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* Emeritus Staff. † Current address: University of Texas Health Science Center, San Antonio, Texas. ‡ Current address: Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina.
In a 52-year-old man with drooping of the right upper eyelid and a palpable mass in the superior temporal quadrant of the right orbit, a biopsy specimen revealed diffuse mixed-type lymphoma with immunostaining evidence of a helper T-cell phenotype. No other foci of lymphoma were found. The orbital lesion was treated with irradiation (total dose, 4,200 cGy administered in 20 treatments). At 4 ½ years after treatment, the patient had had no recurrence.
In general, T-cell malignant lesions in extranodal sites occur infrequently and may be variable in their expression of phenotypic markers, their clinical characteristics, and their morphologic features. To date, most of the T-cell malignant tumors with orbital manifestations reported in the literature occurred in patients with the disseminated or “tumor” stage of mycosis fungoides.
In such patients, the diagnosis usually has been based on biopsy specimens of the skin or of some extracutaneous site of involvement other than the orbit. The orbital manifestation of the systemic process has rarely been subjected to phenotypic marker studies.
Herein we describe a patient with a T-cell lymphoma entirely confined to the orbit, apparently the first lymphoma of this type to be reported solely in this extranodal site. Also noteworthy is the extended period of follow-up observation of our patient.
REPORT OF CASE
In October 1983, a 52-year-old man was examined because of painless swelling and drooping of the right upper eyelid of 2 months' duration (Fig. 1). In addition, he had ptosis (4 mm) and nonerythematous edema of the right upper eyelid. A discrete, nontender, slightly movable, firm mass was palpable in the area of the lacrimal gland. This mass produced some forward displacement of the palpebral lobe of the lacrimal gland, but the patient had neither displacement nor proptosis of the eye. Computed tomography of the orbit confirmed the presence of a tumor limited to the lacrimal gland fossa with no evidence of erosion or destruction of bone (Fig. 2). The mass was homogeneous and had a well-delineated posterior border that was angulated where the mass abutted the bone laterally. These features suggested a benign lacrimal gland neoplasm, a lymphoma, or an inflammatory lesion within the confines of the lacrimal gland.
On several prior occasions, the patient had been examined because of an erythematous, scaling dermatitis of the face and a generalized dryness of the skin of the trunk and extremities. At the time of the initial assessment in January 1974, a skin biopsy specimen from the malar area showed an acute dermatitis with telangiectases. The response to topical therapy was equivocal. Another skin biopsy specimen from the left medial canthal area in March 1974 was diagnosed as a necrotizing dermal granuloma suggestive of rheumatoid granuloma. In December 1975, an additional biopsy was performed on two small subcutaneous nodules that had developed in the skin of the upper nasal area. The biopsy specimen showed fibrinoid change of the dermal collagen with a histiocytic reaction consistent with rheumatoid granuloma or granuloma annulare. Topical therapy was continued intermittently, and the patient experienced remissions and exacerbations of the facial dermatitis during the 9-year period 1974 through 1982.
Several months before the onset of the ptosis and swelling of the right upper eyelid, the pattern of the skin disease changed. In addition to the chronic dermatitis of the face, dirty-brown plaques and ichthyosiform eruptions developed on areas of the trunk and legs, and infiltrative nodules appeared on the thighs. Biopsy of a nodule from the thigh and a plaque from the skin of the chest was performed in November 1983. The biopsy specimen of the nodule was reported as a superficial and deep palisading granuloma with necrobiosis. The biopsy specimen of the plaque was thought to be consistent with ichthyosis and palisading granuloma, features suggestive of necrobiosis lipoidica. A possible clinical diagnosis of mycosis fungoides also was considered, but no proof of this diagnosis was found. Bone marrow studies disclosed no abnormalities. Computed tomography of the abdomen revealed no evidence of hepatosplenomegaly or periaortic lymphadenopathy. Immunoelectrophoretic studies of serum showed no monoclonal proteins. Serum immunoglobulin concentrations were within normal ranges.
On Nov. 8, 1983, an anterolateral superior right orbitotomy was performed (by R.P.Y.). An infiltrative tumor was disclosed in the lacrimal gland area. On frozen-section examination of a specimen, the diagnosis was inconclusive. Several additional tissue specimens from the mass were removed for fixed tissue and immunohistochemical study.
Microscopic study of the fixed tissue specimens revealed a diffuse mixed-type lymphoma with unusual cellular morphologic features suggestive of T-cell phenotype (Fig. 3). Larger cells exhibited abundant clear cytoplasm, and unusually complex folding of the nuclear membrane was present among lymphoid elements, ranging from large to small. Proliferation of epithelioid venules and a diffuse interspersion of inflammatory elements, including plasma cells, eosinophils, and epithelioid histiocytes, were evident. Immunostains of sections from samples of tumor snap-frozen in liquid nitrogen and stored at −70°C showed strong predominant cell surface reactivity for pan-T antigen Leu-1 (CD5) and helper subset antigen Leu-3 (CD4) but not for pan-B antigen Leu-14 (CD22) or κ or λ light chains. These findings were interpreted as most consistent with a peripheral T-cell neoplasm of helper T-cell phenotype, substantially different from the lymphomas localized to the orbit usually encountered in adults. Such lymphomas are characteristically monoclonal B-cell proliferations that show a diffuse, monomorphic collection of small, mature lymphocytes with hyperchromatic, regularly contoured nuclei. Mitotic figures are sparse, and other types of leukocytes are absent. They are classified as well-differentiated lymphoma in the widely used Rappaport classification.
The orbital lesion was treated with irradiation (total dose, 4,200 cGy administered in 20 treatments), and the mass eventually disappeared. Computed tomography of the right orbit on May 17, 1984, showed complete resolution of the tumor (Fig. 4).
At the time of last examination in January 1986, the patient had no clinical evidence of local recurrence of the tumor or of systemic disease. The skin disease was considered stable. When contacted by telephone in May 1988, the patient considered his health to be good and was unaware of any local recurrence or systemic illness that could be related to the orbital tumor.
In the 1970s, the immunologic study and typing of the lymphoproliferative disorders were important supplements to the standard cytomor phologic methods then in use for the diagnosis and classification of the lymphomas. The fact soon emerged that most human non-Hodgkin lymphomas in the Western world were of B-cell lineage.
At that time, the thymus-derived (T-cell) lymphocyte was believed to play only a secondary or reactive role in malignant lymphoma of the orbit.
In the 1980s, the availability of monoclonal antibodies, some of which were highly specific as T-cell lineage markers, facilitated reliable identification of T-cell populations and lymphocytic subsets in tissue preparations,
who analyzed the immunocytologic profile of an excisional biopsy specimen from a mass in the upper eyelid of an 82-year-old woman. The extent of orbital involvement could not be accurately assessed because computed tomography of the orbits was not performed. The tumor showed a preponderance of T lymphocytes (54%), as assessed with OKT3 (CD3) antibody. A large proportion of these lymphocytes reacted with OKT4 (CD4) antibody, considered to detect helper/inducer T-cell subsets. Only 11% of the cells had immunoglobulin on their surfaces, an indication of a paucity of lymphocytes of B-cell lineage. The cells also were devoid of Ia-like antigens, as detected by OKI antibody. Light microscopy showed the tumor to be composed of large lymphoid cells with an irregular cleaved nucleus, dense chromatin pattern, and relatively prominent nucleoli, characteristics suggestive of a possible T-cell origin. On the basis of these features, combined with the cell marker profiles, the tumor was considered a T-cell lymphoma, although Laroche and colleagues pointed out that the monoclonality of the tumor could not be definitely proved. After radiotherapy to the orbit, follow-up of the patient was continued for 4 months.
Interestingly, in the case reported by Laroche and associates,
40% of the mononuclear cells were reactive with OKM antibody, an indication of a sizable content of cells of histiocytic lineage. These cells might be a reactive supplement to the principal population of T cells in the tumor, a reactive feature occasionally evident in both B- and T-cell lymphomas. A less likely possibility is that the histiocytes might have been a principal component of the assumed malignant lesion, in which case the patient might have had a T-cell-rich pseudolymphoma, a possibility suggested by Jakobiec and colleagues.
The chronic skin disorder in our patient raises the question of whether the orbital lesion was a true, isolated, extranodal focus of lymphoma or an early manifestation of the dissemination stage of a previously unappreciated mycosis fungoides. The latter seems unlikely because of the 9-year duration of the skin disorder and the almost 6 years that have elapsed since the orbital tumor was diagnosed. Progression of cutaneous T-cell lymphomas to a higher grade generally occurs rapidly and in widespread distribution.
In retrospect, in our patient the clonality of the lymphoma could have been defined further by use of molecular genetic analysis, had such a procedure been available at the time of biopsy of the orbital lesion (1983). These new molecular genetic techniques can identify rearrangement of the segments of DNA that constitute the antigen receptor genes and allow more accurate assessment of the clonality of a lymphoid neoplasm than has been possible by the standard morphologic assessment and immunologic studies used previously.
Likewise, the presence or absence of so-called mycosis cells in the earlier skin biopsy specimens from our patient might have been clarified by use of the wide spectrum of monoclonal antibodies now available for the identification of various T-cell lymphocytes.
Mycosis fungoides: subcutaneous and visceral tumors, orbital involvement, and ophthalmoplegia.