OBJECTIVE: Within the large umbrella of histiocytosis are a few similar yet heterogenous entities involving the orbit and periocular tissues with or without systemic infiltration, termed adult onset xanthogranuloma or orbital xanthogranuloma. Due to rarity of these conditions, different classifications in use, diverse clinical presentations and still unknown etiology, the aim of this paper was to provide an up-to-date literature review of the actual understanding of histiocytosis and its subgroups involving the orbit and periocular area, diagnostic strategies and therapeutic modalities.
METHODS: We present a review of literature and small case series comprising four patients diagnosed and treated in the period from 2001 until 2023 in our hospital. Clinical files of 4 patients with adult-onset xanthogranulomatous disease of the orbit and ocular adnexa (AOXGD) were reviewed retrospectively. Clinical, laboratory, radiological, histopathological, and immunohistochemical findings were reexamined.
RESULTS: Reviewing medical records of our patients with AOXGD, we found significant overlap between histiocytosis and different immune disorders. A broad workup should be considered in these patients as they can harbour severe immune disfunctions and hematologic disorders. Preferred treatment modality depends on a histopathologic type of AOXGD, clinical presentation and systemic involvement and should be conducted multidisciplinary.
CONCLUSIONS: The diagnosis is often delayed because of its rarity and diverse clinical findings. Development of molecular genetic tests, detection of BRAF V600E mutation and different types of kinase mutations, mutations in transcriptional regulatory genes as well as tyrosine kinase receptors have shed a new light on the etiopathogenesis and potential targeted treatment of histiocytosis.

BACKGROUND: Both xanthogranuloma and xanthoma clinically manifest as yellowish skin lesions. Historically, the gold standard for diagnosis was skin histopathological examination. Currently, the advent of reflectance confocal microscopy (RCM) offers additional diagnostic support for these diseases by revealing their microscopic features, thereby enhancing the theoretical foundation for diagnosis.
OBJECTIVE: This study aimed to elucidate the distinctive characteristics of RCM images in xanthogranuloma and xanthoma, assess their diagnostic value, and investigate the relationship between RCM and histopathological features, ultimately boosting diagnostic accuracy.
METHODS: RCM and histopathological examinations were conducted on 13 patients with xanthogranuloma and 12 with xanthoma, recruited from our Dermatology Clinic between August 2022 and November 2023. The study involved analyzing RCM image features and correlating them with histopathological findings.
RESULTS: The RCM images of 13 xanthogranuloma and 12 xanthoma cases showed similar features. Xanthogranuloma predominantly exhibited epidermal atrophy and thinning in 6 cases (46.15%). Additionally, in 69.23% of cases, scattered small mononuclear inflammatory cells were infiltrated in the superficial and middle dermis layers. Medium to high refractive cells, predominantly vacuolated and resembling foam, were observed in 61.54% of cases. All cases demonstrated high refractive cells with distinct target-shaped, disc-shaped, horseshoe-like, and flower-ring structures. Concordance rates with histopathological examinations were 69.23, 92.31, 92.31, and 100%, respectively. Regarding xanthoma, epidermal atrophy and thinning occurred in two cases (16.67%), and mononuclear inflammatory cell infiltration was observed in 25% of cases. High refractive cells with the previously mentioned shapes were present in 100% of cases, though only 16.67% displayed these characteristics exclusively. The concordance rates were 66.67, 91.67, 100, and 91.67%, respectively.
CONCLUSIONS: RCM imaging of xanthogranuloma and xanthoma presents distinctive, highly consistent features with their histopathology, offering valuable insights for clinicians in diagnosing and differentiating these conditions.

Juvenile xanthogranuloma (JXG) is a rare, benign non-Langerhans cell histiocytosis that primarily affects the skin, with infrequent extracutaneous manifestations. Lesions typically emerge during early childhood and often resolve spontaneously, obviating the need for treatment. This paper details the case of a child diagnosed with a solitary JXG on the sole, necessitating surgical excision due to its functional impairment, specifically a delay in walking and weight bearing.

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.

Pedunculated lesions in the external auditory canal present a broad differential diagnosis. It is crucial to rule out malignant neoplasms and consider the possibility of xanthogranulomas, which are very rare in this location. Management is determined by associated complications, and otolaryngologists must consider this for appropriate treatment.

Orbital inflammatory diseases represent a heterogenous group of idiopathic, autoimmune-related, and sometimes neoplastic conditions with overlapping clinical and histopathologic features, as well as variable levels of IgG4-positive plasma cells detected within tissue biopsies. Some histopathologic features, especially in an appropriate clinical context, may point to a specific diagnosis in a given patient. Diagnoses of non-specific orbital inflammation, orbital inflammation related to autoimmune diseases such as granulomatosis with polyangiitis and IgG4-related disease, lymphoma, and xanthogranulomatous diseases are discussed, contrasted and illustrated.

Pituitary xanthogranulomatomas (XG) are a rare pathological entity caused by accumulation of lipid laden macrophages and reactive granuloma formation usually triggered by cystic fluid leakage or hemorrhage. Our aim was to compare clinical characteristics and presenting features of patients with secondary etiology of XG and those with no identifiable founding lesion (primary -\"pure\" XG) in order to gain new insights into this rare pituitary pathology. In a retrospective review of 714 patients operated for sellar masses, at tertiary center, we identified 16 (2.24%) with histologically confirmed diagnosis of pituitary XG over the period of 7 years (2015-2021). Patients were further analyzed according to XG etiology: \"pure\"- XG (n = 8) with no identifiable founding lesion were compared to those with histological elements of pituitary tumor or cyst - secondary XG (n = 8). We identified 16 patients (11 male), mean age 44.8 ± 22.3 years, diagnosed with pituitary XG. Secondary forms were associated with Ratke\'s cleft cyst (RCC, n = 2) and pituitary adenoma (PA, n = 6). The most common presenting features in both groups were hypopituitarism (75%), headache (68.5%) and visual disturbances (37.5%). Predominance of male sex was noted (males 68.75%, females 31.25%), especially in patients with primary forms. Patients with primary pituitary XG were all males (p = 0.0256) and more frequently affected by panhypopituitarism (87.5% vs. 25%, p = 0.0406) compared to patients with secondary causes. Hyperprolactinemia was noted in pituitary tumor group with secondary etiology only (p = 0.0769). Majority of lesions were solid on magnetic resonance imaging - MRI (81.25%). Distinct clinical phenotype was observed dependent on the etiology of XG.

OBJECTIVE: To evaluate the clinical and histopathological features of a case of xanthogranulomatous keratitis in a mixed-breed dog.
METHODS: Mixed-breed dog.
UNASSIGNED: An 11-year-old spayed female mixed-breed dog was presented for mild blepharospasm, corneal cloudiness, and increasing conjunctival hyperemia OD. Ophthalmic examination revealed multifocal pink and cream-colored consolidated corneal infiltrative lesions and generalized neovascularization with suspected diagnosis of stromal abscessation. There was no improvement after 1 month of medical management, so a keratectomy was performed, and corneal tissue was sent for histopathological evaluation.
RESULTS: The nonulcerative keratitis was refractive to medical management including topical and systemic antibiotics, topical antifungal, and systemic anti-inflammatory, so keratectomy was performed. Histopathologic diagnosis of xanthogranulomatous keratitis was made 1 week postoperatively. The patient was prescribed 0.05% difluprednate ophthalmic emulsion and 0.2% tacrolimus ophthalmic ointment (initially q 8 h, OD). The difluprednate was tapered and discontinued after 2 months, but the tacrolimus was continued (q 12 h, OD). No lesion recurrence had been documented 1 year postoperatively.
CONCLUSIONS: There has been little published on canine xanthogranulomas, especially in veterinary ophthalmology. Ocular xanthogranulomas have been reportedly found intraocularly and at the ocular surface. Histologically, they are characterized by well-delineated nodules that contain histiocytes and abundant lipid-laden macrophages. The treatment in this clinical case was surgical excision followed with topical immunosuppression/anti-inflammatory therapy with no recurrence 1 year postoperatively. Xanthogranulomatous keratitis should be an added differential diagnosis when nonulcerative keratitis is found on examination, specifically with consolidated, corneal infiltrate and minimal pain.

Sellar xanthogranulomas are extremely rare intracranial lesions, particularly in pediatric patients, and their diagnostic and therapeutic challenges prompt thorough investigation. We describe a case of a two-year-old toddler diagnosed with sellar xanthogranuloma, highlighting the challenges encountered in its diagnosis and management. The child presented with symptoms, including headache, ptosis of the left eye, and neurological deficits. Brain computed tomography (CT) and magnetic resonance imaging (MRI) revealed a hypodense sellar lesion. The patient underwent a left pterional craniotomy for resection of the mass. Histopathological examination suggested the diagnosis of sellar xanthogranuloma, characterized by foamy macrophages, giant cells, lymphocytic infiltrates, fibrous proliferation, necrotic detritus, and hemosiderin deposits. Further diagnostic precision was achieved through immunohistochemical staining, including CD1a and langerin, which successfully ruled out the possibility of Langerhans cell histiocytosis (LCH), reinforcing the diagnosis of sellar xanthogranuloma. The successful surgical resection of the lesion led to a favorable outcome, evidenced by the significant alleviation of symptoms as well as the restoration of normal neurological function. Post-operative assessments demonstrated a marked improvement in the patient\'s quality of life, and there were no observed complications or recurrence of the lesion during the follow-up period. In summary, our case report not only highlights the rarity and diagnostic challenges of sellar xanthogranulomas but also emphasizes the importance of collaborative medical expertise in achieving accurate diagnosis and successful therapeutic outcomes in pediatric patients. The successful management of this case offers valuable insights into the clinical presentation, diagnostic complexities, and treatment strategy of sellar xanthogranulomas, further enriching our understanding of this uncommon intracranial pathology.

Xanthogranulomas are considered rare tumors, with their sellar and non-sellar frequency ranging from 1.6 to 7% among intracranial lesions, and described as a separate entity by the World Health Organization in 2000. The diagnosis of sellar xanthogranulomas is challenging, given their uncertain origin and clinical course. In addition, the limited reporting of sellar xanthogranuloma cases and the absence of characteristic images make these entities difficult to distinguish from other cystic lesions of the sellar region, such as adamantinomatous craniopharyngiomas, Rathke\'s cleft cysts, pituitary tumors, arachnoid cysts, epidermoid cysts, and dermoid cysts. Here, we describe the clinical presentation, radiological findings, immunohistochemical/histopathological analysis, and the ultrastructural examination by transmission electron microscopy of five sellar xanthogranulomas cases reported in two care centers in Cordoba, Argentina. Two males and three females between 37 and 73 years of age (average 51.8 years) presented with persistent headaches, generalized endocrine defects, and visual problems. MRI revealed cystic formations in the sellar region, which usually projected into adjacent tissues such as the suprasellar region or cavernous sinuses, and compressed other structures such as the optic chiasm, pituitary gland, and cranial nerves. All patients underwent surgical intervention to remove the tumor tissue. The histopathological analysis of the samples showed cellular tissue with a xanthogranulomatous appearance, inflammatory cellular infiltrate (mainly lymphocytes and macrophages), fibroblasts, abundant collagen fibers, and hemorrhages. An ultrastructural analysis helped to identify cellular infiltrates and granules resulting from tumor cell activity. The data support the hypothesis that sellar xanthogranulomas could occur as an inflammatory reaction secondary to the rupture and hemorrhage of a previous cystic process, thereby generating an expansion of the tumor body toward adjacent tissues. The information obtained from these cases contributes to the current knowledge about this disease\'s origin and clinical and histological evolution. However, the scarcity of patients and the observed phenotypic heterogeneity make its diagnosis still challenging. Undoubtedly, more investigations are needed to provide additional information in order to be able to achieve a more accurate diagnosis and effective treatment of this rare disease.