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.

Genomic determinants in advanced endometrial cancer patients with sustained response to hormonal therapy- case series and review of literature.

The incidence of endometrial cancer is increasing, however treatment options for advanced disease are limited. Hormonal therapy has demonstrated positive outcomes for Stage IV EC. Next generation sequencing (NGS) has increased our understanding of molecular mechanisms driving EC. In this case series, we selected six patients at our institution with Stage IV, hormone receptor positive, endometrial cancer currently being treated with hormonal therapy. All patients achieved SD for at least ≥ 1.5 years. We studied NGS data on all six patients to assess for any common genomic marker which could predict the SD of at least 1.5 years achieved in this group. Institutional Review Board (IRB) approval was obtained from Staten Island University Hospital and Northwell Health, New York. PTEN, PIK3CA, PIK3R1, and ARID1A mutations were found in 83%, 67% 50%, and 67% of patients respectively. TP53 and FGFR2 were both found in 50% of patients. All patients were positive for estrogen and/or progesterone receptor (ER+ and/or PR+). We did not find any one common mutation that could have predicted the observed response (or SD of ≥1.5 years) to hormone therapy. However, our data reflects the prevalence of various mutations reported in literature: (1) Hormone Receptor status is a positive prognostic indicator (2) PTEN/PIK3CA mutations can occur concurrently in EC (3) ARID1A coexists with PTEN (4) FGFR and PTEN pathways may be interlinked. We suggest NGS be employed frequently in patients with endometrial cancer to identify targetable mutations. Additional larger studies are needed to characterize the interplay between mutations.

Synchronous thyroid cancer and malignant struma ovarii: concordant mutations and microRNA profile, discordant loss of heterozygosity loci.

BACKGROUND: Struma ovarii is an unusual ovarian teratoma containing predominantly thyroid tissue. Less than 10% of cases undergo malignant transformation in the thyroid tissue and are considered malignant struma ovarii (MSO). MSO have been reported with concurrent thyroid lesions, but molecular data is lacking. CASE PRESENTATION: A 42-year-old female developed MSO and synchronous multifocal subcentimeter papillary thyroid carcinoma (PTC). The patient underwent a salpingo-oophrectomy, thyroidectomy, and low-dose radioactive iodine ablation. Both the thyroid subcentimeter PTC and MSO were positive for BRAF V600E mutation, and microRNA expression profiles were similar across all tumor deposits. However, only the malignant component demonstrated extensive loss of heterozygosity (LOH) involving multiple tumor suppressor gene (TSG) chromosomal loci. CONCLUSIONS: We present the first reported case of MSO with synchronous multifocal subcentimeter PTC in the thyroid containing concordant BRAF V600E mutations and resulting with discordant LOH findings. This data suggests that loss of expression in tumor suppressor gene(s) may be an important contributor to phenotypic expression of malignancy.

Expression patterns and clinical significance of estrogen receptor in non-small cell lung cancer.

BACKGROUND: Lung cancer death remains the highest among all malignancies. Gender differences show women have an increased cancer incidence while men have worse outcomes. These observations identified that some lung carcinomas express estrogen receptors (ER). This is a promising target as antiestrogen drugs can reduce tumors and improve survival. However, there is a limited understanding of ER distribution and its clinical significance to properly design antiestrogen drug clinical trials. Thus, we comprehensively analyzed ERα and ERß expression patterns by gender, cancer cell type, and receptor location in lung cancer. METHODS: We conducted a systematic review using the PubMed database from all-time through October 2022, using MeSH terms with the keywords "lung cancer," "estrogen receptor," and "immunohistochemistry." We identified 120 studies with 21 reports being evaluated based on our inclusion criteria. RESULTS: We examined 4874 lung cancers from 5011 patients. ERß is the predominant form of ER expressed, mainly found in the nucleus. The ERß positivity rate is 51.5% in males versus 55.5% in females and was not statistically different. In contrast, ERα is predominately extranuclear in location, and ERα expression varies by gender. Males had a positivity rate of 31% versus 26.6% in females, which is statistically different. ERα is associated with a worse prognosis in some studies, while it had no effect in others. Overall, ERß was associated with a better prognosis. CONCLUSION: We characterized ER expression patterns in 4874 lung cancers. Over 50% expressed ERß with equal rates in both sexes and was associated with a better prognosis. ERα expression was slightly higher in males (31%) than females (26.6%) and was associated with a poor prognosis. Our findings suggest estrogen signaling may be a promising drug target in lung cancer.

Intraparenchymal Hemorrhage: A Fatal Presentation of Undiagnosed Acute Myelogenous Leukemia.

We present the case of a 73-year-old patient who was admitted to the neurocritical care unit with spontaneous intracerebral hemorrhage (ICH). Upon further investigation, she was found to have hyperleukocytosis and thrombocytopenia due to acute myelogenous leukemia (AML), likely resulting in coagulopathy, vessel friability, and consequential intraparenchymal bleed. Prior reports of AML presenting with ICH are scant in the literature. As such, a heightened awareness of such a phenomenon is recommended for rapid detection and appropriate tailored management. This hopefully would, in turn, optimize outcomes.

Immunoglobulin D Multiple Myeloma: A Rare Variant.

Immunoglobulin D multiple myeloma (IgD MM) is a rare isotype of multiple myeloma (MM), comprising less than 2% of all cases. It is often associated with advanced disease at the time of diagnosis, an aggressive clinical course, and shorter overall survival (OS) than other subtypes of MM. There is an increased frequency of undetectable or small monoclonal (M-) protein levels on electrophoresis, hypercalcemia, anemia, lytic bony lesions, and renal failure. However, given the rarity of the disease, there are few cases of IgD MM described in the literature. Given the very small amount of IgD immunoglobulins, they may form very small or undetectable M spike on electrophoresis, making the diagnostic error in diagnosing this specific subgroup very easy. Treatment for MM has seen significant advancement, especially over the last decade, with the advent of medications such as proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. It is important to understand how IgD MM responds to these newer agents and why this disease continues to be associated with poor outcomes despite advancements in treatment. Small clinical studies on patients with IgD MM show better outcomes following a combination of high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) compared to standard chemotherapy. Given the rarity of the disease, there are no large studies done to see the effectiveness of these treatments, and most of the data are derived from small case series. We report a case of IgD kappa MM that was incidentally discovered following a traumatic bicycle accident. The patient started treatment with bortezomib and dexamethasone (Vd) as an inpatient while he was in the rehabilitation unit and was later switched to bortezomib, dexamethasone, and lenalidomide (VRd) as an outpatient. He has now completed seven cycles and successfully underwent autologous hematopoietic stem cell transplantation.

Rapid Response of Breast Cancer Cutaneous Metastasis to Single-Agent Palbociclib: A Case Report.

Palbociclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor. Palbociclib combined with endocrine therapy has shown promising results in hormone-receptor-positive (HR+) and human epidermal growth factor receptor-negative (HER-2-) breast cancer progression. We present a case of a woman with a history of infiltrating lobular cancer of the left breast, status post modified radical mastectomy 6 years prior, presenting with nodular erythematous lesions on the left arm and back. Histopathological examination confirmed the diagnosis of recurrent metastatic breast adenocarcinoma. She had complete resolution of cutaneous metastasis with 1 cycle of Palbociclib. We believe our case is unique as the resolution of cutaneous metastasis with 1 cycle of single-agent Palbociclib is rare. Furthermore, it highlights the importance of considering cutaneous metastasis as a possibility in patients with prior history of primary internal malignancy.

Vulvar Cancer with Cutaneous and Breast Metastases.

Vulvar cancer accounts for about 5% of cancer of female genitalia. It may initially present as benign symptoms resulting in potential delay in diagnosis. Few cases of distant metastases to skin or breast have been reported. We present the case of a 76-year-old female with possible delay in diagnosis of her squamous cell carcinoma of vulva. After 4 months of the diagnosis, she presented with concurrent cutaneous and breast metastases.

Embryonal Rhabdomyosarcoma of the Cervix: A Rare Disease at an Uncommon Age.

Embryonal rhabdomyosarcoma (RMS) is a rare type of sarcoma, primarily seen in the pediatric and adolescent population. Three subtypes of embryonal RMS are described, with the botryoid type being the most common. The incidence of this disease in adult females is 0.4% to 1% with the affected age group being patients in the third to fourth decade of life. It is exceedingly rare in patients above 40 years of age. We describe the case of a 48-year-old female, gravida 9 para 5, who presented with abnormal vaginal bleeding and an exophytic mass on examination. Given her lack of requirement of maintaining parity, she underwent radical surgery. The tumor was 8 cm in the largest dimension with a high histologic grade and some cartilaginous differentiation. Immunohistochemical stains were positive for vimentin, CD99, myogenin, and MyoD1 consistent with a diagnosis of embryonal rhabdomyosarcoma, botryoid subtype. Based on high survival rates when treated with aggressive adjuvant chemotherapy, a decision was made to treat the patient with the ARST0331 regimen. We discuss the diagnostic pathologic features of the disease, the epidemiology, and the most common presentation along with prognostic factors, treatment strategies, and outcomes.

Esophageal Granular Cell Tumor: A Case Report and Review of Literature.

Granular cell tumors (GCTs) are soft tissue neoplasms that originate from Schwann cells. They occur predominantly in the oral cavity, skin, and breast tissues. Gastrointestinal GCTs are very rare, accounting for only eight percent of all GCTs, most of which are located in the esophagus. Endoscopic ultrasound has been a breakthrough in diagnosing GCTs because it provides precise information on the depth of tumor invasion, thus narrowing the differential diagnosis of subepithelial lesions in the esophagus. However, the definitive diagnosis requires histological confirmation of the lesion. Here, we report a case of esophageal GCT that was identified incidentally and removed by endoscopic mucosal resection.

Correlation of Antiglobulin Reactivity and Severity of Pancytopenia in a Patient with Hemophagocytic Lymphohistiocytosis: A Case Report and Review of Literature.

A 46­year­old obese male with a medical history of thalassemia minor presented to the emergency room with complaints of severe fatigue and jaundice worsening over two weeks. On further evaluation, the patient was found to have significant hyperbilirubinemia and transaminitis. The hospital course was further complicated by pancytopenia requiring multiple transfusions, worsening hyperbilirubinemia, severe hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia. He was also found to have splenomegaly and evidence of hemophagocytosis on bone marrow biopsy. On further testing, the patient was also found to have evidence of hemolysis along with a positive direct Coomb's test consistent with autoimmune hemolytic anemia (AIHA), and elevated soluble IL-2 receptor level. The patient was subsequently diagnosed with hemophagocytic lymphohistiocytosis (HLH). He was treated with HLH-94 protocol along with rituximab for AIHA which resulted in improvement of patient's condition. We present a case of HLH with no prior history of autoimmune disease, associated with Coomb's positive AIHA that resolved after therapy for HLH. Our case also delineates how the intensity of antiglobulin reactivity, if present, may correlate with severity of the disease, its progression, and response to treatment.

Stage IV EGFR Mutation-Negative and ALK Mutation-Negative Lung Adenocarcinoma: Long-Term Survival is Possible.

Lung cancer is the leading cause of cancer death in the United States with a five-year survival of 16.8% for all stages and median survival of four months for Stage IV disease. We report a case of a 54-year-old male with a seven-year survival after being diagnosed with Stage IV epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK) mutation-negative adenocarcinoma of the lung, demonstrating an exceptional response to treatment.

Long-term Survival in a Patient with Recurrent Pulmonary Metastases from Uterine Leiomyosarcoma.

Chemotherapy is the standard of care for disseminated uterine leiomyosarcoma; however, long-term survival is rarely achieved with this aggressive disease. We report a patient with recurrent pulmonary metastatic disease from uterine leiomyosarcoma who is doing well without significant disease nine years after her initial diagnosis. We discuss her clinical course, the treatment modalities she received, and the clinical evidence supporting these.

Spontaneous Tumor Lysis Syndrome in Small-Cell Lung Cancer: A Rare Complication.

Tumor lysis syndrome (TLS) is a life-threatening condition which consists of a constellation of electrolyte imbalances, acute renal failure, seizure, and arrhythmias. It is most commonly seen with hematologic malignancies after the initiation of chemotherapy. However, it can also occur spontaneously, prior to treatment with cytotoxic agents. TLS has been rarely described with non-hematologic solid tumors, and it is even more uncommon to have spontaneous tumor lysis syndrome (STLS) in solid tumors. To our knowledge, only two cases of STLS in small-cell lung cancer (SCLC) were reported in the literature. Herein, we present the case of a patient with metastatic SCLC who developed STLS. Our case highlights that in the setting of metastatic solid tumors, STLS must be in the differential diagnosis, to allow prompt initiation of prophylaxis and treatment.

Concurrent Acute Monoblastic Leukemia and Multiple Myeloma in a 66-Year-Old Chemotherapy-Naive Woman.

Concurrent acute myeloid leukemia (AML) and multiple myeloma (MM) is rare, more so in chemotherapy-naive patients. Concurrent occurrence of these two malignancies portends poor prognosis. Although anthracycline-based AML regimen, allogeneic hematopoietic stem cell transplantation, tipifarnib and bortezomib have shown promising results in small number of patients, there is a lack of established therapy. We describe a case of concurrent AML and MM in a 66-year-old woman and review previously published literature.

Complete recovery of ischemic cardiomyopathy from thrombotic thrombocytopenic purpura.

A 50 year old male HIV patient on antiretroviral therapy was admitted for chest pain. Upon admission, the patient was found to have elevated cardiac enzymes, acute thrombocytopenia, hemolytic anemia, acute pancreatitis and acute renal failure. The patient was diagnosed with thrombotic thrombocytopenic purpura/haemolytic uremic syndrome and emergency plasma exchange therapy was initiated along with aspirin, beta-blockers, steroids, and antiretroviral therapy. Patient responded well and demonstrated complete resolution of ischemic cardiomyopathy with left ventricular ejection fraction improving from 35% to 55% by the time of discharge. Essentially, prompt diagnosis and treatment can reverse cardiac damage induced by thrombotic thrombocytopenic purpura.

Severe refractory autoimmune hemolytic anemia with both warm and cold autoantibodies that responded completely to a single cycle of rituximab: a case report.

INTRODUCTION: Mixed warm and cold autoimmune hemolytic anemia runs a chronic course with severe intermittent exacerbations. Therapeutic options for the treatment of hemolysis associated with autoimmune hemolytic anemia are limited. There have been only two reported cases of the effective use of rituximab in the treatment of patients with mixed autoimmune hemolytic anemia. We report a case of severe mixed autoimmune hemolytic anemia that did not respond to steroids and responded to four weekly doses of rituximab (one cycle). CASE PRESENTATION: A 62-year-old Caucasian man presented with dyspnea, jaundice and splenomegaly. His blood work revealed severe anemia (hemoglobin, 4.9 g/dL) with biochemical evidence of hemolysis. Exposure to cold led to worsening of the patient's hemolysis and hemoglobinuria. A direct antiglobulin test was positive for immunoglobulin G and complement C3d, and cold agglutinins of immunoglobulin M type were detected. A bone marrow biopsy revealed erythroid hyperplasia. A positron emission tomographic scan showed no sites of pathologic uptake. There was no other evidence of a lymphoid or myeloid disorder. Initial therapy consisted of avoidance of cold, intravenous methylprednisolone and a trial of plasmapheresis. However, there was no clinically significant response, and the patient continued to be transfusion-dependent. He was then started on 375 mg/m2/week intravenous rituximab therapy. After two treatments, his hemoglobin stabilized and the transfusion requirement diminished. Rituximab was continued for a total of four weeks and led to the complete resolution of his hemolytic anemia and associated symptoms. At the patient's last visit, about two years after the initial rituximab treatment, he continued to be in complete remission. CONCLUSION: To the best of our knowledge, this is the first reported case of mixed-type autoimmune hemolytic anemia that did not respond to steroid therapy but responded completely to only one cycle of rituximab. The previous two reports of rituximab use in mixed autoimmune hemolytic anemia described an initial brief response to steroids and the use of rituximab at the time of relapse. In both of these case reports, the response to one cycle of rituximab was short-lived and a second cycle of rituximab was required. Our case report demonstrates that severe hemolysis associated with mixed autoimmune hemolytic anemia can be unresponsive to steroid therapy and that a single cycle of rituximab may lead to prompt and durable complete remission.

Renal epithelioid angiomyolipoma: a malignant disease.

BACKGROUND: Renal angiomyolipomas are recognized as clonal neoplasms with clonal chromosomal aberrations and a common progenitor cell, the perivascular epithelial cell (PEC). The epithelioid variant is a recently identified entity, characterized by predominance of PEC and a unique morphologic and immunohistochemical profile. There is accumulating evidence suggesting that renal epithelioid angiomyolipoma (REA) is a malignant disease. METHODS: We searched the literature for descriptions of clinical behavior of REA. A Pubmed search was performed using the following key words: angiomyolipoma, epithelioid, perivascular epithelial cell or/and renal tumors. We reviewed a case of fatal REA at our institution. A pathologist reviewed slides to confirm the diagnosis. RESULTS: Upon review of 140 articles, 37 eligible articles were found including 10 articles describing the clinical course of REA. Almost all of the patients described, for whom there was a follow-up available, died of neoplastic progression of the disease, with liver, lung and bone metastases. Four cases were reclassified after retrospective pathology review, and they were fatal. Three of these had been misdiagnosed as renal cell carcinoma (RCC), while 1 was diagnosed as classic angiomyolipoma. CONCLUSION: Unlike commonly benign classic angiomyolipoma, REA behaves aggressively. It is crucial for the clinician to be aware of and identify this epithelioid variant as a malignant disease. It should be carefully differentiated from RCC. Resection alone may not be curative, and adjuvant therapy should be considered. A multimodality treatment approach needs to be explored for this newly recognized malignant variant renal angiomyolipoma.

Port-a-cath embolisation to pulmonary artery.

Intravascular embolisation of catheter, a relatively uncommon event associated with the use of totally implanted port devices, can have serious cardiovascular, pulmonary and septic complications with an overall mortality of 1.8%. Here, the authors report an asymptomatic patient with pulmonary artery catheter embolisation diagnosed incidentally in a positron emission tomography scan who underwent successful percutaneous extraction of the catheter in an attempt to avoid the possible dreadful complications.