Authors - College of American Pathologists



Protocol for the Examination of Hematologic Malignancies in Bone MarrowVersion: Bone Marrow 4.0.0.0Protocol Posting Date: February 2019Accreditation RequirementsThe use of this protocol is recommended for clinical care purposes but is not required for accreditation purposes.This protocol is intended to be used for the following procedures AND tumor types:ProcedureDescriptionBone marrow trephine biopsy Includes specimens designated non-targeted bone marrow biopsy and touch preparationsBone marrow aspirationIncludes non-targeted bone marrow aspiration, clot section, and aspirate smear preparationsTumor TypeDescriptionMyeloproliferative neoplasmsMastocytosisMyelodysplastic syndromesMyelodysplastic/myeloproliferative neoplasmsMyeloid/lymphoid neoplasms with eosinophilia and gene rearrangementMyeloid neoplasms with germline predispositionBlastic plasmacytoid dendritic neoplasmAcute myeloid leukemiaAcute leukemia of mixed/ambiguous lineageAcute lymphoblastic leukemia/lymphoma Mature B-cell neoplasms with leukemic presentation (excluding plasma cell myeloma)Mature T- and NK-cell neoplasms with leukemic presentationIncludes most primary myeloid malignancies, acute leukemias, and mature B-cell, T-cell, and NK-cell neoplasms with frequent leukemic presentation. Disease entities in this protocol are based on the 2017 revised fourth edition World Health Organization classification and include provisional entries. The following should NOT be reported using this protocol:ProcedureExtramedullary biopsy specimensPeripheral blood smears (without bone marrow material)Tumor TypePlasma cell myeloma (consider the Plasma Cell Neoplasm protocol)Histiocytic disorders involving the bone marrowNon-neoplastic diseases of the bone marrowSecondary marrow involvement by lymphoma or metastatic cancer (consider the Hodgkin or non-Hodgkin Lymphoma Protocols)AuthorsJoseph D. Khoury, MD*; Diponkar Banerjee, FRCPC, PhD; Gautam Borthakur, MD; Weina Chen, MD, PhD; Eric Duncavage, MD; Eric Hsi, MD; Kathryn Foucar, MD; Philip R. Foulis, MD; Jerald Z. Gong, MD; Robert P. Hasserjian, MD; Todd Kelley, MD, MS; Mei Liang, MD; Megan S. Lim, MD. PhD; Eric Y. Loo, MD; J. Douglas Rizzo, MD, MS; Cordelia Sever, MD; Roland Schwarting, MD; James W. Vardiman, MDWith guidance from the CAP Cancer and CAP Pathology Electronic Reporting Committees.* Denotes primary author. All other contributing authors are listed alphabetically.The pathologist responsible for issuing the diagnostic bone marrow report included in the patient’s medical record and forming the basis of treatment decisions is encouraged to fill out the synoptic report. The pathologist may need to include data elements generated at an external facility (e.g. reference lab) for inclusion in the synoptic report. In these scenarios, it is understood that the pathologist is not assuming responsibility for the technical accuracy of such external data. CAP Bone Marrow Protocol Summary of ChangesVersion 4.0.0.0The following data elements were added:Clinical ContextPeripheral Blood Complete Blood Cell CountBone Marrow CellularityBone Marrow Blasts Bone Marrow LymphocytesBiomarker InformationSurgical Pathology Cancer Case SummaryProtocol posting date: February 2019BONE MARROW: Final Integrated DiagnosisNote: This case summary is recommended for reporting hematologic malignancies in bone marrow but is NOT REQUIRED for accreditation purposes. Core data elements are bolded to help identify routinely reported elements.Note: If the Integrated Diagnosis section is not applicable, proceed to Histological Assessment summary.Select a single response.Final Integrated Diagnosis (Note A)Myeloproliferative neoplasms___ Chronic myeloid leukemia, BCR-ABL1 positive___ Chronic neutrophilic leukemia___ Polycythemia vera___ Primary myelofibrosis___ Essential thrombocythemia___ Chronic eosinophilic leukemia, NOS___ Myeloproliferative neoplasm, unclassifiableMastocytosis___ Systemic mastocytosis ___ Mast cell leukemia Myelodysplastic syndromes (MDS)___ Myelodysplastic syndrome with single lineage dysplasia ___ Myelodysplastic syndrome with ring sideroblasts and single lineage dysplasia___ Myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia___ Myelodysplastic syndrome with multilineage dysplasia___ Myelodysplastic syndrome with excess blasts-1___ Myelodysplastic syndrome with excess blasts-2___ Myelodysplastic syndrome with isolated del(5q)___ Myelodysplastic syndrome, unclassifiable___ Refractory cytopenia of childhoodMyelodysplastic/myeloproliferative neoplasms (MDS/MPN)___ Chronic myelomonocytic leukemia ___ Atypical chronic myeloid leukemia, BCR-ABL1-negative ___ Juvenile myelomonocytic leukemia___ Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis___ Myelodysplastic/myeloproliferative neoplasm, unclassifiableMyeloid/lymphoid neoplasms with eosinophilia and gene rearrangement___ Myeloid/lymphoid neoplasm with PDGFRA rearrangement___ Myeloid/lymphoid neoplasm with PDGFRB rearrangement___ Myeloid /lymphoid neoplasm with FGFR1 rearrangement___ Myeloid /lymphoid neoplasm with PCM1-JAK2Acute myeloid leukemia (AML) and acute leukemias of ambiguous lineage___ Acute myeloid leukemia, NOS___ Acute myeloid leukemia with t(8;21)(q22;q22.1);RUNX1-RUNX1T1___ Acute myeloid leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11___ Acute promyelocytic leukemia with PML-RARA___ Acute myeloid leukemia with t(9;11)(p21.3;q23.3); KMT2A-MLLT3___ Acute myeloid leukemia with t(6;9)(p23;q34.1);DEK-NUP214___ Acute myeloid leukemia with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM___ Acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13.3;q13.1);RBM15-MKL1___ Acute myeloid leukemia with BCR-ABL1___ Acute myeloid leukemia with mutated NPM1___ Acute myeloid leukemia with biallelic mutations of CEBPA___ Acute myeloid leukemia with mutated RUNX1___ Acute myeloid leukemia with myelodysplasia-related changes___ Therapy-related myeloid neoplasm___ Acute myeloid leukemia with minimal differentiation___ Acute myeloid leukemia without maturation___ Acute myeloid leukemia with maturation___ Acute myelomonocytic leukemia___ Acute monoblastic/monocytic leukemia___ Pure erythroid leukemia___ Acute megakaryocytic leukemia___ Acute basophilic leukemia___ Acute panmyelosis with myelofibrosis___ Acute undifferentiated leukemia___ Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2); BCR-ABL1___ Mixed phenotype acute leukemia with t(v;11q23.3); KMT2A rearranged___ Mixed phenotype acute leukemia, B/myeloid, NOS___ Mixed phenotype acute leukemia, T/myeloid, NOS___ Mixed phenotype acute leukemia, NOS___ Acute leukemia of ambiguous lineage, NOS___ Transient abnormal myelopoiesis (TAM) associated with Down syndrome___ Myeloid leukemia associated with Down syndromeBlastic plasmacytoid dendritic cell neoplasm___ Blastic plasmacytoid dendritic cell neoplasmPrecursor lymphoid neoplasms___ B-lymphoblastic leukemia/lymphoma, NOS___ B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2);BCR-ABL1___ B-lymphoblastic leukemia/lymphoma with t(v;11q23.3); KMT2A rearranged___ B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUNX1___ B-lymphoblastic leukemia/lymphoma with hyperdiploidy___ B-lymphoblastic leukemia/lymphoma with hypodiploidy___ B-lymphoblastic leukemia/lymphoma with t(5;14)(q31.1;q32.3); IGH-IL3___ B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3);TCF3-PBX1___ B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like ___ B-lymphoblastic leukemia/lymphoma with iAMP21___ T-lymphoblastic leukemia/lymphoma___ Early T-cell precursor lymphoblastic leukemia___ NK-lymphoblastic leukemia/lymphomaMature B-cell neoplasms___ Chronic lymphocytic leukemia/small lymphocytic lymphoma___ B-cell prolymphocytic leukemia___ Hairy cell leukemia___ Lymphoplasmacytic lymphoma___ Other mature B-cell neoplasm (specify): ___________________________Mature T and NK cell neoplasms___ T-cell prolymphocytic leukemia___ T-cell large granular lymphocytic leukemia___ Chronic lymphoproliferative disorder of NK-cells___ Aggressive NK-cell leukemia ___ Systemic EBV-positive T-cell lymphoma of childhood___ Hepatosplenic T-cell lymphoma___ Adult T-cell leukemia/lymphoma ___ Other mature T/NK-cell neoplasm (specify): ___________________________Other___ Other histologic type not listed (specify): ______________________________ Cannot be determinedSurgical Pathology Cancer Case SummaryProtocol posting date: February 2019BONE MARROW: Histologic AssessmentNote: This case summary is recommended for reporting hematologic malignancies in bone marrow but is NOT REQUIRED for accreditation purposes. Core data elements are bolded to help identify routinely reported elements.Select a single response unless otherwise indicated.Clinical Clinical context ___ New diagnosis, untreated___ New diagnosis, treatment status unknown___ Follow up sample___ Other (specify, or state if unknown): ___________________________Procedure (select all that apply) (Note B)___ Bone marrow aspiration___ Bone marrow aspirate clot ___ Bone marrow core biopsy___ Bone marrow core touch preparation (imprint)___ Other (specify): ___________________________Peripheral Blood Complete Blood Cell Count White blood cell count: ___ x103 / ?LNeutrophils: ___%Monocytes: ___%Lymphocytes: ___%Eosinophils: ___%Basophils: ___% Blasts: ___%Other cells: ___% Cell type (specify): _____________Hemoglobin: ___ g/dLPlatelets: ___ x103 / ?LBone Marrow Morphology (Note C)Bone Marrow Cellularity: ___%Bone Marrow Blasts: ___ % Bone Marrow Lymphocytes (report for lymphoid malignancies): ___ %Dysplasia (report for myeloid malignancies)___ Absent ___ Present (select all that apply)___ Granulocytic lineage___ Erythroid lineage___ Megakaryocytic lineageSpecial Stains (Note D) Iron stain (report for myeloid malignancies) ___ No ring sideroblasts detected___ Positive for ring sideroblasts (specify percent of erythroid precursors): _____%___ Stain not evaluable (explain): ______________Reticulin/Trichrome stains (fibrosis grade) (report if applicable) ___ MF-0___ MF-1___ MF-2 ___ MF-3Histologic Group ___ Myeloproliferative neoplasm___ Mastocytosis___ Myelodysplastic syndrome (MDS)___ Myelodysplastic/myeloproliferative neoplasm (MDS/MPN)___ Acute myeloid leukemia (AML)___ Blastic plasmacytoid dendritic cell neoplasm___ Precursor lymphoid neoplasm (acute lymphoblastic leukemia/lymphoma)___ Mature B-cell neoplasm___ Mature T and NK cell neoplasm___ Other histologic group not listed (specify): ______________________________ Cannot be determinedBiomarker Studies (Note D)___ Testing performed (see Bone Marrow Biomarker Reporting Template)___ Pending ___ Not performed___ Not applicableComment(s)Bone Marrow Biomarker Reporting Template Protocol posting date: February 2019BONE MARROW: Biomarker TemplateNote: This case summary is recommended for reporting hematologic malignancies in bone marrow but is NOT REQUIRED for accreditation purposes. Biomarker Studies (Note D)Immunohistochemistry___ Immunophenotype of neoplastic cells (specify): ______________________ Not performedFlow Cytometry (select all that apply)___ No aberrant populations identified___ Positive for aberrant myeloid blast population___ Immunophenotype (specify): _________________ Positive for aberrant lymphoid blast population ___ Immunophenotype (specify): _________________ Positive for aberrant mixed phenotype blast population ___ Immunophenotype (specify): _________________ Positive for aberrant mature B-cell population ___ Immunophenotype (specify): _________________ Positive for aberrant mature T-cell population ___ Immunophenotype (specify): _________________ Positive for other aberrancy (specify): ______________________ Immunophenotype (specify): _________________ Not performedNote: Specify immunophenotype or refer to separate reportCytogenetics___ Normal diploid karyotype___ Abnormal karyotype___ Karyotype (specify: ______________________ Not performedNote: Specify karyotype or refer to separate reportFluorescence in situ Hybridization ___ Normal pattern (specify panel): _________________________________ Abnormal pattern (specify panel): _________________________________ Not performedMolecular DiagnosticsBCR-ABL1 Transcript by RT-PCR Testing (select all that apply)___ Absent___ Present ___ Present transcript type p210___ Present transcript type p190___ Present transcript type, other (specify): ________________ Cannot be determined (explain): ________________________CEBPA (mono-allelic) Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________FLT3-ITD (internal tandem duplication) Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________FLT3 p.D835 (tyrosine kinase domain) Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________JAK2 p.V617F Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________MYD88 p.L265P Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________NPM1 Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________PML-RARA Transcript by RT-PCR Testing___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________RUNX1 Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________SF3B1 Mutation___ Absent___ Present (specify): ___________________________ Cannot be determined (explain): ________________________Specify Other Mutations (repeat as needed)___ Absent for other mutation(s) (specify): ___________________ ___ Present for other mutation(s) (specify): __________________ Comments:Explanatory NotesIntroductionThe aim of this protocol is to improve the completeness, clarity, and portability of bone marrow reporting in routine clinical practice settings, while being mindful of the wide range of practices in which the data in the report are generated and disseminated. Diagnostic workup of hematologic neoplasms requires the integration of data from multiple sources, including microscopic evaluation, flow cytometry immunophenotyping, cytogenetic analysis, and molecular testing. These requirements are reflected in the World Health Organization (WHO) classification of hematolymphoid malignancies. While this protocol emphasizes diagnostic data elements, it should be noted that many markers considered previously to be diagnostic in nature now provide the basis for frontline treatment decisions thus obscuring the boundaries of diagnostic and biomarker testing (e.g. CD20 and CD33 expression, BCR/ABL1 fusion, JAK2p.V617F and FLT3 mutations, etc.). This protocol is based to a large extent on the following documents: Revised 4th edition of the WHO classification. ADDIN EN.CITE <EndNote><Cite><Year>2017</Year><RecNum>6</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="vxtwaseazrxzeje2z5sv0s9552v9p0fw9zpd" timestamp="1519667766">6</key></foreign-keys><ref-type name="Edited Book">28</ref-type><contributors><authors><author>Swerdlow, H. S.</author><author>Campo, E. </author><author>Harris, N. L.</author><author>Jaffe, E. S. </author><author>Pileri, S. A. </author><author>Stein, H. </author><author>Thele, J. </author></authors></contributors><titles><title>WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues</title></titles><edition>4th (rev)</edition><dates><year>2017</year></dates><pub-location>Lyon</pub-location><publisher>IARC</publisher><urls></urls></record></Cite></EndNote>1CAP bone marrow synoptic reporting guidelines for hematologic neoplasms.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TZXZlcjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl

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ADDIN EN.CITE.DATA 4,5In a disease group where complementary tests may on occasion yield results that challenge the notion of succinct reporting (e.g. complex karyotype, complex mutational profile, etc.), a midway stance was adopted in this protocol to translate complex results into simpler terms that best inform treatment decisions and risk stratification. The synoptic report might thus on occasion lack the full scope of complexity of a given patient’s neoplasm, requiring reliance on source documentation. Previously published templates for reporting biomarker testing for myeloproliferative neoplasms (MPN) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) provide more in-depth details compared to the corresponding generic entries in the present protocol. The choice between the generic entries and the more detailed MPN and CLL/SLL templates, where applicable, is left to local discretion.Integrated DiagnosisIt is understood that the preferred timepoint at which this synoptic report is to be completed might vary by practice patterns and could be influenced by myriad factors, including the information technology environment. Notwithstanding, in the interest of medical record clarity and to avoid effort redundancy, it is recommended that this synoptic report be completed when all tests required for definitive WHO classification are completed. In other words, the use of this protocol would be most appropriate as a template for an “integrated report” in cases with hematologic malignancy, rather than for use as a standard template for morphology-based reporting. To this end, this protocol is structured in a “layered” reporting format as follows: Layer 1: Integrated diagnosis (incorporating all tissue-based information)Layer 2: Histological assessmentLayer 3: Biomarker studiesReferencesSwerdlow HS, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thele J eds. World Health Organization Histological Classification of Tumors of Haematopoietic and Lymphoid Tissues (ed 4th (rev)). Lyon, France: IARC Press; 2017.Sever C, Abbott CL, de Baca ME, et al. Bone Marrow Synoptic Reporting for Hematologic Neoplasms: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2016;140(9):932-949.Arber DA, Borowitz MJ, Cessna M, et al. Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393.Kelley TW, Arber DA, Gibson C, et al. Template for Reporting Results of Biomarker Testing of Specimens From Patients With Myeloproliferative Neoplasms. Arch Pathol Lab Med. 2016;140(7):675-677, cancerportocols.Duncavage E, Advani RH, Agosti S, et al. Template for Reporting Results of Biomarker Testing of Specimens From Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Arch Pathol Lab Med. 2016, cancerportocols.Sample Type and Clinical DataBone marrow evaluation is a critical part of the evaluation of patients suspected of having a hematologic malignancy. At initial presentation, sampling should ideally entail a core (trephine) biopsy and aspiration, with procurement of sufficient material for microscopic evaluation, flow cytometry immunophenotyping, cytogenetics, and molecular studies. It is advisable that a portion of the aspirate material be used to prepare a formalin-fixed paraffin-embedded clot sample (cell block). While this protocol is intended primarily for reporting of bone marrow specimens, applicable elements can be used for reporting extramedullary hematologic neoplasms if needed. Although the availability of clinical and laboratory data may be limited in certain practice settings, efforts to ensure that the pathologist has at their disposal as much pertinent information as possible to inform their diagnostic assessment are highly encouraged. This premise has been endorsed jointly by the College of American Pathologists and the American Society of Hematology.1 Inclusion of pertinent clinical and laboratory data in the bone marrow synoptic report is an evidence-based strong recommendationPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TZXZlcjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl

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ADDIN EN.CITE.DATA 2, which often also serves as a basis for classification or subclassification on certain hematologic malignancies. ReferencesArber DA, Borowitz MJ, Cessna M, et al. Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393.Sever C, Abbott CL, de Baca ME, et al. Bone Marrow Synoptic Reporting for Hematologic Neoplasms: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2016;140(9):932-949.MorphologyBone marrow aspirate smears stained with Wright Giemsa or May-Grunwald-Giemsa stain should be used to perform a 500-cell differential count to enumerate bone marrow blasts (including promonocytes where pertinent) and other marrow cellular elements excluding megakaryocytes. Adequate aspirate smears are also a prerequisite for optimal evaluation for dysplasia. If aspirate smears are limited, touch preparations might provide an alternative; on these a 300-cell differential is recommended. A 200-cell differential is recommended on peripheral blood smears. In instances where sample adequacy does not permit an adequate manual count, the number of blasts and other elements in the bone marrow may be estimated based on ancillary studies, particularly immunohistochemistry, and this would be specified in the pathology report. Descriptors for sample adequacy should be included in the bone marrow report. In this protocol, entries for dysplasia and the percentage of bone marrow blasts and lymphocytes are recommended, as applicable. For instance, reference to dysplasia or the percentage of blasts might not be necessary in a sample involved by chronic lymphocytic leukemia/small lymphocytic lymphoma. Age-matched bone marrow cellularity should be estimated on 3-4 ?m thick sections of formalin-fixed paraffin-embedded tissue sections of the core biopsy and/or clot preparation stained with hematoxylin and eosin, whichever is deemed most representative in a given sample. Normal ranges of bone marrow cellularity vary with age, as described in Table 1.1 Table 1. Normal ranges of bone marrow cellularity. Age (years)% Hematopoietic area20-3060-7040-6040-50≥7030-40ReferencesThiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128-1132.Ancillary and Biomarker StudiesSpecial StainsA number of cytochemical stains may be utilized in the evaluation of hematologic neoplasms. An iron (Prussian blue) stain is required for assessment of stainable iron in erythroid precursors and the identification of ring sideroblasts.1 Stainable iron is best evaluated on an aspirate smear or a touch preparation in cases for which such preparations are available. Evaluation of stainable iron on biopsy specimens should be avoided because of limited visualization of ring sideroblasts and the impact of decalcification on iron content. Aberrant cytoplasmic periodic acid-Schiff (PAS) positivity, either diffuse or granular, is a characteristic of dysplasia in erythroid precursors. Cytochemical detection of myeloperoxidase is a rapid and cost-effective tool in the initial workup of acute myeloid leukemia. Notwithstanding, although useful and practical for lineage determination in some instances, cytochemical stains are no longer required for the diagnostic workup of most hematologic neoplasms.The assessment of bone marrow fibrosis requires a good-quality reticulin stain.2 The WHO classification recommends the use of trichrome stain in samples with moderate or severe fibrosis (see below). Bone marrow fibrosis grading scheme is summarized in Table 2. Table 2. Semi-quantitative grading of bone marrow fibrosis.Myelofibrosis gradeDescriptionMF-0Scattered linear reticulin with no intersections (crossovers) corresponding to normal BM.MF-1Loose network of reticulin with many intersections, especially in perivascular areas.MF-2Diffuse and dense increase in reticulin with extensive intersections, occasionally with focal bundles of thick fibers mostly consistent with collagen, and/or focal osteosclerosis.MF-3Diffuse and dense increase in reticulin with extensive intersections and coarse bundles of thick fibers consistent with collagen, usually associated with osteosclerosis.Fiber density should be assessed only in hematopoietic areas.In grades MF-2 or MF-3 an additional trichrome stain is recommended.Immunophenotyping Immunophenotyping of bone marrow specimens can be performed by flow cytometry or immunohistochemistry for diagnostic evaluation and for biomarker assessment.3 Both techniques provide diagnostic, prognostic, and therapy-guiding data elements, and each technique has advantages and disadvantages. Flow cytometry is rapid (hours), quantitative, and allows multiple antigens to be evaluated on the same cell simultaneously. Flow cytometry is the gold standard for minimal residual disease detection in patients with acute leukemia. Immunohistochemistry permits correlation of antigen expression with architecture and cytomorphology, and it can be performed on archival material. Cytogenetics, Fluorescence in situ Hybridization, and Molecular Genomics StudiesCytogenetic and molecular data are integral to the evaluation of patients with primary bone marrow neoplasms. Cytogenetic analysis typically entails conventional karyotyping and FISH. Conventional karyotyping requires viable cells. FISH may be performed on metaphase spreads from karyotyping studies or on air-dried, fresh unfixed aspirate or touch preparation slides. Array comparative genomic hybridization (aCGH) is used as an adjunct tool to detect copy number changes in certain conditions. Unlike conventional karyotyping, aCGH does not require viable cells. The WHO classification recognizes certain cytogenetic abnormalities as sufficient for a diagnosis of acute myeloid leukemia with myelodysplasia-related change if the bone marrow blast percentage is greater than 20% and the patient has no history of antecedent cytotoxic therapy. These abnormalities are summarized in Table 3. Table 3. Myelodysplasia-related cytogenetic plex karyotype (3 or more abnormalities)Unbalanced abnormalities-7/del(7q)del(5q)/t(5q)i(17q)/t(17p)-13/del(13q)del(11q)del(12p)/t(12p)idic(X)(q13)Balanced abnormalitiest(11;16)(q23.3;p13.3)t(3;21)(q26.2;q22.1)t(1;3)(p36.3;q21.2)t(2;11)(p21;q23.3)t(5;12)(q32;p13.2)t(5;7)(q32;q11.2)t(5;17)(q32;p13.2)t(5;10)(q32;q21.2)t(3;5)(q25.3;q35.1)The advent of next-generation sequencing (NGS) has altered the landscape of molecular diagnostics. Mutation profiling using gene panels that range from tens to hundreds of genes is increasingly becoming widespread, providing valuable diagnostic, prognostic, and therapy-guiding data. Mutation profiling may be done at initial diagnosis or at subsequent timepoints such as at transformation or relapse. There are no definitive approaches to synoptic reporting of NGS-based mutation profiling results. In this protocol, entries for mutation data on key genes are included in the generic portion of the document. Inclusion of mutation results for other genes is kept at the discretion of the pathologist completing the synoptic report. ReferencesDella Porta MG, Travaglino E, Boveri E, et al. Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes. Leukemia 2015;29: 66–75. Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128-1132.Khoury JD, Wang WL, Prieto VG, et al. Validation of Immunohistochemical Assays for Integral Biomarkers in the NCI-MATCH EAY131 Clinical Trial. Clin Cancer Res. 2018;24(3):521-531.Sample synoptic reportsPathologists may use synoptic reporting tools incorporated into pathology informatics systems or use custom template forms to incorporate the data elements and responses into cancer pathology reports. The following are examples of synoptic reports using this version of the protocol. Example 1Integrated Diagnosis: Hairy cell leukemiaProcedure:Bone marrow aspiration, clot, and core biopsyPeripheral blood complete blood cell count: White blood cell count:2.3 x 103/?L Hemoglobin:10.4 g/dL Platelets: 112 x 103/?LBone Marrow Cellularity: 20%Bone Marrow Lymphocytes: 30% Immunohistochemistry: Positive for annexin A1 and BRAF p.V600EFlow cytometry: Aberrant B-cell population: Positive for CD11c, CD19, CD20, CD22, CD25, CD103, CD123, kappa; negative for CD5, CD10, lambdaCytogenetics: Normal diploid karyotypeMolecular Diagnostics: Other mutation testing performed: Positive: BRAF p.V600EExample 2Integrated Diagnosis: Chronic myelomonocytic leukemia-1Procedure:Bone marrow aspiration, clot, and core biopsyPeripheral blood complete blood cell count: White blood cell count:13.7 x 103/?LMonocytes:21%Blasts: 1%Hemoglobin:11.3 g/dLPlatelets: 68 x 103/?LBone Marrow Cellularity: 70%Bone Marrow Blasts: 6% Dysplasia: Present; erythroid, megakaryocyticFlow cytometry: Positive for other aberrancy: CD56+monocytesCytogenetics: Normal diploid karyotypeFluorescence in situ hybridization: Negative for BCR/ABL1 fusionMolecular Diagnostics: Negative for JAK2 p.V617FmutationOther mutation testing performed: Positive: NRAS p.G12D ................
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