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Acquired dermal melanocytosis in an African-American: A case report
Acquired dermal melanocytosis in an African-American: A case report Robert Buka, MD,a Jim Mauch, MD, PhD,b Robert Phelps, MD,b and Donald Rudikoff, MDa New York City, New York We report an unusual case of acquired dermal melanocytosis occurring in a 57-year-old African-American woman. Macular pigmentation over the patient’s cheeks, back, and sclerae developed over the course of 18 months without identifiable antecedent. The patient was taking only hormone replacement therapy and was generally healthy. Histologic examination of the skin revealed dendritic melanocytes and melanophages in the mid- to upper dermis. We briefly review the literature surrounding acquired dermal melanocytosis and continue discussion regarding its pathogenesis. (J Am Acad Dermatol 2000;43:934-6.)
A
cquired dermal melanocytosis (ADM) may have been first described as early as 1948 when Rothman and Pinne reported a case of a 20-year-old Japanese-American woman who noted a black pigmentation of her right sclera, which progressively spread to her right cheek and periocular region as a blue-gray macule. This patient had previously exhibited a nevus of Ota, which became increasingly prominent over the course of several years. The authors attributed the acquired pigmentation to a black telephone receiver the patient often held against her right ear.1 The pathogenesis of ADM is currently unknown. A review of the literature has generated 3, likely interactive, etiologic theories behind ADM: (1) migration of epidermal melanocytes, (2) migration of hair bulb melanocytes, and (3) reactivation of preexisting latent dermal melanocytes triggered by inflammation or some unknown aging stimuli.2
CASE REPORT A 57-year-old African-American woman, with a past medical history significant for insulin-dependent diabetes mellitus, pulmonary sarcoidosis, and bilateral glaucoma, noted a progressive darkening of her cheeks, back, right arm, and the “whites” of both eyes This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. From the Departments of Dermatologya and Pathology,b The Mount Sinai Medical Center. Reprint requests: Donald Rudikoff, Department of Dermatology,The Mount Sinai Medical Center, 5 E 98th St, New York City, NY 10029. Copyright © 2000 by the American Academy of Dermatology, Inc. 0190-9622/2000/$12.00 + 0 16/4/102649 doi:10.1067/mjd.2000.102649
934
over the last 18 months (Fig 1). The patient reported that the pigmentation began on her upper back without preceding inflammation, history of trauma, discoloration, or significant sun exposure. The darkening developed 5 months after initiating therapy with oral conjugated estrogens (Premarin) as part of a hormone replacement therapy regimen. The patient was not taking any other medications and was generally healthy. Family history was significant for a first-degree relative with systemic lupus; however, the patient was unaware of any history of skin cancer in her family. Physical examination revealed macular brownish discoloration of both sclerae as well as patchy hyperpigmentation of the cheeks. On the patient’s right arm and right side of back, there was hypermelanotic streaking along Blaschko’s lines. Examination of the skin, hair, nails, and mucous membranes was otherwise unremarkable. A recent funduscopic examination by the patient’s ophthalmologist revealed benign epithelial melanosis without retinal involvement. Histologic examination of the skin revealed a diffuse increase in melanin in the basal epidermis, consistent with the patient’s ethnicity, without a discernible increase in melanocytes. However, dendritic melanocytes and melanophages were also seen in the mid- to upper dermis. Immunohistochemistry against S100 and HMB45 antigens confirmed hematoxylin-eosin findings; melanocytes were seen in the papillary and upper reticular dermis (Fig 2).
DISCUSSION This case of acquired hyperpigmentation is unusual insofar as it resembled several dermatoses, ie, nevi of Ota and Ito. The patient’s facial lesions bore a striking resemblance to bilateral nevus of Ota, whereas the arm and truncal involvement suggested
Buka et al 935
J AM ACAD DERMATOL VOLUME 43, NUMBER 5
A
B
C
Fig 1. A through C. Extensive pigmentation of patient’s cheeks, sclerae, and right shoulder in Blashko-like distribution.
a process more akin to nevus of Ito along Blaschko’s lines. The presence of dermal melanocytes, and the onset of these lesions late in life, after initiation of estrogen therapy, suggested the diagnosis of ADM. Nearly 40 years after the report by Rothman and Pinne, bilateral nevus of Ota-like macules were described in 22 patients; all but one were female, and the median age of pigmentation onset was 36 years.3 These patients had either blue-brown macules or slate-gray patches involving both sides of the forehead and the temples, eyelids, malar areas, alae, and root of the nose. Unlike our case, none of these patients exhibited ocular pigmentation or involvement of other areas of the face. Histologic examination of all 22 patients revealed scattered pigment-bearing cells in the mid- to upper dermis. These cells were further classified by electron microscopy as active melanocytes surrounded by an extracellular sheath (as
seen in nevus of Ota). They were not associated with fibrosis nor did they disturb the normal architecture of the skin.3 These lesions, like those in our patient, were not fully consistent with nevus of Ota, because this condition typically begins in childhood or adolescence and often includes the mucosal surfaces of the mouth and nose as well as tympanic membranes. There have been additional sporadic case reports akin to ADM, such as nevus of Ota acquisita of late onset involving the face and scalp of an 80-year-old white man, but there is no clinical consensus as to how best categorize this unusual condition.4 We encountered only one other case report from Japan with a lesional distribution similar to our own, which was likewise identified as ADM of the face and extremities.5 The histopathologic features of ADM resemble other dermal melanocytoses. Dermal melanocytes
936 Buka et al
Fig 2. S-100 melanocyte-specific stain was markedly positive. Melanocytes were seen scattered throughout mid- to upper dermis. HMB-45 stain (not shown) for melanocytes was also positive in similar distribution.
seen in ADM are c-KIT positive when examined by immunohistochemistry; these are immature, nonpigmented cells distributed throughout both the upper and lower dermis.6 The distribution of these immature melanocytes is presumably related to a hereditary predisposition, lending support to the leading etiologic theory that ADM is caused by a reactivation of preexisting latent melanocytes. Our patient initiated estrogen therapy 5 months before her pigmentary changes, suggesting estrogen as a possible initiating catalyst for the activation of preexisting, immature dermal melanocytes. Estrogens have been shown to stimulate melanogenesis in a wide variety of species. Experiments using guinea pigs demonstrated increased amounts of melanin both in and outside melanocytes after small doses of IM estrogens. Moreover, when administered alongside progesterone (as is often the case in hormone replacement therapy), melanogenic effects were even more pronounced.7 Our patient’s clinical presentation was remarkably similar to that expected with a concurrent nevus of Ota and nevus of Ito. Nevus of Ota typically arises in early childhood and is characteristically unilateral, in the area innervated by the ophthalmic and maxillary divisions of the trigeminal nerve. The lesions are flat blue-black or slate-gray macules, intermingled with small, flat brown spots that often involve mucous membranes. Scleral pigmentation may be seen as in our patient, and when melanocytosis affects the anterior chamber angle structures, elevated intraocular pressure and narrow angle glaucoma may result. This remains the most common serious complication of
J AM ACAD DERMATOL NOVEMBER 2000
nevus of Ota, seen in approximately 10% of patients.8 Histologically, dermal melanocytes are widely scattered in the dermis, with a greater concentration in the upper dermis, as was seen in our patient. By comparison, nevus of Ito is located in the supraclavicular, scapular, and deltoid regions, in the areas innervated by posterior supraclavicular and lateral brachiocutaneous nerves. This case represents an unusual acquired pigmentary disorder that appears to be the result of dermal melanocytosis, most likely a result of estrogen-stimulated melanin formation in preexisting immature melanocytes. The addition of conjugated estrogens to this patient’s level of endogenous estrogen may have prompted a reactivation of preexisting latent melanocytes. The presentation resembles those cases of ADM reported by Hori et al,3 although their cases did not include mucous membrane involvement in the eye. The patient was referred for evaluation for laser treatments.9-11 Further studies that would be illustrative in this patient include electron microscopy to identify the presence of extracellular sheaths around dermal melanocytes (seen in nevus of Ota). REFERENCES 1. Stanford DG, Georgouras KE. Dermal melanocytosis: a clinical spectrum. Aust J Dermatol 1996;37:19-25. 2. Ono T, Egawa K, Kayashima K, Kitoh M. Late onset dermal melanocytosis: an upper back variant. J Dermatol 1991;18:97103. 3. Hori Y, Kawashima M, Oohara K, Kukita A. Acquired, bilateral nevus of Ota-like macules. J Am Acad Dermatol 1984;10:961-4. 4. Lynn A, Brozena SJ, Espinoza CG, Fenske NA. Nevus of Ota acquisita of late onset. Cutis 1993;51:194-6. 5. Hidano A, Kaneko K. Acquired dermal melanocytosis of the face and extremities. Br J Dermatol 1991;124:96-9. 6. Mizoguchi M, Murakami F, Ito M, Asano M, Baba T, Kawa Y, et al. Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis. Pigment Cell Res 1997;10:176-83. 7. Quevedo WC Jr, Fitzpatrick TB, Szabo G, Jimbow K. Biology of the melanin pigmentary system. In: Fitzpatrick TB, editor. Dermatology and general medicine. New York: McGraw-Hill; 1979. 8. Patel BC, Egan CA, Lucius RW, Gerwels JW, Mamalis N, Anderson RL. Cutaneous malignant melanoma and oculodermal melanocytosis (nevus of Ota): report of a case and review of the literature. J Am Acad Dermatol 1998;38(5 Pt 2):862-5. 9. Tse Y, Levine VJ, McClain SA, Ashinoff R. The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser: a comparative study. J Dermatol Surg Oncol 1994;20:795-800. 10. Watanabe S,Takahashi H.Treatment of nevus of Ota with the Qswitched ruby laser. N Engl J Med 1994;331:1745-50. 11. Taylor CR, Flotte TJ, Gange RW, Anderson RR.Treatment of nevus of Ota by Q-switched ruby laser. J Am Acad Dermatol 1994;30(5 Pt 1):743-51.
A
cquired dermal melanocytosis (ADM) may have been first described as early as 1948 when Rothman and Pinne reported a case of a 20-year-old Japanese-American woman who noted a black pigmentation of her right sclera, which progressively spread to her right cheek and periocular region as a blue-gray macule. This patient had previously exhibited a nevus of Ota, which became increasingly prominent over the course of several years. The authors attributed the acquired pigmentation to a black telephone receiver the patient often held against her right ear.1 The pathogenesis of ADM is currently unknown. A review of the literature has generated 3, likely interactive, etiologic theories behind ADM: (1) migration of epidermal melanocytes, (2) migration of hair bulb melanocytes, and (3) reactivation of preexisting latent dermal melanocytes triggered by inflammation or some unknown aging stimuli.2
CASE REPORT A 57-year-old African-American woman, with a past medical history significant for insulin-dependent diabetes mellitus, pulmonary sarcoidosis, and bilateral glaucoma, noted a progressive darkening of her cheeks, back, right arm, and the “whites” of both eyes This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. From the Departments of Dermatologya and Pathology,b The Mount Sinai Medical Center. Reprint requests: Donald Rudikoff, Department of Dermatology,The Mount Sinai Medical Center, 5 E 98th St, New York City, NY 10029. Copyright © 2000 by the American Academy of Dermatology, Inc. 0190-9622/2000/$12.00 + 0 16/4/102649 doi:10.1067/mjd.2000.102649
934
over the last 18 months (Fig 1). The patient reported that the pigmentation began on her upper back without preceding inflammation, history of trauma, discoloration, or significant sun exposure. The darkening developed 5 months after initiating therapy with oral conjugated estrogens (Premarin) as part of a hormone replacement therapy regimen. The patient was not taking any other medications and was generally healthy. Family history was significant for a first-degree relative with systemic lupus; however, the patient was unaware of any history of skin cancer in her family. Physical examination revealed macular brownish discoloration of both sclerae as well as patchy hyperpigmentation of the cheeks. On the patient’s right arm and right side of back, there was hypermelanotic streaking along Blaschko’s lines. Examination of the skin, hair, nails, and mucous membranes was otherwise unremarkable. A recent funduscopic examination by the patient’s ophthalmologist revealed benign epithelial melanosis without retinal involvement. Histologic examination of the skin revealed a diffuse increase in melanin in the basal epidermis, consistent with the patient’s ethnicity, without a discernible increase in melanocytes. However, dendritic melanocytes and melanophages were also seen in the mid- to upper dermis. Immunohistochemistry against S100 and HMB45 antigens confirmed hematoxylin-eosin findings; melanocytes were seen in the papillary and upper reticular dermis (Fig 2).
DISCUSSION This case of acquired hyperpigmentation is unusual insofar as it resembled several dermatoses, ie, nevi of Ota and Ito. The patient’s facial lesions bore a striking resemblance to bilateral nevus of Ota, whereas the arm and truncal involvement suggested
Buka et al 935
J AM ACAD DERMATOL VOLUME 43, NUMBER 5
A
B
C
Fig 1. A through C. Extensive pigmentation of patient’s cheeks, sclerae, and right shoulder in Blashko-like distribution.
a process more akin to nevus of Ito along Blaschko’s lines. The presence of dermal melanocytes, and the onset of these lesions late in life, after initiation of estrogen therapy, suggested the diagnosis of ADM. Nearly 40 years after the report by Rothman and Pinne, bilateral nevus of Ota-like macules were described in 22 patients; all but one were female, and the median age of pigmentation onset was 36 years.3 These patients had either blue-brown macules or slate-gray patches involving both sides of the forehead and the temples, eyelids, malar areas, alae, and root of the nose. Unlike our case, none of these patients exhibited ocular pigmentation or involvement of other areas of the face. Histologic examination of all 22 patients revealed scattered pigment-bearing cells in the mid- to upper dermis. These cells were further classified by electron microscopy as active melanocytes surrounded by an extracellular sheath (as
seen in nevus of Ota). They were not associated with fibrosis nor did they disturb the normal architecture of the skin.3 These lesions, like those in our patient, were not fully consistent with nevus of Ota, because this condition typically begins in childhood or adolescence and often includes the mucosal surfaces of the mouth and nose as well as tympanic membranes. There have been additional sporadic case reports akin to ADM, such as nevus of Ota acquisita of late onset involving the face and scalp of an 80-year-old white man, but there is no clinical consensus as to how best categorize this unusual condition.4 We encountered only one other case report from Japan with a lesional distribution similar to our own, which was likewise identified as ADM of the face and extremities.5 The histopathologic features of ADM resemble other dermal melanocytoses. Dermal melanocytes
936 Buka et al
Fig 2. S-100 melanocyte-specific stain was markedly positive. Melanocytes were seen scattered throughout mid- to upper dermis. HMB-45 stain (not shown) for melanocytes was also positive in similar distribution.
seen in ADM are c-KIT positive when examined by immunohistochemistry; these are immature, nonpigmented cells distributed throughout both the upper and lower dermis.6 The distribution of these immature melanocytes is presumably related to a hereditary predisposition, lending support to the leading etiologic theory that ADM is caused by a reactivation of preexisting latent melanocytes. Our patient initiated estrogen therapy 5 months before her pigmentary changes, suggesting estrogen as a possible initiating catalyst for the activation of preexisting, immature dermal melanocytes. Estrogens have been shown to stimulate melanogenesis in a wide variety of species. Experiments using guinea pigs demonstrated increased amounts of melanin both in and outside melanocytes after small doses of IM estrogens. Moreover, when administered alongside progesterone (as is often the case in hormone replacement therapy), melanogenic effects were even more pronounced.7 Our patient’s clinical presentation was remarkably similar to that expected with a concurrent nevus of Ota and nevus of Ito. Nevus of Ota typically arises in early childhood and is characteristically unilateral, in the area innervated by the ophthalmic and maxillary divisions of the trigeminal nerve. The lesions are flat blue-black or slate-gray macules, intermingled with small, flat brown spots that often involve mucous membranes. Scleral pigmentation may be seen as in our patient, and when melanocytosis affects the anterior chamber angle structures, elevated intraocular pressure and narrow angle glaucoma may result. This remains the most common serious complication of
J AM ACAD DERMATOL NOVEMBER 2000
nevus of Ota, seen in approximately 10% of patients.8 Histologically, dermal melanocytes are widely scattered in the dermis, with a greater concentration in the upper dermis, as was seen in our patient. By comparison, nevus of Ito is located in the supraclavicular, scapular, and deltoid regions, in the areas innervated by posterior supraclavicular and lateral brachiocutaneous nerves. This case represents an unusual acquired pigmentary disorder that appears to be the result of dermal melanocytosis, most likely a result of estrogen-stimulated melanin formation in preexisting immature melanocytes. The addition of conjugated estrogens to this patient’s level of endogenous estrogen may have prompted a reactivation of preexisting latent melanocytes. The presentation resembles those cases of ADM reported by Hori et al,3 although their cases did not include mucous membrane involvement in the eye. The patient was referred for evaluation for laser treatments.9-11 Further studies that would be illustrative in this patient include electron microscopy to identify the presence of extracellular sheaths around dermal melanocytes (seen in nevus of Ota). REFERENCES 1. Stanford DG, Georgouras KE. Dermal melanocytosis: a clinical spectrum. Aust J Dermatol 1996;37:19-25. 2. Ono T, Egawa K, Kayashima K, Kitoh M. Late onset dermal melanocytosis: an upper back variant. J Dermatol 1991;18:97103. 3. Hori Y, Kawashima M, Oohara K, Kukita A. Acquired, bilateral nevus of Ota-like macules. J Am Acad Dermatol 1984;10:961-4. 4. Lynn A, Brozena SJ, Espinoza CG, Fenske NA. Nevus of Ota acquisita of late onset. Cutis 1993;51:194-6. 5. Hidano A, Kaneko K. Acquired dermal melanocytosis of the face and extremities. Br J Dermatol 1991;124:96-9. 6. Mizoguchi M, Murakami F, Ito M, Asano M, Baba T, Kawa Y, et al. Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis. Pigment Cell Res 1997;10:176-83. 7. Quevedo WC Jr, Fitzpatrick TB, Szabo G, Jimbow K. Biology of the melanin pigmentary system. In: Fitzpatrick TB, editor. Dermatology and general medicine. New York: McGraw-Hill; 1979. 8. Patel BC, Egan CA, Lucius RW, Gerwels JW, Mamalis N, Anderson RL. Cutaneous malignant melanoma and oculodermal melanocytosis (nevus of Ota): report of a case and review of the literature. J Am Acad Dermatol 1998;38(5 Pt 2):862-5. 9. Tse Y, Levine VJ, McClain SA, Ashinoff R. The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser: a comparative study. J Dermatol Surg Oncol 1994;20:795-800. 10. Watanabe S,Takahashi H.Treatment of nevus of Ota with the Qswitched ruby laser. N Engl J Med 1994;331:1745-50. 11. Taylor CR, Flotte TJ, Gange RW, Anderson RR.Treatment of nevus of Ota by Q-switched ruby laser. J Am Acad Dermatol 1994;30(5 Pt 1):743-51.