Search

Pulmonary pleomorphic carcinoma (PPC) is an uncommon primary lung tumor with a low incidence and aggressive biological characteristics that can occur in young people and nonsmokers. Pleomorphic carcinoma (PC) has a worse prognosis than other non-small cell lung tumors. We describe a 45-year-old man who complained of having a dry cough for a month. A well-defined mass in the anterior section of the left lower lobe was identified by chest high-resolution computed tomography (HRCT), and a positron emission tomography (PET) scan confirmed a left lobulated tumor with fluorodeoxyglucose (FDG) uptake in the left mediastinal lymph nodes. An endobronchial ultrasound guided transbronchial needle aspiration (EBUS TBNA) guided biopsy of the tumor was performed and sent for histopathological analysis, which identified pleomorphic squamous cells and giant cells. Positive IHC markers included P63, TTF1, pancytokeratin, Vimentin. Patient was diagnosed with stage IIIa (T3N2M0) pleomorphic carcinoma of the lung. Due to the tumor's advanced stage, the patient received chemotherapy and radiation therapy.

Objectives: We present a case series of patients with granulomatous myocarditis presenting as atrial arrhythmias accompanied by lymphadenopathy. Background: Atrial myocarditis (AM) may be the cause of atrial arrhythmias in patients without risk factors for atrial fibrillation. (AF). Methods: Patients with atrial arrhythmias without traditional risk factors for AF underwent 18F Fluorodeoxyglucose positron emission tomography (18F FDG PET). We performed biopsy of either the myocardium or draining lymph nodes in patients with atrial uptake of 18F FDG PET. We found evidence of AM in 15 patients. Results: The mean age of the patients was 43.33±12.59 years with a male predominance (73.3%). The left ventricular ejection fraction (LVEF) at presentation was 48.07±12.29% and the left atrial volume was 37.6±10.64 ml. All patients had AF at presentation, atrial flutter was noted in 4 patients (26.7%) and 2 patients (13.3%) had atrioventricular nodal reentrant tachycardia (AVNRT). F FDG PET uptake was noted in the atria in all patients and in the ventricles in 3 patients (20%). Cardiac sarcoidosis was the diagnosis in 12 patients (80%) while 3 patients (20%) had evidence of tuberculosis. The mean CHA2DS2 Vasc score of the patients was 1.06±0.93. Four patients (26.7%) presented with ischemic stroke. All patients were treated with disease specific therapy (immunosuppression or anti-tuberculosis therapy) in addition to standard anti-arrhythmic medications. Over a mean follow up of 30.53± 13 months we observed a significant improvement in clinical status commensurate with a decline in atrial uptake. There was a non-significant improvement in LVEF to 56±12.07% with disease specific therapy. (p=0.0853) Conclusions: Atrial arrhythmias with granulomatous lymphadenopathy may be a presenting feature of Atrial myocarditis. The risk of stroke seems to be high in these individuals. This syndrome should be suspected in young individuals presenting with atrial arrhythmias and stroke without conventional risk factors.

Background and aims Published studies on coronavirus disease 19 (COVID-19) associated rhino-orbito-cerebral mucormycosis (CAROCM) were primarily descriptive. Therefore, we aimed to identify features of COVID-19 that could predispose to CAROCM and explore the pathogenic pathways. Patients and methods This retrospective hospital-based study was done during the first (March 2020 - January 2021) and the second (February 2021 - June 2021) waves of the COVID-19 pandemic. Subjects were grouped into four categories: first-wave CAROCM (n-4); second-wave CAROCM (n-27); first-wave non-mucor COVID (n-75), and second-wave non-mucor COVID (n-50). Data elements included age, gender, comorbidities, COVID-19 severity, steroid therapy, peak values of interleukin-6 (IL-6), serum ferritin and D-dimer, nadir values of absolute lymphocyte count (ALC), absolute neutrophil count (ANC) and platelet count (Pl. C). Results Thirty-one patients of CAROCM were included. The mean (SD) age was 51.26 (11.48) years. 27 (87.1%) were aged ≥ 40 years and males. Severe COVID-19 was seen more often in the second wave than the first wave (P-0.001). CAROCM group was significantly younger (P-0.008) and showed a higher incidence of uncontrolled diabetes (P-0.001) and renal dysfunction (P-0.004) than non-mucor COVID. While IL-6, ferritin and D-dimer were significantly elevated in CAROCM than non-mucor COVID, clinical severity, ANC, ALC and Pl. C showed no significant difference. Conclusion CAROCM is seen often in middle-aged diabetic males with uncontrolled hyperglycaemia, diabetic ketoacidosis, renal dysfunction and those infected by more transmissible delta variants and treated with steroids. IL-6, D-dimer, serum ferritin are more often elevated in CAROCM and might play a pathogenic role.

Pancoast's syndrome and subclavian arteritis are rarely caused by Aspergillus sp. . Here we report a case of a 22-yr-old, immunocompetent male who presented with fever, weight loss, right-sided facial anhidrosis and hand weakness of six months duration. Neurological examination confirmed right Horner's syndrome and weakness of small muscles of right hand. Contrast MRI of neck and chest revealed a pleural-based right apical mass abutting subclavian artery and C8-T1 root and multiple enlarged lymph nodes. He developed right hemiataxia due to cerebellar infarct before the planned excision of mass. Surgical exploration showed abscess encasing subclavian artery. Biopsy of the mass resulted in accidental injury of subclavian artery which was repaired. He developed bleeding from suture site postoperatively due pseudo-aneurysm of the subclavian artery which was stented. Histopathology of mass was suggestive of Aspergillus sp. . He was successfully treated with voriconazole. This is probably the first report of Pancoast's syndrome and large vessel angiitis caused by Aspergillus fumigatus which has been successfully managed.

Juvenile xanthogranuloma (JXG) preferentially occurs in childhood and is usually benign and limited to the skin. The systemic form is rare and may be associated with severe morbidity and mortality. We describe a three and a half year old boy with disseminated papular skin lesions and neurological signs and symptoms. Diagnostic workup revealed multiple brain lesions. Skin and brain biopsy was suggestive of systemic JXG. Treatment with prednisolone, vinblastine, and methotrexate caused regression of skin and central nervous system (CNS) lesions. However, 6 months after completion of chemotherapy, cutaneous but not CNS lesions relapsed. Few case reports have been published in the past, particularly with multiple lesions in CNS, which as in our case, is an extremely rare finding.

A 42-yr-male presented with left foot drop of 2 months duration. General examination showed enlarged greater auricular nerve (GAN) and hypoanesthetic patch over dorsum of left leg (figure 1A,B). Neurological examination showed thickened left common peroneal nerve (CPN) at fibular neck and weak dorsiflexors of left leg. Electrophysiological study showed left CPN involvement. High-resolution ultrasound (HRUS) of nerves was done with 15–7 MHz hockey-stick transducer on Philips HD15 machine. GAN was enlarged bilaterally with completely effaced fascicular architecture and thickened epineurium (figure 1C–F). HRUS also revealed enlarged …

Background: CRC is the 3rd most commonly diagnosed malignancy and 4th leading cause of cancer related deaths worldwide. Over two decades of extensive research from the West has revealed three major tumorigenesis pathways responsible for CRC viz. a) Chromosomal Instability (CIN) arising from aberrant activation of Wnt signalling, b) Microsatellite Instability (MSI) caused by inactivation of MisMatch Repair (MMR) genes and c) CpG Island Methylator Phenotype resulting in promoter DNA methylation induced inactivation of tumour suppressor genes. Previous results from our laboratory showed a significant proportion of Early Onset Sporadic Rectal Cancer (EOSRC) to be driven neither by aberrant Wnt signalling nor MSI. We also identified a significant proportion of MSI+ familial CRC not exhibiting loss either of the four major MMR genes indicating involvement of addition MMR or non-MMR genes. We therefore endeavoured to determine status of MSI in sporadic CRC samples from the Indian population. We are performing analysis of the status of other molecular features including CIMP, BRAF/KRAS/p53 mutation status, Wnt, etc. to obtain a wholesome molecular profile of sporadic CRC from the Indian population. Methodology: The microsatellite pattern in CRC tumours was determined using the five microsatellite marker panel as per the Bethesda guidelines. Expression status of MMR proteins (MLH1, MSH2, MSH6 & PMS2) was evaluated using immunohistochemistry. Mutations in BRAF (V600E) and KRAS (Codon 12 and 13) were identified by Sanger sequencing. CIMP status is being determined using the MethyLight technology as well as methylation specific PCR. Results: A comprehensive screen of close to 200 CRC samples revealed a significantly higher proportion of sporadic CRC tumors (41%; 50% of colonic and 31% of rectal cancer samples) exhibiting MSI as compared to 14% reported in The Cancer Genome Atlas (TCGA) data. Among MSI-high tumours, only 27% and 15% showed loss of MLH1 or MSH2 respectively, a significantly lower frequency compared to Caucasian data. Instability in the BAT25 microsatellite was significantly high in tumors harboring MLH1 loss. More importantly, a significant proportion of MSI+ CRC tumors were devoid of loss of either of the four major MMR genes. In addition, the BRAF V600E mutation, a known cause of MLH1 silencing, is absent in all but one MSI+ tumors. Work on determining status of CIMP and Wnt signalling is currently underway. Conclusions: Significantly higher proportion of sporadic CRCs from Indian population exhibit MSI but the underlying mechanism appears to be novel and distinct from those identified from the Caucasian population. Deep sequencing based studies are currently underway to determine molecular aberrations driving MSI in the Indian sporadic CRC. Note: This abstract was not presented at the meeting. Citation Format: Ashmala Naz, Vijaya Tourani, Satish Rao, Murali Dharan Bashyam. Molecular profiling of MSI-high colorectal cancer (CRC) in Indian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3490.

We propose a fast and accurate method for counting the mitotic figures from histopathological slides using regenerative random forest. Our method performs automatic feature selection in an integrated manner with classification. The proposed random forest assigns a weight to each feature (dimension) of the feature vector in a novel manner based on the importance of the feature (dimension). The forest also assigns a misclassification-based penalty term to each tree in the forest. The trees are then regenerated to make a new population of trees (new forest) and only the more important features survive in the new forest. The feature vector is constructed from domain knowledge using the intensity features of nucleus, features of nuclear membrane and features of the possible stroma region surrounding the cell. The use of domain knowledge improves the classification performance. Experiments show at least 4% improvement in F-measure with an improvement in time complexity on the MITOS dataset from ICPR 2012 grand challenge.

The p53 oncoprotein is a tumor suppressor that is stabilized upon various forms of cellular stresses to induce transcription of genes regulating cell cycle arrest or apoptosis. TP53 is the most frequently mutated gene in human cancers and majority of mutations are located in the region encoding the DNA binding domain compromising thereby its transcription activation ability and resulting in loss of function. Recent studies however suggest mutant p53 proteins to exhibit a gain of function property. Specific p53 missense mutations can result in an altered transcription program causing positive regulation of cell proliferation, metastasis and chemoresistance. In our previous studies, we performed comprehensive characterization of squamous cell carcinoma of the oral tongue (SCCOT) with respect to p53, EGFR, Wnt, MSI, LoH of several tumor suppressor loci and HPV status. Mutant p53 was a significant predictor of overall survival and the TP53 codon 72 Proline allele was significantly associated with SCCOT. In order to dissect the role of mutant p53 in tongue cancer, we performed genome wide DNA and RNA profiling of 26 and 40 SCCOT samples, respectively. Both mutant and wild type tumor samples appeared to exhibit comparable levels of DNA copy number alterations. Transcriptome data analyses using a combination of single sample gene set enrichment analysis and comparative marker selection revealed gene sets that could significantly distinguish p53 mutant and wild type tumor samples. Significance analysis of microarrays performed on all genes constituting the differentially enriched gene sets surprisingly identified only two genes to be upregulated in p53 mutant samples at a false discovery rate significantly lower than 10% namely TP53 itself and SMARCD1; the latter a member of the SWI/SNF chromatin remodelling complex. Elevated levels of TP53 transcript in tumors harbouring mutant p53 significantly correlated with levels of ZMAT3, itself induced by p53 and known to stabilize the TP53 transcript. In addition, the analysis revealed several known (ATF3 and others) and novel (GCHFR and others) targets of wild type p53. Differential expression of all targets was validated in additional tongue cancer samples. Ectopic expression of certain (but not all) p53 mutant proteins in p53 null cells induced SMARCD1 (but not canonical wild type p53 targets) while expression of wild type p53 induced GCHFR, ATF3, CDKN1A, etc. (but not SMARCD1). In contrast, p53 stabilization in cells harboring wild type p53 caused elevation of GCHFR, ATF3, CDKN1A, etc., but not of SMARCD1. Validation of novel targets using promoter-luciferase constructs, chromatin immunoprecipitation PCR and a tongue cancer tissue microarray is underway. This is perhaps the first evidence from Head and Neck tumor samples for a gain of function activity of mutant p53. Thus wild type and mutant p53 may support distinct transcription programs in tongue cancer. Citation Format: Raju SR Adduri, Padmavathi Kavadipula, Viswakalyan Kotapalli, Leena Bashyam, Anupama Shirke, Arun kumar Paripati, Swarnalata Gowrishankar, Mukta Srinivasulu, Mohammed Mujtaba Ali, Subramanyeshwar Rao, Snehalatha Dhagam, Mohana Vamsy Chigurupati, Shantveer G. Uppin, Vijaya Tourani, Murali D. Bashyam. Transcriptome analysis of oral tongue cancer reveals novel insights into wild type and mutant TP53 transcription program. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3692.