Clinicopathologic and genetic characteristics of young patients with pleural diffuse malignant mesothelioma

Our plain-English summary of Clinicopathologic and genetic characteristics of young patients with pleural diffuse malignant mesothelioma, by M. Vivero, R. Bueno, L.R. Chirieac (Modern Pathology, 2018).

The study

• Authors: M. Vivero, R. Bueno, L.R. Chirieac
• Journal: Modern Pathology
• Published: 2018;31(1):122-131
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural diffuse malignant mesothelioma typically presents during the seventh decade of life and has poor prognosis. Recent epidemiologic studies have shown differences between young and older mesothelioma patients, but the biology of pleural mesothelioma in young patients is poorly understood. We studied the clinicopathologic and genetic characteristics in pleural mesothelioma patients aged 35 years and younger. Thirty-six consecutive pleural mesothelioma patients aged 35 years and younger were compared with 48 older patients. We examined demographic and clinical characteristics, histologic type, growth patterns, mitotic index, and nuclear grade on hematoxylin and eosin-stained slides, BAP1 protein expression by immunohistochemistry, and CDKN2A and NF2 deletions by fluorescence in situ hybridization. Clinicopathologic and cytogenetic results were compared between young and older groups, and correlated with overall survival. Young patients were more frequently women, reported less asbestos exposure, and had a greater frequency of prior therapeutic radiation and family history of breast cancer than older patients (P<0.05 each). There were no histologic differences between young and older patients (all P>0.05). CDKN2A deletion was less prevalent in young patients (P=0.01), loss of BAP1 protein expression less frequent in young patients (P=0.06), and NF2 deletion rates similar between groups (P>0.05 each). Median overall survival was 40 vs 26 months (P=0.10) in young and older patients, respectively, and 47 vs 31 months (P=0.04) when comparing patients with epithelioid histology only. High mitotic index and non-epithelioid histology were the only characteristics associated with a poor overall survival in young patients. Young patients with pleural mesothelioma have an equal sex distribution and are more likely to have a history of mantle radiation, family history of breast cancer, and lower rates of CDKN2A deletion than older patients. Our results suggest that pleural mesothelioma in young patients has distinctive clinical and genetic characteristics, despite some similarities to pleural mesothelioma in older patients.

In plain English

This study, from Brigham and Women's Hospital in Boston, looked back at the records and tumor samples of 36 patients aged 35 or younger with pleural diffuse malignant mesothelioma. It compared them with 48 patients older than 35. Asbestos exposure was a reported history taken from medical records; no fiber types or fiber counts were reported. Among the young patients, 47% were women, against 13% of older patients. Reported asbestos exposure was less common in young patients (31% vs 75%). Eight young patients (22%) had earlier mantle radiation for Hodgkin lymphoma, against none of the older patients. Tumor appearance under the microscope did not differ significantly between the groups. Deletion of the CDKN2A gene was found in 3 of 18 young patients tested (17%), against 19 of 35 older patients tested (54%). Median survival was 40 versus 26 months, a difference that was not statistically significant. For epithelioid tumors only, it was 47 versus 31 months, which was significant. The authors concluded that mesothelioma in young patients has distinctive clinical and genetic features. They named small patient numbers and the lack of fiber counts as limitations.

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 single-hospital study comparing young patients (aged 35 and younger) with a separate group of older patients (older than 35), using medical records, review of tumor slides, and genetic tests
• Who was studied: 39 consecutive patients aged 35 and younger with pleural diffuse malignant mesothelioma were identified at Brigham and Women's Hospital, Boston, USA. Of these, 36 had enough material for study (ages 18 to 35, mean 30). The methods give the period as January 1990 to September 2015; the results give January 1999 to September 2015. They were compared with 48 patients older than 35 (ages 38 to 84, mean 69) treated April 2012 to September 2015. The older patients were chosen because next-generation sequencing results were available for them.
• Exposure: Reported asbestos exposure and history of therapeutic mantle radiation, both taken from medical records. No fiber types, products, jobs or doses are reported, and no asbestos fiber counts were available.
• Main results:
  • Women made up 17 of 36 (47%) young patients and 6 of 48 (13%) older patients (P = 0.0005).
  • Reported asbestos exposure was found in 31% (11 of 36) of young patients and 75% (36 of 48) of older patients (P = 0.0001).
  • 8 young patients (22%) had a history of therapeutic mantle radiation, all for Hodgkin lymphoma. No older patients had received radiation (P = 0.0007).
  • Young patients were less likely than older patients to have a family history of any cancer (42% vs 73%; P = 0.003). Breast cancer among relatives was more common for young patients than for older patients (40% vs 9%; P = 0.02). The breakdown is in a supplementary table not included in the text.
  • There were no statistically significant differences in tumor histology between young and older patients. Tumors were epithelioid in 78% of young patients and 56% of older patients (P = 0.12).
  • CDKN2A gene deletion was found in 3 of 18 young patients tested (17%) and 19 of 35 older patients tested (54%) (P = 0.01).
  • NF2 gene deletion was found in 12 of 18 young patients tested (67%) and 25 of 33 older patients tested. The table and discussion give the older group's figure as 76%; the results text gives 78%. P = 0.53, not statistically significant.
  • Loss of BAP1 protein was seen in 8 of 36 young patients (22%) and 21 of 48 older patients (44%). This difference was not statistically significant (P = 0.06).
  • In the older group, the BAP1 protein stain was checked against gene sequencing. Complete absence of BAP1 protein had a sensitivity of 90% and specificity of 93% for underlying BAP1 gene abnormalities.
  • Across all tumor types, median overall survival was 40 months in young patients and 26 months in older patients (P = 0.10, not statistically significant).
  • For epithelioid tumors only, median overall survival was 47 months in young patients and 31 months in older patients (P = 0.04).
  • Five-year survival among the young patients was 31%.
  • Among young patients, non-epithelioid histology and a mitotic index above 4 mitoses per 2 square millimetres were the only pathologic features associated with shorter overall survival.
• The authors' conclusion: The authors concluded that pleural mesothelioma in young patients has distinctive clinical and genetic characteristics, despite some similarities to the disease in older patients. In the discussion they suggested radiation could be a major causative agent in young patients, compared with asbestos in older patients. They said their results must be confirmed in larger studies.
• Limitations the authors state:
  • Small numbers of patients in both the young group and the comparison group.
  • No asbestos fiber counts were available as an objective measure of exposure; exposure was as reported in records.
  • For the young patients, a protein stain (immunohistochemistry) had to stand in for direct BAP1 gene testing.
  • The older group was treated in a shorter, more recent period than the young group. Differences in patient management and treatment could affect the survival comparison.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Prognosis, Mesothelioma, Pleural Mesothelioma, Mitotic Index, Nuclear Grade, BAP1, Immunohistochemistry.

Related studies

• Clinicopathologic characteristics of malignant mesotheliomas arising in patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma — L.R. Chirieac, J.A. Barletta, et al. (2013)
• Malignant (Diffuse) Mesothelioma in Patients With Hematologic Malignancies: A Clinicopathologic Study of 45 Cases — X. Li, N.A. Brownlee, et al. (2015)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Multicentric study on malignant pleural mesothelioma in Turkey: clinicopathologic and survival characteristics of 282 patients — E.T. Elkiran, M.A. Kaplan, et al. (2012)
• Distinctive clinical characteristics of malignant mesothelioma in young patients — A. Thomas, Y. Chen, et al. (2015)
• BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma — S.M. McGregor, J. McElherne, et al. (2017)

Browse more research in Modern Pathology, or return to medical research.