Search Results (34)

Background/Objectives: Paraneoplastic syndromes (PNS), characterized by a large diversity of symptoms, may sometimes be the first clinical feature of a severe underlying disorder such as cancer. Methods: We report the case of a middle-aged male patient with no significant previous medical history, a nonsmoker or alcohol heavy drinker, complaining about generalized, recently onset itch. Given no reasonable explanation of pruritus after dermatological consultation and the unsatisfactory response to treatment, the patient was referred to gastroenterology with the suspicion of a cholestatic liver disease. Results: The abdominal ultrasound examination revealed gallstones and no dilation of the biliary tree. Numerous tests were run and came out negative, except for the slight elevation of C-reactive protein, mild dyslipidemia, and positivity for H. pylori antigen. The gut microbiota displayed important dysbiosis with a significant increase in the histamine-producing bacteria. Given this chronic pruritus became suspicious, thorax and abdominal CT were recommended and performed soon after. A large right mid-thoracic tumor image was found. Bronchoscopy came out negative for a tumor. After the CT-guided biopsy, the tumor turned out not to be a lymphoma, but a non-small cell lung carcinoma (NSCLC). Conclusions: Chronic pruritus was not associated with cholestasis in a patient with gallstone disease, but rather with a PNS, as the first clinical manifestation of NSCLC, triggering many diagnostic and therapeutic challenges. Full article

Thrombotic microangiopathy (TMA) is a category of diseases consisting of thrombocytopenia, microangiopathic haemolytic anaemia, and widespread occlusive microvascular thrombosis. We report two cases of a thrombotic microangiopathic syndrome associated with non-invasive mucinous cysts and mucinous adenocarcinoma. TMA was treated in both cases by surgical removal of the tumours. We hypothesise that mucin secretion in the case of non-invasive mucinous cysts and paraneoplastic secretion of antibodies in the case of mucinous adenocarcinomas are the causes of endothelial damage with thrombocytopenia and microangiopathic haemolytic anaemia. Finally, patients with TMA who exhibit unusual clinical characteristics or weak responses to plasma exchange should be examined for an underlying tumour. Tumour treatment is the preferred therapy for tumour-associated TMA. Full article

Nasopharyngeal carcinoma (NPC) with paraneoplastic dermatomyositis (DM) is an exceptionally rare clinical phenomenon, particularly among European populations. This case report details a 46-year-old woman initially diagnosed with DM, later confirmed to have NPC. Such an association is more frequently documented in Asian populations, highlighting its unique presentation in this case. The patient first developed symptoms in December 2016, which progressed significantly by spring 2017, manifesting as progressive proximal muscle weakness, characteristic skin changes, and elevated muscle enzyme levels. Diagnostic workup, including electromyography and biopsy, confirmed DM. Persistent symptoms and secondary DM suspicion prompted further malignancy screening, which identified undifferentiated NPC with strong Epstein–Barr virus RNA positivity. Multimodal treatment comprising corticosteroids, hydroxychloroquine, chemotherapy, and radiotherapy led to temporary symptomatic improvement. Despite initial success, the patient’s condition deteriorated, and she passed away by the end of 2018. This case underscores the importance of comprehensive malignancy screening in DM patients, considering rarer cancers like NPC even in non-endemic regions. It emphasizes the role of multidisciplinary care and adherence to international guidelines for managing such complex cases. Recognizing NPC-associated DM remains critical for early intervention and tailored therapeutic approaches to improve clinical outcomes and survival. Full article

Resting sinus tachycardia is frequently encountered in cancer patients. It affects a wide variety of cancer patients and is associated with distressing symptoms. Cancer-associated resting sinus tachycardia varies in its underlying mechanism. It can stem from the tumor burden or the side effects of chemotherapy/radiotherapy, or it can be secondary to paraneoplastic syndrome or the sequalae of cancer itself (infection, anemia, thrombosis, etc.). The clinical significance of resting sinus tachycardia extends beyond mere symptomatology, as it can potentially indicate severe complications which may facilitate or exacerbate a new or underlying cardiovascular dysfunction. Therefore, this necessitates thorough diagnostic tools to discern the underlying cause and tailor appropriate management strategies, whether pharmacological, non-pharmacological, or conservative. While resting sinus tachycardia has been extensively investigated in the context of cardiovascular disease, its underlying etiology, clinical implication, prognostic value, and treatment options remain vague in the context of cancer. This review aims to explore the topic of resting sinus tachycardia in cancer patients through delving deeper into its underlying mechanism, presenting the current evidence on its effect on cancer-independent cardiovascular and all-cause mortality, as well as providing some insight into the currently available treatment options. It will also propose therapeutic interventions and strategies aimed at optimizing cancer patient care. Lastly, it will highlight research gaps which need to be addressed further, as future research is needed to refine the diagnostic criteria, develop targeted therapies, find alternative cardioprotective/cardio-neutral chemotherapy options, and establish evidence-based guidelines to improve outcomes in this vulnerable patient population. Full article

Paraneoplastic cerebellar degeneration (PCD) is a rapidly progressive, immune-mediated syndrome characterized by the degeneration of Purkinje cells, often associated with the presence of antibodies targeting intracellular antigens within these cells. These autoantibodies are implicated in the induction of cytotoxicity, leading to Purkinje cell death, as demonstrated in in vitro models. However, the precise roles of antibodies and T lymphocytes in mediating neuronal injury remain a subject of ongoing research, with T cells appearing to be the main effectors of cerebellar injury. Notably, at least 50% of PCD cases involve anti-Yo autoantibodies, also referred to as anti-PCA1 (Purkinje cell antigen 1) antibodies, which specifically target cerebellar degeneration-related protein 2 (CDR2) and its paralogue, CDR2-like (CDR2L). Another recognized antigen is CDR 34, a 34 kDa Purkinje cell antigen characterized by tandem repeats and a B-cell epitope; its detection in non-cerebellar tissues necessitates further in situ hybridization studies. Onconeural antigens are expressed in both Purkinje cells and tumour cells, where they localize in the cytoplasm and associate with membrane-bound and free ribosomes, playing critical roles in regulating transcription and calcium homeostasis. Recent studies suggest that the breakdown of immune tolerance is linked to genetic alterations in tumour cell antigens, leading to the formation of neoantigens that can elicit autoreactive T cells, which may underscore the function of Yo antibodies. In vitro studies indicate that anti-Yo antibodies can induce cell death independent of T lymphocytes. The disease progresses by initial lymphocytic infiltration, followed by a rapid loss of Purkinje cells without significant inflammation. However, in vivo models showcase that anti-Yo PCD is primarily T-cell mediated, with antibodies serving as biomarkers rather than direct effectors of neuronal death. This review examines the mechanisms underlying PCD, focusing on the roles of CDR2 and CDR2L in tumour development and their potential role in the degeneration of cerebellar Purkinje neurons. A comprehensive understanding of these processes is essential for advancing diagnostic, prognostic, and therapeutic strategies for PCD and associated malignancies. Full article

Paraneoplastic pemphigus (PNP) is a rare autoimmune disorder associated with underlying neoplasms, predominantly Non-Hodgkin Lymphomas, affecting adults aged 45 to 70. This review analyzed 87 articles from MEDLINE/PubMed, Ovid and Scopus focusing on patients with oral manifestations of PNP, emphasizing histological and serological aspects and discussing recent updates on pathogenetic options. Key findings revealed that PNP is often diagnosed before the neoplasm, with Follicular variant Non-Hodgkin Lymphoma and Castleman Disease being the most common associations. Histopathological analysis showed suprabasal acantholysis and inflammation, and serological tests identify a comprehensive autoantibody panel, underscoring the need for standardized diagnostic criteria and improved serological testing. Full article

A 65-year-old woman was admitted to the neurology department with a suspected demyelinating disease due to complaints of progressive pain and weakness in both upper and lower limbs, as well as urinary incontinence. MRI of the spine revealed complex disc osteophyte with compression of the spinal cord in the cervical and lumbar spine at several vertebral levels, and localized enhancement in the cervical spine at the site of maximal spinal canal stenosis. During her hospitalization, the patient underwent extensive evaluation to rule out any systematic inflammatory diseases, infections, and malignancy. Chest CT revealed bilateral mediastinal lymphadenopathy. Transbronchial mediastinal lymph node biopsy showed numerous non-necrotizing granulomas without evidence of malignancy. After a thorough and careful exclusion of a demyelinating, infectious, and paraneoplastic myelopathies, and based on clinical, radiographic, and pathological findings, the patient was diagnosed with both neurosarcoidosis and spondylotic myelopathy. She was then treated for neurosarcoidosis, including glucocorticosteroids, azathioprine, and a biosimilar of the anti-TNF alpha agent infliximab, resulting in both clinical and radiographic improvement. Intramedullary spinal neurosarcoidosis is very rare and may present with clinical features of spondylotic myelopathy, with typical imaging findings occurring only in areas of spinal canal stenosis. Full article

Cholangiocarcinomas (CCAs), a heterogeneous group of challenging malignant tumours which originate from the biliary epithelium, are associated with an alarming increasing incidence during recent decades that varies between different regions of the globe. Thus, awareness represents the key operating factor. Our purpose was to overview the field of CCAs following a double perspective: the constellation of the risk factors, and the presence of the paraneoplastic syndromes, emphasizing the endocrine features amid the entire multidisciplinary panel. This is a narrative review. A PubMed-based search of English-language original articles offered the basis of this comprehensive approach. Multiple risk factors underlying different levels of statistical evidence have been listed such as chronic biliary diseases and liver conditions, inflammatory bowel disease, parasitic infections (e.g., Opisthorchis viverrini, Clonorchis sinensis), lifestyle influence (e.g., alcohol, smoking), environmental exposure (e.g., thorotrast, asbestos), and certain genetic and epigenetic interplays. With regard to the endocrine panel, a heterogeneous spectrum should be taken into consideration: non-alcoholic fatty liver disease, obesity, type 2 diabetes mellitus, and potential connections with vitamin D status, glucagon-like peptide 1 receptor, or the galanin system, respectively, with exposure to sex hormone therapy. Amid the numerous dermatologic, hematologic, renal, and neurologic paraneoplastic manifestations in CCAs, the endocrine panel is less described. Humoral hypercalcaemia of malignancy stands as the most frequent humoral paraneoplastic syndrome in CCAs, despite being exceptional when compared to other paraneoplastic (non-endocrine) manifestations and to its reported frequency in other (non-CCAs) cancers (it accompanies 20–30% of all cancers). It represents a poor prognosis marker in CCA; it may be episodic once the tumour relapses. In addition to the therapy that targets the originating malignancy, hypercalcaemia requires the administration of bisphosphonates (e.g., intravenous zoledronic acid) or denosumab. Early detection firstly helps the general wellbeing of a patient due to a prompt medical control of high serum calcium and it also provides a fine biomarker of disease status in selected cases that harbour the capacity of PTHrP secretion. The exact molecular biology and genetic configuration of CCAs that display such endocrine traits is still an open matter, but humoral hypercalcaemia adds to the overall disease burden. Full article

Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency and function of mGluR5 in HL and its potential role in causing seropositive paraneoplastic disease. We studied a representative cohort of pediatric HL and NHL patients (n = 57) using immunohistochemistry and fluorescence staining to investigate mGluR5 expression. All lymphoma tissues displayed positive mGluR5 staining, with focus on Hodgkin–Reed–Sternberg (H-RS) cells. We did not detect any mGluR5 staining in tumor-free lymph nodes, which is consistent with the absence of GRM5 transcripts in RNA-sequencing data from non-malignant B and T cells. The frequent presence in pediatric lymphoma falls in line with reports of mGluR5 expression and associated tumor progression in other malignancies. We tested for correlation with clinical features, focusing on disease progression and neurological symptoms. Low mGluR5 expression in H-RS cells correlated with young patient age (<15 years) and positive histology for EBV infection. Paraneoplastic or neurological symptoms were found exclusively in HL patients. While an impact of mGluR5 on HL severity remains possible, a prognostic value of mGluR5 expression levels requires further investigation. Full article

The increasing use of immune checkpoint inhibitors (ICI) in cancer therapy has brought attention to their associated neurotoxicities, termed neurological immune-related adverse events (n-irAEs). Despite their relatively rare incidence, n-irAEs pose a significant risk, potentially leading to severe, long-lasting disabilities or even fatal outcomes. This narrative review aims to provide a comprehensive overview of n-irAEs, focusing on their recognition and management. The review addresses a spectrum of n-irAEs, encompassing myositis, myasthenia gravis, various neuropathies, and central nervous system complications, such as encephalitis, meningitis, and demyelinating diseases. The key features of n-irAEs are emphasized in this review, including their early onset after initiation of ICIs, potential association with non-neurological irAEs and/or concurrent oncological response, the significance of ruling out other etiologies, and the expected improvement upon discontinuation of ICIs and/or immunosuppression. Furthermore, this review delves into considerations for ICI re-challenge and the intricate nature of n-irAEs within the context of pre-existing autoimmune and paraneoplastic syndromes. It underscores the importance of a multidisciplinary approach to diagnosis and treatment, highlighting the pivotal role of severity grading in guiding treatment decisions. Full article

Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such as carcinoid syndrome, which can manifest as a constellation of symptoms significantly impacting patients’ quality of life. The prognosis of NETs is influenced by their tendency for metastasis, especially in cases involving the liver, where the estimated 5-year survival is between 20 and 40%. Although surgical resection remains the preferred curative option, challenges emerge in cases of neuroendocrine tumors with liver metastasis (NELM) with multifocal lobar involvement, and many patients may not meet the criteria for surgery. Thus, minimally invasive and non-surgical treatments, such as locoregional therapies, have surfaced. Overall, these approaches aim to prioritize symptom relief and aid in overall tumor control. This review examines locoregional therapies, encompassing catheter-driven procedures, ablative techniques, and radioembolization therapies. These interventions play a pivotal role in enhancing progression-free survival and managing hormonal symptoms, contributing to the dynamic landscape of evolving NELM treatment. This review meticulously explores each modality, presenting the current state of the literature on their utilization and efficacy in addressing NELM. Full article

Hodgkin’s lymphoma (HL) is a monoclonal lymphoid neoplasm that is mainly characterized by multinucleated Reed–Sternberg cells on a background of non-neoplastic inflammatory cells. The incidence rate of Hodgkin’s lymphoma is 2.5 new cases per 100,000 people per year (1). Paraneoplastic syndromes are conditions that are related to malignancy; however, they are not a result of tumor invasion or compression of malignant tissues. These paraneoplastic syndromes can occur virtually at any point in the disease course, and paraneoplastic syndromes in HL and their various forms are not well studied. In this review article, we will be discussing paraneoplastic syndromes in general and then delve into specific syndromes seen in HL, followed by a brief discourse regarding their early recognition and timely management. Full article

Radiotherapy (RT) plays a key role in brain tumours but can negatively impact functional outcomes and quality of life. The aim of this study was to analyse anti-neural and onconeural autoantibodies and markers of blood–brain barrier (BBB) disruption in patients with primary brain cancer undergoing RT. Materials and methods. A prospective study was conducted on 45 patients with a brain tumour scheduled for intensity-modulated radiotherapy. Assessments were performed at baseline, post-RT, and at three months. We measured serum levels of BBB disruption biomarkers and anti-neural, onconeural, and organ-specific antibodies. Results. Antibodies against nucleosome antigens and neuronal surface antigens were detected in 85% and 3% of cases, respectively; anti-neural and onconeural antibodies were observed in 47% and 5.8%. In 44% patients, ≥2 antibody types were detected. No significant changes in BBB biomarkers were observed. Conclusion. The findings of this study show that a humoral immune response is common in patients undergoing RT for brain cancer. This response appears to be non-organ specific but rather directed against nucleosome antigens, but onconeural antibodies were uncommon, suggesting a low risk of a neurological paraneoplastic syndrome. Our data suggested that radiotherapy may not affect BBB integrity, but larger studies are needed to better characterise the pathophysiological effects of RT. Full article

The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging in the last few decades, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IR^A) content, with (b) an increase in IGF-II high-molecular weight cancer-variants (big-IGF-II), and (c) a stage-progressive increase in the IGF-II autocrine signal in the cancer cell, mostly during the transition from benign to malignant growth. An increasing and still under-exploited combinatorial pattern of the IGF-II signal in cancer is shaping up in the literature with respect to its transducing receptorial system and effector intracellular network. Interestingly, while surgical and clinical reports have traditionally restricted IGF-II secretion to a small number of solid malignancies displaying paraneoplastic hypoglycemia, a retrospective literature analysis, along with publicly available expression data from patient-derived cancer cell lines conveyed in the present perspective, clearly suggests that IGF-II expression in cancer is a much more common event, especially in overt malignancy. These findings strengthen the view that (1) IGF-II expression/secretion in solid tumor-derived cancer cell lines and tissues is a broader and more common event compared to the reported IGF-II association to paraneoplastic hypoglycemia, and (2) IGF-II associates to the commonly observed autocrine loops in cancer cells while IGF-I cancer-promoting effects may be linked to its paracrine effects in the tumor microenvironment. Based on these evidence-centered considerations, making the autocrine IGF-II loop a hallmark for malignant cancer growth, we here propose the functional name of IGF-II secreting tumors (IGF-IIsT) to overcome the view that IGF-II secretion and pro-tumorigenic actions affect only a clinical sub-group of rare tumors with associated hypoglycemic symptoms. The proposed scenario provides an updated logical frame towards biologically sound therapeutic strategies and personalized therapeutic interventions for currently unaccounted IGF-II-producing cancers. Full article

Background: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. Methods: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. Results: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0–18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. Conclusions: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure. Full article