CASE REPORT
Squamous Cell Neoplasm of the Ocular Surface in a Patient With Psoriasis Treated With Tumor Necrosis Factor-Alpha Inhibitors Viviana Patricia Lezcano Carduz, MD, David Mingo Botín, MD, PhD, and Sonia Pilar Durán Poveda, MD
Purpose: To report a case of conjunctival squamous cell carcinoma in a patient with psoriasis treated with tumor necrosis factor-alpha inhibitors.
Methods: Case report and review of the literature. Results: A 44-year-old white woman presented to our hospital 1 year after developing a rapidly growing nodular lesion with papillomatous characteristics on the bulbar conjunctiva. The patient had a medical history of psoriasis since childhood and psoriatic arthritis since 2009. She had received several immunosuppressive medications such as leflunomide, adalimumab, methotrexate, and etanercept. The lesion appeared a few months after commencing treatment with etanercept and methotrexate. A histological examination revealed a squamous intraepithelial neoplasm of the conjunctiva that was negative for human papillomavirus infection. Conclusions: Several case reports have described squamous cell carcinoma in different parts of the body in patients taking tumor necrosis factor-alpha inhibitors. Squamous cell neoplasm of the ocular surface should be considered during differential diagnosis of new conjunctival lesions in such patients. Key Words: etanercept, psoriasis, squamous cell neoplasm, ocular surface, conjunctiva, tumor necrosis factor-alpha inhibitors (Cornea 2015;34:833–834)
degenerations.2 We present a case of ocular neoplasm associated with treatment that included tumor necrosis factor-alpha inhibitors.
CASE REPORT A 44-year-old white woman presented to our hospital with a rapidly growing nodular lesion with papillomatous characteristics on the bulbar conjunctiva. The patient had a medical history of psoriasis since childhood and psoriatic arthritis since 2009. She has received several immunosuppressive medications such as leflunomide and adalimumab since 2009. She had been undergoing treatment with methotrexate and etanercept since November 2012. Before treatment, the patient underwent testing for HIV and hepatitis C and B virus; the results of the tests were negative. Results from the Mantoux test were positive; consequently, chest radiography was performed, revealing no active infection. Based on these findings, the patient received chemoprophylaxis for tuberculosis. The patient presented with a pedunculated papillomatous lesion located in the temporal bulbar conjunctiva of the right eye (Fig. 1), which had grown over 1 year. The visual acuity in both eyes was 20/20. Surgical resection with adequate tumor-free margins was then performed along with reconstruction surgery with a conjunctival autograft. Histopathology revealed a conjunctival intraepithelial squamous cell carcinoma (Fig. 2). Low-grade and high-grade serotype HPVs were negative in the resected specimen. Topical
S
quamous neoplasms of the ocular surface include a wide spectrum of lesions that range from low-grade dysplasia to squamous cell carcinomas.1–3 The etiology of these lesions is multifactorial and includes ultraviolet (UV) radiation, exposure to several carcinogenic chemicals, viral infections such as human immunodeficiency virus (HIV) and human papillomavirus (HPV), immunosuppression, advanced age, male sex, history of xeroderma pigmentosum, and ocular surface
Received for publication January 15, 2015; revision received March 14, 2015; accepted March 20, 2015. Published online ahead of print May 26, 2015. From the Servicio de Oftalmología, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. The authors have no funding or conflicts of interest to disclose. Reprints: Viviana Patricia Lezcano Carduz, MD, Servicio de Oftalmología, Hospital Universitario Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, Madrid 28040, Spain (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Cornea Volume 34, Number 7, July 2015
FIGURE 1. Preoperative appearance of the conjunctival lesion. www.corneajrnl.com |
833
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 7, July 2015
Lezcano Carduz et al
FIGURE 2. Conjunctival biopsy showing conjunctival intraepithelial squamous cell carcinoma. Hematoxylin–eosin, original magnification ·100. adjuvant therapy with interferon alpha 2b was given after surgery. At the time of writing, the patient remained asymptomatic and showed no evidence of recurrence (7 months of follow-up).
reports that describe squamous cell carcinomas in locations other than the skin. Such reports describe squamous cell carcinoma in the penis,5,11 one of them fatal,11 another describing 1 case of invasive ductal carcinoma of the breast,10 and 1 case of oral cavity carcinoma12 in a patient with psoriasis who was receiving treatment with TNF-alpha inhibitors without any other associated risk factors. A case of conjunctival squamous cell carcinoma in a patient with psoriasis treated with PUVA and cyclosporine has also been reported. A review of the literature reveals that there is no conclusive evidence linking the use of TNF-alpha inhibitors with the development of intraepithelial squamous cell carcinoma of the conjunctiva. Nevertheless, the ocular surface could also be affected by this drug and should be taken into account when prescribing this immunosuppressive medication. It is essential for possible use of this drug to be studied as part of patients’ medical records, because it is suspected to be a potential risk factor for this type of neoplasm. Clinicians should be aware of this complication in any patient who takes TNF-alpha inhibitors. A high level of suspicion regarding these malignant lesions is necessary when treating patients with psoriasis who have been treated with other immunosuppressive therapies. REFERENCES
Squamous cell carcinoma of the ocular surface is an uncommon disease, with incidence varying from 0.02 to 3.5 cases per 100,000.4 Although the etiology is multifactorial, one of the major risk factors includes immunosuppression. Tumor necrosis factor-alpha inhibitors could be included in the immunosuppression origin. These drugs inhibit cytotoxic T cells, which play an important role in the initiation and progression of tumor cells, potentially increasing the growth rate of some tumors.5 These drugs should be used with caution in patients with psoriasis because they can be receiving other immunosuppressive therapies that are potentially oncogenic, such as phototherapy or psoralen with UV-A (PUVA) radiation,6–8 methotrexate, and cyclosporine.7,8 Also, these patients may have subclinical infections with potentially oncogenic viruses such as HPV.9 Our patient had received several immunosuppressive treatments and was HPV negative. After therapy with TNF-alpha inhibitors, the mean time for the appearance of squamous cell carcinoma is 11 months (range, 1–17 months).10 It correlates with our case in which the lesion presented approximately 13 months after the initiation of therapy. Despite the lack of randomized clinical trials demonstrating the increase in malignant neoplasms (with the exception of lymphoproliferative malignancies and nonmelanoma skin cancers) in these patients,8,9 there are several case
1. Oellers P, Karp CL, Sheth A, et al. Prevalence, treatment, and outcomes of coexistent ocular surface squamous neoplasia and pterygium. Ophthalmology. 2013;120:445–450. 2. Di Girolamo N. Association of human papilloma virus with pterygia and ocular-surface squamous neoplasia. Eye. 2012;26:202–211. 3. Crim N, Forniés-Paz ME, Monti R, et al. In situ carcinoma of the conjunctiva: surgical excision associated with cryotherapy. Clin Ophthalmol. 2013;7:1889–1893. 4. McKelvie P, Daniell M, McNab A, et al. Squamous cell carcinoma of the conjunctiva: a series of 26 cases. Br J Ophthalmol. 2002;86:168–173. 5. Fryrear RS II, Wiggins AK, Sangueza O, et al. Rapid onset of cutaneous squamous cell carcinoma of the penis in a patient with psoriasis on etanercept therapy. J Am Acad Dermatol. 2004;51:1026. 6. Lindelof B, Sigurgeirsson B, Tegner E, et al. PUVA and cancer risk: the Swedish followup study. Br J Dermatol. 1999;141:108–112. 7. Patel RV, Clark LN, Lebwohl M, et al. Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol. 2009;61:1059. 8. Almousa R, Daya S, Lake D, et al. Conjunctival squamous cell carcinoma following psoriasis treatment. J Cutan Med Surg. 2012;16: 365–367. 9. Pariser DM, Leonardi CL, Gordon K, et al. Integrated safety analysis: short- and longterm safety profiles of etanercept in patients with psoriasis. J Am Acad Dermatol. 2012;67:245–256. 10. Brewer JD, Hoverson Schott AR, Roenigk RK. Multiple squamous cell carcinomas in the setting of psoriasis treated with etanercept: a report of four cases and review of the literature. Int J Dermatol. 2011;50: 1555–1559. 11. Comte C, Guilhou JJ, Guillot B, et al. Rapid onset and fatal outcome of two squamous cell carcinomas of the genitalia in a patient treated with etanercept for cutaneous psoriasis. Dermatology. 2008;217:284–285. 12. Rousseau A, Taberne R, Siberchicot F, et al. Carcinome jugal sous etanercept TNF-alpha inhibitor etanercept and oral cavity carcinoma. Rev Stomatol Chir Maxillofac. 2009;110:306–308.
834
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
DISCUSSION
| www.corneajrnl.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Squamous Cell Neoplasm of the Ocular Surface in a Patient With Psoriasis Treated With Tumor Necrosis Factor-Alpha Inhibitors Viviana Patricia Lezcano Carduz, MD, David Mingo Botín, MD, PhD, and Sonia Pilar Durán Poveda, MD
Purpose: To report a case of conjunctival squamous cell carcinoma in a patient with psoriasis treated with tumor necrosis factor-alpha inhibitors.
Methods: Case report and review of the literature. Results: A 44-year-old white woman presented to our hospital 1 year after developing a rapidly growing nodular lesion with papillomatous characteristics on the bulbar conjunctiva. The patient had a medical history of psoriasis since childhood and psoriatic arthritis since 2009. She had received several immunosuppressive medications such as leflunomide, adalimumab, methotrexate, and etanercept. The lesion appeared a few months after commencing treatment with etanercept and methotrexate. A histological examination revealed a squamous intraepithelial neoplasm of the conjunctiva that was negative for human papillomavirus infection. Conclusions: Several case reports have described squamous cell carcinoma in different parts of the body in patients taking tumor necrosis factor-alpha inhibitors. Squamous cell neoplasm of the ocular surface should be considered during differential diagnosis of new conjunctival lesions in such patients. Key Words: etanercept, psoriasis, squamous cell neoplasm, ocular surface, conjunctiva, tumor necrosis factor-alpha inhibitors (Cornea 2015;34:833–834)
degenerations.2 We present a case of ocular neoplasm associated with treatment that included tumor necrosis factor-alpha inhibitors.
CASE REPORT A 44-year-old white woman presented to our hospital with a rapidly growing nodular lesion with papillomatous characteristics on the bulbar conjunctiva. The patient had a medical history of psoriasis since childhood and psoriatic arthritis since 2009. She has received several immunosuppressive medications such as leflunomide and adalimumab since 2009. She had been undergoing treatment with methotrexate and etanercept since November 2012. Before treatment, the patient underwent testing for HIV and hepatitis C and B virus; the results of the tests were negative. Results from the Mantoux test were positive; consequently, chest radiography was performed, revealing no active infection. Based on these findings, the patient received chemoprophylaxis for tuberculosis. The patient presented with a pedunculated papillomatous lesion located in the temporal bulbar conjunctiva of the right eye (Fig. 1), which had grown over 1 year. The visual acuity in both eyes was 20/20. Surgical resection with adequate tumor-free margins was then performed along with reconstruction surgery with a conjunctival autograft. Histopathology revealed a conjunctival intraepithelial squamous cell carcinoma (Fig. 2). Low-grade and high-grade serotype HPVs were negative in the resected specimen. Topical
S
quamous neoplasms of the ocular surface include a wide spectrum of lesions that range from low-grade dysplasia to squamous cell carcinomas.1–3 The etiology of these lesions is multifactorial and includes ultraviolet (UV) radiation, exposure to several carcinogenic chemicals, viral infections such as human immunodeficiency virus (HIV) and human papillomavirus (HPV), immunosuppression, advanced age, male sex, history of xeroderma pigmentosum, and ocular surface
Received for publication January 15, 2015; revision received March 14, 2015; accepted March 20, 2015. Published online ahead of print May 26, 2015. From the Servicio de Oftalmología, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. The authors have no funding or conflicts of interest to disclose. Reprints: Viviana Patricia Lezcano Carduz, MD, Servicio de Oftalmología, Hospital Universitario Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, Madrid 28040, Spain (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Cornea Volume 34, Number 7, July 2015
FIGURE 1. Preoperative appearance of the conjunctival lesion. www.corneajrnl.com |
833
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 7, July 2015
Lezcano Carduz et al
FIGURE 2. Conjunctival biopsy showing conjunctival intraepithelial squamous cell carcinoma. Hematoxylin–eosin, original magnification ·100. adjuvant therapy with interferon alpha 2b was given after surgery. At the time of writing, the patient remained asymptomatic and showed no evidence of recurrence (7 months of follow-up).
reports that describe squamous cell carcinomas in locations other than the skin. Such reports describe squamous cell carcinoma in the penis,5,11 one of them fatal,11 another describing 1 case of invasive ductal carcinoma of the breast,10 and 1 case of oral cavity carcinoma12 in a patient with psoriasis who was receiving treatment with TNF-alpha inhibitors without any other associated risk factors. A case of conjunctival squamous cell carcinoma in a patient with psoriasis treated with PUVA and cyclosporine has also been reported. A review of the literature reveals that there is no conclusive evidence linking the use of TNF-alpha inhibitors with the development of intraepithelial squamous cell carcinoma of the conjunctiva. Nevertheless, the ocular surface could also be affected by this drug and should be taken into account when prescribing this immunosuppressive medication. It is essential for possible use of this drug to be studied as part of patients’ medical records, because it is suspected to be a potential risk factor for this type of neoplasm. Clinicians should be aware of this complication in any patient who takes TNF-alpha inhibitors. A high level of suspicion regarding these malignant lesions is necessary when treating patients with psoriasis who have been treated with other immunosuppressive therapies. REFERENCES
Squamous cell carcinoma of the ocular surface is an uncommon disease, with incidence varying from 0.02 to 3.5 cases per 100,000.4 Although the etiology is multifactorial, one of the major risk factors includes immunosuppression. Tumor necrosis factor-alpha inhibitors could be included in the immunosuppression origin. These drugs inhibit cytotoxic T cells, which play an important role in the initiation and progression of tumor cells, potentially increasing the growth rate of some tumors.5 These drugs should be used with caution in patients with psoriasis because they can be receiving other immunosuppressive therapies that are potentially oncogenic, such as phototherapy or psoralen with UV-A (PUVA) radiation,6–8 methotrexate, and cyclosporine.7,8 Also, these patients may have subclinical infections with potentially oncogenic viruses such as HPV.9 Our patient had received several immunosuppressive treatments and was HPV negative. After therapy with TNF-alpha inhibitors, the mean time for the appearance of squamous cell carcinoma is 11 months (range, 1–17 months).10 It correlates with our case in which the lesion presented approximately 13 months after the initiation of therapy. Despite the lack of randomized clinical trials demonstrating the increase in malignant neoplasms (with the exception of lymphoproliferative malignancies and nonmelanoma skin cancers) in these patients,8,9 there are several case
1. Oellers P, Karp CL, Sheth A, et al. Prevalence, treatment, and outcomes of coexistent ocular surface squamous neoplasia and pterygium. Ophthalmology. 2013;120:445–450. 2. Di Girolamo N. Association of human papilloma virus with pterygia and ocular-surface squamous neoplasia. Eye. 2012;26:202–211. 3. Crim N, Forniés-Paz ME, Monti R, et al. In situ carcinoma of the conjunctiva: surgical excision associated with cryotherapy. Clin Ophthalmol. 2013;7:1889–1893. 4. McKelvie P, Daniell M, McNab A, et al. Squamous cell carcinoma of the conjunctiva: a series of 26 cases. Br J Ophthalmol. 2002;86:168–173. 5. Fryrear RS II, Wiggins AK, Sangueza O, et al. Rapid onset of cutaneous squamous cell carcinoma of the penis in a patient with psoriasis on etanercept therapy. J Am Acad Dermatol. 2004;51:1026. 6. Lindelof B, Sigurgeirsson B, Tegner E, et al. PUVA and cancer risk: the Swedish followup study. Br J Dermatol. 1999;141:108–112. 7. Patel RV, Clark LN, Lebwohl M, et al. Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol. 2009;61:1059. 8. Almousa R, Daya S, Lake D, et al. Conjunctival squamous cell carcinoma following psoriasis treatment. J Cutan Med Surg. 2012;16: 365–367. 9. Pariser DM, Leonardi CL, Gordon K, et al. Integrated safety analysis: short- and longterm safety profiles of etanercept in patients with psoriasis. J Am Acad Dermatol. 2012;67:245–256. 10. Brewer JD, Hoverson Schott AR, Roenigk RK. Multiple squamous cell carcinomas in the setting of psoriasis treated with etanercept: a report of four cases and review of the literature. Int J Dermatol. 2011;50: 1555–1559. 11. Comte C, Guilhou JJ, Guillot B, et al. Rapid onset and fatal outcome of two squamous cell carcinomas of the genitalia in a patient treated with etanercept for cutaneous psoriasis. Dermatology. 2008;217:284–285. 12. Rousseau A, Taberne R, Siberchicot F, et al. Carcinome jugal sous etanercept TNF-alpha inhibitor etanercept and oral cavity carcinoma. Rev Stomatol Chir Maxillofac. 2009;110:306–308.
834
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
DISCUSSION
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
