眼内肿瘤细针穿刺活检的利与弊

【摘要】 细针穿刺眼内活检（fine-needle aspiration biopsy,FNAB）是眼内肿瘤诊断性活检的重要方法,常用于脉络膜肿瘤以及原发性眼内淋巴瘤的诊断。随着穿刺技术以及标本处理方法的改进,FNAB的诊断敏感性和特异性逐渐增加。与其他眼内活检方法相比,FNAB具有方便、快捷、安全的优点,但肿瘤的播散依然是其潜在的风险。临床应用FNAB需严格掌握其适应证。（眼科,2012,21：217-221）     

Fine‐needle aspiration biopsy and other biopsies in suspected intraocular malignant disease: a review

Ocular oncologists require a strong indication for intraocular biopsy before the procedure can be performed because it carries a risk for serious eye complications and the dissemination of malignant cells. The purpose of this review is to evaluate the extent to which this restricted practice is supported by evidence from previous reports and to outline our main indications and contraindications. The different intraocular biopsy techniques in the anterior and posterior segment are discussed with a focus on our preferred method, fine‐needle aspiration biopsy (FNAB). In the literature, complications are typically under‐reported, which reduces the possibilities of evaluating the risks correctly and of making fair comparisons with other biopsy methods. In FNAB, the exact placement of the needle is critical, as is an accurate assessment of the size of the lesion. Fine‐needle aspiration biopsy is usually not a reliable diagnostic tool in lesions < 2 mm in thickness. It is very advantageous to have a cytopathologist present in the operating theatre or close by. This ensures adequate sampling and encourages repeated biopsy attempts if necessary. This approach reduces false negative results to < 3%. Adjunct immunocytochemistry is documented to increase specificity and is essential for diagnosis and management in about 10% of cases. In some rare pathological processes the diagnosis depends ultimately on the identification of specific cell markers. An accurate diagnosis may have a decisive influence on prognosis. The cytogenetic prognostications made possible after FNAB are reliable. Biopsy by FNA has a low complication rate. The calculated risk for retinal detachment is < 4%. Intraocular haemorrhage is frequently observed, but clears spontaneously in nearly all cases. Only a single case of epibulbar seeding of malignant cells at the scleral pars plana puncture site of transvitreal FNAB has been documented. Endophthalmitis has been reported and adequate standard preoperative preparation is obligatory. An open biopsy is still an option in the anterior segment, but has been abandoned in the posterior segment. Although vitrectomy‐based procedures are becoming increasingly popular, we recommend using FNAB as part of a stepwise approach. A vitrectomy‐assisted biopsy should be considered in cases where FNAB fails. In any adult patient with suspected intraocular malignancy in which enucleation is not the obvious treatment, the clinician should strive for a diagnosis based on biopsy. When the lesion is too small for biopsy or the risks related to the procedure are too great, it is reasonable to be reluctant to biopsy. The standards applied in the treatment of intraocular malignant diseases should be equivalent to those in other fields of oncology. Our view is controversial and contrary to opinion that supports current standards of care for this group of patients.     

细针穿刺细胞学检查在眼内肿瘤诊断中的应用

为对眼内占位性病变进行诊断与鉴别诊断，降低误摘眼球率，对可疑视网膜母细胞瘤和高度怀疑其他眼内肿瘤的病人行细针穿刺细胞学检查。结果，１９例病人中１３例被证实为视网膜母细胞瘤、１例肺癌转移、２例脉络膜黑色素瘤，这组病人经病理检查穿刺道内无肿瘤细胞存留；３例未查到癌细胞，追踪观察６月～４．５年未发现有肿瘤的局部转移。结论：细针穿刺细胞学检查法安全、可靠，可以应用于眼内肿瘤临床诊断和鉴别诊断     

Carcinoma metastatic to the eye

Cancer is a leading cause of death in America. Cancer to the eye is being diagnosed with increasing frequency. It is now considered the most common intraocular malignancy in adults. Although most ocular metastases do not require treatment, they have important prognostic implications for the patient's overall survival. Diagnostic errors leading to enucleation could be reduced if the incidence of metastatic tumors was always well considered. Presented here are two patients with metastatic tumors and a brief discussion of the nature of this ocular disease.     

Extramacular disciform lesions simulating uveal tumors.

PURPOSE: The purpose of this study is to identify clinical, ultrasonographic, and fluorescein angiographic features of extramacular disciform lesions that allow differentiation from uveal tumors. METHODS: This was a retrospective study of 19 patients referred to our ocular oncology unit with a possible malignancy who had a diagnosis of an extramacular disciform lesion made after complete evaluation. RESULTS: The level of accuracy for each diagnostic technique alone was as follows: clinical (79%), ultrasonography (83%), and angiography (83%). Fluorescein angiography had limited utility because of severe media opacities in seven cases. No tumor developed an intraocular malignancy during the follow-up period. CONCLUSION: A combination of the above, noninvasive techniques can be used to correctly diagnose extramacular disciform lesions.     

Netrin-1 promotes epithelium repair in corneal injury

Retinoblastoma (Rb) is the most common intraocular malignancy of childhood caused by inactivation of the Rb genes. The prognosis of Rb is better with an earlier diagnosis. Many diagnostic approaches and appropriate clinical treatments have been developed to improve clinical outcomes. However, limitations exist when utilizing current methods. Recently, many studies have identified identify new Rb biomarkers which can be used in diagnosis, as prognostic indicators and may contribute to understanding the pathogenesis of Rb and help determine specific treatment strategies. This review focuses on recent advances in the discovery of Rb biomarkers and discusses their clinical utility and challenges from areas such as epigenetics, proteomics and radiogenomics.     

New etiological concepts in uveitis

Uveitis remains an important cause of visual impairment, particularly in young patients. Idiopathic forms of intraocular inflammation should no longer be regarded as a presumed clinical entity, and the ophthalmologist must reconsider the specific etiology of primary uveitis when the clinical examination does not yield a definitive diagnosis or when the course of the disease on corticosteroids remains atypical. Laboratory tests based on serum analysis have limited value and should not be considered as diagnostic proof in different clinical presentations. The diagnostic management of infectious uveitis has been greatly improved by the use of molecular techniques applied to ocular fluids and tissues. Polymerase chain reaction (PCR) technology is a powerful tool that should be proposed in atypical cases of uveitis or retinitis of unclear but potentially infectious origin. This strategy is a major step before using unconventional and new immunomodulatory agents such as anti-TNF-alpha molecules. Under strict experimental conditions including adequate testing to rule out a possible contamination, PCR and its variants have changed our practical approach to intraocular inflammatory disorders and have provided new details for the understanding of infectious uveitis. The concept of pathogen-induced intraocular inflammation can be revisited in the light of molecular data obtained after anterior chamber paracentesis or diagnostic vitrectomy.     

Diagnostic yield of vitrectomy in eyes with suspected posterior segment infection or malignancy

PURPOSE: To determine the yield of diagnostic pars plana vitrectomy in eyes with suspected posterior segment inflammation or malignancy when clinical examination and systemic laboratory testing did not yield a specific diagnosis. DESIGN: Non-comparative interventional case series PARTICIPANTS: Eighty-seven consecutive patients (90 eyes) who underwent diagnostic pars plana vitrectomy from 1989 through 1999. INTERVENTIONS: Vitreous samples were analyzed in a directed manner based on the preoperative clinical examination and systemic laboratory testing. MAIN OUTCOME MEASURES: Diagnosis from each test performed on the vitreous samples. RESULTS: Diagnostic vitrectomy was performed alone in 6 eyes (7%) and as part of a therapeutic procedure in the remaining 84 eyes. The diagnostic tests performed most frequently included cytopathology (83%), microbiologic culture and sensitivity (43%), polymerase chain reaction (PCR) (36%), and intraocular antibody levels for T. canis (14%). Of these, intraocular antibody testing and PCR had the highest positive yield, 46% and 39%, respectively. Overall, directed vitreous analysis identified a specific cause in 35 eyes (39%). Of the 65 cases in which an underlying infection was suspected preoperatively, the procedure yielded a specific diagnosis in 27 (42%). When intraocular malignancy was considered preoperatively (71 eyes), a diagnosis of intraocular lymphoma was obtained in seven (10%). This difference between these diagnostic yields was significant (P = 0.02, Fisher's exact test). CONCLUSIONS: Diagnostic vitrectomy with directed vitreous fluid analysis yields a specific cause and guides subsequent therapy in a high percentage of cases. This procedure is a valuable adjunct in cases that cannot be diagnosed by less invasive methods.     

Inaccuracy of fine needle aspiration biopsy

Fine needle aspiration biopsy (FNAB) of orbital tumors has been recently advocated as a reliable diagnostic modality. An accuracy rate of 92% has been claimed by some authors. This figure remains unproven as most patients have not undergone simultaneous pathologic examination. We recently performed FNAB on 34 patients at the time of surgical biopsy. The procedure was performed with direct visualization and the tissue was obtained and prepared as described by Kennerdell. A definitive surgical biopsy was then obtained and submitted for routine pathologic examination. Cytologic diagnosis has been accurate in less than half of the cases biopsied. Reliance on fine needle aspiration biopsy alone in some patients would have resulted in inappropriate therapy. Fine needle aspiration biopsy should be limited to strongly suspected cases of orbital metastases or secondary tumors.     

Nuclear magnetic resonance imaging of intraocular tumors

Of 11 patients with intraocular tumors who underwent magnetic resonance imaging, seven had melanoma and one each had lymphoma, metastatic carcinoma, hemangioma, and hemorrhage. All were localized in the choroid. We compared the results of the magnetic resonance imaging examinations with those of ophthalmic ultrasonography, external inspection, and histopathologic studies. Magnetic resonance imaging detected six of the seven choroidal melanomas. Demarcation between the tumor and the sclera was excellent. Extrascleral tumor extension could be excluded. Hemorrhage in and beside the choroidal melanoma could be seen separately. Magnetic resonance imaging differentiates choroidal tumors from the surrounding intraocular and extraocular tissues better than computed tomography does, making it an important new diagnostic procedure.     

Calcifications in lesions of the fossa of the lacrimal gland

It is frequently reported that calcification in the fossa of the lacrimal gland is a reliable sign of malignancy. We present a small, previously unreported series of lacrimal gland fossa calcifications, in which in three out of five cases the lesion was benign. Calcification can be a misleading radiographic sign and should not, in and of itself, be considered diagnostic of malignancy. This is important because proper preoperative diagnosis of lacrimal fossa tumors is essential as management differs.     

如何认识细针取材组织细胞学活检技术在眼科的应用价值

细针取材组织细胞学活检(FNAB)技术是一种病理检查的取材方式,这种方式由于安全、简便,能够提供病理诊断而被大多数学科广泛使用.FNAB在国内眼科领域并未收到同样的重视,其主要原因可能与目前眼科疾病诊断中除肿瘤外,病理诊断在眼科疾病诊断中重要性的认知不足以及眼科病理检查并未成为眼科临床诊断、治疗的常规标准有关.本文的主要观点是希望临床眼科医师重视FNAB在眼科领域的应用.内眼手术器械的发展,使得手术中取材成为眼科的优势方法.因此呼吁眼科医师关注这种技术,推广病理活检辅助眼病的诊断.     

Immersion ultrasonography: simultaneous A-scan and B-scan

In eyes with opaque media, ophthalmic ultrasound provides a unique source of information that can dramatically affect the course of patient management. In addition, when an ocular abnormality can be visualized, ultrasonography provides information that supplements and complements other diagnostic testing. It provides documentation and differentiation of abnormal states, such as vitreous hemorrhage and intraocular tumor, as well as differentiation of orbital tumors from inflammatory causes of exophthalmos. Additional capabilities of ultrasound are biometric determinations for calculation of intraocular lens implant powers and drug-effectiveness studies. Maximal information is derived from ultrasonography when A-scan and B-scan techniques are employed simultaneously. Flexibility of electronics, variable-frequency transducers, and the use of several different manual scanning patterns aid in detection and interpretation of results. The immersion system of ultrasonography provides these features optimally.     

Ultrasonically guided needle biopsy and cytologic diagnosis of solid intraocular tumors

Six solid intraocular tumors were reliably diagnosed by needle biopsies and cytologic examination of the aspirates. All of the tumors had an unusual clinical or diagnostic feature that raised the possibility of a non-melanomatous tumor. Two intraocular lesions that were obscured by opaque media or a retinal detachment were successfully biopsied under B-scan ultrasonographic guidance of the needle. Cytodiagnosis of narrow spindle B, plump spindle B, and eipthelioid cell types, as well as one case of Coats' disease, was possible and correlated closely with the predominant cell types comprising the lesions discovered on histopathologic examination of the globes that were enucleated. The ocular tissues were not significantly disturbed and hemorrhage was not a serious problem. Details of the biopsy and cytologic techniques, the major clinical indications, for the procedure, and the authors' belief that the procedure is not likely to produce local seeding or extraocular metastasis in cases of melanoma are presented and discussed. Considerable profit may attend the use of this technique for the diagnosis of possible metastatic lesions and tumors of the ciliary body. The technique, however, should not be routinely employed and should be restricted to extremely difficult diagnostic problems.     

Hyperthermic therapy procedures for supplementing radiotherapy of malignant intraocular tumors

Since more than a century ago, temperatures above 40 degrees C have been known to be effective in cancer treatment. Since that time numerous studies have documented that hyperthermia alone causes tumor regression and that the therapeutic effect depends on the amount and duration of heat delivered to a malignant tumor. However, after it was shown that heat combined with irradiation or chemotherapy potentiates the effect of hyperthermia, both thermoradiotherapy and thermochemotherapy were applied in experimental and clinical studies in several medical specialties. In ophthalmic oncology both retinoblastoma and uveal melanoma are treated by irradiation combined with local hyperthermia. In the present paper the use of ultrasound and microwave energy as locally applicable heat sources in intraocular malignancies is described and their suitability discussed. As is the case with malignant skin tumors and malignant tumors of the gastrointestinal and urogenital systems, malignant ocular tumors are accessible to externally applied heat and can thus be treated well by ultrasound and microwave hyperthermia. On the basis of experimental and clinical results gained with both ultrasound and microwave energy the advantages and drawbacks of these two technical modalities in intraocular tumor therapy are pointed out.     

Latent intracellular Epstein-Barr Virus DNA demonstrated in ocular posttransplant lymphoproliferative disorder mimicking granulomatous uveitis with iris nodules in a child.

A case of intraocular posttransplant lymphoproliferative disorder (PTLD) is described in a 9-year-old female who underwent orthotopic liver transplantation at the age of 18 months. The prevalence of ophthalmic involvement in PTLD can be expected to rise with the increasing number of major organ transplantations, as well as improved survivorship. Children are particularly at risk for this posttransplant complication because they are usually seronegative for the Epstein-Barr virus (EBV) prior to transplant. Accurate diagnostic classification of PTLD to include confirmation of EBV infection carries significant therapeutic and prognostic implications.     

Fine needle aspiration biopsy in selecting treatment for inconclusive intraocular disease.

PURPOSE: To evaluate the fine needle aspiration biopsy (FNAB) as a diagnostic tool in cases where it was impossible to make a definitive diagnosis with noninvasive techniques. METHOD: 80 consecutive patients with inconclusive diagnoses were examined by FNAB prior to decision of treatment. Biopsies were performed through a transscleral route in 50 eyes, an anterior chamber route in 16 eyes and a transvitreal approach in 14 eyes. The consequences of FNAB were analysed retrospectively. RESULTS: FNAB confirmed malignancy in 59 eyes. Inconclusive material was obtained from 5 eyes judged clinically to be malignant disorders. One melanoma was misinterpreted as being a metastasis. In 47.5% of our patients this procedure altered the therapeutic plan and 25 patients were spared enucleation. The biopsy material was correctly diagnosed as benign in 16 cases. CONCLUSION: In eyes where the diagnosis remained uncertain after non-invasive tests, FNAB gave important information which greatly influenced our choice of treatment. FNAB contained sufficient tissue elements for cytological diagnosis in 77 eyes. Cytopathological interpretation failed once in relation to tumour type. The procedure of FNAB can be recommended for use in ambiguous tumour cases of the eye. Probably it should only be used in tumour centres with adequate cytology service.     

Ophthalmologic diagnostic procedures and imaging of retinal vein occlusions

Retinal vein occlusions are a common vascular disease of the eye. Ophthalmological diagnostic procedures and imaging are important for the prognosis of the disease, as are the systemic work-up and therapy. Besides routine ophthalmic tests (visual acuity, slit lamp examination, funduscopy) a work-up for glaucoma such as intraocular pressure, visual field or 24?h IOP profile is useful as a diagnostic procedure. Furthermore, new diagnostic and imaging tests such as central corneal thickness and optic nerve head imaging by Heidelberg retina tomography or optical coherence tomography (OCT) should be considered for glaucoma evaluation. Optical coherence tomography also plays a major role in treatment monitoring of macular edema secondary to retinal vein occlusions. Fluorescein angiography is well established and can provide information with regard to size and extent of the occlusion, degree of ischemia, areas of non-perfusion and neovascularization, as well as macular edema.     

Fine-needle aspiration biopsy for suspected uveal metastases

ObjectiveOne indication of fine-needle aspiration biopsy (FNAB) is the diagnostic confirmatory of a clinical suspicion of uveal metastasis. We analyzed our experience in this clinical setting to assess the effectiveness of FNAB technique.DesignRetrospective study.Participants28 patients (28 eyes) underwent FNAB biopsy.MethodsAspirates were performed using 25-gauge needle and were classified into the following categories: positive, atypical, negative, or nondiagnostic. The electronic medical records provided all clinical data. Subsequent clinical course was considered as the diagnostic standard.ResultsSubsequent clinical course was metastatic tumour in 19 cases (68%) and nonmetastatic tumour in other 9 cases, considered as the diagnostic standard. Cytological interpretations for metastases were positive in 19 cases (68%), atypical in 2 cases (7%), negative in 4 cases (14%), and nondiagnostic in 3 cases (11%). The metastasis-positive cases included 9 adenocarcinoma, 3 uveal lymphoma, 3 small cell carcinomas, 3 non–small cell carcinomas, and 1 metastatic paraganglioma. Both of the atypical cases were suggestive for non-Hodgkin lymphoma. The 4 negative cases for metastases included 2 true negative cases, and 2 false negative aspirates that subsequently proved to be metastatic adenocarcinoma. The 3 nondiagnostic cases included 1 schwannoma, 1 low-grade uveal non-Hodgkin lymphoma, and 1 metastatic adenocarcinoma. The overall sensitivity for FNAB was 87.5%, with a specificity of 100%.ConclusionsFNAB of suspected uveal metastases is a reliable diagnostic technique.