Digestive Endoscopy 2014; ••: ••–••
doi: 10.1111/den.12331
Case Report
Esophageal adenocarcinoma with white opaque substance observed by magnifying endoscopy with narrow band imaging Shunsuke Yoshii,1 Motohiko Kato,1 Keiichiro Honma,2 Tetsuji Fujinaga,1 Yoshiki Tsujii,1 Akira Maekawa,1 Takuya Inoue,1 Yoshito Hayashi,1 Tomofumi Akasaka,1 Shinichiro Shinzaki,1 Tsutomu Nishida,1 Hideki Iijima,1 Masahiko Tsujii,1 Eiichi Morii2 and Tetsuo Takehara1 1
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine and Department of Diagnostic Pathology, Osaka University Hospital, Suita, Japan
2
White opaque substance (WOS) is observed in the gastric neoplasia of 0-IIa type using magnifying endoscopy with narrow band imaging (NBI-ME). Colonic and duodenal neoplasms with WOS have also been reported. Immunohistochemical examination with adipophilin reveals WOS in gastric neoplasms as lipid droplets, and WOS is specific for neoplasm with intestinal or gastrointestinal phenotype. We herein report a case of adenocarcinoma of the esophagogastric junction with WOS. A male patient in his sixties was found by esophagogastroduodenoscopy to have an
Key words: adenocarcinoma, esophageal cancer, magnifying endoscopy, narrow band imaging (NBI), white opaque substance (WOS)
INTRODUCTION
CASE REPORT
W
A
HITE OPAQUE SUBSTANCE (WOS) was first reported by Yao et al. in 2008 as a finding of elevatedtype gastric adenoma or adenocarcinoma using magnifying endoscopy with narrow band imaging (NBI-ME). WOS is a white deposit that sometimes interferes with visualization of the subepithelial microvascular pattern in gastric neoplasia.1 It has been pathologically confirmed that WOS observed by NBI-ME represents the accumulation of lipid droplets using oil red O staining and adipophilin immunostaining.2,3 Furthermore, it has been reported to be found in colonic and duodenal neoplasms but not in other gastrointestinal neoplasms.4 Here, we report a case of adenocarcinoma of the esophagogastric junction (EGJ) in which we observed WOS using NBI-ME. To our knowledge, this is the first report describing a WOS-positive esophageal neoplasm.
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Corresponding: Tetsuo Takehara, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Email: [email protected] Received 31 March 2014; accepted 4 July 2014.
esophageal elevated lesion. NBI-ME showed whitish deposits that looked similar to WOS in gastric neoplasms. The patient underwent endoscopic submucosal dissection and the lesion was resected in a single piece. This tumor had diffuse positivity for adipophilin and gastrointestinal phenotype.
MALE IN his sixties was referred for examination for the cause of epigastralgia. Endoscopic examination showed an elevated lesion in the lower esophagus. He had medical histories of hypertension and chronic renal failure on hemodialysis because of nephrosclerosis. He had never smoked and drank socially. He was negative for antiHelicobacter pylori IgG antibody. Conventional white light imaging showed a smooth, flat, elevated lesion of 20 mm in diameter, without ulceration and redness at the adjacent oral side of the squamocolumnar junction (SCJ) in the posterior wall (Fig. 1A). NBI-ME showed irregular microsurface structures with small and high-density pits. In one part, the lesion revealed an irregular mesh-shaped microvascular pattern. In the other part, whitish deposits were observed that were similar to WOS in gastric neoplasms (Fig. 1B). The oral margin of the lesion was covered with squamous epithelium, suggesting subepithelial invasion. Histology of the specimen obtained by endoscopic forceps biopsy revealed well-differentiated adenocarcinoma. Based on the findings described above, he was clinically diagnosed with adenocarcinoma arising
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
1
2
S. Yoshii et al.
Digestive Endoscopy 2014; ••: ••–••
A
B
A
B
C
D
Figure 1 Esophageal adenocarcinoma with white opaque substance (WOS) is shown on upper gastrointestinal endoscopy. (A) Esophageal endoscopy with white light image shows a 20-mm flat elevated lesion on the posterior wall of the lower esophagus. (B) WOS was visualized on the surface of this lesion using magnifying endoscopy with narrow band imaging.
Figure 2 Resected specimen shows a well to moderately differentiated adenocarcinoma of the gastroesophageal junction. (A) Resected specimen shows an intramucosal well to moderately differentiated tubular adenocarcinoma of the esophagus (hematoxylin-eosin stain; loupe view). (B) High-power view of area outlined by black square in part (A) ×100. In the oral margin of the lesion, atypical epithelium invades below the squamous epithelium. (C) High-power view of area outlined by yellow square in part (A) ×100. In the center of the lesion, tumor invades deeply in the lamina propria mucosae and is adjacent to the muscularis mucosae. (D) Specimen after formalin fixation. Orange lines mark the adenocarcinoma invading the lamina propria mucosae (LPM), blue lines mark that adjacent to the muscularis mucosae (MM) and the pink line marks the squamocolumnar junction (SCJ).
from EGJ and it was estimated that invasion depth was within the mucosa. The patient underwent ESD and the lesion was resected in a single piece without major complications. Histology revealed atypical glandular epithelium proliferating widely in the lamina propria mucosae. In the oral margin of the lesion, atypical epithelium invaded below the squamous epithelium (Fig. 2A,B). In the center of the lesion, tumor invaded beyond the mucosa adjacent to the muscularis mucosae (Fig. 2C,D). D2/40 immunohistochemistry showed there was no lymphovascular involvement. Histopathologically, short segmental Barrett’s epithelium was observed, but it had no contact with the lesion. Immunohistochemical
staining revealed that the lesion was focally positive for mucin (MUC) 2, CD10 and MUC6 and negative for MUC5AC. The lesion also had diffuse positivity for caudalrelated homeobox transcription factor (CDX) 2 (Fig. 3). In addition, immunohistochemical staining of adipophilin revealed that lipid droplets accumulated in the neoplastic epithelium. Adipophilin was detected in almost all the neoplastic cells in marginal crypt epithelium, whereas this was not observed in the non-neoplastic epithelium (Fig. 4). The final diagnosis was well to moderately differentiated adenocarcinoma of the gastroesophageal junction E, 20 mm, 0-IIa, tub1 >tub2, pT1a-MM, ly0, v0, pHM0, pVM0 (Japanese Classification of Esophageal Cancer, the 10th Edition,
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Esophageal adenocarcinoma with WOS 3
A
B
D
E
C
Figure 3 Immunohistochemical examination. (A) MUC2, magnification, ×100. (B) MUC5AC, magnification, ×100. (C) MUC6, magnification, ×100. (D) CD10, magnification, ×200. (E) CDX2. Lesion had focal positivity for MUC2, MUC6 and CD10 but negative staining for MUC5AC. The lesion also had diffuse positivity for CDX2, magnification, ×100.
0
100
200
300
400 µm
Figure 4 Immunohistochemical examination of adipophilin. Adipophilin was detected in approximately all of the neoplastic cells.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
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S. Yoshii et al.
revised version).5,6 The patient followed an uneventful clinical course and was discharged 12 days after ESD.
DISCUSSION
R
ECENTLY, NBI-ME HAS been reported to be clinically useful for differentiation of gastric cancerous and non-cancerous lesions. One of the most important findings of cancerous lesions is considered to be the presence of irregularity of the microvascular architecture.7 However, when NBI-ME is applied in clinical practice, a white substance in the superficial area of the neoplasia sometimes interrupts visualization of the precise microvascular morphology. Yao et al. first reported this substance and named it WOS and they also reported that WOS not only interferes with visualization of the epithelial microvascular architecture but is also useful for discriminating gastric adenoma from carcinoma according to the presence or absence of irregular shapes and the distribution of WOS.1 WOS has been pathologically confirmed to be intramucosal accumulation of lipid detected using oil red O staining of the endoscopic biopsy specimen.3 Oil red O staining enables direct visualization of lipid droplets; however, it has a limitation in that it can only be applied to fresh frozen samples but not to paraffin-embedded sections because the lipid is removed during the process of paraffin fixing. Recently, adipophilin has been recognized as a novel marker of lipid accumulation and it can be applied even to paraffinembedded section. It is an adipose differentiation-related protein located on the surface of lipid droplets.8 It was reported that immunohistochemistry of adipophilin of gastric neoplasia was well correlated with WOS observed by NBI-ME.2 To the best of our knowledge, this is the first report describing a WOS-positive esophageal neoplasm, and we confirmed the phenomenon that lipid accumulation may occur in neoplasms arising from the esophagus. Two mechanisms of accumulation of lipid droplets are suggested: lipid absorption and lipid production.2 First, an electron microscopy study using a lipid-staining method has already revealed that the epithelium of the gastric intestinal metaplasia has an ability to absorb lipid droplets similar to the normal small intestinal epithelium.9 This finding suggests that even gastric epithelium can obtain an intestinal phenotype to absorb lipids. Absorbed lipid droplets are retained within the epithelium, and are drained into the lymphatics within the lamina propria after forming chylomicrons in the normal small intestine. In the neoplasm, the accumulation of lipid droplets might be caused by its impaired lymphatic clearance as a result of structural abnormality. Second, the expression process of adipophilin can be enhanced.10 The expression of adipophilin is suspected to be induced during
Digestive Endoscopy 2014; ••: ••–••
the process of carcinogenesis because it is known to be regulated by hypoxia inducible factor (HIF) and the peroxisome proliferator-activated receptor (PPAR) family, both of which are closely involved in carcinogenesis. A previous report demonstrated that WOS is present in either gastrointestinal-type or intestinal-type gastric neoplasia, but absent in gastric-type neoplasia.3 In case mucin expression is heterogeneous, WOS is observed only in the part of intestinal or gastrointestinal phenotype of the tumor.11 In our case, the tumor cells were positive for MUC2, MUC6, CD10, and CDX2 and were considered to have gastrointestinal phenotype. Although the detailed mechanism of lipid droplet accumulation in the esophageal neoplastic epithelium is unknown, the fact that our case expressed gastrointestinal phenotype as well as gastric neoplasm suggests that lipid could accumulate in adenocarcinoma, if the tumor has, at least partly, intestinal phenotype irrespective of the organ where the tumor arises. It would be a useful optical predictor for the mucin-expressing phenotype of the tumor. There are four possible origins of adenocarcinomas of the esophagus; Barrett’s esophagus (epithelium), esophageal glands proper, ectopic gastric mucosa, and esophageal cardiac glands. In our case, a short segmental Barrett’s epithelium was present in the specimen, but it had no contact with the tumor. Tumors arising from esophageal glands proper usually grow in the submucosa and those from ectopic gastric mucosa were reported to localize only in the upper or cervical esophagus;12 therefore, these are unlikely as the origins for our case. The tumor mainly grew in the lamina propria mucosae, and the cardiac glands of the esophagus in a non-cancerous squamous epithelium on the anal side of the tumor had dysplastic changes. Thus, we considered the possible origin of this tumor was esophageal cardiac glands. In summary, we present the first case of esophageal adenocarcinoma with WOS, which seems to arise from esophageal cardiac glands. WOS might be a clue to understanding carcinogenesis and pathophysiology of intestinal-type adenocarcinoma of the digestive system.
CONFLICT OF INTERESTS
A
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES 1 Yao K, Iwashita A, Tanabe H et al. White opaque substance within superficial elevated gastric neoplasia as visualized by magnification endoscopy with narrow-band imaging: A new optical sign for differentiating between adenoma and carcinoma. Gastrointest. Endosc. 2008; 68: 574–80.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Esophageal adenocarcinoma with WOS 5
2 Ueo T, Yonemasu H, Yada N et al. White opaque substance represents an intracytoplasmic accumulation of lipid droplets: Immunohistochemical and immunoelectron microscopic investigation of 26 cases. Dig. Endosc. 2013; 25: 147–55. 3 Yao K, Iwashita A, Nambu M et al. Nature of white opaque substance in gastric epithelial neoplasia as visualized by magnifying endoscopy with narrow-band imaging. Dig. Endosc. 2012; 24: 419–25. 4 Yoshimura N, Goda K, Tajiri H, Ikegami M, Nakayoshi T, Kaise M. Endoscopic features of nonampullary duodenal tumors with narrow-band imaging. Hepatogastroenterology 2010; 57: 462–7. 5 Takubo K, Makuuchi H, Fujita H et al. Japanese Classification of Esophageal Cancer, tenth edition: part 1. Esophagus 2009; 6: 1–25. 6 Takubo K, Makuuchi H, Fujita H et al. Japanese Classification of Esophageal Cancer, tenth edition: parts II and III. Esophagus 2009; 6: 71–94. 7 Yao K, Oishi T, Matsui T, Yao T, Iwashita A. Novel magnified endoscopic findings of microvascular architecture in intramucosal gastric cancer. Gastrointest. Endosc. 2002; 56: 279–84. 8 Heid HW, Moll R, Schwetlick I, Rackwitz HR, Keenan TW. Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res. 1998; 294: 309–21. 9 Rubin W, Ross LL, Jeffries GH, Sleisenger MH. Some physiologic properties of heterotopic intestinal epithelium. Its role in
transporting lipid into the gastric mucosa. Lab. Invest. 1967; 16: 813–27. 10 Matsubara J, Honda K, Ono M et al. Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray. Cancer Epidemiol. Biomarkers Prev. 2011; 20: 2195–203. 11 Ueyama H, Matsumoto K, Nagahara A et al. A white opaque substance-positive gastric hyperplastic polyp with dysplasia. World J. Gastroenterol. 2013; 19: 4262–6. 12 Akanuma N, Hoshino I, Akutsu Y et al. Primary esophageal adenocarcinoma arising from heterotopic gastric mucosa: Report of a case. Surg. Today 2013; 43: 446–51.
SUPPORTING INFORMATION
A
DDITIONAL SUPPORTING INFORMATION may be found in the online version of this article at the publisher’s web-site: Figure S1 Loupe view of the deeper cut examination. Invasion depth and vertical margin are confirmed by hematoxylin-eosin stain. Figure S2 Loupe view of the immunohistochemical examination of desmin. Muscularis mucosae were confirmed to be maintained in the specimen by immunohistochemical examination of desmin.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
doi: 10.1111/den.12331
Case Report
Esophageal adenocarcinoma with white opaque substance observed by magnifying endoscopy with narrow band imaging Shunsuke Yoshii,1 Motohiko Kato,1 Keiichiro Honma,2 Tetsuji Fujinaga,1 Yoshiki Tsujii,1 Akira Maekawa,1 Takuya Inoue,1 Yoshito Hayashi,1 Tomofumi Akasaka,1 Shinichiro Shinzaki,1 Tsutomu Nishida,1 Hideki Iijima,1 Masahiko Tsujii,1 Eiichi Morii2 and Tetsuo Takehara1 1
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine and Department of Diagnostic Pathology, Osaka University Hospital, Suita, Japan
2
White opaque substance (WOS) is observed in the gastric neoplasia of 0-IIa type using magnifying endoscopy with narrow band imaging (NBI-ME). Colonic and duodenal neoplasms with WOS have also been reported. Immunohistochemical examination with adipophilin reveals WOS in gastric neoplasms as lipid droplets, and WOS is specific for neoplasm with intestinal or gastrointestinal phenotype. We herein report a case of adenocarcinoma of the esophagogastric junction with WOS. A male patient in his sixties was found by esophagogastroduodenoscopy to have an
Key words: adenocarcinoma, esophageal cancer, magnifying endoscopy, narrow band imaging (NBI), white opaque substance (WOS)
INTRODUCTION
CASE REPORT
W
A
HITE OPAQUE SUBSTANCE (WOS) was first reported by Yao et al. in 2008 as a finding of elevatedtype gastric adenoma or adenocarcinoma using magnifying endoscopy with narrow band imaging (NBI-ME). WOS is a white deposit that sometimes interferes with visualization of the subepithelial microvascular pattern in gastric neoplasia.1 It has been pathologically confirmed that WOS observed by NBI-ME represents the accumulation of lipid droplets using oil red O staining and adipophilin immunostaining.2,3 Furthermore, it has been reported to be found in colonic and duodenal neoplasms but not in other gastrointestinal neoplasms.4 Here, we report a case of adenocarcinoma of the esophagogastric junction (EGJ) in which we observed WOS using NBI-ME. To our knowledge, this is the first report describing a WOS-positive esophageal neoplasm.
bs_bs_banner
Corresponding: Tetsuo Takehara, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Email: [email protected] Received 31 March 2014; accepted 4 July 2014.
esophageal elevated lesion. NBI-ME showed whitish deposits that looked similar to WOS in gastric neoplasms. The patient underwent endoscopic submucosal dissection and the lesion was resected in a single piece. This tumor had diffuse positivity for adipophilin and gastrointestinal phenotype.
MALE IN his sixties was referred for examination for the cause of epigastralgia. Endoscopic examination showed an elevated lesion in the lower esophagus. He had medical histories of hypertension and chronic renal failure on hemodialysis because of nephrosclerosis. He had never smoked and drank socially. He was negative for antiHelicobacter pylori IgG antibody. Conventional white light imaging showed a smooth, flat, elevated lesion of 20 mm in diameter, without ulceration and redness at the adjacent oral side of the squamocolumnar junction (SCJ) in the posterior wall (Fig. 1A). NBI-ME showed irregular microsurface structures with small and high-density pits. In one part, the lesion revealed an irregular mesh-shaped microvascular pattern. In the other part, whitish deposits were observed that were similar to WOS in gastric neoplasms (Fig. 1B). The oral margin of the lesion was covered with squamous epithelium, suggesting subepithelial invasion. Histology of the specimen obtained by endoscopic forceps biopsy revealed well-differentiated adenocarcinoma. Based on the findings described above, he was clinically diagnosed with adenocarcinoma arising
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
1
2
S. Yoshii et al.
Digestive Endoscopy 2014; ••: ••–••
A
B
A
B
C
D
Figure 1 Esophageal adenocarcinoma with white opaque substance (WOS) is shown on upper gastrointestinal endoscopy. (A) Esophageal endoscopy with white light image shows a 20-mm flat elevated lesion on the posterior wall of the lower esophagus. (B) WOS was visualized on the surface of this lesion using magnifying endoscopy with narrow band imaging.
Figure 2 Resected specimen shows a well to moderately differentiated adenocarcinoma of the gastroesophageal junction. (A) Resected specimen shows an intramucosal well to moderately differentiated tubular adenocarcinoma of the esophagus (hematoxylin-eosin stain; loupe view). (B) High-power view of area outlined by black square in part (A) ×100. In the oral margin of the lesion, atypical epithelium invades below the squamous epithelium. (C) High-power view of area outlined by yellow square in part (A) ×100. In the center of the lesion, tumor invades deeply in the lamina propria mucosae and is adjacent to the muscularis mucosae. (D) Specimen after formalin fixation. Orange lines mark the adenocarcinoma invading the lamina propria mucosae (LPM), blue lines mark that adjacent to the muscularis mucosae (MM) and the pink line marks the squamocolumnar junction (SCJ).
from EGJ and it was estimated that invasion depth was within the mucosa. The patient underwent ESD and the lesion was resected in a single piece without major complications. Histology revealed atypical glandular epithelium proliferating widely in the lamina propria mucosae. In the oral margin of the lesion, atypical epithelium invaded below the squamous epithelium (Fig. 2A,B). In the center of the lesion, tumor invaded beyond the mucosa adjacent to the muscularis mucosae (Fig. 2C,D). D2/40 immunohistochemistry showed there was no lymphovascular involvement. Histopathologically, short segmental Barrett’s epithelium was observed, but it had no contact with the lesion. Immunohistochemical
staining revealed that the lesion was focally positive for mucin (MUC) 2, CD10 and MUC6 and negative for MUC5AC. The lesion also had diffuse positivity for caudalrelated homeobox transcription factor (CDX) 2 (Fig. 3). In addition, immunohistochemical staining of adipophilin revealed that lipid droplets accumulated in the neoplastic epithelium. Adipophilin was detected in almost all the neoplastic cells in marginal crypt epithelium, whereas this was not observed in the non-neoplastic epithelium (Fig. 4). The final diagnosis was well to moderately differentiated adenocarcinoma of the gastroesophageal junction E, 20 mm, 0-IIa, tub1 >tub2, pT1a-MM, ly0, v0, pHM0, pVM0 (Japanese Classification of Esophageal Cancer, the 10th Edition,
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Esophageal adenocarcinoma with WOS 3
A
B
D
E
C
Figure 3 Immunohistochemical examination. (A) MUC2, magnification, ×100. (B) MUC5AC, magnification, ×100. (C) MUC6, magnification, ×100. (D) CD10, magnification, ×200. (E) CDX2. Lesion had focal positivity for MUC2, MUC6 and CD10 but negative staining for MUC5AC. The lesion also had diffuse positivity for CDX2, magnification, ×100.
0
100
200
300
400 µm
Figure 4 Immunohistochemical examination of adipophilin. Adipophilin was detected in approximately all of the neoplastic cells.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
4
S. Yoshii et al.
revised version).5,6 The patient followed an uneventful clinical course and was discharged 12 days after ESD.
DISCUSSION
R
ECENTLY, NBI-ME HAS been reported to be clinically useful for differentiation of gastric cancerous and non-cancerous lesions. One of the most important findings of cancerous lesions is considered to be the presence of irregularity of the microvascular architecture.7 However, when NBI-ME is applied in clinical practice, a white substance in the superficial area of the neoplasia sometimes interrupts visualization of the precise microvascular morphology. Yao et al. first reported this substance and named it WOS and they also reported that WOS not only interferes with visualization of the epithelial microvascular architecture but is also useful for discriminating gastric adenoma from carcinoma according to the presence or absence of irregular shapes and the distribution of WOS.1 WOS has been pathologically confirmed to be intramucosal accumulation of lipid detected using oil red O staining of the endoscopic biopsy specimen.3 Oil red O staining enables direct visualization of lipid droplets; however, it has a limitation in that it can only be applied to fresh frozen samples but not to paraffin-embedded sections because the lipid is removed during the process of paraffin fixing. Recently, adipophilin has been recognized as a novel marker of lipid accumulation and it can be applied even to paraffinembedded section. It is an adipose differentiation-related protein located on the surface of lipid droplets.8 It was reported that immunohistochemistry of adipophilin of gastric neoplasia was well correlated with WOS observed by NBI-ME.2 To the best of our knowledge, this is the first report describing a WOS-positive esophageal neoplasm, and we confirmed the phenomenon that lipid accumulation may occur in neoplasms arising from the esophagus. Two mechanisms of accumulation of lipid droplets are suggested: lipid absorption and lipid production.2 First, an electron microscopy study using a lipid-staining method has already revealed that the epithelium of the gastric intestinal metaplasia has an ability to absorb lipid droplets similar to the normal small intestinal epithelium.9 This finding suggests that even gastric epithelium can obtain an intestinal phenotype to absorb lipids. Absorbed lipid droplets are retained within the epithelium, and are drained into the lymphatics within the lamina propria after forming chylomicrons in the normal small intestine. In the neoplasm, the accumulation of lipid droplets might be caused by its impaired lymphatic clearance as a result of structural abnormality. Second, the expression process of adipophilin can be enhanced.10 The expression of adipophilin is suspected to be induced during
Digestive Endoscopy 2014; ••: ••–••
the process of carcinogenesis because it is known to be regulated by hypoxia inducible factor (HIF) and the peroxisome proliferator-activated receptor (PPAR) family, both of which are closely involved in carcinogenesis. A previous report demonstrated that WOS is present in either gastrointestinal-type or intestinal-type gastric neoplasia, but absent in gastric-type neoplasia.3 In case mucin expression is heterogeneous, WOS is observed only in the part of intestinal or gastrointestinal phenotype of the tumor.11 In our case, the tumor cells were positive for MUC2, MUC6, CD10, and CDX2 and were considered to have gastrointestinal phenotype. Although the detailed mechanism of lipid droplet accumulation in the esophageal neoplastic epithelium is unknown, the fact that our case expressed gastrointestinal phenotype as well as gastric neoplasm suggests that lipid could accumulate in adenocarcinoma, if the tumor has, at least partly, intestinal phenotype irrespective of the organ where the tumor arises. It would be a useful optical predictor for the mucin-expressing phenotype of the tumor. There are four possible origins of adenocarcinomas of the esophagus; Barrett’s esophagus (epithelium), esophageal glands proper, ectopic gastric mucosa, and esophageal cardiac glands. In our case, a short segmental Barrett’s epithelium was present in the specimen, but it had no contact with the tumor. Tumors arising from esophageal glands proper usually grow in the submucosa and those from ectopic gastric mucosa were reported to localize only in the upper or cervical esophagus;12 therefore, these are unlikely as the origins for our case. The tumor mainly grew in the lamina propria mucosae, and the cardiac glands of the esophagus in a non-cancerous squamous epithelium on the anal side of the tumor had dysplastic changes. Thus, we considered the possible origin of this tumor was esophageal cardiac glands. In summary, we present the first case of esophageal adenocarcinoma with WOS, which seems to arise from esophageal cardiac glands. WOS might be a clue to understanding carcinogenesis and pathophysiology of intestinal-type adenocarcinoma of the digestive system.
CONFLICT OF INTERESTS
A
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES 1 Yao K, Iwashita A, Tanabe H et al. White opaque substance within superficial elevated gastric neoplasia as visualized by magnification endoscopy with narrow-band imaging: A new optical sign for differentiating between adenoma and carcinoma. Gastrointest. Endosc. 2008; 68: 574–80.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Esophageal adenocarcinoma with WOS 5
2 Ueo T, Yonemasu H, Yada N et al. White opaque substance represents an intracytoplasmic accumulation of lipid droplets: Immunohistochemical and immunoelectron microscopic investigation of 26 cases. Dig. Endosc. 2013; 25: 147–55. 3 Yao K, Iwashita A, Nambu M et al. Nature of white opaque substance in gastric epithelial neoplasia as visualized by magnifying endoscopy with narrow-band imaging. Dig. Endosc. 2012; 24: 419–25. 4 Yoshimura N, Goda K, Tajiri H, Ikegami M, Nakayoshi T, Kaise M. Endoscopic features of nonampullary duodenal tumors with narrow-band imaging. Hepatogastroenterology 2010; 57: 462–7. 5 Takubo K, Makuuchi H, Fujita H et al. Japanese Classification of Esophageal Cancer, tenth edition: part 1. Esophagus 2009; 6: 1–25. 6 Takubo K, Makuuchi H, Fujita H et al. Japanese Classification of Esophageal Cancer, tenth edition: parts II and III. Esophagus 2009; 6: 71–94. 7 Yao K, Oishi T, Matsui T, Yao T, Iwashita A. Novel magnified endoscopic findings of microvascular architecture in intramucosal gastric cancer. Gastrointest. Endosc. 2002; 56: 279–84. 8 Heid HW, Moll R, Schwetlick I, Rackwitz HR, Keenan TW. Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res. 1998; 294: 309–21. 9 Rubin W, Ross LL, Jeffries GH, Sleisenger MH. Some physiologic properties of heterotopic intestinal epithelium. Its role in
transporting lipid into the gastric mucosa. Lab. Invest. 1967; 16: 813–27. 10 Matsubara J, Honda K, Ono M et al. Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray. Cancer Epidemiol. Biomarkers Prev. 2011; 20: 2195–203. 11 Ueyama H, Matsumoto K, Nagahara A et al. A white opaque substance-positive gastric hyperplastic polyp with dysplasia. World J. Gastroenterol. 2013; 19: 4262–6. 12 Akanuma N, Hoshino I, Akutsu Y et al. Primary esophageal adenocarcinoma arising from heterotopic gastric mucosa: Report of a case. Surg. Today 2013; 43: 446–51.
SUPPORTING INFORMATION
A
DDITIONAL SUPPORTING INFORMATION may be found in the online version of this article at the publisher’s web-site: Figure S1 Loupe view of the deeper cut examination. Invasion depth and vertical margin are confirmed by hematoxylin-eosin stain. Figure S2 Loupe view of the immunohistochemical examination of desmin. Muscularis mucosae were confirmed to be maintained in the specimen by immunohistochemical examination of desmin.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
