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A case of pseudoachalasia hiding a malignant pleural mesothelioma

Abstract

Purpose

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. We describe a case of MPM with an uncommon onset, characterized by pseudoachalasia as demonstrated with high-resolution manometry (HRM).

Methods

A 56-year-old man was referred to our hospital reporting worsening dysphagia. On the hypothesis of an esophageal motor disorder, the patient was referred for an HRM examination, which revealed features consistent with a diagnosis of type II achalasia.

Results

At the time of the first pneumatic dilation the endoscopist stopped the procedure in order to prevent perforation when he noticed only partial expansion of the pneumatic balloon. A CT scan and subsequent CT-guided excisional biopsy revealed an epithelioid pleural mesothelioma infiltrating the muscle wall. Given his good clinical condition, the patient was eligible for chemotherapy with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2, resulting in a good response with partial remission of the disease and resolution of the dysphagia symptoms.

Conclusions

Pseudoachalasia as the first or only manifestation of mesothelioma is a rare occurrence that may expose patients to the risk of diagnostic delay. Close attention should be paid whenever a patient with symptoms and signs consistent with achalasia shows unusual features.

Tumori 2016; 102(Suppl. 2): e50 - e53

Article Type: CASE REPORT

DOI:10.5301/tj.5000521

Authors

Federica Branchi, Andrea Tenca, Claudia Bareggi, Carolina Mensi, Aurelio Mauro, Dario Conte, Roberto Penagini

Article History

Disclosures

Financial support: None.
Conflict of interest: None declared.

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Introduction

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Its annual incidence in Italy is 3.6 and 1.3 cases per 100,000 in men and women, respectively, and 5.1 and 2.1 in the Lombardy region (1). In a large majority of cases MPM is induced by exposure to asbestos fibers, usually in subjects working or living in contaminated environments (2). Exposure to asbestos can be of a small entity both in terms of dose and duration, and the disease occurs after a long latency time. The clinical manifestations of MPM range from dyspnea and pleural pain, generally associated with pleural effusion, to weight loss and hemithorax retraction, more frequently observed at the advanced stages of the disease (2). In this report, we describe a case of MPM with an uncommon onset, characterized by pseudoachalasia as demonstrated with high-resolution manometry (HRM).

With regard to the treatment options for MPM, only a small proportion of patients are eligible for resective surgery at the time of diagnosis, while the majority are referred for chemotherapy or radiation therapy (3). As regards the indications for treatment, our experience with this patient provides an example of how the decision-making process needs to be tailored to the patient’s condition, expectations and motivation, especially in the setting of malignancies with a poor prognosis and when facing symptoms that affect quality of life.

Case presentation

A 56-year-old man was referred to the outpatient service of our hospital in September 2014, reporting worsening dysphagia. The symptoms had started around 9 months earlier, with the onset of occasional dysphagia for solid food, but had gradually developed into daily episodes that arose with the ingestion of both solids and fluids. The man also reported recurring regurgitation and gradual weight loss of 4 kg (from 67 to 63 kg, 173 cm height). Only 1 episode of interscapular pain was reported, which had resolved spontaneously.

The patient had a known history of occasional dyspepsia, without gastroesophageal reflux symptoms. In 2008 he had undergone pleurodesis after posttraumatic left-sided pneumothorax and in 2009 he had been admitted to the hospital for labyrinthitis. The only other relevant comorbidity was supraventricular extrasystole, for which he was on beta-blockers; propranolol was the only current medication.

On initial examination the man appeared fatigued and suffering. Physical examination revealed signs of moderate dehydration and reduced breath sounds at lung auscultation of the left base at the site of the previous intervention.

According to the standard diagnostic approach to dysphagia, an upper gastrointestinal endoscopy was performed, revealing a normal-looking esophagus, stomach and proximal duodenum. On the hypothesis of an esophageal motor disorder, the patient was referred for an HRM examination, which revealed lack of relaxation of the lower esophageal sphincter and pan-esophageal pressurization (Fig. 1), features consistent with a diagnosis of type II achalasia (4). A barium swallow x-ray was done as part of the routine protocol of our clinic for the evaluation of the esophageal diameter, appearance of the cardias, and esophageal emptying; it showed moderate dilation of the esophageal body with the typical “bird-beak” narrowing of the gastroesophageal junction, as well as stasis of barium and delayed esophageal emptying (Fig. 2A). Thus, the patient was prepared for pneumatic esophageal dilation, which has been reported to have long-term efficacy in the treatment of type II achalasia (4, 5). At the time of the first pneumatic dilation (Fig. 2B), however, the endoscopist stopped the procedure when he noticed only partial expansion of the pneumatic balloon (Rigiflex™ II balloon 30 mm, Boston Scientific) at the recommended pressure of 12 pounds per square inch; this was done to prevent perforation (5). The patient was transferred to the radiology department for a computed tomography (CT) scan, which revealed nodular thickening of the left pleura, more evident at the base, along with thickening of the lower esophageal wall. A PET scan confirmed the presence of hypermetabolic tissue in correspondence to the left pleura, the greater pectoral muscle and around the lower portion of the esophagus, possibly infiltrating it (Fig. 3). Shortly after, the patient underwent a CT-guided excisional biopsy in order to obtain a specimen for histological examination: the results were consistent with epithelioid pleural mesothelioma infiltrating the muscle wall. Asbestos exposure was extensively investigated by a trained interviewer operating at the Lombardy Mesothelioma Registry with the aid of a validated questionnaire (6). No occupational, environmental or domestic asbestos exposure emerged from the patient’s history. Therefore, the case was classified as “undetermined asbestos exposure”.

High-resolution manometry showing findings consistent with type II achalasia.

Esophageal x-ray showing esophageal dilation with bird-beak narrowing of the gastroesophageal junction, consistent with achalasia (A). Endoscopic balloon dilation of the lower portion of the esophagus (B). As shown in the picture, the balloon fails to inflate completely at the recommended pressure (“hourglass appearance”), which prompted interruption of the procedure and further investigation.

PET-CT scan findings before (left) and after 3 cycles of chemotherapy (right).

The choice of the most appropriate therapeutic approach was discussed by a multidisciplinary board. The patient’s relatively young age and strong motivation were taken into consideration as well as the advanced stage of the disease (inoperable, stage T4N3M0) and his suboptimal general condition (performance status 2 according to the Eastern Cooperative Oncology Group [ECOG] criteria), which is associated with significantly shorter survival in patients with pleural mesothelioma (7). The histological features were favorable in that epithelioid MPM shows a better response to chemotherapy and better overall survival than non-epithelial forms (3). Therefore, the patient was prepared for systemic chemotherapy, also with the aim of improving the dysphagia which was seriously affecting his quality of life. A standard approach with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 was programmed (8). Before the start of chemotherapy, a percutaneous endoscopic gastrostomy (PEG) tube was positioned in order to ensure appropriate calorie intake and prevent worsening of malnutrition.

From 14 November 2014 to 30 December 2014 three cycles of chemotherapy were administered. During the first cycle the patient was hospitalized in order to monitor and manage any adverse events. Tolerance to treatment was good and we observed major improvement of dysphagia and 6 kg weight gain. After the first 3 cycles, PET-CT scan revealed significant shrinkage of the tumor mass as well as marked reduction of the metabolism of the pleural and lymph node disease (Fig. 3), proving the effectiveness of chemotherapy and explaining the improvement of the pseudoachalasia symptoms.

Chemotherapy was programmed for a further 3 + 3 cycles, given the improvement of the patient’s general condition and the partial remission obtained. The response to treatment was confirmed by imaging reevaluation after 6 cycles. The improvement of dysphagia allowed resumption of oral nutrition and removal of the PEG tube.

The observed toxicities were mild fatigue after the first cycle and self-limiting ototoxicity after 7 cycles, prompting a dose reduction in cycles 8 and 9, when only pemetrexed was administered. After the second cycle supportive care with intravenous fluid and electrolyte solutions was needed. No hematological or gastrointestinal toxicity was reported.

The clinical condition of the patient remained stable until September 2015, when he developed abdominal distension. Radiological examination showed a sustained pleural and lymph nodal response to treatment but suspected abdominal disease progression with evidence of ascites. Considering the good general condition attained by the patient (ECOG performance status 1), rechallenge with systemic treatment (carboplatin and pemetrexed) was considered adequate. The choice of retreatment with similar compounds is largely accepted in case of a good response to first-line chemotherapy (9).

At 14 months from diagnosis the patient is still alive, free of major symptoms including dysphagia, and in stable clinical condition. At the time of this submission, chemotherapy was ongoing.

Discussion

The diagnosis of achalasia has greatly improved since the introduction of HRM, a diagnostic system able to identify dysfunctions of esophageal motility with higher accuracy than standard manometry (4). Pseudoachalasia is defined as the presence of altered esophageal peristalsis and loss of function of the lower esophageal sphincter secondary to other causes, as opposed to primary achalasia (4). It represents a small proportion of achalasia cases, accounting for 2% to 4% of all diagnoses. The most common cause of pseudoachalasia is adenocarcinoma of the gastroesophageal junction (70%), followed by other neoplasms such as lymphoproliferative disorders, metastatic carcinomas and small cell lung carcinomas, and a limited number of benign disorders including amyloidosis and pancreatic pseudocyst. The pathogenesis of this disorder is still far from being clearly understood: the alterations in esophageal motor function are believed to be a consequence of several possible mechanisms: mechanical compression of the esophageal wall, infiltration of the muscle layers, and autoimmune damage to the myenteric plexus (10). Literature data show that pleural mesothelioma was first described in association with pseudoachalasia in 1983, but since then only few cases have been reported (4). Pathological data showed that symptoms usually derive from direct infiltration of the esophageal wall by malignant tissue. Pseudoachalasia as the first and/or only manifestation of mesothelioma, as was the case in our patient, is an occurrence that may expose patients to the risk of diagnostic delay and has been reported even more rarely. This case highlights the need to pay close attention whenever a patient with symptoms and signs consistent with achalasia shows unusual features, such as failure of full expansion of the balloon during the endoscopic therapeutic procedure as reported in this case. In such circumstances, further diagnostic tests, e.g., cross-sectional imaging techniques, are usually able to identify the underlying condition responsible for the onset of pseudoachalasia.

Disclosures

Financial support: None.
Conflict of interest: None declared.
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Authors

Affiliations

  •  Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan - Italy
  •  Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan - Italy
  •  Oncology Unit, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan - Italy
  •  Epidemiology Unit, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan - Italy

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