Achalasia is a neurodegenerative motor disease of the esophagus resulting mainly from a loss of function of the lower esophageal sphincter, the pathophysiology of which is still poorly understood. Its incidence is rare—it is 1.6 per 100,000—and its occurrence in the context of paraneoplastic syndrome has been rarely described in the literature. We report a rare case of paraneoplastic achalasia associated with lung cancer.
Achalasia is a motor disorder of the esophagus characterized by a peristalsis and incomplete lower esophageal sphincter relaxation without evidence of mechanical obstruction. Diagnosis is established by esophageal manometry and may be supported by findings on barium esophagogram , its incidence is 1.6 per 100,000 . Paraneoplastic achalasia is a very rare entity, and we report a case of epidermoid bronchopulmonary carcinoma manifesting as achalasia.
2. Case Report
We report the case of a 70-year-old man who was neither treated for tuberculosis nor has had any recent tuberculosis contagion, and with no notable pathological history or chronic smoking. The patient has reported a productive cough for 2 months, with mucous sputum associated with stage III of mMRC dyspnea, without hemoptysis or chest pain. Moreover, for 1 month he had liquid dysphagia associated with regurgitations, in the context of apyrexia and deterioration of the general state.
Clinical examination finds a conscious patient, eupneic at rest, at ambient air, with a pleuropulmonary examination without particularities.
The posteroanterior chest roentgenogram showed homogeneous right hilar opacity with peripheral nodular opacity with speculated contours (Figure 1). The thoracic computed tomography (CT) showed a right hilar tumoral process, extended to the posterior segment of the right upper lobe with irregular and spiculated contours, measuring without contact with the esophagus, associated with a spiculated nodule of the right upper lobe measuring , without lymphadenopathy mediastinal (Figure 2).
A bronchial fibroscopy was made objectifying a budding mucosa of the right upper lobar bronchus whose biopsy concluded from an epidermoid carcinoma.
As part of the exploration of dysphagia, an oesophagoscopy was normal and an achalasia was evoked and confirmed by esophageal manometry.
Due to the significant alteration of the patient, the patient died before the initiation of treatment.
Paraneoplastic syndromes refer to the remote effects associated with malignancies which are unrelated to direct tumor invasion or metastases. These may occur before the cancer is diagnosed and can be independent in their severity to the stage of the primary tumor. Paraneoplastic syndromes are most commonly associated with lung cancer, reported in approximately 10% of the cases. Endocrine syndromes, particularly the syndrome of inappropriate ADH secretion (SIADH) and humoral hypercalcemia of malignancy (HHM), are the most common paraneoplastic syndromes seen in lung cancer and are related to the histologic type of cancer .
Hypercalcemia has been reported in 2–6% of lung cancer cases; when associated with PTHrP (parathyroid hormone-related protein) production, it is referred to as HHM. Of the four mechanisms of hypercalcemia secondary to HHM (secretion of PTHrP, parathyroid hormone, 1-25 dihydroxy vitamin D, or granulocyte colony stimulating factor), secretion of parathyroid hormone-related protein is the most common in lung cancer. It is associated with a poor prognosis .
SIADH represents a state of euvolemic hypoosmolar hyponatremia, which in the case of lung cancer is secondary to ectopic ADH production; 10–45% of small-cell lung cancers (compared to 1% of non-small-cell lung cancers) can produce ectopic ADH resulting in excessive urinary sodium excretion. Hypothyroidism, volume depletion, and adrenal insufficiency should be excluded .
The secretion of ectopic growth hormone releasing hormone (GHRH) from malignant cells can manifest as acromegaly, and in the case of lung cancer, bronchial carcinoids and epidermoid carcinomas have been implicated; SCLC have been reported less frequently .
Venous thromboembolism (VTE) including DVT, PE, and superficial vein thrombosis occur in nearly 3% of lung cancer patients within the first 2 years of diagnosis. Patients with lung cancer have a 20-fold increase in the risk of VTE compared to the general population. NSCLC confers a higher VTE risk than SCLC, and adenocarcinomas are associated with a higher risk of VTE than squamous cell carcinoma. Distant metastases confer a fold increase in VTE compared to localized tumors. More so, tissue factor (TF), which initiates the coagulation cascade and cancer procoagulant, have an increased expression in lung cancer cells .
Paraneoplastic neurological syndromes (PNSs) are autoimmune in nature; unlike most paraneoplastic syndromes, they are independent of local tumor or metastatic effects. Onconeural antibodies appear to be central to the pathogenesis, though their absence does not preclude a diagnosis of PNS . These antibodies are directed against tumor cells but can also target the nervous system (central and peripheral), resulting in the wide-ranging manifestations of PNS.
The first description of autonomic neuropathy linked to lung cancer dates back to 1975 , and it was not until 1985 that anti-Hu Ab were isolated, from patients suffering from paraneoplastic neuropathies  and in 1993 that the first association between lung cancer, pseudochronic intestinal obstruction, and anti-Hu Ab has been reported . Since then, anti-Hu Ab have been identified in other digestive dysautonomies (achalasia, gastroparesis), as well as in multiple extradigestive neurological disorders . These antibodies are directed against a family of proteins, which are specific to neurons in the central, peripheral, and enteric nervous systems. Although other antineuronal antibodies (anti-YO, anticalcic, and anticalcium) have been demonstrated during paraneoplastic syndromes affecting the digestive system, anti-HU are in the majority .
Fewer than a hundred cases of motor digestive damage of paraneoplastic origin have so far been described in the literature .
The most important series of digestive motor damage of paraneoplastic origin was reported in 1989 by Lucchinetti et al. . Their report included 38 patients, out of which 19 had gastroparesis (50%), 8 had pseudochronic intestinal obstruction (POIC) (21%), and only four had achalasia (10%).
The most commonly associated neoplasia is lung cancer (81%), which perfectly matches the case of our patient.
The term “achalasia” derives from the Greek “khalasis” whose translation is “relaxation” ; it is a motor disorder of the esophagus characterized by a peristalsis and incomplete lower esophageal sphincter relaxation without evidence of mechanical obstruction that results from the degeneration of ganglion cells in the myenteric plexus of the esophageal body and the lower esophageal sphincter, leading to incomplete relaxation of the lower esophageal sphincter and a peristalsis in the distal esophagus .
As mentioned in the Introduction, the incidence is low—approximately 1.6 per 100,000 —equally distributed between men and women and increasing with age, with a peak between 40 and 60 years .
Dysphagia to both solids and liquids is the defining symptom of achalasia (occurring in 90% of patients), and patients may compensate for dysphagia by eating slowly or performing various maneuvers while eating (e.g., raising the arms, lifting the neck, and arching the back) . Paradoxical dysphagia (electively to liquids) is rare but strongly suggestive, as in the case of our patient.
Regurgitation of undigested food or saliva, with or without dysphagia, occurs in 76% to 91% of patients, especially during recumbency at night, which may result in aspiration or cough.
Symptoms of gastroesophageal reflux, such as substernal chest pain, epigastric pain, or heartburn, occur in approximately half of the patients; symptoms do not resolve with a trial of proton pump inhibitors. Other symptoms include odynophagia, halitosis, cough, hoarseness, wheezing, sore throat, and difficulty burping.
Achalasia results from the degeneration of ganglion cells in the myenteric plexus of the esophageal body and the lower esophageal sphincter, leading to an incomplete relaxation of the lower esophageal sphincter and a peristalsis in the distal esophagus. The exact cause of the degeneration leading to achalasia is unknown, but autoimmune, viral, or primary neurodegenerative processes are suspected .
Diagnosis is established by esophageal manometry and may be supported by findings on barium esophagogram .
There is no curative or preventive treatment for the degeneration of the myenteric esophageal plexus. The treatments available are aimed at reducing the pressure of the LES by rupture of the circular muscle fibers. The treatments traditionally proposed are endoscopic pneumatic dilation and laparoscopic Heller’s myotomy. Endoscopic peroral oral myotomy is a technique currently practiced routinely in expert centers; it is effective and safe, and its exact place in the therapeutic management of achalasia remains to be defined .
Paraneoplastic syndromes are most commonly associated with lung cancer, though paraneoplastic achalasia is rarely described in the literature. Through our work, we report a rare paraneoplastic syndrome of lung cancer, which is achalasia, in order to focus on this entity and sensitize practicing physicians to seek an underlying neoplasia when treating achalasia. The exact pysiopathology of this entity is still poorly defined, and new ways of research must be explored in the future to better understand this rare association.
Conflicts of Interest
There are no conflicts of interest between the authors and between the authors and the patient.
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Copyright © 2020 R. Azzeddine et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Paraneoplastic syndrome is a group of rare autoimmune diseases that can occur due to lung cancer, especially small cell lung cancer (SCLC). The group of diseases occur due to the immune system mistakenly attacking nerve cells. People living with SCLC may develop paraneoplastic syndrome.What is the most common paraneoplastic syndrome associated with lung cancer? ›
Endocrine syndromes, particularly syndrome of inappropriate ADH secretion (SIADH) and humoral hypercalcemia of malignancy (HHM) are the most common paraneoplastic syndromes seen in lung cancer and are related to the histologic type of cancer (1).What are some paraneoplastic syndromes that lung carcinoma causes? ›
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).What is the life expectancy for paraneoplastic syndrome? ›
In a long-term study of quality of life and survival in patients with Lambert‐Eaton myasthenic syndrome (LEMS), Lipka and colleagues reported that survival was significantly longer in patients with small cell lung cancer (SCLC) and LEMS than in those with SCLC alone (overall median survival 17 vs 7.0 months, P< 0.0001) ...Can paraneoplastic syndrome be cured? ›
There are no cures for paraneoplastic syndromes. There are no available treatments to stop progressive neurological damage. Generally, the stage of cancer at diagnosis determines the outcome.What are the signs and symptoms of paraneoplastic syndrome? ›
Signs and symptoms may include unsteady or impaired walking, lack of muscle coordination in your limbs, inability to maintain your trunk posture, dizziness, nausea, involuntary eye movement, double vision, difficulty speaking, or difficulty swallowing.Is paraneoplastic syndrome an autoimmune disease? ›
A condition that can occur in some people with cancer when the body's immune system becomes overactive and attacks healthy cells while trying to kill cancer cells.What is a paraneoplastic evaluation? ›
Paraneoplastic autoimmune neurological disorders reflect a patient's humoral and cellular immune responses to cancer.Which of the following is the most common paraneoplastic syndrome? ›
Peripheral neuropathy is the most common neurologic paraneoplastic syndrome. It is usually a distal sensorimotor polyneuropathy that causes mild motor weakness, sensory loss, and absent distal reflexes. Subacute sensory neuropathy is a more specific but rare peripheral neuropathy.What does paraneoplastic syndrome mean? ›
(PAYR-uh-NEE-oh-PLAS-tik SIN-drome) A group of symptoms that may develop when substances released by some cancer cells disrupt the normal function of surrounding cells and tissue.
This is a very rare disorder that consists of inflammation of the small blood vessels of the peripheral nerves and muscles. Patients often develop symptoms of peripheral neuropathy that may initially affect only one arm or leg before involving both sides. Pain often occurs.Can blood test detect paraneoplastic syndrome? ›
To diagnose paraneoplastic syndrome of the nervous system, your doctor will need to conduct a physical exam and order blood tests. He or she may also need to request a spinal tap or imaging tests.Who treats paraneoplastic syndrome? ›
Mayo Clinic doctors trained in nervous system conditions (neurologists), cancer (oncologists) and other specialties have experience evaluating and treating people with paraneoplastic syndromes of the nervous system.Is paraneoplastic syndrome progressive? ›
Paraneoplastic sensory neuronopathy (PSN) is characterised by subacute, rapidly progressive, asymmetric and often painful, sensory symptoms dominated by profound proprioceptive loss affecting upper limbs more than lower limbs.Why is it important to recognize the different paraneoplastic syndromes? ›
Immunologic paraneoplastic syndromes are usually related to autoimmunity. Early recognition of paraneoplastic syndromes is important because delayed diagnosis may contribute to worsened morbidity and mortality, as well as delays in cancer treatment.How do you test for neoplastic disease? ›
- CT scans.
- MRI scans.
- PET scans.
Initial Assessment (PNS-IA)
Built on six of the most well-characterized antibodies found in paraneoplastic disorders, the Paraneoplastic Neurological Syndromes, Initial Assessment profile is a highly-focused diagnostic tool with a three- to five-day turnaround.
The panel costs $400 and has a turnaround time of 2-3 weeks.Does paraneoplastic cause weight loss? ›
Abstract. Cancer anorexia-cachexia syndrome (CACS) is the most frequent paraneoplastic syndrome occurring in half of all oncologic patients and is considered as a poor prognosticator. Patients usually present with weight loss, lipolysis, muscle wasting, anorexia, chronic nausea, inflammation, and asthenia.Can benign tumors cause paraneoplastic syndrome? ›
Physicians should be aware that, although extremely rare, benign tumors also can cause paraneoplastic syndromes.
Direct neurological complications of cancer include: Lung cancer, breast cancer, melanoma, and other cancers that spread or metastasize to the brain. Cancers that spread or metastasize to the spine or peripheral nervous system. Non-Hodgkin's lymphoma affecting the central nervous system.Is paraneoplastic syndrome a disability? ›
Recent findings: Paraneoplastic disorders may affect any part of the central or peripheral nervous system. Although relatively uncommon, these disorders are a significant cause of severe and permanent neurologic disability.What is paraneoplastic antibody? ›
Description. A family of autoantibodies recognising antigens in the brain which are associated with a variety of neurological manifestations occurring as a result of malignancy, usually ovarian or small cell carcinoma of the lung.What is paraneoplastic neuropathy? ›
A neuropathy is defined as paraneoplastic when none of the above causes are detected or when cancer related immunological mechanisms are involved. At least 15% of patients with cancer develop a paraneoplastic sensorimotor neuropathy, which is usually mild and develops during the terminal stage of the disease.Can blood test detect neurological problems? ›
Blood tests can monitor levels of therapeutic drugs used to treat epilepsy and other neurological disorders.What is anti Hu antibody test? ›
The anti-Hu antibody appears, when present, to be a good marker for small cell lung cancer and, when present at high titer, for small cell lung cancer associated with a paraneoplastic syndrome.What is antiy antibody? ›
Background: Anti-Yo antibodies are associated with paraneoplastic cerebellar ataxia and denote an underlying malignancy, usually gynecological tumors. Anti-Yo antibodies are directed against CDR proteins which, in the CNS, are primarily expressed on cerebellar Purkinje cells.What is paraneoplastic fever? ›
Neoplastic fever, a paraneoplastic syndrome caused by cancer itself, represents a diagnostic challenge for the clinician and is an important issue in supportive oncology.What is paraneoplastic myopathy? ›
Paraneoplastic myopathies are disorders of the skeletal muscle or of the neuromuscular junctions which are not caused by direct infiltration by the tumor. The minimal criteria for these disorders are not well established.Is fever a paraneoplastic syndrome? ›
However, particularly in some tumour types, fever can also be a paraneoplastic syndrome, caused by the malignancy itself. This can be a difficult diagnosis to establish and presents a therapeutic challenge to the physician when the underlying malignancy is not easily treated.
Definition of neoplastic
1 : of, relating to, or constituting a tumor or neoplasia. 2 [after French néoplastique or German neoplastisch] : of or relating to de Stijl.
Sometimes, a cancerous tumor is malignant, meaning it can grow and spread to other parts of the body where the nerves are centred, causing muscle twitches, spasms, or jerking.What is paraneoplastic autoantibody evaluation? ›
Paraneoplastic autoimmune neurological disorders reflect a patient's humoral and cellular immune responses to cancer. The cancer may be new or recurrent, is usually limited in metastatic volume, and is often occult by standard imaging procedures.Is anemia a paraneoplastic syndrome? ›
Abstract. Autoimmune hemolytic anemia (AIHA) is a rare paraneoplastic syndrome (PNS) associated with malignant solid tumors. Patients with PNS-AIHA are often refractory to steroid treatment before surgery. The mechanisms underlying PNS-AIHA are not well understood.What is paraneoplastic arthritis? ›
Carcinomatous polyarthritis (or paraneoplastic polyarthritis) is a seronegative form of inflammatory arthritis [2,4,9]. The association between the arthritis and cancer is well known , but a temporal relationship is necessary for a paraneoplastic syndrome to be assumed [3,4,10].What is neoplastic lesion? ›
(NEE-oh-PLA-zum) An abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should. Neoplasms may be benign (not cancer) or malignant (cancer). Benign neoplasms may grow large but do not spread into, or invade, nearby tissues or other parts of the body.How do you manage paraneoplastic syndrome? ›
- Corticosteroids: Medications, such as cortisone or prednisone, that reduce inflammation (swelling).
- Immunosuppression: Drugs that decrease your body's immune response. ...
- Intravenous immunoglobulin: Treatment that destroys the harmful antibodies causing the syndrome.
Paraneoplastic cerebellar ataxia, also known as paraneoplastic cerebellar degeneration, is one of the wide array of paraneoplastic neurological syndromes in which neurological symptoms are indirectly caused by an underlying malignancy, most commonly gynecological, breast, or lung cancer or Hodgkin's lymphoma.Can melanoma cause paraneoplastic syndrome? ›
Purpose: Melanoma-associated retinopathy (MAR) is a known paraneoplastic syndrome in some patients with cutaneous malignant melanoma. It is characterized by the presence of serum auto-antibodies (IgG) against retinal proteins, affecting retinal photoreceptor function and leading to retinal damage.What is the ICD 10 code for paraneoplastic syndrome? ›
0 for Paraneoplastic neuromyopathy and neuropathy is a medical classification as listed by WHO under the range - Diseases of the nervous system .
Paraneoplastic Cushing's syndrome (CushingPS) has been attributed to ectopic adrenocorticotropin (ACTH) secretion (EAS), which may result in several types of tumors, including carcinoid and pancreatic neuroendocrine tumors, small cell lung cancer and thyroid medullary carcinoma (1).Which issue is considered a paraneoplastic syndrome that is common in patients with renal cell carcinoma? ›
Hypercalcemia is the most common of the paraneoplastic syndromes in patients with RCC and of those with hypercalcemia and RCC, approximately 75% have high-stage lesions.What are the genes that commonly affected with carcinogenesis? ›
The most commonly mutated gene in people with cancer is p53 or TP53. More than 50% of cancers involve a missing or damaged p53 gene. Most p53 gene mutations are acquired. Germline p53 mutations are rare, but patients who carry them are at a higher risk of developing many different types of cancer.What causes paraneoplastic cerebellar degeneration? ›
Paraneoplastic cerebellar degeneration (PCD) is an uncommon disorder that can be associated with any cancer; the most commonly associated are lung cancer (particularly small cell lung cancer [SCLC]), gynecologic and breast cancer, and lymphoma (particularly Hodgkin disease [HD]) .How is paraneoplastic cerebellar degeneration detected? ›
Patients suspected to have paraneoplastic cerebellar degeneration should undergo brain imaging with computed tomography scans (CT) and magnetic resonance imaging (MRI) to rule out hemorrhagic strokes, primary and secondary brain tumors, and ischemic strokes as part of their initial workup.What is the life expectancy of someone with paraneoplastic syndrome? ›
Paraneoplastic endocrine syndromes
HHM is usually found in individuals with a significant tumor burden . The median survival time (MST) of 59 patients with hypercalcemia was 3.8 months, which was significantly shorter than that of patients without hypercalcemia (9.5 months, p<0.001) .
There are no cures for paraneoplastic syndromes. There are no available treatments to stop progressive neurological damage. Generally, the stage of cancer at diagnosis determines the outcome.Can paraneoplastic cause hypercalcemia? ›
Background: Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare.How does lung cancer cause Cushing's syndrome? ›
SCLC starts in your lungs' neuroendocrine cells. These cells act like nerve cells in some ways. But they also can make hormones, including glucocorticoids. When your body is exposed to constant hormones made by a tumor that started in your lungs, you can form Cushing syndrome.How does small cell lung cancer cause SIADH? ›
Small-cell lung cancer tumors are made up of neuroendocrine cells – the same kind of cells that release hormones. In the case of SIADH, cancer cells release ADH, causing a spike in levels of this hormone.
In contrast, "big ACTH" and beta lipotropin are found in the plasma and tumor extracts of lung cancers of all types. Calcitonin and the beta chain of human chorionic gonadotropin are also found in the plasma of a considerable portion of patients with all histological types of lung cancers.Is paraneoplastic syndrome an autoimmune disease? ›
A condition that can occur in some people with cancer when the body's immune system becomes overactive and attacks healthy cells while trying to kill cancer cells.Are there different types of lung cancer? ›
There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). A third less common type of lung cancer is called carcinoid.Where are Cushing's tumors located? ›
These tumors, which can be noncancerous (benign) or cancerous (malignant), are usually found in the lungs, pancreas, thyroid or thymus gland. A primary adrenal gland disease. Disorders of the adrenal glands can cause them to produce too much cortisol.Is Cushing's disease a cancer? ›
An abnormality of the adrenal glands, such as an adrenal tumor, may cause Cushing's syndrome. Most of these cases involve non-cancerous tumors called adrenal adenomas, which release excess cortisol into the blood. Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing's syndrome.How long do you live with small cell lung cancer? ›
Limited stage small cell lung cancer has a median survival of 12 to 16 months, with treatment. Extensive stage small cell lung cancer has a median survival of 7 to 11 months, with treatment.What is the best treatment for SIADH? ›
The most commonly prescribed treatment for SIADH is fluid and water restriction. If the condition is chronic, fluid restriction may need to be permanent. Treatment may also include: Certain medications that inhibit the action of ADH (also called vasopressin)What's the prognosis for lung cancer? ›
|SEER stage||5-year relative survival rate|
|All SEER stages combined||26%|
Chest pain: When a lung tumor causes tightness in the chest or presses on nerves, you may feel pain in your chest, especially when breathing deeply, coughing or laughing.What are the 3 types of lung cancer? ›
The three main types are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. They are grouped together because they behave in a similar way and respond to treatment in a similar way.
Rapid growing, with a doubling time of less than 183 days: 15.8% Typical, with a doubling time of 183 to 365 days: 36.5% Slow growing, with a doubling time of over 365 days: 47.6%Is there a blood test for paraneoplastic syndrome? ›
To diagnose paraneoplastic syndrome of the nervous system, your doctor will need to conduct a physical exam and order blood tests. He or she may also need to request a spinal tap or imaging tests.Is paraneoplastic syndrome a disability? ›
Recent findings: Paraneoplastic disorders may affect any part of the central or peripheral nervous system. Although relatively uncommon, these disorders are a significant cause of severe and permanent neurologic disability.Does paraneoplastic syndrome cause pain? ›
This is a very rare disorder that consists of inflammation of the small blood vessels of the peripheral nerves and muscles. Patients often develop symptoms of peripheral neuropathy that may initially affect only one arm or leg before involving both sides. Pain often occurs.