1. Imaging features of Large Cell Neuroendocrine Tumors on Chest CT – A Pictorial Essay
Munir, Sohaib1; Salahudeen, Shafeequr1; Turashvili, Gulisa2; Boag, Alexander2; Nolan, Robert1
Department of Diagnostic Imaging, Kingston General Hospital, Queen's University, Kingston, ON, Canada
Department of Pathology, Kingston General Hospital, Queen’s University, Kingston, ON, Canada
The authors have no disclosures or conflicts of interests to declare
April, 2013

2. ABSTRACT
Purpose:
To describe a spectrum of morphological imaging appearances of Large cell neuroendocrine carcinoma (LCNEC)
of the lung in our practice.
Materials and Methods:
Retrospective analysis of all 12 biopsy proven Large cell neuroendocrine carcinoma of the lung parenchyma
in previous ten years at our institution. We have presented imaging appearances in 8 of such cases in this pictorial essay.
Results:
Neuroendocrine tumors of the lung arise from Kulchitzky cells of the bronchial mucosa and comprise typical
carcinoid, atypical carcinoid, Large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma.
Large cell neuroendocrine tumors are infrequent primary lung carcinomas. Although, they do not differ
significantly in imaging features in comparison to other primary tumors of the lung, we aim to present a few
examples of large cell neuroendocrine tumor with certain imaging features from our experience,
in this pictorial essay.
Conclusion:
In our practice, we find the large cell neuroendocrine tumors are airway related and slightly well defined
with ovoid configuration. All our cases are biopsy proven large cell neuroendocrine differentiation and also
have some common imaging features making it difficult to differentiate solely on cross sectional imaging.

3. Case 1 Case 1 Image guided biopsy confirms Large Cell
Neuroendocrine differentiation.
Axial CT images demonstrate a branching airway related opacity within the apical segment of the left upper lobe. The opacity is related to the subsegmental bronchi level and branches more peripherally. This imaging feature can be typically seen in airway related carcinoid tumors, however, seen in LCNEC.

4. Case 1
Coronal reformatted images demonstrate that the tumor is airway related and follows their tubular branching pattern.

5. Selected axial CT images in lung windows demonstrate the endobronchial mass related to the proximal posterior segmental bronchus extending centrally to the branch point of the right upper lobe bronchus
Case 2

6. Case 2
Coronal reformatted images beautifully demonstrate the airway related process in the right upper lobe extending centrally.
Biopsy proves it to be Large cell neuroendocrine tumor of lung origin.

7. Case 3
Coronal reformatted images demonstrate a rounded and somewhat lobulated contour of the nodule within the right middle lobe lateral segment at sub pleural location. Note the smooth margins of the nodule. Axial CT images on the lung windows demonstrate smooth marginated nodule in the right middle lobe at sub pleural location. Biopsy proves it to be Large cell neuroendocrine tumor of the lung

8. Case 4
Two axial images of the thorax in the lung windows demonstrate a non-specific
spiculated nodule in the left upper lobe anterior segment.
Note the background emphysema.
Biopsy proves confirms a large cell neuroendocrine tumor
of pulmonary origin.

9. Case 5
Nonspecific minimally spiculated left upper lobe nodule in sub pleural location with left hilar lymphadenopathy and a small left pleural effusion. Adjacent bullous emphysematous changes are also noted. Biopsy confirm presence of LCNEC

10. Case 6
Axial and coronal images in lung windows show right upper lobe lobulated subpleural nodule and biopsy proves it to be a large cell neuroendocrine tumor.
Biopsy morphologically consistent with Non small cell with CD56 positive neuroendocrine differentiation

11. Case 7
Axial and coronal images demonstrate minimally branching smooth marginated large cell neuroendocrine tumor

12. Case 8
Axial images demonstrate airway related tubular branching large cell neuroendocrine tumor

13. Case 8
Coronal reformatted images confirms airway related branching large cell neuroendocrine tumor

14. Discussion
Neuroendocrine tumors of the lung has a wide range of spectrum from low grade typical carcinoids , atypical carcinoids to small cell lung carcinoma(SCLC). In 1991, Travis and colleagues, reported a sub type of lung cancer characterized by large cell, abundant cytoplasm, higher mitotic rate and extensive necrosis, however, with neuroendocrine features of growth pattern. This distinct sub type which distinctly differs from small cell lung carcinoma , has been classified as Large cell Neuroendocrine Carcinoma(LCNEC). However, the clinical, histopathological and biological features are closer towards Non Small Cell Lung Carcinomas (NSCLC) than Small Cell Lung Carcinoma (SCLC). LCNEC is an uncommon primary lung carcinoma. LCNEC has a prognosis between that of atypical carcinoid and that of SCLC.
Population of smokers in LCNEC cases was reported to be approximately more than 95%

15. Discussion
In our experience all cases of LCNEC exhibits varied spectrum of morphological imaging appearances as shown above. They appear to share imaging features of both carcinoid, SCLC and NSCLC. The features are shown in the above examples include lobulated , rounded, ovoid contours with smooth margins which usually occur in carcinoid, including larger lymph node metastasis which are typical of SCLC.
Again, tumor growth along the airway with branching pattern is not typical of NSCLC, but were seen in our cases of LCNEC. These features are again typical in carcinoids.
We have also shown examples of nonspecific imaging features of LCNEC including spiculated and nodular morphology. No particular predilection to pleural based, sub pleural or central location has been observed. In the cases shown, the LCNEC can be seen related to both airways as well as parenchyma.
Oshiro and colleagues reported the CT findings of LCNEC usually to be well defined and lobulated tumor with no air bronchograms or calcification.

16. Discussion
LCNEC has high mitotic rates and no one specific marker was expressed in all cases of the tumor. Takei and colleagues reported 86% positive with chromogranin, 91% using synaptophysin and 91% with neural cell adhesion molecule.
Iyoda et al compared large cell carcinoma with neuroendocrine features (LCNF) with other primary neuroendocrine neoplasm of the lung parenchyma such as carcinoids, atypical carcinoids and SCLC. They found that the typical and atypical carcinoids occurred in relatively younger patients in both sexes and included patients who never smoked. However, in contrast, patients with LCNE features or SCLC occurred in older, predominantly males and usually heavy smokers. Histopathologically, tumors with LCNFs and SCLC had frequent larger lymph node metastases, larger tumor size, increased mitotic figures. These patients also obviously had poorer prognosis than those with typical or atypical carcinoids.
Biochemical and histopathological spectral variation seen between the typical carcinoids, atypical carcinoids , LCNEC and SCLC is also reflected in gross morphological imaging appearances . Imaging features of LCNEC resemble that of typical carcinoids, SCLC and NSCLC.
Varied morphological imaging appearances would help imagers recognize different patterns of LCNEC.

17. References
Neuroendocrine tumors of the lung – Chong et al: Radiographics 2006; 26: 41-58
Pulmonary Large cell Neuroendocrine Carcinoma: Its place in the spectrum of Pulmonary Carcinoma – Iyoda et al, Ann Thoracic Surgery 2007; 84:702 – 7
Large cell Neuroendocrine Carcinoma of the lung – Veronesi et al, Lung Cancer 2006; 53: 111-5
Oshiro et al : CT findings of surgically resected large cell neuroendocrine tumors – AJR 2004; 182:87 – 91
Takei et al: Large cell neuroendocrine carcinoma of the lung : a clinicopathologic study of 87 cases – Journal of Thoracic Cardiovasc Surgery 2002; 124:285 – 92
Pulmonary large cell carcinomas with neuroendocrine features are high grade neuroendocrine tumors – Ann Thoracic Surgery 2002; 73: 1049 – 54
Should Large cell Neuroendocrine lung carcinoma be classified and treated as a small cell lung carcinoma or other large cell carcinomas – Varlotto et al : Journal of Thoracic Oncology 2011; 6:
Pulmonary large cell neuroendocrine carcinoma – Hage et al: European Journal of Cardio – thoracic Surgery 2003; 457 – 460
Neuroendocrine tumors of the lung with proposed criteria for large cell neuroendocrine carcinoma – Travis et al: American Journal of Surgical Path 991; 15: