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Background: Microvascular inflammation (MVI) can occur in biopsies showing T‐cell mediated rejection (TCMR), but it is not well established that T‐cells can directly mediate microvascular injury (TCMR‐MVI). Methods: This was a cross sectional RNAseq based Banff Human Organ Transplant (BHOT) gene expression (GE) analysis. The objective of this study was to probe the molecular signature of TCMR‐MVI in comparison with C4d+, DSA+ antibody mediated rejection (ABMR), stable renal function (STA), and TCMR without MVI. Transcriptome analysis utilized CLC genomic workbench and R‐studio software. Results: No gene set was specific for any diagnostic category, and all were expressed at low levels in STA biopsies. BHOT gene set scores could differentiate ABMR from TCMR and TCMR‐MVI, but not TCMR from TCMR‐MVI. TCMR‐MVI underexpressed several genes associated with ABMR including DSATs, ENDAT, immunoglobulin genes, ADAMDEC1, PECAM1 and NK cell transcripts (MYBL1, GNLY), but overexpressed C3, NKBBIZ, and LTF. On the other hand, there was no significant difference in the expression of these genes in TCMR‐MVI versus TCMR. This indicates that the GE profile of TCMR MVI aligns more closely with TCMR than ABMR. The limitations of classifying biopsies using the binary ABMR‐TCMR algorithm, and the occurrence of common pathogenesis mechanisms amongst different rejection phenotype was highlighted by the frequent presence of molecular mixed rejection. Conclusions: T‐cell mediated mechanisms play a significant role in the pathogenesis of MVI. GE was broadly different between rejection phenotypes, but molecular scores varied substantially between biopsies with the same Banff grade. It was not always possible to achieve precise molecular score‐based diagnostic categorization of individual patients. [ABSTRACT FROM AUTHOR]

Background: Adult soft tissue sarcomas (STS) are rare and diverse. Current management is based on limited literature from the West. Therefore, data from different geographical regions is required, including the low‐middle‐income countries. This is our experience managing adult sarcomas in the tertiary cancer center of North India. Materials and methods: This is a retrospective analysis of the structured sarcoma database of patients treated in the surgical oncology department between 1992 and 2020. The descriptive analysis includes demography, site distribution, diagnosis, histopathology variations, prior surgical interventions, and stage. Results: A total of 1106 soft tissue sarcoma patients were treated in three decades. Age distribution was 13%, 43%, 31%, and 11% in <20, 21–40, and 41–60 and >60 years, respectively. The male‐to‐female ratio was 1.73. The anatomical distribution was 17%, 42%, 23%, 7%, 7%, and 3% in upper extremity, lower extremity, trunk, retroperitoneum, head and neck, and viscera, respectively. Overall, 49% of patients had undergone prior suboptimal surgeries at community hospitals. Common histology subtypes were synovial sarcoma (18%), undifferentiated pleomorphic sarcoma (UPS) (13%), dermatofibrosarcoma protuberans (12%), and liposarcoma (9%). A pathological discordance of 13% was identified between the initial and the final histologies. Overall, 61% of tumors were high‐grade. Memorial Sloan Kettering Stages II and III were present in 33% and 35% of patients, respectively. Conclusions: This is one of the largest single institutional experiences of STS from the Asian population. Mostly young adults were affected with male preponderance. The lower extremity and trunk were common subsites. Frequent histologies were synovial sarcoma and UPS. A high rate of suboptimal surgical intervention at the community level and pathological discordance was noted. This study highlights the need to establish prospective structured databases for capturing quality information related to rare malignancies and providing insights for future research. [ABSTRACT FROM AUTHOR]

Byline: Brusabhanu. Nayak, Ravi. Phulware, Ekta. Dhamija, Adarsh. Barwad Dear Editor, Renal angiomyoadenomatous tumour (RAT) is a newly described rare neoplasm with distinctive histopathological appearance and is characterized by leiomyomatous [...]

Genetic focal segmental glomerulosclerosis (FSGS) is an important but underestimated cause of inherited proteinuric chronic kidney disease (CKD) in adults. We discuss a case of familial CKD due to inverted formin 2 (INF2) gene mutation, where three siblings had disparate phenotypic presentations ranging from CKD with subnephrotic proteinuria to nephrotic-range proteinuria with collapsing FSGS on kidney biopsy over a period of 8 years. The youngest sibling was the index case. The family agreed to undergo genetic testing only after two more siblings were diagnosed with kidney disease. This case highlights how clinical heterogeneity, absence of family history in the index case, initial lack of specific biopsy-proven diagnosis and reluctance to undergo genetic testing can delay the diagnosis of genetic kidney disease in adults. [ABSTRACT FROM AUTHOR]

Poorly differentiated colonic carcinoma with rhabdoid features is a rarely described entity. Our knowledge regarding the molecular phenotype of the tumor is evolving. We herein report a similar tumor with rhabdoid differentiation identified in the splenic flexure, which on histological examination showed a poorly differentiated phenotype with epithelioid to spindled morphology, tumor giant cells, and rhabdoid differentiation. The tumor was mismatch repair-proficient, deficient of INI1/SMARCB1, KRAS mutated (A146×), BRAFV600E mutated (c.1799T > A), and NRAS wild-type, indicating serrated differentiation in the tumor. The patient died after 3.5 months post-surgery. INI1-deficient poorly differentiated carcinoma of the colon is a rare, aggressive colonic malignancy showing a serrated phenotype. Routine identification and subtyping are important keeping in mind the distinct tumor phenotype, resistance to conventional chemotherapy, and dismal prognosis. [ABSTRACT FROM AUTHOR]

Byline: Adarsh. Barwad, Ekta. Dhamija, Venkatesan. Kumar, Sameer. Rastogi, Asit. Mridha Kaposiform hemangioendothelioma (KHE) is an uncommon intermediated grade, vascular tumor, which primarily occurs in infants and children. It is [...]

Background: Minimally invasive autopsy (MIA) using post‐mortem magnetic resonance imaging with ancillary investigations is reported as accurate as conventional autopsy. This study assesses MIA's feasibility and accuracy compared to conventional autopsy. Method: MIA and/or conventional autopsy were performed on malformed fetuses (14–20 weeks gestation) and stillbirths (>20 weeks gestation), with/without malformation. Concordance in diagnostic accuracy (95% confidence interval [CI]) and agreement (Kappa coefficient [k]) were assessed in malformed cases where both MIA and autopsy were conducted. Results: We enrolled 200 cases, including 100 malformed fetuses (<20 weeks) and 100 stillbirths (with/without malformations). Concordance of 97.3% was observed between MIA and autopsy in 156 malformed cases. The overall diagnostic accuracy of MIA was 96.04%. Conclusion: While conventional autopsy remains the gold standard, MIA is feasible in tertiary care settings. It can be considered a potential alternative for post‐mortem assessment, particularly in settings with limited facility of conventional autopsy and parental refusal. [ABSTRACT FROM AUTHOR]

Background: "Depth of invasion" is an additional index incorporated in 8th AJCC staging system for oral cavity squamous cell carcinoma based on its prognostic significance. Pre‐operative assessment by clinical palpation and imaging modalities has been used with limitations. The aim of the study is to compare different techniques including clinical palpation, ultrasound, and magnetic resonance imaging with histopathology for assessment of depth of tumor invasion. Materials: Fifty patients of carcinoma tongue (T1–T3) were enrolled. Clinical palpation, Ultrasound tongue, and Magnetic resonance imaging were used to assess depth of tumor invasion. Microscopic depth of invasion was considered as reference. Statistical analysis was done to assess the level of agreement, reliability, and internal consistency. ROC analysis was done to find the "Area Under Curve" for microscopic depth versus ultrasound, MRI, and gross histopathological "depth of invasion". Results: Ultrasound tongue showed highest "area under curve", Intra class correlation (ICC:0.786) with a good consistency (Cronbach's Alpha:0.880) with histological reference compared to MRI(ICC:0.689;CA:0.816). Clinical palpation showed weak agreement (Kappa:0.43) for assessing depth. To observe the concordance between ultrasound and microscopic depth, Lin's Concordance Correlation Coefficient (CCC = 0.782) was calculated with 95% limits of agreement. Lin's concordance correlation between ultrasound and microscopic depth showed a good agreement. Conclusions: Ultrasound tongue is a reliable imaging modality for pre‐operative T staging by assessing tumor "depth of invasion" in carcinoma tongue patients with good internal consistency as per 8th AJCC staging system. Level of Evidence: 2 (CEBM‐Level of Evidence‐2.1) Laryngoscope, 134:215–221, 2024 [ABSTRACT FROM AUTHOR]

Pleomorphic myxoid liposarcoma (PML) is a newly recognized entity with aggressive clinical behavior and a tendency to recur. It has histological features of both myxoid and pleomorphic liposarcoma and lacks the molecular and structural chromosomal abnormalities associated with myxoid and pleomorphic liposarcoma. The data about their response to chemotherapy is quite sparse. We report a case of incidentally detected pleomorphic myxoid liposarcoma of the mediastinum in a 32-year-old gentleman. After resection and adjuvant chemotherapy with doxorubicin and ifosfamide, there was no evidence of residual disease at the end of treatment. During a routine follow-up 5 months later, he was found to have a recurrence of the disease with histological confirmation. He received a trabectedin given its activity in myxoid liposarcoma. However, he had toxicities and progression leading to its discontinuation. Subsequently, eribulin was started as the next line of therapy. After 4 cycles of chemotherapy, response assessment was suggestive of partial response, which is still maintained after 7 cycles of eribulin. This is the first report of this entity responding to a newer chemotherapy regimen. [ABSTRACT FROM AUTHOR]