FISH Panels for LeukemiaS & LYmphomas


  • *Panel recommended for pediatric patients, Adults patients with B-Cell ALL only FISH for BCR/ABL1 and MLL (KMT2A) are recommended
    Disease(s): Acute lymphoblastic (lymphocytic) leukemia, B-Cell
    Probes:
     TEL/AML1 (ETV6/RUNX1) t(12;21)(p13;q11.2)
     BCR/ABL1 Plus t(9;22)(q34;q11.2)
     CEP4, CEP10, CEP17 Hyper- or Hypodiploidy
     MLL (KMT2A) 11q23 rearrangements
     CDKN2A(p16) /CEP9 -9/9p deletion
    Clinical Significance:
    B- Cell precursor ALL is primarily a disease of childhood with 75% of patients under the age of 6 with both blood and bone marrow involvement.
    Extramedullary involvement is typically of the central nervous system, lymph nodes, spleen, liver and testes.
    The morphology of cells is mainly FAB L1 or L2, where only a small percentage of patients have a mature B-cell immunophenotype.
    Cytogenetics still provides the main standard for classification.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
      4-6 days
    CPT Codes:
      2015: 88377x5
  • Disease(s): Acute lymphoblastic (lymphocytic) leukemia, T-Cell
    Probes:
     BCR/ABL1 Plus t(9;22)(q34;q11.2)
     MLL (KMT2A) 11q23 rearrangements
     CDKN2A(p16) /CEP9 -9/9p deletion
     TCR alpha/delta 14q11 rearrangements
    Clinical Significance:
    T-cell ALL accounts for approximately 15% of childhood and 25% of adult ALL patients and has a high risk for malignancy in both groups. Genes involved in various stages of thymocyte development are rearranged or deregulated, resulting in a multistep process for pathogenesis, consistent with multiple genetic changes seen in leukemic cells.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x4
  • Disease(s): Acute myeloid leukemia
    Probes:
     ETO/AML1 (RUNX1T1/RUNX1) t(8;21)(q22;q22) (M2)
     PML/RARα t(15;17)(q22;q21.2) (M3)
     MLL (KMT2A) 11q23 rearrangements (M0-M7)
     MYH11/CBFβ inv(16)(p13q22), t(16;16) (M4)
     EVI1 (MECOM) inv(3)(q21q26) (M1, 2, 4, 6, 7)
    Clinical Significance:
    Acute myelogenous leukemia (AML), the most common type of leukemia in adults with incidence greatly increasing after age 55-60, constitutes 70% of acute leukemias. AML is characterized by an excess accumulation of immature myeloblasts in bone marrow, leading to a lack of differentiated granulocytes, monocytes, thrombocytes and erythrocytes. Classification of AML into major subgroups from morphological, cytochemical and immunophenotype criteria has resulted in the following FAB subtypes, M0-M71,2: minimally differentiated AML (M0); without maturation (M1); with maturation (M2); acute promyelocytic leukemia, hypergranular (M3) or micro- and hypogranular (M3v); acute myelomonocytic leukemia (M4), including M4Eo with eosinophilia; acute monoblastic leukemia (M5a) and monocytic leukemia (M5b); acute erythroleukemia (M6) and acute megaloblastic leukemia (M7). A more recent WHO classification defines four subgroups: 1) AML with recurrent genetic abnormalities (i.e. as revealed by karyotype or tested for by FISH, above); 2) AML with multilineage dysplasia; 3) therapy-related AML (t-AML) and myelodysplastic syndromes (t-MDS); 4) not otherwise categorized.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x5
  • Disease(s): Chronic Lymphocytic Leukemia
    Probes:
     MYB/CEP6 -6, 6q deletion
     ATM/p53 11q and 17p deletion
     CEP12 +12
     D13S319/13qter -13/13q deletion
     CCND1/IGH t(11;14)(q13;q32)
     IGH/BCL2 t(14;18)(q32;q22.1) Reflex Only
    Clinical Significance:
    Chronic lymphocytic leukemia (CLL) and its nodal variant, small lymphocytic lymphoma (SLL) account for 7% of all B- and T/NK-cell lymphomas. Chromosome aberrations occur in more than 80% of CLL with successful stimulation (i.e. with a B-cell mitogen). The neoplastic cells of CLL have low spontaneous mitotic activity and therefore mitogens are necessary. Although standard karyotyping of cells from unstimulated cultures of peripheral blood or bone marrow, as well as cultures stimulated with a B-cell mitogen (interleukin, pokeweed, TNF-α, TPA or some combination) are recommended, FISH is recommended in addition to chromosome analysis.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x5 ( 88377x6 if reflex run)
  • Disease(s): Myelodysplastic Syndrome
    Probes:
     EGR1/5p15.31 -5/5q deletion
     D7S796/D7S486 -7/7q deletion
     CEP7/CEP8 -7/+8
     D20S108/MYBL2 -20/20q deletion/idic(20q)
     EVI1 (MECOM) inv(3)(q21q26) Reflex Only
     MLL (KMT2A) 11q23 rearrangements Reflex Only
     TEL/AML (ETV6/RUNX1) t(12;21)(p13;q11.2) Reflex Only
    Clinical Significance:
    MDS, has an increased incidence in older patients and is a heterogeneous group of clonal bone marrow disorders. They are characterized by the presence of dysplastic hematopoietic cells and cytopenia that can progress to an acute leukemia. 10-15% of patients with MDS have acquired the syndrome through therapy related (t-MDS) treatment following chemotherapy or radiation. Conditions that can mimic MDS include vitamin B12 or folate deficiencies, infections and congenital conditions. A normal karyotype occurs in about 30-60% of MDS patients. If a clonal abnormality is detected about 25% of them can further progress to AML. Chromosome abnormalities in primary MDS, in order of frequency, include -7/del(7), -5/del(5), +8, abnormal 17p, -Y, del(20q), and 11q23 rearrangements. Prognosis typically worsens if more than one abnormality is present.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x4 (88377x7 if reflex run)
  • Disease(s): Multiple Myeloma, Plasma Cell Proliferative Disorders
    Probes:
     IGH 14q32 rearrangements
     TP53/ATM 17p deletion
     D13S319/13qter -13/13q deletion
     CEP9/CEP15 +9 and +15
     FGFR3/IGH t(4;14)(p16.3;q32) IGH Reflex Only
     CCND1/IGH t(11;14)(q13;q32) IGH Reflex Only
     IGH/MAF t(14;16)(q32;q23) IGH Reflex Only
    Clinical Significance:
    Multiple myeloma (MM) is an incurable malignancy with a yearly incidence in the US of ~14,000 people and comprises ~2% of deaths from cancer. The median survival rate for MM is about 3 years. Clinical features include: bone pain; anemia; repeated infections (immunoinsufficiency); features of renal failure and hypercalcemia; abnormal bleeding, lytic bone lesions and destruction of bone tissue; occasional macroglossia; carpal tunnel syndrome; diarrhea due to amyloid disease; hyperviscosity syndrome with purpura, hemorrhage, visual failure, CNS symptoms, etc. MM and non-IgM MGUS (premalignant monoclonal gammopathy of undetermined significance) are neoplastic monoclonal proliferations of bone marrow plasma cells with phenotypic features of PB/long-lived plasma cells. MM is distinguished from MGUS by having >10% plasma cells (PC) in BM. Both MM and non-IgM MGUS show marked increase in prevalence with age, and more prevalent in African American than Caucasians by about 2 fold. The origin of plasma cells is from B-cell immunoblasts which in turn originate in germinal centers of lymph nodes or spleen. Plasma cells initially secrete IgM and later typically migrate to bone marrow to differentiate into long-lived plasma cells, responsible for the heterogeneous production of immoglobulins IgA, IgD, IgE and IgG.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x4 (88377x7 if reflex run)
  • Disease(s): Myeloproliferative Neoplasms
    Probes:
     PDGFRA/FILIP1/CHIC2 4q12 rearrangements (3 color)
     PDGFRB 5q33 rearrangements
     FGFR1 8p12 rearrangements
     BCR/ABL1 Plus t(9;22)(q34;q11.2)
    Clinical Significance:
    Myeloproliferative neoplasms (MPNs) are a group of diseases of the bone marrow in which excess cells are produced. All MPNs arise from precursors of the myeloid lineages in the bone marrow and all of which are related, many evolving into myelodysplastic syndrome and acute myeloid leukemia. This particular neoplasm, MPN, is classified in the hematologic neoplasms category and is further broken down into four main myeloproliferative diseases. These four are categorized by the presence of the Philadelphia chromosome. Essential thrombocytosis (ET), polycythemia vera (PV), and myelofibrosis (MF) are all Philadelphia chromosome negative, and chronic myelogenous leukemia (CML) is Philadelphia chromosome positive.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x4
  • Disease(s): B-Cell Lymphoma
    Probes:
     IGH/BCL2 t(14;18)(q32;q22.1)
     c-MYC 8q24 rearrangements
     BCL6 3q27 rearrangements
     CCND1/IGH t(11;14)(q13;q32) Reflex Only
     cMYC/IGH t(8;14)(q24;q32) Reflex Only
     MALT1 18q21 rearrangements Reflex Only
     CEP3/CEP7/CEP12 +3,+7, and +12 (Tissue Only)
    Clinical Significance:
    B-Cell lymphomas are “blood cancers” in the lymph glands. They develop more frequently in older adults and in immunocompromised individuals. B-Cell lymphomas include both Hodgkin’s and non-Hodgkin’s lymphomas and are typically divided into low and high grade. Prognosis and treatment depends on the specific type of lymphoma as well as the stage and grade. Common types include diffuse large B cell lymphoma, follicular lymphoma, marginal zone lymphoma, mucosa-associated lymphatic tissue lymphoma, small cell lymphocytic lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. Chromosomal translocations involving the immunoglobulin heavy locus (IGH) is a classic cytogenetic abnormality for many B-Cell lymphomas. In these cases, the immunoglobulin heavy locus forms a fusion protein with another protein that has either pro-proliferative or anti-apoptotic abilities.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
     Formalin-Fixed Paraffin Embedded Tissue: Tissue sections 4-5 micron sections, 2 slides per probe, fixation time must be between 6-48 hours, include H&E slide with area of interest marked
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x3 (88377x6 if reflex run; 88377x1 if run for tissue)
  • Disease(s): T-Cell Lymphoma
    Probes:
     TCL1 14q32.1 rearrangements
     D7S796/D7S486 7q deletion/i(7q)
     CEP7/CEP8 -7 and +8
     CDKN2A(p16)/CEP9 -9/9p deletion (Tissue Only)
     MLL (KMT2A) 11q23 rearrangements (Tissue Only)
    Clinical Significance:
    Approximately 10% of non-Hodgkin lymphoma cases are due to T-Cell lymphomas. They are compromised of four classes; Extranodal T cell lymphoma, Cutaneous T-Cell lymphoma, Anaplastic large cell lymphoma, and anioimmunoblastic T-cell lymphoma based on cytologic grading. The survival rate of T cell lymphoma varies widely depending on the subtype. Treatment options also vary, but the standard lymphoma therapies including chemotherapy, radiation, stem cell transplantation, and surgery are effective.
    Specimen Requirements:
     Bone Marrow Aspirate (Preferred): 2-5ml, Green-top sodium-heparinized vacutainer
     Peripheral Blood: 5-10ml, Green-top sodium-heparinized vacutainer
     Formalin-Fixed Paraffin Embedded Tissue: Tissue sections 4-5 micron sections, 2 slides per probe, fixation time must be between 6-48 hours, include H&E slide with area of interest marked
    Storage and Transportation:
     Keep at room temperature.
    Turn Around Time (TAT):
     4-6 days
    CPT Codes:
     2015: 88377x3 (88377x2 if run on tissue)