Quantification of IGF-1 receptor is useful in the differential diagnosis of essential thrombocytosis from reactive thrombocytosis.

BACKGROUND: To make a definite diagnosis of essential thrombocytosis (ET) from reactive thrombocytosis (RT), the most reliable criteria are the presence of driver mutations, namely JAK2, CALR, or MPL gene mutations. In the absence of these driver mutations, so-called triple-negative ET, the differential diagnosis could be difficult. Although bone marrow biopsy could be helpful, it may be difficult in some cases, to do gene sequence analysis to identify other clonal marker gene mutations than the driver mutations, as only very few were found. METHODS: IGF-1R quantification by flow cytometry in mononuclear cells (MNC) from peripheral blood was performed in 33 patients with ET (untreated or off treatment with hydroxyurea), 28 patients with RT, and 16 normal volunteer controls. RESULTS: We found IGF-1R levels were significantly elevated in ET patients compared to RT patients or controls. A cutoff value of 253 was chosen from the logistic regression to predict each patient's group, a value ≥253 meant that a patient belonged to the ET group (sensitivity 96.4% and specificity 68.6%). CONCLUSION: We suggest that adding quantification of IGF-1R in blood MNC by flow cytometry is useful in differentiating ET from RT.

Utilization of Pharmaceutical Patient and Prescription Assistance Programs via a Pharmacy Department Patient Assistance Program for Indigent Cancer Patients.

BACKGROUND: With the advances in cancer treatments, mortality rates in the United States have been consistently falling but they are accompanied by substantial increases in the cost of cancer care. Patient and prescription assistance programs (PPAPs) are offered by pharmaceutical manufacturers to provide free medications to medically indigent patients. To assist the Cancer Care Center (CCC) at Nassau University Medical Center (NUMC) with drug costs for chemotherapies, the pharmacy department uses a patient assistance program (PAP) to obtain medications from the drug companies at no cost. PURPOSE: This study evaluates the impact of the PAP at a public hospital from which indigent cancer patients obtain assistance for chemotherapy. METHODS: We followed all patients requiring assistance with chemotherapy who enrolled in the PAP from January 1, 2011 through December 31, 2012. Medications included both oral and parenteral chemotherapy drugs and antiemetics used in the outpatient clinic setting. RESULTS: The program served 347 patients in 2011 and 579 patients in 2012. The total number of visits in the clinic over 24 months was 9,405. The total cost savings of the medications was $1,066,000 in 2011 and $1,715,538 in 2012. CONCLUSIONS: A pharmacy-based PAP to procure free medications from PPAPs for cancer patients has helped to defray the expense of providing care at NUMC, increased patients' compliance with chemo protocols, and allowed many patients to receive the treatment they otherwise would not be able to afford. The combination of PPAPs and PAP provides a safety net to ensure that indigent cancer patients receive needed prescription medications in the outpatient clinic setting.

Location-dependent ethnic differences in the risk of colorectal adenoma: a retrospective multiethnic study.

BACKGROUND AND AIMS: Epidemiological data have demonstrated that Hispanics have a lower incidence rate of colorectal cancer (CRC) compared with other major race/ethnicity groups in the United States. However, data regarding the relative prevalence of colorectal adenomas (CRAs) in Hispanic versus non-Hispanic populations are currently sparse and inconclusive. METHODS: We conducted a retrospective review of colonoscopy patients (n=1656) at a single tertiary-care community hospital from 2007 to 2011, to evaluate the association of self-reported race/ethnicity status with CRA prevalence and characteristics. Established CRC risk factors were also included in multivariate regression models. RESULTS: Overall, the CRA prevalence was lower in Hispanic subjects than non-Hispanic subjects (14.8% vs. 22.5%) and this difference was statistically significant (adjusted odds ratio, 0.67; 95% confidence interval, 0.47-0.96; P<0.01). Conversely, no difference in CRA prevalence was observed between non-Hispanic white and black subjects. Further analyses by adenoma location revealed more pronounced reduction in proximal CRA prevalence for Hispanics versus non-Hispanics (5.3% vs. 13.1%; adjusted odds ratio, 0.42; 95% confidence interval, 0.26-0.70; P<0.001), whereas CRA prevalence in distal colon, rectum or multiple locations did not differ significantly between race/ethnicity groups. CONCLUSIONS: Our data showed a marked distinction in CRA prevalence, particularly proximal adenomas, between Hispanics and non-Hispanics. Additional multicenter studies are needed to confirm these findings, elucidate the underlying mechanisms, and clarify the implications for CRC screening and other preventive and/or therapeutic interventions.

Hairy cell leukemia in a patient with situs inversus totalis: an extremely rare combination.

Hairy cell leukemia is a rare cancer of the blood. The occurrence of hairy cell leukemia with another very rare genetic disorder makes us question whether it is just a coincidence. This article reports the first case of hairy cell leukemia in a patient with situs inversus totalis in western literature. There have been studies into the pathogenesis of situs inversus totalis that suggest it is caused by the failure of embryonic cells to properly rotate during embryogenesis. On the molecular level, the nodal cilia, which are responsible for embryonic rotation, are built by transport through the KIF3 complex - a kinesin superfamily of molecular motors. The KIF3 complex is also responsible for N-cadherin movement in cells. Furthermore, it is well known that these cell adhesion molecules play an important role in carcinogenesis and its progression. This report attempts to link the rare conditions and propose a possible genetic relationship between the two.

Germ cell cancer presenting as gastrointestinal bleeding and developing brain metastases: case report and review of the literature.

This paper describes a rare case of germ cell cancer with duodenum, brain and lung metastases. The patient presented with melena and left testicle enlargement. Orchiectomy revealed mixed germ cell cancer, enteroscopy revealed duodenal choriocarcinoma, and chest x-ray and computed tomography (CT) showed bilateral lung metastases. The patient received and tolerated cisplatinum-based chemotherapy, and responded well. However, he developed seizures 3 months later. MRI showed brain metastases and he was treated with whole-brain radiation. One month later, he developed progressive dyspnea. Chest CT showed worsening lung metastases. He received second-line chemotherapy, but died due to multiorgan failure. Germ cell cancer with nonpulmonary metastases has poor prognosis and the management of these patients requires a multimodal approach. Head CT should be considered as routine screening for all germ cell cancer patients on initial diagnosis and brain MRI should be considered for high-risk patients (with an embryo- or choriocarcinoma histology, dramatically elevated ß-human chorionic gonadotropin and lung involvement).

Intraoral myeloid sarcoma presenting as toothache and gingival mass.

A female patient in her 70s with a medical history of myelodysplastic neoplasm presented to the outpatient department with a 4-month history of toothache, painful gingival swelling and loose teeth that required extractions. Intraoral examination revealed a swelling in the lower anterior portion of the mandible, which displaced her teeth. Incisional biopsy of the gingival lesion revealed dense aggregates of atypical round cells which stained positive for CD43, CD45, CD33 and myeloperoxidase, consistent with myeloid sarcoma. Subsequent bone marrow biopsy displayed hypercellular marrow with immature myeloid elements and 21% myeloblasts by flow cytometry, compatible with diagnosis of acute myeloid leukaemia (AML). The patient initially went into remission after treatment but later died of AML relapse after 18 months.

Presentation and treatment of aggressive, Triple-Negative carcinosarcoma of the breast.

An extremely rare form of breast cancer, breast carcinosarcoma accounts for less than a percent of all breast malignancies and is highly aggressive. Composed of both cancerous epithelial and mesenchymal cell types, breast carcinosarcoma is associated with a poor prognosis compared to more common breast cancers, and typically lack the receptors typical of other breast carcinomas, which minimize potential targets for treatment. In this case report, we discuss a 56-year-old patient affected by carcinosarcoma of the breast at a T2N1 stage, and the decision-making process that factored into her treatment plan.

SMARCA4-Deficient Undifferentiated Tumor of Lung Mass-A Rare Tumor With the Rarer Occurrence of Brain Metastasis: A Case Report and Review of the Literature.

Among thoracic tumors, these include subsets of a relatively newly described and yet to be fully characterized tumor entity: SMARCA4-deficient Undifferentiated Tumor (SMARCA4-dUT). Mutations of SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and loss of BRG1 (Brahma-related gene-1) is the underlying molecular hallmark of SMARCA4-dUT. They mostly involved the mediastinum, lung, and/or pleura showing undifferentiated round cell or rhabdoid morphology associated with aggressive clinical behavior. The pathogenesis of these tumors is still not clear. Morphologically, SMARAC4-dUT is differentiated from SMARCA4-dNSCLC by the presence of squamous and solid components in the latter. Immunohistochemically SMARC4-dUT has characteristic loss of SMARCA4 and SMARCA2 and strong expression of SOX2, CD34, and SALL4. Common sites of metastasis include lymph nodes, bones, and adrenal glands but rarely brain metastasis. We present a unique and rare case of a 76-year-old male with a right lung mass with documented pathology of SMARCA4-dUT and was found to have multiple brain metastases.

A Rare Case of Epithelioid Hemangioma Presenting as an Isolated Sacral Mass.

Epithelioid hemangioma (EH) is an uncommon benign vascular tumor of mesenchymal origin. It mainly presents as expanding nodules around the ear, the forehead, and long bones. Only a handful of cases have been found in cervical, thoracic, lumbar, and sacral vertebrae as lytic lesions with pain and neurological impairment. We present the case of a 36-year-old female with an incidental finding of a sacral mass along with inguinal lymphadenopathy on imaging. Initially, there were no symptoms. The mass gradually progressed and later showed an extraosseous extension with involvement of sacral neural foramina and nerve roots causing severe low back pain and weakness of the left lower extremity. Differential diagnoses initially included secondary metastases and chordoma. However, the biopsy of the mass revealed findings consistent with an EH. To our knowledge, this is the first case of EH presenting as an isolated mass in the sacrum and the third case of EH involving the sacrum in continuation with other vertebrae. EH should be in our differential diagnoses when there is a sacral mass.

Yolk Sac Tumor in the Anterior Mediastinum Presenting as Acute Pericarditis.

BACKGROUND Mediastinal masses can originate from anatomical structures normally located in the mediastinum, or from structures that travel through the mediastinum during embryogenesis. Initial presenting symptoms usually vary from shortness of breath, cough, chest pain, and superior vena cava syndrome to nonspecific constitutional symptoms (eg, fever, weight loss, fatigue). However, the initial presentation of a mediastinal mass with acute pericarditis has not been reported in the literature as far as we know. CASE REPORT A 20-year-old man presented to the Cardiology Clinic with chest pain and new pericardial effusion on echocardiography, both fulfilling the diagnostic criteria of acute pericarditis. The patient also had venous engorgement on the neck, and a chest X-ray followed by computed tomography imaging showed a large mediastinal mass. The serum tumor marker a-fetoprotein (AFP) was markedly elevated. The biopsy and immunohistochemistry revealed a high-grade malignant neoplasm - yolk sac tumor, which is a type of non-seminomatous germ cell tumor. The acute pericarditis resolved after administration of NSAID and colchicine. The patient was then started on chemotherapy. CONCLUSIONS The discussed case shows the rare presentation of an anterior mediastinal mass with acute pericarditis. This emphasizes the importance of a thorough review of systems and critical analysis of every sign and symptom at the time of initial presentation, which helps the physician to obtain appropriate imaging studies early in the course, leading to an early diagnosis and treatment of the disease, such as in this case of an extremely rare germ cell tumor.

Hematological manifestations and complications of COVID-19.

The virus SARS-CoV-2 commonly causes self-resolving, flu-like illnesses in the majority of patients, but a critical illness can be seen in 5% of cases - especially in the elderly population or in patients with multiple comorbidities. When COVID-19 is severe, it can cause pneumonia and hypoxemic respiratory failure, and can progress to viremia involving multiple organ systems. It causes significant cytopenia, mainly severe lymphopenia, and excessive exhaustion of CD8+ T cells, resulting in an immunocompromised state and cytokine storm. Furthermore, COVID-19 can commonly be complicated with acute thrombotic events, including venous thromboembolism, acute stroke, acute myocardial infarction, clotting of hemodialysis and extracorporeal membrane oxygenation (ECMO) catheters, and acute limb ischemia. This makes SARS-COV-2 a unique virus with an undiscovered pathophysiology. Therefore, patients with COVID-19 need close monitoring of their symptoms and laboratory parameters, and early hospitalization and treatment in severe cases. Early identification of severe cases and the abovementioned complications of COVID-19 could decrease the morbidity and mortality caused by the disease. In the study, we summarize what is currently known about the hematological manifestations and complications of COVID-19.

Observational Study of Thrombotic Events in a Random Cohort of Hospitalized COVID-19 Patients at a Community-Based Hospital of New York City During the Beginning of the 2020 Pandemic.

Coronavirus disease 2019 (COVID-19) continues to pose an unprecedented challenge for the entire world and the healthcare system. Different theories have been proposed elucidating the pathophysiological mechanisms attributing to high mortality and morbidity in COVID-19 infection. Out of them, thrombosis and procoagulant state have managed to earn the maximum limelight. We conducted an observational study based on data from randomly selected 349 hospitalized patients with COVID-19 infection in a community-based hospital in New York City during the first wave of the COVID-19 viral surge in March 2020. The main objective of our study was to assess the risk and occurrence of thrombotic events (both venous and arterial) among the hospitalized patients including the intensive care unit (ICU) and non-ICU admissions with confirmed COVID-19 infection. The primary outcome in our study was defined as the thrombotic events that included myocardial infarction (MI), deep venous thrombosis (DVT), cerebrovascular accidents (CVA), and pulmonary embolism (PE). The study correlated the association of thrombotic events with the level of biomarkers of interest: D-dimer >1000 ng/ml, troponin-I >1 ng/ml, or both. The association of D-dimers and troponin-I with thrombotic events was measured using both univariate and multivariate Cox proportional hazard (PH) regression analysis. Out of a total of 349 patients, 78 patients (22.35%) were found to have elevated biomarkers (D-dimer >1000 ng/ml and/or troponin-I >1 ng/ml) and were categorized as a high-risk group. Eighty-nine patients developed thrombotic complications (evidence of more than one thrombotic event was found in several patients). Two-hundred seventy-one (77.65%) patients had no documentation of thrombosis. The incidence of thrombotic events included myocardial infarction (MI; N=45; 12.8%), cerebrovascular accidents (CVA; N=16; 4.5%), deep venous thrombosis (DVT; N=16; 4.5%), and pulmonary embolism (PE; N=9; 2.57%).

High Incidence of Thrombotic Thrombocytopenic Purpura Exacerbation Rate Among Patients With Morbid Obesity and Drug Abuse.

This study aims to identify the baseline patient characteristics, clinical presentation, and response to treatment of 11 patients who were diagnosed with thrombotic thrombocytopenic purpura (TTP) between 2014 and 2020 at Brookdale University Hospital Medical Center, Brooklyn, NY. Laboratory and clinical parameters were recorded for 29 patients who received plasmapheresis in this time period. Of 29 patients, 11 had confirmed TTP and one was diagnosed with hereditary TTP. Young, black, and female patients made up the majority of our patient population. A high prevalence of obesity and drug abuse were seen among our patients. Five out of 11 were obese and four of them were morbidly obese; six out of 11 patients were positive for the drug screen including cannabinoids (3), opiates (2), benzodiazepines (1), PCP (1), and methadone (1). Four patients with a positive drug screen had acute kidney injury (AKI), and plasmapheresis helped them enhance their kidney function. We observed a high incidence of AKI and high TTP exacerbation rates in patients who were drug abusers and those who were morbidly obese. There is a paucity of data on the relationship of TTP with obesityor drug abuse and this needs further study.

The Association Between Anemia of Chronic Inflammation and Alzheimer's Disease and Related Dementias.

BACKGROUND: Dementia is a spectrum of neurological diseases characterized by memory impairment and cognitive decline with the pathogenesis and effective management remaining elusive. Several studies have identified a correlation between anemia and Alzheimer's disease and related dementias (ADRD); however, anemia subtypes and association with ADRD have yet to be studied conclusively. OBJECTIVE: To study an association between ADRD and anemia of chronic inflammation. METHODS: We conducted a retrospective case-control study of the patients, diagnosed with ADRD at Brookdale Hospital. Pair-wise comparisons between means of controls and cases in terms of iron studies and laboratory results were performed using a Mann-Whitney U test. Pair-wise comparisons between anemia subgroups (moderate and severe) were performed using a Two Sample proportion Z-Test, where for each couple of normally distributed population. RESULTS: There was a total of 4,517 (1,274 ADRD group; 3,243 Control group) patients. There was significant difference in hemoglobin 10.15 versus 11.04 [p-value <0.001]. Iron studies showed a significant difference in ferritin 395±488.18 versus 263±1023.4 [p < 0.001], total iron binding capacity 225±84.08 versus 266±82.30 [p < 0.001] and serum iron level 64±39.34 versus 53±41.83 [p < 0.001]. Folic acid and vitamin B12 levels were normal in both groups. Severe and moderate anemia in the ADRD group were respectively 6.2% [95% CI: 4.2-8.4] and 13% [95% CI: 9.8-16.2] higher. Overall, incidence of moderate-to-severe anemia was found to be 19% higher in ADRD group [95% CI: 15.8-22.1]. CONCLUSION: We demonstrated an association between ADRD and anemia of chronic inflammation independent of age, renal function, and HgbA1C levels.

An Unusual Presentation of Merkel Cell Carcinoma in a HIV Patient: A Case Report and Literature Review.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, aggressive neuroendocrine skin cancer that generally arises on sun-exposed areas of body such as head, neck, upper limbs, and shoulders of people with light complexity. Typically, MCC presents as shiny, flesh-colored or bluish-red, intracutaneous nodule, possibly with ulceration or crusting. In most of the cases, there is an association with Merkel cell polyomavirus. Even though these are very aggressive tumors, early detection and treatment has always given favorable outcome. There seems to be no consensus in definite prognostic markers, and advanced stages have the worst outcome even with treatment. There has been a recent trend in using PD-I/PD-L1 target therapy rather than chemotherapy in these cancers and have shown to improve survival by many months. In this article, we report a very unusual presentation of MCC first found on left frontoparietal skull as an 8-cm diameter fixed, subcutaneous mass without any typical features of MCC and was found to have metastatic spread to lung and liver. The patient was treated with palliative radiotherapy to brain and chemotherapy with cisplatin/etoposide with addition of immunotherapy later.

Hereditary persistence of hemoglobin F is protective against red cell sickling. A case report and brief review.

Fetal hemoglobin (HbF) is a physiologic protein tetramer that is crucial for a developing fetus to survive in utero. Maternal hemoglobin has a relatively lower affinity for oxygen, and thus allows for an efficient transfer of oxygen from maternal to fetal blood. In addition to fulfilling a critical physiologic role, HbF is also known to alleviate symptoms of sickle-cell disease (SCD). The concentration of HbF depends on several factors. HbF is elevated in inherited conditions, such as hereditary persistence of HbF, hereditary spherocytosis, and thalassemia. The level of HbF is also increased in acquired states, such as pregnancy, aplastic anemia, thyrotoxicosis, hepatoma, myeloproliferative disorders, or hypoplastic myelodysplastic syndrome. It has been identified that some genetic loci have significant influence on HbF levels. The XmnI polymorphism, the HMIP locus, and the BCL11A gene are responsible for 45% of variations in HbF levels. Although SCD has been well described in the subpopulations of Africa, it is less common in the subpopulations of India. We describe a case of SCD, in which a patient with high HbF level presented at a very late age (27 years old). We presume the patient's inherently elevated HbF levels were able to compensate for the hypoxic episodes associated with SCD. The onset of symptoms was delayed as a result of elevated HbF levels.

Autoimmune Heparin-Induced Thrombocytopenia: Treatment Obstacles and Challenging Length of Stay.

BACKGROUND Autoimmune heparin-induced thrombocytopenia (aHIT) refers to a condition, in which antiplatelet factor-4 (PF4) antibodies activate platelets even in the absence of heparin (heparin independent platelet activation). This is a severe hypercoagulable state triggering massive thrombin storm needing additional therapies and aggressive anticoagulation apart from stopping heparin. Thrombocytopenia in these cases seems to be very severe and prolonged compared to classic HIT and poses additional clinical challenges in terms of anticoagulation management. Recently, direct oral anticoagulants (DOACs) seem to be an attractive option in the management of HIT as an alternative to vitamin K antagonists (VKA). CASE REPORT We describe a case of a 55-year African American male who presented with pleuritic chest pain and was found to have worsening kidney disease. Clinical and electrocardiogram findings suggested uremic pericarditis, and dialysis was warranted. After 5 days of exposure to heparin flushes during dialysis, the patient developed thrombocytopenia, and subsequently HIT was diagnosed. Argatroban was started initially, however, his platelets count continued to drop, and he developed acute deep venous thrombosis of the right lower leg. IVIG (intravenous immunoglobulin) was started and his platelet count started to improve after several days. The patient was discharged on Eliquis and his platelet count returned to normal levels after 3 months. CONCLUSIONS This case emphasizes the challenge managing HIT, a condition that has a high rate of complications. Several studies have reported platelet recovery with IV immunoglobulin when standard therapies fail. Recent evidence also supports the safety and efficacy of DOACs in offering a simplified way of managing these patients, especially in outpatient settings.

Programmed Cell Death Receptor (PD-1) Ligand (PD-L1) expression in Philadelphia chromosome-negative myeloproliferative neoplasms.

Programmed Cell Death Receptor (PD-1) and its Ligand (PD-L1) pathway inhibitor therapy has been explored in the field of oncology treatment mainly for solid tumors. In hematologic malignancies, there is limited information except for Hodgkin's lymphoma, and there is even less information regarding myeloproliferative neoplasm (MPN). Therefore, we explored this by first measuring PD-1 and PD-L1 levels (percentage of positive cells) in 63 patients with Philadelphia chromosome-negative MPN (Ph(-) MPN), including 16 MF (12 PMF, 2 post-PV-MF, 2 post-ET-MF), 29 ET, and 18 PV. We found there was no significant difference in PD-1 or PD-L1 levels between the different MPN groups but that there was a significant difference when PV, ET and MF were grouped as MPN and compared with controls, of all immune cells including CD4+, CD8+, CD14+ and CD34+ progenitor cells. We further found a higher incidence of higher expression levels (more than 50% of cells with positive expression) of PD-1 and PD-L1 (20% and 26%, respectively) in the CD34+ cells; in contrast, we found a low incidence (0.08-1.8%) in the immune cells in MPN patients. PD-1 and PD-L1 levels were also measured by MFI methods, and we obtained similar results except the measurements by percentage appeared to be more sensitive than the MFI methods. We found no correlation between PD-1 and PD-L1 expression levels and clinical features including WBC, platelet counts, hemoglobin levels, presence or absence of the JAK2, MPL, or CALR gene mutation, or splenomegaly. Since MPN represents stem cell disorders, the presence of elevated expression of PD-1 and PD-L1 in these cells suggests that the exploration of PD-1 and PD-L1 pathway inhibitor therapy may be worthwhile in Ph(-) MPN.

A Case of Ocular Kaposi's Sarcoma Successfully Treated with Highly Active Antiretroviral Therapy (HAART) Combined with Docetaxel.

BACKGROUND Ocular Kaposi's sarcoma (KS) involving the conjunctiva and ocular adnexa is uncommon and is usually treated with cryotherapy or surgical excision. We report a case of ocular KS successfully treated with HAART combined with 8 cycles of weekly docetaxel. CASE REPORT Our patient was a 24-year-old, treatment-naïve, HIV-positive (CD4 cell count 198 cells/mm3), homosexual man treated as having atypical hordeolum and subconjunctival hemorrhage, and later confirmed with pathology to have ocular KS with immunohistochemistry study showing KS with positive HHV8, CD34, CD31, and focal positive staining with Factor VIIIRA. HAART therapy was initiated combined with weekly docetaxel. With 2-month treatment of HAART and 8 cycles of weekly docetaxel, the KS of the bulbar conjunctiva and the eyelid partially resolved. CONCLUSIONS HAART combined with weekly docetaxel is an effective and well-tolerated option for ocular KS, which could be considered before cryotherapy or surgical excision.