Peritoneal mesothelioma is a rare, aggressive, and often fatal cancer originating from the mesothelium—the protective lining of various internal organs. While its overall incidence is low, affecting approximately 0.7 per 100,000 people in the United States (Yan et al., 2007), its presence in young individuals (under 40 years old) is exceptionally rare, with a frequency of less than 0.1 per 100,000 in the U.S. (SEER, 2023). The median age at diagnosis is 68 years (Mazurek et al., 2017), leaving limited information on its occurrence in younger populations (Thomas et al., 2015). This raises a crucial question: what factors contribute to this disease in young individuals?
Why Peritoneal Mesothelioma?
While mesothelioma is most often associated with asbestos exposure, particularly in pleural cases (lung lining), the risk peaks approximately 45 years after exposure (Lanphear & Buncher, 1992). In younger individuals, this latency period often excludes asbestos as a direct cause of peritoneal mesothelioma. Between 1990 and 2010, only 1.7% of all peritoneal mesothelioma cases occurred in individuals under 40, compared to 98.3% in those over 40 (Thomas et al., 2015). Interestingly, while pleural mesothelioma predominates in older patients (90% of cases, p < 0.0001), the distribution between pleural and peritoneal types in younger individuals is nearly equal: 47% pleural vs. 48% peritoneal (p < 0.0001). This suggests unique etiological factors at play in younger patients.
What Causes Peritoneal Mesothelioma in Young Patients?
The absence of a significant asbestos exposure history in most young patients points toward genetic predisposition as a key factor. Germline mutations, such as those in the BAP1 gene, are strongly associated with a higher incidence of mesothelioma and other malignancies (Xu et al., 2014). However, BAP1 mutations alone do not fully explain the disease's occurrence in this age group.
Other genetic syndromes and mutations associated with increased mesothelioma risk include Lynch syndrome, Li-Fraumeni syndrome (TP53 mutation), BRCA2, ATM, NF2, SDHA, and RASAL1 mutations (Malpica, 2023). Environmental and iatrogenic factors, such as therapeutic irradiation, peritoneal irritation from prior surgeries, Crohn’s disease, endometriosis, and long-term use of intra-abdominal catheters, may also contribute to tumor development (Malpica, 2023).
Symptoms of Peritoneal Mesothelioma
The symptoms of peritoneal mesothelioma are nonspecific and often mimic other abdominal or pelvic conditions. According to Malpica (2023), common presentations include:
Abdominal/pelvic pain, distension, or masses.
Gastrointestinal symptoms such as nausea, anorexia, vomiting, diarrhea, and bowel obstruction.
Constitutional symptoms like fever, fatigue, and weight loss.
Less common findings: lymphadenopathy, vaginal bleeding, back pain, or abnormal cervical smears.
Treatment Options and Prognosis
Despite its aggressiveness, treatment advancements have improved outcomes for young patients. Approximately 70% of patients under 40 undergo surgery (p < 0.0001), with a median survival rate of 28 to 35 months (Chua et al., 2009). Notably, younger patients exhibit a relatively high five-year survival rate of 66.9% (Nofi et al., 2024).
Treatment strategies include systemic chemotherapy, hyperthermic intraperitoneal chemotherapy (HIPEC), and cytoreductive surgery. Chemotherapy often incorporates drugs like cisplatin, irinotecan, gemcitabine, and pemetrexed (Chua et al., 2009). HIPEC, performed during surgery, delivers high concentrations of heated chemotherapy agents directly to the peritoneal cavity, maximizing cancer cell destruction while sparing normal tissues (Sugarbaker et al., 1995).
The combination of aggressive cytoreductive surgery with HIPEC remains the most effective approach to extend survival (Hassan et al., 2006; Yan et al., 2007). This dual strategy removes visible tumors and treats microscopic disease, improving outcomes significantly.
Future Directions
Understanding peritoneal mesothelioma in young patients is essential for improving prevention and treatment. With genetic predispositions and environmental factors likely playing larger roles than asbestos exposure, ongoing research is critical. Enhanced genetic screening, earlier diagnosis, and tailored therapies may further improve outcomes for this vulnerable population.
References
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Lanphear, B.P., & Buncher, C.R. (1992). Latent period for malignant mesothelioma of occupational origin. J Occup Med, 34, 718–721.
Malpica, A. (2023). Peritoneal Mesothelioma – An Update. Advances in Anatomic Pathology, 30(4), 262–274.
Mazurek, J.M., Syamlal, G., Wood, J.M., et al. (2017). Malignant Mesothelioma Mortality — United States, 1999–2015. MMWR Morb Mortal Wkly Rep, 66(8), 214–218.
Nofi, C.P., Roberts, B.K., Rich, B.S., Glick, R.D. (2024). Pediatric, Adolescent and Young Adult (AYA) Peritoneal and Pleural Mesothelioma: A National Cancer Database Review. Journal of Pediatric Surgery, 59(6), 1113–1120.
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Thomas, A., Chen, Y., Yu, T., et al. (2015). Distinctive clinical characteristics of malignant mesothelioma in young patients. Oncotarget, 6(18), 16766–16773.
Xu, J., Kadariya, Y., Cheung, M., et al. (2014). Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma. Cancer Res, 74, 4388–4397.
Yan, T.D., Welch, L., Black, D., et al. (2007). A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann Oncol, 18, 827-34.