Ocular Adnexal Lymphomas: Five Case Presentations and a Review of the Literature

doi:10.1016/S0039-6257(02)00337-5

Survey of Ophthalmology

Volume 47, Issue 5, September–October 2002, Pages 470-490

https://doi.org/10.1016/S0039-6257(02)00337-5 Get rights and content

Abstract

The ocular adnexal lymphomas represent the malignant end of the spectrum of lymphoproliferative lesions that occur in these locations. The Revised European and American Lymphoma (REAL) Classification and the new World Health Organization Classification of Tumors of Hemopoietic and Lymphoid Tissues are the most suitable for subdividing the ocular adnexal lymphomas, whereby the extranodal marginal zone B-cell lymphoma represents the most common lymphoma subtype. This review is based on five cases subtyped according to the above classifications—three “typical” lymphomas (an extranodal marginal zone B-cell lymphoma, a diffuse large cell B-cell lymphoma arising from an extranodal marginal zone B-cell lymphoma, and a follicular lymphoma) and two “atypical” lymphomas (a non-endemic Burkitt lymphoma in an immune competent elderly patient, and a primary Hodgkin lymphoma of the eyelid) of the ocular adnexa. Management of patients with ocular adnexal lymphomas includes a thorough systemic medical examination to establish the clinical stage of the disease. The majority of patients with ocular adnexal lymphoma have stage IE disease. Current recommended therapy in stage IE tumors is radiotherapy, while disseminated disease is treated with chemotherapy. Despite usually demonstrating an indolent course, extranodal marginal zone B-cell lymphomas are renowned for recurrence in extranodal sites, including other ocular adnexal sites. Long-term follow-up with 6-month examinations are therefore recommended. Major prognostic criteria for the ocular adnexal lymphomas include anatomic location of the tumor; stage of disease at first presentation; lymphoma subtype as determined using the REAL classification; immunohistochemical markers determining factors such as tumor growth rate; and the serum lactate dehydrogenase level.

Section snippets

Case Histories

A summary of the relevant clinical information is presented in Table 1.

Tissue samples

The five cases were collected from the consultation files of the Reference Center for Hematopathology, Pathology Department of University Hospital Benjamin Franklin, Berlin, Germany. All tissue biopsies had been fixed in 4% buffered formalin and embedded in paraffin. Conventional histological stains included hematoxylin and eosin, Giemsa, and periodic-acid Schiff (PAS).

Immunohistology

Additional slides were stained with several monoclonal and polyclonal antibodies that are reactive in paraffin sections for

Results

The results of the immunohistochemical, in-situ hybridization and molecular biological findings of the cases examined are summarized in Table 2.

Discussion

The lymphomas of the ocular adnexa are almost exclusively extranodal B-cell non-Hodgkin lymphoma.3, 12, 35, 44, 55, 61, 82 They delineate one end of the spectrum of lymphoproliferative lesions which occur in these tissues; the other pole being represented by reactive lymphoid hyperplasia. A group of tumors, termed atypical lymphoid hyperplasia, exists between the two ends of this spectrum: these are lymphoproliferative lesions, which cannot be placed unequivocally in either of the two major

Summary

Lymphoproliferative disease of the ocular adnexa includes a spectrum of lesions that can present with similar clinical and radiological features. They represented considerable diagnostic dilemmas for both the clinician and pathologist in the past; however, by employing morphological, immunohistochemical, and molecular biological criteria, the ocular adnexal lymphoid lesions can be better distinguished today into reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and malignant

Method of Literature Search

Literature selection for this article was based on a Medline search spanning the period 1966 to September 2001 for all articles using the following keywords, singularly and in various combinations: ocular adnexa, orbit, conjunctiva, lymphoma, lymphoproliferative lesion, eye, extranodal marginal zone B-cell lymphoma, “mucosa-associated lymphatic tissue” lymphoma, Burkitt lymphoma, Hodgkin's disease, treatment, prognosis, REAL Classification. The German, French, and Japanese articles were

Acknowledgements

The authors would sincerely like to thank the clinical ophthalmologists (particularly Professor M. H. Foerster) and oncologists involved in the treatment of the above five patients for the provision of clinical files, the confidence of which has been strictly maintained. Furthermore, the authors would like to thank Mr. H-H. Müller for his supportive technical assistance. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.

References (87)

L. Baldini et al.
Treatment and prognosis in a series of primary extranodal lymphomas of the ocular adnexa
Ann Oncol
(1998)
E.M. Bessell et al.
Orbital and conjunctival lymphoma treatment and prognosis
Radiother Oncol
(1988)
S.E. Coupland et al.
T-cell and T/natural killer-cell lymphomas involving ocular and ocular adnexal tissuesa clinicopathologic, immunohistochemical, and molecular study of seven cases
Ophthalmology
(1999)
S.E. Coupland et al.
Lymphoproliferative lesions of the ocular adnexa
Analysis of
(1998)
C. Edelstein et al.
Non-African Burkitt lymphoma presenting with oral thrush and an orbital mass in a child
Am J Ophthalmol
(1997)
J.H. Ellis et al.
Lymphoid tumors of the ocular adnexa. Clinical correlation with the working formulation classification and immunoperoxidase staining of paraffin sections
Ophthalmology
(1985)
O. Esik et al.
A retrospective analysis of different modalities for treatment of primary orbital non-Hodgkin's lymphomas
Radiother Oncol
(1996)
A.E. Flanders et al.
Orbital lymphoma
Role of CT and MRI. Radiol Clin North Am
(1987)
N.L. Harris et al.
A revised European-American classification of lymphoid neoplasmsa proposal from the International Lymphoma Study Group
Blood
(1994)
J.W. Henderson et al.
T-cell lymphoma of the orbit
Mayo Clin Proc
(1989)

A. Hornblass et al.

Orbital lymphoid tumors located predominantly within extraocular muscles

Ophthalmology

(1987)

H. Inagaki et al.

API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphomamultiplex RT-PCR detection using formalin-fixed paraffin-embedded specimens

Am J Pathol

(2001)

F.A. Jakobiec et al.

B- and T-lymphocytes in ocular disease

Ophthalmology

(1984)

F.A. Jakobiec et al.

Genotypic monoclonality in immunophenotypically polyclonal orbital lymphoid tumors. A model of tumor progression in the lymphoid system. The 1986 Wendell Hughes lecture

Ophthalmology

(1987)

B. Jereb et al.

Radiation therapy of conjunctival and orbital lymphoid tumors

Int J Radiat Oncol Biol Phys

(1984)

L.S. Kirsch et al.

Immunoblastic T-cell lymphoma presenting as an eyelid tumor

Ophthalmology

(1990)

D.M. Knowles et al.

Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa (orbit, conjunctiva, and eyelids)a prospective multiparametric analysis of 108 cases during 1977 to 1987

Hum Pathol

(1990)

M.J. Leidenix et al.

Primary T-cell immunoblastic lymphoma of the orbit in a pediatric patient

Ophthalmology

(1993)

J.G. Letschert et al.

Results of radiotherapy in patients with stage I orbital non-Hodgkin's lymphoma

Radiother Oncol

(1991)

H. Liu et al.

Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy

Lancet

(2001)

I.T. Magrath et al.

An effective therapy for both undifferentiated (including Burkitt's) lymphomas and lymphoblastic lymphomas in children and young adults

Blood

(1984)

T. Mannami et al.

Clinical, histopathological, and immunogenetic analysis of ocular adnexal lymphoproliferative disorderscharacterization of malt lymphoma and reactive lymphoid hyperplasia

Mod Pathol

(2001)

L. McNally et al.

Clinical, morphologic, immunophenotypic, and molecular genetic analysis of bilateral ocular adnexal lymphoid neoplasms in 17 patients

Am J Ophthalmol

(1987)

L.J. Medeiros et al.

Immunohistologic features predict clinical behavior of orbital and conjunctival lymphoid infiltrates

Blood

(1989)

L.J. Medeiros et al.

Immunohistologic analysis of small lymphocytic infiltrates of the orbit and conjunctiva

Hum Pathol

(1990)

B. Meekins et al.

Cutaneous T-cell lymphoma presenting as a rapidly enlarging ocular adnexal tumor

Ophthalmology

(1985)

K.J. Minehan et al.

Local control and complications after radiation therapy for primary orbital lymphomaa case for low-dose treatment

Int J Radiat Oncol Biol Phys

(1991)

M. Motegi et al.

API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogeneous products

Am J Pathol

(2000)

A. Neri et al.

Immunoglobulin and T cell receptor beta chain gene rearrangement analysis of ocular adnexal lymphoid neoplasmsclinical and biologic implications

Blood

(1987)

K.L. Park et al.

Hodgkin's lymphoma of the orbit associated with acquired immunodeficiency syndrome

Am J Ophthalmol

(1993)

S. Patel et al.

Nodular sclerosing Hodgkin's disease of the orbit

Ophthalmology

(1983)

D.M. Reifler et al.

Orbital lymphoma associated with acquired immune deficiency syndrome (AIDS)

Surv Ophthalmol

(1994)

C.L. Shields et al.

Conjunctival lymphoid tumorsclinical analysis of 117 cases and relationship to systemic lymphoma

Ophthalmology

(2001)

L.Y. Shih et al.

Non-Hodgkin's lymphomas in Asia

Hematol Oncol Clin North Am

(1991)

J. Sigelman et al.

Lymphoid lesions of the conjunctivarelation of histopathology to clinical outcome

Ophthalmology

(1978)

M.C. Smitt et al.

Radiotherapy is successful treatment for orbital lymphoma

Int J Radiat Oncol Biol Phys

(1993)

R.W. Weisenthal et al.

Burkitt lymphoma presenting as a conjunctival mass

Ophthalmology

(1995)

W.A. White et al.

Ocular adnexal lymphoma. A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type

Ophthalmology

(1995)

A.C. Wotherspoon et al.

Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori

Lancet

(1993)

A.C. Wotherspoon et al.

Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma

Lancet

(1991)

J.H. Yeo et al.

Combined clinical and computed tomographic diagnosis of orbital lymphoid tumors

Am J Ophthalmol

(1982)

A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project

N Engl J Med

(1993)

Statistical analyses of clinico-pathological, virological and epidemiological data on lymphoid malignancies with special reference to adult T-cell leukemia/lymphomaa report of the second nationwide study of Japan

The T- and B-Cell Malignancy Study Group. Jpn J Clin Oncol

(1985)

Cited by (116)

Secondary eyelid pockets: Pitfalls in blepharoplasty surgery
2021, Journal Francais d'Ophtalmologie
Les demandes de chirurgie esthétiques des paupières sont fréquentes. Le chirurgien dit mener un examen clinique complet afin d’écarter toutes pathologies orbitaires responsables de poches palpébrales.
Étude de dix patients ayant consulté dans le service de chirurgie oculopalpébrale de la fondation ophtalmologique de Rothschild pour une chirurgie esthétique des poches palpébrales et chez qui a été diagnostiqué une pathologie sous-jacente.
L’examen clinique attentif permet de rechercher des signes d’alarmes, dominés par les antécédents, de caractère unilatéral, des douleurs et de la présence d’une exophtalmie. Ceux-ci doivent conduire à la réalisation d’un bilan d’imagerie et à la biopsie chirurgicale si une masse orbitaire a été identifiée pour l’analyse histologie qui posera le diagnostic. Nous avons identifié quatre cas de lymphome orbitaire, un corps de granulome à corps étranger, une dacryoadénite chronique bilatérale, une atteinte sarcoïdosique, un AAPOX syndrom, un hémangiome caverneux et une hernie graisseuse simple.
Cette série de cas montre l’importance de ne pas méconnaitre une pathologie orbitaire sous-jacente avant de proposer une chirurgie esthétique pour des poches palpébrales.
Requests for cosmetic eyelid surgery are frequent. The surgeon must carry out a complete clinical examination in order to rule out any orbital pathologies responsible for eyelid pockets.
Study of ten patients who have consulted in the oculopalpebral surgery department of La Fondation Ophtalmologique de Rothschild for cosmetic surgery of the eyelid pockets and in whom an underlying pathology was diagnosed.
The clinical examination allows to look for signs of alarms, such as medical history, unilateral involvement, pain and the presence of exophthalmos. These should lead to perform orbital imaging and surgical biopsy if an orbital mass has been identified for histological analysis which will make the diagnosis. We identified four cases of orbital lymphoma, one foreign body granuloma, chronic bilateral dacryoadenitis, sarcoidosis involvement, AAPOX syndrom, cavernous hemangioma, and simple fatty hernia.
These cases shows the importance of not ignoring an underlying orbital pathology before proposing cosmetic surgery for eyelid pockets.
Pathology of the Conjunctiva, Orbit, Lacrimal Gland, and Intraocular Tumors
2020, Gnepp's Diagnostic Surgical Pathology of the Head and Neck, Third Edition
A large array of pathologies must be considered in the etiologic differential diagnosis of diseases affecting the ocular tissues. Understanding the most common pathologies that explain symptoms in the eye or threaten life or vision even without symptoms, knowledge of the nomenclature and its nuances used to communicate findings, and recognizing challenging differential diagnoses are key to the accurate diagnosis and treatment of ocular diseases. This chapter describes the major causes of neoplastic ocular diseases, the histopathological findings, and major differential diagnoses. This chapter is divided into three sections. The first section describes the most common benign and malignant pathologies of the conjunctiva, some of which may be challenging lesions encountered in surgical pathology practice. The second section is dedicated to pathological processes affecting the orbital tissues and lacrimal gland, providing an overview of the most common diagnoses, the differential diagnoses, and options of treatment for mass lesions that may lead to decreased vision or worse. The third section describes the most common intraocular tumors including metastasis, uveal melanoma, and retinoblastoma. A discussion on the normal histopathology of the ocular tissues in each section will allow the reader to better understand the various pathological processes. The goal of the chapter is to determine the role of pathology in informing treatment strategies for eye diseases, and to illuminate the collaboration between the pathologist and ophthalmologist.
Primary Burkitt-like lymphoma of the orbit diagnosed using ultrasound-guided core needle biopsy: A case study
2016, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Burkitt-like lymphoma, also known as (B-Cell lymphoma, Unclassifiable) is a rare extra-nodal B-cell lymphoma with features intermediate between Burkitt's lymphoma and diffuse large B-cell lymphoma.
A 73-year-old Caucasian female presented to our Emergency Department with orbital pain, deterioration of vision, nausea and vomiting. General examination revealed right orbital proptosis and reduction in visual acuity; and computed tomography confirmed the presence of a right retro-bulbar mass.
Tissue samples were obtained using ultrasound-guided core needle biopsy. An experienced head and neck radiologist (SM) undertook the procedure under general anaesthesia, using a lateral orbital approach. The instrument used was the Toshiba Aplio. The procedure was without complication. Results from histopathological, immunohistochemical and genetic analyses confirmed the diagnosis of stage IV orbital Burkitt-like lymphoma with atypical features.
Despite the ambiguity of immunohistochemistry and cytogenetic results, the patient was treated for Burkitt's lymphoma. The treatment had to be re-adjusted after two rounds of chemotherapy as the patient developed chemotherapy-induced encephalopathy. The patient remained symptom-free for 8 months. This case demonstrates the application of ultrasound-guided core needle biopsy for rapid and accurate lymphoma diagnosis and sub-classification.
Orbital lymphoma
2019, Survey of Ophthalmology
Orbital lymphomas constitute 50–60% of ocular adnexal lymphomas. A total of 2211 cases of orbital lymphoma with a known subtype have been reported in the last 24 years (1994–2017). The vast majority of orbital lymphomas are of B-cell origin (97%), of which extranodal marginal zone B-cell lymphoma (EMZL) (59%) is the most common subtype, followed by diffuse large B-cell lymphoma (23%), follicular lymphoma (9%), and mantle cell lymphoma (5%). Orbital lymphoma is primarily a disease of the elderly. Gender distribution varies according to lymphoma subtype. However, extranodal marginal zone B-cell lymphoma (53%) and follicular lymphoma (75%) show a female predominance, whereas diffuse large B-cell lymphoma shows an even gender distribution. Mantle cell lymphoma has a striking male predominance of 80%. The histopathological subtype and the clinical stage of the disease are the best indicators of prognosis and patient outcome. Low-grade lymphomas such as extranodal marginal zone B-cell lymphoma and FL have a good prognosis, whereas high-grade lymphomas (diffuse large B-cell lymphoma and mantle cell lymphoma) are associated with a poor prognosis. When managing solitary low-grade lymphomas, radiotherapy is the treatment of choice. Chemotherapy, with or without radiotherapy, should be chosen for disseminated and high-grade lymphomas.
Follicle Center Lymphoma (FCL) of the Lower Female Genital Tract (LFGT): A Novel Variant of Primary Cutaneous Follicle Center Lymphoma (PCFCL)
2023, American Journal of Surgical Pathology
Radiological analysis of orbital lymphoma histological subtypes
2023, Orbit (London)

View all citing articles on Scopus

View full text

Clinical pathological reviewsOcular Adnexal Lymphomas: Five Case Presentations and a Review of the Literature

Abstract

Section snippets

Case Histories

Tissue samples

Immunohistology

Results

Discussion

Summary

Method of Literature Search

Acknowledgements

Ann Oncol

Radiother Oncol

Ophthalmology

Analysis of

Am J Ophthalmol

Ophthalmology

Radiother Oncol

Role of CT and MRI. Radiol Clin North Am

Blood

Mayo Clin Proc

Ophthalmology

Am J Pathol

Ophthalmology

Ophthalmology

Int J Radiat Oncol Biol Phys

Ophthalmology

Hum Pathol

Ophthalmology

Radiother Oncol

Lancet

Blood

Mod Pathol

Am J Ophthalmol

Blood

Hum Pathol

Ophthalmology

Int J Radiat Oncol Biol Phys

Am J Pathol

Blood

Am J Ophthalmol

Ophthalmology

Surv Ophthalmol

Ophthalmology

Hematol Oncol Clin North Am

Ophthalmology

Int J Radiat Oncol Biol Phys

Ophthalmology

Ophthalmology

Lancet

Lancet

Am J Ophthalmol

A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project

N Engl J Med

Statistical analyses of clinico-pathological, virological and epidemiological data on lymphoid malignancies with special reference to adult T-cell leukemia/lymphomaa report of the second nationwide study of Japan

The T- and B-Cell Malignancy Study Group. Jpn J Clin Oncol

Clinical pathological reviews
Ocular Adnexal Lymphomas: Five Case Presentations and a Review of the Literature