A CASE OF RELAPSED REFRACTORY MANTLE CELL LYMPHOMA PRESENTING WITH SKIN LESIONS

Objective

Mantle cell lymphoma (MCL) is a rare subtype of B-cell lymphoma characterized by clinical and biological heterogeneity. Lymph nodes are the most commonly involved sites. Other important regions affected by the disease are bone marrow and spleen. However, skin involvement is rare in MCL, and most cases occur due to secondary cutaneous spread of disseminated disease. In this report, a case of relapsed, refractory (R/R) MCL with skin lesions is discussed.

Case report

A 43-year-old male patient was admitted to our clinic with the complaint of palpable cervical and axillary diffuse lymph nodes. The patient was diagnosed with MCL as a result of lymph node biopsy, and was evaluated as stage 4 and a high-risk disease according to the MIPI scoring system, After chemoimmunotherapy, autologous bone marrow transplantation was performed. The patient who was followed up as a complete response, macular lesions raised from the skin appeared on the lower extremities 4 years after the initial diagnosis (Figure 1), and a skin biopsy was performed; MCL was evaluated as R/R disease. In the immunohistochemical study, CD5, CyclinD1 were positive, Sox-11 was weakly positive, and Ki 67 were evaluated as 100%. The patient was delivered rituximab + ibrutinib (R+I) treatments. After treatment, skin lesions disappeared. After 3 cycles of treatment, the patient underwent an allogeneic bone marrow transplant from his fully compatible sibling. During this period, skin lesions appeared on the trunk, and a skin biopsy was performed; It was evaluated as GVHD (graft versus host disease) and prednol treatment was delivered. The patient, who was evaluated as prednol refractory during the follow-up, was delivered JAK-2 inhibitor and his complaints regressed. The patient was evaluated as a complete metabolic response at the 3rd month post-transplant follow-up.

Figure-1 Lower extremity skin involvement

Methodology

Conclusion

MCL is a different type of non-Hodgkin lymphoma that usually affects extranodal sites. The most commonly affected areas are the bone marrow, gastrointestinal tract, and Waldeyer's ring, but the skin is rarely affected. The disease can present with a wide variety of lesions, ranging from petechial erythematous macules to subcutaneous nodules, and very atypical presentations, such as acneiform lesions, have also been reported. Since extremity and trunk involvement is more common, skin involvement can be seen anywhere in the body. Most often, skin lesions are accompanied by systemic symptoms, but a few cases of only cutaneous lesions without systemic involvement have been described. Skin lesions may develop before clinical symptoms appear. In one report describing five cases of MCL involving the skin; 3 patients initially presented with skin lesions but there was evidence of extensive disease at diagnosis. MCL can often involve the skin as a manifestation of disseminated disease and is often associated with blastoid cytological features. Our case also presented with erythematous macular lesions in R/R disease and showed significant improvement in skin lesions and lymphadenopathy with the combination of rituximab + ibrutinib. The poor outcomes seen in MCL patients with TP53 mutations receiving chemoimmunotherapy and second-line Bruton tyrosine kinase inhibitors suggest an urgent need for alternative approaches. There are a number of promising treatments for R/R MCL beyond covalent BTK inhibitors, including CAR T cell therapy and novel immunotherapeutics such as bispecific antibodies. Although most MCL patients have durable responses after chemoimmunotherapy, there is a need to prospectively identify high-risk patient subgroups for whom disease control with standard chemotherapy is poor. Because of the variability of its presentation, which includes nonspecific papules that appear benign, it is important to be aware of the skin manifestations of MCL.