VITRITIS AS THE INITIAL MANIFESTATION OF RECURRENT MYCOSIS FUNGOIDES Michael J. Wan, BSC,* Tom G. Sheidow, MD, FRCSC,*† Glenn W. Jones, BSC, MSC, MD, FRCPC,‡ J. Godfrey Heathcote, MB, PHD, FRCPC§
Purpose: To report a case of mycosis fungoides in which vitritis was the earliest manifestation of recurrence. Methods: A 52-year-old man was followed-up from his initial presentation with vitritis to his death due to recurrent mycosis fungoides over a 5-month period. Results: The patient presented with progressive visual loss in the left eye. Slit-lamp examination revealed severe vitritis, and analysis of a vitreous fluid sample demonstrated a monomorphic population of abnormal T-cell lymphocytes, typical of mycosis fungoides. Three months after developing vitritis, the patient had extraocular recurrence of the disease, and he died 2 months later. Conclusion: Recurrent mycosis fungoides may present with isolated intraocular involvement. RETINAL CASES & BRIEF REPORTS 3:240 –242, 2009
tent of skin involvement and usually presents as regional lymphadenopathy.3 Metastatic spread beyond the lymph nodes typically manifests in the lungs, spleen, liver, or gastrointestinal tract, although any organ, including the eye, can become involved.4 We report an unusual case of mycosis fungoides in which vitritis was the initial manifestation of recurrent disease.
From *Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada; †Ivey Eye Institute, London, Ontario, Canada; ‡Peel Regional Oncology Program, Department of Radiation Oncology, Credit Valley Hospital, Mississauga, and McMaster University, Hamilton, Ontario, Canada; and §Departments of Pathology and Ophthalmology & Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.
ycosis fungoides is the most common type of cutaneous T-cell lymphoma, although it comprises only 0.5% of all cases of nonHodgkin lymphoma. The peak age at onset is between 50 years and 60 years, with a male-to-female ratio of just ⬍2-to-1.1 Patients with mycosis fungoides classically present with scaly patches or plaques on their trunk, buttocks, and proximal thighs. Although generally incurable, the disease tends to run an indolent course provided it remains confined to the skin.2 Extracutaneous spread is highly correlated with the ex-
A 52-year-old man was referred to our institution with a 10-day history of progressive loss of vision in the left eye associated with floaters and flashes of light. There was no history of photophobia, diplopia, ocular pain, jaw pain, headaches, or trauma. Ocular history was noncontributory. Medical history included “skin cancer” and chronic gastritis. At examination, visual acuity was 20/30 in the right eye and 20/50 in the left eye. There was a mildly positive relative afferent pupillary defect in the left eye. Intraocular pressure was 14 mmHg in the right eye and 18 mmHg in the left eye. Results of external examination were unremarkable, but anterior segment evaluation revealed bilateral keratic precipitates, more prominent in the left eye. Slit-lamp examination disclosed marked vitritis with a dense vitreous haze in the left eye and mild vitritis in the right eye. The retina was normal in both eyes with no evidence of hemorrhage, vasculitis, or detachment. After the initial assessment, the differ-
The authors have no proprietary interest in this study. Reprint requests: Tom Sheidow, Ivey Eye Institute, 750 Commissioners Road East, London, Ontario, N6A 4G5, Canada; e-mail: [email protected]
VITRITIS SECONDARY TO MYCOSIS FUNGOIDES
Fig. 1. Funduscopic photograph before pars plana vitrectomy.
Fig. 3. The atypical lymphoid cells have prominent nucleoli and irregular nuclear contours (modified Papanicolaou stain; original magnification, ⫻500).
ential diagnosis included infectious, immunologic, and neoplastic conditions. Results of skin examination were negative. Complete blood cell count, electrolyte levels, serum angiotensinconverting enzyme level, and findings of urine chemistry analysis and chest roentgenography were all unremarkable. Serologic tests were negative for Lyme disease and syphilis. At follow-up 2 weeks later, visual acuity in the left eye had further deteriorated to 20/100 (Fig. 1). Diagnostic pars plana vitrectomy was performed to obtain a sample of vitreous fluid from the left eye. Microscopic examination of the vitreous fluid revealed a monomorphic population of atypical lymphoid cells with thick nuclear membranes, irregular nuclear contours, and one or two recognizable nucleoli (Figs. 2 and 3). There were also numerous apoptotic cells, and mitotic figures were readily identified. A few larger cells with abundant cytoplasm typical of histiocytes were present. Immunohistochemical analysis demonstrated that ⬇50% of the atypical lymphoid cells expressed UCHL1 (Fig. 4), but there was no expression of L26, confirming the T-cell nature of the abnormal cells (Fig. 5). The patient’s radiation oncologist was contacted, and it was discovered that the patient had a biopsy-confirmed diagnosis of mycosis fungoides, which had initially presented in the skin and had been treated with total skin electron beam radiotherapy 18 months earlier. His presenting tumorous, plaque, and patch disease on the skin had cleared completely after radiotherapy, and one subsequent patch on the
Mycosis fungoides has been associated with several diverse ocular manifestations.3 Stenson and Ramsay5 followed 30 patients with mycosis fungoides over a 5-year period and found that 37% developed ocular abnormalities directly related to the underlying malignancy, including eyelid tumors, conjunctival tumors, lacrimal caruncle tumors, keratitis, and optic atrophy.
Fig. 2. Highly cellular vitreous contains numerous atypical lymphoid cells (modified Papanicolaou stain; original magnification, ⫻240).
Fig. 4. Immunoperoxidase study of vitreous aspirate using antibodies to the T-cell antigen UCHL1 (original magnification, ⫻320).
skin 6 months later (i.e., first relapse that was biopsy confirmed) was managed successfully with limited local radiation. Three months after presenting with vitritis (i.e., his second relapse), the patient also developed metastatic involvement of the left breast. He was then treated with local radiation to the left eye and left breast. Before the treatment response could be fully assessed, the patient had a seizure, and magnetic resonance imaging confirmed central nervous system metastasis. The patient received local radiation to the brain but stopped therapy after a few weeks due to progressive neurologic symptoms. He died 1 month later, 24 months after initial diagnosis of mycosis fungoides, and an autopsy was not performed.
RETINAL CASES & BRIEF REPORTSℜ
Fig. 5. Immunoperoxidase study of vitreous aspirate using antibodies to the B-cell antigen L26. There is no expression of the antigen (original magnification, ⫻500).
However, intraocular involvement was uncommon, with uveitis manifesting only in one case. The intraocular spread of mycosis fungoides is very rare, with only a few case reports in the literature.6 –10 Previous reports on mycosis fungoides have demonstrated that malignant lymphocytes can invade the vitreous cavity, inner retina, optic nerve, choroid, and the space between the retinal pigment epithelium and Bruch membrane. Intraocular spread of mycosis fungoides usually becomes apparent late in the course of the disease when there is advanced cutaneous involvement. Our case is unusual in that intraocular metastasis and vitritis occurred as the initial manifestation of the second recurrence, without concomitant overt skin or nodal involvement and without prior episodes of visceral disease. If ocular involvement of mycosis fungoides is suspected, it is important to obtain pathologic confirmation. Ocular metastases elevate the clinical stage of the disease to IVB, which is associated with a very poor prognosis. Treatment at this advanced stage of the disease is limited. In our case, the patient received a palliative course of radiotherapy to the left eye, but he died before the effect of the treatment could be assessed. Previous case reports have indicated that both external beam radiotherapy6 and systemic chemotherapy9 may have beneficial effects on ocular metastases and other visceral sites of disease.4,11 Therefore, for any patient with ocular spread of mycosis fungoides, it is essential to establish close collaboration among the ophthalmologist, dermatologist, pathologist, and medical and
radiation oncologists to optimize management. It is interesting that when mycosis fungoides progresses at any visceral site, in a subset of cases it follows the kinds of patterns of distribution that are well established in other extranodal nonHodgkin lymphomas.11 One such pattern is eye and brain, as demonstrated in our case. In addition to some spatial patterns, clinical progression to multiple visceral sites with mycosis fungoides is typically staggered temporally, with an average interval of ⬇6 months between clinical events.11 In conclusion, ocular involvement with mycosis fungoides is a rare and potentially manageable condition that is associated with a poor prognosis because of serious associated skin or visceral disease. Key words: lymphoma, mycosis fungoides, vitrectomy, vitreous body, vitritis. References 1.
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