As the number of long-term cancer survivors is increasing, the incidence of post-irradiation malignant mesothelioma may also increase. We herein present the case of an 85-year-old female patient with a history of several surgeries for solid tumors and radiotherapy to the pelvis, who presented with abdominal pain and diarrhea. The patient's general condition gradually worsened and she succumbed to cardiopulmonary arrest triggered by vomiting ~3 months after the onset of the abdominal symptoms. An autopsy revealed malignant intestinal obstruction caused by peritoneal mesothelioma. Irradiation is a known risk factor for malignant mesothelioma, which may develop ~10–30 years after radiotherapy. To the best of our knowledge, this is the first report of a patient with malignant mesothelioma developing ~50 years after radiotherapy. The aim of the present study was to remind physicians that malignant mesothelioma should be considered in the differential diagnosis of patients with a history of radiotherapy who present with gastrointestinal symptoms.
Malignant mesothelioma is an aggressive neoplasm that arises from the mesothelial cells lining serosal surfaces. The majority of mesotheliomas arise in the pleura (85.5%), and malignant peritoneal mesothelioma (MPM) is a rare tumor accounting for 13.2% of all malignant mesotheliomas (
Asbestos exposure is the most important risk factor for malignant mesothelioma, including MPM (
We herein report a case of MPM diagnosed on autopsy in a patient who succumbed to intestinal obstruction. The patient had no history of asbestos exposure, but had a history of radiotherapy for ovarian cancer ~50 years earlier. To the best of our knowledge, this is the first report of a patient with malignant mesothelioma that developed this long after radiotherapy.
An 85-year-old Japanese woman presented at the Matsumoto Medical Center with abdominal pain and diarrhea in June, 2017. The patient had no history of asbestos exposure; however, she had a history of several tumor surgeries: Bilateral adnexectomy and postoperative radiotherapy for ovarian tumors in her 30s (details unknown), right upper lobectomy for lung adenocarcinoma at the age of 69 years, thymoma resection at the age of 73 years, and rectal amputation with artificial anostomy for rectal adenocarcinoma at the age of 79 years. The patient had not received postoperative treatment, including radiation therapy, following surgery for rectal cancer. A physical examination revealed bilateral pleural effusion, ascites, and lower leg edema. Laboratory tests revealed an increased white blood cell count (12,270/µl: Reference value 3,300–8,600/µl), anemia (hemoglobin, 7.4 g/dl: Reference value 11.6–14.8 g/dl), hypoalbuminemia (albumin, 1.4 g/dl: Reference value 4.1–5.1 g/dl), and elevated C-reactive protein level (13.3 mg/dl: Reference value 0.00–0.14 mg/dl). The serum levels of tumor markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), were not elevated. Therefore a postoperative adhesive ileus was suspected and the patient was treated with antibiotics and albumin supplementation, in addition to intravenous fluid administration, as neither the patient nor her family wished to have aggressive examinations or treatment. In addition to the presenting symptoms, vomiting, hematemesis and bleeding appeared in September, 2017. The patient's general condition gradually worsened, and she succumbed to cardiopulmonary arrest triggered by vomiting at ~3 months after the onset of the abdominal symptoms.
An autopsy was performed with the consent of the patient's family. Macroscopically, surgical scars were identified in the right chest and the lower abdominal midline. In the pleural cavity, clear yellowish pleural effusion (350 ml on the left side and 250 ml on the right side) and pleural adhesions on the upper right side were observed. There was no evident pleural plaque formation. The abdominal cavity contained 3,000 ml of slightly cloudy, yellowish ascitic fluid, and moderate intestine-to-intestine and intestine-to-pelvic peritoneum adhesions were observed. The ileum exhibited adhesions to the pelvic wall with focal narrowing for a length of ~5 cm (
Clinically, postoperative adhesive ileus and recurrence or metastasis of the prior cancers was suspected due to the patient's medical history. In general, the abdominal symptoms of MPM are non-specific, and may include ascites, retention, abdominal distension, abdominal pain, weight loss, nausea and vomiting (
Histologically, MPM is classified into three subtypes: Epithelioid, sarcomatoid and biphasic. The majority of MPMs are of the epithelioid type, and display a papillotubular or solid pattern (
Asbestos exposure is the most common cause of malignant mesothelioma, including MPM, particularly in men (
However, the patient had a history of multiple maligancies (ovarian cancer, lung cancer, thymoma and rectal cancer) and radiotherapy to the pelvis. In this case, although the patient's history suggested the possibility of a genetic mutation that increases susceptibility to developing multiple malignancies, the main lesion of MPM was located in the ileum and adhered to the pelvis, with superficial spread to a limited serosal area of the stomach, jejunum and spleen; the location of the lesion corresponded to the pelvic irradiation site following ovarian cancer surgery. Malignant mesothelioma can occur after radiotherapy for tumors, which suggests that direct irradiation may be a risk factor for its development. Malignant mesotheliomas following radiation therapy usually develop ~10–30 years after radiotherapy (
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No funding was received.
The datasets during and/or analyzed during the present study available from the corresponding author on reasonable request.
MO and MK designed the study. MO wrote the manuscript and assessed the figures and tables. MK, TS, HK and KN critically revised the manuscript and were involved in data interpretation. MO and MK finalized the manuscript and submitted the paper for publication. All authors have edited the manuscript for intellectual content. All authors have read and approved the final version of this manuscript for publication.
Not applicable.
The patient and her family provided written informed consent for the publication of the case details and any associated images.
The authors declare that they have no competing interests.
Macroscopic findings of the ileum. (A) Focal narrowing was observed over a length of ~5 cm in the ileum. (B) The cut surface of the ileal narrowing revealed thickening of the intestinal wall (arrows).
Histological findings of MPM. (A-C) Hematoxylin and eosin staining and (D-L) immunohistochemistry for (D) CK7, (E) CK20, (F) calretinin, (G) D2-40, (H) TTF-1, (I) CEA, (J) CA125, (K) ER and (L) PAX8. (A) The tumor invaded the subserosal tissue of the ileum and (B and C) was composed of epithelial cells arranged in a papilotubular pattern. These cells were positive for CK7, calretinin and D2-40, and negative for CK20, TTF-1, CEA, CA125, ER and PAX8. Magnification (A) ×40, (B) ×200 and (C-L) ×400. MPM, malignant peritoneal mesothelioma; CK, cytokeratin; TTF, throid transcriprion factor; CEA, carcinoembryonic antigen; CA125, carbohydrate antigen 125; ER, estrogen receptor; PAX8, paired box 8.