Paraneoplastic Manifestation Research Articles

Cancer incidence and mortality among patients with new-onset atrial fibrillation: A population-based matched cohort study

BackgroundUnderstanding the risk of cancer after the diagnosis of another condition can present opportunities for earlier diagnosis. We examined the risk of cancer diagnosis conditional on prior diagnosis of atrial fibrillation (AF). MethodsLinked electronic health records were used to identify patients aged ≥18 with new-onset AF and age-sex-matched controls. Cumulative incidence of and mortality from cancer (overall and cancer-site specific) within three months, three months to five years and beyond five years from diagnosis of AF were examined. Findings were further validated using Mendelian randomisation (MR). ResultsThe cohort included 117,173 patients with new-onset AF and 117,173 matched controls (median age 78). In the first three months, 2.2% of AF patients were diagnosed with cancer vs. 0.47% in controls (relative risk: 4.7 [95%CI 4.2-5.4] in men and 4.4 [95%CI 3.8-5.0] in women). Nearly 80% of cancers related to thoracic or abdominal organs. Differences in cumulative incidence were only evident in women between three months and five years (subdistribution hazard ratio=1.1 [95%CI 1.01-1.12]) and absent in all patients beyond five years. MR analysis did not support the presence of a causal association between AF and major cancer subtypes. ConclusionThere is a large short-term increase in cancer incidence and mortality following new-onset AF. The findings may reflect incidental identification of AF or paraneoplastic manifestation. New-onset AF confers high short-term risk of cancer diagnosis, at levels comparable with symptomatic risk threshold mandating urgent assessment for suspected cancer.

Clonal monocytosis of renal significance

Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Kidney abnormalities, including acute kidney injury and chronic kidney disease, are frequent in patients with chronic myelomonocytic leukemia and are predictors of worse outcomes. In addition, acute kidney injury/chronic kidney disease often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to acute kidney injury and chronic kidney disease, with special emphasis on chronic myelomonocytic leukemia and lysozyme-induced nephropathy. Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage kidney function. Other etiologies of kidney injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, autoimmune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of kidney injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.

The Constellation of Risk Factors and Paraneoplastic Syndromes in Cholangiocarcinoma: Integrating the Endocrine Panel Amid Tumour-Related Biology (A Narrative Review).

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

Classic Hodgkin Lymphoma presenting as ANA positive chronic papular urticaria like skin lesions – A case report

The skin acts as a natural barrier between internal organs and the external environment. Many haematological neoplasms occur in the skin as a primary malignant transformation, as secondary involvement, or as paraneoplastic cutaneous manifestations. Malignant skin involvement in Hodgkin lymphoma is uncommon while paraneoplastic cutaneous involvement can occur as eczema, pruritus, erythema nodosum, and icthyosiform atrophy.1This case report describes a 25-year-old woman with a persistent pruritic rash, who was treated as chronic papular urticaria, before finally being diagnosed as Classic Hodgkin Lymphoma. This highlights the challenge of early diagnosis of cutaneous manifestations of Hodgkin lymphoma and the importance of considering malignancies in refractory dermatological conditions. This case also suggests a potential role for ANA patterns as diagnostic markers in Hodgkin lymphoma.

Persistent hypoglycemia in patients with liver cancer.

Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child-Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon. Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF). Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor. The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon. Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH-IGF axis.

An Unusual Primary Paraneoplastic Manifestation of Adenocarcinoma of Lung

Carcinoma of lung (CoL) is the fourth most common cancer in India. It is classified as either small-cell or non-small-cell lung cancer, with adenocarcinoma being the most common variant. CoL can present either as paraneoplastic or non-paraneoplastic manifestation. We discuss a case of a patient who had an abrupt onset of sustained ventricular tachycardia and was subsequently diagnosed with metastatic non-small cell lung cancer with no cardiac infiltrates.

Nonbacterial thrombotic endocarditis of mitral valve associated with a lymphoproliferative malignancy: case report and literature review

BackgroundNon-bacterial thrombotic endocarditis (NBTE) is a rare condition marked by sterile vegetations on cardiac valves, often linked to rheumatologic diseases, autoimmune disorders, and advanced solid malignancies. An early diagnosis and treatment of the associated clinical condition are mandatory, although they do not usually eliminate valvular vegetations, making anticoagulation essential to prevent embolic events. Despite variability, the prognosis of NBTE is usually unfavorable due to recurrent embolic events and the severity of the primary condition, typically advanced cancer.Case presentationWe present a case of a 57 years-old male who presented to the emergency department with a 5-day history of painful bilateral digital edema and color change episodes (from pallor to cyanosis). Physical examination revealed erythrocyanosis in the distal extremities, prompting consideration of secondary Raynaud syndrome.Despite medical therapy, progressive digital ischemia led to multiple finger amputations. During etiological investigation, anticoagulation tests and autoimmune analysis yielded negative results. A transesophageal echocardiogram was performed, revealing an irregular hyperechogenic mass on the anterior leaflet of the mitral valve without valve dysfunction, and a thoracic computed tomography scan with contrast showed an enlarged right paratracheal lymph node. Histopathological analysis from a transthoracic needle biopsy of the paratracheal lymph node revealed diffuse large B-cell lymphoma. The patient underwent aggressive R-CHOP chemotherapy, achieving a favorable complete response.ConclusionThis is a particular case involving the occurrence of NBTE and Raynaud phenomenon as the initial paraneoplastic manifestations in a previously healthy young man. Reports of NBTE associated with lymphoproliferative conditions are quite rare, with fewer than ten cases described in the literature. To our knowledge, this is the first case of NBTE specifically associated with diffuse large B-cell lymphoma.

Bullous pemphigoid as a paraneoplastic manifestation of metastatic adenocarcinoma of the lung

A 73-year-old male smoker presented with complaints of fever and multiple clear fluid-filled lesions for 3 months. He was initially being treated for primary bullous pemphigoid but lesions recurred. On a chest X-ray, he was found to have a right hilar mass, and contrast-enhanced computed tomography of the chest revealed a right lung mass lesion with cervical, hilar, and mediastinal lymphadenopathy. A bronchoscopy was done, and bronchoalveolar lavage cytology was suggestive of lung adenocarcinoma. An excision biopsy of the left supraclavicular lymph node showed features consistent with adenocarcinoma lung. Hence, he was diagnosed with metastatic adenocarcinoma of the lung with bullous pemphigoid as a paraneoplastic manifestation. He was subsequently treated with chemotherapy, and his skin lesions resolved.

167 Minimal Change Disease as a Paraneoplastic Manifestation of Small Cell Lung Cancer

167 Minimal Change Disease as a Paraneoplastic Manifestation of Small Cell Lung Cancer

214 Rowell Syndrome as a Paraneoplastic Manifestation of Metastatic Mesothelioma

214 Rowell Syndrome as a Paraneoplastic Manifestation of Metastatic Mesothelioma

Paraneoplastic neurological syndrome associated with onconeural autoantibodies: report of two cases

Paraneoplastic neurological syndromes (PNS) are rare and often severe neurological complications of malignancies, significantly impacting patient prognosis and quality of life. They are characterized by a diverse range of onconeural autoantibodies, with further discoveries likely due to ongoing research. Among these, high-risk autoantibodies primarily target intracellular neural cell antigens. We present cases of lung cancer patients who developed limbic encephalitis and seizures at diagnosis, suggestive of PNS. Each case demonstrated distinct autoantibody profiles. Recognition of these potentially life-altering neurological sequelae, as paraneoplastic manifestations of malignancies, is crucial for physicians. PNS may precede primary cancer diagnosis and substantially affect patient presentation and overall outcome. We provide in detail the diagnostic work-up and available treatment options for these complex cases.

Paraneoplastic Cutaneous Manifestations of Hepatocellular Carcinoma. A Systematic Review and Meta-analysis.

Background: There remains a scarcity of published data on the clinical significance of paraneoplastic cutaneous manifestations in hepatocellular carcinoma (HCC). Method: A systematic search of MEDLINE was performed in December 2022. Inclusion criteria comprised studies reporting on patients with HCC, who had paraneoplastic cutaneous manifestations. Outcomes of interests comprise survival and response to cancer-directed and/or skin directed therapy. Results: A total of 48 studies comprising 60 HCC patients were included in the analysis. The most frequent reported skin abnormalities were dermatomyositis, pityriasis rotunda, and porphyria. Most patients presented with dermatomyositis had underlying viral hepatitis, while all reported porphyria and acanthosis cases were associated with metabolic causes of HCC, such as steatosis. Paraneoplastic skin changes were more common in patients with metastatic disease. Pityriasis Rotunda was associated with the lowest risk of death, (OR: 0.05, 95% CI: 0.003 to 0.89; p = 0.04), while dermatomyositis had a statistically significant higher risk of death (OR: 3.37, 95% CI: 1.01-12.1; p = 0.03). Most patients showed an improvement in their cutaneous abnormalities, following cancer-directed therapy. Conclusion: Paraneoplastic cutaneous manifestations are reported more frequently in patients with a higher burden of disease, especially presence of metastases. Certain cutaneous manifestations have prognostic implication.

Autoantibodies Against Bestrophin in Non-Paraneoplastic Acute Exudative Polymorphous Vitelliform Maculopathy.

Acute exudative polymorphous vitelliform maculopathy (AEPVM) has recently been identified as a paraneoplastic manifestation of various cancers. Yet, the first reported cases of AEPVM in the literature were reported in seemingly healthy individuals. It is not clear whether those individuals harbored unidentified mutations or occult cancers, or truly represented a separate subset of AEPVM. Here, we report two cases of mutation-negative, autoantibody-positive non-paraneoplastic AEPVM. We present multimodal ocular imaging to demonstrate the presentation of this subset of AEPVM. [Ophthalmic Surg Lasers Imaging Retina 2024;55:51-54.].

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.

Relapsing Guillain Barré Syndrom in the AMAN form as a paraneoplastic manifestation of a colon adenocarcinoma

Relapsing Guillain Barré Syndrom in the AMAN form as a paraneoplastic manifestation of a colon adenocarcinoma

Remitting seronegative symmetrical synovitis with pitting edema: An unusual paraneoplastic manifestation of metastatic gastrointestinal cancer.

Remitting seronegative symmetrical synovitis with pitting edema: An unusual paraneoplastic manifestation of metastatic gastrointestinal cancer.

SAT170 Paraneoplastic Hypoglycemia Secondary To Hepatocellular Carcinoma

Abstract Disclosure: S. Dejhansathit: None. N. Sheung: None. A. Akofu: None. A. Uddin: None. F. marium: None. N.G. Akabogu: None. W. Salam, MD: None. Introduction: Hypoglycemia is a known but rare Paraneoplastic manifestation of hepatocellular carcinoma and can lead to significant morbidity and mortality. Even though HCC-related hypoglycemia is a known entity, knowledge about prevention and treatment is limited. Case Description: We report a 36-year-old male with no significant past medical history presenting initially to emergency room for abdominal pain and distension for 2 months. He reported associated 10 pounds unintentional weight loss, fatigue, night sweat and loss of appetite in the past 3 months. The patient noted to have hypoglycemia with blood glucose of 20 mg/dl on admission. He was given 2 ampoules of 50% dextrose and started on 5% dextrose solution intravenously. A CT abdomen and pelvis showed enlarged heterogenous liver with numerous hepatic lesions, concerning for multifocal hepatocellular carcinoma. A liver biopsy was done and confirmed hepatocellular carcinoma. Labs showed alpha fetoprotein level over 60500 ng/mL (0-8.3 ng/mL). Hepatitis B surface antigen was reactive with positive hepatitis B DNA, confirming the diagnosis of chronic hepatitis B infection. Gastroenterology, Oncology and Surgical Oncology were consulted. Patient was felt not to be a good surgical or transarterial chemo-embolization. Endocrinology was consulted when patient develops scrotal and legs swelling after receiving high rate of dextrose fluid since admission to maintain blood glucose. Prednisone 20 mg twice a day was initiated and later increased to 30 mg twice day after 2 days without significant improvement. Prednisone was then switched to dexamethasone 4 mg four times a day for longer half-life. 10% dextrose was slowly decreased from 200cc/hr to100cc/hr but resulted in rebound hypoglycemia. Somatropin 4 mg daily was also added with a goal to further decrease fluid rate in order to help with his discomfort from swelling. 10% dextrose was eventually decreased to 75 cc/hr. Patient subsequently opted for hospice care and passed away within 24 hours. Discussion: The paraneoplastic hypoglycemia associated with HCC can be classified into two categories. Type A hypoglycemia is usually found in the late-stage HCC when tumor burden is high. Type B hypoglycemia is caused by an increase in pro-IGF-2 level that is incompletely processed by the tumor cells, stimulating insulin receptors. It is likely our patient had type A hypoglycemia due to the extensive tumor burden. Overall, paraneoplastic hypoglycemia associated with HCC has very poor prognosis and high mortality rate. There is no single effective management and combination of steroids and Somatropin may provide palliative improvement as seen in our patient. Presentation: Saturday, June 17, 2023

Paraneoplastic syndromes in dermatology - cutaneous manifestations of internal malignancy

Introduction: Cutaneous manifestations linked with internal malignancies can exhibit a wide range of appearances.The ideal paraneoplastic marker is one that exclusively appears with a tumor, vanishes upon tumor treatment, and can potentially reemerge with tumor recurrence or metastasis. They are divided into two main categories: acquired and genetic conditions. Among acquired paraneoplastic syndromes a few are strongly correlated with internal malignancies, others have less pronounced associations. 
 Aim of the study: To review the current literature on the topic of dermatological paraneoplastic syndromes.
 Materials and Methods: We reviewed the literature available in PubMed, using the key words: “paraneoplastic syndromes”, “paraneoplastic dermatoses”, “paraneoplastic syndromes in dermatology”. 
 Results: We presented the most common, selected skin paraneoplastic syndromes. We indicated the types of neoplasms associated with these dermatoses and described their clinical appearance along with potential mechanisms of development. 
 Summary: Timely recognition of paraneoplastic skin manifestations is crucial as they can provide an opportunity for diagnosing and treating the underlying neoplasm. That’s why dermatologists and clinicians should be familiar with this topic to perform an early diagnosis of the underlying malignancy.

Cardiac sarcoma presenting as paraneoplastic arthritis and clubbing: a case report and literature review

BackgroundCardiac tumours are rare, and clinical manifestations depend on the anatomical location. Symptoms can be the result of cardiac outflow anomalies, constitutional features such as fever, loss of weight, and/or paraneoplastic manifestations such as arthritis. To date, there has only been one other case report in the literature of cardiac sarcoma presenting as paraneoplastic arthropathy.Case presentationA 52-year-old woman presented with acute onset corticosteroid-resistant inflammatory polyarthralgia, clubbing and a systolic murmur. Transthoracic echocardiogram revealed a dilated left atrium with an echogenic mass and brain magnetic resonance imaging revealed multiple embolic infarcts. Histopathology following emergency resection showed a Grade 3 left atrial intimal sarcoma. The polyarthralgia and clubbing resolved soon after tumour removal. The patient went on to receive chemotherapy and remains in remission.ConclusionsThis case highlights the rare paraneoplastic association of cardiac sarcoma and arthropathy.

P14 Bullous sweet syndrome as a presentation of chronic myelogenous leukaemia

Abstract A variety of cutaneous lesions are frequently encountered in clinical practice that could be secondary to allergic reactions, infections or an underlying systemic illness, including malignancy. Some of the most commonly observed paraneoplastic dermatological manifestations include acanthosis nigricans, necrolytic migratory erythema, acrodermatitis paraneoplastica, exfoliative erythroderma, paraneoplastic pemphigus, pyoderma gangrenosum and Sweet syndrome. Sweet syndrome is a neutrophilic dermatosis characterized by a particular constellation of clinical symptoms, signs and histopathological findings: pyrexia; peripheral leucocytosis; and painful erythematous skin lesions (papules, plaques and nodules) that typically reveal a dense dermal neutrophilic infiltrate and dramatic recovery of both symptoms and physical findings following treatment with systemic corticosteroids. Sweet syndrome is frequently related to malignancies and chronic inflammatory disorders, and it can also be caused by drugs. It can also be triggered by past infections or during pregnancy. We present a case of bullous variant of Sweet syndrome associated with chronic myelogenous leukaemia (CML) where the patient presented with crusted bullae and tender erythematous crusted plaques on all four limbs and face. Investigations revealed leucocytosis with peripherally circulating blasts, myelocytes and metamyelocytes. Skin biopsy revealed Sweet syndrome and bone marrow biopsy confirmed evidence of CML in the accelerated phase. The skin lesions, which had previously been resistant to therapy, surprisingly disappeared within 3 days of initiating systemic corticosteroids. In this case, the skin lesions were a crucial clinical finding in detecting and treating the underlying CML. Because of the early intervention, our patient had a good outcome.