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ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature

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Abstract

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid.

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Funding

This study was partly supported by a grant from the Italian Association for Cancer Research (AIRC) (IG 19238 to MV).

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Authors and Affiliations

  1. Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland

    Stefano La Rosa

  2. Institut Universitaire de Pathologie, CHUV, 25 rue du Bugnon, 1011, Lausanne, Switzerland

    Stefano La Rosa

  3. Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Italy

    Marco Volante & Ida Rapa

  4. Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Silvia Uccella, Roberta Maragliano, Carlo Capella & Fausto Sessa

  5. Center for Thoracic Surgery, Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Nicola Rotolo, Lorenzo Dominioni & Andrea Imperatori

  6. UOC Ginecopatologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Frediano Inzani

  7. UOC Chirurgia Toracica, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy

    Alessandra Siciliani & Pierluigi Granone

  8. Division of Thoracic Surgery, Sant’Andrea Hospital, Faculty of Medicine and Psychology, University of Rome ‘Sapienza’, Rome, Italy

    Alessandra Siciliani

  9. UOC Anatomia Patologica, Fondazione Policlinico Universitario A. Gemelli IRCCS- Università Cattolica del Sacro Cuore, Rome, Italy

    Guido Rindi

  10. Department of Oncology, City of Health and Science, University of Turin, Torino, Italy

    Mauro Papotti

Authors
  1. Stefano La Rosa
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  2. Marco Volante
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  3. Silvia Uccella
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  4. Roberta Maragliano
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  5. Ida Rapa
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  6. Nicola Rotolo
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  7. Frediano Inzani
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  8. Alessandra Siciliani
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  9. Pierluigi Granone
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  10. Guido Rindi
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  11. Lorenzo Dominioni
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  12. Carlo Capella
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  13. Mauro Papotti
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  14. Fausto Sessa
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  15. Andrea Imperatori
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Contributions

All authors have made a substantial contribution to conception and execution of the study including acquisition of data, processing material, analysis, and interpretation of data, as well as writing and reviewing the manuscript. All authors have approved the manuscript.

Corresponding author

Correspondence to Stefano La Rosa.

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This study was performed according to the clinical standards of the 1975 and 1983 Declaration of Helsinki and was approved by the Ethical Committee of the ASST dei Sette Laghi.

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The authors declare that they have no conflict of interest.

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La Rosa, S., Volante, M., Uccella, S. et al. ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature. Virchows Arch 475, 587–597 (2019). https://doi.org/10.1007/s00428-019-02612-x

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  • DOI: https://doi.org/10.1007/s00428-019-02612-x

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