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

Stefano La Rosa, 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

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)587-597
Number of pages11
JournalVirchows Archiv - A Pathological Anatomy and Histopathology
Issue number5
Publication statusPublished - Nov 2019


  • Adrenocorticotropic Hormone/metabolism
  • Adult
  • Aged
  • Carcinoid Tumor/metabolism
  • Cushing Syndrome/metabolism
  • Female
  • Humans
  • Lung/metabolism
  • Lung Neoplasms/metabolism
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Retrospective Studies
  • Survival Rate


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