Histopathology最新文献

The resurgence of measles, syphilis, and HIV presents a significant threat to global health, especially in the wake of the COVID-19 pandemic. These three infections involve lymph nodes and have unique pathologic findings in lymph nodes. We explore the pathological and clinical characteristics of these infections, focusing on their involvement of lymph nodes and their pathologic diagnosis in lymph node specimens. For HIV, lymph nodes are sites of viral replication and reservoirs, and the disease demonstrates multiple patterns within lymph nodes. The recent increase in measles, due in part to declining vaccination rates, signals the need for pathologists to be able to identify the characteristic Warthin-Finkeldey cells present in lymph node specimens. Syphilis, a reemerging sexually transmitted infection, often presents with lymphadenopathy and can mimic other conditions, complicating clinical diagnosis. By revisiting well-established findings and presenting new insights into the histopathological changes within lymphoid tissues, this review provides essential knowledge for pathologists and clinicians to improve diagnostic accuracy and treatment outcomes.

Aims: Atypical ductal hyperplasia and flat epithelial atypia (FEA) have defined diagnostic criteria, yet there is variation in the interpretation of these criteria, particularly when the atypia is present in a background of columnar cell lesions (CCLs). This study focuses upon cases which are especially challenging or difficult to classify reproducibly according to existing criteria.

Methods and results: Thirteen breast pathology experts were asked to classify 10 challenging cases with CLLs as atypical or non-atypical. Interobserver agreement was calculated. After two consensus meetings, which explored the morphological features underlying the decision, the cases were reassessed. Finally, a photomontage was compiled as a visual aid for practising pathologists representing a range of straightforward cases and others where subjective interpretation causes disagreement within current diagnostic criteria. Overall interobserver agreement and pairwise pathologist agreement coefficients were both in the fair range (κ = 0.22 and κ = 0.3-0.4, respectively). This improved to moderate or substantial agreement (κ = 0.6-0.8) after two consensus meetings. The most controversial cases were atypical cases that lacked the regular rounded nuclei of FEA, and non-atypical cases that had florid architectural changes bordering on architectural atypia.

Conclusion: Among expert breast pathologists, interobserver agreement in the diagnosis of atypia in CCLs was higher in cases with classical features of FEA. Consensus was difficult to achieve if nuclear or architectural atypia fell outside the classical definition of FEA, suggesting that this category does not encompass the range of low-grade cytological atypia in CLLs. This study provides rationale for expanding the definition of atypia in CCLs other than FEA.

Aims: Ossifying fibromyxoid tumour is a rare mesenchymal neoplasm predominantly affecting adults characterised by a multinodular growth pattern and the presence of a fibrous pseudocapsule with areas of ossification. Prompted by the recognition of a non-ossifying ossifying fibromyxoid tumour with lipomatous differentiation which caused diagnostic difficulty, we sought to further explore cases of ossifying fibromyxoid tumour with non-osseous heterologous elements.

Methods and results: A search of our institutional and consultation archives revealed three additional cases that demonstrated lipomatous components and two cases with cartilaginous differentiation. RNA-sequencing revealed fusions involving PHF1 (n = 4) or EPC1 (n = 1) in all (five of five) cases tested, including EPC1::PHC1 and JAZF1::PHF1 fusions, which have not been reported before in ossifying fibromyxoid tumour.

Conclusion: These six cases expand the histomorphological spectrum of ossifying fibromyxoid tumour, introducing lipomatous differentiation as a hitherto undocumented feature. Awareness of these rare variants will ensure appropriate diagnosis and clinical management.

Aims: The diagnosis of lymphoplasmacytic lymphoma (LPL) in the bone marrow (BM) is challenged by aberrant phenotypes and by overlapping histological features with marginal zone lymphoma (MZL). To address these issues, we (i) assessed LPL immunophenotype on a large series of BM samples, (ii) drew possible correlations between LPL phenotype and clinical/molecular data and (iii) investigated the role of new phenotypical markers in the differential diagnosis between LPL and MZL.

Materials and methods: The study retrospectively considered 81 clinically annotated LPL diagnosed at Padua University Hospital (Padua, Italy) during a 5-year period. BM findings were correlated with clinical laboratory findings and with MYD88 and CXCR4 mutational status. The obtained results were compared with a series of 77 MZL in the BM, including 46 splenic MZL (SMZL), 14 nodal MZL (NMZL) and 17 extra-nodal MZL (EMZL).

Results: The LPL cohort included 52 males and 29 females (median age at diagnosis = 71 years). Aberrant CD10 and CD5 positivity was documented in 3 of 81 (3.7%) and 13 of 81 (16.1%) cases, respectively. CD23 positivity occurred in 56 of 81 (69.1%) cases, being usually partial/focal. CD23 expression did not correlate with any specific clinical-pathological parameter. Comparison with SMZL, NMZL and EMZL highlighted less frequent splenomegaly, higher serum paraprotein, higher CD23 expression and fewer follicular dendritic cell networks in LPL. A combined clinical-pathological score supported the differential diagnosis between LPL and MZL of any type. The highest diagnostic yield was obtained for the differential diagnosis between LPL and SMZL.

Conclusions: Partial positivity for CD23 is a common feature of LPL in the BM. Together with other clinical and histological parameters, CD23 expression supports the differential diagnosis between LPL and MZL.

Molecular applications have limited use in breast cancer compared to other cancer types. In recent years, with an improving appreciation of the molecular genetics of breast cancer and innovative novel targeted and immune-mediated therapeutics, opportunities have arisen for more biomarker analysis and molecular applications in the diagnosis and treatment of both locally advanced and metastatic breast cancers. In hormone receptor-positive, HER2-negative breast cancers, a growing number of revolutionized personalized therapies are in clinical use or on trials, such as CDK4/6 inhibitors and immune checkpoint inhibitors in adjuvant and neoadjuvant settings, and PIK3CA inhibitors in metastatic disease. In this review, we focus on biomarkers associated with those new therapeutic targets and molecular applications for genetic alterations associated with drug resistance or interaction from a pathology perspective for selecting and optimizing breast cancer treatment.

Aims: The diagnosis of intranodal thyroid inclusions (ITIs) is controversial. We aim to investigate their clinicopathologic features and utilize immunohistochemistry (IHC) to support the diagnosis.

Methods and results: Forty-one cases of incidentally found ITIs between 2019 and 2023 were categorized into three groups, namely, Group A: thyroidectomy due to papillary thyroid carcinoma (PTC) with regional lymph node dissection (n = 33), Group B: thyroidectomy due to benign thyroid disease with incidental perithyroid lymph node sampling (n = 4), and Group C: surgery due to other head and neck cancers with lateral neck lymph node dissection (n = 4). The overall incidence of ITIs was 4.17% (33/792) in Group A and 0.76% (4/524) in Group C. All ITIs sufficient for study were negative for BRAF VE1 IHC. HBME-1 and galectin-3 IHC were also negative in all analysed cases. Although various degrees of nuclear changes were present in ITIs, classical PTC nuclear features, i.e. pseudoinclusions, nuclear grooves, and chromatin alterations, were less commonly seen (0%, 29.3%, and 51.2%, respectively) than in metastatic PTC (90%, 95%, and 95%, respectively) (all P < 0.001). Interestingly, 77.3% (17/22) of cases with lymph node metastasis in Group A had coexistence of ITIs and metastasis in the same lymph node. During follow-up, two cases in Group A had PTC recurrence without accompanying ITIs, while none in Group B or C had recurrent thyroid lesions.

Conclusion: We propose key diagnostic features for ITIs incorporating morphology and BRAF VE1, HBME-1, and galectin-3 IHC. The distinction between ITIs and metastatic PTC can be clinically relevant.

Aims: Oral epithelial dysplasia (OED) carries a risk of malignant transformation to oral squamous cell carcinoma. Clinical risk stratification for these patients is challenging, and reliant upon histological grading. The World Health Organisation (WHO) grading system is the current gold standard, although the binary system, two- and six-point prognostic models have also been proposed. This study assesses the interobserver agreement and malignant transformation outcomes for these four grading systems.

Methods and results: Up to 5 years of outcome data were collected for this retrospective cohort of 137 patients. Archived slides were reviewed by three pathologists, and grades for the WHO, binary, two- and six-point systems were assigned. Interobserver agreement was assessed with Light's kappa coefficient. Kaplan-Meier and Cox regression survival analyses were used to assess the correlation of each grading system with malignant transformation. The WHO, binary, two- and six-point systems had kappa coefficients of 0.42, 0.31, 0.17 and 0.41, respectively. All grading systems stratified lesions by malignant transformation risk, except the two-point model. Moderate OED (WHO) did not show an increased risk of malignant transformation, while severe OED had a hazard ratio (HR) of 13.7 (P = 0.02). The high-risk category for the binary and six-point systems had HRs of 4.67 (P = 0.03) and 5.28 (P = 0.03), respectively.

Conclusions: The interobserver agreement of the WHO, binary and six-point systems is comparable. The six-point and binary systems provided the most useful risk stratification. This study highlights the potential value of the six-point prognostic model for OED grading, which has comparable performance with the current gold standard.