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Research Letters |

Progressive Eyelid and Facial Swelling Due to Follicular Lymphoma FREE

Lauren B. Smith, MD; Melissa A. Pynnonen, MD; Andrew Flint, MD; James L. Adams, MD; Victor M. Elner, MD, PhD
Arch Ophthalmol. 2009;127(8):1068-1070. doi:10.1001/archophthalmol.2009.169.
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Periocular swelling is a cardinal manifestation of Melkersson-Rosenthal syndrome and may occur in many other diseases, including severe acne, vasculitis, sarcoidosis, or impaired venous or lymphatic drainage complicating neoplasia or radiotherapy of the neck.1 Rarely has it been reported as the sole manifesting sign of lymphoma.13

A 43-year-old man developed right eyelid swelling in April 2007. He had no history of trauma, infection, or constitutional symptoms. Physical examination revealed right-sided facial edema, most pronounced in the eyelid and cheek soft tissues (Figure 1A). A right cervical lymph node, palpable by the patient for 6 months, measured 1 cm. Computed tomography revealed diffuse infiltration of right facial soft tissues including the masticator and parapharyngeal spaces, nasopharynx, and maxillary sinus mucosa (Figure 1B and C). Ocular examination showed only right upper eyelid swelling that prompted biopsy, which revealed perivascular inflammatory infiltrates composed predominantly of lymphocytes, plasma cells, occasional eosinophils, and rare tingible-body macrophages. The clinical and histological findings were interpreted as suspicious for Melkersson-Rosenthal syndrome.

Place holder to copy figure label and caption
Figure 1.

Clinical photograph, computed tomographic scans, and positron emission tomographic scans. A, Right eyelid and facial swelling. Coronal (B) and axial (C) computed tomographic scans show erosion of maxilla (arrowheads) and mucosal and soft tissue thickening (arrows). Fluorine 18 (18F)–labeled fluorodeoxyglucose positron emission tomographic scans show widespread lymphoma before (D) and complete response after (E) chemotherapy. R indicates right.

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Additional right cheek skin and sublabial mucosa biopsy results also were consistent with cheilitis granulomatosis of Melkersson-Rosenthal syndrome. However, the marked density of the lymphoid infiltrates raised the possibility of lymphoma (Figure 2A and B).

Place holder to copy figure label and caption
Figure 2.

Dense perivascular lymphocytic infiltrates (hematoxylin-eosin, original magnification ×100) (A), with most having positive immunoreactivity for CD20 (original magnification ×200) (B), in sublabial mucosa. Maxillary mucosa shows a diffuse infiltrate of malignant B lymphocytes (hematoxylin-eosin) (C) with cell membrane CD20 (D) and CD10 (E) immunopositivity and BCL6 nuclear immunoreactivity (F) (original magnification ×400).

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Four months after the onset of facial edema, the patient developed right maxillary tooth hypersensitivity. Reexamination of the computed tomographic scan bone windows revealed bone resorption along the lateral wall of the maxillary sinus, raising suspicion of a malignant neoplasm (Figure 1). Biopsies of the right cervical lymph node, maxillary sinus mucosa, cheek skin, and sublabial mucosa revealed diffuse follicle center cell lymphoma (Figure 2C), a morphologic variant of follicular lymphoma that lacks the usual nodular architecture and instead exhibits diffuse lymphocytic infiltrates composed of centrocytes, with fewer centroblasts. Immunohistochemistry for CD20, CD10, and BCL6 (Figure 2D-F) confirmed the diagnosis.

At staging 8 months after initial symptoms, computed tomographic and fluorine 18 (18F)–labeled fluorodeoxyglucose positron emission tomographic scans showed extensive systemic involvement, the latter showing enhancement in the right maxillary sinus, right temporalis muscle, skull base, mediastinum, retroperitoneum, mesenteric lymph nodes, bones of the thorax and pelvis, both femurs, abdominal soft tissue, and right periformis muscle (Figure 1D). Bone marrow biopsy revealed paratrabecular lymphomatous infiltrates, composing 10% to 20% of the marrow. Final staging was of stage IVE follicular lymphoma. The patient began receiving cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone chemotherapy that resulted in resolution of infiltrates on 18F-fluorodeoxyglucose positron emission tomographic scanning 14 months after symptom onset (Figure 1E). However, repeated bone marrow biopsy showed residual disease. He then received tositumomab (BEXXAR), an iodine I 131–labeled anti-CD20 monoclonal antibody, to target and kill the malignant B lymphocytes, resulting in negative marrow biopsy results 2 months later.

Periocular facial swelling as the manifesting sign of lymphoma is rare. To our knowledge, there are only 3 cases reported in the literature.13 Moreover, follicular lymphoma of the nose and paranasal sinuses is extremely rare. In a series of 70 patients at the M. D. Anderson Cancer Center over 46 years, Logsdon et al4 reported no cases of follicular lymphoma. In contrast, orbital involvement by follicular lymphoma ranges from 10% to 30% of cases.5 Follicular lymphomas arise from germinal center B cells, where antigen exposure occurs, whereas lymphomas of mucosa-associated lymphoid tissue are believed to develop from post–germinal center lymphocytes. Both entities are low-grade lymphomas, but follicular lymphomas have an 8-year survival of 60% to 65% with a failure-free survival of approximately 35%,6 whereas lymphomas of mucosa-associated lymphoid tissue have an 8-year survival of approximately 80% and a failure-free survival of 65%.6 Our case demonstrates a very unusual manifestation of follicular lymphoma, with extensive facial swelling and sinus involvement, that clinically mimicked Melkersson-Rosenthal syndrome and was the only initial indicator of widespread systemic disease.

Correspondence: Dr Elner, W. K. Kellogg Eye Center, University of Michigan, 1000 Wall St, Ann Arbor, MI 48105 (velner@umich.edu).

Financial Disclosure: None reported.

Funding/Support: This work was supported by core grant EY07003 and grant EY09441 (Dr Elner) from the National Institutes of Health. Dr Elner is a recipient of the Lew R. Wasserman Merit Award from Research to Prevent Blindness.

Dragan  LRBaron  JMStern  SShaw  JC Solid facial edema preceding a diagnosis of retro-orbital B-cell lymphoma. J Am Acad Dermatol 2000;42 (5, pt 2) 872- 874
PubMed Link to Article
Ghislanzoni  MGambini  DPerrone  TAlessi  EBerti  E Primary cutaneous follicular center cell lymphoma of the nose with maxillary sinus involvement in a pediatric patient. J Am Acad Dermatol 2005;52 (5) ((suppl 1)) S73- S75
PubMed Link to Article
Jawa  AMehta  SGrupp  SKramer  SSCarpentieri  DFDormans  JP Face and thigh swelling in a 6-year-old girl. Clin Orthop Relat Res 2003;415 (415) 309- 318
PubMed Link to Article
Logsdon  MDHa  CSKavadi  VSCabanillas  FHess  MACox  JD Lymphoma of the nasal cavity and paranasal sinuses: improved outcome and altered prognostic factors with combined modality therapy. Cancer 1997;80 (3) 477- 488
PubMed Link to Article
Nicolò  MTruini  MSertoli  MTaubenberger  JKZingirian  M Follicular large-cell lymphoma of the orbit: a clinicopathologic, immunohistochemical and molecular genetic description of one case. Graefes Arch Clin Exp Ophthalmol 1999;237 (7) 606- 610
PubMed Link to Article
Lister  TACoiffier  BArmitage  JO Non-Hodgkin's lymphoma. Abeloff  MDArmitage  JONiederhuber  JEKastan  MBMcKenna  WGClinical Oncology. 3rd ed Philadelphia, PA Elsevier Churchill, Livingstone2004;3032- 3038

Figures

Place holder to copy figure label and caption
Figure 1.

Clinical photograph, computed tomographic scans, and positron emission tomographic scans. A, Right eyelid and facial swelling. Coronal (B) and axial (C) computed tomographic scans show erosion of maxilla (arrowheads) and mucosal and soft tissue thickening (arrows). Fluorine 18 (18F)–labeled fluorodeoxyglucose positron emission tomographic scans show widespread lymphoma before (D) and complete response after (E) chemotherapy. R indicates right.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Dense perivascular lymphocytic infiltrates (hematoxylin-eosin, original magnification ×100) (A), with most having positive immunoreactivity for CD20 (original magnification ×200) (B), in sublabial mucosa. Maxillary mucosa shows a diffuse infiltrate of malignant B lymphocytes (hematoxylin-eosin) (C) with cell membrane CD20 (D) and CD10 (E) immunopositivity and BCL6 nuclear immunoreactivity (F) (original magnification ×400).

Graphic Jump Location

Tables

References

Dragan  LRBaron  JMStern  SShaw  JC Solid facial edema preceding a diagnosis of retro-orbital B-cell lymphoma. J Am Acad Dermatol 2000;42 (5, pt 2) 872- 874
PubMed Link to Article
Ghislanzoni  MGambini  DPerrone  TAlessi  EBerti  E Primary cutaneous follicular center cell lymphoma of the nose with maxillary sinus involvement in a pediatric patient. J Am Acad Dermatol 2005;52 (5) ((suppl 1)) S73- S75
PubMed Link to Article
Jawa  AMehta  SGrupp  SKramer  SSCarpentieri  DFDormans  JP Face and thigh swelling in a 6-year-old girl. Clin Orthop Relat Res 2003;415 (415) 309- 318
PubMed Link to Article
Logsdon  MDHa  CSKavadi  VSCabanillas  FHess  MACox  JD Lymphoma of the nasal cavity and paranasal sinuses: improved outcome and altered prognostic factors with combined modality therapy. Cancer 1997;80 (3) 477- 488
PubMed Link to Article
Nicolò  MTruini  MSertoli  MTaubenberger  JKZingirian  M Follicular large-cell lymphoma of the orbit: a clinicopathologic, immunohistochemical and molecular genetic description of one case. Graefes Arch Clin Exp Ophthalmol 1999;237 (7) 606- 610
PubMed Link to Article
Lister  TACoiffier  BArmitage  JO Non-Hodgkin's lymphoma. Abeloff  MDArmitage  JONiederhuber  JEKastan  MBMcKenna  WGClinical Oncology. 3rd ed Philadelphia, PA Elsevier Churchill, Livingstone2004;3032- 3038

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