A rare presentation of unicentric Castleman's disease in the thigh:A case report and review of literature

BACKGROUND Castleman's disease(CD)is a rare lymphoproliferative,emulating both benign and malignant diseases.The diagnosis of CD is formulated upon the combination of clinical and laboratory criteria and ultimately confirmed by histopathological assessment.Due to its rarity,CD presents a challenge in treatment selection,with available options encompassing surgery,chemotherapy,and autologous stem cell transplantation.However,studies suggest that surgical resection of the lesion is the most effective treatment modality,especially for unicentric CD(UCD).CASE SUMMARY Here,we describe the case of a 25-year-old woman who presented with painless left thigh swelling for 10 wk.She had been following a low-fat diet to lose weight and had normal laboratory results.Magnetic resonance imaging revealed a wellcircumscribed,demarcated cystic lesion located in the left inguinal region with eccentrically positioned signal void vascular structures,measuring 4.3 cm×3 cm×3.2 cm,likely of lymphoid origin.The patient underwent surgical resection,and the final histopathology showed a vascular proliferation and hyalinization of the vessel walls,along with atretic germinal centers traversed by penetrating vessels,consistent with CD.The patient was discharged home one day after the procedure in good condition,with a follow-up appointment scheduled in our outpatient clinic.CONCLUSION Although surgical resection is the mainstay for UCD,a multidisciplinary approach is needed due the lack of specific diagnostic features and treatments.

Radiologic features of Castleman's disease involving the renal sinus: A case report and review of the literature

BACKGROUND We present a rare case of plasma cell type of Castleman's disease(CD) involving only the right renal sinus in a 65-year-old woman with a duplex collecting system(DCS).CASE SUMMARY The patient presented with a right renal sinus lesion after renal ultrasonography.Subsequent abdominal enhanced computed tomography(CT) and magnetic resonance imaging(MRI) of the kidneys showed DCS and a soft tissue mass with mild enhancement at the lower right renal sinus. The lesion was suspected to be a malignant renal pelvic carcinoma. Hence, the patient underwent a right radical nephrectomy. Histological examination revealed hyperplastic lymphoid follicles in the renal sinus. A detailed review of the patient's CT and MRI images and a literature review suggested that the lesion was hypointense on T2-weighted images and hyperintense on diffusion-weighted image manifestations, and showed mild enhancement, which distinguished the plasma cell type of CD from many other renal sinus lesions. Furthermore, peripelvic soft tissue masses with a smooth internal surface of the renal pelvis were on imaging findings, which suggests that the urinary tract epithelial system is invulnerable and can be used to differentiate the plasma cell type of CD from malignant lymphoma with a focally growth pattern to some extent.CONCLUSION Preoperative diagnosis is often difficult in such cases, as plasma cell type of CD involving only the right kidney is exceedingly rare. However, heightened awareness of this disease entity and its radiographic presentations may alert one to consider this diagnosis.

Multicentric hyaline-vascular Castleman's disease in the retroperitoneum

BACKGROUND:Castleman’s disease is a rare lymphoproliferative disease of unknown cause.Most multicentric cases described have been of the plasma-cell variety.This article presents a case of multicentric hyaline-vascular Castleman’s disease in the retroperitoneum with the ultrasonographic and computed tomography(CT)imaging manifestations. METHODS:During routine physical examination,a mass was detected in the left abdomen of a 53-year-old man with no signs or symptoms.The patient underwent ultrasoundguided aspiration biopsy and operative excision after laboratory examination,ultrasonography,and CT. RESULTS:Ultrasonography demonstrated a dominant hypoechogenic mass with hypervascularity in the retroperitoneum.CT detected a relatively homogenous enhanced lesion and several satellite nodules.After the mass and several lymph nodes were resected, histopathologic examination demonstrated a lymphocytepredominant infiltrate surrounding the germinal centres and extensive capillary proliferation,consistent with the hyaline-vascular type of Castleman’s disease.The patient received postoperative chemotherapy and remained free of recurrence 3 months later. CONCLUSION:Ultrasonography and contrast-enhanced CT can provide a positive differential diagnosis of hyalinevascular Castleman’s disease which is a kind of giant lymph node hyperplasia with hypervascularity.

Castleman's disease of the spleen

Castleman's disease(CD) is a rare lymphoproliferative disorder of unknown etiology.Clinically,it occurs as a localized(unicentric) disease or as a systemic(multicentric) disease.Unicentric Castleman's disease(UCD) presents as a solitary mass and primarily affects the mediastinal,retroperitoneal,and cervical lymph nodes.In contrast to multicentric CD,which involves peripheral lymphadenopathy and numerous systemic symptoms,UCD is not typically associated withgeneralized symptoms.Three main distinct histologic variants are recognized:hyaline-vascular type,plasma cell type,and mixed type.Extranodal CD is rare.Specifically,UCD exclusively in the spleen is extremely rare,with only 2 cases described in the literature to date.Here,we describe an asymptomatic 75-yearold man with a 5.7 cm × 4.5 cm sized heterogenous enhanced mass located in the spleen.He underwent surgical resection for diagnosis and treatment.A pathologic examination indicated the hyaline-vascular type of CD.In this patient,the preoperative diagnosis was difficult to determine,and therefore,invasive procedures were required.

Endoscopic ultrasonography-guided trucut biopsy for the preoperative diagnosis of peripancreatic castleman's disease: A case report

Castleman＇s disease （CD） of the pancreas/peripancreas is extremely rare. The recently introduced, endoscopic ultrasonography （EUS）-guided trucut biopsy （TCB） is a useful diagnostic rnodality for obtaining tissue samples from peripancreatic lesions. However, its role in diagnosing CD remains unknown. We report a case of localized, peripancreatic, hyaline-vascular CD biopsied using EUS. The pathology results were initially interpreted as an extranodal, marginal-zone B-cell lyrnphoma. However, polyrnerase chain reaction （PCR） study for the IgH gene rearrangement revealed a polyclonal pattern. We also reviewed the relevant literature. To our knowledge, this is the first illustrated report on EUS-TCB findings of CD with its pathology results of EUS-TCB mimicked a B-cell lymphoma.

Retrospective Study of Castleman's Disease:A Report of Fourteen Cases and Review of the Literature

OBJECTIVE To enhance the understanding of Castleman’s disease (CD), and to improve its diagnosis and management. METHODS Clinical features and related information on diagnosis and treatment of 14 cases of CD were retrospectively analyzed and the literature reviewed. RESULTS Based on the clinical classification, localized CD was found in 8 of the 14 cases. Both the results of lymph node biopsy and histopathology indicated they were a hyaline-vascular type. The multicentric type CD was detected in 6 cases, among which 4 were plasma cell type and 2 mixed type based on histopathologic examination. There were a variety of clinical situa-tions in the 14 cases, with a lack of specificity. They were previously misdiag-nosed as other diseases, and final diagnosis depended on a histopathologic examination. The 8 patients with localized CD underwent excision, without recurrence up to now. The 6 patients with multicentric-type CD were treated with glucocorticoids or combined chemotherapy, and all achieved remission. CONCLUSIONS CD has complicated clinical manifestations and is difficult to diagnose. Lymph node biopsy is important for early diagnosis. An optimal curative effect can be achieved with a suitable therapeutic option, based on histopathology and clinical classification.

Unicentric Castleman's disease of the pancreas with massive central calcification

Unicentric Castleman＇s disease of the pancreas is extremely rare, with only six cases described in the worldwide literature. An asymptomatic case of unicentric, hyaline, vascular-type Castleman＇s disease （UCD） localized to the tail of bhe pancreas with central calcification imitating a primary neoplasm of the pancreas is presented. This is the first description of endosonographic and endoscopic retrograde pancreatographic findings of pancreatic UCD. Additionally, computed tomography, histological and serologic findings are reported.

Cervical Castleman's disease mimicking lymph node metastasis of esophageal carcinoma

Castleman's disease(CD) is an uncommon benign lymphoproliferative disorder of unknown etiology. A rare case of cervical CD diagnosed at lymph node dissection for esophageal carcinoma is reported. An esophageal tumor was identified in a 67-year-old man during a follow-up examination after surgery for oral carcinoma. Esophagoscopy revealed a type 1 tumor in the cervical esophagus. Histology of esophagoscopic biopsies indicated squamous cell carcinoma. Contrastenhanced computed tomography revealed swollen lymph nodes of the right cervical region. No distant metastasis was detected. Esophageal carcinoma, T2N2M0, Stage ⅢA was diagnosed. Neoadjuvant chemotherapy was recommended, but the patient rejected the chemotherapy. The patient underwent laparoscopic-assisted transhiatal esophagectomy. The histopathological diagnosis was moderately differentiated squamous cell carcinoma with pT1bN0M0, Stage ⅠA. On histology, the swollen lymph nodes of the right cervical region revealed CD. The patient's postoperative course was relatively good.

Liver cirrhosis in a child associated with Castleman's disease: A case report

BACKGROUND Castleman's disease(CD)is a lymphoproliferative disorder.TAFRO syndrome is classified as a variant of CD based on its key clinical manifestations of thrombocytopenia,anasarca(generalized edema and pleural effusion),fever(pyrexia),reticulin fibrosis in the bone marrow and the proliferation of megakaryocytes,and organomegaly(such as hepatosplenomegaly and multiple lymphadenopathies);TAFRO syndrome is mainly reported in Japanese patients.To our knowledge,this is the first pediatric case report detailing a CD-associated disorder progressing to cirrhosis.CASE SUMMARY A 10-year old male patient presented with fever and anemia.Six months before hospitalization,he had remarkable abdominal distention.Subsequently,he visited a clinic for a fever that lasted 5 d.The physical findings were marked hepatosplenomegaly and cervical lymphadenopathy.A blood test revealed leukocytosis,microcytic anemia,aspartate aminotransferase-dominant transaminase elevation,high levels of C-reactive protein,polyclonal hypergammaglobulinemia,and high levels of interleukin-6 and vascular endothelial growth factor.Abdominal contrast computed tomography and magnetic resonance imaging suggested cirrhosis,which was confirmed by liver histology.Histological findings in the enlarged hepatic lymph nodes revealed both hyperplasia and atrophy of lymphoid follicles with some vascular hyperplasia and moderate plasmacytosis between the lymphoid follicles,which is compatible with lymph node histology in TAFRO syndrome.Prednisolone was not effective in reducing the patient’s symptoms;therefore,the patient was prescribed tocilizumab.To date,the patient remains free of fever and continues to receive tocilizumab.CONCLUSION We described the clinicopathological features of TAFRO syndrome to highlight the clinical presentation of this rare disease in a pediatric case.

Unicentric Castleman's disease associated with end stage renal disease caused by amyloidosis

Castleman's disease(CD), also known as angiofolicular lymph node hyperplasia, is a rare heterogenous group of lymphoproliferative disorders. Histologically, it can be classified as hyaline vascular type, plasma cell type, or mixed type. Clinically two different subtypes of the CD are present: Unicentric and multicentric. Unicentric CD is generally asymptomatic and associated with hyaline vascular type, and its diagnoses depend on the localized lymphadenopathy on examination or imaging studies. However, multicentric CD presents with generalized lymphadenopathy and systemic symptoms including malaise, fever, night sweats, weight loss, and it is associated with the plasma cell type and mix type. Herein, we report a patient with unicentric CD of the plasma cell type without systemic symptoms, who developed end stage renal failure caused by amyloidosis 6 years after onset of CD.

Radiotherapy of unicentric mediastinal Castleman's disease

Castleman's disease is a slowly progressive and rare lymphoproliferative disorder.Here,we report a 55-year-old woman with superior mediastinal Castleman's disease being misdiagnosed for a long term.We found a 4.3 cm mass localized in the superior mediastinum accompanied with severe clinical symptoms.The patient underwent an exploratory laparotomy,but the mass failed to be totally excised.Pathologic examination revealed a mediastinal mass of Castleman's disease.After radiotherapy of 30 Gy by 15 fractions,the patient no longer presented previous symptoms.At 3 months after radiotherapy of 60 Gy by 30 fractions,Computed tomography of the chest showed significantly smaller mass,indicating partial remission.Upon a 10-month follow-up,the patient was alive and free of symptoms.

Unicentric Castleman's Disease with Cardiovascular Involvement

CASTLEMAN＇S disease（CD）,a rare lymphoproliferative disorder of unknown etiology, was first described in 1956 as a benign mass in the mediastinum. Although CD can present anywhere in the body, 70% of the cases are in the chest along the tracheobronchial tree or hilum of the lung in the middle mediastinum; however, they can also occur in the anterior or posterior compartments. CD is classi-fied as unicentric （UCD） or multicentric （MCD） based on the anatomical distribution, and histologically as hya-line-vascular, plasma cell, or mixed subtypes.1 Although MCD is less common than UCD, it can be rapidly pro-gressive and often fatal.

Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Amyloid-beta and tau protein beyond Alzheimer's disease

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease.Physiologically,these two proteins are produced and expressed within the normal human body.However,under pathological conditions,abnormal expression,posttranslational modifications,conformational changes,and truncation can make these proteins prone to aggregation,triggering specific disease-related cascades.Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration.Additionally,these proteins have been linked to cardiovascular disease,cancer,traumatic brain injury,and diabetes,which are all leading causes of morbidity and mortality.In this comprehensive review,we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

Lactate metabolism in neurodegenerative diseases

Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins.Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis,while providing nutrients and support for cell survival.Chaperone-mediated autophagy activity can be detected in almost all cells,including neurons.Owing to the extreme sensitivity of neurons to their environmental changes,maintaining neuronal homeostasis is critical for neuronal growth and survival.Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases.It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction.Under certain conditions,regulation of chaperone-mediated autophagy activity attenuates neurotoxicity.In this paper,we review the changes in chaperone-mediated autophagy in neurodegenerative diseases,brain injury,glioma,and autoimmune diseases.We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

Mitophagy in neurodegenerative disease pathogenesis

Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.