March 2022 Medical Image of the Month: Pulmonary Nodules in the Setting of Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH)

Figure 1. Unenhanced chest CT images in the axial plane show solid, non-calcified and well-circumscribed nodules in the right upper lobe (RUL) (A) and lingula (B).  The RUL nodule is FDG-avid on axial fused FDG PET-CT image (C) whereas the lingular nodule is not (D).

Figure 2. Unenhanced chest CT images in the axial plane reconstructed with maximum intensity projection (MIP, A) and minimum intensity projection (MinIP, B) techniques show multiple scattered solid pulmonary nodules (arrows) and pulmonary mosaicism consistent with air-trapping (circled). Axial fused images from a ⁶⁸GA-DOTATATE PET-CT demonstrate some activity in the RUL nodule (C) and more prominent uptake in the lingular nodule (D).

Figure 3.  Hematoxylin and Eosin stained low-power pathological image (A) demonstrates the lingular carcinoid tumor (*) as well as several carcinoid tumorlets (arrows) in the adjacent lung. A separate specimen of lung stained with synaptophysin demonstrates multiple tumorlets in the small sample. When taken in conjunction with imaging findings, pathology is in-keeping with a diagnosis of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH).

A 62-year-old woman presented to an outside hospital with chronic cough, prompting a chest x-ray (CXR). Findings further prompted unenhanced chest CT to evaluate possible pulmonary nodules. The CT demonstrated multiple scattered, solid and centrilobular pulmonary nodules, most of which were small but there were two >1 cm nodules, one in the right upper lobe (RUL) and a second in the lingula (Figure 1A,B). A subsequent FDG PET-CT was performed demonstrating increased metabolic activity in the RUL nodule with no activity in the lingular nodule (Figure 1C,D). Biopsy of the RUL nodule was consistent with a carcinoid. At this point the patient was referred to our center for further management. A repeat chest CT failed to demonstrate any significant change in the nodules. MIP and MinIP reconstructions from that examination demonstrate multiple small, solid pulmonary nodules (arrows) (Figure 2A), many of which were associated with air-trapping resulting in pulmonary mosaicism (circled) (Figure 2B). A ⁶⁸GA-DOTATATE PET-CT was performed, the results of which provide stark contrast to the FDG-PET in that the RUL nodule demonstrated modest uptake (Figure 2C), whereas the lingular nodule showed very prominent update (Figure 2D). The lingular nodule was resected, H & E-stained pathology image (Figure 3A) demonstrated a typical carcinoid (*) with multiple carcinoid tumorlets in the surgical specimen (arrows). A separate specimen stained with synaptophysin demonstrates multiple neuroendocrine tumorlets. Pathological findings, in conjunction with patient demographics and imaging findings, were consistent with Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH).

DIPNECH is recognized as a pre-neoplastic lesion in the 2015 WHO classification of lung tumors (1). There is neuroendocrine cell proliferation within the small bronchi and bronchioles which may progress beyond the basement membrane, forming carcinoid tumorlets and in some cases, eventually carcinoid tumors.  These airway-centered nodules cause obstruction.  In addition, there is often an association between DIPNECH and constrictive bronchiolitis, which causes further airway obstruction (2).  The vast majority of patients are women in their 50s-70s and most patients are symptomatic with the most common presenting symptoms being chronic cough and dyspnea (3,4).  Many of these patients are often mis-diagnosed with asthma initially (4).  The imaging findings of DIPNECH on CT are not specific but can be pathognomonic in some cases.  There are almost always innumerable small solid (and sometimes ground glass) centrilobular nodules and nodular bronchial thickening with associated pulmonary mosaicism related to air trapping.  Nodules are either stable or very slowly growing over years with the largest nodules usually being biopsied or resected and yielding typical carcinoid on pathology (4).  A relatively new nuclear medicine imaging study, 68Ga-DOTATATE PET-CT, shows promise as a higher resolution and more sensitive examination for detection of neuroendocrine tumors (relative to octreotide scans), including pulmonary carcinoid tumors in the setting of DIPNECH (5,6).

Clinton Jokerst MD¹, Henry Tazelaar², Carlos Rojas MD¹, Prasad Panse MD¹, Kris Cummings MD¹, Eric Jensen MD¹ and Michael Gotway MD¹

Departments of Radiology¹ and Pathology²

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. Gosney JR, Austin JHM, Jett J, et al. Diffuse pulmonary neuroendocrine cell hyperplasia. In: Travis WD, Brambilla E, Burke AP, et al., eds. WHO classification of tumours of the lung, pleura, thymus and heart. Lyon, IARC Press, 2015; pp. 78-79.
2. Samhouri BF, Azadeh N, Halfdanarson TR, Yi ES, Ryu JH. Constrictive bronchiolitis in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. ERJ Open Res. 2020 Nov 16;6(4):00527-2020. [CrossRef] [PubMed]
3. Rossi G, Cavazza A, Spagnolo P, Sverzellati N, Longo L, Jukna A, Montanari G, Carbonelli C, Vincenzi G, Bogina G, Franco R, Tiseo M, Cottin V, Colby TV. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome. Eur Respir J. 2016 Jun;47(6):1829-41. [CrossRef] [PubMed]
4. Little BP, Junn JC, Zheng KS, Sanchez FW, Henry TS, Veeraraghavan S, Berkowitz EA. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia: Imaging and Clinical Features of a Frequently Delayed Diagnosis. AJR Am J Roentgenol. 2020 Dec;215(6):1312-1320. [CrossRef] [PubMed]
5. Deppen SA, Blume J, Bobbey AJ, Shah C, Graham MM, Lee P, Delbeke D, Walker RC. 68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. J Nucl Med. 2016 Jun;57(6):872-8. [CrossRef] [PubMed]
6. Fraum TJ, Ritter JH, Chen DL. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia on Somatostatin Receptor Imaging. Am J Respir Crit Care Med. 2018 Nov 1;198(9):1223-1225. [CrossRef] [PubMed]

Cite as: Jokerst C, Tazelaar H, Rojas C, Panse P, Cummings K, Jensen E, Gotway M. March 2022 Medical Image of the Month: Pulmonary Nodules in the Setting of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). Southwest J Pulm Crit Care Sleep;2022:40-42. doi: https://doi.org/10.13175/swjpccs010-22 PDF

February 2022 Medical Image of the Month: Multifocal Micronodular Pneumocyte Hyperplasia in the Setting of Tuberous Sclerosis

Figure 1. Unenhanced chest CT in the axial (A) plane showing multiple subsolid pulmonary nodules in a random distribution (arrows).  Unenhanced chest CT in the axial (A) plane compared to an image from a contrast-enhanced abdominal CT performed 1 year earlier (B) shows relative stability of these nodules (arrows).  In a 22 y/o man with known Tuberous Sclerosis Complex, these findings are consistent with Multifocal Micronodular Pneumocyte Hyperplasia. Click here to view Figure 1 in an enlarged window.

Figure 2.  Unenhanced chest CT in the axial (A) plane, soft tissue window display settings, demonstrate foci of myocardial fat (arrow).  Unenhanced chest CT in the axial (B) and sagittal (C) planes, bone window display settings, shows multiple small scattered sclerotic osseous foci (circles). These ancillary findings are quite common in the setting of tuberous sclerosis. Click here to view Figure 2 in an enlarged window.  

A 22-year-old man with a known diagnosis of Tuberous Sclerosis Complex (TSC) presents for a follow-up unenhanced chest CT to re-evaluate pulmonary nodules seen in the lung bases on a prior abdominal CT.  The patient also has a history of multiple renal lesions consistent with lipid-poor angiomyolipomas based on previous abdominal MRI findings.  The chest CT demonstrated multiple scattered, randomly distributed sub-centimeter pulmonary nodules of solid or subsolid morphology [Figure 1A].  Those nodules visible in the lung bases on the prior abdominal CT had remined stable over the 12-month interval consistent with multifocal microscopic pneumocyte hyperplasia (MMPH)[Figure 1B,C].  Myocardial fatty foci (MFF) were visualized in the heart on soft tissue window display settings [Figure 2A] as were multiple scattered sclerotic bone lesions on bone window display settings [Figure 2B,C]. No pulmonary cysts were seen to suggest lymphangioleiomyomatosis (LAM) and there were no thoracic lymphangiomas.

MMPH represents a benign hamartomatous proliferation of type II pneumocytes which manifest as small, randomly scattered pulmonary nodules that can be solid or subsolid and are self-limited (1).  MMPH is rare in general, but quite common in TSC with a reported incidence as high as 71% (2).  MMPH does not demonstrate a sex predilection (unlike LAM in TSC). It is important to remember MMPH in the setting of TSC as it represents a “don’t touch” lesion; recognizing it as such can save unnecessary trouble for the patient (3). The MFF seen on this chest CT also is a relatively common and specific finding in TSC, seen in at least 50% of TSC patients (4,5).  Although MMPH and MFF appear to be relatively specific imaging findings in the setting of TSC, as of yet they have not been incorporated into the diagnostic criteria for TSC (6). The small sclerotic bone lesions, especially involving the posterior elements of the spine, are also a well described finding in TSC; however, this finding is much less specific and can be seen in many conditions (7).

Clinton Jokerst MD, Carlos Rojas MD, Prasad Panse MD, Kris Cummings MD, Eric Jensen MD and Michael Gotway MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

References

1. Franz DN, Brody A, Meyer C, Leonard J, Chuck G, Dabora S, Sethuraman G, Colby TV, Kwiatkowski DJ, McCormack FX. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med. 2001 Aug 15;164(4):661-8. [CrossRef] [PubMed]
2. Wataya-Kaneda M, Tanaka M, Hamasaki T, Katayama I. Trends in the prevalence of tuberous sclerosis complex manifestations: an epidemiological study of 166 Japanese patients. PLoS One. 2013 May 17;8(5):e63910. [CrossRef] [PubMed]
3. Aswani Y, Gavai B. Multifocal micronodular pneumocyte hyperplasia: A "touch-me-not" pulmonary lesion in tuberous sclerosis complex. Lung India. 2018 Sep-Oct;35(5):445-446. [CrossRef] [PubMed]
4. Adriaensen ME, Schaefer-Prokop CM, Duyndam DA, Zonnenberg BA, Prokop M. Fatty foci in the myocardium in patients with tuberous sclerosis complex: common finding at CT. Radiology. 2009 Nov;253(2):359-63. [CrossRef] [PubMed]
5. Tresoldi S, Munari A, Di Leo G, Pompili G, Magistrelli P, Secchi F, La Briola F, Canevini MP, Cornalba G, Sardanelli F. Myocardial Fatty Foci in Adult Patients with Tuberous Sclerosis Complex: Association with Gene Mutation and Multiorgan Involvement. Radiology. 2015 Nov;277(2):398-405. [CrossRef] [PubMed]
6. Northrup H, Krueger DA; International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct;49(4):243-54. [CrossRef] [PubMed]
7. Baskin HJ Jr. The pathogenesis and imaging of the tuberous sclerosis complex. Pediatr Radiol. 2008 Sep;38(9):936-52. [CrossRef] [PubMed]

Cite as: Jokerst C, Rojas C, Panse P, Cummings K, Jensen E, Gotway M. February 2022 Medical Image of the Month: Multifocal Micronodular Pneumocyte Hyperplasia in the Setting of Tuberous Sclerosis. Southwest J Pulm Crit Care Sleep. 2022;24(2): . doi: https://doi.org/10.13175/swjpccs001-22 PDF