The patient is a 76-year old man who presented with a non-painful mass in his right upper eyelid. Imaging studies demonstrated enlargement of bilateral lacrimal glands and a right orbital mass that was extending to the medial canthus. An ophthalmologic biopsy was performed.
Histological sections revealed a dense monotonous proliferation of small to intermediate-sized lymphoid cells with variably irregular, slightly cleaved nuclei and inconspicuous nucleoli. By immunohistochemistry, lymphoma cells exhibited strong uniform co-expression of B-cell marker CD20 and cyclin D1. CD10 was negative. Ki-67 proliferative index in the lymphoid infiltrate was estimated 50%. A concurrent flow cytometry detected a minute lambda-dominant CD5+ B cell population. The PCR B-cell gene rearrangement studies revealed a monoclonal IgH gene rearrangement.
DIAGNOSIS: OCULAR MANTLE CELL LYMPHOMA
Mantle cell lymphoma accounts for 3-10% of all non-Hodgkin lymphomas. It is a mature B-cell neoplasm that usually occurs in middle-aged to older individuals and commonly involves lymph nodes, and/or gastrointestinal tract in a form of lymphomatous polyposis. Most patients have stage III or IV disease at presentation with the infiltrates of neoplastic cells detected in the bone marrow, spleen and peripheral blood, and in the vast majority of cases it is an incurable disease with 3-5 year median survival.
Mantle cell lymphoma is composed of a proliferation of mature B cells that aberrantly express CD5 while lack CD10. In contrast to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the neoplastic cells have a bright expression of CD20 and surface light chain without CD23. Morphologically, the proliferation has a diffuse pattern and strikingly monomorphic appearance with no centroblasts, paraimmunoblasts and/or proliferation centers. Scattered single epithleioid histiocytes are often seen, and plasma cell component may be present. Immunohistochemical staining for cyclin D1 and/or FISH confirming the translocation t(11:14) (q13;qq32) IGH/CCND1 clench the diagnosis. Lambda restriction, as seen in this case, is more common in mantle cell lymphoma.
There are several histologic types of mantle cell lymphoma. The blastoid variant is of clinical importance, as it is highly aggressive. The blastoid variant is characterized by larger cells with dispersed chromatin and scant cytoplasm, resembling acute leukemia, and a higher proliferative index than the classic variant. However, a high proliferation index assessed by Ki-67 nuclear staining of >40%, and as low as >20% in some studies, has been consistently linked to adverse outcomes and poor survival even in cases with classic cytology, such as in this patient.
Another interesting attribute of this case is the ocular occurrence. While extranodal marginal zone lymphoma is the most common type of B-cell lymphoma in the ocular adnexal region, mantle cell lymphoma has also been reported in this location. According to a recently published large retrospective multicenter study, it comprises 6.8% of the conjunctival lymphomas. Interestingly, the bilateral lacrimal gland involvement with periorbital and orbital swelling, such as in this patient has been reported in other patients. In rare instances, mantle cell involving the eye can even be an initial manifestation of the disease.
- Cherian S, Wood B. Flow Cytometry in Evaluation of Hematopoietic Neoplasms: A Case-Based Approach 1st Edition. College of American Pathologists; 1 ed. (November 1, 2012), p. 40-41.
- Swerdlow SH, Campo E, Harris NL, Jaffe ES, et al, Eds. (2008). WHO classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France, International Agency for Research on Cancer, p. 229-232.
- Chapter 57. Bone Marrow Evaluation for Lymphoma. In: Jaffe ES, Harris NL, Vardiman JW, Campo E, Arber DA, Eds. Hematopathology, Elsevier Saunders Publishers, St. Louis, MO, USA, 2010, p. 900-904
- Jeong TD, Chi HS, Kim MS, Jang S, Park CJ, Huh JR. Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma. Blood Res. 2016 Jun;51(2):127-32
- Cai J, Li Z, Zhou Y.Mantle cell lymphoma in a lacrimal gland in a female and a review of the literature. Eye Sci. 2014 Sep;29(3):178-81.
- Rašić DM, Knežević M, Terzić T, Vlajković G. Bilateral ocular panadnexal mass as initial presentation of systemic blastoid variant of mantle-cell lymphoma. Surv Ophthalmol. 2016 May 30.