•The symptoms depend on the degree of cytopenia:

–Anemia: pallor, fatigue, tachycardia, dyspnea, and occasionally cardiovascular decompensation

–Leukopenia (normal functional cells): low to marked temperature elevation, infections

–Thrombocytopenia: petechiae, mucosal bleeding, epistaxes, prolonged menstrual bleeding

2.2.2Specific Signs and Symptoms

2.2.2.1 Skin

Besides signs of bleeding, in neonatal leukemia, maculopapular skin infiltration, often a purplish color (leukemia cutis), can be observed; more common in acute monocytic subtype of AML

2.2.2.2 Central Nervous System

•At time of diagnosis, less than 5% of patients have CNS leukemia with meningeal signs and symptoms: morning headache, vomiting, papilla edema, or focal neurological signs such as cranial nerve palsies, hemiparesis, seizures

•Diagnosis by analysis of cerebrospinal fluid: CNS I, no lymphoblasts; CNS II, less than 5 cells/cm3, but with leukemic blasts on centrifugation; CNS III, at least 5 cells/cm3, with leukemic blasts on centrifugation, or cranial nerve palsy

2.2.2.3 Eye

• Bleeding due to high white blood cell count (WBC) and/or thrombocytopenia

• Retina: infiltration of local vessels, bleeding

2.2.2.4 Ear, Nose, and Throat

•Lymph node infiltration, isolated or multiple

•Mikulicz syndrome: infiltration of salivary glands and/or lacrimal glands

• Leukemic infiltration or hemorrhage. In anemic patients, there may be cardiac enlargement

• Occasionally cardiac tamponade due to pericardial infiltration

• Tachycardia, low blood pressure, and other signs of cardiac insufficiency

2.2.2.6 Mediastinum

• Enlargement due to leukemic infiltration by lymph nodes and/or thymus

• May cause life-threatening superior vena cava syndrome (especially in T-cell ALL)

2.2.2.7 Pleura/and Pericardium

• Pleural and/or pericardial effusion

2.2.2.8 Gastrointestinal Involvement

• Often moderate to marked hepatoand/or splenomegaly

• Often kidney enlargement of one or both sides

• Gastrointestinal leukemic infiltration is frequent, but mostly asymptomatic, rarely manifestation as typhlitis

• Perirectal infection with ulceration, pain, and febrile episodes

2.2.2.9 Renal Involvement

• Renal enlargement, common in Pre B-/B-cell or T-cell ALL

• Possible symptoms: hematuria, hypertension

2.2.2.10 Testicular Involvement

• Seldom apparent at diagnosis; during treatment period and follow-up, less than 5%. Before 1980, frequency between 10 and 23%, probably reflecting more advanced disease at the time of diagnosis

• Enlargement of one or both testes without pain; hard consistency

2.2.2.11 Penis

• Occasionally priapism in association with elevated WBC causing leukemic involvement of sacral nerve roots and/or mechanical obstruction

2.2.2.12 Bone and Joint Involvement

•Bone pain initially present in 25% of patients

•Bone or joint pain, sometimes with swelling and tenderness due to leukemic infiltration of the periosteum. Differential diagnosis: rheumatic fever or rheumatoid arthritis

•Radiological changes: diffuse demineralization, osteolysis, transverse metaphyseal lucency, increased subperiosteal markings, hemorrhage, or new bone formation