Leser–Trélat syndrome in malignant mesothelioma and pulmonary adenocarcinoma: is the EGFR pathway part of the syndrome?

Our plain-English summary of Leser–Trélat syndrome in malignant mesothelioma and pulmonary adenocarcinoma: is the EGFR pathway part of the syndrome?, by R.K. Jepsen, A.G. Skov, B.G. Skov (Virchows Archiv, 2014).

The study

• Authors: R.K. Jepsen, A.G. Skov, B.G. Skov
• Journal: Virchows Archiv
• Published: 2014;464(1):117-20
• Type of article: Case report
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The syndrome of Leser–Trélat (LT) is characterized by the sudden appearance of multiple seborrhoeic keratoses (SKs) in association with internal occult malignancy. Usually, the syndrome has been associated with adenocarcinoma, most frequently of the gastrointestinal tract and breast. The pathogenesis is unclear but might be explained by circulating tumor-associated growth factors. We present two thoracic malignancies associated with LT: adenocarcinoma of the lung (ACL) and pleural malignant mesothelioma (MM). Both malignant tumors expressed high levels of epidermal growth factor receptors (EGFR) detected by immunohistochemistry (IHC), with membranous staining on the majority of malignant cells corresponding to maximum IHC scores of 290 and 300, respectively, for the MM and the ACL. SKs revealed a universal membranous staining throughout the entire epithelium with no difference in EGFR expression between the two cases and two controls with no malignant history. By fluorescence in situ hybridization, no amplification of the EGFR gene in malignant tumors as well as in SK lesions was observed. Further investigations are needed to see whether tumor-associated EGFR ligands/EGFR autocrine loops in malignant cells expressing high levels of EGFR protein on the surface might play a role for the development of SKs, as well as for the growth of malignant tumors in LT.

In plain English

This case report from Copenhagen, Denmark, described two patients with Leser–Trélat syndrome: the sudden appearance of many seborrhoeic keratoses (benign skin growths) alongside a hidden cancer. A 78-year-old man with biphasic pleural malignant mesothelioma had a history of asbestos exposure 30 years earlier and 12 pack-years of smoking. He had 26 skin growths removed in the prior 8 months. A 69-year-old woman with lung adenocarcinoma, a 26 pack-year smoker, had 18 growths removed over 4 months. The authors tested the tumors and skin growths for the epidermal growth factor receptor (EGFR). Both tumors showed high EGFR levels, with maximum staining scores of 290 for the mesothelioma and 300 for the lung cancer. No EGFR gene mutations were found in the tumors, and no EGFR gene amplification was found in the tumors or skin growths. The patients' skin growths stained no differently from those of two people with similar growths but no cancer history. The authors believed this was the first report of the syndrome with mesothelioma. They said the findings support the hypothesis that EGFR plays a role in tumor growth and in the skin growths, and called for further study. Asbestos was not analyzed further.

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: case report of two patients, with laboratory testing of tumor and skin-lesion tissue (immunohistochemistry, EGFR mutation analysis, FISH) and skin lesions from two controls for comparison
• Who was studied: Two patients reported by pathologists at Rigshospitalet, Copenhagen, Denmark. One was a 78-year-old man with biphasic pleural malignant mesothelioma. The other was a 69-year-old woman with adenocarcinoma of the lung. For comparison, 14 seborrhoeic keratoses from two controls with no malignant history were tested. Dates of the cases were not given.
• Exposure: Asbestos was not the subject of the study. The man with mesothelioma had a history of asbestos exposure 30 years earlier and a 12 pack-year smoking history. Fiber type and job were not stated. No asbestos exposure was mentioned for the woman, who had a 26 pack-year smoking history. The study examined EGFR expression in the tumors and skin lesions.
• Main results:
  • The man's tumor was a biphasic malignant mesothelioma made up of 75% epithelioid and 25% sarcomatoid tumor cells.
  • The man had 26 seborrhoeic keratoses removed during the preceding 8 months. The growths had developed rapidly over 1 year.
  • The woman had 18 lesions removed during the preceding 4 months.
  • Both tumors showed high EGFR protein levels, with maximum immunohistochemistry scores of 290 for the mesothelioma and 300 for the lung adenocarcinoma.
  • Both tumors were EGFR wild-type, meaning no EGFR gene mutation was found.
  • The skin lesions showed EGFR staining throughout the epithelium. There was no difference between the two patients and the two controls.
  • FISH testing found no EGFR gene amplification in the tumors or in the skin lesions.
• The authors' conclusion: The authors stated that, to their knowledge, this was the first report of Leser–Trélat syndrome with malignant mesothelioma. They said the high tumor EGFR expression supports the hypothesis that EGFR has a role in both tumor growth and the eruption of seborrhoeic keratoses. They suggested the overexpression is likely explained by epigenetic regulatory events and called for further investigation.

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, Adenocarcinoma, EGFR, Immunohistochemistry, Epithelium, Fluorescence In Situ Hybridization (FISH).

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• EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells — A. Demiroglu-Zergeroglu, G. Candemir, et al. (2016)
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