Paraneoplastic retinopathies: an update on pathogenesis, diagnosis and management

The paraneoplastic retinopathies are a heterogeneous group of disorders with significant visual consequences occuring in the setting of a systemic malignancy.These conditions may be characterized by the presence of antiretinal antibodies and may predate or follow the diagnosis of an underlying malignancy.Herein I review the clinical findings,pathophysiology,laboratory testing and management of the paraneoplastic retinopathies:cancer-associated retinopathy(CAR),melanoma-associated retinopathy(MAR),bilateral diffuse uveal melanocytic proliferation(BDUMP)and paraneoplastic vitelliform maculopathy(PVM).The pathophysiology of the paraneoplastic retinopathies varies from molecular mimicry resulting in anti-retinal antibody production(CAR,MAR)to relases of soluble factors either by the primary tumor(BDUMP)and/or immune system in response to the primary tumor(PVM)which result in retinal and/or retinal pigment epithelium dysfunction.For each condition,structural and functional multimodal retinal testing can be helpful in establishing the diagnosis.Treatment for the paraneoplastic retinopathies involves a combination of treating the underlying malignancy plus additional local and/or systemic immunosuppressive agents though no systemic therapeutic protocols exist.Despite these interventions,the retinopathy may be progressive or the retinopathy may be a harbinger of poor survival.Nevertheless,prompt diagnosis may help identify an underlying malignancy earlier and may thus improve cancer-related survival.

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.

Paraneoplastic myopathy-related rhabdomyolysis and pancreatic cancer:A case report and review of the literature

BACKGROUND Rhabdomyolysis is a life-threatening condition,often leading to progressive renal failure and death.It is caused by destruction of skeletal muscle and the release of myoglobin and other intracellular contents into the circulation.The most frequent cause of this condition is“crush syndrome”,although several others have been described and paraneoplastic inflammatory myopathies associated with various types of cancer are repeatedly reported.CASE SUMMARY We describe a rare case of a patient with pancreatic cancer who developed rhabdomyolysis early on,possibly due to paraneoplastic myositis leading to acute renal failure and eventually to rapid death.A 78-year-old Caucasian woman was referred to our hospital for obstructive jaundice and weight loss due to a lesion in the pancreatic head.She presented increasingly severe renal insufficiency with anuria,a dramatic increase in creatine phosphokinase(36000 U/L,n.v.20-180 U/L)and myoglobin(>120000μg/L,n.v.12-70μg/L).On clinical examination,the patient showed increasing pain in the lower limbs associated with muscle weakness which was severe enough to immobilize her.Paraneoplastic myopathy linked to the malignant lesion of the pancreatic head was suspected.The patient was treated with hemodialysis and intravenous methylprednisolone.Despite all the efforts to prepare the patient for surgery,her general condition rapidly deteriorated and she eventually died 30 d after hospital admission.CONCLUSION The possible causes of rhabdomyolysis in this patient with pancreatic cancer are discussed,the development of paraneoplastic myopathy being the most likely.Clinicians should bear in mind that these syndromes may become clinically manifest at any stage of the cancer course and their early diagnosis and treatment could improve the patient’s prognosis.

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.

Four kinds of antibody positive paraneoplastic limbic encephalitis: A rare case report

BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.

Paraneoplastic Leukocytosis and Thrombocytosis as Prognostic Biomarkers in Non-small Cell Lung Cancer

Background and Objectives: Search for inexpensive laboratory markers have identified associations between blood counts and lung cancer outcomes. In this study, we evaluated the prognostic value of paraneoplastic leukocytosis(p-Leukocytosis) and paraneoplastic thrombocytosis(p-Thrombocytosis) in patients with non-small cell lung cancer(NSCLC). We also studied their relation to the expression of commonly detected molecular markers. Methods: We conducted a retrospective chart review on 571 consecutive NSCLC patients over a 10 year period. Blood counts were recorded at the time of cancer diagnosis. Kaplan-Meier survival curves were used to compare overall survival(OS) between patients with and without p-Leukocytosis(or) p-Thrombocytosis(p-Leuko/Thrombocytosis). Cox regression was used to determine if leukocytosis/thrombocytosis was a predictor of OS in NSCLC.Results: Patients with p-Leukocytosis and p-Thrombocytosis had a significantly poorer survival compared patients with normal blood counts(P<0.001). In a multivariate survival analysis, both continued to correlate even when adjusted for histology, gender, stage and chemotherapy(P<0.01, 0.03 respectively). Stage I and II NSCLC with p-Leuko/Thrombocytosis did not perform poorly compared to stage I/II NSCLC patients without paraneoplasia. Patients with the combined leukothrombocytosis syndrome did not have worse outcomes compared to those with either paraneoplastic syndrome alone. Conclusions: p-Leuko/Thrombocytosis is an accessible laboratory parameter of prognostic value in NSCLC. Evidence of p-Leuko/Thrombocytosis portends poor survival. The role of various cytokines in tumor pathobiology provides a rationale for identifying cytokine factors responsible for the paraneoplasia and administering anti-cytokine therapies alongside traditional chemotherapy in an attempt to improve survival outcomes in these subset of patients.

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.

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.

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.

Gallbladder adenocarcinoma and paraneoplastic parathyroid hormone mediated hypercalcemia

Parathyroid hormone mediated hypercalcemia is not always exclusively primary hyperparathyroidism and rarely could be due to ectopic parathyroid hormone secretion from tumor cells.We present a case of 86-yearold female with metastatic gall bladder adenocarcinoma diagnosed eight months back who presented with generalized fatigue and poor oral intake and was found to be hypercalcemic with elevated parathyroid hormone levels.Imaging with technetium 99 m sestamibi scintigraphy with dual phase,subtraction thyroid scan(dual isotope scintigraphy),magnetic resonance imaging and ultrasonography did not demonstrate any parathyroid lesion in normal or ectopic sites.We believe that the tumor cells were the source of ectopic parathyroid hormone secretion as we had excluded all the other possibilities with extensive combined imaging thereby increasing the sensitivity of our testing.We report the first case of metastatic gall bladder adenocarcinoma with paraneoplastic ectopic parathyroid hormone secretion.

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.

Intra-abdominal inflammatory pseudotumor-like follicular dendritic cell sarcoma associated with paraneoplastic pemphigus: A case report and review of the literature

BACKGROUD Follicular dendritic cell(FDC)sarcomas are rare neoplasms that occur predominantly in the lymph nodes.They can also occur extranodally.Extranodal FDC sarcomas most commonly present as solitary masses.Inflammatory pseudotumor(IPT)-like FDC sarcomas,a subcategory of FDC sarcomas,are rarer than other sarcoma subtypes.They are composed of spindle or ovoid neoplastic cells and exhibit an admixture of plasma cells and prominent lymphoplasmacytic infiltration.Paraneoplastic pemphigus(PNP),also known as paraneoplastic autoimmune multiorgan syndrome,is a rare autoimmune bullous disease that is associated with underlying neoplasms.PNP has a high mortality,and its early diagnosis is usually difficult.CASE SUMMARY We describe a 27-year-old woman who presented with stomatitis,conjunctivitis,and skin blisters and erosions as her first symptoms of PNP with an intraabdominal IPT-like FDC sarcoma.The patient underwent surgical tumor resection and received tapering oral corticosteroid treatment.She showed no recurrence at the 1-year follow-up.CONCLUSION IPT-like FDC sarcomas are rare underlying neoplasms that have an uncommon association with PNP.PNP-associated FDC sarcomas predominantly occur in intra-abdominal sites and suggest a poor prognosis.Surgical resection is an essential and effective treatment for PNP and primary and recurrent FDC sarcomas.

Paraneoplastic hyperinsulinism and secondary hypoglycaemia in a patient with advanced colon cancer: A rare association

We review the case of a 74-year-old patient with ad-vanced colon cancer who suffered recurrent bouts of hypoglycemia. A state of inappropriate, non-suppressed hyperinsulinism in the presence of severe hypoglycemia was diagnosed. We finally discuss the known mecha-nisms behind fasting hypoglycemia in patients with ad-vanced cancer, the diagnosis, and possible treatments of this rare paraneoplastic endocrine complication.

Anti-Yo antibody-positive paraneoplastic cerebellar degeneration in a patient with possible cholangiocarcinoma:A case report and review of the literature

Paraneoplastic cerebellar degeneration(PCD),which is rare in clinical practice,is closely related to autoimmunity.Cases positive for anti-Yo antibodies(anti-Purkinje cytoplasmic antibody 1)are the main subtype of PCD.PCD is subacute cerebellar degeneration,and while it progresses over weeks to months,its resultant deficits last much longer.Cancer patients with anti-Yo antibody-positive PCD are very rare.Most of them are breast cancer or ovarian cancer patients but also occasionally lung cancer patients.CASE SUMMARY A 61-year-old woman presented with sudden vertigo,nausea,and vomiting for approximately 10 d.The patient's neurological examination showed torsion with downbeat nystagmus and ataxia of the right limb and trunk.Laboratory examination found that the patient's cerebrospinal fluid and serum were anti-Yo antibody-positive,positron emission tomography computed tomography showed an increased metabolic rate in the retroperitoneal lymph nodes,and the pathology of lymph node punctures in the retroperitoneum and neck suggested adenocarcinoma of the pancreaticobiliary duct,which strengthens the hypothesis of paraneoplastic origin.Intravenous immunoglobulin(IVIg)0.4 g/kg/d for 5 d and methylprednisolone 160 mg for 3 d were initiated,which was reduced to 80 mg for 3 d and then to 40 mg for 7 d.After treatment with IVIg and a steroid,the patient's vertigo and ataxia alleviated.CONCLUSION The patient's vertigo and ataxia alleviated after treatment,suggesting that early immunotherapeutic intervention may have certain value in stopping neurological loss.

Paraneoplastic dermatological manifestation of gastrointestinal malignancies

Numerous dermatological disorders have been associated with underlining malignancies of the gastrointestinal (GI)tract.Such cutaneous manifestations might have an important diagnostic value if they are the sole expressions of otherwise asymptomatic carcinomas.The recognition of some typical paraneoplastic dermatologic disorders can lead to the prompt diagnosis of the underlying malignancy,timely administration of therapy,and ultimately,better prognosis.In this review we discuss the most common paraneoplastic dermatological syndromes from the perspective of the practicing gastroenterologist. We also outline a comprehensive practical approach for the evaluation for occult malignancy in patients presenting with cutaneous findings potentially associated with GI cancers.

Paraneoplastic leukemoid reaction in a patient with sarcomatoid hepatocellular carcinoma: A case report

BACKGROUND Sarcomatoid hepatocellular carcinoma (SHC) combined with paraneoplastic leukemoid reaction (PLR), which is associated with a poor prognosis, is rarely seen in the clinic. Here, we report the case of a patient in the above situation. CASE SUMMARY A 75-year-old female patient with a past medical history of hypertension and cerebral infarction paid a hospital visit as a result of right upper quadrant abdominal pain and anorexia for two months. Laboratory examination revealed a white blood cell (WBC) count of 43790/μL, which was then increased up to 77050/μL. In addition, the results of bone marrow examination suggested a leukemoid reaction. Computed tomography (CT) revealed a focal hepatic mass, which was confirmed through pathological examination to be an SHC postoperatively. In addition, the WBC count had fallen to a normal level before she left the hospital. However, the patient died two and a half months after the second hospital admission. CONCLUSION This is a rare case of SHC combined with PLR, both of which have an extremely poor prognosis.

Carcinoma of unknown primary and paraneoplastic dermatomyositis

Dermatomyositis is known to be associated with neoplastic disorders,however the presentation of carcinoma of unknown primary as dermatomyositis is rare. We describe a case index of 50-year-old female who presented with enlarged inguinal lymph nodes accompanied with symmetric proximal muscle weakness and erythematous plaques. Conventional basic work-up did not reveal the diagnosis,however,positron emission tomography-computed tomography and re-staining of the pathology specimen suggested the ovaries as the primary site. Chemotherapy including carboplatin paclitaxel and bevacizumab led to complete response of disease and improvement in the dermatomyositis. The present case emphasizes the importance of a thorough directed evaluation for the underlying cancer in patients with carcinoma of unknown primary presenting as dermatomyositis. We further provide an up-to-date detailed review of published data describing these clinical entities.

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.

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.