The treatment team, after taking a thorough medical history and making a thorough medical examination of the patient, should undertake the following investigations under the guidance of a specialist.

A definitive tissue diagnosis is always required before initiating lymphoma-specific treatment. Biopsy may have been performed before referral. Both fresh and fixed tissue samples should be collected from the tissue biopsy for anatomical pathology and potentially flow cytometry, cytogenetics and gene mutation testing (e.g. TP53 mutation testing for MCL). Additional immunohistochemical stains may in the future provide information that affects therapy (e.g. Ki67 for FL).

Lymph node architecture is a key part of the pathological examination and therefore excisional biopsy is the preferred biopsy method where possible. Where excision biopsy or large incisional biopsy is not possible, a core needle biopsy that samples the maximum number of cores with the largest calibre possible should be considered (NICE 2016).

FNA is not suitable for diagnosing lymphomas (Armitage et al. 2017). However, FNA may be an appropriate investigation in circumstances where excision or needle core biopsy is overly invasive or unfeasible (e.g. mediastinal disease). Construction of tissue blocks from cytological samples may aid diagnosis.

For low-grade lymphomas, surgery is a diagnostic procedure and rarely therapeutic. Therefore, the least invasive surgical method is recommended for diagnosis. If a highly invasive or extensive surgical procedure is being considered, consultation with the lymphoma multidisciplinary team is required.

Pathology specimens should be reviewed by a pathologist with expertise in diagnosing low-grade lymphomas. This should be done at the treatment centre conducting the MDM, before a treatment plan has been instituted.

Additional blood tests – B2M, immunoglobulins, serum protein electrophoresis – are part of the diagnostic work-up.

Evaluate relevant organ function based on history, clinical examination and, where appropriate, laboratory or imaging investigations (cardiac, respiratory, renal, hepatic). Autoimmune screens are sometimes warranted in MZL, specifically autoimmune haemolytic anaemia.

Test for occult or latent infections (e.g. HIV, hepatitis B and C, tuberculosis) that may be affected by therapy or pose a risk of reactivation due to the immunosuppressive effects of treatment. For MZL, site-specific infectious disease testing should be performed.