BACKGROUND: The \"C group\" of the histiocytic disorders is characterized by non-Langerhans-cell histiocytic lesions in the skin, mucosal surfaces, or both, out of which Juvenile xanthogranuloma (JXG) is the most common typically affecting the skin. The eye is the most common extra-cutaneous site of JXG., we aim at providing our clinical and histopathological experience with this group of diseases including the adult-onset xanthogranuloma (AXG).
METHODS: This is a retrospective cohort study of all patients with the tissue diagnosis of ocular and periocular cutaneous and mucocutaneous non-LCH disorders who presented to us over a period of 25 years (January 1993 to December 2018).
RESULTS: Twenty patients were diagnosed as \"Group C\" disease with an age range of 2 months-60.9 years. Eleven patients were females (55%) and nine were males (45%). The involvement was mostly unilateral in 80.9%. All cases fell into the xanthogranuloma family with 11 JXG patients, 8 AXG patients of skin and ocular surface, and one patient with solitary reticulohistiocytoma (SRH). The clinical site of involvement in JXG was primarily in the eyelid in 5 patients (45%), ocular surface lesions in 2 (18%), iris in 2 (18%), choroidal and bilateral orbital lesions in 1 patient each (9%). The group of AXG, presented equally with eyelid lesions in 4/8 and ocular surface lesions in 4/8. The non-Langerhans\' histiocytic infiltrate showed supportive immunohistochemical staining properties (reactive to CD68 marker and negative to S-100 and langerin markers).
CONCLUSIONS: Among the rare histiocytic disorders, xanthogranulomatosis is the commonest and has wide clinical manifestations. Accurate diagnosis needs to be supported by typical histopathological findings. JXG was the commonest in our study with relatively older mean age at presentation and frequent eyelid rather than iris involvement. AXG is often confused with xanthelasma when involving the eyelids with corneal limbal involvement is relatively frequent.

Juvenile xanthogranuloma is a benign histiocytic cell proliferative disorder that occurs in early childhood. The most common presentation occurs within the first 2 years of life with papular or nodular changes to the skin on the head, neck or upper trunk. This case study documents the findings and treatment of a single solitary soft tissue mass in the forefoot of a 17-year-old patient. Unique to this case, the initial diagnosis of tuberous xanthoma was made and, with referral to an outside hospital, changed to a juvenile xanthogranuloma. In addition, unlike most juvenile xanthogranulomas in the literature, there was no superficial dermatological abnormality seen clinically. This change was not a dramatically different diagnosis, but further immunohistochemical staining was necessary for ultimate diagnosis. The soft tissue mass was self-contained to the deeper tissue layers and not the epidermis. The patient was followed for 12 months for possible recurrence and medical workup, without postoperative complications. The purpose of this study was to report on a unique finding and presentation of a xanthogranulomatous soft tissue mass in the forefoot of a pediatric patient.

OBJECTIVE: To evaluate the clinical, histopathological, and immunohistochemical features of 17 cases of ocular surface xanthogranuloma (OSX) in dogs.
METHODS: Archived records from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were searched for cases of canine OSX. Cases were evaluated for lipid-laden macrophages and Touton giant cells. Seventeen cases matching those criteria were identified (1993-2018). Clinical and epidemiological data were collected from the submission forms and additional follow-up survey.
RESULTS: Ocular surface xanthogranuloma in dogs presented as small bland nodules. OSX commonly occurred at the limbus (8/17) or cornea (4/17). Three of 17 affected animals were less than 1-year-old and the average age was 6.9 years (range 0.7-14 years). Fourteen of 17 cases did not report any lipid or metabolic abnormalities. Histologically, lesions were composed mainly of dense sheets of vacuolated lipid-laden macrophages and Touton giant cells with scant additional inflammatory cells and an intact overlying epithelium. No recurrence was noted in cases where complete surgical resection was achieved, and medical treatment either pre or post-resection led to only partial resolution.
CONCLUSIONS: Xanthogranulomas are histiocytic lesions characterized by abundant lipid-laden macrophages. The authors use the term, ocular surface xanthogranuloma, to describe nodules with rigidly defined cellular characteristics. Although these lesions share characteristics with human limbal xanthogranulomas, further investigation is needed to suggest the different subsets that have been reported in the medical literature. Complete surgical excision is the most effective treatment for OSX in dogs, and intralesional triamcinolone and topical steroids can be useful adjunctive therapies to surgery.

To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination.
Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1 -weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2 -weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2* relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1 , T2 , and T2* values of lesions was performed. After imaging, brain specimens were examined using histological methods.
In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6 mm(3) and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2* values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2* components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma.
Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. J. Magn. Reson. Imaging 2016;44:673-682.

Solitary (juvenile) xanthogranuloma (SXG) is an uncommon, benign lesion that usually occurs in children. The cell of origin of SXG has been the subject of debate, with hypotheses including endothelium, dermal dendrocytes, dermal indeterminate cells, and the plasmacytoid monocyte, among others. We further characterized the immunophenotype of SXG with an extended immunohistochemical panel, paying special attention to recently described or novel markers of histiocytic lineage. Forty-one SXG and 23 benign fibrous histiocytomas (BFHs) were immunostained for factor XIIIa, CD4, CD11c, CD163, CD31, CD45, lysozyme, and S-100. The mononuclear cells of SXG and the spindled cells of BFH were scored as \"negative,\" \"1+\" (<10% positive), \"2+\" (10%-50% positive), and \"3+\" (>50% positive). SXG immunohistochemistry showed the following: factor XIIIa, 35/40 (88%); CD4, 34/36 (94%); CD11c, 36/37 (97%); CD163, 36/36 (100%); CD31, 14/31 (45%); CD45, 14/32 (44%); lysozyme, 23/30 (77%); and S-100, 0/32 (0%). The 5 factor XIIIa-negative cases all showed 2+-3+ CD4, CD11c, and CD163 expression. In contrast, only 8 (35%) of 23 BFH cases were factor XIIIa positive. All other stains were universally negative in the lesional cells of BFH, although these tumors frequently contained interspersed cells expressing various histiocytic markers. Our results strongly support histiocytic lineage for the mononuclear cells of SXG. CD11c expression has not been previously described in SXG. CD163 expression appears to be characteristic of SXG, as it was not expressed by the lesional cells of BFH, in contrast to previous reports. CD31 expression in SXG represents a potential diagnostic pitfall, as many (dermato)pathologists are unaware of CD31 expression in histiocytes.