (RAF1 and FGFR2 fusions).

Conclusion: These findings broaden the current spectrum of gene rearrangements in head and neck carcinomas and support the utility of clinical NGS in identifying unusual, actionable alterations in diagnostically challenging cases.

Background: Knowledge regarding adenocarcinoma of the rete testis (ACRT) is extremely limited due to its scarcity.

Methods and results: This study enrolled 18 patients with ACRT from multiple institutions. Clinicopathological and immunohistochemical features were investigated, together with a comprehensive review of 95 previously reported cases. One case was assessed using next-generation sequencing (NGS). The median age of the patient cohort was 54 years (range = 20-69 years), with the majority presenting with a testicular mass (13 of 18); predominantly right-sided (11 of 18). Six patients died within the second year following diagnosis. The morphology of ACRT spans a wide spectrum, including newly identified mucinous carcinoid-like features, with mucous cells floating in mucus and signet-ring cells. Notably, transition from a benign to a malignant rete epithelium was noted in 38.9% of cases (seven of 18). Immunohistochemically, tumour cells most frequently showed strong positivity for CK7 (12 of 16) and CK20 (10 of 17), with occasionally positivity for calretinin (three of 16), WT-1 (two of 17) and PAX-8 (two of 15). According to NGS in a single case, MET was amplified, leading to the patient benefiting from mesenchymal-epidermal transition factor (MET) inhibitors. Furthermore, MET amplification was assessed in 13 cases using fluorescence in-situ hybridisation and detected in two cases (15.4%). No significant correlation between MET amplification and mesenchymal-epidermal transition factor (MET) levels was observed in the cases studied.

Conclusions: Primary ACRT is a rare malignant tumour which poses a diagnostic challenge, and is associated with poor prognosis. Cases of ACRT with MET amplification might represent promising candidates for the treatment with MET inhibitors.