Correct!
3. Carcinoid tumor with diffuse neuroendocrine cell hyperplasia

While one lesion with calcium or bone matrix is present within the right lower lobe, metastatic disease from a primary sarcoma forming either bone or chondroid matrix would be expected to produce multiple nodules with such features, and not a single right lower lobe nodule with calcium associated with large and small airway abnormalities. Similarly, benign metastasizing leiomyomas would manifest as multiple variably-sized nodules and / or masses, usually in a female patient with uterine leiomyomas or a history of hysterectomy for leiomyomas- such history was not provided in this case. Pulmonary lymphomatoid granulomatosis presents with multiple nodules or masses, with or without cavitation, but would not be expected to produce a nodule with calcification and diffuse large and small airway abnormalities. Finally, pulmonary vasculitis due to granulomatosis / ANCA-associated granulomatous vasculitis (formerly known as Wegener’s granulomatosis) usually manifests as multiple nodules or masses, often with cavitation, or multifocal pulmonary hemorrhage, at thoracic CT, rather than as a single partially calcified nodule with a background of large and small airway disease. The best answer is choice “3. Carcinoid tumor with diffuse neuroendocrine cell hyperplasia”.

Diagnosis: Diffuse idiopathic neuroendocrine cell hyperplasia

Diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) I a rare condition recognized as a preinvasive precursor to carcinoid tumors and tumorlets. Coincident carcinoid tumors are seen in up to 40% of affected patients, and coexistent tumorlets are seen in more than two-thirds of patients as well. Histopathologically, DIPNECH presents with pulmonary neuroendocrine cell proliferation confined to the respiratory epithelium of large and small airways. The involvement is pronounced in small bronchi and bronchioles, but initially remains confined to the airway mucosa. When the neuroendocrine cell proliferation extends beyond the airway mucosa, and becomes extraluminal, the term tumorlet is employed. Somewhat arbitrarily, if a tumorlet exceeds 0.5 cm in diameter, the lesion is classified as a carcinoid tumor. Ultimately the small airway compromise that occurs in patients with DIPNECH may become widespread enough that clinical symptoms develop and the typical thoracic CT manifestations of small airway obstruction / constrictive bronchiolitis- are seen. Note, however, that neuroendocrine cell hyperplasia not uncommonly is encountered in the vicinity of peripheral carcinoid tumors, and thus the presence of such proliferation does not automatically establish the diagnosis of DIPNECH. In fact, the minority of patients with peripheral carcinoid tumors and pathologically-proven neuroendocrine cell hyperplasia will actually have clinical evidence of airflow obstruction.

DIPNECH presents over a fairly wide age range, but a female, middle-age predominance is recognized. Patients with DIPNECH may detected incidentally, when undergoing lung biopsy or resection for other reasons (typically the evaluation of a lung nodule), although most patients present with symptoms such as cough, dyspnea, and wheezing. Pulmonary function testing typically shows obstruction.

Chest radiographs are commonly non-specifically abnormal, showing one or more lung nodules and/or non-specific linear or reticular opacities. Thoracic CT often shows one or more small lung nodules and multifocal inhomogeneous lung opacity representing a combination of mosaic perfusion (the more lucent areas) and ground-glass attenuation (the higher attenuating areas). The inhomogeneous lung attenuation accentuates on post-expiratory imaging (meaning the lucent areas remain equally lucent or become more lucent, whereas the higher attenuation areas increase in attenuation) - this pattern indicates that the mosaic perfusion is due to air-trapping. Airway thickening and bronchiectasis are seen in the minority of patients.

The diagnosis of DIPNECH usually requires surgical lung biopsy, but can be established with bronchoscopy and transbronchial biopsy / bronchoalveolar lavage in some patients, in the proper clinical and imaging context. Bronchoscopy is often recommended prior to surgical lung biopsy to exclude competing diagnosis, such as infection or other more common diagnoses.

Patients are commonly treated with corticosteroids and bronchodilators and inhaled corticosteroid therapy. About 40% of affected patients remain stable, whereas about one-fourth of patients experiencing clinical deterioration, and the remaining showing improvement. 

References

  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. 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:e14-17.

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