Cancer, Mesothelioma, Benign

Article Author:
David Myers
Article Editor:
Hani Babiker
10/27/2018 12:31:25 PM
PubMed Link:
Cancer, Mesothelioma, Benign


Mesotheliomas represent a proliferative neoplasm made up of epithelial and mesenchymal cells of the mesothelium which make up part of the serosal covering and lining of various organ surfaces within the body. Mesotheliomas can be broadly divided into benign and malignant types. This article will focus on the benign form. Although they are referred to as "benign," after removal, these lesions have been shown to have a high propensity for local recurrence, and in some rare cases, it has been suspected to undergo malignant transformation.[1] A common form of the benign mesothelioma is known as benign multicystic mesothelioma of the peritoneum (BMMP). Mesotheliomas are very rare neoplasms, usually arising from the serosal surface of organs in the pelvic region such as the bladder, uterus, ovaries, or rectum. Benign mesotheliomas also have been commonly reported to develop from the pleura, pericardium, and peritoneum.[2] The developmental pathogenesis of these neoplasms is unclear, and unlike their malignant counterpart, there is not an established relationship to asbestos exposure. Patients will often present with abdominal pain or abdominal masses, unexpected weight gain, shortness of breath, and/or pleural effusion.[3]


Although a clear association has been made between the malignant form of mesotheliomas and exposure to such noxious agents as asbestos and silica, the exact etiology for the development of benign mesotheliomas remains somewhat in question.[1] The more popular theories seek to explain their development by appealing to reactive changes such as the hyperplasia that mesothelial cells undergo in response to various stimuli. Some of these postulated stimuli include foreign material, dust, and small fibers as well as trauma or mechanical injury. The resulting injury may result in over-proliferation of mesothelial cells and also may be associated with metaplasia of underlying connective tissue leading to a pathologic lesion. Mononuclear cells attaching to mesothelial surfaces and undergoing similar differentiation may also play a role in the development of these lesions.[4] They are also found in patients in association with inflammatory disease.[5]


Benign mesotheliomas are a very rare entity, much rarer than their malignant counterpart. One review states the incidence of a certain type of benign mesotheliomas, the multicystic peritoneal version, to be 0.15/100,000 annually.[6] Benign multicystic mesotheliomas are more common in women in their 20s to 40s and may be associated with endometriosis and pelvic inflammatory disease. Males who develop benign mesotheliomas are usually older, with the mean age 67 years. Because the disease is rarer in males than females, there is not abundant data to suggest associations though there may be a link to the history of previous abdominal surgeries. Females who develop benign mesotheliomas may also show an association with previous abdominal surgeries. Cadmium has also been associated with the development of mesotheliomas. Social risk factors for developing benign mesotheliomas include alcohol use and smoking history; other risk factors include a history of trauma and family history of the development of these lesions.[7][2]


Hematoxylin and eosin interpretation considered in tandem with immunohistochemistry and molecular markers are necessary for an accurate diagnosis of this benign mesothelioma. In addition, the diagnosis should fit with the associated clinical, radiologic, surgical, and gross findings. Of equal importance is making certain the biopsy or specimen is adequate in amount and representation of the lesion in question to make an accurate diagnosis. Cellular mesothelial proliferations have varied histological appearances and should always be approached with caution as small biopsies may not represent the mass or lesion as a whole. It is also possible for benign or reactive mesothelial proliferations to exhibit worrisome features usually only encountered in malignant, atypical, or dysplastic neoplasms such as increased cellularity, cytologic atypia with increased mitotic forms, papillary formations, and even necrosis. Another worrisome feature that may deceptively lead one to wrongly assume a malignant nature is increased fibrosis encasing and surrounding benign mesothelial cells, mimicking invasion. Indeed, one of the most helpful distinguishing histologic features of malignancy is the presence of true invasion. Invasion is a key feature which may be focal and difficult to appreciate. Keratin stains are helpful in these cases to highlight invasive cells diving deep within the stroma.[8] 

Some features that are more commonly found in mesothelial hyperplasia or benign mesothelioma are lack of invasion and no increased cellularity within the stroma; if papillary formations are present they should be simple, small to medium, and lined by a single layer of cells with only mild to moderate atypia, growth should be uniform. Inflammation is a common associated finding, and although necrosis has been reported in association with benign mesothelial proliferations, this should be a rare and focal finding if present. Pathologists are often reluctant to definitively diagnose a benign mesothelial proliferation on cytology alone and prefer permanent tissue examination due to the rarity of these samples and the need for an adequate sample.[8] With the continued development and growing knowledge of molecular pathology, it is important to note that one of the more common molecular findings in malignant mesothelioma is the homozygous deletion of the 9p21 locus, which also includes the cyclin-dependent kinase inhibitor CDKN2A.[9][10]

Another immunohistochemical indication of a benign diagnosis may be desmin positivity, while EMA, p53, GLUT-1, and IMP-3 may be markers of malignancy. Keratin is positive in both benign and malignant mesothelial cells.[11] Benign mesotheliomas may be expected to stain positive for calretinin and D2-40.[2]

History and Physical

Patients who have benign mesothelial proliferations may present endorsing abdominal masses or abdominal fullness, abdominal pain, chest pain with or without pleural effusions, or unexpected weight gain, among other non-specific symptoms. Importantly, if the patient does present with a pleural effusion, and it turns out to be a hemorrhagic pleural effusion, as regards mesotheliomas, this greatly weighs in favor of a malignant process as opposed to a benign process.[11] It is important to remember, however, that there are other causes of hemorrhagic effusions, such as trauma and pneumonia.[12]If the mesothelial proliferation grows adequately large, it is possible for the patient to report shortness of breath, intestinal obstruction, reflux symptoms, or urinary issues.[11]


Important methods of evaluation include radiographic methods such as CT, ultrasound, and MRI. These can indicate which structures within the body the mass arises as well as give a picture of the complexity of the mass and its relationship to surrounding structures. If a pleural effusion is present, aspiration of the fluid with chemical, microbiological, and cytopathologic analysis is important to consider. These studies can lend diagnostic clues as to the cause of the effusion. Ultimately, resection of the mass will need to be sent for gross and histopathologic examination for definitive diagnosis. Molecular analysis is also becoming increasingly useful to guide the diagnosis.[13]

Treatment / Management

Generally, resection is considered an adequate treatment of benign mesotheliomas. However, in cases where the mass is incompletely excised, local recurrence is common. Some recommend more aggressive surgical excision for certain variants such as the benign cystic mesothelioma of the peritoneum with heated intraperitoneal chemotherapy to prevent recurrence.[1]

Differential Diagnosis

Any neoplasms of the organs which are affected by mesotheliomas should be considered in the differential diagnosis. This includes, but is not limited to, malignant mesothelioma, pleural lipomas, sarcomas, malignant fibrous tumor of the pleura, and localized fibrous tumor of the pleura. Lymphomas involving the pleura are quite rare but do occur. This is far from an exhaustive list, and it is important to remember that malignant mesotheliomas are more common than benign mesotheliomas. Of course, if mesothelioma is suspected, separating and distinguishing benign from malignant is arguably the most important consideration. Radiology exams may not be able to distinguish between benign and malignant forms of mesotheliomas or pleural neoplasms. Another very important consideration in the world population, though not as pertinent in the United States, is to include hydatid cysts in the differential, especially if a biopsy is considered such as through fine needle aspiration, as rupturing a hydatid cyst can lead to anaphylaxis.[14][2][15][16]


Prognosis for benign mesotheliomas is generally quite good as long as the lesion is completely surgically excised. Recurrences are common though and should also be completely excised. No definitive risk factors for recurrence have been identified.[5]

Enhancing Healthcare Team Outcomes

Benign mesotheliomas are a rare entity and as such should be approached with caution. Close collaboration between treating clinicians and surgeons and the operating team of nurses, technicians, anesthesiology staff, as well as radiologists and pathologists, is necessary to arrive at the correct diagnosis and treatment plan. Proper collaboration should aim for maximal treatment as well as limit unnecessary morbidity and/or mortality associated with the treatment of benign mesotheliomas. Unfortunately, benign versus malignant mesothelial proliferations and neoplasms can be quite difficult to distinguish from one another, such that even experts in these fields may not agree on their classification on a case by case basis. Upcoming and developing molecular analysis methods may be able to aid the classification of benign vs. malignant mesotheliomas.[17][18][19] In patients presenting with pleural effusions, ultrasound-guided thoracentesis should be performed to characterize the effusion.[20][21][22][23] (Level I)