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The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer-associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti-tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro-tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti-tumorigenic M1-like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR-M cells). While CAR-T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR-M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third-generation CAR-M technology, offering insight into in-vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early-stage TAM-targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes.
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Monkeypox infection (Mpox) is caused by the Orthopoxvirus (OPXV) genus of the Poxviridae family, closely resembling its more famous sibling smallpox. Recently World Health Organization (WHO), have renamed monkeypox as Mpox citing racial concerns, so we will be referring to monkeypox as Mpox. There has been a recent outbreak in May 2022 when Mpox cases were identified in all six WHO regions. On July 23, 2022, WHO declared it a public health emergency. Before the current outbreak, Mpox had been reported in people from several parts of central and west African countries; and almost all Mpox cases in people outside of Africa were linked to international travel to countries where the disease commonly occurs or through imported animals. With the waning of smallpox vaccine-induced immunity, Mpox can spread in the global population. Though the virus generally does not cause high mortality in immunocompetent individuals, however, severe disease and mortality may result if the virus spreads to immunocompromised individuals, children, elderly individuals, pregnant women, and individuals living with comorbidities such as diabetes. The current transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. It was found that 98% of the persons with infection were either gay or bisexual men, with 41% suffering from HIV infection. The reasons behind this current epidemiological behavior have to be studied further to formulate a hypothesis that, is it the homosexuals who need to be more concerned or is it a global concern, and is monkeypox changing its behaviour to a sexually transmitted infection? The rash, along with associated lymphadenopathy, is a clue toward Mpox infection, but polymerase chain reaction is needed for the confirmative diagnosis. With the discovery of a vaccine, repurposed antivirals, and precautionary steps to prevent the spread of infection, it might help in the containment of the virus. In addition, what we already know about Mpox has to be re-evaluated, because most of the information gathered is from low-resource settings in Africa. The world at large and health care agencies specifically needs to galvanize a well-funded global plan and research initiatives to contain the spread of Mpox. In this article, we have attempted to make the readers aware of the biology, etiopathogenesis including the changes at the cellular level the virus is causing, the changing trends of the virus transmission, and the clinical manifestations. We have also attempted to elaborate on the potential challenges and the need for early diagnosis and containment of this Mpox outbreak. This could be achieved by effectieve use of vaccination and taking social safety measures, especially by the communities at risk.
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COVID-19 , Infecções por HIV , Mpox , Feminino , Gravidez , Animais , Masculino , Humanos , Mpox/epidemiologia , Pandemias , Surtos de DoençasRESUMO
The past few decades have witnessed a major leap in knowledge relating to the role of tumor microenvironment (TME) in carcinogenesis and evolving behavior of the tumor. Multiple factors within the TME modulate the cancer cells and the associated therapies. Stephen Paget first asserted that the microenvironment plays an important role in the growth of tumor metastasis. The most important player in the TME is cancer-associated fibroblast (CAF) which significantly participates in the proliferation, invasion, and metastasis of tumor cells. CAFs show phenotypic and functional heterogeneity. Mostly CAFs originate from quiescent resident fibroblast or mesoderm-derived precursor cells (mesenchymal stem cells), although several alternate sources of origin have been noted. However, due to lack of specific fibroblast-restricted markers, it is very difficult to trace lineage and identify the biological origin of distinct subtypes of CAFs. CAFs are predominantly shown by several studies to mainly act as tumor-promoting agents, however, tumor-inhibiting actions are also being validated by several studies. A more objectified and comprehensive functional and phenotypic classification of CAF is required, which will help in better way for tumor management. Here, in this review, we have tried to review the current status of CAF origin, along with phenotypic and functional heterogeneity, and recent progress in CAF research.
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Fibroblastos Associados a Câncer , Neoplasias , Humanos , Fibroblastos Associados a Câncer/patologia , Neoplasias/patologia , Fibroblastos/patologia , Carcinogênese/patologia , Transformação Celular Neoplásica , Microambiente TumoralRESUMO
We describe a case of primary extracranial meningioma of the nasal cavity. FNAC showed loose clusters of epithelioid cells with splayed cytoplasm, focal whorling, and occasional psammoma bodies suggestive of meningioma. This case highlights the importance of FNAC in diagnosing meningioma when encountering similar morphology at a rare location.
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The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to multiple waves of infections globally. As the virus continues to evolve, new variants have emerged, some with concerning changes in transmissibility and virulence. Among these variants, the "FLiRT Variants" have recently gained attention due to their potential to alter the dynamics of transmission and disease severity. According to the Infectious Disease Society of America, the nickname 'FLiRT' is based on the technical names for their mutations. The FLiRT variants, particularly KP.2, seem to exhibit heightened transmissibility in comparison to earlier Omicron sub-variants. Additionally, they demonstrate a capacity to evade immunity conferred by prior infection and vaccines, although the full extent of this evasion is still being investigated. In this article, we review the characteristics of the FLiRT variants, including their genetic mutations, epidemiological features, potential impact on public health measures, and implications for vaccine efficacy. We also discuss strategies for surveillance, prevention, and mitigation efforts to control the spread of this variant and mitigate its impact on global health.
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The much-hyped artificial intelligence (AI) model called ChatGPT developed by Open AI can have great benefits for physicians, especially pathologists, by saving time so that they can use their time for more significant work. Generative AI is a special class of AI model, which uses patterns and structures learned from existing data and can create new data. Utilizing ChatGPT in Pathology offers a multitude of benefits, encompassing the summarization of patient records and its promising prospects in Digital Pathology, as well as its valuable contributions to education and research in this field. However, certain roadblocks need to be dealt like integrating ChatGPT with image analysis which will act as a revolution in the field of pathology by increasing diagnostic accuracy and precision. The challenges with the use of ChatGPT encompass biases from its training data, the need for ample input data, potential risks related to bias and transparency, and the potential adverse outcomes arising from inaccurate content generation. Generation of meaningful insights from the textual information which will be efficient in processing different types of image data, such as medical images, and pathology slides. Due consideration should be given to ethical and legal issues including bias.
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Inteligência Artificial , Humanos , Patologia , Patologia Clínica , Processamento de Imagem Assistida por Computador/métodos , PrevisõesRESUMO
Background: Dysgerminomas constitute around 1-2% of all germ cell tumours. It is very very rare to have dysgerminoma with concurrent pregnancy with an incidence of 0.2-1 per 100,000 pregnancies. It is extremely difficult to conceive with no assisted reproductive interventions and carry it till completion with no complications in a concurrent dysgerminoma. Dysgerminoma has a characteristic specific histomorphology and is easy to diagnose. However, occasionally, syncytiotrophoblastic differentiation can be seen in dysgerminoma although it is a rare histopathological finding. Also, the raised serum B-HCG levels due to the syncytiotrophoblast giant cells seen can lead to a diagnostic dilemma. Clinical presentation: Here we report a case of a 27-year-old 8-week pregnant female who came to the hospital with chief complaints of left-sided abdominal pain and a lump abdomen. Clinical and radiological examination revealed a left ovarian tumour of malignant aetiology with the presence of right ectopic pregnancy. A staging laparotomy with left salpingoophorectomy was performed and sent for histopathological examination. It was reported as dysgerminoma with syncytiotrophoblastic giant cells. The right fallopian tube showed products of conception. Finally, she was planned for adjuvant chemotherapy and serial B-HCG levels. Summary: This case is reported not only just for its rare histopathological finding but also for the diagnostic dilemma it causes both to the surgeon as well as the pathologist. There are various factors which can act as prognosticators such as early suspicion of a tumor, radiological findings, surgery, histopathological examination, and oncology team.
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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with an increased frequency of lymph node metastasis at the time of presentation. Tumour budding, characterised by the presence of a single cell or a small grouping of tumour cells (a cluster containing fewer than five malignant cells) at the invasive front and composition of the fibrotic cancer stroma has been demonstrated to have a growing impact on the behaviour of the solid tumour. However exact role played by them is yet to be defined and a standardized scoring system needs to be incorporated. MATERIAL AND METHODS: A total of 45 histopathologically confirmed cases of HNSCC were included in the study. Hematoxylin and Eosin staining (H&E staining), and immunohistochemistry for CK and alpha-SMA were applied to study the tumour budding and fibrotic cancer stroma in all HNSCC cases. The tumour budding was graded as, Grade 1: 0-4 tumour buds, Grade 2: 5-9 buds and Grade 3: ≥ 10 buds and the nature of fibrotic cancer stroma was categorized as mature, intermediate or immature. RESULTS: Among 45 cases analyzed, well differentiated squamous cell carcinoma (WDSCC; Grade 1) accounted for 42.22% (19 cases), whereas moderately differentiated squamous cell carcinoma (MDSCC; Grade 2) and poorly differentiated squamous cell carcinoma (PDSCC; Grade 3) comprised 48.89% (22 cases) and 8.89% (4 cases) respectively. Tumour budding showed instances of 0-4 buds in 33.3% (Grade 1), 5-9 buds in 48.9% (Grade 2), and ≥ 10 buds in 17.8% of cases. Evaluating tumour stroma, Intermediate stroma led at 51.1%, Mature at 37.8%, and 11.1% displayed Immature stroma. Histologically, < 5 buds were seen in 47.4% of Grade 1 cases, while ≥ 10 buds were in 75.0% of Grade 3 cases, proven statistically significant (p = 0.021). However, an association between T&N Stage and tumour budding lacked significance. WDSCC notably had more mature stroma than MDSCC and PDSCC, whereas MDSCC showed higher rates of intermediate and immature stroma (p < 0.001). Comparatively, no significant correlation existed between fibrotic stroma and tumour budding (p = 0.076). Also, fibrotic stroma was compared with tumour budding, however, no significant correlation was found (p = 0.076) CONCLUSION: This study reveals a significant link between tumour budding, cancer stroma, and WHO tumour grade. Thus, evaluating these factors in HNSCC cases can serve as valuable histological prognostic indicators, aiding in treatment planning and prognosis assessment.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Prognóstico , Diferenciação CelularRESUMO
Vulval fibroadenoma is an extremely rare lesion, mostly seen in young adults. A 51-years-old woman presented with a painless, mobile, and pedunculated vulval mass. Fine-needle aspiration (FNA) was performed and was diagnosed as a benign fibroepithelial lesion possibly fibroadenoma vulva, which was later confirmed as fibroadenoma vulva histopathologically. It is just not rare to find fibroadenoma vulva, but this should also be kept as a differential when diagnosing such cytomorphology in FNA lesions. This is important to avoid unnecessary incisional biopsy before excision.
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Colorectal carcinoma (CRC) is the second most common cancer and third leading cause of cancer-related deaths worldwide. Although the staging system provides a standardized guidance in treatment regimens, the clinical outcome in patients with colon cancer at the same TNM stage may vary dramatically. Thus, for better predictive accuracy, further prognostic and/or predictive markers are required. Patients who underwent curative surgery for colorectal cancer in past 3 years at a tertiary care hospital were retrospectively included in this cohort study to evaluate the prognostic indicators, tumor-stroma ratio (TSR) and tumor budding (TB) on histopathological sections and correlated them with pTNM staging, histopathological grading, tumor size, and lymphovascular and perineural invasion in patients with colo-rectal cancer. TB was strongly associated with advanced stage of the disease along with lympho-vascular and peri-neural invasion and it can be used as an independent adverse prognostic factor. TSR showed a better sensitivity, specificity, PPV and NPV as compared to TB in patients having poorly differentiated adenocarcinoma than those with moderately or well differentiated.
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The COVID-19 pandemic with multiple waves of infection has caused panic and distress globally. Cancer patients being immuno-compromised are more susceptible to infection leading to increased morbidity and unpredictability of their survival. There has been a halt in the diagnosis and treatment of patients suffering from cancer because of the COVID-19 pandemic. Oncologists have the tedious task of assessing the urgency of managing cancer patients against the risk of Coronavirus infection. Timely diagnostic services along with the treatment strategy are needed for the proper management of cancer patients. Since the laboratories are already overwhelmed with the investigations related to the COVID-19 management, there has been a compromise and delay in the diagnosis, thus leading to an overall lag in the management of cancer patients.
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Gout is a chronic arthropathy caused due to the deposition of monosodium urate crystals. Gouty tophus can be the initial presenting feature of gout with or without any clinical symptoms. Demonstration of urate crystals in synovial fluid or biopsy helps in confirming the diagnosis of gout. However, fine-needle aspiration cytology (FNAC) of periarticular soft-tissue nodules is a valuable tool in the diagnosis of gout. We present two such cases of isolated soft-tissue lesions wherein the initial diagnosis of gouty tophus was made on FNAC and subsequently followed by a clinical and biochemical workup.
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Objectives: Cytological examination of effusion sample is a preliminary and minimally invasive method for the diagnosis of body fluids. Recently, the International System For Reporting Serous Fluid Cytopathology (ISRSFC) and the Indian Academy of Cytologist (IAC) have published guidelines for reporting effusion cytology and calculating the risks of malignancy (ROMs) for each defined category. We report our 2 years of experience in reclassifying and assessing the feasibility of applying ISRFSC and IAC categories to effusion fluid and to provide an estimate of the risk of malignancy for each diagnostic category. Material and Methods: Cytological reports of patients from January 2019 to December 2020 were retrieved and reclassified into a five-tiered classification scheme as per ISRSFC guidelines. Cellblock and immunohistochemistry were performed in selected cases. Clinico radiological and histopathological information were obtained and correlated with the cytological findings wherever available. Results: In the study, 652 cases were included during the 2 years. Out of these, 328 (50.3%) were women and 314 (47.3%) were men. Patient's ages ranged between 2 92 years with a mean age of 47.4 years. There were 366 (56.1%) cases of ascitic fluid followed by 262 (40.1%) cases of pleural fluid and 24 (3.8%) cases of pericardial fluid in the analysis. Of all the cases, 13 (2%) were non-diagnostic (ND), 464 (71.6%) were negative for malignant (NFM) cells, 16 (2.4%) were atypia of uncertain significance, 31 (4.7%) were suspicious of malignancy, and 125 (19.3%) were malignant. Cellblock was prepared in 65 cases. Lung cancer followed by breast cancer was the most common malignancies involving the pleural effusion and ovarian cancer was the most common cause of peritoneal effusion. ROM for each diagnostic category was 23% for ND, 25% for NFM, 56% for the atypical category, 80.6% in suspicious, and 90% were for positive for malignancy category. Conclusion: The use of a five-tiered system as per the ISRFC and IAC guidelines are feasible for the standardized reporting of effusion samples, thus avoiding subjective variation of reporting.
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Tubercular infection of the parotid gland often confuses clinicians, it being a rare entity even in an endemic area. Its similarity in presentation with that of parotid neoplasms, nonspecific symptoms, low incidence and non-contributory radiological findings often leads to its misdiagnosis as parotid neoplasm, which in the due course results in parotidectomy. Therefore, FNAC of parotid swelling is helpful to avoid unnecessary surgery and patient discomfort. We report four cases of FNAC of parotid swelling with suspicion of neoplasm/inflammatory lesion and were diagnosed as tuberculosis of the parotid gland. They were advised antitubercular drugs for 6 months and followed up. These case are reported not just to highlight that parotid is a rare site for tuberculosis, but also to ascertain that FNAC can be an easy and fast diagnostic modality for confirmation of tubercular parotitis rather than going through the long way of resection and confirmation on histopathology.
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Neoplasias Parotídeas , Tuberculose , Humanos , Glândula Parótida/patologia , Tuberculose/diagnóstico , Tuberculose/patologia , Neoplasias Parotídeas/patologia , Antituberculosos , Biópsia por Agulha FinaRESUMO
Primary pleomorphic liposarcoma of the breast is a very rare mesenchymal tumor. Sarcoma arising in the breast constitutes <1% of all malignant breast tumors, and liposarcoma of the breast has an incidence of 0.3% of all mammary sarcomas. It is a very aggressive tumor with a high incidence of recurrences and distant metastasis. They can mimic primary invasive breast cancer clinically as well as radiologically. Histology and radiological evaluation of the patient help correctly type and grade this malignancy. On microscopy, the tumor is composed of pleomorphic tumor cells with atypical lipoblast with areas of necrosis and mitosis. We report one such rare case here.
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Epithelioid leiomyosarcoma of the uterus is a rare soft-tissue tumor of the pelvis with <1% cases. It can be asymptomatic or can reach an enormous size, resulting in chronic pelvic pain, postmenopausal bleeding, or may cause bowel and bladder dysfunction. The diagnostic dilemma arises especially when they have epithelioid morphology. This case is being presented because of its rare incidence along with the diagnostic dilemma it presented due to epithelioid morphology which is a very rare presentation, especially challenging on small biopsies. This case also highlights the usefulness of immunohistochemical markers, such as WT1, p53, and p16, which has important diagnostic as well as prognostic values in rare variants of usual tumors. Leiomyosarcoma per se is a highly aggressive tumor, therefore, timely diagnosis and management are advised.
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Myocardial bridging (MB) is a relatively uncommon congenital anomaly where a segment of the coronary artery dips inside the myocardium and takes a tunneled course under a bridge of the myocardium. This leads to the compression of the coronary artery during systole resulting in hemodynamic changes and their clinical manifestations. However, it is an incidental finding but can present with multiple complications like myocardial ischemia, infarction, and sudden death, primarily when associated with other risk factors like left ventricular hypertrophy of the heart. Therefore, a careful examination of the heart is essential for evaluating the clinical significance of the MB. Here, we presented a case of a 30-year-old young female who had a sudden death, and her histological examination of the heart showed MB of left anterior descending coronary artery (LAD).
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Vasos Coronários/patologia , Morte Súbita/etiologia , Ponte Miocárdica/diagnóstico , Miocárdio/patologia , Adulto , Feminino , Técnicas Histológicas , Humanos , Fatores de RiscoRESUMO
With the decrease in severity of COVID-19 there is a sense of relief in the general population. However, there has been an increased incidence of cardiovascular and other organ complications post-infection, which have raised concerns about long COVID. The term "long COVID" was first used by Perego on social media to denote the persistence of symptoms weeks or months after initial SARS-CoV-2 infection and the term 'long haulers' was first described by Watson and by Yong to identify post-COVID conditions. There has been an increased incidence of sudden cardiac death and MI post-COVID-19 in healthy individuals, sports persons and prominent movie stars. Potential mechanisms contributing to the pathophysiology of post-acute COVID-19 may include 1) Damage to tissues and cells that are important for blood flow, so clotting of blood is increased. 2) Persistence of fragments of virus or its sub-particles/ protein material in a wide range of body sites and, 3) an immune system gone haywire. As the majority of countries across the globe are easing coronavirus precautionary measures, there is an urgent need by health care organizations and policymakers worldwide to generate awareness by educating the public at large, about the ill effects of long-COVID and varied types of post-acute sequelae of COVID-19.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicações , Pulmão , Síndrome de COVID-19 Pós-AgudaRESUMO
BACKGROUND: Localized tenosynovial giant cell tumor (GCT) or giant cell tumor of tendon sheath (GCTTS), is a benign nodular lesion that arises from the synovium of the tendon sheath of the hands and foot. GCTTS is characterized by the presence of multinucleated giant cells and proliferation of synovial-like mononuclear cells. A clinical diagnosis of GCTTS is kept as a differential when a firm, nodular mass shows decreased signal intensity on both T1-and T2-weighted MR imaging. Treatment is usually marginal excision of the mass. MATERIAL AND METHODS: It is a retrospective study, observed in the past 3 years at a tertiary care hospital. Those cases were included in the study in which histopathological confirmation was available or if clinico-radiological features were confirmatory of the diagnosis of GCTTS when correlated with cytological features. RESULTS: There was a total of 24 cases, out of which 16 were females and 8 males. The tumor was located in the upper limb in 21 cases and in 3 cases the tumor was present in the lower limb. In the upper limb, 18 cases were on the right side and three cases were on the left side. In the lower limb, 1 case was present on the left and 2 on the right side. The cytomorphology consisted of mononuclear stromal cells, multinucleated giant cells, and hemosiderin-laden macrophages in variable numbers. CONCLUSION: It is important to accurately diagnose and categorize giant cell-containing lesions because their prognosis depends on the exact categorization of the tumor.
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Tumor de Células Gigantes de Bainha Tendinosa , Tumores de Células Gigantes , Masculino , Feminino , Humanos , Estudos Retrospectivos , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico por imagem , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Radiografia , Células Gigantes/patologia , Imageamento por Ressonância Magnética , Tumores de Células Gigantes/diagnóstico por imagem , Tumores de Células Gigantes/patologiaRESUMO
In the current era of COVID-19 pandemic where at least some degree of social distancing is the norm and hospitals have emerged as hotspots for acquiring the infection, it has become important for oncologists to devise methods of providing care to cancer patients while minimizing patients' exposure to healthcare settings. In light of the on-going pandemic, it has been recommended that in-patient visits for cancer patients should be substituted by virtual visits and patients should be advised to proceed directly for infusion treatment. Telemedicine and tele-health based interventions have emerged as reasonably practical solutions to these impediments in the delivery of care to cancer patients. Technological advancements have resolved the issue of connectivity for telemedicine even to the remotest places. Teleconsultation is becoming an acceptable alternative for patients and health care providers in this era of information technology. Albeit the challenges that we are facing are diverse and therefore cannot have a singular full proof answer, telemedicine and tele-health based interventions seem to offer promise in effectively complementing our efforts in that direction. Telemedicine is beneficial for both patients and doctors in term to provide quality care without shifting to physical location.