*Corresponding author: Gye-Hyeong Woo Laboratory of Histopathology, Department of Clinical Laboratory Science, Semyung University, 65 Semyeong-ro, Jecheon 27136, Korea Xanthogranulomatous inflammation is a rare, chronic, non-neoplastic lesion in animals. Although uncommon in humans, it is a recognized condition that can affect various organs. This inflammation has been reported in multiple animal species, including dogs, cats, and horses. It has been described in the middle ear and small intestine of dogs [1,2], the choroid plexus of horses [3], and the lungs and uterus of cats [4,5]. Cholesterol granulomas arising in the feline uterus have been characterized, with emphasis on their histopathological features [5]. Here, we report one such rare case, detailing both the histopathological and immunohistochemical findings.
A 5-year-old Korean short-haired cat was referred to a local veterinary hospital due to mild vaginal discharge and loss of appetite. The cat had been living on the streets, and no additional health information was available, except for a generally poor-looking appearance. Ultrasound examination revealed a uterine nodule, prompting an ovariohysterectomy for diagnostic purposes. Macroscopically, a white to yellowish-white nodule, measuring 1 × 2 cm, was observed in one uterine horn (Fig. 1A). The nodule had a distinct border and extended from the endometrium into the myometrium. The uterine cavity contained a large amount of colorless, viscous fluid (Fig. 1B).
Uterine tissue was fixed with 10% neutral-buffered formalin, processed, and embedded in paraffin. Paraffin sections were stained with hematoxylin and eosin, Grocott’s methenamine silver, Ziehl-Neelsen, Giemsa, and Gram’s stains. Additionally, immunohistochemistry was performed using Iba-1 (1:1,000, polyclonal rabbit, 019-19741; Wako, Japan) and Major Histocompatibility Complex (MHC) class II (1:40, monoclonal mouse, M0746; Dako, Denmark) as primary antibodies to identify the cellular components of the uterine nodule.
Histopathological examination revealed inflammatory nodules in the endometrium, myometrium, and adjacent perimetrium. The uterine lumen was markedly dilated and contained a large amount of eosinophilic proteinaceous material, and cellular debris (Fig. 2A). The inflammatory nodules primarily consisted of numerous macrophages with foamy cytoplasm, along with a smaller population of multinucleated giant cells and lymphocytes. Fibrosis and hemorrhage also were observed (Fig. 2B). Immunohistochemically, macrophages with foamy cytoplasm were strongly positive to both Iba-1 and MHC II (Fig. 3). No infectious agents such as bacteria were present in the lesion or cytoplasm of the macrophages on appropriate special stains.
Xanthogranulomatous metritis is a rare condition characterized by chronic uterine inflammation in both humans and animals [5,6]. In humans, the main symptoms include bleeding, excessive discharge, and cervical stenosis [6,7]. In animals, yellow vulvar discharge, anorexia, and recurrent vomiting have been reported [5]. In this case, clinical symptoms were not observed due to the cat’s status as a stray; however, based on gross findings, clear vulvar discharge likely had occurred.
The first case of xanthogranulomatous metritis in cats was reported by Zanghì et al. in 1999 [5], who suggested that cystic endometrial hyperplasia and pyometra were potential etiological factors. However, in the present case, no cystic endometrial hyperplasia or pyometra was observed; inflammation extended beyond the endometrium into the perimetrium. In cats, xanthogranulomatous inflammation also has been reported in the lungs [4]. Although the exact pathogenesis in the lungs remains unclear, obstructive lung disease has been suggested as the primary cause; other conditions (e.g., lung cancer and various inflammatory, infectious, and circulatory diseases) also are implicated [8,9]. In humans, xanthogranulomatous pneumonia (endogenous lipid pneumonia) is thought to result from the accumulation of extracellular lipids due to cell destruction, increased epithelial secretion, vascular leakage, hypoxia, altered oxygen and carbon dioxide tension, enzyme activation in anoxic tissue, and lung cancer [10,11].
Xanthogranulomatous inflammation is characterized by the infiltration of macrophages with abundant cytoplasmic lipid, lymphocytes and multinucleated giant cells [12]. Additionally, cholesterol cleft, necrosis, hemorrhage, and occasionally purulent lesions may be present. In the present case, however, no purulent inflammation and cholesterol cleft was noted. Histochemical staining, including periodic acid-Schiff, Grocott’s methenamine silver, Ziehl-Neelsen, Giemsa, and Gram’s stains, was negative for infectious agents, ruling out microbial causes of this unusual pattern of uterine inflammation. Immunohistochemical staining for histiocytic markers confirmed that the infiltrating foamy cells are macrophages.
In pathogenesis, sexual steroid hormones including estrogen and progesterone may influence the development of xanthogranulomatous metritis. Estrogen promotes the uterine endometrial proliferation and increases the susceptibility of uterine tissues to inflammatory responses [13]. Additionally, progesterone may regulate inflammatory activity in the reproductive organ by its immunomodulatory effect [12]. However, imbalance of these steroid hormone during natural estrous cycle or in case of endocrine disorder may disrupt the uterine immune system, leading to prolonged macrophage infiltration and granulomatous inflammation [14]. Although cystic endometrial hyperplasia or pyometra was not shown in this case, effects of sexual steroid hormones must be further investigated on the pathogenesis of xanthogranulomatous metritis in cats. Although additional hormonal testing was not possible in this case because the cat was feral, measurement of estrogen and progesterone concentrations could provide additional information to investigate the pathogenesis of this rare uterine disease. Additionally, the estrous cycle can also be indirectly inferred through ovarian tissue, no tissue other than the uterus was requested in this case. This report describes the second documentation of xanthogranulomatous metritis. However, additional cases are needed to evaluate the significance, incidence, and clinical importance of such conditions in animals.
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