慢性泪腺炎演变为眼黏膜相关淋巴组织淋巴瘤一例

doi:10.3877/cma.j.issn.2095-2007.2022.03.007

患者女性，33岁。因双眼眼睑肿胀复发9个月于2020年10月就诊于首都医科大学附属北京同仁医院眼科中心。主诉3年前有双眼眼睑肿胀伴压痛史，于外院筛查免疫八项、甲状腺功能及免疫球蛋白(immunoglobulin，Ig)G亚型检查，结果均在正常范围内；IgA、IgG、IgM、补体3及补体4均在正常范围；IgE高于正常值4倍余(IgE为413.5，正常值<100)，总补体活性67 kU/L(正常值23 kU/L~46 kU/L)。2年前眼眶磁共振成像(magnetic resonance imaging，MRI)显示双侧泪腺增大，疑似炎性或淋巴增生性病变，诊断为双眼泪腺炎，并于首都医科大学附属北京同仁医院眼科行右眼病变泪腺活检术，病理组织学检查结果显示右眼泪腺组织可见大量淋巴细胞浸润伴淋巴滤泡形成，部分区腺泡略萎缩，免疫组织化学检查结果显示间变性淋巴瘤激酶(－)、B淋巴细胞瘤－2(+)，分化簇(cluster of differentiation，CD)138(－)，CD20(+)、CD21(+)、CD3(+)、血清CD34(+)、IgG4(－)、细胞增殖Ki－67指数为25%、抑癌基因P53(－)、B细胞特异性激活蛋白5(+)、平滑肌肌动蛋白(－)、免疫球蛋白轻链κ(+)、免疫球蛋白轻链λ(－)及EB病毒的核糖核酸(－)。病理诊断为泪腺呈炎症性改变，未见淋巴瘤病变。术后给予口服甲泼尼龙片(美国辉瑞公司生产)，6片/d，晨服，1周后双眼眼睑肿胀逐渐递减，至消失。9个月前因双眼睑肿胀复发，复查眼眶MRI成像显示双侧眼睑肿胀伴泪腺增大，眼上肌群略增粗。见图1。4个月前再次复查眼眶MRI成像结果显未见明显变化。见图2。后于某中医院就诊，诊断为双眼泪腺炎，给予中药和针灸治疗(具体不详)，治疗后左眼睑肿物明显减小。因双眼眼睑肿胀复发收入院，右眼泪腺区可扪及肿物，质韧，表面较光滑，边界欠清，活动度可；左眼睑未触及肿块，眼眶MRI扫描成像显示双侧泪腺肿大。见图3。行右眼眶内肿物摘除术以明确诊断，术后病理学诊断为黏膜相关淋巴组织(mucosa－associated lym－phoid tissuel，MALT)淋巴瘤。病理组织学检查结果显示黏膜淋巴组织增生，可见淋巴滤泡，生发中心形成，部分区可见单核样分化，滤泡植入。免疫组织化学染色显示B淋巴细胞瘤－2(+)、CD20(+)、CD3(+)、内质网CD21(+)、细胞增殖指数Ki－67为30%、少量IgG(+)、IgG4(－)、CD79α(+)、细胞周期蛋白D1(－)及CD43(+)。综合形态学、病理组织学及免疫组织化学检查结果，诊断为MALT淋巴瘤。经聚合酶链式反应－Ig基因克隆性重排，结果显示有IgK基因克隆性重排，诊断为B细胞淋巴瘤。术后给予口服甲泼尼龙片，6片/d，晨服，1周后逐渐递减，定期门诊复查眼眶MRI，随访10个月，未复发。

图4 电子显微镜下免疫组织化学染色的检查结果(×100)　图4A~图4F分别示淋巴细胞增生、分化簇20(+)、B淋巴细胞瘤－2(+)、内质网分化簇21(+)、细胞周期蛋白D1(－)及细胞增殖Ki－67指数为30%

表1 原发性眼附属器淋巴瘤的临床分期

分期		原发肿瘤	淋巴结受累	远端转移
X		淋巴瘤范围不明	区域淋巴结无法评估	无法评估
0		无淋巴瘤的证据	无淋巴结受累的证据	无淋巴结以外受累证据
1		淋巴瘤只累及结膜，未累及眼眶
	1a	仅球结膜受累		眼附属器以外的组织和器官不连续受累(如腮腺、下颌下腺、肺、脾、肾及乳房)
	1b	眼睑结膜，伴或不伴穹窿和泪阜受累		淋巴瘤累及骨髓
	1c	广泛结膜受累	累及同侧区域淋巴结	M1a和M1b均受累
2		淋巴瘤累及眼眶，伴或不伴结膜受累	累及对侧或双侧区域淋巴结
	2a	只累及眼眶前部，未累及泪腺，伴或不伴结膜受累
	2b	只累及眼眶前部和泪腺，伴或不伴结膜受累
	2c	只累及眼眶后部，伴或不伴结膜和眼外肌受累
	2d	鼻泪引流系统受累，未累及鼻咽，伴或不伴结膜受累
3		淋巴瘤累及眼睑，伴或不伴眼眶和结膜受累	累及眼附属器区域外的淋巴结
4		淋巴瘤累及到邻近结构，例如骨和脑	累及中央淋巴结
	4a	累及鼻咽
	4b	累及骨(包括骨膜)
	4c	累及颌面，筛骨，伴或不伴额窦受累
	4d	蔓延至颅内

表1 原发性眼附属器淋巴瘤的临床分期

分期		原发肿瘤	淋巴结受累	远端转移
X		淋巴瘤范围不明	区域淋巴结无法评估	无法评估
0		无淋巴瘤的证据	无淋巴结受累的证据	无淋巴结以外受累证据
1		淋巴瘤只累及结膜，未累及眼眶
	1a	仅球结膜受累		眼附属器以外的组织和器官不连续受累(如腮腺、下颌下腺、肺、脾、肾及乳房)
	1b	眼睑结膜，伴或不伴穹窿和泪阜受累		淋巴瘤累及骨髓
	1c	广泛结膜受累	累及同侧区域淋巴结	M1a和M1b均受累
2		淋巴瘤累及眼眶，伴或不伴结膜受累	累及对侧或双侧区域淋巴结
	2a	只累及眼眶前部，未累及泪腺，伴或不伴结膜受累
	2b	只累及眼眶前部和泪腺，伴或不伴结膜受累
	2c	只累及眼眶后部，伴或不伴结膜和眼外肌受累
	2d	鼻泪引流系统受累，未累及鼻咽，伴或不伴结膜受累
3		淋巴瘤累及眼睑，伴或不伴眼眶和结膜受累	累及眼附属器区域外的淋巴结
4		淋巴瘤累及到邻近结构，例如骨和脑	累及中央淋巴结
	4a	累及鼻咽
	4b	累及骨(包括骨膜)
	4c	累及颌面，筛骨，伴或不伴额窦受累
	4d	蔓延至颅内

[1]	刘骁，马建民，葛心. 结膜黏膜相关淋巴组织淋巴瘤一例[J]. 中华眼科医学杂志，2015，5(3)：153-154.
[2]	Olsen TG, Heegaard S. Orbital Lymphoma[J]. Surv Ophthalmol, 2019, 64(1): 45-66.
[3]	Ferry JA, Fung CY, Zukerberg L, et al. Lymphoma of the ocular adnexa: a study of 353 cases[J]. Am J Surg Pathol, 2007, 31(2): 170-184.
[4]	孙梅，马建民. 眼眶淋巴瘤流行病学特点[J]. 中华实验眼科杂志，2020，38(11)：979-982.
[5]	Mannami T, Yoshino T, Oshima K, et al. Clinical, histopathological, and immunogenetic analysis of ocular adnexal lymphoproliferative disorders: characterization of malt lymphoma and reactive lymphoid hyperplasia[J]. Mod Pathol, 2001, 14(7): 641-649.
[6]	Moslehi R, Devesa SS, Schairer C, et al. Rapidly increasing incidence of ocular non－hodgkin lymphoma[J]. J Natl Cancer Inst, 2006, 98(13): 936-939.
[7]	Yuen CA, Pula JH, Mehta M. Primary ocular adnexal extranodal marginal zone mucosa－associated lymphoid tissue (MALT) lymphoma presenting as orbital apex syndrome[J]. Neuro－ophthalmology, 2017, 41(2): 94-98.
[8]	Uno T, Isobe K, Shikama N, et al. Radiotherapy for extranodal, marginal zone, B－cell lymphoma of mucosa－associated lymphoid tissue originating in the ocular adnexa: a multiinstitutional, retrospective review of 50 patients[J]. Cancer, 2003, 98(4): 865-871.
[9]	Fung CY, Tarbell NJ, Lucarelli MJ, et al. Ocular adnexal lymphoma: clinical behavior of distinct world health organization classification subtypes[J]. Int J Radiat Oncol Biol Phys, 2003, 57(5): 1382-1391.
[10]	Ferreri AJM, Dolcetti R, Du MQ, et al. Ocular adnexal MALT lymphoma: an intriguing model for antigen－driven lympho－magenesis and microbial－targeted therapy[J]. Ann Oncol, 2008, 19(5): 835-846.
[11]	张程芳，孙丰源，武劲圆. 原发性眼附属器MALT淋巴瘤的临床分析[J]. 中国实用眼科杂志，2017，35(8)：825-829.
[12]	赵桂秋. 眼附属器MALT淋巴瘤的诊断与治疗[J]. 中华眼科杂志，2020，56(9)：716-720.
[13]	Suzuki J, Ohguro H, Oguri N, et al. Clinicopathologic and immunogenetic analysis of mucosa－associated lymphoid tissue lymphomas arising in conjunctiva[J]. Jpn J Ophthalmol, 1999, 43(3): 155-161.
[14]	Raderer M, Kiesewetter B, Ferreri AJM. Clinicopathologic characteristics and treatment of marginal zone lymphoma of mucosa－associated lymphoid tissue (MALT lymphoma)[J]. CA Cancer J Clin, 2016, 66(2): 152-171.
[15]	Tanimoto K, Kaneko A, Suzuki S, et al. Long－term follow－up results of no initial therapy for ocular adnexal malt lymphoma[J]. Ann Oncol, 2006, 17(1): 135-140.
[16]	Defrancesco I, Arcaini L. Overview on the management of non－gastric malt lymphomas[J]. Best Pract Res Clin Haematol, 2018, 31(1): 57-64.
[17]	Coupland SE, Hellmich M, Auw－Haedrich C, et al. Prognostic value of cell－cycle markers in ocular adnexal lymphoma: an assessment of 230 cases[J]. Graefes Arch Clin Exp Ophthalmol, 2004, 242(2): 130-145.
[18]	Coupland SE, Hellmich M, Auw－Haedrich C, et al. Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases[J]. Br J Ophthalmol, 2005, 89(3): 352-359.
[19]	Decaudin D, De Cremoux P, Vincent－Salomon A, et al. Ocular adnexal lymphoma: a review of clinicopathologic features and treatment options[J]. Blood, 2006, 108(5): 1451-1460.
[20]	Annibali O, Sabatino F, Mantelli F, et al. Mucosa－associated lymphoid tissue (MALT)－type lymphoma of ocular adnexa. biology and treatment[J]. Crit Rev Oncol Hematol, 2016, 100: 37-45.
[21]	Yen MT, Bilyk JR, Wladis EJ, et al. Treatments for ocular adnexal lymphoma: a report by the american academy of ophthalmology[J]. Ophthalmology, 2018, 125(1): 127-136.
[22]	Seresirikachorn K, Norasetthada L, Ausayakhun S, et al. Clinical presentation and treatment outcomes of primary ocular adnexal MALT lymphoma in Thailand[J]. Blood Res, 2018, 53(4): 307-313.
[23]	Ejima Y, Sasaki R, Okamoto Y, et al. Ocular adnexal mucosa－associated lymphoid tissue lymphoma treated with radiotherapy[J]. Radiother. Oncol, 2006, 78(1): 6-9.
[24]	Dhakal B, Fenske TS, Ramalingam S, et al. Local disease control in ocular adnexal lymphoproliferative disorders: com－parative outcomes of malt versus non－MALT histologies[J]. Clin Lymphoma, 2017, 17(5): 305-311.
[25]	Park HH, Lee SW, Sung SY, et al. Treatment outcome and risk analysis for cataract after radiotherapy of localized ocular adnexal mucosa－associated lymphoid tissue (MALT) lymphoma[J]. Radiat Oncol J, 2017, 35(3): 249-256.
[26]	Fukutsu K, Kase S, Ishijima K, et al. The clinical features of radiation cataract in patients with ocular adnexal mucosa－associated lymphoid tissue lymphoma[J]. Radiat Oncol, 2018, 13(1): 1-7.
[27]	Ferreri AJM, Dolcetti R, Magnino S, et al. Chlamydial infection: the link with ocular adnexal lymphomas[J]. Nat Rev Clin Oncol, 2009, 6(11): 658-669.
[28]	Bhardwaj M, Sharma A, Sen S, et al. Chlamydia and ocular adnexal lymphomas: an indian experience[J]. Exp Mol Pathol, 2016, 101(1): 74-80.
[29]	Ferreri AJM, Guidoboni M, Ponzoni M, et al. Evidence for an association between chlamydia psittaci and ocular adnexal lymphomas[J]. J Natl Cancer Inst, 2004, 96(8): 586-594.
[30]	Ferreri AJM, Ponzoni M, Guidoboni M, et al. Bacteria－eradicating therapy with doxycycline in ocular adnexal malt lymphoma: a multicenter prospective trial[J]. J Natl Cancer Inst, 2006, 98(19): 1375-1382.
[31]	Han JJ, Kim TM, Jeon YK, et al. Long－term outcomes of first－line treatment with doxycycline in patients with previously untreated ocular adnexal marginal zone B cell lymphoma[J]. Ann Hematol, 2015, 94(4): 575-581.
[32]	Celiker H, Toker E, Kaygusuz AI. A case of conjunctival MALT lymphoma: successfully treated with solely extended rituximab therapy[J]. Int Ophthalmol, 2019, 39(3): 687-691.
[33]	Ferreri AJM, Sassone M, Miserocchi E, et al. Treatment of MALT lymphoma of the conjunctiva with intralesional rituximab supplemented with autologous serum[J]. Blood Adv, 2020, 4(6): 1013-1019.
[34]	McNab AA. The 2017 Doyne lecture: the orbit as a window to systemic disease[J]. Eye, 2018, 32(2): 248-261.
[35]	Kalogeropoulos D, Papoudou－Bai A, Kanavaros P, et al. Ocular adnexal marginal zone lymphoma of mucosa－associated lymphoid tissue[J]. Clin Exp Med, 2018, 18(2): 151-163.
[36]	Travaglino A, Varricchio S, Pace M, et al. Hepatitis C virus in MALT－lymphoma of the ocular adnexa[J]. Pathol Res Pract, 2020, 216(4): 152864.
[37]	Ponzoni M, Ferreri AJM. Bacteria associated with marginal zone lymphomas[J]. Best Pract Res Clin Haematol, 2017, 30(1－2): 32-40.
[38]	Du MQ, Isaccson PG. Gastric MALT lymphoma: from aetiology to treatment[J]. Lancet Oncol, 2002, 3(2): 97-104.
[39]	Zucca E, Bertoni F. The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance[J]. Blood, 2016, 127(17): 2082-2092.
[40]	Sohn EJ, Ahn HB, Roh MS, et al. Immunoglobulin G4 (IgG4)－positive ocular adnexal mucosa－associated lymphoid tissue lymphoma and idiopathic orbital inflammation[J]. Ophthal Plast Reconstr Surg, 2018, 34(4): 313-319.
[41]	Kahl B, Yang D. Marginal zone lymphomas: management of nodal, splenic, and MALT NHL[J]. Hematology Am Soc Hematol Educ Program, 2008: 359-364.
[42]	Wöhrer S, Troch M, Streubel B, et al. MALT lymphoma in patients with autoimmune diseases: a comparative analysis of characteristics and clinical course[J]. Leukemia, 2007, 21(8): 1812-1818.
[43]	Streubel B, Simonitsch－Klupp I, Müllauer L, et al. Variable frequencies of malt lymphoma－associated genetic aberrations in malt lymphomas of different sites[J]. Leukemia, 2004, 18(10): 1722-1726.
[44]	Tanimoto K, Sekiguchi N, Yokota Y, et al. Fluorescence in situ hybridization (FISH) analysis of primary ocular adnexal MALT lymphoma[J]. BMC Cancer, 2006, 249(6): 1-9.
[45]	Streubel B, Vinatzer U, Lamprecht A, et al. T(3；14)(P14.1；Q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma[J]. Leukemia, 2005, 19(4): 652-658.
[46]	武犁. 原发性眼附属器MALT淋巴瘤的遗传学变化及预后分析[D]. 武汉：武汉大学，2012.
[47]	Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma[J]. N Engl J Med, 1991, 325(16): 1127-1131.
[48]	Suarez F, Lortholary O, Hermine O, et al. Infection－associated lymphomas derived from marginal zone b cells: a model of antigen－driven lymphoproliferation[J]. Blood, 2006, 107(8): 3034-3044.
[49]	Andrew NH, Coupland SE, Pirbhai A, et al. Lymphoid hyperplasia of the orbit and ocular adnexa: a clinical pathologic review[J]. Surv Ophthalmol, 2016, 61(6): 778-790.
[50]	Usui Y, Rao NA, Takase H, et al. Comprehensive polymerase chain reaction assay for detection of pathogenic dna in lymphoproliferative disorders of the ocular adnexa[J]. Sci Rep, 2016: 36621.
[51]	Coupland SE. Molecular pathology of lymphoma[J]. Eye, 2013, 27(2): 180-189.
[52]	Bende RJ, Aarts WM, Riedl RG, et al. Among B cell non－Hodgkin′s lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity[J]. J Exp Med, 2005, 201(8): 1229-1241.
[53]	刘宏艳，吕宁. MALT淋巴瘤的分子遗传学进展及其在诊断中的价值[J]. 诊断病理学杂志，2011，18(5)：380-383.
[54]	Coupland SE, White VA, Rootman J, et al. A TNM－based clinical staging system of ocular adnexal lymphomas[J]. Arch Pathol Lab Med, 2009, 133(8): 1262-1267.

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One case of chronic lacrimal gland inflammation evolving into ocular mucosa associated lymphoid tissue lymphoma

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One case of chronic lacrimal gland inflammation evolving into ocular mucosa associated lymphoid tissue lymphoma