Lidlift Kenneth D. Steinsapir, M.D.
Cosmetic, Facial & Eye Plastic Surgery

Dr. Steinsapir, M.D

Ultrasound Backscatter Microscopy in the Management of Eyelid Cancer

Preoperative assessment of basal cell carcinoma involving the eyelid is generally limited to a routine orbital examination and a biopsy of the lesion to confirm its histopathology prior to definitive excision and reconstruction. Where orbital involvement is suspected, orbital imaging with computerized tomography or magnetic resonance imaging may be performed. However, the most pressing issue in dealing with basal cell carcinoma of the eyelid is clinically occult microscopic spread. This determines the extent of tumor excision and the nature of the reconstructive surgery. The routine use of wide excision with or without frozen section control rather than curettage, cryotherapy, or radiation therapy has reduced the risk of recurrence. Mohs’ cancer surgery has made it possible to precisely remove the skin cancer while at the same time preserving as much of the normal tissue as possible. The surgeon must anticipate the extent of excision and the nature of the reconstruction to help prepare the patient. This often means discussing a broad range of reconstructive possibilities. Rather than comforting the patient, this discussion can have the unintended effect of creating alarm. It would be ideal to have a noninvasive, relatively inexpensive means to map the true microscopic extent of the tumor. This information would permit relatively precise preoperative communication and help the surgeon to anticipate the likely reconstruction.

We investigated the use of ultrasound backscatter microscopy to assess the extent of microscopic tumor involvement in eyelid basal cell carcinomas. Ultrasound backscatter microscopy was originally developed to image skin. However, ophthalmologists are familiar with this instrument for imaging the anterior segment. The term ultrasound sound backscatter microscopy is used to distinguish this ultrasound method from lower frequency ultrasound B scan and a technique of examining glass mounted tissue sections with an ultrasound technique. This paper will discuss the basis of this technology and the findings of our current investigations.

Material and Methods

A commercial anterior segment ultrasound backscatter microscope (Humphrey Ultrasound Biomicroscope Model 840, Humphrey Instruments, San Leandro, CA) was used for this study (figure 1). This system was developed for imaging the anterior segment of the eye. It employs an ultrasound frequency of 50 MHz with a focal length of 5 mm. The instrument employs a standard pulse-echo technique to provide a real-time 2 dimensional image. The system can obtain two image sizes. One is 5 by 5 mm and another is a higher magnification mode measuring 2.5 by 2.5 mm. The transducer tip is scanned over the area of interest to create a two-dimensional image. The transducer is coupled to the skin by an acrylic cup filled with methylcellulose solution. This permits the transducer to standoff from the tissue allowing the piezo electric transducer to oscillate in space. Backscatter signals are picked up by the transducer and processed into standard video signals to create the two-dimensional tissue image. The system has an axial and lateral resolution of 50 microns. Images after amplification and processing are displayed on a monitor with a display resolution of 1024 X 480 pixels. A keyboard input permits complete annotation of the displayed images. Display functions include a caliper to accurately measure structures. Images can be displayed in a B-scan or A scan mode. Images on the screen can be saved to storage media or printed to create a hard copy for the medical record.

Figure 1.

Ultrasound backscatter microscopy was performed on the eyelid and cheek skin of two normal volunteers. Three consecutive patients with biopsy proven basal cell carcinoma were selected for this study. The patients were first identified with clinically suspicious lesions. In each case an initial diagnostic biopsy was performed with a 1.5 mm punch or a shave technique with a number 11 scalpel blade after infiltration of lidocaine 1% with epinephrine 1: 100,000. Once a diagnosis of basal cell carcinoma was confirmed, ultrasound backscatter microscopy was performed. Imaging was carried out in both the axial and sagittal planes. The lesions were excised with Mohs’ cancer surgery by a dermatologic surgeon. The first level of the Mohs’ excision was sectioned in a sagittal orientation. Photomicrographs were prepared from the histopathologic sections. Ultrasound backscatter microscopy images of the lesion were obtain in the 5 X 5 mm format and calibrated using the internal standard of the instrument.

Results

Controls: Two control subjects were studies to establish the normal ultrasound backscatter microscopy anatomy of the eyelid. Figure 2 demonstrates the ultrasound backscatter microscopy appearance of the lower eyelid. The acrylic cup used to couple the probe partially rest on the anesthetized cornea and partially on the lower eyelid. The epidermis is echogenically bright and the dermis is less echogenic. The orbicularis appears as another echogenically bright layer. The tarsus is not well imaged because the separation of the probe from the skin surface places the tarsus at the limit of what can be imaged by this system.

Figure 2. Ultrasound backscatter microscopy of a normal eyelid.

Case 1: The patient is a 77 year old who spends several hours a day playing tennis. He developed a nonhealing nodule on the right lower eyelid (figure 3). Clinically, the lesion demonstrated a raised pearly edge with loss of lashes. There were significant chronic inflammatory changes in the eyelid margin and clinically the lesion appeared to extend temporally beyond the confines of the nodular component of the lesion. In contrast, ultrasound backscatter microscopy suggested that the lesion was sharply limited in its temporal extent and extended beyond the nasal edge of the nodule (figure 4). The tumor appear echogenically weak compared to the initial reflection of the epidermis or adjacent orbicularis. On sagittal section the tumor appeared plaque like with no obvious evidence of invasion through the orbicularis. Based on the information obtained from the ultrasound backscatter microscopy study, the patient was advised that it was highly likely that most of his tarsus would be preserved but more of the nasal anterior lamella of the pretarsal eyelid would likely need to be removed. The sagittal section through the Mohs’ excision closely matches the shape of the area of weak echogenicity seen in the sagittal ultrasound backscatter microscopy of the eyelid (figure 5). Additionally, the excision spared the tarsus and extended medially, as predicted by the ultrasound backscatter microscopy (figure 6).

Figure 3.

Figure 4. Ultrasound backscatter microscopy of the lower eyelid showing the basal cell carcinoma.

Figure 5. Asterisk indicates basal cell carcinoma infiltrating the eyelid in the excised specimen.

Figure 6. Mohs’ excision.

Case 2: The patient was a 67 year old with a history of a nonhealing lesion involving the left lower eyelid (figure 7). The patient noted that the lesion had been present for at least one year. The lesion appeared to involve the lateral two thirds of the left lower eyelid. The most prominent aspect of the lesion appeared nodular with both medial and lateral extension. There was significant effacement of normal eyelid architecture and loss of eyelashes. A biopsy confirmed the clinical diagnosis of basal cell carcinoma. Given the extent of the lesion, the patient was advised that it was highly likely that a tarsoconjunctival graft from the upper eyelid would be a necessary component of the eyelid reconstruction. Ultrasound backscatter microscopy was performed. The nodular component of the lesion was cystic (figure 8). Imaging of the extent of the lesion did not alter the clinical impression of the extent of the lesion. The Mohs’ excision closely approximated the volume of lower eyelid that was clinically suspected of being involved by basal cell carcinoma (figure 9).

Figure 7. Lower eyelid margin largely replaced by infiltrating basal cell carcinoma.

Figure 8. Ultrasound backscatter microscopy demonstrating a cystic component in the lesion.

Figure 9. Left lower eyelid immediately following Mohs’ excision of the lesion.

Case 3: A 47-year old male with a significant history of sun exposure presented with a small depression in the central aspect of the left lower eyelid. The area was devoid of eyelashes (figure 10). A biopsy was positive for basal cell carcinoma. Ultrasound backscatter microscopy demonstrated that the lesion was limited in size with little or no spread beyond the clinically apparent area of abnormal skin (figure 11). Only a small Mohs’ cancer surgery excision was required to clear the eyelid of tumor (figure 12).

Figure 10. Notice the small notch along the left lower eyelid with loss of eyelashes. Biopsy of this site demonstrated basal cell carcinoma.

Figure 11. Ultrasound backscatter microscopy of the left lower eyelid. Area to the right of the blue line indicates the basal cell carcinoma.

Figure 12. Eyelid following Mohs’ excision.

Discussion

The instrument utilized for this study is a commercial ultrasound backscatter microscope operating at 50 MHz. This instrument was specifically adapted for studying the anterior structures of the eye. It has been used to image cilliary body and iris tumors, and elucidate angle closure glaucoma mechanisms. , This system has a lateral and axial resolution of 50 microns permitting the type of anatomic analysis that previously could only be obtain with histopathologic sections and optical microscopes. The ultrasound backscatter microscope permits the realization of in vivo microscopy for superficial anatomic structures. The anterior segment ultrasound backscatter microscopy was used in this study without any modification of the existing instrument. As such, it is readily available in many eye hospitals and centers.

The application of ultrasound backscatter microscopy to the skin is not novel. The first reported measurements of skin thickness made by ultrasound date from 1979. The methods have become more refined over the past 15 years. A higher frequency ultrasound backscatter microscope for skin imaging has been developed which operates in the 40-100 MHz range. This instrument has an axial resolution between 17 and 30 microns and lateral resolution between 33 and 94 microns and is able to image into subcutaneous tissues. Ultrasound imaging systems operating at 20 MHz have been used to image basal cell carcinoma of the skin. These lower frequency systems suffered from limited lateral and axial resolution. More recently a 40 MHz system was investigated with an axial resolution of 30 microns and a lateral resolution of 94 microns. The depth of 12 basal cells carcinomas measured by ultrasound backscatter microscopy and histopathology was highly correlated (P=0.0004, r=0.92). The conceptualized applications of ultrasound backscatter microscopy of the skin include evaluation of skin tumors, inflammatory skin conditions, and the response to topical therapy.

Eyelid basal cell carcinoma excision and reconstruction is a major concern of the ophthalmic plastic surgeon. The needs to completely excise the tumor and at the same time maximize the function of the reconstructed eyelid are conflicting goals. Preserving the functional integrity of the eyelid following complete cancer excision is a significant surgical challenge. This fact is not always appreciated by other disciplines. Mohs’ cancer surgery has become a preferred method for removing basal cell carcinoma of the eyelid or periocular region. This method satisfies the two needs of completely excising the lesion and at the same time conserving eyelid structure.

One of the important potential roles for ultrasound backscatter microscopy in the management of eyelid tumors is patient counseling and education. Presently, patients are counseled preoperatively that the extent of tumor excision and of subsequent reconstruction is uncertain. This can mean the difference between a reconstruction limited to just one eyelid or the need to use a tarsoconjunctival graft from the opposing eyelid. This difference has a tremendous impact on the patient because it means suturing closed the eyelid for several weeks when grafts are used from the opposing eyelid. For many patients, having one eye sutured closed translates into a nearly complete temporary disability. Patients in this situation are usually unable to drive or work. The potential need to sacrifice the proximal lacrimal system is another source of anxiety for patients. While the surgeon may be confident in the skills to reconstruct the tear outflow system, for the patient it means an uncertain number of reconstructive procedures and perhaps dependence on a glass Jones tube for tear drainage.

Consequently, the ability to predict with greater precision the likely extend of tumor excision and reconstruction has the potential to allay patient fears. In other cases, a lesion that is well defined by ultrasound backscatter microscopy may be deemed resectable by frozen section control or simple block excision avoiding the additional step of Mohs’ cancer surgery. In this pilot study we did not evaluate the usefulness of the technique in assessing basal cell carcinoma involvement in the proximal lacrimal system. However, the instrument has obvious promise in this regard. Finally, in the evolving healthcare environment, it is often necessary to obtain prior approval for any surgical procedures. The ultrasound backscatter microscopy promises to provide an additional means of documenting the likely extend of post cancer excision reconstruction prior to any surgery.

This study was performed with a commercially available anterior segment ultrasound backscatter microscopy. No modifications to this instrument were necessary. The probe of the scanner was coupled to the eyelid through an acrylic cup filled with methylcellulose solution. The diameter of the cup was 30 mm. It does not fit conveniently into the medial canthal region. Cups of smaller diameter are less practical because the probe oscillates and frequently strikes the edge of the smaller cup. Additional development is needed for a probe tip with less travel and coupling mechanisms that will permit more convenient study of the eyelids and medial canthal structures. Design of the scanners continues to progress. In the future higher frequency scanners with more sensitive piezoceramic transducers will result in improved resolution. This will translate into greater detail in resolving histopathologic abnormalities in the eyelid and periocular tissues. Software is being developed to combine sequential B-scans to create a three-dimensional map of the imaged structures. This should permit detailed analysis of eyelid tumors prior to their excision. The basal cell carcinomas presented in this paper were nodular. We did not examine the ability of ultrasound backscatter microscopy to resolve morpheaform basal cell carcinoma. This will be an important issue for future research. While ultrasound backscatter microscopy will not replace histopathologic control of surgical margins, it is a technology with the potential to improve our diagnostic accuracy and preoperative management of eyelid tumors.

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