Ectopic ACTH syndrome caused by pulmonary carcinoid tumourlets

Abstract

The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.

Lung Adenocarcinoma Complicated with a Carcinoid Microtumor: A Case Report and Literature Review

“…The main symptoms are closely related to the accompanying lung diseases. When hyperplastic PNECs cause tracheal obstruction, stenosis and in ammatory reactions, they can manifest as cough, expectoration, hemoptysis, chest tightness, shortness of breath or progressive dyspnea, and some patients have carcinoid syndromes, such as facial ushing, skin pigmentation, muscle weakness, and diarrhea [7]. Pulmonary carcinoid tumorlets are usually multiple pulmonary nodules that can occur in a single lobe, in multiple lobes, or even in both lungs, and the number ranges from several to dozens [8].…”

Tumorlets in Familial History of Bronchopulmonary Carcinoid

“…1 Carcinoid tumors can also manifest as tumorlets, but their relationship has not been firmly established. Some authors have claimed that they are a different stage of the same neuroendocrine proliferation, 2 and that tumorlets are simply the intramucosal spread of neoplastic neuroendocrine cells from carcinoids. In this instance, genetic analysis could resolve the pathogenetic relationship between tumorlets and carcinoids.…”

Autopsy of a Patient with Cushing's Syndrome Who Was Revealed to Have Pulmonary Tumorlets Producing Ectopic ACTH

“…The histopathological diagnosis was multiple peripheral cartinoid tumors and tumorlets of a carinoid type showing positive immunostaining for ACTH. Povedano et al [13] reported a patient with an aggressive case of Cushing's syndrome that required a bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent in a chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid tumor surrounded by tumorlets.…”