Unusual case of malignant pleural mesothelioma

Abstract

We present the case of a 65-year-old woman who presented with progressive dysphagia and was diagnosed with achalasia. She subsequently developed bilateral chylous pleural effusions, with no cause identified despite extensive investigations (including computed tomography (CT) scans, gastroscopy and medical thoracoscopy (MT)) and review at a dedicated pleural multidisciplinary team meeting.

Despite optimal supportive management she deteriorated and was admitted to the intensive care unit, where she passed away due to sepsis and respiratory failure 10 months after initial presentation. A postmortem returned a diagnosis of epithelioid mesothelioma, encasing the carina, distal oesophagus and coeliac axis.

Mesothelioma only very rarely presents with either chylous effusions or achalasia. Additionally while MT normally conveys excellent sensitivity for pleural malignancy, it was insufficient here. This case highlights how an unusually located mesothelioma can produce an unusual clinical picture. It also suggests a role for early video-assisted thoracoscopy to aid diagnosis.

Background

Mesotheliomas are an uncommon malignancy affecting the lining of certain organs, but most often occurring in the lung pleura (malignant pleural mesothelioma (MPM)). MPM is unique in that the association between the malignancy and its primary causative agent, asbestos is very well established.¹ Due to the considerable lag phase (typically between 30 and 40 years) between initial exposure and development of disease, presentation if often in older adults with little recollection of exposure.²

The prognosis and treatment of advanced MPM remain poor despite intensive research, therefore, early detection is key to improving outcomes. Additionally, for many patients and their families, the entitlement to compensation for asbestos exposure-related diseases, including MPM, depends on a definitive diagnosis.

The typical presentation of MPM is of a patient with a known history of asbestos exposure, presenting with dyspnoea and/or chest pain (less common symptoms include weight loss, fatigue, fever and cough). Usual clinical and radiological findings include a unilateral pleural effusion and irregular parietal pleural thickening.³ While diagnosis can be difficult to obtain, medical thoracoscopy (MT) has been demonstrated to have a very good sensitivity and specificity for detection (>90% sensitivity and specificity).⁴

This case, however, is unusual as it resisted reliable diagnostic approaches due to its unusual mediastinal distribution. This location also led to atypical gastrointestinal (GI) findings, and bilateral chylous pleural effusions which are very rarely seen with MPM. While a MT was unable to gain access to the involved area to retrieve tissue for a diagnosis, an early video-assisted thoracoscopy (VATS) might have been able to do so.

We hope to use this case to raise awareness about MPM at this time of predicted peak incidence, and highlight some unusual presentations and the consideration of early VATS.

Case presentation

A 65-year-old woman with an unremarkable medical history and a 20 pack-year smoking history presented to the emergency department with complete dysphagia of solids and liquids, reflux of saliva/mucus and epigastric pain and vomiting after eating. These symptoms were superimposed on a background of intermittent heartburn for the preceding 9 months. The patient underwent numerous GI investigations (detailed below), and was diagnosed with oesophagitis, duodenitis and Helicobacter pylori infection. On subsequent outpatient assessment she was diagnosed with type 2 achalasia and an oesophageal stricture. Her difficulty feeding persisted, and she was managed principally with nasogastric (NG) feeding, with eventual deployment of an oesophageal stent.

The patient then went on to develop shortness of breath associated with bilateral pleural effusions. Sampling revealed these to be chylous. Despite repeated interval CT scans of the thorax, abdomen and pelvis, and MT with pleural biopsy, no definitive diagnosis was achieved. Her clinical course and investigations were reviewed in a pleural multidisciplinary team (MDT). Due to multiple negative tissue biopsies (oesophageal, pleural and lymph node), a working diagnosis of fibrosing mediastinitis was established, for which she was commenced on steroid therapy.

Despite this treatment along with supportive measures, she continued to deteriorate both in terms of her feeding and respiratory function. She continued to lose weight and developed a hospital acquired pneumonia. She was admitted to intensive care unit (ICU) where, despite aggressive antimicrobial therapy and fluid management she failed to improve. She sadly died approximately 10 months after her initial presentation to the emergency department.

A postmortem was performed and a soft-tissue mass encasing the carina, distal oesophagus and coeliac axis was found to have histological features in keeping with epithelioid mesothelioma. No asbestos bodies were identified on stained lung sections.

Investigations

1. Functional GI investigations including oesophageal manometry and barium swallow were performed to confirm the diagnosis of type 2 achalasia.

2. Twelve days after presenting to the ED, the patient underwent oesophagogastroduodenoscopy (OGD) with biopsies. This supported the initial diagnosis of oesophagitis and duodenitis, with a positive test for H. pylori. Follow-up OGDs demonstrated oesophageal spasms and a stricture.

3. A laproscopic Heller myotomy was performed, which found significant scarring around the hiatus and enlarged gastro-oesophageal junction and left gastric lymph nodes. Biopsies were taken from various areas, including paraoesophageal and left gastric lymph nodes and a nodular area of the cardia. These samples suggested the presence of atypical mesothelial cells, with the overall appearance favouring a florid mesothelial cell proliferation that can mimic mesotheliomia. There were no unequivocal features of malignancy. Additionally, p16 loss fluorescence in situ hybridisation tests on the samples were negative (while fairly specific for confirming malignancy in a mesothelial proliferation, it is negative in approximately 25% of MPMs).

4. The patient underwent three contrast-enhanced abdominal pelvic CT scans and an additional CT pulmonary angiogram. These scans identified mild distal oesophageal and crus of the diaphragm (hiatus) thickening, and revealed the bilateral pleural effusions (figure 1). There was mild pleural enhancement, but no nodularity, which is atypical for mesothelioma.

5. Thoracic ultrasound guided pleural aspiration revealed chylous effusions, with no evidence of malignant cells on cytology.

6. An MT was performed with large full-depth pleural biopsies. Histology was in keeping with non-specific pleuritis (including a patchy lymphoid infiltrate and reactive mesothelial cells), but no evidence of malignancy.

7. A postmortem was undertaken which established the unifying diagnosis of epithelioid mesothelioma.

Figure 1.

Two cross-sectional images from the patient’s CT scans 3 months apart. The arrows demonstrate the area of soft-tissue thickening present in the mediastinum. Note the interval development of bilateral chylous pleural effusions in the second image.

Differential diagnosis

In light of her initial presentation, the first investigations were mainly of the GI tract. A positive test for H. pylori coupled with the inflammatory changes of the oesophagus and duodenum led to the first diagnosis of an infection-driven process.

Further functional GI investigations suggested additional pathology, with manometry suggesting a possible diagnosis of achalasia type 2 (however, the patient admitted to not fully understanding the instructions and performing multiple small swallows which may have also accounted for the result). However, with a stricture visualised and the patient suffering continuing weight loss, there was also concern about a potential underlying malignancy.

The various biopsies mentioned previously were unable to equivocally confirm a malignancy (limited by the ability to gain tissue from the inaccessible mediastinal soft tissue thickening seen on imaging). In light of the clinical picture, possible differential diagnoses included: MPM, lymphoma or fibrosing mediastinitis. After review of the case and imaging at a pleural MDT, a working diagnosis of rapidly progressive fibrosing mediastinitis was felt to be most likely. There are numerous possible causes of which, including vasculitis, IgG₄ disease, medications, viral diseases, retroperitoneal fibrosis, sclerosing cholangitis, Riedel thyroiditis or idiopathic, however, no potential causes were proved.

It was only at postmortem where there was sufficient access to the mediastinum to establish the final diagnosis of epithelioid MPM.

Outcome and follow-up

Initial treatment was tailored to the GI complications. Antimicrobial and proton pump therapy were initiated for H. pylori infection. Additionally, she was treated with antiemetics and NG feeding with dietician input to attempt to maintain her weight. Eventually oesophageal stenting was required, which was inserted during one of her OGD procedures.

For her respiratory symptoms, dietary modification failed to ameliorate the progression of her chylous effusions. Following repeated therapeutic pleural aspirations, bilateral indwelling pleural catheters were placed. Recurrent pneumonias were treated with antimicrobial therapy and supportive fluid and oxygen therapy, with escalation to ICU. After discussion with her family a decision to escalate to mechanical ventilation was deemed to not be in the patient’s best interests and she passed away approximately 10 months after initial presentation.

Discussion

We present an unusual case of patient with no known asbestos exposure, who developed an MPM with an atypical mediastinal tumour that made diagnosis extremely challenging. This location produced unusual, initially obstructive GI symptoms, diagnosed as achalasia. When it did produce respiratory manifestations, specifically bilateral chylothoraces, these were very non-specific and uncharacteristic of mesothelioma. Finally diagnosis was not achieved after high sensitivity MT, which has documented sensitivity and specificity of >90%.⁴

Asbestos fibres when inhaled cause multiple changes in the pleura, including cycles of damage and repair, DNA alteration and inflammatory changes which contribute to the production of MPM.⁵ Therefore, those at highest risk are those who formerly worked with asbestos (eg, in manufacturing or construction, etc) or their family members who were exposed to their clothing.

A case of MPM presenting with oesophageal achalasia is very rare (at the time of writing a search of the PubMed database using both of these medical subject heading terms yielded only eight case reports).

MPM effusions are most often unilateral and also unlikely to be chylothoraces. A chylothorax is caused by damage to the thoracic duct with leakage of chyle (a classically milky fluid of predominantly lipids and lymphatic fluid) into the pleural space. Causes can be traumatic (eg, after thoracic surgery) or due to medical causes including malignancies, tuberculosis or lymphatic malformations.⁶ Malignancies which result in chylothoraces are most often lymphomas, and only very rarely MPMs, with one recent report in 2018 stating that there were only six documented cases of MPMs producing chylothoraces at the time of writing.⁷

We attributed these unusual features to the unusual location of this MPM. Being located in the mediastinum meant that it could infiltrate and obstruct the oesophagus and thoracic duct, which would account for the presentation. Finally, while MT has excellent sensitivity for conventionally located MPMs, it appears that only a VATS would have had the potential to reliably reach this location.

The British Thoracic Society offers guidance on the workup of patients where MPM is suspected (figure 2).^{3 8}

Figure 2.

An adaptation of the BTS guidelines for the diagnosis of MPM into a flow chart. BTS, British Thoracic Society; CXR, Chest X-ray; IHC, Immunohistochemistry; MPM, malignant pleural mesothelioma; MT, medical thoracoscopy; PET, Positron emission tomography.

There are no definitive instances where VATS should be preferred to MT, with both methods having documented diagnostic yields of over 90%.⁹ A VATS is a more costly and invasive procedure, requiring a thoracic surgical team and general anaesthesia. Therefore, there are many instances where it would be contraindicated (eg, patient frailty, health services where the cost of VATS is prohibitively high). However, a VATS also lends greater access to the pleural cavity, including the mediastinal pleural, and this case highlights where it may be superior and should be considered.¹⁰

Patient’s perspective.

From the patient’s husband: I suppose that after an horrific experience the fact that my wife suffered from such a rare complaint is in a way quite fitting as she was a rare woman. I was in awe of her grit and determination and I hope this report will help others. I know that’s what she would want.

Learning points.

• We would like to use this case to highlight how an atypically positioned malignant pleural mesothelioma (MPM) can produce an unusual clinical picture, and for clinicians to consider the diagnosis when not presenting as it might usually do (eg, chest pain, dyspnoea, abnormal chest X-ray, known history of asbestos exposure).

• Unusual features of mediastinal MPM to consider include obstructive gastrointestinal tract symptoms, bilateral chylous effusions and resistance to diagnosis with medical thoracoscopy.

• There should be a consideration of the early use of video-assisted thoracoscopy in patients where there is a high suspicion of an MPM, but no definitive diagnosis.

Ethics statements

Patient consent for publication

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