Chronic Lymphocytic Leukemia of the Orbit

A 78-year-old man was referred to our clinic for evaluation of bilateral ptosis that developed over the previous 2 months. His ocular history was remarkable for cataract extraction and intraocular lens implantation in both eyes 1 year prior to initial examination. His medical history was significant for chronic lymphocytic leukemia (CLL) diagnosed 7 years earlier during a laboratory workup for anemia (hematocrit, 22.1%) and lymphocytosis (white blood cell count, 150 × 10³/µL), which was detected on results of routine blood work. There was no lymphadenopathy or splenic enlargement at the time of diagnosis, consistent with stage 0 CLL. He did not require treatment.

At initial examination, his visual acuity was 20/30 OU. The examination findings were notable for normal pupils, severely limited ductions in all directions in both eyes, and bilateral ptosis (Figure 1). Levator function was 2 mm OU. Palpation revealed marked resistance to retropulsion in both eyes.

Computed tomography demonstrated enlargement of all extraocular muscles in both eyes, with mild enlargement of the lacrimal glands and soft tissues of both upper and lower eyelids (Figure 2).

The patient underwent anterior orbitotomy with biopsy specimens obtained from the anterior orbital fat. Histologic examination revealed a dense infiltrate of small lymphocytes that stained positive for IgD kappa, CD5, CD19, CD20, and CD23, consistent with B-cell CLL. These marker studies were identical to the pattern observed at the time of initial diagnosis of CLL.

He was treated with local radiation to both orbits consisting of 200 rad (200 cGy) per fraction over 10 fractions. This resulted in complete resolution of his ptosis and restoration of normal motility in both eyes at 1 month after initiating treatment (Figure 3). A computed tomography scan obtained 3 months after beginning radiation treatment demonstrated reduction in the size of the extraocular muscles.

When the diagnosis of orbital CLL was made, he was referred to his hematologist/oncologist for systemic evaluation. Blood work results revealed a white blood cell count of 8.3 × 10³/µL and hematocrit of 30%. There was no lymphadenopathy or splenomegaly. These findings suggested that the orbital recurrence of the CLL was not associated with systemic recurrence. He remained unchanged at last follow-up 14 months after initial examination and had no evidence of recurrence, either within the orbit or systemically.

Chronic lymphocytic leukemia is the most common type of leukemia in the United States. It is usually B cell in origin and is characterized by the proliferation of lymphocytes that accumulate within the blood, bone marrow, lymph nodes, and extranodal tissues. Patients are typically older than 50 years, and the disease is more common in men.

Leukemia, in general, has been reported in tissues throughout the eye, as well as in the orbit and adnexal structures. Clinically, these structures are more involved in acute leukemias, with retinal findings most frequently observed. Acute leukemia is well known for its ability to manifest within the orbit as a granulocytic sarcoma, or chloroma, usually in children.

Autopsy studies have shown ocular and periocular involvement of chronic leukemia in 75% of patients.^1,2 Clinically, CLL may be observed in structures throughout the eye.³ Several manifestations of CLL have been reported in and around the orbit, including infiltration of the lacrimal sac resulting in epiphora and dacryocystitis,^4-6 lacrimal gland swelling,⁷ sicca syndrome (without lacrimal gland enlargement),⁸ optic nerve infiltration,⁹ proptosis,^10,11 ophthalmoplegia,^10,11 ptosis,¹¹ and orbital apex syndrome.¹¹

The patient in this report differs from previous reports of CLL involving the orbit in several ways. First, previously reported manifestations of orbital CLL infiltration include a diffuse orbital mass¹⁰ and unilateral extraocular muscle enlargement.¹¹ Radiographically, our patient had findings suggestive of thyroid-associated orbitopathy, namely, enlargement of the extraocular muscles bilaterally. We are unaware of this manifestation of CLL having been reported previously. Clinically, his near total ophthalmoplegia and ptosis suggested a disease entity other than thyroid-associated orbitopathy. However, the radiographic findings shown here suggest that CLL should be included in the differential diagnosis of bilateral extraocular muscle enlargement.

Second, CLL seen within the orbit has been described as the initial manifestation of the disease or occurring in patients with active and, in some cases, worsening systemic disease.^4-6,9,10 Our patient had no evidence of systemic disease activity at the time of diagnosis and, in fact, his blood cell counts at the time of diagnosis of his orbital CLL were at their best since his initial CLL diagnosis. To our knowledge, there have been no reports of periocular or orbital manifestation of CLL in the setting of systemic remission. While secondary lymphopoietic tumors have been reported in association with CLL (Richter syndrome),^12-14 the identical tumor markers in specimens from the orbit and from initial diagnosis suggest that the orbital manifestation was part of the same disease process. This observation suggests that the possibility of local orbital recurrence should be considered despite a seemingly indolent disease course.

Corresponding author and reprints: Peter A. D. Rubin, MD, Department of Oculoplastics, Orbit, and Cosmetic Surgery, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114. (e-mail: eye_plastics@meei.harvard.edu).