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Natural killer T-cell lymphoma (NKTL) is an uncommon form of systemic lymphoma that derives from natural killer (NK) cells or cytotoxic T lymphocytes, or both. Although nasal or paranasal sinuses are characteristically involved, occurrence within the ocular adnexa is rare where B-cell lymphomas predominate.
We report an NKTL that was initially confined to a lower eyelid, mimicking a follicular conjunctivitis.
A 39-year-old male noted painless, nonpruritic swelling and redness of the right lower eyelid for 2 days. He denied trauma, fever, respiratory infection, or infectious contacts. He took oral medications for diabetes mellitus, hypertension, and hypercholesterolemia. On examination, he appeared healthy except for erythema and follicular reaction of the right lower tarsal conjunctiva without discharge. There was mild lid edema. No local lymphadenopathy was palpable, and there was no proptosis. Uncorrected visual acuity was 20/30 OD and 20/20 OS. Treatment was initiated with bacitracin/polymyxin B ointment for presumed conjunctivitis. Subsequent lid thickening and edema prompted treatment for 10 days with oral amoxicillin/clavulanate for possible preseptal cellulitis with minimal improvement (Fig. 1A, 1B). Consequently, topical tobramycin/dexamethasone, azithromycin, erythromycin, as well as oral doxycycline were prescribed successively for possible chlamydial disease or deep lipogranulomas. There was no change in the lid after 1 month of treatment.
Complete blood count, angiotensin-converting enzyme, Bartonella serology, and HIV testing were all negative or noncontributory. A PPD skin test was positive, but chest radiographs were normal. Subsequently, computed tomography showed enhancement of the right lower eyelid and premaxillary tissues with anterior orbital extension. There was no paranasal sinus or lymph node involvement.
A tarsal conjunctival biopsy revealed perivascular lymphocytic infiltration surrounded by extensive necrotic tissue. Immunohistochemistry showed positive lymphocyte staining for CD3 (T cells) and negativity for CD20 (B cells). Lymphocytes also stained positively for CD2, CD3, CD56, and Epstein–Barr virus (EBV; in situ hybridization), but negatively for CD5, a pattern consistent with the NKTL immunophenotype (Fig. 2).
Further oncologic evaluation disclosed an ulcerated lesion of the left calf and a right testicular mass. Positron emission tomography scan showed increased uptake only in these regions, as well as the eyelid. A bone marrow biopsy result was normal. Results of skin biopsy and orchiectomy were consistent with NKTL, and patient was categorized as stage IV. Chemotherapy was administered using the SMILE regimen (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide), resulting in dramatic improvement in the eyelid swelling after 3 months (Fig. 3). Allogeneic hematopoietic stem cell transplantation is planned.
NKTL is a rare subset of lymphoma within the ocular adnexa. The largest study of ocular adnexal lymphomas documents only 1 NKTL within 353 cases.
The tumour appears to be driven by EBV and is highly aggressive, previously having a poor prognosis. Treatment with l-asparaginase–containing regimens such as SMILE represents a recent promising advance in clinical trials.
This case began as a puzzling lid swelling that subsequently spread to the orbit. Eyelid biopsy should be considered whenever there is poor response to anti-infectious medications.
When faced with a challenging case such as this one, the clinician should communicate verbally with the pathologist about biopsy requirements. If a lymphoid infiltrate is suspected, a 5-mm2 (pencil eraser size) portion of the specimen should be submitted unfixed (fresh) for flow cytometry that will sort leukocytes into their various immunophenotypes; this often provides a rapid diagnosis. The remainder of the specimen is placed in 10% buffered formalin that will allow processing for routine stains, immunohistochemistry, polymerase chain reactions, and electron microscopy that are chosen by the pathologist.
For tarsal biopsy, after lidocaine injection, a chalazion or other lid clamp stabilizes the lid. Target tissue is outlined with a scalpel blade and excised with Westcott or other fine scissors in a gentle fashion to avoid histologic crush artifact. Bulbar conjunctival biopsy involves “ballooning” up tissue by subconjunctival injection and excising with fine scissors.
Although the clinical diagnosis of NKTL may be elusive, the necrotizing histopathologic pattern of perivascular lymphocytes with overwhelming majority staining for T-cell markers such as CD3 and CD56 is characteristic. CD56, a glycoprotein involved in cell–cell adhesion, may be found in melanoma cells and neuroendocrine malignancies. Within lymphocytes, however, it is diagnostic for the NK phenotype. Also important in identifying the EBV-driven lymphoma is the demonstration of EBV-encoded RNA within lymphocytes by in situ hybridization.
Lymphoma of the ocular adnexa: a study of 353 cases.