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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 [...]

Ewing sarcoma (ES) of the spine is a rare childhood cancer with sparse literature on treatment outcomes. We aimed to describe survival outcomes and prognostic factors in patients with spinal ES treated at a single institute in a resource-challenged setting. We conducted a retrospective analysis of patients with spinal ES registered at a tertiary care oncology center between 2003–2019. Clinical patient data was retrieved from hospital records. Cox regression analysis was used to identify the association of baseline clinical parameters with event free survival (EFS) and overall survival (OS). A cohort of 85 patients was analyzed including 38 (45%) patients with metastatic disease. The median age was 15 years with 73% being male. Local therapy was administered in 62 (72.9%) patients with surgery alone in 8 (9.4%), radiotherapy alone in 36 (42.4%) and both in 18 (21.2%) patients. A higher proportion of males received local therapy than females (80.3% versus 59.1%; p = 0.049). The median EFS and OS were 20.1 and 28.6 months, respectively. On univariable analysis, age ≤ 15 years, female sex, serum albumin ≤3.5 g/dL and hemoglobin ≤11 g/dL were associated with inferior EFS while younger age, female sex, hypoalbuminemia and metastatic disease were associated with inferior OS. On multivariable analysis, only hypoalbuminemia was predictive for inferior EFS (HR:2.41; p = 0.005) while hypoalbuminemia (HR:2.06;p = 0.033) and female sex (HR:1.83; p = 0.046) were associated with inferior OS. We concluded that hypoalbuminemia confers poor prognosis in ES spine. Survival outcomes are poorer in females treated in our setting, possibly due to prevailing sex-based biases. [ABSTRACT FROM AUTHOR]

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]

Byline: Shilpi. Budhiraja, Rajeev. Kumar, Gaurav. Khanna, Prem. Sagar, Sudhir. Arava, Adarsh. Barwad, Asit. Mridha Secretory carcinoma (SC) of the salivary gland is considered to be a low-intermediate grade tumor [...]

A 29-year-old, otherwise healthy Indian male, presented to us with a 2-year history of repeated episodes of painful erythematous nodules associated with high-grade fever. Equal rates of drug resistance in leprosy cases with relapse and recurrent/chronic Type 2 reaction: time to revise the guidelines for drug-resistance testing in leprosy?. [Extracted from the article]

Synovial sarcoma (SS) is one of the commonest non-rhabdomyosarcoma soft tissue sarcoma with limited treatment options in the relapsed and advanced settings. The combination of gemcitabine and docetaxel has demonstrated its role predominantly in leiomyosarcoma and pleomorphic sarcomas but has not been prospectively studied in SS. This trial assesses the efficacy, tolerability and quality of life (QoL) with this regimen in metastatic/unresectable locally advanced relapsed SS. Patients and methods This was a single-arm, two-stage, phase II, investigator-initiated interventional study among patients with metastatic or unresectable locally advanced SS who had progressed after at least one line of chemotherapy. Gemcitabine 900 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8 were administered intravenously every 21 days. The primary endpoint was 3-month progression-free rate (PFR); overall survival (OS), progression-free survival (PFS), overall response rate (ORR), safety and quality of life (QoL) constituted the secondary endpoints. Results Twenty-two patients were enrolled between March 2020 and September 2021 and the study had to be closed early due to slow accrual. The study population comprised of 18 (81.8%) patients with metastatic disease and 4 (18.2%) patients with locally advanced, unresectable disease. The most common primary sites of disease were extremity in 15 (68%) and the median number of lines of prior therapies received was 1 (range 1–4). 3-month PFR was 45.4% (95% CI 24.8–66.1) and ORR was 4.5%. Median progression-free survival (PFS) was 3 months (95% CI 2.3–3.6) and median OS was 14 months (95% CI 8.9–19.0). 7 (31.8%) patients experienced grade 3 or worse toxicities, including anemia (18%), neutropenia (9%) and mucositis (9%). QoL analysis demonstrated significant decline in certain functional and symptom scales, while financial and global health scales remained stable. Conclusion This is the first prospective study on the combination of gemcitabine and docetaxel performed specifically in patients with advanced, relapsed SS. Although the accrual of patients could not be completed as planned, the therapy did produce clinically meaningful outcomes and met its primary endpoint of 3-month PFR. This result, along with the manageable toxicity profile and stable global health status on QoL analysis, should encourage further studies. Trial registration This trial was prospectively registered under the Clinical Trials Registry of India on 26/02/2020 (Registration number: CTRI/2020/02/023612). [ABSTRACT FROM AUTHOR]

Introduction: The outcomes of osteosarcoma in low middle income countries (LMICs) are different due to patients presenting in advanced stages, resource constraints and the use of non-high-dose-methotrexate (HDMTX)-based regimens. This study derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol. Materials and methods: A retrospective study including osteosarcoma patients enrolled for treatment at a single tertiary care centre in India between 2003-19 was conducted. Baseline biologic and social characteristics were extracted from medical records and survival outcomes were noted. The cohort was randomised into a derivation and validation cohort. Multivariable Cox regression was used to identify baseline characteristics that were independently prognostic for survival outcomes in the derivation cohort. A score was derived from the prognostic factors identified in the derivation cohort and further validated in the validation cohort with estimation of its predictive ability. Results: 594 patients with osteosarcoma were eligible for inclusion in the study. Around one-third of the cohort had metastatic disease with 59% of the patients residing in rural areas. The presence of metastases at baseline (HR 3.39; p<0.001; score=3), elevated serum alkaline phosphatase (SAP) >450 IU/L (HR 1.57; p=0.001; score=1) and baseline tumour size > 10 cm (HR 1.68; p<0.001; score=1) were identified to be independent factors predicting inferior event free survival (EFS) and were included in development of the prognostic score. Patients were categorized as low risk (score 0), intermediate risk (score 1-3) and high risk (4-5). Harrell's cindices for the score were 0.682, 0.608 and 0.657 respectively for EFS in the derivation, validation and whole cohort respectively. The timed AUC of ROC was 0.67 for predicting 18-month EFS in the derivation, validation and whole cohorts while that for 36-month EFS were 0.68, 0.66 and 0.68 respectively. Conclusions: The study describes the outcomes among osteosarcoma patients from an LMIC treated uniformly with a non-HDMTX-based protocol. Tumor size, baseline metastases and SAP were prognostic factors used to derive a score with good predictive value for survival outcomes. Social factors did not emerge as determinants of survival. [ABSTRACT FROM AUTHOR]

Byline: Aparna. Sharma, Ilavarasi. Vanidassane, Aditi. Aggarwal, Asit. Mridha, Rambha. Pandey, Ekta. Dhamija, Adarsh. Barwad, Sameer. Rastogi PURPOSE: There is no study till date determining the spectrum of adverse events [...]

Background: Aggressive fibromatosis (AF) is a benign tumor that usually has a locally aggressive and recurrent disease course. Reports of association between AF and malignancies have been reported infrequently. Case: We report a case of a 49-years lady who had papillary thyroid carcinoma associated with a distinct desmoid tumor occurring concurrently on the right side of the neck. Initial management comprised of total thyroidectomy followed by radio-iodine therapy and desmoid tumor resection. Recurrent AF developed at the same site as before after 2 years of resection. The recurrent tumor was managed with sorafenib, the patient responded with a resolution of symptoms, and the tumor remained stable. Beta-catenin mutation done by Sanger sequencing was negative in the tumor specimen. Conclusion: AF can occur as a separate tumor in association with PTC. If symptoms are not life-threatening medical management may be a better choice in management. [ABSTRACT FROM AUTHOR]

Introduction: Paratesticular sarcoma are extremely rare malignant tumours. Unlike other sites, they tend to be lower grade and have higher propensity of lymphatic spread. They tend to fail locally and occasionally in the regional lymph nodes. In the absence of target volume delineation guidelines and technical illustration of conformal planning, we have made an attempt to illustrate conformal planning methodology and define target volume based on current evidence in a case of paratesticular sarcoma. Methods: We are presenting a case of 62-year-old male who presented with 15-cm scrotal swelling and underwent high inguinal orchidectomy with ligation of spermatic cord. Histopathology presented a well-differentiated leiomyosarcoma of epididymis. Post-operative radiotherapy target volume included the tumour bed, ipsilateral inguinal nodes and lower pelvic nodes as the clinical target volume. Conclusion: Adjuvant radiotherapy using advanced delivery technique such as volumetric arc technique can provide good dose distribution with good sparing of organs at risk. The downside of conformal radiation delivery is that it is a resource-intensive and has no established target volume delineation guidelines. [ABSTRACT FROM AUTHOR]

HLA‐B*15:05:01:02 differs from HLA‐B*15:05:01:01 by one nucleotide change in intron 2 at position 517 (C > A). [ABSTRACT FROM AUTHOR]

HLA‐A*11:01:01:68 differs from HLA‐A*11:01:01:01 by one nucleotide change in intron 3 at position 1474 (G > A). [ABSTRACT FROM AUTHOR]

HLA‐B*40:01:02:47 differs from HLA‐B*40:01:02:01 by one nucleotide change in the 3′UTR at position 2739 (A>T). [ABSTRACT FROM AUTHOR]

A 20-year-old male without any prior comorbidities presented with 6-month history of hemoptysis as the sole symptom. Clinico-radiological profile and bronchoscopy were suggestive of a tracheal mass. This clinico-pathologic conference discusses the differential diagnoses of primary tumors of the trachea and their management options. [ABSTRACT FROM AUTHOR]

Introduction: Primary intravenous leiomyosarcomas are rare vascular tumors with aggressive disease biology. The diagnosis and management have been challenging as little data exist from large databases. Methods: A literature search was done to identify all cases of primary leiomyosarcomas in the last five years. Clinicopathological features and management strategies were evaluated. Results: The median age was 53 years, predominantly females (2.5:1), presenting as metastases in up to 12.1% cases. Most tumors were locally advanced with a median size of 10cm. Inferior vena cava involvement from renal veins to infrahepatic veins remains the most frequent site (57.1%cases) while nearly half (52.8%) proceeded for surgery without histological proof. Most patients could undergo upfront resection (88.0%) with few patients receiving neoadjuvant chemotherapy (4.3%) or neoadjuvant radiotherapy (2.2%). Significant multivisceral resections included right nephrectomy (41.3%), liver resection (25.7%) and left nephrectomy (2.2%). Most patients (91.8%) needed an inferior vena cava graft placement with remarkable microscopically negative margins (85.5% cases). Doxorubicin and ifosfamide were the most frequently used combination chemotherapy regimens in both pre and postoperative settings with partial responses. The median overall and disease free survival among operated patients was 60 months and 28 months respectively. In multivariate analysis large tumor, extensive inferior vena cava involvement, and need for adjuvant chemotherapy appeared significant predictors for overall survival. Conclusions: Aggressive upfront surgical resection with clear margin remains the key for long-term survival. Doxorubicin-based regimens were preferred as neoadjuvant chemotherapy while adjuvant treatment with chemotherapy, radiotherapy, or both may be considered in high-risk patients. [ABSTRACT FROM AUTHOR]