TY - JOUR
T1 - ACTH-producing tumorlets and carcinoids of the lung
T2 - clinico-pathologic study of 63 cases and review of the literature
AU - La Rosa, Stefano
AU - Volante, Marco
AU - Uccella, Silvia
AU - Maragliano, Roberta
AU - Rapa, Ida
AU - Rotolo, Nicola
AU - Inzani, Frediano
AU - Siciliani, Alessandra
AU - Granone, Pierluigi
AU - Rindi, Guido
AU - Dominioni, Lorenzo
AU - Capella, Carlo
AU - Papotti, Mauro
AU - Sessa, Fausto
AU - Imperatori, Andrea
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
KW - Adrenocorticotropic Hormone/metabolism
KW - Adult
KW - Aged
KW - Carcinoid Tumor/metabolism
KW - Cushing Syndrome/metabolism
KW - Female
KW - Humans
KW - Lung/metabolism
KW - Lung Neoplasms/metabolism
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local
KW - Prognosis
KW - Retrospective Studies
KW - Survival Rate
U2 - 10.1007/s00428-019-02612-x
DO - 10.1007/s00428-019-02612-x
M3 - Review article
C2 - 31264037
VL - 475
SP - 587
EP - 597
JO - Virchows Archiv - A Pathological Anatomy and Histopathology
JF - Virchows Archiv - A Pathological Anatomy and Histopathology
SN - 0945-6317
IS - 5
ER -