Pigmented squamous intraepithelial neoplasia of the esophagus

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 esophagus.

Keywords: Intraepithelial squamous neoplasia; esophagus; melanocytes; squamous cell carcinoma.

Figure 1

A: Endoscopic mucosal resection specimen of Case 1 showing a slightly depressed lesion with a black spot in the esophagus (arrow). B: Endoscopic findings of Case 2 showing a depressed lesion in the esophagus (arrow).

Figure 2

Histopathological findings. A: Case 1. Atypical squamous proliferation is observed in the lower third of the squamous epithelium accompanied by dendritic melanocytes without atypia. HE, x 400. B: Melanocytosis is also present in the non-neoplastic squamous mucosa. HE, x 400. C: Case 2. Atypical squamous proliferation is noted in the lower half of the squamous epithelium with proliferation of dendritic melanocytes without atypia. HE, x 400. D: Case 3. Atypical squamous cell proliferation is observed in the entire layer of the squamous mucosa accompanied by dendritic melanocytes. Dendritic melanocytes are without atypia, and melanin pigment is present within the cytoplasm of the atypical squamous cells (inset). HE, x 200, x 400 (inset).

Figure 3

Immunohistochemical features of Case 3. Melan A is expressed in the dendritic melanocytes within the IEN. Melan-A-positive dendritic melanocytes are present in the non-neoplastic squamous epithelium (inset). x 200.