Esophageal Xanthoma - Semantic Scholar

Esophageal Xanthoma – Report of Two New Cases and Review of the Literature Gabriel Becheanu1, Mona Dumbrava1, Tudor Arbanas1, Mircea Diculescu1, Nadia Hoyeau-Idrissi2, Jean-François Fléjou2 1) Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Bucharest, Romania; 2) Pathology Department, Saint-Antoine Hospital, Paris, France

Abstract Background: Esophageal xanthoma is a very rare lesion which can be incidentally discovered during endoscopy. Only eleven cases have been reported, including ours. Case reports: We present two new cases of esophageal xanthoma localized in the lower esophagus in a 56-year-old woman and a 62-year-old man. Endoscopically, esophageal xanthoma appears as yellowish granular spots or a slightly elevated lesion. Microscopically, it consists of fat accumulation in foamy histiocytes beneath the squamous epithelium. Conclusions: The clinical and pathological importance of these lesions and what they mean in patients is discussed, along with a review of the literature.

Key words Esophagus – xanthoma – foamy macrophages – immunohistochemistry.

Introduction Xanthomas are rare, smooth, yellowish tumor–like lesions which can be incidentally discovered in the upper gastrointestinal tract during gastrointestinal endoscopy [1]. Considering their benign nature and the endoscopic resemblance to ectopic sebaceous glands, xanthomas have not been reported frequently in the literature. The reported incidence in the upper gastrointestinal tract varies among endoscopy series, the most frequent location being the stomach [1], followed by the duodenum and esophagus. Xanthomas can develop as solitary or multiple nodules or plaques with a diameter of less than 10 mm, usually less than 5 mm [1-5]. Esophageal xanthomas, like all upper gastrointestinal tract xanthomas, are asymptomatic, the patients being usually Received: 27.06.2011 Accepted: 19.07.2011 J Gastrointestin Liver Dis December 2011 Vol. 20 No 4, 431-433 Address for correspondence: Gabriel Becheanu MD Gastroenterology and Hepatology Department, Fundeni Clinical Institute Bucharest, Romania Email: [email protected]

investigated for other conditions. Histologically, the lesions appear as clusters of large foamy xanthoma cells within the connective tissue in the lamina propria [1, 6]. In the esophageal mucosa only nine cases have been described in the literature, prior to our two cases, occurring in a 62 year old man and a 56 year old woman. A review of the published literature on esophageal xanthoma is presented; a search was conducted to find all articles on esophageal xanthoma, from 1984 to 2010. Medical subject headings used to search the PubMed database (National Institutes of Health, United States) included upper gastrointestinal xantomatosis, as well as a keyword search using “esophageal xanthoma”, “esophageal xanthelasma”, “lipid islands in the esophagus”. A total number of 12 articles were originally identified. Limitation of the findings to human series and English language reduced the number of publications to 7.

Case reports Case 1 The patient was a 56-year-old woman presenting with pain in the upper abdomen, upper abdominal fullness, accompanied by bloating, nausea and heartburn. The physical examination revealed only mild epigastric tenderness. An endoscopic examination was performed, which revealed a 4 mm sessile polyp close to the gastroesophageal junction. There were no other abnormalities in the stomach or esophagus, and a polypectomy was accomplished. Case 2 The patient was a 62-year-old man. His past medical history was significant for Biermer anemia, chronic viral C hepatitis and a polyp in the gastric antrum. He did not complain of any gastrointestinal symptoms. He had a gastrointestinal endoscopy for evaluation of Biermer anemia and control of the previously diagnosed polyp in the gastric antrum. In addition, a small esophageal lesion was identified in the lower esophagus, which measured 3 mm in dimension. Gastric biopsies revealed an antral hyperplastic polyp with focal adenocarcinoma, severe atrophic fundic gastritis and extensive intestinal metaplasia – compatible with type A gastritis.

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Pathological examination The biopsy specimens obtained from the esophageal mucosal polyp in each case were stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Alcian blue, and were evaluated by the pathologist. Histologically, on H&E stained sections, both esophageal lesions were composed of medium to large islets of foamy macrophages in the lamina propria, under the squamous epithelium, with small nuclei, centrally or eccentrically located (Fig. 1). The covering squamous epithelium did not show any atypical cells, and in the first case showed some degree of parakeratosis. The cells were negative for PAS and Alcian blue reaction. Immunohistochemical tests were performed on formalinfixed paraffin embedded sections. The immunohistochemical staining revealed the same findings in both cases. The cells were strongly positive for CD68 (Figs. 2, 4), and no reactivity was present for cytokeratin/AE1/AE3 (Fig. 3), S-100 protein and CD1a.

Fig 3. Case 1, negative immunocytochemistry for AE1/AE3 (400x).

Fig 4. Case 2, positive immunocytochemistry for CD68 (400x).

Fig 1. Microscopic features of case 1 - foamy histiocytes islands in the lamina propria under the squamous epithelium (H&E stain, 400x).

Fig 2. Case 1, positive immunocytochemistry for CD68 (600x).

Discussion Esophageal xanthoma is a benign asymptomatic lesion, always diagnosed by histological examination. The most common location within the esophagus seems to be distal. Endoscopically, esophageal xanthoma appears as yellowish granular spots or a slightly elevated lesion, measuring 2 to 10 mm. Microscopically, it consists of foamy histiocytes

containing lipids, located beneath the squamous epithelium [1-3, 6]. They may be solitary or multiple. The first reported case occurred in the upper esophagus and was defined as “lipid islands” in 1984 by Remmele and Engelsing [7]. Since 1984 to present, only 11 cases (the present ones included) have been reported [7-14], summarized in Table I. The patients diagnosed with esophageal xanthoma were 6 males and 3 females (two of them not specified), with an average age of 54 years. The reported incidence of xanthoma in the upper gastrointestinal tract for endoscopy series was 0.23%, 12% of the cases occurring in the esophagus. Most of the lesions occurred in the lower esophagus, two in the middle and one in the upper (two of them not specified). The size of the xanthomas varied between 2 and 10 mm. Eight cases appeared as a solitary lesion. Endoscopic findings showed yellow-white, granular nodules or slightly elevated lesions, and one sessile appearance was reported. There is no report of malignant esophageal xanthoma. The etiopathogeny and the significance of esophageal xanthoma remain unknown, and in contrast to cutaneous xanthoma, no correlation between esophageal xanthoma and hyperlipemia has been shown. The association of inflammatory cells suggests a response to a focal mucosal damage [15-17]. This theory would explain why gastric xanthomas appear to be more frequent than esophageal xanthomas, as traumatism and inflammation may be better tolerated by esophageal squamous epithelium than by gastric columnar epithelium.

Two new cases of esophageal xanthoma

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Table I. Esophageal xanthomas in the literature from 1984 to present Age/sex

Site

Number

Size (mm)

1

Remmele and Engelsing (1984)

Authors/year

54/M

Upper

Solitary

10

Endoscopic findings

Other conditions

Yellow spot

Gastrectomy

2

Stole and Seifert (1985)

45/M

Middle

Three

Not specified

Yellow flat elevation

Hyperlipidemia, diabetes mellitus

3

Vimala et al (2000)

37/F

Lower

Multiple

2-5

Yellowish nodular (lymphoma)

Gastric xanthoma

4

Hirokawa et al (2003)

52/F

Lower

Solitary

2

Yellowish granular (sebaceous gland)

Duodenal ulcer

5

Hirokawa et al (2003)

67/M

Lower

Solitary

2

Yellow spots (sebaceous gland)

Hepatocellular carcinoma, hypertension, cholelithiasis

6

Herrera-Goepfert et al (2003)

61/M

Middle

Solitary

Not specified

Verruciform

Non-Hodgkin lymphoma of the testis

7

Gencosmanoglu et al (2004)

Not specified

Not specified

Multiple

Less than 5 mm in diameter

Yellow-white colored plaques

Not specified

8

Gencosmanoglu et al (2004)

Not specified

Not specified

Solitary

Less than 5 mm in diameter

Yellow-white colored plaques

Not specified

9

Dong-Sik Cho et al (2008)

49/M

Lower

Solitary

3

Yellowish elevated granular lesion

Atrophic gastritis

10

Becheanu et al (2011)

62/M

Lower

Solitary

3

Yellowish elevated lesion

Biermer anemia, HCV, antral hyperplastic polyp with focal adenocarcinoma, atrophic gastritis

11

Becheanu et al (2011)

56/F

Lower

Solitary

4

Sessile polyp

-

Some studies also suggested a disturbance of carbohydrate or fat metabolism involved in the pathogenesis of gastrointestinal xanthomas. But there is no evidence yet indicating this kind of pathogenesis for esophageal xanthoma.

Conclusions Esophageal xanthoma seems to be a very rare lesion, as only eleven cases, included our two cases, are reported in the literature. It has to be distinguished on endoscopy from carcinoid tumor, granular cell tumour, and ectopic sebaceous glands, and histologically a differential diagnosis of signet ring cell carcinoma must be performed, as in other locations in the gastrointestinal tract.

Acknowledgement This paper is partially supported by the Sectoral Operational Programme Human Resources Development, financed from the European Social Fund and by the Romanian Government under the contract number POSDRU/89/1.5/S/64153.

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