Blindness in a patient with chronic lymphocytic leukemia
Authors: Karin A. Ackermann, Werner J. Z'Graggen, Marwan El‐Koussy, Marco Caversaccio, Istvan Vajtai, Giuseppe Colucci
Journal: American Journal of Hematology (2011)

A 73-year-old patient with newly diagnosed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma fulfilling the criteria for CLL Rai stage II, Binet B, was treated with the single agent fludarabine. After four cycles of therapy, staging demonstrated treatment failure, and six courses of combination chemotherapy with fludarabine, cyclophosphamide, and rituximab were performed. The patient achieved complete remission and the subsequent clinical course was uneventful. Three years later, he developed recurrent upper airway infections and complained of chronic postnasal drip. Over 2 months, he developed, in addition, a slowly progressive, painless, bilateral visual loss with concentric restriction of visual fields and was referred to our institution. Ophthalmologic examination of the patient revealed visual acuity of hand motions OD, finger counting OS, and poorly reactive pupils. Ophthalmoscopy showed atrophy of the optic nerve on both sides. Neurological examination was otherwise normal. Extended laboratory and clinical findings were consistent with CLL Rai stage IV (white blood cell count 41.4 G/l, 77% lymphocytes, hemoglobin 131 g/l, platelet count 92 G/l). Investigation of the cerebrospinal fluid showed slight lymphocytic pleocytosis (11 M/l) and protein elevation (0.56 g/l). Results of a biopsy of the vitreous body revealed unspecific, polyclonal lymphocytic infiltrates. Magnetic resonance imaging of the head and orbita showed a mass in the left nasal cavity (Image 1A and B), thickening of the respiratory mucosa (Image 1A–C), and an enlarged chiasma opticum (Image 1D). After administration of gadolinium, enhancement of the respiratory mucosa and optic chiasma was observed (Image 1B, C, and E). The mass in the nasal cavity was removed by ethmoidectomy. Histological examination showed a pleomorphic adenoma and infiltrates of lymphocytes in the respiratory mucosa, consistent with CLL infiltration without signs of transformation into a high-grade lymphoma (Image 2A–C). After surgery, the patient was treated with high-dose of intravenous steroids, which did not improve his vision. As infiltration of the optic nerve and the chiasma opticum was apparent, local radiation therapy was applied. Despite all therapeutic efforts, the patient went blind and died 6 months later. Magnetic resonance imaging of the head and orbita. (A,B) Solid mass lesion (*) in the left nasal cavity just anterior to the left middle nasal concha, maximal diameter 19 × 10 mm. The mass is isointense to the soft tissues in the T1-weighted images (A) and enhances homogeneously after intravenous administration of contrast medium (B). (C) Thickening of the respiratory mucosa in the T1-weighted, contrast-enhanced image. (D) The optic chiasm appears hyperintense and slightly enlarged (arrow) on the coronal T2-weighted image. (E) Coronal T1 fat-saturated post-gadolinium image showing faint enhancement in the optic chiasm. Histopathological features of chronic lymphocytic leukemia involving the sinonasal mucosa. (A) Overview of biopsy sample from the ethmoid sinus shows diffuse infiltration of the subepithelial connective tissue layer by a population of monomorphous small lymphocytes. Rudimentary follicular aggregate of neoplastic cells is evident between arrows (hematoxylin and eosin; original magnification ×100). (B,C) Immunophenotype of the infiltrate to indicate composition by B lymphocytes. Membrane-bound expression of CD20 is shown in B, while C shows the lineage-related transcription factor PAX-5 localized to the nucleus. Note the absence of destruction of seromucinous glands by the tumor cells. Scarcity of reactive intralesional T lymphocytes is apparent in the lower right corner in C (inset). The monotypic character of B lymphocytes is not shown (3-3′ diaminobenzidine; original magnification ×400). Progressive loss of visual acuity is very rare as an early clinical manifestation of CLL [1]. In advanced disease, opportunistic infection, extraocular muscle or ocular infiltration, and central nervous system, optic nerve, or chiasm involvement, as in this case, should be ruled out [2, 3]. On clinical suspicion, a diagnostic workup is needed to exclude transformation of CLL into a high-grade lymphoma.