Lymphoma of mucosa-associated lymphoid tissue (MALT) has been estimated to represent about 8% of all non-Hodgkin lymphomas (NHLs) and was categorized among the extranodal marginal zone B-cell lymphomas in the 2001 World Health Organization classification. Although extranodal marginal zone B-cell lymphoma of MALT type occurs most frequently in the stomach, it has also been described in various nongastrointestinal sites such as the conjunctiva. Conjunctival melanoma represents only 1.6% of all ocular tumors. Herein we report the case of a patient with consecutive melanoma and extranodal marginal zone B-cell lymphoma of MALT type of the conjunctiva, questioning a relationship between both rare entities.
A 38-year-old man was referred to the ocular oncology unit for a pigmented conjunctival lesion of his left eye. The lesion was situated at the limbus at the 12-o’clock position, measured 15 mm at the largest basal diameter, and showed progression. There was no sign of primary acquired melanosis. A complete excision showed conjunctival malignant melanoma (Figure 1) and was followed by contact radiation therapy of the resected tumor scleral bed. Four months later, a nodular relapse of melanoma developed at the margin of the radiation field. Surgery was successful and follow-up was uneventful for 3 years, at which point a conjunctival thickening of the nasal bulbar conjunctiva (3 mm) in the same eye was observed at the margin of the radiation field, questioning a possible relapse of the melanoma. There was no clinical evidence of lymphadenopathy, organomegaly, or systemic lymphoma–related symptoms. Resection of the lesion was performed, and the histologic examination revealed extranodal marginal zone B-cell lymphoma of MALT type. Immunohistochemical analyses showed CD20 positivity, CD3 negativity, and Bcl-2 positivity (Figure 2A-C). Polymerase chain reaction analysis of paraffin-embedded tissue was performed and detected a clonal rearrangement of the immunoglobulin heavy-chain gene at the FR3 locus (Figure 2D). No local recurrence of the melanoma was observed. The staging of the disease, including magnetic resonance imaging of the orbit, computed tomography of the chest and abdomen, bone marrow biopsy, and gastric endoscopy, found an exclusive conjunctival localization with good performance status and a normal serum lactate dehydrogenase level. Because of the complete resection of the lesion and previous irradiation, no complementary treatment was necessary. After follow-up of 24 months, the patient remains in complete remission.
A, Conjunctival malignant melanoma with a diffuse pattern of infiltration of the conjunctiva (hematoxylin-eosin-saffron, original magnification ×10). B, The tumoral cells appear large and epithelioid with atypical nuclei and large nucleoli with no mitotic figure. The epithelium of the conjunctiva is thinner and infiltrated with tumoral cells (hematoxylin-eosin-saffron, original magnification ×40). C and D, Immunostainings with the anti-HMB-45 (C) and anti-PS100 (D) antibodies showing intracytoplasmic positivity of the tumoral cells (original magnification ×40).
A, Mucosa-associated lymphoid tissue lymphoma composed of small lymphomatous cells with round nuclei and dense chromatin. The tumoral cells show a diffuse pattern of infiltration and focally infiltrate the conjunctival epithelium (hematoxylin-eosin-saffron, original magnification ×20). The lymphomatous cells are CD20 positive (B) and Bcl-2 positive (C). B, Immunostaining showing a membranous positivity with the anti-CD20 antibody (original magnification ×20). C, Immunostaining showing intracytoplasmic positivity with the anti–Bcl-2 antibody (original magnification ×20). D, IgH gene rearrangement studies by polymerase chain reaction (PCR) at the FR3 locus on polyacrylamide gel. Lane 1 corresponds to the PCR with DNA extracted from paraffin-embedded conjunctival biopsy. A band in lane 1 between 100 and 150 base pair (bp) assesses the presence of a monoclonal B-cell population. Plus sign indicates positive control; M, bp marker; 1, patient; and minus sign, negative control.
Until now, few patients with both cutaneous melanoma and lymphoproliferative disease have been described in the literature. To our knowledge, the association of a conjunctival melanoma with an NHL of the same localization has never been described until now. A significantly elevated risk of NHL among survivors of cutaneous melanoma and of cutaneous melanoma among survivors of NHL has been reported, supporting the hypothesis of shared genetic or etiologic factors such as immunosuppression, UV radiation, and genetic factors.1,2 The p16 gene, which inhibits cyclin-dependent kinase and was reported to be mutated or deleted in melanoma and lymphoma, has been proposed as a potential candidate for the common pathogenesis of both neoplasms.3
Our observation is noteworthy for the occurrence of 2 different malignant diseases in the same tumor localization. All previously mentioned explanations could be proposed; MALT-type lymphomagenesis is now well described. The lymphomatous process could be a local inflammatory reaction induced by previous irradiation of the conjunctiva; a deregulation of the Fas/CD95/APO-1 pathway, inducing tumor cell tolerance4; and/or an inhibition of the apoptotic process through the Bcl-10 or HIAP-1(human inhibitor of apoptosis protein 1) genes.5,6 In this patient it could be speculated that a dysregulation of apoptotic function, in particular the CD95 pathway, was the mechanism for both melanoma and lymphoma.
This peculiar observation further underlines the need for continued observation in patients treated for a conjunctival malignancy to detect relapses of the initial disease and assess the presence of associated diseases that could arise, as well as the need for additional studies to detect any associated genetic abnormalities.
Correspondence: Dr Lumbroso-Le Rouic, MD, Service d’Ophtalmologie, Institut Curie, 26 rue d’Ulm, 75248 Paris CEDEX 05, France (firstname.lastname@example.org).
Financial Disclosure: None.
Lumbroso-Le Rouic L, Vincent-Salomon A, Desjardins L, Molina TJ, Dendale R, Des Guetz G, Decaudin D. Consecutive Conjunctival Melanoma and Extranodal Marginal Zone B-Cell Lymphoma of MALT Type in an Adult Patient. Arch Ophthalmol. 2005;123(3):397–399. doi:10.1001/archopht.123.3.397