Case Report Dermatology 1992;185:146-150
”
GR Welss
Malignant Melanoma in a Hispanic Male with Nevus of Ota
University of Texas Health Science Center at San Antonio and Audie L. Murphy Memorial Veterans Administration Hospital. San Antonio. Tex., USA; Brooke Army Medical Center, Fort Sam Houston. Tex., USA
Abstract Nevus of Ota is uncommon in the non-Oricntal population. We report a case of malignant melanoma with metastasis to the genitourinary tract in a Hispanic male with nevus of Ota. Thirty-six prior cases of nevus of Ota with malignant melanoma reported in the English language are reviewed. Sixty-eight percent were women; 76% were Caucasians. Metastatic disease was reported in 16%. Three patients had liver metastases. Our case was the first involving the genito urinary tract. All but one patient with metastatic disease died within 1 month of presentation. Despite the increased frequency of nevus of Ota in the Japanese, only 4 cases of malignant melanoma have been reported. Nevus of Ota would appear to be a risk factor for developing malignant melanoma in the Caucasian population.
Nevus of Ota is a benign mesodermal melanocytosis over the first (ophthalmic) and second (maxillary) branches of the trigeminal nerve [1], Called ‘naevus fuscocacrulcus ophthalmomaxillaris’, it was first described in 1938 by Ota. Later, Fitzpatrick et al. [2] suggested the term oculodermal melanocytosis. However, the term nevus of Ota is com monly used to refer to this syndrome. Ocular involvement may include the sclera, choroid, iris, optic disk, ocular mus cles and conjunctiva [3, 4]. Ipsilateral dermal involvement may include the oral mucosa, palate, tympanic membrane, orbit, cranial bones and the lcptomcningcs. The melanin granules that cause the usually macular pigment changes are found in special dendritic cells deep in the corium of the skin. The epithelium is not pigmented. Pathologically, it is similar to Mongolian spots (sacral hyperpigmentation that usually disappears during the first few years after birth) and the nevus of Ito, found on the shoulders, back and outer
Received: Oclober 30, 1991 Accepted: March 25. 1992
aspect of the upper arm in the distribution of the posterior subclavicular and lateral brachial cutaneous nerves. It is important to distinguish nevus of Ota from melanosis oculi, which is an epidermal hyperpigmentation confined to the eye that carries a 25% risk of progressing to melanoma [5, 6], The nevus of Ota is most common in Orientals, where it has been reported to be seen in 0.5% of dermatology visits in a university setting. Hidano et al. [7] collected 240 patients in 3 years at two Tokyo dermatology clinics. The incidence in the Caucasian population is unknown but likely less frequent. The description of melanoma in nevus of Ota is represented by scattered reports. Except for cosmesis, the only complications are glau coma [8] and melanoma. We present a case of nevus of Ota in a Hispanic male who subsequently presented with left temporal lobe and bladder melanoma.
Geoffrey R. Weiss. MD Department of Mcdicinc/Medical Oncology 7703 Floyd C url Drive San Antonio. TX 78284-7884 (USA)
© 1992 Kargcr AG. Basel 1018-8665/92/1852-0146 $ 2.75A)
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Key Words Malignant melanoma Oculodermal mclanocytosis Nevus of Ota Bladder
A 64-year-old Hispanic male previously in good health, with nevus of Ota on the left face since childhood, presented with complaints of light-headedness, upper-extremity paresthesias and acute left hearing loss. A subsequent CT scan of the head revealed a 1.55x2.0 cm left temporal lobe lesion. A subsequent angiogram and magnetic reso nance imaging were felt to be diagnostic for an arteriovenous malfor mation. A follow-up CT scan in November 1988 showed the lesion to be increasing in size. On precraniotomy evaluation, significant hematuria was noted. Cystoscopy revealed five 0.3- to 0.6-cm smooth, black papules on the posterior and lateral bladder wall. Excisional biopsies of all lesions were consistent with malignant melanoma. A subsequent left craniot omy removed a 2.5 x 2.5 cm black temporal lobe mass that was also histopathologic-ally consistent with melanoma. The contiguous brain tissue, overlying meninges and temporal bone were heavily stained with a black pigment. Postoperatively, the patient received 3.900 cGy whole-brain radiation. The patient did well until November 1989 when a routine repeat cystoscopy noted recurrent black papules consistent with melanoma. Three weeks later, the patient presented to the hospi tal complaining of diffuse abdominal pain and expanding abdominal girth. He denied fever, chills, night sweats, shortness of breath, cough or changes in his bowel movements. On physical examination, his vital signs were stable. A black mac ular pigmented area was noted on his left forehead, face and sclera, sparing his lower face, a distribution consistent with nevus of Ota. The lung and cardiovascular examinations were unremarkable. The abdo men was distended with tenderness and a fluid wave. The liver was 7 cm below the right costal margin. The lower extremities were edema tous, the neurological examination was normal and nonfocal to include vision and cxtraocular mobility. An ultrasound of the abdo men was remarkable for significant ascites and an irregular heteroge neous liver which was suggestive of metastatic disease. Shortly after admission, the patient's livcrfunction tests deteriorated, he developed coagulopathy, progressive encephalopathy and died on the sixth hos pital day. No autopsy was permitted.
Discussion Malignancy associated with the nevus of Ota was first described by Hulkc in 1860 [9]. There have subsequently been 35 more patients reported in the English literature (table 1). The median age is 51 years (range 15-72). Women have been reported to be affected more than men with a ratio of 2:1. Caucasians represented 76% of the cases in the literature. Two Black patients and single cases of Oriental, Malaysian. East Indian and Israeli patients have been reported. (Our case is the second Hispanic patient with nevus of Ota and malignant melanoma [10].) Although nevus of Ota is uncommon in the Caucasian population, it should not be surprising that a review of English language journals would result in a preponderance of Caucasian cases. Yamamoto [11] reported a case of cho
roidal malignant melanoma in a Japanese patient with nevus of Ota. His review of the literature noted 2 prior cases in Japanese males. Only 1 additional case [12] in a Japanese male has been reported. Despite the predomi nance of nevus of Ota in Japanese females, no cases of malignant melanoma have been reported. European cases in the non-English literature have had similar findings [13, 14]. A review by Gonder et al. [15] of 1.250 Caucasian patients with uveal melanomas reported 3 patients with associated oculodermal melanocytosis. Similarly, Velaz quez and Jones [16] reported 2 cases of oculodermal mclanocytosisin a reviw of 1,210 patients with uveal melanoma. Other cases of malignant melanoma arising in patients with nevus of Ota have occurred but have not yet been singly reported [17-19]. A single patient with a dermal malignant melanoma arising within a nevus of Ito [20] has recently been reported. The primary locations of the melanoma are shown in table 1. Two patients had two separate primary melanomas [ 10,21]. The choroid was the most frequent primary site of malignancy involved, occurring in 17/39 (44%) of reported cases. Other sites included the CNS (23%), orbit (18%) and skin (15%). The primary melanoma was ipsilatcral to the nevus in 97%. The only case where a primary mel anoma was contralateral to the nevus occurred in the CNS [22]. Six patients presented with cutaneous primary malig nant melanoma [21,23-25], all arising within the nevus of Ota. The remaining 85% presented as noncutancous pri mary melanoma, all in structures involved with abnormal melanocytosis. No cases of other malignancies have been reported with nevus of Ota, nor have any cases of cuta neous melanoma been identified arising in tissues not affected with nevus of Ota. Presenting complaints were closely correlated with the anatomical site of the primary tumor. Decreased visual acuity was most frequently associated with choroid tumors, commonly presenting with retinal distortion [26, 27] or detachment [6. 10, 11, 13]. Two patients were described with ipsilateral increase in intraocular pressure by applana tion tonometry consistent with open-angle glaucoma [5, 17], These melanomas arose in the iris [ 17] and choroid [5]. Two other patients [ 11,22] had an increase in their ipsilat eral intraocular pressure without a change in visual acuity. Orbital lesions frequently presented with unilateral exoph thalmos [25. 28-301. Patients whose melanoma originated in the CNS presented with headaches [21.22, 31], ipsilat eral abducens nerve palsy and ptosis [32], hemiparesis [33] or partial seizures [14], Only 2 patients presented with abdominal complaints [34. present case].
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Case Report
Table 1. Reported cases of malignant melanoma with nevus of Ota
Case No-
A8e - years
Sex
Race
Primary
Metastasis
Reference
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 IS 1‘) 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37
62 24 16 46 65 64 52 70 68 41 66 51 37 58 43 29 58 66 37 68 44 63 18 66 51 61 40 45 23 43 15 67 72 41 50 16 64
F F M F F F F M F M F M M M M F M F F F F F F F M F F F F F M F F F M F M
C C C C C C C C
choroid skin skin meninges choroid orbit orbit choroid choroid iris brain choroid choroid choroid pineal orbit CL brain choroid brain choroid, skin choroid orbit skin choroid choroid choroid choroid choroid brain meninges orbit orbit choroid brain, skin skin choroid brain
N/A liver none N/A N/A multiple N/A none N/A N/A N/A N/A none N/A meninges. brain liver none none none none none none none none none none N/A N/A none none none none liver none none N/A bladder
9 23 23 35 40 28 26 41 5 17 36 6 11 27 33 29 22 13 31 10 43 30 24 15, 42 15 15 16 16 14 32 37 37 34 21 25 38 present case
c c c c O
c c c c c
In N/A B Is C C C C B C C N/A C C M C C C H
C = Caucasian; B = Black; In = Indian; Is = Israeli; M = Malaysian; O = Oriental; H = Hispanic; N/A = not available; C L = contralateral.
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The pathogenesis of the primary malignant melanoma arising within a nevus of Ota is unknown. A causal relation ship between nevus of Ota and malignant melanoma has not been established; however, our review suggests that this is likely. The reported frequency of malignant mel anoma in ocular melanocytosis is 25% [5, 6], One may anticipate that oculodermal melanocytosis might have a similar risk. The frequency of ipsilateral primary melano mas in the region of the nevus of Ota and in deeper struc tures involved with melanocytosis is 100%. In this review
Nevus of Ota and Malignant Melanoma
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Generally, the disease has been local, with therapy (sur gery) directed at local control. Radiation therapy has been reported in 4 patients for unresectable disease [22], for local recurrence [34] and as adjuvant to surgery [32, present case]. Metastatic disease was seen in 16% of the cases. Three cases of liver metastasis have been reported. Our case represents the only case with bladder involvement. In patients who presented with metastatic disease, only 2 patients lived longer than 1 month [28, present case].
we found that the patients with CNS primary melanomas had extensive melanocytosis of the meninges [14, 21, 22, 31,33,35,36], patients with orbital primary melanoma had melanocytosis involving orbital structures [17. 26-29, 37], and patients with a cutaneous primary developed their melanoma in skin affected by nevus of Ota [10, 15, 23-25]. The one contralateral lesion similarly arose in the frontal lobe, adjacent to extensive meningeal melanocytosis [22]. These data suggest that malignant melanoma develops in areas where abnormal melanocytes may have been depos ited in the migration from the neural crest to the dermis [15, 38]. The deep dermal layers of the adult arc normally free of melanocytic cells. Dermal melanocytes represent anom alous persistence [37], There are histopathological differ ences between the hyperpigmented dermal lesions. The dermal melanocytes in the nevus of Ota predominate in the upper corium. while in Mongolian spots they predominate in the lower half of the corium [39]. Most cases of nevus of Ota (60%) are noted at birth; the remaining cases have their onset around puberty. The lesions are persistent. In contrast, Mongolian spots occur at birth or soon after and fade in the first years of life. The deeper pigmentation in Mongolian spots explains why their macules are more con sistently bluish. Nevus of Ota is similar to nevus of Ito, the difference being their anatomical location [1]. Individually, melanocytes in nevus of Ota and blue nevi arc similar in
location and structure, except that the former does not dis turb the normal architecture [37]. Clinically, their pattern of distribution allows easy discrimination. However, distin guishing primary malignant melanoma from malignant blue nevi in patients with nevus of Ota has been difficult [23-25,29]. Some authors have questioned the existence of the latter condition [29]. Dompmartin etal. [25] noted that the presence of nuclear pleomorphism. abnormal mitosis and necrosis favored malignant melanoma. Although the association of malignant melanoma with nevus of Ota would appear to be established in the Cauca sian population, the risk of developing melanoma is unknown. There have been no prospective studies of asymptomatic nevus of Ota. It is also unclear why so few cases of malignant melanoma have been reported in the Oriental population, where the lesion is most common. Orientals and other dark-skinned races have a decreased incidence of melanoma in general [44], One possibility is that the Caucasian lesions behave more aggressively [18]. Our case is unusual in two respects. First, our patient represents the second Hispanic reported with this condi tion. Second, this is the first reported patient with meta static disease to the genitourinary tract. Finally, non-Orientals who are noted to have a nevus of Ota may be at an increased risk of melanomas. The actual risk can only be ascertained by prospective evaluation of an asymptomatic population with nevus of Ota.
References 8 Kopf AW. Weidman AI: Nevus of Ota. Arch Dermatol 1962:85:195-207. 9 HulkeJW: Scries of cases of carcinoma of eye ball (case 2). Ophthalmol Hosp Rep 1861:3: 279-286. 10 Croxatto JO. Charles DE. Mallran ES: Neuro fibromatosis associated with nevus of Ota and choroidal melanoma. Am J Ophthalmol 1981:92:578-580. 11 Yamamoto T: Malignant melanoma of the choroid in nevus of Ota. Ophthalmologica 1969:151:1-10. 12 Kabuto M. Ilayashi M. Kawano H. Kobayashi H. Shirasaki N. Hirose S. Kubota T. Sugihara II: Primary intracranial malignant melanoma associated with nevus of Ota: A case report (in Japanese). No Shinkei Geka 1988:16:875-880. 13 Mohandessan M. Fetkanhour C. O'Grady R: Malignant melanoma of the choroid in a case of nevus of Ota. Ann Ophthalmol 1979:11: 189-192.
14 Sagar HJ. Ilgren EB. Adams CBT: Nevus of Ota associated with meningeal melanosis and intracranial melanoma. J Neurosurg 1983:58: 280-283. 15 Gonder JR. Shields EB. Albert DM. Augsburger JJ. Lavin PT: Uveal malignant melanoma associated with ocular and oculodermal mela nocytosis. Ophthalmology 1982:89:953-959. 16 Velazquez N. Jones IS: Ocular and oculoder mal melanocytosis associated with uveal mel anoma. Ophthalmology 1983;90:1472-1476. 17 Font RL. Reynolds AM Jr, Zimmerman I.E: Diffuse malignant melanoma of the iris in the nevus of Ota. Arch Ophthalmol 1967:77: 513-518. 18 Reed WB. Sugarman GL: Unilateral nevus of Ota with sensorineural deafness. Arch Derma tol 1974:109:881-883. 19 Lerncr AB. Nordlund JJ. Kirkwood JM: Effects of oral contraceptives and pregnancy on melanomas. N Engl J Med 1979:301:47. 20 Van Kricken JHJM. Boom BW. Scheffer E: Malignant transformation in a naevus of Ito. A case report. Histopathology 1988:12:100-102.
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1 Gupia A. Gangwais DN: Nevus of Ota. Br J Ophthalmol 1965;49:364-368. 2 Fitzpatrick TB. Zeller R. Kukila A. Kitamura H: Ocular and dermal melanocytosis.. Arch Ophthalmol 1956;56:830-833. 3 Mackie RM: Tumours of melanocytes; in Rock A. Wilkinson DS. F.bling FJG. Champio RH. Burton JL (cds): Textbook of Dermatology. Oxford. Blackwell Scientific Publications. 1986. pp 2441-2445. 4 Dodd WA: Nevus of Ota and nevus of lto: in Demis DJ (cd): Clinical Dermatology. Phila delphia. JB Lippincott. 1990; vol. 2. pp 1-4. 5 M akleyTAJr. King CM: Malignant melanoma of the choroid in melanosis oculi. Trans Am Acad Ophthalmol 1967:71:638. 6 Frezzotti R. Guerra R. Dragoni GP. Bonamsi P: Malignant melanoma of the choroid in a case of naevus of Ota. Br J Ophthalmol 1968:52: 922-924. 7 Hidano A. Kajima H. Ikeda S. Mizutani. Miyasato H. Niimura M: Natural history of nevus of Ota. Arch Dermatol 1967:95: 187-195.
30 Haim T. Meyer E. Kerner H. Zonis S: Oculo dermal melanocytosis and orbital malignant melanoma. Ann Ophthalmol 1982:14: 1132-1136. 31 Horsey WJ. Bilbao JM. Nethencotl J. Myers R. Hoffman HJ: Oculodermal melanosis com plicated by multiple intracranial tumors. Can J Neurol Sci 1980;7:101-107. 32 Botticelli AR, Villani M. Angiori P. Peserice L: Meningeal melanocytoma of Meckel’s cave associated with ipsilatcral Ota nevus. Cancer 1983;51:2304-2310. 33 Enriquez R. Egbert B. Bullock J: Primary malignant melanoma of central nervous sys tem. Pineal involvement in a patient with nevus of Ota and multiple pigmented skin nevi. Arch Pathol 1972:95:392-395. 34 Singh M. Kaur B. Annuar HM: Malignant mel anoma of the choroid in nevus of Ota. Br J Ophthalmol 1988:72:131-133. 35 Willis RA: Pathology of Tumors. London. Buttcrworth. 1967. p 930. 36 Yanoff M. Zimmerman LE: Histogenesis of malignant melanomas of the uvea. Arch Oph thalmol 1967:77:331-336. 37 Dutton JJ. Anderson RL. Sehclper RL. Purcell JJ. Tse DT: Orbital malignant melanoma and oculodermal melanocytosis: Report of two cases and review of the literature. Ophthalmol ogy 1984:91:497-507.
38 Ticho BH. Tso MO. Kishi S: Diffuse iris nevus in oculodermal melanocytosis: A light and electron microscopic study. J Pcdiatr Ophthal mol Strabismus 1989:26:244-250. 39 Mishima Y. Mevorah B: Nevus Ota and nevus Ito in American negroes. J Invest Dermatol 1961:36:133-154. 40 Albert DM. Scheie HG: Naevus of Ota with malignant melanoma of the choroid. Report of a case. Arch Ophthalmol 1963:69:774-777. 41 Ray PE. Schaeffer EM: Nevus of Ota and cho roidal melanoma. Surv Ophthalmol 1967:12: 130-131. 42 GonderJR. Shields JA. Albert DM: Malignant melanoma of the choroid associated with ocu lodermal melanocytosis. Ophthalmology 1981: 88:372-376. 43 Nik NA. Glew WB. Zimmerman LE: Malig nant melanoma of the choroid in the nevus of Ota of a black patient. Arch Ophthalmol 1982: 100:1641-1643. 44 Balch CM. Houghton A. Peters L: Cutaneous melanoma; in DeVita VT Jr. Heilman S. Rosenberg SA (eds): Cancer Principles and Practice of Oncology, ed 3. Philadelphia. Lip pincott. 1989. vol 2. pp 1499-1542.
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21 Hartmann LC. Oliver GF. Winkleman RK. Colby TV. Sundt TM. O'Neill BP: Blue nevus and nevus of Ota associated with dural mel anoma. Cancer 1989;64:182-186. 22 Sang DN. Albert DM. Sober AJ. McMcckin TO: Nevus of Ota with contralateral cerebral melanoma. Arch Ophthalmol 1977:95: 1820-1824. 23 Dorsey CS. Montgomery H: Blue nevus and its distinction from Mongolian spot and the nevus of Ota. J Invest Dermatol 1954;22:225-236. 24 Kopf AW. Bart RS: Tumor Conference No 42. J Dermatol Surg Oncol 1982;8:442-445. 25 Dompmartin A. Leroy D. Labbe D. Letessier JB. Mandard JC: Dermal malignant melanoma developing from a nevus of Ota. hit J Derma tol 1989:28:535-536. 26 Haglcr WS. Brown CC: Malignant melanoma of the orbit arising in the nevus of Ota. Trans Am Acad Ophthalmol Otolaryngol 1966:70: 817-822. 27 Ilalasa A: Malignant melanoma in a case of bilateral nevus of Ota. Arch Ophthalmol 1970;84:176-178. 28 Jay B: Malignant melanoma of the orbit in a case of oculodermal melanosis. Br J Ophthal mol 1965;49:359-363. 29 Spcakman JS. Phillips MJ: Cellular and malig nant blue nevus complicating oculodermal melanosis. Can J Ophthalmol 1973;8:539-547.
”
GR Welss
Malignant Melanoma in a Hispanic Male with Nevus of Ota
University of Texas Health Science Center at San Antonio and Audie L. Murphy Memorial Veterans Administration Hospital. San Antonio. Tex., USA; Brooke Army Medical Center, Fort Sam Houston. Tex., USA
Abstract Nevus of Ota is uncommon in the non-Oricntal population. We report a case of malignant melanoma with metastasis to the genitourinary tract in a Hispanic male with nevus of Ota. Thirty-six prior cases of nevus of Ota with malignant melanoma reported in the English language are reviewed. Sixty-eight percent were women; 76% were Caucasians. Metastatic disease was reported in 16%. Three patients had liver metastases. Our case was the first involving the genito urinary tract. All but one patient with metastatic disease died within 1 month of presentation. Despite the increased frequency of nevus of Ota in the Japanese, only 4 cases of malignant melanoma have been reported. Nevus of Ota would appear to be a risk factor for developing malignant melanoma in the Caucasian population.
Nevus of Ota is a benign mesodermal melanocytosis over the first (ophthalmic) and second (maxillary) branches of the trigeminal nerve [1], Called ‘naevus fuscocacrulcus ophthalmomaxillaris’, it was first described in 1938 by Ota. Later, Fitzpatrick et al. [2] suggested the term oculodermal melanocytosis. However, the term nevus of Ota is com monly used to refer to this syndrome. Ocular involvement may include the sclera, choroid, iris, optic disk, ocular mus cles and conjunctiva [3, 4]. Ipsilateral dermal involvement may include the oral mucosa, palate, tympanic membrane, orbit, cranial bones and the lcptomcningcs. The melanin granules that cause the usually macular pigment changes are found in special dendritic cells deep in the corium of the skin. The epithelium is not pigmented. Pathologically, it is similar to Mongolian spots (sacral hyperpigmentation that usually disappears during the first few years after birth) and the nevus of Ito, found on the shoulders, back and outer
Received: Oclober 30, 1991 Accepted: March 25. 1992
aspect of the upper arm in the distribution of the posterior subclavicular and lateral brachial cutaneous nerves. It is important to distinguish nevus of Ota from melanosis oculi, which is an epidermal hyperpigmentation confined to the eye that carries a 25% risk of progressing to melanoma [5, 6], The nevus of Ota is most common in Orientals, where it has been reported to be seen in 0.5% of dermatology visits in a university setting. Hidano et al. [7] collected 240 patients in 3 years at two Tokyo dermatology clinics. The incidence in the Caucasian population is unknown but likely less frequent. The description of melanoma in nevus of Ota is represented by scattered reports. Except for cosmesis, the only complications are glau coma [8] and melanoma. We present a case of nevus of Ota in a Hispanic male who subsequently presented with left temporal lobe and bladder melanoma.
Geoffrey R. Weiss. MD Department of Mcdicinc/Medical Oncology 7703 Floyd C url Drive San Antonio. TX 78284-7884 (USA)
© 1992 Kargcr AG. Basel 1018-8665/92/1852-0146 $ 2.75A)
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Key Words Malignant melanoma Oculodermal mclanocytosis Nevus of Ota Bladder
A 64-year-old Hispanic male previously in good health, with nevus of Ota on the left face since childhood, presented with complaints of light-headedness, upper-extremity paresthesias and acute left hearing loss. A subsequent CT scan of the head revealed a 1.55x2.0 cm left temporal lobe lesion. A subsequent angiogram and magnetic reso nance imaging were felt to be diagnostic for an arteriovenous malfor mation. A follow-up CT scan in November 1988 showed the lesion to be increasing in size. On precraniotomy evaluation, significant hematuria was noted. Cystoscopy revealed five 0.3- to 0.6-cm smooth, black papules on the posterior and lateral bladder wall. Excisional biopsies of all lesions were consistent with malignant melanoma. A subsequent left craniot omy removed a 2.5 x 2.5 cm black temporal lobe mass that was also histopathologic-ally consistent with melanoma. The contiguous brain tissue, overlying meninges and temporal bone were heavily stained with a black pigment. Postoperatively, the patient received 3.900 cGy whole-brain radiation. The patient did well until November 1989 when a routine repeat cystoscopy noted recurrent black papules consistent with melanoma. Three weeks later, the patient presented to the hospi tal complaining of diffuse abdominal pain and expanding abdominal girth. He denied fever, chills, night sweats, shortness of breath, cough or changes in his bowel movements. On physical examination, his vital signs were stable. A black mac ular pigmented area was noted on his left forehead, face and sclera, sparing his lower face, a distribution consistent with nevus of Ota. The lung and cardiovascular examinations were unremarkable. The abdo men was distended with tenderness and a fluid wave. The liver was 7 cm below the right costal margin. The lower extremities were edema tous, the neurological examination was normal and nonfocal to include vision and cxtraocular mobility. An ultrasound of the abdo men was remarkable for significant ascites and an irregular heteroge neous liver which was suggestive of metastatic disease. Shortly after admission, the patient's livcrfunction tests deteriorated, he developed coagulopathy, progressive encephalopathy and died on the sixth hos pital day. No autopsy was permitted.
Discussion Malignancy associated with the nevus of Ota was first described by Hulkc in 1860 [9]. There have subsequently been 35 more patients reported in the English literature (table 1). The median age is 51 years (range 15-72). Women have been reported to be affected more than men with a ratio of 2:1. Caucasians represented 76% of the cases in the literature. Two Black patients and single cases of Oriental, Malaysian. East Indian and Israeli patients have been reported. (Our case is the second Hispanic patient with nevus of Ota and malignant melanoma [10].) Although nevus of Ota is uncommon in the Caucasian population, it should not be surprising that a review of English language journals would result in a preponderance of Caucasian cases. Yamamoto [11] reported a case of cho
roidal malignant melanoma in a Japanese patient with nevus of Ota. His review of the literature noted 2 prior cases in Japanese males. Only 1 additional case [12] in a Japanese male has been reported. Despite the predomi nance of nevus of Ota in Japanese females, no cases of malignant melanoma have been reported. European cases in the non-English literature have had similar findings [13, 14]. A review by Gonder et al. [15] of 1.250 Caucasian patients with uveal melanomas reported 3 patients with associated oculodermal melanocytosis. Similarly, Velaz quez and Jones [16] reported 2 cases of oculodermal mclanocytosisin a reviw of 1,210 patients with uveal melanoma. Other cases of malignant melanoma arising in patients with nevus of Ota have occurred but have not yet been singly reported [17-19]. A single patient with a dermal malignant melanoma arising within a nevus of Ito [20] has recently been reported. The primary locations of the melanoma are shown in table 1. Two patients had two separate primary melanomas [ 10,21]. The choroid was the most frequent primary site of malignancy involved, occurring in 17/39 (44%) of reported cases. Other sites included the CNS (23%), orbit (18%) and skin (15%). The primary melanoma was ipsilatcral to the nevus in 97%. The only case where a primary mel anoma was contralateral to the nevus occurred in the CNS [22]. Six patients presented with cutaneous primary malig nant melanoma [21,23-25], all arising within the nevus of Ota. The remaining 85% presented as noncutancous pri mary melanoma, all in structures involved with abnormal melanocytosis. No cases of other malignancies have been reported with nevus of Ota, nor have any cases of cuta neous melanoma been identified arising in tissues not affected with nevus of Ota. Presenting complaints were closely correlated with the anatomical site of the primary tumor. Decreased visual acuity was most frequently associated with choroid tumors, commonly presenting with retinal distortion [26, 27] or detachment [6. 10, 11, 13]. Two patients were described with ipsilateral increase in intraocular pressure by applana tion tonometry consistent with open-angle glaucoma [5, 17], These melanomas arose in the iris [ 17] and choroid [5]. Two other patients [ 11,22] had an increase in their ipsilat eral intraocular pressure without a change in visual acuity. Orbital lesions frequently presented with unilateral exoph thalmos [25. 28-301. Patients whose melanoma originated in the CNS presented with headaches [21.22, 31], ipsilat eral abducens nerve palsy and ptosis [32], hemiparesis [33] or partial seizures [14], Only 2 patients presented with abdominal complaints [34. present case].
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Case Report
Table 1. Reported cases of malignant melanoma with nevus of Ota
Case No-
A8e - years
Sex
Race
Primary
Metastasis
Reference
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 IS 1‘) 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37
62 24 16 46 65 64 52 70 68 41 66 51 37 58 43 29 58 66 37 68 44 63 18 66 51 61 40 45 23 43 15 67 72 41 50 16 64
F F M F F F F M F M F M M M M F M F F F F F F F M F F F F F M F F F M F M
C C C C C C C C
choroid skin skin meninges choroid orbit orbit choroid choroid iris brain choroid choroid choroid pineal orbit CL brain choroid brain choroid, skin choroid orbit skin choroid choroid choroid choroid choroid brain meninges orbit orbit choroid brain, skin skin choroid brain
N/A liver none N/A N/A multiple N/A none N/A N/A N/A N/A none N/A meninges. brain liver none none none none none none none none none none N/A N/A none none none none liver none none N/A bladder
9 23 23 35 40 28 26 41 5 17 36 6 11 27 33 29 22 13 31 10 43 30 24 15, 42 15 15 16 16 14 32 37 37 34 21 25 38 present case
c c c c O
c c c c c
In N/A B Is C C C C B C C N/A C C M C C C H
C = Caucasian; B = Black; In = Indian; Is = Israeli; M = Malaysian; O = Oriental; H = Hispanic; N/A = not available; C L = contralateral.
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The pathogenesis of the primary malignant melanoma arising within a nevus of Ota is unknown. A causal relation ship between nevus of Ota and malignant melanoma has not been established; however, our review suggests that this is likely. The reported frequency of malignant mel anoma in ocular melanocytosis is 25% [5, 6], One may anticipate that oculodermal melanocytosis might have a similar risk. The frequency of ipsilateral primary melano mas in the region of the nevus of Ota and in deeper struc tures involved with melanocytosis is 100%. In this review
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Generally, the disease has been local, with therapy (sur gery) directed at local control. Radiation therapy has been reported in 4 patients for unresectable disease [22], for local recurrence [34] and as adjuvant to surgery [32, present case]. Metastatic disease was seen in 16% of the cases. Three cases of liver metastasis have been reported. Our case represents the only case with bladder involvement. In patients who presented with metastatic disease, only 2 patients lived longer than 1 month [28, present case].
we found that the patients with CNS primary melanomas had extensive melanocytosis of the meninges [14, 21, 22, 31,33,35,36], patients with orbital primary melanoma had melanocytosis involving orbital structures [17. 26-29, 37], and patients with a cutaneous primary developed their melanoma in skin affected by nevus of Ota [10, 15, 23-25]. The one contralateral lesion similarly arose in the frontal lobe, adjacent to extensive meningeal melanocytosis [22]. These data suggest that malignant melanoma develops in areas where abnormal melanocytes may have been depos ited in the migration from the neural crest to the dermis [15, 38]. The deep dermal layers of the adult arc normally free of melanocytic cells. Dermal melanocytes represent anom alous persistence [37], There are histopathological differ ences between the hyperpigmented dermal lesions. The dermal melanocytes in the nevus of Ota predominate in the upper corium. while in Mongolian spots they predominate in the lower half of the corium [39]. Most cases of nevus of Ota (60%) are noted at birth; the remaining cases have their onset around puberty. The lesions are persistent. In contrast, Mongolian spots occur at birth or soon after and fade in the first years of life. The deeper pigmentation in Mongolian spots explains why their macules are more con sistently bluish. Nevus of Ota is similar to nevus of Ito, the difference being their anatomical location [1]. Individually, melanocytes in nevus of Ota and blue nevi arc similar in
location and structure, except that the former does not dis turb the normal architecture [37]. Clinically, their pattern of distribution allows easy discrimination. However, distin guishing primary malignant melanoma from malignant blue nevi in patients with nevus of Ota has been difficult [23-25,29]. Some authors have questioned the existence of the latter condition [29]. Dompmartin etal. [25] noted that the presence of nuclear pleomorphism. abnormal mitosis and necrosis favored malignant melanoma. Although the association of malignant melanoma with nevus of Ota would appear to be established in the Cauca sian population, the risk of developing melanoma is unknown. There have been no prospective studies of asymptomatic nevus of Ota. It is also unclear why so few cases of malignant melanoma have been reported in the Oriental population, where the lesion is most common. Orientals and other dark-skinned races have a decreased incidence of melanoma in general [44], One possibility is that the Caucasian lesions behave more aggressively [18]. Our case is unusual in two respects. First, our patient represents the second Hispanic reported with this condi tion. Second, this is the first reported patient with meta static disease to the genitourinary tract. Finally, non-Orientals who are noted to have a nevus of Ota may be at an increased risk of melanomas. The actual risk can only be ascertained by prospective evaluation of an asymptomatic population with nevus of Ota.
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1 Gupia A. Gangwais DN: Nevus of Ota. Br J Ophthalmol 1965;49:364-368. 2 Fitzpatrick TB. Zeller R. Kukila A. Kitamura H: Ocular and dermal melanocytosis.. Arch Ophthalmol 1956;56:830-833. 3 Mackie RM: Tumours of melanocytes; in Rock A. Wilkinson DS. F.bling FJG. Champio RH. Burton JL (cds): Textbook of Dermatology. Oxford. Blackwell Scientific Publications. 1986. pp 2441-2445. 4 Dodd WA: Nevus of Ota and nevus of lto: in Demis DJ (cd): Clinical Dermatology. Phila delphia. JB Lippincott. 1990; vol. 2. pp 1-4. 5 M akleyTAJr. King CM: Malignant melanoma of the choroid in melanosis oculi. Trans Am Acad Ophthalmol 1967:71:638. 6 Frezzotti R. Guerra R. Dragoni GP. Bonamsi P: Malignant melanoma of the choroid in a case of naevus of Ota. Br J Ophthalmol 1968:52: 922-924. 7 Hidano A. Kajima H. Ikeda S. Mizutani. Miyasato H. Niimura M: Natural history of nevus of Ota. Arch Dermatol 1967:95: 187-195.
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21 Hartmann LC. Oliver GF. Winkleman RK. Colby TV. Sundt TM. O'Neill BP: Blue nevus and nevus of Ota associated with dural mel anoma. Cancer 1989;64:182-186. 22 Sang DN. Albert DM. Sober AJ. McMcckin TO: Nevus of Ota with contralateral cerebral melanoma. Arch Ophthalmol 1977:95: 1820-1824. 23 Dorsey CS. Montgomery H: Blue nevus and its distinction from Mongolian spot and the nevus of Ota. J Invest Dermatol 1954;22:225-236. 24 Kopf AW. Bart RS: Tumor Conference No 42. J Dermatol Surg Oncol 1982;8:442-445. 25 Dompmartin A. Leroy D. Labbe D. Letessier JB. Mandard JC: Dermal malignant melanoma developing from a nevus of Ota. hit J Derma tol 1989:28:535-536. 26 Haglcr WS. Brown CC: Malignant melanoma of the orbit arising in the nevus of Ota. Trans Am Acad Ophthalmol Otolaryngol 1966:70: 817-822. 27 Ilalasa A: Malignant melanoma in a case of bilateral nevus of Ota. Arch Ophthalmol 1970;84:176-178. 28 Jay B: Malignant melanoma of the orbit in a case of oculodermal melanosis. Br J Ophthal mol 1965;49:359-363. 29 Spcakman JS. Phillips MJ: Cellular and malig nant blue nevus complicating oculodermal melanosis. Can J Ophthalmol 1973;8:539-547.
