Paraneoplastic syndromes associated with lung cancer

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy(Trousseau's syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cyto-kines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.

Immunohistochemical study on gastroenteric nervous system in trisomy 16 mice:an animal model of Down syndrome

AIM To study the development of gastroentericnervous system in trisomy 16 mouse embryos.The gastroenteric nervous system in trisomy 16mice and their normal littermates,serving ascontrols from embryonic days 13 to 18(ED13-18)was identified by using primary antibody againstprotein gene product(PGP)9.5.METHODS Trisomy 16 mouse breeding andtrisomy 16 mouse embryos were identified fromtheir normal littermates by chromosomeexamination;PGP 9.5 immunohistochemicalstainning.CONCLUSION Trisomy 16 mice, as an animal model for Down syndrome, has abnormality not only in several systems and organs but also in gastroenteric innervation. This report describes for the first time that the development of the gastroenteric nervous system was not only delayed but also pathological.

Two uncommon manifestations of leptospirosis:Sweet's syndrome and central nervous system vasculitis

To leptospirosis is the commonest spirocheatal infection in the tropical and temperate countries of Indian sub-continent and Africa and the most common zoonosis worldwide.The protean manifestation of this infectious disease is a challenge for practising clinicians across the world. In poor developing countries,at most clinical suspicion it is essential in the diagnosis of this disease.In this report,we are able to document two uncommon manifestations of leptospirosis, namely Sweet’s syndrome and central nervous system vasculitis.

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.

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.

Studies on Plasma Norepinephrine and EpinephrineContents and Vegetative Nervous SystemFunction in Various Liver Syndrome

Objective: To study the characteristics of plasma norepinephrine (NE) and epinephrine (E) contents alternation and vegetative nervous function disturbance in patients with various Liver Syndrome of TCM. Methods: Subjects were selected on the principle of combination of disease diagnosis and Syndrome Differentiation. Plasma NE and E contents were determined by high performance liquid chromatography (HPLC) and electrochemical detector. The vegetative nervous function were assessed by comprehensive analysis of sympathetic and parasympathetic hyperfunction symptoms, physiologic indexes and physical loading tests. Results: Patients of Liver Excess Syndrome had an elevated plasma NE and E contents and those with the vegetative nervous system disturbance mainly hypersympathetic. On the contrary, patients of Liver Deficiency Syndrome had lowered plasma NE and E contents and those with the vegetative nervous system disturbance mainly hyperparasympathetic. Conclusion: Plasma NE and E contents and vegetative nervous function disturbance can be taken as the auxiliary laboratory diagnostic indexes for Syndrome Differentiation of Liver Excess and Liver Deficiency.

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.

胸腺瘤相关重症肌无力合并炎性肌病三例报道并文献复习

目的分析重症肌无力(myasthenia gravis,MG)合并炎性肌病(inflammatory myopathy,IM)患者的临床特点及其与胸腺瘤的相关性。方法分析北京医院2010-3-1—2020-3-31收治的3例MG合并IM患者的临床特点,并结合文献进行复习。结果3例MG-IM中1例合并谷氨酸脱羧酶抗体阳性的僵肢综合征(stiff limb syndrome,SLS)。3例患者均有胸腺瘤,血清肌酸激酶和肌酸激酶同工酶升高,横纹肌抗体和心肌抗体阳性,而肌炎特异性抗体(myositis specific antibodies,MSA)和肌炎相关抗体(myositis associated antibodies,MAA)均阴性;肌电图提示肌源性损害和神经肌肉接头受累;心电图和超声心动图提示心肌受累;肌肉病理诊断多发性肌炎。联合46篇文献中的93例患者,共96例MG-IM患者纳入汇总分析。MG与IM同时发生者占42.7%,以MG症状首发者占34.4%,以IM症状首发者占22.9%。EMG检查提示肌源性损害和神经肌肉接头突触后膜疾病。乙酰胆碱受体(acetylcholine receptor,AChR)抗体阳性者占91.3%(84/92),MSA抗体阳性者仅占3.0%(2/66),MAA抗体阳性者仅占6.3%(2/32),横纹肌抗体阳性者占95.2%(20/21),6例行心肌抗体检测者均呈阳性。CT检查发现胸腺瘤者占64.4%(58/90)。53例行胸腺瘤手术的患者中,47例描述了胸腺瘤病理分型,以胸腺瘤B2型最常见(19例,40.4%),其次为B1型10例(21.3%),B3型9例(19.1%),AB型8例(17.0%),C型1例(2.1%)。89例行骨骼肌病理检查,其中以多发性肌炎最常见(62例,69.7%),其次为皮肌炎13例(14.6%),肉芽肿性肌炎9例(10.1%),免疫坏死性肌病2例(2.2%),嗜酸性粒细胞肌炎2例(2.2%),包涵体肌炎1例(1.1%)。7例尸体解剖患者行心肌病理检查,均诊断巨细胞性心肌炎。结论MG-IM多见于胸腺瘤患者,部分MG-IM患者同时合并心肌炎。大多数MG-IM患者血MSA和MAA抗体阴性。血横纹肌抗体和心肌抗体阳性提示骨骼肌和心肌受累,巨细胞性心肌炎是MG-IM患者死亡的主要原因之一。MG、IM和SLS全面准确的诊断依赖于临床、电生理、免疫学和肌肉病理的综合评估。

以急性多发性脑梗死为主要表现的特鲁索综合征3例

目的 分析以急性多发性脑梗死为主要表现的特鲁索综合征(Trousseau’s syndrome,TS)的临床及影像学特征。方法回顾分析2019年12月至2021年12月阜阳市人民医院神经内科收治的3例以急性多发性脑梗死为主要表现的TS病人的临床资料,并结合相关文献分析该病的临床和影像特征。结果 其中男1例,女2例;发病年龄范围为52~85岁;3例病人D-二聚体均明显升高;头颅MRI均显示为以“三流域征”为特点的急性多发性脑梗死;伴腹腔转移瘤1例,伴静脉系统血栓2例;1例予低分子肝素抗凝+双抗抗血小板聚集,2例予低分子肝素抗凝治疗。结论 急性多发性脑梗死是TS的一个重要表现;对于不符合血管分布的急性多发性脑梗死,病因需考虑恶性肿瘤所致高凝状态可能;D-D是诊断TS的重要线索。

结肠腺癌致异位促肾上腺皮质激素综合征1例报道

异位促肾上腺皮质激素综合征(ectopic ACTH syndrome, EAS)又称异位ACTH综合征,是副肿瘤综合征内分泌系统的一种特殊类型,与垂体以外的肿瘤组织分泌过量有生物活性的ACTH或其类似物,刺激肾上腺皮质增生有关。临床观察发现,多种不同起源的肿瘤与EAS相关,其中以支气管类癌和小细胞肺癌最为常见,其次是胸腺肿瘤、胰腺神经内分泌肿瘤、甲状腺髓样癌等,这些肿瘤多具有神经内分泌特征[1-2]。

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.

Mononeuropathy multiplex associated with systemic vasculitis:A case report

BACKGROUND Vasculitis,a systemic disorder with inflammation of blood vessel walls,can develop broad spectrum of signs and symptoms according to involvement of various organs,and therefore,early diagnosis of vasculitis is challenging.We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex,rectal perforation and antiphospholipid syndrome(APS)presented with pulmonary embolism.CASE SUMMARY A 61-year-old woman visited hospital with complaints of myalgia and occasional fever.She was initially diagnosed as proctitis and treated with antibiotics,however,there was no improvement.In addition,she also complained right foot drop with hypesthesia,and left 2^(nd) and 3^(rd) finger tingling sensation.She underwent nerve conduction study for evaluation,and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs.Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy.Based on nerve biopsy and clinical manifestation,she was diagnosed with vasculitis and treated with immunosuppressive therapy.During treatment,sudden rectal perforation and pulmonary thromboembolism occurred,and further laboratory study suggested probable concomitant APS.Emergency Hartmann operation was performed for rectal perforation,and anti-coagulation therapy was started for APS.After few cycles of immunosuppressive therapy,tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary.CONCLUSION Vasculitis can be presented with a variety of signs and symptoms,therefore,clinicians should always consider the possibility of diagnosis.

Refractory diarrhea: A paraneoplastic syndrome of neuroblastoma

Neuroblastoma(NB) is the most common extracranial solid tumor in children. Diarrheal NB is quite rare and is not easy to diagnose in the early stage. Six cases of diarrheal NB in our hospital treated from 1996 to 2006 were retrospectively analyzed, including characteristics such as electrolyte imbalance, pathologic features, vasoactive intestinal peptide(VIP) immunohistochemical staining results, treatment, and prognosis. All patients were boys with 3-8 loose or watery stools each day and routine fecal tests were normal. Abdominal tumors were identified by B-ultrasound. Drugs were ineffective. Three patients underwent surgery, and the remaining three patients received surgery and chemotherapy. Diarrhea stopped after treatment in five patients. Two patients died due to intractable hypokalemia. The tumor was located in the adrenal gland in four patients, in the upper retroperitoneum in one patient, and in the presacral area in one patient. Pathologic findings were NB and ganglioneuroblastoma. Five patients were at clinical stage Ⅰ-Ⅱ, and one was at stage Ⅲ. Four patients survived(followed-up for 6 mo to 4 years). Immunohistochemical staining for VIP was positive. Refractory diarrhea is a paraneoplastic syndrome of NB and is rare. Patients aged 1-3 years who present with chronic intractable diarrhea should be followed closely. Intractable diarrhea, hypokalemia, and dysplasia are the initial clinical manifestations. Increased VIP is characteristic of this disease. Potassium supplementation plays a vital role in the treatment procedure, especially preoperatively. The prognosis of diarrheal NB is good following appropriate treatment.

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.

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 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.

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.