Intestinal Glandular Inclusions (Glandular Choristoma) in the Mesenteric Lymph Node of a Goat

Intestinal Glandular Inclusions (Glandular Choristoma) in the Mesenteric Lymph Node of a Goat

ARTICLE IN PRESS J. Comp. Path. 2007,Vol. 136,193^196 www.elsevier.com/locate/jcpa SHORT PAPER Intestinal Glandular Inclusions (Glandular Choristom...

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ARTICLE IN PRESS J. Comp. Path. 2007,Vol. 136,193^196

www.elsevier.com/locate/jcpa

SHORT PAPER

Intestinal Glandular Inclusions (Glandular Choristoma) in the Mesenteric Lymph Node of a Goat ´mez-Laguna, L. Carrasco, A. Gordon, Y. Milla´n, M. R. F. Garrido*, J. Go S. Rodrı´guez-Solera*, A. Espinosa de los Monterosy and J. Martı´n de las Mulas *

Departamento de Anatom|¤a y Anatom|¤a PatoloŁgica Comparadas and Departamento de Sanidad Animal, Edi¢cio Sanidad Animal, Campus Universitario Rabanales, Universidad de CoŁrdoba, and yInstituto de Sanidad Animal y Seguridad Alimentaria, Las Palmas de Gran Canaria, Spain

Summary A glandular choristoma found in the mesenteric lymph node of a goat would appear to represent the ¢rst reported case of non-neoplastic glandular inclusions in domestic animals. The origin of this type of lesion may be di⁄cult to determine, but in the present case cytokeratin expression patterns suggested that the inclusions had an intestinal origin. r 2007 Elsevier Ltd. All rights reserved. Keywords: choristoma; glandular inclusions; goat

Choristoma consists in normal tissue in an ectopic location (Cullen et al., 2002). It has been reported in all domestic animal species, most commonly in the form of exocrine pancreas in the intestinal submucosa (Cullen et al., 2002), skin with hair on the surface of the canine cornea (Lee et al., 2005), adrenal gland within the ovary, especially in mares (MacLachlan and Kennedy, 2002), and adjacent to, or within, the testicle, epididymis or spermatic cord (MacLachlan and Kennedy, 2002). Two types of choristoma have been described in goats, namely, mammary tissue in the vulva (Gameel et al.,1992) and cervix (Ramadan and Hassan, 1975), and thymus in the thyroid gland (Roy et al.,1976).To our knowledge, this is the ¢rst reported case of lymph node choristoma in a domestic animal. In man, glandular choristomas have been reported both in association with, and independently of, neoplastic diseases (Edlow and Carter, 1973: Murayama et al.,1978; Gritsman and Schwartz,1985; Carr et al., 1987; Arai et al., 1992; Douglas-Jones, 1994; Fisher et al.,1994; von Rahden et al., 2005). This paper describes Correspondence to: J. Mart|¤ n de las Mulas, Edi¢cio de Sanidad Animal, Campus de Rabanales, Universidad de CoŁrdoba, Carretera de Madrid-CaŁdiz km.396,14014 CoŁrdoba, Spain (e-mail: [email protected]) 0021-9975/$ - see front matter

doi:10.1016/j.jcpa.2006.12.001

the histological and immunohistochemical characteristics of a choristoma located in the mesenteric lymph node of a goat with paratuberculosis. In the course of a ¢eld study on paratuberculosis, tissue samples were collected from a 7-year-old female Payoya goat, belonging to a £ock raised semi-intensively. Paratuberculosis was diagnosed by serum ELISA and mycobacterial culture. At necropsy, samples from mesenteric lymph nodes and intestinal tract were ¢xed in10% bu¡ered formalin and embedded in paraf¢n wax for histopathological examination. Sections (4 mm) were stained with haematoxylin and eosin (HE), periodic acid-Schi¡ (PAS) and Ziehl-Neelsen (ZN). For immunohistochemical analysis, 3 mm tissue sections were labelled by the avidin--biotin--peroxidase complex method (ABC) with the monoclonal antibody anti-cytokeratin 20 (AntiCK20), diluted 1 in 40 (Espinosa de los Monteros et al., 1999), and the polyclonal antibodyAE1-AE3 diluted 1 in 100. Necropsy revealed that the intestinal mucosa was thickened and the mesenteric and ileocaecal lymph nodes were enlarged. Microscopically, di¡use granulomatous in£ammation was observed in the r 2007 Elsevier Ltd. All rights reserved.

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lamina propia of the intestinal mucosa, with abundant macrophages containing numerous acid-fast bacilli. In addition, scattered groups of macrophages containing Johne’s bacilli were observed in all mesenteric lymph nodes examined. In one mesenteric lymph node, randomly distributed glandular structures, some of them cystic, were seen in the cortex and medulla (Fig. 1). These structures consisted of a single layer of cylindrical cells without atypia, together with interspersed foamy-cytoplasm cells resembling goblet cells. PAS staining revealed microvilli at the apical end of the cylindrical cells and intense positivity in goblet cell cytoplasm (Fig.1, inset). No neoplastic lesions were observed in the intestinal mucosa or lymph nodes. All glandular epithelial cells reacted to AE1--AE3 antibody (Fig. 2), the reaction being observed in the cytoplasm, often with apical reinforcement. Small groups of immunoreactive cells were also observed in the subcapsular sinus and the paratrabecular sinuses of the lymph node. With anticytokeratin 20 antibody, an intracytoplasmic reaction was observed in the same cells and the same locations. This is the ¢rst report of choristoma in a caprine lymph node, formed by glandular clusters whose immunophenotype was consistent with intestinal epithelium. Choristomas formed by benign glandular inclusions, with or without other lesions, have been reported in human lymph nodes. Pancreatic tissue has been observed in lymph nodes around the hepatic artery (Murayama et al., 1978), mammary tissue within axillary lymph nodes (Edlow and Carter,1973) and colonic epithelium in mesenteric lymph nodes (Gritsman

Fig.1. Mesenteric lymph node of goat. Two glandular structures are seen, lined by a single layer of columnar cylindrical epithelial cells without atypia. In addition, goblet cells with foamy cytoplasm are present. HE. Bar, 300 mm. Inset: Detail of one glandular inclusion, showing PAS positivity in the microvilli at the apical end of the cylindrical cells and in the cytoplasm of goblet cells. PAS. Bar, 300 mm.

Fig. 2. Mesenteric lymph node of goat. Intense immunoreactivity to AE1/AE3 antibody is observed in the cytoplasm of the columnar cells. ABC method, counterstaining with Mayer’s haematoxylin. Bar,100 mm.

and Schwartz, 1985). In addition, lymph node glandular choristomas associated with neoplastic processes such as gastric adenocarcinoma (Arai et al., 1992), primary mammary tumours (Douglas-Jones,1994; Fisher et al., 1994) or ovarian tumours (Douglas-Jones, 1994) have also been reported; such cases necessitate distinction between choristoma and a possible metastasis of the primary tumour (Huntrakoon, 1985; DouglasJones,1994; Fisher et al., 1994). Choristomas can be distinguished from metastatic lesions by the absence of cellular atypia (Cullen et al., 2002).The‘‘cohesive mass’’ nature of the ‘‘aberrant or heterotopic tissue’’ was highlighted by Roberts et al. (1980). Carr et al. (1987) observed that ganglionar choristoma in man gave rise to adenomegaly. In the present case, because the mesenteric lymph nodes were enlarged as a result of paratuberculosis, adenomegaly due to the glandular inclusions could not be con¢rmed. The exact histogenesis of glandular inclusions in lymph nodes is not known, but two major hypotheses are currently in vogue.The ¢rst, suggested by a number of authors (Laughan, 1965; Karp and Czernobilsky, 1969; Kempson,1978), is that these glandular inclusions are due to a metaplasic proliferation of peritoneal mesothelium, derived from embryonic coelomic epithelium. Since Muºllerian epithelium is also derived from embryonic coelomic epithelium, it is not surprising that there should be some confusion between the two (Huntrakoon,1985). The second hypothesis, put forward by Zinsser and Wheeler (1982), maintains that glandular inclusions are secondary to in£ammation. The mechanism underlying the development of these inclusions is unclear, but possibilities include involvement of a non-speci¢c factor or an inductive substance, sloughing of the epithelium,

ARTICLE IN PRESS Glandular Choristoma in a Caprine Lymph Node

or haematogenic or lymphatic dissemination. The latter possibility is supported by the ¢nding of dysplastic epithelial cells within the lymphatic vessels of the submucosa and in the mesenteric lymph node (Roberts et al.,1980). The case reported here was associated with a regional in£ammatory process and would therefore support the second hypothesis. However, changes such as herniation or in¢ltration of the epithelial cells through the muscularis mucosae into the submucosa, or epithelial dysplasia (Roberts et al.,1980), were absent in the present case. Immunohistochemical examination not only con¢rmed the glandular epithelial nature of the cells and clusters observed in the goat mesenteric lymph node (expression of cytokeratin 8 and 19) but also clearly demonstrated the intestinal origin of the epithelium (expression of cytokeratin 20), already suggested by the presence of goblet cells. Low molecular weight cytokeratins 8, 18 and 19, recognized by AE1/ AE3 monoclonal antibody, are expressed in the gastrointestinal epithelium of man and domestic animals (Moll et al., 1982; Vos et al., 1992; Mart|¤ n de las Mulas et al., 1994). In addition, cytokeratin 20 is speci¢c to Merkel cells and taste buds, isolated bronchial epithelial cells, intestinal epithelium, gall bladder epithelium and urothelium (Moll et al.,1990; Espinosa de los Monteros et al., 1999). Both the gastrointestinal epithelium and the glandular inclusions of the mesenteric lymph node of the goat under study reacted for these cytokeratins. As the location of the lymph node excluded other possible origins, the combined pattern of cytokeratin expression was used to indicate the probable origin of the glandular inclusions.

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Received, May 9th, 2006 Accepted, December 11th, 2006