• Children and young people who present with symptoms and signs of cancer should be referred to a paediatrician or a specialist children's cancer service, if appropriate (D).
• Childhood cancer is rare and may present initially with symptoms and signs associated with common conditions. Therefore, in the case of a child or young person presenting several times (for example, three or more times) with the same problem, but with no clear diagnosis, urgent referral should be made (D).
• The parent is usually the best observer of the child's or young person's symptoms. The primary healthcare professional should take note of parental insight and knowledge when considering urgent referral (D).
• Persistent parental anxiety should be a sufficient reason for referral of a child or young person, even when the primary healthcare professional considers that the symptoms are most likely to have a benign cause (D).
• Persistent back pain in a child or young person can be a symptom of cancer and is indication for an examination, investigation with a full blood count and blood film, and consideration of referral (C).
• There are associations between Down's syndrome and leukaemia, between neurofibromatosis and CNS tumours, and between other rare syndromes and some cancers. The primary healthcare professional should be alert to the potential significance of unexplained symptoms in children or young people with such syndromes (D).
• The primary healthcare professional should convey information to the parents and child/young person about the reason for referral and which service the child/young person is being referred to so that they know what to do and what will happen next (D).
• The primary healthcare professional should establish good communication with the parents and child/young person in order to develop the supportive relationship that will be required during the further management if the child/young person is found to have cancer (D).

• Leukaemia usually presents with a relatively short history of weeks rather than months. The presence of one or more of the following symptoms and signs requires investigation with full blood count and blood film. If the blood film or full blood count indicates leukaemia then an urgent referral should be made (C [DS]).
• Pallor
• Fatigue
• Unexplained irritability
• Unexplained fever
• Persistent or recurrent upper respiratory tract infections
• Generalised lymphadenopathy
• Persistent or unexplained bone pain
• Unexplained bruising
• The presence of either of the following signs in a child or young person requires immediate referral: (C)
• Unexplained petechiae
• Hepatosplenomegaly

Hodgkin's lymphoma presents typically with non-tender cervical and/or supraclavicular lymphadenopathy. Lymphadenopathy can also present at other sites. The natural history is long (months). Only a minority of patients have systemic symptoms (itching, night sweats, fever). Non-Hodgkin's lymphoma typically shows a more rapid progression of symptoms, and may present with lymphadenopathy, breathlessness, superior vena-caval obstruction or abdominal distension.

• Lymphadenopathy is more frequently benign in younger children but urgent referral is advised if one or more of the following characteristics are present, particularly if there is no evidence of local infection: (C)
• Lymph nodes are non-tender, firm or hard
• Lymph nodes are greater than 2 cm in size
• Lymph nodes are progressively enlarging
• Other features of general ill-health, fever or weight loss
• The axillary nodes are involved (in the absence of local infection or dermatitis)
• The supraclavicular nodes are involved
• The presence of hepatosplenomegaly requires immediate referral (C).
• Shortness of breath is a symptom that can indicate chest involvement but may be confused with other conditions such as asthma. Shortness of breath in association with the above signs, particularly if not responding to bronchodilators, is an indication for urgent referral (C).
• A child or young person with a mediastinal or hilar mass on chest X-ray should be referred immediately (C).

Children 2 years of age and older, and young people

• Persistent headache in a child or young person requires a neurological examination by the primary healthcare professional. An urgent referral should be made if the primary healthcare professional is unable to undertake an adequate examination (D).
• Headache and vomiting that cause early morning waking or occur on waking are classical signs of raised intracranial pressure, and an immediate referral should be made (C).
• The presence of any of the following neurological symptoms and signs should prompt urgent or immediate referral: (D)
• New-onset seizures
• Cranial nerve abnormalities
• Visual disturbances
• Gait abnormalities
• Motor or sensory signs
• Unexplained deteriorating school performance or developmental milestones
• Unexplained behavioural and/or mood changes
• A child or young person with a reduced level of consciousness requires emergency admission (C).

Children younger than 2 years of age

• In children younger than 2 years of age, any of the following symptoms may suggest a CNS tumour, and referral (as indicated below) is required (C).
• Immediate referral:
• New-onset seizures
• Bulging fontanelle
• Extensor attacks
• Persistent vomiting
• Urgent referral:
• Abnormal increase in head size
• Arrest or regression of motor development
• Altered behaviour
• Abnormal eye movements
• Lack of visual following
• Poor feeding/failure to thrive
• Urgency contingent on other factors:
• Squint

• Most children and young people with neuroblastoma have symptoms of metastatic disease which may be general in nature (malaise, pallor, bone pain, irritability, fever or respiratory symptoms), and may resemble those of acute leukaemia. The presence of any of the following symptoms and signs requires investigation with a full blood count: C (DS)
• Persistent or unexplained bone pain (and X-ray)
• Pallor
• Fatigue
• Unexplained irritability
• Unexplained fever
• Persistent or recurrent upper respiratory tract infections
• Generalised lymphadenopathy
• Unexplained bruising
• Other symptoms which should raise concern about neuroblastoma and prompt urgent referral include: (C)
• Proptosis
• Unexplained back pain
• Leg weakness
• Unexplained urinary retention
• In children or young people with symptoms that could be explained by neuroblastoma, an abdominal examination (and/or urgent abdominal ultrasound) should be undertaken, and a chest X-ray and full blood count considered. If any mass is identified, an urgent referral should be made (C [DS]).
• Infants younger than 1 year of age may have localised abdominal or thoracic masses, and in infants younger than 6 months of age, there may also be rapidly progressive intra-abdominal disease. Some babies may present with skin nodules. If any such mass is identified, an immediate referral should be made (C).

• Wilms' tumour most commonly presents with a painless abdominal mass. Persistent or progressive abdominal distension should prompt abdominal examination, and if a mass is found an immediate referral be made. If the child or young person is uncooperative and abdominal examination is not possible, referral for an urgent abdominal ultrasound should be considered (C).
• Haematuria in a child or young person, although a rarer presentation of a Wilms' tumour, merits urgent referral (C).

• A soft tissue sarcoma should be suspected and an urgent referral should be made for a child or young person with an unexplained mass at almost any site that has one or more of the following features. The mass is: (C)
• Deep to the fascia
• Non-tender
• Progressively enlarging
• Associated with a regional lymph node that is enlarging
• Greater than 2 cm in diameter
• A soft tissue mass in an unusual location may give rise to misleading local and persistent unexplained symptoms and signs, and the possibility of sarcoma should be considered. These symptoms and signs include: (C)
• Head and neck sarcomas:
• Proptosis
• Persistent unexplained unilateral nasal obstruction with or without discharge and/or bleeding
• Aural polyps/discharge
• Genito-urinary tract:
• Urinary retention
• Scrotal swelling
• Bloodstained vaginal discharge

• Limbs are the most common site for bone tumours, especially around the knee in the case of osteosarcoma. Persistent localised bone pain and/or swelling requires an X-ray. If a bone tumour is suspected, an urgent referral should be made (C).
• History of an injury should not be assumed to exclude the possibility of a bone sarcoma (C).
• Rest pain, back pain and unexplained limp may all point to a bone tumour and require discussion with a paediatrician, referral or X-ray (C).

• In a child with a white pupillary reflex (leukocoria) noted by the parents, identified in photographs or found on examination, an urgent referral should be made. The primary healthcare professional should pay careful attention to the report by a parent of noticing an odd appearance in their child's eye (C).
• A child with a new squint or change in visual acuity should be referred. If cancer is suspected, referral should be urgent, but otherwise referral should be non-urgent (C).
• A family history of retinoblastoma should alert the primary healthcare professional to the possibility of retinoblastoma in a child who presents with visual problems. Offspring of a parent who has had retinoblastoma, or siblings of an affected child, should undergo screening soon after birth (C).

• When cancer is suspected in children and young people, imaging is often required. This may be best performed by a paediatrician, following urgent or immediate referral by the primary healthcare professional (D).
• The presence of any of the following symptoms and signs requires investigation with full blood count: (C [DS])
• Pallor
• Fatigue
• Irritability
• Unexplained fever
• Persistent or recurrent upper respiratory tract infections
• Generalised lymphadenopathy
• Persistent or unexplained bone pain (and X-ray)
• Unexplained bruising

The referral timelines used in this guideline are as follows:

• Immediate: an acute admission or referral occurring within a few hours, or even more quickly if necessary.
• Urgent: the patient is seen within the national target for urgent referrals (currently 2 weeks).
• Non-urgent: all other referrals.