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Mantle cell lymphoma: conjunctival mass in a female patient

Published:October 24, 2017DOI:https://doi.org/10.1016/j.jcjo.2017.09.005
      Mantle cell lymphoma (MCL) is a rare neoplasm in the ocular adnexa, accounting for 3%–5% of conjunctival B-cell non-Hodgkin lymphomas (NHL).
      • Coupland S.E.
      • Hellmich M.
      • Auw-Haedrich C.
      • Lee W.R.
      • Stein H.
      Prognostic value of cell-cycle markers in ocular adnexal lymphoma: an assessment of 230 cases.
      • Ferry J.A.
      • Fung C.Y.
      • Zukerberg L.
      • et al.
      Lymphoma of the ocular adnexa: a study of 353 cases.
      Conjunctival MCL typically presents in male patients in the eighth decade and is often advanced at the time of presentation.
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      Treatment typically consists of chemotherapy or radiation, although the prognosis is poor.
      • Chandran R.
      • Gardiner S.K.
      • Simon M.
      • Spurgeon S.E.
      Survival trends in mantle cell lymphoma in the United States over 16 years 1992–2007.
      The authors present a rare case of conjunctival MCL in a female patient. Collection and evaluation of protected patient health information complied with the Health Insurance Portability and Accountability Act.

      Case Report

      A 61-year-old female presented with a painless, salmon-colored conjunctival lesion approximately 8 × 5 mm in size in the medial canthal region of the right eye (Fig. 1). The mass had been present for 2 weeks, and at her follow-up visit 1 month later it appeared to have grown. She had no visual symptoms or complaints in the right eye, although she had been experiencing flashes and floaters in the left eye, which was found to be a posterior vitreous detachment. Ophthalmic examination was otherwise within normal limits. No palpable or visible posterior extension could be appreciated. Patient denied B-symptoms such as fever, night sweats, or lymphadenopathy. She had no history of malignancy.
      Fig. 1
      Fig. 1Right eye in abduction showing a salmon-colored conjunctival lesion near the medial canthus, approximately 8 × 5 mm in size.
      There was high clinical suspicion of lymphoma, and the patient subsequently underwent biopsy of the right conjunctival lesion. Histopathology showed soft tissue infiltration of fairly uniform atypical lymphocytes with slightly irregular nuclear membranes and focally vesicular chromatin without prominent nucleoli. Occasional mitoses were identified. Immunohistochemical staining showed CD20+, CD5+, Bcl-2+, CyclinD1+, CD10−, CD23−, and 50% Ki-67 proliferation consistent with MCL. Computed tomography (CT) of orbits showed no other ocular involvement. Staging positron emission tomography (PET) and CT showed multiple small, mildly hypermetabolic axillary, mediastinal, hilar, retroperitoneal, mesenteric, and external iliac lymph nodes as well as splenomegaly. Bone marrow biopsy showed 10% MCL involvement.
      She subsequently started rituximab, bendamustine, and cytarabine for stage IV MCL but was switched to rituximab and bendamustine after severe cytopenias after the second cycle. PET/CT showed complete remission with resolution of lymphadenopathy and splenomegaly after the third cycle. Remission was maintained after completion of 6 cycles. She did not require maintenance therapy. Marrow biopsy after completion of chemotherapy was normocellular. She subsequently developed rituximab-induced delayed neutropenia, which resolved with filgrastim. As of 10 months after completion of chemotherapy, she continues to be in remission.

      Discussion

      MCL is a rare type of B-cell NHL that accounts for approximately 3%–5% of conjunctival lymphomas.
      • Coupland S.E.
      • Hellmich M.
      • Auw-Haedrich C.
      • Lee W.R.
      • Stein H.
      Prognostic value of cell-cycle markers in ocular adnexal lymphoma: an assessment of 230 cases.
      • Ferry J.A.
      • Fung C.Y.
      • Zukerberg L.
      • et al.
      Lymphoma of the ocular adnexa: a study of 353 cases.
      It is a high-grade, aggressive lymphoma that typically presents in the eighth decade. Males are 6 times more likely to be diagnosed with ocular adnexal MCL than females.
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      Although female patients with conjunctival MCL have been reported in the literature,
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      • Rasmussen P.
      • Sjö L.D.
      • Prause J.U.
      • Ralfkiaer E.
      • Heegaard S.
      Mantle cell lymphoma in the orbital and adnexal region.
      • Choi C.J.
      • Stagner A.M.
      • Jakobiec F.A.
      • Lee N.G.
      Limbal mantle cell lymphoma of the conjunctiva.
      • Kirkegaard M.M.
      • Rasmussen P.K.
      • Coupland S.E.
      • et al.
      Conjunctival lymphoma—an international multicenter retrospective study.
      these have mostly represented minor percentages within larger conjunctival lymphoma studies
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      • Kirkegaard M.M.
      • Rasmussen P.K.
      • Coupland S.E.
      • et al.
      Conjunctival lymphoma—an international multicenter retrospective study.
      with the exception of one prior case report.
      • Choi C.J.
      • Stagner A.M.
      • Jakobiec F.A.
      • Lee N.G.
      Limbal mantle cell lymphoma of the conjunctiva.
      Conjunctival MCL in a female patient is a rare presentation that warrants attention from clinicians.
      Conjunctival MCL presents as a painless “salmon-colored” mass
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      that tends grow rapidly and is more often bilateral than unilateral.
      • Rasmussen P.
      • Sjö L.D.
      • Prause J.U.
      • Ralfkiaer E.
      • Heegaard S.
      Mantle cell lymphoma in the orbital and adnexal region.
      Patients typically seek medical treatment soon after the appearance of the mass.
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      When there is clinical suspicion, a full ophthalmologic examination along with tissue histopathology is necessary to make the diagnosis.
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      At the genetic level, MCL is characterized by the t(11;14)(q13;32) translocation, which causes overexpression of cyclin D-1 and subsequent cellular proliferation and dysregulation.
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      Occult disease is present in approximately 80% of patients who initially present with ocular adnexal MCL.
      • Ferrer A.
      • Salaverria I.
      • Bosch F.
      • et al.
      Leukemic involvement is a common feature in mantle cell lymphoma.
      Thus, staging with PET and CT/magnetic resonance imaging as well as bone marrow biopsy is warranted upon diagnosis.
      • Kirkegaard M.M.
      • Coupland S.E.
      • Prause J.U.
      • Heegaard S.
      Malignant lymphoma of the conjunctiva.
      • Rasmussen P.
      • Sjö L.D.
      • Prause J.U.
      • Ralfkiaer E.
      • Heegaard S.
      Mantle cell lymphoma in the orbital and adnexal region.
      Nodal involvement and splenomegaly, as noted in this patient, are often present.
      • Vali Khojeini E.
      • Durham B.H.
      • Chen M.
      Mantle cell lymphoma and involvement of the orbit and ocular adnexa.
      The mainstay of treatment for MCL is chemotherapy, usually involving R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone), although a combination of rituximab, bendamustine, and cytarabine is a valid alternative for older patients.
      • Visco C.
      • Finotto S.
      • Zambello R.
      • et al.
      Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation.
      The prognosis is typically poor for advanced MCL, with a 5-year overall survival of 40%.
      • Chandran R.
      • Gardiner S.K.
      • Simon M.
      • Spurgeon S.E.
      Survival trends in mantle cell lymphoma in the United States over 16 years 1992–2007.
      However, a different study showed that patients who receive rituximab-containing regimens have a 3-year survival rate of 57% compared to 40% for patients who received regimens without rituximab.
      • Abrahamsson A.
      • Albertsson-Lindblad A.
      • Brown P.N.
      • et al.
      Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study.
      For patients younger than 65 years, allogeneic hematopoietic stem cell transplant is a potentially curative option.
      • Chandran R.
      • Gardiner S.K.
      • Simon M.
      • Spurgeon S.E.
      Survival trends in mantle cell lymphoma in the United States over 16 years 1992–2007.
      Although conjunctival MCL overwhelmingly present in male patients, female sex does not necessarily preclude MCL from the differential diagnosis of conjunctival lymphomas.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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