Medical Licensing (MD/DO) · Independent exam preparation
Hematopathology Subspecialty Examination Study Guide
Practise integrated blood, marrow and lymph-node diagnosis, select discriminating tests, and apply WHO fifth-edition and ICC 2022 criteria through focused cases.
By CertMedbry · Updated 15 October 2026
Build defensible hematopathology diagnoses by connecting morphology with immunophenotype, genetics and clinical findings. Practise choosing informative specimens, distinguishing reactive from clonal disease, recognizing urgent leukemia findings and applying classification-specific criteria. This selective 60-concept guide addresses all nineteen blueprint domains. Use the complete ABPath blueprint and content specifications to define examination scope; the issuer also states that its specifications are not exhaustive.
Try 20 free practice questionsWhat is the exam format?
Check the question types, timing and outline before planning your revision.
Which certification and examination does this guide address?
The ABPath Hematopathology Subspecialty Examination is a physician subspecialty certification examination. Its content includes fellow-level knowledge and applicable core and advanced resident topics.
ABPath: Hematopathology Exam Description · ABPath Hematopathology Content Specifications: April 7, 2026
How many questions are listed, and how many are scored or pretest?
ABPath lists 220 combined written/practical questions and 45 virtual microscopy questions, totaling 265. Its examination description does not identify separate scored and pretest counts, so these totals should not be interpreted as verified scored-item counts.
What duration and delivery format are verified?
The examination is a one-day computer-based examination. Written/practical sections receive 4 hours 25 minutes, and virtual microscopy receives 2 hours 39 minutes. These section times total 7 hours 4 minutes; they do not establish the complete appointment length or break schedule. ABPath's description does not specify adaptive delivery.
ABPath: Hematopathology Exam Description · ABPath Hematopathology Exam Blueprint: Updated for 2026
Which question styles and microscopy materials are used?
ABPath describes multiple-choice questions using one best answer. Practical material includes blood and marrow smears, imprints, body fluids and tissue sections. Microscopy uses virtual slides, with no glass slides. The twenty text-based questions here are independent learning drills and do not reproduce the virtual microscopy experience or predict examination performance.
Which blueprint and specification dates apply?
The blueprint is marked Updated for 2026. The content-specification index links the final Hematopathology document dated April 7, 2026. A separate effective date is not stated.
ABPath: Content Specifications for Examinations · ABPath Hematopathology Exam Blueprint: Updated for 2026 · ABPath Hematopathology Content Specifications: April 7, 2026
How should the separate blueprint weights guide study?
Written/practical and virtual microscopy have separate approximate percentage distributions. Myeloid neoplasms account for 20% and 18%, lymphoid neoplasms for 19% and 38%, and hemostasis and thrombosis for 11% and 4%, respectively. Each column totals 100%. This guide emphasizes those major domains while retaining every smaller domain; a small learning bank cannot reproduce both distributions exactly.
Which disease classifications must candidates know?
ABPath explicitly requires familiarity with both ICC 2022 and the WHO fifth edition. Compare names, blast thresholds and defining genetic criteria within each system. When a case depends on a difference between systems, identify the system before assigning the diagnosis.
ABPath: Hematopathology Exam Description · International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms · WHO Fifth Edition: Lymphoid Neoplasms
This guide addresses the American Board of Pathology physician Hematopathology Subspecialty Examination. Its learning questions and flashcards are independently authored educational materials, without ABPath endorsement.
Outline used: ABPath Hematopathology Exam Blueprint, marked Updated for 2026, and final Hematopathology Content Specifications dated April 7, 2026. A separate effective date is not stated. The assigned workbook label maps to ABPath's Hematopathology Subspecialty Examination; the assigned slug is preserved.
60 key concepts: understand, apply and avoid the traps
Work through the questions by exam domain. Explain the answer in your own words, try the example, then check the common pitfall.
Basic methodology and test armamentarium8% written/practical; 0% virtual microscopy
1.How should a suspected lymphoma specimen be divided?
Specimen triage preserves complementary diagnostic information. Fixed tissue supports architecture and immunohistochemistry, whereas viable unfixed material permits flow cytometry and selected cytogenetic studies. The allocation should reflect the suspected disease and available tissue rather than follow an automatic panel. Architecture is particularly important when sparse tumor cells or a characteristic tissue background determine the diagnosis. An adequate biopsy can become diagnostically limited if all material enters an incompatible fixative.
Apply it
A node is excised for suspected lymphoma. Before fixation, coordinate allocation of viable tissue for flow cytometry while preserving sufficient intact tissue for histology, particularly because Hodgkin lymphoma remains in the clinical differential.
Common pitfall: Sending the entire specimen for flow cytometry can sacrifice architecture; placing everything in formalin can eliminate useful viable-cell studies and reduce diagnostic flexibility.
Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
3.How should an immunohistochemical panel establish lineage?
Immunohistochemistry is strongest when a panel tests competing lineage hypotheses in morphologically identified cells. A single positive marker may reflect aberrant expression, activation or background cells. Establish whether staining belongs to the atypical population, then assess its distribution and intensity alongside complementary markers. For example, strong CD30 expression supports several activated or neoplastic populations and cannot independently distinguish classical Hodgkin lymphoma from anaplastic large cell lymphoma.
Apply it
A node contains pleomorphic CD30-positive large cells. Examine ALK, T-cell markers, B-cell transcription factors and the cellular background to distinguish anaplastic large cell lymphoma from classical Hodgkin lymphoma and other CD30-positive proliferations.
Common pitfall: Equating one familiar antigen with one disease ignores overlapping expression and can misclassify both lineage and entity despite a technically convincing stain.
International Consensus Classification of Mature Lymphoid Neoplasms · ASH Image Bank: ALK-Positive Anaplastic Large Cell Lymphoma, CD30
4.What does a positive molecular clonality result establish?
A reproducible antigen-receptor rearrangement supports a restricted lymphoid population, but clonality is not synonymous with malignancy. Restricted immune responses and small sampled populations can yield clonal or apparently clonal patterns. Conversely, a lymphoma may test negative because of assay coverage, somatic hypermutation or limited tumor content. Use clonality testing to resolve a defined diagnostic question after morphology and immunophenotyping, rather than as a stand-alone screening diagnosis of lymphoma.
Apply it
A small biopsy shows reactive architecture and a restricted T-cell rearrangement. Review clinical findings, immunophenotype and sampling before diagnosing lymphoma; the molecular result alone does not override otherwise convincing reactive tissue findings.
Common pitfall: Calling lymphoma solely because a rearrangement is clonal converts evidence of population restriction into an unsupported conclusion about biological behavior and tissue classification.
CAP: Laboratory Workup of Lymphoma in Adults · Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
Normal hematopoiesis & hemostasis3% written/practical; 0% virtual microscopy
2.How are coagulation, physiological anticoagulation and fibrinolysis coordinated?
Tissue factor–factor VIIa initiates coagulation by activating factors IX and X. On activated platelet phospholipid surfaces, IXa–VIIIa generates Xa, and Xa–Va converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin and activates factor XIII, which crosslinks fibrin. Antithrombin restrains thrombin and Xa; thrombomodulin-bound thrombin activates protein C, which with protein S inactivates Va and VIIIa. Tissue plasminogen activator promotes conversion of plasminogen to plasmin on fibrin. Plasmin digests fibrin, while PAI-1 and alpha-2-antiplasmin limit fibrinolysis. D-dimer arises from degradation of crosslinked fibrin.
Apply it
A patient has increased D-dimer. Explain that crosslinked fibrin has formed and undergone degradation; the result reflects coagulation followed by fibrinolysis and requires clinical context to identify the cause.
Common pitfall: PT and aPTT measure selected plasma clotting reactions rather than platelet-supported coagulation, natural anticoagulant function and fibrinolysis as a complete system. D-dimer is not specific for venous thrombosis.
ABPath Hematopathology Content Specifications: April 7, 2026
5.How does normal marrow maturation provide a diagnostic reference?
Normal hematopoiesis produces recognizable maturation sequences. Erythroid precursors progressively decrease in cell size and nuclear-to-cytoplasmic ratio while their chromatin condenses. Increasing hemoglobinization changes cytoplasm from deep blue in basophilic normoblasts through gray-blue in polychromatophilic normoblasts to gray-pink in orthochromic normoblasts. Granulocytic maturation proceeds from myeloblasts with fine chromatin and nucleoli to promyelocytes with abundant azurophilic primary granules. Myelocytes have round nuclei, more condensed chromatin, no visible nucleolus, and both primary and secondary specific granules; the proportion of secondary granules increases with maturation. Metamyelocytes develop indented, kidney-shaped nuclei, bands have curved unsegmented nuclei, and mature neutrophils have distinct nuclear lobes connected by thin filaments. Assess these sequences alongside age-appropriate cellularity, lineage distribution and marrow architecture.
Apply it
During recovery after chemotherapy, a cellular marrow contains promyelocytes with prominent primary granules, myelocytes with round nuclei and emerging pink-lilac specific granules, metamyelocytes with nuclear indentation, and bands and segmented neutrophils. This spectrum demonstrates granulocytic maturation and supports regenerating hematopoiesis when blood counts are recovering. Compare erythroid cells using the ASH erythroid example's progression toward smaller cells, condensed nuclei and pinker cytoplasm; use the ASH myelocyte example to distinguish a granulated myelocyte from a blast. Assess the actual blast population and any leukemia-associated phenotype separately.
Common pitfall: Increased cellularity, a left shift or circulating myelocytes alone does not establish recurrent leukemia. Myelocytes may occur in blood during inflammation or growth-factor stimulation. Conversely, preserved maturation does not exclude a coexisting neoplasm; an abnormal blast population or defining genetic finding still requires evaluation.
ABPath Hematopathology Content Specifications: April 7, 2026 · International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · Erythroid Precursors · Myelocyte
6.Why does von Willebrand factor connect platelet adhesion and coagulation?
Von Willebrand factor supports platelet adhesion at injured vascular surfaces and carries factor VIII in plasma. A deficiency or functional defect can therefore impair primary hemostasis and reduce factor VIII stability. Mucocutaneous bleeding reflects the platelet-adhesion component, while sufficiently low factor VIII can influence coagulation testing. This dual role explains why evaluation includes VWF antigen, platelet-dependent VWF activity and factor VIII rather than a platelet count alone.
Apply it
A patient has recurrent epistaxis, normal platelet numbers and reduced factor VIII. Include VWF antigen and platelet-dependent activity in the investigation because an abnormal carrier protein can connect these apparently different laboratory findings.
Common pitfall: A normal platelet count does not establish normal primary hemostasis, and reduced factor VIII does not automatically identify an isolated factor VIII disorder.
ASH ISTH NHF WFH Guidelines on VWD Diagnosis: Executive Summary
RBC disorders, non-neoplastic9% written/practical; 7% virtual microscopy
7.How do iron studies distinguish absolute iron deficiency from inflammatory iron restriction?
Absolute iron deficiency depletes stores: ferritin falls, transferrin or total iron-binding capacity usually rises, and transferrin saturation falls. Microcytosis and hypochromia develop as iron-restricted erythropoiesis progresses. In inflammation, hepatic hepcidin binds ferroportin and promotes its internalization and degradation, reducing iron export from macrophages and enterocytes. Serum iron and transferrin saturation fall despite retained stores; ferritin may be normal or increased, and transferrin is often reduced or normal. Reduced erythropoietin production or responsiveness and shortened red-cell survival can also contribute. Both conditions can coexist, and an inflammatory ferritin elevation can conceal depleted stores.
Apply it
Microcytic anemia with ferritin 8 ng/mL and increased total iron-binding capacity strongly supports absolute iron deficiency. Low serum iron with elevated ferritin and reduced transferrin during active inflammation instead supports iron sequestration, while leaving possible concurrent deficiency to be assessed.
Common pitfall: Low serum iron or low transferrin saturation alone does not distinguish depleted stores from inflammatory restriction. Normal or elevated ferritin during inflammation cannot reliably exclude concurrent absolute deficiency.
NIDDK: Anemia of Inflammation or Chronic Disease · ABPath Hematopathology Content Specifications: April 7, 2026
8.What distinguishes beta-zero from beta-plus thalassemia?
HBB variants reduce beta-globin synthesis and create an imbalance between alpha- and beta-globin chains. A beta-zero allele produces no beta globin, whereas a beta-plus allele retains some production. Excess unmatched alpha chains damage developing erythroid cells and circulating red cells. Severity depends on the combination of alleles and modifying factors, so the allele designation describes globin output rather than guaranteeing one clinical phenotype or transfusion requirement.
Apply it
Two affected siblings have different HBB variants. Explain that an allele retaining partial beta-globin synthesis is beta-plus, while an allele abolishing synthesis is beta-zero; interpret each child's phenotype using both alleles and clinical findings.
Common pitfall: Beta-plus does not mean increased beta-globin production. The plus sign indicates residual synthesis, and genotype categories do not independently determine an individual patient's severity.
9.Which findings distinguish megaloblastic anemia from other causes of macrocytosis?
Vitamin B12 or folate deficiency impairs DNA synthesis, producing nuclear–cytoplasmic maturation asynchrony. Macro-ovalocytes and hypersegmented neutrophils support megaloblastic hematopoiesis; marrow may show megaloblasts and giant granulocytic precursors. Ineffective erythropoiesis can cause high LDH and indirect bilirubin despite an inadequate reticulocyte response. Methylmalonic acid rises in B12 deficiency but generally remains normal in isolated folate deficiency; homocysteine can rise in either. Renal impairment can also elevate methylmalonic acid. Neurologic abnormalities particularly raise concern for B12 deficiency.
Apply it
A patient has macro-ovalocytes, hypersegmented neutrophils, high LDH and few reticulocytes. Low B12 with elevated methylmalonic acid supports B12 deficiency and explains ineffective production. Evaluate this reversible cause before attributing the abnormal marrow maturation to MDS.
Common pitfall: Macrocytosis alone does not establish megaloblastosis: alcohol, liver disease, reticulocytosis and medications have other mechanisms. Concurrent iron deficiency can mask an increased mean corpuscular volume.
ABPath Hematopathology Content Specifications: April 7, 2026 · International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
10.How does flow cytometry identify a PNH population?
Paroxysmal nocturnal hemoglobinuria involves deficient expression of glycosylphosphatidylinositol-anchored surface proteins. Flow cytometry identifies populations with reduced or absent GPI-associated markers; FLAER provides a complementary assessment of the GPI anchor on appropriate leukocyte populations. Concordant abnormalities across suitable markers and lineages support a true clone. Red-cell findings require special caution after transfusion or selective destruction of affected cells, which can make the erythrocyte clone appear smaller than the underlying population.
Apply it
An individual with hemolysis recently received red-cell transfusions. A granulocyte population lacks FLAER binding and a GPI-linked marker. Interpret the leukocyte findings as strong evidence of a PNH population despite a smaller abnormal erythrocyte fraction.
Common pitfall: An isolated abnormal marker or a post-transfusion erythrocyte percentage should not substitute for a validated, lineage-appropriate assessment of GPI-anchor deficiency across complementary measurements.
ASH Image Bank: PNH Flow Cytometry · International Clinical Cytometry Society
11.How do morphology and the direct antiglobulin test distinguish immune hemolysis?
Hemolysis is supported by increased indirect bilirubin and LDH, reduced haptoglobin and usually reticulocytosis. Warm autoimmune hemolytic anemia commonly involves IgG coating of erythrocytes, splenic macrophage removal of membrane and spherocyte formation; the direct antiglobulin test is usually positive for IgG, with or without C3. Cold antibody-mediated hemolysis commonly involves complement fixation by IgM, with a C3-positive direct antiglobulin test and red-cell agglutination. Interpret the test alongside evidence of hemolysis and review transfusion and medication history because immune coating has several causes.
Apply it
An anemic patient has spherocytes, reticulocytosis, elevated indirect bilirubin and an IgG-positive direct antiglobulin test. The combination supports warm immune hemolysis. Spherocytes with a negative test and a lifelong family history would instead raise hereditary spherocytosis.
Common pitfall: A positive direct antiglobulin test alone does not establish active hemolysis. Conversely, a negative routine test does not exclude every immune hemolytic process, and a weak reticulocyte response can reflect concurrent marrow suppression or deficiency.
ABPath Hematopathology Content Specifications: April 7, 2026 · iwCLL.pdf
WBC disorders, non-neoplastic5% written/practical; 2% virtual microscopy
12.How does reactive neutrophilia differ from CML?
Reactive neutrophilia reflects a stimulus such as infection, inflammation or marrow recovery, whereas chronic myeloid leukemia is defined by BCR::ABL1 in the appropriate clinicopathologic setting. Toxic changes and a resolving count favor a reactive process, while persistent granulocytic expansion with basophilia raises concern for CML. Morphology establishes the differential but does not replace genetic confirmation. Interpret molecular findings with specimen quality and the overall hematologic pattern.
Apply it
A patient with bacterial infection develops neutrophilia, toxic granulation and a left shift that resolves after recovery. Favor a reactive process; persistent basophilia and sustained granulocytosis would instead justify evaluation for BCR::ABL1-associated disease.
Common pitfall: A left shift alone does not diagnose CML. Both reactive granulopoiesis and neoplastic expansion can release immature granulocytes into the peripheral blood circulation.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
13.Why does hemophagocytosis require clinical correlation?
Hemophagocytosis alone neither establishes nor excludes HLH. HLH-2004 permits a compatible molecular diagnosis or fulfillment of at least five of eight criteria: fever; splenomegaly; cytopenias affecting at least two lineages; fasting triglycerides at least 265 mg/dL and/or fibrinogen at most 1.5 g/L; tissue hemophagocytosis; low or absent NK-cell activity; ferritin at least 500 µg/L; and soluble CD25 at least 2400 U/mL. Cytopenia thresholds are hemoglobin below 9 g/dL, platelets below 100 × 10^9/L and neutrophils below 1.0 × 10^9/L, with an infant-specific hemoglobin threshold. These pediatric criteria are not formally validated in adults and require clinical judgment. Deteriorating patients may require urgent decisions before five criteria are documented; pending specialized tests must not delay necessary action.
Apply it
A febrile adult with splenomegaly, anemia and thrombocytopenia has occasional hemophagocytosis. Assess triglycerides, fibrinogen, ferritin, soluble CD25 and NK-cell activity while investigating infection, lymphoma and other triggers. Interpret the accumulating criteria alongside organ dysfunction and clinical progression.
Common pitfall: Neither isolated hemophagocytosis nor hyperferritinemia is specific for adult HLH. Conversely, absent hemophagocytosis or incomplete criteria early in illness cannot safely exclude an evolving syndrome.
Benign hematopoietic disorders with abnormalities in more than one lineage1% written/practical; 2% virtual microscopy
14.Which findings connect giant platelets with MYH9-related disease?
MYH9-related disease is an autosomal dominant disorder associated with macrothrombocytopenia and characteristic inclusions in neutrophils. Giant platelets can also cause automated platelet counts to underestimate the true number. Hearing loss, renal disease and cataracts may develop, connecting a blood-film pattern with a broader inherited disorder. The combination of lifelong thrombocytopenia, large platelets and leukocyte inclusions is more discriminating than any one finding considered without family or clinical information.
Apply it
A patient labeled as having immune thrombocytopenia has lifelong low platelet counts, giant platelets, neutrophil inclusions and an affected parent. Reconsider an inherited MYH9-related disorder and review associated hearing and renal findings before retaining the acquired diagnosis.
Common pitfall: Large platelets alone can occur during increased platelet turnover. The inherited history and leukocyte inclusions provide the stronger distinction from acquired immune thrombocytopenia.
Infectious disorders expressed in the peripheral blood2% written/practical; 4% virtual microscopy
15.Which smear findings favor Babesia over malaria?
Babesia infects erythrocytes and can appear as delicate ring forms resembling malaria parasites. Tetrads forming a Maltese-cross pattern strongly support babesiosis, although they are not present in every infected specimen. Extracellular organisms and pleomorphic forms can provide additional clues. Blood-film morphology supports recognition of infection, but species identification is limited and may require molecular testing. Exposure history and parasitemia assessment strengthen interpretation without replacing organism identification.
Apply it
A patient with fever and hemolysis has intraerythrocytic rings and a rare four-organism cross configuration. Favor babesiosis, quantify parasitemia and use appropriate confirmatory testing rather than assigning a Babesia species from the tetrad alone.
Common pitfall: Ring forms alone are not specific for malaria. Conversely, failure to find a Maltese cross does not exclude babesiosis in an otherwise compatible specimen.
Benign disorders involving bone marrow not otherwise classifiable3% written/practical; 2% virtual microscopy
16.What does a giant pronormoblast suggest in a reticulocytopenic patient?
Parvovirus B19 targets erythroid precursors and can suppress red-cell production. Marrow may show giant pronormoblasts with striking nuclear changes, often against a background of reduced effective erythropoiesis. These cells provide a diagnostic clue, especially when anemia accompanies marked reticulocytopenia. Morphology should lead to appropriate viral confirmation and assessment of immune status. A single large abnormal erythroid precursor should not automatically be classified as a leukemic blast.
Apply it
An immunocompromised patient develops severe anemia with very few reticulocytes. Marrow contains giant pronormoblasts. Investigate parvovirus B19 and interpret the erythroid suppression in that context before assigning a myelodysplastic or acute leukemic diagnosis.
Common pitfall: The enlarged precursor can resemble a malignant cell. Recognizing erythroid identity and confirming infection prevents morphology alone from producing an unsupported leukemia diagnosis.
ASH Image Bank: Giant Pronormoblast in Parvovirus B19 Infection
17.How should recent therapy change the interpretation of marrow dysplasia?
Cytotoxic treatment and marrow regeneration can alter cellularity, maturation and nuclear morphology. Such changes can resemble myelodysplasia without independently establishing a persistent myeloid neoplasm. Integrate the treatment timeline, previous specimens, blood-count trajectory and defining genetic evidence. Persistence after recovery increases concern, while resolving abnormalities support a transient effect. A history of cytotoxic exposure is clinically important, but it does not make every subsequent atypical marrow a therapy-related neoplasm.
Apply it
A marrow obtained shortly after chemotherapy shows atypical megakaryocytes and left-shifted granulopoiesis during count recovery. Compare with pretreatment findings and follow the clinical course before attributing isolated atypia to a new clonal myeloid disorder.
Common pitfall: Prior chemotherapy is a risk context, not a sufficient diagnosis. Transient treatment-associated atypia must be distinguished from a myeloid neoplasm meeting integrated criteria.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
Benign disorders of lymphoid tissues4% written/practical; 11% virtual microscopy
18.How does lymph-node architecture help distinguish reactive hyperplasia?
Reactive lymphoid responses often retain recognizable compartments and display cellular variation appropriate to immune stimulation. Evaluation considers follicles, interfollicular regions, sinuses and the distribution of immunophenotypically defined cells. A mixed population supports reactivity only when it fits the architectural and clinical pattern; some lymphomas contain abundant reactive cells. Adequate tissue is therefore important when the distinction depends on organization rather than merely detecting a small abnormal population in suspension.
Apply it
A node has variable follicles, polarized germinal centers and preserved interfollicular compartments. Correlate the organized pattern with immunophenotyping and clinical findings before interpreting an isolated unusual cell population as evidence of diffuse architectural replacement.
Common pitfall: A heterogeneous cell suspension can coexist with lymphoma. Conversely, an immunologically restricted population can occur in reactive tissue, making architecture an essential additional discriminator.
Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
19.What does emperipolesis indicate in Rosai-Dorfman disease?
Emperipolesis is the presence of intact hematopoietic cells within the cytoplasm of another cell, classically conspicuous within Rosai-Dorfman histiocytes. It differs from destructive phagocytosis because the enclosed cells remain recognizable and relatively intact. The finding becomes diagnostically useful when accompanied by appropriate histiocytic morphology and immunophenotype. It should be interpreted as part of a pattern, because isolated cell-in-cell appearances are not uniquely diagnostic of Rosai-Dorfman disease.
Apply it
A node contains large pale histiocytes enclosing intact lymphocytes. Assess the broader histiocytic pattern and supporting stains for Rosai-Dorfman disease, while distinguishing intact internalized cells from fragmented material undergoing destructive phagocytosis within the lesional cells.
Common pitfall: Calling every internalized cell hemophagocytosis obscures the distinction between emperipolesis and destructive ingestion; neither observation should replace assessment of the complete lesion pattern.
ASH Image Bank: Emperipolesis in Rosai-Dorfman Disease · ABPath Hematopathology Content Specifications: April 7, 2026
20.How are the three Castleman disease entities distinguished?
Unicentric Castleman disease has compatible histology confined to one lymph-node region, which may contain several involved nodes; HHV8 is usually absent. Multicentric disease involves multiple nodal stations. In that setting, compatible histology with HHV8 infection demonstrated by LANA staining in the relevant nodal plasmablasts supports HHV8-associated multicentric Castleman disease. Idiopathic multicentric Castleman disease requires both major criteria: characteristic Castleman-spectrum histology and enlarged nodes at least 1 cm in at least two nodal stations. It also requires at least two minor criteria, including at least one laboratory criterion. Laboratory criteria include elevated CRP or ESR, anemia, thrombocytopenia or thrombocytosis, hypoalbuminemia, renal dysfunction or proteinuria, and polyclonal hypergammaglobulinemia. Clinical criteria include constitutional symptoms, hepatosplenomegaly, fluid accumulation, characteristic vascular skin lesions and lymphocytic interstitial pneumonitis. Exclude HHV8-associated disease, other explanatory infections, autoimmune or autoinflammatory disease, lymphoma and other malignancies, and POEMS-associated disease before assigning the idiopathic category.
Apply it
Castleman-pattern histology in one nodal region supports unicentric disease after staging. Similar histology in several stations with LANA-positive plasmablasts supports HHV8-associated multicentric disease. If LANA is negative, establish the idiopathic multicentric major and minor criteria and exclude mimics; generalized adenopathy and viral negativity alone are insufficient.
Common pitfall: HHV8 negativity does not establish idiopathic multicentric Castleman disease. Neither plasmacytosis nor systemic inflammation overrides nodal distribution, required clinical criteria or exclusion of another cause of Castleman-like changes.
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms | Leukemia · International Consensus Classification of Mature Lymphoid Neoplasms
Fluid specimens2% written/practical; 2% virtual microscopy
21.Why combine CSF cytology with flow cytometry?
CSF cytology evaluates cellular appearance, while flow cytometry can detect small immunophenotypically abnormal populations that are difficult to recognize morphologically. The methods provide complementary information and should be coordinated when evaluating possible lymphoma involvement. Low cellularity, rapid cell deterioration and contamination complicate interpretation. A result should identify its evidentiary basis and limitations, including whether an abnormal population could reflect peripheral-blood contamination rather than unequivocal involvement of the CSF compartment.
Apply it
A patient with known lymphoma develops neurologic symptoms. Submit CSF promptly for both morphology and flow cytometry, then compare any abnormal population with the known tumor and assess specimen quality and possible blood contamination.
Common pitfall: Using only cytology can miss a small abnormal population, while interpreting flow without morphology or contamination assessment can overstate the significance of rare cells.
Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
Immunodeficiency disorders2% written/practical; 2% virtual microscopy
22.How should immune dysfunction be incorporated into lymphoid reporting?
Immune deficiency and dysregulation influence the spectrum and interpretation of lymphoid proliferations. WHO fifth-edition reporting connects the histologic lesion with viral associations and the immune deficiency or dysregulation setting. This preserves information that a morphology-only label can lose. An EBV-positive proliferation in a transplant recipient, for example, requires assessment of its tissue pattern and immune context rather than automatic assignment to a single lymphoma category based on EBV positivity.
Apply it
A transplant recipient develops an EBV-positive nodal proliferation. Characterize the histologic lesion, document the viral association and state the transplant-related immune setting so the report communicates the integrated disease context to the treating team.
Common pitfall: EBV positivity alone does not distinguish reactive proliferation, polymorphic disease and a defined lymphoma. Immune setting and tissue morphology remain necessary classification components.
Hemostasis and Thrombosis11% written/practical; 4% virtual microscopy
23.How does the VWF activity-to-antigen ratio identify a qualitative defect?
VWF antigen estimates quantity, whereas platelet-dependent activity measures function. Disproportionately reduced activity suggests a qualitative defect; a ratio below 0.7 supports evaluation for type 2A, 2B or 2M VWD without establishing the subtype. Test at baseline health when feasible because VWF rises with bleeding, trauma and other stresses. For type 1 VWD, a VWF level below 0.30 IU/mL supports diagnosis regardless of bleeding, while a level below 0.50 IU/mL supports diagnosis in patients with abnormal bleeding.
Apply it
VWF activity of 24 IU/dL and antigen of 60 IU/dL give a ratio of 0.40, prompting qualitative-defect studies. If a patient with lifelong mucosal bleeding instead has normal results during acute illness, repeat testing at baseline health before excluding VWD.
Common pitfall: A low ratio does not uniquely diagnose type 2B. Normal results during stress can mask baseline deficiency, while borderline low values require interpretation with bleeding history.
ASH ISTH NHF WFH Guidelines on VWD Diagnosis: Executive Summary
24.How does a mixing study distinguish factor deficiency from an inhibitor?
Mixing patient plasma 1:1 with normal plasma supplies deficient factors. Correction of a prolonged aPTT supports deficiency; persistent prolongation suggests an inhibitor or anticoagulant effect. Factor VIII inhibitors can be time dependent, so initial correction followed by loss of correction after two hours at 37°C raises concern for acquired hemophilia A. Confirm with factor VIII activity and a Nijmegen-modified Bethesda assay, while assessing anticoagulant interference and lupus anticoagulant. Mixing studies alone cannot establish or exclude acquired hemophilia. These distinctions follow the [international acquired hemophilia recommendations](https://haematologica.org/article/view/9931).
Apply it
An older adult with new extensive soft-tissue bleeding has isolated aPTT prolongation. The immediate mix corrects, but the incubated mix does not. Prioritize factor VIII activity and inhibitor measurement rather than concluding that immediate correction proves congenital factor deficiency.
Common pitfall: Noncorrection is not specific for a factor VIII inhibitor: lupus anticoagulant and anticoagulant drugs can interfere. Conversely, immediate correction does not exclude a time-dependent inhibitor.
ABPath Hematopathology Content Specifications: April 7, 2026
25.Why is severe ADAMTS13 deficiency central to TTP diagnosis?
ADAMTS13 cleaves large VWF multimers. Severe deficiency permits highly adhesive multimers to promote platelet-rich microvascular thrombosis, producing thrombocytopenia and microangiopathic hemolysis. Activity below 10% strongly supports TTP in a compatible setting. Collect a sample before plasma exchange or plasma-containing treatment, without delaying urgent care. Schistocytes demonstrate fragmentation rather than a specific cause. DIC more often produces prolonged clotting times, increased fibrin turnover and falling fibrinogen, whereas TTP often preserves routine coagulation results. Neither pattern is absolute.
Apply it
A patient has thrombocytopenia, schistocytes and neurologic changes. Obtain pretreatment ADAMTS13 and communicate urgently. Assess coagulation studies and clinical context for DIC and other microangiopathies; marked coagulopathy with sepsis favors DIC over isolated TTP.
Common pitfall: Do not await the full clinical pentad or equate every fragmentation syndrome with TTP. Inflammation can preserve fibrinogen during DIC, and plasma treatment can obscure ADAMTS13 deficiency.
British Society for Haematology: Diagnosis and Management of TTP and Thrombotic Microangiopathies
26.Why can normal PT and aPTT fail to exclude a direct oral anticoagulant?
PT and aPTT responses to direct oral anticoagulants vary with the drug, concentration and reagent. Normal results, particularly with apixaban, do not exclude clinically relevant drug levels. When quantitative assessment of a direct factor Xa inhibitor is needed, use a validated chromogenic anti-Xa assay calibrated for that drug. Interpret the concentration with the last dose, sampling time and renal function. INR is designed for vitamin K antagonist monitoring and does not quantify these agents. The [ACC consensus pathway](https://www.jacc.org/doi/10.1016/j.jacc.2020.04.053) distinguishes routine screening tests from drug-specific measurement.
Apply it
A patient taking apixaban requires urgent assessment before a procedure, but PT and aPTT are normal. Establish dose timing and request an appropriately calibrated apixaban assay when the result will inform the decision.
Common pitfall: A heparin-calibrated anti-Xa result is not automatically an apixaban concentration. Assay calibration, analytical limits and the actual clinical question determine what can be concluded.
ABPath Hematopathology Content Specifications: April 7, 2026
27.How should clinical probability guide testing for heparin-induced thrombocytopenia?
Immune HIT involves antibodies to PF4–heparin complexes that can activate platelets, producing thrombocytopenia with substantial thrombotic risk. Estimate pretest probability using the 4Ts: magnitude of platelet decline, timing, thrombosis and other causes. With reliable information, a low score of 0–3 generally argues against testing. Intermediate or high probability prompts a PF4–heparin immunoassay; a positive result generally warrants a functional platelet-activation assay when available. Binding antibodies alone do not prove platelet activation. This sequence is described in the [ASH HIT diagnostic guidance](https://www.hematology.org/-/media/hematology/files/education/clinicians/guidelines-quality/documents/watermarked-pocket-guides/watermark-ash_vte_hit_pocketguide.pdf).
Apply it
A patient develops a substantial platelet decline and new thrombosis after heparin exposure. Calculate the 4Ts and urgently communicate significant suspicion. Distinguish an immunoassay detecting PF4–heparin binding from a functional assay demonstrating platelet activation.
Common pitfall: A positive immunoassay in a patient with a low clinical probability can mislabel incidental antibodies as HIT. Reassess uncertain or missing timing and platelet-count information before relying on a low score.
ABPath Hematopathology Content Specifications: April 7, 2026
Myeloid neoplasms20% written/practical; 18% virtual microscopy
28.How are CHIP and CCUS separated from myelodysplastic neoplasia?
Under ICC, mutation-based CHIP requires a myeloid-neoplasm-associated somatic mutation with variant allele frequency at least 2%, without a defined myeloid neoplasm or otherwise unexplained cytopenia. A qualifying acquired clonal cytogenetic abnormality that does not define MDS can alternatively establish CHIP when these exclusions are satisfied. CCUS adds otherwise unexplained cytopenia persisting at least four months, with clonality but without diagnostic dysplasia, increased blasts or other findings establishing MDS or another defined myeloid neoplasm. Exclude nutritional deficiency, medications, infection, inflammation and other explanatory conditions. A qualifying mutation establishes clonality; it does not independently establish MDS. The ICC CHIP exclusion concerns a defined myeloid neoplasm and should not be broadened to every hematologic neoplasm.
Apply it
A patient has a pathogenic DNMT3A mutation at 6% VAF and normal counts: without a defined myeloid neoplasm, this supports CHIP. The same result with unexplained anemia lasting six months, no diagnostic dysplasia, no excess blasts and no defining myeloid-neoplasm genetics supports CCUS after alternative causes are excluded. If the anemia instead reflects documented iron deficiency and corrects with iron replacement, the anemia does not establish CCUS; the qualifying clone may still represent CHIP.
Common pitfall: A 1% mutation VAF does not meet the ICC mutation-based 2% threshold, and six weeks of unexplained anemia does not meet the CCUS duration requirement. Conversely, an MDS-defining abnormality must be interpreted under the applicable MDS criteria rather than classified automatically as CCUS because dysplasia is absent.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
29.How should dysplasia be integrated into an MDS diagnosis?
MDS assessment integrates persistent cytopenia with dysplasia, blast enumeration and relevant genetic findings. Significant dysplasia is generally assessed using a 10% threshold within an evaluated lineage, but selected defining genetic categories can change the diagnostic pathway. Nutritional deficiency, infection and treatment effects can mimic dysplasia. Specify the classification system and apply its complete criteria rather than using one abnormal megakaryocyte or one mutation as a diagnostic shortcut.
Apply it
A patient with persistent neutropenia has hypogranular neutrophils and abnormal nuclear segmentation. Quantify dysplasia, assess blasts and genetics, and exclude reversible mimics before deciding whether the complete findings satisfy an MDS category in the chosen classification.
Common pitfall: The dysplasia threshold concerns a lineage population, not the presence of any atypical cell. Adequate sampling and exclusion of mimics remain essential diagnostic safeguards.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
30.How do ICC and WHO differ in describing CML progression?
CML is a BCR::ABL1-associated myeloproliferative neoplasm, but progression terminology differs between classifications. ICC retains accelerated phase, including 10–19% blasts or peripheral-blood basophils of at least 20%, with additional qualifying cytogenetic criteria. WHO fifth edition does not retain accelerated phase as a formal category. State which system is being applied so that a correct observation is not paired with terminology from a different framework.
Apply it
A patient with established CML has 12% marrow blasts. Under ICC, this meets an accelerated-phase criterion; explain the classification used rather than presenting the same phase label as universally shared by WHO fifth edition.
Common pitfall: Mixing ICC phase thresholds with WHO terminology creates an internally inconsistent diagnosis even when the measured blast percentage and BCR::ABL1 result are accurate.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
31.Which findings support polycythemia vera over secondary erythrocytosis?
ICC defines the erythrocytosis major criterion as hemoglobin greater than 16.5 g/dL in men or 16.0 g/dL in women, hematocrit greater than 49% or 48%, respectively, or increased red-cell mass. Its other major criteria are JAK2 V617F or exon 12 mutation and age-adjusted marrow hypercellularity with panmyelosis. Subnormal serum erythropoietin is the minor criterion. ICC requires all three major criteria or its first two—erythrocytosis and JAK2 mutation—plus the minor criterion. Its biopsy-omission provision addresses sustained marked absolute erythrocytosis with a JAK2 mutation. Borderline erythrocytosis warrants marrow assessment rather than assuming that low erythropoietin alone establishes PV.
Apply it
A woman has hemoglobin 16.2 g/dL, hematocrit 49%, JAK2 V617F and marrow panmyelosis. Her values exceed the ICC female thresholds, and the integrated findings meet all three major criteria. Investigate possible masking by iron deficiency when red-cell measures appear less conspicuous.
Common pitfall: JAK2 V617F also occurs in other myeloproliferative neoplasms. A threshold-crossing hemoglobin, a low erythropoietin level or a mutation considered alone does not establish the complete diagnosis.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
32.How does marrow morphology distinguish ET from prefibrotic PMF?
ET predominantly expands enlarged, mature megakaryocytes with deeply hyperlobulated nuclei, without significant granulocytic or erythroid expansion. Prefibrotic PMF shows severe megakaryocytic maturation abnormalities: hyperchromatic, hypolobulated or cloud-like nuclei, abnormal nuclear-to-cytoplasmic ratios and abnormal dense clustering. Its marrow is hypercellular for age with granulocytic proliferation, often reduced erythropoiesis, and fibrosis below grade 2, meaning grade 0 or 1. Under ICC, prefibrotic PMF requires all three major criteria: this marrow pattern; JAK2, CALR or MPL mutation, another clonal marker or absence of reactive marrow fibrosis; and exclusion of BCR::ABL1-positive CML, PV, ET, MDS and other myeloid neoplasms. At least one minor criterion must also be confirmed on two consecutive determinations: otherwise unexplained anemia, leukocytosis at least 11 × 10^9/L, palpable splenomegaly or LDH above the reference range.
Apply it
Two patients have CALR-mutated thrombocytosis. Mature hyperlobulated megakaryocytes without significant granulocytic or erythroid expansion favor ET. Severe megakaryocytic nuclear abnormalities, dense clusters, granulocytic proliferation and grade 1 fibrosis favor prefibrotic PMF; after satisfying the other major criteria, leukocytosis of at least 11 × 10^9/L on two consecutive determinations supplies a qualifying minor criterion.
Common pitfall: A shared driver mutation or platelet count cannot separate these entities. Grade 0 or 1 fibrosis does not establish ET, and an isolated unconfirmed minor finding does not complete the ICC criteria for prefibrotic PMF.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
33.When does persistent monocytosis suggest CMML?
WHO requires persistent monocytes at least 0.5 × 10^9/L and at least 10% of leukocytes, fewer than 20% blood and marrow blasts including promonocytes, and exclusion of CML, other MPNs and defining tyrosine kinase fusion neoplasms. At 0.5 to less than 1.0 × 10^9/L, both marrow dysplasia affecting at least 10% of a myeloid lineage and acquired cytogenetic or molecular clonality are required. At at least 1.0 × 10^9/L, one supporting criterion suffices: dysplasia, clonality or abnormal monocyte partitioning. ICC additionally specifies cytopenia, allowing rare early exceptions, compatible marrow proliferation and clonality; a qualifying mutation has at least 10% variant allele frequency. Without demonstrated clonality, ICC requires monocytes at least 1.0 × 10^9/L plus increased blasts, dysplasia or an abnormal CMML-consistent immunophenotype.
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Persistent monocytes of 0.8 × 10^9/L comprising 14% of leukocytes meet the numerical floor. Under WHO, establish both qualifying dysplasia and acquired clonality alongside all prerequisites. Under ICC, assess its marrow, cytopenia and clonality requirements; a mutation without compatible marrow findings can instead support a precursor condition.
Common pitfall: Do not apply the older 1.0 × 10^9/L floor universally or diagnose CMML from counts alone. The WHO low-count pathway requires both supporting findings, while ICC uses a different supporting framework.
Table 6 Diagnostic criteria of chronic myelomonocytic leukaemia. | Leukemia · International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
34.Why does suspected APL require immediate targeted testing?
Acute promyelocytic leukemia is associated with PML::RARA and can present with a dangerous coagulopathy. Abnormal promyelocytes and the clinical pattern should trigger rapid communication and urgent testing capable of detecting the defining rearrangement. Routine completion of a broad leukemia panel should not delay this targeted diagnostic pathway. Morphology can raise a strong suspicion, including in less heavily granulated variants, but genetic confirmation establishes the defining lesion.
Apply it
A new leukemia specimen shows abnormal promyelocytes, and the patient has falling fibrinogen. Immediately alert the clinical team and prioritize PML::RARA testing while the broader acute leukemia workup continues in parallel with urgent clinical assessment.
Common pitfall: Waiting for all cytogenetic and sequencing results can delay an urgent diagnosis. A less granular appearance also does not reliably exclude an APL variant.
CAP: Initial Diagnostic Workup of Acute Leukemia · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
35.How does RUNX1::RUNX1T1 alter the ICC blast threshold?
Genetically defined AML categories do not all require the conventional 20% blast threshold. Under ICC, AML with RUNX1::RUNX1T1 requires at least 10% blasts in blood or marrow. The fusion therefore changes how a case with intermediate blast numbers is classified. Morphology, immunophenotype and genetics should remain concordant, and the threshold must be attributed to ICC rather than generalized to every AML entity or classification system.
Apply it
A marrow contains 14% myeloid blasts and a confirmed RUNX1::RUNX1T1 fusion. Applying ICC, classify the case within the corresponding genetically defined AML category instead of assigning MDS solely because blasts remain below 20%.
Common pitfall: A universal 20% rule misclassifies selected genetically defined leukemias. Conversely, the 10% ICC threshold should not be extended indiscriminately to every genetic abnormality.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
36.How does NPM1-mutated AML differ between ICC and WHO?
NPM1 mutation can define an AML category, but the blast requirement differs by classification. ICC requires at least 10% blasts for AML with mutated NPM1. WHO fifth edition does not impose a fixed minimum blast cutoff for this category, requiring appropriate clinicopathologic correlation. A low-blast NPM1-mutated case therefore demands explicit identification of the framework and careful confirmation of the mutation's relationship to the hematologic disease being classified.
Apply it
A cytopenic patient has an NPM1-mutated myeloid process with 8% marrow blasts. Explain why WHO and ICC categorization may differ, and document the selected classification instead of silently combining one system's name with another's threshold.
Common pitfall: The absence of a fixed WHO blast cutoff does not make an isolated sequencing result a complete diagnosis; morphology and clinical context still matter.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
37.Why do myelodysplasia-related AML categories require genetic precision?
WHO AML, myelodysplasia-related requires at least 20% blood or marrow blasts and can be established through antecedent MDS or MDS/MPN, defining cytogenetics, or mutation of ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1 or ZRSR2, after excluding higher-priority defining AML categories. Morphologic multilineage dysplasia alone is insufficient. ICC adds RUNX1 to that eight-gene list. After recurrent-genetic AML categories take precedence, the ICC hierarchy is AML with mutated TP53, then AML with myelodysplasia-related gene mutations, then AML with myelodysplasia-related cytogenetic abnormalities, then AML NOS. ICC AML with mutated TP53 requires a somatic TP53 mutation with VAF greater than 10% and either at least 20% blood or marrow blasts or fulfillment of pure erythroid leukemia criteria. The other listed residual ICC AML categories require at least 20% blasts; corresponding MDS/AML categories address 10–19%. In ICC, antecedent MDS or MDS/MPN is a diagnostic qualifier rather than an independent route into an MR category.
Apply it
A case with 25% blasts, SRSF2 mutation and a defining NPM1 mutation follows the NPM1 category first. Without a higher-priority recurrent-genetic category, a case meeting pure erythroid leukemia criteria with TP53 VAF 35% can enter ICC AML with mutated TP53 through the erythroid pathway. A TP53 mutation at 3% VAF does not meet that category's molecular threshold.
Common pitfall: Do not apply a blanket 20% conventional-blast requirement to ICC TP53-mutated AML, omit its greater-than-10% VAF requirement, import RUNX1 into the WHO eight-gene list or overlook classification hierarchy.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemias · WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms · Table 8 Cytogenetic and molecular abnormalities defining acute myeloid leukaemia, myelodysplasia-related. | Leukemia
38.Why should eosinophilia prompt a kinase-fusion differential?
Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions can produce eosinophilia and variable myeloid or lymphoid presentations. Detecting a defining fusion can change the classification even when the initial impression is an otherwise nonspecific eosinophilic myeloid disorder. Relevant rearrangements include PDGFRA, PDGFRB, FGFR1 and JAK2-associated fusions. Integrate marrow findings and targeted molecular or cytogenetic testing; eosinophilia alone neither proves clonality nor identifies a specific fusion.
Apply it
A patient has persistent eosinophilia, splenomegaly and abnormal marrow proliferation. Investigate defining kinase fusions before assigning a residual eosinophilic neoplasm category, because an identified rearrangement provides a more specific disease classification and important clinical information.
Common pitfall: The presence of eosinophilia does not establish a kinase-fusion neoplasm, and the absence of a conspicuous conventional cytogenetic abnormality does not exclude cryptic fusions.
WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms · International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
Acute leukemias of ambiguous lineage1% written/practical; 0% virtual microscopy
39.Which markers truly assign lineage in mixed-phenotype acute leukemia?
WHO B-lineage assignment requires strong CD19 plus at least one strongly expressed CD10, CD22 or CD79a, or weak CD19 plus at least two of those markers. CD79a cannot contribute when T lineage is under consideration. Strong CD19 means expression in part exceeds 50% of normal B-cell progenitor intensity; weak expression does not exceed that benchmark. T lineage requires cytoplasmic or surface CD3, using an appropriate epsilon-chain reagent, with intensity in part exceeding 50% of mature T-cell intensity by flow. Myeloid lineage requires MPO with intensity in part exceeding 50% of mature neutrophil intensity, or monocytic differentiation demonstrated by at least two of nonspecific esterase, CD11c, CD14, CD64 or lysozyme. These are intensity comparisons, not percentages of positive blasts.
Apply it
Blasts with weak CD19, strong CD10 and strong CD22 meet the WHO B-lineage combination. If the same population also meets the MPO intensity criterion, assess B/myeloid MPAL after excluding competing defining entities. CD7 and CD13 alone would not establish either lineage.
Common pitfall: Do not substitute nonspecific associated antigens for lineage criteria, use CD79a to support B lineage when T lineage is being considered, or confuse the 50% intensity benchmark with a 50%-positive-cell cutoff.
Table 13 Lineage assignment criteria for mixed-phenotype acute leukaemia. | Leukemia · International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
Lymphoid neoplasms19% written/practical; 38% virtual microscopy
40.How is a lymphoblastic neoplasm distinguished from a mature lymphoid tumor?
Establish lineage and developmental stage separately. A precursor B-cell pattern can comprise strong CD19 with CD22, cytoplasmic CD79a and CD10, absent surface immunoglobulin, and TdT with variable CD34; an ETV6::RUNX1 fusion can define the corresponding B-ALL subtype. A precursor T-cell pattern combines convincing cytoplasmic CD3 epsilon expression with CD7 and often CD2 or CD5, TdT and variable CD34; surface CD3 may be absent. NOTCH1 mutations are common supportive genetic findings in T-ALL but do not independently establish that diagnosis. Blastoid mantle cell lymphoma instead can show bright CD20, monotypic surface immunoglobulin, CD5, cyclin D1 and SOX11, with IGH::CCND1. TdT and CD34 usually support immaturity but are neither lineage markers nor universally expressed in lymphoblastic disease; occasional mature lymphomas can express TdT.
Apply it
TdT-positive, CD34-positive blasts with strong CD19, CD10, CD22, absent surface light chains and ETV6::RUNX1 support precursor B disease. TdT-positive, cytoplasmic CD3-positive, CD7-positive blasts lacking B-lineage evidence support precursor T disease. Blastoid cells with monotypic surface IgM, bright CD20, CD5, cyclin D1 and IGH::CCND1 favor mantle cell lymphoma.
Common pitfall: CD7 alone does not establish T lineage, and TdT alone does not establish a lymphoblastic neoplasm. Absent CD34 does not exclude precursor disease. Reconcile immaturity markers with lineage, surface immunoglobulin, morphology and entity-associated genetics.
WHO Fifth Edition: Lymphoid Neoplasms · International Consensus Classification of Mature Lymphoid Neoplasms · Table 13 Lineage assignment criteria for mixed-phenotype acute leukaemia. | Leukemia
41.Which integrated pattern supports CLL/SLL?
CLL/SLL typically has small mature B cells expressing CD5 and CD23 with relatively weak surface immunoglobulin and B-cell antigens. The usual iwCLL blood requirement for CLL is at least 5 × 10^9/L circulating clonal B cells sustained for at least three months. Below that threshold, a CLL-like clone without attributable adenopathy, organomegaly, cytopenias or symptoms supports MBL. Tissue-based disease with a compatible biopsy and fewer than 5 × 10^9/L circulating clonal B cells supports SLL when cytopenia from marrow infiltration is absent. Importantly, cytopenia caused by a typical marrow infiltrate can establish CLL regardless of the circulating B-cell count. These distinctions follow the [iwCLL criteria](https://doi.org/10.1182/blood-2017-09-806398).
Apply it
A patient with 3 × 10^9/L CLL-phenotype blood B cells and no attributable manifestations may have MBL. A diagnostic nodal lesion supports SLL, while anemia proven to result from a typical marrow infiltrate can establish CLL despite the same low blood count.
Common pitfall: Count clonal B cells rather than total lymphocytes. Do not apply the blood threshold without assessing tissue disease and the marrow-cytopenia exception, or assign CLL/SLL from CD5 positivity alone.
WHO Fifth Edition: Lymphoid Neoplasms · International Consensus Classification of Mature Lymphoid Neoplasms
42.How can mantle cell lymphoma be cyclin D1 negative?
Most mantle cell lymphomas have CCND1 rearrangement and cyclin D1 expression, but a minority lack this usual combination. Some cyclin D1-negative cases have CCND2 or CCND3 rearrangements and retain a compatible integrated phenotype, often including SOX11. SOX11 is supportive rather than uniquely diagnostic. When morphology and phenotype strongly suggest mantle cell lymphoma, negative cyclin D1 should prompt a reasoned alternative genetic evaluation rather than automatic exclusion.
Apply it
A small B-cell lymphoma has mantle-cell-like morphology, CD5 and SOX11 expression, but negative cyclin D1. Investigate an alternative cyclin rearrangement and assess competing entities instead of rejecting mantle cell lymphoma solely because its usual protein is absent.
Common pitfall: Cyclin D1 negativity does not exclude every mantle cell lymphoma, while SOX11 positivity alone cannot establish the diagnosis without an appropriate integrated disease pattern.
International Consensus Classification of Mature Lymphoid Neoplasms
43.How do WHO and ICC terminology affect follicular lymphoma reporting?
Follicular lymphoma requires integration of follicular architecture, germinal-center differentiation, cytology and relevant genetics. WHO fifth edition groups many conventional cases as classic follicular lymphoma and makes grading optional within that category, while using follicular large B-cell lymphoma for the former grade 3B pattern. ICC retains a grading framework. State the classification used and distinguish a germinal-center phenotype from the complete diagnosis, because reactive follicles also express germinal-center markers.
Apply it
A follicular lesion consists predominantly of large centroblasts. Review architecture and the chosen classification's terminology before reporting it, and avoid mixing WHO follicular large B-cell lymphoma terminology with an unexplained ICC grading label in one diagnosis.
Common pitfall: Germinal-center marker positivity alone does not prove follicular lymphoma, and terminology from one classification should not be silently combined with grading rules from another.
WHO Fifth Edition: Lymphoid Neoplasms · International Consensus Classification of Mature Lymphoid Neoplasms
44.Why is MYD88 L265P supportive rather than diagnostic of LPL?
MYD88 L265P is frequent in lymphoplasmacytic lymphoma and can support that diagnosis in a compatible lymphoplasmacytic marrow infiltrate. It also occurs in other B-cell conditions, and a negative result does not exclude every LPL case. An IgM paraprotein similarly has a differential diagnosis. Integrate morphology, immunophenotype, clinical findings and molecular results rather than allowing one mutation or one serum protein to replace classification of the underlying cellular proliferation.
Apply it
A marrow contains a small B-cell infiltrate with plasmacytic differentiation and MYD88 L265P. Assess the complete pattern and alternative B-cell lymphomas before diagnosing LPL; the mutation strengthens an appropriate interpretation but cannot supply missing morphologic evidence.
Common pitfall: Neither an IgM paraprotein nor MYD88 L265P is uniquely specific for LPL. Their diagnostic value depends on the accompanying tissue and clinical findings.
International Consensus Classification of Mature Lymphoid Neoplasms
45.Which findings distinguish classic hairy cell leukemia?
Classic hairy cell leukemia integrates characteristic lymphoid cytology with a phenotype commonly including CD11c, CD25, CD103 and CD123, supported by annexin A1 and frequent BRAF V600E. Related splenic B-cell disorders can share projections or selected markers without the complete pattern. Evaluate the combined evidence, including the clinical and marrow distribution. A cytoplasmic projection is a descriptive clue, while the coordinated phenotype and genetics provide stronger entity-level discrimination.
Apply it
A splenic B-cell process shows hairy cytoplasmic projections, CD25 and CD103 expression, annexin A1 positivity and BRAF V600E. The integrated findings favor classic hairy cell leukemia over a related splenic lymphoma sharing only some morphologic features.
Common pitfall: Hairy cytoplasm alone is not diagnostic. Related splenic disorders may have projections, so classification should use the full phenotype and relevant molecular evidence.
46.Why does an aggressive large B-cell lymphoma need integrated genetic assessment?
MYC and BCL2 protein coexpression does not establish rearrangements. WHO fifth edition recognizes DLBCL/high-grade B-cell lymphoma with MYC and BCL2 rearrangements, including cases with an additional BCL6 rearrangement. MYC/BCL6-only rearranged tumors instead fall under WHO DLBCL, NOS or HGBL, NOS according to morphology. ICC recognizes high-grade B-cell lymphoma with MYC and BCL2 rearrangements and a provisional high-grade B-cell lymphoma category with MYC and BCL6 rearrangements. Therefore, the actual rearrangement combination, cell morphology and named classification determine the category.
Apply it
A tumor has large-cell morphology with MYC and BCL6 rearrangements but no BCL2 rearrangement. Under WHO, classify within DLBCL, NOS when the morphology fits; under ICC, assess the provisional MYC/BCL6-rearranged HGBL category. Strong BCL2 protein expression would not supply the missing BCL2 rearrangement.
Common pitfall: Do not use dual protein expression as a synonym for dual rearrangement, or place MYC/BCL6-only cases into the WHO MYC/BCL2-defined entity.
WHO Fifth Edition: Lymphoid Neoplasms · International Consensus Classification of Mature Lymphoid Neoplasms
47.What makes a MYC-rearranged tumor Burkitt lymphoma?
Burkitt lymphoma is an integrated diagnosis combining characteristic monomorphic medium-sized cells, germinal-center differentiation, a very high proliferation fraction and an appropriate MYC-associated genetic context. A starry-sky pattern reflects abundant turnover and is not specific. MYC rearrangements also occur in other aggressive B-cell lymphomas. Assess cytology, phenotype and competing genetic categories before assigning Burkitt lymphoma; neither rapid proliferation nor MYC rearrangement alone establishes the complete entity.
Apply it
A MYC-rearranged tumor contains pleomorphic large cells and strong BCL2 expression. Reassess the aggressive B-cell lymphoma differential rather than calling Burkitt lymphoma solely because MYC is rearranged and the proliferation index is very high.
Common pitfall: A starry-sky appearance and MYC rearrangement are powerful clues but not unique identifiers. Cytologic mismatch should trigger review of competing aggressive B-cell entities.
WHO Fifth Edition: Lymphoid Neoplasms · International Consensus Classification of Mature Lymphoid Neoplasms
48.How is classical Hodgkin lymphoma recognized despite sparse tumor cells?
Classical Hodgkin lymphoma often contains relatively few neoplastic cells within a prominent inflammatory background. Diagnosis depends on recognizing the large atypical cells in their architectural context and applying an appropriate immunophenotypic panel. Strong CD30 with weak B-cell transcriptional features can support the diagnosis, but no single stain replaces the complete pattern. Sparse tumor representation helps explain why a negative routine flow cytometry result cannot independently exclude the disease.
Apply it
A node contains scattered large atypical cells in a mixed inflammatory background, while flow cytometry is unrevealing. Evaluate tissue morphology and a Hodgkin-focused immunopanel rather than allowing the negative suspension study to end the diagnostic assessment.
Common pitfall: The abundant reactive background can dominate flow cytometry and small samples. CD30 positivity also overlaps with other diseases, requiring careful identification of the atypical cells.
International Consensus Classification of Mature Lymphoid Neoplasms · Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
49.How is ALK-positive anaplastic large cell lymphoma established?
ALK-positive anaplastic large cell lymphoma combines characteristic large-cell morphology, strong CD30 expression and ALK positivity in the appropriate lymphoid setting. T-cell-associated antigen expression can be incomplete, so absence of one expected marker does not exclude the entity. ALK expression also occurs in other neoplasms, making lineage assessment essential. The diagnosis therefore rests on a coordinated morphologic and immunophenotypic pattern rather than either ALK or CD30 considered in isolation.
Apply it
A node shows large horseshoe-nucleated cells with strong diffuse CD30 and ALK expression. Establish the lymphoid context and assess competing ALK-positive tumors before diagnosing ALK-positive anaplastic large cell lymphoma from the two positive stains alone.
Common pitfall: CD30 is an activation marker expressed in several conditions, and ALK is not restricted to this lymphoma. Both require interpretation in identified tumor cells.
ASH Image Bank: ALK-Positive Anaplastic Large Cell Lymphoma, CD30 · International Consensus Classification of Mature Lymphoid Neoplasms
50.Which findings support a follicular helper T-cell lymphoma?
WHO defines a TFH phenotype by expression of at least two TFH markers in addition to CD4, interpreted in the abnormal mature T-cell population. Useful markers include PD1, ICOS, CXCL13, CD10 and BCL6. Nodal TFH lymphoma, angioimmunoblastic type shows a polymorphous infiltrate, prominent arborizing high endothelial venules and expanded follicular dendritic-cell meshworks extending beyond follicles. The follicular type has a predominantly follicular growth pattern of neoplastic TFH cells. NOS has a qualifying TFH neoplasm without the defining angioimmunoblastic or follicular architecture. Reactive TFH cells can express the same markers, so localization and morphology are essential.
Apply it
An abnormal CD4-positive population coexpresses PD1, ICOS and CXCL13 amid arborizing vessels and extrafollicular dendritic-cell expansion. The combined pattern supports the angioimmunoblastic type rather than assigning NOS merely because several TFH markers are positive.
Common pitfall: Scattered PD1-positive reactive cells do not establish a TFH lymphoma. The minimum phenotype establishes differentiation; architecture then helps determine the appropriate nodal TFH category.
WHO Fifth Edition: Lymphoid Neoplasms · International Consensus Classification of Mature Lymphoid Neoplasms
51.Why must EBV be localized to the relevant cells in an NK/T-cell lesion?
Extranodal NK/T-cell lymphoma assessment integrates a destructive cytotoxic lymphoid lesion with EBV in the neoplastic cells and an appropriate phenotype. EBV-positive bystander B cells do not supply the same evidence as viral localization to the tumor population. Necrosis and inflammation can make sampling difficult, so viable tissue and careful morphologic localization matter. Interpret EBV studies alongside cytotoxic markers, lineage findings and the anatomic presentation rather than as an isolated positive result.
Apply it
A destructive nasal lesion has extensive necrosis and scattered EBV-positive cells. Obtain or identify viable diagnostic tissue and determine whether EBV belongs to the atypical cytotoxic population before classifying the lesion as extranodal NK/T-cell lymphoma.
Common pitfall: A positive EBV study anywhere in the specimen is insufficient. Viral localization to the relevant atypical cells distinguishes meaningful entity support from incidental infected bystanders.
WHO Fifth Edition: Lymphoid Neoplasms · International Consensus Classification of Mature Lymphoid Neoplasms
Plasma cell neoplasms, paraprotein disorders & amyloidosis4% written/practical; 4% virtual microscopy
52.Which biomarkers can define active myeloma before CRAB injury?
With the required clonal plasma-cell or plasmacytoma foundation, active myeloma can be established by myeloma-defining biomarkers even without attributable CRAB organ injury. These include at least 60% clonal marrow plasma cells, an involved-to-uninvolved free light-chain ratio of at least 100 with involved light chain at least 100 mg/L, or more than one MRI focal lesion at least 5 mm. Each biomarker has specific numerical conditions that must be satisfied.
Apply it
A patient has 18% clonal marrow plasma cells, no attributable CRAB findings, a free light-chain ratio of 125 and involved light chain of 180 mg/L. The light-chain biomarker meets a myeloma-defining criterion despite absent organ injury.
Common pitfall: A ratio of at least 100 is insufficient if the involved light-chain concentration is below 100 mg/L; both parts of that biomarker must be met.
53.How are precursor plasma-cell states separated from active myeloma?
For non-IgM MGUS, serum monoclonal protein is below 30 g/L and clonal marrow plasma cells are below 10%, without attributable CRAB injury or amyloidosis. Smoldering myeloma can meet serum IgG or IgA monoclonal protein at least 30 g/L, urinary monoclonal protein at least 500 mg/24 hours and/or clonal marrow plasma cells at least 10%. Its marrow burden must remain below the myeloma-defining 60% threshold, and no other myeloma-defining event or amyloidosis may be present. Active myeloma requires the clonal foundation plus a defining biomarker or attributable CRAB event. Unrelated anemia or renal dysfunction does not supply that event.
Apply it
A patient with 12% clonal marrow plasma cells and serum monoclonal protein of 20 g/L can have smoldering myeloma despite the serum concentration being below 30 g/L, provided defining events and amyloidosis are absent. Anemia clearly caused by gastrointestinal bleeding does not independently establish active myeloma.
Common pitfall: The smoldering criteria use alternatives rather than requiring every protein and marrow threshold simultaneously. Always assess myeloma-defining biomarkers and causation of organ injury before assigning a precursor state.
54.Why must amyloid be typed despite a monoclonal protein?
Amyloid is a tissue deposition pattern that can result from different precursor proteins. A circulating monoclonal protein establishes a potential clonal source but does not prove that the deposits are immunoglobulin light chain. Demonstrating amyloid and identifying its biochemical type are separate diagnostic steps. Attribution to AL amyloidosis requires evidence linking the deposits to light chains, alongside the appropriate clinical and clonal findings, rather than assuming causation from coexistence.
Apply it
An older patient has tissue amyloid and a small monoclonal gammopathy. Pursue reliable amyloid typing before attributing organ disease to AL amyloidosis, because an incidental clone can coexist with deposits derived from a different precursor protein.
Common pitfall: A monoclonal protein is not a substitute for deposit typing. Misattributing amyloid to an incidental clone can direct the entire clinical interpretation incorrectly.
Histiocytic/dendritic cell neoplasms2% written/practical; 2% virtual microscopy
55.Which findings establish Langerhans cell differentiation?
Langerhans cell histiocytosis features lesional cells with characteristic nuclear grooves in an appropriate inflammatory background, supported by CD1a and langerin expression. Eosinophils can be conspicuous but are neither required nor specific. Diagnosis connects this cellular pattern with the clinical lesion and disease distribution. MAPK-pathway abnormalities are biologically relevant, but a shared pathway mutation alone does not distinguish LCH from every other histiocytic neoplasm or replace lineage-defining tissue findings.
Apply it
A bone lesion contains grooved histiocytic cells and eosinophils. Demonstrate CD1a and langerin in the lesional cells and correlate with imaging and clinical distribution before classifying the process and assessing its overall disease extent.
Common pitfall: Eosinophils or a BRAF-pathway mutation alone cannot establish LCH. The diagnostic population must show appropriate morphology and convincing evidence of Langerhans cell differentiation.
56.How is histiocytic sarcoma separated from its mimics?
Histiocytic sarcoma requires malignant morphology with convincing histiocytic differentiation and exclusion of competing lineages. Large pleomorphic cells can resemble carcinoma, melanoma, lymphoma or other dendritic-cell neoplasms. Histiocytic markers such as CD163 and lysozyme are interpreted as a panel rather than as individually decisive stains. Demonstrating that the atypical cells themselves express the relevant markers is essential, because abundant reactive macrophages can otherwise create a misleading immunohistochemical impression.
Apply it
A pleomorphic nodal tumor has many macrophages and apparent CD163 staining. Determine whether staining belongs to the malignant cells, then apply epithelial, melanocytic and lymphoid exclusions before diagnosing histiocytic sarcoma from a macrophage-rich specimen.
Common pitfall: Reactive macrophages can dominate a stain without defining the tumor's lineage. A positive histiocytic marker must be localized to the malignant population itself.
WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
Metastatic neoplasms1% written/practical; 2% virtual microscopy
57.How should a possible metastatic tumor in marrow be approached?
Marrow involvement by a nonhematopoietic tumor can mimic a hematologic malignancy when cells are dispersed, poorly differentiated or associated with fibrosis. Begin with morphology and a broad lineage differential, then use targeted immunohistochemistry to distinguish epithelial, melanocytic and hematolymphoid possibilities. Clinical history helps select subsequent organ-associated studies but should not predetermine the result. A lineage panel is especially valuable before interpreting a cytokeratin-positive population as an unusual lymphoma or leukemia.
Apply it
A marrow biopsy shows cohesive atypical cells in a fibrotic background. Test the competing epithelial and hematolymphoid hypotheses, then use clinical history and organ-associated markers to characterize a supported metastatic lineage rather than ordering an undirected exhaustive panel.
Common pitfall: A history of lymphoma can anchor interpretation of every later marrow lesion. The current cells may represent a second malignancy requiring independent lineage assessment.
ABPath Hematopathology Content Specifications: April 7, 2026 · Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
Administration/Laboratory Management-Hematology2% written/practical; 0% virtual microscopy
58.How should specimen inadequacy be handled in a lymphoma service?
A quality system should distinguish an adequate negative examination from a specimen that cannot answer the clinical question. Tissue quantity, architecture, viability and the suspected entity determine adequacy. When persistent suspicion exceeds the evidence available from a limited biopsy, communicate the limitation and coordinate additional sampling. Reviewing recurrent inadequacy patterns can identify correctable problems in collection, transport or triage and improve the service beyond an individual case.
Apply it
Several suspected lymphoma biopsies arrive as tiny fixed fragments unsuitable for architecture and flow studies. Review the collection pathway with the procedural team and establish a triage plan that preserves diagnostically useful tissue for future patients.
Common pitfall: Reporting only no abnormal population can imply adequate exclusion when the specimen was limited. Quality assessment must address the diagnostic question and sampling limitations.
Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
59.What should follow an analytical quality-control failure?
An out-of-control analytical system requires containment, investigation, correction and verification. Hold affected patient results and identify the interval since acceptable performance was last demonstrated. Review control preparation and stability, reagent lots, calibration, instrument maintenance and comparison data. Correct the demonstrated cause, then verify acceptable control and patient-sample performance before resuming reporting. Assess previously released results for possible impact and communicate corrections when indicated. Document responsibility and monitor subsequent control trends and recurrence to establish effectiveness. This operational approach follows [WHO laboratory quality guidance](https://extranet.who.int/lqsi/content/monitor-and-investigate-failure-internal-controls-and-improve-accordingly).
Apply it
Platelet controls at multiple levels develop a sustained negative shift after a reagent-lot change. Hold affected results, compare the suspect lot with a verified alternative using controls and patient samples, and investigate calibration and instrument factors. After resolving the cause, review potentially affected reports and monitor for recurrence.
Common pitfall: Repeatedly measuring the same control until one result passes does not explain a systematic shift. A corrective action is incomplete until restored performance and continuing effectiveness are demonstrated.
ABPath Hematopathology Content Specifications: April 7, 2026
Professionalism, practice-based learning and improvement, interpersonal and communication skills, systems-based practice1% written/practical; 0% virtual microscopy
60.How should an acute leukemia diagnosis be handed off between institutions?
Continuity of acute leukemia diagnosis requires transfer of the available report, relevant diagnostic materials and information about pending studies. The receiving team needs to know which findings are established, which are provisional and which results may change classification. Urgent concerns such as suspected APL require direct timely communication. A complete handoff reduces unnecessary repeat procedures and prevents important molecular or cytogenetic results from becoming disconnected from the patient's ongoing care.
Apply it
A patient transfers before leukemia genetics are complete. Send the available diagnostic findings and materials, identify pending studies and arrange transmission of final results, while directly communicating any urgent concern that could affect immediate care.
Common pitfall: Sending only a provisional diagnosis leaves the receiving team unaware of pending classification-changing tests. A handoff is incomplete until responsibility for communicating those results is clear.
What to focus on during revision
The following are CertMedbry study suggestions. Use the official outline to check the full scope of your examination.
- Connect smear and tissue morphology with phenotype and genetics; identify the single finding that changes the differential or classification.
- Give myeloid and lymphoid neoplasms sustained attention, with additional virtual-slide practice for lymphoid architecture and sparse-cell lesions.
- Maintain separate WHO fifth-edition and ICC 2022 comparison notes for blast thresholds, CML progression, AML category hierarchy and lymphoma terminology.
- Practise anemia differentials, normal coagulation and fibrinolysis, VWF interpretation, factor deficiency versus inhibitor assessment, anticoagulant measurement, HIT testing and ADAMTS13 sampling.
- Review all smaller blueprint domains, including fluids, inherited abnormalities, marrow infections, metastatic tumors, analytical quality failures and diagnostic handoffs.
A practical preparation plan
1. Map preparation to both official blueprint columns
Use the complete 2026 blueprint and final April 7 specifications to build a topic inventory. Track written/practical and virtual microscopy preparation separately because their emphases differ substantially.
2. Build integrated diagnostic comparisons
For each major differential, record morphology, key phenotype, defining genetics and exclusion criteria. Include reactive mimics and identify which additional test would actually separate the competing diagnoses.
3. Practise microscopy with a fixed reporting sequence
Describe the dominant cells and architecture, identify abnormal populations, propose a focused differential and select confirmatory tests. Include blood, marrow, lymph nodes, fluids and metastatic lesions.
4. Rehearse classification and laboratory decisions
Work through blast thresholds, low-count CMML, VWF ratios, mixing studies, plasma-cell biomarkers and analytical quality failures. State units, classification system and attribution requirements whenever they influence the conclusion.
5. Use errors to direct the next review
Complete the independent questions before reading explanations. For each error, identify whether the problem was recognition, mechanism, classification, calculation or specimen limitation, then revisit the corresponding official topic and an appropriate primary reference.
Use your sample score as a starting point
The free set contains 20 original practice questions. It is a small learning sample, not an official examination or a validated pass prediction. Review each explanation and its source before moving to another topic.
Start the free sampleOfficial sources and updates
- ABPath: Hematopathology Exam Description
- ABPath: Content Specifications for Examinations
- ABPath Hematopathology Exam Blueprint: Updated for 2026
- ABPath Hematopathology Content Specifications: April 7, 2026
- International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
- International Consensus Classification of Mature Lymphoid Neoplasms
- WHO Fifth Edition: Myeloid and Histiocytic/Dendritic Neoplasms
- WHO Fifth Edition: Lymphoid Neoplasms
- CAP: Laboratory Workup of Lymphoma in Adults
- Laboratory Workup of Lymphoma in Adults: Summary of Recommendations
- CAP: Initial Diagnostic Workup of Acute Leukemia
- ASH Image Bank: PNH Flow Cytometry
- MedlinePlus Genetics: Beta Thalassemia
- NIDDK: Anemia of Inflammation or Chronic Disease
- British Society for Haematology: Diagnosis and Management of TTP and Thrombotic Microangiopathies
- ASH ISTH NHF WFH Guidelines on VWD Diagnosis: Executive Summary
- CDC DPDx: Babesiosis
- International Myeloma Working Group: Diagnostic Criteria
- ASH Image Bank: Emperipolesis in Rosai-Dorfman Disease
- ASH Image Bank: ALK-Positive Anaplastic Large Cell Lymphoma, CD30
- NCI PDQ: Langerhans Cell Histiocytosis
- MedlinePlus Genetics: Alpha Thalassemia
- MedlinePlus Genetics: MYH9-Related Disorder
- ASH Image Bank: Giant Pronormoblast in Parvovirus B19 Infection
- Table 6 Diagnostic criteria of chronic myelomonocytic leukaemia. | Leukemia
- Table 8 Cytogenetic and molecular abnormalities defining acute myeloid leukaemia, myelodysplasia-related. | Leukemia
- Table 13 Lineage assignment criteria for mixed-phenotype acute leukaemia. | Leukemia
- International Clinical Cytometry Society
- HLH_ASH_GUIDE.pdf
- The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms | Leukemia
- International recommendations on the diagnosis and treatment of acquired hemophilia A | Haematologica
- 2020-acc-expert-consensus-decision-pathway-on-management-of-bleeding-in-patients-on-oral-anticoagulants.pdf
- watermark-ash_vte_hit_pocketguide.pdf
- Laboratory Quality Stepwise Implementation tool
- iwCLL.pdf
- blood746933.pdf
- Erythroid Precursors
- Myelocyte
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