From the Authors:
We appreciate the interest and comments by Dr. Rossi and colleagues regarding our article (1). As with many diseases, awareness and recognition encourage progress in treatment. Recent publications and discussions within the past year have brought to the forefront treatment strategies in extrapulmonary neuroendocrine tumors that may be relevant to pulmonary proliferations expressing somatostatin receptors (SSR) (2, 3). Although little is known about the expression of SSR and mammalian target of rapamycin (mTOR) in DIPNECH, the information highlighted by Gorshtein, Righi, and colleagues (4, 5) complements our clinical paper and illustrates the need to better understand the important role of somatostatin analogs (SSA) and their potential for treatment in DIPNECH. Neuroendocrine cell proliferation with somatostatin receptor expression is the fundamental pathologic response to probable injury, so it makes teleological sense that SSA may be beneficial in the therapeutic paradigm.
The discussion of immunohistochemistry evidence, including the activation of the mTOR pathway in DIPNECH, is an excellent example of the progress that can be made with recognition and international collaboration on this disease. These leads may result in successful treatment strategies utilizing mTOR inhibitors in DIPNECH.
Another point of importance is the role of octreotide analog radio-labeled nuclear scintigraphy with positron emission/computed tomography imaging (6) in perhaps guiding treatment where the density of SSR in DIPNECH patients may predict therapeutic success with SSA.
As with most uncommon and often unrecognized diseases, collaboration may be the only way to obtain the volume of patients required to properly strategize and assess treatments. True progress and treatment algorithms would be best served with the establishment of an international registry for patients, a tissue repository, and the synergy of knowledge and experience between institutions.
| 1. | Nassar AA, Jaroszewski DE, Helmers RA, Colby TV, Patel BM, Mookadam F. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a systematic overview. Am J Respir Crit Care Med 2011;184:8–16. |
| 2. | Turaga KK, Kvols LK. Recent progress in the understanding, diagnosis, and treatment of gastroenteropancreatic neuroendocrine tumors. CA Cancer J Clin 2011;61:113–132. |
| 3. | Cameron CM, Roberts F, Connell J, Sproule MW. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an unusual cause of cyclical ectopic adrenocorticotrophic syndrome. Br J Radiol 2011;84:e14–e17. |
| 4. | Gorshtein A, Gross DJ, Barak D, Strenov Y, Refaeli Y, Shimon I, Grozinksky-Glasberg S. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and the associated lung neuroendocrine tumors. Cancer (In press) |
| 5. | Righi L, Volante M, Rapa I, Tavaglione V, Inzani F, Pelosi G, Papotti M. Mammalian target of rapamycin signaling activation patterns in neuroendocrine tumors of the lung. Endocr Relat Cancer 2010;17:977–987. |
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