Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy

Our plain-English summary of Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy, by M. Lee, H.R. Alexander, A. Burke (Pathology, 2013).

The study

• Authors: M. Lee, H.R. Alexander, A. Burke
• Journal: Pathology
• Published: 2013;45(5):464-73
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Diffuse peritoneal mesothelioma (DPM) forms a spectrum of indolent surface tumours to malignant invasive cancers. There are few pathological series that span well and poorly differentiated lesions that show diffuse peritoneal spread.

Methods: Sixty-four DPM treated by initial cytoreductive therapy were retrospectively reviewed. Tumours were classified by surface and invasive growth pattern and correlated with risk factors, peritoneal cancer index (PCI) and completeness of cytoreduction (CCR). Degree of invasion was quantitated as absent (0), into stroma (I), into fat (II), and into adjacent structures (III) and was correlated with cytological features. Selected immunohistochemical stains were performed.

Results: There were three well differentiated papillary mesotheliomas (WDPM; type A), four multicystic mesothelioma (type B), 22 tubulopapillary epithelioid mesotheliomas (type C), and 35 poorly differentiated epithelioid mesotheliomas with solid or sarcomatoid growth (Type D). Seven type D tumours had prominent sarcomatoid areas, 12 deciduoid areas, and four lymphohistiocytoid features. Risk factors were present in all groups except type A, and included prior abdominal surgery (n=24), asbestos exposure (n=5) and radiation (n=2). Extra-pleural mesothelioma was present in all groups except type B (total n=7, 11%). Two type A and eight type C tumours lacked invasion; only type D showed level III invasion. The invasive portion of one type A tumour and two type B tumours showed adenomatoid features. PCI and CCR were greater in type D compared to the other groups (p=0.02), as well as mitotic rate, degree of necrosis, and nuclear pleomorphism (p<0.001). Degree of invasion was strongly correlated with CCR (p=0.007), necrosis (p<0.0001), nuclear grade (p<0.0001), and mitotic rate (p=0.001), but not PCI (p=0.1). Immunohistochemical results were similar across groups, with frequent positivity for CA125 (94%), EGFR (94%) and calretinin (93%), followed by p16 (85%), cytokeratin 5,6 (76%), D2-40 (71%) and WT-1 (47%). PAX-8 was negative in all tumours, except one type A tumour that showed diffuse nuclear positivity.

Conclusions: Diffuse peritoneal mesotheliomas can be classified into four groups that reflect invasive potential, degree of adverse histological features, and amenability for CCR. Non-invasive tumours include both type A and type C tumours.

In plain English

This was a retrospective pathology study of 64 patients (35 women, 29 men; mean age 55) with diffuse peritoneal mesothelioma, a mesothelioma of the lining of the abdomen. All were treated with cytoreductive surgery, with or without heated chemotherapy inside the abdomen, between 2006 and 2012. The authors work at the University of Maryland Medical Center. They sorted the tumours into four types: 3 well differentiated papillary (type A), 4 multicystic (type B), 22 tubulopapillary (type C) and 35 poorly differentiated (type D). Recorded risk factors included prior abdominal surgery in 24 patients, asbestos exposure in 5 and radiation in 2. The article gives no details of the asbestos exposure, and 31 patients had none of these risk factors. Ten tumours (two type A and eight type C) showed no invasion. Type D tumours were significantly more likely to invade adjacent structures, to show high-grade features, and to have greater tumour burden and less complete removal. None of the eight patients with non-invasive type C tumours had a recurrence in limited follow-up. The authors concluded that these tumours form a spectrum from indolent non-invasive tumours to deeply invading high-grade lesions. They did not study survival.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective pathological review of a series of patients (case series)
• Who was studied: 64 patients (77 specimens) with diffuse peritoneal mesothelioma treated with cytoreductive therapy with or without hyperthermic intraperitoneal chemotherapy (HIPEC), 2006 to 2012. There were 35 women and 29 men, with a mean age of 55 (range 17 to 80). The authors are at the University of Maryland Medical Center, Baltimore, USA.
• Exposure: This was not an exposure study. Asbestos exposure was one of several recorded risk factors: asbestos exposure in 8% (5 patients), abdominal radiation in 3%, and prior abdominal surgery in 38%. No fiber type or exposure details are given.
• Main results:
  • Tumour types among the 64 patients: 3 type A (well differentiated papillary), 4 type B (multicystic), 22 type C (tubulopapillary) and 35 type D (poorly differentiated).
  • 31 of the 64 patients had none of the recorded risk factors.
  • 10 tumours were non-invasive: two type A and eight type C.
  • Type D tumours were significantly more likely than the other groups to have extensive surgically estimated tumour burden (PCI) and less complete cytoreduction (CCR).
  • Type D tumours were significantly more likely than the other groups to show level III invasion (into adjacent structures), high nuclear grade, mitotic activity and necrosis.
  • Across 69 cytoreduction specimens, deeper invasion went with significantly less complete cytoreduction (p = 0.007) but not with tumour burden (PCI, p = 0.1).
  • None of the eight patients with non-invasive type C tumours had recurrences, with limited follow-up.
  • The study found no added prognostic significance of sarcomatoid features over other undifferentiated patterns.
  • Lymph nodes were sampled in 19 cases. One showed invasion by direct extension, one showed lymphovascular invasion, and the rest were negative.
  • Calretinin was positive in 38 of 41 tumours tested (93%). Three tumours were negative, including one tubulopapillary tumour.
  • PAX-8 was negative in most tumours tested.
• The authors' conclusion: The authors concluded that diffuse mesothelial tumours of the peritoneum requiring debulking form a broad spectrum, from indolent non-invasive tumours to high-grade lesions invading deeply into adjacent structures. They recommended using the term 'malignant' for invasive epithelioid and poorly differentiated tumours.
• Limitations the authors state:
  • Follow-up data were not attempted because length of follow-up varied widely and growth was often indolent.
  • The study did not address survival.
  • Only three well differentiated papillary mesotheliomas met the inclusion criteria.
  • Telling lymph nodes apart from mesenteric tumour nodules with surrounding lymphoid reaction was difficult.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Peritoneum, Cytoreductive Surgery, Peritoneal Mesothelioma, Peritoneal Cancer Index (PCI), Well-Differentiated Papillary Mesothelioma, Multicystic Mesothelioma (MCM), Tubulopapillary.

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• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases — T.C. Chua, L.E. Quinn, et al. (2013)
• Malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is GLUT1 expression a major prognostic factor? A preliminary study — J. Hommell-Fontaine, S. Isaac, et al. (2013)
• Cytoreductive surgery with selective versus complete parietal peritonectomy followed by hyperthermic intraperitoneal chemotherapy in patients with diffuse malignant peritoneal mesothelioma: a controlled study — D. Baratti, S. Kusamura, et al. (2012)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)

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