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similar to Paget&#39;s disease cells&#44; which is the cause for the name of this condition&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although easily identified&#44; they can be misdiagnosed&#44; due to the similarity of these cells with those in other diseases such as Paget cells&#44; Toker cells of the nipple and koilocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a> Therefore&#44; the identification of this condition can be of great importance in the differential diagnosis with other skin diseases&#44; in addition to helping understand the keratinization process of the epidermis&#44; as subsequently demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 19-year-old female patient reported that she had small erythematous papules on the palmar surface of the proximal phalanges of the 2<span class="elsevierStyleSup">nd</span>&#44; 3<span class="elsevierStyleSup">rd</span> and 4<span class="elsevierStyleSup">th</span> fingers of the right hand and 3<span class="elsevierStyleSup">rd</span>&#44; 4<span class="elsevierStyleSup">th</span> and 5<span class="elsevierStyleSup">th</span> fingers of the left hand for a year &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; She reported intermittent lesions&#44; with spontaneous improvement one week after their onset&#44; with new worsening after constant use of pens&#44; palm-sweating&#44; when snapping the fingers with the palms touching each other or when the hands were clenched for long periods&#46; She reported mild local pain and denied any other associated symptoms&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Due to the lack of lesion improvement&#44; a skin biopsy was performed&#44; which showed hyperkeratosis&#44; hypergranulosis and mild acanthosis&#59; amidst the keratinocytes&#44; 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becoming unrecognizable in the stratum corneum&#44; after undergoing dissolution of the nucleus during the keratinization process&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> At the end of their report&#44; they concluded that the presence of these cells in specimens from unrelated conditions suggested an artifact&#44; possibly related to moisture or other unknown physical factors&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Although PD was originally considered an artifact&#44; it was Tschen et al&#44; in 1988&#44; who first suggested that PD could represent a reactive process of early keratinization&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> For them&#44; the definition of the epidermis as comprising two cell compartments &#8211; one being the basal layer&#44; which represented undifferentiated proliferative cells and the other being the suprabasal cells undergoing differentiation &#8211; was an exaggerated simplification&#44; as it is possible to find cells undergoing mitosis in the suprabasal layer&#44; as well as cells in the basal layer expressing suprabasal keratins&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Therefore&#44; instead of considering clear epithelial cells as an artifact that repeated itself throughout the specimens&#44; Tschen et al&#46; speculated that these cells were probably a small part of the normal keratinocyte population in the basal layer that underwent mitosis and developed their own cytoplasmic characteristics&#44; possibly resulting from their proliferation after stimuli such as trauma&#44; and thus&#44; could be induced by friction&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5</span></a> Since then&#44; PD has been recognized as a dyskeratotic process and classified among the epidermal maturation defects &#40;it seems to be an accelerated keratinization process&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In 2015&#44; Santos-Briz et al&#46; conducted a study to assess the occurence of pagetoid dyskeratotic cells&#44; considered to this day an incidental finding in skin biopsies&#44; without clinical significance&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> They analyzed all biopsies performed over one year at the Department of Dermatology at Hospital Universitario de Salamanca &#8211; Spain&#44; totaling 3&#44;565 biopsies&#44; of which 80 had PD cells &#40;2&#46;24&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;7</span></a> Although the patients did not report significant mechanical trauma&#44; most cases of PD appeared in exophytic lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Moreover&#44; in 80&#37; of polypoid lesions&#44; PD cells were located in the middle and upper layers of the epidermis&#44; which would be more commonly exposed to physical trauma&#44; such as friction&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Hyperkeratosis &#40;89&#46;3&#37;&#41; and hypergranulosis &#40;82&#46;5&#37;&#41; were found in most biopsies&#44; which also indirectly indicates friction&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In addition&#44; Pique-Duran et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> demonstrated that the axillary location is frequent for PD&#44; which also corroborates the theory that moisture and friction are related to its presence&#44; findings that are consistent with previous data&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">These cells have been reported as an incidental histological finding in several cutaneous diseases that are unrelated to each other&#44; such as melanocytic nevi&#44; lichen simplex chronicus&#44; acrochordons&#44; seborrheic keratoses&#44; among others&#44; and in several different anatomical locations&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;9</span></a> However&#44; contrary to other sites where PD is a finding&#44; pagetoid dyskeratosis on the hands usually presents with discrete changes at the site&#44; as in the case of the abovementioned patient&#44; in addition to being quite uncommon&#44; with only 10 cases reported to date&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In summary&#44; PD&#44; with the exception of the hands&#44; is an incidental&#44; but not uncommon&#44; finding present in more than 2&#37; of skin biopsies&#44; which can be interpreted as a type of accelerated keratinization in a keratinocyte population induced to proliferate after traumatic stimuli&#46; Pathologists should be aware of this finding to avoid misdiagnosing it as other conditions&#44; such as mammary and extramammary Paget&#39;s disease&#44; squamous cell carcinoma <span class="elsevierStyleItalic">in situ</span>&#44; epidermotropic metastases&#44; superficial spreading pagetoid malignant melanoma&#44; clear cell papulosis&#44; and koilocytosis&#44; which represent the differential diagnoses of the disease&#46; A better understanding of PD could probably improve the present understanding of the keratinization process and other epidermal keratinization disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Authors&#8217; contributions</span><p id="par0060" class="elsevierStylePara elsevierViewall">Tauana Ogata Coelho da Rocha&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Fernanda Gon&#231;alves Moya&#58; Effective participation in research orientation&#59; intellectual participation in propaedeutic and&#47;or therapeutic conduct of the studied cases&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">V&#237;vian Moreira Vilella&#58; Statistical analysis&#59; collection&#44; analysis&#44; and interpretation of data&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Rute Facchini Lellis&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; critical review of the manuscript&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Currently&#44; pagetoid dyskeratosis is believed to involve an accelerated keratinization process&#44; possibly induced by mechanical trauma&#46; It represents&#44; in almost its totality&#44; incidental histological findings of specific cells&#44; except when it occurs in the hands&#44; where it usually occurs simultaneously with skin lesions and local dyschromia&#46; These are large&#44; rounded keratinocytes&#44; with pale cytoplasm and a pyknotic nucleus surrounded by a clear halo&#44; which can be easily mistaken by other skin diseases&#46; Its etiology is not completely elucidated&#44; and the correct identification of this entity can be of great importance in the differential diagnosis of skin disorders and the understanding of the keratinization process of the epidermis&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">How to cite this article&#58; Rocha TOC&#44; Moya FG&#44; Vilella VM&#44; Lellis RF&#46; Pagetoid dyskeratosis in dermatopathology&#46; An Bras Dermatol&#46; 2021&#59;96&#58;454&#8211;7&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical presentation of pagetoid dyskeratosis on the hands&#46; &#40;A&#41; Small erythematous papules on the palmar surface of proximal phalanges of 2<span class="elsevierStyleSup">nd</span>&#44; 3<span class="elsevierStyleSup">rd</span> and 4<span class="elsevierStyleSup">th</span> fingers of the right hand and &#40;B&#41; 3<span class="elsevierStyleSup">rd</span>&#44; 4<span class="elsevierStyleSup">th</span> and 5<span class="elsevierStyleSup">th</span> fingers of the left hand&#46;</p>"
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Dermatopathology
Pagetoid dyskeratosis in dermatopathology
Tauana Ogata Coelho da Rochaa,
Autor para correspondência
tauana_ogata@hotmail.com

Corresponding author.
, Fernanda Gonçalves Moyab, Vívian Moreira Vilellac, Rute Facchini Lellisd,e
a Department of Dermatology, Complexo Hospitalar Heliópolis, São Paulo, SP, Brazil
b Department of Pathology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
c Private Clinic, Araçatuba, SP, Brazil
d Department of Pathology, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil
e Department of Pathology, AC Camargo Câncer Center, São Paulo, SP, Brazil
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similar to Paget&#39;s disease cells&#44; which is the cause for the name of this condition&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although easily identified&#44; they can be misdiagnosed&#44; due to the similarity of these cells with those in other diseases such as Paget cells&#44; Toker cells of the nipple and koilocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a> Therefore&#44; the identification of this condition can be of great importance in the differential diagnosis with other skin diseases&#44; in addition to helping understand the keratinization process of the epidermis&#44; as subsequently demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 19-year-old female patient reported that she had small erythematous papules on the palmar surface of the proximal phalanges of the 2<span class="elsevierStyleSup">nd</span>&#44; 3<span class="elsevierStyleSup">rd</span> and 4<span class="elsevierStyleSup">th</span> fingers of the right hand and 3<span class="elsevierStyleSup">rd</span>&#44; 4<span class="elsevierStyleSup">th</span> and 5<span class="elsevierStyleSup">th</span> fingers of the left hand for a year &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; She reported intermittent lesions&#44; with spontaneous improvement one week after their onset&#44; with new worsening after constant use of pens&#44; palm-sweating&#44; when snapping the fingers with the palms touching each other or when the hands were clenched for long periods&#46; She reported mild local pain and denied any other associated symptoms&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Due to the lack of lesion improvement&#44; a skin biopsy was performed&#44; which showed hyperkeratosis&#44; hypergranulosis and mild acanthosis&#59; amidst the keratinocytes&#44; bulky cells with a large and eosinophilic cytoplasm&#44; pyknotic nucleus&#44; and perinuclear clear halo were observed&#59; the superficial and deep dermis were congested and showed discrete perivascular lymphohistiocytic infiltrate &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The anatomoclinical correlation led to the conclusion that the patient had pagetoid dyskeratosis of the hands&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">In 1980&#44; Mehregan assessed 15 patients with varied skin lesions&#44; all of which contained clear epithelial cells characterized by a pyknotic nucleus surrounded by a clear halo and a pale cytoplasm&#44; without keratohyalin granules and intercellular connections between them and neighboring keratinocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> These cells were found in the spinous layer above the basal layer and were well recognized in the granular layer&#44; becoming unrecognizable in the stratum corneum&#44; after undergoing dissolution of the nucleus during the keratinization process&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> At the end of their report&#44; they concluded that the presence of these cells in specimens from unrelated conditions suggested an artifact&#44; possibly related to moisture or other unknown physical factors&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Although PD was originally considered an artifact&#44; it was Tschen et al&#44; in 1988&#44; who first suggested that PD could represent a reactive process of early keratinization&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> For them&#44; the definition of the epidermis as comprising two cell compartments &#8211; one being the basal layer&#44; which represented undifferentiated proliferative cells and the other being the suprabasal cells undergoing differentiation &#8211; was an exaggerated simplification&#44; as it is possible to find cells undergoing mitosis in the suprabasal layer&#44; as well as cells in the basal layer expressing suprabasal keratins&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Therefore&#44; instead of considering clear epithelial cells as an artifact that repeated itself throughout the specimens&#44; Tschen et al&#46; speculated that these cells were probably a small part of the normal keratinocyte population in the basal layer that underwent mitosis and developed their own cytoplasmic characteristics&#44; possibly resulting from their proliferation after stimuli such as trauma&#44; and thus&#44; could be induced by friction&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5</span></a> Since then&#44; PD has been recognized as a dyskeratotic process and classified among the epidermal maturation defects &#40;it seems to be an accelerated keratinization process&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In 2015&#44; Santos-Briz et al&#46; conducted a study to assess the occurence of pagetoid dyskeratotic cells&#44; considered to this day an incidental finding in skin biopsies&#44; without clinical significance&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> They analyzed all biopsies performed over one year at the Department of Dermatology at Hospital Universitario de Salamanca &#8211; Spain&#44; totaling 3&#44;565 biopsies&#44; of which 80 had PD cells &#40;2&#46;24&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;7</span></a> Although the patients did not report significant mechanical trauma&#44; most cases of PD appeared in exophytic lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Moreover&#44; in 80&#37; of polypoid lesions&#44; PD cells were located in the middle and upper layers of the epidermis&#44; which would be more commonly exposed to physical trauma&#44; such as friction&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Hyperkeratosis &#40;89&#46;3&#37;&#41; and hypergranulosis &#40;82&#46;5&#37;&#41; were found in most biopsies&#44; which also indirectly indicates friction&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In addition&#44; Pique-Duran et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> demonstrated that the axillary location is frequent for PD&#44; which also corroborates the theory that moisture and friction are related to its presence&#44; findings that are consistent with previous data&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">These cells have been reported as an incidental histological finding in several cutaneous diseases that are unrelated to each other&#44; such as melanocytic nevi&#44; lichen simplex chronicus&#44; acrochordons&#44; seborrheic keratoses&#44; among others&#44; and in several different anatomical locations&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;9</span></a> However&#44; contrary to other sites where PD is a finding&#44; pagetoid dyskeratosis on the hands usually presents with discrete changes at the site&#44; as in the case of the abovementioned patient&#44; in addition to being quite uncommon&#44; with only 10 cases reported to date&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In summary&#44; PD&#44; with the exception of the hands&#44; is an incidental&#44; but not uncommon&#44; finding present in more than 2&#37; of skin biopsies&#44; which can be interpreted as a type of accelerated keratinization in a keratinocyte population induced to proliferate after traumatic stimuli&#46; Pathologists should be aware of this finding to avoid misdiagnosing it as other conditions&#44; such as mammary and extramammary Paget&#39;s disease&#44; squamous cell carcinoma <span class="elsevierStyleItalic">in situ</span>&#44; epidermotropic metastases&#44; superficial spreading pagetoid malignant melanoma&#44; clear cell papulosis&#44; and koilocytosis&#44; which represent the differential diagnoses of the disease&#46; A better understanding of PD could probably improve the present understanding of the keratinization process and other epidermal keratinization disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Authors&#8217; contributions</span><p id="par0060" class="elsevierStylePara elsevierViewall">Tauana Ogata Coelho da Rocha&#58; Drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Fernanda Gon&#231;alves Moya&#58; Effective participation in research orientation&#59; intellectual participation in propaedeutic and&#47;or therapeutic conduct of the studied cases&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">V&#237;vian Moreira Vilella&#58; Statistical analysis&#59; collection&#44; analysis&#44; and interpretation of data&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Rute Facchini Lellis&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; critical review of the manuscript&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Currently&#44; pagetoid dyskeratosis is believed to involve an accelerated keratinization process&#44; possibly induced by mechanical trauma&#46; It represents&#44; in almost its totality&#44; incidental histological findings of specific cells&#44; except when it occurs in the hands&#44; where it usually occurs simultaneously with skin lesions and local dyschromia&#46; These are large&#44; rounded keratinocytes&#44; with pale cytoplasm and a pyknotic nucleus surrounded by a clear halo&#44; which can be easily mistaken by other skin diseases&#46; Its etiology is not completely elucidated&#44; and the correct identification of this entity can be of great importance in the differential diagnosis of skin disorders and the understanding of the keratinization process of the epidermis&#46;</p></span>"
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