Primary cutaneous mantle-cell lymphoma C83.1

Mantle cell lymphoma is classified as indolent (cytic) B-cell lymphoma, but shows a heterogeneous, in some patients aggressive course. Pathognomonic is the chromosomal translocation t(11;14) with consecutive overexpression of cyclin D1 (via bcl-1). The tumor cells show a co-expression of B-cell markers and CD5, but in contrast to CLL no CD23. The vast majority of patients is diagnosed in already advanced stages.

5 to 7% of malignant lymphomas in Europe are classified as mantle cell lymphomas. The incidence is 2/100,000/year. Mantle cell lymphoma (MCL) rarely affects the skin. In reviews, the cutaneous collective is reported to be 1% -6.% of MCL cases (Kim DH et al. 2019; Geropoulos G et al. 2020; Wehkamp U et al. 2015). m:w=4:1

Pathognomonic for mantle cell lymphoma is a chromosomal translocation between the immunoglobulin heavy chain gene on chromosome 14 and the cyclin D1 gene on chromosome 11. The translocation t(11;14)(q13;q32), which is found in approximately 95% of all cases, leads to aberrant overexpression of cyclin D1 and proliferative activation of the cell cycle. Additional genetic aberrations influence the clinical picture, with p53 mutations and deletions playing a central role.

The mean age at the time of skin infestation was 66 years (range 36 to 85 years). Thus, it does not differ from the classic "extracutaneous" form of progression. (The mean age of onset in this collective is 65 years).

Preferably the extremities are affected (about 60%). Especially in the blastoid forms, diffuse large B-cell lymphoma of the leg type must be excluded (cyclin D1 staining).

About 80% of the patients with cutaneous mantle cell lymphoma were in an advanced stage (III/IV) of the disease.

In about 30% of the patients, the skin lesions occurred as the initial manifestation of MCL. Multiple skin infiltrates were seen in about 80% of patients.

In about 70% of patients, the skin manifestations presented as part of a relapse or previously documented systemic MCL or as a sign of progression (sometimes under chemotherapy) of MCL. In these cases, solitary (non-disseminated) nodules, nodules or plaques developed predominantly (in about 65% of cases).

Microscopically, a dense, diffuse, cutaneous infestation pattern was seen. The infiltrate-free border zone is characteristic. In about 2/3 of the patients a blastoid or pleomorphic variant of MCL was found, in about 25% of the patients around a classic (cytic) variant. The Ki-67 proliferation rate was significantly higher in the aggressive variants than in the classic variant of MCL (90% vs. 20%).

In the patients of Kim DH et al who had skin lesions as a manifestation of recurrence or progression, 16 patients initially had a classic variant of MCL. In 10 of 16 patients, MCL progressed to an aggressive variant over time (interval: 4.1 years). The overall survival of patients with an aggressive variant of MCH was worse than that of patients with a classic variant of MCL.

Prognosis can be estimated using the clinical MCL International Prognostic Index (MIPI) or established biological factors (blastic variant, Ki-67, p53 alteration (mutations in PCR or NGS, overexpression in immunohistochemistry). The MIPI-c merges the clinical prognosis estimation with the biological marker Ki67, and allows a more sophisticated risk estimation. The median survival time is about 5 years for all patients, with significant differences in the different risk groups. In case of skin involvement, a rather aggressive course of the disease has to be expected.

1. Aukema SM et al. (2018) Expression of TP53 is associated with the outcome of MCL independent of MIPI and Ki-67 in trials of the European MCL Network. Blood 131:417-420.
2. Dreyling M et al. (2005) Early consolidation with myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood 105:2677-2684.
3. Dreyling M et al. (2017) ESMO Guidelines Working Group. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28 Suppl 4:iv62-iv71.
4. Geropoulos G et al. (2020) Cutaneous manifestations of mantle cell lymphoma: an extensive literature review. Acta Dermatovenerol Alp Pannonica Adriat 29:185-191.
5. Hoster E et al. (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111:558-565
6. Hoster E et al. (2016) Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma. J Clin Oncol 34:1386-1389.
7. Hermine OE et al. (2016) Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet 388:565-575.
8. Jain P et al (2020) Blastoid Mantle Cell Lymphoma. Hematol Oncol Clin North Am 34:941-956.
9. Kim DH et al (2019) Mantle cell lymphoma involving skin: A clinicopathologic study of 37 cases. Am J Surg Pathol 43:1421-1428.
10. Le Gouill S et al (2018) Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med 377:1250-1260
11. Robak T et al. (2018) Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study... Lancet Oncol 19:1449-1458.
12. Wehkamp U et al (2015) Skin involvement of mantle cell lymphoma may mimic primary cutaneous diffuse large B-cell lymphoma, leg type. Am J Surg Pathol 39:1093-1101.
13. Wang M et al (2020) KTE-X19 CAR T-cell therapy in relapsed or refractory mantle cell lymphoma. N Engl J Med 382:1331-1342.