Signs and symptoms		Suspicious clinical characteristics	Suggested malignancies
Pallor, fatigue, malaise		Especially if persistent and associated with signs of bone marrow infiltration (unexplained fever, recurrent infections, hemorrhagic diathesis) and/or lymphadenopathy10–12	Leukemia, lymphoma, neuroblastoma, Ewing sarcoma, histiocytosis
Fever		Prolonged (> 2 weeks) with no identifiable cause; associated with weight loss, night sweats, pallor, petechiae, mass, bone pain, lymphadenopathy	Leukemia, lymphoma, neuroblastoma, Ewing sarcoma, Wilms tumor, histiocytosis, nasopharyngeal carcinoma
Recurrent or treatment-resistant infections		May be associated with pallor, petechiae, weight loss, bone pain, lymphadenopathy, hepatosplenomegaly, or a palpable mass	Leukemia, lymphoma, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma
Anorexia and weight loss		Protracted, unexplained anorexia, especially if accompanied by significant weight loss or other suspicious findings (recurrent infections, fever, pallor, lymphadenopathy, hepatosplenomegaly)	Leukemia, lymphoma, central nervous system tumors, abdominal tumors
Lymphadenopathy
	Localized	Persistent or progressive that does not resolve after 4 to 6 weeks or that does not respond to antibiotic treatment; lymph nodes > 2 cm, firm, nontender; supraclavicular and epitrochlear location	Lymphoma, rhabdomyosarcoma, nasopharyngeal carcinoma
	Generalized or localized	Coexisting fever, night sweats, weight loss, malaise, pallor, hepatosplenomegaly	Lymphoma, leukemia, neuroblastoma
Hemorrhagic manifestations (petechiae, ecchymoses, recurrent epistaxis, bleeding gums)		Persistent and combined with other signs of bone marrow infiltration (pallor, fatigue, recurrent infections)	Leukemia, lymphoma, neuroblastoma, Ewing sarcoma
Headaches		Of new onset, persistent, occur in the morning or awaken the child from sleep; without history of migraine; associated with vomiting or neurologic deficits (cranial nerve palsies, motor and sensory signs); occipital location; worse when lying down	Brain tumor, neuroblastoma, leukemia, lymphoma, nasopharyngeal carcinoma
School performance deterioration; personality and mood changes		Of recent onset, progressive, and not otherwise explained	Brain tumor
Palpable abdominal mass		Any mass discovered outside the neonatal period has high probability of malignancy, especially when associated with vomiting, abdominal pain, constipation, hematuria, or hypertension	Neuroblastoma, nephroblastoma, lymphoma, hepatic tumors, ovarian tumors
Hepatosplenomegaly		Should always be investigated even if no associated symptoms are found	Leukemia, lymphoma, hepatic tumors
Vomiting		Persistent and recurring; associated with morning headaches; associated with abdominal mass	Brain tumors, abdominal tumors (neuroblastoma, Wilms tumor, lymphoma, hepatoblastoma)
Bone pain, joint pain/arthritis		Bone pain that awakens the child at night, lasts > 2 weeks, is localized, is associated with swelling, and does not improve with nonsteroidal anti-inflammatory drugs	Osteosarcoma, Ewing sarcoma, leukemia, neuroblastoma, histiocytosis
Limp or refusal to walk			Same as the above, and central nervous system tumors
Back pain, kyphoscoliosis, lordosis, torticollis		Back pain of sudden onset; age < 4 years; worse at night; accompanied by fever or neurologic abnormalities; not associated with trauma; not relieved by nonsteroidal anti-inflammatory drugs	Spinal cord/brain tumors, neuroblastoma, leukemia
Masses or lumps on extremities, head, neck, trunk		Any palpable mass that appeared recently; is located deep in the fascia; is nontender, hard, and > 2 cm in diameter; or is associated with regional lymphadenopathy	Soft tissue sarcoma
Urine retention/enuresis		Of recent origin, associated with neurologic deficits or abdominal masses	Neuroblastoma, tumors of the spinal cord or pelvis (ovarian, soft tissue sarcoma)
Scrotal swelling or mass		Of recent origin	Germ cell tumors, leukemia, soft tissue sarcoma
		Isolated right-sided varicocele	Renal tumor, lymphoma, sarcoma
Gingival swelling/bleeding		Not otherwise explained	Histiocytosis, leukemia
Dermatologic manifestations		“Eczema” not responding to conventional treatment	Histiocytosis
		Subcutaneous nodules	Neuroblastoma, leukemia, histiocytosis