Sandbox:Hannan

Myeloproliferative neoplasms (MPN)	Clinical manifestations		Diagnosis												Other features
	Symptoms	Physical examination	CBC & Peripheral smear									Bone marrow biopsy	Gold standard	Other investigations
			WBCs							RBCs	Platelets
			Leukocytosis	Blasts	Left shift	Basophilia	Eosinophilia	Monocytosis	Others
Chronic myeloid leukemia (CML), BCR-ABL1+	Asymptomatic Constitutional symptoms Hyperviscosity and/or anemia related Bleeding Infection	Splenomegaly (46–76%) Purpura Anemia related Priapism	Absolute leukocytosis (median of 100,000/µL)	Usually <2% but may present with blast crisis	Left shift with classic myelocyte bulge (myelocytes > metamyelocytes on the blood smear)	Absolute basophilia is almost always present	Absolute eosinophilia in 90% of patients	Often present		Anemia	Platelet count is usually normal or elevated but thrombocytopenia indicates advanced stage or an alternative diagnosis	Hypercellurarity with ↑ granuloscytosis and ↓ erythrocytosis Fibrosis	Marrow aspirate & unilateral biopsy with cytogenetics and flow cytometry	FISH for t(9;22)(q34;q11.2) Reverse transcriptase quantitative PCR (RQ-PCR) for BCR-ABL	Granulocytic dysplasia is minimal/absent
Chronic neutrophilic leukemia (CNL)	Asymptomatic Constitutional symptoms Bleeding Infection	Splenomegaly Heptomegaly Purpura Anemia related	Leukocytosis with chronic neutrophilia	Minimal to none	Significantly less than that of CML	Absent	Absent	Absent	↑ Lactate dehydrogenase (LDH) ↑ Vitamin B12 levels	Anemia	Thrombocytopenia	Uniforme and intense hypercellularity with minimal to none fibrosis Neutrophil toxic granulations and Dohle bodies		FISH Imaging for hepatosplenomegaly	Associationed with polycythemia vera and plasma cell disorders
Polycythemia vera (PV)	Constitutional Thromboembolism and bleeding Pruritus after a warm bath PUD related	Facial ruddiness Related to underlying cause Splenomegaly Renal bruit	Normal to mild	None	None	May be present	May be present	Usually absent	↓ Serum ferritin ↓ Folate levels ↑↑B12 levels	↑↑ Hb and Hct levels (> 16 and 48%)	None to moderate	Hypercellularity for age with tri-lineage growth Myelofibrosis (in up to 20% of patients)	JAK2 mutation studies are diagnostic in 95% of patients	Radioisotope studies Serum EPO levels LFTs RFTs Imaging studies	May transform into myelofibrosis or leukemia
Primary myelofibrosis (PMF)	Constitutional Anemia related Bleeding Infection Abdominal Pain	Hepatosplenomegaly Petechiae & ecchymoses Abdominal distension Lymphadenopathy	Variable with leukocytosis or leukopenia	Erythroblasts may be seen	None	Abset	Absent	Absent	↑ LAP ↑ LAD ↑ uric acid ↑ vitamin B12	Normochromic normocytic anemia	Thrombocytopenia	Variable with fibrosis or hypercellularity	WHO diagnostic criteria for primary myelofibrosis	JAK2 mutation CALR mutation MPL mutation	Bone marrow aspiration shows a dry tap
Essential thrombocythemia (ET)	Headache Dizziness Visual disturbances Priapism Acute chest pain	Splenomegaly Skin bruises	None/may be	None	None	decreased or absent basophils	None	None	None	Normocytic, normochrmoic	Marked thrombocytosis	Normal/Hypercellular	WHO diagnostic criteria for essential thrombocythemia	JAK2 mutation CALR mutation MPL mutation	Thrombosis Hemorrhage Pregnancy loss
Chronic eosinophilic leukemia, not otherwise specified (NOS)	Constitutional Rash Rhinitis Gastritis Thromboembolism related	Hypertension Eczema, mucosal ulcers, erythema Angioedema Ataxia Anemia Lymphadenopathy hepatosplenomegaly	Leukocytosis	Present	Present	Mild basophilia	Severe eosinophilia	Mildly increased monocytes	↑ B12 levels ↑ LDH	Anemia	Thrombocytopenia	Hypercelluar with ↑ eosinophilic precursors, ↑ eosinophils, and atypical mononuclear cells	Biopsy combined with peripheral eosinophilia and absence of Philadelphia chromosome	FISH Cytogenetic analysis of purified eosinophils and X-chromosome inactivation analysis	Heart failure Lung fibrosis Encephalopathy Erythema annulare centrifugam
MPN, unclassifiable	Similar to other myeloproliferative neoplasms	Similar to other myeloproliferative neoplasms	Leukocytosis	Variable	Variable	Variable	Variable	Variable	May resemble other myeloproliferative neoplasms	Variable	Thrombocytosis in most cases	↑ megakaryocyte proliferation with variable hypercellularity in granulocytic or erythrocytic cell lines	None		Similar to other myeloprolifeartive neoplasms but do not fulfil the criteria to be classified to a specific type
Mastocytosis	Constitutional Pruritus & Flushing Urticaria & Blisters Hypotension & PUD Bleeding Bronchoconstriction	Mastocytosis exanthema Blistering Swelling Lymphadenopathy Bleeding Fibrosis	Leukocytosis	None	None		Eosinophilia		↑ Alkaline phosphatase ↑ LDH	Anemia	Thrombocytopenia or thrombocytosis	Multifocal dense infiltrates of mast cells with atypical morphology in >25 %	Bone marrow or lesional (Cutaneous mastocytosis) biopsyand histopathological studies	Cytogenetic analysis for c-KIT receptor mutations Serum tryptase levels 24-hour urine test for N-methyl histamine and 11-beta-prostaglandine	Skin most commonly involved Susceptibility to anaphylaxix Osteoporosis

Myeloproliferative neoplasms (MPN)		Clinical manifestations		Diagnosis												Other features
		Symptoms	Physical examination	CBC & Peripheral smear									Bone marrow biopsy	Gold standard	Other investigations
				WBCs							RBCs	Platelets
				Leukocytosis	Blasts	Left shift	Basophilia	Eosinophilia	Monocytosis	Others
Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 Myeloid/lymphoid neoplasms with PDGFRA rearrangement Myeloid/lymphoid neoplasms with PDGFRB rearrangement Myeloid/lymphoid neoplasms with FGFR1 rearrangement Provisional entity: Myeloid/lymphoid neoplasms with PCM1-JAK		Asymptomatic Constitutional Rash Cough & breathlessness Peripheral neuropathy/encephalopathy														May present or evolve into acute myeloid or lymphoblastic leukemia
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)	Chronic myelomonocytic leukemia (CMML)	Constitutional Anemia related Bleeding Infections Bone pain Leukemia Cutis	Organomegaly Bruising	MD-CMML: WBC ≤ 13 × 109/L  MP-CMML: WBC > 13 × 109/L (FAB)	< 20% blasts			Eosinophilia	Absolute monocytosis > 1 × 109/L (defining feature)	↑ LDH	Anemia	Thrombocytopenia	Myelodysplastic and myeloproliferative feature	Exclusion of distinctive rearrangements and translocation i.e; Ph chromosome and presence of monocytosis	Cytogenetic analysis Flow cytometry	Overlapping of both, MDS and MPN
	Atypical chronic myeloid leukemia (aCML), BCR-ABL1-	Similar to chronic myeloid leukemia	Similar to chronic myeloid leukemia	WBC > 13 × 109/L	<20% myeloblats	Present	<2% of leukocytes				Anemia	Thrombocytopenia	Granulocytic hyperplasia with prominent dysplasia		Cytogenetic analysis Flow cytometry	Granulocytic dysplasia is prominent Absence of BCR-ABL or PDGFRA, PDGFRB, or FGFR1 rearrangements
	Juvenile myelomonocytic leukemia (JMML)	Infections Anemia related	Hepatosplenomegaly Lymphadenopathy Rash	Leukocytosis	Present				Monocytosis	↓Serum Iron ↑vitamin B12	Anemia	Thrombocytopenia	Hypercelluar with ↑ myeloid cells in stages of maturation		Cytogenetic analysis Flow cytometry	Polyclonal hypergammaglobulinemia
	MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)	Constitutional Anemia related Thrombosis	Variable	Variable	None or minimal	None	None or minimal absolute basophilia			↑Serum Iron	Anemia	Thrombocytosis	Hypercellularity with dyserythropoiesis and increased megakaryocytes		Cytogenetic analysis Flow cytometry	Large atypical megakaryocytes Ringed sideroblasts SF3B1 mutation
	MDS/MPN, unclassifiable
Myelodysplastic syndromes (MDS)		Constitutional Anemia related Bleeding Infection	Pallor Petechiae Organomegaly	Leukopenia	None	None	Decreased	Decreased	Decreased	Macro-ovalocytes Basophilic stippling Howell-Jolly body Acquired or pseudo-Pelger-Huët anomaly	Anemia	Thrombocytosis	Hypercellular / normocellular bone marrow with dysplastic changes		Cytogenetic analysis Flow cytometry	Leukemia transformation
Acute myeloid leukemia (AML) and related neoplasms AML with recurrent genetic abnormalities AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1 AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11 APL with PML-RARA AML with t(9;11)(p21.3;q23.3);MLLT3-KMT2A AML with t(6;9)(p23;q34.1);DEK-NUP214 AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2, MECOM AML (megakaryoblastic) with t(1;22)(p13.3;q13.3);RBM15-MKL1 Provisional entity: AML with BCR-ABL1 AML with mutated NPM1 AML with biallelic mutations of CEBPA Provisional entity: AML with mutated RUNX1 AML with myelodysplasia-related changes Therapy-related myeloid neoplasms AML, NOS AML with minimal differentiation AML without maturation AML with maturation Acute myelomonocytic leukemia Acute monoblastic/monocytic leukemia Pure erythroid leukemia Acute megakaryoblastic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis Myeloid sarcoma Myeloid proliferations related to Down syndrome Transient abnormal myelopoiesis (TAM) Myeloid leukemia associated with Down syndrome
Blastic plasmacytoid dendritic cell neoplasm
B-lymphoblastic leukemia/lymphoma		Constitutional Anemia related Bleeding Infection Bone pain	Pallor Petechiae Organomegaly Lymphadenopathy	Variable	>25% blasts		Variable	Variable	Variable	Auer bodies	Anemia	Thrombocytopenia	Hypercellular with blast infilteration with or without myelodysplasia	Bone marrow aspiration and biopsy	Cytogenetic analysis Flow cytometry FISH	May present as extramedullary disease (Myeloid sarcoma)
T-lymphoblastic leukemia/lymphoma	T-lymphoblastic leukemia/lymphoma	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	Variable, often leukocytosis	>25% blasts (Leukemia) <25% blasts (Lymphoma)	Variable	Variable	Variable	Variable	↑ LDH Positivite for TdT	Variable	Variable		Bone marrow and tissue aspiration and biopsy	Cytogenetic analysis Flow cytometry FISH	May involve brain, skin, and testes.
	Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph
	Provisional entity: Early T-cell precursor lymphoblastic leukemia	Similar to T-cell precursor lymphoblastic leukemia but is more aggressive clinically and cell are characterized by cytometry as CD1a−, CD8−, CD5− (dim), and positivity for 1 or more stem cell or myeloid antigens. Gene expression indicates more immature cells as compared to other subtypes of T-cell neoplasms.

• 50% of patients are asymptomatic

• Clinical features are generally nonspecific such as left upper quadrant pain, early satiety, fatigue & lethargy (most common presenting symptom), weight loss, and night sweats.
• symptoms of anemia
• bleeding
• priapism
• bone pain
• Abdominal mass or fullness
• Infection
• Headache
• Dyspnoea
• Visual disturbances
• Weakness
• Arthralgia
• Cough
• Malaise
• Dizziness
• Nausea/vomiting
• Ankle oedema
• Mental change