Lacrimal gland extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue type associated with massive amyloid deposition
Editor, E xtranodal marginal zone lymphoma (EMZL) is a mature B cell neoplasm characterized bymonotypic immunoglobulin light chain expression, occurring in a variety of extranodal tissue sites, often arising in the setting of autoimmune disease or chronic inflammation. Generally, EMZL are low grade and manifest a clinically indolent behaviour usually responding well to localized radiotherapy (Ryan et al. 2012) Amyloid light chain (AL) amyloidosis, the commonest form of systemic amyloidosis, is typically secondary to a plasma cell dyscrasia producing amyloid forming monotypic immunoglobulin light chains resulting in widespread organ deposition and dysfunction (Leibovitch et al. 2006) Although not an unprecedented finding extraocularly, extensive amyloid deposition associated with EMZL is rare in the orbit (Haas &Margo 2007) or ocular adnexa (Topalkara et al. 2007) and has not been previously reported in the lacrimal gland. A 72 year old man was referred with painless progressive swelling and ptosis of his left upper lid for 2 years, restricting his visual field (Fig. 1A) He was systemically well. Computed tomography (CT) scanning showed a 2.6 9 1 9 2 cm homogenous mass in the left lacrimal gland with no calcification or fatty component. The mass was separate from the globe with no adjacent bony destruction (Fig. 1B) Lacrimal gland biopsy revealed a lowgrade EMZL of mucosa associated lymphoid tissue (MALT) type (Fig. 1C E) A solitary smooth painless occipital lump was also noticed. Excision biopsy was consistent with low grade marginal zone lymphoma of the posterior cervical lymph nodes, that is the same type as in the orbit. Whole body staging CT scan did not identify organomegaly nor any other lymphadenopathy. Full blood count was normal suggesting no bone marrow involvement. No paraprotein was detected in the blood. Renal and liver functions were normal. The tumour was unresponsive to localized radiotherapy (24 Gy) with no significant change in size on magnetic resonance imaging. The residual mass was therefore excised via an anterior orbitotomy approach (Fig. 1F) Histological sections consisted of lacrimal gland with focal lymphocytic infiltrates and adjacent multinucleate giant cells with extensive deposition of amorphous acellular material with birefringence in the Congo red stain, consistent with amyloid (Fig. 1G I) The lymphocytes were positive for CD20 and were monotypical for the immunoglobulin (Ig) light chain lambda and for IgM. Serum free light chains showed a normal kappa:lambda ratio and urine was negative for Bence Jones protein, suggestive of localized AL amyloidosis associated with a lacrimal gland EMZL. In the largest series (20 cases) all patients with EMZL and simultaneous amyloid deposition demonstrated both diseases at the same body site (Ryan et al. 2012) None had amyloid involving the heart, kidneys or liver. Amyloid subtyping in these patients showed monotypic binding of antibodies consistent with the amyloid arising from excess monoclonal immunoglobulin light chains produced by neoplastic plasma cells of the EMZL, representing a form of localized AL amyloidosis. Lacrimal gland localized AL amyloi dosis has been previously attributed to deposition of monoclonal immuno globulin light chains by a local clone of benign plasma cells (Conlon et al. 1991; Leibovitch et al. 2006) but never due to lacrimal gland EMZL. Similarly, in our case, amyloid deposition remained localized to the lacrimal gland. The extensive amyloid deposition perhaps explains the poor response of our patient's EMZL to radiotherapy, requiring surgical debulking, which remains the principle treatment modality for localized orbital AL amyloidosis (Leibovitch et al. 2006) In conclusion, the presence of amyloid in EMZL does not seem to be associated with systemic AL amyloidosis or poor prognosis. It is not an indication for more extensive investigations for systemic amyloidosis or aggressive therapy than would otherwise be warranted for EMZL of similar clinical stage (Ryan et al. 2012) Furthermore, ophthalmic pathologists should be aware of this association when reviewing orbital biopsies because bulky amyloid deposits may mask an underlying lymphoid neoplasm.
Acta ophthalmologica