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Int J Clin Exp Pathol 2013;6(9):1868-1873
Pigmented squamous intraepithelial neoplasia of the esophagus
Mitsuaki Ishida, Yosuke Mochizuki, Muneo Iwai, Keiko Yoshida, Akiko Kagotani, Hidetoshi Okabe
Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Division of Digestive Endoscopy, Shiga University of Medical
Science, Shiga, Japan
Received July 16, 2013; Accepted August 15, 2013; Epub August 15, 2013; Published September 1, 2013
Abstract: Squamous cell carcinoma (SCC) usually lacks melanocytes within the tumor. A few reports have documented invasive SCC or SCC
in situ (intraepithelial neoplasia, IEN) with melanocytic hyperplasia within the tumor, referred to as pigmented SCC, in some organs. However,
case series of pigmented SCC or IEN of the esophagus have not yet been reported. This is the first study to analyze the incidence and
clinicopathological features of pigmented SCC or IEN of the esophagus. We reviewed 18 surgically-resected and 122 endoscopically-resected
esophageal specimens, including 79 cases of IEN. Three cases of pigmented IEN were observed in this series, and all of them were located
in the middle to lower third of the esophagus. Two of 3 cases had melanocytosis in the non-neoplastic squamous epithelium around the IEN.
The incidence of pigmented IEN was 2.5% of all endoscopically resected specimens and 3.8% of IEN cases. No pigmented invasive SCC was
detected in both endoscopically-resected and surgically-resected specimens. The mechanism of pigmentation of esophageal IEN is unknown.
However, production of melanocyte chemotactic factors by tumor cells has been demonstrated in pigmented SCC of the oral mucosa.
Moreover, two of 3 cases of pigmented IEN in the present series had melanocytosis in the non-neoplastic squamous epithelium, and
melanocytosis is thought to be associated with chronic esophagitis, therefore, it has been hypothesized that various stimuli can cause
pigmentation in squamous epithelium. Additional studies are needed to clarify the mechanism of pigmentation in squamous IEN of the
Keywords: Intraepithelial squamous neoplasia, squamous cell carcinoma, esophagus, melanocytes
Address correspondence to: Dr. Mitsuaki Ishida, Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga
University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan. Tel: +81-77-548-2603; Fax: +81-77-548-2407; E-mail: