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Benign Mesothelioma

Editor: Hani M. Babiker Updated: 5/3/2023 10:25:23 AM


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 broadly divide 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 demonstrated a high propensity for local recurrence, and in some rare cases, there are suspicions that they may undergo malignant transformation.[1] A common form of benign mesothelioma is known as benign multicystic mesothelioma of the peritoneum (BMMP). Mesotheliomas are 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 no 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]


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Although a clear association exists 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 may correlate 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 developing these lesions.[4] They are also present 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 correlate 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 demonstrated an association 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 developing 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. Also, 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 that 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 common 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 there have been reports of necrosis 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 essential 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 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, the patient can 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 and 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 vital to consider. These studies can lend diagnostic clues as to the cause of the effusion. Ultimately, resection of the mass will need to undergo 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 there is incomplete excision of the mass, local recurrence is common. Some recommend more aggressive surgical excision for specific variants such as the benign cystic mesothelioma of the peritoneum with heated intraperitoneal chemotherapy to prevent a recurrence.[1](B2)

Differential Diagnosis

Any neoplasms of the organs which are affected by mesotheliomas should merits consideration 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 list is far from exhaustive, 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 significant consideration in the world population, though not as pertinent in the United States, should 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]


The prognosis for benign mesotheliomas is generally quite good as long as the lesion is completely surgically excised. Recurrences are common, though, and also require complete excision. There are no definitive risk factors for recurrence yet identified.[5]


Although benign mesothelioma is generally non-problematic long-term, complications are possible following surgery, even though it is a relatively harmless disease. The most common complication encountered is fluid buildup in the pleural spaces, which can potentially lead to pressure in the lungs and heart. In these instances, treatment is to surgically remove the excess fluid and install a fitted chest drain to remove excess fluid and prevent effusion.[17][18]

Deterrence and Patient Education

While surgical treatment is relatively straightforward, these patients need to understand the potential risk of the surgical procedure as outlined above, as well as the potential for recurrence and the very rare possibility of malignant transformation.

Enhancing Healthcare Team Outcomes

Benign mesotheliomas are a rare entity and, as such, require a cautious approach. Close collaboration between treating clinicians and surgeons and the operating team of nurses, technicians, anesthesiology staff, and radiologists and pathologists, is necessary to arrive at the correct diagnosis and treatment plan. Proper collaboration should aim for maximal treatment and 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 disagree 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.[19][20][21] In patients presenting with pleural effusions, ultrasound-guided thoracentesis can help the clinician characterize the effusion.[22][23][24][25] [Level 1]



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