Lacrimal Sac Lymphoma in a Child

CLINICOPATHOLOGIC REPORTS, CASE REPORTS, AND SMALL CASE SERIES

SECTION EDITOR: W. RICHARD GREEN, MD

The 3 most common cancers in children in the United States include leukemia (33%), brain tumors (20%), and non-Hodgkin lymphoma (10%).1 Non-Hodgkin lymphoma in children most commonly mani- fests in the abdomen (35%), anterior mediastinum (26%), and pe- ripheral lymph nodes (19%). Less Figure 1. External photograph demonstrates an inferomedial lacrimal sac fullness (arrow) causing lateral than 5% of such cases occur ini- displacement of the left globe. tially in the orbit.2 In a review of 250 pediatric orbital tumors, Shields and of the lacrimal sac fossa and bone re- coworkers3 found 6 cases (2.4%) of modeling (Figure 3). Based on orbital lymphoma, none of which these findings, the lesion was sus- were in the lacrimal sac. Using a pected to be a lacrimal sac cyst ob- MEDLINE search of the English lan- structing the nasolacrimal duct. Sur- guage literature from 1970 to 2002, gical repair revealed a firm, distended we identified 21 reported cases of lacrimal sac. The opened sac dis- primary non-Hodgkin lymphoma of closed a pink, solid mass conform- the lacrimal sac,4-13 and only 1 pa- ing to the sac wall, and complete tient was younger than 18 years.4 We dacrocystectomy was performed. report a case of a primary non- Histopathologic examination Hodgkin lymphoma of the lacrimal showed an intense diffuse infiltrate sac in a 10-year-old child. of atypical lymphocytes, consistent with extranodal marginal B-cell lym- Report of a Case. A 10-year-old oth- phoma of the mucosa-associated Figure 2. B-scan ultrasonography demonstrates erwise healthy Hispanic male had a lymphoid tissue type in the stroma a subcutaneous, nearly dumbbell-shaped sonolucent area with a dense wall (arrows at 3-week history of painful swelling of the lacrimal sac (Figure 4). The margins), consistent with a solid mass in the and epiphora in the left medial can- infiltrate lacked germinal centers and lacrimal sac region of the left eye. thus (Figure 1). He recalled blunt contained prominent foci of mono- trauma to the right side of his fore- cytoid lymphocytes (Figure 5). The ment-related complications and no head 3 months earlier. On exami- malignant cells expressed B-cell– persistent epiphora. nation, his visual acuity was 20/25 specific antigens (CD20, CD79A) OD and 20/30 OS. The only ocular and coexpressed T-cell marker CD43 Comment. Nasolacrimal disorders abnormality was a firm, tender mass but lacked other T-cell–specific an- are common in young children. Pri- in the left lacrimal sac region strad- tigens (CD3, CD5). Polymerase mary congenital nasolacrimal duct dling the medial canthal ligament chain reaction performed on paraf- obstruction is the most frequent dis- and fixed to the orbital rim. There fin-embedded tissue disclosed a order of the lacrimal system, occur- were no secretions from the lacri- clonal rearrangement of immuno- ring in approximately 5% of all new- mal punctum, and epiphora with- globulin heavy-chain genes. borns. In infants, the obstruction is out blood was noted. Lacrimal sac Systemic evaluation revealed no usually secondary to incomplete ca- ultrasonography disclosed an acous- findings of lymphoma. The patient nalization of the valve of Hasner in tically hollow subcutaneous mass was then treated with 2 cycles of che- the lower nasolacrimal duct.14 Sec- measuring 11 mm in base and 18 motherapy, consisting of vincris- ondary acquired nasolacrimal duct mm in height, consistent with a cys- tine, cyclophosphamide, doxorubi- obstruction can also occur in chil- tic mass (Figure 2). Orbital com- cin, and prednisone. Thirty months dren owing to infectious, inflamma- puted tomography revealed a solid after diagnosis, he remains alive with tory, traumatic, or mechanical mass involving the left lacrimal sac no evidence of disease clinically or causes.6 However, secondary infec- region, with associated effacement radiographically. He has no treat- tions or inflammatory causes most

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 frequently accompany congenital nonpatent nasolacrimal systems. Nontraumatic spontaneous nasolacrimal duct obstruction in older children, as in our 10-year-old patient, is distinctly unusual. Neoplasms of the lacrimal sac are uncommon, especially in children. They include epithelial (75%) and nonepithelial (25%) tumors, such as mesenchymal tumors (12%), mela- noma (5%), and malignant lymphomas (Ͻ6%).10 The lacrimal sac may also be involved secondarily in pa- Figure 3. Computed tomography of the left orbit demonstrates the solid, noncalcified lacrimal sac mass tients with leukemia, particularly (arrow) with associated effacement of the lacrimal sac fossa and bone remodeling. older patients with chronic lympho- cytic leukemia.15 In a review by the Armed Forces Institute of Pathol- ogy, of 35 nonepithelial tumors of the lacrimal sac, 8 patients (23%) had malignant lymphoma of the lacrimal sac.10 The median age of these patients was 64 years, and the young- est patient was 39 years old. Lymphoma in the periocular region generally originates in the conjunctiva or orbit.16,17 Lymphoma of the lacrimal sac, however, is unusual. Twenty-one cases of primary lymphoma of the lacrimal sac have been reported during the past 30 years (Table).4-13 The median age at onset was 51 years, and only 1 case oc- curred in a child, similar to our case.4 The most common initial manifesta- Figure 4. Diffuse infiltrate of lymphoid cell compresses the lumen of the lacrimal sac (hematoxylin-eosin, ϫ tions in these cases were epiphora and original magnification 25). painless swelling of the lacrimal sac area (Table 1). The mean duration of epiphora prior to diagnosis was 9 months, and the mean duration of swelling was 2 months. Our case dif- fered in that our patient had acute signs and symptoms, including pain, of 3 weeks’ duration. Imaging studies, such as computed tomography or magnetic resonance imaging can be helpful in the diagnosis of lacrimal sac lymphoma. In 9 reported cases, imaging was performed, and an isodense homogeneous mass was found. Six patients (66%) demonstrated effacement of the lacrimal sac fossa and/or erosion of the medial orbital wall (Table 1). In our case, computed tomography showed Figure 5. Monomorphic population of lymphocytes comprising infiltrate has a monocytoid appearance a solid mass, and ultrasonography consistent with mucosa-associated lymphoid tissue lymphoma (hematoxylin-eosin, original magnification misinterpreted it as a hollow mass, ϫ250). owing to the homogeneous density of the compact lymphoma. Erickson et lacrimal sac, as magnetic resonance The management of lacrimal al9 found magnetic resonance imag- imaging provided better tumor defi- sac lymphoma remains controver- ing to be superior to computed to- nition and determination of the cys- sial. In the 22 reported cases, all pa- mography for imaging tumors of the tic or solid nature of the mass. tients underwent incisional biop-

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Histologic Treatment, Follow-up, Case Source Age, y Sex Symptoms (mo) CT Findings Findings Phenotype Gy (mo) 1 Carlin and 10 M Epiphora (12); CT not performed Poorly Not EBRT, 3600 NED (11) Henderson painless differentiated mentioned 2 Jordan et al 63 F Epiphora (1); painless Sac enlarged, no Diffuse large B-cell EBRT NED (30) swelling (1) bony erosion 3 Bartley 76 F NA NA NA NA NA NA 4 Kheterpal 82 F Epiphora (12); painful Not performed Low grade B-cell Excision; EBRT NED (6) et al swelling (3) 5 Saccogna 21 M Epiphora (7); painless Soft tissue mass, Diffuse large B-cell Systemic chemotherapy NED (24) et al swelling (1); nasal orbital wall (8 cycles)* obstruction (1) bowing 6 Erickson et al 48 M Epiphora (several Homogeneous Diffuse large B-cell EBRT, 46.8 NEB (54) mos); diplopia: mass recent 7 Erickson et al 39 M Epiphora (several Soft tissue mass Large cell B-cell EBRT, 3750; systemic NED (30) mos); painless with orbital wall chemotherapy swelling (1.5) erosion (3 cycles)* 8 Erickson et al 68 M Epiphora (2); painless CT not performed; Large cell B-cell EBRT, 41.4 NED (36) swelling (2) MRI: mass with bony erosion 9 Erickson et al 66 F Epiphora (48); painful Homogeneous Well-differentiated; B-cell EBRT, 36 AWR (36) swelling (several mass, bony small cleaved months) erosion 10 Erickson et al 53 M Epiphora (12); Mass, no bony Large cell B-cell EBRT, 34.2; systemic NED (12) painless swelling erosion immunoblastic chemotherapy (12) (6 cycles) 11-18 Pe’er et al 39-73 5 M, 3 F Not mentioned Not mentioned 4 Diffuse large B-cell Not mentioned Not 1 Diffuse small cell mentioned 3 malignant small noncleaved 19 Nakamura 70 F Epiphora (12); Enhancing mass, Diffuse large B-cell EBRT, 50; systemic NED (26) et al painless swelling bony erosion, chemotherapy (3) dilated duct (1 cycle)* 20 El-Hakim and 35 F Epiphora (6); CT sinus: periosteal High-grade B-cell Excision; systemic NED (9) Nunez pansinusitis thickening, chemotherapy air-fluid level (6 cycles),* intrathecal methotrexate 21 Mori et al 55 F Painless swelling Homogeneous Natural-killer cell B-cell Systemic chemotherapy DOD mass, no bone (6 cycles),* intrathecal erosion cytarabine, methotrexate, prednisolone; EBRT 22 Schefler et al 10 M Epiphora (1 week); Effacement of the Marginal zone B-cell Excision; systemic NED (30) painful swelling lacrimal sac MALT type chemotherapy (3 weeks) fossa, bone (2 cycles): prednisone, remodeling vincristine, cyclophosphamide, doxorubicin

Abbreviations: AWR, alive with recurrence; CT, computed tomography; DOD, dead of disease; EBRT, external beam radiation therapy; MALT, mucosa-associated lymphoid tissue; MRI, magnetic resonance imaging; NA, not applicable; NED, no evidence of disease. *Chemotherapy regimen: cyclophosphamide, adriamycin, vincristine, and prednisone.

sies, and the most common 13 patients free of local recurrence alone may be avoidance of this treatment was external beam radia- and systemic disease at a mean of complication, as demonstrated in tion, either alone (5 patients) or in 24 months’ follow-up. Because the our case. combination with systemic chemo- clinical course of lymphoma is In summary, we report an un- therapy (4 patients) or excisional bi- lengthy and indolent, our patient usual case of a child with a lacrimal opsy (1 patient). Two patients (cases will require long-term follow-up. sac tumor that proved histopatho- 5 and 20), and our patient (case Four of the 9 patients who received logically to represent a non-Hodg- 22), received excisional biopsy and external beam radiation developed kin B-cell lymphoma. We advise that systemic chemotherapy, with no postirradiation stenosis of the na- older children with nontraumatic external beam radiation treatment. solacrimal duct, and 2 required nasolacrimal duct obstruction un- Overall, the patients’ prognoses dacrocystorhinostomy.4,8,9 One ad- dergo imaging studies of the lacri- were favorable, with 11 (85%) of vantage of systemic chemotherapy mal sac to rule out a solid tumor. Pa-

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 tients with this diagnosis appear to thelial tumors of the lacrimal sac. Am J Oph- for primary open-angle glaucoma, for thalmol. 1994;118:650-658. have a favorable prognosis with a va- 11. Nakamura K, Uehara S, Omigari J, et al. Pri- which she underwent a bilateral la- riety of treatment approaches. Sys- mary non-Hodgkin’s lymphoma of the lacri- ser trabeculoplasty 1 year prior to our temic chemotherapy rather than ra- mal sac. Cancer. 1997;80:2151-2155. initial examination. She was also a 12. el-Hakim H, Nunez DA. Non-Hodgkin’s lym- diotherapy may avoid potential phoma of the lacrimal sac and concomitant pan- steroid-responder, with intraocular persistent epiphora due to radiation- sinusitis. J Laryngol Otol. 1998;112:969-970. pressures rising up to the high 30s 13. Mori T, Tokuhira M, Morei S, et al. Primary induced lacrimal duct stenosis. natural killer call lymphoma of the lacrimal sac. (mm Hg) while taking topical 1% Ann Hematol. 2001;80:607-610. prednisolone acetate. Her medical Amy C. Schefler, MD 14. Meyer DR. Lacrimal drainage system pathol- history was negative for any known ogy. In: Stephenson CM, Ed. Ophthalmic Plas- Carol L. Shields, MD tic, Reconstructive, and Orbital Surgery. Boston, diseases, and review of systems was Jerry A. Shields, MD Mass: Butterworth-Heinemann; 1997:31-43. remarkable only for mild exer- Hakan Demirci, MD 15. Bernardini FP, Moin M, Kersten RC, Reeves D, Kulwin DR. Routine histopathologic evalua- tional dyspnea. Marlon Maus, MD tion of the lacrimal sac during dacryocystorhi- On initial examination, the in- Ralph C. Eagle, Jr, MD nostomy: how useful is it? Ophthalmology. 2002; traocular pressures were within nor- 109:1214-1217. Philadelphia, Pa 16. Shields JA, Bakewell B, Augsburger JJ, Flana- mal limits while she was receiving gan JC. Classification and incidence of space- treatment with topical 1% brinzol- occupying lesions of the orbit: a survey of 645 amide and 0.2% brimonidine. Vi- This research was supported by the biopsies. Arch Ophthalmol. 1984;102:1606- Paul Kaiser International Award of 1611. sual acuity was 20/20 OU. External 17. Shields CL, Shields JA, Carvalho C, et al. Con- examination disclosed eyelid mar- Merit in Retina Research (Dr J. junctival lymphoid tumors: clinical analysis of Shields), the Rosenthal Award of the 117 cases and relationship to systemic lym- gin telangiectases and irregularity, Macula Society (Dr C. Shields), the phoma. Ophthalmology. 2001;108:979-984. along with mild meibomian gland Noel T. and Sara L. Simmonds En- dysfunction in both eyes. Slitlamp dowment for Ophthalmic Pathology, examination demonstrated moder- Wills Eye Hospital, Philadelphia, Pa ate bilateral bulbar conjunctival hy- Topical Cyclosporin peremia with subtle lower forni- (Dr Eagle), and the Eye Tumor Re- in the Treatment search Foundation, Philadelphia ceal follicules and conjunctival of Chronic Sarcoidosis (Dr C. Shields). subepithelial fibrosis (Figure 1). The authors have no relevant fi- of the Conjunctiva The corneas were clear with no nancial interest in this article. punctate epitheliopathy. The rest of Corresponding author and re- Sarcoidosis is a multisystem, the anterior segment findings were prints: Carol L. Shields, MD, Ocular T-lymphocyte–mediated granuloma- unremarkable. Ophthalmoscopic ex- Oncology Service, Wills Eye Hospi- tous inflammatory process of un- amination showed a cup-disc ratio tal, 840 Walnut St, Philadelphia, PA known cause. The clinical spectrum of 9/10 OU. A Schirmer test per- 19107. varies in severity from single-organ in- formed on the right eye with topi- volvement and self-limiting disease to cal anesthesia revealed a wetting of 1. Shad A, Magrath I. Malignant non-Hodgkin’s multisystem inflammation with po- 7 mm at 5 minutes. lymphoma in children. In: Pizzo PA, Poplack DG. Principles and Practice of Pediatric Oncol- tential mortality. The characteristic A conjunctival biopsy speci- ogy. 3rd ed. Philadelphia, Pa: Lippincott Raven noncaseating granulomatous infil- men was harvested from the infe- Publishers; 1997:545-587. trations can affect almost any tissue, rior fornix of the left eye for diag- 2. Gilchrist GS. Lymphoma. In: Behrman RE, 1 Kliegman RM, Jenson HB. Nelson Textbook of including conjunctivae. The granu- nosis. Histopathologic examination Pediatrics. 16th ed. Philadelphia, Pa: WB Saun- lomatous inflammation of the con- of the specimen showed foci of non- ders & Co; 2000:1548-1552. 3. Shields JA, Bakewell B, Augsburger JJ, et al. junctivae in the form of conjunctival caseating granulomas intermingled Space-occupying orbital masses in children: a nodules resembling follicular con- and surrounded by moderately in- review of 250 consecutive biopsies. Ophthal- junctivitis is a common initial find- tense infiltration of normal-appear- mology. 1986;93:379-384. 2 4. Carlin R, Henderson JW. Malignant lym- ing. We describe a patient with ing lymphocytes (Figure 2). No phoma of the nasolacrimal sac. Am J Ophthal- chronic conjunctivitis who was sub- evidence of acid-fast bacilli, fungi, mol. 1974;78:511-513. sequently diagnosed as having sar- and foreign bodies was found. The 5. Jordan JR, Nerad JA. Diffuse large-cell lymphoma of the nasolacrimal sac. Can J Ophthal- coidosis and successfully treated with patient underwent a systemic evalu- mol. 1988;23:34-37. topical cyclosporin. ation for presumed sarcoidosis, in- 6. Bartley GB. Acquired lacrimal drainage obstruction: an etiologic classification system, case re- cluding complete physical exami- ports, and a review of the literature. Ophthal Report of a Case. A 58-year-old nation, computed tomography of the Plast Reconstr Surg. 1992;8:237-242. white woman was referred for fur- chest, pulmonary function tests, and 7. Kheterpal S, Chan SY, Batch A, Kairkby GR. Pre- viously undiagnosed lymphoma presenting as ther management of ocular rosacea serum angiotensin-converting en- recurrent dacrocystitis. Arch Ophthalmol. 1994; and keratoconjunctivitis sicca, which zyme analysis. The angiotensin- 112:519-520. had been refractory to treatment with converting enzyme level was within 8. Saccogna PW, Strauss M, Bardenstein DS. Lymphoma of the nasolacrimal drainage sys- multiple medications, including oral normal limits. Computed tomogra- tem. Otolaryngol Head Neck Surg. 1994;111: and topical doxycycline, 1% topical phy showed bilateral hilar lymph- 647-651. 9. Erickson BA, Massaro BM, Mark LP, Harris GJ. prednisolone acetate, 0.5% ketoro- adenopathy with no parenchymal in- Lacrimal collecting system lymphomas: inte- lac tromethamine, 0.1% olopata- volvement. Results of pulmonary gration of magnetic resonance imaging and dine hydrochloride, and preserva- function tests were normal. therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1994;29:1095-1103. tive-free artificial tears for 7 months. A pulmonologist elected to de- 10. Pe’er JJ, Stefanyszyn M, Hidayat AA. Nonepi- Her ocular history was remarkable fer the oral corticosteroid treatment

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