Paradigm shift in the management of metastatic nonsmall cell lung cancer.

BACKGROUND: Lung cancer is one of the leading causes of cancer mortality in the United States. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced nonsmall cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations and patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. AIMS: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. MATERIALS AND METHODS: A literature search was conducted on Medline (via PubMed) and National Comprehensive Cancer Network Guidelines using the keywords "precision diagnosis," "advanced non-small cell lung cancer," "target therapies," and "immunotherapy." CONCLUSION: The use of next-generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune checkpoint inhibitors (ICI) leading to better survival rates and lesser toxicity.

Pericarditis Induced by Methotrexate: A Case Report and Literature Review.

Methotrexate (MTX) is a crucial part of the management of rheumatoid arthritis (RA). Although MTX is generally well tolerated, it is not exempt from adverse effects. The side effects of MTX are diverse, and pericarditis, as demonstrated in our case, is one of the rarest adverse effects. Therefore, it is crucial to rule out common causes of pericarditis, such as infections, malignancies, or other underlying conditions. However, once common causes are excluded, MTX-induced pericarditis should always be considered, and MTX should be discontinued without resumption due to potential relapse. Furthermore, the timing of MTX initiation is not significant; patients may have been on chronic MTX treatment or have recently started it. Moreover, pericarditis secondary to MTX is not exclusive to patients with rheumatological conditions but can also occur in other conditions.

Presentation of Colorectal Carcinoma as Abdominal Wall Phlegmon.

Colorectal cancer (CRC) is the third most common malignancy and the second most common deadly cancer worldwide as of 2020. Unusual presentation of this cancer with locally advanced disease is rare and seen in only 5% to 22% of cases. We present the case of a 53-year-old male who had invasive cecal adenocarcinoma with phlegmon of the abdominal wall musculature at presentation and an aggressive course that did not respond to the standard lines of therapy. In the current era of ongoing tremendous developments in colorectal cancer diagnosis and treatment, this uncommon case reminds us that locally advanced CRC is still a challenge to manage. Precision medicine with treatment strategies tailored to an individual's genetic, environmental and lifestyle factors is the current need.

A Successfully Treated COVID-19 Vaccine Induced Immune Thrombocytopenic Purpura.

Immune Thrombocytopenic Purpura (ITP) is a life-threatening condition where an accurate initial assessment is essential to be able to offer the proper therapy in a timely matter to improve the outcome of the patient. Here, we present a case of ITP secondary to the coronavirus disease 2019 (COVID-19) vaccine (BioNTech, Pfizer vaccine). A 61-year-old obese African American female presented to the emergency room (ER) from a clinic with a platelet count of 11k/ul 21 days after she received the second dose of the BioNTech, Pfizer vaccine. The patient was immediately started on intravenous immunoglobulin (IVIG) 1g/kg twice daily (bid) and dexamethasone 20 mg IV every 12 hrs (q12h). The next day, the platelet count increased to 63 k/ul, and after the second dose of IVIG, the platelet count improved to 122 k/ul and trended up. The early detection of ITP induced by the mRNA COVID-19 vaccine is determinant to guide the early and proper therapy with immunoglobulins and steroids to improve the outcome of our patients.

Lymphoplasmacytic Lymphoma with Only Lambda Light Chain Monoclonal Paraprotein Expression.

Introduction: Lymphoplasmacytic lymphoma (LPL) is a rare low-grade B-cell neoplasm that accounts for approximately 2% of all haematological malignancies. Most patients have the clinical syndrome of Waldenstrom macroglobulinemia (WM), which is defined as LPL with an associated immunoglobulin M (IgM) serum monoclonal protein. Roughly 5% of LPL patients secrete non-IgM paraproteins (e.g., IgG, IgA, kappa, lambda) or are non-secretory. Case description: We report the case of a 41-year-old woman who was diagnosed with non-IgM LPL with lambda light chain monoclonal paraprotein production and normal serum immunoglobulin levels. The MYD88 L265P mutation was detected on fluorescence in-situ hybridization (FISH) analysis of the bone marrow. The patient underwent treatment with a combination of ibrutinib and rituximab. There was an initial response but she died 8 months after diagnosis. Discussion: Non-IgM LPL poses diagnostic and therapeutic challenges to clinicians as it is an exceptionally rare malignancy with a heterogeneous clinicopathological presentation and scarce literature. Among non-IgM LPL cases, those with lambda light chain production are even more rare. To the best of our knowledge, none have been reported to date. The addition of MYD88 L265P testing to the diagnostic armamentarium of non-IgM LPL cases is advisable for potential therapeutic reasons. LEARNING POINTS: Our case report and literature review provide insight into non-IgM lymphoplasmacytic lymphoma (LPL), an extremely rare malignancy.Our case report highlights the importance of the need for new treatments for non-IgM LPL.

Vaginal Malignant Melanoma: Case Report and Review of the Literature.

Introduction: Primary vaginal malignant melanomas are rare tumours with a limited number of cases published in the literature. They primarily affect post-menopausal women with a median age of 57-68 years and have a dismal prognosis. The 5-year survival rate, regardless of treatment, is approximately 5-25%. Case description: We present the case of an 87-year-old female who presented with haematuria and urinary incontinence. She was diagnosed with AJCC stage IIIC vaginal melanoma. Considering her age and the extent of malignancy, surgery was not a viable option and immunotherapy with nivolumab and ipilimumab was initiated as treatment. Discussion: The diagnosis of vaginal melanomas includes pathological analysis and immunohistochemistry (IHC) of the mass, imaging to determine extent, and genetic testing. Surgery is the preferred treatment in suitable cases. For metastatic or unresectable cases, immunotherapy or targeted therapy is the preferred first-line treatment. Due to the lack of an adequate number of cases to conduct randomized clinical trials, prognostic factors and treatment protocols for vaginal melanomas are not clearly defined. At present, the management of these tumours is largely based on retrospective studies and anecdotal evidence accompanied by significant knowledge gaps. Our case will be a valuable addition to the existing literature on vaginal melanomas that are managed non-surgically. LEARNING POINTS: Vaginal melanomas are extremely rare entities that require early diagnosis to ensure the best prognosis.Providers need to stress the importance of elderly gynaecological examination so crucial diagnoses are not missed.Further research is necessary to develop the most effective treatment plan for vaginal melanomas.

Apical lung mass-A rare presentation of multiple myeloma.

Multiple myeloma is a neoplastic proliferation of immunoglobulin-producing plasma cells with clinical features resulting from infiltration of plasma cells into bones and other organs. Multiple myeloma manifesting as an apical lung mass is less common and very few cases have been reported. We report the case of a 50-year-old female who presented with an apical lung mass which happened to be multiple myeloma arising from the upper ribs into the lung. At the time of diagnosis, patient had axillary lymph node metastasis with extensive bony involvement. This case report and literature review provides insight to a rare but significant presentation of multiple myeloma and highlights the need to consider multiple myeloma as a possible differential for Pancoast tumor in the appropriate clinical setting as this could potentially affect management options and patient outcome.

Ovarian Vein Thrombosis Can Be a Complication of Hysteroscopy.

Ovarian vein thrombosis is not well understood, and there is no consensus regarding treatment. It can present with subtle symptoms and is not usually high on the list of differentials. Traditionally, most cases are linked to pregnancy and postpartum state, but our case adds to the growing list of non-puerperal patients diagnosed with ovarian vein thrombosis after an outpatient procedure. In an era where there is a drive for minimally invasive procedures and shorter hospital stays, there is a need to have specific guidelines to direct the diagnosis and treatment of this rare form of thromboembolism.

A Case of Systemic Toxicity Related to Intravesical Bacillus Calmette-Guerin for the Treatment of Bladder Cancer.

Intravesical administration of Bacillus Calmette-Guerin (BCG) has been utilized for the treatment of superficial bladder cancer for the past several decades. Though this treatment is well tolerated in general, both local and systematic side effects have been reported. We present a case of a patient who presented with systemic symptoms of fever with chills associated with leucopenia, thrombocytopenia, abnormal liver function tests (LFTs), and splenomegaly a few weeks after an episode of traumatic instillation of intravesical BCG. Though the mycobacterial cultures were negative, he was started on an anti-mycobacterial regimen empirically to which he responded and ultimately fully recovered.

The use of direct acting oral anticoagulants in patients with COVID-19 infection.

The use of direct-acting oral anticoagulants (DOACs) has increased rapidly in the last decade; becoming the mainstay for both the prophylaxis and the treatment of venous thromboembolism in various situations including non-valvular atrial fibrillation, joint replacement surgeries and acute DVT/PE, etc. In the present times, DOACs are possibly one of the most widely prescribed medications in the developed world. The worldwide epidemic caused by COVID-19 caused significant changes in the practice of medicine worldwide. Patients who developed severe respiratory illness caused by COVID-19 were noted to develop a wide range of complications, including both arterial and venous thromboembolic complications including deep vein thrombosis and pulmonary embolism, etc. This review is an attempt to identify the role of DOACs in the treatment and prevention of these complications as well as the safety of continuing therapy with DOACs in the patients who were receiving them before contracting the infection.

Survival Disparities of Diffuse Large B-Cell Lymphoma in a Community-Based Inner-City Cancer Center.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) comprises approximately 30% of all non-Hodgkin lymphomas. Multiple studies have demonstrated race-based disparities in survival among patients with DLBCL across all stages of disease, in the era both before and after rituximab. The etiology for the racial disparities in survival among patients with DLBCL is still unknown. Moreover, the Revised International Prognostic Index (R-IPI), a tool that predicts the DLBCL patients' outcome, has not yet been validated in African Americans (AA). PATIENTS AND METHODS: We conducted a cohort study of patients diagnosed with DLBCL from January 1, 2007, to December 31, 2017, from our tumor registry in a single community-based inner-city cancer center. We abstracted demographic, clinical, histopathologic, treatment, and R-IPI variables. A total of 181 patients (47.5%) with biopsy-proven DLBCL were included in the retrospective analysis. The median age was 65 years, 47% were men, 41% were AA, and 44% were white. RESULTS: The AA group had a younger median age, higher lactate dehydrogenase levels, higher frequency of B symptoms, and higher HIV infection than the non-AA group. The AA group had significantly decreased median overall survival than the non-AA group (15.7 months; 95% confidence interval, 10.3 to 23.9, vs. 93.6 months; 95% confidence interval, 61.5 to 142.6, respectively; P < .001). The survival disparities persisted after excluding patients with HIV and who did not receive chemotherapy. In addition, AA race predicts a reduced survival by univariate and multivariate analysis. CONCLUSION: AA with DLBCL may have a poorer prognosis than the non-AA population. Further studies should investigate the biology of DLBCL in the AA population.

Usage of Direct Acting Oral Anticoagulants in Cirrhotic and Non-Cirrhotic Portal Vein Thrombosis: A Systematic Review.

Thrombosis of the portal vein (PVT) is generally seen in the setting of liver cirrhosis and to a lesser extent in the absence of cirrhosis. There is no clear guidance in relation to approaching treatment with anticoagulation in this condition. The professional societies and guidelines recommend treatment with traditional anticoagulation like low-molecular-weight heparin and vitamin-K antagonists in patients presenting with acute portal vein thrombosis. There is no clarity in relation to treatment in the setting of chronic PVT and in patients with cirrhosis. Also, the role of direct-acting oral anticoagulants (DOACs) that are becoming a preferred choice for anticoagulation for various other indications is not clear in the case of PVT. There are a very few studies in the medical literature that have investigated the role of DOACs in patients with PVT in different settings. Thus, we performed a systematic review of the literature to study the use of DOACs in PVT in patients with and without cirrhosis. The results of the available studies show that DOACS appears to be a promising choice for the treatment of patients with PVT. The availability of more data in the future along with better availability of the approved reversal agents for various DOACs is expected to make DOACS a preferred choice for the clinicians to treat patients with PVT.

Coronavirus Disease 2019 and Cold Agglutinin Syndrome: An Interesting Case.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. While patients with COVID-19 most frequently present with pneumonia, respiratory failure and acute respiratory distress syndrome, increasing cases of immune-mediated disorders such as autoimmune thrombocytopenia, haemolytic anaemia and antiphospholipid syndrome have been reported. In this article we describe a rare case of cold agglutinin syndrome (CAS) in a patient with COVID-19. The patient was a 77-year-old man with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency who presented with COVID-19 infection and acute respiratory failure. Initially he was started on intravenous steroids, antibiotics and hydroxychloroquine. Laboratory analysis revealed haemolytic anaemia with a positive direct anti-globulin test (DAT) and high titres of cold agglutinins. Hydroxychloroquine was stopped due to suspicion of haemolysis due to G6PD deficiency but the haemolysis persisted. Unfortunately, the respiratory failure progressed and the patient died. In summary, this article describes a rare case of CAS associated with COVID-19. CAS is a heterogenous group of cold autoimmune haemolytic anaemias occurring secondary to infections or malignancies. No definite treatment for CAS in COVID-19 patients has been approved so far. LEARNING POINTS: Autoimmune haemolytic anaemia has been reported in COVID-19 patients.Cold agglutinin syndrome (CAS) can occur in patients with COVID-19.Efforts to determine the optimal management of CAS in COVID-19 patients must continue.

B7-H3 and PD-L1 Expression Are Prognostic Biomarkers in a Multi-racial Cohort of Patients with Colorectal Cancer.

BACKGROUND: Immunotherapy has emerged as an effective and durable treatment modality for solid cancers. However, its use in colorectal cancer (CRC) is limited to deficient mismatch repair (dMMR) tumors. As such, assessing immune regulatory proteins from the B7-CD28 family, other than PD-1, PD-L1, and CTLA-4, is critical. This study aimed to evaluate the expression of novel protein regulators in a racially diverse population of patients with CRC. METHODS: A tumor microarray was created for 214 samples from a multiracial patient population with metastatic CRC, and expression of HHLA2, B7-H3, PD-L1, CK7, CK20, and CDX2 was determined. The expression pattern was scored as 0 to 12, based on tumor tissue prevalence and the intensity. Clinical information was obtained by chart review and vital statistics from the National Death Index. Associations between low and high expression groups for each protein by race/ethnic groups were assessed, and Kaplan-Meier curves were plotted to evaluate association with survival. RESULTS: The median age at diagnosis was 61 years, with a female predominance. The majority of the patients were diagnosed with de novo metastatic disease with left-sided, moderately differentiated tumors. There were no racial disparities in the expression of any protein. Overall, a high frequency of tumors had no expression of B7-H3 (62.5%) or PD-L1 (43.5%). Low expression of both PD-L1 and B7-H3 was a significant prognostic biomarker associated with better survival (median overall survival, 43.3 months vs. 24.6 months; P < .01). CONCLUSION: In this multiracial tumor microarray of CRC samples, low PD-L1 and B7-H3 expression was associated with an improved prognosis. There was no significant variation among races with respect to the relevant CRC protein markers.

Case Report: IgG multiple myeloma and chronic myeloid leukemia in a single patient.

A 58-year-old man presented with recurrence of chronic myeloid leukemia (CML) after complete molecular remission in the setting of non-compliance with imatinib. He was restarted on imatinib and was also noted to have IgG kappa monoclonal gammopathy of undetermined significance (MGUS). The patient re-achieved molecular remission after resumption of imatinib, but his MGUS progressed to smoldering myeloma and he was eventually diagnosed with multiple myeloma (MM) and initiated on treatment for MM with thalidomide, bortezomib and dexamethasone. He has responded well to treatment of the myeloma and continues concurrent maintenance imatinib treatment for CML and is being evaluated for bone marrow transplant. The association of two concurrent hematological malignancies, CML and MM, is very rare and has been infrequently reported in literature. The pathophysiology of this has not yet been fully understood. This case report reviews the various theories to explain this and discusses the potential challenges of simultaneous treatment of MM and CML.

Incidental early diagnosis of biphasic pulmonary blastoma in a patient with history of stage IV lung adenocarcinoma.

Biphasic pulmonary blastoma is a rare but lethal type of lung malignancy with characteristic histology of both epithelial and mesenchymal components. Previously reported cases have been limited to presentation at advanced stages, suggesting that the clinical course of the disease is usually aggressive. Here, we report a case of incidental diagnosis of biphasic pulmonary blastoma by imaging surveillance in a patient previously treated for adenocarcinoma of the lung. The patient was diagnosed with stage 1 disease and underwent successful resection. Next-generation sequencing (NGS) revealed a high mutation burden, a finding not previously reported in a patient with biphasic pulmonary blastoma.

Evolving Paradigms in the Management and Outcomes of Sarcomatoid Renal Cell Carcinoma in the Era of Immune Checkpoint Inhibitors.

Renal cell carcinoma (RCC) is a common cancer that affects a significant number of patients every year around the world. The presence of sarcomatoid features in these tumors is considered a poor prognostic feature. Patients with RCC with sarcomatoid features had significantly worse outcomes when treated with sunitinib, the previous first-line standard of care therapy when compared to patients without such features. Multiple immune checkpoint inhibitors have recently been approved for the treatment of RCC. In this article, we review the literature available on the outcomes of patients with sarcomatoid RCC treated with immune checkpoint inhibitors.

Clinical Advancement and Challenges of ex vivo Expansion of Human Cord Blood Cells.

Apart from peripheral blood stem cell (PBSC), umbilical cord blood (UCB) is now a recognized source of stem cells for transplantation. UCB is an especially important source of stem cells for minority populations, which would otherwise be unable to find appropriately matched adult donors. UCB has fewer mature T lymphocytes compared with peripheral blood, thus making a UCB transplantation (UCBT) with a greater degree of HLA mismatch possible. The limited cell dose per UCB sample is however associated with delayed engraftment and a higher risk of graft failure, especially in adult recipients. This lower cell dose can be optimized by performing double unit UCBT, ex vivo UCB expansion prior to transplant and enhancement of the capabilities of the stem cells to home to the bone marrow. UCB contains naïve and immature T cells, thus posing significant challenges with increased risk of infections, graft versus host diseases (GVHD) and relapse following UCBT. Cell engineering techniques have been developed to circumnavigate the immaturity of the T cells, and include virus-specific cytotoxic T cells (VSTs), T cells transduced with disease-specific chimeric antigen receptor (CAR T cells) and regulatory T cell (Tregs) engineering. In this article, we review the advances in UCB ex vivo expansion and engineering to improve engraftment and reduce complications. As further research continues to find ways to overcome the current challenges, outcomes from UCBT will likely improve.

Case Report: Heparin-induced thrombocytopenia in a patient with COVID-19.

With the spread of the novel coronavirus disease of 2019 (COVID-19) worldwide and associated high incidence of thromboembolic complications, the use of heparin is on the rise. It therefore is crucial to identify patients with contraindications for heparin. Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin. We report a 66-year-old woman, who was admitted to the hospital with COVID-19 infection. Her course was complicated by pulmonary embolism and dialysis catheter thrombosis. Our patient had a known history of HIT. Treatment of this patient with heparin would have been catastrophic. The COVID-19 pandemic has overwhelmed healthcare systems and is causing a global health crisis. Nevertheless, this case serves as a reminder of the importance of making every effort to obtain thorough history and review of records of every patient.