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Show / oll", al of Clillical Nellro~ ophtha{ I1I,,{ oglfSO): 47-- l8, 1988 Invited Editorial , 19xx Raven Press, Ltd, New York Evaluation of Lymphoproliferative Disorders The Ophthalmologist's Role In response to the preceding editorial, the following remarks were kindly provided by Or. Grossniklalls, who was recommended hi another nlelnba of the Editorial Board as being essen'tially " Joe Immunology" f J. L. s. Our immune surveillance system is truly amazing, with a cadre of cells, each specifically designed to carry out a preordained mission in the battle against potential disease. Macrophages and various types of lymphocytes are the foot soldiers of our immune surveillance army. These cells may proliferate in their battle against foreign antigens, and just as any tissue in the body may react to a stimulus, so do these cells. The critical distinction to the clinician and the pathologist is whether the cellular response is benign or malignant. Benignity implies a self- limited process, whereas malignancy portends invasion, destruction, uncontrolled growth, and metastatic spread. Other questions raised include: What is the natural history of benign lymphocytic proliferations? What are " atypical" or " borderline" lymphoid proliferations) What is the clinician's role in establishing a diagnosis? To answer these questions one must realize that malignancy implies monoclonality; that is to say, one cell in a presumably benign proliferative process goes awry and reproduces exact copies of itself in an uncontrolled manner. Methods of detecting malignancy include microscopic examination of tissue, histochemical studies ( including immunoperoxidase staining), and computerized counting of individual cells labeled from a specimen ( cell flow cytometry). Benign proliferations are polyclonal; however, just by virtue of the fact that the lymphoid tissue is active, a malignant monoclonal cell line or new genotypically distincct clones of cells may arise, being harbingers of aggressive behavior ( 1,2). For this reason, complete excision and/ or radiation therapy is advised for polyclonal ( benign) lymphoid hyperplasias of the ocular adnexa ( 2). Borderline lymphoproliferative lesions are those that 47 are not unequivocally benign on histologic examination. These mayor may not progress to malignant lymphoma ( 3). In such cases, information about the c10nality of the lesion determined by immunohistochemistry and cell flow cytometry of fresh tissue is particularly helpful ( 3). The clinician's role in establishing a diagnosis includes, first and foremost, physical examination of the patient. Are the tonsils or any lymph nodes enlarged? Is hepatosplenomegaly present? You may wish to refer your patient to an internist or oncologist to aid in answering these questions. Computed tomography of the chest and abdomen may disclose occult enlarged lymph nodes. If a biopsy is obtained ( periocular, bone marrow, etc.), the " gold standard" for pathologic evaluation is direct histologic examination ( light microscopy). The tissue may be placed in a special fixative suitable for preservation of lymphoid cellular detail ( e. g., B- 5). If enough tissue is obtained, frozen sections may be made for determination of cell markers by immunohistochemical stains. If a relatively large amount of tissue ( in ophthalmologic terms, greater than 1 g) is available, a portion may be sent for flow cytometry. The most important examination of fluids ( e. g., spinal fluid) in the evaluation of lymphoproliferative processes is again direct light microscopy ( cytology). Smears or cytospins of fluid should be quickly fixed in alcohol or another fixative for preservation of cellular detail. Immunohistochemical stains may be performed on cytology specimens. Here again, if enough fluid is obtained, cell flow cytometry is the next step. The currently available methods of immunohistochemistry and cell flow cytometry are aids to light microscopic examination of lymphoid tissue to determine if it is benign, atypical, or malignant. The pathologist will consider all information available ( including clinical information) when he or she interprets the case. Do you need to remember how tissue should be submitted and for what purposes when evaluating a patient with a lymphoproliferative disorder? No! You just need to remember one thing- call your pathologist before 48 INVITED EDITORIAL you obtain the specimen so he or she may advise you how to submit it. Hans E. Grossniklaus, M. D. Departments of Ophthalmology and Pathology Case Western Reserve University Cleveland, Ohio. I Clin Nt'I/ ro- ophthlll/ llIJ/. \' ltJ. 8. ;'\; 0. J. 19S,.... · REFERENCES 1. McNally L, Jakobiec FA Knowles OM. Clinical, morphologic, immunophenotypic, and molecular genetic analysis of bilateral ocular adnexal Ivmphoid neoplasms in 17 patients. Alii' OpiJIlwllllo/ 1987; 103: 555- 68. 2. Jakobiec FA, Neri A Knowles OM. Genotypic monoclonality in immunophenotypically polyclonal orbital lymphoid tumors. A model of tumor progression in the lymphoid system. The 1986 Wendell Hughes Lecture. Ophthallllology 1987; 94: 980- 94. 3. Harris NL. Harmon DC, Pilch BZ, Goodman ML, Bhan AK. Immunohistologic diagnosis of orbital lymphoid infiltrates. Alii' Surg Plltho/ 1984; 8: 83- 91. |
