Conjunctival extranodal marginal zone B‐cell lymphoma with crystal‐storing histiocytosis

Abstract

Crystal-storing histiocytosis (CSH) is a rare immunoglobulin storage disorder, associated with lymphoproliferative diseases or seldom with inflammatory or infective conditions (Coupland et al. 2002). The head-and-neck region is most commonly affected by CSH, usually in association with plasma cell neoplasms (Tsuji et al. 2014). Conjunctival involvement by CSH is distinctly uncommon (Yu et al. 2013). Herein, we describe a case of conjunctival CSH associated with an extranodal marginal zone B-cell lymphoma (EMZL). A 58-year-old man was referred to the Liverpool Ocular Oncology Centre in 2008 with a tumour of the right (OD) eye of 2 years duration. The patient had been treated previously for retinal detachment OD, bilateral cataracts and bilateral primary open-angle glaucoma. The best-corrected visual acuity was 6/60 OD and 6/6 OS. A subconjunctival, pink ‘salmon-coloured’ tumour with prominent blood vessels was visible infero-temporally OD (Fig. 1A), extending up to the fornix. There was restriction of right lateral gaze. On echography, the conjunctival tumour had a low internal acoustic reflectivity and measured 12.4 × 10.4 × 6.2 mm on magnetic resonance imaging (MRI). The clinical suspicion was of lymphoma: consequently, a large incisional biopsy was performed and processed for pathological assessment. Conventional histological sections demonstrated conjunctival tissue with diffuse and dense infiltration of small- to medium-sized lymphoid cells (Fig. 1B), comprising small lymphocytes, centrocyte-like cells, monocytoid cells and plasma cells. There were interspersed sheets of larger ‘Gaucher-like’ cells taking up at least 40% of the lesion with abundant eosinophilic pale cytoplasm and small-sized nuclei (Fig. 1C). At higher magnification, ill-defined crystal-like structures could be seen within the cytoplasm of these cells. Immunohistochemically, the atypical lymphoid cells expressed B-cell antigens (Fig. 1E) and demonstrated a monotypical expression for IgM. They were negative for CD5, CD23, CD10 and cyclin D1. In contrast, the above-described larger cells were immunoreactive for CD68 (Fig. 1F), and the cytoplasmic crystals were positive for immunoglobulin kappa light chain. These findings were consistent with conjunctival EMZL with CSH, confirmed on polymerase chain reaction. Subsequent clinical staging investigations revealed Ann-Arbor stage III disease and T2N3 with involvement of mediastinal and abdominal lymph nodes. The bone marrow trephine excluded any underlying plasma cell dyscrasia, such as multiple myeloma or monoclonal gammopathy of unclear significance. The patient was subsequently treated with R-CHOP (rituximab 375 mg/m2 iv; cyclophosphamide 750 mg/m2 iv; vincristine 1.4 mg/m2 iv; prednisone 40 mg/m2 iv). Two months after initiation of chemotherapy, MRI scanning showed complete regression of the residual conjunctival tumour. Five years after initial diagnosis, the patient was disease free but undertaking regular oncological review. This case illustrates a very rare example of conjunctival EMZL with CSH: to date only nine cases of CSH involving the ocular adnexa have been described (Grossniklaus et al. 1990; Coupland et al. 2002; Yu et al. 2013; Radhakrishnan et al. 2014). Most CSH cases have involved the orbit with the conjunctiva being less commonly affected. The CSH component of the tumour can be extensive and can potentially lead to misdiagnoses through sampling error, particularly if a fine needle (aspiration) biopsy has been employed. CSH associated with EMZL typically has a good prognosis, particularly if diagnosed at an early clinical stage, and it usually responds either to localized surgery, radiotherapy and chemotherapy, or combinations thereof. Included in the list of differential diagnosis are infectious aetiologies – for example tuberculosis and fungal infections – as well as non-lymphoid neoplastic conditions, including rhabdomyosarcoma, and pleomorphic sarcoma. These diagnoses are, however, usually possible to exclude on the basis of morphological and immunohistochemical features, as well as special stains for micro-organisms. In conclusion, when diagnosing conjunctival EMZL, a simultaneous CSH should always be considered.