Fumarate hydratase-deficient renal cell carcinoma: an oncology care institutional experience.

Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)-deficient RCC. FH-deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH-deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo-cytoplasmic expression of S-(2-succino)-cysteine (2-SC), with loss of FH in seven cases. FH-deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2-SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members.

Extradural spinal melanoma: is it primary or metastatic? A case report with a brief review of literature.

Melanocytic lesions involving the central nervous system are extremely rare and pose a diagnostic challenge owing melanoma being the third most common malignancy metastasizing to the spine. Morphology and immunohistochemistry are identical in both primary and secondary cases, and hence may not help in rendering a final diagnosis. Molecular alterations involving melanomas of the spine and melanomas elsewhere are distinct and help establish the appropriate diagnosis. We report an interesting case where molecular profiling of the tumor tissue helped render the final diagnosis.

Diagnostic utility of LMO2 immunohistochemistry in distinguishing T-lymphoblastic leukemia/lymphoma from thymoma.

Distinguishing T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) from thymomas (especially B1 or B2 type) can be challenging particularly in limited trucut biopsy material where appreciating architecture is difficult or the background epithelial component does not provide tangible evidence for definite diagnosis. As a pathologist, it is important to accurately diagnose these neoplasms because they have entirely distinct management protocols. Recent studies have reported that LIM Domain Only 2 (LMO2) is expressed in neoplastic lymphoblasts of T-ALL/T-LBL and is absent in thymocytes of normal thymuses or thymomas. An observational study was done to test the sensitivity and specificity of LMO2 in differentiating neoplastic lymphoblasts from thymocytes of thymomas/normal thymuses. Our study showed that LMO2 had sensitivity of 70% and specificity of 100% in diagnosing LBL. None of the thymomas (B1 or B2 type) showed expression of LMO2 in the neoplastic cells. LMO2 is a reliable marker of transformed T-cell precursors and should be routinely included in immunohistochemical panel when evaluating thymic/mediastinal neoplasms.

FH deficient uterine leiomyomas-a case series.

Introduction: Fumarate hydratase (FH) deficient uterine leiomyomas account for only 0.4 % of all uterine leiomyomas. They are characterized by some distinct histological features and may be associated with Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Methods: Herein we present a series of five cases of FH deficient uterine leiomyomas in patients with a mean age of 30 years. All five patients underwent myomectomy. Three of these cases had an outside histopathologic diagnosis ranging from Smooth muscle tumor of uncertain malignant potential (STUMP) to Leiomyosarcoma while two cases were operated at our centre. All five cases were reported as suggestive of FH deficient leiomyomas and were advised germline testing along with genetic counselling. Results: Immunohistochemically four of the cases showed moderate to strong positivity for 2-SC with a complete loss or reduced expression of FH while one case showed absence of 2-SC staining. Discussion: Mutations in FH lead to reduced enzyme activity and accumulation of fumarate leading to a complete loss or aberrant reduced expression seen on immunohistochemistry, which confirms the diagnosis. It is important to differentiate it from a leiomyosarcoma or other malignant spindle cell tumors as these tumors follow a benign course. Their association with HLRCC also needs to be established for a suitable follow up since HLRCC-associated RCCs are often aggressive. Conclusion: Management of such leiomyomas is myomectomy or hysterectomy with advice of genetic testing to rule out HLRCC. Histomorphology and immunohistochemistry are imperative for a correct and timely diagnosis.

Primary pulmonary NUT midline carcinoma: An elusive and a rare diagnostic entity.

Nuclear protein in testis (NUT) midline carcinoma is a poorly differentiated tumor, is more common in midline anatomic sites, and involves young adults and children mainly. Primary pulmonary NUT midline carcinoma (NMC) is a rare and poorly defined entity in the prevailing literature. Being a highly aggressive and fatal neoplasm, it gets incumbent for the oncologists and the pathologists to be aware of this entity as it holds distinct management protocol and prognosis. Currently, BET inhibitors (BETi) and histone deactylase inhibitors have shown promising results as targeted therapies in clinical trials in head and neck NMC. We present a case report of NMC of primary pulmonary location in a young male with widespread bony metastasis.

A review on fake news detection 3T's: typology, time of detection, taxonomies.

Fake news has become an industry on its own, where users paid to write fake news and create clickbait content to allure the audience. Apparently, the detection of fake news is a crucial problem and several studies have proposed machine-learning-based techniques to combat fake news. Existing surveys present the review of proposed solutions, while this survey presents several aspects that are required to be considered before designing an effective solution. To this aim, we provide a comprehensive overview of false news detection. The survey presents (1) a clarity to problem definition by explaining different types of false information (like fake news, rumor, clickbait, satire, and hoax) with real-life examples, (2) a list of actors involved in spreading false information, (3) actions taken by service providers, (4) a list of publicly available datasets for fake news in three different formats, i.e., texts, images, and videos, (5) a novel three-phase detection model based on the time of detection, (6) four different taxonomies to classify research based on new-fangled viewpoints in order to provide a succinct roadmap for future, and (7) key bibliometric indicators. In a nutshell, the survey focuses on three key aspects represented as the three T's: Typology of false information, Time of detection, and Taxonomies to classify research. Finally, by reviewing and summarizing several studies on fake news, we outline some potential research directions.

Intrathyroidal Plasmacytoma with Pleomorphic Multilobated Bizarre Cells: A Rare Primary Clinicopathological Presentation Mimicking Anaplastic Carcinoma of Thyroid.

BACKGROUND: Plasmacytoma involving thyroid gland is infrequent and can present as either primary extramedullary plasmacytoma or secondary to multiple myeloma. METHODS AND RESULTS: We present a case of 71 years old male who complained of a huge anterior neck swelling accompanied by dysphagia and dyspnoea. Fine needle aspiration cytology was suggestive of anaplastic carcinoma of thyroid (ATC), however, the subsequent histomorphology supported by immunohistochemistry (IHC) astoundingly favoured the diagnosis of plasmacytoma. Further evaluation revealed the presence of lymphadenopathy and single bone lesion in the present case which was rather suggestive of secondary involvement of thyroid to multiple myeloma. However, the case was unique in view of its presentation as a rapidly enlarging thyroid mass associated with stridor and cytomorphological findings which were of an undifferentiated malignancy favouring ATC. The use of a broad and judicious IHC panel clinched the final diagnosis of plasmacytoma. CONCLUSION: The present case emphasizes the diligent use of IHC in such cases given different therapeutic and prognostic implications.

Disinformation detection on social media: An integrated approach.

The emergence of social media platforms has amplified the dissemination of false information in various forms. Social media gives rise to virtual societies by providing freedom of expression to users in a democracy. Due to the presence of echo chambers on social media, social science studies play a vital role in the spread of false news. To this aim, we provide a comprehensive framework that is adapted from several scholarly studies. The framework is capable of detecting information into various types, namely real, disinformation and satire based on authenticity as well as intention. The process highlights the use of interdisciplinary approaches derived from fundamental theories of social science and integrating them with modern computational tools and techniques. Few of these theories claim that malicious users suggest writing fabricated content in a different style to attract the audience. Style-based methods evaluate the intention i.e., the content is written with an intent to mislead the audience or not. However, the writing style can be deceptive. Thus, it is important to involve user-oriented social information to improve model strength. Therefore, the paper used an integrated approach by combining style based and propagation-based features with a total of thirty-one features. The extracted features are divided into ten categories: relative frequency, quantity, complexity, uncertainty, sentiment, subjectivity, diversity, informality, additional, and popularity. The features have been iteratively utilized by supervised classifiers and then selected the best-correlated ones using the ANOVA test. Our experimental results have shown that the selected features are able to distinguish real from disinformation and satirical news. It has been observed that the Ensemble machine learning model outperformed other models over the developed multi-labelled corpus.

Epithelioid haemangioma of bone: A series of four cases with a revision of this contentious entity.

Epithelioid hemangioma of bone is a rare and locally aggressive vascular neoplasm of bone associated with a good prognosis. Because of its worrisome histomorphologic features and aggressive clinicoradiologic findings, at times with multifocal presentation, they tend to simulate malignant tumors. We report a series of four cases of epithelioid hemangioma of bone with their clinicopathologic characteristics. All had adjacent soft tissue involvement and two had multifocal bone disease. Microscopically, all cases had a tumor in lobular configuration, composed of epithelioid endothelial cells with the formation of well-formed vessels or grew in solid sheets. The tumor cells lacked significant cytologic atypia, necrosis, and increased mitosis. All cases were immunohistochemically positive for vascular markers CD34, CD31, ERG1, whereas negative for CK. Two of the cases were treated with excision, and the other two underwent curettage. None had local recurrence or metastasis on follow-up. This study highlights the importance of recognizing histomorphological and clinicoradiological features for distinguishing epithelioid hemangiomas from malignant vascular neoplasms of bone because of their distinct therapeutic implications and clinical outcomes.

TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma.

SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non-small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.

Adenoid Cystic Carcinoma of the Nasopharynx-a Rare Entity: Our Institutional Experience and Therapeutic Approach.

Adenoid cystic carcinoma of the nasopharynx is a rare, slow growing, and locally aggressive neoplasm. Three cases presented with recurrent epistaxis. Endoscopy-guided biopsy proved the diagnosis of adenoid cystic carcinoma. The location and the extent of the tumor were confirmed on imaging. Surgery followed by radiation therapy was the treatment modality used. All three cases showed good clinical response. The aim is to discuss the surgical approach and review of literature concerning this malignancy.

SMARCA4/BRG1 protein-deficient thoracic tumors dictate re-examination of small biopsy reporting in non-small cell lung cancer.

BACKGROUND: SMARCA4/BRG1 protein-deficient lung adenocarcinomas and thoracic sarcoma are recently described entities that lack distinctive histological features, transcription termination factor 1 (TTF1) reactivity, and actionable driver mutations. The current diagnostic path for small lung biopsies as recommended by the World Health Organization (WHO, 2015) is likely to categorize these as non- small cell carcinoma-not otherwise specified (NSCC-NOS). The present study attempts to define the subtle but distinctive clinicopathologic features of SMARCA4/BRG1 protein-deficient thoracic tumors; highlight their unique biology; and addresses the unmet need to segregate these using a new, tissue-proficient diagnostic pathway. METHODS: All lung biopsies and those from metastatic sites in patients with suspected advanced lung cancer and classified as NSCC-NOS as per WHO (2015) guidelines were subjected to BRG1 testing by immunohistochemistry. SMARCA4/BRG1 protein-deficient thoracic tumors were evaluated by an extended immunohistochemistry panel. Predictive biomarker and programmed death-ligand 1 testing was conducted in all cases. RESULTS: Of 110 cases, nine were found to be SMARCA4/BRG1 protein-deficient; six were identified as SMARCA4/BRG1 protein-deficient lung adenocarcinomas, and three were SMARCA4/BRG1 protein-deficient thoracic sarcomas. The histology ranged from poorly differentiated to undifferentiated to rhabdoid. None of the cases showed significant expression of TTF1 or p40, and no actionable mutation was identified. CONCLUSIONS: It is difficult to separate BRG1-deficient lung adenocarcinomas and thoracic sarcomas based on morphology alone. We propose a diagnostic pathway for small biopsies of thoracic tumors to segregate these distinct entities so that they can be studied more efficaciously for new biomarkers and therapeutic options.

Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies.

BACKGROUND: Data on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce. OBJECTIVE: To study 14-day mortality in patients who received CPT. PATIENTS & METHODS: Retrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed. RESULTS: The median age of the study cohort was 62 years (18-80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2-25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy. CONCLUSIONS: We provide a large series of patients with hematological malignancies and role of CPT in this group.

Hepatoid adenocarcinoma of lung: A diagnostic challenge - Series of six cases with histopathological, predictive molecular and PD.L1 assessment.

Hepatoid adenocarcinoma of lung is a rare entity, accounting for 5% of all hepatoid adenocarcinoma. Distinguishing it from metastatic hepatocellular carcinoma is essential, but occasionally can be very challenging, especially with concurrent liver mass. A judicious immunohistochemical panel is warranted for accurate diagnosis and subsequent preservation of tissue for molecular testing. There is limited data on the mutational status, behavior and management strategies of this type of lung adenocarcinoma. We report largest series of six cases of hepatoid adenocarcinoma of lung citing the clinical, histopathological, immunohistochemical and molecular parameters including PD-L1 immunoexpression as a predictive biomarker for immunotherapy. None of the evaluated cases showed targetable mutation; however, four out of six cases showed significant PD-L1 expression. All the cases presented with advanced stage and received chemotherapy, however overall prognosis was dismal. In view of significant PD-L1 expression in these tumors and poor response to conventional chemotherapy, these cases might be considered for upfront immunotherapy.

Metastatic low-grade myoepithelial carcinoma of lung managed with low-dose external beam radiotherapy.

Myoepithelial tumor of lung is a rare tumor; the histopathological findings resemble the myoepithelial tumors of the salivary gland. Distinguishing low-grade nonmetastatic myoepithelial carcinoma from benign myoepithelioma can be challenging both radiologically and histomorphologically. We present a case report of a low-grade myoepithelial carcinoma of lung with contralateral lung metastasis which was treated with low-dose external beam radiotherapy.

Effect of age, comorbidity and remission status on outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. METHODS: Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. RESULTS: Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7-49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age < 60 years (p = 0.05). CONCLUSIONS: Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.

Peripheral Blood and Bone Marrow Findings in Chronic Alcoholics with Special Reference to Acquired Sideroblastic Anemia.

Anemia associated with alcoholism has numerous causes, most common being megaloblastic anemia and acquired sideroblastic anemia (SA). The bone marrow aspirate (BMA) and bone marrow iron (BMIr) findings and their correlation with peripheral blood smear (PBS) have not been extensively described in literature. We aim to study the spectrum of hematological abnormalities in chronic alcoholics. Complete blood count (CBC), PBS, BMA and BMIr of 71 chronic alcoholics were studied retrospectively over a period of 3 years. The slides were reviewed by 2 pathologists. The clinical history, CBC, PBS, BMA and BMIr findings were recorded. Out of 71 patients, 68 (95.77%) had anaemia. Red cell morphology varied from normocytic-normochromic, microcytic-hypochromic, macrocytic, to dimorphic anaemia. Principal findings seen on BMA were erythroid hyperplasia and megaloblastic maturation. BMIr was available in 41 patients; iron stores were decreased in 2 (4.88%), normal in 14 (34.15%), increased in 25 (60.97%). Seven (17.07%) cases showed presence of ring sideroblasts. Chronic alcoholics show a variety of abnormalities in BMA, which closely mimic many haematological disorders. A history of alcoholism should always be taken in these circumstances. SA should be ruled out in all chronic alcoholics with anaemia not responding to vitamin B12/folic acid, even with macrocytic picture on PBS.