Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and the associated lung neuroendocrine tumors: clinical experience with a rare entity.

BACKGROUND: Normal adult lungs contain pulmonary neuroendocrine cells (PNECs). PNEC hyperplasia may be either reactive or idiopathic, and the idiopathic type is defined as diffuse idiopathic PNEC hyperplasia (DIPNECH). It is believed that DIPNECH is a neuroendocrine proliferative process associated with carcinoid tumors. The available data regarding this rare condition are very limited. The objective of the current study was to describe the clinical, radiologic, and pathologic characteristics of patients with DIPNECH and the effect of various therapeutic modalities on patient well being. METHODS: The authors retrospectively studied 11 consecutive patients with DIPNECH who were followed at 2 referral centers in Israel between 2000 and 2010. RESULTS: All patients were women, and their median age was 62.8 years. Six patients presented with respiratory symptoms, such as prolonged dyspnea, wheezing, and cough. All patients had carcinoid tumor together with multiple, small pulmonary nodules observed on thoracic high-resolution computerized tomography images. The mean size of the dominant lesion was 19.4 ± 9.6 mm. Nine patients underwent thoracotomy and resection of the dominant lesion. The disease was stable in 5 of 11 patients; in 6 of 10 patients, it progressed, and the patients received treatment with somatostatin analogs, which induced disease stabilization in all patients. Metastatic disease was diagnosed in 3 of 11 patients (36%). All patients were alive at the end of follow-up (mean, 4.63 ± 2.04 years; ongoing). CONCLUSIONS: The association of lung neuroendocrine tumor with multiple nodules in women, together with complains of chronic cough and wheezing, should raise suspicion of DIPNECH. Whenever possible, these patients should undergo surgical excision of the dominant lesion, and somatostatin analogs may be considered for symptomatic or tumor control in patients with progressive disease.

Peptide receptor radioligand therapy is an effective treatment for the long-term stabilization of malignant gastrinomas.

BACKGROUND: Gastrinomas, a rare group of neuroendocrine tumors, are responsible for severe peptic disease and diarrhea. Although symptomatic control may be achieved with proton-pump inhibitors (PPIs) and somatostatin analogues (SSAs), data are limited regarding the possible antitumor effect of the peptide receptor radioligand therapy (PRRT) with radiolabeled SSAs in gastrinoma patients. The goal of this study was to assess the effect of PRRT on symptoms, gastrin secretion, and tumor load in patients with progressive malignant gastrinomas. METHODS: We retrospectively studied 11 patients with metastatic gastrinomas followed for a mean period of 6 years. All patients were symptomatically treated with PPIs, and 9 of 11 patients received monthly injections of SSAs; all patients had an Eastern Cooperative Oncology Group score of 0-1, and received PRRT ((90) Yttrium- or (177) Lutetium-DOTATOC) for progressive disease. Serum gastrin measurements and radiological assessment (using the Response Evaluation Criteria in Solid Tumors criteria) were performed before and every 3-6 months following PRRT. RESULTS: PRRT induced symptomatic improvement in all patients. The mean serum gastrin decreased significantly from 4831 mI/L to 932.6 mI/L (normal, 40-108 mI/L; P < .001). Periodic radiological surveillance showed complete response in 1 (9%) patient, partial tumor response in 5/11 (45%) patients, and tumor stabilization in 5/11 (45%) patients. In 7/11 (64%) patients, the antitumor effect of PRRT persisted after a median period of 14 months. Four of 11 (36%) patients died due to tumor progression (median time to progression, 11 months); in this group, the mean survival time after the last PRRT was 14 ± 6.9 months. CONCLUSIONS: PRRT seems to be a promising tool for the management of patients with inoperable or progressive metastatic gastrinomas.

Long-acting somatostatin analogues are an effective treatment for type 1 gastric carcinoid tumours.

BACKGROUND: Gastric carcinoid tumours type 1 (GCA1) originate from hyperplastic enterochromaffin-like (ECL) cells secondary to hypergastrinaemia. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. We conducted a multicentre prospective study to assess the effects of long-acting SSA on hypergastrinaemia and ECL-cell proliferation in patients with GCA1. METHODS: We studied 15 patients with GCA1 treated with monthly long-acting release octreotide (LAR) (20-30 mg; n=14) or Lanreotide 90 mg (n=1) for at least 6 months. Patients had serum gastrin and chromogranin A measurements performed and biopsies taken from both tumours and surrounding mucosa before, and every 6-12 months following treatment. Sections were immunostained for neuroendocrine markers. The cell proliferation index Ki-67, intensity of staining before and after treatment and the degree of gastric wall invasion were also assessed. RESULTS: All patients tolerated treatment well (mean follow-up of 18 months). In 11 patients (73%), a complete disappearance of the tumours at 1 year of treatment was observed on endoscopy, while in three patients (20%), the tumours decreased significantly in number and size. Gastrin levels normalized in 25% of patients, and were reduced by more than 80% in the remaining 75%. CONCLUSIONS: Treatment with SSAs in GCA1 leads to a substantial tumour load reduction, with a concomitant decrease of serum gastrin levels. Our data indicate an important anti-proliferative effect of SSA on ECL cells, providing clinical benefit and obviating, at least temporarily, the need for invasive therapies for GCA1.