Small (and large) Blue Cell Tumors of the Skull Base

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1 Small (and large) Blue Cell Tumors of the Skull Base Jennifer L. Hunt, MD, MEd Aubrey J. Hough Jr, MD, Endowed Professor of Pathology Chair of Pathology and Laboratory Medicine University of Arkansas for Medical Sciences 1

2 Sino-Nasal Lesions High Grade Epithelial Tumors Tumors with neuroendocrine differentiation Other lesions in the differential diagnosis 2

3 Sinonasal Undifferentiated Carcinoma Incidence: Rare Clinical Present with large invasive tumors Metastases are frequent Symptoms include nasal obstruction, epistaxis, visual and headache Prognosis is poor ~20-25% overall survival at 5 years 3

4 Sinonasal Undifferentiated Carcinoma Histopathology Undifferentiated tumor cells Mitoses and necrosis Vascular invasion and adjacent structures Immunohistochemistry Positive for Cytokeratin Controversy: Neuroendocrine marker positivity 4

5 SNUC, H&E 5

6 SNUC, H&E 6

7 SNUC, H&E 7

8 SNUC, H&E 8

9 Differential Diagnosis Melanoma Ewings/PNET Rhabdomyosarcoma NUT midline carcinoma Lymphoepithelial carcinoma Lymphoma Neuroendocrine carcinoma 9

10 Mucosal Melanoma, H&E 10

11 Ewing s, H&E 11

12 Rhabdomyosarcoma, H&E

13 Work-Up of High Grade Tumor Cytokeratin stains Neuroendocrine stains S100 HMB45 CD99 Myogenin Desmin Lymphoma markers 13

14 NUT Midline Carcinoma Nut midline carcinomas More common in young people Average age 17 years Very aggressive (lethal) tumors Histology Undifferentiated morphology Abrupt keratinization in 82% NUT-BRD4 translocation French CA, JCO, 22(20):4135,

15 NUT midline carcinoma, H&E

16 SNUC and NUT Translocation Stelow, et al Undifferentiated carcinomas of UADT NUT rearrangement in 5/28 cases NUT IHC positive in 3/5 cases Bishop, et al NUT IHC in 151 primary sinonasal carcinomas 2 of 13 SNUCs positive 1/87 squamous cell carcinomas positive Stelow E, et al. AJSP, 32(6), 2008 Bishop J, et al. AJSP, 36(8),

17 Sino-Nasal Lesions High Grade Epithelial Tumors Tumors with neuroendocrine differentiation Other lesions in the differential diagnosis 17

18 Incidence Olfactory Neuroblastoma Relatively rare (2% of sinonasal tumors) Broad age range Clinical Peaks in 2 nd and 6 th decades Sinonasal symptoms: nasal obstruction, epistaxis, non-specific symptoms Usually arises in the upper nasal cavity (superior nasal concha, upper septum, roof of nose, cribriform plate) 18

19 Olfactory Neuroblastoma Histopathology Small to medium sized cells in nests Usually minimal pleomorphism Rosettes Homer Wright: Central fibrillary material Up 30-50% Flexner-Wintersteiner: True lumen Rare (~5%) Neuropil 19

20 Olfactory neuroblastoma 20

21 Involvement of the specialized olfactory epithelium 21

22 Olfactory neuroblastoma, Homer Wright 22

23 Olfactory neuroblastoma: Flexner-Wintersteiner 23

24 Olfactory Neuroblastoma Immunohistochemistry Synpatophysin, chromogranin positive S100 can have sustentacular pattern CAM5.2 occasionally focally positive 24

25 Olfactory neuroblastoma, S100 stain 25

26 Olfactory neuroblastoma, Synaptophysin 26

27 Olfactory Neuroblastoma Hyams grading (histologic grade) Kadish stage (clinical staging) Vs. AJCC staging system 27

28 Olfactory Neuroblastoma Divergent Differentiation Often high grade tumors Other components present Rhabdomyosarcoma Epithelial (Carcinoma) Glandular (Adenocarcinoma) Ganglion cells 28

29 Olfactory neuroblastoma with divergent differentiation

30 Olfactory neuroblastoma with divergent differentiation, S100

31 Olfactory neuroblastoma with divergent differentiation Synaptophysin Cytokeratin

32 Differential Diagnosis Sinonasal neuroendocrine carcinoma Paraganglioma Ectopic pituitary adenoma 32

33 Sinonasal Neuroendocrine Carcinoma Incidence Rare tumor Sinonasal neuroendocrine carcinoma (SNEC) Etiology Possibly from olfactory epithelium Treatment and Prognosis Combination therapy 33

34 Histology Sinonasal Neuroendocrine Carcinoma Solid sheets, ribbons, or trabeculae Large cells with coarse chromatin and nucleoli Necrosis and mitoses IHC Chromogranin, syaptophysin, NSE Cytokeratin 34

35 Neuroendocrine carcinoma 35

36 Neuroendocrine carcinoma 36

37 Neuroendocrine carcinoma, synaptophysin

38 Clinical Ectopic Pituitary Occur along the embryological migration and invagination pathway of Rathke s Pouch Distinguish radiologically, clinically and surgically from invasive pituitary adenoma Broad age range; most common in 6 th decade Frequently mis-diagnosed 38

39 Pathology Ectopic Pituitary Bland appearing neuroendocrine lesion Hormones: FSH, LH, GH, TSH, ACTH, PRL, Calcitonin 39

40 Ectopic pituitary adenoma

41 Ectopic pituitary adenoma, ACTH

42 Summary High Grade Tumors Sinonasal undifferentiated carcinoma Differential Diagnosis: Ewings/PNET, melanoma, Rhabdomyosarcoma Tumors with neuroendocrine differentiation Sinonasal neuroendocrine carcinoma Olfactory neuroblastoma Ectopic pituitary adenoma 42