Original Investigation
Malignant Melanoma of the Lacrimal Drainage Apparatus Complicating Conjunctival Melanoma Khami Satchi, M.B.B.Chir., F.R.C.Ophth.*, Penny McKelvie, M.D., F.R.C.P.A.†, and Alan A. McNab, D.MedSc., F.R.A.N.Z.C.O.*‡§ *Orbital Plastic and Lacrimal Clinic, Royal Victorian Eye and Ear Hospital; †Department of Anatomical Pathology, St Vincent’s Hospital; ‡Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne; and §Centre for Eye Research Australia, Department of Surgery, University of Melbourne, Melbourne, Australia
Purpose: Melanoma of the conjunctiva may occasionally involve the lacrimal drainage apparatus (LDA). This makes clinical management difficult. The authors describe 5 cases of conjunctival melanoma with LDA disease and make recommendations about its management. Methods: Retrospective review of case notes and histopathology reports. Results: Five cases of LDA melanoma arising in patients with conjunctival melanoma are described. All 5 had orbital exenteration as part of their treatment. Melanoma of the LDA was clinically present at the time of exenteration in 1 case, found unexpectedly in 2 cases, and developed subsequent to exenteration in 2 cases. One patient died within 8 months of exenteration from metastatic melanoma. Two patients were disease free 3 and 5 years after exenteration. One patient developed metastasis in the parotid gland 4 years after exenteration but remained disease free 7 years after exenteration. One more patient has had a local recurrence in the maxilla and lateral nasal wall 4 years after exenteration, and after resection of that lesion and radiotherapy is disease free after 18 months. Seventeen patients underwent orbital exenteration for conjunctival melanoma over the period 1996–2013 at the authors’institution, with 5 having or developing LDA disease (29%). In the same period, there were 52 patients with conjunctival melanoma overall, with LDA involvement occurring in 5 of 52 patients (9.6%). Conclusions: Melanoma of the LDA may complicate conjunctival melanoma in a significant percentage of cases having orbital exenteration. The surgical technique for orbital exenteration in patients with conjunctival melanoma should take this into account by intentionally removing the lacrimal sac and upper nasolacrimal duct as well as the lacrimal canaliculi. If melanoma is found in the LDA, consideration should be given to wider en bloc excision of the LDA. (Ophthal Plast Reconstr Surg 2015;31:207–210)
C
onjunctival melanoma is a relatively uncommon ocular adnexal malignancy, but has a significant potential for metastasis and death.1,2 It may also spread to involve the
Accepted for publication June 11, 2014. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Alan A. McNab, D.Medsc., F.R.A.N.Z.C.O., Suite 216, 100 Victoria Parade, East Melbourne, 3002 Victoria, Australia. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000256
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lacrimal drainage apparatus (LDA). Late involvement of the nasal cavity has been described.1,3–8 Disease in inaccessible areas such as the LDA and nasal cavity make monitoring and treatment of melanocytic lesions problematic, and conjunctival melanoma is most commonly managed with globe sparing treatments such as local excision, cryotherapy, and topical antimetabolites.2 The authors describe 5 cases of melanoma affecting the LDA in patients who had initially presented with conjunctival melanoma.
CASE 1 This patient has previously been reported.6 An 81-year-old woman presented with multinodular melanoma of the right conjunctiva and eyelid margins. Over a period of 22 years, she had local excision of several conjunctival melanomas. Prior to her final presentation, a pigmented nodule had grown rapidly on the right upper eyelid margin, overlying the lacrimal punctum. There were several other scattered small nodules of melanoma of the bulbar, forniceal and tarsal conjunctiva. A right orbital exenteration was performed. At the time of surgery, the lacrimal sac was exposed and noted to be black in color. The surgical margins were extended to include a lateral rhinotomy with en bloc excision of the orbital contents and entire LDA within the medial wall of the maxilla. The specimen showed extensive in situ melanoma in the bulbar and tarsal conjunctiva of both eyelids, the upper lacrimal canaliculus and lacrimal sac, with foci of invasive melanoma on the eyelid margins and within the lacrimal sac. The maximal thickness of invasive melanoma, on the eyelid margin, was 8 mm. The lower nasolacrimal duct (NLD) was free of tumor. Eight months later, she died of metastatic melanoma.
CASE 2 A 57-year-old man presented in early 2007 with a 5-year history of ocular surface disease in the OS, which had been attributed to herpes simplex infection, rosacea, and blepharitis. In late 2006, he had developed a small limbal plaque, which was treated with topical steroids. Shortly after, a nonpigmented lump was found in the inferior conjunctival fornix. This was biopsied and found to be amelanotic melanoma. At presentation, he had normal vision in OU. In the OS, there was a multinodular, nonpigmented lesion in the inferior fornix, measuring 6 mm in length and 2 mm to 3 mm in diameter. There was a dusting of fine brown pigmentation on the medial bulbar conjunctiva. On the limbus from 12 to 3 o’clock, there was a slightly elevated pale plaque.
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Clinically, there was no nodal disease. A CT scan of the chest and abdomen was normal as was an MRI of the head and neck. A left orbital exenteration was performed, including the lacrimal sac and upper NLD. There was primary acquired melanosis (PAM) of the conjunctiva with multiple foci of invasive melanoma, with a maximum thickness of 1.8 mm. Both the upper and lower canaliculi were normal. Within the lacrimal sac, there was extensive in situ melanoma and PAM extending in the upper NLD to the excision margin. Because of melanosis extending to the margin in the upper NLD, a formal excision of the NLD was performed, as a combined external and endonasal procedure. This revealed PAM with mild atypia in the upper NLD, without disease at the lower cut end in the inferior meatus. Four years later (early 2011), he presented with a lump in the left parotid region. A positron emission tomography (PET)– CT scan showed no distant metastases. He underwent a superficial parotidectomy and radical neck dissection. Three nodes were found to be involved. He remained well with no evidence of disease 7 years after his original presentation.
CASE 3 This man was first presented to us in June 2006 at the age of 60 years. He had developed a lump under his right upper eyelid, which had bled repeatedly. He was found to have a pigmented, ulcerated medial tarsal conjunctival mass, which on biopsy was found to be invasive melanoma. He underwent a wide local excision. The melanoma was 5.6 mm in depth and10 mm wide, with an in situ component extending to the lateral excision margin. The upper canaliculus was within the excision and was normal. A further full thickness excision was performed laterally, and no further in situ melanoma or melanosis was identified. He remained clinically disease free, but in early 2008 developed right epiphora. He was found to have an obstruction in his remaining inferior canaliculus just proximal to the lacrimal sac, without any palpable mass in the lacrimal sac. He was listed for elective lacrimal surgery, but presented 3 months later with a lump in the region of the lacrimal sac. A biopsy from the lacrimal sac identified invasive melanoma. At the same time, he was noted to have a small mass in the inferior conjunctival fornix. Staging investigations including a PET–CT scan were normal. He underwent a right orbital exenteration with en bloc excision of the entire lacrimal system within the medial wall of the orbit and maxilla. There was invasive and in situ melanoma within the inferior forniceal conjunctiva, with a maximal depth of 1.2 mm. The inferior lacrimal canaliculus had no tumor or melanosis within it, but the lacrimal sac had a large deposit of invasive melanoma of 6.5 mm depth. The inferior margin of the NLD was clear of tumor, and the nasal mucosa was also normal. He remained well until late 2012 when he developed a lump in the inferomedial aspect of the exenterated orbit. A CT scan showed a soft tissue mass with adjacent bone erosion. Fine needle aspirate confirmed recurrent melanoma. He had a further en bloc resection of the residual medial maxilla and medial orbit. The lesion measured 18 mm × 17 mm × 10 mm, but was reported to be completely excised. He had 60 Gy of adjuvant radiotherapy. At his last follow up in early 2014, he remained clinically disease free.
CASE 4 A 25-year-old woman was presented initially in 2006. She had a small nonpigmented, slightly elevated lesion at the
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left superolateral limbus from early childhood. Over the preceding 6 months, the lesion had enlarged. The lesion was found to be raised, fleshy, and vascular. It was locally excised and found to be an invasive melanoma of 0.5 mm thickness with clear but narrow margins of excision. The lesion recurred at the same site 12 months later and was excised as a lamellar dissection. This was reported again as invasive melanoma with clear margins of excision. In 2008, a further recurrence at the superior limbus was locally excised with reported clear margins. In 2010, she presented with another limbal recurrence and also upper eyelid ptosis. She now had melanoma arising in the superior tarsal conjunctiva. Staging investigations including a PET–CT scan were normal. She underwent an orbital exenteration. The exenteration specimen had a spindle and epithelioid melanoma within the superior tarsal conjunctiva of 1.4 mm thickness, and a limbal nodule of 1.8 mm thickness, without vascular, lymphatic, or perineural invasion. There was no evidence of PAM. The upper and lower lacrimal canaliculi were normal. She returned in mid 2012 with a lump in the anterior inferomedial exenterated orbit. A biopsy specimen was obtained from within the lacrimal sac and confirmed recurrent melanoma up to 6 mm in thickness. She underwent an en bloc excision of the medial orbit and medial maxilla. Melanoma was confined to the lacrimal sac and upper NLD. The inferior NLD and nasal mucosa were free of tumor. She has remained in clinical remission since, with a normal recent PET and MRI scan.
CASE 5 A 58-year-old woman presented in early 2007 with a small, pigmented limbal lesion of the OS. Local excision was performed. A recurrence occurred 12 months later on the inferolateral limbus, which underwent a lamellar excision. At that time, she was also noted to have a pigmented lesion on the lower eyelid margin and a separate lesion on the inferior tarsal conjunctiva. Excisional biopsies of these areas showed PAM with atypia, with areas of the lesions having full-thickness in situ melanoma. Within 3 months, further nodules of melanoma had developed on the lower eyelid tarsal conjunctiva and the superior limbus. Orbital exenteration was performed. The tarsal conjunctival lesion was a 1.25-mm thick melanoma, and the limbal lesion a 0.48-mm thick melanoma. Melanoma in situ was adjacent to the melanomas, with scattered areas of PAM with atypia. The upper and lower lacrimal canaliculi were normal. Three years later, she presented with a lump in the region of the lacrimal sac of her exenterated orbit. A biopsy was obtained from the lacrimal sac and found to be melanoma. En bloc resection of the medial orbital wall and lateral nasal wall, as well as medial maxilla was performed, with a radial forearm free flap repair. Tumor free margins were obtained. She was given 48 Gy in 20 fractions of postoperative radiotherapy. In 3 further years of follow up, she has remained disease free, with normal MRI and PET scans in late 2013.
DISCUSSION Conjunctival melanoma is most commonly managed with globe-sparing treatments such as local excision, cryotherapy, and antimetabolites.2 For an extensive or widely recurrent disease, orbital exenteration is often used.1 More than 50% of patients will develop local recurrences with conservative
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
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treatments, and up to 20% will require orbital exenteration for disease control.9–11 Survival rates of 83% to 86% of patients at 5 years and 69% to 74% of patients at 10 years are found in larger series.1,9,10 Involvement of the LDA by conjunctival melanoma has been rarely reported.2–8 The earliest large series of conjunctival melanoma cases looking at prognostic factors in 256 cases found 8 patients (3.1%) who developed involvement of the nasal cavity and paranasal sinuses.1 This group did not specify involvement of the LDA in these patients, but spread via the LDA from the conjunctiva could well have been the mechanism of nasal and paranasal sinus involvement in some or all of these patients. In another large published series of conjunctival melanoma, 3 of 382 (0.8%) consecutive cases were found to involve the canaliculus or lacrimal sac.2 The authors’ own experience has been somewhat different. Over the period from 1996 to 2013, 52 cases of conjunctival melanoma have been seen at their institution. Of these, 17 cases (32.7%) have undergone orbital exenteration, and of these, 5 cases (29% of the 17 exenterations and 9.6% of cases of conjunctival melanoma) have been found to have involvement of the LDA. This is a much higher rate of LDA involvement than that seen by Shields et al.2 (3 of 382 [0.8%] cases of conjunctival melanoma) and than 3.1% (8 of 256 cases) of nasal and paranasal sinus involvement reported by Paridaens et al.1 The rate of exenteration in the authors’ institution is also significantly higher than that reported in several series (up to 20%),9–11 but similar to that reported by Paridaens et al.12 from the United Kingdom (95/256, 37.1%). The authors can offer no clear explanation for this. It is likely that they deal with a biased sample of cases, with more aggressive and advanced cases referred to them. It is also possible that they have a higher incidence of conjunctival melanoma in their population than elsewhere, although there are no data to support this. Australia and New Zealand have the highest incidence of cutaneous melanoma in the world,13 and there is published data showing a relationship between latitude and incidence of eyelid and conjunctival melanoma.14 This relationship between latitude and sun exposure in a fair skinned population explains the high incidence of cutaneous melanoma in Australia, and could be extrapolated to conjunctival melanoma. It does not, however, explain why the rate of exenteration should be higher in the authors’ institution than elsewhere. It may simply reflect the views of their clinicians regarding the role of exenteration in the management of conjunctival melanoma for which there is no broad evidence base. Only 1 of 5 cases (Case 3) had clinically obvious disease in the lacrimal sac prior to exenteration. Two others were found to have melanoma in the LDA, one with macroscopic disease (Case 1), and the other found only on histopathology (Case 2). In the second case, the lacrimal sac and upper NLD were intentionally included in the exenteration, and extension of melanosis into the residual NLD was secondarily surgically removed, with final clear margins. Cases 4 and 5 presented with mass lesions in the lacrimal sac 2 and 3 years after exenteration. Neither of these patients had excision of the entire lacrimal sac and upper NLD at the time of their exenteration. It is possible that later recurrence in the LDA may have been prevented if this had occurred. How melanoma occurs within the LDA (or nasal cavity) in patients with conjunctival melanoma is unclear. Case 2 had evidence of melanosis within the lacrimal sac and NLD, suggesting that the melanosis may have spread intraepithelially from the conjunctiva or may have involved the LDA as well as the conjunctiva in a “field” change. But both the upper and lower
Lacrimal Drainage Apparatus Melanoma and Conjunctival Melanoma
canaliculi were normal, so there was discontinuity between the conjunctival and lacrimal sac diseases. Within the conjunctiva, there are often areas of discontinuity between areas of PAM. Case 4 developed melanoma within a preexisting nevus, and then a second lesion on the tarsal conjunctiva opposite to the limbal lesion. She later developed lacrimal sac melanoma, and both the upper and lower lacrimal canaliculi were found to be free of melanosis or melanoma in the exenteration specimen. Case 5 was also found to have normal lacrimal canaliculi in the exenteration specimen and later developed lacrimal sac melanoma. In these patients, it is possible that melanoma cells may have implanted in the LDA after exfoliating into the tears. Exfoliated atypical melanocytes have been found in tears.15 Such a means of spread might account for patients with conjunctival melanoma developing melanoma in the nasal cavity, sometimes many years after treatment of their conjunctival melanoma.3,5 It seems highly unlikely that hematogenous or lymphatic spread would lead to melanoma occurring in the LDA or nasal cavity in patients with conjunctival melanoma. Whatever is the means of spread or involvement of the LDA melanoma in patients with conjunctival melanoma, the possibility of disease in the LDA should be considered in all cases. Lacrimal or nasal symptoms should lead to a careful assessment of the lacrimal system and nasal cavity. If orbital exenteration is to be performed for conjunctival melanoma, the lacrimal sac and its surrounding periosteum and the upper NLD at least should be removed en bloc with the orbital contents. The LDA should then be carefully examined for involvement and further treatment guided by this. Adjunctive treatment with radiotherapy may be appropriate where excision margins are narrow, and this applies particularly to cases with medial conjunctival involvement, where the excision margins, even with exenteration, are narrow.12
ACKNOWLEDGMENT The authors thank Dr John D McKenzie for allowing us to include his case, Case 5.
REFERENCES 1. Paridaens AD, Minassian DC, McCartney AC, et al. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases. Br J Ophthalmol 1994;78:252–9. 2. Shields CL, Markowitz JS, Belinsky I, et al. Conjunctival melanoma: outcomes based on tumor origin in 382 consecutive cases. Ophthalmology 2011;118:389–95.e1-2. 3. Robertson DM, Hungerford JL, McCartney A. Malignant melanomas of the conjunctiva, nasal cavity, and paranasal sinuses. Am J Ophthalmol 1989;108:440–2. 4. Paridaens AD, McCartney AC, Curling OM, et al. Impression cytology of conjunctival melanosis and melanoma. Br J Ophthalmol 1992;76:198–201. 5. Paridaens AD, McCartney AC, Lavelle RJ, et al. Nasal and orbital recurrence of conjunctival melanoma 21 years after exenteration. Br J Ophthalmol 1992;76:369–71. 6. McNab AA, McKelvie P. Malignant melanoma of the lacrimal sac complicating primary acquired melanosis of the conjunctiva. Ophthalmic Surg Lasers 1997;28:501–4. 7. Strempel I, Kroll P. Conjunctival malignant melanoma in children. Ophthalmologica 1999;213:129–32. 8. Missotten GS, Gambrelle J, de Wolff-Rouendaal D, de Keizer RJW. Epistaxis or epiphora as a sign for extension of conjunctival melanoma. A series of six patients with nasolacrimal recurrence. Br J Ophthalmol 2010;94:1328–31. 9. Shields CL. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Trans Am Ophthalmol Soc 2000;98:471–92.
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10. Missotten GS, Keijser S, De Keizer RJ, De Wolff-Rouendaal D. Conjunctival melanoma in the Netherlands: a nationwide study. Invest Ophthalmol Vis Sci 2005;46:75–82. 11. Damato B, Coupland SE. Management of conjunctival melanoma. Expert Rev Anticancer Ther 2009;9:1227–39. 12. Paridaens ADA, McCartney ACE, Minassian DC, Hungerford JL. Orbital exenteration in 95 cases of primary conjunctival melanoma. Br J Ophthalmol 1994;78:520–8.
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13. Sneyd MJ, Cox B. A comparison of trends in melanoma mortality in New Zealand and Australia: the two countries with the highest melanoma incidence in the world. BMC Cancer 2013; 13:372. 14. Yu GP, Hu DN, McCormick SA. Latitude and incidence of ocular melanoma. Photochem Photobiol 2006;82:1621–6. 15. Weiss JS, Perusse P, Reale F. Tear cytology in conjunctival melanoma. Am J Ophthalmol 1991;111:648–9.
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Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Malignant Melanoma of the Lacrimal Drainage Apparatus Complicating Conjunctival Melanoma Khami Satchi, M.B.B.Chir., F.R.C.Ophth.*, Penny McKelvie, M.D., F.R.C.P.A.†, and Alan A. McNab, D.MedSc., F.R.A.N.Z.C.O.*‡§ *Orbital Plastic and Lacrimal Clinic, Royal Victorian Eye and Ear Hospital; †Department of Anatomical Pathology, St Vincent’s Hospital; ‡Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne; and §Centre for Eye Research Australia, Department of Surgery, University of Melbourne, Melbourne, Australia
Purpose: Melanoma of the conjunctiva may occasionally involve the lacrimal drainage apparatus (LDA). This makes clinical management difficult. The authors describe 5 cases of conjunctival melanoma with LDA disease and make recommendations about its management. Methods: Retrospective review of case notes and histopathology reports. Results: Five cases of LDA melanoma arising in patients with conjunctival melanoma are described. All 5 had orbital exenteration as part of their treatment. Melanoma of the LDA was clinically present at the time of exenteration in 1 case, found unexpectedly in 2 cases, and developed subsequent to exenteration in 2 cases. One patient died within 8 months of exenteration from metastatic melanoma. Two patients were disease free 3 and 5 years after exenteration. One patient developed metastasis in the parotid gland 4 years after exenteration but remained disease free 7 years after exenteration. One more patient has had a local recurrence in the maxilla and lateral nasal wall 4 years after exenteration, and after resection of that lesion and radiotherapy is disease free after 18 months. Seventeen patients underwent orbital exenteration for conjunctival melanoma over the period 1996–2013 at the authors’institution, with 5 having or developing LDA disease (29%). In the same period, there were 52 patients with conjunctival melanoma overall, with LDA involvement occurring in 5 of 52 patients (9.6%). Conclusions: Melanoma of the LDA may complicate conjunctival melanoma in a significant percentage of cases having orbital exenteration. The surgical technique for orbital exenteration in patients with conjunctival melanoma should take this into account by intentionally removing the lacrimal sac and upper nasolacrimal duct as well as the lacrimal canaliculi. If melanoma is found in the LDA, consideration should be given to wider en bloc excision of the LDA. (Ophthal Plast Reconstr Surg 2015;31:207–210)
C
onjunctival melanoma is a relatively uncommon ocular adnexal malignancy, but has a significant potential for metastasis and death.1,2 It may also spread to involve the
Accepted for publication June 11, 2014. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Alan A. McNab, D.Medsc., F.R.A.N.Z.C.O., Suite 216, 100 Victoria Parade, East Melbourne, 3002 Victoria, Australia. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000256
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lacrimal drainage apparatus (LDA). Late involvement of the nasal cavity has been described.1,3–8 Disease in inaccessible areas such as the LDA and nasal cavity make monitoring and treatment of melanocytic lesions problematic, and conjunctival melanoma is most commonly managed with globe sparing treatments such as local excision, cryotherapy, and topical antimetabolites.2 The authors describe 5 cases of melanoma affecting the LDA in patients who had initially presented with conjunctival melanoma.
CASE 1 This patient has previously been reported.6 An 81-year-old woman presented with multinodular melanoma of the right conjunctiva and eyelid margins. Over a period of 22 years, she had local excision of several conjunctival melanomas. Prior to her final presentation, a pigmented nodule had grown rapidly on the right upper eyelid margin, overlying the lacrimal punctum. There were several other scattered small nodules of melanoma of the bulbar, forniceal and tarsal conjunctiva. A right orbital exenteration was performed. At the time of surgery, the lacrimal sac was exposed and noted to be black in color. The surgical margins were extended to include a lateral rhinotomy with en bloc excision of the orbital contents and entire LDA within the medial wall of the maxilla. The specimen showed extensive in situ melanoma in the bulbar and tarsal conjunctiva of both eyelids, the upper lacrimal canaliculus and lacrimal sac, with foci of invasive melanoma on the eyelid margins and within the lacrimal sac. The maximal thickness of invasive melanoma, on the eyelid margin, was 8 mm. The lower nasolacrimal duct (NLD) was free of tumor. Eight months later, she died of metastatic melanoma.
CASE 2 A 57-year-old man presented in early 2007 with a 5-year history of ocular surface disease in the OS, which had been attributed to herpes simplex infection, rosacea, and blepharitis. In late 2006, he had developed a small limbal plaque, which was treated with topical steroids. Shortly after, a nonpigmented lump was found in the inferior conjunctival fornix. This was biopsied and found to be amelanotic melanoma. At presentation, he had normal vision in OU. In the OS, there was a multinodular, nonpigmented lesion in the inferior fornix, measuring 6 mm in length and 2 mm to 3 mm in diameter. There was a dusting of fine brown pigmentation on the medial bulbar conjunctiva. On the limbus from 12 to 3 o’clock, there was a slightly elevated pale plaque.
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Clinically, there was no nodal disease. A CT scan of the chest and abdomen was normal as was an MRI of the head and neck. A left orbital exenteration was performed, including the lacrimal sac and upper NLD. There was primary acquired melanosis (PAM) of the conjunctiva with multiple foci of invasive melanoma, with a maximum thickness of 1.8 mm. Both the upper and lower canaliculi were normal. Within the lacrimal sac, there was extensive in situ melanoma and PAM extending in the upper NLD to the excision margin. Because of melanosis extending to the margin in the upper NLD, a formal excision of the NLD was performed, as a combined external and endonasal procedure. This revealed PAM with mild atypia in the upper NLD, without disease at the lower cut end in the inferior meatus. Four years later (early 2011), he presented with a lump in the left parotid region. A positron emission tomography (PET)– CT scan showed no distant metastases. He underwent a superficial parotidectomy and radical neck dissection. Three nodes were found to be involved. He remained well with no evidence of disease 7 years after his original presentation.
CASE 3 This man was first presented to us in June 2006 at the age of 60 years. He had developed a lump under his right upper eyelid, which had bled repeatedly. He was found to have a pigmented, ulcerated medial tarsal conjunctival mass, which on biopsy was found to be invasive melanoma. He underwent a wide local excision. The melanoma was 5.6 mm in depth and10 mm wide, with an in situ component extending to the lateral excision margin. The upper canaliculus was within the excision and was normal. A further full thickness excision was performed laterally, and no further in situ melanoma or melanosis was identified. He remained clinically disease free, but in early 2008 developed right epiphora. He was found to have an obstruction in his remaining inferior canaliculus just proximal to the lacrimal sac, without any palpable mass in the lacrimal sac. He was listed for elective lacrimal surgery, but presented 3 months later with a lump in the region of the lacrimal sac. A biopsy from the lacrimal sac identified invasive melanoma. At the same time, he was noted to have a small mass in the inferior conjunctival fornix. Staging investigations including a PET–CT scan were normal. He underwent a right orbital exenteration with en bloc excision of the entire lacrimal system within the medial wall of the orbit and maxilla. There was invasive and in situ melanoma within the inferior forniceal conjunctiva, with a maximal depth of 1.2 mm. The inferior lacrimal canaliculus had no tumor or melanosis within it, but the lacrimal sac had a large deposit of invasive melanoma of 6.5 mm depth. The inferior margin of the NLD was clear of tumor, and the nasal mucosa was also normal. He remained well until late 2012 when he developed a lump in the inferomedial aspect of the exenterated orbit. A CT scan showed a soft tissue mass with adjacent bone erosion. Fine needle aspirate confirmed recurrent melanoma. He had a further en bloc resection of the residual medial maxilla and medial orbit. The lesion measured 18 mm × 17 mm × 10 mm, but was reported to be completely excised. He had 60 Gy of adjuvant radiotherapy. At his last follow up in early 2014, he remained clinically disease free.
CASE 4 A 25-year-old woman was presented initially in 2006. She had a small nonpigmented, slightly elevated lesion at the
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left superolateral limbus from early childhood. Over the preceding 6 months, the lesion had enlarged. The lesion was found to be raised, fleshy, and vascular. It was locally excised and found to be an invasive melanoma of 0.5 mm thickness with clear but narrow margins of excision. The lesion recurred at the same site 12 months later and was excised as a lamellar dissection. This was reported again as invasive melanoma with clear margins of excision. In 2008, a further recurrence at the superior limbus was locally excised with reported clear margins. In 2010, she presented with another limbal recurrence and also upper eyelid ptosis. She now had melanoma arising in the superior tarsal conjunctiva. Staging investigations including a PET–CT scan were normal. She underwent an orbital exenteration. The exenteration specimen had a spindle and epithelioid melanoma within the superior tarsal conjunctiva of 1.4 mm thickness, and a limbal nodule of 1.8 mm thickness, without vascular, lymphatic, or perineural invasion. There was no evidence of PAM. The upper and lower lacrimal canaliculi were normal. She returned in mid 2012 with a lump in the anterior inferomedial exenterated orbit. A biopsy specimen was obtained from within the lacrimal sac and confirmed recurrent melanoma up to 6 mm in thickness. She underwent an en bloc excision of the medial orbit and medial maxilla. Melanoma was confined to the lacrimal sac and upper NLD. The inferior NLD and nasal mucosa were free of tumor. She has remained in clinical remission since, with a normal recent PET and MRI scan.
CASE 5 A 58-year-old woman presented in early 2007 with a small, pigmented limbal lesion of the OS. Local excision was performed. A recurrence occurred 12 months later on the inferolateral limbus, which underwent a lamellar excision. At that time, she was also noted to have a pigmented lesion on the lower eyelid margin and a separate lesion on the inferior tarsal conjunctiva. Excisional biopsies of these areas showed PAM with atypia, with areas of the lesions having full-thickness in situ melanoma. Within 3 months, further nodules of melanoma had developed on the lower eyelid tarsal conjunctiva and the superior limbus. Orbital exenteration was performed. The tarsal conjunctival lesion was a 1.25-mm thick melanoma, and the limbal lesion a 0.48-mm thick melanoma. Melanoma in situ was adjacent to the melanomas, with scattered areas of PAM with atypia. The upper and lower lacrimal canaliculi were normal. Three years later, she presented with a lump in the region of the lacrimal sac of her exenterated orbit. A biopsy was obtained from the lacrimal sac and found to be melanoma. En bloc resection of the medial orbital wall and lateral nasal wall, as well as medial maxilla was performed, with a radial forearm free flap repair. Tumor free margins were obtained. She was given 48 Gy in 20 fractions of postoperative radiotherapy. In 3 further years of follow up, she has remained disease free, with normal MRI and PET scans in late 2013.
DISCUSSION Conjunctival melanoma is most commonly managed with globe-sparing treatments such as local excision, cryotherapy, and antimetabolites.2 For an extensive or widely recurrent disease, orbital exenteration is often used.1 More than 50% of patients will develop local recurrences with conservative
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. 31, No. 3, 2015
treatments, and up to 20% will require orbital exenteration for disease control.9–11 Survival rates of 83% to 86% of patients at 5 years and 69% to 74% of patients at 10 years are found in larger series.1,9,10 Involvement of the LDA by conjunctival melanoma has been rarely reported.2–8 The earliest large series of conjunctival melanoma cases looking at prognostic factors in 256 cases found 8 patients (3.1%) who developed involvement of the nasal cavity and paranasal sinuses.1 This group did not specify involvement of the LDA in these patients, but spread via the LDA from the conjunctiva could well have been the mechanism of nasal and paranasal sinus involvement in some or all of these patients. In another large published series of conjunctival melanoma, 3 of 382 (0.8%) consecutive cases were found to involve the canaliculus or lacrimal sac.2 The authors’ own experience has been somewhat different. Over the period from 1996 to 2013, 52 cases of conjunctival melanoma have been seen at their institution. Of these, 17 cases (32.7%) have undergone orbital exenteration, and of these, 5 cases (29% of the 17 exenterations and 9.6% of cases of conjunctival melanoma) have been found to have involvement of the LDA. This is a much higher rate of LDA involvement than that seen by Shields et al.2 (3 of 382 [0.8%] cases of conjunctival melanoma) and than 3.1% (8 of 256 cases) of nasal and paranasal sinus involvement reported by Paridaens et al.1 The rate of exenteration in the authors’ institution is also significantly higher than that reported in several series (up to 20%),9–11 but similar to that reported by Paridaens et al.12 from the United Kingdom (95/256, 37.1%). The authors can offer no clear explanation for this. It is likely that they deal with a biased sample of cases, with more aggressive and advanced cases referred to them. It is also possible that they have a higher incidence of conjunctival melanoma in their population than elsewhere, although there are no data to support this. Australia and New Zealand have the highest incidence of cutaneous melanoma in the world,13 and there is published data showing a relationship between latitude and incidence of eyelid and conjunctival melanoma.14 This relationship between latitude and sun exposure in a fair skinned population explains the high incidence of cutaneous melanoma in Australia, and could be extrapolated to conjunctival melanoma. It does not, however, explain why the rate of exenteration should be higher in the authors’ institution than elsewhere. It may simply reflect the views of their clinicians regarding the role of exenteration in the management of conjunctival melanoma for which there is no broad evidence base. Only 1 of 5 cases (Case 3) had clinically obvious disease in the lacrimal sac prior to exenteration. Two others were found to have melanoma in the LDA, one with macroscopic disease (Case 1), and the other found only on histopathology (Case 2). In the second case, the lacrimal sac and upper NLD were intentionally included in the exenteration, and extension of melanosis into the residual NLD was secondarily surgically removed, with final clear margins. Cases 4 and 5 presented with mass lesions in the lacrimal sac 2 and 3 years after exenteration. Neither of these patients had excision of the entire lacrimal sac and upper NLD at the time of their exenteration. It is possible that later recurrence in the LDA may have been prevented if this had occurred. How melanoma occurs within the LDA (or nasal cavity) in patients with conjunctival melanoma is unclear. Case 2 had evidence of melanosis within the lacrimal sac and NLD, suggesting that the melanosis may have spread intraepithelially from the conjunctiva or may have involved the LDA as well as the conjunctiva in a “field” change. But both the upper and lower
Lacrimal Drainage Apparatus Melanoma and Conjunctival Melanoma
canaliculi were normal, so there was discontinuity between the conjunctival and lacrimal sac diseases. Within the conjunctiva, there are often areas of discontinuity between areas of PAM. Case 4 developed melanoma within a preexisting nevus, and then a second lesion on the tarsal conjunctiva opposite to the limbal lesion. She later developed lacrimal sac melanoma, and both the upper and lower lacrimal canaliculi were found to be free of melanosis or melanoma in the exenteration specimen. Case 5 was also found to have normal lacrimal canaliculi in the exenteration specimen and later developed lacrimal sac melanoma. In these patients, it is possible that melanoma cells may have implanted in the LDA after exfoliating into the tears. Exfoliated atypical melanocytes have been found in tears.15 Such a means of spread might account for patients with conjunctival melanoma developing melanoma in the nasal cavity, sometimes many years after treatment of their conjunctival melanoma.3,5 It seems highly unlikely that hematogenous or lymphatic spread would lead to melanoma occurring in the LDA or nasal cavity in patients with conjunctival melanoma. Whatever is the means of spread or involvement of the LDA melanoma in patients with conjunctival melanoma, the possibility of disease in the LDA should be considered in all cases. Lacrimal or nasal symptoms should lead to a careful assessment of the lacrimal system and nasal cavity. If orbital exenteration is to be performed for conjunctival melanoma, the lacrimal sac and its surrounding periosteum and the upper NLD at least should be removed en bloc with the orbital contents. The LDA should then be carefully examined for involvement and further treatment guided by this. Adjunctive treatment with radiotherapy may be appropriate where excision margins are narrow, and this applies particularly to cases with medial conjunctival involvement, where the excision margins, even with exenteration, are narrow.12
ACKNOWLEDGMENT The authors thank Dr John D McKenzie for allowing us to include his case, Case 5.
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Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
