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CLINICAL PATHOLOGY HEMATOPATHOLOGY ROTATION

I. Overall Goals

The overall goal of the rotation is to educate the residents so that they can (1)establish and direct a hematopathology laboratory that includes clinical hematology, urinanalysis, clinical microscopy, flow cytometry and diagnostic hematopathology and (2) to provide consultation to clinicians on patient problems related to hematopathology. These goals are achieved by having a four month rotation in the service, weekly didactic teaching and slide sessions throughout the two years of clinical pathology, and assigned reading. During the four month rotation, the residents are individually or in pairs “covering” the service, enabling them to learn and test their level of expertise by exposure to clinical cases and laboratory problems and to integrate information obtained from various diagnostic tests in the field of hematopathology.

The ACGME endorsed six competencies are covered approximately as follows:

A. Patient Care: This is the emphasis of the four month rotation described below.

B. Medical Knowledge: The fundamentals are taught in the year long hematopathology course given as weekly lectures (see details below). These principles are then applied to study cases and expanded upon in weekly slide review sessions presented by the attending. Residents are required to attend and participate throughout their two years of CP and are welcome to attend during their AP rotations. Reinforcement of the pathophysiology of disease and discussion of recent publications continues during the clinical rotation as it applies to current clinical problems.

C. Practice Based Learning and Improvement: During the rotation, residents are expected to acquire the ability to apply their knowledge to specific cases and to incorporate information from multiple sources in the final diagnosis. In select challenging cases, they are expected to research the scientific literature as it applies to the problem at hand.

D. Interpersonal and Communication Skills: In addition to their presentations, residents are expected to hone their ability to communicate on a more individual basis. During their 4 month rotation, they are expected to interact effectively with laboratory personnel, reference laboratory personnel, and clinicians to both obtain and provide patient information. This includes the ability to communicate verbally, in person and over the telephone, and by writing to document action taken. They are expected to demonstrate increasing autonomy although attending support is always available.

E. Professionalism: The resident is always expected to conduct his or herself in a professional manner from the outset.

F. Systems Based Practice: Using both the information about instrumentation, appropriate laboratory testing and diagnostic criteria obtained during the didactic sessions and the first hand experience gained in the laboratory rotations, the residents should be able to understand the functioning of this specialty laboratory, the necessity and interpretation of specific tests and the regulatory standards as they apply. They should also be familiar with the steps required to establish new protocols in this type of facility.

II. Didactic Seminar and Slide Review Series

A. Seminars
Topics are assigned to the residents the first day of the academic year. In addition to resident presentations (always with the attending present), some seminars are given by the attending, the laboratory supervisor, or technical advisors from companies. Residents are expected to use multiple and recent sources for their presentations and demonstrate the capability to critically analyze the scientific literature as it applies to clinical issues. All topics are assigned in the beginning of the academic year to allow adequate time for preparation. The attending is available for advice and literature resources. A specialty book collection, kodachromes, and journals are available in the hematopathologist’s office and may be borrowed on a signup basis. In addition the medical library at SUNY Downstate Medical Center has many reference books and journal available, both in hard copy and on line. The latter may be accessed by the residents from any location, including distant sites at any time.

Topics covered include:

Hematology Analyzers, including reticulocytes
Coagulation instruments
Coagulation pathway and disorders
Flow cytometry
Molecular Pathology including PCR and Southern blots, FISH, karyotype with painting and gene microarray analysis
Normal Peripheral Blood and Bone Marrow Smear Morphology
Erythrocyte Abnormalities
Anemia, primary and hemolytic
Functional Granulocyte Abnormalities
Reactive White Blood Cell Morphology
WHO Classification of Hematological Malignancies
Myeloid Malignancies (Chronic & Acute)
Lymphoid Malignancies (Precursor, Peripheral T & Peripheral B)
Hodgkin Lymphoma
Iron Metabolism
Hemoglobin Electrophoresis
Hemoglobinopathies/Thalessemias
Urine Analysis with analyzers

Seminars are from 9:00-10:30 Friday mornings in the KCH Pathology conference room.

B. Slide Sessions
Review of study sets of hematopathology slides is conducted by the attending at the projection microscope in the pathology conference room B4-5, Fridays at 3-4:30pm. Cases are from a study set collection and recent interesting cases gathered by attending. Where appropriate they correspond to the topics discussed in the AM lecture that day. Information reviewed includes clinical presentation, immunophenotype and cytogenetics where relevant. A discussion of the pathophysiology of the entity under consideration occurs concurrently.

III. Description of Laboratory Rotation:

The goal is for the resident to learn by exposure, work-up and discussion of cases coming through the two hospitals (KCH and UH) over the four month period. They are expected to function with growing independence (with close supervision) for the work-up of cases. Final diagnosis is the responsibility of the attending. The resident is expected to act as consultant to the clinical hematology service to guide their choices of specialized testing required for a definitive diagnosis. They are expected to act as a liaison between the hematologists and specialty labs such as flow cytometry and cytogenetics. Information from all these areas is incorporated into the final diagnosis. All preceding steps are under the guidance of the attending hematopathologist.

A. Hematology Labs: KCHC/UHB

Priority Call: The resident is paged for specified abnormal results; i.e. malignant cells, organisms, in peripheral blood or fluid specimens. Resident must evaluate smears, obtain patient history, write up conclusions and present case to attending. They are expected to act as a liaison between the laboratory and the clinical service.

Review of Abnormals: Each laboratory sets aside 3-5 abnormal smears/weekday for resident review. Criteria are outlined in each lab. In addition, UH sets aside all fluids for clinical microscopy for daily resident review. This gives them a background in the morphology of reactive processes.

CAP and State Surveys: The resident is to review the CAP and state surveys done by the lab before they are submitted.

CAP surveys (pathologist): The resident is given the hematopathology CAP surveys to complete independently. Answers are reviewed and discussed with lab director before submitting.

Instruments: Residents are expected to familiarize themselves with the instrumentation in the labs.

B. Hematopathology: KCHC/UHB Surgical Pathology

Bone marrows: All bone marrow specimens are worked up by the resident. This responsibility includes obtaining the peripheral blood smear, aspirate smear, relevant lab results and history. The resident reviews all the material and then presents the case to the attending.

Lymph nodes: Fresh samples are processed by the resident with the attending’s supervision. At least one half is immediately fixed in formalin. After a review of the clinical history and an assessment of the size of the sample, decisions are made on the remaining sample based on review of touch preparation slides. At least 5 additional touch preps are prepared and fixed in cold acetone for possible immediate immunoperoxidase stains. The remainder is either frozen or placed into formalin. Lymph nodes received in fixative are processed by the surgical pathology resident. Histological slides are reviewed the next day and presented to the attending with suggestions for special stains if necessary.

All other tissues: Any other samples with suspected hematological malignancies are referred by surgical pathology to the hematopathology service. Any additional workup needed is done by the hematopathology resident and then presented to the attending.

Specialty Tests: the hematopathology service functions as consultants for the clinical service with respect to specialty test ordering and result interpretation. This includes the need for and specifics of tests ordered for flow cytometry, cytogenetics, FISH for specific translocations, gene rearrangement studies, PCR for residual disease, and serum measurements for serological positivity and for soluble receptors.

C. Hematology/Pathology Combined Rounds

• Combined rounds take place every Wednesday morning at 8:30 in A21 KCH. At that time all adult patients from both hospitals are reviewed and the hematology fellows present the history, physical exam, therapy and clinical course. Slides on all new cases are shown and any specialty tests, flow cytometry, cytogenetics and FISH are discussed.

• Tumor Board: Residents are expected to attend tumor board at University Hospital when it does not conflict with clinical pathology seminars.

D. Clinical Hematology Service


A portion of the four month rotation is spent with the clinical hematology service. The residents get experience interviewing and examining patients and performing bone marrows. The residents are expected to continue in their role as pathology consultant and liaison between the clinical and pathology services.

IV. Expected Skills (adapted from Academy of Clinical Laboratory Physicians and Scientists. Curriculum content and evaluation of resident competency in Clinical Pathology (Laboratory Medicine): a proposal)

By the end of a complete year of lectures and the 4 month rotation, the residents are expected to have mastered the following skills and will be evaluated on such:

A. Hematology/Body Fluids/ Urinanalysis

1. Automated Hematology

Skill Level I:

Understand the principles of automated cell counting including RBC indices and their derivation and the principles by which each instrument type arrives at a 5 part differential.
Understand the effect of clots, hemolysis, and lipemia on automated CBC results
Understand the effect of nucleated RBC on WBC counting, and appropriate WBC correction
Understand the importance of absolute versus relative counts and the absolute neutrophil count (ANC) and its clinical utility, as well as problems associated with band counts
Understand principles of automated Reticulocyte enumeration

Skill Level II:

Interpret results of automated and manual cell counts and scattergrams. Anticipate how the automated instruments will interpret each abnormal or atypical cell type.
Review abnormal results, correlate results with peripheral blood smear findings and clinical history

2. Peripheral Blood Smear Analysis

Skill Level I:

Learn proper preparation and handling of peripheral blood smear
Learn normal RBC, WBC and platelet morphology
Estimate WBC and platelet counts

Skill Level II:

Recognize abnormal RBC, WBC, platelet morphology, formulate a differential diagnosis, and suggest appropriate laboratory testing for follow-up

3. Body Fluid Analysis: Cerebrospinal fluid, ascitic/pleural fluid, joint fluid

Skill Level I:

Learn manual Hemocytometer cell counting
Understand cytocentrifuge preparation and slide staining
Identify blood and body fluid cell morphology

Skill Level II:

Recognize malignant cells and recommend appropriate confirmatory tests. Correlate with clinical history and other laboratory results.
Identify crystals in body fluid (usually synovial fluid). Distinguish between uric acid and calcium pyrophosphate crystals using polarized light
Identify organisms: bacteria, fungi, parasites and recommend appropriate confirmatory tests. Correlate with clinical history

4. Manual Methods

Skill Level I:

Understand principles of microhematocrit determination and correlation with automated Hct
Understand the principles of erythrocyte sedimentation rate
Understand the principle and utility of supravital stains, reticulocyte stain, Hgb H prep and Heinz body prep

5. Urinalysis

Skill Level I:

Understand the principles of methods involved in urine chemistry and urine cytology
Understand indications for urinalysis

Skill Level II:

Interpret routine urinalysis and identify abnormal cells and organisms, provide clinical follow-up as appropriate
Understand the principles of automated urine cytology analysers

6. WBC Disorders

Skill Level I:

Understand the principle and clinical utility of cytochemical stains, their interpretation, and applications

Skill Level II:

Interpret cytochemical results to distinguish between hematologic malignancy, chronic granulomatous disease, and myeloproliferative disorders

7. RBC Disorders:

Skill Level I:

Understand the role of Fe in RBC production/hemoglobin synthesis
Describe Fe metabolism and laboratory tests for Fe depletion
Understand Hemoglobin synthesis and degradation and genetic mechanisms of abnormal Hgb and thalessemias
Know pathophysiology and characteristic laboratory findings of the major disorders causing anemia microcytic, hypochromic and macrocytic
Know pathophysiology and laboratory features of intravascular and extravascular hemolysis
Understand the principles of hemoglobin screening by HPLC and electrophoresis at acid and alkaline pH and sickle solubility screening
Understand the principle and clinical utility of Kleihauer Betke and/or flow cytometric analysis for fetal hemoglobin
Understand the principle and clinical application of the osmotic fragility test

Skill Level II:

Interpret hemoglobin electrophoretic patterns and ancillary tests for the diagnosis of
major hemoglobinopathies (Sickle cell anemia, alpha/beta thalassemia, Hgb E disease and Hgb C disease)
RBC disorders related to enzyme defects (G6PD deficiency, methemoglobinemia)
Hereditary spherocytosis
Paroxysmal hemoglobinuria
Hemolytic Anemia
Congenital dyserythropoietic anemias

8. Platelet Disorders

Skill Level 1

Thrombocytopenia: Understand the pathophysiology of ITP, TTP, and distinguish from lack of platelet production
Understand the principles of platelet discrimination and counting by automated hematology analyzers.

B. Coagulation

Skill Level I:

Understand the principles of routine coagulation analysis (PT, APTT, fibrinogen, Thrombin Time)
Understand the difference between qualitative and quantitative testing.
Understand the principle of clot based and chromogenic coagulation factor assays, and recommend their appropriate use
Understand the effect of hematocrit and blood drawing technique on anticoagulation of blood sample for coagulation testing
Understand the INR derivation and its clinical significance
Understand the principle of tests involved in monitoring heparins (unfractionated vs LMW)
APTT, anti Xa activity
Understand the method of action of direct thrombin inhibitors and their effect on coagulation testing
Understand the pathophysiology of Vit K deficiency or antagonism and appropriate laboratory monitoring tests
Develop basic understanding of hemostatic and thrombotic disorders
Understand the coagulopathy of liver disease
Understand the laboratory evaluation of DIC
Understand the pathophysiology of the hemophilias (A B, C)
Understand the principles of molecular analysis of thrombotic risk factors (Factor V Leiden, Prothrombin G20210A, MTHFR)
Understand results of mixing studies to guide further coagulation testing
Understand results of tests involved in the identification of lupus anticoagulant and antiphospholipid antibody syndromes
Recognize the effect of circulating anticoagulants on coagulation testing

Skill Level II:

Interpret results of Bethesda assays for factor inhibitors
Interpret results of coagulation tests in the setting of fibrinolytic therapy
Interpret results of Heparin Induced Thrombocytopenia testing (ELISA tests vs serotonin release assay/platelet aggregation studies) in the appropriate clinical context
Interpret platelet function studies including platelet aggregation and secretion studies, and screening studies, such as the Bleeding Time and “in vitro” screening tests of platelet function
Be able to perform the bleeding time test
Recognize platelet function abnormalities associated with acquired thrombocytopathies: aspirin, Plavix, GPIIb-IIIa antagonists
Recognize platelet function abnormalities associated with congenital thrombocytopathies (thrombasthenia, Bernard Soulier Syndrome, Storage Pool Disease)
Interpret studies performed for the evaluation of vWD
Understand the pathophysiology leading to major vWD subtypes and expected laboratory results
Interpret results of tests measuring components of the fibrinolytic system
Interpret results of test for thrombotic risk factor identification: Protein C, S, ATIII, and Activated Protein C Resistance
Discuss risk factors leading to arterial and venous thromboembolic disease, and suggest appropriate work-up
Interpret results of laboratory tests utilized in the management of bleeding and thrombotic disorders
Demonstrate competency in interpreting coagulation studies for the diagnosis of bleeding and thrombotic complications
Understand the mechanism of action of platelet directed inhibitors and fibrinolytic agents, and their effects on laboratory testing
Understand monitoring and complications of Biologics as drugs (recombinant Activated Protein C, Recombinant F VIIa)

C. Flow Cytometry

Skill Level I:

Understand the physical components and operating principles of a flow cytometer
Understand quality control procedures
Understand the principles of routine flow cytometry evaluation of leukocytes, including both surface and intracellular markers, and recognize clonal abnormalities
Understand principles of tests designed to evaluate the DNA content (ploidy) and cell cycle
Understand platelet antibody testing and its clinical applications
Understand the diagnostic, prognostic information provided by flow cytometry
Understand the principles of lymphocyte subset analysis: know the commonly used antigens to define T helper, T suppressor, natural killer and B cells
Appreciate the effect of age on lymphocyte subset normal ranges
Observe/perform lymphoma/leukemia panel performed on blood and/or bone marrow. Coordinate with clinical presentation and slide morphology.
Observe /perform lymphoma panel on lymph node or spleen specimens. Coordinate with clinical presentation and slide morphology.

Skill Level II:

Evaluate and interpret results of flow cytometry in conjunction with cytochemistry, immunocytochemistry and immunohistochemistry studies as related to hematopoietic and lymphoproliferative diseases
Understand the characteristic clinical, morphologic, immunophenotypic, cytochemical and cytogenetic/molecular features of
acute myeloid leukemia
acute lymphoid leukemia
myelodysplastic syndromes
PNH
Plasma cell dyscrasias: Plasma cell myeloma, MGUS, and Waldenstrom’s macroglobulinemia
non-Hodgkin’s and Hodgkin’s lymphoma
neuroblastoma
chronic lymphoproliferative disorders
post transplant lymphoproliferative disorder
polymorphic and lymphomatoid papulosis
T/NK cell neoplasms
Interpret specific flow cytometric abnormalities associated with immunodeficiency syndromes
Interpret CD34 counts for stem cell transplantation and for prognostics in myeloproliferative disorders

D. Hematopathology/Bone Marrow

Skill Level I:

Learn technical aspects of performing and analyzing bone marrow aspiration and biopsy
Learn handling, preparation and interpretation of bone marrow specimen including special stains (e.g. Silver stain, Prussian blue)
Correctly assess bone marrow cellularity, storage iron and fibrosis.
Recognize normal WBC, RBC and platelet maturation, as well as cellular dysplasia
Recognize normal lymph node and spleen morphology and changes associated with lymphoma
Recognzine reactive bone marrow and lymph node patterns
Recognize effects of chemotherapy and growth factor stimulation on blood and bone marrow
Understand common drug effects leading to benign cytopenias

Skill Level II:

Integrate morphology, cytochemistry, immunophenotype and molecular and cytogenetics in the differential diagnosis of
acute and chronic leukemia,
myelodysplastic syndromes
myeloproliferative disease
lymphoma,
immunodeficiency related lymphoma/lymphoproliferative diseases
Hodgkins Lymphoma
T cell Lymphoma
Extranodal lymphoma
and myeloproliferative diseases
Integrate peripheral blood smear and bone marrow findings, aspirate and tissue sections, and incorporate relevant flow cytometry and cytogenetic data and render a preliminary diagnosis.

E. Additional Competencies specific to Hematology

Patient Care

Demonstrate technical skill in performing bone marrow aspirates and biopsies
Appreciate special considerations in Pediatric Hematology/Coagulation and Hematopathology
Understand laboratory methods to follow patients with diagnosed hematological disorders, including their sensitivities and relevance in different clinical scenarios. These would include soluble serum markers of tumor load based on release of surface molecules and molecular pathology techniques for minimal residual disease.


F. Immunoglobulin Quantitative and Qualitative Disorders as they relate to underlying hematopoietic disorders

Skill Level I:

Understand the basic biology of immunoglobulins
Know the structure of immunoglobulin molecules.
Know the classes of immunoglobulins and the types of immunoglobulin fragments
Understand the function and binding sites of various portions of immunoglobulin molecules.
Understand the mechanisms for generation of immunoglobulin diversity
Understand the principles of protein electrophoresis & immunofixation
Interpret the protein electrophoresis patterns observed in normal serum, normal plasma, normal urine, and in large monoclonal gammopathies such as multiple myeloma and Waldenstrom’s macroglobulinemia
Interpret protein and clinical findings in patients with monoclonal gammopathy of undetermined significance (MGUS)
Understand and interpret findings in sera with oligoclonal banding
Understand and interpret CSF oligoclonal banding patterns

Skill Level II:

Correlate electrophoretic data on urine and serum with bone marrow findings.

G. Proteins of Innate Immunity and Inflammation

Skill Level I:

Understand the role of the complement system or proteins in health and disease.
Understand the use of complement protein measurements to assess inherited and acquired deficiency states, including deficiency of complement components and deficiency of regulatory proteins such as C1-esterase inhibitor.
Understand role of complement protein measurements to assess activation of the complement system.
Understand the acute phase response and acute phase proteins, such as C-reactive protein, to assess inflammatory conditions.
Understand cytokines as mediators and markers of immune and inflammatory responses. Understand classification of cytokines, including those associated with helper T-cell subsets (Th1 and Th2), inflammatory conditions, etc.


H. Immune Function: Since many hematological neoplasms are malignant transformation of cells of the immune system, it is deemed that an important part of this rotation is the understanding of the normal immune system.

Skill Level I:

Understand the cells that comprise the immune system and the principles of structural and functional evaluation of B-cells, T-cells, NK-cells, and phagocytic cells.
Understand the role of the T-cell receptor, processed antigen peptides, HLA class I and class II molecules, and accessory molecules in antigen presentation and formation of the acquired immune response.
Understand the principles of lymphocyte development including rearrangements of the B-cell receptor/immunoglobulin genes and the T-cell receptor genes.
Understand the principles of cellular and molecular events in germinal center formation and function.
Understand assessment of lymphocyte immunophenotyping and activation, and be able to interpret flow cytometry data used to characterize leukocyte populations
Understand the immune pathogenic principles of acquired immunodeficiency disorders.
Understand the principles of immune modulating drugs.
Understand effects of drugs designed to deplete target cell populations, and uses of flow cytometry and other techniques to monitor efficacy or toxicity of those drugs.

Skill Level II:

Understand principles of neutrophil and phagocyte function assays, and methods to evaluate
Understand the molecular changes in lymphoid neoplasms and be able to correlate with clinical behavior of disease and current and potential therapy.

I. Molecular Pathology (includes Cytogenetics): An understanding of molecular pathology as it relates to hematological disorders is required.

1. Cytogenetics

a) Acquisition of Knowledge of Specific Tests Using Cytogenetic Methods

Skill Level I:

Understand basic cytogenetic concepts
Recognition of abnormal karyotyping with respect to chromosome number, translocations, deletions, duplications.
Correlation of chromosomal abnormalities with specific hematologic disorders such as myelodysplastic syndromes, hematologic malignancies, and myeloproliferative disorders


Skill Level II:

Knowledge of fluorescence in situ hybridization (FISH) analysis for common disorders involving aneuplodies, microdeletions, or chromosomal translocations, including hematologic disorders such as acute promyelocytic leukemia and chronic myelogenous leukemia
Knowledge of FISH for analysis of fixed tissue sections for translocations common in hematological malignancies such as c-myc translocation and bcl-1 translocation and requirements for diagnosis.

b) Analytical and Technical Training

Skill Level I:

Awareness of sample types, preparation and storage conditions for cytogenetic tests
Understand harvesting, slide preparation, banding, and staining
Understand microscopic analysis for karyotyping
Knowledge of fluorescence in situ hybridization for both single copy probes and chromosome painting
Be familiar with basic cell and tissue culture techniques

2. Molecular Pathology

a) Acquisition of knowledge of specific tests using molecular biology methods

Skill Level I:

Understand basic molecular biology concepts
Know molecular testing methods for inherited causes for thrombophilia, such as factor V Leiden, prothrombin 20210 mutation, MTHFR, and platelet glycoprotein III polymorphisms (PlA 1/2)
Knowledge of molecular testing for hematologic malignancies, including non-Hodgkin’s lymphomas (T and B cell gene rearragements) and chronic myelogenous leukemia (bcr-Abl detection and quantitation for therapeutic monitoring), and other translocation detection or quantitation assays

b) Analytical and Technical Training

Skill Level I:

Awareness of sample types, preparation and storage for molecular biology tests
Understand applicability of testing to samples of blood, bone marrow, body fluids (CSF, pleural and peritoneal samples), lymph node, and spleen
Knowledge of storage media and conditions for cells, DNA, and RNA
Knowledge and experience of DNA extraction and purification from a variety of biological specimens
Knowledge of restriction endonuclease digestion of purified DNA or amplified DNA
Understand electrophoretic separation of DNA fragments, native DNA gel electrophoresis for verification of DNA quality,
Knowledge of total cellular RNA extraction, quantitation, separation of mRNA and reverse transcription to generate cDNA
Understand Southern blot DNA hybridization
Understand gene microarray analysis

Skill Level II:

• Experience and knowledge of in vitro DNA amplification using the polymerase chain reaction (PCR), and alternative amplification systems, as well as awareness of methods to prevent contamination and applicability to clinical situation.
• Knowledge of real-time quantitative PCR and RT-PCR
• Knowledge of DNA and gene expression microarrays and applicability
• Knowledge of purification methods for cell subsets for subsequent molecular assays
• Interpret and report molecular results in association with pathologic and laboratory findings and clinical history to reach a final diagnosis
• Make recommendations for follow-up or confirmatory studies
• Assess the sensitivity and specificity of testing for an individual patient’s disease state

References
Darzynkiewicz, Crissman, Robinson: Methods in Cell Biology, Cytometry
Foucar K: Bone Marrow Pathology
Jaffee: WHO Tumors of Hematopoietic and Lymphoid Tissues
Kjeldsberg: Practical Diagnosis of Hematologic Disorders
Knowles: Neoplastic Hematopathology
Williams: Hematology
Ferry & Harris: Atlas of Lymphoid Hyerplasia and Lymphoma
Bain, Clark, Lampert, & Wilkins: Bone Marrow Pathology
Janeway CA, Travers P. Walport M, Shlomchik MJ. Immunobiology: the immune system in health and disease, 6th edition. New York, NY: Garland Science
Abbas K., Lichtman AH, Porter JH. Cellular and Molecular Immunology, Fifth Edition. Philadelphia, PA: WB Saunders 2003
Austen A, Frank MM, Atkinson JP, Cantor HI. Samter's Immunologic Diseases. Sixth Edition. Philadelphia, PA: Lippincott Williams & Wilkins 2001
Rose NR, Hamilton RG, Detrick B. Manual of Clinical Laboratory Immunology, 6th Edition, American Society of Microbiology
Heim, Sverre and Mitelman, Felix. Cancer Cytogenetics. Alan R. Liss, Inc.: New York, 1995.
Killeen, AA Principles of Molecular Pathology, Humana Press, 2004
Leonard, DGB, Diagnostic Molecular Pathology, Saunders, 2003
Strachan, T, Read AP. Human Molecular Genetics. 3rd Ed. Garland Press, 2004
Persing, DH, et al., eds. Molecular Microbiology: Diagnostic Principles and Practice. ASM Press. 2003.
Kumar, Abbas, & Fausto: Robbins and Cotran Pathologic Basis of Disease, 7th Edition, 2005.