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7 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
An aggressive lymphoma of natural killer cells, always driven by Epstein-Barr virus, that destroys the tissues in the middle of the face: the nose, the palate and the sinuses. It is common in east Asia and Latin America and uncommon in Europe, and it is the one lymphoma in which ordinary anthracycline chemotherapy does not work at all.
What it is. A lymphoma of natural killer cells, and in a minority of cases of cytotoxic T cells, in which every tumour cell carries Epstein-Barr virus. The virus is part of the definition: a tumour with this appearance that does not carry it is a different disease. The cells grow around and into blood vessels, which cuts off the blood supply to the tissue they sit in, and that is why the disease destroys what it grows in rather than simply displacing it.
Where it starts and what it does. Most often in the nose and the structures around it: the nasal cavity, the sinuses, the hard palate, the back of the throat. It presents as blockage, bleeding, crusting or a hole in the palate, and it is often treated as sinusitis for months before anybody biopsies it. Extranasal sites include the skin, the gut, the testis and the soft tissues, and disease starting outside the nose behaves worse. WHO-HAEM5 dropped the qualifier nasal type from the name in 2022 for exactly that reason, because the disease is recognised at several extranodal sites; the International Consensus Classification kept it, so a report in 2026 may carry either name.
| Setting | Approach | Guideline |
|---|---|---|
| Making the diagnosis, and why it is usually late | The presentation looks like sinusitis: blockage, bleeding, crusting and pain in the nose, often treated with antibiotics and steroids for months. A biopsy taken through the nose is often necrotic and non-diagnostic, so repeat biopsies are common and are not a failure. The diagnosis needs in situ hybridisation for Epstein-Barr-encoded RNA, which is positive in every tumour cell by definition, together with an NK-cell phenotype: CD56 positive, surface CD3 negative with cytoplasmic CD3-epsilon positive, and cytotoxic granule proteins present. A gut lesion with the same markers but no virus is the indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, which regresses on its own; WHO-HAEM5 says it is most important not to mistake one for the other. | not mapped |
| Staging and the risk score | PET-CT of the whole body, magnetic resonance imaging of the face and sinuses to map local destruction, examination of the nose and throat, and a measurement of Epstein-Barr virus DNA in the blood, which tracks the disease and is an independent predictor of survival. The index in use is PINK, built from 527 patients treated without anthracyclines at 38 hospitals in 11 countries, which counts age over 60, stage III or IV, involvement of distant lymph nodes, and disease starting outside the nose: three-year overall survival was 81 per cent with none of those, 62 per cent with one and 25 per cent with two or more. Adding the viral DNA level gives a second version, PINK-E. | not mapped |
| Extranodal NK/T-cell lymphoma, nasal type: asparaginase, and why anthracyclines do not work | An Epstein-Barr virus-driven lymphoma that destroys the midline structures of the face, common in east Asia and Latin America and uncommon in Europe. It expresses P-glycoprotein, which pumps anthracyclines out of the cell, so CHOP is ineffective and must not be used. Every effective regimen contains asparaginase, which the tumour cannot resist because it lacks asparagine synthetase. Early-stage disease (stage I and II, confined to the upper aerodigestive tract) is treated with radiotherapy at a relatively high dose of about 50 Gy, given concurrently with or sandwiched between asparaginase-containing chemotherapy. Radiotherapy is the single most important component in early disease and delaying it worsens outcome. Advanced and relapsed disease is treated with an asparaginase-containing regimen. SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) was tested in 38 patients with newly diagnosed stage IV, relapsed or refractory disease: the overall response rate after two cycles was 79 per cent, complete response 45 per cent, and one-year overall survival 55 per cent, with grade 4 neutropenia in 92 per cent and grade 3 or 4 infection in 61 per cent. Nineteen of the 28 who completed treatment went on to a stem cell transplant. Gentler asparaginase-based regimens such as P-GEMOX and DDGP are widely used in China. Pegylated asparaginase has largely replaced native L-asparaginase. Plasma Epstein-Barr virus DNA is used to monitor response. PD-1 blockade has substantial activity in relapsed disease and is used where available. | not mapped |