http://informahealthcare.com/jdt ISSN: 0954-6634 (print), 1471-1753 (electronic) J Dermatolog Treat, 2014; 25(6): 516–518 ! 2014 Informa UK Ltd. DOI: 10.3109/09546634.2013.849793
CASE REPORT
Periocular photodynamic therapy for squamous intra-epidermal carcinoma Natasha Casie Chetty1, Bridget Hemmant 2, and Anne-Marie Skellett1 1
Department of Dermatology and 2Department of Ophthalmology, Norfolk and Norwich University Hospital, Norwich, UK
Abstract
Keywords
Objectives: To evaluate the response of Metvix photodynamic therapy (PDT) for the treatment of periocular Bowen’s disease. Methods: Four patients with biopsy-proven Bowen’ disease were treated with Metvix PDT between November 2010 and January 2012. A detailed description of the technique used is described. Results: All of the patients tolerated the PDT well. All had some clinical response to the treatment, although there was not complete, lasting resolution beyond one year in three out of the four cases. Conclusion: PDT can be a good treatment in its own right in selected cases of periocular Bowen’s disease.
Actinic keratosis, Bowen’s disease, pre-malignant
Topical photodynamic therapy (PDT), using a photosensitising agent, Metvix, is an effective treatment for Bowen’s disease and actinic keratosis (AK), with equivalence or superiority to other nonsurgical methods such as cryotherapy and topical 5-FU (1). Whilst Mohs micrographic surgery (MMS) is the treatment of choice for periocular basal cell carcinomas (2), when dealing with preinvasive disease at this sensitive anatomic location, it is reasonable to consider PDT as an alternative or additional option. Bowen’s disease is thought to transform into squamous cell carcinoma (SCC) in about 8% of cases, and 5% of these are reported to metastasize (3). In contrast, the risk of transformation of AK is considered to be approximately 0.24% per year (4). Complete response rates of PDT in Bowen’s disease have been cited as 93% at 3 months and 68% at 24 months (5). This risk of malignant transformation, taken together with the risk of recurrence in the periorbital region, highlights the need for careful choice of therapy taking into account patient preference, comorbidities and precise site of disease with attendant risks of damage to vital structures. We report four cases in which PDT was preferentially used in the periocular region. Our report highlights the benefits of a multidisciplinary approach and the utility of a full therapeutic armamentarium to the benefit of each patient’s individual needs.
PDT treatment protocol All patients underwent ophthalmology review prior to undertaking PDT. Local anaesthetic eye drops were applied prior to insertion of a contact lens to protect the ocular surface from Correspondence: Dr Natasha Casie Chetty, Department of Dermatology, Norfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK. Tel: 01603 286286. Fax: 01603 288601. E-mail: natasha. [email protected]
Received 5 August 2013 Revised 27 August 2013 Accepted 27 August 2013 Published online 11 November 2013
contact with the Metvix cream, the photosensitiser. The lesions were scraped in preparation to remove the surface scale. Metvix cream was applied for a period of 3 hours prior to the treatment. A dressing held the cream in situ and an eye protector was placed to cover the eye. After 3 hours, the Metvix was removed. More local anaesthetic was applied before Laserguard was applied over the contact lens. The Aktilite CL128 was used for 7 minutes and 24 seconds (37 J/cm2). Following treatment, the contact lens and Laserguard were removed and a dressing was placed over the eye as protection from ambient light. Each course of PDT consisted of two treatments, 1 week apart. A 5-mm rim of clinically normal skin was included in the irradiation field for well-defined lesions, with 10 mm if the lesion was poorly defined. This was difficult to achieve, however, if the lesion lay very close to the conjunctiva.
Results
20 14
Introduction
History
Four patients were treated between November 2010 and January 2012. Follow-up ranged from 18 months to 29 months. Patient 1
A 68-year-old man had a biopsy-proven bowenoid AK to the left medial canthus, measuring 20 mm in diameter. In January 2012, he underwent two sessions of PDT, 1 week apart. He had a crusting reaction to the left medial canthus which settled by day four following the second dose of PDT. Following PDT, he was left with an area of thickening over the left medial canthus, measuring 10 mm in diameter. A punch biopsy confirmed SCC in situ, but extended to the deep margin of the biopsy; hence, an invasive carcinoma could not be excluded. An MRI scan ruled out any intraorbital extension. He underwent MMS, with reconstruction the following day. Histology confirmed SCC in situ, with no evidence of invasive disease.
Periocular photodynamic therapy
DOI: 10.3109/09546634.2013.849793
Patient 2 An 85-year-old man was referred from ophthalmology with biopsy-proven Bowen’s disease to the left periocular area (Figure 1). His extensive ophthalmic history dates back to 1969 when he had a squamous cell carcinoma excised from the left upper lid, with a recurrence in 1976 which was repaired with a split skin graft. In 1982, a further SCC was excised from the left lower eyelid. In view of the extensive procedures, he was keen to explore nonsurgical options and underwent two treatments with PDT to the upper and lower eyelids in March 2011. He had a good response to the lesions to the upper eyelid, but had residual change to the lower eyelid (Figure 2) for which two further PDT sessions were administered in January 2012. He has had no further recurrence and remains under ophthalmology follow-up. Patient 3 A 95-year-old lady was referred with a patch of Bowen’s disease to the left lower eyelid. She underwent a course of PDT in August 2011, with complete resolution of the lesion. She remains under ophthalmology follow-up. Patient 4 An 84-year-old man was referred in 2010 with a biopsy-proven area of squamous carcinoma in situ over the right upper lid. In 1997, he had been treated with the carbon dioxide (CO2) laser for recurrent keratosis of the right upper lid, having previously had no response to cryotherapy. He had an initial good result, but in view of the difficulty of reconstruction following excision, further recurrences were again treated with CO2 laser ablation in 2000
Figure 1. Bowen’s disease left lateral upper eyelid and medial aspect lower eyelid on background of surgical scars.
Figure 2. One month post PDT, residual Bowen’s disease left lower lid with clinical clearance over upper lid.
517
and 2002. The present lesion was extensive, involving more than half of the upper lid and extending across towards the lateral canthal area (Figure 3). He underwent two sessions of PDT in November 2010, following which he had a very good, although not complete response (Figure 4), and remained under regular follow-up. In September 2011, he was noted to have a central area of crusting in the upper lid. A shave biopsy showed bowenoid AK with atypia extending onto the margins of the shave excision. The patient did not wish to have any further procedure and opted for observation as further management.
Discussion Our small case series demonstrates that PDT is a useful treatment option in carefully selected patients. Using our treatment protocol utilising topical anaesthetic, all of the patients tolerated the PDT well and no additional local anaesthetic injections were required. One patient developed a temporary conjunctivitis of the treated eye which settled with chloramphenicol ointment. No long-term complications of the treatment were noted. All our patients had biopsy-proven Bowen’s disease or bowenoid AK. All had some clinical response to the first cycle of treatment, although there was not complete, lasting resolution beyond 1 year, in three out of the four cases. Two of these patients proceeded to surgical procedures to the same site within 12 months of the PDT, whereas the other responded to a further course of PDT following incomplete initial response. However, where surgical procedures were used as second-line treatments, the surgery was not as extensive as would otherwise have been needed as if used at the initial stage. Attili et al. reported similar results, with three of the five patients with Bowen’s disease
Figure 3. Bowen’s disease right upper eyelid extending over lateral half of upper lid.
Figure 4. Three months post PDT, disease is more localised to the lateral aspect.
518
Natasha Casie Chetty et al.
treated with PDT not remaining clear at 2 years of follow-up (6). Long-term data are needed on the use of PDT in periocular Bowen’s disease to ascertain whether it provides a worthwhile, cost-effective option for treatment. Two of our patients had previous treatments to the eyelid area, and a less invasive option of PDT was preferred. However, the previous surgery with resultant scarring made the response to PDT more difficult to assess, resulting in a lower threshold for biopsy to confirm histological clearance. Cosmesis may also be a factor in favour of PDT over treatments such as cryotherapy or topical 5-fluorouracil at other sites.However, in the periocular region, other considerations such as immediate and long-term potential for functional impairment as a result of the treatment, as well as due to recurrence of the disease itself, become paramount. Temporary conjunctivitis and ocular stinging have been reported with the use of Imiquimod, with staphylococcal keratitis and preseptal cellulitis also reported (7). Malhotra et al., reporting a prospective series of 53 patients undergoing MMS for periocular Bowen’s disease, report significant subclinical tumour extension (42 cm) in 25% of cases. With most cases followed up for more than five years, they report a recurrence of rate of 5.3% for primary periocular IEC following MMS, attributed by Attili et al. to the presence of skip lesions (6). Given these risks, even with MMS which is considered to be the most effective means of treating periocular IEC, the risks and benefits of PDT treatment need to be carefully discussed in the select group of patients for whom we consider the treatment to be a valuable option. Whilst our retrospective case
J Dermatolog Treat, 2014; 25(6): 516–518
series is limited by its size and long-term follow-up data, the cases demonstrate that PDT does have a role in this functionally sensitive area.
Declaration of interest Authors declare no conflict of interest.
References 1. Morton CA, Mckenna KE, Rhodes LE. Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008;159:1245–66. 2. Malhotra R, Huilgol SC, Huynh NT, Selva D. The Australian Mohs database, part II: periocular basal cell carcinoma outcome at 5-year follow up. Ophthalmology. 2004;111:631–6. 3. Malhotra R, James CL, Selva D, et al. The Australian Mohs database: periocular squamous intraepidermal carcinoma. Ophthalmology. 2004;111:1925–9. 4. Bernadini FP. Management of malignant and benign eyelid lesions. Curr Opin Ophthalmol. 2006;17:480–4. 5. Lehman P. Methyl aminolaevulinate – photodynamic therapy: a review of clinical trials in the treatment of actinic keratosis and nonmelanoma skin cancer. Br J Dermatol. 2007;156:793–801. 6. Attili SK, Ibbotson SH, Fleming C. Role of non-surgical therapies in the management of periocular basal cell carcinoma and squamous intra-epidermal carcinoma: a case series and review of the literature. Photodermatol Photoimmunol Photomed. 2012;28:68–79. 7. Cannon PS, O’Donnell B, Huilgol SC, Selva D. The ophthalmic side-effects of imiquimod therapy in the management of periocular skin lesions. Br J Ophthalmol. 2011;95:1682–5.
Copyright of Journal of Dermatological Treatment is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
CASE REPORT
Periocular photodynamic therapy for squamous intra-epidermal carcinoma Natasha Casie Chetty1, Bridget Hemmant 2, and Anne-Marie Skellett1 1
Department of Dermatology and 2Department of Ophthalmology, Norfolk and Norwich University Hospital, Norwich, UK
Abstract
Keywords
Objectives: To evaluate the response of Metvix photodynamic therapy (PDT) for the treatment of periocular Bowen’s disease. Methods: Four patients with biopsy-proven Bowen’ disease were treated with Metvix PDT between November 2010 and January 2012. A detailed description of the technique used is described. Results: All of the patients tolerated the PDT well. All had some clinical response to the treatment, although there was not complete, lasting resolution beyond one year in three out of the four cases. Conclusion: PDT can be a good treatment in its own right in selected cases of periocular Bowen’s disease.
Actinic keratosis, Bowen’s disease, pre-malignant
Topical photodynamic therapy (PDT), using a photosensitising agent, Metvix, is an effective treatment for Bowen’s disease and actinic keratosis (AK), with equivalence or superiority to other nonsurgical methods such as cryotherapy and topical 5-FU (1). Whilst Mohs micrographic surgery (MMS) is the treatment of choice for periocular basal cell carcinomas (2), when dealing with preinvasive disease at this sensitive anatomic location, it is reasonable to consider PDT as an alternative or additional option. Bowen’s disease is thought to transform into squamous cell carcinoma (SCC) in about 8% of cases, and 5% of these are reported to metastasize (3). In contrast, the risk of transformation of AK is considered to be approximately 0.24% per year (4). Complete response rates of PDT in Bowen’s disease have been cited as 93% at 3 months and 68% at 24 months (5). This risk of malignant transformation, taken together with the risk of recurrence in the periorbital region, highlights the need for careful choice of therapy taking into account patient preference, comorbidities and precise site of disease with attendant risks of damage to vital structures. We report four cases in which PDT was preferentially used in the periocular region. Our report highlights the benefits of a multidisciplinary approach and the utility of a full therapeutic armamentarium to the benefit of each patient’s individual needs.
PDT treatment protocol All patients underwent ophthalmology review prior to undertaking PDT. Local anaesthetic eye drops were applied prior to insertion of a contact lens to protect the ocular surface from Correspondence: Dr Natasha Casie Chetty, Department of Dermatology, Norfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK. Tel: 01603 286286. Fax: 01603 288601. E-mail: natasha. [email protected]
Received 5 August 2013 Revised 27 August 2013 Accepted 27 August 2013 Published online 11 November 2013
contact with the Metvix cream, the photosensitiser. The lesions were scraped in preparation to remove the surface scale. Metvix cream was applied for a period of 3 hours prior to the treatment. A dressing held the cream in situ and an eye protector was placed to cover the eye. After 3 hours, the Metvix was removed. More local anaesthetic was applied before Laserguard was applied over the contact lens. The Aktilite CL128 was used for 7 minutes and 24 seconds (37 J/cm2). Following treatment, the contact lens and Laserguard were removed and a dressing was placed over the eye as protection from ambient light. Each course of PDT consisted of two treatments, 1 week apart. A 5-mm rim of clinically normal skin was included in the irradiation field for well-defined lesions, with 10 mm if the lesion was poorly defined. This was difficult to achieve, however, if the lesion lay very close to the conjunctiva.
Results
20 14
Introduction
History
Four patients were treated between November 2010 and January 2012. Follow-up ranged from 18 months to 29 months. Patient 1
A 68-year-old man had a biopsy-proven bowenoid AK to the left medial canthus, measuring 20 mm in diameter. In January 2012, he underwent two sessions of PDT, 1 week apart. He had a crusting reaction to the left medial canthus which settled by day four following the second dose of PDT. Following PDT, he was left with an area of thickening over the left medial canthus, measuring 10 mm in diameter. A punch biopsy confirmed SCC in situ, but extended to the deep margin of the biopsy; hence, an invasive carcinoma could not be excluded. An MRI scan ruled out any intraorbital extension. He underwent MMS, with reconstruction the following day. Histology confirmed SCC in situ, with no evidence of invasive disease.
Periocular photodynamic therapy
DOI: 10.3109/09546634.2013.849793
Patient 2 An 85-year-old man was referred from ophthalmology with biopsy-proven Bowen’s disease to the left periocular area (Figure 1). His extensive ophthalmic history dates back to 1969 when he had a squamous cell carcinoma excised from the left upper lid, with a recurrence in 1976 which was repaired with a split skin graft. In 1982, a further SCC was excised from the left lower eyelid. In view of the extensive procedures, he was keen to explore nonsurgical options and underwent two treatments with PDT to the upper and lower eyelids in March 2011. He had a good response to the lesions to the upper eyelid, but had residual change to the lower eyelid (Figure 2) for which two further PDT sessions were administered in January 2012. He has had no further recurrence and remains under ophthalmology follow-up. Patient 3 A 95-year-old lady was referred with a patch of Bowen’s disease to the left lower eyelid. She underwent a course of PDT in August 2011, with complete resolution of the lesion. She remains under ophthalmology follow-up. Patient 4 An 84-year-old man was referred in 2010 with a biopsy-proven area of squamous carcinoma in situ over the right upper lid. In 1997, he had been treated with the carbon dioxide (CO2) laser for recurrent keratosis of the right upper lid, having previously had no response to cryotherapy. He had an initial good result, but in view of the difficulty of reconstruction following excision, further recurrences were again treated with CO2 laser ablation in 2000
Figure 1. Bowen’s disease left lateral upper eyelid and medial aspect lower eyelid on background of surgical scars.
Figure 2. One month post PDT, residual Bowen’s disease left lower lid with clinical clearance over upper lid.
517
and 2002. The present lesion was extensive, involving more than half of the upper lid and extending across towards the lateral canthal area (Figure 3). He underwent two sessions of PDT in November 2010, following which he had a very good, although not complete response (Figure 4), and remained under regular follow-up. In September 2011, he was noted to have a central area of crusting in the upper lid. A shave biopsy showed bowenoid AK with atypia extending onto the margins of the shave excision. The patient did not wish to have any further procedure and opted for observation as further management.
Discussion Our small case series demonstrates that PDT is a useful treatment option in carefully selected patients. Using our treatment protocol utilising topical anaesthetic, all of the patients tolerated the PDT well and no additional local anaesthetic injections were required. One patient developed a temporary conjunctivitis of the treated eye which settled with chloramphenicol ointment. No long-term complications of the treatment were noted. All our patients had biopsy-proven Bowen’s disease or bowenoid AK. All had some clinical response to the first cycle of treatment, although there was not complete, lasting resolution beyond 1 year, in three out of the four cases. Two of these patients proceeded to surgical procedures to the same site within 12 months of the PDT, whereas the other responded to a further course of PDT following incomplete initial response. However, where surgical procedures were used as second-line treatments, the surgery was not as extensive as would otherwise have been needed as if used at the initial stage. Attili et al. reported similar results, with three of the five patients with Bowen’s disease
Figure 3. Bowen’s disease right upper eyelid extending over lateral half of upper lid.
Figure 4. Three months post PDT, disease is more localised to the lateral aspect.
518
Natasha Casie Chetty et al.
treated with PDT not remaining clear at 2 years of follow-up (6). Long-term data are needed on the use of PDT in periocular Bowen’s disease to ascertain whether it provides a worthwhile, cost-effective option for treatment. Two of our patients had previous treatments to the eyelid area, and a less invasive option of PDT was preferred. However, the previous surgery with resultant scarring made the response to PDT more difficult to assess, resulting in a lower threshold for biopsy to confirm histological clearance. Cosmesis may also be a factor in favour of PDT over treatments such as cryotherapy or topical 5-fluorouracil at other sites.However, in the periocular region, other considerations such as immediate and long-term potential for functional impairment as a result of the treatment, as well as due to recurrence of the disease itself, become paramount. Temporary conjunctivitis and ocular stinging have been reported with the use of Imiquimod, with staphylococcal keratitis and preseptal cellulitis also reported (7). Malhotra et al., reporting a prospective series of 53 patients undergoing MMS for periocular Bowen’s disease, report significant subclinical tumour extension (42 cm) in 25% of cases. With most cases followed up for more than five years, they report a recurrence of rate of 5.3% for primary periocular IEC following MMS, attributed by Attili et al. to the presence of skip lesions (6). Given these risks, even with MMS which is considered to be the most effective means of treating periocular IEC, the risks and benefits of PDT treatment need to be carefully discussed in the select group of patients for whom we consider the treatment to be a valuable option. Whilst our retrospective case
J Dermatolog Treat, 2014; 25(6): 516–518
series is limited by its size and long-term follow-up data, the cases demonstrate that PDT does have a role in this functionally sensitive area.
Declaration of interest Authors declare no conflict of interest.
References 1. Morton CA, Mckenna KE, Rhodes LE. Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008;159:1245–66. 2. Malhotra R, Huilgol SC, Huynh NT, Selva D. The Australian Mohs database, part II: periocular basal cell carcinoma outcome at 5-year follow up. Ophthalmology. 2004;111:631–6. 3. Malhotra R, James CL, Selva D, et al. The Australian Mohs database: periocular squamous intraepidermal carcinoma. Ophthalmology. 2004;111:1925–9. 4. Bernadini FP. Management of malignant and benign eyelid lesions. Curr Opin Ophthalmol. 2006;17:480–4. 5. Lehman P. Methyl aminolaevulinate – photodynamic therapy: a review of clinical trials in the treatment of actinic keratosis and nonmelanoma skin cancer. Br J Dermatol. 2007;156:793–801. 6. Attili SK, Ibbotson SH, Fleming C. Role of non-surgical therapies in the management of periocular basal cell carcinoma and squamous intra-epidermal carcinoma: a case series and review of the literature. Photodermatol Photoimmunol Photomed. 2012;28:68–79. 7. Cannon PS, O’Donnell B, Huilgol SC, Selva D. The ophthalmic side-effects of imiquimod therapy in the management of periocular skin lesions. Br J Ophthalmol. 2011;95:1682–5.
Copyright of Journal of Dermatological Treatment is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
![[Squamous cell carcinoma following photodynamic therapy].](/assets/img/hold.png)
