Tertiary lymphoid structures in epithelioid malignant peritoneal mesothelioma are associated with neoadjuvant chemotherapy, but not with prognosis

Our plain-English summary of Tertiary lymphoid structures in epithelioid malignant peritoneal mesothelioma are associated with neoadjuvant chemotherapy, but not with prognosis, by N. Benzerdjeb, P. Dartigues, V. Kepenekian, et al (Virchows Archiv, 2021).

The study

• Authors: N. Benzerdjeb, P. Dartigues, V. Kepenekian, S. Valmary-Degano, E. Mery, G. Avérous, A. Chevallier, M.H. Laverriere, I. Villa, O. Harou, F.G. Sallé, L. Villeneuve, O. Glehen, S. Isaac, J. Hommell-Fontaine, F. Bibeau, RENAPE Network
• Journal: Virchows Archiv
• Published: 2021;479(4):765-772
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. The relationship between a strong adaptive immune response and a better prognosis in malignant solid tumors is widely known. Due to the low incidence of epithelioid malignant peritoneal mesothelioma (EMPM), very little is known about their immune micro-environment. We encountered several cases of tertiary lymphoid structures in EMPM in a previous study and aimed to investigate in the same series the prevalence, clinicopathological features, and the prognostic impact associated with tertiary lymphoid structures in EMPM (TLS-EMPM). Cases of EMPM, from 1995 to 2018, were retrieved from 7 French institutions from the RENAPE Network. The predictions in terms of overall survival (OS) and progression-free survival (PFS) of TLS-EMPM were analyzed. We report 52 cases of TLS-EMPM among a series of 138 cases of EMPM. TLS-EMPM was significantly associated with neoadjuvant chemotherapy, and was not a prognostic indicator for OS (p = 0.652) and PFS (p = 0.804) in our series. TLS is a component of the host immune response to EMPM significantly associated with neoadjuvant chemotherapy, but was not a predictor of prognosis for overall and progression-free survivals in this series. These findings provide another possible etiology for tertiary lymphoid structures.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

In plain English

This study reviewed tumor samples from 138 patients with epithelioid malignant peritoneal mesothelioma (mesothelioma of the abdominal lining) diagnosed between 1995 and 2018 at 7 French institutions in the RENAPE network. Pathologists looked for tertiary lymphoid structures, meaning numerous clusters of immune cells in the tumor. The article did not examine asbestos exposure. The structures were found in 52 of 138 patients (37.6%). They were significantly associated with chemotherapy given before surgery (neoadjuvant chemotherapy). Of the 52 patients with the structures, 36 had received it and 3 had no data (73.5% of those with data). Of the 86 without them, 42 had received it and 2 had no data (50.0%) (p = 0.010). They were also associated with the nuclear atypia score, a measure of how abnormal tumor cell nuclei looked (p = 0.009). Their presence did not predict overall survival (p = 0.652) or progression-free survival (p = 0.804). The authors concluded that the structures are part of the immune response to this tumor and are linked to neoadjuvant chemotherapy, but did not predict survival in this series. They noted that patients were recruited over a long period.

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: Observational multicenter study of registry cases: pathology slide review, comparison with clinical factors, and survival analysis
• Who was studied: 138 patients with epithelioid malignant peritoneal mesothelioma diagnosed 1995 to 2018 at 7 French institutions (RENAPE network); median age 61 years (range 17 to 89), 49.3% men
• Exposure: No asbestos exposure was studied. The study compared tumors with and without tertiary lymphoid structures (numerous lymphoid aggregates) against clinical factors, including neoadjuvant chemotherapy, and against survival
• Main results:
  • Tertiary lymphoid structures were found in 37.6% of patients (52 of 138). Of these patients, 73.5% had received neoadjuvant systemic chemotherapy. Table 2 lists chemotherapy data as missing for 3 of the 52.
  • Neoadjuvant chemotherapy was given to 36 (73.5%) of the 52 patients with the structures, with data missing for 3. It was given to 42 (50.0%) of the 86 patients without them, with data missing for 2. The difference was statistically significant (p = 0.010).
  • The structures were significantly associated with nuclear atypia score (p = 0.009), specifically with scores 2 and 3. Atypia score 1 occurred in 1 patient (1.9%) with the structures, compared with 16 patients (18.6%) without them.
  • The structures did not predict overall survival (p = 0.652; 138 patients analyzed) or progression-free survival (p = 0.804; 134 patients analyzed).
  • Lymphoid aggregates were located at the tumor border in 19 patients and between clusters of tumor cells in 33. Of the 33, 23 had small aggregates and 10 had large aggregates.
  • Platinum-based regimens made up 88.5% of the chemotherapy used (data not shown).
• The authors' conclusion: The authors concluded that tertiary lymphoid structures are a component of the host immune response to this tumor. They found the structures significantly associated with neoadjuvant chemotherapy but not a predictor of overall or progression-free survival in this series.
• Limitations the authors state:
  • Patients were recruited over a long period of time.
  • The series was heterogeneous in the drugs used, the number of chemotherapy lines, whether specimens were taken before or after chemotherapy, and the treating institutions.

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: Epithelioid, Peritoneal Mesothelioma, Neoadjuvant Chemotherapy, Prognosis, Mesothelioma, Overall Survival, Progression-Free Survival, Etiology.

Related studies

• Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study — N. Benzerdjeb, P. Dartigues, et al. (2021)
• Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study — S. Valmary-Degano, P. Colpart, et al. (2017)
• 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)
• Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies — G. Passot, N. Bakrin, et al. (2014)
• Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — M. Alyami, F. Mercier, et al. (2021)
• Complete pathological response to neoadjuvant pemetrexed/cisplatin in combination with regional hyperthermia in a patient with sarcomatoid peritoneal mesothelioma — S. Kruger, M.K. Angele, et al. (2014)

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