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Essentials in Ophthalmology |
Oculoplastics and Orbit |
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R. F. Gutho J. A. Katowitz |
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Editors |
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Essentials in Ophthalmology |
Glaucoma |
G. K. Krieglstein R. N. Weinreb |
Cataract and Refractive Surgery |
Series Editors |
Uveitis and Immunological Disorders |
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Vitreo-retinal Surgery |
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Medical Retina |
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Oculoplastics and Orbit |
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Pediatric Ophthalmology, |
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Neuro-Ophthalmology, Genetics |
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Cornea and External Eye Disease |
Editors Rudolf F. Gutho
James A. Katowitz
Oculoplastics
and Orbit
Aesthetic and Functional
Oculofacial Plastic
Problem-Solving
in the 21st Century
With 181 Figures, Mostly in Colour
and 18 Tables
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Series Editors |
Volume Editors |
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Günter K. Krieglstein, MD |
Rudolf F. Gutho , MD |
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Professor and Chairman |
Professor of Ophthalmology |
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Department of Ophthalmology |
University of Rostock |
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University of Cologne |
Department of Ophthalmology |
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Joseph-Stelzmann-Straße 9 |
Doberaner Straße 140 |
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50931 Köln |
18055 Rostock |
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Germany |
Germany |
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Robert N. Weinreb, MD |
James A. Katowitz, MD |
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Professor of Ophthalmology |
||
Professor and Director |
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Children’s Hospital of Philadelphia |
||
Hamilton Glaucoma Center |
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R. D. Wood Ambulatory Care Building |
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Department of Ophthalmology – 0946 |
||
Division of Ophthalmology |
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University of California at San Diego |
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34th Street Civic Center Blvd. |
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9500 Gilman Drive |
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Philadelphia, PA 19104 |
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La Jolla, CA 92093-0946 |
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USA |
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USA |
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ISBN: 978-3-540-85541-5 |
e-ISBN: 978-3-540-85542-2 |
DOI: 10.1007/978-3-540-85542-2
Library of Congress Control Number: 2009933987
© Springer-Verlag Berlin Heidelberg 2010
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Foreword
The Essentials in Ophthalmology series represents an unique updating publication on the progress in all subspecialties of ophthalmology.
In a quarterly rhythm, eight issues are published covering clinically relevant achievements in the whole field of ophthalmology. This timely transfer of advancements for the best possible care of our eye patients has proven to be e ective. The initial working hypothesis of providing new knowledge immediately following publication in the peer-reviewed journal and not waiting for the textbook appears to be highly workable.
We are now in the third cycle of the Essentials in Ophthalmology series, having been encouraged by readSeries Editors
Preface
This third volume of Oculoplastic and Orbital Surgery promises to challenge the reader with stimulating new concepts at the cutting edge of this subspecialty. A variety of innovative techniques is described in this volume, covering both cosmetic and functional aspects of oculoplastic and orbital surgery.
Pearls in cosmetic and oculofacialplastic surgery are presented in great detail, based on extensive experience. Rather than presenting merely anecdotal solutions, specific steps are outlined for problem solving in this rapidly evolving field.
The latest therapies in the management of capillary hemangiomas, periorbital infections, and orbital and periorbital malignancies using specific targeted therapies demonstrate the increasingly important interaction between ophthalmic plastic surgery and the broad field of modern oncology.
Appearance issues are also discussed in relation to managing ophthalmic anomalies in congenital anophthalmic and microphthalmic patients. Controversies in enucleation techniques, implant selection, and implant preparation are presented, and the role of pegging an implant to ultimately improve prosthesis motility is critically evaluated.
It is our hope, as with the previous two volumes, that this presentation of the latest concepts and management techniques for a variety of problem areas in the field of oculoplastic surgery will be of value for both comprehensive ophthalmologists and subspecialists with a particular interest in this field.
Rudolf F. Gutho
James A. Katowitz
Contents
Chapter 1
Ocular Adnexal Lymphoproliferative Disease
Timothy J. Sullivan
1.1 |
Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . |
2 |
1.2 |
Chronic Antigen Stimulation . . . . . . . . . . . |
3 |
1.3 |
Immunosuppression . . . . . . . . . . . . . . . . . . . |
3 |
1.4 |
Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
4 |
1.5 |
Cytogenetics. . . . . . . . . . . . . . . . . . . . . . . . . . . |
4 |
1.6 |
Clinical Features. . . . . . . . . . . . . . . . . . . . . . . . |
7 |
1.7 |
Imaging Findings . . . . . . . . . . . . . . . . . . . . . . |
8 |
1.8 |
Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
9 |
1.9 |
Positron Emission Tomography . . . . . . . . . |
9 |
1.10 |
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
9 |
1.11 |
Follicular Lymphoma . . . . . . . . . . . . . . . . . . . |
11 |
1.12 |
Mantle Cell Lymphoma. . . . . . . . . . . . . . . . . |
11 |
1.13 |
Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . |
11 |
1.14 |
Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . |
12 |
1.15 |
Immunotherapy. . . . . . . . . . . . . . . . . . . . . . . . |
12 |
1.16 |
Radioimmunotherapy . . . . . . . . . . . . . . . . . . |
13 |
1.17 |
Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
13 |
1.18 |
The Future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
13 |
|
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
14 |
Chapter 2
Pearls in Cosmetic Oculofacial Plastic Surgery
Jonathan A. Hoenig
2.1 |
General Introduction . . . . . . . . . . . . . . . . . . . |
21 |
2.2 |
The Aging Process and Facial Analysis. . . |
22 |
2.3 |
Endoscopic Brow Lift . . . . . . . . . . . . . . . . . . . |
23 |
2.3.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
23 |
2.3.2 |
Endoscopic Browlift Anesthesia Pearls . . . . |
26 |
2.3.3Endoscopic Browlift Surgical
Procedure Pearls . . . . . . . . . . . . . . . . . . . . . . . 26
2.3.4Endoscopic Browlift Postoperative
|
Care Pearls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
27 |
2.4 |
Upper Blepharoplasty . . . . . . . . . . . . . . . . . . |
29 |
2.4.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
29 |
2.4.2 |
Patient Evaluation. . . . . . . . . . . . . . . . . . . . . . |
29 |
2.4.3Upper Blepharoplasty
Anesthesia Pearls . . . . . . . . . . . . . . . . . . . . . . 30
2.4.4Upper Blepharoplasty Surgical
Procedure Pearls . . . . . . . . . . . . . . . . . . . . . . . 30
2.5Lower Blepharoplasty, Fillers,
|
and Midface Augmentation . . . . . . . . . . . . |
33 |
2.5.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
33 |
2.5.2 |
Patient Evaluation. . . . . . . . . . . . . . . . . . . . . . |
33 |
2.5.3Lower Blepharoplasty
Anesthesia Pearls . . . . . . . . . . . . . . . . . . . . . . 37
2.5.4Lower Blepharoplasty Surgical
Procedure Pearls . . . . . . . . . . . . . . . . . . . . . . . 38
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Chapter 3
Current Concepts in the Management
of Idiopathic Orbital Inflammation
Katherine A. Lane and Jurij R. Bilyk
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3.2 What Is the Diagnosis? . . . . . . . . . . . . . . . . . 47
3.2.1 Pitfalls of Diagnosis. . . . . . . . . . . . . . . . . . . . . 48
3.2.2 A Diagnostic Corticosteroid Trial? . . . . . . . 54
3.2.3 The Question of Biopsy . . . . . . . . . . . . . . . . . 56
3.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
3.3.1 Corticosteroids. . . . . . . . . . . . . . . . . . . . . . . . . 57
3.3.2 Radiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
3.3.3 Other Agents . . . . . . . . . . . . . . . . . . . . . . . . . . 58
3.4 Special Circumstances. . . . . . . . . . . . . . . . . . 60
3.4.1 Pediatric IOIS. . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.4.2 Sclerosing Pseudotumor . . . . . . . . . . . . . . . 60
3.4.3 Tolosa–Hunt Syndrome. . . . . . . . . . . . . . . . . 62
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Chapter 4
Lacrimal Canalicular Inflammation and Occlusion:
Diagnosis and Management
David H. Verity and Geo rey E. Rose
4.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
67 |
4.2Embryology, Anatomy, Physiology, and Pathophysiology of the Canalicular
|
System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
67 |
4.3 |
Infective Causes. . . . . . . . . . . . . . . . . . . . . . . . |
69 |
xContents
4.3.1 |
Periocular Herpes Simplex Infection . . . . |
69 |
4.3.2 |
Bacterial Canaliculitis. . . . . . . . . . . . . . . . . . . |
70 |
4.4 |
Systemic Inflammatory Disease . . . . . . . . . |
70 |
4.4.1 |
Lichen Planus . . . . . . . . . . . . . . . . . . . . . . . . . . |
70 |
4.4.2 |
Ocular Cicatricial Pemphigoid . . . . . . . . . . |
70 |
4.4.3Drug Eruptions (Stevens–Johnson
|
Syndrome) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
71 |
4.5 |
Iatrogenic Causes . . . . . . . . . . . . . . . . . . . . . . |
71 |
4.5.1 |
Systemic Drugs . . . . . . . . . . . . . . . . . . . . . . . . |
71 |
4.5.1.1 |
5-Fluorouracil (5-FU) . . . . . . . . . . . . . . . . . . . |
71 |
4.5.1.2 |
Docetaxel (Taxotere) . . . . . . . . . . . . . . . . . . . |
72 |
4.5.2 |
Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . |
72 |
4.5.3 |
Topical Ophthalmic Treatments . . . . . . . . . |
73 |
4.5.3.1Preservative-Related Chronic
|
Conjunctivitis . . . . . . . . . . . . . . . . . . . . . . . . . . |
73 |
4.5.3.2 |
Mitomycin C Therapy. . . . . . . . . . . . . . . . . . . |
73 |
4.5.4 |
Lacrimal Stents and Plugs . . . . . . . . . . . . . . |
73 |
4.6The Surgical Approach to Managing
Canalicular Disease. . . . . . . . . . . . . . . . . . . . . 74
4.6.1Surgical Technique for Dacryocystorhinostomy with
Retrograde Canaliculostomy. . . . . . . . . . . . 74
4.6.2Placement of a Jones Canalicular
Bypass Tube. . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Chapter 5
Orbitofacial Neurofibromatosis 1:
Current Medical and Surgical Management
William R. Katowitz and James A. Katowitz
5.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
79 |
5.2 |
Nomenclature. . . . . . . . . . . . . . . . . . . . . . . . . . |
79 |
5.3 |
Clinical Manifestations of NF1 . . . . . . . . . . |
79 |
5.4 |
Orbitofacial Tumors in NF1 . . . . . . . . . . . . . |
80 |
5.4.1 |
Neurofibromas . . . . . . . . . . . . . . . . . . . . . . . . . |
80 |
5.4.2Malignant Peripheral Nerve
|
Sheath Tumors . . . . . . . . . . . . . . . . . . . . . . . . . |
81 |
5.4.3 |
Optic Pathway Gliomas . . . . . . . . . . . . . . . . . |
81 |
5.5 |
Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
83 |
5.5.1 |
The NF1 Gene . . . . . . . . . . . . . . . . . . . . . . . . . . |
83 |
5.5.2Overlapping NF1-Like Phenotype
(SPRED1). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.6Management of Neurofibromatosis
|
Type 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
84 |
5.6.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
84 |
5.6.2Medical Management of
Neurofibromas . . . . . . . . . . . . . . . . . . . . . . . . . 84
5.7Surgical Management of Orbitofacial
Tumors in NF1 . . . . . . . . . . . . . . . . . . . . . . . . . 84
5.7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
5.7.2 Timing of Surgery . . . . . . . . . . . . . . . . . . . . . . 84
5.7.3 Periorbital Involvement . . . . . . . . . . . . . . . . 85
5.7.3.1 |
The Upper Eyelid . . . . . . . . . . . . . . . . . . . . . . . |
85 |
5.7.3.2 |
The Lower Eyelid and Midface . . . . . . . . . . |
85 |
5.7.4 |
Orbital Involvement . . . . . . . . . . . . . . . . . . . . |
86 |
5.7.4.1 |
Proptosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
86 |
5.7.4.2 |
Proptosis Due to Orbital |
|
|
Neurofibromas . . . . . . . . . . . . . . . . . . . . . . . . . |
87 |
5.7.4.3 |
Proptosis Due to Optic Nerve Glioma . . . |
87 |
5.7.4.4Orbital Enlargement with Dystopia
and Hypoglobus . . . . . . . . . . . . . . . . . . . . . . . 87
5.8The Natural History of NF1 Tumor
Growth from Birth to Senescence . . . . . . . 90 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Chapter 6
Clinicopathologic Features of Lesions
A ecting the Lacrimal Drainage System
in External Dacryocystorhinostomy
Ludwig M. Heindl, Anselm G. M. Jünemann, and Leonard M. Holbach
6.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
95 |
6.2Surgical Anatomy of the Lacrimal
Drainage System . . . . . . . . . . . . . . . . . . . . . . . 96
6.3Basic Diagnostics for Disorders
of the Lacrimal Drainage System. . . . . . . . 97
6.4Selective Lacrimal Sac Biopsy
in External Dacryocystorhinostomy . . . . . 97
6.5Definitive Treatment and Prognosis of Lesions A ecting the Lacrimal
Drainage System . . . . . . . . . . . . . . . . . . . . . . . 99
6.5.1 Case A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6.5.2 Case B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6.5.3 Case C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
6.5.4 Case D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
6.5.5 Case E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
6.5.6 Case F . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
6.5.7 Case G . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Chapter 7
Systemic and Ophthalmic Anomalies in Congenital Anophthalmic
or Microphthalmic Patients
Michael P. Schittkowski and Rudolf F. Gutho
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
7.2 Patients and Methods . . . . . . . . . . . . . . . . . . 106
7.2.1 Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
7.2.2 Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
7.3 Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
7.3.1 Patient Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
7.3.2 Age. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
7.3.3 Family History. . . . . . . . . . . . . . . . . . . . . . . . . . 106
7.3.4 Pregnancy History. . . . . . . . . . . . . . . . . . . . . . 107
7.3.5 |
Birth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
107 |
7.3.6Associated Systemic and
Ocular Diseases . . . . . . . . . . . . . . . . . . . . . . . . 107
7.3.7Developmental Anomaly and Potential Visual Capacity of the
Fellow Eye in Unilateral Disease. . . . . . . . . 110
7.3.8 Neuroradiological Findings (Brain MRI). . 111
7.3.9 Nasolacrimal System Findings . . . . . . . . . . 111
7.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
7.4.1 Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
7.4.2 Obstetric and Family History. . . . . . . . . . . . 112
7.4.3 Associated Pathologies . . . . . . . . . . . . . . . . . 113
7.4.3.1Ophthalmological Findings
|
in Unilateral Disease. . . . . . . . . . . . . . . . . . . . |
113 |
7.4.3.2 |
Neuroradiological Findings . . . . . . . . . . . . . |
113 |
7.4.3.3 |
Systemic Diseases . . . . . . . . . . . . . . . . . . . . . . |
114 |
7.4.3.4 |
Nasolacrimal Duct Findings. . . . . . . . . . . . . |
114 |
7.5 |
Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . |
115 |
|
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
116 |
Chapter 8
Brow Suspension in Complicated Unilateral Ptosis: Frontalis Muscle Stimulation via Contralateral Levator Recession
Markus F. Pfei er
8.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
117 |
8.2 |
Evaluation of Complicated Ptosis . . . . . . . |
117 |
8.2.1 |
Compensatory Eyebrow Elevation . . . . . . |
117 |
8.2.2Examples of Complicated Unilateral Ptosis with Insu cient Compensatory
Brow Elevation . . . . . . . . . . . . . . . . . . . . . . . . . 118
8.2.3Innervation Patterns of the Frontalis
Muscle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
8.2.4Checklist of Preoperative Evaluation
of Complicated Ptosis . . . . . . . . . . . . . . . . . . 118
8.2.5Planning Partial or Total Levator Muscle Recession Combined with
Unilateral or Bilateral Brow
Suspension . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
8.3Surgical Technique of Levator Muscle
|
Recession . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
119 |
8.3.1 |
Principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
119 |
8.3.2 |
Approach to the Levator. . . . . . . . . . . . . . . . |
119 |
8.3.3 |
Partial Levator Recession . . . . . . . . . . . . . . . |
119 |
8.3.4 |
Total Levator Recession. . . . . . . . . . . . . . . . . |
119 |
8.3.5The Lid-Lowering E ect and Eyelid Symmetry: Evolution of the Eyelid
|
Level After Levator Recession . . . . . . . . . . . |
121 |
8.3.6 |
Undercorrection and Overcorrection. . . . |
121 |
8.4Surgical Technique of Brow
|
Suspension . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
121 |
8.4.1 |
Materials for Brow Suspension . . . . . . . . . . |
121 |
Contents xi
8.4.1.1 |
Nonautogenous Materials . . . . . . . . . . . . . . |
121 |
8.4.1.2 |
Autogenous Fascia Lata . . . . . . . . . . . . . . . . |
121 |
8.4.2Our Technique of Harvesting
Autogenous Fascia Lata . . . . . . . . . . . . . . . . 121
8.4.3Mechanical Principals of Brow
Suspension . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
8.4.4 Upper Lid Approach. . . . . . . . . . . . . . . . . . . . 122
8.4.5 Fascia Implantation . . . . . . . . . . . . . . . . . . . . 122
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Chapter 9
Modern Concepts in Orbital Imaging
Jonathan J. Dutton
9.1 |
Computerized Tomography . . . . . . . . . . . . |
125 |
9.2 |
Three-Dimensional Imaging . . . . . . . . . . . . |
129 |
9.3 |
Magnetic Resonance Imaging . . . . . . . . . . |
129 |
9.3.1 |
The T1 Constant. . . . . . . . . . . . . . . . . . . . . . . . |
130 |
9.3.2 |
The T2 Constant. . . . . . . . . . . . . . . . . . . . . . . . |
131 |
9.3.3 |
Creating the MR Image . . . . . . . . . . . . . . . . . |
131 |
9.4Imaging of Common Orbital
|
Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
134 |
9.4.1 |
Adenoid Cystic Carcinoma. . . . . . . . . . . . . . |
134 |
9.4.2 |
Cavernous Hemangioma . . . . . . . . . . . . . . . |
134 |
9.4.3 |
Dermoid Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . |
134 |
9.4.4 |
Fibrous Dysplasia . . . . . . . . . . . . . . . . . . . . . . |
135 |
9.4.5 |
Lymphangioma . . . . . . . . . . . . . . . . . . . . . . . . |
136 |
9.4.6 |
Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
136 |
9.4.7 |
Myositis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
136 |
9.4.8 |
Optic Nerve Glioma . . . . . . . . . . . . . . . . . . . . |
138 |
9.4.9 |
Pseudotumor . . . . . . . . . . . . . . . . . . . . . . . . . . |
139 |
9.4.10 |
Rhabdomyosarcoma . . . . . . . . . . . . . . . . . . . |
139 |
9.5Di usion MRI (Di usion-Weighted
Imaging). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
9.6 Positron Emission Tomography . . . . . . . . . 141
9.7 Orbital Ultrasound . . . . . . . . . . . . . . . . . . . . . 142
9.7.1 Physics and Instrumentation. . . . . . . . . . . . 142
9.7.1.1 Topographic Echography . . . . . . . . . . . . . . . 143
9.7.1.2 Quantitative Echography . . . . . . . . . . . . . . . 143
9.7.1.3 Kinetic Echography. . . . . . . . . . . . . . . . . . . . . 143
9.7.2 Extraocular Muscles . . . . . . . . . . . . . . . . . . . . 145
9.7.3 Optic Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Chapter 10
Management of Periorbital Cellulitis
in the 21st Century
Michael P. Rabinowitz and Scott M. Goldstein
10.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
149 |
10.2The Infection: Stages, Symptoms,
|
and E ects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
149 |
10.3 |
Etiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
151 |
10.4 |
Microbiology. . . . . . . . . . . . . . . . . . . . . . . . . . . |
151 |
xii Contents
10.5 |
Changing Pathogens and Resistance. . . . |
152 |
12.5 |
Localization . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
174 |
|
10.5.1 |
CA-MRSA Versus Hospital-Acquired |
|
12.6 |
Clinical Features. . . . . . . . . . . . . . . . . . . . . . . . |
175 |
|
|
MRSA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
152 |
12.7 |
Imaging and Patterns of Orbital |
|
|
10.5.2 |
Orbital MRSA. . . . . . . . . . . . . . . . . . . . . . . . . . . |
153 |
|
Metastatic Disease . . . . . . . . . . . . . . . . . . . . . |
176 |
|
10.6 |
Evaluation of Orbital Cellulitis . . . . . . . . . . |
154 |
12.8 |
Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
177 |
|
10.7 |
Medical Treatment of Orbital Cellulitis . . |
155 |
12.9 |
Common Types of Orbital Metastases . . . |
178 |
|
10.8 |
Surgical Treatment of Orbital Cellulitis . . |
156 |
12.9.1 |
Breast Carcinoma . . . . . . . . . . . . . . . . . . . . . . |
178 |
|
10.9 |
Prevention of Orbital Cellulitis |
|
12.9.2 |
Lung Carcinoma . . . . . . . . . . . . . . . . . . . . . . . |
178 |
|
|
after Orbital Fracture . . . . . . . . . . . . . . . . . . . |
158 |
12.9.3 |
Prostatic Cancer. . . . . . . . . . . . . . . . . . . . . . . . |
179 |
|
|
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
159 |
12.9.4 |
Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
179 |
|
|
|
|
12.9.5 |
Carcinoid Tumor . . . . . . . . . . . . . . . . . . . . . . . |
179 |
|
Chapter 11 |
|
12.10 |
Di erential Diagnosis . . . . . . . . . . . . . . . . . . |
180 |
||
Current Concepts in the Management |
|
12.11 |
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
180 |
||
of Capillary Hemangiomas: Steroids, |
|
12.11.1 |
Radiotherapy |
180 |
||
Beta-Blockers, or Surgery |
|
|||||
|
12.11.2 |
Chemotherapy |
180 |
|||
François Codère and Julie Powell |
|
|||||
|
12.11.3 |
Hormonal Therapy . . . . . . . . . . . . . . . . . . . . . |
180 |
|||
11.1 |
Clinical Picture |
161 |
12.11.4 |
Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
181 |
|
12.12 |
Prognosis and Survival |
181 |
||||
11.1.1 |
Clinical Phases |
161 |
||||
|
References |
181 |
||||
11.1.2 |
Etiology, Histology, and Classification |
161 |
|
|||
|
|
|
||||
11.1.3 |
Di erential Diagnosis of Infantile |
|
Chapter 13 |
|
||
|
Hemangioma |
162 |
|
|||
|
Targeted Therapy in the Treatment |
|
||||
11.2 |
Ocular Complications |
163 |
|
|||
of Orbital and Periorbital Malignancies |
|
|||||
11.3 |
Investigation |
163 |
|
|||
Aaron Savar and Bita Esmaeli |
|
|||||
11.3.1 |
Angiography |
164 |
|
|||
|
|
|
||||
11.4 |
Management . . . . . . . . . . . . . . . . . . . . . . . . . . |
165 |
13.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
187 |
|
11.4.1 |
Active Nonintervention. . . . . . . . . . . . . . . . . |
165 |
13.2 |
Rituximab. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
188 |
|
11.4.2 |
Indications for Treatment . . . . . . . . . . . . . . . |
165 |
13.3 |
Yttrium-90-Labeled Ibritumomab |
|
|
11.5 |
Modalities of Treatment . . . . . . . . . . . . . . . . |
165 |
|
Tiuxetan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
189 |
|
11.5.1 |
Steroids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
165 |
13.4 |
Imatinib Mesylate . . . . . . . . . . . . . . . . . . . . . . |
190 |
|
11.5.1.1 |
Topical Steroids . . . . . . . . . . . . . . . . . . . . . . . . |
165 |
13.5 |
Cetuximab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
191 |
|
11.5.1.2 |
Intralesional Corticosteroid Injection. . . . |
165 |
|
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
192 |
|
11.5.1.3 |
Oral Corticosteroids . . . . . . . . . . . . . . . . . . . . |
166 |
|
|
|
|
11.5.2 |
Interferon-Alfa . . . . . . . . . . . . . . . . . . . . . . . . . |
166 |
Chapter 14 |
|
||
11.5.3 |
Vincristine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
167 |
Controversies in Enucleation Technique |
|
||
11.5.4 |
Laser. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
167 |
and Implant Selection: Whether to Wrap, |
|
||
11.5.5 |
Embolization |
167 |
Attach Muscles, and Peg? |
|
||
|
|
|
||||
11.5.6 |
Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
167 |
David R. Jordan and Stephen R. Klapper |
|
||
11.5.7Beta-Blockers: A New Promising
|
Modality of Treatment |
168 |
14.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
195 |
|
14.2 |
Porous Orbital Implants |
196 |
||
|
References |
170 |
|||
|
14.3 |
Orbital Implant Selection in Adults |
199 |
||
|
|
|
|||
Chapter 12 |
|
14.4 |
Orbital Implant Selection |
|
|
|
|
in Children |
200 |
||
Evaluation and Management |
|
|
|||
|
14.5 |
Volume Considerations |
|
||
of Metastatic Orbital Tumors |
|
|
|||
Alejandra A. Valenzuela and Alan A. McNab |
|
|
in Orbital Implant Selection . . . . . . . . . . . . |
201 |
|
|
14.6 |
Orbital Implant Wrapping |
|
||
|
|
|
|
||
12.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
173 |
|
and Attaching Extraocular Muscles . . . . . |
202 |
12.2 |
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . |
173 |
14.7 |
Which Wrap to Use . . . . . . . . . . . . . . . . . . . . . |
203 |
12.3 |
Biological Behavior and Timing |
|
14.8 |
To Peg or Not to Peg Porous Implants . . . |
204 |
|
of Metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . |
174 |
14.9 |
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
206 |
12.4 |
Lateralization . . . . . . . . . . . . . . . . . . . . . . . . . . |
174 |
|
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
206 |
Chapter 15
Non-surgical Volume Enhancement
with Fillers in the Orbit and Periorbital Tissues: Cosmetic and Functional Considerations
Ana M. Susana Morley and Raman Malhotra
15.1 |
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . |
213 |
15.2 |
Etiology and Presentation . . . . . . . . . . . . . . |
213 |
15.2.1 |
Etiology of Orbital Volume Loss . . . . . . . . . |
213 |
15.2.2 |
Etiology of Periorbital Volume Loss . . . . . |
213 |
15.2.3 |
Features of Orbital Volume Loss. . . . . . . . . |
214 |
15.2.4 |
Features of PeriOorbital Volume Loss. . . . |
215 |
15.3Background to Injectable
Soft-Tissue Fillers. . . . . . . . . . . . . . . . . . . . . . . 215
15.3.1Historical Perspective on Volume
Replacement. . . . . . . . . . . . . . . . . . . . . . . . . . . 215
15.3.2Advantages of Injectable
Soft-Tissue Fillers. . . . . . . . . . . . . . . . . . . . . . . 215
15.3.3Complications of Injectable
Soft-Tissue Fillers. . . . . . . . . . . . . . . . . . . . . . . 215
Contents xiii
15.4 Types of Injectable Soft-Tissue Filler. . . . . 216 15.4.1 Collagen Fillers. . . . . . . . . . . . . . . . . . . . . . . . . 216 15.4.2 Hyaluronic acid Fillers . . . . . . . . . . . . . . . . . . 216
15.4.3Semipermanent Injectable
|
Soft-Tissue Fillers. . . . . . . . . . . . . . . . . . . . . . . |
216 |
15.5 |
Treatment Areas . . . . . . . . . . . . . . . . . . . . . . . |
217 |
15.5.1 |
Orbit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
217 |
15.5.2 |
Upper Eyelid and Brow . . . . . . . . . . . . . . . . . |
220 |
15.5.3 |
Tear Trough . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
220 |
15.5.4 |
Temple and Brow . . . . . . . . . . . . . . . . . . . . . . |
223 |
15.6Other Periorbital Uses
of Injectable Soft-Tissue Fillers . . . . . . . . . . 225
15.6.1 Upper Eyelid Loading . . . . . . . . . . . . . . . . . . 226
15.6.2 Lower Eyelid Elevation. . . . . . . . . . . . . . . . . . 226
15.6.3 Treatment of Cicatricial Ectropion. . . . . . . 226
15.7 Future Developments . . . . . . . . . . . . . . . . . . 226
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
231 |
Contributors
Jurij R. Bilyk |
Anselm G.M. Jünemann |
Oculoplastic and Orbital Surgery Service, |
Department of Ophthalmology and Eye Hospital, |
Wills Eye Institute, 840 Walnut St., |
University Erlangen-Nürnberg, Schwabachanlage 6, |
Philadelphia, PA 19107, USA |
91054 Erlangen, Germany |
François Codère |
James A. Katowitz |
Department of Ophthalmology, Hôpital Ste-Justine, |
Children’s Hospital of Philadelphia, |
Université de Montréal, 3175 Côte Ste-Catherine, |
Division of Ophthalmology, |
Montreal, Quebec, Canada, H3T 1C5 |
R.D. Wood Ambulatory Care Building |
Jonathan J. Dutton |
34th Street Civic Center Blvd. |
Philadelphia, PA 19104, |
|
Department of Ophthalmology, |
USA |
University of North Carolina, |
William R. Katowitz |
Chapel Hill, NC 27599-7040, USA |
|
Bita Esmaeli |
Oculoplastic Surgery, Children’s Hospital of Philadelphia |
Division of Ophthalmology, |
|
Section of Ophthalmology, |
34th Street Civic Center Blvd. |
Department of Head and Neck Surgery, |
Philadelphia, PA 19104, USA |
The University of Texas M.D. Anderson Cancer Center, |
Stephen R. Klapper |
1515 Holcombe Blvd., Unit 1445, Houston, |
|
Texas 77030, USA |
Klapper Eyelid and Facial Plastic Surgery, |
Scott M. Goldstein |
11900 North Pennsylvania Street, Suite 104, |
Carmel, IN 46032, USA |
|
Oculoplastic Service, Wills Eye Institute, |
Katherine A. Lane |
Thomas Je erson University, Philadelphia, PA, USA |
|
Rudolf F. Gutho |
Department of Ophthalmology, |
The Children’s Hospital of Philadelphia, |
|
Department of Opthalmology, Rostock University, |
34th and Civic Center Blvd., |
Doberaner Straβe 140, 18055 Rostock, Germany |
Philadelphia, PA 19104, USA |
Ludwig M. Heindl |
Raman Malhotra |
Department of Ophthalmology and Eye Hospital, |
Queen Victoria Hospital, Corneoplastic Unit, |
University Erlangen-Nürnberg, Schwabachanlage 6, |
Holtye Road, East Grinstead, RH19 3DZ, |
91054 Erlangen, Germany |
West Sussex, UK |
Jonathan A. Hoenig |
Alan A. McNab |
9735 Wilshire Blvd. #308, Beverly Hills, CA 90212, USA |
Royal Victorian Eye and Ear Hospital, |
Leonard M. Holbach |
Orbital, Lacrimal and Plastic Clinic, |
Suite 216, 100 Victoria Parade, East Melbourne 3002, |
|
Department of Ophthalmology and Eye Hospital, |
Victoria, Australia |
University Erlangen-Nürnberg, Schwabachanlage 6, |
Ana M. Susana Morley |
91054 Erlangen, Germany |
|
David R. Jordan |
Queen Victoria Hospital, Corneoplastic Unit, |
East Grinstead, West Sussex, UK |
|
University of Ottawa Eye Institute, 301 O’Connor Street, |
St. Thomas’ Hospital, Department of Ophthalmology, |
Ottawa, Ontario, Canada, K2P 1V6 |
Westminster Bridge Rd., London SE1 7EH, UK |
xvi Contributors
Markus J. Pfei er |
Timothy J. Sullivan |
Augenklinik Herzog Carl Theodor, |
University of Queensland, Eyelid, |
Nymphenburger Str.43, |
Lacrimal and Orbital Clinic, |
80335 München, Germany |
Royal Brisbane and Women’s Hospital, |
Julie Powell |
Butterfield Street, Herston, Brisbane, |
Queensland, 4029, Australia |
|
Division of Pediatric Dermatology, |
Alejandra A. Valenzuela |
Hôpital Ste-Justine, Université de Montréal, |
|
3175 Côte Ste-Catherine, Montreal, Quebec, |
Orbital, Lacrimal and Oculoplastic Clinic, |
Canada, H3T 1C5 |
Department of Ophthalmology and Visual Sciences, |
Michael P. Rabinowitz |
Division of Neurosurgery, QEII Health Sciences Centre, |
Dalhousie University, Room 2035, 2W Victoria Building, |
|
Wills Eye Institute, Oculoplastic Service, |
1276 South Park Street, Halifax, NS, B3H 2Y9, Canada |
Thomas Je erson University, Philadelphia, PA, USA |
David H. Verity |
|
|
Geo rey E. Rose |
Moorfields Eye Hospital, City Road, |
Moorfields Eye Hospital, Adnexal Service, City Road, |
London EC1V 2PD, UK |
London EC1V 2PD |
Lacrimal Clinic, Moorfields Eye Hospital, City Road, |
Aaron Savar |
London EC1V 2PD, UK |
|
|
Department of Head and Neck Surgery, |
|
Section of Ophthalmology, |
|
The University of Texas M.D. Anderson Cancer Center, |
|
Houston, Texas, USA |
|
Michael P. Schittkowski |
|
Georg-August University, |
|
University Medical Center Goettingen, |
|
Department of Ophthalmology, |
|
Section for Strabismus, |
|
Neuroophthalmology and Oculoplastic Surgery |
|
R.-Koch-Str. 40 |
|
D 37075 Goettingen, Germany |
|
Chapter 1 |
|
Ocular Adnexal Lymphoproliferative |
1 |
Disease |
Timothy J. Sullivan
Core Messages
■Lymphoma is the most common orbital malignancy, usually presenting clinically with a short history of painless swelling, proptosis, or a salmon patch. The incidence of ocular adnexal lymphoproliferative disease Ocular adnexal lymphoproliferative disease (OALD) is increasing at 6% per year. The majority of adnexal lymphomas are extranodal marginal zone lymphoma (EMZL) or mucosa-associated lymphoid tissue (MALT).
■Chronic antigen stimulation and immunosuppression, including ultraviolet (UV) irradiation, contribute to pathogenesis. Improvements
in molecular genetic techniques have led to more accurate diagnosis. Advances in imaging mean our ability to stage the presence and extent of systemic involvement has increased.
■Computed tomographic (CT) images usually show homogeneous, well-circumscribed lesions, molding to the globe, of greater than brain density with moderate enhancement. Magnetic resonance imaging (MRI) lesions are isointense to extraocular muscles on T1and T2-weighted images and show moderate enhancement with gadolinium. Positron emission tomography (PET) scanning provides improved detection of the presence and extent of systemic involvement.
■While radiotherapy remains the mainstay of treatment, management approaches are undergoing major changes. Treatments directed to reduce chronic antigen stimulation or to use immunotherapy or radioimmunotherapy result in greater response to treatment as well as improved quality of life and survival.
Summary for the Clinician
■MALT lymphoma is the most common OALD.
■MALT arises in response to chronic antigen stimulation, and increasing genetic aberrations lead to malignancy.
■Molecular genetic testing with polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) is being routinely performed to complement morphological findings to allow more rapid accurate diagnosis of OALD.
Malignant lymphomas represent neoplastic proliferation of cells predominantly located in lymphoid tissues. Lymphoma can be broadly divided into non-Hodgkin lymphoma (NHL; 70%) and Hodgkin disease (30%) [145]. There are 65,000 new cases of NHL annually as well as 19,000 deaths each year in the United States [83].
The annual incidence for mature B-cell neoplasms, which form the largest subgroup of lymphoma, ranges from 15/100,000 in the United States, Europe, and Australia to only 1.2/100,000 in China [61].
While the overall incidence of lymphoma has been increasing annually by 3–4% per year for many decades [22, 48], the rate of extranodal disease has been increasing at a greater rate [36, 50]. Within the extranodal subgroup, OALD has shown the greatest increase in incidence at a rate of up to 6.3% per year [106, 116, 137]. OALD represents a spectrum, ranging from benign reactive lymphoid hyperplasia (RLH) to malignant ocular adnexal lymphomas (OALs). Almost all OALs are B-cell NHLs.
OALD disease has provided many challenges for the clinician and pathologist. Because of limitations in pathological techniques and understanding, previous workers were unable to correlate clinical behavior with pathological diagnosis in between 20% and 50% of cases [77, 114, 115]. This mismatch applied to both benign-appearing
21 Ocular Adnexal Lymphoproliferative Disease
lesions, which followed an aggressive course, and frankly malignant orbital lesions on histology, which failed to disseminate [94, 96]. With the discovery in the early 1970’s [74, 75, 155], that separate B- and T- lymphocyte subsets
1existed and also through insights gained with electron microscopy [78], pathologists began to understand that lymphomacomprisedmanydistinctentities.Unfortunately, however, despite these advances, they were still unable to correlate clinical behavior with morphological appearance. This only came with an appreciation of immunophenotype and the use of the cluster of differentiation (CD) nomenclature [37, 54, 74, 77, 94–97]. The first CD discovered was B1, now known as CD20, a pan B-cell marker and target for monoclonal antibody therapy. The application of molecular genetics to pathological specimens [76, 80, 98, 108–110] has finally given pathologists the ability to precisely define the genetic aberrations underlying these lesions.
Shortly after extranodal lymphomas of MALT were described elsewhere in the body [62, 68, 71, 72], similar lesions were recognized in the orbit [76, 79] but had probably been described in the orbit prior to the systemic recognition of this entity [78]. Since the early descriptions of MALT lymphoma, a greater appreciation of the importance of this entity in the ocular adnexa has developed, where it constitutes the majority of primary OALs [8, 15, 26, 84, 104, 113, 117, 153, 154]. There were also problems of applicability of existing classification schemes to OALD because of an inability to incorporate extranodal lesions. Fortunately, the classification in current use, the World Health Organization (WHO) modification of the Revised European American Lymphoma Classification, recognizes both extranodal disease and marginal zone MALT lymphomas and is designed to accommodate new entities as further diagnostic progress elucidates additional subtypes [69, 73].
OAL may be a primary process, arising within adnexal structures, but it may also be secondary from primary lesions elsewhere in the body. Less commonly, the adnexa may be involved by direct extension from primary lesions in adjacent structures such as the sinuses.
OAL is usually subdivided into orbital, eyelid, conjunctival, and lacrimal sac lesions. Most large series confirmed that EMZL of MALT comprise one half to two thirds of OALs in Western countries and up to 90% in Asian communities, where the incidence of follicular lymphoma (FL) is very low. Other common indolent lesions include follicular (FL) and lymphoplasmacytic lymphoma, while the two more common aggressive lesions are the diffuse large B-cell lymphoma (DLBCL) and Mantle cell lymphoma (MCL). Less commonly, other non-Hodgkin B-cell lesions (e.g., small cell lymphoma)
may occur, and T- and NK (natural killer) cell lymphomas also occur rarely [27, 149, 156].
1.1Pathogenesis
Lymphomas represent a malignant, clonal proliferation of lymphocytes, although clonality does not always constitute malignancy. The various lymphoma subtypes largely correspond to clonal proliferations of cells arrested at specific stages of lymphocyte development. This process begins in the marrow with precursor B lymphoblasts, which undergo immunoglobulin VDJ recombination to become surface immunoglobulin-positive naïve B cells [99]. These recirculating naïve B cells are found in blood, primary lymphoid follicles, and follicle mantle zones. Exposure to antigen leads to transformation to blast cells, which migrate into the center of the primary follicle, establishing the germinal center by filling the follicular dendritic cell meshwork, where they are now known as centroblasts. BCL-6 is necessary for germinal center formation, and then its downregulation is important for further lymphocyte development [21]. Here, the cells undergo somatic mutations of the immunoglobulin variable region gene and BCL-6 as part of the normal immune response, eventually becoming centrocytes. Centrocytes interact with surface molecules to differentiate into memory B cells or plasma cells. The memory B cells are found in the marginal zone of the lymph follicle, whereas plasma cells home to marrow [61].
There is site specificity for the homing of postgerminal center B cells, orchestrated by adhesion molecules and cytokines [122, 130]. Thus, MALT-derived B cells home to their specific MALT and nodal B cells to specific lymph nodes. Corresponding to these stages of development, EMZL and lymphoplasmacytic lymphoma arise from memory B cells and FLs and DLBCLs from the germinal center, whereas MCL arises from mature naïve B cells, found in the mantle region of the lymph node. A range of chromosomal translocations, deletions, and mutations occurs during the different phases of lymphocyte development, eventually establishing a clone of malignant cells. The clinical behavior of the tumor usually reflects the behavior of the normal cell counterpart. This corresponds to the lymphocyte stage at which the abnormal cell has accumulated sufficient genetic abnormalities to proliferate without control or avoid programmed cell death, constituting malignancy. Malignant cell clones that have low turnover produce indolent lymphomas such as MALT and FL, whereas cell stages that are more active will give rise to more aggressive lesions such as MCL or DLBCL. A small percentage of the low-grade lymphomas will
undergo transformation to a higher-grade lesion, for example, follicular and MALT lesions can transform into DLBCL.
The most common OAL is the MALT lymphoma. Although the orbit itself has no lymph nodes or true lymphatic drainage system, studies have confirmed the presence of small lymphatic channels associated with the optic nerve [55, 56]. There is also a well-established ocular MALT system extending from the lacrimal gland, encompassing the conjunctival tissues, and including the lacrimal drainage apparatus. This can be broken down into the conjunctiva-associated lymphoid tissue and lacrimal drainage-associated lymphoid tissue (CALT and LDALT, respectively) with an overall designation of eyeassociated lymphoid tissue (EALT) [92, 93]. Lymphoid follicles from these tissues participate in the normal immune response to antigens with production of antibodies and effector plasma cells. While most OAL is MALT derived, presumably arising from these tissues, lymphocytes destined to reside in the EALT system pass through the normal lymphocyte development cycle, and this may explain why we see other primary B-cell lymphomas in the ocular adnexal region. Lymphomas originating in ocular adnexal tissues can have systemic lymphoid involvement of the marrow and other tissues. Conversely, systemic lymphomas may involve adnexal tissue secondarily.
Primary ocular adnexal T- and NK cell lymphomas may also be seen, but are less common, possibly reflecting the fewer gene rearrangements that occur in their normal development compared to B lymphocytes [89].
1.2Chronic Antigen Stimulation
Chronic antigen stimulation and infectious agents have an important role in pathogenesis of lymphomas. Chronic low-grade infection and inflammation may induce and promote carcinogenesis, altering DNA and providing a carcinogenic environment bathed in cytokines and growth factors [131]. Ocular adnexal MALT often develops in a setting of chronic inflammation [44] (Fig. 1.1) and has been shown to be associated with Chlamydia psittaci and a number of other pathogens [1, 41, 133]. There is considerable regional variability with a number of studies showing no association with Chlamydia [34, 66, 159]. There may be different pathogens in different regional locations predisposing to the development of ocular adnexal MALT lymphoma. For example, the hepatitis C virus (HCV) has been detected in a small number of patients with ocular adnexal MALT [43]. In contrast, analysis of 49 cases of ocular adnexal MALT lymphoma from Florida
1.3 Immunosuppression |
3 |
Fig. 1.1 Clinical image showing conjunctival MALT lymphoma that had arisen in response to chronic antigen stimulation from chronic conjunctival inflammation
with PCR techniques using universal bacterial primers failed to detect bacterial DNA [107].
Chlamydia causes chronic infections with inhibition of apoptosis and tumorogenic immunomodulatory effects that predispose to lymphoma formation [14, 112, 138]. The chronic systemic infection may be present for years, providing long-term chronic antigen stimulation. The pathogen may elaborate antigens that lead to molecular mimicry, allowing the organism to be tolerated, while other factors contribute to chronic antigen stimulation of both humoral and cell-mediated responses, creating an environment suitable for development of ocular adnexal MALT lymphoma. Ocular adnexal Mucosa Associated Lymphoid Tissue (MALT) lymphomas show a limited number of similar VH gene segments, and analysis of the mutations in these VH gene segments also suggests chronic antigen stimulation plays a role in their development [9].
1.3Immunosuppression
Immunosuppression has long had an association with lymphoma development, which was underlined by increased incidence of lymphoma paralleling the AIDS era [58]. Lymphoma associated with immunosuppression tends to have a high prevalence of Epstein–Barr virus (EBV), defects in immunoregulation, as well as abnormal immunoglobulin and T-cell receptor gene rearrangement during lymphopoiesis [46] Disorders of immunity such as primary congenital immune deficiency, ataxia telangiectasia, and Wiscott–Aldridge syndrome all predispose to lymphoma development. Immunosuppressive therapy after organ transplantation is associated with a high rate of lymphoma, often with reduced latency and aggressive behavior [23, 91]. Interestingly, environments with high
41 Ocular Adnexal Lymphoproliferative Disease
UV light exposure such as Australia and Florida have high rates of both nonmelanoma skin cancer and lymphoma, suggesting a common role in immunosuppression from UV light in these tumors [7, 106]. There is good
1epidemiological support for this hypothesis, but mechanisms remain unclear [2, 65, 86, 129].
1.4Pathology
The MALT-type OAL resembles MALT lymphoma elsewhere, comprised of morphologically small marginal zone cells, monocytoid cells, with occasional immunoblasts, centroblasts, and small lymphocytes (Fig. 1.2). There may be some plasmacytic differentiation and infiltration of epithelial tissues with malignant cells to form so-called lymphoepithelial units (Fig. 1.3 and 1.4). Dutcher bodies Periodic Acid-Schiff (PAS+ pseduointranuclear inclusions) are seen in about 25% of cases. Immunohistochemically, the cells are CD20 and CD79a+ and CD5 (95%), CD10, and CD23– [62, 68, 70–72].
Follicular lymphoma recapitulates the normal follicle formation with tumor cells but with poor definition, absence of mantle zone, and effacement of normal architecture with tumor cells (Fig 1.5). These cells are of two types, small cleaved centrocytes and larger noncleaved centroblasts. They are positive for pan B-cell markers CD19, CD20, CD22, and CD79a; are Bcl2+; and express germinal center markers BCL6, CD38, and CD10, but are CD5 and CD43− [11].
DLBCL diffusely involves tissues with a monotonous proliferation of large neoplastic B cells with large nuclei, which most commonly resemble centroblasts. Again, they are usually positive for pan B-cell markers CD19,
Fig. 1.3 MALT lymphoma. Hematoxylin and eosin ×400 showing a well-formed lymphoepithelial unit
Fig. 1.4 MALT lymphoma. Cytokeratin stain ×400 highlighting the epithelial component in a lymphoepithelial unit
CD20, and CD79a and may be CD5+, although they do not express cyclin D1, in contrast to MCL.
Mantle cell lymphoma can show somewhat nodular patterns but with loss of normal architecture and infiltration by abnormal centrocyte-like cells, without blast forms (Fig. 1.6). They have a characteristic immunophenotype with CD5+ and CD43+ and BCL6 and CD10– (Fig. 1.7). They are all bcl2 and cyclin D1+ (Fig. 1.8).
T-cell lesions include a broad range of subtypes but are typically CD20− and CD3+.
1.5Cytogenetics
Fig. 1.2 MALT lymphoma. Hematoxylin and Eosin ×400 showing predominantly small marginal zone cells and monocytoid cells with occasional centroblasts and small lymphocytes
The acquisition of genetics aberrations in lymphocytes causes clonal cell proliferation and suppression of apoptotic mechanisms, immune suppression, and altered cell signaling functions, which result in tumor initiation,
Fig. 1.5 Follicular lymphoma histology. Hematoxylin and eosin ×400, showing effacement of normal architecture with tumor cells. Most cells are small cleaved centrocytes, with occasional larger noncleaved centroblasts
promotion, and growth. The delicate balance between oncogenes and tumor suppressor genes becomes altered, leading to lymphoid malignancy.
Certain cytogenetic abnormalities are characteristically seen in different lymphoma types. The first abnormality to be detected was the 8;14 translocation seen in Burkitt’s lymphoma, using standard karyotypic methods. Since that time, there have been many advances in molecular genetics, allowing more refined diagnosis of OALDs. Molecular testing is important to establish clonality and to establish a diagnosis. This is relevant in OALD to differentiate between small B-cell lymphomas (such as MALT, FL, chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) MCL). Certain cytogenetic abnormalities may also point to prognosis or response to particular treatments.
1.5Cytogenetics 5
Conventional cytogenetics, usually performed with cell culture of a single-cell suspension from a mechanically disrupted lymph node, is not always rewarding due to difficulty in establishing a culture, low mitotic rates for many of the chronic and indolent lesions, and a poor response to mitogens. Southern blot methods are used but are labor intensive and time consuming, restricting their use in a routine setting. PCR techniques are usually the initial molecular diagnostic test in most pathology laboratories for assessment of lymphoid lesions. They can be performed quickly using DNA or RNA as templates, on small amounts of tissue, which may be fresh, fixed, or archival [143]. FISH uses labeled DNA probes that hybridize to sequences of interest, allowing detection of structural and numerical chromosomal abnormalities. There are a wide variety of commercially available FISH probes that are routinely used in lymphoma diagnosis in most laboratories [16]. Multiple chromosomal targets can be assessed with multicolor FISH (M-FISH) and spectral karyotyping (SKY). Comparative genome hybridization (CGH) permits analysis of DNA sequence copy number to detect loss or gain across the genome. Complementary DNA (cDNA) microarray testing allows gene expression profiling of lymphomas, which may be useful to correlate clinical behavior, response to treatment, and prognosis with improved lymphoma diagnosis [143]. Not all of these modalities are currently in routine laboratory use, but they will have increasing importance as more data are assembled on their application.
Looking at OALD, the most common lesion is the EMZL of MALT type. These lymphomas show a range of cytogenetic abnormalities that vary from those seen in MALT lesions elsewhere in the body. These include t(11;18)(q21;q21) of the API2 and MALT1 genes (occurs in 0–10% ocular adnexal MALT lymphoma); t(14;18)
Fig. 1.6 Mantle cell lymphoma histology. Hematoxylin and eosin ×400, showing loss of normal architecture and infiltration by abnormal centrocyte-like cells
Fig. 1.7 Mantle cell lymphoma histology ×400 showing strongly positive CD5 immunostain
61 Ocular Adnexal Lymphoproliferative Disease
(q32;q21) of the IGH and MALT1 genes (occurs in 7–11% ocular adnexal MALT lymphoma); t(1;14)(p22;q32) of the Bcl-10 and IGH genes (not reported to occur in ocular adnexal MALT lymphoma); and t(3;14)(p14;q32) of
1the FOXP1 and IGH genes (not reported to occur in ocular adnexal MALT lymphoma) [136]. These different
abnormalities result in activation of the transcription factor NF-κB (nuclear factor kappa B), which upregulates
various proliferation genes in B cells [87]. Other abnormalities seen include trisomy 3 (occurs in 40–60% of ocular adnexal MALT lymphoma) and trisomy18 (occurs in 14–50% of ocular adnexal MALT lymphoma) [146]. The incidence of these cytogenetic abnormalities varies greatly, with MALT lymphomas derived from different tissues (e.g., gastric, lung, skin, and ocular adnexa [101]. Interestingly, given the low percentage of ocular adnexal MALT lymphomas showing the aberrations common in other MALT lymphomas, there may be other as-yet- undiscovered abnormalities associated with this entity.
Follicular lymphoma develops from centrocytes and centroblasts of the germinal centers that fail to undergo apoptosis because BCL2 expression is preserved as a result of the initial t(14;18) chromosomal rearrangement [61]. Additional genetic alterations occur, leading to FL, which may have a better or worse prognosis, depending on which secondary alterations take place [11].
We have already learned that BCL6 plays an important role in germinal center formation and subsequent lymphocyte development. Failure to downregulate BCL6 after affinity maturation may be lymphomagenic [21, 81]. BCL6 is necessary for survival of human DLBCL cells. DLBCL commonly shows alterations of the BCL6 gene at the 3q27 locus, but other complex karyotypes may be seen [51]. These different abnormalities may explain the
Fig. 1.8 Mantle cell lymphoma histology ×400 showing strongly positive cyclin D1immunostain
morphologically and immunohistochemically different centroblastic and immunoblastic subtypes of DLBCL [51]. There are at least three distinct entities grouped together under the DLBCL banner based on distinct chromosomal imbalances. These are germinal center B-cell-like (best prognosis), activated B-cell-like (intermediate-to-poor prognosis), and a poor prognosis non-germinal center B-cell-like (non-GCB-like) non-ABC-like subgroup [32].
Mantle cell lymphoma develops from a combination of dysregulation of cell proliferation and survival pathways with a high level of chromosome instability. The genetic hallmark of MCL is the t(11;14)(q13;q32) translocation that juxtaposes CCND1, at chromosome 11q13, to the immunoglobulin (Ig) heavy chain gene at chromosome 14q32 [82]. CCND1 is a proto-oncogene that encodes cyclin D1, resulting in cyclin D1 overexpression. This translocation occurs in the bone marrow in an early B cell at the pre-B stage of differentiation when the cell is initiating the Ig gene rearrangement with the recombination of the VDJ segments. The cell of origin is a mature B cell found in the mantle region of normal lymphoid follicles. Although the initial translocation occurs in immature B cells in the marrow, the oncogenic advantage is realized only when additional genetic aberrations occur as the cell matures into a naïve pregerminal center B cell [82, 139]. Diagnosis of this small cell lymphoma can be confirmed by immunohistochemical staining for cyclin D1 and with FISH techniques (Fig. 1.9) [24].
T-cell malignancies comprise two main groups: precursor T-cell lymphoblastic neoplasms, derived from maturing thymocytes, and peripheral T-cell lymphomas (PTCLs), arising from mature postthymic T cells (Figs. 1.10 and 1.11). Physiological T-cell development is regulated by numerous oncogenes and oncogenic pathways, suggesting a balance between normal differentiation and malignant transformation [4]. The molecular pathogenesis of T-cell lymphomas is still poorly understood, but it is recognized that there are often complex karyotypic abnormalities present [3].
Summary for the Clinician
■OAL usually presents with a short history (5–7 months) of painless proptosis or a salmon patch.
■MRI and CT are both useful, with MRI showing soft tissue involvement better and CT showing bone changes better.
■PET scanning has an important role in the systemic staging of OAL, but CT and MRI show the orbital disease better.