microcytosis without anaemia and cancer risk

Last edited 11/2021 and last reviewed 09/2023

Studies have previously identified microcytosis as a potential early risk marker for certain cancers including: lymphoma (1), oesophago-gastric, (2) colorectal (3) and kidney cancer (4).

• risks were independent of any anaemia
• precise role of microcytosis in primary care across all cancers is not currently known, particularly in patients without anaemia

Microcytosis as an indicator for possible cancer has also been examined via a cohort study of patients aged >= 40 years using UK primary care electronic patient records (5):

• 1-year cancer incidence was compared between cohorts of patients with a mean red cell volume of <85 femtolitres (fL) (low) or 85-101 fL (normal). Further analyses examined sex, age group, cancer site, and haemoglobin values
• of 12 289 patients with microcytosis, 497 had a new cancer diagnosis within 1 year (4.0%, 95% confidence interval [CI] = 3.7 to 4.4), compared with 1465 of 73 150 without microcytosis (2.0%, CI = 1.9 to 2.1)
• in males, 298 out of 4800 with microcytosis were diagnosed with cancer (6.2%, CI = 5.5 to 6.9), compared with 940 out of 34 653 without (2.7%, CI = 2.5 to 2.9)
• in females with microcytosis, 199 out of 7489 were diagnosed with cancer (2.7%, CI = 2.3 to 3.1), compared with 525 out of 38 497 without (1.4%, CI = 1.3 to 1.5)
• in patients with microcytosis but normal haemoglobin, 86 out of 2637 males (3.3%, CI = 2.6 to 4.0) and 101 out of 5055 females (2.0%, CI = 1.6 to 2.4) were diagnosed with cancer
• cancer sites that made up a greater proportion of cancers diagnosed in the microcytosis cohort than the normal cohort were: colorectal (113, 23%), lung (67, 13%), lymphoma (24, 5%), kidney (22, 4%), and stomach (15, 3%)
• study authors concluded that microcytosis is a predictor of underlying cancer even if haemoglobin is normal. Although a benign explanation is more likely, clinicians in primary care should consider simple testing for cancer on encountering unexplained microcytosis, particularly in males

Summary suggested diagnostic workup (5):

• for GPs, an MCV is only reported alongside the haemoglobin value
• anaemia accompanied by microcytosis strongly suggests iron deficiency, and therefore measurement of iron stores would be the usual next step
• if iron deficiency is identified, its cause will be sought, which would generally involve testing for gastrointestinal blood loss
• this diagnostic pathway does not remove the need to enquire about other symptoms suggestive of the malignancies reported here, particularly lung cancer
• patients with microcytosis but without anaemia
• some may be iron deficient, simplifying the investigation strategy
• seems sensible for all these patients to be also offered faecal immunochemical testing for hidden gastrointestinal blood loss, and a chest X-ray if respiratory symptoms suggest lung cancer is possible

Reference:

• Shephard E et al.
Quantifying the risk of non-Hodgkin lymphoma in symptomatic primary care patients aged ≥40 years: a large case-control study using electronic recordsBr J Gen Pract2015
• Stapley S et al. The risk of oesophago-gastric cancer in symptomatic patients in primary care: a large case-control study using electronic recordsBr J Cancer2013;108:12531
• Hamilton W et al. The importance of anaemia in diagnosing colorectal cancer: a case-control study using electronic primary care recordsBr J Cancer2008;82:323-327
• Shephard E et al. Clinical features of kidney cancer in primary care: a case-control study using primary care recordsBr J Gen Pract2013
• Hopkins R et al. Microcytosis as a risk marker of cancer in primary care: a cohort study using electronic patient records. Br J Gen Pract 2020; 70 (696): e457-e462