Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

Lee-Wang M, Oryschak A, Attariwala G et al.: Rosai–Dorfman disease presenting as bilateral lacrimal gland enlargement. Am J Ophthalmol 131:677, 2001

Malone M: The histiocytosis of childhood. Histopathology 19:105, 1991

Meyer CT, Sel S, Hörle S et al.: Rosai–Dorfman disease with bilateral retinal detachment. Arch Ophthalmol 121:733, 2003

Miller ML, Sassani JW, Sexton FM: Di use histiocytosis X involving the eyelid of a 65-year-old woman. Am J Ophthalmol 113:458, 1992

Mittleman D, Apple DJ, Goldberg MF: Ocular involvement in Let- terer–Siwe disease. Am J Ophthalmol 75:261, 1973

Trocme SD, Baker RH, Bartley GB et al.: Extracellular deposition of eosinophil major basic protein in orbital histiocytosis X. Ophthalmology 98:353, 1991

Tsai JH, Galaydh F, Ching SST: Anterior uveitis and iris nodules that are associated with Langerhans cell histiocytosis. J Ophthalmol 140:1143, 2005

Woda BA, Sullivan JL: Reactive histiocytic disorders. Am J Clin Pathol 99:459, 1993

Tumors: Inflammatory Pseudotumor

Ahn Yuen SJ, Rubin PAD: Idiopathic orbital inflammation. Distribution,clinical features,and treatment outcome.Arch Ophthalmol 121:491, 2003

Cockerham GC, Hidayat AA, Bijwaard KE et al.: Re-evaluation of “reactive lymphoid hyperplasia of the uvea”: An immunohistochemical and molecular analysis of ten cases. Ophthalmology 107:151, 2000

Coupland SE, Krause L, Delecluse H-J et al.: Lymphoproliferative lesions of the ocular adnexa: Analysis of 112 cases. Ophthalmology 105:1430, 1998

Feinberg AS, Spraul CW, Holden JT et al.: Conjunctival lymphocytic infiltrate associated with Epstein–Barr virus. Ophthalmology 107:159, 2000

Jakobiec FA, Neri A, Knowles DM: Genotypic monoclonality in immunophenotypically polyclonal orbital lymphoid tumors: A model of tumor progression in the lymphoid system. Ophthalmology 94:980, 1987

Krishnan J, Danon AD, Frizzera G: Reactive lymphadenopathies and atypical lymphoproliferative disorders. Am J Clin Pathol 99:385, 1993

Mahr MA, Salomao DR, Garrity JA: Inflammatory pseudotumor with extension beyond the orbit. Am J Ophthalmol 138:396, 2004

Mombaerts I, Goldschmeding R, Schlingemann R et al.: What is orbital pseudotumor? Surv Ophthalmol 41:66, 1996

Pettinato G, Manivel C, De Rose N et al.: Inflammatory myofibroblastic tumor (plasma cell granuloma). Am J Clin Pathol 94:538, 1990

Rootman J, McCarthy M, White V et al.: Idiopathic sclerosing inflammation of the orbit. Ophthalmology 101:570, 1994

Sheren SB, Custer PL, Smith ME: Angiolymphoid hyperplasia with eosinophilia of the orbit associated with obstructive airway disease. Am J Ophthalmol 108:167, 1989

Sigudardoottir M, Sigurdsson H, Björk Bakardottir R et al.: Lymphoid tumors of the ocular adnexa: a morphologic and genotypic study of 15 cases. Acta Ophhthalmol Scand 81:299, 2003

Yano M, Nix R, Arvan D: Bilateral lacrimal gland enlargement associated with a di use gamma globulin elevation: A case report. Ophthalmol Res 1:245, 1970

Tumors: Malignant Lymphoma

Akpek EK, Polcharoen W, Ferry JA et al.: Conjunctival lymphoma masquerading as chronic conjunctivitis. Ophthalmology 106:757, 1999

Al-Hazzaa SAF, Green WR, Mann RB: Uveal involvement in systemic angiotropic large cell lymphoma. Ophthalmology 100:961, 1993

Antle CM, White VA, Horsman DE et al.: Large cell orbital lymphoma in a patient with acquired immune deficiency syndrome. Ophthalmology 97:1494, 1990

Arcaini L, Burcheri S, Rossi A et al.: Nongastric marginal-zone B-cell MALT lymphoma: prognostic value of disease dissemination. Oncologist 11:285, 2006

Au Eong KG, Choo CT: Burkitt lymphoma manifesting as acute proptosis. Am J Ophthalmol 123:856, 1997

Bairey O, Kremer I, Radkowsky E et al.: Orbital and adnexal involvement in systemic non-Hodgkin’s lymphoma. Cancer 73:2395, 1994 Banthia V, Jen A, Kacker A. Sporadic Burkitt’s lymphoma of the head

and neck in the pediatric population. Int J Pediatr Otorhinolaryngol 67:59, 2003

Banks PM, Isaacson PG: MALT lymphomas in 1997. Am J Clin Pathol 111(Suppl. 1):S75, 1999

Barcos M: Mycosis fungoides. Am J Clin Pathol 99:452, 1993 Bardenstein DS. Ocular adnexal lymphoma: classification, clinical

disease, and molecular biology. Ophthalmol Clin North Am 18:187, 2005

Ben-Ezra JM, Kornstein MJ: Antibody NCL-CD5 fails to detect neoplastic CD5+ cells in para n sections. Am J Clin Pathol 106:370, 1996

Bertoni F, Zucca E. Delving deeper into MALT lymphoma biology. J Clin Invest 116:22, 2006

Buchan J, McKibbin M, Burton T. The prevalence of ocular disease in chronic lymphocytic leukaemia. Eye 17:27, 2003

Burke JS: Are there site-specific di erences among the MALT lymphomas: Morphologic, clinical? Am J Clin Pathol 111(Suppl. 1):S133, 1999

Burke JS: Extranodal hematopoietic/lymphoid disorders. Am J Clin Pathol 111(Suppl. 1):S40, 1999

Carbone A, Gloghini A, Volpe R et al.: Follicular lymphoma of compartmentalized small cleaved center cells and mantle zone lymphocytes. Am J Clin Pathol 98:437, 1992

Chan JKC, Banks PM, Cleary ML et al.: A revised European-American classification of lymphoid neoplasms proposed by the International Lymphoma Study Group. Am J Clin Pathol 103:543, 1995

Chang YC, Chang CH, Liu YT et al.: Spontaneous regression of a largecell lymphoma in the conjunctiva and orbit. Ophthalm Plast Reconstr Surg 20:461, 2004

Chi-chu S, Wong K-F, Siu LL et al.: Large cell transformation of Sézary syndrome: A conventional and molecular cytogenetic study. Am J Clin Pathol 113:792, 2000

Chott A, Vesely M, Simonitsch I et al.: Classification of intestinal T-cell neoplasms and their di erential diagnosis. Am J Clin Pathol 111(Suppl. 1):S68, 1999

Clarke B, Legodi E, Chrystal V et al.: Systemic anaplastic large cell lymphoma presenting with conjunctival involvement. Arch Ophthalmol 121:569, 2003

Cockerham GC, Hidayat AA, Bijwaard KE et al.: Re-evaluation of “reactive lymphoid hyperplasia of the uvea”: An immunohistochemical and molecular analysis of ten cases. Ophthalmology 107:151, 2000

Co ee R, Lazarchick J, Chėvez-Barrios P et al.: Rapid diagnosis of orbital mantle cell lymphoma utilizing in situ hybridization technology. Am J Ophthalmol 140:554, 2005

Cook BE Jr, Bartley GB, Pittelkow MR: Ophthalmic abnormalities in patients with cutaneous T-cell lymphoma. Ophthalmology 106:1339, 1999

Corbally N, Grogan L, Keane MM et al.: Bcl-2 rearrangement in Hodgkin’s disease and reactive lymph nodes. Am J Clin Pathol 101:756, 1994

Coupland SE, Krause L, Delecluse H-J et al.: Lymphoproliferative lesions of the ocular adnexa: Analysis of 112 cases. Ophthalmology 105:1430, 1998

Demirci H, Shields CL, Shields JA et al.: Orbital tumors in the older population. Ophthalmology 109:243, 2002

Edelstein C, Shields JA, Shields CL et al.: Non-African Burkitt lymphoma presenting with oral thrush and an orbital mass in a child. Am J Ophthalmol 124:859, 1997

Elghetany MT, Kurec AS, Schuehler K et al.: Immunophenotyping of non-Hodgkin’s lymphomas in para n-embedded tissue sections. Am J Clin Pathol 95:517, 1991

Feinberg AS, Spraul CW, Holden JT et al.: Conjunctival lymphocytic infiltrate associated with Epstein–Barr virus. Ophthalmology 107:159, 2000

Fernandez-Suntay JP, Gragoudas ES, Ferry JA et al.: High-grade uveal B-cell lymphoma as the initial feature in Richter syndrome. Arch Ophthalmol 120:1383, 2002

Frizzera G, Wu CD, Inghirami G: The usefulness of immunophenotypic and genotypic studies in the diagnosis and classification of hematopoietic and lymphoid neoplasms. Am J Clin Pathol 111(Suppl. 1):

S13, 1999

Frost M, Newell J, Lones MA et al.: Comparative immunohistochemical analysis of pediatric Burkitt lymphoma and di use large B-cell lymphoma. Am J Clin Pathol 121:384, 2004

Galindo LM, Garcia FU, Hanau CA et al.: Fine-needle aspiration biopsy in the evaluation of lymphadenopathy associated with cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome). Am J Clin Pathol 113:865, 2000

Gilles FJ, O’Brian SM, Keating MJ: Chronic lymphocytic leukemia in (Richter’s) transformation. Semin Oncol 25:117, 1998

Gordon KB, Rugo HS, Duncan JL et al.: Ocular manifestations of leukemia: leukemic infiltration vs infectious process. Ophthalmology 108:2293, 2001

Groom D, Wong D, Brynes RK et al.: Auer rod-like inclusions in circulating lymphoma cells. Am J Clin Pathol 96:111, 1991

Hara Y, Nakamura N, Kuze T et al.: Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal zone B-cell lymphoma.

Invest Ophthalmol Vis Sci 42:2450, 2001

Harris NL: Lymphoid proliferations of the salivary glands. Am J Clin Pathol 111(Suppl. 1):S94, 1999

Harris NL, Isaacson PG: What are the criteria for distinguishing MALT from non-MALT lymphoma at extranodal sites? Am J Clin Pathol 111(Suppl. 1):S126, 1999

Hasegawa M, Kojima M, Shioya M et al.: Treatment results of radiotherapy for malignant lymphoma of the orbit and histopathologic review according to the WHO classification. Int J Radiat Oncol Biol Phys 57:172, 2003

Hoang-Xuan T, Bodaghi B, Toublanc M et al.: Scleritis and mucosalassociated lymphoid tissue lymphoma: A new masquerade syndrome.

Ophthalmology 103:631, 1996

Hsu MW, Chung CH, Chang CH et al.: Ptosis as an initial manifestation of orbital lymphoma: a case report. Kaohsiung J Med Sci 22:194, 2006

Hudock J, Chatten J, Miettinen M: Immunohistochemical evaluation of myeloid leukemia infiltrates (granulocytic sarcomas) in formalde- hyde-fixed tissue. Am J Clin Pathol 105:55, 1994

Inghirami G, Frizzera G: Role of the bcl-2 oncogene in Hodgkin’s disease. Am J Clin Pathol 101:681, 1994

Ja e ES, Harris NL, Diebold J et al.: World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Am J Clin Pathol 111(Suppl. 1):S8, 1999

Ja e ES, Krenacs L, Kumar S et al.: Extranodal peripheral T-cell and NK-cell neoplasms. Am J Clin Pathol 111(Suppl. 1):S46, 1999

Jamal S, Picker LJ, Aquino DB et al.: Immunophenotypic analysis of peripheral T-cell neoplasms: A multiparameter flow cytometric approach. Am J Clin Pathol 116:512, 2001

Kadin ME: Primary Ki-1-positive anaplastic large cell lymphoma: A distinct clinicopathologic entity. Ann Oncol 5(Suppl. 1):S25, 1994

Kahwash SB, Qualman SJ. Cutaneous lymphoblastic lymphoma in children: report of six cases with precursor B-cell lineage. Pediatr Dev Pathol 5:45, 2002

Kim H: Composite lymphomas and related disorders. Am J Clin Pathol 99:445, 1993

Kinney MC: The role of morphologic features, phenotype, genotype, and anatomic site in defining extranodal T-cell or NK-cell neoplasms. Am J Clin Pathol 111(Suppl. 1):S104, 1999

Kinney MC, Kadin ME: The pathologic and clinical spectrum of anaplastic large cell lymphoma and correlation with ALK gene regulation. Am J Clin Pathol 111(Suppl. 1):S56, 1999

Kirsch LS, Brownstein S, Codere F: Immunoblastic T-cell lymphoma presenting as an eyelid tumor. Ophthalmology 97:1352, 1990

Kohno T, Uchida H, Inomata H et al.: Ocular manifestations of adult T-cell leukemia/lymphoma. Ophthalmology 100:1794, 1993

Kornstein MJ, Bonner H, Gee B et al.: Leu M1 and S100 in Hodgkin’s disease and non-Hodgkin’s lymphomas. Am J Clin Pathol 85:433, 1986

Kumar SR, Gill PS, Wagner DG et al.: Human T-cell lymphotropic virus type I-associated retinal lymphoma: A clinicopathologic report.

Arch Ophthalmol 112:954, 1994

Kurtin PL: How do you distinguish benign from malignant extranodal small B-cell proliferations? Am J Clin Pathol 111(Suppl. 1):S119, 1999

Lai R, Weiss LM, Chang KL et al.: Frequency of CD43 expression in non-Hodgkin lymphomas: A survey of 742 cases and further characterization of rare CD43+ follicular lymphoma. Am J Clin Pathol 111:488, 1999

Lee JL, Kim MK, Lee KH et al.: Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue-type of the orbit and ocular adnexa. Ann Hematol 84:13, 2005

Leidenix MJ, Mamalis N, Olson RJ et al.: Primary T-cell immunoblastic lymphoma of the orbit in a pediatric patient. Ophthalmology 100:998, 1993

Liang R. Diagnosis and management of primary nasal lymphoma of T- cell or NK-cell origin. Clin Lymphoma 1:33, 2000

Looi A, Gascoyne RD, Chhanabhai M et al.: Mantle cell lymphoma in the ocular adnexal region. Ophthalmology 112:114, 2005

Lowen MS, Saraiva VS, Martins MC et al.: Immunohistochemical profile of lymphoid lesions of the orbit. Can J Ophthalmol 40:634, 2005

Macgrognan G, Vergier B, Dubois P: CD30-positivite cutaneous largecell lymphomas: A comparative study of clinicopathologic and molecular features of 16 cases. Am J Clin Pathol 105:440, 1996

Mann RB: Are there site-specific di erences among extranodal aggressive B-cell neoplasms? Am J Clin Pathol 111(Suppl. 1):S144, 1999

Matteucci C, Galieni P, Leoncini L et al.: Typical genomic imbalances in primary MALT lymphoma of the orbit. J Pathol 200:656, 2003

Matzkin DC, Slamovits TL, Rosenbaum PS: Simultaneous intraocular and orbital non-Hodgkin’s lymphoma in the acquired immune deficiency syndrome. Ophthalmology 101:850, 1994

Meunier J, Lumbroso-Le RL, Vincent-Salomon A et al.: Ophthalmologic and intraocular non-Hodgkin’s lymphoma: a large single centre study of initial characteristics, natural history, and prognostic factors.

Hematol Oncol 22:143, 2004

Meyer D, Yano M, Hanno H: Di erential diagnosis in Mikulicz’s syndrome, Mikulicz’s disease and similar disease entities. Am J Ophthalmol 71:516, 1971

Nowell PC, Croce CM: Chromosome translocations and oncogenes in human lymphoid tumors. Am J Clin Pathol 94:229, 1990

Ohtsuka K, Hashimoto M, Suzuki Y. High incidence of orbital malignant lymphoma in Japanese patients. Am J Ophthalmol 138:881, 2004

Ohtsuka K, Hashimoto M, Suzuki Y: A review of 244 orbital tumors in Japanese patients during a 21-year period: origins and locations. Jpn J Ophthalmol 49:49, 2005

O’Keefe JS, Sippy BD, Martin DF et al.: Anterior chamber infiltrates associated with systemic lymphoma. Report of two cases and review of the literature. Ophthalmology 109:253, 2002

Pangalis GA, Boussiotis VA, Kittas C: Malignant disorders of small lymphocytes. Am J Clin Pathol 99:402, 1993

Perkins SL: Immunophenotypic analysis of CD5 positivity in para n- embedded tissues: Still waiting for an e ective diagnostic antibody. Am J Clin Pathol 106:273, 1996

Pileri S, Bocchia M, Baroni CD et al.: Anaplastic large cell lymphoma (CD30+Ki-1+) results of a prospective clinico-pathological study of 69 cases. Br J Haematol 86:513, 1994

Pinyol M, Campo E, Nadal A et al.: Detection of the bcl-1 rearrangement at the major translocation cluster in frozen and para n-embed- ded tissues of mantle cell lymphomas by polymerase chain reaction.

Am J Clin Pathol 105:532, 1996

Quintanilla-Martínez L, Zukerberg LR, Ferry JA et al.: Extramedullary tumors of lymphoid or myeloid blasts: The role of immunohistology in classification. Am J Clin Pathol 104:431, 1995

Raderer M,Traub T, Formanek M et al.: Somatostatin-receptor scintigraphy for staging and follow-up of patients with extraintestinal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT)-type. Br J Cancer 85:1462, 2001

Salhany KE, Pietra GC: Extranodal lymphoid disorders. Am J Clin Pathol 99:472, 1993

Segal ZI, Cohen I, Szvalb S et al.: Solitary extranodal anaplastic large cell lymphoma, Ki-1+, of the eyelid. Am J Ophthalmol 124:105, 1997

Sigudardoottir M, Sigurdsson H, Björk Bakardottir R et al.: Lymphoid tumors of the ocular adnexa: a morphologic and genotypic study of 15 cases. Acta Ophhthalmol Scand 81:299, 2003

Sharara N, Holden JT, Wojo TH et al.: Ocular adnexal lymphoid proliferations. Clinical, histologic, flow cytometric, and molecular analysis of forty-three cases. Ophthalmology 110:1245. 2003

Shields CL, Shields JA, Caravlho C et al.: Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to systemic lymphoma. Ophthalmology 108:979, 2001

Shields JA, Stopyra GA, Marr BP et al.: Bilateral orbital myeloid sarcoma as initial sign of myeloid leukemia: case report and review of the literature. Arch Ophthalmol 121:33, 2003

Shin SS, Sheibani K: Monocytoid B-cell lymphoma. Am J Clin Pathol 99:421, 1993

Streeten BW: Burkitt’s lymphoma of the conjunctiva. Presented at the meeting of the Verhoe Society, 1990

Streubel B, Simonitsch-Klupp I, Mullauer L et al.: Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of di erent sites. Leukemia 18:1722, 2004

Suh CO, Shim SJ, Lee SW et al.: Orbital marginal zone B-cell lymphoma of MALT: radiotherapy results and clinical behavior. Int J Radiat Oncol Biol Phys 65:228, 2006

Suzuki J, Ohguro H, Satoh M et al.: Clinicopathologic and immunogenetic analysis of mucosa-associated lymphoid tissue lymphomas arising in conjunctiva. Jpn J Ophthalmol 43:155, 1999

Swerdlow S: Extranodal hematopoietic/lymphoid disorders: Pathology patterns. Am J Clin Pathol 111(Suppl. 1):S1–S152, 1999

Variakojis D, Anastasi J: Unresolved issues concerning Hodgkin’s disease and its relationship to non-Hodgkin’s lymphoma. Am J Clin Pathol 99:436, 1993

Watkins LM, Remulla HD, Rubin PAD: Orbital granulocytic sarcoma in an elderly patient. Am J Ophthalmol 123:854, 1997

Weisenburger DD: Progress in the classification of non-Hodgkin’s lymphoma. Am J Clin Pathol 99:367, 1993

Weisenburger DD, Chan WC: Lymphomas of follicles: Mantle cell and follicle center cell lymphomas. Am J Clin Pathol 99:409, 1993

Weisenthal RW, Streeten BW, Dubansky AS et al.: Burkitt lymphoma presenting as a conjunctival mass. Ophthalmology 102:129, 1995

Wender A, Adar A, Maor E et al.: Primary B-cell lymphoma of the eyes and brain in a 3-year-old boy. Arch Ophthalmol 112:450, 1994

White WL, Ferry AP, Harris NL et al.: Ocular adnexal lymphomas: A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type. Ophthalmology 102:1994, 1995

Williams GC, Holz E, Lee AG et al.: T-cell lymphoproliferative disorder of vitreous associated with mycosis fungoides. Arch Ophthalmol 118:278, 2000

Winberg CD: Peripheral T-cell lymphoma. Am J Clin Pathol 99:426, 1993

Yaghouti F, Nouri M, Mannor GE: Ocular adnexal granulocytic sarcoma as the first sign of acute myelogenous leukemia relapse. Am J Ophthalmol 127:361, 1999

Yano M, Scheie HG: Malignant lymphoma of the orbit: Di culties in diagnosis. Surv Ophthalmol 12:133, 1967

Yoshikawa T, Ogata N, Takahashi K et al.: Bilateral orbital tumor as initial presenting sign in human T-cell leukemia virus-1 associated adult T-cell leukemia/lymphoma. Am J Ophthalmol 140:327, 2005

Zucker JL, Doyle MF: Mycosis fungoides metastatic to the orbit. Arch Ophthalmol 109:688, 1991

Zukerberg LR, Medeiros JL, Ferry JA et al.: Di use low-grade B-cell lymphomas. Am J Clin Pathol 100:373, 1993

Tumors: Leukemia

Arber DA, Lopategui JR, Brynes RK: Chronic lymphoproliferative disorders involving blood and bone marrow. Am J Clin Pathol 99:494, 1993

Bhattacharjee K, Bhattacharjee H, Das D et al.: Chloroma of the orbit in a non-leukemic adult: A case report. Orbit 22:293, 2003

Chen E, Morrison DG, Donahue SP: Acute myeloid leukemia presenting as bilsteral proptosis from di use extraocular muscle infiltration.

Am J Ophthalmol 137:948, 2004

Cook BE, Bartley GB: Acute lymphoblastic leukemia manifesting in an adult as a conjunctival mass. Am J Ophthalmol 124:104, 1997

Dickstein JI, Vardiman JW: Issues in the pathology and diagnosis of the chronic myeloproliferative disorders and the myelodysplastic syndromes. Am J Clin Pathol 99:513, 1993

Frizzera G, Wu CD, Inghirami G: The usefulness of immunophenotypic and genotypic studies in the diagnosis and classification of hematopoietic and lymphoid neoplasms. Am J Clin Pathol 111(Suppl. 1): S13, 1999

Jordan DR, Noel LP, Carpenter BF: Chloroma. Arch Ophthalmol

109:734, 1991

Ja e ES, Harris NL, Diebold J et al.: World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Am J Clin Pathol 111(Suppl. 1):S8, 1999

Locurto M, D’Angelo P, Lumia F et al.: Leukemic ophthalmopathy: A report of 21 pediatric cases. Med Pediatr Oncol 23:8, 1994

Ohta K, Kondoh T, Yasuo K et al.: Primary granulocytic sarcoma in the sphenoidal bone and orbit. Childs Nerv Syst 19:674, 2003

Porto L, Kieslich M, Schwabe D et al.: Granulocytic sarcoma in children. Neuroradiology 46:374, 2004

Quintanilla-Martínez L, Zukerberg LR, Ferry JA et al.: Extramedullary tumors of lymphoid or myeloid blasts: The role of immunohistology in classification. Am J Clin Pathol 104:431, 1995

Shome DK, Gupta NK, Prajapati NC et al.: Orbital granulocytic sarcomas (myeloid sarcomas) in acute nonlymphocytic leukemia. Cancer

70:2298, 1992

Traweek ST: Immunophenotypic analysis of acute leukemia. Am J Clin Pathol 99:504, 1993

Tumuluri K, Woo T, Crowston J et al.: Bilateral leukemic orbital infiltration presenting as proptosis and narrow-angle glaucoma. Ophthalm Plast Reconstr Surg 20:248, 2004

van Veen S, Kluin PM, de Keizer RJW et al.: Granulocytic sarcoma (chloroma). Am J Clin Pathol 95:567, 1991

Shaen DF, Fardeau C, Roberge FG et al.: Rearrangement of immunoglobulin gene in metastatic Waldenström macroglobulinemia. Am J Ophthalmol 129:395, 2000

Ugurlu S, Bartley GB, Gibson LE: Necrobiotic xanthogranuloma: Long-term outcome of ocular and systemic involvement. Am J Ophthalmol 129:651, 2000

Yano M, Nix R, Arvan D: Bilateral lacrimal gland enlargement associated with a di use gamma globulin elevation: A case report. Ophthalmol Res 1:245, 1970

Tumors: Melanotic

See Chapter 17.

Tumors: Monoclonal and

Polyclonal Gammopathies

Alexanian R, Jagannath S: Plasma cell dyscrasias. JAMA 268:2946, 1992

Barlogie B, Alexanian R, Jagannath S: Plasma cell dyscrasias. JAMA

268:2946, 1992

Bullock JD, Bartley RJ, Campbell RJ et al.: Necrobiotic xanthogranuloma with paraproteinemia: Case report and a pathogenetic theory.

Ophthalmology 93:1233, 1986

Ezra E, Mannor G, Wright JE et al.: Inadequately radiated solitary extramedulllary plasmocytoma of the orbit requiring exenteration. Am J Ophthalmol 120:803, 1995

Keren DF, Morrison N, Gulbranson R: Evolution of a monoclonal gammopathy. Lab Med 5:313, 1994

Lam S, Tessler HH: Iris crystals and hypergammaglobulinemia. Am J Ophthalmol 110:440, 1990

Peterson LC, Bradley AB, Crosson JT et al.: Application of the immunoperoxidase technic to bone marrow trephine biopsies in the classification of patients with monoclonal gammopathies. Am J Clin Pathol 85:688, 1986

Sen HN, Chan C-C, Caruso RC et al.: Waldenström’s macroglobulin- emia-associated retinopathy. Ophthalmology 111:535, 2004

Secondary Orbital Tumors

Albert DM, Rubenstein RA, Scheie HG: Tumor metastasis to the eye. Incidence in 213 adult patients with generalized malignancy: II. Clinical study in infants and children. Am J Ophthalmol 63:723, 727, 1967

Callejo SA, Kronish JW, Decker SJ et al.: Malignant granular cell tumor metastatic to the orbit. Ophthalmology 107:550, 2000

Fan JT, Buettner H, Bartley GB et al.: Clinical features and treatment of seven patients with carcinoid tumor metastatic to the eye and orbit.

Am J Ophthalmol 119:211, 1995

Font RL, Ferry AP: Carcinoma metastatic to the eye and orbit: III. A clinicopathologic study of 28 cases metastatic to the orbit. Cancer 38:1326, 1976

Johnson LN, Krohel GB, Yeon EB et al.: Sinus tumors invading the orbit. Ophthalmology 91:209, 1984

Ormerod LD, Weber AL, Rauch SD et al.: Ophthalmic manifestations of maxillary sinus mucoceles. Ophthalmology 94:1013, 1987

Riddle PJ, Font RL, Zimmerman LE: Carcinoid tumors of the eye and orbit: A clinicopathologic study of 15 cases, with histochemical and electron microscopic observations. Hum Pathol 13:459, 1982

NATURAL HISTORY

I.Diabetes mellitus (DM) is a heterogeneous group of disorders characterized by elevated blood glucose and other metabolic abnormalities.

Elevated blood glucose levels cause an elevated retinal glucose level, resulting in a hypoxic-like redox imbalance that may contribute to the ischemia that precedes the development of diabetic retinopathy (DR).

A.The disorder may result from decreased circulating insulin or from ine ective insulin action in target cells.

Diabetes accompanied by renal disease (in the form of focal and segmental glomerulosclerosis) is found in adult individuals with mitochondrial tRNA (Leu) genetic mutation. In patients with the A3243G mutation, deafness is almost consistently found, and extrarenal manifestations also include neuromuscular, cardiac, and retinal disease. The latter is in the form of macular dystrophy. The extrarenal manifestations, including diabetes, tend to occur later in the course of the disease.

B.DM, which a ects approximately 5% of the United States population and 29% of the population 65 years or older, is classified as either type 1 (previously called insulin-dependent) or type 2 (previously called noninsu- lin-dependent) DM.

Type 2 DM accounts for approximately 90% of diabetic patients. Target cell resistance occurs in both types, but is a central feature in type 2. Genetic defects in the cellular insulin receptor

may account for the insulin resistance. In animal experiments, C-peptide, a cleavage product in the processing of proinsulin but retained in the secretory granule and cosecreted with insulin in response to glucose stimulation, seems to prevent the vascular and neural dysfunction in diabetic rats.

II.DR is a leading cause of blindness in the United States.

A.Over three-fourths of the blind are women.

B.There is a significantly higher prevalence of DR in individuals of black or latino descent compared to whites or Chinese.

C.The most important factor in the occurrence of DR is how long the patient has been diabetic.

1.Although approximately 60% of patients develop retinopathy after 15 years of diabetes, and almost

100% after 30 years, the risk of legal blindness in a given diabetic person is only 7% to 9% even after 20 to 30 years of DM.

a.When the onset of type 1 DM is before 30 years of age and no DR is present at onset, approximately 59% of patients have developed DR 4 years later, and almost 100% 20 years later. In this group, the incidence of proliferative DR (PDR) stabilizes after 13 to 14 years of diabetes at between 14% and 17%.

b.When the onset of type 1 DM is after 30 years of age and no DR is present at onset, approximately

47% of patients have developed DR 4 years later. Among patients older than 30 years of age who develop type 2 DM, 34% develop DR 4 years later. In this group of patients with type 1 DM, 7% who were free of PDR at onset of DM developed PDR 4 years later; 2% of the patients with type 2 DM developed PDR 4 years later.

2.Once blindness develops, the average life expectancy is less than 6 years.

3.Ocular symptoms occur in approximately 20% to

40% of diabetic patients at the clinical onset of the disease, but these symptoms are mainly caused by refractive changes, rather than by DR.

4.The low frequency of retinopathy in secondary diabetes (e.g., chronic pancreatitis, pancreatectomy, hemochromatosis, Cushing’s syndrome, and acromegaly) may be due to the decreased survival among patients with secondary diabetes.

A positive correlation exists between the presence of DR and nephropathy (Kimmelstiel–Wilson disease).

5.It appears that the risk for developing DR in type 1 DM is reduced if glycemic control is achieved from the time of diagnosis; conversely, if DR is already present, early intensive insulin treatment can initially worsen the DR.

6.Among diabetic individuals, plasma lipid levels are associated with the presence of hard retinal exudates, and carotid artery intima–media wall thickness is associated with retinopathy; however, other manifestations of atherosclerosis and most of its risk factors are not associated with the severity of

DR.

III.In juvenile DM, PDR is uncommon in patients younger than 20 years of age, and almost unheard of in patients younger than 16 years of age.

A.Background DR (BDR; especially microaneurysms), however, can be demonstrated on fluorescein angiography in juvenile diabetic patients as young as 3 years of age, and is present in most patients older than 10 years of age.

Evidence suggests that a virus, perhaps coxsackievirus B4, can cause some cases of juvenile-onset diabetes, probably by damaging the pancreatic cells. Autoimmune mechanisms may also play a role. Recently, DR has been found to have characteristics of chronic inflammatory disease and neurodegenerative disease. Elevated vitreous levels of interleukins-6 and 8 in PDR support immune or inflammatory mechanisms in the pathogenesis of PDR.

IV. Most diabetic patients never acquire PDR, and in those who do, it develops only after at least 15 years of

DM.

Rarely, a patient presents with BDR, or even with PDR before any systemic evidence of DM (such as hyperglycemia) is discovered.

V.Other associations

A.Primary openand closed-angle glaucoma occurs more often in diabetic patients than in nondiabetic individuals.

B.DR is approximately 6% more frequent in diabetic patients who have a diagonal earlobe crease than in

those individuals who do not have a diagonal earlobe crease. A positive association exists between a diagonal earlobe crease and coronary artery disease in patients with diabetes.

C.A positive association also exists between DR and the presence of elevated blood pressure (especially increased diastolic blood pressure), glycosylated hemoglobin, and smoking.

Poor control in DM adversely impacts nerve fiber layer thickness as measured by the scanning laser polarimeter. This finding does not appear to be acute because it is not reversed by short-term blood glucose regulation.

D.Other risk factors for the development of DR include hypertension and abdominal obesity.

RETINAL VASCULATURE IN NORMAL SUBJECTS AND DIABETIC PATIENTS

Figure 15.1 shows examples of retinal vasculature in normal subjects and diabetic patients (see also section Neurosensory

Retina, later in this chapter).

CONJUNCTIVA AND CORNEA

I.Conjunctival microaneurysms may be found in diabetic individuals, but they are of questionable diagnostic signifi-

cance because they also occur in nondiabetic subjects.

II.Transmural lipid imbibition may occur in conjunctival capillaries in diabetic lipemia retinalis (Fig. 15.2). Histologically, lipid-laden cells, either endothelial cells or subintimal macrophages, are present projecting into and encroaching

on conjunctival capillary lumens.

III.The conjunctiva may show decreased vascularity in the capillary bed, increased capillary resistance, and decreased area occupied by the microvessels.

Microvascular abnormalities have even been detected in the conjunctiva of pediatric diabetic patients. The severity of these findings correlates with hemoglobin A1c levels, but not with the duration of the disease. Such conjunctival microvascular changes correlate significantly with disease severity in type 2 diabetes, but not with disease duration since diagnosis.

IV. Corneal epithelium and its basement membrane may be abnormal, and epithelial erosions are common. Corneal sensation may be reduced, and the stroma may be thickened. Tear production is more frequently reduced in diabetic patients than in nondiabetics.

A.Diabetic ocular surface disease following cataract surgery is ameliorated with oral aldose reductase inhibitor treatment by improving ocular surface sensitivity.

Keratoepitheliopathy, conjunctival squamous metaplasia, and abnormal corneal sensitivity, tear break-up time, Schirmer test, and tear secretion level are all related to the status of metabolic control, diabetic neuropathy, and stage of DR. The prevalence of keratoepithelialiopathy is 22.8% in diabetic individuals, but 8.5% in nondiabetics, and is associated with tear film abnormalities, particularly nonuniformity of the tear lipid layer, in diabetic patients.

B.Decreased penetration of “anchoring” fibrils from the corneal epithelial basement membrane into the corneal stroma may be responsible for the loose adhesion between the corneal epithelium and the stroma.

The corneal epithelium in diabetic patients is much easier to wipe off, often in a single sheet (e.g., during vitrectomy procedures), than is the epithelium of nondiabetic patients. Approximately 50% of diabetic patients undergoing vitrectomy surgery have corneal complications following the procedure, with 44.6% having an epithelial disturbance, and 23.8% exhibiting corneal edema. These complications are significantly correlated with the degree of surgical invasion during the procedure.

Specular microscopic studies show corneal endothelial structural abnormalities reflected in an increased coe cient of variation of cell area, a decreased percentage of hexagonal cells, an increased corneal autofluorescence, and an increased intraocular pressure. The changes in corneal endothelium resemble those that occur with aging. In the Ocular Hypertension Treatment Trial* increased central corneal thickness was associated with younger age, female gender, and diabetes.

Decreased corneal endothelial cell density and increased coefficient of variability in cell size are noted in high-risk PDR patients undergoing cataract surgery by phacoemulsification, but not in normal individuals.

C.Contact lens studies in patients who have type 2 DM have demonstrated that the diabetic corneal endothelium shows significantly lower function than the nondia-

*Brandt JD, Beiser JA, Kass MA et al.: Central corneal thickness in the Ocular HypertensionTreatment Study (OHTS).Ophthalmology 108:1779,

2001.

Fig. 15.3 Cataract. Histologic section shows marked cortical and nuclear cataractous changes in diabetic patient. The changes are nonspecific and, therefore, indistinguishable from those in nondiabetic patients.

beticcornealendothelium,eventhoughthemorphometry of corneal endothelial cells and central corneal thickness in diabetic patients who wear soft contact lenses are not appreciably di erent from the values found in contact lens-wearing control individuals.

D.Corneal endothelial cells of diabetic individuals are more susceptible to damage during cataract surgery than nondiabetics, and exhibit a delay in recovering from postoperative corneal edema. Diabetes is also a significant risk factor for unsuccessful initial corneal transplant grafts because of endothelial failure.

V.Corneal nerve tortuosity may relate to the severity of the neuropathy in diabetic patients.

Corneal confocal microscopy also demonstrates that corneal nerve fiber density and branch density are reduced in diabetic patients compared to control individuals, and these measures tend to be worse in individuals with more severe neuropathy.

LENS

I.“Snowflake” cataract of juvenile diabetic patient

A.The cataract consists of subcapsular opacities with vacuoles and chalky-white flake deposits.

B.The whole lens may become a milky-white cataract

(occasionally the process is reversible), and even may be bilateral.

C.The histopathology has not been defined.

II.Adult-onset diabetic cataract (Fig. 15.3)

A.The cataract (cortical and nuclear) is indistinguishable clinically and histopathologically from the “usual” agerelated cataracts. Diabetic patients, however, are at an increased risk for development of cataracts compared with nondiabetic subjects. Nevertheless, diabetes is not universally accepted as a risk factor for nuclear cataracts.

1.Diabetes is a strong risk factor for the development of posterior subcapsular cararact.

2.Apoptosis plays an important role in the development of cataracts in DR compared to senile cataract.

3.Nuclear fiber compaction analysis demonstrates no di erence in compaction between diabetic and nondiabetic cataracts,although diabetes does appear to accelerate the formation of cataracts that are similar to age-related nuclear cataracts.

Reversible lens opacities, even posterior subcapsular opacities, may be seen. Aldose reductase probably plays a key role in initiating the formation of lens opacities in diabetic patients, as it does in galactosemia. Calpains may be responsible for the unregulated proteolysis of lens crystallins, thereby contributing to diabetic cataract development.

B.Patients with diabetes may have transient lens opacities and induced myopia during hyperglycemia.

C.Cataract surgery and progression of DR

1.The visual prognosis for patients who have preexisting DR, both nonproliferative and proliferative, and who undergo cataract extraction and posterior-chamber lens implantation is less favorable than for patients who have no retinopathy.

2.The poorer prognosis results from increased progression of DR, both background and proliferative, after cataract extraction.

3.Posterior capsule opacification is greater in diabetic individuals following cataract surgery than in nondiabetic control patients; however, among diabetic individuals, neither the stage of DR nor the systemic status of the diabetes correlates with the degree of posterior capsule opacification.

IRIS

I.Vacuolation of iris pigment epithelium (Fig. 15.4)

A.Vacuolation of the iris pigment epithelium is present in 40% of enucleated diabetic eyes. The vacuoles contain glycogen.

Rupture of the vacuoles when the intraocular pressure is suddenly reduced, as in entering the anterior chamber during cataract surgery, results in release of pigment into the posterior chamber. The pigment is visible clinically as a cloud moving through the pupil into the anterior chamber. Lacy vacuolation and “damage” to the overlying dilator muscle may be the cause of delayed dilatation of the iris after instillation of mydriatics.

B.Pinpoint “holes” may be seen clinically with the slit lamp when transpupillary retroillumination is used. The holes may be seen in at least 25% of known diabetic patients who have blue irises.

In autopsy eyes from diabetic patients, vacuolation of the iris pigment epithelium may be related to increased blood glucose levels before death. The vacuolation is also seen histologically in neonates and in patients who have systemic mucopolysaccharidoses (the vacuoles contain acid mucopolysaccharides), Menkes’ syndrome, and multiple myeloma.

II.Neovascularization of iris (rubeosis iridis; Fig. 15.5; see also Figs 9.13 and 9.14)

A.Rubeosis iridis is the clinical term for iris neovascularization.

1.It is present in fewer than 5% of diabetic patients without PDR, but in approximately 50% of patients who have PDR.

2.The new iris vessels arise from venules.

Neovascularization of the iris appears to be related to an angiogenic factor derived from hypoxic neural retina. The

lens–zonular diaphragm and a vitreous antiangiogenic factor seem to decrease the anterior flow of the neural retinal angiogenic factor into the aqueous compartment; therefore, lensectomy and vitrectomy remove these barriers and facilitate the development of iris neovascularization in approximately 50% of cases. An alternative explanation for its development is a generalized hypoxic state of the anterior segment of the eye in diabetic patients.

B.Neovascularization of the iris may arise from the ante- rior-chamber angle, the pupillary border, midway between, or all three.

Infrequently, the anterior iris stroma, between the pupil and the collarette, may show a very fine neovascularization that can remain stationary for years without the development of angle neovascularization.