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.

Knowledge of xanthogranuloma (XG) of the sellar region comes from short series or single cases. We performed a systematic review, using the PubMed, Web of Science, Embase, Scopus, eLibrary, and BIOSIS Preview databases, of all cases reported from 2000 to the present. We also describe one unreported patient treated in our institution. A search of the literature revealed that of 71 patients 50.7% were male and that mean age at diagnosis was 34.7 ± 19.2 years old. Median time from clinical onset until diagnosis was 7 (3-21) months. Hypopituitarism (70.4%), visual disorders (64.7%), headache (53.5%), and polyuria-polydipsia (28.2%) were the most common symptoms. On MRI, median tumor size was 20 (16-29) mm, while 71.8% were sellar/suprasellar and less frequently exclusively suprasellar (15.5%) or sellar (12.7%). On T1-weighted imaging, XG was hyperintense in 76.3% of patients, while it showed variable appearance on T2-weighted imaging. The tumor showed cystic features in 50.7%, gadolinium enhancement in 45.1%, and calcification in 22.5% of patients. All patients underwent surgery (77.4% transphenoidal approach and 18.3% craniotomy), with hypopituitarism (56.4%), diabetes insipidus (34.5%), and visual defects (7.3%) being the most common complications. Total/subtotal resection was achieved in 93.5%, while the tumor was partially removed in 6.6%. Median follow-up was 24 (6-55) months and no tumor recurrence or remnant growth was reported in 97.5% of cases. In conclusion, XG affects the younger population, manifested by hormonal deficit and mass effect symptoms. Surgery is safe and offers excellent outcomes, though hypopituitarism is frequent post-surgery. Tumor recurrence or remnant growth is rare and radiological surveillance is a good option for patients with remnant lesions.

Juvenile Xanthogranuloma (XG) is a rare disorder that belongs to the heterogeneous group of histiocytic neoplasms, characterized by a clonal expansion of non-Langerhans cell histiocytes that share a dermal macrophage phenotype. Although the head and neck region is the most common reported site of involvement by the Juvenile Xanthogranuloma family, laryngeal localization is extremely rare. We report a unique case of Adult Onset Xanthogranuloma with subglottic localization, presenting as a solitary laryngeal mass without other systemic or cutaneous lesions. A review of the previously described cases of laryngeal Xanthogranuloma has been performed, highlighting 7 cases of Juvenile Xanthogranuloma and only 3 cases of Adult Onset Xanthogranuloma. Despite the extreme rarity of laryngeal localization of XG, this histiocytic neoplasm should be considered as a differential diagnosis for laryngeal masses causing airway obstruction, even in the absence of other concomitant manifestations.

Xanthogranuloma of the sellar region is a rare chronic inflammatory lesion resulting from secondary hemorrhage, inflammation, infarction, and necrosis of an existing Rathke\'s cleft cyst, craniopharyngioma, or pituitary adenoma. Sellar xanthogranulomas are challenging to differentiate from other cystic lesions preoperatively due to the lack of characteristic imaging features. We performed a literature overview of the clinical and paraclinical features, treatment options, and long-term outcomes of patients with sellar xanthogranuloma, focusing on the preoperative radiological diagnosis. The hyperintense signal in both T1- and T2-weighted sequences, cystic or partially cystic morphology, ovoid shape, sellar epicenter, intra- and suprasellar location, intratumoral calcifications, linear rim contrast enhancement, and the absence of cavernous sinus invasion suggest xanthogranuloma in the preoperative differential diagnosis. An endoscopic endonasal gross total resection without radiotherapy is the preferred first-line treatment. Given the low rate of recurrence rate and low chance of endocrinological recovery, a mass reduction with decompression of the optic apparatus may represent an appropriate surgical goal. Identifying the xanthogranulomas\' mutational profile could complement histopathological diagnosis and give insight into their histo-pathogenesis. A better preoperative neuroimagistic diagnosis of sellar xanthogranulomas and differentiation from lesions with a poorer prognosis, such as craniopharyngioma, would result in an optimal personalized surgical approach.

Purpose: To describe and illustrate recent reclassification and clinical descriptions of the histiocytoses, diagnosis and management, and effects on the eye and adnexaePatients and methods: Literature review with an illustrative case series of seven patients with histiocytosis and ophthalmic involvement from a single tertiary centre.Results: Skin lesions with signs including eyelid mass, orbital bone destruction, bizarre keratic precipitates, limbal or iris mass, haemorrhagic anterior uveitis, subretinal lesions of uncertain etiology, ischaemic retinopathy, optic neuropathy, and apparent steroid-resistant inflammations should be comprehensively investigated.Conclusions: Ophthalmic involvement in histiocytosis is rare. Clinical manifestations vary from limited single-organ disease to lethal systemic infiltration or malignancy. Radiology may identify lesions for biopsy. Histology with appropriate markers is essential. Oncology advice may be required.

Histiocytoses are one of the ultimate diagnostic challenges that every physician face at least once in his/her life. Giving their protean manifestation and differentiated therapeutic needs, histiocytosis requires extensive characterization and multidisciplinary management. Mixed histiocytosis is an emerging group of syndromes defined by the overlap of Langerhans cell histiocytosis and another histiocytic disorder of different type. Despite rare, it may account for up to a fifth of systemic histiocytosis patients in some series. In this work, we comprehensively review for the first time the clinical, radiological, histopathological and molecular features of mixed histiocytosis in children and adults. Moreover, we propose a clinical classification in three groups that differentiate patients with systemic involvement and worse overall survival to other groups with more localized manifestations and indolent behavior, wanting to ease their recognition and treatment. Interestingly we also found that mixed histiocytosis harbor BRAFV600E mutations with a higher frequency comparing to all other histiocytoses, and may therefore benefit of specific inhibitory drugs.

Intracranial xanthogranulomas (XG) are a rare benign histiocytic neoplasm and most often within the choroid. The majority are asymptomatic and are found incidentally on imaging or post-mortem examination or autopsy. We present a case of symptomatic XG in a pregnant patient who underwent a delayed transcortical, transventricular approach for lateral ventricle XG resection following the completion of her pregnancy. Four years post-operatively, the patient is neurologically intact and without recurrence. Our review of the literature showed differences among XG depending on location. The clinical and radiological features of XG are often indistinguishable from tumors arising from the choroid plexus and should be considered as a rare etiology in the differential of newly diagnosed intraventricular lesions.

Cystic lesions in the sellar region include a variety of entities, such as craniopharyngioma, Rathke cleft cyst (RCC), intrasellar arachnoid cyst, cystic pituitary adenomas, cholesterol granulomas (CGs), and xanthogranulomas (XGs). The distinction among them remains a preoperative challenge due to similarities in their clinical and radiologic findings.
We describe 3 cases with cystic sellar lesions. The first patient is a woman who presented with headache and hormonal disturbances, including high levels of prolactin, with a sellar and suprasellar cystic lesion discovered on magnetic resonance imaging. She was initially treated with dopamine agonists with normalization of prolactin levels but no changes on the size of the lesion. She underwent an endoscopic endonasal resection and the histology resulted in a CG/XG. The second patient is a woman who consulted for an incidentally discovered sellar cyst. During the follow-up, the lesion demonstrated enlargement with compression of the optic chiasm. With a preoperative diagnosis of RCC, the lesion was removed through an endoscopic endonasal transsellar approach. Final pathologic diagnosis was consistent with CG/XG. The third case was that of a man who presented with refractory headaches and vision loss, with a sellar/suprasellar cystic lesion on magnetic resonance imaging. He underwent endoscopic endonasal transsellar surgery for resection of what preoperatively was thought to be a giant RCC; final pathology again was consistent with CG/XG.
CG/XG is an uncommon pathology with unspecific clinical and radiologic features. However, this pathology should be considered in the differential diagnosis of mixed cystic/solid lesions in the sellar region.

Objectives  We present a patient with a prolactin-secreting adenoma with extensive secondary, noninfectious, xanthogranulomatous changes due to remote intratumoral bleeding and provide a literature review of xanthogranulomas (XGs) of the sellar region with emphasis on prolactinomas with xanthogranulomatous features. Design  Case report, with PubMed search of cases of sellar XG, focusing on neuroimaging and surgical approach. Results  A 35-year-old male was found to have a large sellar/suprasellar calcified/cystic mass. Endoscopic transsphenoidal approach for extradural resection was performed and diagnosis made. Review generated 31 patients with the diagnosis of sellar XG. In a minority (6 patients), the underlying lesion for the XG was a pituitary adenoma. Headache was the most common presenting symptom and panhypopituitarism the most common endocrinological abnormality. Examples of hyperprolactinemia associated with sellar XG are also uncommon and due to stalk effect. Neuroimaging of XG on T1-weighted magnetic resonance imaging (MRIs) showed 18 cases (56.3%) were hyperintense, 1 case (3.13%) was isointense, 4 (12.5%) had mixed-signal intensity, and 2 (6.25%) were hypointense. On T2-weighted MRIs, five lesions (15.6%) were hyperintense, three (9.38%) were isointense, nine (28.1%) were heterogeneous, and nine (28.1%) were hypointense. Only one case (3.1%) had calcifications on computed tomography scan similar to ours. In 14 cases (43.7%), the lesions enhanced with contrast administration on MRI. Conclusion  Prolactinomas with secondary xanthogranulomatous change represent a rare cause of XG of the sella. With no radiological or clinical signs specific for XG of the sellar region, preoperative diagnosis can be challenging, if not impossible.

Xanthogranulomas are rare intracranial lesions with controversial etiology. The sellar location is exceedingly rare. Here we report a clinical case and a review of the English-language literature of histologically confirmed xanthogranulomas in order to furnish useful tools in diagnosis and management of this unusual disease. We performed an English-language literature MEDLINE search for the last 18 years and analyzed the reports of the published series and the present case. The clinical, radiological, pathological features and outcome of the published cases of Xanthogranuloma have also been compared with the traits of Craniopharyngioma and Rathke Cleft Cyst. The data collection has been hindered by the lack of important details in the published series. The available clinical and radiological data have been reported in Table 1 (28 papers for a total of 59 patients reported). A clinical-radiological comparison among common pathologies of the sellar-parasellar region has been performed in Table 2. Endocrine impairment was a common finding in the clinical presentation and it was often worsened by surgery. Natural history of Xanthogranuloma is similar to other benign pathologies of the sellar area, but some typical features might help in distinguishing it before the pathological exam.