Cerebral involvement in sitosterolemia.

BACKGROUND: Sitosterolemia, an autosomal recessive condition, is characterized by impaired metabolism of plant sterols. Clinical symptoms include skin xanthoma, premature atherosclerotic disease, arthritis, and unexplained hematological abnormalities. However, there is a dearth of studies on sitosterolemia-related brain damage. METHODS: This study focused on the family of two sitosterolemia patients who presented with severe hypercholesterolemia and xanthoma. Radiological examinations, biopsies, whole-exome sequencing (WES), and plant sterol tests were conducted. RESULTS: The index patient, a 66-year-old female, initially exhibited weakness in both lower limbs and later developed urinary and fecal incontinence. Neuroimaging showed that the falx of the brain had irregular fusiform thickening. Significant tissue edema was observed around the lesions in the bilateral frontal-parietal lobes. Pathological analysis of the biopsied brain lesion revealed extensive cholesterol crystal deposition and lymphocyte infiltration in the matrix. The index patient who experienced cerebral impairment and her sister both carried two compound heterozygous variants in ATP binding cassette transporter G5 (ABCG5). These included the nonsense variants NM_022436: c.751 C > T (p.Q251X) in exon 6 and NM_022436: c.1336 C > T (p.R446X) in exon 10. A notable increase in plant sterol levels was observed in the younger sister of the index patient. CONCLUSION: This study highlights a previously unreported neurological aspect of sitosterolemia. Imaging and pathology findings suggest that cholesterol crystals may be deposited in connective tissues such as the cerebral falx and pia mater through blood circulation.

Intrasellar xanthogranuloma mimicking macroadenoma.

Intracranial xanthogranulomas (XGs) have been found at various sites, but xanthogranuloma of the sellar region is extremely rare. We report about a case of sellar XG in a 34-year-old female. Magnetic resonance imaging showed a solid-cystic mass located at the sella turcica. The cystic component was hyperintense on the T1-weighted image (WI) and T2WI. The solid component was hyperintense on T1WI and hypointense on T2WI. There was peripheral enhancement after gadolinium administration. The diagnosis of cystic macroadenoma was considered before surgery. Final diagnosis of XG was confirmed by histopathological examination after surgical resection. Gross total resection of the lesion was achieved using the microscope through endoscopic endonasal transsphenoidal approach. The patient had a good outcome and no symptom of diabetes insipidus, hormonal evaluation did not show any alterations compatible with hypopituitarism and prolactin levels were normal XG should receive diagnostic consideration for the sellar mass lesions with cystic components hyperintense on T1WI and T2WI, solid components hyperintense on T1WI and hypointense on T2WI, and CT without evidence of calcifications. It is important to consider the possibility of XG when pertinent, as it facilitates a proper surgical approach strategy.

Xanthoma of rib: a case report and review of the literature.

BACKGROUND: Xanthomas are well-circumscribed benign proliferative lesions seen mainly in soft tissues. Usually, they are found in hyperlipidemia and familial hyperlipoproteinemia. Histologically, are characterized by macrophage-like mononuclear cells, multinucleated giant cells and abundant foam cells. The bone involvement, however, is notoriously rare and rib localization is extremely rare. CASE PRESENTATION: A 55-year-old man performed a chest X-ray and a subsequent chest Computed Tomography scan showing a rib lesion that was surgically removed and a diagnosis of rib xanthoma was made. The patient presented an unknown condition of hyperlipidemia. CONCLUSION: Rib xanthoma can be discovered accidentally and can be helpful in identifying an unrecognized condition of hyperlipidemia.

Esophageal xanthoma with nearby coexistent squamous cell carcinoma observed using magnifying endoscopy with narrow-band imaging.

We report the case of a 63-year-old man who underwent annual surveillance esophagogastroduodenoscopy, during which a small squamous cell carcinoma and a tiny yellowish granular lesion were found in the middle esophagus, slightly apart from each other. Magnifying endoscopy with narrow-band imaging of the yellowish granular lesion showed yellowish spots and blots scattered within an approximately 2-mm area. The larger spots appeared nodular and were overlaid with tortuous microvessels. Subsequently, both the lesions were excised en masse via endoscopic submucosal dissection, and the yellowish lesion was determined to be xanthoma. Histologically, an aggregated nest of foam cells surrounded by intrapapillary capillary vessels filled the intraepithelial papillae; the foam cells also extended inferiorly, below the rete ridges, and were sparsely distributed through the lamina propria mucosae. To our knowledge, the latter finding is the first to be described in literature, which leads us to postulate that the number of foam cells in the lamina propria mucosae may affect how thick and yellow a xanthoma appears on endoscopy. We believe that this case that presents a highly detailed comparison between endoscopic and histologic findings improves our understanding of the endoscopic appearance of esophageal xanthomas and may facilitate a precise diagnosis of this rare disease.

Symptomatic bilateral choroid plexus xanthogranuloma in a pediatric patient.

INTRODUCTION: Central nervous system xanthogranulomas are uncommon clinical entities, and symptomatic bilateral choroid plexus xanthogranulomas are rare. CASE PRESENTATION: We present the case of a 15-year-old male patient with bilateral choroid plexus xanthogranulomas with symptoms of increased intracranial pressure. Gross total resection of the tumor in the left lateral ventricle was performed. The patient improved, and asymptomatic right-sided tumor was monitored at follow-up. CONCLUSION: The main treatment objective in these tumors is gross total resection. Asymptomatic tumors can be followed without intervention. However, surgery should be performed for symptomatic tumors that cause hydrocephalus or symptoms of increased intracranial pressure.

Noninvasive preoperative differential diagnosis of gallbladder carcinoma and xanthogranulomatous cholecystitis: A retrospective cohort study of 240 patients.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an extremely rare entity. Due to XGC's clinical and radiological resemblance to gallbladder carcinoma (GBC), intraoperative frozen section during cholecystectomy is often performed to exclude the diagnosis of GBC. Our study is aiming to find a noninvasive indicator of XGC. To our knowledge, this is the largest XGC cohort ever studied. METHODS: This study retrospectively collected clinical characteristics, serological tests, and imaging features of 150 GBC patients and 90 XGC patients. The diagnosis of these 150 GBC patients and 90 XGC patients was based on intraoperative frozen section histopathology. T-test was utilized to compare differences between XGC and GBC. Receiver operating characteristic (ROC) curve was conducted and the area under the curve (AUC) was managed to evaluate the validity. RESULTS: The carcinoembryonic antigen (CEA) level in blood tests was significantly elevated in GBC patients than in XGC patients (p = 0.007). The presence of submucosal hypo-attenuated nodules (80% in XGC, 16% in GBC, p < 0.001), low density border (60% in XGC, 21% in GBC, p = 0.001), and nodular thickening in the bottom of the gallbladder with calcification (70% in XGC, 37% in GBC, p = 0.004) is significantly associated with XGC patients, whereas massive hilar infiltration (0% in XGC, 21% in GBC, p < 0.001), multiple lymph nodes in the hilar area (10% in XGC, 72% in GBC, p = 0.001), and gallbladder mucosal line continuity (50% in XGC, 95% in GBC, p = 0.002) are highly associated with GBC patients. The ROC curve was performed and the gallbladder mucosal line continuity (AUC = 0.708) and the AUC of low density border around the occupation (AUC = 0.654) showed a good prediction of XGC. CONCLUSIONS: Gallbladder mucosal line continuity and low density border around the occupation presented good indication value for the diagnosis of XGC. Our study proposed a noninvasive differential diagnosis method for XGC and GBC.

Extent of lipid core plaque in patients with Achilles tendon xanthoma undergoing percutaneous coronary intervention for coronary artery disease.

BACKGROUND: It has been reported that Achilles tendon xanthoma (ATX), being one of the important diagnostic criteria for familial hypercholesterolemia, is independently associated with the severity of coronary artery disease (CAD). The aim of this study was to investigate plaque vulnerability in CAD patients with ATX. METHODS: Patients with CAD who underwent percutaneous coronary intervention (PCI) with near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) guidance were enrolled. Soft X-ray radiography of the Achilles tendon was performed, and a maximum thickness of 9 mm or more was regarded as ATX. Using NIRS-IVUS, the degree of lipid core plaque (LCP) was evaluated by calculating the maximum value of lipid core burden index (LCBI) for any of the 4-mm segments (maxLCBI4mm) in the target lesion and non-target vessel. RESULTS: In a total of 156 patients, 14 patients (9.0%) had ATX. MaxLCBI4mm in the ATX group was significantly greater in the target lesion (p<0.001) and in the non-target vessel (p=0.032) compared to the non-ATX group. When patients were divided into tertiles according to Achilles tendon thickness, maxLCBI4mm was progressively increased in favor of thickness, although there was only a tendency in the target lesion (p=0.062), and no statistical significance in the non-target vessel (p=0.189). Multiple linear regression analysis determined ATX as an independent predictor for maxLCBI4mm in the target lesion and non-target vessel. CONCLUSIONS: ATX was associated with the degree of LCP in CAD patients requiring PCI. High-risk patients with lipid-rich vulnerable plaque can possibly be detected by evaluating Achilles tendon thickness.

Xanthomatous Hypophysitis: A Case Report and Comprehensive Literature Review.

Purpose: Xanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its clinical characteristics, diagnosis and treatment is needed. Methods: Here, we report a case study and conduct a systematic review of XHP. Thirty-six cases were included, and their clinical manifestations, endocrine assessment, imaging features, treatment and follow-up data were collected and analyzed. Results: The mean age at diagnosis was 39.1 years, and females were predominant (75.0%). The most common symptom was headache (68.6%), and 66.7% of female patients presented menstrual disorders. The most common pituitary dysfunction was growth hormone (GH) deficiency. More than half of patients exhibited central diabetes insipidus (CDI). The majority of patients had an imaging presentation of a cystic lesion with peripheral enhancement. Pituitary stalk thickening was observed in half of the patients. Total lesion resection was achieved in 57.1% of cases. The recurrence rate after partial resection and biopsy was significantly higher than that after total lesion resection (57.1% vs. 0.0%, P = 0.0147). The most common pituitary hormone abnormalities to resolve after surgery were hyperprolactinemia (100.0%) and GH deficiency (91.7%). The typical pathological feature was inflammatory infiltration of foamy histiocytes, which showed positivity for CD68. Conclusion: Diagnosis of XHP is difficult when relying on clinical symptoms and imaging features. Therefore, surgical histopathology is necessary. Based on the available evidence, total lesion resection is recommended for treatment. However, the long-term prognosis for this rare disease remains unclear.

Carotid sheath xanthoma: A rare manifestation of lipid disorders.

Xanthomas are visibly deformed cholesterol deposits that are commonly associated with lipid disorders, such as familial hypercholesterolemia (FH) or rare sitosterolemia. We present the first report of two cases of carotid sheath xanthomas in patients with lipid disorders. Case 1 involved a 26-year-old woman presenting with two heterogeneous mutations on the ABCG5 gene-as noted on genetic testing-who was finally diagnosed with sitosterolemia. Ultrasonography (US) revealed hypoechoic masses centered in the bilateral carotid sheath, which gradually reduced in size after diet control and the use of ezetimibe. Case 2 involved a 27-year-old man who was diagnosed with possible FH and had recurrent bilateral buttock xanthomas, as well as bilateral carotid sheath masses detected by US. Postoperative pathological examination of the resected right neck mass confirmed a xanthoma with proliferation of multinucleated giant cells and deposition of cholesterol clefts.

Can Achilles tendon xanthoma be distinguished from Achilles tendinopathy using Dixon method MRI? A cross-sectional exploratory study.

BACKGROUND: Familial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture. Misdiagnosis of xanthoma can delay the commencement of potentially life-saving lipid-lowering therapy. Our primary purpose was to determine whether analysis of separated fat and water magnetic resonance images may be able to differentiate between xanthomatic and nonxanthomatic Achilles tendons through quantification of intratendinous fat content. The main hypothesis was that Achilles tendon xanthomas will demonstrate greater lipid content than Achilles tendinopathy or healthy control tendons. METHODS: Bilateral MRI scans of Achilles tendons from 30 participants (n = 10 Achilles tendon xanthoma, n = 10 Achilles overuse tendinopathy, n = 10 healthy controls) were analyzed for total lipid content using the Dixon method of fat and water signal separation. Secondary outcome measures included tendon water content, as well as ultrasound characterization of tendon tissue organization and thickness. RESULTS: Fat content was greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p < 0.0001). Water content was also greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p = 0.0002). Ultrasound tissue characterization revealed worse tissue organization in Achilles tendon xanthoma tendons compared to Achilles tendinopathy (p < 0.05) but demonstrated largely overlapping distributions. Achilles tendon xanthoma tendons were, on average, significantly thicker than the tendons of the other two groups (p < 0.01 and p < 0.001, respectively). CONCLUSION: MRI-derived measures of Achilles tendon fat content may be able to distinguish xanthomas from control and tendinopathic tissue. Dixon method MRI warrants further evaluation in an adequately powered study to develop and test clinically relevant diagnostic thresholds.

Possible Neoangiogenesis in Achilles Tendon Xanthoma with Familial Hypercholesterolemia: A Novel Approach to Achilles Tendon Xanthoma.

Achilles tendon xanthoma (ATX) is one of the typical features of familial hypercholesterolemia (FH). The morphological evaluation of ATX by X-ray radiography is widely recognized; however, the utility of other imaging modalities remains unclear. We herein report two cases of FH in which Doppler ultrasound imaging demonstrated a microvascular flow in ATX that only rarely could be observed in normal Achilles tendons. Neoangiogenesis accompanies chronic inflammation and it may play an important role in the deposition of cholesterol crystals leading to ATX. In addition to the morphological evaluation of ATX, the assessment of neoangiogenesis may therefore be essential for the evaluation of ATX.

A case of xanthogranulomatous appendicitis in the female pelvis.

Xanthogranulomatous inflammation is an uncommon form of chronic inflammatory process. Only a few isolated case reports of xanthogranulomatous appendicitis (XA) have been published. XA has nonspecific imaging findings and cannot be reliably differentiated on imaging from locally advanced malignancy. XA however follows a benign course and can potentially be treated with surgical resection.

Xanthogranulomatous cholecystitis: a review of 31 patients.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory gallbladder disease which is difficult to diagnose and treat; XGC may be confused with gallbladder cancer. The present study aimed to evaluate the clinical and radiological features and surgical outcomes, with the aim to determine the appropriate treatment approaches for XGC. METHODS: This retrospective study analyzed the clinical characteristics, intraoperative findings, and postoperative outcomes of 31 patients (2.0%) who were diagnosed with XGC based on histopathological findings among 1513 patients who underwent cholecystectomy at our hospital between January 2010 and July 2019. RESULTS: Preoperative ultrasonography and computed tomography findings indicated acute cholecystitis, chronic cholecystitis, and suspicious XGC in 26 (83.9%) patients with thickening of the gallbladder wall and suspicious gallbladder cancer in 5 (16.1%) patients. Abdominal pain and jaundice were observed in 18 (58.1%) patients and 5 (16.1%) patients, respectively. Biliary drainage before surgery was performed in 21 (67.7%) patients. Laparoscopic cholecystectomy, which was performed in 23 (74.2%) patients, was converted to open cholecystectomy in 12 (52.2%) of these 23 patients. Among the patients with other diseases treated during the study period, laparoscopic cholecystectomy was performed in 1377 patients and converted to open surgery in 71 (5.2%) patients. Five patients with suspicious gallbladder cancer underwent open surgery. In these patients, intraoperative frozen section analysis was useful in distinguishing between XGC and gallbladder cancer and was important in avoiding unnecessarily extended surgery. CONCLUSION: Laparoscopic cholecystectomy for XGC is possible, but often difficult due to severe inflammation. The frequency of conversion to open surgery is higher in patients with XGC than those with other forms of cholecystitis. XGC may resemble gallbladder cancer based on the diagnostic imaging findings, and intraoperative frozen section analysis is essential to avoid unnecessarily extended surgery.

Symptomatic xanthogranuloma of the lateral ventricle in a pregnant patient treated with delayed resection: A case report and systematic review.

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.