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including hyperthyroidism&#44; estrogen-producing ovarian cysts&#44; growth hormone excess&#44; renal phosphate wasting with or without rickets&#47;osteomalacia&#44; and Cushing syndrome could be seen in association with the original triad&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">MAS is most often identified by dermatologic findings&#46; <span class="elsevierStyleItalic">Caf&#233;-au-lait</span> macules appear in the neonatal period or in the first months of life&#46; These macules have irregular borders &#40;described as &#8220;coast of Maine&#8221;&#41; and are unilateral&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">There are yet substantial knowledge gaps about MAS pathophysiology and natural history<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and very little information about its <span class="elsevierStyleItalic">caf&#233;-au-lait</span> macules&#44; which were examined by light microscopy&#44; immunohistochemistry&#44; and Transmission Electron Microscopy &#40;TEM&#41; in this report&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">The authors examined a 22-year-old female patient who presented since birth with segmental hyperchromic <span class="elsevierStyleItalic">caf&#233;-au-lait</span> spots in the right side of the abdomen&#44; with a chessboard-like distribution&#44; respecting the midline &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41;&#44; extending to the right thigh with geographical contours &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figs&#46; 1</a>b and c&#41;&#46; The patient was submitted to surgical correction of scoliosis in childhood and presented also an ovarian cyst and truncal obesity&#46; She had been diagnosed with neurofibromatosis type 1 in her childhood&#44; however&#44; without the presence of neurofibromas&#44; Lish nodules&#44; or axillary ephelides&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Biopsies were taken from the hyperpigmented area and processed for light microscopy &#40;hematoxylin-eosin and immunohistochemistry with HMB-45 and Melan-A&#41; and for TEM&#44; in the latter&#44; ultrathin sections targeted the epidermis&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">Light microscopy showed increased melanin pigment with HE is staining &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a&#41;&#44; in some areas the pigment was seen also in suprabasal layers &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>b&#41;&#46; Immunohistochemistry with melanocytic markers &#40;HMB-45 and Melan-A&#41; revealed a normal number of melanocytes &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figs&#46; 2</a>c and d&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">TEM demonstrated normal epidermal structures&#44; such as desmosomes&#44; cytokeratin filaments&#44; basement membrane and hemidesmosomes &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figs&#46; 3</a>a and b&#41;&#46; A high amount of melanosomes in keratinocytes was observed &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>b&#41;&#44; which measured 0&#46;38 to 0&#46;67&#8239;nm&#44; a variation in the form and size could also be observed &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figs&#46; 3</a>b&#44; <a class="elsevierStyleCrossRef" href="#fig0020">4</a>a and <a class="elsevierStyleCrossRef" href="#fig0025">5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">With high magnifications indentations in melanosomes&#8217; outline &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>a and b&#41; could be seen&#44; as well as an irregular melanosomal contour was observed &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#44; in contrast to normal melanosomes&#44; which show a regular contour and an oval shape &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a> inset&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">The clinical signs of the examined patient are in accordance with the literature&#44; with the segmental <span class="elsevierStyleItalic">caf&#233;-au-lait</span> macule&#44; bone&#44; and ovarian involvement&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Light microscopy observed an increase in the melanin pigment with a normal number of melanocytes in hyperchromic MAS lesions&#44; showed by melanocyte markers&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">There are no reports of ultrastructural studies in <span class="elsevierStyleItalic">caf&#233;-au-lait</span> macules of MAS&#44; the authors found only one study that evaluated <span class="elsevierStyleItalic">caf&#233;-au-lait</span> spots using electron microscopy in neurofibromatosis in 1992&#46; No abnormal ultrastructural findings were observed in the melanocytes or epidermal keratinocytes&#44; melanosomes &#40;either in melanocytes or in epidermal keratinocytes&#41; had a normal aspect&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The authors&#8217; findings have also demonstrated a similar pigment increase&#46; With a high-power view&#44; however&#44; the melanosomes present an abnormal aspect&#44; suggesting a defect in their synthesis in MAS&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">This study presents the first description of the electron microscopic features of <span class="elsevierStyleItalic">caf&#233;-au-lait</span> spots in a patient with MAS&#44; describing ultrastructural changes in melanosomes&#44; which appeared with an irregular outline in high magnifications&#46; Dermatologists should recognize this disorder&#44; given the possibility that these macules seen in MAS can be confused with neurofibromatosis&#44; as in the case described here&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Financial support</span><p id="par0070" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Authors&#8217; contributions</span><p id="par0075" class="elsevierStylePara elsevierViewall">Victor Garcia Neto&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the manuscript&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Hiram Larangeira de Almeida Jr&#46;&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; effective participation in research orientation&#59; critical review of the manuscript&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Cla&#250;dia Fernandes Lorea&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the manuscript&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Val&#233;ria Magalh&#227;es Jorge&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the manuscript&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Ant&#244;nia Larangeira de Almeida&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the manuscript&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">McCune - Albright syndrome is a genetic disease with cutaneous mosaicism caused by post-zygotic activating mutations in GNAS locus&#44; it has a triad of fibrous bone dysplasia&#44; caf&#233;-au-lait macules and precocious puberty&#46; We examined a 22-year-old female patient with caf&#233; au lait spot in right side of the abdomen&#44; with a chessboard - like distribution&#44; extending to right thigh with geographical contours&#44; she has also an ovarian cyst&#44; scoliosis and truncal obesity&#46; Biopsies were taken from the hyperpigmented area and processed for light microscopy and for transmission electron microscopy&#46; Light microscopy showed increased melanin pigment with HE staining&#46; Immunohistochemistry with melanocytic markers &#40;HMB-45 and Melan-A&#41; revealed a normal number of melanocytes&#46; Transmission electron microscopy demonstrated normal epidermal structures&#44; such as desmosomes&#44; cytokeratin filaments and hemidesmosomes&#46; With high magnifications an irregular melanossomal contour was seen&#44; with some indentations in their outline&#46;</p></span>"
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