1. As a member
and also as , i feel as a host too.

2. LARGE CELL NEUROENDOCRINE CARCINOMA OF LUNG Case 55
AMR SPLIT 2018
Lovorka Batelja Vuletić
Departmen of pathology School of Medicine University of Zagreb

3. LCNEC WHO classification (3th edition)
a NSCLC that shows histological features of neuroendocrine morphology and expresses immunohistochemical neuroendocrine markers
LCNEC
COMBINED LCNEC with adenocarcinoma, squamous cell carcinoma, spindle cell carcinoma / giant cell carcinoma

4. Case history
LCNEC- Literature date
a man born 1957.
a former smoker
periodically febrile: 2016.y, without cough and dyspnoea
highly related to smoking
most commonly located in the peripheral lung
in 20% of cases- a central location
cough, haemoptysis, dyspnoea, pneumonia and chest pain
! unlike SCLC paraneoplastic syndrome are uncommon

5. 9/2016 a chest x-ray : nodules 1.8 cm in diametar
Radiological findings
9/2016 a chest x-ray : nodules 1.8 cm in diametar
5/2017 MSCT: a soft tissue mass opened etiology
2.5 cm in diametar
12 /2017 CT of torax: a solide lesion in the left superior lung’s lobe
3.6 cm in diametar
3/ 2018 an operation precedure:
Thoracotomy
Superior Lobectomy
Mediastinal Lymphadenectomy
MSCT: multislides CT

6. Literature date
Macroscopy
average diametar 3-4cm
circumscribed tumor
occasionally present haemorrhage

7. Macroscopic features superior lung lobe with stasis changes
tumor 4 cm in diametar, ~40% necrotic
lymph nodes;
regions I-X

8. LARGE OR NOT SMALL
Medium size

9. What is the mesaure

10. T cells are about 7-8 micrometers

11. Ø of tumor cell> Ø

12. Histological Findings
or giant multinuclear cells and probably represents SCC and AD. One histological variant is large cell neuroendocrine carcinoma, and confirmation of neuroendocrine differentiation is required using immune histochemical markers (Figure 1D).
sheets or nests of middle size polygonal tumor cells

14. Histopathology of LCNEC
Neuroendocrine morphology: organoid nesting, trabecular growth, rosette-like structures
Nucleoli are frequent
Mitotic counts> 10 M / 2mm2
Necrosis: punctate or large
Confirmation of neuroendocrine differentiation is required
One positive marker is enoug

15. Histopathology of LCNEC
Neuroendocrine morphology: organoid nesting, trabecular growth, rosette-like structures
Nucleoli are frequent
Mitotic counts> 10 M / 2mm2
Necrosis: punctate or large
Confirmation of neuroendocrine differentiation is required
One positive marker is enoug

17. MI >10 M / 10HPF

18. Differential diagnosis
SCLC
Carcinoid (atypical)
Basaloid squamous cell carcinoma
Other large cell carcinoma
!!the diagnosis can be difficult in small biopsy speciments

19. Immunohistochemical Findings
LCA
p40

20. CK 7
TTF1

21. A confirmation of neuroendocrine differentiation
CD56

22. Literature date IHC profile: 92-100 % LCNET + CD 56
80-85% LCNET+ chromogranin A
50-60% LCNET + synaptophisin
~ 50 % LCNET + TTF1
~ 100 % LCNET + AE1 / AE3, CK7; dot- like / diffuse

23. Diagnosis: large (non small cell) neuroendocrine carcinoma
pTNM: pT2apN0

24. PDL1 status
DAKO 22C3
negative

25. Molecular profiling
ALK +
(Cell signaling antibody)
EGFR -

26. Why did we choose this case ?
Rare pulmonary tumor
Heterogenic group of tumors
Tumor spread:
lymph nodes
lung parenhima
liver
brain
bone

27. Kerr K. M. , Bubendorf L. , Edelman M. J. et. all
Kerr K.M., Bubendorf L., Edelman M.J. et. all. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer.Annals of Oncology :
CAP/ IASLC (the International Association for the Study of Lung Cancer) /AMP Molecular Testing Guideline for Selection of Patients with Lung Cancer for Treatment with ALK Thyrosine Kinase Inhibitors; Summary of Recomendation 2013, 2015
Dietel M et al. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group Thorax 2016;71:177–184
routine EGFR i ALK mutation analysis „..has been recommended for all non-squamous tumours..”

28. according Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology, published in March 2018.
...Upon systematic review, no new evidence established the routine molecular testing of any genes for typical squamous cell carcinoma, small cell carcinoma, or other neuroendocrine lung tumors... !!!

29. !!
...In nonadenocarcinoma non–small cell histologies, the finding of EGFR, ALK,or ROS1 alterations has been most commonly reported in situations in which patients had a minimal (1–10 packs per year) or no history of tobacco exposure. Similarly, some studies have suggested associations between the presence of ALK or ROS1 alterations and younger patient age...

30. References
Kerr K. M., Bubendorf L., Edelman M. J. et all. Second ESMO consensus conference on lung cancer:pathology and molecular biomarkers for non-small-cell lung cancer. Annals of Oncology : 1681–1690.
Bergethon K., . Shaw A.T, Ignatius Ou Sai-Hong, et all.ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers. Journal of Clinical Oncology 2012 (8)
Kim H, Yoo SB, Choe JY, et al. Detection of ALK gene rearrangement in non-small cell lung cancer: a comparison off fluorescence in situ hybridization and chromogenic in situ hybridization with correlation of ALK protein expression.JThoracOncol.2011;6(8):1359–1366
Lindeman NI,Cagle PhT,Aisner DL et all. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Journal of Thoracic Oncology Vol. 13 No. 3:
Rodig SJ, Mino-Kenudson M, Dacic S, et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res. 2009;15(16):5216–5223.
Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol.2009;27(26):4247–4253
WHO classification of Tumours of the Lung, Thymus and Heart. Edited by Travis WD, Brambilla E, Burke AP , Marx A and Nicholson AG.