Histopathology最新文献

Aims: Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes. However, the applicability of molecular classification is unclear in rare but aggressive histotypes of EC, e.g. de-differentiated and undifferentiated endometrial cancers (DD/UDEC). Here, we aim to assembled a cohort of DD/UDEC from a single institution and analysed the prognostic significance of ProMisE molecular subtypes and the expression of SWItch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complex members, previously implicated in the pathogenesis of DD/UDEC.

Methods and results: We accrued 88 DD/UDEC cases, assessed POLE status by Sanger sequencing and performed immunohistochemistry for p53, mismatch repair and SWI/SNF proteins on the tissue microarrays assembled. Assignment of molecular subtypes was possible in 80 tumours; POLE sequencing failed in the remaining eight cases. There were 12 (15%) POLEmut, 44 (55%) MMRd, 14 (17.5%) p53abn and 10 (12.5%) NSMP DD/UDEC. POLEmut DD/UDECs had excellent outcomes, but the other three molecular subtypes all had poor outcomes, with no significant differences among them. The loss of one or more SWI/SNF proteins [AT-rich interactive domain-containing protein 1A (ARID1A), ARID1B, SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), SMARCA2], observed in 66% (55 of 83) cases, was not of prognostic significance.

Conclusions: These results indicate that all molecular subtypes of DD/UDEC except POLEmut behave in an aggressive fashion. Further study is needed to determine whether these molecular alterations can be targeted with adjuvant therapy, in order to improve outcomes of patients with DD/UDEC.

Aims: Threonine and tyrosine kinase (TTK) is up-regulated in triple-negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment-naïve pre-treatment cores and paired pre- and post-NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.

Methods and results: Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut-off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post-NACT in a paired cohort. Conversely, decreased TTK protein expression pre-NACT was correlated with improved overall survival.

Conclusions: High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1-deficient cancer cells.

Aims: Our study aimed to further confirm the clinical significance of the tumour budding activity and cell nest size-based (TBNS) grading scheme in cervical squamous cell carcinomas (SCC).

Methods and results: We applied the TBNS system to assess the prognostic value in an institutional cohort of well-annotated cervical SCC consisting of 312 consecutive cases with surgical resection, no neoadjuvant chemotherapy and higher than stage pT1a. We found that high budding activity, single cell and TBNS grade 3 were more frequently associated with a decreased overall survival (OS) time and disease-free survival (DFS) time (P < 0.001) and several other clinicopathological factors, including lymphovascular space invasion, lymph node metastasis, advanced Federation of Gynecology and Obstetrics (FIGO) stage and deep invasion of the cervical wall (> 2/3) (P < 0.05). On multivariate analysis, TBNS grade 3 was an adverse indicator for OS and DFS independently of age, invasion of the cervical wall and FIGO stage (P < 0.05). By comparison, the conventional three-tiered grading system was not associated with OS and DFS in cervical SCC (P > 0.05).

Conclusions: Our study further confirms that the TBNS grading scheme is robust in prognostic assessment in cervical SCC that outperforms the conventional three-tiered grading system. It is applicable to add TBNS grade into routine diagnostic practice.

Aims: The hepatic perivascular epithelioid cell tumour (PEComa), including angiomyolipoma, exhibits diverse morphology and clinical behaviour; however, its prognostic features remain undefined. This study aimed to investigate its histological features and prognostic factors.

Methods and results: In total, 132 patients were included. Clinical data and histopathological slides were assessed along with the p53 and Ki-67 immunohistochemistry. Targeted next-generation sequencing was performed in three cases. Based on the histologic subtypes, 7 (10%), 36 (51%), 13 (18%), and 15 (21%) patients were classified as inflammatory angiomyolipoma, conventional angiomyolipoma, epithelioid angiomyolipoma, and PEComa not otherwise specified (NOS), respectively, among 71 patients who underwent surgical resection. We proposed the risk prediction criteria after defining primary tumour size ≥7 cm, infiltrative border, mitotic rate >1/10 mm², necrosis, vascular invasion, and PEComa NOS as worrisome features, as follows: high-risk: ≥3 worrisome features; intermediate-risk: 1-2 features; low-risk: none of the features. Applying these criteria, 4 (6%), 31 (44%), and 36 (51%) patients were classified into high-, intermediate-, and low-risk groups, respectively. One patient each in the high-risk (25%) and intermediate-risk (3%) groups developed peritoneal metastases and intrahepatic recurrence, respectively, whereas none in the low-risk group showed disease progression. A literature review of clinically malignant hepatic PEComa family tumours was conducted, and upon application of our criteria, 62% (16/26) of the patients were classified as high-risk and 35% (9/26) as intermediate- or high-risk.

Conclusion: Our risk prediction criteria can effectively predict the clinical outcomes in primary hepatic PEComa.

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.