Diagnosing MCL and Making Informed Treatment Decisions

Jonathon Cohen, MD, MS: The case that we highlighted today is a very typical presentation for a patient with mantle cell lymphoma. Although it’s an unusual disease, it does constitute up to 10% of all cases of non-Hodgkin lymphoma, and fortunately it can be fairly easy to diagnose based on the fact that it almost always has a translocation 11;14 as well as cyclin D1 overexpression by IHC [immunohistochemistry]. So from the pathologic standpoint, this is a very clear-cut case.

It also is a disease that tends to impact men over women, and tends to present in patients in their sixties, similar to what we saw in this case.

Now, not all cases of mantle cell lymphoma are the same. There are some patients who present who are entirely asymptomatic, for which disease is really found either on blood work or on a scan that’s obtained for some other reason. On the other hand, there are patients who present as our patient did, with weight loss and symptomatic lymphadenopathy and splenomegaly.

There are a number of different ways that we can identify a patient’s prognosis. Ultimately, a patient who is ill and who has rapidly progressive disease is one for whom you’re going to worry about more than a patient who is asymptomatic. But there are also objective criteria, including the Mantle Cell Lymphoma International Prognostic Index, or MIPI, which was calculated in this case as well, that can help inform what a patient’s overall survival will be. These are factors that can be identified early on, that include lab work as well as age and performance status.

Making the diagnosis of mantle cell lymphoma can be relatively straightforward. There are a number of markers that we can look for, including translocation 11;14 as well as overexpression of cyclin D1 and expression of CD5, which is not typically expressed on B cells.

In addition, however, to making the diagnosis, there are a number of different pathologic criteria that we can use to help inform our understanding of a patient and their prognosis. One easy-to-calculate index is the MIPI, or Mantle Cell Lymphoma International Prognostic Index, which incorporates lab work as well as other clinical features. Pathologically, however, there are additional markers that we rely on. For example, the Ki-67 proliferative index can be determined by the pathologist who is reviewing tissue biopsy. This is an IHC [immunohistochemistry] stain. When a patient has a Ki-67 proliferative index greater than 30%, it tends to confer an inferior prognosis. In fact, in some instances the Ki-67 has been combined with MIPI to form an even more robust prognostic index.

Additionally, there are some emerging genetic markers that we can look at that do identify patients who may be at an increased risk for early progression and potentially death from the disease. One of the most well-known genes is TP53. This can be screened for at the time of diagnosis, and patients who have a mutation in TP53 are known to have an inferior prognosis and tend to not respond well to our standard therapies.

Transcript edited for clarity.

Case: A 68-Year-Old Male with Mantle Cell Lymphoma

Initial presentation

• A 68-year-old man presented with generalized lymphadenopathy, fatigue and an unintentional 8-lb weight loss
• PMH: HTN, medically controlled
• PE: abdominal distention, splenomegaly
  
  

Clinical workup

• LDH 345 U/I, ANC 3500/mm3, beta-2-microglobulin 4.4 µg/L, leukocytes, 5.98 X 109/L, hemoglobin 9.6 gm/dL
• FISH: t (11;14)
• Immunocytochemistry: cyclin D1+, CD5+, CD20++
• BMB positive for lymphoid cells with cyclin D1
• PET/CT scan showed widespread lymphadenopathy in numerous nodal regions including left mesenteric (3.4 cm), bilateral axillary (3.9 cm, 5.3 cm), and cervical (5.1 cm)
• Ann Arbor stage IV; MIPI score 6.3; ECOG PS 1
  
  

Treatment

• Patient was started on bendamustine + rituximab
  • Achieved PR
  • Continued on maintenance rituximab q8W
• At 9 months the patient had clinical disease relapse
  • He was started on ibrutinib 560 mg PO qDay
  • Imaging at 12-week follow-up showed no evidence of disease