Series 4 : Diagnostic Challenges in Plasma Cell Neoplasms- 📌Post 5 : Beyond the Plasma Cell : The 2026 Immune Atlas of Myeloma ➖The largest single cell study to date ( Pitcher et al.,Nature Cancer 2026 ) profiles nearly 1.4 million bone marrow cells from 337 newly diagnosed patients . ⏩Key findings relevant to pathologists : ➖Distinct immune states at diagnosis predict early relapse - independent of ( and additicr to ) cytogenetics . ➖Rapid progressors show a proinflammatiry " immune senescence- associated secretory phenotype" and accumulation of dysfunctional, immunosupressive T cells . ➖del(7p) cases showing unique type-1 interferon signatures . ➖Integrating Immune signatures with traditional cytogenetics significantly improves outcome prediction. ⏩ Why this matters now : As CAR-T and bisoecific antibodies become earlier- line therapy , the immune context in which they work will become part of future risk stratification and potentially residual- disease assessment. #Myeloma #HemePath #Hematology #Hematopathology #MultipleMyeloma #PlasmaCellNeoplasm #Hematopathology

Series 2: Ductal Carcinoma in Situ ( DCIS ) , - Stage 0 , Stage 1- Debate 📌Post 12 : Is it time to routinely test HER2 in DCIS ? ➖Unlike invasive breast cancer , HER2 testing is still not standard practice in pure DCIS. Yet growing evidence suggests we may be missing clinically useful information. ➖A 2024 perspective in Breast Cancer Research makes a compelling case for systematic HER2 assessment in DCIS : ⏩Strong correlation with grade - Approximately 4 out of 5 HER2-positive well known inter observer variability in n morphologic grading, HER2 IHC can add objectivity and robustness . ⏩Association with higher local recurrence risk : Multiple studies link HER2 positivity to increased ipsilateral breast events ( though it remains less clear whether this applies more to in-sity or invasive recurrence. ) ⏩Larger lesions and higher rates of positive margins - HER2 positive DCIS tends to be more extensive , which has direct surgical implications. ⏩Greater benefit from radiotherapy - HER2- positive patients appear to derive a substantially larger reduction in local recurrence from adjuvant radiation after breast conserving surgery compared with HER2- negative cases. ⏩Higher risk of upstaging - When pure DCIS is diagnosed on biopsy, HER2 positivity is a/w a greater likelihood of finding invasive carcinoma on final excision. This information can influence surgical planning ( eg wider margins or consideration of sentinel node biopsy) . ⏩Practical pathology pearl ( recently highlighted at USCAP 2026): In an intraductal proliferation with apocrine features and intermediate to high grade atypia , diffuse strong (3+) HER2 staining supports a diagnosis of DCIS and is not expected in usual hyperplasia .It doesn't however, help distinguish low grade DCIS from atypical Ductal Hyperplasia . ⏩The bigger picture : We already subtype invasive breast cancer by ER/PR/HER2 status to guide therapy . The same biological diversity exists in DCIS . The time may be approaching for more nuanced, subtype informed management - appropriate local therapy intensification for HER2 positive DCIS and potential de-escalation for hormone receptor positive , HER2 negative disease. ❓What is your current practice regarding HER2 testing in pure DCIS ? #DCIS #BreastCancer #BreastCancerAwarenessMonth #HER2 #Molecular #Histopathology