Specialized Laboratory Services

Chemistry Laboratory — New England • Project management and data coordination • Rapid Data View system for viewing data online This laboratory performs a wide variety of routine and esoteric chemistries utilizing automated-, and semi-automated MCLCT understands the laboratory parameters as related to techniques. specific patient groups and the relationship of laboratory values to disease states. MCLCT provides appropriate support in test • Quantitation of immunoglobulins (IgG, IgA, IgM), as selection, utilization, specimen collection, and preparation well as various other immunoproteins procedures. • Microalbuminuria and Hemoglobin A1c testing for diabetic monitoring Consultation by laboratory professionals on analyte, time point, • Blood lead analysis by graphite furnace atomic methodology selection, and result interpretation is available for absorption a single protocol or for a clinical program. For assistance with • Zinc protoporphyrin analysis to monitor metal exposure protocol design or result interpretation, MCLCT clinical trials’ • Endocrine function testing clients can draw upon Mayo’s tradition of excellence, high • Anemia testing standards in health care, and experience with relating laboratory • Customized allergen profiles medicine to clinical outcomes. • Tumor marker testing • STAT fertility and cardiac marker testing Please call 800-533-1710 or U.S. access code plus 507-266- • High sensitivity CRP testing 5700 or see our Website at www.mayocts.com for information • Comprehensive menu of thyroid hormone assays for the on the following services: routine detection and monitoring of both hyperthyroidism and hypothyroidism • Mayo Clinical Trial Services (our Contract Research • Routine chemistry testing available including iron and Organization) iron-binding capacity, aldolase, lipase and amylase • Angio Core Laboratory • ECG Core Laboratory Clinical Trials - Central Laboratory Services Coagulation Mayo Central Laboratory for Clinical Trials (MCLCT) provides specialized global service to the pharmaceutical and The Mayo Special Coagulation Laboratory has extensive device industries in support of clinical trials being run to experience in providing high-quality hemostatic testing and evaluate the safety and efficacy of experimental drugs and interpretation of results, including more than 30 years of devices. Our personnel are trained in the practice of supplying experience with mailed-in specimens. In addition to experience centralized clinical laboratory services in conjunction with and quality, our strength especially results from the expertise of sponsored clinical research protocols. our staff which includes:

MCLCT has tailored its clinical trial services to meet the routine • Physician director (hematology, internal medicine, and and esoteric testing needs of the research community and to laboratory medicine) provide quality service which includes: • Seven consulting hematologists or vascular medicine specialists with expertise and interest in clinical and • Consultation for laboratory services, customized to laboratory hemostasis and thrombosis to provide test protocol requirements panel interpretation • Development and validation of biomarkers in our Center • Clinical technical coagulation specialist available to for Biomarker Research assist clients with questions regarding appropriate • Data management and data validation testing, specimen requirements, and interpretation of • Electronic data transfer results • Long-term specimen storage • Highly qualified laboratory personnel • Management reports • Visit-specific collection kits and shipping materials Additional strengths and features of the Special Coagulation • Investigator training and instruction manual Laboratory include: • Large repertoire of test procedures available, using state- staff, 20 technical specialists, and more than 150 trained of-the-art technology, to address virtually all clinical cytogenetic technologists and ancillary staff. We have 8 coagulation disorders development technologists devoted to new test and method • Extensive clinical correlation with Mayo Clinic development and validation as well as testing of new and experience, large esoteric test volume (>325,000 tests in emerging technologies. Our 2 internal quality control 2006), and experience with many unusual cases help specialists monitor the success and failure rates for testing, as ensure broad expertise. well as manage the standard operating procedures followed by • Close liaison with coagulation research aids laboratory personnel. development of new testing procedures, refinements of older procedures, and investigation of unusual cases. The Cytogenetics Laboratory boasts quality testing for an • Ready access to the personnel and expertise of the increasingly large number of specimens received from clinics federally funded Mayo Comprehensive Hemophilia and all across the U.S. and beyond. Providing quality service from Mayo Thrombophilia Centers for assistance in diagnosis culturing to reporting of results with a low turnaround time is and management of patients with hereditary or acquired the main concern for each case. bleeding or thrombosing disorders • Establishment (1996) of the Special Coagulation DNA- The Cytogenetics Laboratory offers: Diagnostic Laboratory (>60,000 genotyping assays in 2006) to facilitate testing for hereditary bleeding and • Rapid turnaround times with reports available in 24 to 48 thrombosing disorders hours for specific tests and upon request • In addition to individually ordered tests, we emphasize • Consultants, genetic counselors, and technical specialists availability of consultative test groupings (available as readily available for phone consultation “Coagulation Consultations”) for complex or difficult • Significantly superior and documented success rates: diagnostic problems such as: Bone marrow — 96% —#550 Thrombotic diathesis Amniotic fluid — 99% —#551 Bleeding diathesis Blood — 99% —#552 Lupus-like anticoagulant Products of conception — 83% —#553 Prolonged prothrombin time/activated partial • FISH testing for the following (includes assays unique to thromboplastin time our laboratory): —#554 von Willebrand disease —Aneuploidy detection of prenatal, neonatal, and —#1501 Coagulation factor VIII inhibitor panel miscarriage samples • In contrast to individually ordered coagulation tests, —Subtelomere rearrangements “Coagulation Consultation” testing is reflexive; and an —Congenital disorders (deletion/duplication): interpretation is formulated by a coagulation consultant. • 1p Deletion • Electronic reporting of test results and interpretations • Wolf-Hirschhorn • Consultation and test interpretation readily available by • Cri-du-chat phone from experienced physicians with coagulation • Williams subspecialty • 15q Deletion/duplication (Prader-Willi/ Angelman syndromes and deletion Cytogenetics characterization) • Smith-Magenis The strength of our Cytogenetics Laboratory at Mayo Medical • Miller-Dieker Laboratories (MML) is its state-of-the-art services in the • 22q Deletion/duplication (DiGeorge/ detection of congenital disorders both prenatally and velocardiofacial syndrome) postnatally as well as acquired abnormalities associated with • Neurofibromatosis hematologic disorders and solid tumors. We offer chromosome • Kallmann analysis (G-banded, breakage studies, sister chromatid • Steroid sulfatase deficiency exchange, and other special stains) and fluorescence in situ • SRY and XIST hybridization (FISH) assays. —Sex chromosome mosaicism • Solid tumors: Our staff includes 7 Board-certified cytogenetic directors, 3 —HER2 - breast cancer Board-certified or eligible genetic counselors, 7 supervisory —n-MYC Amplification - neuroblastoma —22q12 Rearrangements - Ewing sarcoma —+8, Cen8/c-MYC —18q11.2 Anomalies - synovial sarcoma —13q-, D13S319/D13S327 —1p/19q Deletion - glioma —20q-, JAG1/D20S108 • Hematologic malignancies: —inv(3), RPN1/EVI1 —BCR/ABL - t(9;22) • Plasma cell proliferative disorder: —CHIC2 deletion or rearrangement —-13/13q-, D13S319/D13S327 —PDGFRB/TEL fusion - t(5;12) —t(11;14), CCND1/IgH —Sex-mismatch bone marrow transplant —t(14;var), 5'IgH/3'IgH • Acute lymphocytic leukemia panel: —17p-, P53/Cen17 —t(9;22), BCR/ABL —+3/+7, Cen3/Cen7 —t(12;21), TEL/AML1 —+9/+15, Cen9/Cen15 —t(1;19), PBX1/TCF3 • t(4;14) Reflex, FGFR3/IgH —+4, +10, +17, Cen4/10/17 • t(14;16) Reflex, IgH/C-MAF —t(11q23;var), MLL —del (9p), P16/Cen9 Dermatopathology and Immunodermatology • Acute myelogenous leukemia panel —t(8;21), [M2], ETO/AML1 Dermatopathology and Immunodermatology encompass the —t(15;17), [M3], PML/RARA microscopic evaluation of cutaneous diseases. Our staff is —t(11q23;var), [M0-M7], MLL available for interpretation of frozen or fresh specimens sent —t(9;11) reflex, [M4, M5], AF9/MLL for processing and examination as well as for consultation on —inv(16), [M4, Eos], MYH11/CBFbeta outside slides. Reports include description of the histological —+8, [M0-M7], Cen8/c-MYC or immunological patterns, diagnosis, and differential —t(6;9), [M2, M4], DEK/CAN diagnosis when appropriate. The following studies are —inv(3), [M1,2,4,6,7], RPN1/EVI1 available in our laboratories: • Chronic lymphocytic leukemia panel: —6q-, c-MYB/Cen6 • Dermatopathology —11q-, ATM/Cen11 —Examination of hematoxylin-and-eosin stained —+12, Cen12/MDM2 sections, histochemical stains (eg, for mucin, fungi, —13q-, D13S319/LAMP1 elastic tissue), special immunohistochemical stains —17p-, P53/Cen17 useful in the differential diagnosis of cutaneous —t(11;14), CCND1/IgH epithelial, mesenchymal (soft tissue), and —Reflex for IgH anomaly: melanocytic and lymphocytic neoplasms and in • t(14;18), IgH/BCL2 situ hybridization studies for viral infections • t(14;19), IgH/BCL3 (herpes simplex virus, varicella-zoster virus, • Lymphoma panel: Epstein-Barr virus, and cytomegalovirus) —t(11;14), CCND1/IgH —T- and B-cell gene rearrangement studies for the evaluation of cutaneous lymphocytic neoplasms —t(14;18), IgH/BCL2 • Immunodermatology —t(8q24.1;var), c-MYC —Direct immunofluorescence testing of tissue and —t(8;14), c-MYC/IgH indirect immunofluorescence (IIF) testing of sera —t(18q21;var), MALT1 indicated in the evaluation of autoimmune bullous —t(11;18) Reflex, API2/MALT1 diseases, connective tissue diseases, lichen planus, —t(14;18) Reflex, IgH/MALT1 urticarial eruptions, vasculitis, and a variety of —Cen3/Cen7 other dermatoses —Cen12/Cen18 —IIF testing on serum for endomysial antibody and —t(2p23;var), ALK tissue transglutaminase (enzyme-linked —t(3q27;var), BCL6 immunosorbent assay [ELISA]) for gluten- • Myelodysplastic syndrome panel: sensitive enteropathy, dermatitis herpetiformis, or —-5/5q-, D5S23/EGR1 celiac disease —-7/7q-, D7S486/Cen7 Education Programs Flow Cytometry

MML offers education opportunities through Continuing The Flow Cytometry Laboratory performs several assays for Education Conferences, Interactive Satellite Programs, and clinical diagnostic testing. Major clinical applications include: Visiting Faculty Programs. • Leukemia immunophenotyping by flow cytometry (see • Continuing Education Conferences are offered #3287 “Leukemia/Lymphoma Immunophenotyping by throughout the year at various locations and are designed Flow Cytometry” [p. 352]) for physicians, medical technologists, medical —Applicable to anticoagulated peripheral blood, technicians, and other allied health professionals. Clients bone marrow aspirates, tissues, or body fluids (for also have access to the vast number of courses offered by tissue, see #9439 “Leukemia/Lymphoma Immunophenotyping by Flow Cytometry, Tissue” the Mayo Clinic College of Medicine. The conferences [p. 354]) include lectures, case discussions, and panel discussions. —Useful for: • Interactive Satellite Programs are offered multiple times • Evaluating lymphocytoses of undetermined each year. Each session is broadcast live via satellite or etiology webcast from Mayo Clinic. These presentations by • Identifying B- and T-cell chronic physicians and medical technologists include lectures lymphoproliferative disorders involving and case discussions on various topics of interest to blood and bone marrow health professionals. • Distinguishing acute lymphoblastic leukemia • MML’s Visiting Faculty Program features presentations (ALL) from acute myeloid leukemia (AML) on a variety of subjects of interest to clinicians, • Immunologic subtyping of ALL pathologists, technologists, technicians, management • Distinguishing reactive lymphocytes/ personnel, and other allied health professionals. lymphoid hyperplasia from malignant lymphoma Fertility Testing • Distinguishing between malignant lymphoma and acute leukemia The need for increased diagnostic abilities in the area of • Phenotypic subclassification of B- and T-cell infertility has grown dramatically over the last 10 years. These chronic lymphoproliferative disorders, needs have required the development of more sophisticated including chronic lymphocytic leukemia, and diverse analysis capabilities. The Fertility Testing mantle cell lymphoma, and hairy cell Laboratory deals specifically with procedures to diagnose and leukemia treat infertility and also serves as a bank (storage facility) for • Recognizing AML with minimal patients wishing to cryopreserve (freeze) sperm before medical morphologic or cytochemical evidence of differentiation or surgical procedures which may temporarily or permanently • DNA ploidy analysis of solid tumor (see #9319 “DNA result in reduced fertility or sterility. Ploidy of Solid Tumor by Flow Cytometry, Paraffin Block” [p. 223]) • The lab features: —Applicable to formalin-fixed, paraffin-embedded —State-of-the-art facilities and procedures tissue —Close interaction with research groups —Useful for: —Direct involvement with development of new • Determining the prognosis for patients with testing and treatments for infertility certain tumors, including: prostate, colon, • Current test offerings through MML include: endometrial, and breast carcinoma —Post-vasectomy semen check • Products of conception (triploidy) —Semen analysis with World Health Organization • T- and B-cell quantitation (see #9336 “T- and B-Cell morphology Quantitation by Flow Cytometry” [p. 530] and #84348 —Semen cryopreservation “CD4 Count for Monitoring, Blood” [p. 132]) —Anti-sperm antibody testing —Applicable to peripheral blood —Strict criteria sperm morphology —Quantitation of total T-cells, CD4 and CD8 —Qualitative fructose assay subpopulations, B-cells, and NK cells —Useful for: Hematopathology Consultations • Determining immune status in a variety of acquired and inherited immunodeficiencies The Division of Hematopathology offers a variety of • Monitoring total CD4 counts comprehensive laboratory and pathology tests for benign and • Monitoring CD3 populations following anti- malignant disorders of the peripheral blood and bone marrow. CD3 therapy post-transplantation Our goal is to provide the referring physician with an accurate • PI-linked antigen hematologic evaluation in the most efficient and cost-effective —Detects the presence or absence of glycosyl- manner. All requests will be processed as a consultation first. phosphatidylinositol-linked antigens on the surface Special studies will be performed only if diagnostically of peripheral blood granulocytes, monocytes, and indicated. erythrocytes —Useful in screening or confirming the diagnosis of • Morphologic consultation (see #5434 paroxysmal nocturnal hemoglobinuria “Hematopathology Consultation” [p. 280]) —Essential for accurate interpretation of any Hematology hematologic study —Peripheral blood smears, bone marrow aspirate Morphologic consultation for peripheral blood and bone smears, and/or bone marrow biopsy sections/ marrow disorders, as well as a variety of other diagnostic assays blocks are available. Please see the “Hematopathology Consultations” —Body fluids for the evaluation of possible section for further description of the services offered. hematologic malignancy • Enzyme cytochemical stains (see #5434 MML also provides facilities for the diagnosis of hereditary “Hematopathology Consultation” [p. 280]) - These are disorders that principally affect erythrocytes. Example performed as part of a hematopathology consultation and disorders include: are not available as stand-alone tests. —Applicable to air-dried blood or marrow aspirate • Hemoglobinopathies smears • Hereditary hemolytic disorders —Useful for subclassification of acute myelogenous • Methemoglobinemia or sulfhemoglobinemia leukemia (AML) • Thalassemias —Useful in the evaluation of some myelodysplastic syndromes/myeloproliferative disorders The Metabolic Hematology Laboratory: —Useful to confirm diagnosis of hairy cell leukemia (TRAP stain) • Performs approximately 20,000 tests annually for —Must be correlated with routine morphology hemoglobin variants or thalassemias • Immunophenotyping • Has an extensive library of hemoglobin variants for —Flow cytometric analysis (see #3287 “Leukemia/ purpose of comparison with specimens received Lymphoma Immunophenotyping by Flow • Accepts specimens for measurement of hemoglobin-O 2 Cytometry” [p. 352]) affinity (dissociation curve) • Applicable to anticoagulated peripheral • Performs assays of nearly all the erythrocyte enzymes blood, bone marrow aspirates, or body fluids, that have been described as being abnormal in patients and to unfixed tissue from any site other than with hereditary hemolytic anemia blood or bone marrow • Performs osmotic fragility studies • Performs measurement of methemoglobin and • Preferred method for immunophenotyping sulfhemoglobin, methemoglobin reductase (cytochrome acute leukemias, lymphoproliferative disorders, and lymphomas involving blood B5 reductase, NADH-diaphorase), plasma hemoglobin, and methemalbumin and bone marrow. Must be correlated with routine morphology. Our medical staff welcomes telephone consultation concerning • Useful for: hereditary disorders of the erythrocyte and iron deficiency. — Evaluating lymphocytoses of undetermined etiology —Identifying B- and T-cell chronic Inborn Errors of Metabolism lymphoproliferative disorders involving blood and bone marrow Genetic disorders are recognized to play an increasingly greater —Distinguishing acute lymphoblastic role in clinical medicine. In the aggregate, 6% to 8% of diseases leukemia (ALL) from acute myeloid among hospitalized children have been ascribed to Mendelian leukemia (AML) traits inherited as single gene defects. Hundreds of inborn errors —Immunologic subtyping of ALL of metabolism (IEM) have been identified to date, primarily —Distinguishing reactive lymphocytes/ through the detection of endogenous metabolites abnormally lymphoid hyperplasia from malignant accumulated in biological fluids and tissues. The clinical impact lymphoma of biochemical genetics is driven by the constant expansion of —Distinguishing between malignant the number of metabolites and enzyme activities which can be lymphoma and acute leukemia assayed in human body fluids and tissues for diagnostic —Phenotypic subclassification of B- and purposes. Consequently, testing for hereditary metabolic T-cell chronic lymphoproliferative disorders has developed from a highly specialized and disorders, including chronic fragmented activity, provided mostly by research-oriented lymphocytic leukemia, mantle cell scientists, to a critical component at the forefront of the lymphoma, and hairy cell leukemia laboratory work-up of patients of all ages. —Recognizing AML with minimal morphologic or cytochemical evidence The Mayo Biochemical Genetics Laboratory is an of differentiation interdisciplinary group of laboratorians with a mission to —Distinguishing polyclonal from provide biochemical testing and result interpretation and monoclonal plasma cell populations consultation of the highest quality for the diagnosis, study, and • Can aid in the classification of non-Hodgkin’s clinical care of patients with a broad spectrum of IEM. lymphomas • Performed in the context of a The laboratory offers close to 200 procedures for the screening, hematopathology or surgical pathology biochemical diagnosis, and carrier detection, when applicable, consultation of many IEM which include disorders of: —Immunohistochemical stains (see #5434 “Hematopathology Consultation” [p. 280]) - These • Amino acid metabolism are performed only as part of a hematopathology • Carbohydrate metabolism such as galactosemia consultation and are not available as stand-alone • Congenital disorders of glycosylation tests. • Cholesterol biosynthesis • Applicable to paraffin sections of bone • Cofactor and vitamin metabolism marrow or other tissue • Lysosomal metabolism and storage (see p. 692, “Table • Useful in demonstrating various cell- of Lysosomal Storage Disorders”) associated antigens for characterizing • Mitochondrial energy metabolism (primary lactic malignant disorders of the bone marrow acidemias) • Plasma cell labeling index (see #84376 “Plasma Cell • Fatty acid metabolism (mitochondrial ß-oxidation) and Labeling Index [PCLI] Profile” [p. 452]) carnitine homeostasis —Applicable to fresh bone marrow specimens • Organic acid disorders suspicious for a plasma cell disorder • Peroxisomal biogenesis and metabolism —Indicated for patients with monoclonal • Porphyrin metabolism gammopathy • Purine and pyrimidine metabolism —Important indicator of clinical prognosis in • Urea cycle disorders multiple myeloma • Disorders of creatine metabolism —Report includes percent cytoplasmic immunoglobulin-positive cells Procedures for the qualitative detection and quantitative —Determination of clonality (kappa vs. lambda), determination of diagnostic markers are based on a variety of percent of plasma cells in S-phase (LI), and overall methods: interpretation of findings • Thin-layer chromatography (TLC) • Immunoassays for the diagnosis of parasitic infections • High-performance liquid chromatography (HPLC) including rapid detection of giardia, cryptosporidium, • Ion-exchange chromatography and Entamoeba histolytica antigens in stool and • Capillary gas chromatography antibodies to babesia, taenia (cysticercosis), • Gas chromatography-mass spectrometry (GC-MS) echinococcus, strongyloides, toxocara, toxoplasma, • Tandem mass spectrometry (MS/MS) trichinella, trypanosoma, and visceral leishmania in • Liquid chromatography-tandem mass spectrometry (LC- serum MS/MS) • Stool antigens, breath test, and serology tests available • Colorimetric/fluorometric for detection of infections • Enzyme-linked immunosorbent assay (ELISA) • Nucleic acid testing (bDNA, PCR, strand displacement • Acrylamide electrophoresis amplification, or transcription-mediated amplification, signal amplification) for several microbial agents: Microbiology — Chlamydia trachomatis (genital) —Hepatitis B virus (quantitative, genotyping) The Division of Clinical Microbiology at Mayo Clinic offers a —Hepatitis C virus (qualitative, quantitative, broad selection of tests designed for rapid identification of the genotyping) causative agents of infectious diseases and prompt reporting of —HIV (quantitative, genotyping) results. Through Mayo’s testing practice, our laboratory has —Human papillomavirus developed culture techniques and molecular methods for rapid —Mycobacterium tuberculosis complex detection and identification of unusual as well as common (transcription-mediated amplification) microbial pathogens. — (genital) • Identification of selected mycobacteria, aerobic Other features: actinomycetes, and using DNA sequencing • LightCycler™ PCR for rapid detection of: • Complete range of organism identification and — Babesia microti susceptibility testing for bacteria and fungi — • Expert consultants in areas of bacteriology, molecular —BK virus ([plasma, urine], qualitative, quantitative) microbiology, mycology, mycobacteriology, parasitology, — pertussis/Bordetella parapertussis and virology — Borrelia burgdorferi • Pulsed-field gel electrophoresis of bacterial isolates (eg, —Cytomegalovirus (qualitative, quantitative) methicillin-resistant Staphylococcus aureus and — (agent of human monocytic vancomycin-resistant enterococci) useful for ), /Ehrlichia canis, demonstrating strain differences among isolates and and Anaplasma phagocytophilum (agent of human epidemiologic studies of nosocomial infections granulocytic ehrlichiosis) • Extensive experience in routine detection of DNA of —Enterovirus herpesviruses (cytomegalovirus, Epstein-Barr virus, —Epstein-Barr virus (qualitative, quantitative) herpes simplex virus, and varicella-zoster virus) in —Herpes simplex virus types 1 & 2 (genital and cerebrospinal fluid by polymerase chain reaction (PCR) dermal) • Rapid detection of most mycobacteria within 7 to 10 —Human herpesvirus-6 days and identification of some species within 1 day —Influenza virus types A and B using nucleic acid probes (BSL3 facility) —JC virus (cerebrospinal fluid) • Qualitative, quantitative detection and genotyping of —Malaria hepatitis C virus —Parvovirus • Viral load and genotypic determinations of human —Pneumocystis immunodeficiency virus (HIV) —Toxoplasma gondii (amniotic fluid, cerebrospinal • Consolidated infectious disease serology laboratory fluid) (bacterial, fungal, parasitic, and viral infections) —Tropheryma whipplei (Whipple’s disease) • Rapid identification of dimorphic fungi using nucleic —Vancomycin-resistant enterococci acid probes —Varicella-zoster virus (dermal) • Molecular testing for biochemical disorders: —West Nile virus —Ashkenazi Jewish panel • Panel includes carrier screening for: CF, Molecular Genetics canavan disease, familial dysautonomia, Gaucher, Tay-Sachs disease, Bloom, Fanconi The rapid advancements of genetic testing technology and the anemia C, mucolipidosis IV, and Niemann- exciting information gleaned from The Human Genome Project Pick types A and B. Each of these tests can greatly enhance the diagnostic capabilities of clinical genetic also be ordered separately. testing laboratories. The Molecular Genetics Laboratory at —Galactosemia Mayo Clinic has embraced this forward progress and, as a —Hyperoxaluria result, is able to offer a broad selection of tests in 3 general • Alanine-glyoxylate aminotransferase categories: (AGXT) molecular analysis for pyridoxine responsiveness • Congenital inherited diseases: —Isovaleric acidemia (IVD) —Alpha-1-antitrypsin gene analysis —Medium chain acyl-CoA deficiency (MCAD) —Alpha-thalassemia —Niemann Pick type C (NPC) —Apolipoprotein E —Short chain acyl-CoA deficiency (SCAD) —Beckwith-Wiedemann syndrome (BWS) —Wilson disease —Cystic fibrosis (CF) —Dentatorubral-pallidoluysian atrophy (DRPLA) The Molecular Genetics Laboratory also maintains active test —Fragile X syndrome development and basic research programs. The basic research —Frontotemporal dementia (MAPT gene sequencing) program is particularly interested in the area of cancer genetics, —Hemophilia A and this translates to cutting edge clinical tests and testing —Hereditary hemochromatosis algorithms for inherited cancer syndromes. The large, unique —Hereditary pancreatitis (cationic trypsinogen gene) patient population of Mayo Clinic is an invaluable resource and —Prader-Willi/Angelman syndrome is of significant benefit to the laboratory with regard to test —Specimen identification validation and clinical correlation studies. —Spinobulbar muscular atrophy (SBMA)/Kennedy’s disease Pathology —Transthyretin associated familial amyloidosis —Uniparental disomy The Division of Anatomic Pathology is the largest and most —Y-Chromosome microdeletion comprehensive anatomic pathology consultative practice in the —Zygosity determination U.S. The consulting staff in the Division of Anatomic Pathology has expertise in surgical pathology, cytopathology, • Inherited cancer syndromes: autopsy, as well as a wide range of subspecialty areas to support —Familial adenomatous polyposis (FAP) Mayo Clinic practice. —Hereditary nonpolyposis colorectal cancer (HNPCC) Other features: • Tumor testing: —hMLH1 hypermethylation/BRAF • Approximately 40 pathologists with subspecialty (V600E) expertise —Microsatellite instability and • Consultative expertise provided for over 45,000 cases immunohistochemistry from referring physicians each year • Germline testing: • Experience from approximately 60,000 Mayo Clinic —hMLH1, hMSH2, and hMSH6 surgical and 120,000 cytology cases annually sequencing and MLPA for large • Results phoned to you by consulting pathologists deletions/duplications • Competitive fees —Multiple endocrine neoplasia type 2 • Rapid turnaround time —MYH gene analysis • State-of-the-art methods in: —Digital image analysis • Multiple myeloma —Electron microscopy • Monoclonal gammopathy of undetermined significance —Fluorescence in situ hybridization (FISH) (benign monoclonal gammopathy) —Histochemistry • Primary systemic amyloidosis —Immunohistochemistry • Waldenström’s macroglobulinemia —In situ hybridization • Lymphoproliferative syndromes —Molecular diagnosis • Heavy-chain diseases

Serology Laboratory — New England Tissue Typing

Serology is a dynamic laboratory that is rapidly expanding and The Tissue Typing Laboratory provides: is on the forefront of new technologies and procedures. This laboratory currently performs a variety of infectious and • Cell-bound platelet antibody testing autoimmune tests on a routine and STAT basis. • Granulocytic antibody testing • HLA Class I and HLA Class II molecular typing for • Complete hepatitis profile (9 markers) and HIV solid organ and bone marrow transplantation screening • HLA-B27 testing for disease association • Autoimmune antibody detection • Narcolepsy-associated antigen testing • STAT services for respiratory syncytial virus antigen • Serum platelet antibody testing detection, bacterial antigens, and detection of Cryptococcus neoformans infection The serum platelet antibody test and the cell-bound platelet • Infectious disease antibody detection autoantibody test (enzyme-linked immunoassay methods) can be used to detect autoantibodies (such as those seen in Special Protein Studies idiopathic thrombocytopenic purpura) or alloantibodies such as those in refractory or alloimmunized patients. The cell-bound The Special Protein Laboratory performs: test is frequently positive in autoimmune thrombocytopenia.

• Immunofixation of serum with monospecific antisera to The HLA-B27 test detects the presence or absence of the HLA- IgG, IgA, IgM, kappa, and lambda B27 antigen. HLA-B27 is a major histocompatibility complex • Immunofixation analysis is used to screen sera for Class I molecule. There is a strong association between the elevations of IgD and IgE in all patients in whom a presence of the HLA-B27 antigen and an increased incidence of monoclonal light chain is found. ankylosing spondylitis as well as several other disorders. • Quantitation of IgG, IgA, and IgM • Quantitation of serum immunoglobulin kappa- and Narcolepsy-associated antigen testing is performed to lambda-free light chains determine if the patient is positive or negative for the allele • Measurement of serum viscosity on sera with large DQB1*0602. The test is performed using polymerase chain amounts of IgM, IgG, or IgA monoclonal proteins reaction (PCR)-SSP. The absence of the strongly associated • Immunofixation on urine specimens with monospecific DQB1*0602 is very strong evidence that the patient does not kappa and lambda antisera and appropriate heavy-chain have narcolepsy. antisera as indicated by the serum • Cryoglobulin studies on sera and plasma The granulocyte antibody test by the indirect (cryofibrinogen) immunofluorescence method detects antibodies to white blood cells which are a frequent cause of nonhemolytic, febrile The demonstration of a monoclonal protein in the serum or transfusion reactions and may also be involved in autoimmune urine raises the possibility of a neoplastic or potentially neutropenia. The test cannot distinguish between allo- and neoplastic process. The differential diagnosis includes: autoantibodies. HLA Class I and HLA Class II are performed using molecular • Very cost-effective essential element analysis using ICP- typing methods for solid organ and bone marrow atomic emission spectroscopy and toxic element analysis transplantation. The matching of both Class I and Class II using ICP-MS antigens of donor/recipient pairs results in better graft survival • Due to the methodologies used for metals testing, for most solid organ transplants and less alloimmunization in occasionally an abnormal result for an analyte not the recipient. Linkage disequilibrium exists between some ordered is identified. These results will be reported, diseases and their association with specific Class I and Class II along with the originally requested results, at no antigens. additional charge.

Toxicology — Rochester Toxicology Laboratory — New England

Toxicology assessment is supported by the Drug Laboratory The Toxicology Laboratory provides 24 hour, 7 day a week and the Metals Laboratory. These laboratories provide a broad coverage with the majority of the testing available on a STAT range of toxicology testing with special expertise in basis. A wide range of toxicology testing is performed including consultation on clinical problems related to therapeutic drug therapeutic drug monitoring, overdose drug analyses, and drug monitoring, drug toxicity, trace and heavy metal toxicity, and of abuse testing. detection of drug abuse. All test results are clinically correlated and in-depth phone consultation with toxicology experts is • Emergency Drug Testing available. —Comprehensive Drug Analysis (CDA) utilized by the emergency room for overdose situations covers Special features of the Drug Laboratory: a wide range of drugs. Screening is by gas chromatography-mass spectrometry (GC-MS) and • Testing performed by state-of-the-art technology immunoassay. Quantitative serum results are including: available by immunoassay, high-pressure liquid —Immunoassay chromatography (HPLC), or gas chromatography —Ultraviolet and fluorescence spectrophotometry (GC) for volatile analysis. Refer to “Drugs (SP) Detectable by Comprehensive Drug Analysis - —Gas chromatography (GC) New England” (p. 637) for a complete list of drugs —High-performance liquid chromatography (HPLC) detected and quantitated by this offering. —Liquid chromatography-mass spectrometry-mass • Drug of Abuse Testing spectrometry (LC-MS/MS) —Immunoassay drug of abuse screening is offered —Gas chromatography-mass spectrometry (GC-MS) with or without GC-MS confirmation of positive • Emphasis on monitoring of drugs used in cardiovascular results. Positive drug of abuse testing results diseases, infection, neurologic diseases, psychiatry, and without GC-MS confirmation should be considered presumptive, and are designed for situations where transplantation confirmed positive results are not necessary. All • Broad-spectrum clinical drug screening confirmed by non-GC-MS confirming drug of abuse testing is GC-MS denoted by test name ending with and X (eg, DAU7X). Special features of the Metals Laboratory: • Therapeutic Drug Monitoring (TDM) —TM is performed using either immunoassay or • Testing performed by state-of-the-art technology HPLC. Most STAT TDM results are available including: within 2 hours of the laboratory receiving the —Inductively coupled plasma-mass spectrometry specimen, routine results are available the (ICP-MS) following morning. —Inductively coupled plasma (ICP)-emission • Chain-of-Custody spectroscopy —The New England Laboratory does not perform —Graphite furnace atomic absorption spectroscopy any medicolegal testing/use of Chain-of-Custody —Fourier transform infrared spectrometry documentation. Testing requiring Chain-of- • Ultra-clean class 100 laboratory with particulate matter Custody procedures should be directed to the in the air <100 parts per billion Toxicology Laboratory in Rochester.