Sandbox:Hannan

Myeloproliferative neoplasms (MPN)		Clinical manifestations		Diagnosis											Other features
		Symptoms	Physical examination	CBC & Peripheral smear									Bone marrow biopsy	Other investigations
				WBCs							Hb	Plat- elets
				Leukocytosis	Blasts	Left shift	Baso- phils	Eosino- phils	Mono- cytes	Others
Chronic myeloid leukemia (CML), BCR-ABL1+		Asymptomatic Constitutional Hyperviscosity and/or anemia related Bleeding Infection	Splenomegaly (46–76%) Purpura Anemia related Priapism	Absolute leukocytosis (median of 100,000/µL)	<2%	+	↑	↑	↑	N/A	↓	NL	Hypercellurarity with ↑ granuloscytosis and ↓ erythrocytosis Fibrosis	FISH for t(9;22)(q34;q11.2) Reverse transcriptase quantitative PCR (RQ-PCR) for BCR-ABL	Granulocytic dysplasia is minimal/absentMay present with blast crisis classic myelocyte bulge thrombocytopenia indicates advanced stage
Chronic neutrophilic leukemia (CNL)		Asymptomatic Constitutional symptoms Bleeding Infection	Splenomegaly Heptomegaly Purpura Anemia related	Leukocytosis with chronic neutrophilia	Minimal	+	NL	NL	NL	↑ LDH ↑ B12 levels	↓	↓	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	-	↑ or ↓	NL or ↑	NL	↓ Serum ferritin ↓ Folate levels ↑↑ B12 levels	↑↑	NL	Hypercellularity for age with tri-lineage growth Myelofibrosis (in up to 20% 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	-	Absent	NL	NL	↑ LAP ↑ LAD ↑ Uric acid ↑ B12 levels	↓	↓	Variable with fibrosis or hypercellularity	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	-	↓ or absent	NL	NL	N/A	↓	↑↑	Normal/Hypercellular	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	+	↑	↑↑	↑	↑ B12 levels ↑ LDH	↓	↓	Hypercelluar with ↑ eosinophilic precursors, ↑ eosinophils, and atypical mononuclear cells	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	±	↑ or ↓	↑ or ↓	↑ or ↓	May resemble other myeloproliferative neoplasms	↓	↑	↑ megakaryocyte proliferation with variable hypercellularity in granulocytic or erythrocytic cell lines	N/A	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	-	NL	↑	NL	↑ Alkaline phosphatase ↑ LDH	↓	↓ or ↑	Multifocal dense infiltrates of mast cells with atypical morphology in >25 %	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
Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2		Asymptomatic Constitutional Rash Cough & breathlessness Peripheral neuropathy/ encephalopathy	Fever Lymphadenopathy	Leukocytosis (30 - 59 × 109/L	NL	-	NL	↑	↑	None	NL	↓	Myeloid expansion with eosinophilia	FISH shows t(8;13) and t(8;22)	May present or evolve into acute myeloid or lymphoblastic leukemia
B-lymphoblastic leukemia/lymphoma		Constitutional Anemia related Bleeding Infection Bone pain	Pallor Petechiae Organomegaly Lymphadenopathy	Variable	>25%	N/A	↑ or ↓	↑ or ↓	↑ or ↓	Auer bodies	↓	↓	Hypercellular with blast infilterationwith or without myelodysplasia	Cytogenetic analysisFlow cytometry FISH	May present as extramedullary disease (Myeloid sarcoma)
Myelodysplastic syndromes (MDS)		Constitutional Anemia related Bleeding Infection	Pallor Petechiae Organomegaly	Leukopenia	Variable	-	↓	↓	↓	Macro-ovalocytes Basophilic stippling Howell-Jolly body	↓	↓	Hypercellular/ normocellular bone marrow with dysplastic changes	Cytogenetic analysisFlow cytometry	Leukemia transformationAcquired or pseudo-Pelger-Huët anomaly
Acute myeloid leukemia (AML) and related neoplasms		Constitutional Anemia related Bleeding Bone pain Joint pain Infections	Infection related Pallor Leukemia cutis Bruising & petechiae Lymphadenopathy Hepatosplenomegaly	Variable	↑	N/A	↑ or ↓	↑ or ↓	↑ or ↓	↑ Potassium ↑ Uric acid ↑ Phosphorus ↓ Calcium ↑ LDH	↓	↓	Increased immature myeloid cells with dysplastic features	Cytogenetic analysis Flow cytometry FISH	Common in Down syndrome
Blastic plasmacytoid dendritic cell neoplasm		Cutaneous symptoms (brown/purple nodular lesions) on face, scalp, lower limb & trunk	Brown/violaceous bruise like lesions Lymphadenopathy Splenomegaly	None	↑		NL	NL	NL	Neutropenia	↓	↓	Malignant cells	Immunohistochemistry or flow cytometry, CD4 & CD56 positive	TdT expression positive, may develop chronic myelomonocytic leukemia (CMML)
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%		NL	↑	↑↑	↑ LDH	↓	↓	Myelodysplastic and myeloproliferative feature	Cytogenetic analysis Flow cytometry	Overlapping of both, MDS and MPNAbsolute monocytosis > 1 × 109/L (defining feature)
	Atypical chronic myeloid leukemia (aCML), BCR-ABL1-	Similar to chronic myeloid leukemia	Similar to chronic myeloid leukemia	WBC > 13 × 109/L	<20%	+	<2% of WBCs	N/A	N/A	N/A	↓	↓	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	↑	N/A	N/A	N/A	↑	↓ Serum Iron ↑ B12 levels	↓	↓	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	NL	-	NL	N/A	N/A	↑ Serum Iron	↓	↑	Hypercellularity with dyserythropoiesis and increased megakaryocytes	Cytogenetic analysis Flow cytometry	Large atypical megakaryocytes Ringed sideroblasts SF3B1 mutation
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	↑	>25% blasts (Leukemia) <25% blasts (Lymphoma)	±	↑ or ↓	↑ or ↓	↑ or ↓	↑ LDH Positive for TdT	↓	↓	Hypercelluarity with increased T cells precursors	Cytogenetic analysisFlow cytometry FISH	May involve brain, skin, and testes.
	Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	↑	±	↑ or ↓	↑ or ↓	↑ or ↓	↑ LDH	↓	↓	N/A	Cytogenetic analysisFlow cytometry FISH	Similar to T-cell lymphoblastic leukemia but may have more aggressive clinical course. Diagnosis is usually based on presence of CD56 expression, and T-cell-associated markers such as CD2 and CD7. B-cell markers are absent.
	Provisional entity: Early T-cell precursor lymphoblastic leukemia	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	↑	±	↑ or ↓	↑ or ↓	↑ or ↓	↑ LDH	↓	↓	Hypercelluarity with increased T cells precursors	Cytogenetic analysisFlow cytometry FISH	Similar to T-cell 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