Metastatic Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans With Lung Metastasis: A Case Report.

Dermatofibrosarcoma protuberans (DFSP) is a low- to intermediate-grade dermal soft tissue malignant tumor (sarcoma) with a high local recurrence rate but low metastatic potential. DFSP is characterized by uniform spindle cell fascicles arranged classically in a storiform pattern and by CD34 immunoreactivity. On gross examination, DFSP usually manifests as a white or yellow soft tissue mass with a smooth outer surface and poor circumscription. In this study, we report a case of DFSP with fibrosarcomatous transformation, a rare but well-known phenomenon encountered in DFSP that is correlated with an increased risk of adverse outcomes in patients with DFSP. A 45-year-old male presented with a progressively enlarging lump on his left shoulder, initially suspected of being a lipoma but diagnosed as a fibrosarcomatous transformation of DFSP. Surgical resection was performed, with the subsequent identification of metastatic sarcoma in pulmonary nodules. Robotic-assisted thoracoscopy excised the nodules, confirming metastatic sarcoma with aggressive behavior. Despite negative adjuvant treatment plans, the patient remains under surveillance with imaging, showing no recurrence in recent scans. Continued follow-up with medical and surgical oncology is planned. DFSP is a rare soft tissue sarcoma characterized by indolent growth and low metastatic potential, except in fibrosarcomatous transformation cases. Molecularly, DFSP is defined by a COL1A1-PDGFB fusion transcript that is targetable with imatinib therapy. Treatment involves wide surgical resection, with adjuvant radiation therapy in select cases. Radiation therapy may be employed in cases with close or positive margins, while conventional chemotherapy has limited utility. Multidisciplinary collaboration is crucial for optimal management. Overall, this case underscores the challenges in diagnosing and managing aggressive sarcomas like fibrosarcomatous DFSP, emphasizing the importance of vigilant surveillance and multidisciplinary collaboration in optimizing patient outcomes. Further research is needed to understand the mechanisms underlying fibrosarcomatous transformation and to explore novel therapeutic avenues for this challenging malignancy.

COVID-Induced Thrombotic Thrombocytopenic Purpura: A Case Report and Treatment-Focused Review.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease that is part of a vast spectrum of thrombotic microangiopathies (TMAs). Despite the rarity of TTP, clinicians must maintain a high suspicion of this disease. The condition is characterized by fever, low platelets, hemolytic anemia, renal abnormalities, and neurological dysfunction. However, all these symptoms are not necessarily present in all the patients. In this review, we describe a case of a 51-year-old female who presented to the emergency department (ED) with chief complaints of dizziness and lightheadedness, subsequently leading to a diagnosis of TTP, caused as a result of COVID-19. This review raises awareness so that there is early recognition of any hematological manifestations associated with COVID-19, reducing the morbidity and mortality associated with the disease. Due to the unpredictability of COVID-19 and its complications, robust research is needed to understand the mechanism and determine which patients are more at risk for adverse outcomes.

A Meta-Analysis of Randomized Clinical Trials Assessing the Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to better characterize the progression-free survival (PFS) and overall survival (OS) in metastatic CRPC patients treated with PARPis. A systemic review search was conducted using National Clinical Trial (NCT), PubMed, Embase, Scopus, and Central Cochrane Registry. The improvement in overall survival was statistically significant, favoring PARPis (hazard ratio (HR) 0.855; 95% confidence interval (CI) 0.752-0.974; p = 0.018). The improvement in progression-free survival was also statistically significant, with results favoring PARPis (HR 0.626; 95%CI 0.566-0.692; p = 0.000). In a subgroup analysis, similar results were observed where the efficacy of PARPis was evaluated in a subgroup of patients without homologous recombination repair (HRR) gene mutation, which showed improvement in PFS favoring PARPis (HR 0.747; 95%CI 0.0.637-0.877; p = 0.000). Our meta-analysis of seven RCTs showed that PARPis significantly increased PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide.

A Repeat Case of Cefotetan-Induced Hemolytic Anemia in a Surgical Patient.

Drug-induced hemolytic anemia is a rare hematologic condition in which the immune system creates antibodies against red blood cell antigens in response to a medication exposure. This condition is commonly triggered by antibiotics, nonsteroidal anti-inflammatory drugs, and certain chemotherapies. Here, we describe a patient who experienced a repeat episode of drug-induced hemolytic anemia related to prophylactic cefotetan given before surgery. This case is important for increasing awareness of cephalosporin-induced hemolytic anemia, illustrating the significance of early detection and treatment of the condition, and highlighting the need for careful review of medication history in the surgical setting.

The Association Between Gastroesophageal Reflux Disease and Non-Small Cell Lung Cancer: A Retrospective Case-Control Study.

Background: Lung cancer is a leading cause of mortality in the USA. Non-small cell lung cancer (NSCLC) contributes to 85% of all lung cancers. It is the most prevalent subtype amongst non-smokers, and its incidence has risen in the last 20 years. In addition, gastroesophageal reflux disease (GERD) has been associated with several lung pathologies, namely idiopathic pulmonary fibrosis and asthma. We aimed to investigate the association between GERD and NSCLC by performing a retrospective, multicenter, case-control study. This is the first study of this nature to be carried out in the USA. Methods: Data were retrieved from 17 Northwell health care facilities in the New York area between the years 2010 and 2018. Inclusion criteria were patients > 18 years of age with NSCLC (large cell, adenocarcinoma, and squamous cell). They were appropriately matched with controls based on age, gender, weight, comorbidities, and medication use. Our exposure group had a diagnosis of GERD based on the International Classification of Diseases, Ninth/10th Revision (ICD 9/10) codes and endoscopic, in addition to histological evidence if present. We excluded patients with secondary lung cancers, esophageal adenocarcinoma, other primary malignancies, Barrett's esophagus, and smokers. Logistic regression was conducted to determine the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between NSCLC and GERD. Results: A total of 1,083 subjects were included in our study: 543 (50%) patients were diagnosed with NSCLC. In this population, GERD was twice as prevalent compared to controls (20.4% vs. 11.6%, P < 0.001). Multivariate analysis demonstrated that GERD was associated with a higher risk of NSCLC compared to matched controls (OR = 1.86, 95% CI = 1.26 - 2.73). In addition, GERD patients treated with either antihistamines or proton pump inhibitors did not demonstrate an overall reduced risk of NSCLC (OR = 1.01, 95% CI = 0.48 - 2.12). Conclusions: Our study demonstrates that GERD is associated with a higher risk of NSCLC, irrespective of GERD treatment. We postulate that GERD patients suffer from chronic micro-aspirations leading to a prolonged inflammatory state within the lung parenchyma, triggering specific proliferative signaling pathways that may lead to malignant transformation.

Carfilzomib Induced Tumor Lysis Syndrome and Other Adverse Events.

In the area of multiple myeloma (MM) therapy, proteasome inhibitors (PI) have emerged with promising responses both in the first- and second-line setting. Carfilzomib (CFZ) is a second-generation, selective PI approved in 2012 for the treatment of relapsed/refractory multiple myeloma (RRMM) in patients who received 2 prior therapies or have evidence of disease progression within 60 days of completion of last therapy. Its safety profile reported adverse events (AEs) ranging from drug-related AEs (nausea and vomiting), hematologic AEs (neutropenia and thrombocytopenia), and nonhematologic AEs (electrolyte imbalances). As CFZ use is gaining popularity, various hematological, renal, cardiovascular, pulmonary, and neurological toxicities have been reported. We are presenting this case to describe a rare occurrence of tumor lysis syndrome (TLS) with the use of this novel targeted therapy.

Emerging role of immunotherapy in precursor B-cell acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia that carries poor prognosis in adults especially in the setting of high risk cytogenetics and relapsed/refractory (R/R) disease. Advancements in immunotherapy have led to the development of several monoclonal antibodies (MoAbs) and chimeric antigen receptor (CAR) T cells that are capable of targeting certain surface antigens on leukemic cells, resulting in their destruction. Areas covered: This article reviews the mechanism of action, outcomes of various trials, and adverse effects of MoAbs and CAR-T cells used in the treatment of precursor B-cell ALL. Expert commentary: Some of the immunotherapeutic agents that have been approved for the treatment of R/R precursor B-cell ALL have shown superior efficacy and safety profile compared to chemotherapy in advanced disease. Several trials are now being conducted to evaluate the role of certain MoAbs in combination with chemotherapy in the treatment of B-cell ALL. Additionally, their use in the frontline setting with more favorable host characteristics may also result in superior outcomes compared to the current standard of care.

Correction: Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute Leukemia.

[This corrects the article DOI: 10.7759/cureus.1096.].

Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute Leukemia.

Myelodysplastic syndrome (MDS) refers to a group of various stem cell disorders, characterized by dysplastic and ineffective production in one or more cell lines. In general, MDS tends to present slowly over months to years and is commonly detected with routine bloodwork by primary care physicians. Patients may be asymptomatic and depending on age, comorbidities and risk classification of MDS may not require aggressive therapy. However, MDS carries the risk of progressing to acute leukemia over time. We present a case of rapidly progressive MDS in a previously healthy middle-aged female, originally presenting and treated as acute leukemia.

Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA.

BACKGROUND: Solitary plasmacytoma (SP) is a localized neoplastic plasma cell disorder with an annual incidence of less than 450 cases. Given the rarity of this disorder, it is difficult to conduct large-scale population studies. Consequently, very limited information on the disorder is available, making it difficult to estimate the incidence and survival rates. Furthermore, limited information is available on the efficacy of various treatment modalities in relation to primary tumor sites. METHODS: The data for this retrospective study were drawn from the Surveillance, Epidemiology and End Results (SEER) database, which comprises 18 registries; patient demographics, treatment modalities and survival rates were obtained for those diagnosed with SP from 1998 to 2007. Various prognostic factors were analyzed via Kaplan-Meier analysis and log-rank test, with 5-year relative survival rate defined as the primary outcome of interest. Cox regression analysis was employed in the multivariate analysis. RESULTS: The SEER search from 1998 to 2007 yielded records for 1691 SP patients. The median age at diagnosis was 63 years. The patient cohort was 62.4% male, 37.6% female, 80% Caucasian, 14.6% African American and 5.4% other races. Additionally, 57.8% had osseous plasmacytoma, and 31.9% had extraosseous involvement. Unspecified plasmacytoma was noted in 10.2% of patients. The most common treatment modalities were radiotherapy (RT) (48.8%), followed by combination surgery with RT (21.2%) and surgery alone (11.6%). Univariate analysis of prognostic factors revealed that the survival outcomes were better for younger male patients who received RT with surgery (p < 0.05). Additionally, patients who received neoadjuvant RT had increased survival rates compared to those receiving adjuvant RT (86% vs 73%, p < 0.05). Furthermore, the analyses revealed that 5-year survival rates for patients with axial plasmacytoma were superior when RT was combined with surgery (p < 0.05). In the multivariate analysis, age <60 years and treatment with either RT or surgery showed superior survival rates. Progression to multiple myeloma (MM) was noted in 551 patients. Age >60 years was associated with a lower 5-year survival in patients who progressed to MM compared to those who were diagnosed initially with MM (15.1 vs 16.6%). Finally, those who received RT and progressed to MM still had a higher chance of survival than those who were diagnosed with MM initially and treated with RT/surgery (21.8% vs 15.9%, p < 0.05). CONCLUSIONS: A review of the pertinent literature indicates that we provided the most comprehensive population-based analysis of SP to date. Moreover, our study contributes to the establishment of the optimal SP treatment modality, as RT is the favored option in frontline settings. Consensus is currently lacking regarding the benefits of combined treatment including surgery. Thus, the findings reported here elucidate the role of primary treatment modalities while also demonstrating the quantifiable benefits of combining RT with surgery in relation to different primary tumor sites. While our results are promising, they should be confirmed through further large-scale randomized studies.

An Unusual Presentation of Nocardiosis in an Allogeneic Transplant Recipient.

Nocardiosis is a rare cause of opportunistic infection post hematopoietic stem cell transplant (HSCT) occurring in about 0.3% of patients. The risk factors include delayed immune reconstitution, prolonged neutropenia, and graft-versus-host disease. The most common site of infection is the lung, followed by the brain and the skin. Concomitant pulmonary and central nervous system (CNS) nocardiosis is an extremely rare entity as presented in our case. We present the case of a 72-year-old male at 137 days post transplant presenting with complaints of headache and slurred speech. A magnetic resonance imaging (MRI) brain scan revealed two ring-enhancing lesions: 1.6 cm in the right frontal lobe and 1 cm in the left parietal lobe. The patient had an outpatient computed tomography (CT) chest scan a month prior showing a 1.4 cm solid right upper lobe nodule prompting bronchoalveolar lavage (BAL) that was nondiagnostic. On repeat inpatient CT chest scan, the nodule had increased in size to 3.3 x 2.5 x 2.1 cm, prompting a percutaneous fine-needle aspiration biopsy. He was started on empiric trimethoprim-sulfamethoxazole (TMP-SMX) and liposomal amphotericin B. The tissue mycology and acid-fast cultures were reported positive for nocardia species. The patient was discharged on intravenous TMP-SMX. A follow-up CT chest scan and MRI brain scan four months later showed resolution of the right upper lobe nodule and significant decrease in size of the brain lesions. The patient will continue TMP-SMX for a total of nine to 12 months. Given the increase in transplant recipients and the ongoing risk of developing nocardiosis several months post transplant, there is a need for standardized diagnostic and treatment guidelines. Meanwhile, our case highlights the importance of aggressiveness in pursuing a prompt diagnosis including invasive procedures, if required, in order to begin specific treatment.

Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

The treatment landscape for multiple myeloma (MM) is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development.

Anaplastic lymphoma kinase inhibitors in elderly patients with advanced non-small cell lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in the USA and worldwide. At diagnosis, half of the patients are over 70 years of age, and most present with advanced disease for which chemotherapy provides modest benefit with significant toxicity. Older patients often have more comorbidities than their younger counterparts and tend to be excluded from clinical trials. AREAS COVERED: A small percentage (less than 7%) of patients with NSCLC have the anaplastic lymphoma kinase (ALK) rearrangement. Compared to the general NSCLC population, this clinically distinct group has a relatively younger median age of 51 years at diagnosis. As such, elderly patients with ALK-positive disease are both a minority within this group and are expected to be underrepresented in clinical trials. Expert commentary: Despite promising results in the general population, data about the efficacy and safety of ALK inhibitors in the elderly population remains scarce. In our review, we briefly discuss the current evidence of ALK inhibitors in the general population and we shed light on this subgroup of elderly patients with advanced ALK-positive disease.

Novel Drugs and Combination Therapies for the Treatment of Metastatic Melanoma.

Metastatic melanoma (MM) still remains as one of the most worrisome cancer known to mankind. In last two decades, treatment of melanoma took a dramatic turn with the discovery of targeted therapy which targets the mutations in mitogen-activated protein kinase (MAPK) pathway and immune checkpoint inhibitors. These new findings have led to emergence of many novel drugs that have been approved by FDA. Targeted therapy drugs such as vemurafenib, trametinib and dabrafenib target the MAPK pathway whereas immunotherapies such as ipilimumab, nivolumab and pembrolizumab block immune checkpoint receptors on T lymphocytes. All these drugs have shown to improve the overall survival in MM. Despite these recent discoveries, treatment of MM remains challenging because of rapid development of resistance to targeted therapy. This review will discuss recently approved drugs and their adverse effects and also shed light on combination therapy in treatment of melanoma.

Bronchial myeloid sarcoma with concurrent Aspergillus fumigatus infection in a patient presenting with hemoptysis.

Myeloid sarcoma (MS) is an extramedullary myeloid neoplasm characterized by proliferation of myeloblasts which can occur in any organ or site. Bronchial and pulmonary involvement, however, is uncommon. We describe a case of bronchial MS in an 81-year-old female with a history of high-grade myelodysplastic syndrome; she was started on treatment few months before, and she presented with fever, cough and profuse hemoptysis. She was found to be pancytopenic with bilateral airspace consolidations, most notably in the right upper and lower lobes, on imaging studies. She was treated with broad-spectrum antibiotics and antifungals without much improvement in her clinical or radiological status. Ultimately, biopsy of the lung lesions showed myeloid sarcoma with concurrent Aspergillus fumigatus infection. Bronchial/pulmonary MS should be considered in the list of differential diagnoses in a patient with a history of myeloid neoplasm and presenting with respiratory related symptoms, as early administration of chemotherapy may help to improve survival rates.

Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature.

Topotecan (TPT), a chemotherapeutic agent, is a topoisomerase-I inhibitor. Topoisomerase-I is a nuclear enzyme that relieves torsion strain in DNA by opening single strand breaks which helps in DNA replication. TPT inhibits this enzyme, thus preventing DNA replication and causes cell death. TPT has demonstrated to have broad spectrum of antitumor activity in tumors like cervical, ovarian, endometrial and small cell lung cancers (SCLCs). The intravenous (IV) formulation of the drug is currently approved by the US Food and Drug Administration for the treatment of patients with SCLC and ovarian cancer at a dose of 1.5 mg/m2 administered daily for five consecutive days, with treatment cycles repeated every 3 weeks. TPT has shown some promising activity in the treatment of non-small cell lung cancer (NSCLC) with favorable side effect profile. Several clinical trials have been conducted with TPT in either IV or oral formulation for the treatment of NSCLC as a first or second-line treatment. Here we reviewed all the clinical trials done with TPT to date in the treatment of NSCLC both as a single-agent and combination therapy.

IgM Myeloma or Waldenstrom's Macroglobulinemia Is the Big Question?

ABSTRACT: Although critical from therapeutic and prognostic perspectives, differentiating IgM Myeloma (MM) from Waldenstrom's macroglobulinemia (WM) is fraught with failure. WM can usually be distinguished from IgM MM by the lymphoplasmacytic versus pure plasmacytic morphology, absent versus present lytic bone lesions, and immunophenotypic findings. However, all these features have their own limitations; hence, it requires constant vigilance and periodic re-evaluation. Here we describe a case of a 70-year-old woman initially diagnosed as smoldering IgM MM, who eventually turned out to have WM.

Telephone-based anticoagulation management in the homebound setting: a retrospective observational study.

BACKGROUND: Anticoagulation management is currently performed through anticoagulation clinics or self-managed with or without the help of medical services. Homebound patients are a unique population that cannot utilize anticoagulation clinics or self-testing. Telephone-based anticoagulation management could be an alternative to the traditional methods of monitoring warfarin in this subgroup. The objective of this retrospective, observational study is to investigate the feasibility of warfarin management in homebound patients. METHODS: This study was performed through the use of telephone-based adjustments of warfarin dose based on an international normalized ratio (INR) result. Four hundred forty-eight homebound patients referred to the anticoagulation clinic at Staten Island University Hospital were visited at home by a phlebotomist; a blood sample was drawn for initial laboratory testing. A nurse practitioner then called the patient or designated person to relay the INR result and to direct dosage adjustment. INR results and dosage changes were entered into an electronic medical record and analyzed statistically. RESULTS: The mean percentage of INR values in range was 58.39%. The mean time when the INR was in the therapeutic range was 62.75%. The percent of patients who were therapeutically controlled decreased as the number of medications increased. The complication rate was 4% per patient year, with an equal distribution between bleeding and clotting. These values compared favorably to other studies in which monitoring was performed through anticoagulation clinics or self-monitoring. The cost per visit at our anticoagulation clinic was found to be approximately $300 compared with $82 when utilizing our homebound service. CONCLUSION: Telephone-based management of warfarin therapy in the homebound setting is feasible. It can lower the cost of health care expenditures compared to other modalities of anticoagulation management.

Development of myelodysplastic syndrome and acute myeloid leukemia 15 years after hydroxyurea use in a patient with sickle cell anemia.

We report a 41 year old male with sickle cell disease who developed a myelodysplastic syndrome and acute myeloid leukemia with complex karyotype involving chromosomes 5, 7 and 17 after 15 years of hydroxyurea treatment. He responded poorly to induction chemotherapy with cytarabine/idarubicin followed by high dose cytarabine and succumbed to neutropenic sepsis. Multiple systematic reviews, observational studies and clinical trials were conducted to identify the toxicity profile of hydroxurea. Only six cases of leukemia/myelodysplastic syndrome were identified in patients with sickle cell anemia treated with hydroxyurea. Subsequently, it was concluded that hydroxyurea is not leukemogenic. However, it was noted that most of the published studies had only up to 9 years of follow-up. Our patient was started on hydroxyurea in 1990, before the widespread use of the drug and took hydroxyurea for 15 years. His presentation may reflect an outcome otherwise not yet observed because of the short follow-up of prior studies. We believe that the leukemogenic risk of hydroxyurea should be discussed with the patients and their families. Studies evaluating the adverse effects of hydroxyurea should have longer follow-up before definitive conclusions are drawn.