CASE REPORT
Multifocal Melanoma of the Conjunctiva in an African American Patient With Neurofibromatosis Type 1 Carlos A. Medina Mendez, MD, and Arun D. Singh, MD
Abstract: A 22-year-old African American female with neurofibromatosis type 1 and multifocal conjunctival melanoma with scleral invasion. The lesion was detected during pregnancy, and after early induction of childbirth, staging by sentinel lymph node biopsy and imaging studies were performed. Systemic evaluation was negative, and the patient was treated with excisional biopsy and cryotherapy. The recurrent multifocal melanoma with scleral extension was treated with brachytherapy by a 2-stage procedure. Follow-up at 2 years reveals the absence of recurrence and 20/25 visual acuity. Key Words: conjunctiva, melanoma, brachytherapy (Cornea 2014;33:750–751)
CASE PRESENTATION A 22-year-old African American female with a recent history of a pigmented conjunctival mass self-referred to the oncology clinic for a second opinion regarding her recently diagnosed recurrent multifocal conjunctival melanoma of the left eye for which exenteration had been advised. She was initially seen 2 month before presenting to our clinic when she complained of an enlarging pigmented mass of her left eye. She was in the third trimester of pregnancy and was encouraged to have an early induction for staging with imaging and sentinel lymph node biopsy. After the early induction, negative computed tomography (CT) scan, positron emission tomography (PET) scan, and negative sentinel lymph node biopsy, she was treated with excision and cryotherapy. Her medical history is significant for neurofibromatosis type 1 (NF-1) with cafe au lait spots and neurofibromas but no history of melanoma. Her mother also carried the diagnosis of NF-1. She denied any surgical, ocular, or social history of significance. At presentation to our clinic, the visual acuity was 20/20 in the right eye and 20/25 in the left. External examination confirmed cafe au lait spots, neurofibromas in the face and neck but no palpable lymphadenopathy (Fig. 1A). Slit-lamp examination of the right eye was remarkable for Lisch nodReceived for publication February 3, 2014; revision received February 12, 2014; accepted February 13, 2014. Published online ahead of print April 2, 2014. From the Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH. The authors have no funding or conflicts of interest to disclose. Reprints: Arun D. Singh, Department of Ophthalmic Oncology, Cleveland Clinic Cole Eye Institute, 9500 Euclid Ave, Desk i32, Cleveland, OH 44195 (e-mail [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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ules. Examination of the left eye revealed an amelanotic nodular lesion nasally at the 8:30 o’clock position. This lesion measured approximately 3.5 · 2.5 · 1.5 mm in size. Melanotic melanoma measuring 6 · 3 · 0.5 was observed from the 12–5 o’clock position. Scattered areas of suspected primary acquired melanosis were seen on the nasal bulbar conjunctiva and along the left lower palpebral conjunctiva and the temporal and inferonasal cornea (Fig. 1B, C). Lisch nodules were also observed. Fundus examination of both eyes was unremarkable. Ultrasound biomicroscopy confirmed scleral extension of the nasal amelanotic lesion (Fig. 1D). The patient underwent a second excisional biopsy of the corneo–conjunctival tumor with 2-mm conjunctival margins. Alcohol epitheliectomy, deep corneo–scleral dissection, cryotherapy, and a map biopsy were also performed. Biopsies of the main tumors confirmed the presence of melanoma with positive deep margins involving the limbus and sclera. Map biopsy ruled out the presence of primary acquired melanosis. The patient was counseled about the clinical findings. To avoid exenteration, the decision was made to proceed with plaque brachytherapy to the scleral bed of amelanotic and melanotic melanoma. A 12-mm Collaborative Ocular Melanoma Study (COMS) plaque was placed at the 8-o’clock meridian and adjusted to cover the entire lesion. Calculations were set to deliver 85 Gy at a depth of 3 mm over 45 hours. Tutoplast (IOP Ophthalmics) was used to cover the plaque, and a temporal tarsorrhaphy was performed. A second procedure was performed, and the plaque was moved to cover the area of temporal involvement. The same dose to the apex was prescribed over 48 hours. No postoperative complications were noted. The visual acuity at month 1 was 20/25, and pigment regression was noted. At 2-year follow-up, the patient remains phakic without signs of limbal stem cell deficiency, significant cataract, or tumor recurrence (Fig. 2).
DISCUSSION Von Recklinghausen neurofibromatosis (NF-1) is one of the most common inherited human disorders with an occurrence of approximately 1 in 3000 births. It is characterized by benign and malignant tumors involving multiple organ systems. A complication of NF-1 is the development of disorders of neural crest–derived neoplasms. Although a causal association has not been established, the association between NF-1 and melanoma (cutaneous, conjunctival, and choroidal) has been speculated.1 The relationship with the growth of melanocytic conjunctival lesions during pregnancy has also been Cornea Volume 33, Number 7, July 2014
Cornea Volume 33, Number 7, July 2014
Multifocal Melanoma of the Conjunctiva
FIGURE 1. A, Neurofibromas on the neck. B, Nasal amelanotic and temporal pigmented recurrent melanoma. C, Ultrasound biomicroscopy of the amelanotic lesion confirms scleral invasion (arrow). D, Hematoxylin and eosin stain at ·40 magnification. Atypical melanocytes are present within the scleral section. Sections along the deep surgical margin were positive for Melan-A stain (not shown).
established. In fact, Bredow et al2 reported that both nevi and melanoma express hormone receptors (estrogen and/or progesterone), which could explain why these tumors can alter their appearance under hormonal changes. Our patient underwent sentinel lymph node biopsy.3 Evidence is controversial, however some experts recommend it be considered for staging of patients with high-risk conjunctival melanoma, especially those with a nonlimbal location or conjunctival melanoma that is of thickness $2 mm. Standard treatment of conjunctival melanoma includes complete excision with clear surgical margins and adjuvant
cryotherapy.4 Management of scleral invasion is challenging.5 Untreated residual melanoma may extend intraocularly; topical chemotherapy such as mitomycin eye drops is not likely to be effective, and scleral resection of microscopic disease may lead to inadvertent uveal complications. Such cases have been treated with brachytherapy with excellent local control.6 Brachytherapy delivered to our patient was unique because 2 areas of focal scleral extension were treated. Histopathology including immunohistochemistry confirmed that these lesions did not coalesce. A single plaque could be used sequentially with time adjusted to deliver the desired dose to the tumor depth. At 2-year follow-up, the patient remains phakic without signs of limbal stem cell deficiency, significant cataract, or tumor recurrence. Continued biannual surveillance is planned. REFERENCES
FIGURE 2. External photograph of the treated eye, 2 years after the treatment.
2014 Lippincott Williams & Wilkins
1. Friedman SM, Margo CE. Choroidal melanoma and neurofibromatosis type 1. Arch Ophthalmol. 1998;116:694–695. 2. Bredow L, Stutzel L, Bohringer D, et al. Progesterone and estrogen receptors in conjunctival melanoma and nevi. Graefes Arch Clin Exp Ophthalmol. 2014;252:359–365. 3. Esmaeli B. Regional lymph node assessment for conjunctival melanoma: sentinel lymph node biopsy and positron emission tomography. Br J Ophthalmol. 2008;92:443–445. 4. Singh AD, Campos OE, Rhatigan RM, et al. Conjunctival melanoma in the black population. Surv Ophthalmol. 1998;43:127–133. 5. Aronow ME, Singh AD. Radiation therapy: conjunctival and eyelid tumors. Dev Ophthalmol. 2013;52:85–93. 6. Karim R, Conway RM. Conservative resection and adjuvant plaque brachytherapy for early-stage conjunctival melanoma. Clin Exp Ophthalmol. 2011;39:293–298.
www.corneajrnl.com |
751
Multifocal Melanoma of the Conjunctiva in an African American Patient With Neurofibromatosis Type 1 Carlos A. Medina Mendez, MD, and Arun D. Singh, MD
Abstract: A 22-year-old African American female with neurofibromatosis type 1 and multifocal conjunctival melanoma with scleral invasion. The lesion was detected during pregnancy, and after early induction of childbirth, staging by sentinel lymph node biopsy and imaging studies were performed. Systemic evaluation was negative, and the patient was treated with excisional biopsy and cryotherapy. The recurrent multifocal melanoma with scleral extension was treated with brachytherapy by a 2-stage procedure. Follow-up at 2 years reveals the absence of recurrence and 20/25 visual acuity. Key Words: conjunctiva, melanoma, brachytherapy (Cornea 2014;33:750–751)
CASE PRESENTATION A 22-year-old African American female with a recent history of a pigmented conjunctival mass self-referred to the oncology clinic for a second opinion regarding her recently diagnosed recurrent multifocal conjunctival melanoma of the left eye for which exenteration had been advised. She was initially seen 2 month before presenting to our clinic when she complained of an enlarging pigmented mass of her left eye. She was in the third trimester of pregnancy and was encouraged to have an early induction for staging with imaging and sentinel lymph node biopsy. After the early induction, negative computed tomography (CT) scan, positron emission tomography (PET) scan, and negative sentinel lymph node biopsy, she was treated with excision and cryotherapy. Her medical history is significant for neurofibromatosis type 1 (NF-1) with cafe au lait spots and neurofibromas but no history of melanoma. Her mother also carried the diagnosis of NF-1. She denied any surgical, ocular, or social history of significance. At presentation to our clinic, the visual acuity was 20/20 in the right eye and 20/25 in the left. External examination confirmed cafe au lait spots, neurofibromas in the face and neck but no palpable lymphadenopathy (Fig. 1A). Slit-lamp examination of the right eye was remarkable for Lisch nodReceived for publication February 3, 2014; revision received February 12, 2014; accepted February 13, 2014. Published online ahead of print April 2, 2014. From the Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH. The authors have no funding or conflicts of interest to disclose. Reprints: Arun D. Singh, Department of Ophthalmic Oncology, Cleveland Clinic Cole Eye Institute, 9500 Euclid Ave, Desk i32, Cleveland, OH 44195 (e-mail [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
750
| www.corneajrnl.com
ules. Examination of the left eye revealed an amelanotic nodular lesion nasally at the 8:30 o’clock position. This lesion measured approximately 3.5 · 2.5 · 1.5 mm in size. Melanotic melanoma measuring 6 · 3 · 0.5 was observed from the 12–5 o’clock position. Scattered areas of suspected primary acquired melanosis were seen on the nasal bulbar conjunctiva and along the left lower palpebral conjunctiva and the temporal and inferonasal cornea (Fig. 1B, C). Lisch nodules were also observed. Fundus examination of both eyes was unremarkable. Ultrasound biomicroscopy confirmed scleral extension of the nasal amelanotic lesion (Fig. 1D). The patient underwent a second excisional biopsy of the corneo–conjunctival tumor with 2-mm conjunctival margins. Alcohol epitheliectomy, deep corneo–scleral dissection, cryotherapy, and a map biopsy were also performed. Biopsies of the main tumors confirmed the presence of melanoma with positive deep margins involving the limbus and sclera. Map biopsy ruled out the presence of primary acquired melanosis. The patient was counseled about the clinical findings. To avoid exenteration, the decision was made to proceed with plaque brachytherapy to the scleral bed of amelanotic and melanotic melanoma. A 12-mm Collaborative Ocular Melanoma Study (COMS) plaque was placed at the 8-o’clock meridian and adjusted to cover the entire lesion. Calculations were set to deliver 85 Gy at a depth of 3 mm over 45 hours. Tutoplast (IOP Ophthalmics) was used to cover the plaque, and a temporal tarsorrhaphy was performed. A second procedure was performed, and the plaque was moved to cover the area of temporal involvement. The same dose to the apex was prescribed over 48 hours. No postoperative complications were noted. The visual acuity at month 1 was 20/25, and pigment regression was noted. At 2-year follow-up, the patient remains phakic without signs of limbal stem cell deficiency, significant cataract, or tumor recurrence (Fig. 2).
DISCUSSION Von Recklinghausen neurofibromatosis (NF-1) is one of the most common inherited human disorders with an occurrence of approximately 1 in 3000 births. It is characterized by benign and malignant tumors involving multiple organ systems. A complication of NF-1 is the development of disorders of neural crest–derived neoplasms. Although a causal association has not been established, the association between NF-1 and melanoma (cutaneous, conjunctival, and choroidal) has been speculated.1 The relationship with the growth of melanocytic conjunctival lesions during pregnancy has also been Cornea Volume 33, Number 7, July 2014
Cornea Volume 33, Number 7, July 2014
Multifocal Melanoma of the Conjunctiva
FIGURE 1. A, Neurofibromas on the neck. B, Nasal amelanotic and temporal pigmented recurrent melanoma. C, Ultrasound biomicroscopy of the amelanotic lesion confirms scleral invasion (arrow). D, Hematoxylin and eosin stain at ·40 magnification. Atypical melanocytes are present within the scleral section. Sections along the deep surgical margin were positive for Melan-A stain (not shown).
established. In fact, Bredow et al2 reported that both nevi and melanoma express hormone receptors (estrogen and/or progesterone), which could explain why these tumors can alter their appearance under hormonal changes. Our patient underwent sentinel lymph node biopsy.3 Evidence is controversial, however some experts recommend it be considered for staging of patients with high-risk conjunctival melanoma, especially those with a nonlimbal location or conjunctival melanoma that is of thickness $2 mm. Standard treatment of conjunctival melanoma includes complete excision with clear surgical margins and adjuvant
cryotherapy.4 Management of scleral invasion is challenging.5 Untreated residual melanoma may extend intraocularly; topical chemotherapy such as mitomycin eye drops is not likely to be effective, and scleral resection of microscopic disease may lead to inadvertent uveal complications. Such cases have been treated with brachytherapy with excellent local control.6 Brachytherapy delivered to our patient was unique because 2 areas of focal scleral extension were treated. Histopathology including immunohistochemistry confirmed that these lesions did not coalesce. A single plaque could be used sequentially with time adjusted to deliver the desired dose to the tumor depth. At 2-year follow-up, the patient remains phakic without signs of limbal stem cell deficiency, significant cataract, or tumor recurrence. Continued biannual surveillance is planned. REFERENCES
FIGURE 2. External photograph of the treated eye, 2 years after the treatment.
2014 Lippincott Williams & Wilkins
1. Friedman SM, Margo CE. Choroidal melanoma and neurofibromatosis type 1. Arch Ophthalmol. 1998;116:694–695. 2. Bredow L, Stutzel L, Bohringer D, et al. Progesterone and estrogen receptors in conjunctival melanoma and nevi. Graefes Arch Clin Exp Ophthalmol. 2014;252:359–365. 3. Esmaeli B. Regional lymph node assessment for conjunctival melanoma: sentinel lymph node biopsy and positron emission tomography. Br J Ophthalmol. 2008;92:443–445. 4. Singh AD, Campos OE, Rhatigan RM, et al. Conjunctival melanoma in the black population. Surv Ophthalmol. 1998;43:127–133. 5. Aronow ME, Singh AD. Radiation therapy: conjunctival and eyelid tumors. Dev Ophthalmol. 2013;52:85–93. 6. Karim R, Conway RM. Conservative resection and adjuvant plaque brachytherapy for early-stage conjunctival melanoma. Clin Exp Ophthalmol. 2011;39:293–298.
www.corneajrnl.com |
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