0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Epstein-Barr Virus–Positive T-Cell Lymphoma Involving the Lacrimal Gland of an Adult FREE

Frederick A. Jakobiec, MD, DSc; Fouad R. Zakka, MD; Maria Kirzhner, MD; Nancy Kim, MD
[+] Author Affiliations

Author Affiliations: David G. Cogan Laboratory of Ophthalmic Pathology and Division of Oculoplastic Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston.


Arch Ophthalmol. 2012;130(4):523-525. doi:10.1001/archophthalmol.2011.1728.
Text Size: A A A
Published online

Systemic T-cell lymphomas metastatic to the orbit are much rarer than non-Hodgkin B-cell neoplasms (predominantly marginal zone and follicular).1 We describe an adult with an Epstein-Barr virus (EBV)–positive T-cell lymphoma of the lacrimal gland associated with multiorgan disease that was not of the expected natural killer/T-cell subtype.2 Because of the unusual clinical findings and imaging study results, the diagnosis was elusive. A lacrimal biopsy evaluated with an EBV probe established the correct diagnosis; this technique should probably be used for all unusual or atypical orbital lymphomas.

A 57-year-old man developed abrupt right eye swelling and erythema with chemosis that worsened over 6 days and was nonresponsive to intravenous antibiotics (Figure 1A). He had had a febrile illness with fatigue for 4 years. Earlier lung, liver, and bone marrow biopsies revealed an EBV-positive T-cell lymphoma with a clonal rearrangement of the T-cell receptor gene. Visual acuity was 20/20 OU. The motility was moderately decreased and there was no proptosis. Magnetic resonance imaging showed enlargement of the lacrimal gland on the right side with a nonenhancing center (Figure 1A) and bilateral involvement of the extraocular muscles (Figure 1B). Biopsy of the periorbita (Figure 1C) and lacrimal gland (Figure 1D) showed chronic inflammation with necrosis (Figure 1C and D) and scattered larger cells with ground-glass nuclei (Figure 1C). The lymphocytes were positive for CD3 and CD5 (Figure 2A) and negative for CD56; there were rare CD20-positive cells. Brown-Hopps, Steiner, and Gomori methenamine silver stains disclosed no organisms. In situ hybridization with an EBV probe demonstrated marked positivity in the lymphocytes in both the periorbita and lacrimal gland (Figure 2B). The lung biopsy showed a striking perivascular lymphocytic distribution (Figure 2C) with identical immunohistochemical and EBV-positive (Figure 2D) findings. Radiotherapy delivered to both orbits caused complete resolution of the patient's symptoms, and he has recently received an allogenic bone marrow transplant.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Magnetic resonance imaging, clinical, and biopsy findings. A, Coronal projection of a magnetic resonance imaging scan reveals a large area of central lucency (arrow) in an enlarged lacrimal gland, consistent with extensive necrosis or a sterile abscess. Inset, Swollen, erythematous right upper eyelid with prolapse of the chemotic conjunctiva. B, Swelling is present bilaterally and more posteriorly in the orbit's lateral rectus muscle (arrows) and inferior rectus muscle (arrowheads). The optic nerves (ON) are not compressed. C, Focal hemorrhagic necrosis in the periorbita (hematoxylin-eosin, original magnification ×100). Inset, Large nuclei with a ground-glass characteristic (arrows) suggestive of viral infection (hematoxylin-eosin, original magnification ×400). D, Abundant inflammatory cells are present between the acini (AC) of the lacrimal gland (hematoxylin-eosin, original magnification ×100). Inset, Focus of granular necrosis of the lacrimal parenchyma (hematoxylin-eosin, original magnification ×100).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Histopathologic findings. A, In the lacrimal gland, the CD3-positive T-lymphocytic population is intense (immunoperoxidase reaction, toluidine blue with diaminobenzidine chromogen, original magnification ×200). B, Plentiful Epstein-Barr virus–positive T lymphocytes are located between the acini (AC) of the lacrimal gland parenchyma (in situ hybridization with Epstein-Barr virus probe, original magnification ×100). ID indicates intralobular duct. C, The lung biopsy manifests a lymphocytic infiltrate with striking perivascular cuffing toward the bottom right (hematoxylin-eosin, original magnification ×25). Inset, The cells are shown to be CD3-positive T lymphocytes (immunoperoxidase reaction, toluidine blue with diaminobenzidine chromogen, original magnification ×100). D, Epstein-Barr virus–positive lymphocytes are responsible for the perivascular lung infiltrate (in situ hybridization with Epstein-Barr virus probe, original magnification ×100).

Ascending ductular and hematogenous infections of the lacrimal gland are vanishingly rare. Our patient's orbital “cellulitis” with lacrimal gland cavitation and no response to antibiotic therapy was confusing. The biopsy revealed necrosis of the lacrimal gland (probably at the margins of a sterile abscess) and the profuse presence of CD3- and CD5-positive T lymphocytes that were CD56 negative, thereby ruling out a natural killer/T-cell lymphoma. The number of T cells was much greater than that normally expected in the gland,3 and in situ hybridization established T-cell EBV positivity.

The liver biopsy had disclosed that the lymphocytic infiltrate showed a monoclonal T-cell receptor gene rearrangement, rendering the condition a true lymphoma rather than a lymphoproliferative disorder. Angiodestruction and necrosis frequently accompany EBV-induced lymphoproliferations by means of locally released chemokines4; an open lung biopsy displayed a prominent tendency for vascular cuffing by EBV-positive T cells. The multisystem involvement of lung, liver, and bone marrow and the favorable response to bilateral orbital radiotherapy support the neoplastic character of the condition.

The closest analog to the current lesion is the T-cell lymphoproliferative disorder of childhood without a known clonal rearrangement.5,6 To our knowledge, our case is the first orbital example of an EBV-positive monoclonal T-cell lymphoma not of the natural killer/T-cell subtype in an adult.7 The EBV-positive lymphomas of the orbit have mostly, but not exclusively, been B-cell neoplasms such as Burkitt lymphoma, lymphomatoid granulomatosis, and AIDS-associated and posttransplantation lymphomas.4,8,9 Orbital natural killer/T-cell lymphoma (CD3, CD5, and CD56 positive) with EBV infection can also cause a clinical inflammatory picture.10

Correspondence: Dr Jakobiec, David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Room 321, Boston, MA 02114 (fred_jakobiec@meei.harvard.edu).

Financial Disclosure: None reported.

Jakobiec FA. Ocular adnexal lymphoid tumors: progress in need of clarification.  Am J Ophthalmol. 2008;145(6):941-950
PubMed   |  Link to Article
Woog JJ, Kim YD, Yeatts RP,  et al.  Natural killer/T-cell lymphoma with ocular and adnexal involvement.  Ophthalmology. 2006;113(1):140-147
PubMed   |  Link to Article
Wieczorek R, Jakobiec FA, Sacks EH, Knowles DM. The immunoarchitecture of the normal human lacrimal gland: relevancy for understanding pathologic conditions.  Ophthalmology. 1988;95(1):100-109
PubMed
Jaffe ES, Pittaluga S. Lymphomatoid granulomatosis. In: Jaffe E, Harris N, Vardiman J, Campo E, Arber D, eds. Hematopathology. St Louis, MO: Elsevier/Saunders; 2011:382-390
Quintanilla-Martinez L, Kimura H, Jaffe ES. EBV-positive T-cell lymphoproliferative disorders of childhood. In: Swerdlow SH, Campo E, Harris NL, eds. Classification of Tumors of the Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer; 2008:278-280
Ko YH, Jaffe ES. Epstein-Barr virus-positive systemic lymphoproliferative disorders and related lymphoproliferations of childhood. In: Jaffe ES, Harris NL, Vardiman JW, Campo E, Arber DA, eds. Hematopathology. St Louis, MO: Elsevier/Saunders; 2011:492-505
Park S, Kim K, Kim WS, Yoo KH, Koo HH, Ko YH. Systemic EBV+ T-cell lymphoma in elderly patients: comparison with children and young adult patients.  Virchows Arch. 2008;453(2):155-163
PubMed   |  Link to Article
Reifler DM, Warzynski MJ, Blount WR, Graham DM, Mills KA. Orbital lymphoma associated with acquired immune deficiency syndrome (AIDS).  Surv Ophthalmol. 1994;38(4):371-380
PubMed   |  Link to Article
Douglas RS, Goldstein SM, Katowitz JA,  et al.  Orbital presentation of posttransplantation lymphoproliferative disorder: a small case series.  Ophthalmology. 2002;109(12):2351-2355
PubMed   |  Link to Article
Papalkar D, Sharma S, Francis IC, Downie JA, Thanakrishnan G, Hughes LJ. A rapidly fatal case of T-cell lymphoma presenting as idiopathic orbital inflammation.  Orbit. 2005;24(2):131-133
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Magnetic resonance imaging, clinical, and biopsy findings. A, Coronal projection of a magnetic resonance imaging scan reveals a large area of central lucency (arrow) in an enlarged lacrimal gland, consistent with extensive necrosis or a sterile abscess. Inset, Swollen, erythematous right upper eyelid with prolapse of the chemotic conjunctiva. B, Swelling is present bilaterally and more posteriorly in the orbit's lateral rectus muscle (arrows) and inferior rectus muscle (arrowheads). The optic nerves (ON) are not compressed. C, Focal hemorrhagic necrosis in the periorbita (hematoxylin-eosin, original magnification ×100). Inset, Large nuclei with a ground-glass characteristic (arrows) suggestive of viral infection (hematoxylin-eosin, original magnification ×400). D, Abundant inflammatory cells are present between the acini (AC) of the lacrimal gland (hematoxylin-eosin, original magnification ×100). Inset, Focus of granular necrosis of the lacrimal parenchyma (hematoxylin-eosin, original magnification ×100).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Histopathologic findings. A, In the lacrimal gland, the CD3-positive T-lymphocytic population is intense (immunoperoxidase reaction, toluidine blue with diaminobenzidine chromogen, original magnification ×200). B, Plentiful Epstein-Barr virus–positive T lymphocytes are located between the acini (AC) of the lacrimal gland parenchyma (in situ hybridization with Epstein-Barr virus probe, original magnification ×100). ID indicates intralobular duct. C, The lung biopsy manifests a lymphocytic infiltrate with striking perivascular cuffing toward the bottom right (hematoxylin-eosin, original magnification ×25). Inset, The cells are shown to be CD3-positive T lymphocytes (immunoperoxidase reaction, toluidine blue with diaminobenzidine chromogen, original magnification ×100). D, Epstein-Barr virus–positive lymphocytes are responsible for the perivascular lung infiltrate (in situ hybridization with Epstein-Barr virus probe, original magnification ×100).

Tables

References

Jakobiec FA. Ocular adnexal lymphoid tumors: progress in need of clarification.  Am J Ophthalmol. 2008;145(6):941-950
PubMed   |  Link to Article
Woog JJ, Kim YD, Yeatts RP,  et al.  Natural killer/T-cell lymphoma with ocular and adnexal involvement.  Ophthalmology. 2006;113(1):140-147
PubMed   |  Link to Article
Wieczorek R, Jakobiec FA, Sacks EH, Knowles DM. The immunoarchitecture of the normal human lacrimal gland: relevancy for understanding pathologic conditions.  Ophthalmology. 1988;95(1):100-109
PubMed
Jaffe ES, Pittaluga S. Lymphomatoid granulomatosis. In: Jaffe E, Harris N, Vardiman J, Campo E, Arber D, eds. Hematopathology. St Louis, MO: Elsevier/Saunders; 2011:382-390
Quintanilla-Martinez L, Kimura H, Jaffe ES. EBV-positive T-cell lymphoproliferative disorders of childhood. In: Swerdlow SH, Campo E, Harris NL, eds. Classification of Tumors of the Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer; 2008:278-280
Ko YH, Jaffe ES. Epstein-Barr virus-positive systemic lymphoproliferative disorders and related lymphoproliferations of childhood. In: Jaffe ES, Harris NL, Vardiman JW, Campo E, Arber DA, eds. Hematopathology. St Louis, MO: Elsevier/Saunders; 2011:492-505
Park S, Kim K, Kim WS, Yoo KH, Koo HH, Ko YH. Systemic EBV+ T-cell lymphoma in elderly patients: comparison with children and young adult patients.  Virchows Arch. 2008;453(2):155-163
PubMed   |  Link to Article
Reifler DM, Warzynski MJ, Blount WR, Graham DM, Mills KA. Orbital lymphoma associated with acquired immune deficiency syndrome (AIDS).  Surv Ophthalmol. 1994;38(4):371-380
PubMed   |  Link to Article
Douglas RS, Goldstein SM, Katowitz JA,  et al.  Orbital presentation of posttransplantation lymphoproliferative disorder: a small case series.  Ophthalmology. 2002;109(12):2351-2355
PubMed   |  Link to Article
Papalkar D, Sharma S, Francis IC, Downie JA, Thanakrishnan G, Hughes LJ. A rapidly fatal case of T-cell lymphoma presenting as idiopathic orbital inflammation.  Orbit. 2005;24(2):131-133
PubMed   |  Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles