Pranay Tanwar

Acute Myeloid Leukemia Presenting as “Bowel Upset”: A Case Report

Myeloid sarcomas (MS) are the extramedullary presentation of acute myeloid leukemias. At times, they are difficult to diagnose due to lack of any supportive findings in peripheral blood/bone marrow aspirate examination. The involvement of gastrointestinal tract (GIT) by myeloid sarcoma is rare phenomenon. This diagnostic challenge becomes more complex when it is added by vague clinical symptoms. Many times, they have been misdiagnosed as Non-Hodgkins lymphoma, small round cell tumour or carcinoma. Here, we are reporting a case of myeloid sarcoma with no haematological abnormality which presented with the symptoms of bowel obstruction and a rare combination of inv. (16) and trisomy 22. The journey to reach the conclusive diagnosis in this case is interesting and sensitizes us to have high index of suspicion in a case, where there is paucity of clinical evidences.

Genetic landscape of gallbladder cancer: Global overview

Gallbladder cancer (GBC) is a rare malignancy of biliary tract cancer (BTC), characterized by late presentation and poor prognosis. It exhibits wide geographical as well as ethnical variations. So, diverse epidemiology along with etiological factors have been discussed in the current article. Present review unravels the germ line polymorphisms contributing to GBC susceptibility through candidate gene approach and GWAS. GBC is enriched with multiple mutations consisting of both passenger and driver mutations. The identification of the hotspot driver mutations which are involved in the etiopathogenesis of this cancer is necessary, before targeted therapies could be implemented clinically. Thus, this review sheds lights on both traditional low throughput methods along with high throughput NGS used to determine somatic mutations in cancer. With the advent of GWAS and high throughput sequencing methods, it is possible to comprehend the mutational landscape of this enigmatic disease. This article is the first one to provide insights into the genetic heterogeneity of GBC along with somatic mutational data from Catalogue of Somatic Mutations in Cancer (COSMIC) database. In addition, management of tumor heterogeneity as a therapeutic challenge has been discussed. Future goals involve liquid biopsy based research for better clinical management of the disease. Therefore, research efforts involving discovery of non- invasive markers for early stage cancer detection along with novel therapies should be directed.

Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium

Solid tumors are covered by stroma, which is hypoxic in nature and composed of various non‐malignant components such as endothelial cells, fibroblasts, and pericytes that support tumor growth. Tumor stroma represents a mechanical barrier for tumor infiltration of CD8+ effector T cells in particular. In this context, our previous studies have demonstrated the therapeutic impact of Low‐Dose Radiation (LDR)‐primed and M1‐retuned (iNOS+) peritumoral macrophages that produce inducible nitric oxide, have immunological roles on tumor infiltration of effector T cells, cancer‐related inflammation, and subsequent tumor immune rejection in a mouse model of pancreatic cancer. These findings suggested a possible modification of tumor endothelium by LDR‐primed macrophages. In line with these observations, here we demonstrate the influence of LDR in down‐modulating HIF‐1 in irradiated tumors in the course of polarization of irradiated tumor‐associated macrophages toward an M1 phenotype. Furthermore, we demonstrate that M1 macrophages which are primed by LDR can directly influence angiogenic responses in eNOS+ endothelial cells which produce nitric oxide having both vascular and physiological roles. Furthermore, we demonstrate that naïve macrophages, upon differentiating to an M1 phenotype either by Th1 stimuli or LDR, potentially modify sphingosine‐1‐phosphate/VEGF‐induced angiogenic signaling in tumor‐derived endothelial cells with tumorigenic potential, thus indicating the significance of iNOS+ macrophages in modulating signaling in eNOS+ tumor‐derived endothelium. Our study suggests that iNOS+ macrophages can activate tumor endothelium which may contribute to cancer‐directed immunotherapy in particular.

Real-Time Compensation in Flow Cytometry: A Real Need of Time

Dear Sir, Compensation is done to prevent spectral overlap and spill-over during data acquisition in fluorescence activated cell sorting (FACS). Spectral overlap occurs because the fluorophores used in flow cytometry emit photons of multiple energies and wavelengths, where emission spectra overlap, fluorescence from more than one fluorochrome may be detected in a channel [1–3]. With newer advanced machines with more lasers and many more detectors or ‘‘channels’’, the importance of compensation cannot be undermined. The conventional single Antibody (Ab) stained cell tube run before standardization of a protocol experiment, and getting a desired compensation settings is not sufficient in this age of multicolor and multi-tube experiments, real time compensation takes care of other problems apart from compensation like steric hinderance and tube specific ‘‘spill overs’’. In our experience, even if an experimental protocol is standardized beforehand with single tube run experiments, a ‘‘real time’’ compensation setting contributes significantly to the results. Hence we recommend after standardization of protocol by single Ab experiments for compensation, a tube specific compensation should be applied and voltage and gain settings adjusted during acquisition to simulate real time data collection. This procedure of real time compensation has better results as compared to single tube runs in standardized protocols as explained in Fig. 1. To elaborate this point we acquired data from two sets of experiments one which was run on standardized settings (single Ab tube experiment) of protocol and the other when compensation was done in real time while acquisition (Figs. 1 and 3). The difference in voltages in different channels was also compared (Fig. 2). The compensation algorithm needs to be performed both on positive population and a negative population (Fig. 1). For best compensation, selection of controls is important— either internal control with similar fluorescence as that of the test cells or external beads can be used, when added to the same tube which have surface test markers acting as controls. Internal control should have adequate adherence to fluorochromes and the individual samples should have the same carrier particles for the fluorochromes, [3–5] this can be done by using known positive controls and comparing their fluorescence [4]. In our experiment, the voltage and compensation settings of single Ab tube (Fig. 2) were saved in the general

Aspirate from an abdominal lump in a known case of breast carcinoma

A 63-year-old woman with a history of breast carcinoma diagnosed and treated 9 years previously presented with a 2 9 2 cm swelling in her abdominal wall. There was no history of anorexia, weight loss or lymphadenopathy. Computed tomography of the chest and abdomen was performed and did not reveal any metastatic deposits. Positron emission tomography scan revealed uptake in the abdominal wall swelling.

Prospective Evaluation for Mutational Frequency of Wilm’s Tumor-1 (WT1) Gene in De Novo Cases of Acute Myeloid Leukaemia

Background: Haploidentical related donor stem cell transplantation (haplo-SCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of those alternative donors in patients aged more than 65 years. Patient: 76-year-old male patient presented in November 2015 for one-week history of headache, dizziness, fever, bruising and pancytopenia. (WBC 7800/mm, 38% blasts, platelets 18000/mm, hemoglobin 8 g/dL). CT brain showed a left subdural hematoma with mild midline shift necessitating a left parietal burr hole for evacuation. Bone marrow evaluation showed AML with positive NPM-1 (NCN 1⁄4 1297) and negative FLT3, C-KIT, CEBPA. Karyotype: 47, XY, +8. He received induction therapy with 5-Azacitidine 75 mg/ m/day for 7days every 28 days and achieved complete remission (CR1) but positive minimal residual disease (MRD) (NPM1 positive, NCN 1⁄4 3.69) at day 28. He continued 15 additional cycles, remained in CR1, with undetected MPM1 after the third cycle. On December 2016, he progressed with leukemia cutis, neutropenia, but no evidence of disease by morphology or flow but a positive MRD (NPM1 NCN 1⁄4 0.31). He received induction chemotherapy age adjusted with Idarubicin, Cytarabine and achieved CR2 with MRD negative, followed by one consolidation with idarubicin, Cytarabine, then haplo-SCT from his son on March 2017 with Fludarabine, cyclophosphamide (Cy) and TBI 2Gy as conditioning protocol, and post-transplant Cy at day +3 and +5. GVHD prophylaxis with cyclosporine, mycophenolate mofetyl and GCSF at day +6 were given. In May 2017, he started maintenance therapy with 5Azacytidine 32mg/ m daily for 5 days every 28 days. There was no development of acute or chronic GVHD, and he remained in CR, chimerism 98% donor with negative MRD one-year post haplo-SCT. Conclusion: Haplo-SCT is highly feasible in selected very elderly population with AML. Thus, the absence of a HLAidentical donor should not limit the consideration of haplo-SCT for the elderly population aged more than 75 years. Prospective multicenter randomized studies as well as registry analyses reporting on “real-life” medical practices are required to confirm these findings.

Isolated bone marrow metastasis of testicular tumor: A rare cause of thrombocytopenia

Isolated bone marrow metastasis of testicular tumor is very rare. Here, we report this case of a 21-year-old male who was admitted to our hospital with generalized body pain, which was severe and weakness for one month. He had a history of an operative intervention for the left testicular mass about 6 months ago which was diagnosed as mixed germ cell tumor on histopathological examination. The blood investigations showed anemia, low platelets, and elevated tumor markers. Bone marrow aspiration and biopsy examination showed metastatic deposits of mixed germ cell tumor. There were no foci of disease in any other part of the body. The patient was given chemotherapy, i.e. cisplatin, etoposide, and bleomycin. After completion of chemotherapy, there was drastic improvement in pain and weakness. A repeat examination of bone marrow done after 3 month was free of tumor.

A case of leprosy, erythema nodosum leprosum, and hemophagocytic syndrome: A continuum of manifestations of same agent-host interactions

A young adult man with 4-years history of lepromatous leprosy (received irregularly multidrug therapy) presented with two and half years history of symptoms suggestive of chronic erythema nodosum leprosum (ENL), initially responded to steroids and thalidomide, but later on failed. During the last 2-months, he developed fever, vomiting, and subsequently altered sensorium. On evaluation, he had hepatosplenomegaly, hyponatremia, hyperferritinemia, hemophagocytosis in bone marrow aspiration, lobular panniculitis in skin biopsy, and multiple parenchymal nodules in chest imaging. Hence diagnosis of ENL with hemophagocytic lymphohistiocytic (HLH) syndrome was established and treatment with dexamethasone (10 mg/m2) started. During hospitalization, he developed sinus bradycardia, QT prolongations, recurrent ventricular tachycardia, and moderate systolic dysfunction. The cardiac complications recovered using a temporary pacemaker and were presumed to be due to micronodular cardiac deposition of ENL. This case iterates that ENL can present with varied presentations like asymptomatic lung nodules and storming cardiac complications. More importantly leprosy, ENL, and HLH are a continuum of manifestations of the same agent-host interactions.

Dr. A.P.J Abdul Kalam-“A Man Beyond Science”

Dear Sir, The extraordinary charismatic personality of Dr. Kalam has sensitized every individual in our nation. His reach to the people was beyond the bar of caste, color and creed. An ordinary man, who came from a humble family of Rameswaram, Tamil Nadu, India, reached to the highest national rank by being the 11th President in Indian Republic. He has been a very sincere worker of his field and was a continuous source of inspiration for all generation of people. Among the awards which he deservingly earned in his lifetime, few of them include Padambhushan (1981), Padma Vibushan (1990), Bharat Ratna (1997) King Charles Medal-II (2007) and many more. However, the greatest award was the respect he commanded among common man and specially youth for whom he is an unyielding source of inspiration. His speeches and his perspective towards “Science and its Utilization for People” are a worth beyond words. He graduated from Madras Institute of Technology in aerospace engineering and later remained associated with Defense Research and Development Organization for nearly 40 years. He started his career with a project of developing a small helicopter for Indian army. Dr Kalam developed India’s first indigenous Satellite Launch Vehicle (SLV-3) which successfully placed the satellite, Rohini in the near orbit of earth in July 1980 and made India an exclusive member of Space Club. Subsequently, he played important role in development of missiles like Agni and Prithvi which made India a self sufficient in its Defense Power. He was called as “Missile Man” for his contribution in missiles development. Dr Kalam has played a pivotal role as Chief scientific Advisor to Prime Minister between July 1992 to December 1999, it was during this time that “Pokhran-II” the nuclear test was conducted. His hard work in this field made India a Nuclear Power. Dr Kalam had significant contributions to medical science which are less discussed in Indian media and literature. He advocated, the role of biotechnology in medical science research, emphasized the use of science and technology for the benefit of common man. India’s first indigenous low cost cardiac stent was developed by him in collaboration with Dr. Somaraju Bhupathiraju known as Kalam-Raju stent during 1994 – 1996. It reduced the cost of stents by 1/4th compared to prevailing market rate. Approximately 2000 Kalam-Raju cardiac stent has been fitted to many needy patients and showed the path of affordable health care [1]. Although, the medical field has progressed to drug eluting stents, this invention was a landmark in its time. In 2012, they developed a tablet computer for purpose of rural health care service, which was named the ‘Kalam-Raju tablet’. One of his great achievement was the development of light weight calipers for polio affected children by using carbon-carbon and carbon-polymer materials (glass-filled polypropylene which are used in missiles) during 1995 – 1996, thus reducing weight of the caliper to 1/10th of the original weight. Over 50,000 children were benefitted with these calipers which reduced their pain significantly, while walking. Throughout his life, he took up the mission to ignite and inspire young minds towards national spirit by meeting school students across the country. He has also written many thought provoking and inspirational books such as “ Wings of Fire”, “ Ignited Minds” and “ India 2020”, which has become house hold names with youth of India. During the last decade, Dr. Kalam has addressed over five million youth below the age of 17 and inspired them to become an active participant of India Vision 2020. He had addressed several Children Science Congresses across the country. Though, everyone who is born has to leave for the heavenly abode, but Dr. Kalam has left the legacy of his scientific achievements, thoughts and teachings as a source of inspiration for generation to come in future India and the world. Today, we really are gratefull to the almighty for giving us the opportunity to live in an era when we could share the sunlight with such a great personality. May his soul rest in peace.