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Figure 1.
Patient 2. A, A slitlamp photograph of perilimbal squamous conjunctival neoplasia. B and C, The tumor's surface(arrows) is highly reflective, and the stroma is hypoechoic (20-MHz transverse[B] and longitudinal [C] sections).

Patient 2. A, A slitlamp photograph of perilimbal squamous conjunctival neoplasia. B and C, The tumor's surface(arrows) is highly reflective, and the stroma is hypoechoic (20-MHz transverse[B] and longitudinal [C] sections).

Figure 2.
Patient 4. A slitlamp photograph(A) demonstrated a perilimbal tumor with evidence of neovascularization of the deep and superficial cornea. A 20-MHz high-frequency B-scan ultrasonographic image (B) demonstrates blunting of the anterior chamber angle (arrow). This finding is correlated with histopathologic features demonstrating anterior chamber angle (C) and uveal (D) invasion (arrowheads) (hematoxylin-eosin, original magnification ×40).

Patient 4. A slitlamp photograph(A) demonstrated a perilimbal tumor with evidence of neovascularization of the deep and superficial cornea. A 20-MHz high-frequency B-scan ultrasonographic image (B) demonstrates blunting of the anterior chamber angle (arrow). This finding is correlated with histopathologic features demonstrating anterior chamber angle (C) and uveal (D) invasion (arrowheads) (hematoxylin-eosin, original magnification ×40).

Figure 3.
Patient 6. A, A slitlamp photograph shows how the tumor had grown to cover a functioning filtering bleb. B, No intraocular invasion was seen on examination of the filtering bleb (arrow) on the 20-MHz high-frequency B-scan ultrasonographic image.

Patient 6. A, A slitlamp photograph shows how the tumor had grown to cover a functioning filtering bleb. B, No intraocular invasion was seen on examination of the filtering bleb (arrow) on the 20-MHz high-frequency B-scan ultrasonographic image.

Figure 4.
Patient 7. A, A slitlamp photograph shows a multifocal squamous conjunctival tumor with massive extension onto the cornea. In this patient, the tumor did not allow for slitlamp evaluation of corneal extension. B, A composite figure of 50-MHz high-frequency ultrasonographic images demonstrates an intact cornea and sclera, with no evidence of intraocular extension.

Patient 7. A, A slitlamp photograph shows a multifocal squamous conjunctival tumor with massive extension onto the cornea. In this patient, the tumor did not allow for slitlamp evaluation of corneal extension. B, A composite figure of 50-MHz high-frequency ultrasonographic images demonstrates an intact cornea and sclera, with no evidence of intraocular extension.

Figure 5.
Patient 10. Transverse (A) and longitudinal (B) sections of a 50-MHz high-frequency B-scan ultrasonographic image show presumed intrascleral extension of squamous carcinoma as replacement of the normally hyperechoic sclera by hypoechoic tumor tissue (white arrows). There is also more normal-appearing sclera (black arrow).

Patient 10. Transverse (A) and longitudinal (B) sections of a 50-MHz high-frequency B-scan ultrasonographic image show presumed intrascleral extension of squamous carcinoma as replacement of the normally hyperechoic sclera by hypoechoic tumor tissue (white arrows). There is also more normal-appearing sclera (black arrow).

Clinical and Ultrasonographic Characteristics*
Clinical and Ultrasonographic Characteristics*
1.
Tunc  MChar  DHCrawford  BMiller  T Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases. Br J Ophthalmol. 1999;8398- 103Article
2.
Peksayar  GSoyturk  MKDemiryont  M Long-term results of cryotherapy on malignant epithelial tumors of the conjunctiva. Am J Ophthalmol. 1989;107337- 340
3.
Wilson  MWCzechonska  GFinger  PTRausen  AHooper  MEHaik  BG Chemotherapy for eye cancer. Surv Ophthalmol. 2001;45416- 444Article
4.
Pavlin  CJFoster  FS Conjunctival and adnexal disease. In:Pavlin  CJFoster  FSeds.Ultrasound Biomicroscopy of the Eye. New York Springer-Verlag NY Inc1994;196- 208
5.
Katz  NRFinger  PTMcCormick  SA  et al.  Ultrasound biomicroscopy in the management of malignant melanoma of the iris. Arch Ophthalmol. 1995;1131462- 1463Article
6.
Finger  PTMcCormick  SALombardo  JTello  CRitch  R Epithelial inclusion cyst of the iris. Arch Ophthalmol. 1995;113777- 780Article
7.
Reminick  LRFinger  PTRitch  RWeiss  SIshikawa  H Ultrasound biomicroscopy in the diagnosis and management of anterior segment tumors. J Am Optom Assoc. 1998;69575- 581
8.
Marigo  FAFinger  PTMcCormick  SA  et al.  Iris and ciliary body melanomas: ultrasound biomicroscopy with histopathologic correlation. Arch Ophthalmol. 2000;1181515- 1521Article
9.
Marigo  FAEsaki  KFinger  PT  et al.  Differential diagnosis of anterior segment cysts by ultrasound biomicroscopy. Ophthalmology. 1999;1062131- 2135Article
10.
Byrne  SFGreen  RL Examining techniques for the eye. In:Greene  RByrne  SFeds.Ultrasound of the Eye and Orbit. 2 Philadelphia, Pa Mosby–Year Book Inc2002;15- 44
11.
Kearsley  JHFitchew  RSTaylor  RG Adjunctive radiotherapy with strontium-90 in the treatment of conjunctival squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 1988;14435- 443Article
12.
Zehetmayer  MMenapace  RKulnig  W Combined local excision and brachytherapy with ruthenium-106 in the treatment of epibulbar malignancies. Ophthalmologica. 1993;207133- 139Article
13.
Mahmood  MAAl-Rajhi  ARiley  FKarcioglu  ZA Sclerokeratitis: an unusual presentation of squamous cell carcinoma of the conjunctiva. Ophthalmology. 2001;108553- 558Article
14.
Wexler  SAWallow  IHL Squamous cell carcinoma of the conjunctiva presenting with intraocular extension. Arch Ophthalmol. 1985;1031175- 1177Article
15.
Char  DHKundert  GBove  RCrawford  JB 20 MHz high frequency ultrasound assessment of scleral and intraocular conjunctival squamous cell carcinoma. Br J Ophthalmol. 2002;86632- 635Article
16.
Tabbara  KFKersten  RDaouk  NBlodi  FC Metastatic squamous cell carcinoma of the conjunctiva. Ophthalmology. 1988;95318- 321Article
Clinical Sciences
February 2003

High-Frequency Ultrasonographic Evaluation of Conjunctival Intraepithelial Neoplasia and Squamous Cell Carcinoma

Author Affiliations

From The New York Eye and Ear Infirmary (Drs Finger, Tran, Abramson, Della Rocca, and Ritch), The New York Eye Cancer Center (Drs Finger and Chin), and the Departments of Ophthalmology, New York University School of Medicine(Dr Finger) and Cornell University Medical College (Dr Abramson), New York; the Departments of Ophthalmology, New York Medical College, Valhalla (Drs Tran, Della Rocca, and Ritch), and the University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark (Dr Turbin); and North Shore Health System, Manhasset, NY (Dr Perry).

Arch Ophthalmol. 2003;121(2):168-172. doi:10.1001/archopht.121.2.168
Abstract

Objective  To evaluate the high-frequency B-scan ultrasonographic characteristics of squamous conjunctival neoplasia (conjunctival intraepithelial neoplasia and squamous cell carcinoma).

Methods  Each of 11 patients was examined with 20- and/or 50-MHz ultrasonography in a retrospective consecutive case series.

Main Outcome Measures  Ultrasonographic findings with clinical and histopathologic correlations.

Results  Eleven eyes of 11 patients (8 men) were affected. Disease involved the right eye in 6 (55%) of the patients and the left eye in 5 (45%) of the patients; it was multifocal in 5 (45%) of the eyes. All tumors extended to, or primarily involved, the limbal conjunctiva. One patient developed superficial spread overlying a functioning partial-thickness filtering bleb, 1 developed intraocular extension, 1 developed scleral invasion, and 3 developed orbital involvement before treatment. Results of ultrasonographic examinations showed that the superficial aspect of the smaller limbal tumors appeared as fusiform thickening of the conjunctiva. In all patients, the tumor surface was highly reflective in contrast to the characteristically low reflectivity seen within the tumor stroma. Intraocular tumor extension was variably reflective, but evidenced by blunting of the anterior chamber angle and thickening of the uvea. Orbital extension was viewed as low reflective tumor extension into the relatively hyperechoic orbital tissues.

Conclusions  High-frequency ultrasonography may be used to assess the extent of squamous conjunctival neoplasia. While the 50-MHz system offered better resolution, 20-MHz ultrasonography allowed for a wider and deeper field of view. High-frequency ultrasonography was useful in determining tumor thickness, shape, and internal reflectivity, and especially in revealing tumor extension into the sclera, eye, and orbit.

SQUAMOUS CONJUNCTIVAL neoplasia (SCN) can be confined to the conjunctival epithelium (conjunctival intraepithelial neoplasia) or termed squamous cell carcinoma if it invades the conjunctival substantia propia, the sclera, the eye, or the orbit.1

The most common conjunctival malignancy in the United States, SCN has been causally related to UV-B radiation and human papillomaviruses 16 and 18.1 Most SCN lesions affect the bulbar conjunctiva at the corneal-scleral limbus, are well demarcated, and can be surgically removed. Adjuvant cryotherapy is commonly used to treat the deep and peripheral margins.2 Many diffuse or multifocal tumors have been controlled with topical chemotherapy, which has recently become widely used.3 Before treatment, the extent of most SCN lesions is defined by slitlamp biomicroscopy and documented by photography.

The current method to assess whether the tumor invades the eye wall is to use a probe (eg, a cotton-tipped applicator) to induce movement of the tumor. A freely mobile tumor is less likely to have invaded subjacent tissues. This type of assessment is crude, so posterior margins are typically revealed either during surgery or by histopathologic examination.

The use of high-frequency ultrasonography to examine conjunctival tumors was originally described by Pavlin and Foster.4 The present study reports the use of high-frequency ultrasonography (20 and 50 MHz) to examine patients with conjunctival intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva. We describe the high-frequency ultrasonographic characteristics of SCN and high-frequency ultrasonography's ability to uncover local invasion.

METHODS

Eleven patients were examined with high-frequency ultrasonography for SCN during the consultative examination. No specific consent was needed in that there were no known risks and there were proved potential benefits to ultrasonographic imaging.59

The 20-MHz images were obtained using a B-scan probe (Innovative Imaging Inc, Sacramento, Calif) covered with a cap (Tono-Pen) filled with water. Images were acquired, seen on the ultrasound machine (Innovative Imaging Inc), and captured on thermographic paper and in electronic formats. Longitudinal (anterior-posterior) and transverse images were acquired.

The 50-MHz images were obtained using an ultrasound biomicroscope (Paradigm Medical Industries, Salt Lake City, Utah). Photographs were taken and recorded on thermographic paper and in electronic formats. These images had 50-µm resolution.

A transverse scan is acquired when the back-and-forth movement of the transducer occurs parallel (tangential) to the limbus. Depending on how far anterior the probe sweeps, this movement can produce a cross-sectional image of the cornea and iris, the sclera and ciliary body, or the sclera and anterior choroid. For longitudinal scanning, the probe movement is rotated 90° from the position of the transverse scan. The back-and-forth movement can be seen as perpendicular to the limbus. High-frequency longitudinal B-scan cuts are oriented much like the spokes on a wheel with the pupil at its center.10 Longitudinal and transverse B-scan images were acquired in this study.

RESULTS

Eleven patients were examined and their results were reviewed by one of us (P.T.F.) between 1999 and 2002. Eight (73%) of the patients were men; 6 tumors (55%) involved the right eye, and 5 (45%) were multifocal (Table 1).

GENERAL ULTRASONOGRAPHIC CHARACTERISTICS

The tumor surface was hyperechoic in all patients (at 20 and 50 MHz). This finding was likely due to the abrupt change in acoustic impedance between the water and the solid tumor surface. In contrast, the tumor stroma was generally hypoechoic. As demonstrated by patient 2, this finding suggests that SCN (conjunctival intraepithelial neoplasia and squamous cell carcinoma) tends to form few intrastromal echogenic interfaces. The perilimbal aspect of the tumor typically appeared as fusiform thickening (Figure 1).

SPECIFIC ULTRASONOGRAPHIC FINDINGS
Intraocular Tumor Extension

Slitlamp findings consistent with intraocular tumor extension include neovascularization of the cornea and iris (Figure 2A). High-frequency ultrasonography revealed 2 findings suggestive of ocular penetration (blunting of the anterior chamber angle and uveal thickening[patient 4; Figure 2B]). Simialarly, these findings were also seen on histopathologic evaluation (Figure 2C and D).

In another patient (patient 6), the tumor covered a functioning filtering bleb (Figure 3). In this patient, although the conjunctiva was covered by the tumor, there was no evidence of intraocular invasion (by clinical examination and ultrasonography) before and during surgery (visual inspection).

When the Corneal Surface Is Obscured by a Tumor

A multifocal tumor (in patient 7) exhibited massive extension of 2-mm-thick SCN onto the cornea (Figure 4A). High-frequency ultrasonographic imaging was used as an adjunctive examination to suggest there was no evidence of intraocular extension. Although no confirmatory histopathologic analysis was (at first) performed, the combination of clinical and ultrasonographic findings strongly argued against intraocular invasion(Figure 4B). These findings allowed for chemoreduction (with topical mitomycin), followed by resection with adjuvant cryotherapy. No evidence of intraocular extension was observed at excision.

Scleral Invasion

As in patient 10, high-frequency B-scan ultrasonography can reveal diminished reflectivity within the sclera beneath the tumor, consistent with intrascleral tumor invasion (Figure 5). This patient refused treatment and was unavailable for follow-up.

Orbital Extension

Three patients had orbital extension. In these patients, the relatively low reflective tumor could be differentiated from the relatively amorphous, but more hyperechoic, orbital tissues. High-frequency imaging is limited by the maximum penetration of 20- and 50-MHz ultrasonography. Therefore, it was not always possible to define the posterior margins of these tumors.

COMMENT

High-frequency ultrasonographic imaging (20 and 50 MHz) allowed preoperative imaging of conjunctival tumors. This technology improved our ability to assess ocular invasion before surgery, which proved valuable in the care of patients with SCN. For example, in patient 4, massive intraocular invasion prompted exenteration of the orbit. In patient 6, no evidence of intraocular invasion was present despite a tumor growing over an active sclerotomy site. This patient was treated with excision and cryotherapy. In patient 7, no evidence of scleral or corneal invasion was seen on the ultrasonographic scan, allowing chemoreduction with mitomycin, followed by excision and cryotherapy of the unifocal tumor residue. When documented, the absence of intraocular invasion allowed for the use of less invasive therapies.

Although not performed in this study, high-frequency ultrasonography could also allow for the measurement of tumor thickness. This method could be used in an assessment of tumor response to and treatment planning for conservative treatments (eg, topical chemotherapy and brachytherapy).3,11,12

Primary or recurrent SCN may masquerade as blepharoconjunctivitis, uveitis, or orbital disease.13,14 Delays in diagnosis put patients at risk for intraocular extension and metastasis.1416 High-frequency ultrasonography's ability to monitor the sclera, the anterior chamber, and the uvea offers the potential to reduce the number of patients subject to delays in diagnosis.

In this study, we have provided cross-sectional views of the tumor surface, internal reflectivity, borders, and posterior margins of SCN. The tumor stroma was hypoechoic compared with the sclera, iris, and orbital tissues. This finding helps differentiate tumor from healthy tissues. Ultrasonographic evidence of blunting of the anterior chamber angle was correlated to its histopathologic appearance. High-frequency ultrasonographic imaging was clearly helpful for evaluating superficial and invasive SCN.

Corresponding author and reprints: Paul T. Finger, MD, The New York Eye Cancer Center, 115 E 61st St, New York, NY 10021 (e-mail: pfinger@eyecancer.com).

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Article Information

Submitted for publication June 11, 2002; final revision received October 9, 2002; accepted October 15, 2002.

This study was supported by The Eye Care Foundation, Inc, the Donald Engel Research Fund of the Glaucoma Research Institute, The New York Eye and Ear Infirmary Research Fund, and Research to Prevent Blindness, Inc, New York; and the Fund for the New Jersey Blind, the Lions Eye Research Foundation of New Jersey, and the Eye Institute of New Jersey, Newark.

We thank Janet Roen, MD, James Milite, MD, David Ritterband, MD, Jeffrey M. Liebmann, MD, and Steven A. McCormick, MD, for their contributions.

References
1.
Tunc  MChar  DHCrawford  BMiller  T Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases. Br J Ophthalmol. 1999;8398- 103Article
2.
Peksayar  GSoyturk  MKDemiryont  M Long-term results of cryotherapy on malignant epithelial tumors of the conjunctiva. Am J Ophthalmol. 1989;107337- 340
3.
Wilson  MWCzechonska  GFinger  PTRausen  AHooper  MEHaik  BG Chemotherapy for eye cancer. Surv Ophthalmol. 2001;45416- 444Article
4.
Pavlin  CJFoster  FS Conjunctival and adnexal disease. In:Pavlin  CJFoster  FSeds.Ultrasound Biomicroscopy of the Eye. New York Springer-Verlag NY Inc1994;196- 208
5.
Katz  NRFinger  PTMcCormick  SA  et al.  Ultrasound biomicroscopy in the management of malignant melanoma of the iris. Arch Ophthalmol. 1995;1131462- 1463Article
6.
Finger  PTMcCormick  SALombardo  JTello  CRitch  R Epithelial inclusion cyst of the iris. Arch Ophthalmol. 1995;113777- 780Article
7.
Reminick  LRFinger  PTRitch  RWeiss  SIshikawa  H Ultrasound biomicroscopy in the diagnosis and management of anterior segment tumors. J Am Optom Assoc. 1998;69575- 581
8.
Marigo  FAFinger  PTMcCormick  SA  et al.  Iris and ciliary body melanomas: ultrasound biomicroscopy with histopathologic correlation. Arch Ophthalmol. 2000;1181515- 1521Article
9.
Marigo  FAEsaki  KFinger  PT  et al.  Differential diagnosis of anterior segment cysts by ultrasound biomicroscopy. Ophthalmology. 1999;1062131- 2135Article
10.
Byrne  SFGreen  RL Examining techniques for the eye. In:Greene  RByrne  SFeds.Ultrasound of the Eye and Orbit. 2 Philadelphia, Pa Mosby–Year Book Inc2002;15- 44
11.
Kearsley  JHFitchew  RSTaylor  RG Adjunctive radiotherapy with strontium-90 in the treatment of conjunctival squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 1988;14435- 443Article
12.
Zehetmayer  MMenapace  RKulnig  W Combined local excision and brachytherapy with ruthenium-106 in the treatment of epibulbar malignancies. Ophthalmologica. 1993;207133- 139Article
13.
Mahmood  MAAl-Rajhi  ARiley  FKarcioglu  ZA Sclerokeratitis: an unusual presentation of squamous cell carcinoma of the conjunctiva. Ophthalmology. 2001;108553- 558Article
14.
Wexler  SAWallow  IHL Squamous cell carcinoma of the conjunctiva presenting with intraocular extension. Arch Ophthalmol. 1985;1031175- 1177Article
15.
Char  DHKundert  GBove  RCrawford  JB 20 MHz high frequency ultrasound assessment of scleral and intraocular conjunctival squamous cell carcinoma. Br J Ophthalmol. 2002;86632- 635Article
16.
Tabbara  KFKersten  RDaouk  NBlodi  FC Metastatic squamous cell carcinoma of the conjunctiva. Ophthalmology. 1988;95318- 321Article
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