Outcomes in patients with adenoid cystic carcinoma of the lacrimal gland

PURPOSE: To evaluate the outcomes among patients with adenoid cystic carcinoma of the lacrimal gland treated at various stages of their disease at a tertiary care cancer center. METHODS: A retrospective case series of 20 patients with adenoid cystic carcinoma of the lacrimal gland treated at a single institution between 1952 and 2002. Clinical records were available for all 20 patients; histologic sections from 12 of the 20 patients were available for review. Disease-free survival was measured from the completion of treatment; overall survival was measured from the date of initial diagnosis. RESULTS: The study included 6 men and 14 women. The mean age at diagnosis was 39.5 years. The median follow-up time was 34 months (range, 6 to 264 months). The local/regional treatment modalities included exenteration with bone removal and radiation therapy (RT) in 5 patients, exenteration with RT (no bone removal) in 8 patients, exenteration (no RT or bone removal) in 1 patient, exenteration with bone removal (no RT) in 1 patient, local resection with RT in 3 patients, and local resection without RT in 2 patients. Overall, 16 patients had RT as part of their treatment regimen. Seven patients (35%) had local recurrence. Sixteen patients (80%) had distant metastasis during the study period. At the time of this report, 13 (65%) of the patients had died of disease. The median disease-free survival for the entire group was 18 months. Eight patients had a predominantly basaloid histologic pattern. Ten patients had verifiable histologic evidence of perineural invasion. CONCLUSIONS: This study underscores the generally grave prognosis for patients with adenoid cystic carcinoma of the lacrimal gland and the difficulty in making any conclusive recommendations for local therapy for this disease.     

Microdissection genotyping analysis of the effect of intraarterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma

PURPOSE: To investigate the feasibility of integrating molecular analysis into standard histopathology for lacrimal gland adenoid cystic carcinoma (ACC), and to gain insights into the molecular pathogenesis of this tumor and its response to intraarterial cytoreductive chemotherapy (IACC) that is of clinical use. DESIGN: A retrospective, comparative case series. METHODS: setting: Institutional. patient population: Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. intervention procedure: Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci was performed with 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serving as markers for the presence of gene deletion. main outcome measure: A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness. RESULTS: Allelic imbalance (loss of heterozygosity [LOH]) for microsatellite markers at 1p36 was the single most common site affected by imbalance in this series, followed by LOH in temporal sequence involving 9p21, 22q12, 10q23, and 9q22. CONCLUSIONS: Microdissection genotyping holds promise as a clinical tool in integrating molecular analysis into standard histopathology to advance the understanding of lacrimal gland ACC tumorigenesis. A unique time course for temporal mutation acquisition in ACC is proposed, consisting of 1p36 loss first. Allelic loss for microsatellite markers at 1p36 may be a common as well as an early event in ACC formation and progression.     

泪腺腺样囊性癌的分期及临床治疗进展

泪腺腺样囊性癌是泪腺最常见的恶性上皮性肿瘤,手术治疗效果不理想。近年来,随着多种放射治疗和化学治疗的应用,泪腺腺样囊性癌的治疗模式发生较大转变。一方面,临床分期逐步完善,以新的分期为基础的综合治疗得到规范化应用; 另一方面,在质子放疗、中子放疗、经动脉细胞减容化疗等新辅助治疗的支持下,保眼手术逐渐增多,局部复发率和转移率逐渐降低,无病生存期获得延长,但还需要长期观察。本文就近年来国际上泪腺腺样囊性癌相关方面的治疗进展进行综述,以提供新的参考依据。     

Combined therapeutic approach to malignant lacrimal gland tumors.

The medical records of 13 patients with primary malignant lesions of the lacrimal gland revealed adenoid cystic carcinoma as the most common malignant tumor. The histologic cell type, neural invasion, and bony destruction were correlated with localized control and ultimate survival. Surgical removal of the lacrimal gland was adequate treatment for low-grade mucoepidermoid carcinoma confined to the gland itself. Combining a radical surgical removal of the area in planned sequence with high voltage radiation therapy offered the only reasonable hope for localized control in the more aggressive cell types or in tumors with neural invasion or bony involvement. A 40%-localized control and survival rate was achieved in the adenoid cystic carcinoma group of patients. Radiation therapy administered for cancer that obviously recurs after surgical resection was generally unsuccessful.     

Space-occupying lesions of the lacrimal gland at one tertiary eye center in China: a retrospective clinical study of 95 patients

AIM: To investigate the treatment status and prognosis of space-occupying lacrimal gland lesions at one tertiary eye center in China. METHODS: A retrospective clinical study was performed on 95 patients with space-occupying lesions of the lacrimal gland surgically treated at the Eye & ENT Hospital of Fudan University from 2003 to 2007. The reviewed clinical data included age, gender, side of the lesion, duration of signs and symptoms, histopathological diagnosis, treatment modality, recurrence (local, regional, and distant metastasis) and survival. RESULTS: Of the 95 cases (99 eyes), pleomorphic adenomas were the most common lesions (43 cases), followed by lymphoid disorders (14), inflammatory pseudotumors (11), carcinoma ex-pleomorphic adenomas (11), and adenoid cystic carcinomas (ACC, 6). There were 8 patients with relapsed pleomorphic adenomas. Five of these 8 cases had malignant pathological changes. All patients with ACC had metastasis and three of them died during their follow-up. CONCLUSION: Our study indicated that the most common lacrimal gland lesions were pleomorphic adenomas. Multiple recurrence and surgical procedures may increase the risk of tumor progression. ACC had a high incidence of tumor metastasis and a poor prognosis.     

Surgical management of locally advanced adenoid cystic carcinoma of the lacrimal gland

PURPOSE: To review our experience with multidisciplinary surgical management of locally advanced adenoid cystic carcinoma of the lacrimal gland. METHODS: We present a case series of 7 patients with lacrimal gland adenoid cystic carcinoma treated at our institution between June 2001 and October 2003. Clinical records, histologic sections, and radiographic images were reviewed. RESULTS: The study included 3 men and 4 women (mean age at diagnosis, 44 years). All 7 patients underwent an orbital exenteration with bone removal. Five patients had an orbitectomy through a craniotomy approach and 2 patients had an exenteration through a fronto-orbito-zygomatic approach, all with removal of the bone of the superior and lateral wall. Six patients underwent reconstruction of the socket through the use of a vascularized flap. The surgical approach involved a neurosurgeon, an oculoplastic or head and neck surgeon, and a plastic surgeon. Six patients received postoperative radiation therapy. One patient with a recurrent tumor had already received radiation therapy, which precluded additional radiation therapy after surgical resection. The radiation field included the orbit and the skull base because all patients had evidence of perineural invasion. As of this writing, there have been no local recurrences. Five patients had development of distant metastases and died of disease, at follow-up times from 12 to 32 months after surgery. Two patients are alive without evidence of disease, both at 24 months' follow-up. CONCLUSIONS: Orbitectomy with bone removal may be indicated for achieving local and regional control in advanced cases of adenoid cystic carcinoma of the lacrimal gland. This surgery does not decrease the risk of distant metastasis. The cases in our series highlight the locally invasive and metastatic behavior of this cancer.     

Primary malignant neoplasms of the lacrimal gland.

The clinical characteristics and outcome of 50 primary malignant neoplasms of the lacrimal gland are reviewed: 38 (76%) adenoid cystic carcinomas, six (12%) carcinomas arising in pleomorphic adenoma, and six (12%) adenocarcinomas or other types of carcinoma. Most patients presented with a short history and pain, though pain tended to occur less often and later with adenocarcinoma than with adenoid cystic carcinoma. Pain was unrelated to the duration of symptoms, invasion of bone, loss of trigeminal nerve function, or the frequency and time of tumour recurrence. The estimated disease-free survival for patients with adenoid cystic carcinoma was significantly (p less than 0.01) reduced where half or more of the biopsy specimen showed basaloid differentiation. Eleven patients underwent extended cranio-orbital resection, and the others received a combination of total dacryoadenectomy adenectomy and/or radiotherapy. Survival after adenoid cystic carcinomas appears to be significantly (p less than 0.05) greater when tumour resection is combined with radiotherapy than after radiotherapy alone. At present, however, the rate of disease-free survival after treatment of adenoid cystic carcinoma appears unaltered by cranio-orbital resection, though these latter patients form a relatively greater proportion of those surviving for more than 10 years. Further long-term follow-up is needed to see if this technique does influence survival.     

泪腺腺样囊性癌生物标志物的研究进展

泪腺腺样囊性癌是泪腺最常见的恶性上皮肿瘤,具有易复发、易转移及预后差的特点,目前临床治疗方式主要有手术切除、放疗、化疗等,但其生存率仍低。因此,进一步研究泪腺腺样囊性癌的发病机制和寻找泪腺腺样囊性癌的生物标志物尤为迫切。本文将对泪腺腺样囊性癌的生物标志物的研究进展作一综述。     

Adenoid cystic carcinoma of the lacrimal gland: report of two cases and literature review

The adenoid cystic carcinoma of the lacrimal gland is a rare malignant orbital tumour, which has a generally poor prognosis. The therapy for adenoid cystic carcinoma of the lacrimal gland remains controversial. We present two cases of patients with adenoid cystic carcinoma of the lacrimal gland, who were treated with radical surgery in combination with radiotherapy. The therapeutic results are discussed with reference to relevant literature reports.     

E-cadherin和β-catenin在泪腺多形性腺瘤和腺样囊性癌中的表达

目的研究E-cadherin及β-catenin在泪腺多形性腺瘤和腺样囊性癌中的表达。方法选取经病理检查确诊为泪腺多形性腺瘤的患者11例11眼和腺样囊性癌的患者6例6眼,分别行E-cadherin和β-catenin免疫组织化学染色。选取泪腺脱垂患者的泪腺组织6例作为正常对照组。结果正常泪腺组织中E-cadherin呈强阳性表达,主要位于细胞膜;而在泪腺多形性腺瘤中E-cadherin呈弱阳性表达,主要位于细胞质。E-cadherin在腺样囊性癌中未见表达。3组中E-cadherin阳性表达的样本数差异有统计学意义（H=16.492,P=0.000）;正常泪腺组E-cadherin阳性表达的样本数明显高于多形性腺瘤组和腺样囊性癌组,差异均有统计学意义（U=-3.561,P=0.000;U=-3.108,P=0.002）,多形性腺瘤组中E-cadherin阳性表达的样本数明显高于腺样囊性癌组,差异有统计学意义（U=-2.147,P=0.032）。正常泪腺β-catenin细胞膜呈中度或强阳性表达,多形性腺瘤和腺样囊性癌中β-catenin的表达较正常泪腺组织表达阳性程度差异无统计学意义（P〉0.05）,腺样囊性癌组中β-catenin细胞核阳性的比例（33.3%,2/6）较多形性腺瘤组（72.7%,7/11）低。结论 E-cadherin表达的下降是参与泪腺上皮性肿瘤发生及癌变的重要因素,而E-cadherin的进一步下降甚至缺失,以及β-catenin的核转位可能是参与泪腺多形性腺瘤恶性转化的因素之一。     

An atypical presentation of adenoid cystic carcinoma of the lacrimal gland

PURPOSE: To report a case of lacrimal gland adenoid cystic carcinoma (ACC) with an atypical initial presentation and to postulate an anatomical explanation for this unusual biologic behavior. DESIGN: Interventional case report. METHODS: An orbital magnetic resonance imaging study of a 58-year-old man who complained of progressive diplopia and orbital discomfort disclosed a soft tissue mass in the left cavernous sinus and orbital apex. The left lacrimal gland and the contiguous bone appeared normal. RESULTS: Biopsy of the intracranial mass revealed ACC of unknown origin which was judged to be unresectable. He underwent two cycles of intraarterial cytoreductive chemotherapy followed by a left medial maxillectomy with sphenoethmoidectomy, orbital exenteration, and chemoradiation. ACC tumor cells were identified in nerve fiber bundles surrounding and within the lacrimal gland. CONCLUSIONS: In patients presenting with an infiltrative mass in the cavernous sinus or orbital apex, metastatic disease from an occult lacrimal gland primary should be considered, even with a normal-appearing lacrimal gland.     

关注泪腺腺样囊性癌诊断和治疗中需要注意的问题

泪腺腺样囊性癌是泪腺最为常见的恶性肿瘤之一,具有较高的复发率和死亡率.此病发病机制不明,预后较差.目前,泪腺腺样囊性癌尚无标准化的诊疗方案,在临床诊疗过程中也存在着一些问题.为了提高有关泪腺腺样囊性癌的诊疗质量,本文将从泪腺腺样囊性癌的流行病学、临床表现、影像学检查方法 的选择、诊断与鉴别诊断、病理组织学改变和免疫组织化学指标、治疗方案的选择及预后等方面加以述评,以期有助于临床医师加强对该病的认识,提高早期诊断率,减少误诊率.     

眼眶腺样囊性癌的影像学研究

目的分析眼眶腺样囊性癌(ACC)的超声、CT及MRI等影像学特征。设计回顾性病例系列。研究对象经病理诊断证实的泪腺腺样囊性癌38例和副鼻窦来源的腺样囊性癌4例。方法分析眼眶腺样囊性癌超声、CT和MRI等各种影像学检查结果,记录图像特征。主要指标标准化A/B超、CT和MRI影像。结果ACC标准化A超表现为前部高波峰,后部低波峰和不规则高低混杂波峰两种类型。B超可显示肿瘤的轮廓,对于瘤内钙化及液化坏死等病变显示优良。CT扫描显示ACC有梭形、扁平形、团块状和不规则形等四种形状,对于肿瘤的边界、空间位置,骨破坏和骨吸收等继发改变显示清晰。ACC在T_1加权像为中信号,T_2加权像有均一的等信号,等、低信号混杂和等、高信号混杂三种,多数不均匀强化。强化MRI有利于显示肿瘤的蔓延途径,泪腺ACC有多种蔓延途径。副鼻窦ACC易累及筛窦和上颌窦。结论各种影像学检查可显示眼眶ACC的不同特性。综合运用和分析各种影像学检查结果可提高诊断水平。(眼科,2007,16:391-394)     

泪腺肿瘤38例临床分析

目的：分析泪腺肿瘤的临床特点和治疗结果。方法：回顾性研究38例45眼泪腺肿瘤。结果38例45眼中，男17例17眼，女21例28眼；年龄5～63岁，平均40．6岁；其中泪腺癌5眼，腺样囊性癌5眼。恶性泪腺混合瘤5眼，良性泪腺混合瘤14眼，炎性假瘤13眼，慢性泪腺炎2眼，泪腺潴留性囊肿1眼。42眼行前路或侧壁开眶肿瘤摘除术，恶性肿瘤中4眼行眶内容物剜除。恶性肿瘤患者全部于术后1个月接受放疗。术后随访观察3个月～8年。术后症状完全缓解35眼，好转5眼，复发5眼。结论：泪腺肿瘤为眼眶常见肿瘤，结合病史，临床表现和影像学检查。绝大部分可以作出术前定性诊断，良性泪腺混合瘤预后较好，但易复发。恶性泪腺混合瘤及腺样囊性癌复发率、死亡率较高，应联合眶内容物剜除，放疗及化疗。     

A clinicopathologic study of primary adenoid cystic carcinoma of the lacrimal gland

A retrospective study of 26 patients with the diagnosis of primary adenoid cystic carcinoma of the lacrimal gland was performed with use of randomly selected tissue from each tumor. An attempt was made to determine any associations among clinical presentation, survival, and tumor histologic patterns. We found that lower tumor grades were associated with a predominantly Swiss-cheese (cribriform) pattern. Both lower tumor grade and Swiss-cheese pattern were associated with longer survival. The basaloid (solid) pattern or bone invasion was not associated with a shorter survival. Between men and women, there were no differences in clinical presentation, histologic patterns, or survival. Survival was not affected by surgical or radiation therapy.     

泪腺腺样囊性癌临床治疗进展

泪腺腺样囊性癌(adenoid cystic carcinoma,ACC)是最常见的泪腺恶性上皮肿瘤,单纯手术切除疗效不满意,易复发,预后差。我们总结近年来国内外报道的相关泪腺ACC的临床综合治疗手段,包括改进手术入路、采取手术前后化学治疗、放射治疗等综合治疗方案,特别还报告了青年泪腺ACC患者的治疗策略,并分析了原发于泪腺以外ACC的诊断与治疗,为眼科临床医生提供更广阔的思路。     

泪腺恶性肿瘤—附27例报告

本文报告泪腺恶性肿瘤27例(其中腺样囊性癌12例,恶性多形性腺瘤9例,其它腺癌6例)。讨论和分析了临床表现、影象诊断特征、诊断、鉴别诊断、治疗和予后问题。     

眼眶泪腺癌26例的CT诊断价值

目的：探讨泪腺腺癌的CT诊断价值。 方法：回顾性分析26例26眼经病理证实眼眶泪腺腺癌患者的CT影像资料。 结果：泪腺腺癌26例均为单眼发病,右眼15例,左眼11例。CT表现：病变呈圆形、卵圆形15例,不规则形、分叶形11例。15例边界尚清楚,11例轮廓呈锯齿状。肿瘤密度不均匀,内见低密度灶或钙化。26例病变包绕并压迫眼球,14例沿眶外壁向眶尖区生长,与眼肌分界不清,并浸润视神经。眼眶骨质虫蚀样破坏21例,溶骨性破坏5例。 结论：泪腺癌有特异性CT征象,其诊断准确率高,是本病最主要影像检查方法。     

泪腺腺样囊腺癌的MRI特征分析

目的 探讨泪腺腺样囊腺癌（adenoid cystic carcinoma,ACC）的MRI特征,为临床早期诊断提供依据。设计 回顾性病例系列。研究对象 北京同仁医院经手术证实ACC患者26例,术前均行MRI扫描。方法 所有ACC患者常规MRI扫描;同时对动态增强磁共振成像（DCE-MRI）及磁共振扩散加权成像（DWI）图像进行后处理获得相应量化指标。主要指标 ACC动态增强的峰值强化指数（CIpeak）、峰值强化时间（Tpeak）、最大强化指数（CImax）、强化指数曲线（I型为持续上升型,II型为平台型,III型为流出型）、肿瘤平均表观扩散系数（ADC）值。结果  26例均起自泪腺眶部,20例形态不规则,14例边界不清,12例边界清晰,6例累及颅内,9例出现骨质破坏。T1WI呈等或略低信号,其中3例内部出现高信号区;T2WI呈等或稍高信号为主,增强后仅1例强化均匀,25例呈不均匀强化,其中16例伴有内部囊变、坏死区。泪腺ACC峰值强化指数（CIpeak）为0.9±0.41,峰值强化时间（Tpeak）为（109.3±58.5）s, 最大强化指数（CImax）为0.95±0.45。22例时间强化指数曲线中2例为I型,14例为II型,6例为III型。平均ADC值为（1.25±0.30×10-3）mm2·s－1。结论 MRI可以清晰显示泪腺ACC的部位、形态、范围、边界及骨质侵犯,DCE-MRI及DWI为肿瘤的诊断及鉴别诊断提供辅助量化特征。（眼科,2013, 22： 314-319）     

Adenoid cystic carcinoma of the superonasal conjunctival fornix

The case of a 32-year-old female with a mass in the superonasal conjunctival fornix is described. Histological examination revealed an adenoid cystic carcinoma, which we consider to be most likely derived from an accessory lacrimal gland. The clinical presentation, histological features, management and follow-up are described. A literature review of orbital adenoid cystic carcinoma arising outside the main lacrimal gland is presented.