Heme/Onc

1. Provide details on how embryonic stem cells and induced pluripotent stem cells can be used to potentially cure various genetic diseases. Give one example where stem cell therapies would provide benefit. (MKS1a) 2. State two benefits and two challenges of making red blood cells in culture. (MKS1a) 3. Compare and contrast the progression of hematopoiesis in fish, mice and humans. (MKS1a) 4. Explain the various forms of HSC transplantation and a strategy to improve its efficiency. (MKS1a)

1. Describe the components of the erythron. List direct and indirect measures of the red blood cell mass. (MKS,1a) 2. Identify the factors that influence erythropoiesis, including the role of erythropoietin. (MKS,1a) 3. Describe the components of the red blood cell, and the structure of hemoglobin. (MKS,1a) 4. Describe the function of hemoglobin. List factors that influence the affinity of hemoglobin for oxygen. (MKS, 1a) 5. Explain degradation of the red blood cell. (MKS, 1a)

1. Understand the definition of each red cell parameter (such as MCV, MCH and MCHC) and “rule of three” (MKS 1a) 2. Identify the most common interferences that may cause false CBC results (MKS 3c) 3. Recognize variations in red cell morphology and the associated underlying clinical conditions (MKS 1b)

1. Define anemia and list the common laboratory tests used to evaluate anemia. (MKS 3c) 2. Explain normal physiologic compensatory mechanisms in response to anemia. (MKS 1b) 3. Know typical symptoms and physical exam findings of those who are anemic. (NKS 1d) 4. Be familiar with common findings of red blood cells on peripheral blood smear associated with specific types of anemia (MKS 1d) 5. Derive a differential diagnosis for anemia based on the kinetic as well as the morphologic approach to

1. Describe the normal structure, organization and function of the RBC membrane (MKS, 1a) 2. Explain the normal metabolic pathways in the RBC responsible for generating reducing power (pentose phosphate shunt) and producing energy (glycolysis) (MKS, 1a) 3. Describe the pathophysiologic mechanisms, epidemiology and clinical findings associated with the most common inherited disorders of the RBC membrane (spherocytocis, ovalocytosis) and metabolic pathways (GGPD deficiency, PK deficiency) (MKS,

1. Describe the basic structure and function of hemoglobin and how these are altered by sickle cell disease (MKS, 1a, 1b) 2. Explain the genetic basis for normal globin gene regulation and hemoglobin switching (MKS, 1a) 3. Explain the genetic, molecular and pathophysiological basis of sickle cell disease (MKS, 1a, 1b) 4. Describe the clinical findings of sickle cell disease and its management (MKS, 1b, 3c)

1. Describe the genetic and molecular differences among the thalassemia syndromes (MKS 1b) 2. Explain how the pathophysiology in thalassemia results in the clinical manifestations of thalassemia.(MKS 1d, 1b) 3. Understand the clinical considerations of thalassemia, including diagnosis and disease management (MKS 1d, 1e) 4. Ascertain the consequences of transfusional iron overload in thalassemia (MKS 1e)

1. Describe the absorption, transportation, and storage of iron—MKS 1a 2. Describe the central role that the hepcidin-ferroportin axis plays in regulating iron absorption—MKS 1a 3. Describe the clinical, laboratory manifestations, and treatment of iron deficiency anemia—MKS 1b, 1d, 1e 4. Describe the concept of iron sequestration that is central to the anemia of inflammation—MKS 1b, 1d 5. Describe the consequences of hepcidin deficiency as it pertains to hereditary hemochromatosis, a

1. Describe the bone marrow and peripheral blood consequences of megaloblastosis (MKS 1a, MKS 1d) 2. Describe the metabolism and absorption of vitamin B12 and folic acid metabolism, and accordingly, associated disease states that lead to deficiency states (MKS 1a,1b, 1d) 3. Describe the rational approach to treating vitamin B12 and folic acid deficiency (MKS 1e)

1. Explain the mechanisms of red blood cell hemolysis and acquired hemolytic anemias. (MKS, 1b) 2. Describe the pathologic mechanism of immune-mediated red blood cell hemolysis. (MKS, 1b) 3. List the basic approach to the treatment of hemolytic anemias (MKS, 1e) 4. Describe the laboratory tests used in the diagnosis of hemolytic anemias. (MKS, 1d)

1. Describe the steps of RBC compatibility testing: ABO and Rh(D) blood typing, RBC antibody testing, and crossmatching (MKS1a/ knowledge). 2. Correctly perform blood-bank specimen phlebotomy and blood administration to achieve transfusion safety (CLQI 5/ patient safety). 3. Evaluate when RBC transfusion is needed (MKS3d/ clinical reasoning).

Verification is a three-way process: the blood bag label with the unit number and blood type the patient’s identity, confirmed by the facility wristband and if possible, the patient the transfusion tag applied on the unit by the blood bank, linking the unit number and the intended recipient Some hospitals have an extra blood bank wristband code Two providers must cross-check the patient and blood-unit information together at the bedside before transfusion, unless the hospital has a bedsid

1. Define the term “coagulation cascade”, and discuss how it enhances thrombin generation MKS1a/ knowledge 2. Describe the basis for the partial thromboplastin time and the prothrombin time, and which clotting factors contribute to these tests MKS1a/ knowledge 3. Understand the contribution of platelets in establishing the hemostatic plug (thrombus) MKS1a/ knowledge 4. Describe “microparticles” and how they contribute to thrombus formation. MKS1a/ knowledge 5. Identify the hemostati

1. The student will be able to accurately summarize the steps involved in normal platelet biogenesis. (MKS 1a) 2. The student will be able to locate the sites of normal platelet production and discuss the major determinants of platelet life-span and fate. (MKS 1a) 3. The student will be able to explain the major features of platelet function and how platelets contribute to hemostasis. (MKS 1a) 4. The student will be able to evaluate altered platelet functions in congenital & acquired platelet

1. Describe the pathophysiology of thrombus formation in the venous system (MKS1a knowledge) 2. Identify risk factors for venous thrombosis and pulmonary embolism (MKS1a knowledge) 3. Apply the concept of pretest probability to the diagnosis of venous thromboembolism (MKS1a knowledge) 4. Describe the complications of deep vein thrombosis and pulmonary embolism (MKS1a knowledge)

1. Recognize that there are many factors that contribute to or prevent thrombosis, leading to the concept of hemostatic balance. MKS1a/ knowledge 2. Distinguish between arterial thrombosis and venous thrombosis. MKS1a/ knowledge 3. Describe the common mutations associated with venous thrombosis, & their population frequency. MKS1a/ knowledge 4. Review mechanisms by which the natural anticoagulants, antithrombin, protein C, & protein S, protect against thrombosis. MKS1a/ knowledge 5. Indicate

1. List the various classes of anticoagulants (vitamin K antagonists, heparins, direct thrombin inhibitors) and their loci of action. (MKS, 1e) 2. List the clotting factors affected by warfarin, and the order of their disappearance from plasma (MKS, 1b, 1e) 3. Define “International Normalized Ratio” and its use to monitor warfarin therapy (MKS, 1d, 1e) 4. Describe the factors that potentiate, antagonize, and reverse warfarin effect (MKS, 1e) 5. Review the historical development of unfrac

1. Explain the role of von Willebrand Factor in hemostasis and delineate its interaction with platelets, clotting proteins and the endothelium. (MKS-1a) 2. Classify the types of von Willebrand Disease, their inheritance pattern and pathophysiologic effects (MKS-1b) 3. Identify the pattern of bleeding produced by each type of VWD and the resulting clinical signs and symptoms (MKS-1d) 4. Predict the results of laboratory tests for patients with each type of VWD (MKS-1d) 5. Explain local, suppo

CBC with peripheral smear  review platelet morphology & number Abnormalities on smear which may aid diagnosis schistocytes, helmet cell microangiopathic process: HUS, TTP large platelets,  number, normal RBC, WBC production defect immune mediated process: ITP, drug induced antibody large inclusion granules Chediak - Higashi large platelets Bernard - Soulier and May Heggelin small platelets,  number Wiskott - Aldrich gray or washed-out platelets Gray Platelet Syndrome

• List the various acquired defects leading to a coagulopathic state. (MKS 1b) • Understand the role of Vitamin K in coagulation, and how a deficiency in this vitamin could lead to a bleeding diathesis. (MKS 1a, 1b) • Understand the various effects liver disease has on hemostasis and thrombosis, and how various disturbances can predispose to abnormal hemostasis and/or inappropriate clot formation. (MKS 1b) • Understand the pathophysiology of acquired hemophilia, its clinical presentat

• List the various causes of thrombocytopenia (MKS 1b) • Understand the pathophysiology, presentation, and treatment of primary autoimmune thrombocytopenia/ITP (MKS 1b,1e, 1d) • Be familiar with the various ways drugs can cause thrombocytopenia (MKS 1b, 1e) • Know the pathophysiology, presentation, and treatment of heparin-induced thrombocytopenia (MKS 1b,1d,1e) • Know some of the congenital causes of thrombocytopenia (MKS 1b)

1. List some causes of microangiopathic hemolytic anemia.(MKS 1b) 2. Describe the pathophysiology of thrombotic thrombocytopenic purpura (TTP). (MKS 1b) 3. Describe the clinical presentation for patients with TTP. (MKS 1d) 4. Describe the treatment for TTP. (MKS 1e) 5. Describe the similarities and differences between TTP and hemolytic uremic syndrome (HUS). (MKS 1b) 6. List the various causes of disseminated intravascular coagulation (DIC). (MKS 1b) 7. Describe the pathophysiology of DIC.

1. Summarize the contents of and expected responses to transfusions of platelets, plasma, and cryoprecipitate (MKS1e/ core knowledge). 2. Evaluate when platelet transfusion is needed (MKS3d/ clinical reasoning). 3. Evaluate when plasma and cryoprecipitate transfusion is needed (MKS3d/ clinical reasoning).

1. Describe normal lymph node structure including primary location of the major cell types (MKS 1) 2. Describe how normal lymph node structure/architecture relates to neoplastic lymphoid proliferations (MKS 1) 3. Differentiate the relationship and differences between normal and neoplastic lymphoid cells (MKS 1) 4. Understand that lymphoma is a clinicopathologic entity – describe the morphology, phenotype, genotype and clinical features that are required to correctly classify the disease (SA

1. Define chronic lymphocytic leukemia (CLL) and other lymphoproliferative disorders (medical knowledge).(MKS 1b) 2. Discuss the clinical, pathologic, and immunologic features of chronic lymphocytic leukemia, hairy cell leukemia, and prolymphocytic leukemia (medical knowledge). (MKS 1d, 1b) 3. Compare and contrast the clinical, pathologic and epidemiologic characteristics of large granular lymphocyte leukemia, adult T cell leukemia/lymphoma, and Sézary syndrome (medical knowledge). (MKS 1b, 1

1. Describe the classification of peripheral T-cell/NK-cell lymphoma, and Hodgkin lymphoma. (MKS 1b) 2. Familiar with the clinical features of Hodgkin lymphoma and major subtypes of peripheral T-cell lymphoma. (MKS 1b, 1d) 3. Know the immunohistochemical and/or genetic markers for some T-cell lymphoma subtypes and Hodgkin lymphoma. (MKS 1b, 1d)

1.) Discuss the diagnostic evaluation of monoclonal gammopathies (MKS-1d) 2.) Delineate the diagnostic criteria for MM, plasmacytomas and MGUS as well as their pathology and clinical manifestations (MKS-1d) 3.) Discuss the clinical features of primary amyloidosis and how it differs from MM (MKS-1d) 4.) Describe the goals of treatment for MM (MKS-1e)

1. Know definitions of mild, moderate, and severe neutropenia (MKS-1b) 2. Understand that disorders of neutrophils secondary to bone marrow pathology have a higher risk of bacterial infection than those with normal bone marrow pathology (MKS-1b) 3. Describe the common acquired and inherited disorders of neutropenia (MKS-1b) 4. Describe the disorders of neutrophil function (MKS-1b) 5. Know the tests obtained to diagnose disorders for neutrophil number and function (MKS-1d) 6. Know the manage

1. Define acute myeloid leukemia, acute lymphoblastic leukemia, aplastic anemia and MDS by laboratory, histology, and molecular criteria (MKS, 1b, 1d) 2. Describe the pathogenesis of AML, ALL, aplastic anemia and MDS (MKS, 1b) 3. Describe the treatment approaches to aplastic anemia and MDS (MKS, 1e)

1. The student will be able to describe HLA typing and how to use it to determine which is the better donor (MKS 3c) 2. The student will be able to know the different types of transplants and the indications for it. Autologous vs. allogeneic, syngeneic and the different types of conditioning regimens. (MKS 1e) 3. The student will have an understanding of the procedure itself and understand the risks and benefits of the process of transplantation with some examples of survival , we will also ad

1. Describe characteristic molecular abnormalities identified in the classical myeloproliferative neoplasms contribute to disease pathogenesis (MKS 1a and 1b) 2. Describe the distinction between BCR-ABL as a disease specific molecular abnormality, compared to JAK2 V617F, which represents a normal pathway placed into overdrive; recognize the implications regarding treatment (MKS 1a, MKS 1b, MKS 1e) 3. Describe the diagnosis, clinical features, and treatment options for patients with classical M

1. Understand the concept of oncogene and signal transduction pathway (MKS1b) 2. Understand the concept of tumor suppressor gene (MSK1b) 3. Understand the clinical impact of molecular aberrations in the above mentioned genes (MSK1d)

1. Define the histopathology of neoplasia: neoplasia, dysplasia, anaplasia. (MKS,1b) 2. Understand the nomenclature/classification of neoplasms and the differences between benign and malignant tumors. (MKS, 1b) 3. Identify the intrinsic properties of malignant tumors that distinguish them from benign neoplasms. (MKS, 1b) 4. Compare and contrast grading versus staging of tumors. (MKS, 1b) 5. Explain the role of molecular testing and immunohistochemistry in the workup of tumor specimens. (MKS,

1. Know the concept of the Immune Surveillance and Immuno-editing theory. (MKS 1b) 2. Know the antigens expressed by cancer cells (MKS 1b) 3. Understand how cancers evade immune system (MKS 1b) 4. Describe the approaches used in Cancer Immunotherapy (MKS 1e) 5. Discuss the potential and limitations concerning the use of immunotherapy drugs in the treatment of cancer. (MKS 1e) 6. Describe the nature and therapeutic use of genetically modified T cells expressing chimeric antigen receptors (CA

1. Describe which viruses are associated with cancer in humans. (MKS 1b) 2. Describe the mechanisms of how viruses contribute to cancer. (MKS 1b) 3. Describe the differences between DNA and RNA oncogenic viruses. (MKS 1b) 4. Describe how viral-associated cancers are treated and how their occurrence can be reduced. (MKS 1b)

. Describe the approach to chemotherapy drug development (MKS 1e) 2. Describe the rationale for chemotherapy regimen design, including use of combination chemotherapy, timing of chemotherapy vs. surgery/radiotherapy and dose intensive administration of agents even with a low therapeutic index (MKS 1e) 3. Explain how pharmacokinetics, pharmacodynamics and pharmacogenetics are used to design chemotherapy regimens and modify drug administration (MKS 1e) 4. Explain mechanisms of action for ma

1. Explain the difference between clinical and pathologic staging (MKS1b+1d) 2. Use cancer staging to select the optimal treatment strategy for a patient with newly diagnosed lung cancer (MKS 1d, 1f + 3a) 3. Based on tumor anatomy and biology, determine the optimal operation for a patient with early stage lung cancer (MKS 1a + 1b) 4. Determine if a patient with early stage lung cancer will tolerate the optimal surgical resection based on pulmonary and cardiac physiology (MKS 1c + 3a)

1. List three primary events in the history of chemical carcinogenesis (MKS 1b) 2. Distinguish mutagenic and non-mutagenic carcinogens and their modes of action in chemical carcinogenesis. (MKS 1b) 3. Design in vitro and in vivo assays to test whether a new compound may be carcinogenic. (MKS 1b) 4. Explain the distinct events occurred during the different steps of chemical carcinogenesis. (MKS 1b) 5. Design an experiment using the skin cancer mouse model to demonstrate the different effects

1. List risk factors for the development of thyroid cancers of follicular cell origin (MKS1b) 2. Describe the components of the treatment of differentiated thyroid cancers of follicular cell origin (MKS3d) 3. List the genes that, when mutated, lead to multiple endocrine neoplasia (MEN) 1 and MEN 2 (MKS1b). 4. Describe the endocrine tumors and non-endocrine manifestations of MEN 1 and MEN 2 (MKS1d) 5. Describe the tumors that arise from each layer of the adrenal cortex and medulla, the h

1. Describe types of paraneoplastic syndromes (MKS 1b) 2. Describe approaches to diagnosing and treating paraneoplastic syndromes (MKS 1d, 1e) 3. Describe outcomes of paraneoplastic syndromes (MKS 1b)

1. Describe the two major causes of breast cancer. (MKS1a) 2. Explain why staging is an important exercise in the initial evaluation of breast cancer patients. (MKS1a) 3. Summarize the evidence for the safety of breast conservation in the therapy of breast cancer. (MKS1a) 4. Apply the new biological classification of breast cancer to the recommendations for treatment (MKS1a) 5. Distinguish between the goals of local and systemic therapy for breast cancer (PBMR2) 6. Summarize the major optio

1. Describe the goals of radiation therapy (RT) in the management of cancer patients (MKS 1c) 2. Recognize scenarios in which RT is used alone and in conjunction with other treatment modalities. (MKS 1e) 3. Delineate the major steps for the initiation of RT. (MKS, 1e) 4. Describe the basics of radiation physics – how dose is deposited in tissue. (MKS, 1a) 5. Describe the basics of radiation biology – the mechanism of radiation induced cell kill. (MKS 1b) 6. Explain differences between d

1. List 5 potential organ systems that can be impacted by a late effect of cancer treatment. [MKS-1a] 2. List common psychological issues that cancer survivors face. [MKS-1b, MKS-1c] 3. Describe the purpose of a survivorship treatment summary and care plan. [PCMC-6, PCMC-7]

1. Describe the most frequent clinical symptoms associated with each genitourinary malignancy (bladder, prostate, kidney and testicular cancer) (MKS1d). 2. Understand how staging impact the treatment plan and goals of genitourinary malignancies (MKS3d). 3. Identify patients at high risk for prostate cancer and its implication for screening strategies (MKS1f). 4. Understand the importance of androgen receptor signaling for prostate cancer growth at castrate levels of testosterone as a parad

1. List the risk factors of head and neck cancer (MKS 1b) 2. Apply the knowledge of clinical features and anatomy to diagnose head and neck cancer in a patient (MKS 1d) 3. Describe the basic principles of head and neck cancer treatment (MKS 1e) 4. Describe the functions of the head and neck that must be preserved during treatment (MKS 1e)

1. Identify the most common pediatric cancers and their incidence across the childhood age spectrum (MSK1s/knowledge) 2. Understand how pediatric cancers differ from adult malignancies in both prognosis and distribution by histology and tumor site (MSK1s/knowledge) 3. Describe the general approach to treatment of childhood malignancies including the role cooperative group clinic trials (MSK1s/knowledge) 4. Identify aspects of treatment and survivorship that are unique to children with cancer