Hematology Quiz on Megakaryocytes and JAK2 Pathway

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Questions and Answers

What mutation is commonly associated with adult cutaneous mastocytosis?

KIT p.D816A mutation in exon 16

KIT p.D816V mutation in exon 17 (correct)

KIT p.D816V mutation in exon 18

KIT p.F822L mutation in exon 17

Which subtype of cutaneous mastocytosis is mostly seen in adults?

Monomorphic MPCM (correct)

Mastocytoma

Polymorphic MPCM

Diffuse cutaneous mastocytosis

What are the clinical features of Diffuse Cutaneous Mastocytosis (DCM)?

Generalized erythroderma and thickened skin (correct)

Small localized lesions and wheals

Pigmented macules and plaques

Erythematous papules on the trunk

Which common clinical feature is associated with Mastocytoma?

Blisters upon rubbing Signup and view all the answers

Which is NOT a desirable diagnostic criterion for cutaneous mastocytosis?

Presence of systemic mastocytosis signs Signup and view all the answers

What is a common characteristic of Polymorphic MPCM?

Brown, yellow, or pale red lesions of varying types Signup and view all the answers

What is a distinguishing feature of mastocytosis in children?

Higher percentage of D816V mutations Signup and view all the answers

What is the primary treatment for relapsed Hodgkin lymphoma and ALCL?

Brentoximab Signup and view all the answers

What signifies a lack of dysplastic features in bone marrow evaluation?

Megakaryocytic hyperplasia Signup and view all the answers

What characteristic feature is commonly associated with Rosai-Dorfman disease?

Abundant plasma cells in the background Signup and view all the answers

Which germline mutation is associated with H syndrome?

SLC29A3 mutation Signup and view all the answers

In classic (nodal) Rosai-Dorfman disease, which lymph nodes are most commonly involved?

Cervical lymph nodes Signup and view all the answers

What is a feature of immune-related Rosai-Dorfman disease?

Association with autoimmune conditions like SLE Signup and view all the answers

Which subtype of Rosai-Dorfman disease is linked to family history?

Familial RDD Signup and view all the answers

What immunostaining profile is indicative of ALK-positive histiocytosis?

Positive for two or more histiocytic markers Signup and view all the answers

Which histiocytic marker is least likely to be expressed in ALK-positive histiocytosis?

CD1a Signup and view all the answers

Which of the following is NOT associated with the classic (nodal) Rosai-Dorfman disease?

Extranodal involvement Signup and view all the answers

In what form of Rosai-Dorfman disease is splenic involvement most frequently seen?

Extranodal RDD Signup and view all the answers

What histological feature is characterized by the presence of histiocytes with foamy cytoplasm in ALK-positive histiocytosis?

Variable positivity for histiocytic markers Signup and view all the answers

What is a major criterion for diagnosing prefibrotic primary myelofibrosis?

Megakaryocytic proliferation and atypia Signup and view all the answers

Which marker is commonly associated with juvenile myelomonocytic leukemia?

CD7 Signup and view all the answers

What does a major criterion for myelofibrosis entail in terms of fibrosis grades?

Grade 2 or 3 reticulin and/or collagen fibrosis Signup and view all the answers

Which of the following mutations is associated with a more aggressive course in JMML?

PTPN11 Signup and view all the answers

In the context of primary myelofibrosis, what does a complex karyotype indicate?

Unfavorable prognosis Signup and view all the answers

What classification does juvenile myelomonocytic leukemia fall under?

Myeloproliferative neoplasm Signup and view all the answers

Which of the following describes the presentation of NF1?

Neurofibromas and café-au-lait spots Signup and view all the answers

What is a minor criterion for diagnosing primary myelofibrosis?

Exclusion of reactive processes Signup and view all the answers

Which of the following is a poor prognostic factor associated with juvenile myelomonocytic leukemia?

Older age (> 2 years) Signup and view all the answers

What role does neurofibromin-1 play in relation to GTPases?

Negative modulator of GTPase activity Signup and view all the answers

What is the major feature indicating leukoerythroblastosis?

Immature myeloid cells in blood Signup and view all the answers

What is required for the diagnosis of myeloproliferative neoplasm NOS?

Presence of features indicating myeloproliferative neoplasm Signup and view all the answers

Which factor significantly contributes to the prognosis of patients with myelofibrosis?

Degree of reticulin fibrosis Signup and view all the answers

What is a common associated feature of patients with B-ALL/LBL with BCR::ABL1 fusion?

Deletion or splicing abnormalities of IKZF1 Signup and view all the answers

Which immunophenotype is typically observed in KMT2A rearranged cases of B-ALL/LBL?

CD19+ and CD10− Signup and view all the answers

What is the prognosis associated with ETV6::RUNX1 fusion in B-ALL/LBL?

Favorable prognosis Signup and view all the answers

Which genetic alteration is linked to a poor prognosis in B-ALL/LBL?

Del(17p) Signup and view all the answers

Which marker is consistently positive in cases with DUX4 rearrangement in B-ALL/LBL?

CD2 Signup and view all the answers

What is an unfavorable characteristic of B-lymphoblastic leukemia with TCF3::PBX1 fusion?

Bright CD9 expression Signup and view all the answers

In patients with CRLF2 rearrangements, what is their typical response to gleevac?

Poor response Signup and view all the answers

Which of the following is indicative of poor prognosis in monoclonal B-cell lymphocytosis?

Del(17p) Signup and view all the answers

Which rearrangement in B-ALL/LBL is known for its benign disposition?

NUTM1 rearrangement Signup and view all the answers

What is a key immunophenotypic feature of B-lymphoblastic leukemia with ETV6::RUNX1-like features?

CD27-positive, CD44-low-to-negative Signup and view all the answers

Which condition is characterized by hypercalcemia and coagulopathy?

B-lymphoblastic leukemia with TCF3::HLF fusion Signup and view all the answers

Which marker is often associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL)?

Zap-70 Signup and view all the answers

What is a common feature associated with patients showing monocytic differentiation in B-ALL/LBL?

Loss of B-cell antigens Signup and view all the answers

What chromosomal abnormality is frequently seen in cases of marginal zone lymphoma?

t(14;18) Signup and view all the answers

What is a major criterion for diagnosing systemic mastocytosis?

Multifocal dense infiltrates of mast cells in the bone marrow Signup and view all the answers

Which antigen expressions are considered aberrant in systemic mastocytosis?

CD2, CD25, CD30 Signup and view all the answers

In well-differentiated systemic mastocytosis, which is a common finding?

CD25+ and CD2−/low markers Signup and view all the answers

Which finding is true for the subtype ASM (Accelerated Systemic Mastocytosis)?

Often has the KIT p.D816V mutation present Signup and view all the answers

Which finding would suggest a diagnosis of systemic mastocytosis in the context of serum tryptase levels?

Baseline serum tryptase concentration of > 20 ng/mL Signup and view all the answers

What morphological feature is observed in the bone marrow for systemic mastocytosis diagnosis?

Atypical mast cell morphology greater than 25% Signup and view all the answers

In bone marrow smears for systemic mastocytosis, what percentage of mast cells should be observed?

At least 5% Signup and view all the answers

Which mutation is commonly associated with systemic mastocytosis?

KIT p.D816V mutation Signup and view all the answers

What is an expected finding in bone marrow for well-differentiated mastocytosis?

Presence of dense fibrotic stroma Signup and view all the answers

Which of the following indicates a more aggressive form of systemic mastocytosis?

High tryptase levels with organomegaly Signup and view all the answers

In systemic mastocytosis, what does a diagnosis of BMM (Bone Marrow Mastocytosis) typically involve?

No evidence of skin involvement and low mast cell burden Signup and view all the answers

Which statement is true regarding the findings in ASM?

Skins lesions are frequently observed Signup and view all the answers

How is the SF3B1 mutation detected in systemic mastocytosis cases?

By observing ring sideroblasts Signup and view all the answers

What is considered a diagnostic feature of the ASM subtype?

Increased burden of mast cells in the bone marrow Signup and view all the answers

Study Notes

Platelet Count and Bone Marrow Findings

Platelet count of ≥ 450 × 10^9/L can indicate a myeloproliferative neoplasm.
Bone marrow biopsy shows proliferation of megakaryocytes, characterized by enlarged, mature forms with hyperlobulated nuclei.
No significant increase or left shift in neutrophil granulopoiesis or erythropoiesis; minimal increase in reticulin fibers is sometimes observed.
WHO criteria for conditions like BCR-ABL1-positive CML, polycythemia vera (PV), primary myelofibrosis (PMF), and other myeloid neoplasms are not met.
Presence of mutations in JAK2, CALR, or MPL is indicative of myeloproliferative neoplasms.

Minor Criteria for Diagnosis

Clonal markers must be present to support a diagnosis.
Reactive conditions must be excluded.

Primary Myelofibrosis (PMF)

Unfavorable karyotype features include complex karyotype, inv(3), monosomy 5, del(5q), monosomy 7, del(7q), and others.
Prefibrotic PMF requires three major criteria and at least one minor criterion from two consecutive biopsies.

Major and Minor Criteria for PMF

Major criteria include megakaryocytic proliferation and atypia with reticulin/collagen fibrosis graded 2 or 3.
Minor criteria may include leukoerythroblastosis.

Fibrosis Grades in PMF

MF-0: Normal reticulin with no intersections; normal collagen.
MF-1: Loose reticulin network with focal collagen deposition.
MF-2: Dense reticulin with extensive intersections and occasional osteosclerosis.
MF-3: Dense reticulin with coarse bundles of collagen, causing osteosclerosis and effacement of marrow spaces.

Juvenile Myelomonocytic Leukemia (JMML)

Splenomegaly present in approximately 90% of cases at diagnosis.
Commonly associated with thrombocytopenia.
Aberrant blast populations display specific surface markers (CD7, reduced CD13/CD33).
Poor prognosis linked to age over 2 years, low platelet counts, high hemoglobin F levels, or LIN28B overexpression.
Around 25% of cases involve germline mutations, with PTPN11 or KRAS mutations leading to aggressive disease presentation.

Associated Syndromes

Neurofibromatosis Type 1 (NF1): Characterized by xanthomas and café-au-lait spots.
Noonan Syndrome: Features facial dysmorphia, congenital heart defects, and a possible link to JMML through PTPN11 mutations.
CBL: Linked to autoimmune conditions and Noonan syndrome-like disorders.

Clinical and Genetic Criteria for JMML

All clinical, hematological, and laboratory criteria must be met alongside at least one genetic marker from the RAS pathway (e.g., PTPN11, KRAS mutations).
Absence of significant monocytosis and eosinophilia required for diagnosis.

Myeloproliferative Neoplasm NOS

Diagnosis requires all three criteria suggesting MPN features, without significant monocytosis or eosinophilia.
Bone marrow hypercellularity must occur without dysplastic features.

Mastocytosis

Cutaneous Mastocytosis:
- Adults primarily exhibit KIT p.D816V mutation, while children may have various KIT mutations or be wild-type.
- Subtypes include maculopapular cutaneous mastocytosis and diffuse cutaneous mastocytosis, each with distinct clinical features.
Systemic Mastocytosis:
- Requires multifocal mast cell infiltrates and specific minor criteria for diagnosis, including aberrant expression of CD2, CD25, and CD30, along with elevated serum tryptase levels.

Diagnostic Considerations

Essential criteria: specific cutaneous lesions and skin biopsies showing increased mast cells.
Desirable criteria include aberrant mast cell immunophenotype and detection of KIT mutations in lesions.

Differential Diagnostic Features

Subtype variants in systemic mastocytosis based on morphologic and diagnostic criteria differentiate between well-differentiated and aggressive presentations, including extensive mast cell involvement and elevated tryptase levels.### Rosai-Dorfman Disease
Characterized by large histiocytes with round nuclei, prominent nucleoli, and abundant pale cytoplasm; often exhibits emperipolesis.
Background contains abundant plasma cells; S100 immunostaining highlights emperipolesis.
In cases that are difficult to diagnose, expression of OCT2 and cyclin D1 may be present without CD1a, CD207 (Langerin), or ALK.
Associated with germline mutations in SLC29A3 (H syndrome/Faisalabad histiocytosis) and heterozygous mutations in FAS (TNFRSF6) leading to autoimmune lymphoproliferative syndrome.

Subtypes of Rosai-Dorfman Disease

Classic (nodal) RDD: Most common; primarily involves cervical (>87%), inguinal (26%), axillary (24%), and mediastinal (15%) lymph nodes.
Extranodal RDD: Affects 43% of patients, primarily in the nasal cavity, sinuses, salivary glands, skin, soft tissue, upper respiratory tract, bone, retro-orbital tissue, and CNS; rare splenic involvement.
Familial RDD: Linked to germline mutations in SLC29A3 (20%) and FAS (41%).
Neoplasia-related RDD: Associated with lymphoma, leukemia, and other histiocytoses like Langerhans cell histiocytosis.
Immune-related RDD: Associated with systemic lupus erythematosus (SLE), juvenile arthritis, autoimmune hemolytic anemia, and HIV, often showing increased IgG4+ plasma cells.

ALK-Positive Histiocytosis

Identified by tissue infiltration of histiocyte aggregates lacking high-grade atypia.
Positive for multiple histiocytic markers (CD163, CD68, CD14, CD4, lysozyme).
Histiocytes demonstrate ALK positivity (cytoplasmic pattern), rarely nuclear patterns.
Associated chromosomal abnormalities include the Philadelphia chromosome and various monosomies and trisomies.

B-lymphoblastic Leukemia/Lymphoma Classes

BCR::ABL1-like Features: 50% have rearrangements of CRLF2 linked with poor response to treatment.
KMT2A Rearrangement: Linked to unfavorable prognosis; typically shows distinct immunophenotype.
ETV6::RUNX1 Fusion: Most common and favorable; frequent expression of myeloid-associated antigens.
TCF3 rearrangements: Several defined variants with diverse prognoses, including TCF3::PBX1 and TCF3::HLF fusions linked to aggressive clinical presentations.
Other Genetic Alterations: Various subtypes with unique genetic features and differential prognoses, e.g., DUX4 with monocytic differentiation and potentially better outcomes.

Preneoplastic and Neoplastic Small Lymphocytic Proliferations

Monoclonal B-cell Lymphocytosis: Defined by absolute monoclonal B cell count; identified by specific immunophenotypes and associated genetic alterations.
Richter Transformation: Can lead to transformation into DLBCL or classic Hodgkin lymphoma; must differentiate from reversible transformation linked to ibrutinib treatment.
Genetics at Transformation: Often involves complex karyotype, del(17p), or MYC rearrangement.

Marginal Zone Lymphoma

Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT): Displays features resembling Peyer’s patch lymphoid tissue, highlighting its origin from mucosal-associated lymphoid tissue.

Prognostic Indicators in CLL

Genetic factors play a significant role, with del(13q) indicating good prognosis, while del(17p) and certain mutations signal poor outcomes.
Prognostic variables include CD38 and Zap 70 levels, reflecting underlying genetic profiles in chronic lymphocytic leukemia outcomes.

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Description

Test your knowledge on platelet counts and bone marrow findings related to megakaryocytes. This quiz covers the criteria for various myeloid neoplasms including CML, PV, and PMF, along with the significance of JAK2 mutations. Prepare to dive deep into hematological concepts and determine your understanding of these critical components.