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The association of recognisable neurological conditions with an underlying malignancy is well described. In this review we explore the complex interplay of genetic, environmental and tumour factors which contribute to autoimmunity and paraneoplastic conditions. We review the current understanding of the pathogenesis of well recognised paraneoplastic conditions in children including Opsoclonus myoclonus ataxia syndrome, N-Methyl-D Aspartate receptor encephalitis and limbic encephalitis, and the broad approaches to treatment. Rapid advances in oncological treatment has expanded the arsenal of therapeutic modalities. We explore the broad spectrum of immune therapies in childhood cancer, and the potential neurological complications of these novel therapies, and discuss the fine balance of risk and benefit that these bring. • Sex, age, ethnicity, genetic vulnerability and malignancy are factors associated with brain directed autoimmunity. • In OMAS NMDARE immune and oncological management are required for optimal management of these rare childhood conditions. • Immunotherapy in the treatment of childhood cancers has potential to improve both survival and quality of life. • Immune check-point inhibitors are associated with neurological immune-related adverse events in at least 10 % of patients. [ABSTRACT FROM AUTHOR]

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neuroimmune disease with peak onset at 18 months, associated with neural crest tumors in 50% of patients. In part due to its rarity, misdiagnosis at onset is common, can delay treatment, and may contribute to adverse outcomes. Patient-reported registries may overcome some of these challenges in rare disease research. In this context, the OMSLife Foundation collaborated with the National Organization of Rare Diseases to create a patient-reported registry in OMAS. Retrospective analysis was performed of data entered by parents of patients with OMAS into nine online surveys assessing demographics, symptoms at onset, triggers, time of diagnosis, treatment, and additional therapies. A total of 194 patients were enrolled. There was a female predominance (54%) and high rate of parental autoimmunity (31%). Age at onset peaked between 12 and 18 months overall. The age of onset was older in female patients (median [interquartile range]: females 22 [15 to 31] vs males 18 [14 to 23], P = 0.0223, P = 0.0223). Symptoms at onset most commonly included ataxia (84%) and were typically severe. Initial misdiagnosis occurred in nearly 50% and tumor discovery was delayed in 18 patients, but overall median time to correct diagnosis was 25 days. Most patients (56%) received combination immunomodulatory therapies, and nearly all underwent supportive therapies. Patient- and parent-powered research is feasible in OMAS and created the second largest published cohort of pediatric patients with OMAS. Results were similar to other large cohorts and also validated findings from prior case reports and smaller case series. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling paraneoplastic neurological syndromes. Unlike other neurological adverse events caused by these drugs, post-immune checkpoint inhibitor paraneoplastic neurological syndromes predominantly affect the CNS and are associated with neural antibodies and cancer types commonly found also in spontaneous paraneoplastic neurological syndromes. Furthermore, post-immune checkpoint inhibitor paraneoplastic neurological syndromes have poorer neurological outcomes than other neurological adverse events of immune checkpoint inhibitors. Early diagnosis and initiation of immunosuppressive therapy are likely to be crucial in preventing the accumulation of neurological disability. Importantly, the neural antibodies found in patients with post-immune checkpoint inhibitor paraneoplastic neurological syndromes are sometimes detected before treatment, indicating that these antibodies might help to predict the development of neurological adverse events. Experimental and clinical evidence suggests that post-immune checkpoint inhibitor paraneoplastic neurological syndromes probably share immunological features with spontaneous paraneoplastic syndromes. Hence, the study of post-immune checkpoint inhibitor paraneoplastic neurological syndromes can help in deciphering the immunopathogenesis of paraneoplastic neurological syndromes and in identifying novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival. This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors. From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59–74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3–13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1–6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4–17·8 and HR 6·6, 1·4–31·0, respectively). Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment. The Instituto de Salud Carlos III and the European Union. [ABSTRACT FROM AUTHOR]

We report a case of an 80-year-old woman with botulism from 2020 in Osaka, Japan. The patient complained of dysarthria and dizziness. On the same day, the patient developed respiratory failure, and was intubated and placed on mechanical ventilation. Subsequently, ophthalmoparesis and quadriparesis progressed rapidly. Ten days after onset, the patient failed to respond to any external stimulation. Blood tests showed anemia, and computed tomography revealed undiagnosed cervical cancer. Initially, diagnosis of neuromuscular junction disorder and acute motor neuropathy, including paraneoplastic syndrome, were considered. However, intravenous immunoglobulin therapy and plasma exchange were ineffective. A fecal sample on day 30 showed a large number of C. botulinum spores. On day 34, a mouse bioassay revealed botulinum toxin type A in the patient's serum; therefore, a botulinum antitoxin was administered. Later, the patient's muscle strength was gradually improved. However, severe muscle paralysis persisted, and the patient died of cachexia owing to cervical cancer on day 196. The etiology of this case was unknown because no contaminated food was identified during an inspection of the patient's home. Fecal 16S rRNA gene sequencing revealed dysbiosis of the intestinal microbiota with abundant Enterococcus species. Long-lasting excretion of substantial botulinum spores even on day 30 indicated colonization of C. botulinum in the intestinal tract. This case suggests that C. botulinum colonization with co-existing intestinal dysbiosis may be associated with severe and prolonged symptoms of botulism. [ABSTRACT FROM AUTHOR]

Annular and acral/facial dyskeratotic paraneoplastic disorders are inflammatory dermatoses that occur in association with distant cancers but are not precursors, extensions, or metastases of them. There are four classical entities under this rubric: two gyrate entities, erythema annulare centrifugum and erythema gyratum repens, and two acral/facial dyskeratotic entities, acrokeratosis paraneoplastic (Bazex syndrome) and tripe palms. Each of these entities may also occur in association with another etiopathogenesis and may present either as a classical entity or as a barely recognizable disease. We discuss these entities, their associated causes, and their differential diagnoses in turn. [ABSTRACT FROM AUTHOR]

• NSCLC small biopsy exfoliates tumour cells of good cellularity in fixative media. • Cell pellet collection is encouraged while TBLB samples are being processed. • Residual cell pellet retention post a thoracic small biopsy aids ancillary testing. • Combining cell pellets with traditional sampling is beneficial in advanced NSCLC. Lung cancer tissue obtained using small biopsies are relatively fragile, leaving behind some tiny tissue fragments or cell clusters in the fixative medium that are difficult to collect for processing as a paraffin-embedded tissue block. Usually, the cellular component of the residual fixative medium is discarded as medical waste as per routine laboratory protocol. No protocol exists for utilizing the cellular component of the residual fixative medium after processing the tissue blocks to improve lung cancer ancillary testing. This study aimed to undercover the potential value of these samples for lung cancer diagnosis and targeted therapy development. A protocol was developed for cell pellet sample collection from the residual fixative medium of a transbronchial forceps lung biopsy sample. Tumour cell number and fraction in a paired cell pellet and matching formalin-fixed paraffin-embedded tissue section were evaluated from 324 non-smallcell lung carcinoma (NSCLC) cases. We defined the adequacy of the cell pellet for molecular analysis as ≥ 200 tumour cells and ≥ 10 % tumour cells. Real-time polymerase chain reaction and next-generation sequencing were performed on adequate cell pellet samples. We discovered that the fixative medium of most transbronchial forceps lung biopsy samples was enriched in tumour cells. Among 324 biopsy samples, 70 (21.6%) exhibited inadequate formalin-fixed paraffin-embedded tissue sections, whereas 53 (75.7%) yielded adequate cell pellet samples. Somatic mutations detected in the formalin-fixed paraffin-embedded tissue section samples were also detected in the matching cell pellets. Cell pellets collected from the fixative medium of thoracic small biopsies are a beneficial supplemental material for ancillary testing. Combined use of cell pellets with traditional tissue-based samples can enhance the detection rate of informative mutations in patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

This review aims to elucidate the bidirectional relationship between heart failure and cancer by identifying their common and reciprocal risk factors. It seeks to provide a comprehensive understanding of the mechanistic interactions between these two conditions, supported by evidence from preclinical and clinical investigations. A thorough review of peer-reviewed articles was conducted to identify all possible interactions between cancer and heart failure. Multiple search engines were utilized with queries incorporating terms such as cardio-oncology, heart failure, cancer, risk factors, and mechanistic interactions. Selected studies were analysed to identify shared risk factors and to explore the mechanistic junctions that link the two diseases. The review identified several common risk factors, including, inflammation, smoking, obesity, clonal haematopoiesis of indeterminate potential, and reduced exercise potential. The pathophysiological mechanisms linking heart failure with cancer include metabolic reprogramming in cancer, cancer-induced thrombosis, cardiac metastasis, paraneoplastic syndrome, cancer-associated cachexia, and anorexia. Additionally, it was found that cancer therapies, such as anthracyclines and radiation, can induce cardiotoxicity, leading to heart failure. The pathophysiological mechanisms that contribute to cancer in heart failure patients were identified as neurohormonal activation, state of hypoxia, secretion of Cardiokines, heart failure medication, innate immune reprograming & cardiac remodelling and coronary atherosclerotic disease. By highlighting the interconnected nature of heart failure and cancer, this review promotes a cardio-oncologic discourse, encouraging cardiologists and oncologists to consider these diseases as interrelated rather than separate entities. This perspective can lead to the development of novel therapeutic strategies and improve patient management by addressing the dual disease burden. Future research should focus on exploring the translational potential of existing drugs and developing new interventions to target the shared characteristics of heart failure and cancer. [Display omitted] • Integration over segregation: Cardiologists & Oncologists teaming up to fight against Cancer & HF for better patient care. • Holistic patient management: A dual disease perspective for optimal therapeutic success. • Treatment innovation: Spotlighting commonalities paves the way for integrated therapies, opening up new treatment avenues. • Translational focus: A way for researchers to use current insights & develop vialbe solutions as a dual disease paradigm. [ABSTRACT FROM AUTHOR]

• In selected cases, with high index of suspicion for paraneoplastic syndromes, cancer screening should be prolonged beyond the current recommendations. • The long disease course may be related to the anti-tumour effect of anti-VGCC Abs that slowed neoplasm growth. • DELTA-P score is a highly sensitive tool to discriminate between SCLC-LEMS and nontumour LEMS, by contrast anti-SOX1 antibodies have limited value as paraneoplastic biomarkers in clinical practice. Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular junction disorder, paraneoplastic in 55% of cases and commonly associated with small-cell lung cancer (SCLC). We report the case of a 61-year-old man presented who with a 3-month history of lower limb proximal weakness, progressing to upper limbs, associated with dysphagia, xerostomia and erectile dysfunction. Electrodiagnostic studies and anti voltage-gated calcium channel (VGCC) antibodies (Abs) detection confirmed LEMS diagnosis. Contrast-enhanced thorax computed tomography (CT) scan and subsequently [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed no malignancy. Two years after the onset of LEMS, he was diagnosed with anti-Hu limbic encephalitis (LE). FDG-PET/CT scan remained negative for the following seven years. Nine years after LEMS onset, a hypermetabolic lesion of the left lung hilus was detected. This is a case of a paraneoplastic LEMS where the interval between the onset of neurological disease and tumour detection was as long as nine years. [ABSTRACT FROM AUTHOR]

Primary neuroendocrine tumours of the thymus (NETTs) are exceedingly rare tumours, usually presenting around mid-life, which have a propensity towards males and smokers. They are seen more often in those with MEN-1, but multiple different genetic mutations have been found to be involved in the tumorigenesis of NETTs. Histologically, NETTs are classified according to number of mitoses, the presence of necrosis, and the presence or absence of small cell features. NETTs display a wide spectrum of behavior, and they can be incidentally found on chest imaging, on screening in MEN-1, or present with symptoms of local compression. Advanced disease and paraneoplastic syndromes are common. CT-, PET/CT-, MRI-scans, and somatostatin receptor scintigraphy are the imaging modalities of choice both for the initial assessment as well as for monitoring after treatment. For patients with localized disease, complete surgical resection with lymphadenectomy provides the best chance of long-term, disease-free survival, and can be achieved through either an open or thoracoscopic approach. While chemotherapy-regimens based on platinum, taxane, and temozolomide are used most often, the optimum chemotherapy regimen in the adjuvant and palliative settings remains unclear, as does the role of radiotherapy. Ongoing research on the most effective use of somatostatin analogues, peptide receptor radionuclide therapy (PPRT), kinase inhibitors and immunotherapy in patients with other types of advanced neuroendocrine tumours may lead to further treatment options for NETTs in the future. [ABSTRACT FROM AUTHOR]

Subacute cutaneous lupus erythematosus (SCLE) is a photosensitive dermatosis characterized by a nonscarring papulosquamous eruption and specific antibodies in the patient's serum. Genetic and environmental factors represent the leading causes of SCLE; however, several case reports in the literature link SCLE to various types of cancer. This review assesses the association between SCLE and neoplastic disorders. A PubMed search was performed for all relevant publications on cancer-associated SCLE from 1982 to 2022. This review supports the hypothesis that SCLE should be considered a facultative paraneoplastic phenomenon. It also emphasizes the importance of cancer screening in patients presenting SCLE manifestations. [ABSTRACT FROM AUTHOR]

Paraneoplastic encephalitis (PE) represents a rare but significant complication in patients with testicular cancer (TC). Given the paucity of comprehensive literature on this topic, our review seeks to consolidate current knowledge and provide evidence-based recommendations for the diagnosis, prognosis, and management of PE in the context of TC. In adherence to PRISMA guidelines, a systematic literature review was conducted from 1950 to April 2024 using PubMed. The search focused on articles where TC was identified as the primary etiology of PE. The Mixed Methods Appraisal Tool and the Oxford Centre for Evidence-Based Medicine's levels of evidence tool were employed for assessing study quality, and a thematic analysis was conducted to identify trends and patterns. Out of 91 articles identified, 29 met the inclusion criteria, encompassing 5 retrospective chart reviews, 3 case series, and 22 case reports. Findings indicate that PE symptoms can manifest at any stage of TC—before tumor detection, during treatment, or even years posttreatment. A notable observation was the frequent oversight of microscopic testicular tumors in ultrasound imaging, leading to diagnostic delays. The outcomes of PE in the context of TC were diverse, reflecting the heterogeneity of the studies included. PE, although rare, is a critical consideration in patients with TC presenting with neuropsychiatric symptoms. Early recognition and appropriate diagnostic workup, including consideration for microscopic neoplasms, are essential for timely intervention and improved patient outcomes. Paraneoplastic encephalitis (PE) is a rare but significant complication in testicular cancer (TC) patients. This systematic review consolidates current knowledge on PE in TC, highlighting the importance of early recognition and diagnostic workup, including consideration for microscopic neoplasms. Timely intervention is crucial for improved patient outcomes, as PE symptoms can manifest at any stage of TC. [ABSTRACT FROM AUTHOR]

The thymus is a primary lymphoid organ that plays a key role in the immune system development. Normally, it is located in the anterior mediastinum and it changes tissue composition with progressive fatty involution with age. The spectrum of pathological processes involving the thymus include enlargement, tumour development, and cystic change. In addition, other local pathology can mimic thymic disease. Differentiating these entities can be challenging; however, recognizing key features on imaging is essential to appropriately guide further investigation and therapy. The focus of this pictorial review will be to highlight the important distinguishing features of thymic hyperplasia, thymomas, thymic cysts, thymic neuroendocrine tumours (NETs), thymolipomas, mediastinal teratomas, and other mimics of thymic disease. Knowledge of the varying imaging findings on computed tomography and magnetic resonance imaging is valuable for radiologists to appropriately classify disease, avoid misdiagnosis, and expedite therapy. • Chemical shift MR imaging can differentiate thymic hyperplasia from thymic tumours. • Recognition of macroscopic invasion in thymomas helps guide therapy. • Thymomas associated with paraneoplastic syndromes can be identified on imaging. • Cystic thymomas can mimic thymic cysts and MRI is useful to differentiate these. • Thymic NETs may avidly enhance on CT as a possible clue to distinguish from thymoma. [ABSTRACT FROM AUTHOR]

The frequency of corticospinal tract (CST) T2/FLAIR hyperintensity in disorders with neuroglial antibodies is unclear. Herein, we retrospectively reviewed brain MRIs of 101 LGI1-antibody encephalitis patients, and observed CST hyperintensity in 30/101 (30%). It was mostly bilateral (93%), not associated with upper motor neuron signs/symptoms (7%), and frequently decreased over time (39%). In a systematic review including patients with other neuroglial antibodies, CST hyperintensity was reported in 110 with neuromyelitis optica (94%), myelin oligodendrocyte glycoprotein-associated disease (2%), Ma2-antibody (3%) and GAD65-antibody paraneoplastic neurological syndrome (1%). CST hyperintensity is not an infrequent finding in LGI1-Ab encephalitis and other disorders with neuroglial antibodies. [Display omitted] • Brain MRI corticospinal tract hyperintensity elicits a broad differential diagnosis. • Its overall frequency in brain disorders with neuroglial antibodies is unclear. • It is present in 30% among 101 patients with LGI1-antibody encephalitis. • In the literature it is reported in 110 patients with diverse neuroglial antibodies. • Corticospinal tract hyperintensity is not rare in autoimmune brain disorders. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurological syndromes (PNS) are rare neurological disorders arising from malignancy-triggered autoimmunity, yet their association with urothelial carcinoma remains unclear. This systematic review intends to explore any connection, alongside patient/clinical features and management. A literature search identified 25 cases of bladder and upper tract carcinoma linked to PNS. Overall, while infrequent, a meaningful association between PNS and urothelial carcinoma was found in that 84% of cases met a 'possible'-or-'higher-likelihood' PNS diagnosis. Most cases presented with high-risk PNS phenotypes, predominantly cerebellar syndromes and encephalomyelitis/sensory neuronopathy, ∼17 months within cancer diagnosis/recurrence. Review findings suggest a female preponderance in suspected PNS despite higher male incidence of urothelial cancer. Main treatments consisted of surgery alongside chemotherapy or immunotherapeutics (IVIG and/or corticosteroids), which improved symptoms for a slight majority (60%). Ultimately, while common PNS-associated neoplasms should always first be excluded in suspected PNS, in the absence of alternative causes, urothelial carcinomas do merit clinical consideration. [Display omitted] • The association between PNS and urothelial carcinoma to date remains unclear. • Findings suggest that PNS can occur in the context of urothelial carcinoma but rare. • Most PNS-suspected cases met 'possible' or higher PNS scores, notably elderly women. • Key PNS signs include syndrome type, high-risk Abs and tumour antigen expression. • Immunomodulation plus tumour resection may help to lead to PNS symptom improvement. [ABSTRACT FROM AUTHOR]

• Good Syndrome is a complex disease integrating a medical history of thymoma and either humoral and/or cellular immunodeficiency. • Recurrent infections, autoimmunity, paraneoplastic syndromes, and aberrations immunological profile are the main clinical manifestations of Good syndrome. • Patients with recurrent respiratory infections and de novo autoimmune manifestations could benefit from early screening of thymoma and immunodeficiency. • Understanding the possible discordances in clinical presentation and immunological alterations is key to prevent misdiagnosis and complications. • There are no current guidelines for the diagnosis and management of patients with Good Syndrome. Good Syndrome is a rare clinical entity first described as the conjunction of thymoma and hypogammaglobulinemia, and more recently depicted as a complex disease integrating a medical history of thymoma with humoral immunodeficiency (more accurately stated: hypogammaglobulinemia) with or without cellular immunodeficiency, recurrent infections, autoimmunity, paraneoplastic syndromes and diverse aberrations in the immunological profile. This condition has an ominous prognosis with a high mortality rate secondary to recalcitrant infectious diseases. Understanding the possible discordances in clinical presentation and the temporal relationship between manifestations and immunological alterations is key to prevent misdiagnosis and complications. To this end, here we provide two illustrative patients with Good Syndrome that share common clinical manifestations and yet show unique and opposed immunological profiles, thereby highlighting the pivotal interest of a comprehensive immunological profiling in these patients. We conducted a thorough review of existing literature on the elusive molecular mechanisms underlying the syndrome and provide a clinical assessment algorithm to facilitate the management of these challenging patients. [ABSTRACT FROM AUTHOR]

Highly invasive and rapidly fatal, small-cell lung cancer (SCLC) has been an insurmountable gulf since discovery. Innate immunity plays a vital role in anti-tumor response, among which macrophages contribute to an indispensable character. Here, we found that macrophage infiltration in SCLC reduced significantly in a stage-dependent manner, attributed to the decreased expression of CCL2, a potent chemoattractant for monocytes. Validated by ChIP-qPCR and MassArray methylation analysis, CCL2 expression was inhibited by EZH2-mediated H3K27me3 in the enhancer regions and DNMT1-mediated DNA methylation in the promoter regions, the process of which could be reversed by small-molecular compounds, EPZ011989 and Decitabine. Direct cell-cell contact between SCLC cells and macrophages skewed the phenotype of macrophages to be more M1-like. Furthermore, in an ectopic engraft model of SCLC, disruption of EZH2/DNMT1 function using the combination treatment of EPZ011989 and Decitabine potently abrogated the inhibition of macrophage infiltration and thus suppressed tumor growth, the effect of which was impaired by CCL2 neutralization or macrophage depletion. Overall, this work provides new insights into the role of macrophages in SCLC and establishes a rationale for constructing novel therapeutic avenues for SCLC patients. [ABSTRACT FROM AUTHOR]

The development of pneumonia following bronchoscopy is a very important post-bronchoscopic complication, while lung abscesses after bronchoscopy are rare. However, bronchoscopic techniques have advanced, and recently, we have observed patients with lung abscess after bronchoscopy. Therefore, the risk factors might vary from those in past reports. This study was performed to identify the incidence of and risk factors for post-bronchoscopy respiratory infections. We retrospectively studied adult patients diagnosed with lung cancer by bronchoscopy at Fukujuji Hospital from January 2017 to June 2019. The infection and noninfection groups were compared. The incidence of lung abscess was compared between recent periods and 2013, when endobronchial ultrasonography with a guide sheath (EBUS-GS) was not yet used in our hospital. We reviewed 327 patients, including 20 patients (6.1%) with infections. The risk factors for infection were necrosis and/or a cavity in the tumor (p < 0.001), a large tumor diameter (≥30 mm) (p = 0.010), and a low serum albumin level (<4.0 g/dL) (p = 0.010). We developed a predictive score with these risk factors, and the area under the curve was 0.737 (95% Cl: 0.610–0.864). No significant differences in age, current smoking status, or abnormal bronchoscopic findings were observed, although these were previously reported as risk factors. In total, 12 patients had lung abscesses (3.7%), which is a higher incidence than that in 2013 (0.8%). The risk factors for developing post-bronchoscopy respiratory infection in our study varied from those in past reports, possibly because of the advancements in bronchoscopic techniques, such as EBUS-GS. [ABSTRACT FROM AUTHOR]

Pemphigus and its variants, viz., vulgaris, foliaceous, vegetans, Ig A pemphigus, paraneoplastic pemphigus and Senear-Usher syndrome are rare autoimmune blistering diseases of the skin and/or mucous membranes. The autoantibodies involved in the pathogenesis of pemphigus against desmoglein result in the breach of the skin and mucosal barrier, which acts as the first line of defence against pathogens. In this paper we underscore the importance of the integumentary system as a shield against the acquisition as well as transmission of SARS-CoV-2 virion. We have also made an attempt to delineate the various treatment modalities available and the viral-drug dynamics involved in choosing the optimum therapeutic modality. [ABSTRACT FROM AUTHOR]

Skin rashes have exanthema as a synonym, a term derived from the Greek words exanthem, meaning "to appear," and anthos, which denotes "flourishing." The relevant factors for characterization of a rash include distribution, configuration, and organization of the lesions, in addition to evidence of systemic involvement through toxemia, adenopathy, and conjunctive lesions, hepatosplenomegaly, excoriations or phlogosis, neck rigidity, or neurologic dysfunction. A rash may evolve to cutaneous ulceration in many instances, which is relevant for the diagnosis, the followup, and the therapeutic management of the patient. Systemic diseases with exanthemas that result in ulcerations prevail over diseases that are restricted to signs and/or merely cutaneous clinical manifestations. A variety of etiologies can present cutaneous rashes with ulcers, subject or not to systemic involvement by the underlying disease, among which stand out the bullous diseases, infectious and parasitic diseases, noninfectious granulomatous diseases, vasculitis, paraneoplastic syndromes, autoimmune diseases of the connective tissue, neutrophilic diseases, lichen planus, and drug hypersensitivity syndrome. The authors present a detailed review of some diseases corresponding to each one of the mentioned etiologies, updating the clinical manifestations and therapeutic proposals. [ABSTRACT FROM AUTHOR]

Maintaining cellular homeostasis relies on the interplay between apoptosis and autophagy, and disruption in either of these processes can contribute to the development of cancer. Autophagy can hinder the apoptotic process, and when autophagy is inhibited in such instances, it can enhance the rate of apoptosis. However, evidence suggests that excessive autophagy can also lead to apoptotic cell death. Also, excess autophagy can cause excessive digestion of cellular organelles, causing autophagic cell death. Targeting autophagy in non-small cell lung cancer (NSCLC), the most common form of lung cancer, can be very tricky due to the dual nature of autophagy. According to genetic analysis, various mutations in p53 and EGFR, G:C to A:T transversions seem responsible for the development of lung cancer in smokers and non-smokers. These events trigger cytoprotective autophagy or induce apoptotic cell death through different but interconnected signalling pathways. Lung cancer being the leading cause of death worldwide, calls for more attention to disease prognosis and new therapeutics in the market. However, molecules responsible for autophagy to apoptosis transition are yet to be studied elaborately. Also, the role of effector caspases during this shift needs to be elucidated in future. To comprehend how therapeutics operate through the modulation of autophagy and apoptosis and to target such pathways, it is crucial to emphasize these intricate connections. Many therapeutics discussed in this review targeting both apoptosis and autophagy have shown promising results in vitro and in vivo, however, few have crossed the hurdles of clinical trial. Nevertheless, the quest for safer and better efficacious agents is still alive, with the sole aim to develop novel cancer chemotherapeutic(s). • Autophagy is cell survival mechanism cell under stress. • Excess stress causes increase of autophagy leads to apoptosis. • Mechanism of cross talk between autophagy and apoptosis are discusssed. • These cross talk are being targeting to develop anti-cancer drug(s). [ABSTRACT FROM AUTHOR]

Purkinje cell cytoplasmic autoantibody type 1 (PCA1), also known as anti-Yo, is a 'high-risk' paraneoplastic antibody, associated with rapidly progressive cerebellar syndrome. In patients with this syndrome, various MRI abnormalities have been documented, including atrophy in the cerebellum and brainstem, T2 hyperintensity in the brainstem and spinal cord, and cranial nerve enhancement. This report introduces an imaging finding, cerebellar leptomeningeal enhancement, which was observed in all three cases at early stages. Despite neurological deterioration, all patients underwent immunotherapy, and subsequent follow-up MRI revealed resolution of the leptomeningeal enhancement, suggesting that this feature is distinct from meningeal carcinomatosis. • Cerebellar leptomeningeal enhancement can be observed in the early stages of PCA1 autoimmunity [ABSTRACT FROM AUTHOR]

Anti-Sry-like high mobility group box 1 (anti SOX-1) proteins are rare onconeural antibodies associated with paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS). Few patients with anti-SOX-1 antibodies and negative anti-glial nuclear antibody reactivity have been described to date. Our case involves a 72-year-old female patient with progressive girdle weakness, sensation of heaviness in the lower limbs, predominantly distal and associated with circulatory problems together with instability when walking, with a high suspicion of an autoimmune myopathic disorder. Immunoblot test for autoimmune myopathies antibodies detection were all negative. Onconeuronal antibodies were determined in serum by indirect immunofluorescence being negative as well. Given the high suspicion, we also checked for the presence of other antineuronal antibodies whose patterns are not visible by IIF. Onconeuronal antibodies by immunoblot for the following antibodies: Hu, Ri, Yo, Zic4, Tr, PCA-2, MA-TA, CV2, GAD65, Zic4, Titin, SOX1, Recoverin and Amp, revealed an unexpected clear band in SOX-1, which are highly suggestive of paraneoplastic LEMS. We hypothesize that discordant onconeuronal antibodies results were due to the fact that positivity in IIF is associated with other SOX-B group proteins (normally related to cases of non-paraneoplastic neuropathy), while negativity in IIF and subsequent confirmed presence of specific SOX1 antibody by immunoblot could indicate an underlying tumor. [ABSTRACT FROM AUTHOR]

The causes of death among cancer patients are multifactorial, and the mechanisms that drive pathological conditions that are associated with, but take place outside of, the tumor are still poorly characterized. In this issue of Developmental Cell , Kim et al. (2021) identify a paraneoplastic syndrome that affects blood-brain barrier permeability and host survival. [ABSTRACT FROM AUTHOR]

Objective: Renal cell carcinoma (RCC) is the most typical type of kidney cancer in adults. Hypercalcemia is a well known paraneoplastic syndrome associated with RCC and recent studies have reported that hypercalcemia is closely related to the poor prognosis of RCC patients. Clear cell RCC (ccRCC) is the most common and aggressive subtype of RCC. Although the histological classification of RCC is important for determination of appropriate treatment strategies, effective biomarkers for predicting prognosis of ccRCC have not yet been identified. Since calcium levels affect the prognosis of RCC patients, we evaluated whether the calcium-sensing genes on the plasma membrane, including those encoding calcium channels, CaSR, GPRC6a, and DYSF, could be used as biomarkers to predict the prognosis of ccRCC patients.Methods: Information from 537 patients from The Cancer Genome Atlas (TCGA; n = 446) and International Cancer Genome Consortium (ICGC; n = 91) was used in this study. Among these genes, DYSF was the only gene whose expression correlated with overall survival of both TGCA and ICGC patients.Results: Although DYSF gene expression was higher in ccRCC tissue than in normal kidney tissue, Kaplan-Meier curves showed that the survival rate of ccRCC patients with high DYSF expression was significantly higher than that of patients with low DYSF expression (TCGA, P < 0.0001; ICGC, P = 0.0011). We also validated the potential of DYSF as a prognostic biomarker for ccRCC by conducting a time-dependent area under the curve (AUC) analysis and 5-years receiver operating characteristic curve analysis. Finally, multivariate regression analysis revealed that the expression of DYSF is independent of other prognostic parameters (TCGA, P = 0.017; ICGC, P = 0.006).Conclusions: These results suggested that DYSF may play a suppressive role in the progression of ccRCC and could act as a promising prognostic biomarker for predicting the survival of ccRCC patients. [ABSTRACT FROM AUTHOR]

Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition associated with a neoplasm. Paraneoplastic movement disorders are a heterogeneous group of syndromes encompassing both hyperkinetic and hypokinetic conditions, characterized by acute/sub-acute onset, rapidly progressive evolution, and multifocal localizations with several overlapping features. These movement disorders are immune-mediated, as shown by the rapid onset and by the presence of antineuronal antibodies in biological samples of patients, fundamental for the diagnosis. Antineuronal antibodies could be targeted against intracellular or neuronal surface antigens. Paraneoplastic movement disorders associated with anti-neuronal surface antigens antibodies respond more frequently to immunotherapy. The underlying tumors may be different, according to the clinical presentation, age, and gender of patients. Our search considered articles involving human subjects indexed in PubMed. Abstracts were independently reviewed for eligibility criteria by one author and validated by at least one additional author. In this review, we sought to critically reappraise the clinical features and the pathophysiological mechanisms of paraneoplastic movement disorders, focusing on diagnostic and therapeutic strategies. Our main aim is to make clinicians aware of paraneoplastic movement disorders, and to provide assistance in the early diagnosis and management of these rare but life-threatening conditions. • Acute-onset movement disorders should be promptly recognized by clinicians. • Different tumors are associated with different paraneoplastic movement disorders. • Paraneoplastic movement disorders are possibly treatable conditions. • Early diagnosis and immunotherapy might modify the disease course. • Management of these conditions requires both oncologists and neurologists. [ABSTRACT FROM AUTHOR]

Objective: Tumor-induced osteomalacia is a rare paraneoplastic syndrome usually caused by phosphaturic mesenchymal tumors, which commonly occur in bone. This study aimed to investigate the radiological features of tumor-induced osteomalacia lesions in bone, and their correlation with its histopathology.Materials and Methods: This study included 13 patients with tumor-induced osteomalacia treated between January 2000 and April 2018 at our hospital. All patients were surveyed to detect the tumor causing the condition. Diagnostic imaging studies of the suspected tumors were obtained before tumor removal. We evaluated the radiological features of all tumors, investigated histopathological findings in 10 cases that underwent surgery, and obtained evaluable tumor specimens.Results: The tumors were classified into the following three types by CT: sclerotic (n = 4), lytic (n = 7), and mixed (n = 2). In two cases, lytic lesions focally invaded the surrounding cancellous bone, detected by the soft tissue-window of CT, not the bone-window. Histopathology revealed inter-trabecular invasion in all cases, regardless of radiological features. Osteoclasts were seen in lytic types, and creeping substitution-like thickened trabecular bone and calcification were observed in sclerotic types. In all cases, focal invasion of the tumor into cortical bone was seen.Conclusions: Tumor-induced osteomalacia lesions in bone showed a wide variety of radiological features, and tended to invade into cancellous and cortical bone. These findings suggest that extended curettage or resection of thinned cortical bone may be necessary. This might improve the cure rate of surgeries for tumor-induced osteomalacia lesions in bones. [ABSTRACT FROM AUTHOR]

Acquired polyneuropathies (PN) are rare in childhood and adolescent. We report on a 15-year-old male patient who presented with progressive gait instability, ataxia, neuropathic pain, distal muscle weakness and progressive loss of ambulation. Nerve conduction studies (NCS) revealed a progressive demyelinating sensorimotor polyneuropathy predominantly of the lower limbs. Cerebrospinal fluid (CSF) analyses revealed a cytoalbuminologic dissociation. Extensive diagnostic workup for autoantibodies and inflammatory markers was inconclusive. Corticosteroids and intravenous immunoglobulins did not affect. Cranial MRI revealed leptomeningeal enhancement of the cerebellum and the brainstem. Brain biopsy of the cerebellar lesions revealed an unclassifiable sarcoma. The patient was treated according to the CWS guidance study resulting in a decrease in enhanced lesion size. After two years NCS still revealed a demyelinating sensorimotor PN. This case report describes for the first time the clinical course of a chronic PN, putative paraneoplastic, associated with isolated unclassifiable CNS-sarcoma in an adolescent patient. Paraneoplastic pathogenesis should be considered in an unusual sequence of subacute progressive neurological symptoms even in children and adolescents. • Acquired sensorimotor polyneuropathy in an adolescent boy with primary intracranial sarcoma. • Common cause of acquired PN in children are the sensorimotor neuropathies, such as GBS and CIDP. • A very rare cause of PN in childhood is the paraneoplastic neurological syndrome (PNS). • Presently no established treatment guidelines for paraneoplastic neuropathies in children. [ABSTRACT FROM AUTHOR]

• Paraneoplastic forms of neuromyelitis optica (NMOSD) may occur in rare cases. • We describe 3 cases of NMOSD in the context of underlying ovarian teratoma. • All three patients presented initially with area postrema symptomatology. • Strong immune infiltrates colocalize with AQP4+ glial component in the teratomas. Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disease of the central nervous system, characterized by the presence of auto-antibodies directed against aquaporin-4 (AQP4) expressed on astrocyte end-feet. Despite NMOSD does not primarily belong to the spectrum of paraneoplastic neurological syndromes, rare cases of association with neoplasia have been outlined. Here, we report the association of NMOSD with ovarian teratoma in 3 cases. Pathological analysis of teratomas revealed glial component strongly expressing AQP4 and closely localized to immune infiltrates. Our series highlight the rare association of teratoma with NMOSD and the possible paraneoplastic mechanism. [ABSTRACT FROM AUTHOR]

Abstract Paraneoplastic myelopathy is rare paraneoplastic neurological syndromes. We reviewed patients through medical records system and screened patients who presented with myelopathy, and/or coexisting cancer, and/or onconeural antibodies. Nine patients were identified as paraneoplastic myelopathy presenting with progressive subacute (2/9) or insidious (7/9) myelopathy. CSF abnormalities included elevated protein, 5; pleocytosis, 4; excess oligoclonal bands, 6. Seven patients had onconeural antibody. Cancer was confirmed histopathologically in 6 and diagnosed by PET-CT in 1. Four patients had symmetric, longitudinally extensive grey matter or tract-specific changes on spinal cord MRI. It was associated with significant morbidity and had poor response to treatment. Graphical abstract Spinal cord MRI from patient 1(A1–6) and patient 8 (D1–3) with paraneoplastic myelopathy. Patient 1 had longitudinally extensive T2 signal abnormality extending across 18 spinal segments (A1, A2) that symmetrically involved the central grey matter on axial T2-weighted images (A3, A4, A5, A6). Patient 8 had tract-specific T2 signal abnormality on the sagittal section extending across 4 segments from T8 to T11 (D1) with symmetric involvement of the lateral columns (D2, D3). Unlabelled Image Highlights • Paraneoplastic myelopathy is rare paraneoplastic syndromes and presents with myelopathy of insidious or subacute onset. • Paraneoplastic myelopathy usually precedes cancer detection. • Paraneoplastic myelopathy has autoimmune characteristics with CSF pleocytosis or ologoclonal bands in early stage. • Nearly half of patients have symmetric, longitudinally extensive grey matter or tract-specific changes on spinal cord MRI. • Paraneoplastic myelopathy is associated with significant morbidity and poor response to therapy. [ABSTRACT FROM AUTHOR]

Abstract Purpose Hypertrophic osteoarthropathy (HOA) is a condition that can be inherited or acquired. It causes diffuse periosteal new bone formation on the long bones, with a predilection for the appendicular skeleton. When acquired, it is a nonspecific indicator of systemic disease that arises following a primary condition. This paper reviews the palaeopathological literature associated with this rare condition. It also describes the first possible case of co-morbidity associated with hypertrophic osteoarthropathy in an adult skeleton (cal. BC 170 – 1 cal. AD) from the mobile pastoralist Sarmatian culture of the Volga steppes of Russia. Methods Macroscopic and radiological examination provide differential diagnoses of the lesions, while clinical and bioarchaeological analyses offer insights into the possible experience of disease and social implications of care among the nomadic populations of Iron Age Russia. Results The analysis of Sk. 6524.102 displays lesions that may be due to both hypertrophic osteoarthropathy and osteomalacia. The man was physically impaired and his participation in physically challenging activities would have been limited. Conclusions The study stresses that co-morbidity is a key parameter when interpreting disease in past populations, particularly when the diagnosis involves hypertrophic osteoarthropathy. Significance This is the first case of hypertrophic osteoarthropathy identified in Eurasian prehistoric populations. The research emphasises the significance of co-morbidity in the past. Limitations The diagnosis of co-morbid diseases in human remains is extremely complex and the conditions were identified as most probable by a process of elimination. Suggestions for further research Further studies should be dedicated to understanding co-morbidity in the past. [ABSTRACT FROM AUTHOR]

• [18F]FDG PET/CT has been proved as a valuable tool in detecting underlying malignancy in patients suspected of having a paraneoplastic syndrome. However, [18F]FDG PET/CT imaging in the diagnosing paraneoplastic dermatoses (PD) has not been clearly defined. • In our retrospective study of 60 patients with suspected PD, [18F]FDG PET/CT could identify the underlying neoplasms in 18/19 (94.7 %) PD patients and changed the clinical management in 9/19 (47.4 %) PD patients. • [18F]FDG PET/CT is a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients. We retrospectively evaluate the diagnostic performance of 2-deoxy-2[18F]fuoro-D-glucose ([18F]F-FDG) PET/CT and its impact on clinical management in patients with suspected paraneoplastic dermatoses (PD). From an institutional PET/CT database (2014–2022), we retrospectively analyzed patients who were clinically suspected with PD and underwent [18F]F-FDG PET/CT for screening an underlying malignancy. For all scans, positive mucocutaneous lesions and PET-indicated malignancies were assessed, and the degree of FDG avidity among different dermatoses were quantified. The final diagnoses of dermatoses and neoplasms were based on pathologic results, international diagnostic standard and follow-up. We assessed the recommended and applied therapies before and after [18F]F-FDG PET/CT and noted whether the patient management changed on the basis of the [18F]F-FDG PET/CT results. We analyzed 60 patients with 10 types of dermatoses in this study. Finally, 19 of the 60 patients who had both of specific dermatosis and contemporaneous neoplasm were diagnosed with PD. [18F]F-FDG PET could identify the underlying neoplasms in 18/19 (94.7%) PD patients, and led to a change of the management in 9/19 (47.4%) PD patients. In addition, the mucocutaneous manifestations of [18F]F-FDG PET/CT associated with several specific dermatoses were characteristic. This study highlighted the value of [18F]F-FDG PET/CT as a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients. [ABSTRACT FROM AUTHOR]

Immune-mediated cerebellar ataxias were initially described as a clinical entity in the 1980s, and since then, an expanding body of evidence has contributed to our understanding of this topic. These ataxias encompass various etiologies, including postinfectious cerebellar ataxia, gluten ataxia, paraneoplastic cerebellar degeneration, opsoclonus-myoclonus-ataxia syndrome and primary autoimmune cerebellar ataxia. The increased permeability of the brain-blood barrier could potentially explain the vulnerability of the cerebellum to autoimmune processes. In this manuscript, our objective is to provide a comprehensive review of the most prevalent diseases within this group, emphasizing clinical indicators, pathogenesis, and current treatment approaches. • Immune-mediated processes can give rise to disabling cerebellar ataxia. • The immune-mediated cerebellar ataxias are potentially treatable. • The early treatment in autoimmune cerebellar conditions is imperative. • Acute cerebellar ataxia with vermian involvement should raise suspicion. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TMicroE) and tumor macroenvironment (TMacroE) are defining features of classical Hodgkin lymphoma (cHL). They are of critical importance to clinicians since they explain the common signs and symptoms, allow us to classify these neoplasms, develop prognostic and predictive biomarkers, bioimaging and novel treatments. The TMicroE is defined by effects of cancer cells to their immediate surrounding and within the tumor. Effects of cancer cells at a distance or outside of the tumor define the TMacroE. Paraneoplastic syndromes are signs and symptoms due to effects of cancer at a distance or the TMacroE, which are not due to direct cancer cell infiltration. The most common paraneoplastic symptoms are B-symptoms, which manifest as fevers, chills, drenching night sweats, and/or weight loss. Less common paraneoplastic syndromes include those that affect the central nervous system, skin, kidney, and hematological autoimmune phenomena including hemophagocytic lymphohistiocytosis (HLH). Paraneoplastic signs such as leukocytosis, lymphopenia, anemia, and hypoalbuminemia are prognostic biomarkers. The neoplastic cells in cHL are the Hodgkin and Reed Sternberg (HRS) cells, which are preapoptotic germinal center B cells with a high mutational burden and almost universal genetic alterations at the 9p24.1 locus primarily through copy gain and amplification with strong activation of signaling via PD-L1, JAK-STAT, NFkB, and c-MYC. In the majority of cases of cHL over 95% of the tumor cells are non-neoplastic. In the TMicroE, HRS cells recruit and mold non-neoplastic cells vigorously via extracellular vesicles, chemokines, cytokines and growth factors such as CCL5, CCL17, IL6, and TGF-β to promote a feed-forward inflammatory loop, which drives cancer aggressiveness and anti-cancer immune evasion. Novel single cell profiling techniques provide critical information on the role in cHL of monocytes-macrophages, neutrophils, T helper, Tregs, cytotoxic CD8+ T cells, eosinophils, mast cells and fibroblasts. Here, we summarize the effects of EBV on the TMicroE and TMacroE. In addition, how the metabolism of the TMicroE of cHL affects bioimaging and contributes to cancer aggressiveness is reviewed. Finally, we discuss how the TMicroE is being leveraged for risk adapted treatment strategies based on bioimaging results and novel immune therapies. In sum, it is clear that we cannot effectively manage patients with cHL without understanding the TMicroE and TMacroE and its clinical importance is expected to continue to grow rapidly. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic osteoarthropathy (HOA) is a musculoskeletal pathology that often occurs as a paraneoplastic syndrome. 90% of HOA cases occur secondary to malignancy. 60 to 80% of which are lung cancers.Case Report: We present a case of a 61-year-old man who had worsening knee pain. HOA was incidentally noted on extremity X-ray. The patient was found to have a soft-tissue attenuating mass on chest X-ray. The diagnosis of non-small cell lung cancer was made after bronchoscopy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: HOA can be an indication of malignancy, most commonly lung cancer, so it is important to recognize the key radiographic findings associated with HOA. When treating patients with bone pain and clubbed digits, emergency physicians should strongly consider screening for more severe primary pathology. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia is a rare cause of acquired hypophosphatemia due to the paraneoplastic overproduction of fibroblast growth factor-23. Unlike many causes of osteomalacia, tumor-induced osteomalacia is curable by resection of the offending tumor. If a patient has a tumor that is unidentifiable, unresectable, or makes the decision to forgo surgery, medical treatment is recommended. Burosumab (KRN23) is a fully human monoclonal antibody against fibroblast growth factor-23 that was recently approved for the treatment of X-linked hypophosphatemia. We present a case of tumor-induced osteomalacia due to two somatostatin receptor avid meningiomas. The patient initially was wheelchair bound due to symptoms of diffuse bone and muscle pain with recurrent traumatic and nontraumatic fractures. Serum phosphate was 1.8mg/dL (reference range: 2.4-5.0mg/dL) with no other laboratory or historical cause. Workup revealed two widely separated intracranial meningiomas with typical magnetic resonance imaging characteristics. The duplicity of tumors precluded safe surgery and the potential delay in, or lack of, efficacy using radiosurgery prompted the treatment team to opt for medical treatment. Burosumab was initiated resulting in improvement in pain symptoms and mobility. Serum phosphate normalized. Trials are ongoing to assess the utility of burosumab in the treatment of tumor-induced osteomalacia. [ABSTRACT FROM AUTHOR]

Highlights • The positive-margin resection model differs to primary tumor in dynamics and TME. • GH alone had no potency in tumor inhibition but can prominent prolong survival. • GH had a synergy in tumor inhibition and QOL improvement when combined with CTX. • The underlying mechanisms were related to reverse Th1/Th2 shift caused by CTX. Abstract Non-small-cell lung cancer (NSCLC) is recognized as the most common malignant disease worldwide and combination treatment is recommended as its first line therapy. As a Ph2 clinical product, Ginsenoside H dripping pills (GH) is proposed as an adjuvant of chemotherapy. In the present study, we utilized a postoperative model to evaluate the efficacy of GH on the functions of anti-recurrence and improvement of life quality when combined with chemotherapeutic drug cyclophosphamide (CTX). Specifically, the anti-recurrence effect was evaluated by tumor inhibiting rate and the improvement of life quality was evaluated by the remission of splenomegaly and emaciation. The underlying mechanisms were explored via quantitative real time-PCR, Elisa and IHC staining. Results showed that GH had a synergy when combined with CTX against tumor recurrence, significantly improved the life quality of postoperative patients via remitting splenomegaly and emaciation. H&E staining showed that GH could increase the number of splenic T cells, which were inhibited after CTX administration. Furthermore, the reversion of Th1/Th2 shift, which had been verified by different methods, may account for one of the mechanisms of the synergy. All these results indicated Ginsenoside H dripping pills as a promising adjuvant for postoperative chemotherapy of NSCLC. [ABSTRACT FROM AUTHOR]

Abstract Paraneoplastic autoimmune multiorgan syndrome (PAMS) is characterized by a heterogenous group of signs and symptoms including severe desquamative stomatitis, a polymorphous cutaneous eruption, humoral immunity against plakin proteins, contribution of cell-mediated autoimmunity and commonly a progressive respiratory failure. Autoantibodies in PAMS target a wide array of antigens including plakins, cadherins, alpha-2-macroglobulin like 1 (A2ML1), BP180, plakophilin-3, and several neuromuscular antigens. Originally described as paraneoplastic pemphigus in 1990 due to some of its clinical and immunologic similarities to classic pemphigus (pemphigus vulgaris and pemphigus foliaceus), PAMS is a multiorganopathy with several distinct features from these classic forms of pemphigus. Epidemiologically, PAMS is associated with underlying neoplasia and has a differing HLA-II allele predisposition compared to classic forms of pemphigus. Clinically, lesion morphology is polymorphous, and lesion distribution fundamentally differs from that seen in classic pemphigus. PAMS has a significantly higher mortality rate and a poorer response to treatments typically effective in pemphigus. Histologically, PAMS is characterized by the presence of interface dermatitis, vacuolar changes, and dyskeratotic keratinocytes which are not seen in classic pemphigus. PAMS demonstrates not only intercellular IgG as seen in classic pemphigus, but the presence of linear basement membrane zone deposition. Antibodies against desmoglein 3 (Dsg3) map to a broader array of epitopes than in pemphigus vulgaris and there is a higher prevalence of complement binding anti-Dsg3 IgG autoantibodies in PAMS. Autoantibodies can in rare cases be absent in the more cell-mediated form of PAMS. Considering these numerable differences, we review the entity of PAMS, and provide similarities and differences to classic forms of pemphigus. [ABSTRACT FROM AUTHOR]

In 208 children with opsoclonus-myoclonus syndrome (OMS), CSF IgG oligoclonal bands (OCB) and 22 immunomarkers in CSF and 21 in serum/blood were measured. In 36 untreated OMS, 58% were OCB(+), whereas 55% of treated OMS were OCB(−). OCB positivity or negativity did not alter concentrations or frequencies of immunomarkers. The phenotypes of OCB(+) and OCB(−) patients were not distinctive. CSF B cells were expanded in untreated OMS regardless of OCB positivity. These data reveal a much higher frequency of OCB positivity in untreated OMS than previously realized and a disconnect between intrathecal OCB and inflammatory mediator production. [ABSTRACT FROM AUTHOR]

Seesaw nystagmus is characterized by the rhythmic combination of vertical and torsional dysconjugate oscillations where one eye moves up and inward while the other moves down and outward. Common association of seesaw nystagmus with accessory optic track lesions lead to traditional hypothesis that it is due to the mismatch in the vision and vestibular systems. Here we propose a novel mechanism for seesaw nystagmus. We hypothesize that reverberations due to abnormal increases in the excitability of the reciprocally innervating circuit of excitatory burst neuron in the midbrain interstitial nucleus of Cajal causes the seesaw nystagmus. Analogous oscillations of the brainstem burst generators may be responsible for generation of saccadic oscillations or opsoclonus. The key difference is that the interstitial nucleus of Cajal lacks inhibitory burst neurons, hence the lack of post-inhibitory rebound, and relatively lower frequency of the oscillatory cycles causing pendular seesaw nystagmus. In contrast the brainstem burst generator, with reciprocally innervating excitatory and inhibitory burst neurons, and further inhibitory influence of the omnipause neurons results in the post-inhibitory rebound at the burst neurons, hence high oscillation frequency. This novel concept is supported by a unique observation in a patient with antineuronal nuclear autoantibody type 2 due to breast cancer who had combined seesaw nystagmus and superimposed saccadic oscillations. The patient neither had cerebellar deficits typically thought to cause paraneoplastic opsoclonus nor visual deficits that are known cause of seesaw nystagmus. We propose that hyperexcitability of the burst neurons in the interstitial nucleus of Cajal due to paraneoplastic antibody caused pendular seesaw nystagmus. On the other hand, increased excitability of brainstem burst generators and reduced efficacy of the omnipause neurons caused saccadic oscillations. [ABSTRACT FROM AUTHOR]

Background: Stauffer's syndrome corresponds to a set of clinical and analytical changes of paraneoplastic nature firstly recognized more than 50 years ago, in association to renal cell carcinoma. A definitive review including universal diagnostic criteria and updated knowledge since the original description is lacking.Basic Procedures: The authors conducted a comprehensive bibliographical review and propose updated diagnostic criteria to standardize diagnosis for clinical practice purposes and avoid misclassification.Main Findings: Although having been described in association with renal cell carcinoma, the syndrome has been reported in correlation with other malignancies-either solid or hematological tumors. Additionally, a variant syndrome presenting with jaundice has also been characterized, but appears to have a similar clinical course to that of the classical Stauffer's syndrome. Although often described as rare, it may be more frequent than previously recognized. Stauffer's syndrome etiopathogenesis is still poorly understood, but immune mechanisms seem to play a role underscored by the malignancies to which the syndrome is associated, several of which having immunotherapy drugs approved for their treatment.Principal Conclusions: A set of diagnostic criteria should be used to simplify, broaden and standardized diagnosis, under the entity characterized by reversible paraneoplastic intrahepatic cholestasis. Clinicians should be aware of the syndrome, namely consider further investigation if a plausible cause for unexplained intrahepatic cholestasis in an otherwise healthy patient is not found. Even though no universal approach is available, investigation should be considered regarding metastatic disease after resection of a primary tumor which has revealed persistence or recurrence of symptoms. [ABSTRACT FROM AUTHOR]