Malignant Peritoneal Mesothelioma Features Shown by FDG-PET/CT
1Department of Respiratory Medicine and Hematology, School of Medicine, Hyogo Medical University, Nishinomiya, Japan
2Department of Radiology, School of Medicine, Hyogo Medical University, Nishinomiya, Japan
3Division of Lower GI, Department of Surgery, School of Medicine, Hyogo Medical University, Nishinomiya, Japan
Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive type of cancer of mesothelial cells in the peritoneum that represents 7-30% of all mesothelioma cases diagnosed and commonly caused by exposure to asbestos (1,2). MPeM is typically presented as a rapid, diffuse, and extensive spread throughout the abdomen, with most patients dying from the disease within a year. Related signs and symptoms are non-specific and include abdominal pain, abdominal distension, and weight loss. However, diagnosis is often delayed because of rarity and non-specific presentation. A median period of 4-6 months between initial presentation and diagnosis has been reported (3). Confirmation of diagnosis is challenging, with performance of a biopsy and histological and immunohistochemical findings required for definitive determination.
Computed tomography (CT) is the first-line imaging modality used as part of a diagnostic workup of suspected MPeM and typical findings include ascites, peritoneal thickening, omental disease, small bowel involvement with solid and cystic masses, and pleural plaque (4-7). However, CT findings are nonspecific and similar to metastatic peritoneal carcinomatosis, primary peritoneal serous carcinoma, malignant lymphoma, peritoneal lymphomatosis, pseudomyxoma peritonei, cystic lymphangioma, tuberculous peritonitis, and nontuberculous peritonitis, are thus considered inadequate for a specific diagnosis of MPeM. On the other hand, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has recently been reported as effective, as shown in a few studies of diagnosis of a single case (8-11) or small groups of patients (12), though its clinical utility remains to be established. The present study was performed to identify the characteristic features of pretreatment FDG-PET/CT in MPeM cases aiming to establish imaging diagnostic factors.
Patients and Methods
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the Hyogo Medical College of Medicine (Date 2021/3/26/No 1894). Written informed consent was obtained from all participants included in the study.
To the best of our knowledge, the data presented herein represent the largest number of MPeM patients who underwent pretreatment FDG-PET/CT examinations reported. Diffuse type was found in 45 (75.0%) and localized type in 15 (25.0%) cases. Although previous reports each reported positive FDG-PET scans (8-12), 55 patients (91.7%) in our series showed FDG-avid results, while 5 (8.3%) showed no FDG uptake, with a variety of SUVmax values noted (mean=7.32±4.05, range=0-16.77). The mean SUVmax of the 53 epithelial cases (mean=7.09±4.07, range=0-16.77) tended to be slightly lower than that of the 4 biphasic (mean=8.30±4.70, range=2.35-13.36) and 3 sarcomatoid (mean=10.08±2.64, range=8.21-13.10) cases, though they were not significantly different. Among the three, similar percentages of diffuse and focal disease patterns were noted. Nodal metastasis was more common in the epithelial group, while the biphasic and sarcomatoid groups more often showed extra-abdominal metastasis. Many of the present patients had findings indicating diffuse type, ascites, pleural effusion, and pleural plaque.
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A definitive diagnosis of MPeM must be based on pathological results, because of the nonspecific nature of symptoms, imaging findings, and serum markers. Many affected patients are presented with ascites and a cytological examination of abdominal paracentesis fluid can occasionally yield a diagnosis. However, there is a low number of malignant cells in ascites and significant cytological diversity in tumor cells, thus cytological analysis of sample ascitic fluid is often inconclusive, with a low diagnostic yield (15). Using immunohistochemistry, fine-needle aspiration of a tumor implant can yield useful findings, though due to the variability of tumor marker expression, diagnostic accuracy increases with solid tumor samples, which can be obtained using direct sampling during a diagnostic laparoscopy or with an ultrasound-guided core-needle biopsy procedure. An advantage of diagnostic laparoscopy is direct visualization of the peritoneal cavity, which can assist with diagnosis and planning future therapy. Additionally, in cases with pleural effusion, thoracentesis, or video-assisted thoracic surgery (VATS) is indicated for thoracic spread evaluation (1). Diagnosis of MPeM based solely on histological patterns can be difficult, thus immunohistochemical markers are important.
MPeM is classified histologically into three subtypes; epithelial, sarcomatoid, and biphasic (mixed). The epithelioid subtype is the most common, noted in approximately 75% of MPeM patients, and also has the best prognosis. Approximately 25% of MPeM patients are biphasic, while the sarcomatoid subtype is exceedingly rare, and both of these subtypes have a significantly worse prognosis, similar to corresponding pleural mesothelioma variants (1). Solid organs are not typically invaded by epithelial mesothelioma, while omentum infiltration is found in most cases (16). Generally, the disease remains confined to the abdomen, with multiple sites reported throughout the peritoneum. The sarcomatoid type tends to be more infiltrative and grows more rapidly, while the biphasic type has radiological and gross pathological features of both the epithelial and sarcomatoid types. In advanced stage cases, pleural cavity involvement and distant metastatic disease may be encountered.
Cases of MPeM show two basic forms, diffuse and localized type, in which the first is composed of diffuse nodules and plaques that tend to envelope the bowel viscera, while the other is manifested by a large tumor mass, usually in the upper abdomen, and discrete nodules scattered throughout the peritoneum (13). Another study noted that the diffuse type accounts for approximately 82.1% of all cases (17). Contrast-enhanced CT is universally accepted as the best imaging modality for management of MPeM, with advantages that include exquisite spatial anatomical details, examination speed, and wide availability. Common CT findings indicating MPeM are ascites, peritoneal thickening, caking, thickening or masses in the omentum, mesenteric nodules, small bowel involvement with solid and cystic masses, scalloping of intraabdominal organs, and pleural plaque (1,4-7). Cases with local–regional invasion are commonly encountered. On the other hand, lymph node involvement (5-10%) and extra-abdominal metastasis (3-5%) are relatively rare complications and considered to be associated with advanced late-stage disease (18,19).
Cisplatin and pemetrexed-based systemic chemotherapy are used to treat MPeM, though poor tumor response rates and negligible improvement in overall survival have been reported, in contrast with use of those for pleural mesothelioma (20). Research is presently underway for new drugs, such as antiangiogenic medications, immunotherapy, and growth factor agents (17). Because of its locoregional nature, contemporary treatment options for MPeM have been evolving towards aggressive surgical approaches in combination with intraperitoneal chemotherapy in the form of hyperthermic intraperitoneal chemoperfusion (19).
Our study has several limitations. First, it was conducted as a retrospective review and included a small number of patients treated at a single Center, with the numbers of biphasic and sarcomatoid type cases being especially small. As a result, generalization of the findings is limited, and statistical errors are possible. Nevertheless, the findings presented are considered a first step towards a future prospective study with a greater number of patients. Additionally, because four different types of PET/CT scanners were used, PET quantitative values were harmonized by use of a software program developed to harmonize SUVs obtained with different PET/CT systems using phantom data (14).
On the other hand, despite its limitations, considering the rarity of the disease, the new findings of this study from the relatively high volume of patients for a single institution, show that FDG-PET/CT is an extremely useful modality for identifying the biopsy site of MPeM.
In addition, as CRS/HIPEC for MPeM patients with good performance status (PS) remains the gold standard of treatment, it is highly important to detect patients with MPeM who often present only with vague, nonspecific symptoms including abdominal distention, pain, nausea, and weight loss using FDG-PET/CT (21).
In conclusion, FDG-PET/CT findings showed a variety of FDG uptake (SUVmax) values, which were nonspecific and inadequate to pinpoint specific diagnosis. FDG-PET/CT representing glucose metabolism is a useful modality to evaluate tumor viability of MPeM as guidance for biopsy. When a diagnosis of MPeM is suggested from FDG-PET/CT imaging, examinations to determine history of exposure to asbestos as well as presence of ascites, pleural effusion, and pleural plaque are important, because histological and immunohistochemical results are needed for diagnostic accuracy. FDG-PET/CT can help in decision-making for the therapeutic management of MPeM.
Conflicts of Interest
The Authors have no relevant financial or non-financial interests to disclose.
Kozo Kuribayashi: Conceptualization/writing – original draft and supervision; Kazuhiro Kitajima: methodology and project administration; Toshiyuki Minami: formal analysis and visualization; Masataka Ikeda: data curation; Koichiro Yamakado: investigation; Takashi Kijima: funding acquisition, validation, writing/reviewing and editing. All Authors have read and approved the final article.