Search

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.

We present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat.

BACKGROUND: Pituitary carcinomas (PC) are very uncommon, accounting for only 0.1 % of all pituitary tumors and representing a treatment challenge. Diagnosis is based on presence of intra- and/or extracranial metastases. PC is resistant to current treatment regimens, with a median overall survival of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Temozolomide (TEM)-based regimens are being used in progressive PC, but its effectiveness and the schedule/duration of treatment have not been established. The aim of this study is to report our experience with TEM in patients with progressive PC. METHODS: Three adult patients with progressive PC who were treated with TEM at MDACC between 01/2010-06/2014 were identified. Clinical and radiographic data were extracted from medical records. RESULTS: All three cases had prior history of pituitary macroadenoma. Clinical presentation of PC included visual field deficits, headaches and/or Cushing syndrome. Pathology revealed a mean Ki67 index of 11.5 % (0.4-24.2%) with positive p53 staining in one case. Cavernous sinus invasion was common and metastases involved lymph nodes, liver, bone and leptomeninges. Case 1 received a combined regimen consisting of capecitabine and TEM (CAPTEM). Case 2 was treated with standard-dose TEM, CAPTEM, and chemoradiation with TEM followed by TEM. Case 3 with dissemination to the bone and leptomeninges was initially treated with standard-dose TEM, followed by dose-dense TEM at progression. In the two patients who received chemoradiation with TEM for extracranial disease, the progression-free survival (PFS) was 15 and 17 months, whereas the PFS after TEM-only was 13 months. The median overall survival was 41 months, with all the patients still alive. CONCLUSION: TEM-based therapy seems to be an appropriate initial treatment for PC, prolonging the PFS and leading to tumor-stabilization.