Mitomycin C in sebaceous gland carcinoma with pagetoid spread
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《英国眼科学杂志》
Department of Oculoplastic and Orbital Surgery, Sydney Eye Hospital, Sydney, Australia
Correspondence to:
Dr Georgina Kourt
Eye Associates, 149 Macquarie Street, Sydney 2000, Australia; ginaharr@ozemail.com.au
Accepted for publication 26 September 2003
Keywords: mitomycin C; sebaceous gland carcinoma; pagetoid spread
Sebaceous gland carcinoma is a rare eyelid tumour comprising less than 1% of all eyelid malignancies.1 It commonly arises from the meibomian glands of the tarsus, but may also arise from the glands of Zeis or from the sebaceous glands of caruncle.2 It can present in a nodular or diffuse infiltrative form. The latter form with intraepithelial (pagetoid) invasion has poor prognosis as a result of delay in diagnosis as well as more extensive involvement of ocular tissues. Topical application of mitomycin C, a non-cell cycle specific alkylating agent, has been advocated for pagetoid spread of sebaceous gland carcinoma.3 We report the use of mitomycin C as adjuvant therapy in a patient with completely excised sebaceous gland carcinoma and pagetoid spread.
Case report
A 78 year old man was referred to the oculoplastic clinic with epiphora and irritation of right eye for 2 years. There was no previous ocular or medical history. Clinically he had a unilateral right upper lid entropion with tarso-conjunctival cicatrisation (fig 1) and bilateral dermatochalasis. The patient underwent bilateral blepharoplasty and biopsy of right upper lid tarsal plate and conjunctiva. The biopsy confirmed sebaceous gland carcinoma with pagetoid invasion of the conjunctival epithelium (fig 2).
Figure 1 Upper lid tarso-conjunctival scarring.
Figure 2 Conjunctival biopsy demonstrating intraepithelial invasion of malignant cells.
He had a full thickness wedge excision of the right upper lid with tarsoconjunctival biopsies. These showed sebaceous gland carcinoma to the margin of the excision with pagetoid invasion of the conjunctiva and epidermis of the lid margin. A wider excision of the lid and further conjunctival biopsies were performed with frozen section revealing complete excision of the tumour. Reconstruction of the posterior lamellae was achieved using a hard palate graft and the anterior lamellae was repaired by a myocutaneous flap with post auricular skin graft and a bilobed flap medially.
Conjunctival map biopsies were clear of tumour 1 and 6 months post excision. In view of pagetoid spread, the patient was commenced on three cycles of topical mitomycin C 0.02% four times a day. Each cycle consisted of 2 weeks of mitomycin C and 2 weeks off therapy. Corneal epithelial toxicity and ulceration was noted with mitomycin C therapy, requiring preservative free lubricants and lateral tarsorrhaphy. Two years after excision of tumour, the patient remains disease free.
Comment
Intraepithelial invasion in sebaceous gland carcinoma is noted to occur in 41–80% of cases.1,4 Diagnosis may be delayed as the presenting symptoms are often benign and non-specific such as blepharoconjunctivitis. Diagnosis requires biopsy of the abnormal area and conjunctival map biopsies in the presence of intraepithelial invasion.3,5 Various treatments have been used for pagetoid invasion including surgical excision with cryotherapy, external beam radiotherapy, and orbital exenteration.6 Eyes with pagetoid invasion are more likely to undergo exenteration.7
In our case the suspicion of malignancy was raised because of the unilaterality of the clinical features. Our patient underwent extensive excision of the tumour with tumour free conjunctival biopsies. Mitomycin C as adjuvant treatment was commenced as a result of the difficulty in clinically assessing for recurrence with pagetoid invasion. Mitomycin C was associated with moderate epithelial toxicity which was self limiting.
Mitomycin C is a non-cell cycle specific alkylating agent which acts to inhibit cell proliferation, and is used successfully in the treatment of corneal intraepithelial neoplasia.8 This is only the second reported article where mitomycin C has been used in the treatment of sebaceous gland carcinoma. In the pilot study by Shields et al3 there was complete resolution of tumour with no recurrences over 12 month follow up. Mitomycin C as adjuvant treatment in pagetoid spread of sebaceous gland carcinoma may reduce the need for more invasive treatment options.
References
Doxanas MT, Green WR. Sebaceous gland carcinoma: review of 40 cases. Arch Ophthalmol 1984;102:245–9.
Cook B, Bartley G. Treatment options and future prospects for the management of eyelid malignancies. Ophthalmology 2001;108:2088–100.
Shields CL, Naseripour M, Shields J, et al. Topical mitomycin C for pagetoid invasion of the conjunctiva by eyelid sebaceous gland carcinoma. Ophthalmology 2002;109:2129–33.
Rao NA, Hidayat AA, McLean JW, et al. Sebaceous carcinoma of the ocular adnexa: a clinicopathologic study of 104 cases with five year follow-up data. Human Pathol 1982;13:113–22.
Putterman AM. Conjunctival map biopsy to determine pagetoid spread. Am J Ophthalmol 1986;102:87–90.
Kass LG, Hornblass A. Sebaceous carcinoma of the ocular adnexa. Surv Ophthalmol 1989;33:477–90.
Chao AN, Shields CL, Krema H, et al. Outcome of patients with periocular sebaceous gland carcinoma with and without conjunctival intraepithelial invasion. Ophthalmology 2001;108:1877–83.
Frucht-Pery J, Sugar J, Baum J, et al. Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia: a multicenter experience. Ophthalmology 1997;104:2085–93.(K Tumuluri, G Kourt and P)
Correspondence to:
Dr Georgina Kourt
Eye Associates, 149 Macquarie Street, Sydney 2000, Australia; ginaharr@ozemail.com.au
Accepted for publication 26 September 2003
Keywords: mitomycin C; sebaceous gland carcinoma; pagetoid spread
Sebaceous gland carcinoma is a rare eyelid tumour comprising less than 1% of all eyelid malignancies.1 It commonly arises from the meibomian glands of the tarsus, but may also arise from the glands of Zeis or from the sebaceous glands of caruncle.2 It can present in a nodular or diffuse infiltrative form. The latter form with intraepithelial (pagetoid) invasion has poor prognosis as a result of delay in diagnosis as well as more extensive involvement of ocular tissues. Topical application of mitomycin C, a non-cell cycle specific alkylating agent, has been advocated for pagetoid spread of sebaceous gland carcinoma.3 We report the use of mitomycin C as adjuvant therapy in a patient with completely excised sebaceous gland carcinoma and pagetoid spread.
Case report
A 78 year old man was referred to the oculoplastic clinic with epiphora and irritation of right eye for 2 years. There was no previous ocular or medical history. Clinically he had a unilateral right upper lid entropion with tarso-conjunctival cicatrisation (fig 1) and bilateral dermatochalasis. The patient underwent bilateral blepharoplasty and biopsy of right upper lid tarsal plate and conjunctiva. The biopsy confirmed sebaceous gland carcinoma with pagetoid invasion of the conjunctival epithelium (fig 2).
Figure 1 Upper lid tarso-conjunctival scarring.
Figure 2 Conjunctival biopsy demonstrating intraepithelial invasion of malignant cells.
He had a full thickness wedge excision of the right upper lid with tarsoconjunctival biopsies. These showed sebaceous gland carcinoma to the margin of the excision with pagetoid invasion of the conjunctiva and epidermis of the lid margin. A wider excision of the lid and further conjunctival biopsies were performed with frozen section revealing complete excision of the tumour. Reconstruction of the posterior lamellae was achieved using a hard palate graft and the anterior lamellae was repaired by a myocutaneous flap with post auricular skin graft and a bilobed flap medially.
Conjunctival map biopsies were clear of tumour 1 and 6 months post excision. In view of pagetoid spread, the patient was commenced on three cycles of topical mitomycin C 0.02% four times a day. Each cycle consisted of 2 weeks of mitomycin C and 2 weeks off therapy. Corneal epithelial toxicity and ulceration was noted with mitomycin C therapy, requiring preservative free lubricants and lateral tarsorrhaphy. Two years after excision of tumour, the patient remains disease free.
Comment
Intraepithelial invasion in sebaceous gland carcinoma is noted to occur in 41–80% of cases.1,4 Diagnosis may be delayed as the presenting symptoms are often benign and non-specific such as blepharoconjunctivitis. Diagnosis requires biopsy of the abnormal area and conjunctival map biopsies in the presence of intraepithelial invasion.3,5 Various treatments have been used for pagetoid invasion including surgical excision with cryotherapy, external beam radiotherapy, and orbital exenteration.6 Eyes with pagetoid invasion are more likely to undergo exenteration.7
In our case the suspicion of malignancy was raised because of the unilaterality of the clinical features. Our patient underwent extensive excision of the tumour with tumour free conjunctival biopsies. Mitomycin C as adjuvant treatment was commenced as a result of the difficulty in clinically assessing for recurrence with pagetoid invasion. Mitomycin C was associated with moderate epithelial toxicity which was self limiting.
Mitomycin C is a non-cell cycle specific alkylating agent which acts to inhibit cell proliferation, and is used successfully in the treatment of corneal intraepithelial neoplasia.8 This is only the second reported article where mitomycin C has been used in the treatment of sebaceous gland carcinoma. In the pilot study by Shields et al3 there was complete resolution of tumour with no recurrences over 12 month follow up. Mitomycin C as adjuvant treatment in pagetoid spread of sebaceous gland carcinoma may reduce the need for more invasive treatment options.
References
Doxanas MT, Green WR. Sebaceous gland carcinoma: review of 40 cases. Arch Ophthalmol 1984;102:245–9.
Cook B, Bartley G. Treatment options and future prospects for the management of eyelid malignancies. Ophthalmology 2001;108:2088–100.
Shields CL, Naseripour M, Shields J, et al. Topical mitomycin C for pagetoid invasion of the conjunctiva by eyelid sebaceous gland carcinoma. Ophthalmology 2002;109:2129–33.
Rao NA, Hidayat AA, McLean JW, et al. Sebaceous carcinoma of the ocular adnexa: a clinicopathologic study of 104 cases with five year follow-up data. Human Pathol 1982;13:113–22.
Putterman AM. Conjunctival map biopsy to determine pagetoid spread. Am J Ophthalmol 1986;102:87–90.
Kass LG, Hornblass A. Sebaceous carcinoma of the ocular adnexa. Surv Ophthalmol 1989;33:477–90.
Chao AN, Shields CL, Krema H, et al. Outcome of patients with periocular sebaceous gland carcinoma with and without conjunctival intraepithelial invasion. Ophthalmology 2001;108:1877–83.
Frucht-Pery J, Sugar J, Baum J, et al. Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia: a multicenter experience. Ophthalmology 1997;104:2085–93.(K Tumuluri, G Kourt and P)