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Primary Choroidal Melanoma in Phakomatosis Pigmentovascularis IIa
Primary Choroidal Melanoma in Phakomatosis Pigmentovascularis IIa Hoai Viet Tran, MD, Leonidas Zografos, MD Purpose: To describe a previously unreported association between phakomatosis pigmentovascularis (PPV) IIa and primary choroidal melanoma. Design: Case series. Participants: Three patients with PPV type IIa and choroidal melanoma. Results: Nevus flammeus was present unilaterally in each patient, involving the hemiface, the hemithorax, or both. Ocular melanocytosis also was present unilaterally in all patients involving the sclera, the iris, the choroid, the distribution of the trigeminal nerve, or a combination thereof. Renal cysts were noted in patient 1, and a nevus anemicus of the neck was noted in patient 3. A unilateral choroidal melanoma was detected in each of these 3 patients, in each patient involving the same eye in which melanocytosis had been seen. No metastases were found in any patient. Conclusions: Clinicians should be aware of the possibility that PPV, and in particular that occurring in patients with ocular melanocytosis, can be associated with choroidal melanoma. Ophthalmology 2005;112: 1232–1235 © 2005 by the American Academy of Ophthalmology.
The combination of vascular and melanocytic nevi in the same patient, termed phakomatosis pigmentovascularis (PPV), was first described in 1947 by Ota et al.1 Phakomatosis pigmentovascularis is the result of developmental abnormalities of both neural crest-derived vasomotor nerves and melanocytes.2 Phakomatosis pigmentovascularis has been classified into 5 types (Table 1),2 each of which may occur as a localized (subtype a) or systemic (subtype b) condition, based on the presence or absence of extracutaneous manifestations. Type II is the most common variant of PPV, and in most patients with systemic involvement, alterations indicative of Sturge-Weber syndrome or KlippelTrenaunay-Weber syndrome have been observed.3 Herein we describe 3 patients with PPV IIa. Each case of PPV IIa occurred in a white patient, was characterized by the presence of nevus flammeus and ocular melanocytosis, and was accompanied by adult-onset primary choroidal melanoma. To our knowledge, this association has not been reported previously.
Originally received: November 3, 2004. Accepted: February 9, 2005. Manuscript no. 2004-255. From the Jules Gonin University Eye Hospital, Lausanne, Switzerland. Presented at: American Academy of Ophthalmology Annual Meeting, October, 2004; New Orleans, Louisiana. The authors have no financial interest in the materials or methods used in the study. Supported in part by the Asile des Aveugles Foundation, Lausanne, Switzerland. Correspondence to Leonidas Zografos, MD, Hospital Jules Gonin, 15, Av. De France, 1004 Lausanne, VD, Switzerland. E-mail: leonidas.zografos@ ophtal.vd.ch.
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© 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
Case Reports Patient 1 A 35-year-old-woman was referred to the ocular oncology unit of Jules Gonin University Eye Hospital (Lausanne, Switzerland) with a 1-month history of decreased visual acuity in the left eye. General physical examination revealed the presence of a nevus flammeus involving the left side of the body (Fig 1A). Visual acuity was 20/33 in the right eye and 20/20 in the left eye. Slit-lamp examination revealed melanocytosis and hyperpigmentation of the iris of the left eye (Fig 1B). Intraocular pressure was of 16 mmHg in each eye. There was a paramacular choroidal melanoma of the left eye with an overlying exudative retinal detachment threatening the macular region (Fig 1C). B-scan ultrasonography showed the lesion to be 2.7 mm in thickness. Because of the diagnosis of PPV, general imaging was performed to exclude any other lesions and was relevant for the finding of 3 cysts in the left kidney, noted on low-frequency ultrasonography. The patient underwent an uncomplicated course of proton beam radiation therapy to the right eye, receiving a total dose of 60 Gy (4 fractions of 15 Gy over 4 days). The 5-year follow-up showed a cicatricial lesion that measured 1.7 mm in thickness; visual acuity was 20/20.
Patient 2 A 32-year-old man was referred to our institution for a suspected choroidal melanoma of the left eye. General physical examination revealed a unilateral facial nevus flammeus on the left side involving the upper lid, the nose, the cheek, and the mouth (Fig 2A). Visual acuity was 20/20 in each eye and intraocular pressure was 15 mmHg. Slit-lamp examination revealed a slight ocular melanocytosis of the left eye (Fig 2B). In this eye, a pigmented mass was invading the ciliary body (Fig 2C) and was located in the temporal inferior quadrant in a segmental area of ocular melanocytosis. The vitreous showed some local pigment dispersion. On B-scan ultrasonography, the tumor was 7.6 mm thick. The patient ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2005.02.019
Tran and Zografos 䡠 PPV IIa and Melanoma Table 1. Classification of Phakomatosis Pigmentovascularis Type
Features
I a, b II a, b
Nevus flammeus and nevus pigmentosus et verrucosus Nevus flammeus and nevus fuscoceruleus, without nevus anemicus Nevus flammeus and nevus spilus, without nevus anemicus Nevus flammeus and nevus spilus and mongolian spots, without nevus anemicus Cutis marmorata telangiectatica congenita and mongolian spot
III a, b IV a, b V a, b
a ⫽ cutaneous involvement only; b ⫽ cutaneous and systemic involvement.
underwent an uncomplicated course of proton beam radiation therapy for a total dose of 60 Gy (4 fractions of 15 Gy over 4 days). Follow-up 18 months after radiation therapy revealed the tumor thickness to be reduced to 4.8 mm, and visual acuity remained 20/20.
Patient 3 A 62-year-old woman was first seen with a 3-week history of flashes of light in the left eye and was referred to our institution because of a suspected choroidal melanoma of the left eye. Past medical history was relevant for a bilateral ductal breast carcinoma treated surgically (left mastectomy 17 years previously and right mastectomy 3 years previously), and an ovarian tumor (of unknown type) treated by a hysterectomy and bilateral oophorectomy 13 years previously. General physical examination revealed a nevus flammeus on the left half side of the thorax, a nevus anemicus of the neck (which results from locally increased vascular reactivity to catecholamines with normal vascular structures), and a nevus of Ota with accompanying melanocytosis along the distribution of the trigeminal nerve, up to the larynx and with bulbar involvement (Fig 3A). Visual acuity was 20/20 in each eye. Slit-lamp examination revealed marked bilateral ocular melanocytosis (Fig 3B), but the anterior segments and irides were normal. Intraocular pressure was 16 mmHg in each eye. On ophthalmoscopy, the left eye showed a pigmented tumor in the inferior nasal quadrant with an associated inferior exudative retinal detachment (Fig 3C). Primary extraocular lesion was excluded. On B-scan ultrasonography, the tumor was 6.1 mm thick; fluorescein and indocyanine green angiography showed a vascularized tumor. The patient underwent an uncomplicated course of proton beam radiation therapy for a total dose of 60 Gy (4 fractions of 15 Gy over 4 days). Follow-up examination 2 years after radiation therapy revealed a cicatricial lesion, a visual acuity of 20/22, and a decrease in choroidal thickening to 4.5 mm.
Discussion Phakomatosis pigmentovascularis is characterized by a combination of cutaneous or systemic vascular malformations of the capillary type and dermal melanocytic nevus and is found almost exclusively in Asians. The most common vascular abnormality of PPV type II is nevus flammeus, in association with Sturge-Weber or Klippel-TrenaunayWeber syndrome. Other vascular components that have been described are hypoplasia of the portal veins,4 hypoplasia of the inferior cava vein,5 renal angiomas,6 and Takayasu arteritis.7
Anomalies of dermal pigmentation may occur in 4 different variants: nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris), nevus of Ito (nevus fuscoceruleus acromiodeltoideus), nevus fuscoceruleus zygomaticus, or mongolian spot. Nevus of Ota is characterized by hyperpigmentation of the facial skin in the distribution of the ophthalmic, maxillary, and on occasion, the mandibular division of the trigeminal nerve. Approximately 30% of these patients also have ocular hyperpigmentation, in which case the pigmentary lesion is called oculodermal melanocytosis and can involve episcleral, scleral, corneal stromal, trabecular meshwork, anterior lens surface pigment deposits, and choroidal melanocytosis.8 Other ocular alterations associated with PPV type II are iris hamartomas and mamillations9 and congenital glaucoma.10 The initial concept of phakomatosis, introduced during the Oxford Ophthalmological Congress in 1923 by Van der Hoeve to classify hereditary diseases characterized by tumorous growths arising de novo in disparate organ systems in later life,11 included recognition that some growths may become malignant and that there may be an inborn predisposition for malignancy to develop in individuals of these families. Although malignant transformation is known to be a potential complication of PPV, such as malignant polyposis of the colon or multiple granular cell tumors,12,13 this is the first time that it has been associated with choroidal melanoma and, in 1 of our patients, with ductal breast and ovarian cancer. The pigmented lesion in PPV is characterized histologically by dermal melanocytosis without an increase in epidermal melanocytosis.14 This finding is similar to Mongolian spot but not to nevus of Ota or Ito, which are characterized by an increase in epidermal melanocytes and the presence of dermal melanocytes.15 A genetic anomaly or a pathogenic factor can cause some clones of melanoblasts to proliferate in a malignant form, resulting in melanoma. However, all of our patients were white and had ocular melanocytosis at presentation, and both of these features are common risks factors for choroidal melanoma. The association between ocular melanocytosis and uveal melanoma is well established among white persons.16 –18 Further, our third patient showed a genetic inclination to the development of tumorous processes, and data on a small subgroup of patients with breast cancer and melanoma suggest that there may be a genetic association in some patients. The Breast Cancer Linkage Consortium19 found a statistically significant increased in the risk of cutaneous melanoma among patients with BRCA2 loss of function, with a risk ratio of 2.58. In addition, recent studies provide evidence that a BRCA2 mutation may be a predisposing gene for ocular melanoma.20,21 Nevertheless to our knowledge, fewer than 15 patients with PPV and ocular melanocytosis have been reported,1,7,9,14,15,22,23 and none have experienced ocular melanoma. However, most of these patients were not white. We therefore suggest that the occurrence of melanoma in our case series in large part is the result of ocular melanocytosis. Even so, we cannot exclude the possibility that the pathogenesis of PPV may play some role in ocular melanoma. In conclusion, we report 3 cases of PPV associated with
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Figure 1. Patient 1. A, Extensive nevus flammeus with a midline separation on the thorax and abdomen. B, Ocular melanocytosis and iris hyperpigmentation. C, Fundus photograph showing a choroidal melanoma surrounded by a retinal exudative detachment involving the macula.
Figure 2. Patient 2. A, Unilateral facial and periorbital nevus flammeus. B, Ocular melanocytosis. C, Fundus photograph showing peripheral choroidal melanoma involving the ciliary body.
Figure 3. Patient 3. A, Nevus anemicus of the neck (arrowhead) and thoracic nevus flammeus (asterisk). B, Oculodermal melanocytosis. C, Fundus photograph showing achoroidal melanoma in the inferior nasal quadrant and an associated exudative retinal detachment.
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Tran and Zografos 䡠 PPV IIa and Melanoma primary choroidal melanoma. Although it is generally accepted that ocular melanocytosis and mutated BRAC2 locus promotes an increased risk for melanoma, we believe that melanoma may be a true association with PPV. We suggest that PPV patients with oculodermal melanocytosis should be followed up carefully for the development of uveal melanoma.
References 1. Ota M, Kawamura T, Ito N. Phakomatosis pigmentovascularis Ota [in Japanese]. Jpn J Dermatol 1947;52:1–3. 2. Enjolras O, Mulliken JB. Vascular malformations. In: Harper J, Oranje AP, Prose NS, eds. Textbook of Pediatric Dermatology. Vol. 2. Oxford, United Kingdom: Blackwell Science Ltd.; 2000:975–96. 3. Furukawa T, Igata A, Toyokura Y, Ikeda S. Sturge-Weber and Klippel-Trenaunay syndrome with nevus of Ota and Ito. Arch Dermatol 1970;102:640 –5. 4. Kaise M, Watanabe A, Kobayashi Y. A case of phacomatosis pigmentovascularis accompanied with esophageal varices due to hypoplasia of the portal veins. Gastroenterol Jpn 1992;27: 546 –9. 5. Park JG, Roh KY, Lee HJ, et al. Phakomatosis pigmentovascularis IIb with hypoplasia of the inferior vena cava and the right iliac and femoral veins causing recalcitrant stasis leg ulcers. J Am Acad Dermatol 2003;49(suppl):S167–9. 6. Di Landro A, Tadini GL, Marchesi L, Cainelli T. Phakomatosis pigmentovascularis: a new case with renal angiomas and some considerations about the classification. Pediatr Dermatol 1999;16:25–30. 7. Reinke RT, Haber K, Josselson A. Ota nevus, multiple hemangiomas, and Takayasu arteritis. Arch Dermatol 1974;110: 447–50. 8. Gonder JR, Nichol J, Augsburger JJ, Shields JA. Ocular and oculodermal melanocytosis. Can J Ophthalmol 1985;20:176 – 8. 9. Gilliam AC, Ragge NK, Perez MI, Bolognia JL. Phakomatosis pigmentovascularis type IIb with iris mammillations. Arch Dermatol 1993;129:340 –2.
10. Teekhasaenee C, Ritch R. Glaucoma in phakomatosis pigmentovascularis. Ophthalmology 1997;104:150 –7. 11. Van der Hoeve J. Eye symptoms in tuberous sclerosis of the brain and in Recklinghausen’s disease. Trans Ophthalmol Soc U K 1923;43:534 – 41. 12. Horio T, Ogawa M. Pigmentovascular nevus. Arch Dermatol 1973;107:463– 4. 13. Guiglia MC, Prendiville JS. Multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child. J Am Acad Dermatol 1991;24:359 – 63. 14. Ortonne JP, Floret D, Coiffet J, Cottin X. Ocular and cutaneous melanosis associated with the Sturge-Weber syndrome: clinical, histological, and ultrastructural studies of one case [in French]. Ann Dermatol Venereol 1978;105:1019 –31. 15. Ruiz-Maldonado R, Tamayo L, Laterza AM, et al. Phacomatosis pigmentovascularis: a new syndrome? Report of four cases. Pediatr Dermatol 1987;4:189 –96. 16. Gonder JR, Shields JA, Albert DM, et al. Uveal malignant melanoma associated with ocular and oculodermal melanocytosis. Ophthalmology 1982;89:953– 60. 17. Velazquez N, Jones IS. Ocular and oculodermal melanocytosis associated with uveal melanoma. Ophthalmology 1983;90: 1472– 6. 18. Singh AD, De Potter P, Fijal BA, et al. Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology 1998;105:195– 8. 19. Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91:1310 – 6. 20. Sinilnikova OM, Egan KM, Quinn JL, et al. Germline BRCA2 sequence variants in patients with ocular melanoma. Int J Cancer 1999;82:325– 8. 21. Scott RJ, Vajdic CM, Armstrong BK, et al. BRCA2 mutations in a population-based series of patients with ocular melanoma. Int J Cancer 2002;102:188 –91. 22. Kitamura W, Iwai M, Sakamoto K. A case of phakomatosis pigmentovascularis. Rinsho Hinfuka 1981;35:399 – 405. 23. Saricaoglu MS, Guven D, Karakurt A, et al. An unusual case of Sturge-Weber syndrome in association with phakomatosis pigmentovascularis and Klippel-Trenaunay-Weber syndrome. Retina 2002;22:368 –71.
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The combination of vascular and melanocytic nevi in the same patient, termed phakomatosis pigmentovascularis (PPV), was first described in 1947 by Ota et al.1 Phakomatosis pigmentovascularis is the result of developmental abnormalities of both neural crest-derived vasomotor nerves and melanocytes.2 Phakomatosis pigmentovascularis has been classified into 5 types (Table 1),2 each of which may occur as a localized (subtype a) or systemic (subtype b) condition, based on the presence or absence of extracutaneous manifestations. Type II is the most common variant of PPV, and in most patients with systemic involvement, alterations indicative of Sturge-Weber syndrome or KlippelTrenaunay-Weber syndrome have been observed.3 Herein we describe 3 patients with PPV IIa. Each case of PPV IIa occurred in a white patient, was characterized by the presence of nevus flammeus and ocular melanocytosis, and was accompanied by adult-onset primary choroidal melanoma. To our knowledge, this association has not been reported previously.
Originally received: November 3, 2004. Accepted: February 9, 2005. Manuscript no. 2004-255. From the Jules Gonin University Eye Hospital, Lausanne, Switzerland. Presented at: American Academy of Ophthalmology Annual Meeting, October, 2004; New Orleans, Louisiana. The authors have no financial interest in the materials or methods used in the study. Supported in part by the Asile des Aveugles Foundation, Lausanne, Switzerland. Correspondence to Leonidas Zografos, MD, Hospital Jules Gonin, 15, Av. De France, 1004 Lausanne, VD, Switzerland. E-mail: leonidas.zografos@ ophtal.vd.ch.
1232
© 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
Case Reports Patient 1 A 35-year-old-woman was referred to the ocular oncology unit of Jules Gonin University Eye Hospital (Lausanne, Switzerland) with a 1-month history of decreased visual acuity in the left eye. General physical examination revealed the presence of a nevus flammeus involving the left side of the body (Fig 1A). Visual acuity was 20/33 in the right eye and 20/20 in the left eye. Slit-lamp examination revealed melanocytosis and hyperpigmentation of the iris of the left eye (Fig 1B). Intraocular pressure was of 16 mmHg in each eye. There was a paramacular choroidal melanoma of the left eye with an overlying exudative retinal detachment threatening the macular region (Fig 1C). B-scan ultrasonography showed the lesion to be 2.7 mm in thickness. Because of the diagnosis of PPV, general imaging was performed to exclude any other lesions and was relevant for the finding of 3 cysts in the left kidney, noted on low-frequency ultrasonography. The patient underwent an uncomplicated course of proton beam radiation therapy to the right eye, receiving a total dose of 60 Gy (4 fractions of 15 Gy over 4 days). The 5-year follow-up showed a cicatricial lesion that measured 1.7 mm in thickness; visual acuity was 20/20.
Patient 2 A 32-year-old man was referred to our institution for a suspected choroidal melanoma of the left eye. General physical examination revealed a unilateral facial nevus flammeus on the left side involving the upper lid, the nose, the cheek, and the mouth (Fig 2A). Visual acuity was 20/20 in each eye and intraocular pressure was 15 mmHg. Slit-lamp examination revealed a slight ocular melanocytosis of the left eye (Fig 2B). In this eye, a pigmented mass was invading the ciliary body (Fig 2C) and was located in the temporal inferior quadrant in a segmental area of ocular melanocytosis. The vitreous showed some local pigment dispersion. On B-scan ultrasonography, the tumor was 7.6 mm thick. The patient ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2005.02.019
Tran and Zografos 䡠 PPV IIa and Melanoma Table 1. Classification of Phakomatosis Pigmentovascularis Type
Features
I a, b II a, b
Nevus flammeus and nevus pigmentosus et verrucosus Nevus flammeus and nevus fuscoceruleus, without nevus anemicus Nevus flammeus and nevus spilus, without nevus anemicus Nevus flammeus and nevus spilus and mongolian spots, without nevus anemicus Cutis marmorata telangiectatica congenita and mongolian spot
III a, b IV a, b V a, b
a ⫽ cutaneous involvement only; b ⫽ cutaneous and systemic involvement.
underwent an uncomplicated course of proton beam radiation therapy for a total dose of 60 Gy (4 fractions of 15 Gy over 4 days). Follow-up 18 months after radiation therapy revealed the tumor thickness to be reduced to 4.8 mm, and visual acuity remained 20/20.
Patient 3 A 62-year-old woman was first seen with a 3-week history of flashes of light in the left eye and was referred to our institution because of a suspected choroidal melanoma of the left eye. Past medical history was relevant for a bilateral ductal breast carcinoma treated surgically (left mastectomy 17 years previously and right mastectomy 3 years previously), and an ovarian tumor (of unknown type) treated by a hysterectomy and bilateral oophorectomy 13 years previously. General physical examination revealed a nevus flammeus on the left half side of the thorax, a nevus anemicus of the neck (which results from locally increased vascular reactivity to catecholamines with normal vascular structures), and a nevus of Ota with accompanying melanocytosis along the distribution of the trigeminal nerve, up to the larynx and with bulbar involvement (Fig 3A). Visual acuity was 20/20 in each eye. Slit-lamp examination revealed marked bilateral ocular melanocytosis (Fig 3B), but the anterior segments and irides were normal. Intraocular pressure was 16 mmHg in each eye. On ophthalmoscopy, the left eye showed a pigmented tumor in the inferior nasal quadrant with an associated inferior exudative retinal detachment (Fig 3C). Primary extraocular lesion was excluded. On B-scan ultrasonography, the tumor was 6.1 mm thick; fluorescein and indocyanine green angiography showed a vascularized tumor. The patient underwent an uncomplicated course of proton beam radiation therapy for a total dose of 60 Gy (4 fractions of 15 Gy over 4 days). Follow-up examination 2 years after radiation therapy revealed a cicatricial lesion, a visual acuity of 20/22, and a decrease in choroidal thickening to 4.5 mm.
Discussion Phakomatosis pigmentovascularis is characterized by a combination of cutaneous or systemic vascular malformations of the capillary type and dermal melanocytic nevus and is found almost exclusively in Asians. The most common vascular abnormality of PPV type II is nevus flammeus, in association with Sturge-Weber or Klippel-TrenaunayWeber syndrome. Other vascular components that have been described are hypoplasia of the portal veins,4 hypoplasia of the inferior cava vein,5 renal angiomas,6 and Takayasu arteritis.7
Anomalies of dermal pigmentation may occur in 4 different variants: nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris), nevus of Ito (nevus fuscoceruleus acromiodeltoideus), nevus fuscoceruleus zygomaticus, or mongolian spot. Nevus of Ota is characterized by hyperpigmentation of the facial skin in the distribution of the ophthalmic, maxillary, and on occasion, the mandibular division of the trigeminal nerve. Approximately 30% of these patients also have ocular hyperpigmentation, in which case the pigmentary lesion is called oculodermal melanocytosis and can involve episcleral, scleral, corneal stromal, trabecular meshwork, anterior lens surface pigment deposits, and choroidal melanocytosis.8 Other ocular alterations associated with PPV type II are iris hamartomas and mamillations9 and congenital glaucoma.10 The initial concept of phakomatosis, introduced during the Oxford Ophthalmological Congress in 1923 by Van der Hoeve to classify hereditary diseases characterized by tumorous growths arising de novo in disparate organ systems in later life,11 included recognition that some growths may become malignant and that there may be an inborn predisposition for malignancy to develop in individuals of these families. Although malignant transformation is known to be a potential complication of PPV, such as malignant polyposis of the colon or multiple granular cell tumors,12,13 this is the first time that it has been associated with choroidal melanoma and, in 1 of our patients, with ductal breast and ovarian cancer. The pigmented lesion in PPV is characterized histologically by dermal melanocytosis without an increase in epidermal melanocytosis.14 This finding is similar to Mongolian spot but not to nevus of Ota or Ito, which are characterized by an increase in epidermal melanocytes and the presence of dermal melanocytes.15 A genetic anomaly or a pathogenic factor can cause some clones of melanoblasts to proliferate in a malignant form, resulting in melanoma. However, all of our patients were white and had ocular melanocytosis at presentation, and both of these features are common risks factors for choroidal melanoma. The association between ocular melanocytosis and uveal melanoma is well established among white persons.16 –18 Further, our third patient showed a genetic inclination to the development of tumorous processes, and data on a small subgroup of patients with breast cancer and melanoma suggest that there may be a genetic association in some patients. The Breast Cancer Linkage Consortium19 found a statistically significant increased in the risk of cutaneous melanoma among patients with BRCA2 loss of function, with a risk ratio of 2.58. In addition, recent studies provide evidence that a BRCA2 mutation may be a predisposing gene for ocular melanoma.20,21 Nevertheless to our knowledge, fewer than 15 patients with PPV and ocular melanocytosis have been reported,1,7,9,14,15,22,23 and none have experienced ocular melanoma. However, most of these patients were not white. We therefore suggest that the occurrence of melanoma in our case series in large part is the result of ocular melanocytosis. Even so, we cannot exclude the possibility that the pathogenesis of PPV may play some role in ocular melanoma. In conclusion, we report 3 cases of PPV associated with
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Figure 1. Patient 1. A, Extensive nevus flammeus with a midline separation on the thorax and abdomen. B, Ocular melanocytosis and iris hyperpigmentation. C, Fundus photograph showing a choroidal melanoma surrounded by a retinal exudative detachment involving the macula.
Figure 2. Patient 2. A, Unilateral facial and periorbital nevus flammeus. B, Ocular melanocytosis. C, Fundus photograph showing peripheral choroidal melanoma involving the ciliary body.
Figure 3. Patient 3. A, Nevus anemicus of the neck (arrowhead) and thoracic nevus flammeus (asterisk). B, Oculodermal melanocytosis. C, Fundus photograph showing achoroidal melanoma in the inferior nasal quadrant and an associated exudative retinal detachment.
1234
Tran and Zografos 䡠 PPV IIa and Melanoma primary choroidal melanoma. Although it is generally accepted that ocular melanocytosis and mutated BRAC2 locus promotes an increased risk for melanoma, we believe that melanoma may be a true association with PPV. We suggest that PPV patients with oculodermal melanocytosis should be followed up carefully for the development of uveal melanoma.
References 1. Ota M, Kawamura T, Ito N. Phakomatosis pigmentovascularis Ota [in Japanese]. Jpn J Dermatol 1947;52:1–3. 2. Enjolras O, Mulliken JB. Vascular malformations. In: Harper J, Oranje AP, Prose NS, eds. Textbook of Pediatric Dermatology. Vol. 2. Oxford, United Kingdom: Blackwell Science Ltd.; 2000:975–96. 3. Furukawa T, Igata A, Toyokura Y, Ikeda S. Sturge-Weber and Klippel-Trenaunay syndrome with nevus of Ota and Ito. Arch Dermatol 1970;102:640 –5. 4. Kaise M, Watanabe A, Kobayashi Y. A case of phacomatosis pigmentovascularis accompanied with esophageal varices due to hypoplasia of the portal veins. Gastroenterol Jpn 1992;27: 546 –9. 5. Park JG, Roh KY, Lee HJ, et al. Phakomatosis pigmentovascularis IIb with hypoplasia of the inferior vena cava and the right iliac and femoral veins causing recalcitrant stasis leg ulcers. J Am Acad Dermatol 2003;49(suppl):S167–9. 6. Di Landro A, Tadini GL, Marchesi L, Cainelli T. Phakomatosis pigmentovascularis: a new case with renal angiomas and some considerations about the classification. Pediatr Dermatol 1999;16:25–30. 7. Reinke RT, Haber K, Josselson A. Ota nevus, multiple hemangiomas, and Takayasu arteritis. Arch Dermatol 1974;110: 447–50. 8. Gonder JR, Nichol J, Augsburger JJ, Shields JA. Ocular and oculodermal melanocytosis. Can J Ophthalmol 1985;20:176 – 8. 9. Gilliam AC, Ragge NK, Perez MI, Bolognia JL. Phakomatosis pigmentovascularis type IIb with iris mammillations. Arch Dermatol 1993;129:340 –2.
10. Teekhasaenee C, Ritch R. Glaucoma in phakomatosis pigmentovascularis. Ophthalmology 1997;104:150 –7. 11. Van der Hoeve J. Eye symptoms in tuberous sclerosis of the brain and in Recklinghausen’s disease. Trans Ophthalmol Soc U K 1923;43:534 – 41. 12. Horio T, Ogawa M. Pigmentovascular nevus. Arch Dermatol 1973;107:463– 4. 13. Guiglia MC, Prendiville JS. Multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child. J Am Acad Dermatol 1991;24:359 – 63. 14. Ortonne JP, Floret D, Coiffet J, Cottin X. Ocular and cutaneous melanosis associated with the Sturge-Weber syndrome: clinical, histological, and ultrastructural studies of one case [in French]. Ann Dermatol Venereol 1978;105:1019 –31. 15. Ruiz-Maldonado R, Tamayo L, Laterza AM, et al. Phacomatosis pigmentovascularis: a new syndrome? Report of four cases. Pediatr Dermatol 1987;4:189 –96. 16. Gonder JR, Shields JA, Albert DM, et al. Uveal malignant melanoma associated with ocular and oculodermal melanocytosis. Ophthalmology 1982;89:953– 60. 17. Velazquez N, Jones IS. Ocular and oculodermal melanocytosis associated with uveal melanoma. Ophthalmology 1983;90: 1472– 6. 18. Singh AD, De Potter P, Fijal BA, et al. Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology 1998;105:195– 8. 19. Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91:1310 – 6. 20. Sinilnikova OM, Egan KM, Quinn JL, et al. Germline BRCA2 sequence variants in patients with ocular melanoma. Int J Cancer 1999;82:325– 8. 21. Scott RJ, Vajdic CM, Armstrong BK, et al. BRCA2 mutations in a population-based series of patients with ocular melanoma. Int J Cancer 2002;102:188 –91. 22. Kitamura W, Iwai M, Sakamoto K. A case of phakomatosis pigmentovascularis. Rinsho Hinfuka 1981;35:399 – 405. 23. Saricaoglu MS, Guven D, Karakurt A, et al. An unusual case of Sturge-Weber syndrome in association with phakomatosis pigmentovascularis and Klippel-Trenaunay-Weber syndrome. Retina 2002;22:368 –71.
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