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Germ cell tumors of childhood are tumors arising from germline cells in gonadal or extragonadal locations. Extragonadal germ cell tumors are characteristically located in the midline, arising intracranially or in the mediastinum, retroperitoneum, or pelvis. These tumors are generally easily diagnosed due to typical sites of origin, characteristic imaging findings, and laboratory markers. However, germ cell tumors can be associated with unusual clinical syndromes or imaging features that can perplex the radiologist. This review will illustrate atypical imaging/clinical manifestations and complications of abdominal germ cell tumors in childhood. These features include unusual primary tumors such as multifocal primaries; local complications such as ovarian torsion or ruptured dermoid; atypical presentations of metastatic disease associated with burned-out primary tumor, growing teratoma syndrome, and gliomatosis peritonei; endocrine manifestations such as precocious puberty and hyperthyroidism; and antibody mediated paraneoplastic syndrome such as anti-N-methyl-D-aspartate-receptor antibody-mediated encephalitis. This review aims to illustrate unusual imaging features associated with the primary tumor, metastatic disease, or distant complications of abdominal germ cell tumors of childhood. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurological syndromes (PNS) are a complex of neurological symptoms caused by the body’s autoimmune reaction against the tumour. The autoimmune process can affect different structures in both the peripheral and central nervous systems, thus the clinical manifestation of PNSs can be very diverse. This article presents a 53-year-old man who developed psychosis for the first time in his life. The disorder manifested with atypical clinical symptoms and a limited response to psychopharmacotherapy was observed, which raised the suspicion of an organic origin of the disorder. A detailed diagnostic workup revealed carcinoma of the right kidney. This pathology was assessed as unrelated to the mental disorder. A diagnosis of unspecified dementia was made, suspecting Lewy body dementia. After the patient had completed active oncological treatment, a significant positive dynamics in his mental status was observed during a follow-up consultation with a psychiatrist. The diagnosis of dementia was excluded. Restrospecitvely assesed, the psychiatric disorder was of secondary origin, i.e. a manifestation of paraneoplastic neurological syndrome. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The co‐occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases. Myasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co‐occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co‐occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67‐year‐old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti‐AchR‐Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late‐onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x‐ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co‐occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases. [ABSTRACT FROM AUTHOR]

The "hot cross bun" sign (HCBs) is a cruciform hyperintensity on T2-weighted imaging within the pons initially found in patients diagnosed as multiple system atrophy. However, recent findings have broadened the disease spectrum presented with HCBs. Here is a case report at an academic medical center. Cerebral magnetic resonance imaging (MRI), electroneuromyography, serum, and CSF analysis were performed. Literature is comprehensively reviewed. We investigated a woman presented with blurred speech and cerebellar ataxia. Her MRI showed the vertical line of HCBs 2 weeks after disease onset and gradually enhanced, presenting as an intact HCBs in a year. Glutamic acid decarboxylase 65-kDa isoform (GAD65) antibody IgG was detected in serum and CSF. The patient was diagnosed as GAD65 associated cerebellar ataxia and treated with corticosteroid and rituximab. We found 6 previously reported autoimmune cerebellar ataxia patients with HCBs. Anti-KLHL-11, anti-Homer-3, anti-Ri, and anti-Amphiphysin were associated. All patients had cerebellar ataxia with other neurological symptoms. Five patients were diagnosed with tumor. First-line immunotherapy including corticosteroid, intravenous immunoglobulin, and plasma exchange for most patients was unsatisfied. This case highlights the importance of considering GAD65 IgG evaluation in patients with progressive cerebellar syndrome and HCBs. Early diagnosis and therapy are challenging but imperative. Further studies are required in regard to therapeutic management. [ABSTRACT FROM AUTHOR]

Anti‐pituitary‐specific transcription factor‐1 (PIT‐1) hypophysitis, a paraneoplastic syndrome resulting from an autoimmune response against PIT‐1, typically manifests with undetectable levels of growth hormone (GH) and prolactin (PRL), and significantly low levels of serum thyroid‐stimulating hormone (TSH) at diagnosis. These hormonal levels are highly specific to this disease and serve as key diagnostic indicators. Herein, we present a detailed clinical course of a 69‐year‐old male with a history of gastric cancer and lymph node metastases who developed anti‐PIT‐1 hypophysitis after the initiation of immune checkpoint inhibitor (ICI) therapy, specifically nivolumab, oxaliplatin, and capecitabine. The patient was referred to our department owing to decreased TSH, free triiodothyronine (T3), and free thyroxine (T4) levels after two doses of nivolumab. Initially suspected as central hypothyroidism due to ICI‐related hypophysitis, further assessment confirmed the diagnosis of anti‐PIT‐1 hypophysitis. Notably, GH, PRL, and TSH levels markedly declined, leading to complete deficiencies 2 months after the first nivolumab dose—a pattern consistent with that of previous cases of anti‐PIT‐1 hypophysitis. Therefore, this report not only presents an atypical subset of ICI‐related hypophysitis but also delineates the process of hormone impairment leading to complete deficiencies in anti‐PIT‐1 hypophysitis. This case highlights the importance of vigilant monitoring for endocrine issues in patients undergoing ICI therapy, given the escalating incidence of immune‐related adverse events associated with the extensive use of ICI therapy for various cancers. [ABSTRACT FROM AUTHOR]

Background and purpose: Paraneoplastic neurological autoimmunity is well described with small‐cell lung cancer, but information is limited for other neuroendocrine neoplasms (NENs). Methods: Adult patients with histopathologically confirmed non‐pulmonary NENs, neurological autoimmunity within 5 years of NEN diagnosis, and neural antibody testing performed at the Mayo Clinic Neuroimmunology Laboratory (January 2008 to March 2023) were retrospectively identified. Control sera were available from patients with NENs without neurological autoimmunity (116). Results: Thirty‐four patients were identified (median age 68 years, range 31–87). The most common primary tumor sites were pancreas (nine), skin (Merkel cell, eight), small bowel/duodenum (seven), and unknown (seven). Five patients received immune checkpoint inhibitor (ICI) therapy before symptom onset; symptoms preceded cancer diagnosis in 62.1% of non‐ICI‐treated patients. The most frequent neurological phenotypes (non‐ICI‐treated) were movement disorders (12; cerebellar ataxia in 10), dysautonomia (six), peripheral neuropathy (eight), encephalitis (four), and neuromuscular junction disorders (four). Neural antibodies were detected in 55.9% of patients studied (most common specificities: P/Q‐type voltage‐gated calcium channel [seven], muscle‐type acetylcholine receptor [three], anti‐neuronal nuclear antibody type 1 [three], and neuronal intermediate filaments [two]), but in only 6.9% of controls. Amongst patients receiving cancer or immunosuppressive therapy, 51.6% had partial or complete recovery. Outcomes were unfavorable in 48.3% (non‐ICI‐treated) and neural autoantibody positivity was associated with poor neurological outcome. Discussion: Neurological autoimmunity associated with non‐pulmonary NENs is often multifocal and can be treatment responsive, underscoring the importance of rapid recognition and early treatment. [ABSTRACT FROM AUTHOR]

Background and objectives: Dysautonomia has been associated with paraneoplastic neurological syndrome (PNS)-related mortality in anti-Hu PNS, but its frequency and spectrum remain ill-defined. We describe anti-Hu patients with dysautonomia, estimate its frequency, and compare them to patients without dysautonomia. Methods: Patients with anti-Hu antibodies diagnosed in the study centre (1990–2022) were retrospectively reviewed; those with autonomic signs and symptoms were identified. Results: Among 477 anti-Hu patients, 126 (26%) had dysautonomia (the only PNS manifestation in 7/126, 6%); gastrointestinal (82/126, 65%), cardiovascular (64/126, 51%), urogenital (24/126, 19%), pupillomotor/secretomotor (each, 11/126, 9%), and central hypoventilation (10/126, 8%). Patients with isolated CNS involvement less frequently had gastrointestinal dysautonomia than those with peripheral (alone or combined with CNS) involvement (7/23, 30% vs. 31/44, 70% vs. 37/52, 71%; P = 0.002); while more frequently central hypoventilation (7/23, 30% vs. 1/44, 2.3% vs. 2/52, 4%; P < 0.001) and/or cardiovascular alterations (18/23, 78% vs. 20/44, 45% vs. 26/52, 50%; P = 0.055). Median [95% CI] overall survival was not significantly different between patients with (37 [17; 91] months) or without dysautonomia (28 [22; 39] months; P = 0.78). Cardiovascular dysautonomia (HR: 1.57, 95% CI [1.05; 2.36]; P = 0.030) and central hypoventilation (HR: 3.51, 95% CI [1.54; 8.01]; P = 0.003) were associated with a higher risk of death, and secretomotor dysautonomia a lower risk (HR: 0.28, 95% CI [0.09; 0.89]; P = 0.032). Patients with cardiovascular dysautonomia dying ≤ 1 year from clinical onset had severe CNS (21/27, 78%), frequently brainstem (13/27, 48%), involvement. Discussion: Anti-Hu PNS dysautonomia is rarely isolated, frequently gastrointestinal, cardiovascular and urogenital. CNS dysfunction, particularly brainstem, associates with lethal cardiovascular alterations and central hypoventilation, while peripheral involvement preferentially associates with gastrointestinal or secretomotor dysautonomia, being the latest more indolent. [ABSTRACT FROM AUTHOR]

Background: The clinical spectrum of melanoma-associated neurological autoimmunity, whether melanoma-associated paraneoplastic neurological syndromes (PNS) or induced by immune checkpoint inhibitors (ICI), is not well characterized. We aim to describe the clinical spectrum of melanoma-associated neurological autoimmunity. Methods: A systematic review of the literature combined with patients from French databases of paraneoplastic neurological syndromes was conducted. All melanoma patients with a possible immune-mediated neurologic syndrome were included and classified according to whether they had previously been exposed to ICI (ICI-neurotoxicity) or not (ICI-naïve) at first neurological symptoms. Results: Seventy ICI-naïve (literature: n = 61) and 241 ICI-neurotoxicity patients (literature: n = 180) were identified. Neuromuscular manifestations predominated in both groups, but peripheral neuropathies were more frequent in ICI-neurotoxicity patients (39.4% vs 21.4%, p = 0.005) whereas myositis was more frequent in ICI-naïve patients (42.9% vs 18.7%, p < 0.001). ICI-naïve patients had also more frequent central nervous system (CNS) involvement (35.7% vs 23.7%, p = 0.045), classical paraneoplastic syndrome (25.7% vs 5.8%, p < 0.001), and more frequently positive for anti-neuron antibodies (24/32, 75.0% vs 38/90, 42.2%, p = 0.001). Although more ICI-neurotoxicity patients died during the acute phase (22/202, 10.9% vs 1/51, 2.0%, p = 0.047), mostly myositis patients (14/22, 63.6%), mortality during follow-up was higher in ICI-naïve patients (58.5% vs 29.8%, p < 0.001). There was no significant difference in the frequency of life independence (mRS ≤ 2) in the surviving patients in both groups (95.5% vs 91.0%, p = 0.437). Conclusions: Melanoma-associated PNS appear remarkably rare. The clinical similarities observed in neurological autoimmunity between ICI-treated and ICI-naïve patients, characterized predominantly by demyelinating polyradiculoneuropathy and myositis, suggest a potential prior immunization against melanoma antigens contributing to ICI-related neurotoxicity. [ABSTRACT FROM AUTHOR]

Association between anti-GABAAR encephalitis and myasthenia gravis is extremely rare with few reported cases. Herein, we report a case of a female patient diagnosed with anti-GABAAR encephalitis and thymoma at the first admission. She was administered glucocorticoids for long-term immunotherapy, and thymectomy with biopsy demonstrated a type A thymoma. After 4 months, the symptoms of encephalitis were relieved, but she then developed post-thymectomy myasthenia gravis with anti-AChR and anti-titin dual positivity. Antibodies to connective tissue (anti-ANA, anti-PCNA) and those characteristics of paraneoplastic syndrome (anti-Ma2/Ta) were also positive. She received oral glucocorticoids and tacrolimus as immunosuppressive therapy, and myasthenic symptoms were stable during a 2-year follow-up. Our case revealed that anti-GABAAR encephalitis and myasthenia gravis can appear in patient with type A thymoma at different periods, which alerts physicians to take long-term follow-up for anti-GABAAR encephalitis with thymoma, even after thymectomy. Concurrent positivity for more than one antibody after thymectomy is rarely observed, and their contribution to the clinical course and treatment decision remains to be further investigated. [ABSTRACT FROM AUTHOR]

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One‐third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15‐year‐old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. Methods: Thirty‐seven antibody‐positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti‐GAD65 antibodies. Results: Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti‐GAD65 antibodies. Anti‐LGI1 and anti‐NMDAR were the most frequently detected NSAbs, with anti‐NMDAR cases having an older‐than‐expected age distribution (median age 40, range 17–72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti‐LGI1, anti‐CASPR2, and anti‐IgLON5 had an eightfold longer time to immunotherapy than anti‐NMDAR and anti‐GABA‐B (p =.0016). There was a seasonal variation in onset for patients with non‐tumor‐related NSAbs and anti‐GAD65 antibodies, with most patients (72%) falling ill in spring or summer. Conclusion: Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti‐NMDAR encephalitis, with older onset than expected. The onset of non‐tumor‐related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Ectopic olfactory neuroblastoma is an uncommon manifestation of an already rare neoplasm. We aimed to systematically review the literature for cases of ectopic olfactory neuroblastoma to better characterize this rare disease entity and to present two new case reports. Methods A search of the PubMed and Embase databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify English-language articles reporting cases of ectopic olfactory neuroblastoma, published from 1955 through November 2021. Results Sixty-six cases of ectopic olfactory neuroblastoma were identified in 62 articles including the current review. Ectopic olfactory neuroblastoma arose in a wide age range (2–89 years) without significant sex predilection. It occurred most commonly in the ethmoid (25%), maxillary (25%), and sphenoid (16%) sinuses. Seventy-three percent of cases presented with low Hyams grade (I and II). The most common symptoms were nasal obstruction (32%) and epistaxis (32%). Paraneoplastic syndromes were observed in 27% of patients. The most common treatment was surgical resection followed by adjuvant radiotherapy. Overall, 76% of all patients were disease-free at the time of last follow-up. Locoregional recurrences and distant metastases were found in 19 and 5% of cases, respectively. Conclusion This systematic review describes previously reported cases of ectopic olfactory neuroblastoma, a disease entity with poorly understood characteristics. Physicians should consider olfactory neuroblastoma in the differential diagnosis for sinonasal masses, as their ectopic presentation may present considerable diagnostic and therapeutic difficulties. Patients with olfactory neuroblastoma may benefit from long-term follow-up and routine endoscopic examinations for surveillance of ectopic recurrences. [ABSTRACT FROM AUTHOR]

PNS are uncommon manifestations of cancer. The current literature about these syndromes in the setting of cHL is disintegrated. A systematic literature review of all published literature was conducted. One hundred twenty-eight patients from 115 publications met the inclusion/exclusion criteria. Eight-five patients were of the NS subtype (66.4%). The most frequent clinical presentation of the PNS was CNS manifestation (25.8%). The majority of patients were diagnosed with the cHL and PNS simultaneously (42.2%). In 33.6% of patients, the lymphoma diagnosis preceded the PNS diagnosis. In 16.4% of patients, the PNS diagnosis preceded the lymphoma diagnosis. The presence of PNS antibodies was reported in 35 patients (27.3%). Age older than 18 was associated with higher prevalence of PNS. The CR rate of the lymphoma was 77.3%. The complete resolution rate of the PNS was 54.7%. Relapse of lymphoma was reported in 13 patients, and recurrence of the PNS upon relapse was reported in 10/13 patients. [ABSTRACT FROM AUTHOR]

This case report expands the reported range of clinical presentations of CV2/CRMP5 antibody‐related syndromes with two novel findings (manic psychosis and psychogenic polydipsia). A systematic literature review highlights a potentially higher incidence of psychosis than previously reported, clinical features that should prompt antibody testing, and the potential for treatment response. [ABSTRACT FROM AUTHOR]

Background Case Presentation Conclusions Autoimmune neurological syndromes pose diagnostic challenges due to their resemblance to neurodegenerative conditions. Autoimmune spastic ataxia is a rare phenomenon. This case presents a 56‐y‐old woman with subacute‐onset spastic ataxia, highlighting the complexities in diagnosis and the role of autoimmunity in such cases.A woman in her fifties developed progressive spastic ataxia over a year and presented to our outpatient department for evaluation. The patient exhibited clinical signs including saccadic intrusions, gaze‐evoked nystagmus, mixed dysarthria, spasticity, exaggerated reflexes, and cerebellar dysfunction. Brain magnetic resonance imaging (MRI) displayed the “hot cross bun sign” and cerebral and cerebellar atrophy. Initial tests yielded minimal abnormalities, but a positive antinuclear antibody (ANA) emerged. The patient initially declined immunotherapy. Upon symptom progression, a repeat cerebrospinal fluid (CSF) analysis showed inflammatory changes and a whole‐body positron emission tomography (PET) scan indicated reduced uptake in the cerebellum and brainstem. Subsequent paraneoplastic antibody testing revealed an unspecified neuronal antibody targeting capillaries and arterioles. Treatment with steroids, plasmapheresis, and azathioprine led to sustained improvement, reducing spasticity, and enabling her to walk short distances.This case emphasizes the diagnostic complexity of autoimmune neurological syndromes, particularly spastic ataxia. Autoimmune etiology should be considered even when neurodegenerative conditions seem likely. The presence of neuronal antibodies, inflammatory CSF, and response to immunotherapy underscores the role of autoimmunity in this case. Additionally, the “hot cross bun sign” may not always signify neurodegeneration, but can indicate immune‐mediated neural damage. Recognizing autoimmune involvement early offers therapeutic possibilities and highlights the need for a comprehensive diagnostic approach in such cases. [ABSTRACT FROM AUTHOR]

Background: Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. Detecting the primary tumour in TIO is challenging using conventional imaging methods. This study assesses the efficacy of [68Ga]Ga-DOTATATE PET/CT in identifying the primary tumour. Methods: Six patients with suspected TIO underwent [68Ga]Ga-DOTATATE PET/CT. The patients' clinical history and biochemical parameters were analysed. Results: [68Ga]Ga-DOTATATE PET/CT successfully identified primary tumours in four patients (femoral bones for two, iliac bone for one, subcutaneous tissue of pubic region for one). Tumour removal led to clinical and laboratory improvement. In one patient, PET/CT showed rib uptake, but the biopsy was negative. One patient showed no tumour lesions on PET/CT despite clinical evidence. Two patients had focal recurrence at the primary tumour site, detected by follow-up PET/CT. Conclusions: [68Ga]Ga-DOTATATE PET/CT is a valuable tool for detecting primary tumours in TIO, aiding in accurate diagnosis and guiding surgery, leading to improved outcomes. Further research is needed to validate these findings and explore [68Ga]Ga-DOTATATE PET/CT in other paraneoplastic syndromes. [ABSTRACT FROM AUTHOR]

The Castleman triad has been described in a select few patients presenting with a retroperitoneal mass, mucocutaneous pemphigus vulgaris, and bronchiolitis obliterans. Here, we describe the Castleman triad in a 19-year-old male with unicentric hyaline vascular type Castleman disease (HV-CD). This patient presented with an array of positive antibodies, including anti-cyclic citrullinated peptide, anti-double-stranded DNA, and Sjogren's IgG. Interestingly, the patient's rheumatologic symptoms resolved after tumor resection, while his antibody profile remained relatively unchanged. HV-CD, with a triad presentation, was thought to be from a paraneoplastic syndrome secondary to an underlying lymphoproliferative disorder. The findings presented here identify multiple autoantibodies potentially contributing to this patient's presentation with HV-CD. [ABSTRACT FROM AUTHOR]

Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic syndromes (PNS). NEPC is becoming more frequent. It can initially manifest as PNS, complicating diagnosis. Therefore, we reviewed the literature on the different PNS associated with NEPC. We systematically reviewed English-language articles from January 2017 to September 2023, identifying 17 studies meeting PRISMA guidelines for NEPC and associated PNS. A total of 17 articles were included in the review. Among these, Cushing's Syndrome (CS) due to ectopic Adrenocorticotropic hormone (ACTH) secretion was the most commonly reported PNS. Other PNS included syndrome of inappropriate Anti-Diuretic Hormone secretion (SIADH), Anti-Hu-mediated chronic intestinal pseudo-obstruction (CIPO), limbic encephalitis, Evans Syndrome, hypercalcemia, dermatomyositis, and polycythemia. Many patients had a history of prostate adenocarcinoma treated with androgen deprivation therapy (ADT) before neuroendocrine features developed. The mean age was 65.5 years, with a maximum survival of 9 months post-diagnosis. NEPC is becoming an increasingly more common subtype of PCa that can result in various PNS. This makes the diagnosis and treatment of NEPC challenging. Further research is crucial to understanding these syndromes and developing standardized, targeted treatments to improve patient survival. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lambert–Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX‐1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56‐year‐old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX‐1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow‐up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long‐term follow‐up and screening for occult SCLC in LEMS patients with positive SOX‐1 antibodies are very important. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Paraneoplastic movement disorders, though rare, can be the initial symptoms of malignancies like leiomyosarcoma, as in our case. Clinicians should keep malignancies in their differential diagnosis in cases of unexplained movement abnormalities. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response‐mediator protein 5 (CRMP5)‐IgG paraneoplastic neurologic disorders (PND). Methods: This is a retrospective study of patients with CV2/CRMP5‐IgG PND evaluated between 2002–2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan–Meier estimates were used to determine the probability of survival. Results: Twenty‐seven patients (56% female) with CV2/CRMP5‐IgG PND were identified with a median follow‐up of 54 months (IQR = 11–102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow‐up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87–30.64, P = 0.005). Moderate–severe mRS = 3–5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18–41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55–93.04, P < 0.001) was significantly associated with mortality, while thymoma was not. Interpretation: In this retrospective longitudinal study of CV2/CRMP5‐IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population. [ABSTRACT FROM AUTHOR]

Association of MOGAD with various autoimmune and paraneoplastic antibodies has been described in the literature. However, MOGAD with systemic manifestations is rarely encountered and requires a high index of suspicion for evaluation. Searching various databases, we identified 107 studies. After independently assessing the eligibility, finally, 29 studies were selected for review. A total of 1458 MOG patients were included in the study among whom systemic manifestations were present in 253 (17.3%) patients. SLE with ANA positivity was found in a total of 72 (28.4%) patients. Among them, anti‐dsDNA was positive in 10 (3.9%), anti‐smith in 3 (1.2%), anti‐SSA/SSB in 13 (5.1%), anti‐RNP in 3 (1.1%), anti‐Ro 52 in 1 (0.5%), and ENA in 1 (0.5%). APLA was positive in 10 (3.9%), ANCA in 10 (3.9%), RA in 31(12.9%) and thyroid antibody in 35 (13.8%) patients. Simultaneous CNS and PNS involvement was also seen in 21 (8.3%) patients. Systemic involvement is not an uncommon phenomenon in MOGAD and in future may add to the spectrum of the disease. [ABSTRACT FROM AUTHOR]

Background: Leukocytoclastic vasculitis (LCV) is an atypical form of cutaneous paraneoplastic manifestation. Its association with multiple myeloma (MM) is even rarer and is associated with poor prognosis and short survival, regardless of the therapy instituted. Different treatment approaches are necessary. We present a case in which LCV was the first manifestation of MM, and high-intensity laser therapy (HILT) was used as an option to accelerate healing and control pain. Case Report: A 76-year-old woman presented with pain and paresthesia in her lower limbs, associated with palpable purpura. The clinical diagnosis was small-vessel vasculitis. Laboratory tests showed an elevated gamma globulin monoclonal peak on protein electrophoresis. The immunophenotypic study of bone marrow aspirates led to the diagnosis of MM. Due to pain refractory to conventional analgesics, and the progressive evolution of the lesions, despite corticosteroid therapy, we performed photo-biomodulation with a neodymium-doped yttrium aluminum garnet laser (Nd: YAG), wavelength 1064 nanometers, using a 7-mm probe and energy density 6 J/cm². After the first session, the patient was referred for pain management, and after 5 weeks, we observed complete healing in ulcerated lesions and involution of bullous lesions. Conclusions: This case report shows the positive effects of the Nd: YAG laser in modulating healing and reducing pain. HILT is an innovative, non-invasive, and effective treatment and should be considered a promising technique to accelerate healing and controlling pain. [ABSTRACT FROM AUTHOR]

Background: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. Methods: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. Results: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. Conclusions: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast. [ABSTRACT FROM AUTHOR]

Secondary polycythemia is a paraneoplastic syndrome observed in tumors with excessive erythropoietin (EPO) production. Renal cell carcinoma (RCC) and cerebellar hemangioblastoma are the 2 most well-known tumors to induce secondary polycythemia. Hemangioblastomas occurring in the kidney are rare. In this work we present a case of renal hemangioblastoma that caused erythrocytosis in a 19-year-old man. We demonstrated intratumoural EPO production by immunohistochemistry, and conducted whole-exome sequencing to evaluate possible genetic alterations that reported to induce tumor-related polycythemia. In spite of an indolent clinical behavior, renal hemangioblastoma is difficult to differentiate from RCC not only clinically, but also histopathologically. Given that RCC is the most well-known renal tumor to induce erythrocytosis, the uncommon manifestation of polycythemia in renal hemangioblastoma, as shown in our case, can cause further diagnostic challenges. Renal hemangioblastoma should be listed in the differential diagnoses of renal tumors presenting with erythrocytosis, apart from the most common RCC. [ABSTRACT FROM AUTHOR]

This article presents a case report and literature review on neuronal intermediate filament autoimmunity manifesting as ataxia and peripheral neuropathy. The patient, a 64-year-old man, presented with dizziness, unsteady gait, numbness, and weakness in his lower extremities. Various tests were conducted, including neuroimaging, antibody testing, and whole-body scans, to rule out other potential causes. The patient was tentatively diagnosed with an autoimmune disease, and treatment with prednisone resulted in significant improvement. The article highlights the importance of considering neuronal intermediate filament autoimmunity in the differential diagnosis of patients with ataxia and peripheral neuropathy. [Extracted from the article]

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti‐aquaporin‐4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year‐old woman with metastatic triple‐negative breast cancer. She received multiple lines of anti‐neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti‐aquaporin‐4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low‐dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine lymphoma is the most common malignant hematopoietic tumor. It is mainly seen in middle-aged or older dogs, and it is characterized by a clonal proliferation of B or T lymphocytes. The development of hemostatic changes is associated with malignant tumors in human medicine and is also reported in dogs. These hemostatic alterations may contribute unfavorably to the morbidity and mortality associated with the disease. The aim of this study was to evaluate, in a large group of dogs affected by lymphoma compared to dogs with other diseases, whether there is an alteration of hemostatic parameters in canine lymphoma and, if so, whether these were correlated with the type (B or T) of lymphoma and with the stage of the disease. Multiple hemostatic abnormalities are associated with paraneoplastic syndrome and some malignant tumors. Lymphoma is the most common hematopoietic neoplasm in dogs, sometimes associated with hemostatic changes. The objectives of this study were to evaluate the behavior of coagulation parameters in dogs with multicentric lymphoma compared with diseased dogs without lymphoma, to separately evaluate the effect of immunophenotype (B lymphoma versus T lymphoma) on the variables of interest as well as the effect of disease stage (stage II to IV versus stage V). Specifically, a cross-sectional study was performed with a matched comparison group considering 170 dogs with B or T lymphoma (group 1) and 170 dogs with no lymphoma or other neoplastic processes but other diseases (group 0). Eight coagulation parameters were evaluated: platelet count (Plt), activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, fibrin/products of fibrinogen degradation (FDPs), fibrin D-dimers, and antithrombin (AT). Dogs with lymphoma showed prolonged PT and TT, decreased fibrinogen, increased FDP, and decreased Plt compared with group 0. The effect of disease stage was evaluated separately for dogs with stage II to IV lymphoma and dogs with stage V lymphoma; patients with stage II–IV lymphoma showed no significant differences, while in dogs with stage V lymphoma, a prolongation of PT and TT, a decrease in fibrinogen, an increase in FDPs and a decrease in Plt were found compared with the group 0. Finally, the comparison between B lymphoma and T lymphoma showed no significant differences in coagulation parameters between the two groups. Logistic regression analysis demonstrated that low fibrinogen and platelet levels were the most significant predictors of lymphoma in a cohort of canine patients. These hemostatic abnormalities in lymphoma appeared to be associated with the stage of the disease rather than the lymphoma immunophenotype. These findings pave the way for the possible scenario of lymphoma-associated fibrinolysis and the so far undescribed pattern of hyperfibrinolysis associated with the most severe stage of lymphoma. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors. While recognizing specific syndromes can aid early cancer detection, overutilization of paraneoplastic assays in the absence of a classic syndrome can precipitate overdiagnosis and overtreatment. PNS involve autoantibodies targeting intracellular or extracellular antigens, with variable immunotherapy responses based on antigen type. Diagnosing PNS is challenging, requiring exclusion of other differential diagnoses. New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence. Patients with cell surface antibodies respond better to immunotherapies compared to those with intracellular antigen targets. Understanding PNS syndromes, serological markers, and oncological features guides management, which facilitates initiation of immunosuppression for PNS alongside treatment of the underlying neoplasm, thereby improving neurologic and oncologic outcomes. Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins. Second-line immunosuppressants like rituximab or cyclophosphamide may be necessary if initial treatments fail. Specific therapies vary based on antibody target. Here, we summarize the current approach to the investigation, diagnosis, and treatment of patients with suspected PNS. [ABSTRACT FROM AUTHOR]

Abdominal emergencies in cancer patients encompass a wide spectrum of oncologic conditions caused directly by malignancies, paraneoplastic syndromes, reactions to the chemotherapy or often represent the first clinical manifestation of an unknown malignancy. Not rarely, clinical symptoms are the tip of an iceberg. In this scenario, the radiologist is asked to exclude the cause responsible for the patient's symptoms, to suggest the best way to manage and to rule out the underlying malignancy. In this article, we discuss some of the most common abdominal oncological emergencies that may be encountered in an emergency department. [ABSTRACT FROM AUTHOR]

This article discusses the importance of autoimmunity panels in diagnosing and treating movement disorders caused by autoimmune conditions. The diagnosis of antibody-related movement disorders is based on serum and CSF analysis, and there are various techniques for assessing the presence of antibodies. However, these tests are generally expensive and may only be available in larger centers or referral units. In underdeveloped regions, the availability of autoimmune panels is limited, and the cost and timing of testing can be a barrier to early diagnosis and treatment. The article suggests that widespread education of neurologists is necessary to recognize the classic phenotypes of autoimmune movement disorders and that more funding should be made available for investigations and therapies. [Extracted from the article]

Background: Malignant peritoneal mesothelioma (MPM) is a rare and highly aggressive tumor. Its clinical manifestations are diverse, and the symptoms are not specific. Some patients will develop paraneoplastic syndrome (PS) during the disease course. This study aims to analyze the risk factors of PS in patients with MPM and their impacts on prognosis. Methods: The clinical data of MPM patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) at our center from June 2015 to May 2023 were retrospectively analyzed. MPM patients were divided into PS group and non-PS group according to the diagnostic criteria. Univariate and multivariate analyses were performed to explore the risk factors of PS in MPM patients, and to analyze the impact of PS on prognosis. Results: There were 146 MPM patients in this study, including 60 patients (41.1%) with PS and 86 patients (58.9%) without PS. The highest incidence of PS was thrombocytosis (33.6%), followed by neoplastic fever (9.6%). Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: prior surgical scores, targeted therapy history, Karnofsky performance status score, preoperative carbohydrate antigen (CA) 125 level, vascular tumor embolus, peritoneal cancer index, completeness of cytoreduction (CC) score and intraoperative ascites. Multivariate analysis identified 3 independent factors associated with PS: preoperative CA 125 level, vascular tumor embolus, and CC score. Survival analysis demonstrated that MPM patients with PS had worse prognosis, although PS was not an independent prognostic factor. Conclusions: PS is not rare in patients with MPM, and is independently associated with preoperative CA 125 level, vascular tumor embolus and CC score. PS often indicates advanced disease and poor prognosis. [ABSTRACT FROM AUTHOR]

The relentless advancement of chemotherapeutic agents has enhanced survival rates among cancer patients. However, this success comes with an increased prevalence of chemotherapy-induced neurotoxicity, which often mimics the symptoms of metastatic disease or paraneoplastic syndromes and poses a diagnostic challenge for clinicians. Imaging, particularly MRI, plays a pivotal role in unraveling this conundrum. This comprehensive review explores the MRI patterns associated with central neurotoxicities induced by various chemotherapeutic agents. Our objective is to provide radiologists and clinicians with illustrative diagrams that offer a structured approach to diagnosing these conditions. By enhancing the understanding of these distinctive MRI patterns, we aim to facilitate accurate and timely diagnosis, ultimately improving patient care in the context of evolving cancer treatments. Critical relevance statement This article describes the essential role of MRI in identifying distinct patterns of chemotherapy-induced central neurotoxicity, enabling early diagnosis and improved patient care within the field of clinical radiology. Key points • Chemotherapy-induced neurotoxicity is a growing concern for cancer patients, and MRI is a key tool in diagnosis. • This review highlights distinctive MRI patterns associated with various chemotherapy-induced neurotoxicities. • Understanding these patterns improves patient care, ensuring timely intervention and accurate diagnosis in the complex world of cancer treatment. [ABSTRACT FROM AUTHOR]

The pathogenesis of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis was gradually revealed as cases emerged. Our comprehensive analysis, including all reported cases, identified a new instance of anti-PIT-1 hypophysitis postimmune checkpoint inhibitor therapy. All 9 patients exhibited extremely low growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) levels; 2 had a slightly atrophic pituitary gland; 4 had thymoma, and 5 had malignant neoplasms of diffuse large B-cell lymphoma (DLBCL) and other origins. Patients with thymoma showed multiple autoimmune diseases. HLA-A*24:02 and/or A*02:06 were present in six and DR53 in 5 cases analyzed. High anti-PIT-1 antibody titers and ectopic PIT-1 expression in the cytosol and nucleus of the tumor tissues were observed in patients with thymoma or DLBCL, whereas it was exclusively observed in the nuclei of a bladder cancer patient. These findings provide new insights into the pathophysiology of paraneoplastic autoimmune hypophysitis. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AE) is a group of inflammatory conditions that can associate with the presence of antibodies directed to neuronal intracellular, or cell surface antigens. These disorders are increasingly recognized as an important differential diagnosis of infectious encephalitis and of other common neuropsychiatric conditions. Autoantibody diagnostics plays a pivotal role for accurate diagnosis of AE, which is of utmost importance for the prompt recognition and early treatment. Several AE subgroups can be identified, either according to the prominent clinical phenotype, presence of a concomitant tumor, or type of neuronal autoantibody, and recent diagnostic criteria have provided important insights into AE classification. Antibodies to neuronal intracellular antigens typically associate with paraneoplastic neurological syndromes and poor prognosis, whereas antibodies to synaptic/neuronal cell surface antigens characterize many AE subtypes that associate with tumors less frequently, and that are often immunotherapy-responsive. In addition to the general features of AE, we review current knowledge on the pathogenic mechanisms underlying these disorders, focusing mainly on the potential role of neuronal antibodies in the most frequent conditions, and highlight current theories and controversies. Then, we dissect the crucial aspects of the laboratory diagnostics of neuronal antibodies, which represents an actual challenge for both pathologists and neurologists. Indeed, this diagnostics entails technical difficulties, along with particularly interesting novel features and pitfalls. The novelties especially apply to the wide range of assays used, including specific tissue-based and cell-based assays. These assays can be developed in-house, usually in specialized laboratories, or are commercially available. They are widely used in clinical immunology and in clinical chemistry laboratories, with relevant differences in analytic performance. Indeed, several data indicate that in-house assays could perform better than commercial kits, notwithstanding that the former are based on non-standardized protocols. Moreover, they need expertise and laboratory facilities usually unavailable in clinical chemistry laboratories. Together with the data of the literature, we critically evaluate the analytical performance of the in-house vs commercial kit-based approach. Finally, we propose an algorithm aimed at integrating the present strategies of the laboratory diagnostics in AE for the best clinical management of patients with these disorders. [ABSTRACT FROM AUTHOR]

The heterogeneity of autoantibody targets in autoimmune encephalitides presents a challenge for understanding cellular and humoral pathophysiology, and the development of new treatment strategies. Thus, current treatment aims at autoantibody removal and immunosuppression, and is primarily based on data generated from other autoimmune neurological diseases and expert consensus. There are many subtypes of autoimmune encephalitides, which now entails both diseases with autoantibodies targeting extracellular antigens and classical paraneoplastic syndromes with autoantibodies targeting intracellular antigens. Here, we review the current knowledge of molecular and cellular effects of autoantibodies associated with autoimmune encephalitis, and evaluate the evidence behind the proposed pathophysiological mechanisms of autoantibodies in autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We presented a patient, diagnosed with lymphoma‐associated CLIPPERS, 11 years after lymphoma treatment. Therefore, CLIPPERS may be paraneoplastic neurological syndrome of lymphoma, which needs to be considered in the follow‐up of lymphoma cases. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system disorder with a recent increase in incidence. There are few reports of lymphoma‐associated CLIPPERS, although the relationship between these two diseases and the pathophysiology of CLIPPERS in general need further investigation. Here, we present a patient with a history of Hodgkin's lymphoma (HL) more than 10 years before the onset of CLIPPERS, in contrast to the majority of previously reported lymphoma‐associated cases, and discuss the possibility that CLIPPERS is the paraneoplastic neurological syndrome of HL. This highlights the need to consider CLIPPERS as a differential diagnosis during follow‐up of patients with a history of lymphoma. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP. Case Presentation: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation. Conclusion: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications. [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]

Objective: Rare coexistence of disease or pathology Background: Immunoglobulin A (IgA) vasculitis is a systemic vasculitis that involves the small vessels. It is mainly characterized by skin symptoms such as purpura, arthritis/arthralgia, abdominal symptoms, and nephropathy, which are caused by IgA adherence to the vessel walls. Herein, we report the case of an advanced non-small cell lung cancer (NSCLC) and a purpuric skin rash of the legs that developed during fourth-line chemotherapy with tegafur/gimeracil/oteracil (S-1). Case Report: A 68-year-old man diagnosed with NSCLC 2 years ago was undergoing S-1 as fourth-line chemotherapy when he developed purpura and edema on the lower extremities. Biopsy renal specimens were consistent with IgA vasculitis. Considering his medical history, both IgA vasculitis induced by S-1 and a paraneoplastic syndrome were considered, although the exact cause could not be identified. Subsequently, chemotherapy was discontinued because of his deteriorating general condition, and he received optimal supportive care. The purpura spontaneously disappeared; however, his ascites and renal function deteriorated. Systemic steroids improved renal function, but the ascites did not resolve. One month after being diagnosed with IgA vasculitis, the patient died due to deterioration of his general condition. Conclusions: This case emphasizes the occurrence of IgA vasculitis during lung cancer treatment and its potential impact on the disease course of lung cancer. Moreover, the possible causes of IgA vasculitis in this case were paraneoplastic syndrome or S-1 adverse effects, but further case series are needed to gain a more comprehensive understanding. Refractory, steroid-unresponsive ascites may occur as an abdominal manifestation of IgA vasculitis. [ABSTRACT FROM AUTHOR]

Background. To present a rare case of a bilateral immune checkpoint inhibitor- (ICI-) induced photoreceptor injury with a bacillary layer detachment (BALAD) and a dissection of the photoreceptor inner and outer segment, accompanied by ICI-induced Vogt-Koyanagi-Harada- (VKH-) like uveitis after initial administration of nivolumab and ipilimumab. Case Presentation. A 52-year-old female with metastatic malignant cutaneous melanoma experiencing bilateral progressive visual acuity reduction, after treatment initiation with 1 mg/kg nivolumab and 3 mg/kg ipilimumab two weeks prior symptom onset. An extensive laboratory workup, including uveitis workup, onconeuronal and retinal antibodies, ruled out a paraneoplastic autoimmune disorder and a granulomatous disease. Furthermore, a B-scan was performed to exclude a posterior scleritis. Ensuing temporary treatment discontinuation of nivolumab and complete discontinuation of ipilimumab, treatment with high-dose systemic steroids was initiated, which resulted in alleviation of her symptoms and stability of ocular findings. Conclusions. ICIs can induce significant ocular side effects. As ocular inflammation can be well controlled using systemic steroids, treatment with ICIs can be continued whenever possible, in particular, if there is a good treatment response of the systemic malignancy. [ABSTRACT FROM AUTHOR]

This hematological study was aimed to investigate the hematological abnormalities associated with mammary gland carcinoma (CMT) in dogs at various stages of progression. Blood smear examinations were initially conducted on 45 cases, with exclusion criteria applied for hemoparasitic infections. Subsequently, 28 cases were selected for comprehensive analysis, focusing on complete blood count parameters, including haematocrit, haemoglobin, erythrocytes, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, leukocytes, and thrombocytes. The findings revealed hematological abnormalities associated with CMTs, notably characterized by anemia, erythropenia, thrombocytopenia, and leukocytosis. The differential white blood cell count showed negligible variation. These findings underscore the potential diagnostic value of hematological parameters in understanding and monitoring CMT-associated hematological alterations. [ABSTRACT FROM AUTHOR]

Background: Tumor‐induced osteomalacia (TIO) belongs to a rare disease of the paraneoplastic syndrome. Phosphate uric mesenchymal tumor (PMT) is the most common cause of TIO, while the possibility of other tumors cannot be excluded. Case presentation: We present a case of a 36‐year‐old female patient with systemic skeletal abnormalities. The woman complained of low back pain with mild motor dysfunction for 2 years. Laboratory examination showed abnormalities in markers of bone metabolism, parathyroid hormone (PTH), vitamin D and serum phosphorus. Pooled imaging examination indicated extension abnormalities in the skeletal system and a single lesion in the right femoral head. The lesion of the right femoral was imaging with somatostatin receptor‐positive, which was highly suggestive of a single neuroendocrine tumor. CT guided right femoral tumorectomy and bone grafting were performed when medical treatment failed. Postoperative pathological diagnosis was phosphate urinary mesenchymal tumor secreting fibroblast growth factor 23 (FGF23), which accorded with pre‐operative expectations. The postoperative symptoms were effectively relieved, and indicators returned to normal. Conclusion: The tumors causing TIO exhibited significant heterogeneity in terms of tissue origin, pathological characteristics and biological behavior, but the unique common characteristic is the secretion of FGF23. With significant progress in diagnosis and treatment, the clinical follow‐up of most TIO patients shows a good prognosis, but the prognosis of those with malignant tumors is relatively poor. [ABSTRACT FROM AUTHOR]

Objective: Small‐cell lung cancer (SCLC) is the malignancy most frequently associated with paraneoplastic neurological syndromes (PNS) and can trigger different antibody responses against intracellular (Hu) or neuronal surface (GABABR) antigens. Our aim was to clarify whether the genomic and transcriptomic features of SCLC are different in patients with anti‐GABABR or anti‐Hu PNS compared with SCLC without PNS. Methods: A total of 76 SCLC tumor samples were collected: 34 anti‐Hu, 14 anti‐GABABR, and 28 SCLC without PNS. The study consisted of 4 steps: (1) pathological confirmation; (2) next generation sequencing using a panel of 98 genes, including those encoding the autoantibodies targets ELAVL1‐4, GABBR1‐2, and KCTD16; (3) genome‐wide copy number variation (CNV); and (4) whole‐transcriptome RNA sequencing. Results: CNV analysis revealed that patients with anti‐GABABR PNS commonly have a gain in chromosome 5q, which contains KCTD16, whereas anti‐Hu and control patients often harbor a loss. No significantly different number of mutations regarding any onconeural genes was observed. Conversely, the transcriptomic profile of SCLC was different, and the differentially expressed genes allowed effective clustering of the samples into 3 groups, reflecting the antibody‐based classification, with an overexpression of KCTD16 specific to anti‐GABABR PNS. Pathway analysis revealed that tumors of patients with anti‐GABABR encephalitis were enriched in B‐cell signatures, as opposed to those of patients with anti‐Hu, in which T‐cell‐ and interferon‐γ‐related signatures were overexpressed. Interpretation: SCLC genetic and transcriptomic features differentiate anti‐GABABR, anti‐Hu, and non‐PNS tumors. The role of KCTD16 appears to be pivotal in the tumor immune tolerance breakdown of anti‐GABABR PNS. ANN NEUROL 2023;94:1102–1115 [ABSTRACT FROM AUTHOR]

Objective: Co‐occurring anti‐tripartite motif‐containing protein 9 and 67 autoantibodies (TRIM9/67‐IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67‐IgG detection are not known. Methods: We performed a retrospective, multicenter study to evaluate the cerebrospinal fluid and serum of candidate TRIM9/67‐IgG cases by tissue‐based immunofluorescence, peptide phage display immunoprecipitation sequencing, overexpression cell‐based assay (CBA), and immunoblot. Cases in which TRIM9/67‐IgG was detected by at least 2 assays were considered TRIM9/67‐IgG positive. Results: Among these cases (n = 13), CBA was the most sensitive (100%) and revealed that all cases had TRIM9 and TRIM67 autoantibodies. Of TRIM9/67‐IgG cases with available clinical history, a subacute cerebellar syndrome was the most common presentation (n = 7/10), followed by encephalitis (n = 3/10). Of these 10 patients, 70% had comorbid cancer (7/10), 85% of whom (n = 6/7) had confirmed metastatic disease. All evaluable cancer biopsies expressed TRIM9 protein (n = 5/5), whose expression was elevated in the cancerous regions of the tissue in 4 of 5 cases. Interpretation: TRIM9/67‐IgG is a rare but likely high‐risk paraneoplastic biomarker for which CBA appears to be the most sensitive diagnostic assay. ANN NEUROL 2023;94:1086–1101 [ABSTRACT FROM AUTHOR]

Key Clinical Message: Stiff‐Person Syndrome (SPS) can be associated with various malignancies, including lymphomas. Therefore, clinicians should always remain vigilant for the presence of an underlying malignancy, especially in older patients presenting with SPS. Stiff‐person syndrome (SPS) is a rare neurological disorder characterized by painful muscle spasms. It can occur as a paraneoplastic syndrome associated with various malignancies. We present a case of an older male adult with a history of recurrent fever episodes and elevated inflammatory markers for 1 year who subsequently developed neurological symptoms. The presence of positive amphiphysin antibodies led to the diagnosis of SPS, which prompted further investigations revealing an underlying Gray Zone lymphoma (GZL). This case highlights the challenges in diagnosing lymphoma and emphasizes the importance of considering SPS as a paraneoplastic syndrome in guiding toward the final diagnosis. The diagnostic challenge in our case is summarized in Chart 1. [ABSTRACT FROM AUTHOR]