Virchows Archiv

, Volume 475, Issue 5, pp 587–597 | Cite as

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

  • Stefano La RosaEmail author
  • Marco Volante
  • Silvia Uccella
  • Roberta Maragliano
  • Ida Rapa
  • Nicola Rotolo
  • Frediano Inzani
  • Alessandra Siciliani
  • Pierluigi Granone
  • Guido Rindi
  • Lorenzo Dominioni
  • Carlo Capella
  • Mauro Papotti
  • Fausto Sessa
  • Andrea Imperatori
Original Article


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.


ACTH Adrenocorticotropic hormone-producing lung carcinoid Cushing syndrome Prognostic factors Ki67 index 


Author contribution

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.


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

Compliance with ethical standard

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.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2019_2612_MOESM1_ESM.docx (165 kb)
ESM 1 (DOCX 165 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Stefano La Rosa
    • 1
    • 2
    Email author
  • Marco Volante
    • 3
  • Silvia Uccella
    • 4
  • Roberta Maragliano
    • 4
  • Ida Rapa
    • 3
  • Nicola Rotolo
    • 5
  • Frediano Inzani
    • 6
  • Alessandra Siciliani
    • 7
    • 8
  • Pierluigi Granone
    • 7
  • Guido Rindi
    • 9
  • Lorenzo Dominioni
    • 5
  • Carlo Capella
    • 4
  • Mauro Papotti
    • 10
  • Fausto Sessa
    • 4
  • Andrea Imperatori
    • 5
  1. 1.Institute of PathologyUniversity Hospital and University of LausanneLausanneSwitzerland
  2. 2.Institut Universitaire de Pathologie, CHUVLausanneSwitzerland
  3. 3.Department of OncologyUniversity of TurinOrbassanoItaly
  4. 4.Pathology Unit, Department of Medicine and SurgeryUniversity of InsubriaVareseItaly
  5. 5.Center for Thoracic Surgery, Department of Medicine and SurgeryUniversity of InsubriaVareseItaly
  6. 6.UOC Ginecopatologia e Patologia MammariaFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
  7. 7.UOC Chirurgia ToracicaFondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro CuoreRomeItaly
  8. 8.Division of Thoracic Surgery, Sant’Andrea Hospital, Faculty of Medicine and PsychologyUniversity of Rome ‘Sapienza’RomeItaly
  9. 9.UOC Anatomia PatologicaFondazione Policlinico Universitario A. Gemelli IRCCS- Università Cattolica del Sacro CuoreRomeItaly
  10. 10.Department of Oncology, City of Health and ScienceUniversity of TurinTorinoItaly

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