Paraneoplastic Research Articles

NCMP-26. PATIENTS WITH ANTI-HU/ANNA1 PARANEOPLASTIC NEUROLOGICAL DISORDERS DEVELOP PROGRESSIVE DISABILITY BUT HAVE INCREASED SURVIVAL

Abstract ANNA-1/Hu-IgG paraneoplastic neurological disorders (PND) are rare and factors associated with disability and survival outcomes are unknown. We aimed to 1) examine disability and survival in ANNA1/Hu-IgG PND and 2) compare survival to a control group of small cell lung cancer (SCLC) without PND. METHODS This is a retrospective cohort study of ANNA1/Hu-IgG+ with PND and a control cohort of SCLC without PND (n=1513). Cox proportional hazard models examined clinical predictors of disability and survival. Kaplan-Meier curves examined time to mortality and mRS>2. Cox proportional hazard models compared survival between ANNA1/Hu-IgG PND and SCLC without PND, adjusting for age, sex, cancer stage, and brain metastases. RESULTS Forty-five patients with ANNA/Hu1-IgG PND were included (73% female, mean age=63 years [SD=13]). Phenotypes included; neuropathy (16, 36%), ataxia (11, 24%), encephalitis (10, 22%), myasthenic syndromes (3, 7%), myelopathy (2, 4%), enteric neuropathy (2, 4%), myoclonus (1, 2%). Cancers were identified in 78%; SCLC (26, 74%), non-SCLC (4, 11%), other (5, 14%). Immunosuppressive therapy for PND was given in 53%. At 5-year follow-up, 74% had mRS>2. Limbic encephalitis had greater hazard of mRS>2 at last follow-up (HR=7.76, [95% CI=2.20-27.39], p=0.001). At 5-year follow-up, 58% had died. Survival was not influenced by phenotype nor immunosuppressive treatment. Patients with SCLC and ANNA1/Hu-IgG (n=26) were compared to SCLC without PND (n=1513) and had 54% lower hazard of death (adjusted HR =0.46, [95% CI = 0.28–0.76], p=0.003). In ANNA-1/Hu-IgG PND, most patients experienced disability and greater disability was associated with limbic encephalitis, suggesting a potential modifiable factor. However, patients with SCLC and ANNA1/Hu-IgG PND survived longer than patients with SCLC without ANNA1/Hu-IgG PND, suggesting a possible survival advantage due to earlier cancer detection (lead time bias) and/or increased antitumor immunity.

NCMP-12. AN ATYPICAL CASE OF POEMS WITH MACROFOCAL MYELOMA

Abstract Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell dyscrasia. Symptoms of peripheral neuropathy dominate the clinical picture and is postulated to be related to serum vascular endothelial growth factor (VEGF) mediated altered permeability of the blood nerve barrier. The classic presentation includes a solitary osteosclerotic plasmacytoma and an elevation of VEGF. In this case, we present a patient with neither of these features who met diagnostic criteria for POEMS though had predominantly osteolytic lesions and was diagnosed with macrofocal myeloma, a unique subset of multiple myeloma. Our patient is a young male who presented with progressive leg numbness/weakness and was found to have marked ankle weakness, diffuse areflexia and unilateral gynecomastia on examination. EMG showed a motor predominant demyelinating polyneuropathy. Labs showed a serum IgG lambda M protein, low estradiol and low testosterone. He had a normal serum VEGF level though the lab was drawn after treatment initiation. Bone biopsy of a dominant osteolytic lesion was consistent with a plasma cell neoplasm (light chain restricted). Of note, he had mild cauda equina nerve root and ventral conus enhancement initially concerning for leptomeningeal involvement however, two lumbar punctures were negative for malignant cells. Spinal enhancement has been reported in POEMS. The patient underwent chemotherapy, radiation therapy and autologous stem cell transplantation. We present a patient diagnosed with MFMM, a rare subset of multiple myeloma, comprising only 3% of all cases, along with POEMS, a rare paraneoplastic syndrome. Interestingly, as osteolytic lesions can be seen in POEMS alone though not predominantly so, it is possible the patient could have atypical POEMS without underlying multiple myeloma. POEMS may remain under-recognized when presentations or setting are atypical.

A Paradigm Shift in Renal Cell Carcinoma: Recognizing Hypoglycaemia as a Significant Paraneoplastic Syndrome

A Paradigm Shift in Renal Cell Carcinoma: Recognizing Hypoglycaemia as a Significant Paraneoplastic Syndrome

Emerging Ocular Side Effects of Immune Checkpoint Inhibitors: A Comprehensive Review

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering significant improvements in patient survival across various malignancies. However, their use is associated with a broad spectrum of immune-related adverse events (irAEs), including those affecting the eye and its surrounding structures, collectively termed ocular irAEs (OirAEs). Although rare, OirAEs (e.g., keratitis, uveitis, retinal vasculitis, etc.) can significantly impact a patient’s quality of life, leading to ocular complications if left untreated. This review provides a comprehensive overview of OirAEs associated with ICIs, including their clinical manifestations, underlying mechanisms, and current management strategies. We delve into the anterior and posterior segment adverse events, highlighting conditions such as dry eye, uveitis, and retinal disorders, as well as neuro-ophthalmic and orbital complications. Furthermore, we discuss the challenges in diagnosing and treating these conditions, particularly given the overlap with other autoimmune and paraneoplastic syndromes. Finally, we identify key knowledge gaps and suggest future research directions aimed at optimizing the management of OirAEs while maintaining the efficacy of cancer therapy. This review underscores the need for increased awareness among clinicians to prevent irreversible ocular damage and enhance patient outcomes.

Vanishing Bile Duct Syndrome in Pediatric Hodgkin Lymphoma: First Statistical Analysis of All Published Cases in Children and a Case Report.

Hodgkin lymphoma with vanishing bile duct syndrome is a rare paraneoplastic syndrome and has never been studied in the pediatric population. The objectives of this study were to determine the clinical characteristics of this rare condition in children through a literature review, and a descriptive analysis of all published cases with the index case report. All reported cases fulfilling the inclusion criteria were found through a literature search, and analyzed in descriptive statistics. A total of 10 cases were included in the study with a median age of 9.5 years and a male-to-female ratio of 9:1. The median duration of symptoms was 5.5 weeks with 3 cases having jaundice before the symptoms of lymphoma. The median bilirubin level was 8.4mg/dL. Seven cases received modified chemotherapy, and 5 used ursodeoxycholic acid. The survival rate was 50%. Normalization of liver functions after the lymphoma treatment was observed in 4 cases and was the only statistically significant factor (P=0.01) associated with the outcome. This is a rare entity in the pediatric population with a guarded prognosis comparable to the adult counterparts but a marked male predominance.

COVID-19-induced paraneoplastic polydermatomyositis seropositive for Brucella spp antibodies

Paraneoplastic syndromes, including paraneoplastic dermatoses, represent a pressing problem for dermatovenereologists, infectious disease specialists and therapists due to the necessity of having broad knowledge in related disciplines. Our article examines a clinical case of the onset of paraneorplastic polydermatomyositis against the background of a new coronavirus infection in a patient with exacerbation of paranoid schizophrenia. When paraneoplastic syndrome manifested itself in this clinical situation, a differential diagnostic search was carried out at the junction of several nosological units, such as the locomotor primary latent form of brucellosis, trichinosis, polydermatomyositis, and steroid myopathy. Taking into account the epidemiological history and the fact of the patient’s residing in a rural area, it was first necessary to exclude the infectious nature of these manifestations, as well as autoimmune pathology involving muscles and skin. A wide range of laboratory and instrumental examination methods were carried out, including false-positive IgM results for the causative agent of brucellosis, which can be explained within the framework of paraneoplastic syndrome and the tumor’s synthesis of biologically active substances. The results formed the basis for the entire clinical picture of the disease. Identification of the oncological process, which became possible with the appearance of pathognomonic clinical symptoms, made it possible to establish the histological picture of the disease and to launch treatment for this patient. In addition, the final clinical diagnosis was complicated by the presence of an underlying disease that required constant use of antipsychotics and the lack of control of the ongoing basic pharmacotherapy in the form of monitoring prolactin levels and assessing the general condition of the body systems.

Association of ovarian teratoma with anti-N-methyl-D-aspartate receptor encephalitis: a case report and narrative review.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a potentially life-threatening autoimmune disorder which is strongly associated with ovarian teratomas in young female patients. The primary aim is to highlight the importance of considering NMDAR encephalitis in the differential diagnosis of young female patients presenting with acute or subacute neuropsychiatric symptoms, especially when accompanied by ovarian teratomas. This case report and literature review detail the presentation, diagnosis, and treatment of a 35-year-old G4P3 Indigenous woman who initially presented with neuropsychiatric symptoms and fever, having a history of extensive drug and alcohol use. Misdiagnosed initially, the patient's lack of response to standard treatments led to further investigations, revealing paraneoplastic anti-NMDAR encephalitis secondary to a left ovarian teratoma. The report examines the treatment regimen followed, including prednisolone, intravenous immunoglobulin, rituximab injections, and laparoscopic bilateral salpingo-oophorectomy. This case underscores the critical need for increased clinical vigilance for anti-NMDAR encephalitis in patients, particularly young females, presenting with neuropsychiatric symptoms and potential ovarian teratomas. The literature review accompanying the case report provides valuable insights into the presentation, diagnosis, and management of this complex condition. Lastly, this study emphasised the diagnostic challenges inherent in paraneoplastic neuropsychiatric syndromes, advocating for a multidisciplinary approach in similar clinical scenarios.

Phosphaturic Mesenchymal Tumor and Tumor-Induced Osteomalacia: A Report of 5 Cases, Including 2 Skull Base Cases With Arterial Spin Label Perfusion.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired bone mineralization secondary to secretion of fibroblast growth factor 23 (FGF23) from mesenchymal tumors (phosphaturic mesenchymal tumors, PMTs). PMTs have wide anatomical distribution but typically affect extremities and craniofacial bones. Diagnosis of TIO/PMT is often delayed, and a high index of suspicion is essential in patients with unexplained fractures, but many physicians lack familiarity with TIO/PMT and simply attribute fractures to the more common diagnosis of osteoporosis. We present 5 cases of TIO, with 4 having long histories of multiple insufficiency fractures prior to recognition of TIO and localization of a PMT. Four patients were treated surgically, while 1 preferred medical management. Two patients had lesions localized to the skull base, both of which showed marked hypervascularity on arterial spin label perfusion imaging. Thus, arterial spin label may not only help to localize these tumors, but may also be a helpful supplemental imaging finding in supporting this diagnosis. PMT should be considered in the differential diagnosis for hypervascular skull base masses, especially if the patient has any history of insufficiency fracture or imaging evidence of osteopenia, as early diagnosis of TIO can help prevent disabling complications.

Hypercalcemia as a Paraneoplastic Syndrome in Bladder Squamous Cell Carcinoma: A Case Report

Hypercalcemia as a Paraneoplastic Syndrome in Bladder Squamous Cell Carcinoma: A Case Report

Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance.

Autoimmune encephalitis (AIE) and paraneoplastic neurologic syndromes (PNSs) encompass a heterogeneous group of antibody-associated disorders. Both the number of syndromes and commercially available antibody tests have increased considerably over the past decade. High-quality population-based data on epidemiology of these disorders and real-world performance of antibody tests are needed. In this nationwide retrospective cohort study, we identified all serum and CSF samples tested for antibodies against intracellular antigens (IAs: Hu [ANNA1], Yo [PCA1], CV2 [CRMP5], Ri [ANNA2], Ma1, Ma2 [Ta], amphiphysin, GAD65, GFAP, KLHL11, CARP VIII) or extracellular antigens (EAs: NMDAR, LGI1, Caspr2, GABA-B-R, GABA-A-R, AMPAR, DPPX, GlyR, mGluR1, VGCC, IgLON5, Tr [DNER]) between January 2016 and December 2021 in the Netherlands. Nationwide coverage was guaranteed for all antibodies except anti-GAD65 and anti-VGCC. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV); obtained clinical information about patients who tested positive; assigned diagnosis of AIE/PNS according to diagnostic criteria; and calculated incidence rates for IA, EA, and individual antibody-associated syndromes. In the study period, 2,877 (9.5%) of 30,246 samples, belonging to 1,228 patients, tested positive. Sensitivity and specificity were high (>95%) to very high (>99%) for most tests in both serum and CSF. PPVs for several tests were moderate to poor, especially for serum testing of IA antibodies (25%-80%). Clinical data were available for 940 (76.5%) of 1,228 patients. A total of 578 AIE/PNS diagnoses were made. The incidence rate for AIE/PNS (per million person-years) increased from 4.70 (95% CI 3.72-5.85) in 2016 to 5.76 (4.69-7.00) in 2021. Overall, the incidence rate was 5.57 (5.13-6.05), 2.96 (2.64-3.31) for the EA and 2.61 (2.31-2.94) for the IA subgroup. The 4 most common AIE/PNS types were anti-NMDAR, anti-LGI1, anti-Hu, and anti-GAD65, together comprising almost two-thirds of all diagnoses (364/578, 63.0%). Most commercial antibody tests perform well overall, but important pitfalls remain. Although almost all tests had high specificity, PPV was only modest in the setting of these rare diseases and mass testing. We observe trends toward increasing incidence of antibody-associated AIE/PNS.

Pre-existing Lambert-Eaton Myasthenic Syndrome and scleroderma in a patient with neuroendocrine carcinoma undergoing immune checkpoint inhibitor cancer immunotherapy

IntroductionParaneoplastic neurological syndromes (PNS) can worsen with immune checkpoint inhibitor (ICI) cancer immunotherapy. Case reportA 66-year-old female with paraneoplastic Lambert-Eaton Myasthenic Syndrome (LEMS), which led to the diagnosis of metastatic neuroendocrine carcinoma, was treated with intravenous immune globulin (IVIg) (with minimal response), chemotherapy, and radiation, resulting in neurological improvement. However, sclerodermatous changes developed after a year. Due to cancer progression, dual ICI therapy was initiated, and the patient remained stable for eight months until the progression of both LEMS and cancer, ultimately leading to death. DiscussionThis case highlights the challenges of managing pre-existing PNS during ICI therapy, emphasizing the need for a multidisciplinary approach and the consideration of unusual clinical presentations in therapeutic decision-making.

Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma.

To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC). Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 17 patients were identified in our center and 30 in the systematic review, resulting in an overall cohort of 47 patients. The median age was 65 years (range 41-90), and 30 of 46 (65%) were men. Lambert-Eaton myasthenic syndrome (LEMS) (14/47, 29%), rapidly progressive cerebellar syndrome (11/47, 23%), and encephalomyelitis (EM) (8/47, 17%) were the most common associated clinical phenotypes. The most frequently associated neural antibodies (Abs) were voltage-gated calcium channel (VGCC)-Abs (14/45, 31%), followed by Hu-Abs (8/45, 17%) and neurofilament (NF)-Abs (8/45, 17%). Patients with NF-Abs only exhibited CNS disorders (8/8, 100%) and often had antibodies against >1 NF subunit (6/8, 75%). At onset, 26 of 43 patients (60%) had no identifiable primary skin tumor but had lymph node metastasis; these patients were more frequently men (21/26, 80%, vs 7/17, 41%; p = 0.007), had more frequently VGCC-Abs (12/26, 46%, vs 2/17, 11%, p = 0.02) predominantly among those with LEMS, and presented reduced mortality than patients with a known primary tumor (5/25, 20%, vs 8/15, 53%; p = 0.02). MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.

Successful Adjunctive Treatment of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) with High-Dose Intravenous Immunoglobulin Therapy (IVIG).

Purpose: The management of bilateral diffuse uveal melanocytic proliferation is controversial, with most earlier reports advocating for plasmapheresis. Here, we report a case of bilateral diffuse uveal melanocytic proliferation secondary to gastric adenocarcinoma that was successfully treated with adjunctive intravenous immunoglobulin, using a loading dose followed by a treat-and-extend strategy. Methods: Clinical case report with 3 years of follow-up including serial ophthalmologic examinations. Functional assessments included visual acuity and subjective visual complaints. Periodic anatomic assessments were performed including serial optical coherence tomography, ultra-widefield fundus imaging, multimodal angiography, and ophthalmic ultrasound. Results: A 75-year-old man presented with a 6-month history of blurry vision and difficulty with dark and light adaptation in both eyes. A diagnosis of bilateral diffuse uveal melanocytic proliferation was established based on clinical findings and subsequent discovery of an underlying gastric malignancy; the diagnosis of a paraneoplastic syndrome was further substantiated by documentation of cancer-associated antiretinal antibodies and serum reactivity against human retina by immunohistochemistry. Treatment with high-dose (2 g/kg) intravenous immunoglobulin was initiated with biweekly, followed by monthly, then q2-3 monthly dosing intervals. Meanwhile, the patient received surgical resection and systemic chemotherapy resulting in complete radiographic remission of the primary cancer. Over the course of 3 years, the patient has demonstrated clinically significant improvements in visual acuity and subjective visual function. Rapid and sustained anatomic improvements were observed in serous retinopathy and choroidal thickness. Conclusion: Intravenous immunoglobulin may be a viable adjunctive treatment option for some patients with bilateral diffuse uveal melanocytic proliferation.

Paraneoplastic acral vascular syndrome in a patient with advanced oropharyngeal squamous cell carcinoma; case report and literature review

Paraneoplastic acral vascular syndrome in a patient with advanced oropharyngeal squamous cell carcinoma; case report and literature review

Paraneoplastic Resolution Holds Prognostic Utility in Patients with Metastatic Renal Cell Carcinoma.

Background/Objectives: The presence of paraneoplastic syndromes (PNS) in patients with renal cell carcinoma (RCC) is associated with worse survival; however, little is known about whether resolution of PNS after intervention has any prognostic value. We sought to determine if resolution of PNS by one year after cytoreductive nephrectomy was significantly associated with improved overall survival (OS) and cancer-specific survival (CSS). Methods: We retrospectively reviewed a prospectively maintained nephrectomy database for patients with any histology metastatic RCC (mRCC) who underwent nephrectomy between 2000 and 2022. Patients with the necessary laboratory studies available within 90 days before and by one year after surgery were included for study. PNS resolution was defined as an abnormal value compared to established laboratory cutoffs by one year after surgery. Multiple PNS in one patient was allowed, and resolution of each PNS was measured separately. OS and CSS were assessed using Kaplan-Meier curves and Cox proportional hazards models. Results: A total of 253 patients met inclusion criteria. A total of 177 patients (70.0%) met criteria for at least one PNS resolution by one year. Five-year OS and CSS rates were 15.7% and 36.2% for no PNS resolved, 24.5% and 31.6% for 1 PNS resolved, and 43.0% and 58.2% for ≥2 PNS resolved, respectively (p < 0.001). On multivariable analysis, no PNS resolution was associated with worse OS (HR 2.75, p < 0.001) and CSS (HR 2.62, p < 0.001) compared to ≥2 PNS resolved. Conclusions: Resolution of preoperative PNS abnormalities by one year following surgery is associated with improved OS and CSS in patients with mRCC.

First reported case of thymoma-associated multiorgan autoimmunity induced by COVID-19.

Thymoma-associated multiorgan autoimmunity (TAMA) presents with skin symptoms similar to those of graft-versus-host disease (GVHD), liver dysfunction, and enteritis, in the absence of a history of hematopoietic stem cell or bone marrow transplantation. TAMA is a type of paraneoplastic syndrome associated with thymoma. Its etiology is unclear but is thought to be a result of breakdown of immune tolerance. Histopathologically, TAMA is characterized by epidermal acanthosis with parakeratosis, individual cell keratinization, liquefaction degeneration, and intraepidermal infiltration of CD8-positive lymphocytes. A 64-year-old female patient with a history of myasthenia gravis and thymoma treated with prednisolone (10 mg/day) and cyclosporine (150 mg/day) experienced erythema on her trunk after coronavirus disease 2019 (COVID-19) onset. A psoriatic drug eruption was suspected and the possible causative drug was discontinued, but the skin rash failed to improve. A skin biopsy demonstrated GVHD-like histopathological findings. Diarrhea, abdominal pain, and duodenal perforation occurred concurrently, leading to the diagnosis of TAMA. Thereafter, the patient continued prednisolone and cyclosporine in the same doses as the TAMA treatment and added topical steroids. During the disease course, candida fungemia and cytomegalovirus infection developed, resulting in the patient's death. The TAMA was considered to have been caused by the release of inflammatory cytokines, autoreactive T cell activation, and regulatory T cell dysfunction induced by COVID-19.

Systemic effect of the oncological process on the dog’s body

The article presents the results of an analysis of a non-randomized study of the prevalence of paraneoplastic syndromes in primary spontaneous malignant neoplasms in dogs. The study was conducted in 2022–2024 on the basis of the Department of Diseases of Small Domestic, Laboratory and Exotic Animals and the Research Laboratory of Oncology, Ophthalmology and Animal Biochemistry of the Russian Biotechnological University “ROSBIOTECH”. The object of the study were 948 dogs with primary spontaneous malignant neoplasms confirmed by morphological methods.The aim of the work was to study the frequency of paraneoplastic syndromes in dogs with neoplasia.The diagnosis of paraneoplastic syndrome was made by excluding other possible etiological factors for the development of clinical and laboratory abnormalities identified during a comprehensive examination of dogs. As a result of the study, the incidence of paraneoplasia was 54.54% of cases. Hematological (44.41%) and gastrointestinal (37.13%) paraneoplastic syndromes were most often recorded, less often endocrine (3.27%) and ophthalmological (3.38%), extremely rarely renal (1.27%), osteoarticular (0.42%) and dermatological (0.42%). The main hematological manifestations of the systemic effect of the oncological process were: anemia (12.87%), neutrophilic leukocytosis (12.76%) and thrombocytopenia (8.86%). Gastrointestinal paraneoplastic syndrome in most cases was manifested by a decrease in body weight (33.65%) and hyporexia (18.04%), inflammatory and erosive ulcerative lesions of the gastrointestinal tract (7.59%). During the study, a case of a nonspecific systemic reaction to a malignant tumor in the form of fever in the absence of infectious and inflammatory processes (0.11%) was registered.

Paraneoplastic neurological syndrome and its impact on the treatment outcomes of small-cell lung cancer: A single-center retrospective analysis.

Paraneoplastic neurological syndrome (PNS) is associated with small-cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real-world data from patients with PNS complicated by SCLC. Patients diagnosed with Stage II-IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3-4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23). A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS.

Tumor-induced phosphopenic osteomalacia: modern approaches to diagnostics and treatment

Phosphopenic osteomalacia (PPOM) is a rare variant of paraneoplastic syndrome caused by tumor synthesis of fibroblast growth factor 23 (FGF23). FGF23 secretion leads to a decrease in phosphate reabsorption and calcitriol levels, which leads to the development of severe hypophosphataemia and hypocalcaemia. FGF23 synthesis is predominantly associated with benign mesenchymal tumors, but has also been described in malignant neoplasms. The main clinical manifestations of PPOM are generalized myalgias and myopathy, ostealgia, pathological fractures, etc. The diagnosis of the disease requires a step-by-step investigation using somatostatin receptor-based imaging techniques, as these have the highest sensitivity for the detection of neoplasms causing osteomalacia. Surgical intervention is clearly the treatment of choice. Promising non-surgical methods include treatment with burosumab and somatostatin analogues.

Oral Manifestations in Paraneoplastic Syndromes: ASystematic Review and Meta-Analysis.

This study examined the prevalence of oral signs and symptoms in paraneoplastic syndromes. A systematic search on oral paraneoplastic syndromes was conducted in MEDLINE/PubMed, Ovid, and Scopus databases from inception to April 1, 2024. Risk of bias was evaluated using the MURAD or Quality in Prognosis Studies tools, and a random-effects meta-analysis was performed. Evidence quality was rated using the GRADE approach. The study sample comprised 811 participants from 487 studies. Oral manifestations predominantly affected patients with paraneoplastic pemphigus, mucous membrane pemphigoid, and acanthosis nigricans. Palate is the most frequently affected site (18.2%; 95% confidence interval [CI] 14.7-21.9), while erosion was the most common lesion type (83.3%; 95% CI 72.2-92.0) associated with the underlying malignancy. The prevalence of death in people with paraneoplastic syndromes was 50.9% (95% CI 39.9-61.7), while the prevalence of remission after neoplasm treatment was 63.4% (95% CI 49.9-76.0). GRADE assessment revealed uniformly low to very low certainty for all outcomes studied. Further research is needed to understand the mechanisms behind these oral manifestations, which is crucial for earlier paraneoplastic syndrome diagnosis and optimal patient management. PROSPERO number: CRD42022328921.