A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype

Our plain-English summary of A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype, by K. Valente, A.U. Blackham, E. Levine, et al (The American Journal of Surgical Pathology, 2016).

The study

• Authors: K. Valente, A.U. Blackham, E. Levine, G. Russell, K.I. Votanopoulos, J.H. Stewart, P. Shen, K.R. Geisinger, S.J. Sirintrapun
• Journal: The American Journal of Surgical Pathology
• Published: 2016;40(9):1243-8
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype.

In plain English

This study reviewed 51 cases of diffuse malignant peritoneal mesothelioma (cancer of the abdominal lining) treated at Wake Forest from 1984 to 2013. All patients had cytoreductive surgery followed by heated chemotherapy given inside the abdomen. Two pathologists reviewed the slides. The 46 epithelioid cases were scored for nuclear abnormality and number of dividing cells and graded low (18 cases) or high (28 cases). Median overall survival was 11.9 years in the low-grade group (57% surviving at 5 years) and 3.3 years in the high-grade group (21%), a statistically significant difference (P = 0.002). Progression-free survival was calculated only for patients whose resections the authors counted as complete (13 low-grade and 19 high-grade cases). It was 65% versus 35% at 5 years, a difference that was not statistically significant (P = 0.089). The two groups did not differ significantly in sex, age, completeness of surgery or chemotherapy drug. The authors concluded that the two-tier grade was prognostically effective for overall survival. The study did not examine asbestos exposure.

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 case series: microscopic review of archived pathology slides, with Kaplan-Meier survival analysis comparing two grade groups
• Who was studied: 51 cases of diffuse malignant peritoneal mesothelioma from the Wake Forest School of Medicine Department of Pathology (Winston-Salem, NC), 1984 to 2013. All patients received cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. Women with a history of ovarian carcinoma or suspected primary serous carcinoma were excluded. 46 cases were epithelioid subtype.
• Exposure: Asbestos exposure was not studied. The factor examined was a histologic grade: a nuclear atypia score (1 to 3) plus a mitotic score (1 to 3). A total of 3 or less was low grade; 4 to 6 was high grade.
• Main results:
  • Of 51 cases, 46 were epithelioid and 5 were nonepithelioid (4 biphasic, 1 undifferentiated sarcomatoid). Of the 46 epithelioid cases, 18 were low grade and 28 were high grade.
  • Overall survival in epithelioid cases: low-grade group median 11.9 years and 57% at 5 years; high-grade group median 3.3 years and 21% at 5 years (P = 0.002, statistically significant).
  • Progression-free survival in epithelioid cases was calculated only for patients without incomplete (R2b or R2c) resections. Low-grade group: 13 patients, 65% at 5 years, reported median 4.7 years (the table notes this median was not yet reached). High-grade group: 19 patients, median 1.9 years and 35% at 5 years. P = 0.089, not statistically significant.
  • The low-grade and high-grade groups showed no statistically significant differences in sex, age (mean 48 vs 52 years, P = 0.39), surgical resection categories (P = 0.32), or chemotherapy regimen (mitomycin-C P = 0.21; cisplatin P = 0.53).
• The authors' conclusion: The authors concluded that a 2-tier histomorphologic grading system for epithelioid diffuse malignant peritoneal mesothelioma is prognostically effective for overall survival, with low-grade cases surviving longer than high-grade cases.
• Limitations the authors state:
  • Fewer cases could be used in the progression-free survival analysis, because patients with incomplete resections (5 of 18 low grade, 9 of 28 high grade) were excluded. The authors offered this as a possible reason the result was not statistically significant.
  • Only 5 nonepithelioid cases were available, too few for statistical comparison with epithelioid cases.
  • All patients received the same treatment, so the authors said the grade should be considered prognostic, not predictive of response to hyperthermic intraperitoneal chemotherapy.
  • The results come from a single institution and have not yet been validated at other centers.

Topics

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

Medical terms in this study, explained in our Lexicon: Overall Survival, Peritoneal Mesothelioma, Epithelioid, Serosal Surface, Pleural Mesothelioma, Nuclear Grading, Prognosis, Progression-Free Survival.

Related studies

• A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma — K. Kadota, K. Suzuki, et al. (2012)
• Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases — D.B. Chapel, J.J. Schulte, et al. (2021)
• Histopathologic features predict survival in diffuse pleural malignant mesothelioma on pleural biopsies — C. Habougit, B. Trombert-Paviot, et al. (2017)
• Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series — J.C. Leinwand, R.N. Taub, et al. (2020)
• Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study — L.E. Rosen, T. Karrison, et al. (2018)
• Postoperative Complications Independently Predict Cancer-Related Survival in Peritoneal Malignancies — M.H.A. Choudry, Y. Shuai, et al. (2018)

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