Ординатура / Офтальмология / Английские материалы / Tumors of the Eye and Ocular Adnexa_Char_2001

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not useful as has been suggested.23,24 As an example, on US the soft tissue mismatch and impedance characteristics of lymphoma, pseudotumor, and metastases are similar; placing a patient correctly in this broad diagnostic category is not specific enough for most management decisions. Similarly, while US would substantiate the CT diagnosis of a cystic lesion, it cannot distinguish between a mucocele and a dermoid; an MRI or CT scan can usually be used to do so.3,9,22

Magnetic Resonance Imaging

MRI was derived from nuclear magnetic resonance experiments performed at analytical chemistry laboratories since the late 1940s.25 It is based on the principle that nuclei with an odd number of nucleons (protons and neutrons) behave as small magnets or dipoles. In the human body, hydrogen nuclei (protons) are ubiquitous, and their resonance is the basis of clinical MRI techniques. When the object under study is placed in a magnetic field, there is a net alignment of protons within the field. When exposed to a radiofrequency (RF) excitation, there is a reversal of polarity of some of these hydrogen nuclei and they are raised to a higher energy level. When the RF is terminated, the proton returns to the original polarity, or is remagnetized, and the emitted energy can be measured. This phenomenon is called T1 relaxation, vertical relaxation, or spin lattice relaxation. It is an event that is best measured immediately after the RF is terminated. Differences in the rates of repolarization vary with the molecular environment and are partially the basis for tissue contrast in MRI. Exposure to RF excitation also initiates a uniform synchronous precession, or spin, among the protons. When the RF is terminated, this precession diminishes at differing rates for protons in different molecular environments. The energy emission measured from this event is called T2 relaxation, horizontal relaxation, or spin-spin relaxation time. Since the RF-initiated events are dependent on the frequency and magnetic field strength, the location of these events in three-dimensional space can be determined by imposing a gradient (approximately 1 kilogauss per centimeter) on the magnetic field and varying the RF.

Field strengths used for clinical imaging range from 0.15 to 4.5 tesla.26–33 Presently, optimal orbital or intraocular anatomic detail is obtained with 1.5T MRI units, usually with surface coils and thin-sec- tion scans. Signal-to-noise ratio improves with increasing field strength. The components of the magnetic resonance signal that form an image reflect proton density, T1 relaxation, T2 relaxation, and vascular flow, if present.

There are a number of similarities in the generation of a CT and an MR image. The relative intensity of the MRI signal is displayed as a pixel matrix on a gray scale similiar to that of CT. The major differences are the techniques and tissue properties that are imaged. In CT, tissue density is related to the attenuation of X-rays coursing through that area of the body. In MRI, relative rates of remagnetization and loss of precessional frequency and proton density are responsible for signal intensity differences. These are influenced by imaging techniques, field strength and tissue magnetic susceptibility. Because of this host of variables, MRI intensity values are not related to a standard reference but, rather, to other tissues in the volume being imaged with a given set of imaging parameters.

In the generation of a CT image, numbers are produced that are directly related to the X-ray attenuation in a finite volume of tissue; represented by an individual number, termed a “voxel.” The numerical representation of the MR image is the same as for CT; however, the physical property that results in the MRI numerical value of a voxel is the intensity of the radiowave signal of the perturbed hydrogen nuclei in a given volume of tissue.

Unlike the photon–tissue interaction, which can be characterized as a single-moment event, an MRI signal has two major temporal factors that influence it: (1) the alignment of protons in tissue varies at the time they are stimulated by both the radiowaves and the magnetic field, and their initial status affects both initial signal intensity and decay; and (2) once the tissue protons are perturbed, they have a characteristic decay envelope.

Retrobulbar fat which has both a short T1 and medium T2 relaxation will produce a relatively strong signal. Muscle is intermediate in signal intensity, and cerebrospinal fluid and vitreous have long

T1 and long T2 relaxation times. Cortical bone is displayed as black (signal void), as there is no mobile hydrogen, and therefore no MRI signal.

Instrument parameters (repetition time [TR] and echo delay [TE]) can be varied to emphasize T1 or T2 relaxation. The TR indicates the time interval between excitations and usually ranges from 50 to 4,000 milliseconds (msecs). TE is the time after excitation at this resonant energy, and can range from 2.5 to 120 msec. Images with relatively short TRs (< 500 msec) and short TEs (< 40 msec) are T1 weighted. Images obtained with long TRs (approximately 2,000 msec) and long TEs (> 60 msec) are T2 weighted. T1 and T2 can also be measured as an absolute number. It has been hoped that these objective values would be useful in developing a tissue specificity.34–36 Thus far, it appears that there is substantial overlap, as discussed in the following chapters between benign and malignant orbital processes.

In the years since the first edition of Clinical Ocular Oncology, there has been substantial MRI data published on orbital tumors.26–46 Several modifications and scan techniques have improved the quality and utility of orbital MRI.43–46 T1-weighted images (TR < 500 msec) and TE (< 40 msec) optimally display anatomic features. Newer MRI approaches have not yet shown a marked impact on the management of orbital tumors. Some of these include fluid-attenuated inversion recovery and diffusion-weighted imaging.47 In addition, a number of cases have been reported in which poor quality MRI, especially those due to chemical shift artifacts, has resulted in incorrect diagnosis and uninterpretable scans.48

In addition to observing TR values displayed alongside the MR image, orbital fat is bright (white) on T1, and these images will be best for assessing anatomic relationships of an orbital tumor. T2 features of a lesion are best displayed on scans with a long TR (> 2,000 msec) and these scans can be identified by the relatively dark orbital fat. Table 15–2 lists T1 and T2 patterns of some orbital tumors. Unfortunately, there are limitations with MRI scans. For patients, these scans take longer and are more costly. In young children, sedation or anesthesia is necessary. In some patients, a large amount of dental hardware can also produce an MRI scan with insufficient artifact to obviate its usefulness as shown in Figure 15–3.

Table 15–2. MRI T1 AND T2 CHARACTERISTICS

OF ORBITAL TUMORS

CNS = central nervous system; ISD = isodense to tissue listed; HPD = hyperdense to tissue listed.

*Usually a mixed, heterogeneous pattern.

† May have fluid level; if none is present, fat is isodense to muscle.

SUMMARY OF SCAN FINDINGS

As discussed in subsequent chapters, there are a few situations where MRI scans are superior to CT, and a few clinical settings where CT data are more useful. Generally, for intraocular tumors, only in three settings is MRI definitely superior to US: (1) as

Figure 15–3. Large amount of dental hardware has resulted in a bizarre appearance of this axial MRI scan.

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described in the chapter on posterior uveal tumor diagnosis, in some cases of extramacular disciform lesions, bright signal on both T1-weighted and T2-weighted images is distinct from the pattern of a uveal melanoma; (2) in patients in whom there is suspected localized extrascleral extension of a melanoma, MRI as, discussed in that chapter, is probably a more accurate technique; and (3) in retinoblastomas with optic nerve extension, MRI may be more sensitive at detecting localized extraocular spread than US or CT.

In orbital tumor diagnosis, MRI with fat saturation and gadolinium contrast should be used in patients with suspected meningiomas of the optic nerve sheath or of the sphenoid wing, or those with possible compressive optic neuropathy due to thyroid orbitopathy. As discussed in the chapter on optic nerve tumors, this technique is much more sensitive than CT for detecting the tumor. MRI also is more sensitive in the detection of soft tissue orbital apical tumors or those that invade the CNS. In some atypical vascular orbital lesions, MRI and the ability to obtain MR angiography have been diagnostically helpful. In other cases, such as an orbital varix (see chapter on intraconal tumors), spiral CT, performed with and without Valsalva maneuver, established the diagnosis when it was not clear on MRI. As is the case with CT, the quality of equipment (field strength, surface coils, ability to perform thin sections) and personnel are integral to the quality of the scan produced.49

In a cost-conscious era, as a general rule, a goodquality, thin-section CT is the imaging test of choice in a patient with orbital disease that does not produce decreased vision. While exceptions occur, with the caveats listed above, in most cases MRI has not increased the accuracy of our diagnosis or changed the management of orbital tumors. We have evaluated many orbital tumor patients who were referred with MRI and CT scans; the results have usually been concordant. In patients with benign and malignant lacrimal gland masses of various etiologies, we did not observe any improvement in diagnostic accuracy with MRI, compared with CT.34 In addition to being less expensive, CT is probably still superior to MRI for orbital diagnosis in two areas: (1) CT is the imaging technique of choice in patients with

orbital bone involvement; and (2) in young children, a spiral CT can be obtained without anesthesia, and if the data are adequate, CT presents a safer method of evaluation than MRI on a sleeping child. In cases in which we are going to use an endoscopic approach to an apical tumor through the nasal sinuses, the direct visualization of bone on CT (as contrast with the signal void noted on MRI) allows us to plan surgery more precisely.

MRI does have a potential additional unique quality in that an image may be obtained directly in any plane, simply by altering the orientation of the gradients. This means that images in any plane will have identical spatial and contrast detail. Surface coil techniques have facilitated a significant improvement in the spatial detail that appears to be superior to that of CT.50

A number of publications discuss basic principles of CT, MRI, and US.18,20,22,25,36,43,46 The reader is referred to those reports for more technical information on these imaging techniques. In the chapters on orbital tumors, CT and MR images have been incorporated to show our use of these modalities in the management of orbital lesions.

We prefer, for the most part, multiplanar MRI scans, if they are available from machines utilizing high-magnetic-field, thin-section, and surface coils. Multiplanar scans or CT scans with computer reconstruction are crucial if that modality is used. Figure 15–4 shows the axial MRI scan of a patient referred with bilateral apical tumors; this patient had compressive thyroid neuropathy due to enlarged extraocular muscles, especially the inferior recti. The diagnosis would have been obvious on CT with computer re-formation or on multiplanar MRI scans but was not apparent to the referring ophthalmologist or the radiologist on the basis of only an axial MRI scan.

FINE-NEEDLE BIOPSY

The concept of needle biopsy is not new. This technique was first attempted in the 1880s and had transient use in major American cancer centers in the 1920s and 1930s.51–53 Early needle aspiration biopsies were performed with large needles, generally between 15and 18-gauge, and some tumor dissemination did occur.54

In the 1950s, a number of European centers adopted the use of a smaller-gauge FNAB technique with excellent results.55 Using a 22-gauge or smaller needle, there have been very few documented cases of local or distant tumor dissemination.56–60

Much data support the concept that FNAB is a safe procedure. Berg and Robbins retrospectively analyzed a matched group of breast carcinoma patients with 15year actuarial survival, who either had or did not have FNAB. There was no difference in the incidence of local disease, metastases, or tumor-related mortality.61 Similarly, a number of investigators have used highly malignant animal models to study the effects of FNAB on tumor dissemination. Most investigators have demonstrated a small number of tumor cells in the needle track, but those cells are too small in number to form a viable colony and develop a tumor nodule.62,63 Eriksson and co-workers used five different types of highly malignant animal tumors and were unable to establish a difference in tumor metastases or tumor-related mortality among those animals that had excisional biopsy, incisional biopsy, or FNAB of a limb tumor.62

Lalli and colleagues studied 157 salivary gland pleomorphic adenomas that had received FNAB and found no evidence of tumor dissemination.58 The safety in over 500,000 nonophthalmic FNABs has been demonstrated. Less than 10 reports of local spread have been published, and almost all were with a 20-gauge or larger needle.56,59,60 It is highly doubtful that orbital or ocular tumor dissemination would be different from that of systemic tumors.

We recently reported our results with 731 patients with uveal melanoma who did or did not have an FNAB. With Cox multivariate analysis, there is no adverse affect on survival in patients who received FNAB.64

The detection of a lesion and the accuracy of diagnosis with FNAB are highly dependent on the correct placement of the needle and, equally importantly, experience in cytopathologic interpretation.53 Some series have noted improvement in accuracy from 73 to 92 percent with increased experience.65 In a series from Toronto of 259 nonophthalmic FNABs, detection of malignancy increased from 83 to 93 percent in a 10-year interval.66 In addition to expertise in correctly placing the needle into a

Figure 15–4. Axial MR image in a patient referred with an apical tumor. CT with re-formation would have demonstrated enlarged apical muscles and compressive thyroid optic neuropathy as the correct diagnosis.

lesion, and cytopathologic interpretation, technical factors in handling the specimen, and slide preparation can have a major impact on the accuracy of diagnosis. In our experience, the quality of cytologic preparation can markedly influence the sensitivity of the technique. Figures 15–5A and B show samples from the same eye prepared in different laboratories. The difference in cytologic detail graphically illustrates this point.

Cytologic interpretation is different from analysis of standard histologic materials. We have examined three cases of intraocular lymphoma in which a definitive diagnosis could be made on the cytologic material; all had been misdiagnosed at other institutions because inexperienced people had attempted to render a cytopathologic diagnosis (unpublished data).

The use of FNAB of orbital lesions was pioneered in Europe in the late 1970s.66,67 In the United States, Kennerdell and associates have been responsible for popularizing this technique.68–70 In their experience with 156 cases, a correct diagnosis was possible in 80 percent.70 They have stressed that fibrous tumors, lymphoid lesions, and apical masses are often difficult to diagnose correctly, but especially in the latter group, this technique can be very helpful.70

294 TUMORS OF THE EYE AND OCULAR ADNEXA

A

is in the middle to outer one-third of a tumor. In this area, necrosis should be minimal. It should be noted that if the needle position is not confirmed by CT, it is impossible to determine whether the lesion has been sampled, and a negative biopsy finding will not be meaningful or may be deceptive. Once the needle position is confirmed by CT, a syringe or suction apparatus is attached to the needle. Suction is applied with a slight anteroposterior movement (1 to 2 mm) of the needle. A suction-cutting technique is used because aspiration is sometimes not sufficient to obtain biopsy material from solid tumors. We attempt to cut some tissue with the edge of the needle and aspirate it into the needle, but not the syringe. Greater anteroposterior movement (up to 5 mm) is most effective for obtaining a good sample in large tumors. In small orbital lesions, tumors near the orbital apex, those contiguous with the CNS with orbital roof defects, or intraocular masses, we limit the anteroposterior movement to 1 to 2 mm. Suction is released after three or four gentle movements of the needle, and the needle is withdrawn from the orbit. The needle is disconnected, air is drawn into the syringe and then used to expel the material from

B

Figure 15–5. A, Vitreous biopsy prepared in one laboratory; diagnosis is not clear, and cellular detail is not optimal. B, Second vitreous biopsy obtained 72 hours later from the same eye, but prepared in another laboratory. This shows better cellular detail due to superior preparation technique.

We have used orbital FNAB in approximately 300 cases with excellent results. We have had no significant morbidity with this technique in properly selected cases. While an easily palpable lesion does not require CT-directed biopsy, lesions in the intraconal or posterior orbital areas should be biopsied with CT confirmation. As Czerniak and co-workers have demonstrated, marked improvement in diagnostic accuracy was noted when CT was used to confirm needle placement, in contrast to those performed before the amalgamation of these two techniques.71

We routinely perform orbital FNAB using a 25-gauge needle. The needle is placed into the orbital lesion and a single CT scan is performed to localize its tip (Figure 15–6). Optimal placement of a needle

Figure 15–6. CT scan demonstrating needle tip as evidenced by the dark shadow that shows the tip in a posterior orbital tumor.

the tip of the needle onto slides for cytologic evaluation. In a large series of intraocular cases, we have routinely obtained 0.5 to 2.0 × 106 cells from a 25gauge FNAB (Figure 15–7). In some centers, the use of just a needle with capillary action rather than aspiration has been shown to be adequate to obtain an excellent specimen.72

One of the major requirements for CT-guided FNAB is the presence of an expert cytopathologist. We routinely perform all our orbital needle biopsies in the neuroradiology CT scanner with a cytopathologist in attendance. The availability of a cytopathologist in the neuroradiology suite allows us to immediately rebiopsy the lesion if the initial biopsy was negative, without removing the patient from the scanner.

As Kennerdell, Czerniak, and others have noted, the major indication for FNAB is in patients who require cytologic diagnosis of an orbital mass or lesion, but do not require surgical therapy. As an example, Figure 15–8 demonstrates the axial CT pattern in an older patient with a diffuse orbital mass. A metastasis to the orbit was suspected, even though the patient had no history, radiologic evidence, or laboratory findings of a primary malignancy. Aspiration cytology demonstrated an adenocarcinoma, and this patient was treated with irradiation. Figure 15–9 demonstrates the CT scan of a probable sphenoid ridge meningioma; diagnosis was confirmed with FNAB. Other workers have similarly duplicated these results.73

Figure 15–8. Axial orbital CT demonstrating diffuse orbital mass consistent with but not diagnostic of a metastatic tumor.

We do not use FNAB in lesions that are going to be watched regardless of the outcome or in those in which orbitotomy is going to be performed regardless of the aspiration cytology results. In one orbital FNAB series, a very low incidence of correct diagnoses was obtained, probably because in many cases, the indications for FNAB were inappropriate.74,75 In several series with small numbers of cases, there is approximately an 80 percent diagnostic accuracy.76,77

We have not observed significant morbidity due to intraocular or orbital FNAB. Others have noted similar findings.78–80 However, the possibility of complications, including death from FNAB, has

Figure 15–7. Overlay of 22-, 23-, and 25-gauge needles on fineneedle aspirate. An average of 106 cells are obtained. (Photo courtesy of T. Miller, MD, San Francisco, CA.)

Figure 15–9. Needle positioned just anterior to probable sphenoid ridge meningioma. Biopsy confirming meningioma.

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been demonstrated in other sites, and in inexperienced hands, possible damage to the eye and brain or death could result.75,76 We have particularly avoided the use of orbital endoscopy, since these instruments have more potential to cause damage and possible tumor spread.81 Using an endoscope in the combined orbital sinus surgery, it is obvious, with current technology, that the orbital fat makes the use of this instrument intraorbitally cumbersome and significantly less valuable.

Over 1,000 orbital FNABs have been reported in meetings or in print.81–94 We have had two worrisome hemorrhages, but in neither case was vision lost nor was an invasive maneuver required after FNAB. In most cases, needle biopsies have obviated the need for an open surgical procedure. In some cases, FNAB does not adequately sample a tumor due to small size, poor technique, or a fibrous matrix. In some settings, a clear case of false-negative diagnosis occurs. FNAB accuracy is also dependent on the experience in the unit and the type of tumor studied. In one analysis, only 22 of 36 malignancies were diagnosed using this technique.95 In the chapter on anterior uveal tumors, a patient with orbital and CNS extension from an untreated malignant medulloepithelioma is shown (see Figure 9–44). In that case, it appears clinically that the tumor had destroyed the eye; an orbital FNAB showed a pattern most consistent with a lymphoid lesion. Flow cytometry was not consistent with that diagnosis. Open biopsy of orbital tissue was also nondiagnostic, but when the eye was decalcified, the true nature of the lesion and the secondary nature of the lymphoid component were appreciated. Similarly, in rare cases, we have only obtained lymphoid reactivity surrounding a neoplastic process.

The appropriate use of the above diagnostic modalities, with examples, is discussed in the subsequent chapters on orbital tumors.

Summary

It is difficult to provide a short, lucid overview of the diagnosis and management of adult orbital tumefactions discussed in the following chapters. Adult proptosis usually has an insidious onset, chronic course, and does not require rapid therapeutic intervention. The rapid onset of proptosis is more com-

mon with infectious processes or hemorrhage; occasionally, hemorrhage is associated with an orbital neoplasm, most commonly a metastasis.

Thyroid orbitopathy is the most common cause of either unilateral or bilateral proptosis in adults.3 The extraocular muscles are the major site of orbital involvement in thyroid eye disease.96

The discussion of adult orbital tumors has been arbitrarily divided on the basis of the orbital areas they most frequently involve. Usually, an optimal differential diagnosis of an orbital tumor cannot be established from clinical evaluation; it can be proposed on the basis of the orbital area involved, as revealed by either CT or MRI studies. The discussion of adult orbital tumors is divided into lesions in the extraconal area (lacrimal fossa, extraocular muscles, and other extraconal tumors), those lesions involving the contiguous sinuses and orbital walls, and tumefactions of the intraconal space and optic nerve neoplasms.

As in other sections of this book, very rare lesions that can only be diagnosed after complete histologic evaluation have not been discussed. A discussion of most of these entities can be found in other books.96,97

Both positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) have been described by us and others in orbital processes, but they are currently research tools.98–100 We have recently reported a case in which PET data helped us establish the diagnosis of a recurrent fibrous histiocytoma. It is doubtful that this technology will be useful in most orbital conditions. Some patients who are being followed up after nonsurgical treatment may benefit by this PET technology, especially as cameras allow us to accurately image lesions < 7 mm in maximum diameter.99 Similarly, while color Doppler imaging can demonstrate orbital vessels, it is uncertain whether this will have any application in the diagnosis or management of eye tumors.101,102 In thyroid orbitopathy, MRS data have the intriguing possibility to more accurately delineate when this orbital process changes from a predominantly inflammatory to a fibrotic one.103 This type of MRS data might be helpful to monitor chemotherapy or radiation of some orbital processes.100 While three-dimensional radiologic studies have been used in plastic surgery, their efficacy in tumor diagnosis remains uncertain.98

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