1. THE SPECTRUM OF NEUROENDOCRINE LUNG TUMORS, CLINICOPATHOLOGICAL FEATURES AND MORPHOLOGY
First author: Roman Adina
Co-author: Andone Sebastian
Coordinator: Tibor Mezei, MD

2. Introduction
First described as carcinoid tumors in the ileum in 1888 (in 1937 bronchial carcinoid)
Clear cells belonging to the APUD system
Capability of producing hormonal products or substances commonly found in cells belonging to the nervous system introduced the idea of NEUROENDOCRINE CONCEPT
Hago et al “Update in Pulmonary Carcinoid Tumors: A review article” Annals of Surgical Oncology, 10(6):

3. Introduction
Neuroendocrine lung tumors widely accepted histological classification:
Typical carcinoids (TC)
Atypical carcinoids (AC)
Small cell lung carcinoma (SCLC)
Large cell neuroendocrine carcinoma (LCNEC)
Brambilla, Travis et al : “The new World Health [..] “ERJ December 1, 2001 vol. 18 no

4. Introduction
Common morphologic, ultrastructural, molecular characteristics
Specific histological features:
Presence or lack of mitosis
Presence or lack of necrosis
Tissue architecture, cellular shape and size
Nuclear characteristics
Immunohistochemistry findings:
Chromogranin A
Synaptophysin
CD56
Cytokeratin
Hammar et al “Neuroendocrine tumors”, Dail And Hammar 3rd Edition, vol 2,

7. Objective Main purpose: Secondary purposes:
To review and study neuroendocrine lung tumors incidence and pathological features
Secondary purposes:
The evaluation of immunohistochemistry features
Establish a minimal antibody panel sufficient for diagnosing most of the cases

8. Material and method
52 cases diagnosed between at the Pathology Department of Targu Mures County Clinical Emergency Hospital
Inclusion criteria:
Tumor morphology
Immunohistochemistry suggestive neuroendocrine differentiation
Surgical resection specimens (no biopsy, core/fine needle aspiration or other cytology specimens)

9. Results The following parameters were included in the database:
Histological type
Location, dimension, focality
Histological grade, tumor extension, resection margin status
TNM descriptors and stage
Immunohistochemical profiles

10. Results We included neuroendocrine tumors into two groups:
Well differentiated tumors
Typical carcinoids
Atypical carcinoids
Undifferentiated tumors
Small cell lung carcinoma
Large cell neuroendocrine carcinoma

11. Results 10.8% of all malignant tumors included in our study
Data shows that neuroendocrine tumors predominantly affects men (68%)
Mean age: 56 years
Well-differentiated tumors present a younger age of diagnosis (p=0.02)

12. Age distribution of neuroendocrine tumors
Results
Age distribution of neuroendocrine tumors

13. Results Well differentiated tumors average size: 25 mm
Undifferentiated tumors average size: 38 mm
P=0.07
Location data: First group presented an even distribution, the latter presented an inferior lobe extension preference
Unifocal type distribution (one tumor per lobe)

15. Results Immunohistochemical markers: Chromogranin A Synaptophysin CD56
Other markers: CTK7, TTF1, NSE, CK20 (CK – dot like)
59.6 % of cases presented immunohistochemical staining results
Both groups were intensly positive for Chromogranin A

17. Discussions
Neuroendocrine tumors comprise worldwide approximately % of all malignancies [1]
The importance of differentiating AC, TC, SCLC or LCNEC and it’s impact on survival rate (87% to 2% for undifferentiated tumors) [2]
Impact on treatment: perioperative chemotherapy and surgical resection for all NSCLC
[1]Taal, B.G.; Visser, O. Epidemiology of neuroendocrine tumours.  Neuroendocrin 2004, 80, 3–7
[2] Anette Fisseler: “Neuroendocrine tumors of the lung” , Cancers 2012, 4(3),

18. Discussions
It is speculated that NSCLC with neuroendocrine differentiation present a higher rate of response to treatment
Currently, there is no consensus on clinical management and therefore no treatment guideline for LCNEC [1]
All neuroendocrine tumors present high risk of metastasis (20-80%) [2]
[1] Travis et al: “World Health Organization Classification of Tumors [..] “; IARC Press: Lyon, France, 2004; pp. 19–25.
[2] Anette Fisseler: “Neuroendocrine tumors of the lung” , Cancers 2012, 4(3),

19. Conclusions
Comparison with other studies showed the importance of other markers as well as the necessity of immunohistochemical stains to support diagnosis
Verifying large cell carcinoma for it’s possible neuroendocrine differentiation (in case of suggestive architecture)
Reevaluation of some cases without immunohistochemical staining results
Establishing an antibody panel sufficient for immunohistochemical valid diagnosis in neuroendocrine tumors
International Registry of Pulmonary Neuroendocrine Tumors

20. Novelty and limitations
Despite the fact that there are studies regarding lung tumors in selected Romanian population, to our best knowledge so far there are no recently published data concerning tumors with neuroendocrine differentiation in particularly
Limitations include
funding regarding immunohistochemical markers
use of immunohistochemical stains to a less extent in the past