Acute popliteal thrombus workup leads to discovery of primary peritoneal mesothelioma in the absence of any known asbestos exposure

Abstract

A 75-year-old man presented to the emergency department with 1-day history of right lower limb pain and 3-month history of vague abdominal pain. In the emergency department a thrombus was discovered in the right popliteal artery. CT scan of the abdomen and pelvis revealed high-density material in the pelvis, multiple hypodensities on the liver, ascites with omental nodularity, and high-density material along the stomach wall. He underwent thrombectomy and was started on anticoagulation therapy. The core needle biopsy revealed primary omental mesothelioma. There was no history of any known asbestos exposure. He also had to undergo therapeutic paracentesis twice due to abdominal distension. Mesothelioma treatment of carboplatin and pemetrexed was started, and the patient is currently receiving this chemotherapy treatment regimen.

Background

Mesothelioma is a rare cancer that affects the internal linings of the body, including the pleura, peritoneum and pericardium. Efforts to identify the risk factors and establish diagnostic criteria for mesothelioma began at the International Expert Meeting for Asbestos, Asbestosis, and Cancer in 1997 which compiled the Helsinki Criteria.¹ Based on the Helsinki Criteria, 80% of malignant mesothelioma is attributable to asbestos exposure.¹ The other minor causes of mesothelioma are exposure to erionite fibres, thorium dioxide contrast, radiation therapy for lymphoma and Wilms tumour, simian virus 40 and spontaneous occurrences.^1–3

Primary peritoneal mesothelioma is a rare disease with a crude incidence rate of 0.12 per 100 000 person years.⁴ Peritoneal mesothelioma may pose a diagnostic challenge since there is no definitive way to recognise this malignancy based solely on radiologic or clinical appearances.⁵ The non-specific symptoms that the patients with mesothelioma present with are abdominal distention, pain, nausea and ascites. The diagnosis becomes even more difficut when there is no clear known exposure to asbestos. As a result, the estimated average duration from presentation to diagnosis in a patient of peritoneal mesothelioma without any known exposure to asbestos is 122 days.⁶ We report a case of primary peritoneal mesothelioma in a 75-year-old man without any known asbestos exposure. He initially presented with leg pain and was diagnosed with popliteal artery thrombosis. Although extremely rare, physicians should consider primary peritoneal mesothelioma in their list of differential diagnoses when treating a patient with similar symptoms.

Case presentation

A 75-year-old man with past medical history of hypertension presented to the emergency department with acute right lower limb pain since that morning and chronic abdominal pain for the last 3 months. The leg pain started in the morning when he was sitting in his chair. He started having constant, dull aching pain in his right leg and foot that had gradually increased to 6/10 in intensity and was not relieved or aggravated by ambulation. He initially attributed the pain in his right foot as ‘falling asleep’, but the pain worsened when he tried to ambulate. He was also complaining of chronic diffuse abdominal pain. The abdominal pain was dull aching, throughout his abdomen, waxing and waning in nature, 5/10 in intensity when severe, with symptoms beginning almost 3 months ago. There was no radiation, no diurnal variation and was unrelated to diet, stool or urine. The patient had undergone upper GI endoscopy for the abdominal pain and early satiety 1 week ago. The endoscopy found gastritis. There was no history of dysphagia, odynophagia, jaundice or change in the colour of his stool. He denied any fever, chest pain, dyspnea, palpitation, nausea or vomiting.

On examination, the patient was found to be well developed. He was in mild distress due to the pain in the right lower limb. The right lower limb was cold to touch and the pulses were diminished. There was no discoloration, skin changes or tenderness of the right lower limb. Abdominal examination showed mild diffuse tenderness with some distention. Bowel sounds were normal. The vitals were stable. He was saturating well on room air.

Investigations

The right lower limb Doppler ultrasound and noninvasive leg arterial study revealed a thrombus within the popliteal artery extending to the level of bifurcation. Ultrasound of his abdomen could only visualise the proximal aorta which was normal and showed ascites. Due to the ascites and acute kidney injury, a non-contrast CT abdomen and pelvis was done. This scan showed a high density material occupying the majority of the pelvis, moderate amount of ascites with omental nodularity, multiple cystic hypodensities within the liver, and hyperdensities along the anterior wall of the body of the stomach, which were felt to be reflective of omental metastases vs a gastric mass (figure 1). A Positron Emission Tomography – Computed Tomography scan showed hypermetabolic mesenteric masses within the abdomen and pelvis (figure 2) and associated hypermetabolic implants along the peritoneum above the liver and in the right lower quadrant.

Figure 1.

CT abdomen showing the complex high density perihepatic ascites.

Figure 2.

PET/CT scan showing increased metabolic activity in the mesentric mass in the pelvis.

On the oncologist’s recommendation, a peritoneal biopsy was taken. The histological sections from the biopsy showed an atypical mitotically active epithelial proliferation with papillary structures and complex architecture. The cells were frankly malignant and were seen extensively invading underlying fibroadipose tissue. The pathological diagnosis was mesothelioma. His serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, alpha-fetoprotein (AFP) and prostate specific antigen (PSA) were within normal limits. Tumour cells in the biopsy were positive for CAM5.2, Calretinin, CK7, D2-40 and WT-1. Immunohistochemical staining for CK20, GATA-3, TTF-1, Ber-ep4, CDX2 and MOC-31 was negative.

Treatment

He underwent thrombectomy for the popliteal artery clot and was started on heparin. He was seen by an oncologist while in the hospital. The patient was transitioned from heparin to apixaban and was discharged from the hospital. He was followed up by oncology department and was started on carboplatin and pemetrexed. He was readmitted to the hospital twice and underwent therapeutic paracentesis to relieve his abdominal distension and pain. He is currently under the chemotherapy regimen.

Outcome and follow-up

Currently the patient is on chemotherapy treatment with carboplatin and pemetrexed. His condition is stable.

Discussion

Asbestos exposure remains the leading cause of peritoneal mesothelioma. 33%–50% of the cases of peritoneal mesothelioma is attributable to asbestos exposure as compared with 80% in pleural mesothelioma.⁷ Peritoneal mesothelioma is an aggressive cancer which only accounts for 10%–30% of mesothelioma cases.⁸ Though asbestos exposure remains the major cause of mesothelioma, other causes such as erionite fibres, thorium dioxide contrast used in radiology studies, radiation therapy for the treatment of lymphoma and Wilms tumours, simian virus 40, irritation due to chronic pancreatitis, and spontaneous occurrences are also recognised as a cause of mesothelioma in recent years.^{2 3} Peritoneal exposure to asbestos could be through inhalation, ingestion or direct contact.⁹

Patients presenting with the diffuse symptoms of abdominal pain, distention, nausea or an abdominal mass potentially pose a challenge because these symptoms could suggest a multitude of differential diagnoses.¹⁰ Abdominal pain, distention and nausea could be symptoms of gastrointestinal diseases, and abdominal masses may be observed in cases of fibrosis, adenocarcinoma or lymphoma.^{5 11 12}

Although CT scans with contrast are an excellent modality for discovering abdominal masses and densities, this scanning method alone is nonspecific and unable to reliably diagnose mesothelioma.¹³ Ascites is seen in a majority of mesothelioma cases, but paracentesis and cytology of ascitic fluid is generally not a reliable approach for diagnosing mesothelioma.^{5 13 14} Mesothelioma can only be definitively diagnosed by surgical biopsy with histological analysis.⁵ Immunohistochemistry at the earliest possible stage can definitively determine if the biopsy sample is actually mesothelioma instead of another potential tumour such as pleural fibrosis, reactive mesothelial hyperplasia, metastatic adenocarcinoma, pyothorax-associated lymphoma or a rare variant of mesothelioma.¹¹

The modalities for treatment include surgery and chemotherapy. Surgical cytoreduction of peritoneal mesothelioma tumours lead to a fivefold increase in overall survival time, although reportedly only 40% of patients with this diagnosis elect to undergo surgery.¹⁵ A systemic first-line treatment option, pemetrexed has halted the disease progression for up to 12 months in cases of diffuse malignant peritoneal mesothelioma, with follow-up therapy of cisplatin along with a second round of pemetrexed showing stability of the intrathoracic malignancy for an additional 6 months.¹⁶ Cytoreduction along with heated intraperitoneal chemotherapy is shown to have the best outlook for survival duration, with the median survival ranging from 34 to 92 months, with nuclear size being the dominant determining factor of survival time in patients.5 13 17–19

Learning points.

• When a patient is diagnosed with peritoneal mesothelioma, a detailed history should be sought regarding previously neglected asbestos exposure.

• Diagnosis of peritoneal mesothelioma is more likely in the setting of asbestos exposure but should not be missed even when there is no known exposure to asbestos.

• Surgical biopsy with histopathological analysis is needed for the definite diagnosis.

• Surgical cytoreduction of the peritoneal mesothelioma tumour leads to increase in survival time.