Dermatomyositis in a young patient: A rare paraneoplastic syndrome of renal cell carcinoma.

Introduction: Paraneoplastic syndromes are frequent in patients with renal cell carcinoma. Dermatomyositis is an idiopathic inflammatory myopathy that may be associated with neoplasms. This case aims to describe the rare association of dermatomyositis with renal cell carcinoma and to increase clinical suspicion of this neoplasm when systemic rheumatologic symptoms are present. Case presentation: A 35-year-old female developed severe rheumatologic symptoms (progressive muscle weakness, heliotrope rash, and Gottron's papules). Clinical and laboratory findings indicated dermatomyositis. During the investigation, computed tomography revealed a left kidney solid mass. She underwent a left radical nephrectomy, and histology confirmed renal cell carcinoma. After 3 months, dermatomyositis manifestations disappeared and the patient withdrawn steroid therapy. Conclusion: Most paraneoplastic syndromes associated with renal cell carcinoma are only cured with nephrectomy. We highlight the potential role of surgery in dermatomyositis caused by renal cell carcinoma. The recurrence of symptoms related to the syndrome should alert for disease progression.

Renal cell carcinoma preceded by a rheumatoid­like paraneoplastic syndrome: A case report.

A man with polycystic kidney disease and a history of renal transplantation at the age of 55 years developed seronegative rheumatoid arthritis (RA) at the age of 68 years. Treatment with a biological derivative led to remission; however, the patient relapsed 2 years later. After being switched to baricitinib, the patient again achieved remission. After 2 years, when the patient was aged 72 years, RA recurred, and the right native kidney became enlarged due to the presence of a large tumor. Surgical nephrectomy was performed, and the tumor was classified as renal cell carcinoma (RCC), not otherwise specified. The cancer tissue comprised sarcomatoid and rhabdoid cells with marked neutrophil infiltration, and the tumor cells were positive for interleukin-6. The patient, aged 73 years, experienced a resolution of joint pain following surgical intervention; however, they died because of systemic metastases ~10 weeks post-operation. Based on the clinical course, the RA-like lesions and subsequent RCC were considered to represent a paraneoplastic syndrome.

Human stem cell-derived neurons and astrocytes to detect novel auto-reactive IgG response in immune-mediated neurological diseases.

Background and objectives: Up to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known central nervous system (CNS) antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and cerebrospinal fluid (CSF) using neurons and astrocytes derived from human-induced pluripotent stem cells (hiPSCs). Methods: Human iPSC-derived astrocytes or neurons were incubated with serum/CSF from 99 patients [42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND)]. The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG binding to fixed CNS cells was detected using fluorescently-labeled antibodies and analyzed through automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout. Results: Using our CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 subjects. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases, and to both cell types in two cases, as confirmed by microscopy single-cell analyses. Highlighting the significance of our comprehensive 96-well CBA assay, neural-specific antibody binding was more frequent in IND (15 of 42) than in NIND patients (4 of 57) (Fisher's exact test, p = 0.0005). Two of four AQP4+ NMO and four of seven definite AIE/PNS with intracellular-reactive antibodies [1 GFAP astrocytopathy, 2 Hu+, 1 Ri+ AIE/PNS)], as identified in diagnostic laboratories, were also positive with our CBA. Most interestingly, we showed antibody-reactivity in two of six seronegative NMOSD, six of 12 probable AIE/PNS, and one of 13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC-detected antibody binding in 13 versus zero patients, respectively, establishing the specificity of the detected antibodies for neural tissue. Conclusion: Our unique hiPSC-based CBA allows for the testing of novel neuron-/astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in established routine laboratories, opening new perspectives in establishing a diagnosis of such complex diseases.

[Muscle pain in myositis in a young female patient: what is behind this?] / Muskelschmerzen bei Myositis bei einer jungen Patientin ­ was steckt dahinter?

Myositis is a connective tissue disease which is most frequently diagnosed in women aged 40-60 years. Due to a clear association with underlying malignant diseases, general tumor screening is recommended whenever it is diagnosed. Colorectal carcinoma (CRC) is a common malignant disease, and the typical at-risk group comprised, to date, patients older than 55 years. However, with the rising incidence of so-called early-onset colorectal carcinoma (EO-CRC), an increasingly important patient population is emerging in the 20- to 50-year age range. One reason for the rising incidence is suggested to be an increase in classic risk factors at younger ages. Here, the case of a 34-year-old female patient who presented with the leading paraneoplastic syndrome of myositis and was diagnosed with a sporadic form of CRC is reported. Monitoring of known risk factors as early on as in young adulthood and greater attention in the presence of symptoms such as gastrointestinal hemorrhage or paraneoplastic syndromes seem necessary to compensate for the time delay in diagnosis that currently still exists and the associated worse oncologic outcome.

Paraneoplastic Syndrome After Kidney Transplantation: Frequency, Risk Factors, Differences to Paraneoplastic Occurrence of Glomerulonephritis in the Native Kidney, and Implications on Long-Term Kidney Graft Function.

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney transplant recipients, due to factors inherent to concomitant medication and common comorbidities. Recent advances in the field of molecular and clinical nephrology led to a significant improvement in our understanding of glomerular diseases and their more targeted treatment. On the other hand, introduction of novel anticancer drugs tremendously increased patients' survival, at the cost of kidney-related side effects. Our review aims to provide insights into diagnosis and treatment of paraneoplastic glomerular diseases, with a special attention to kidney transplant recipients.

Paraneoplastic dermatomyositis and Hodgkin's lymphoma in a 14-year-old girl: a case report and literature review.

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune myopathy whose main clinical manifestations include a characteristic rash, symmetrical proximal muscle weakness, and elevated muscle enzymes. While approximately one-third of adult patients with dermatomyositis (DM) develop malignancies, typically within a year of diagnosis, this phenomenon is not commonly observed in patients with JDM. In this study, we present a rare case of both JDM and Hodgkin's lymphoma (HL) diagnosed in an adolescent female patient. Case description: A 14-year-old girl with proximal muscle weakness and myalgia for 8 weeks was admitted to the hospital and ultimately received a diagnosis of DM. A thorough physical examination revealed enlarged lymph nodes on both sides of the cervical, and a lymph node biopsy was performed to diagnose HL. After she underwent radiotherapy and chemotherapy, her symptoms of both HL and DM were alleviated. Conclusion: The phenomenon of JDM as a paraneoplastic syndrome associated with HL is very rare. Thus, routine cancer screening for DM in adolescents is currently not recommended. The diagnosis of JDM requires a detailed physical examination, and further tumor screening is necessary for patients with unusual physical findings, such as atypical rashes, enlarged lymph nodes, and enlargement of the spleen and/or liver. Even if no malignancy is detected when JDM is diagnosed, long-term follow-up is necessary.

Microangiopathic Hemolytic Anemia as a Paraneoplastic Syndrome in a Patient with Metastatic Gastric Cancer.

Cancer-associated microangiopathic hemolytic anemia (CA-MAHA) is a rare paraneoplastic syndrome. The most effective approach to treating CA-MAHA is to address the underlying malignancy. Documented cases of CA-MAHA are limited to fewer than 50 patients in the literature. Herein, we present a 51-year-old female patient who developed CA-MAHA as a complication of gastric adenocarcinoma. Despite receiving neoadjuvant and adjuvant chemotherapy for gastric cancer, the patient experienced disease progression with metastatic lesions in the liver, pancreas, and other sites. This report highlights the challenges in diagnosing and distinguishing CA-MAHA from other similar conditions such as disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and rheumatological paraneoplastic syndromes. Additionally, it concludes that CA-MAHA is associated with a poor prognosis and limited clinical benefit from treatment, emphasizing the need for early diagnosis and effective management strategies.

Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis Presenting as Refractory Seizures.

Autoimmune encephalitis (AE) is a rare immune-mediated disorder comprised of non-infectious neuroinflammatory disease processes. Clinical presentation overlaps with a broad range of neurodegenerative disorders and infectious encephalitis; therefore, AE remains a diagnosis of exclusion. Patients may present with nonspecific symptoms such as psychiatric disturbances, cognitive deficits, seizures, movement disorders, and confusion. Prompt diagnosis and management are necessary for patients with AE to decrease mortality and improve quality of life. First-line therapy includes immunosuppression with corticosteroids, intravenous immunoglobulin, and plasmapheresis. We report the case of an 86-year-old female with a medical history of Parkinson's disease who presented with nonspecific seizure-like activity and was diagnosed with AE.

Autoimmune Encephalitis: Insights Into Immune-Mediated Central Nervous System Injury.

Autoimmune encephalitis (AE) is a category of immune-mediated disorders of the central nervous system (CNS) affecting children and adults. It is characterized by the subacute onset of altered mentation, neurocognitive issues, refractory seizures/drug-resistant epilepsy, movement disorders, and/or autonomic dysfunction. AE is mediated by autoantibodies targeting specific surface components or intracytoplasmic antigens in the CNS, leading to functional or structural alterations. Multiple triggers that induce autoimmunity have been described, which are mainly parainfectious and paraneoplastic. The imaging features of AE often overlap with each other and with other common causes of encephalitis/encephalopathy (infections and toxic-metabolic etiologies). Limbic encephalitis is the most common imaging finding shared by most of these entities. Cortical, basal ganglia, diencephalon, and brainstem involvement may also be present. Cerebellar involvement is rare and is often a part of paraneoplastic degeneration. Owing to an improved understanding of AE, their incidence and detection have increased. Hence, in an appropriate setting, a high degree of suspicion is crucial when reporting clinical MRIs to ensure prompt treatment and better patient outcomes. In this review, we discuss the pathophysiology of AE and common etiologies encountered in clinical practice.

Doege-Potter syndrome due to a solitary fibrous tumor of the pleura: a case report.

BACKGROUND: Doege-Potter syndrome is a rare paraneoplastic phenomenon associated with solitary fibrous tumors of the pleura (SFTPs). It is characterized by the presence of severe, sustained, and treatment-refractory hypoglycemia. Hypoglycaemia, which may be the sole symptom at disease onset, is mediated by the secretion of high-molecular-weight insulin-like growth factor (IGF-2). Most tumors exhibit benign behavior, with a 100% survival rate at 5 years. However, 10% of these tumors may display aggressive behavior with local or metastatic recurrence. We present a clinical case of a patient with a benign solitary fibrous tumor of the pleura who presented with symptomatic hypoglycemia and required pulmonary and pleural surgical resection to control the paraneoplastic phenomenon. CASE PRESENTATION: A Hispanic 46-year-old man presented with a 15-day history of transient alterations in consciousness worsened by fasting. The relevant medical history included obstructive sleep apnea treated with continuous positive air pressure (CPAP) and previous smoking. In-hospital studies revealed noninsulinemic hypoglycemia and a benign SFTP. Complete surgical resection was performed while the patient received dextrose fluids and corticosteroids perioperatively for hypoglycemia. Subsequently, the hypoglycemia resolved, and the patient was followed-up without disease recurrence. CONCLUSION: Doege-Potter syndrome is challenging to recognize. However, effective treatment can be achieved with a high survival rate. Raising awareness among healthcare professionals about the recognition of this paraneoplasic syndrome patients will improve diagnostic suspicion, biochemical confirmation, the development of diagnostic and therapeutic guidelines, and the creation of predictive indices for aggressive presentations requiring closer monitoring.

Renal Neoplasms with Concurrent Castleman-Like Regional Lymphadenopathy.

INTRODUCTION: Renal cell neoplasms are known to be associated with paraneoplastic syndromes, and the association with Castleman-like regional lymphadenopathy has been rarely reported. We aim to characterize the association between renal neoplasms and Castleman-like lymphadenopathy. METHODS: A search for renal neoplasms with concurrent Castleman-like lymphadenopathy in one single medical institution from 2000 to 2023 resulted in 4 specimens. A literature search for "Castleman" and "renal neoplasm" resulted in 8 reports. Patients' demographics, clinical presentation, gross and histologic features, results of ancillary studies, treatment, and follow-up were evaluated. RESULTS: Our patients included 3 men and 1 woman, with a mean age of 60 years. Four different subtypes of renal neoplasms were diagnosed, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, and mucinous cystadenoma of the renal pelvis. For Castleman-like regional lymphadenopathy, 2 were plasma-cell predominant, and 2 were hyaline-vascular. After a median follow-up of 84 months, all patients were alive with no recurrence or progression of Castleman-like features following nephrectomies. CONCLUSION: Castleman-like regional lymphadenopathy should be considered in patients with renal tumors and lymphadenopathy. Although more prevalent in clear cell RCC, it can be also associated with other renal neoplasms. The concurrent lymphadenopathy was remitted following the renal tumor resections.

Ectopic Cushing syndrome in metastatic castration­resistant prostate cancer: A case report and review of literature.

Cushing's syndrome (CS), as a result of ectopic adrenocorticotropic hormone (ACTH) production, constitutes a common paraneoplastic manifestation of various malignancies, with the most common being small cell lung carcinoma. In the literature, fewer than fifty cases associating ectopic CS with prostate cancer have been documented. In the present study, the case of a 76-year old man suffering from castration-resistant prostate adenocarcinoma that had been treated with enzalutamide and luteinizing hormone-releasing hormone (LHRH) analogue for the last four years is presented. The patient presented to the emergency department with lower extremity muscle weakness, bradypsychia and hypokalemia. Following a thorough diagnostic evaluation, hypercortisolemia was identified. No suppression after low- and high-dose dexamethasone challenge, increased cortisol 24 h excretion and normal pituitary magnetic resonance imaging led to the diagnosis of ectopic CS. Immediate targeted therapy was initiated with adrenal steroidogenesis inhibitors, including metyrapone and ketoconazole along with chemotherapy with docetaxel and prednisolone. There was a remarkable decrease in cortisol levels within days and hospitalization was no longer required. The patient managed to complete three cycles of chemotherapy; unfortunately, he succumbed within three months of the diagnosis of ectopic CS. In the present study, all existing cases of paraneoplastic CS related to prostate cancer are reviewed. The aim of the current study was to highlight the need of early diagnosis and treatment of this entity as it may present with atypical clinical findings and potentially evolve to a life-threatening condition.

Paraneoplastic syndromes in patients with melanoma.

Paraneoplastic syndromes are a group of rare clinical conditions characterized by a diverse array of systemic manifestations that arise in association with malignant tumours, often due to the production of bioactive substances by the tumour or an autoimmune response to the tumour. Melanoma, a malignant skin neoplasm originating from melanocytes, has been associated with various paraneoplastic syndromes. This paper provides an overview of the key paraneoplastic syndromes observed in patients with melanoma. Paraneoplastic syndromes in melanoma can manifest with neurological, dermatological, endocrine, haematological, and rheumatological symptoms, among others. Melanoma-associated retinopathy was the most reported paraneoplastic syndrome; this entity is characterized by a spectrum of retinal abnormalities. Paraneoplastic neurological syndromes, such as paraneoplastic encephalitis and paraneoplastic cerebellar degeneration, are among the most frequently reported. The pathophysiology of paraneoplastic syndromes often involves the production of autoantibodies against neuronal or tumour antigens, immune-mediated reactions, or the release of cytokines and growth factors from the tumour. Management strategies for paraneoplastic syndromes associated with melanoma primarily focus on treating the underlying malignancy, which may lead to resolution or improvement of the paraneoplastic manifestations. Immune-modulating therapies, including corticosteroids, intravenous immunoglobulins, and plasmapheresis, may be considered in selected cases to ameliorate symptoms and suppress the autoimmune response. In conclusion, paraneoplastic syndromes in patients with melanoma are a complex and diverse group of clinical entities with a broad range of presentations. Further research is needed to enhance our understanding of the mechanisms and therapeutic options for paraneoplastic syndromes associated with melanoma.

Case Report: Longitudinal Evaluation and Treatment of a Melanoma-Associated Retinopathy Patient.

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR. Electroretinograms are used to measure the impact of TRPM1 autoantibodies on ON-BC function and represent another important diagnostic tool for MAR. To date, MAR case reports have included one or both diagnostic components, but only for a single time point in the course of a patient's disease. Here, we report a case of MAR supported by longitudinal analysis of serum autoantibody detection, visual function, ocular inflammation, vascular integrity, and response to slow-release intraocular corticosteroids. Integrating these data with the patient's oncological and ophthalmological records reveals novel insights regarding MAR pathogenesis, progression, and treatment, which may inform new research and expand our collective understanding of the disease. In brief, we find TRPM1 autoantibodies can disrupt vision even when serum levels are barely detectable by western blot and immunohistochemistry; intraocular dexamethasone treatment alleviates MAR visual symptoms despite high levels of circulating TRPM1 autoantibodies, implicating antibody access to the retina as a key factor in MAR pathogenesis. Elevated inflammatory cytokine levels in the patient's eyes may be responsible for the observed damage to the blood-retinal barrier and subsequent entry of autoantibodies into the retina.

Research progress of malignant peritoneal mesothelioma with paraneoplastic syndrome: A review.

Malignant peritoneal mesothelioma (MPM) is a rare and invasive tumor, and some patients will develop paraneoplastic syndrome (PS) during the course of the disease. This review summarizes PS associated with MPM, focusing on the clinical characteristics and treatment progress in hematological, endocrine, rheumatic, neurological, urinary, and other systems to decrease missed diagnosis and misdiagnosis, help early diagnosis and prompt treatment, and provide guidance for the clinical decision-making of this kind of patients.

Nephrotic syndrome associated with solid malignancies: a systematic review.

BACKGROUND: Nephrotic syndrome (NS) can occur as a paraneoplastic disorder in association with various types of carcinoma. However, paraneoplastic nephrotic syndrome (PNS) is often misdiagnosed as idiopathic nephrotic syndrome or as an adverse effect of oncology treatment, leading to delayed diagnosis and suboptimal treatment. The characteristics of NS associated with solid malignancies are not yet elucidated. We systematically summarized the clinical data for 128 cases of NS combined with solid malignancies with the aim of informing the clinical management of PNS. METHODS: We searched the PubMed database for articles published from the date of inception through to October 2023 using the following keywords: "cancer" or "malignant neoplasms" or "neoplasia" or "tumors" and "nephrotic syndrome", "nephrotic" or "syndrome, nephrotic". All data were extracted from case reports and case series, and the extraction included a method for identifying individual-level patient data. RESULTS: A literature search yielded 105 cases of PNS and 23 of NS induced by cancer therapy. The median age at diagnosis was 60 years, with a male to female ratio of 1.8:1. In patients with PNS, manifestations of NS occurred before, concomitantly with, or after diagnosis of the tumor (in 36%, 30%, and 34% of cases, respectively). Membranous nephropathy (49%) was the most prevalent renal pathology and found particularly in patients with lung, colorectal, or breast carcinoma. Regardless of whether treatment was for cancer alone or in combination with NS, the likelihood of remission was high. CONCLUSION: The pathological type of NS may be associated with specific malignancies in patients with PNS. Prompt identification of PNS coupled with suitable therapeutic intervention has a significant impact on the outcome for patients.

A Cadaveric Case of Bilateral Adrenal Hyperplasia With Lung Cancer: A Paraneoplastic Syndrome?

Bilateral adrenal hyperplasia associated with primary lung cancer may arise from either an adrenocorticotropic hormone (ACTH)-dependent paraneoplastic syndrome or metastatic hyperplasia. Ectopic Cushing's syndrome manifests as a paraneoplastic syndrome characterized by the secretion of ACTH from malignant cells. This secretion can in turn overstimulate the adrenal cortex, resulting in adrenal cortical hyperplasia followed by hypercortisolism. Though rare, lung cancer can metastasize to the adrenal glands bilaterally, occasionally resulting in hemorrhage causing a rapid increase in size. This cadaveric report aims to delineate an unusual case of metastatic lung cancer, presenting with bilateral adrenal hyperplasia and two abdominal aortic aneurysms (AAA). An 84-year-old white male cadaver was dissected during routine coursework. Dissection of the right lung revealed a pale-yellow mass measuring 10.0 x 7.4 x 7.0cm. An irregularly defined, necrotic, ulcerated lesion measuring 5.5 x 4.5 x 3.3cm was evident on the lateral surface of the left shoulder, consistent with a history of metastatic lung carcinoma. Upon abdominal dissection, bilaterally enlarged adrenal glands and two AAAs were observed. These AAAs measured 6.0cm and 11.0cm at their respective widest transverse diameters. The right and left adrenal glands measured 10.0 x 6.5 x 4.5cm and 7.3 x 4.7 x 3.5cm, respectively. We aim to discuss the possible pathophysiological correlation of these unusual findings in this cadaver.

Understanding Palmar Fasciitis and Polyarthritis Syndrome as a Rheumatologic Paraneoplastic Syndrome: A Case Report.

Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint pains. It is known to be associated with gynecological malignancy, especially ovarian adenocarcinoma, gastric cancer, pancreatic, prostate, breast, and lung cancer. We present a unique case of a 75-year-old Caucasian female with PFPAS preceding the diagnosis of ovarian cancer by eight months. Our case highlights the importance of considering PFPAS as a potential paraneoplastic syndrome. It underscores the need for increased awareness and further studies to enhance the early detection of underlying malignancies in patients presenting with similar nonspecific hand symptoms.

Hide-and-Seek With Spindle-Cell-Component-Poor Metaplastic Thymoma.

Metaplastic thymoma is a rare biphasic thymic tumor with indolent behavior and recurrent YAP1::MAML2 gene rearrangement. Although the diagnosis of this tumor is usually straightforward based on hematoxylin and eosin (H&E) findings alone, cases with scant spindle-cell ("pseudosarcomatous stroma") components can be easily confused with more commonly occurring type A thymoma. We present a case of metaplastic thymoma with a sparse stroma-like spindle-cell component, discussing its histological and immunohistochemical hints and drawing attention to the visual similarity to type A thymoma. This is also the first published case of metaplastic thymoma with associated psoriasis.