What Does Lugano Criteria Mean?

The Lugano classification is the staging and response system for lymphoma. The American Joint Committee on Cancer has adopted it, so it is what appears in current staging manuals.

It replaced the Ann Arbor system, agreed at a conference in Ann Arbor in 1971 and modified 18 years later at a meeting in Cotswolds. If you see an older report using Ann Arbor language, that is why. The stage numerals look similar, but the rules behind them changed.

One change catches people out. Hodgkin lymphoma still uses the A or B letter after the stage, where B signals fever, night sweats, or weight loss. NCI states that A and B are no longer used in non-Hodgkin lymphoma. If you have a non-Hodgkin lymphoma and your report has no letter, nothing is missing.

Stage I means involvement of a single lymphatic site. That site can be a nodal region, Waldeyer's ring, which is the tonsil and adenoid tissue at the back of the throat, the thymus, or the spleen.

Stage IE means a single site outside the lymph system with no nodes involved. NCI notes this is rare in Hodgkin lymphoma.

Stage II means two or more lymph node regions on the same side of the diaphragm, the muscle sheet that separates chest from abdomen. Stage IIE means the disease has spread directly from a node into neighboring tissue, still on one side of the diaphragm.

Stage III means node regions on both sides of the diaphragm, or nodes above the diaphragm together with the spleen.

Stage IV means diffuse or scattered involvement of one or more organs outside the lymph system. NCI adds that stage IV specifically includes any involvement of the cerebrospinal fluid, bone marrow, liver, or multiple lung lesions.

Stages I and II are grouped as limited stage. Stages III and IV are grouped as advanced stage.

Reports often add the word bulky. Lugano does not attach one measurement to it.

NCI spells out the variation. In Hodgkin lymphoma, bulk means a mass larger than one third of the chest diameter on CT, or a mass over 10 cm. In follicular lymphoma, 6 cm has been suggested. In diffuse large B-cell lymphoma, published cutoffs range from 5 cm to 10 cm, and 10 cm is the recommended figure.

Stage II bulky sits in an awkward place. NCI notes it may be treated as either early or advanced stage, depending on the lymphoma type and other prognostic factors. So a stage II bulky report does not by itself tell you which treatment path you are on. Ask. Diffuse large B-cell lymphoma shows how bulk feeds into treatment choice there.

Lugano keeps a shorthand for proven organ involvement. A plus sign follows the letter for the site: N for nodes, H for liver, L for lung, M for bone marrow, S for spleen, P for pleura, O for bone, and D for skin.

NCI also distinguishes clinical stage, based on examination and imaging, from pathological stage, based on tissue taken by an invasive procedure. Its worked example is worth reading twice: someone with groin nodes and no systemic symptoms could be clinical stage IIA and pathological stage IVA(H+)(M+), once liver and marrow involvement are proven.

Those are the same person on the same day. If two numbers in your chart disagree, check whether one is clinical and the other pathological.

Lugano staging is only as good as the biopsy underneath it.

A French review of more than 32,000 lymphoma cases found that 40% of diagnoses came from core needle biopsy and 60% from excisional biopsy, in which the whole node is removed. After expert review, core needle gave a definite diagnosis in 92.3% of cases and excisional biopsy in 98.1%.

That six-point gap is small in percentage terms and large in practice. Ask which method was used, and whether the pathologist felt the sample was sufficient.

Lugano relies heavily on PET-CT using fluorine F 18-fludeoxyglucose, a radioactive sugar that collects in metabolically active tissue.

For initial staging, that is settled. For scans done partway through treatment, it is not. NCI's summary states that multiple studies have shown interim PET scans after two to four cycles do not provide reliable prognostic information. It cites a large cooperative group trial that found problems with agreement between readers, plus two prospective trials and a meta-analysis showing no outcome difference between PET-negative patients and PET-positive but biopsy-negative patients.

Elsewhere the same NCI summary cites a meta-analysis supporting the predictive value of interim PET in diffuse large B-cell lymphoma treated with R-CHOP. Both statements sit in the current literature. Neither has been withdrawn.

The practical consequence: before an interim scan, ask what result would actually change your treatment. If the honest answer is none, the scan is reassurance rather than a decision point. What a Deauville score means covers the scoring used to report these scans.

This is one of the more welcome changes. In a study of 130 people with diffuse large B-cell lymphoma, PET scanning identified all clinically important marrow involvement, and bone marrow biopsy did not upstage a single patient. In 580 people with follicular lymphoma across seven NCI-sponsored trials, adding bone marrow biopsy to imaging did not improve response assessment.

NCI's position is that the workup should include bone marrow biopsy when the result would change management, such as separating limited from advanced stage, or when low blood counts need explaining. Otherwise it may not be needed.

If a marrow biopsy is being scheduled, it is fair to ask which of those two reasons applies.

• Which stage number, and is it clinical or pathological?
• Does the report call any mass bulky, and by which centimeter cutoff?
• If this is stage II bulky, is the plan an early-stage or advanced-stage plan?
• Was the diagnosis made from a needle core or a whole removed node?
• Would an interim scan result change the treatment, or only confirm it?

Complete versus partial response explains the response wording that follows the same framework at the end of treatment.

Some of these need an emergency room rather than a phone call.

• Call 911 or go to an emergency department if new back pain comes with leg weakness, numbness, or trouble passing or holding urine. Lymphoma pressing on the spinal cord is treated in hours, not days.
• Call 911 or go to an emergency department if your face or neck swells and the veins on your chest wall stand out, especially with a headache or trouble breathing. That pattern points to a blocked vein above the heart.
• Call your care team immediately, day or night, if your temperature reaches 100.4 degrees F (38 C) while you are having chemotherapy or other cancer drug treatment. CDC calls this a medical emergency, because treatment can strip out the white cells that hold infection back. If you cannot reach them quickly, go to an emergency department and tell staff you are on treatment.
• Call your care team the same day if you are not in treatment and you get a new fever at that level with drenching night sweats. MedlinePlus uses 100.4 F here; NCI's infection page uses 100.5 F.
• Call your care team within a day or two if a lymph node grows measurably in under two weeks.

• https://www.cancer.gov/types/lymphoma/hp/aggressive-b-cell-lymphoma-treatment-pdq
• https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq
• https://www.cancer.gov/about-cancer/treatment/side-effects/infection
• https://medlineplus.gov/ency/patientinstructions/000913.htm
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html