Diagnostic Pathology最新文献

DNA mismatch repair (MMR) is critical for maintaining genome integrity through correction of single-base mismatches and insertion-deletion loops arising from DNA replication. Heterozygous germline alteration of MMR genes (MSH2, MSH6, MLH1, PMS2) cause autosomal dominant Lynch syndrome (LS), most commonly manifesting as colonic or endometrial cancers, although brain, ovarian, and other organ systems may be involved. Neoplasia in LS usually arises after the age of 30 years. Constitutional mismatch repair deficiency (CMMRD) is inherited in an autosomal recessive manner due to biallelic germline alteration in one of the four MMR genes. Individuals with CMMRD typically develop cancer in the first decade of life, although some may present during the second decade. We present a series of five children who developed cancer prior to the age of 20 years (range: 2-12 years) with malignancies including colonic adenocarcinoma (N = 1), T-lymphoblastic lymphoma (N = 3), and high-grade glioma (N = 4). Two patients with MSH6 alterations developed a constellation of three primary tumors: high-grade glioma, T-lymphoblastic lymphoma, and colonic neoplasia including colonic adenocarcinoma in one patient and a tubular adenoma in the other.

Background: Breast cancer is a leading global health concern, with lymph node metastasis (LNM) being a key prognostic factor affecting patient outcomes. Glycosylation-related enzymes such as calcium-activated nucleotidase 1 (CANT1) and Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) have been implicated in tumour progression, yet their roles in breast cancer, particularly invasive ductal carcinoma (IDC), are not well defined. This study investigates the immunohistochemical expression and correlation of CANT1 and B3GNT3 in IDC and their potential role in predicting LNM and clinical outcomes.

Materials and methods: Slides from paraffin blocks of 140 IDC cases and 108 corresponding metastatic axillary lymph nodes were stained with CANT1 and B3GNT3 antibodies. Associations between markers' immunoreactivity and clinicopathological variables were evaluated. Progression-free survival (PFS) was analysed using the Kaplan-Meier method. The prognostic significance of each variable was evaluated using both univariate and multivariate Cox proportional hazards regression analyses.

Results: High CANT1 and B3GNT3 expression was observed in 47.1% and 45.7% of cases, respectively. Both markers were significantly associated with tumour grade, tumour stage, Nottingham prognostic index, lymph node status, lymph node ratio, Her2 status, Ki-67 proliferative index and distant metastasis. A significant positive correlation was found between CANT1 and B3GNT3 expression (p < 0.001). Co-expression of both markers was strongly associated with LNM, along with a significant difference in the expression levels of each marker between primary tumours and corresponding LNM. Univariate analysis showed that tumour grade, stage, ER status and high B3GNT3 expression were all significantly associated with worse PFS. Multivariate Cox regression identified B3GNT3 expression, tumour grade and tumour stage as independent predictors of poor prognosis in IDC. High expression levels of CANT1 and B3GNT3 were associated with reduced PFS across all IDC cases (p = 0.035 and p = 0.001, respectively).

Conclusions: High CANT1 and B3GNT3 expressions are associated with aggressive clinicopathological features in IDC and predict unfavourable outcomes. These markers may serve as potential prognostic indicators and independent predictors of LNM in IDC patients.

Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by clonal proliferation of abnormal Langerhans cells. We report a case of neonatal LCH diagnosed shortly after birth, an exceptionally early presentation in the neonatal period that is exceedingly rare. The BRAF V600E mutation was detected in this neonate.

Case presentation: We report a full-term male neonate delivered via forceps assistance. Within 24 hours of birth, a firm 1×1 cm subcutaneous nodule on the left medial thigh progressively enlarged and ulcerated. By postnatal day 19, a dark red non-blanchable papule appeared on the left sole and rapidly spread to postauricular, cervical, truncal, and palmar regions, developing multiple ulcerative lesions. Skin biopsy confirmed Langerhans cell histiocytosis (LCH), with immunohistochemistry demonstrating diagnostic markers CD1a(+), Langerin(+), and S-100(+). Molecular testing detected the BRAF V600E mutation. Based on the early onset of the disease, rapidly progressive multifocal ulcerative skin lesions, and the presence of a high-risk BRAF mutation suggesting potential systemic dissemination, we initiated induction chemotherapy with vincristine combined with prednisone. Following treatment, the skin lesions resolved completely. The child is now 30 months old. During follow-up, an episode of otitis media occurred, but no recurrence or systemic organ involvement has been observed since.

Conclusion: In this neonate, the initial localized skin lesions suggested potential spontaneous resolution. However, subsequent detection of the poor-prognosis BRAF V600E mutation indicated risk of systemic dissemination, prompting initiation of combination chemotherapy. Skin lesions resolved completely following vinblastine/prednisone therapy. Otitis media (an extracutaneous manifestation) emerging during follow-up further validated the treatment necessity, with no recurrence or new systemic manifestations observed thereafter.