Immunologic characterization of ocular adnexal lymphoid neoplasms.

We correlated the light microscopic features of ten ocular adnexal lymphoid neoplasms with the results of selected immunologic and histochemical lymphocyte marker studies. The lesions were divided into three histomorphologic patterns: inflammatory pseudotumor, reactive follicular hyperplasia, and malignant lymphoma. The six inflammatory pseudotumors, and reactive follicular hyperplasia, despite diverse histomorphology, were immunologically polyclonal and consisted of from 45 to 73% T cells and 27 to 60% B cells, the B cells being polyclonal with respect to light chain determinants. The four malignant lymphomas were immunologically monoclonal. Each consisted of a predominant B-cell proliferation, greater than 50% of the cells, which were monoclonal with respect to surface light chain determinants. No T-cell proliferations were observed. Our preliminary data indicate that, as in systemic lymphoid neoplasms, benign reactive lymphoid hyperplasias are immunologically polyclonal whereas malignant lymphomas are immunologically monoclonal. The systematic application of immunologic and histochemical techniques to the study of ocular adnexal lymphoid neoplasms may elucidate the natural history of these lesions.     

Nontuberculous mycobacterial ocular and adnexal infections

The nontuberculous (also called "atypical") mycobacteria have become increasingly important causes of systemic as well as ocular morbidity in recent decades. All ocular tissues can become infected with these organisms, particularly in patients who are predisposed following ocular trauma, surgery, use of corticosteroids, or are immunocompromised. Because of their relative resistance to available antibiotics, multidrug parenteral therapy continues to be the mainstay of treatment of more serious ocular and adnexal infections caused by nontuberculous mycobacteria (NTM). Periocular cutaneous, adnexal, and orbital NTM infections remain rare and require surgical debridement and long-term parenteral antibiotic therapy. NTM scleritis may occur after trauma or scleral buckling and can cause chronic disease that responds only to appropriate antibiotic therapy and, in some cases, surgical debridement and explant removal. NTM infectious keratitis following trauma or refractive surgical procedures is commonly confused with other infections such as Herpes simplex keratitis and requires aggressive topical therapy and possible surgical debridement, particularly in those cases occuring after laser in situ keratomileusis. Only 18 cases of endophthalmitis due to NTM have been reported. Systemic and intraocular antibiotic therapy and multiple vitrectomies may be needed in NTM endophthalmitis; the prognosis remains poor, however. Disseminated NTM choroiditis in acquired immune deficiency syndrome patients with immune reconstitution during highly active anti-retroviral therapy is a rare infection that can present as a necrotizing chorioretinitis with dense vitritis, mimicking many other entities and needs to be recognized so that timely, life-saving treatment can be administered. Regardless of which ocular tissue is infected, all NTM ocular infections present similar challenges of recognition and of therapeutic intervention. We clarify diagnosis and delineate modern, effective therapy for these conditions.     

眼附属器淋巴瘤组织病理学及免疫表型研究

目的 探讨眼附属器淋巴瘤的临床特点，组织学分型及免疫表型。方法 收集眼附属器淋巴瘤病例33例。采用HE染色常规观察形态学特点。采用多种抗体标记B淋巴细胞，行T细胞鉴别，检测细胞增殖活性及探讨B细胞起源，进行免疫组织化学染色诊断和鉴别诊断，判定免疫表型，细胞分化及增殖状态。结果 29例（87.9%)瘤细胞B细胞标记物CD20，CD79a阳性，并出现k或λ的克隆性增生，诊断为结外边缘区B细胞淋巴瘤，黏膜相关淋巴组织型（MZL-MALT）。2例（6.1%)诊断为弥漫性大B细胞淋巴瘤。1例（3%）为组织学典型的浆细胞瘤分化，1例（3%）为此部位极为罕见的T细胞淋巴瘤，免疫表型为T细胞分化。结论 MZL-MALT型淋巴瘤是眼附属器淋巴瘤中最常见的一类，免疫组化抗体标记在诊断和鉴别诊断中起重要作用，其他类型的淋巴瘤较少见。     

眼附属器淋巴瘤预后研究进展

眼附属器淋巴瘤是临床较常见的恶性肿瘤，影响其预后的因素较多，包括肿瘤的病理类型，临床分期，发病部位，免疫表型特征和遗传学异常等。本文就眼附属器淋巴瘤的预后研究进展进行综述。     

免疫球蛋白重链基因重排检测对眼附属器淋巴增生性病变的诊断研究

目的 探讨多聚酶链反应(PCR)检测免疫球蛋白重链(IgH)基因重排在眼附属器淋巴增生性病变良恶性鉴别中的应用价值.设计 实验性研究.研究对象 32例眼附属器淋巴增生性病变存档蜡块标本.方法 应用PCR检测眼附属器淋巴增生性病变的IgH基因重排,结合常规HE染色和免疫组织化学染色结果进行分析.主要指标 组织病理形态,免疫表型特征及基因重排形式.结果 17例淋巴瘤中12例IgH基因呈单克隆性重排,阳性率为70.6%;10例反应性淋巴细胞增生中1例呈单克隆性重排,阳性率为10%.两者差异有统计学意义(P=O.004).5例不典型淋巴细胞增生中,3例基因呈单克隆性重排,支持恶性淋巴瘤的诊断;2例呈多克隆性重排,支持良性反应性增生的诊断.结论 依靠常规HE染色和免疫组织化学染色有时难以明确眼附属器淋巴增生性病变的良恶性,此时应用PCR检测病变的IgH基因重排,有助于鉴别其良恶性.(眼科,2008,17:33-36)     

BCL10 expression in ocular adnexal lymphomas

PURPOSE: To study BCL10 expression in ocular adnexal lymphoma in the US population and its association with clinical outcomes. DESIGN: Institutional, retrospective study. METHODS: Immunohistochemistry was performed with antibody against BCL10 on two tissue microarray blocks that were constructed with paraffin-embedded tissues from the same cohort of 48 patients with ocular adnexal lymphomas. The main outcomes that were measured include extraorbital involvement, recurrence rate, and time to recurrence. The median length of the follow-up period was 40 months. RESULTS: Aberrant BCL10 expression (nuclear [moderate intensity] and cytoplasmic [weak to moderate intensity] staining) was observed in 10 of 33 cases (30.3%) of mucosa-associated lymphoid tissue (MALT) lymphoma, in 4 of 10 cases (40%) of follicular lymphoma (grade 1, 9 cases; grade 2, 1 case), in 0 of 2 cases of diffused large B-cell lymphoma, in 0 of 1 case of chronic lymphocytic leukemia/small lymphocytic lymphoma and in 1 of 1 case (100%) of mantle cell lymphoma. There were no differences in clinical parameters at examination (ie, average age, gender, site of occurrence, laterality, extraorbital involvement at diagnosis), recurrence rate, and time to recurrence for patients (MALT lymphoma or follicular lymphoma) with or without aberrant nuclear BCL10 expression. CONCLUSION: Aberrant BCL10 expression can occur in other types of ocular adnexal lymphomas besides MALT lymphoma. Ocular adnexal MALT lymphoma may have slightly lower frequency of aberrant BCL10 expression than gastric/pulmonary MALT lymphomas that have been reported in the literature. Furthermore, aberrant BCL10 nuclear expression in ocular adnexal lymphoma does not seem to correlate with clinical outcome. Further studies that include a larger number of cases and longer follow-up period are needed to confirm our observation.     

Histopathologic, immunophenotypic and genotypic analyses in ocular adnexal lymphoproliferative disorders.

This study reports on fourteen biopsies from patients presenting to our orbital and oncology service with ocular adnexal lymphoid proliferations between November 1988 to September 1991. The biopsies were studied using histologic, immunophenotypic and genotypic analyses. By histologic criteria, there were two reactive, five indeterminate and seven lymphomatous lesions. On immunophenotypic analysis, there were two monoclonal and 10 polyclonal lesions in the 12 specimens analysed. Genotypic analysis confirmed the histopathologic diagnoses for the reactive lesions by showing them to be germline. It also confirmed that both the histopathologic lymphomas and immunophenotypically monoclonal lesions were clonally rearranged. Genotypic analysis was able to separate the histologically indeterminate group into two subsets: clonally rearranged, of which there was one, and germline, of which there were four. In addition, it demonstrated that immunophenotypic polyclonality cannot always be equated with genotypic polyclonality as was the situation in four out of 10 lesions in our series. The significance of clonal arrangements in the histologically indeterminate and immunophenotypically polyclonal groups can only be determined by prospective study.     

Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal zone B-cell lymphoma

PURPOSE: To clarify the cellular origin of extranodal marginal-zone B-cell lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular adnexa, the somatic mutation was analyzed in the immunoglobulin heavy-chain variable region (VH) gene. METHODS: Eight cases of EZML in the orbit and four in the conjunctiva were studied. The VH genes were amplified by a seminested PCR and sequenced directly. These were compared with the closest published VH germline segments to determine the somatic mutation frequency. Intraclonal microheterogeneity, which was termed the ongoing mutation frequency in the current study, was estimated by counting the number of single nucleotide substitutions in individual clones and dividing by the total number of nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for comparison. RESULTS: The somatic mutation frequency varied between 2.0% and 12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity showed between one and six further substitutions. The average of ongoing mutation frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs, the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing mutation frequency was 0.51% (0.25%-0.75%). CONCLUSIONS: The average of ongoing mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from postgerminal center memory B cells, but the low ongoing mutation frequencies of ocular adnexal EMZL may result from less antigen stimulation and follicular colonization in the orbit relative to gastrointestinal EMZL.     

眼附属器MALT淋巴瘤的临床分析

目的 探讨黏膜相关组织淋巴瘤(MALT)在眼附属器包括眼睑、眼眶、泪腺等部位的特殊临床特征与治疗方法.方法 回顾性分析32例眼附属器MALT淋巴瘤患者的临床表现、B超、CT、MRI检查结果,病理组织学和免疫组织化学结果以及综合治疗疗效与预后情况.结果 32例眼附属器MALT淋巴瘤患者中男22例,女10例;年龄23.0～74.0岁,平均年龄64.1岁.18例发生于结膜,占56.3%(18/32);9例发生于眼眶,占28.1%(9/32);5例发生于泪腺,占15.6%(5/32).B超检查肿块多表现为内回声不均匀(84.4%,27/32)或内回声高(28.1%,9/32);CT检查多表现为中等密度(43.8±10.7)HU,密度均匀(84.6%,22/26);MRI检查T1WI及T2WI多呈等信号,信号均匀.影像学检查后均行手术治疗联合放疗.随访1～12年,复发率为12.5%(4/32).结论 影像学检查可辅助诊断眼附属器MALT淋巴瘤,术后病理活体检查及免疫组织化学分型检查可确诊本病,眼附属器MALT淋巴瘤若早期诊断和治疗(手术治疗联合术后放疗)则预后较好.     

Imaging features of ocular adnexal lymphoproliferative disease

PURPOSE: To evaluate the imaging characteristics of a cohort of patients with ocular adnexal lymphoproliferative disease (OALD). METHODS: A noncomparative retrospective review between 1992 and 1995 and prospective study from 1995 to 2005 of the clinical, imaging and treatment of 105 patients presenting to tertiary orbital referral centre presenting with OALD. RESULTS: One hundred and five patients (mean age 61 years, range 11-90 years) with equal gender distribution were included. Fifty-three were primary and 52 were secondary. Computed tomography (CT) usually showed a well-circumscribed lesion of greater than brain density, moulding to adjacent tissues with moderate enhancement. Aggressive histology was associated with bone destruction, while moulding was associated with indolent histology (P<0.005).MRI in OALD showed intermediate signal intensity on T1- and T2-weighted images and moderate enhancement with gadolinium. Gallium scanning sensitivity to detect ocular adnexal disease was 25 and 57% for systemic involvement. Positron emission tomography (PET) upstaged (71%) of patients with systemic lymphoproliferative involvement, having a higher sensitivity than CT in detecting distant disease (86 vs 72%). CONCLUSIONS: CT and/or MRI are essential in the evaluation of OALD and can be used to establish that an orbital lesion may be lymphoprolifetaive in nature. Further, these imaging modalities may predict the behaviour of the lymphoma in certain cases. Gallium scanning provides no additional information to CT and does not influence patient treatment. PET represents an important addition to the assessment of OALD with real impact on patient management.     

Treatment of ocular adnexal Kaposi's sarcoma in acquired immune deficiency syndrome.

PURPOSE: To determine the most effective, safe, and cost-efficient treatment for ocular adnexal Kaposi's sarcoma in the acquired immune deficiency syndrome. METHODS: Eighty-two patients with ocular adnexal Kaposi's sarcoma related to the acquired immune deficiency syndrome were examined, and 25 were selected to participate in a 3-year study that treated the ocular lesions based on stage of development and location. RESULTS: Of 14 patients with bulbar conjunctival Kaposi's sarcoma treated with surgical excision, 2 stage III lesions recurred during a follow-up that ranged from 8 to 31 months; no stage I or stage II lesion recurred. Of 7 patients with eyelid Kaposi's sarcoma treated with cryotherapy, 2 stage III lesions recurred during a follow-up that ranged from 9 to 24 months; no stage I or stage II lesion recurred. Four patients with stage III Kaposi's sarcoma of the bulbar conjunctiva were treated with fluorescein angiography-based surgical excision. None of these lesions recurred during a follow-up that ranged from 4 to 8 months. CONCLUSION: A treatment regimen for ocular adnexal Kaposi's sarcoma related to the acquired immune deficiency syndrome based on tumor stage and location, using cryotherapy and surgical excision with or without fluorescein angiography, is effective, safe, and cost-efficient.     

Immunohistochemical and immunogenetic analyses of ocular adnexal lymphoid proliferation

PURPOSE: To compare polymerase chain reaction (PCR) results with histological, immunohistochemical, and clinical findings to understand the nature of ocular adnexal lymphoid proliferation. METHODS: We examined 20 cases (21 specimens) of ocular adnexal lymphoid proliferation, using histological, immunohistochemical, and molecular genetic methods. The latter two types of experiments were performed to examine the light chain restriction of immunoglobulin using the peroxidase-antiperoxidase method, and the clonality of immunoglobulin heavy chains using the PCR method. RESULTS: Although in 8 cases it could not be determined morphologically whether the tumors were neoplastic or not, clonality was revealed in 1 case by immunohistochemistry and in 4 cases by PCR. Two cases showed disparate results between immunohistochemistry and PCR, probably due to somatic mutation of the framework region of the immunoglobulin heavy chain gene. CONCLUSION: Examination using these methods contributes to a better understanding of the nature of the ocular adnexal lymphoid proliferation. Furthermore, the immunoglobulin gene PCR method is very useful in practice for examination of specimens, as it can be used with formalin-fixed and paraffin-embedded specimens.     

The tale and molecular trail of a disseminated ocular adnexal malt lymphoma.

PURPOSE: To report a case of a MALT lymphoma of the eyelid, which recurred in several sites over a time period of 14 years, and where the identical B-cell clone could be demonstrated in most samples using polymerase chain reaction (PCR) and GeneScan analysis. METHODS: Clinical, histologic, immunohistochemical, PCR and GeneScan analysis findings are presented. RESULTS: A 58-year-old woman presented with a swelling of the left lower lid. Excisional biopsy of the tumour revealed a low-grade malignant B-cell Non-Hodgkin lymphoma (NHL) of MALT type. Despite localized radiochemotherapy, the patient developed recurrences occurring in the pharynx, in the right orbit, in the skin of the right foot, and in the bone marrow 1, 7, 11 and 14 years, respectively, after establishment of the first diagnosis. PCR for a rearrangement of the immunoglobulin heavy chains (IgH) and GeneScan analysis of the samples produced amplificates identical in size at most sites, indicating derivation from the same B-cell clone. CONCLUSIONS: It is generally assumed that ocular adnexal MALT lymphoma is associated with an indolent clinical course. Using IgH-PCR and GeneScan analysis, we demonstrate that the current case illustrates that these lymphomas do indeed require regular control examinations following treatment, as they often recur and disseminate in some patients in an unpredictable manner.     

Sentinel node biopsy for orbital and ocular adnexal tumors

PURPOSE: To describe a technique for sentinel node mapping and biopsy in patients with orbital or adnexal tumors. METHODS: Five patients with orbital and adnexal tumors were studied. Two patients had malignant eyelid melanomas (one of the skin and one of the conjunctiva), one with orbital invasion. Two patients had sebaceous gland carcinoma, and one patient had a mucoepidermoid carcinoma of the conjunctiva; 500 microCi of Technetium-99m sulfur nanocolloid (Nycomed Amersham, Princeton, NJ) diluted to 1.0 mL was injected intradermally at the lateral canthus. The patients were positioned as they would be during surgery. Lymphoscintigraphy was performed by means of anterior, lateral, and oblique views. The tracer was followed to the first lymphatic basin, and the sentinel node was identified. Cutaneous markers were placed to denote the site. During surgery, lymphoscintigraphy scans and a hand-held gamma probe were used to locate the sentinel node. Once excised, the sentinel node was sent for histopathology. Frozen sectioning confirmed the presence of lymphoid tissue. Permanent sections with immunohistochemical markers were performed to examine for metastatic disease. RESULTS: The sentinel node biopsy technique was applied to 5 patients with orbital and adnexal tumors. All lymph nodes were free of tumor on histopathologic examination. CONCLUSIONS: Sentinel node mapping and biopsy are possible for orbital and adnexal tumors. The morbidity of elective lymph node dissection and adjuvant radiotherapy can be avoided. Our results are preliminary, and further work must be done to identify the lymphatic basins of the orbit and ocular adnexa.     

眼附属器MALT淋巴瘤的发生与病原体感染关系的研究

近年的研究发现眼附属器MALT淋巴瘤的发生与病原体的感染密切相关,通过病原体对免疫系统的慢性刺激,最终导致淋巴组织的增生和转化,是一种抗原驱动的肿瘤性病变.本文对眼附属器MALT淋巴瘤的发生与鹦鹉热衣原体、幽门螺杆菌、丙型肝炎病毒感染的相关性研究进行综述.     

The clinical characteristics and treatment results of ocular adnexal lymphoma

PURPOSE: To assess the clinical pattern, the histopathological findings, the response to treatments, the recurrence pattern and the prognosis of malignant lymphoma in the ocular adnexa. METHODS: This study was performed on 22 total eyes from 17 patients who were diagnosed with ocular adnexal malignant lymphoma. We retrospectively analyzed the medical records for patient information including the histological classification based on age, the gender of each patient, the symptoms and signs at the initial diagnosis, the presence of binocular invasion, the findings of the surgical biopsy, the clinical stage of each patient's tumor, and the treatment methods used and their effectiveness. The mean follow-up period was 24.8 months. RESULTS: The mean age of patients studied was 46.8 years old. Six females and 11 males were included in the study. Fifteen cases consisting of 20 total eyes represented extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Five of seven patients (71.4%) whose lymphoma occurred within the conjunctiva relapsed after irradiation or chemotherapy, and four of the relapsed patients were salvaged with further therapy. CONCLUSIONS: Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) constituted 88.2% of all lymphomas involving the ocular adnexa. Lymphoma in the ocular adnexa responded well to conventional treatment, but the recurrence rate of lymphoma in the conjunctiva was significantly high.