Paraneoplastic syndromes in cholangiocarcinoma

Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy,due to complex interactions between the body’s immune system and malignant neoplasm.Cholangiocarcinoma(CCA)is an aggressive epithelial malignancy of hepatobiliary tree and it is found to be associated with various paraneoplastic syndromes.These syndromes can present as dermatological,neurological,renal,hematological,or multi-systemic manifestations.Clinical suspicion and timely recognition of these syndromes can lead to early diagnosis of covert malignancies like CCA.The management plan remains the removal of the underlying cause which in this case is CCA.

Paraneoplastic Syndromes of Hypercalcemia and Leukocytosis Associated with Colonic Metastases from Squamous Cell Carcinoma of the Lung: a Case Report

Lung cancer is the most common cancer-related death in both men and women in the world. Approximately 25% of all cancer deaths are attributable to lung carcinoma. Moreover, about one-half of patients with lung cancer have metastases at the time of initial diagnosis, most frequently of lymph nodes, adrenals, liver, bone and brain. However metastasis to the colon is very rare. Over the past 25 years about 13 cases of symptomatic colonic metastases from lung malignancies of all types have been reported in the literature. Hypercalcemia and leukocytosis are two of the most common paraneoplastic syndromes associated with various malignancies. However, concomitant manifestation of hypercalcemia and leukocytosis are occasionally observed in the same cancer patients. Here, we present a rare case of colonic metastasis from a squamous cell carcinoma of the lung associated with paraneoplastic syndromes of hypercalcemia and leukocytosis.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and signs.The CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this type.It damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral neuropathy.Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis.However,because of the low incidence of this disease,few repo rts and no reviews have been published about it so far.This article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease.Additionally,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years.

Role of F-18 FDG PET/CT imaging in the diagnosis of paraneoplastic neurological syndromes

Paraneoplastic neurological syndromes(PNS) is a series of rare neurologic disorders which happen with an underlying malignancy. It has various clinical symptoms proceding to the diagnosis of tumors. Although the abnormality of anti-neuronal antibodies is suggestive of PNS and tumors, there exist many false positive and false negative cases. The diagnosis of PNS is usually a challenge in clinic. Positron emission tomography/computed tomography(PET/CT) imaging is an anatomical and functional fusion imaging method, which provides the whole-body information by single scan. Fluorodeoxyglucose(FDG) PET/CT imaging can not only detect potential malignant lesions in the whole body, but also assess functional abnormality in the brain. In this review, the mechanism, clinical manifestation, diagnostic procedure and the recent progress of the utility of FDG PET/CT in PNS are introduced respectively.

Metastatic gastric cancer from breast carcinoma presenting with paraneoplastic rheumatic syndrome:A case report

BACKGROUND Breast cancer is the most frequently diagnosed cancer worldwide.It is the leading cause of death by malignant disease in women.CASE SUMMARY A female patient,73 years of age,sought care due to weakness,mild abdominal pain,arthralgia,and weight loss.She was taking anastrazole as maintenance therapy for localized breast cancer and had moderate anemia and elevated acutephase markers.Upper digestive endoscopy showed isolated erosion in the gastric corpus.This lesion was compatible with signet-ring cell adenocarcinoma in anatomopathological study and was confirmed as metastasis of a breast carcinoma in immunohistochemistry,which was positive for estrogen antibody.Further imaging studies determined numerous proximal bone metastases.The patient was treated with prednisone for paraneoplastic syndrome,which improved the anemia and rheumatic disease,and with chemotherapy,which greatly improved the symptoms.She has been followed-up for 6 mo,and her anemia,arthralgias,and acute phase markers have normalized.CONCLUSION Systemic treatment strategies seem to be the best choice for gastric metastasis from breast cancer,resulting in disease control and relapse-free survival.Prospective studies with longer follow-up are needed to better understand the biological,pathological,and clinicopathological characteristics and outcomes of the endoscopic features associated with metastatic gastric cancer from breast carcinoma.

Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations

Anti-N-methyl-D-aspartate receptor-associated encephalitis(NMDARE)is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction.The mechanism of pathogenesis remains incompletely understood,but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways.Young adults are most frequently affected;the median age at diagnosis is 21 years.There is a strong female predilection with a female sex predominance of 4:1.NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma.However,NMDARE has also been described in patients with small cell lung cancer,clear cell renal carcinoma,and other benign and malignant neoplasms.Diagnosis is based on correlation of the clinical presentation,electro-encephalography,laboratory studies,and imaging.Computed tomography,positron emission tomography,and magnetic resonance imaging are essential to identify an underlying tumor,exclude clinicopathologic mimics,and predict the likelihood of long-term functional impairment.Nuclear imaging may be of value for prognostication and to assess the response to therapy.Treatment may involve high-dose corticosteroids,intravenous immunoglobulin,and plasma exchange.Herein,we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria,treatment regimens,and proposed pathogenetic mechanisms.

Chronic urticaria associated with lung adenocarcinoma—a paraneoplastic manifestation:A case report and literature review

BACKGROUND Urticaria is one of the most common causes of emergency room visits.It is defined as an acute inflammatory dermatosis,characterized by localized degranulation of mast cells,with consequent dermal microvascular and formation of edematous and pruritic plaques called hives.Urticaria affects the skin and tissues of the superficial mucosa.Sometimes it is accompanied by angioedema,which is characterized by deeper edema of the dermis and subcutaneous cellular tissue known as the urticarial-angioedema syndrome.About 15%-25%of the general population has suffered at least one type of urticaria at some point during their lifetime and hyperpermeability estimated at 7.6%-16%and has experienced acute urticaria that is usually self-limited and spontaneously resolves without requiring medical attention.CASE SUMMARY We present the case of a young male patient who was referred to our department with a clinical picture of 4 mo of pruritus associated with hives of variable sizes,irregular borders,with interlesional confluence,that were non-painful,without involvement of the palms and soles of the feet but with a tendency to progression in a generalized manner.He had multiple emergency room visits and poor response to antihistamines and systemic corticosteroids.Imaging studies demonstrated nodules in the lower lingula segment,at the level of the greater fissure and in the anterior contour of the left anterior basal segment associated with parahiliar adenopathies in the absence of findings suggestive of infectious or autoimmune etiology.Segmental lobectomy was performed by thoracoscopy with resection of a lung nodule in the lingula and biopsy of the para-aortic mediastinal ganglion.The histopathological report showed the presence of poorly differentiated invasive adenocarcinoma with a solid morphological and acinar pattern with immunohistochemical description of lung tissue that expresses strong positive and diffuse reaction for thyroid transcription factor 1(TTF-1)with negativity to P40 for a histopathological diagnosis of malignant epithelial neoplasia with expression of infiltrating adenocarcinoma.Spontaneous chronic urticaria is considered possibly secondary to lung adenocarcinoma.CONCLUSION Chronic spontaneous urticaria is considered a paraneoplastic dermatosis with a controversial association in the literature.In the presented case,a young patient presented with chronic refractory urticaria and after an exhaustive clinical work-up was found to have a diagnosis of poorly differentiated lung adenocarcinoma with high expression of TTF-1.According to the Curth criteria,the urticaria presented by the patient is related to the oncological diagnosis.In addition,the high expression of TTF-1 documented in this case could be acting as an autoantigen that would cause chronic spontaneous urticaria.Further research evaluating a causal relationship between the TFF-1 protein and urticaria in lung cancer is needed.

Persistent cough as a paraneoplastic presenting symptom in six patients with renal cell carcinoma

Objective:With today’s modern imaging modalities,patients diagnosed with renal cell carcinoma(RCC)rarely present symptomatically.In some cases,however,they can develop paraneoplastic syndromes with associated symptoms.To date,only three cases of RCC presenting with chronic dry cough have been reported.We describe six patients who presented with cough that improved following radical nephrectomy.Methods:A retrospective review of patients undergoing partial or radical nephrectomy for renal masses between January 2015 and March 2016 was performed,and patients presenting with a cough were examined.Results:Six patients presented with chronic cough and were discovered to have a large renal mass.Postoperative spontaneous resolution of cough was noted in all but one patient,in whom coughing was reduced and limited to the mornings.Cough duration ranged from 3 months to just over a year.All patients were treated with radical nephrectomy,which was cytoreductive in four patients.Average tumor size was 10.9 cm(SD=2.2 cm).Five of the tumors had clear cell pathology,and every tumor was Fuhrman grade IV,unifocal,and demonstrated necrosis.Sarcomatoid features were reported in four of the tumors.Conclusion:Our study presents the largest series of patients with RCC who presented with a chronic cough that was significantly improved following radical nephrectomy.We believe the cause of cough is multifactorial and further investigation is needed to clearly elucidate the etiology.

Acute pancreatitis with hypercalcemia caused by primary hyperparathyroidism associated with paraneoplastic syndrome:A case report and review of literature

BACKGROUND Although acute pancreatitis associated with hyperparathyroidism has occasionally been reported,acute pancreatitis with metabolic encephalopathy caused by hyperparathyroidism combined with paraneoplastic syndrome is an extremely rare entity and poorly described in the literature.CASE SUMMARY We present a case of a 56-year-old female with upper abdominal discomfort and intermittent nausea and vomiting for 1 wk,without apparent abdominal pain or bloating,no jaundice and decreased blood pressure at the outset.The patient was ultimately diagnosed with moderately severe acute pancreatitis(according to the revised Atlanta classification of acute pancreatitis)combined with metabolic encephalopathy secondary to hypercalcemia caused by primary hyperparathyroidism associated with paraneoplastic syndrome.After active treatment of acute pancreatitis,massive fluid resuscitation,resection of parathyroid and uterine malignant tumors,neoadjuvant chemotherapy and other treatments,her serum calcium eventually returned to the normal level.The patient was successfully discharged from hospital.CONCLUSION This is the first case of acute pancreatitis caused by primary hyperparathyroidism associated with paraneoplastic syndrome.

Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies:A case report

BACKGROUND Paraneoplastic neurological syndrome(PNS)is a rare complication in patients with cancer.PNS can affect the central,peripheral,autonomic nervous system,neuromuscular junction,or muscles and cause various neurological symptoms.Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibodypositive neurological paraneoplasms are common,but coexistence of both types has not been described in the literature.CASE SUMMARY Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers.A 55-year-old woman was admitted to our hospital with unsteadiness while walking.The patient had a history of breast cancer two years previously.Chest computed tomography revealed a 4.6 cm×3.6 cm mass in the right lung,which was diagnosed as small-cell lung cancer(SCLC).Blood test was positive for anti-Yo antibodies,and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies,and the neurological symptoms were considered to be related to the paraneoplasm.The patient was treated with a course of intravenous immunoglobulin,without noticeable improvement.After being discharged from hospital,the patient underwent regular chemotherapy for SCLC and periodic reviews.The patient’s neurological symptoms continued to deteriorate at the follow-up visit in April 2021.CONCLUSION This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies.The clinical appearance of two or more paraneoplastic tumors requires additional attention.

Sweet syndrome as a paraneoplastic manifestation of cholangiocarcinoma:A case report

BACKGROUND Sweet’s syndrome,also known as acute febrile neutrophilic dermatosis,is a rare skin disorder that may be associated with cancer.CASE SUMMARY A 58-year-old female presented with a cholestatic syndrome and significant weight loss three months before admission.Five months earlier,she had abruptly developed skin lesions with erythematous papules that evolved to erythematous blisters.Clinical evaluation and laboratory tests confirmed hepatic cholangiocarcinoma.Skin lesions histopathological findings showed neutrophilic dermatosis,massive edema,fibrin,necrosis,and elastosis.These results,in association with the macroscopic aspects of the findings,led to the diagnosis of paraneoplastic Sweet’s syndrome due to cholangiocarcinoma.As staging was consistent with an advanced tumor without a cure perspective,we opted to perform percutaneous biliary drainage,and subsequently,palliative care.Eventually,after a few weeks,the patient died.CONCLUSION In conclusion,the diagnosis of the underlying disease-causing Sweet’s syndrome must be accurate,and patients need to be followed-up,as neoplasia such as cholangiocarcinoma may be a later manifestation.

Paraneoplastic focal segmental glomerulosclerosis associated with gastrointestinal stromal tumor with cutaneous metastasis: A case report

BACKGROUND Gastrointestinal stromal tumor(GIST)with cutaneous metastasis is very rare.As a result,cutaneous GISTs have not been well characterized.Focal segmental glomerulosclerosis(FSGS)is also a rare symptom among paraneoplastic nephritic syndromes(PNS).CASE SUMMARY In this case report,we describe a patient with cutaneous metastatic GIST accompanied by nephrotic syndrome occurring as a malignancy-associated PNS,for whom symptomatic treatment was ineffective,but clinical remission was achieved after surgery.Moreover,the patient has a missense mutation in NPHP4,which can explain the occurrences of GIST and FSGS in this patient and indicates that the association is not random.CONCLUSION This is the first reported case of a GIST with cutaneous metastasis accompanied by nephrotic syndrome manifesting as a PNS.

Paraneoplastic neurological syndrome caused by cystitis glandularis: A case report and literature review

BACKGROUND Paraneoplastic neurological syndrome(PNS)is an unusual event.PNS caused by cystitis glandularis(CG)or a bladder tumor is extremely rare;hence,missed diagnosis or misdiagnosis can easily occur.To date,approximately 21 cases have been reported in PubMed.CASE SUMMARY We report a case of PNS caused by CG and describe the clinical and imaging features.The main clinical feature was advanced cognitive impairment,and early clinical features were memory impairment,decreased computational ability,and abnormal behavior.Later clinical features were dementia,vomiting,inability to eat and walk,urinary incontinence,and hematuria.Imaging features on cranial magnetic resonance imaging were diffuse white matter lesions.Paraneoplastic tumor markers were normal.A total abdominal computed tomography scan showed multiple thickened areas on the bladder wall with local prominence.Cystoscopy revealed a volcanic protuberance on the posterior wall of the bladder with a diameter of 6 cm and no pedicle.The postoperative pathological diagnosis was CG.The patient recovered well following resection of CG.PNS cases caused by previous bladder tumors can be retrieved from PubMed to describe the clinical signs and prognosis of PNS.CONCLUSION The main clinical feature of PNS caused by CG was dementia,and the imaging features were diffuse cerebral white matter lesions.Resection of CG lesions is the fundamental treatment for PNS induced by CG.This case highlights the importance of etiological treatment.

Gastric signet-ring cell carcinoma with paraneoplastic eosinophilia: A case report and literature review

We report the case of a 40-year-old female Chinese patient with gastric signet-ring cell carcinoma that was first diagnosed because of paraneoplastic eosinophilia.The patient’s eosinophil count reduced markedly to normal levels within 24 h after radical gastrectomy and Billroth II anastomosis.The patient recovered well after the surgery and no abnormalities were found during the regular follow-ups.Paraneoplastic eosinophilia is an unusual manifestation that usually remains asymptomatic;moreover,cases of solid malignant tumors with eosinophilia are uncommon.To our knowledge,this is the first reported case of paraneoplastic eosinophilia in a patient with gastric carcinoma.We considered eosinophilia as a manifestation of a paraneoplastic syndrome,which can be the first clinical manifestation of a malignancy.

Carcinoid syndrome caused by a pulmonary carcinoid mimics intestinal manifestations of ulcerative colitis:A case report

BACKGROUND Pulmonary carcinoids are rare,low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior.Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi.Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5%of patients with neuroendocrine tumors.Due to such nonspecific presentation,most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed.CASE SUMMARY We report the case of a 48-year-old male who presented with cough,dyspnea,a history of recurrent pneumonitis,and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid.CONCLUSION We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

Can Autoimmune Encephalitis Occur with Negative Markers? A Rare Case Report

In our case, we present a case of a 27-year-old male who presented with progressively worsening altered mental status and seizures. Over the course of his admission to the hospital and intensive care unit, laboratory testing failed to find an offending agent to his presentation. Testing did result in the diagnosis of encephalitis, but an underlying cause was not found. After careful exclusion of bacterial, viral, and other types of encephalopathy, autoimmune encephalopathy was diagnosed despite the absence of commonly used markers of autoimmune encephalopathy. The presentation and symptoms of our patient led to a wide range of differentials, and a high index of suspicion was needed throughout his admission in order to obtain the appropriate tests. Although appropriate testing might be ordered, due to the sensitivities and specificities of all laboratory tests, these objective tests do produce false negative results at times. It is in these times that one must weigh the physical exam, clinical judgment, and the process of elimination to diagnose an underlying pathology. Autoimmune Encephalitis diagnosis can be broken down into possible, probable, and definitive diagnoses based on antibody testing results. In this case, we present a patient with probable autoimmune encephalitis that failed to yield positive autoimmune markers after extensive testing of other possible causes of encephalitis.

Gastric linitis plastica with autoimmune pancreatitis diagnosed by an endoscopic ultrasonography-guided fine-needle biopsy: A case report

BACKGROUND Gastric linitis plastica(GLP)is a subset of gastric cancer with a poor prognosis.It is difficult to obtain a definitive diagnosis by endoscopic mucosal biopsies,and the usefulness of an endoscopic ultrasonography-guided fine-needle biopsy(EUSFNB)for GLP has been recently reported.Meanwhile,autoimmune diseases are occasionally known to coexist with malignant tumors as paraneoplastic syndrome.We herein report the usefulness of an EUS-FNB for detecting GLP and the possibility of paraneoplastic syndrome coexisting with GLP.CASE SUMMARY An 81-year-old man was admitted to our hospital for a 1-mo history of epigastric pain that increased after eating.His laboratory data revealed high levels of serum carbohydrate antigen 19-9 and immunoglobulin-G4.Endoscopic examinations showed giant gastric folds and reddish mucosa;however,no epithelial changes were observed.The gastric lumen was not distensible by air inflation,suggesting GLP.Computed tomography showed the thickened gastric wall,the diffuse enlargement of the pancreas,and the peripancreatic rim,which suggested autoimmune pancreatitis(AIP)coexisting with GLP.Because the pathological findings of the endoscopic biopsy showed no malignancy,he underwent an EUSFNB and was diagnosed with GLP.He received chemotherapy for unresectable gastric cancer due to peritoneal metastasis,after which both the gastric wall thickening and diffuse enlargement of the pancreas were improved.CONCLUSION An EUS-FNB for GLP with a negative endoscopic biopsy is useful,and AIP may develop as a paraneoplastic syndrome.

Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period

Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.

Non-islet cell tumor hypoglycemia as an initial presentation of hepatocellular carcinoma coupled with end-stage liver cirrhosis: A case report and review of literature

BACKGROUND Non-islet cell tumor hypoglycemia(NICTH)is a rare cause of persistent hypoglycemia seen in patients with hepatocellular carcinoma(HCC).It is likely to be underdiagnosed especially in the patients with poor hepatic function and malnutrition.Herein,we report a rare case of NICTH as the initial presentation of HCC in a patient with chronic hypoglycemia due to end-stage liver cirrhosis.CASE SUMMARY A 62-year-old male with chronic fasting hypoglycemia secondary to end-stage hepatitis C-related cirrhosis,presented with altered mental status and dizziness.He was found to have severe hypoglycemia refractory to glucose supplements.Imaging studies and biopsy discovered well differentiated HCC without metastasis.Further evaluation showed low insulin,C-peptide and betahydroxybutyrate along with a high insulin-like growth factor-2/insulin-like growth factor ratio,consistent with the diagnosis of NICTH.As patient was not a candidate for surgical resection or chemotherapy,he was started on prednisolone with some improvements in the glucose homeostasis,but soon decompensated after a superimposed hospital acquired pneumonia.CONCLUSION NICTH can occur as the sole initial presentation of HCC and is often difficult to correct without tumor removal.Clinicians should maintain high clinical suspicion for early recognition of paraneoplastic NICTH in patients at risk for HCC,even those with chronic fasting hypoglycemia in the setting of severe hepatic failure and malnutrition.

Microangiopathic Hemolytic Anemia and Diffuse Bone Metastasis by Signet Ring Cell Adenocarcinoma

Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome and is typically associated with gastric adenocarcinoma. We report a 47-year-old woman who presented with asthenia, lower back pain and bleeding. Twelve years ago the patient underwent total gastrectomy due to gastric adenocarcinoma and achieved complete remission. The patient was diagnosed with MAHA and diffuses bone metastasis of signet ring cell adenocarcinoma of unknown origin and was treated successfully with polichemotherapy based on cisplatin and 5-fluorouracil.