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.     

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。     

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.     

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.     

Similar therapeutic effects of 125I seed radiotherapy andγ-ray radiotherapy on lacrimal gland adenoid cystic carcinoma

AIM:To evaluate the survival outcomes of patients with lacrimal gland adenoid cystic carcinoma who underwent eye-sparing surgery combined with ^125Iseed implantation radiotherapy or local externalγ-ray radiotherapy.METHODS:In this retrospective comparative case series,the clinical records of 27 primary and 8 recurrent patients were reviewed.Univariate and multivariate analyses were used to identify risk factors associated with distant metastasis(DM),and the overall survival(OS)after the initial surgery was analyzed.RESULTS:The median follow-up after radiotherapy was 36 mo(range 6-120 mo).At the last follow-up after radiotherapy,26(74.3%)patients had no evidence of disease,7(20%)patients had DM,2(5.9%)patients died of DM,and 1 patient with DM was lost to follow-up.Univariate analyses showed that duration of symptoms,bone destruction,T stage classification,and wide excision surgery were risk factors influencing DM(P<0.05).The 5-year and 10-year OS rates after the initial surgery were 95.8%and 79.9%,respectively.The 5-year DM-free survival and disease-free survival rates after radiotherapy were 66.4%and 52.7%,respectively.CONCLUSION:^125Iseed radiotherapy and local externalγ-ray radiotherapy may have similar therapeutic effects in preventing DM.Patients with T1/T2 stage disease have a better prognosis than those with T3/T4 stage disease.     

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

PURPOSE: To determine the effect of intraarterial cytoreductive chemotherapy (IACC) as an adjunct to conventional surgery and radiation therapy for lacrimal gland adenoid cystic carcinoma (ACC). DESIGN: A retrospective, comparative, interventional 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 in the same institution. intervention procedure: Clinical records, imaging studies, histologic sections, and archival specimens from all 16 patients were reviewed. Information analyzed included site of disease, histologic characteristics, extent of disease, incidence of locoregional recurrence or distant metastases, and disease-free survival and overall survival time. main outcome measure: The effect of IACC was assessed by the radiographic and histologic response and survival outcome in comparison to a historical cohort of patients managed by conventional local therapies. RESULTS: The difference between the carcinoma cause-specific death rate of the study group versus conventional treatment was significant (P = .029, log rank test). The cumulative 5-year carcinoma cause-specific death rate in the IACC treated group was 16.7% compared with 57.1% in the conventional treatment group. The cumulative 5-year recurrence rate in the IACC treated group was 23.8% compared with 71.4% in the conventional treatment group. CONCLUSIONS: The preliminary data suggest that IACC as an integral component of a multimodal treatment strategy is potentially effective in improving local disease control and overall disease-free survival in lacrimal gland adenoid cystic carcinoma.     

Management of lacrimal sac tumours

PURPOSE: To report a series of 15 primary lacrimal sac tumours and present an algorithm in managing this rare condition. DESIGN: Noncomparative interventional case series. METHODS: A retrospective review of the clinical, radiological, and pathological records of 15 patients with primary lacrimal sac tumours.Main outcome measures Histologic evaluation and clinical follow-up, including tumour clearance and recurrence, were assessed. RESULTS: Of the patients, 11 were female and the median age at presentation for the whole group was 59 years (range 22-94 years). The commonest tumour was non-Hodgkins B-cell lymphoma (five cases), followed by two cases each of squamous cell carcinoma and transitional cell carcinoma, one case of benign transitional papilloma, haemangiopericytoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, mixed (squamous/transitional) carcinoma, and a highly malignant undifferentiated tumour. Treatment modalities included surgery, radiotherapy and chemotherapy and, with a median follow-up of 30 months (range 2 months to 17 years), two patients had died from metastatic disease but nine patients remained without evidence of recurrent tumour. CONCLUSIONS: Primary lacrimal sac tumours are extremely rare, require long-term follow-up for recurrence and metastasis, and can be fatal.     

Plaque radiotherapy for selected orbital malignancies: preliminary observations: the 2002 Montgomery Lecture,part 2

PURPOSE: To describe the principles and preliminary results of plaque brachytherapy for selected orbital malignancies. METHODS: A custom-designed Iodine-125 plaque, designed to deliver a target dose of 50 Gray, was placed surgically in the region from which an orbital malignancy was partially resected. The mean dose to the target area was 50 Gray. The initial and follow-up patient data were reviewed. RESULTS: Of the 8 patients, the diagnosis was adenoid cystic carcinoma of the lacrimal gland (4 cases), orbital invasion by basal cell carcinoma (2), orbital extension of conjunctival melanoma (1), and metastatic carcinoma (1). Of the 4 with adenoid cystic carcinoma, there was microscopic residual tumor after excision and orbital exenteration was considered. Three have tumor control with follow-up of 1, 3, and 6 years. One patient required exenteration for recurrence separate from the field of brachytherapy and is free of tumor after 10 years. All 4 patients are alive and well with tumor control. Of the 2 patients with orbital extension of basal cell carcinoma, tumor control without recurrence has been achieved in both after 2 years. The patient with orbital metastasis responded to plaque radiotherapy, with no orbital recurrence, but died of systemic metastasis. The patient with orbital melanoma had local orbital recurrence separate from the area of irradiation and is currently being treated for systemic metastasis. CONCLUSIONS: Based on preliminary observations, plaque radiotherapy appears to be a reasonable alternative to exenteration and external irradiation for selected orbital malignancies.     

An unusual clinical course of adenoid cystic carcinoma of the lacrimal gland

The case of a 25-year-old woman with adenoid cystic carcinoma of the lacrimal gland is reported. Her complaints, including pain and localized swelling, first started six years earlier. She was diagnosed elsewhere as orbital pseudotumor based on clinical and computed tomographic features and was prescribed oral corticosteroids. The regimen completely relieved her signs and symptoms, which regularly recurred in the ensuing years. When she finally presented with rapidly worsening proptosis and pain, she underwent incisional biopsy followed by exenteration and 6000 cGy of radiotherapy. This patient is a rare example of adenoid cystic carcinoma of the lacrimal gland with an atypical clinical course of long duration during which corticosteroids completely suppressed the clinical signs and symptoms.     

An unusual clinical course of adenoid cystic carcinoma of the lacrimal gland

The case of a 25-year-old woman with adenoid cystic carcinoma of the lacrimal gland is reported. Her complaints, including pain and localized swelling, first started six years earlier. She was diagnosed elsewhere as orbital pseudotumor based on clinical and computed tomographic features and was prescribed oral corticosteroids. The regimen completely relieved her signs and symptoms, which regularly recurred in the ensuing years. When she finally presented with rapidly worsening proptosis and pain, she underwent incisional biopsy followed by exenteration and 6000 cGy of radiotherapy. This patient is a rare example of adenoid cystic carcinoma of the lacrimal gland with an atypical clinical course of long duration during which corticosteroids completely suppressed the clinical signs and symptoms.     

Cystic adenocarcinomas of the lacrymal gland

Adenoid cystic carcinoma of the lacrimal gland. BACKGROUND: Adenoid cystic carcinoma is the most frequent epithelial tumour of the lacrimal gland. It represents 1.6 % of the orbital tumours. The aim of this study is to present a series of such patients who were followed up in our clinic and to discuss their clinical management in order to achieve a better life prognosis. MATERIALS AND METHODS: The cases we followed up in our department were presented, the treatment modalities were discussed, and conclusions were drawn. RESULTS: Six patients with this pathology were examined, 3 men and 3 women, aged 31 to 69 years. A large excision was performed in 5 patients (exenteration alone or extended exenteration with complementary radiotherapy) and in 1 patient with excision of the tumour followed by radiotherapy. One patient died due to carcinoma six years after the first surgery. The median follow-up period of our cases is 25 months. CONCLUSION: Adenoid cystic carcinoma of the lacrimal gland is a malignant tumour with a reserved prognosis. Various treatments were proposed to improve the mortality rate of the disease. At present radical surgery with or without complementary therapy seems to give the best chances of healing, at least with short or mid-term follow-up.     

Choroidal metastasis from submandibular salivary gland adenoid cystic carcinoma.

A case of choroidal metastasis from an adenoid cystic carcinoma ofsubmandibular salivary gland is described. A 50-year-old woman with loss of vision in her left eye for 1 week was evaluated clinically, radiologically, and pathologically. A fundus image of the left eye showed an amelanotic, plateau-shaped choroidal mass measuring 17 x 12 X 4 mm with overlying exudative retinal detachment. A choroidal biopsy was consistent with metastatic adenoid cystic carcinoma from her submandibular salivary gland treated 5 years previously. She was treated with external beam radiotherapy but developed liver and lung metastases 3 months later and died within 1 month. All of the metastases demonstrated a basaloid histologic variant of adenoid cystic carcinoma that is known for its aggressive potential. Salivary gland carcinoma rarely metastasizes to the choroid; however, evaluation of patients with this carcinoma should include ophthalmic examination.     

Adenoid cystic carcinoma arising in the inferior orbit without evidence of lacrimal gland involvement

A 60-year-old woman sought treatment for right orbital fullness and intermittent headache. CT revealed an inferior orbital mass along the inferior rectus muscle. Incisional biopsy revealed an adenoid cystic carcinoma. Orbital exenteration followed by concurrent radiotherapy and chemotherapy was performed. The lacrimal gland was uninvolved by tumor microscopically. Although rare, adenoid cystic carcinoma must be considered in the differential diagnosis of an orbital tumor, because the unusual location of an orbital adenoid cystic carcinoma may make its early detection difficult.     

眼眶腺样囊性癌的治疗与预后分析

目的 分析总结眼眶腺样囊性癌的治疗方法及影响预后的因素,为改善预后提供帮助.方法 采用回顾性系列病例研究,分析1991年1月至2006年7月就诊的75例眼眶腺样囊性癌患者的手术记录、病理分型及随访记录.相关数据采用χ2检验和Fisher精确检验进行统计分析.结果 眼眶实体型腺样囊性癌的2年复发率为85%(17/20)、5年复发率为100%(19/19),而腺样.管状型则分别为23.53%(8/34)和64.52%(20/31),差异有统计学意义(2年,χ2=19.14,P=0.000;5年,Fisher精确检验,P=0.003).前者发生局部蔓延和远处转移例数亦多于后者.肿瘤切除术后放射治疗的5年复发率为70%(14/20),低于单纯手术切除的复发率92.86%(13/14)(Fisher精确检验,P=0.198).首次手术行眶内容物剜除术的5年复发率为25%(1/4),低于复发后再行眶内容物剜除术的病例为75%(6/8)(Fisher精确检验,P=0.222),γ刀、粒子刀、化疗及生物治疗的效果不能确定.局部蔓延主要是至颅内、副鼻窦和颞窝,远处转移可到达肺、骨、肝、耳前淋巴结.5年远处转移率为25.71%(9/35),肺转移和骨转移各占33.33%(3/9).5年生存率74.29%(26/35),死亡率25.71%(9/35),无瘤生存率37.14%(13/35),10年无瘤生存率17.14%(6/35).最常见的死亡原因是颅内蔓延.肿瘤切除联合放射治疗可以使5年生存率提高到80%(16/20).结论 腺样囊性癌是高度恶性的眼眶肿瘤,复发率和死亡率均较高,病理分型、治疗方法均影响预后.采取综合治疗方法,可以减少复发,提高生存率.     

Adenoid squamous carcinoma of the conjunctiva—a clinicopathological study of 14 cases

AIMS—In order to determine the clinicopathological features and optimum management of a series of patients with adenoid squamous cell carcinoma of the conjunctiva, all cases of squamous cell carcinoma (SCC) of the conjunctiva and cornea on file in the registry of the ophthalmic pathology at the Armed Forces Institute of Pathology were reviewed.
METHODS—On histopathological examination, a predominant adenoid or pseudoglandular pattern due to islands of neoplastic squamous or epidermoid cells surrounded by acantholytic cells was necessary for inclusion in the study. Histochemical and transmission electron microscopic studies (TEM) were performed. Clinical features of all the patients were extracted from the charts.
RESULTS—The anatomical location of the 14 tumours was corneoscleral limbus (seven patients) and bulbar conjunctiva (seven patients). Eight patients presented with inflammatory signs and irritation (red eye, tearing, foreign body sensation), while six patients developed a slowly growing, painless mass. Histochemical and TEM studies showed extracellular hyaluronic acid and no intracellular mucin. Of the two patients initially treated by enucleation, one was free of disease after 2 years while the second patient had recurrence in the socket and died of brain metastases despite wide orbital excision and radiotherapy. All five patients with recurrent tumours initially had irritated red eyes and two required enucleation. One such patient, after orbital exenteration and radiotherapy, died of unrelated disease.
CONCLUSION—The study demonstrates that adenoid SCC of the conjunctiva often presents with inflammatory signs. The tumour is locally aggressive and may metastasise and should, therefore, be histopathologically differentiated from the less aggressive conventional squamous cell carcinoma. Optimum treatment includes wide excision with documented histological clear margins of resection on permanent sections and frequent follow up.

     

Adenoid cystic carcinoma presenting as an orbital apex syndrome

Adenoid cystic carcinomas (cylindromas) are distinctive neoplasms characterized by slow growth, perineural spread, extensive local invasion, frequent recurrence, and high mortality. A case of paranasal sinus adenoid cystic carcinoma presenting as an orbital apex syndrome is described.     

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。     

Iodine-125 interstitial brachytherapy for malignant lacrimal sac tumours: an innovative technique

ObjectivesPrimary malignant tumours of the lacrimal sac are rare, surgery and radiotherapy may induce substantial side effects for patients. Here, this article reports an innovative technique of interstitial brachytherapy developed for the treatment of malignant lacrimal sac tumours.Patients and methodsFour patients (male 3, female 1), with an average age of 52.7 years (range 41–72 years), were individually diagnosed with squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma and lymphoma. All patients received Iodine-125 interstitial brachytherapy after surgical resection for malignant lacrimal sac tumours. Visual function examination (vision, intraocular tension, fundus photography, fluorescein angiography, and optical coherence tomography) and CT/MRI/PET-MRI were performed to look for signs of recurrent tumours or metastasis.ResultsFour patients were followed for an average of 28 months (range, 23–37 months). All patients were free from local disease. Their visual function was normal, and CT/MRI did not reveal any tumour recurrence.ConclusionsIodine-125 interstitial brachytherapy can be used as an alternative to wide excision or exenteration of these tumours. There was good local control, reasonable maintenance of vision, and good cosmesis.Subject terms: Lacrimal apparatus diseases, Eye cancer, Radiotherapy     

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.