Diagnostic Workup for Mantle Cell Lymphoma

Brad S. Kahl, MD:This is a 72-year-old gentleman who presented to his physician with a 2-month history of night sweats and weight loss. He also had increasing fatigue. When he was evaluated, it was noted that he had right supraclavicular lymphadenopathy and his spleen was palpable. Blood work showed a normal white blood cell count, but a high LDH. So, the patient underwent an excisional biopsy of that right supraclavicular lymph node, which showed a definite lymphoma. The cells were CD5-positive, CD20-positive, and CD23-negative. The cells were positive for cyclin D1 by immunohistochemistry, and the cells had 11;14 translocations by FISH. All of that is consistent with a diagnosis of mantle cell lymphoma.

The patient went on to have a full staging evaluation, and that included PET imaging and the bone marrow evaluation. The PET scan showed widespread lymphadenopathy in multiple nodal regions as well as uptake in the spleen and splenic hilum, and the bone marrow was involved. So, this patient has symptomatic, high tumor burden stage 4 mantle cell lymphoma.

This is a rather typical presentation for mantle cell lymphoma. It’s a disease that affects older males, predominantly. Patients often come in with symptoms, and those symptoms can be typical lymphoma symptoms like fevers, night sweats, and weight loss. The patients might have pain from increasing lymphadenopathy. They might have early satiety and weight loss from splenomegaly. It’s very typical to have an advanced stage in mantle cell lymphoma. Most people have stage 3 or 4 disease. So, there’s nothing about this case that is particularly unusual in the presentation. The patient is quite symptomatic, and he does have a high LDH. Only a minority of patients have a high LDH with their mantle cell presentation, so that does make me worry that this particular case is a little more aggressive than the average case.

Some patients will come in and their disease is just found incidentally: They just noted a lump, but they feel OK. You do the whole staging evaluation, they have a low tumor burden, they’re asymptomatic, and their blood counts are good. So, there is a subset of patients with mantle cell lymphoma who can start out on a watch-and-wait strategy, maybe 10% or 20% of every newly diagnosed patient with mantle cell lymphoma can start off on that strategy. But certainly, the majority of patients with newly diagnosed mantle cell lymphoma do need to start on treatment at the time of diagnosis. And I would say that’s true in this case. This patient needs to start on treatment.

To make a diagnosis of mantle cell lymphoma, the patient’s biopsy needs to show the right histology and the right morphology. The cells need to have a typical appearance for mantle cell lymphoma. It needs to have the typical mantle cell immunophenotype: CD-positive, CD2-positive, CD10-negative, and CD23-negative. That’s typical for mantle cell lymphoma. Most importantly, the cells should be cyclin D1-positive on immunohistochemistry. That’s a pretty specific test. There are a few other conditions that can have positive cyclin D1 staining, but not many. And it should have an 11;14 translocation by FISH testing. So, applying those 3 strategies—the flow cytometry, the immunohistochemistry, and the FISH testing— mantle cell lymphoma is not a particularly hard or difficult diagnosis nowadays.

Transcript edited for clarity.

April 2016

• A 72-year-old male presents to his physician complaining of night sweats, intermittent fever (101°-102°) and fatigue lasting 2 months
• PMH: remarkable for hypertension; controlled on a beta-blocker and diuretic
• Physical exam:
  • Right supraclavicular lymph node, markedly enlarged
  • Spleen, palpable
• Laboratory findings:
  • Leukocytes, 6.73 X 10⁹/L
  • LDH, 420 U/L
• Excisional biopsy of the right supraclavicular node:
  • Immunophenotyping: IgD+, CD5+, CD10+, CD19+, CD20+, CD22+, CD23-, cyclin D1+
  • Cytogenetics: t(11;14)(q13;q32)
  • Bone marrow biopsy confirmed the presence of cyclin D1+ lymphoid cells
• PET-CT: diffuse¹⁸F-FDG uptake in lymph nodes and spleen; the largest involved nodes are the right supraclavicular (4.2 cm), right mesenteric (3.8 cm), and splenic hilar (5.7 cm) nodes
• Diagnosis: Mantle-cell lymphoma, Ann Arbor stage IV
• The patient was started on therapy with bendamustine + rituximab

November 2016

• PET/CT findings at 3 months and 6 months showed a partial response to upfront chemoimmunotherapy
• The patient continues to report symptoms of fatigue
• He was started on therapy with ibrutinib