Pitfalls in Sinonasal Pathology

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1 Pitfalls in Sinonasal Pathology 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 Agenda Inflammatory Conditions Fungal sinusitis Invasive fungal disease Mid-line destructive diseases Epithelial proliferations Low and high grade carcinomas 2

3 Allergic Fungal Sinusitis 3

4 Incidence Allergic Fungal Sinusitis 5-10% of chronic sinusitis Gross Polyposis Thick, green mucus Peanut butter consistency 4

5 Allergic mucus

6 Allergic Fungal Sinusitis Histopathology Fungus Ball Allergic type mucus Allergic fungal sinusitis 6

7 Fungus ball 7

8 Fungus ball 8

9 Allergic mucus 9

10 Allergic mucus

11 Invasive Fungal Sinusitis Classification Acute necrotizing (immunocompromised) Chronic invasive (diabetics) Granulomatous (immunocompetent) Histology Necrosis Vascular invasion Granulomas and giant cells 11

12 Invasive fungal sinusitis 12

13 Invasive fungal sinusitis 13

14 Invasive fungal sinusitis 14

15 Invasive fungal sinusitis

16 Invasive fungal sinusitis 16

17 Treatment of Fungal Disease Non-invasive Surgery to remove mucus Oral then inhaled steroids (up to 1 year) Invasive Complete debridement to viable tissue Intravenous antifungal drugs 17

18 Pitfalls Midline Destructive Diseases Traumatic Infectious Toxic Inflammatory Neoplastic Physical trauma Bacterial Cocaine Sarcoid Basal cell carcinoma Iatrogenic trauma Mycobacterial Chromium salts Foreign body Squamous cell carcinoma Self-induced Fungal Wegener s Lymphoma Vasculitis Other tumors 18

19 Wegener s Granulomatosis 19

20 Clinical Wegener s Granulomatosis C-ANCA Respiratory tract & Kidney Localized vs. systemic disease Histopathology Necrotizing granulomatous inflammation Vasculitis Neutrophilic microabscesses 20

21 Wegener s 21

22 Wegener s 22

23 Wegener s 23

24 Wegener s, elastic stain 24

25 Agenda Inflammatory Conditions Fungal sinusitis Invasive fungal disease Mid-line destructive diseases Epithelial proliferations Low and high grade carcinomas 25

26 Inverted Papilloma 26

27 Incidence Schneiderian Papilloma Men > women Adult age Clinical Mass lesion, nasal obstruction Three types Inverted, Exophytic, Oncocytic 27

28 Histology Inverted Papilloma Epithelium >10 cell layers thick Epithelial morphology Transitional Squamous, respiratory, mucinous Transmigrating neutrophils Decreased or absent minor salivary glands 28

29 Inverted papilloma 29

30 Inverted papilloma 30

31 Inverted papilloma

32 Exophytic Papilloma Location: Septum Histologoy Resembles squamous papilloma of skin Residual goblet cells 32

33 Exophytic papilloma 33

34 Exophytic papilloma 34

35 Oncocytic Schneiderian Papilloma 35

36 Oncocytic Schneiderian Papilloma Location: Usually lateral nasal wall Histology Oncocytic epithelium Microcysts in epithelium Containing inflammatory debris or mucin 36

37 Oncocytic schneiderian papilloma 37

38 Oncocytic schneiderian papilloma 38

39 Pitfalls Early changes of inverted papilloma Frozen section diagnosis Identifying malignant transformation 39

40 Schneiderian Papilloma

41 Schneiderian Papilloma

42 Malignant Transformation Clinical course Synchronous tumors (61%) Asynchronous tumors (29%) Classification Dysplasia (5-20%) Invasive carcinoma (2-27%) Tumor types: squamous cell carcinoma, schneiderian carcinoma, other 42

43 Agenda Inflammatory Conditions Fungal sinusitis Invasive fungal disease Mid-line destructive diseases Epithelial proliferations Low and high grade carcinomas 43

Sinonasal Adenocarcinomas 50 40 30 20 10 0 Salivary ITAC

44 Sinonasal Adenocarcinomas Salivary ITAC Non-ITAC Site % Nasal 40% Ethmoid 30% Maxillary 13% Multiple 18% 44

45 Clinical Low Grade Non-ITAC: Histology Rare lesion with generally good prognosis Histology Highly variable architecture Papillary, cystadenomatous, tubular Back-to-back glands with no myoepithelial cells Usually no vascular or perineural invasion Cytology Single layer of bland epithelial lining cells Bland nuclei 45

46 Low grade Adenocarcinoma, non-itac 46 46

47 Low grade Adenocarcinoma, non-itac 47

48 Low grade Adenocarcinoma, non-itac 48

49 Incidence Intestinal Type Adenocarcinoma Rare Men>Women Ethmoid sinus in >80% Clinical Sinonasal symptoms Occupational exposure Wood and leather dust Formaldehyde 49

50 Intestinal Type Adenocarcinoma Histopathology: Resembles GI tumors IHC CDX2 positive CK20 positive CK 7 positive (most cases) 50

51 Intestinal type adenocarcinoma 51

52 Intestinal type adenocarcinoma 52 52

53 ITAC, CDX2 ITAC, CK20 53

54 Sinonasal Undifferentiated Carcinoma Clinical Rare and very aggressive tumors Histopathology Undifferentiated tumor cells Mitoses and necrosis Vascular invasion and adjacent structures Immunohistochemistry Positive for Cytokeratin Rarely positive for NSE 54

55 SNUC, H&E 55

56 SNUC, H&E 56

57 SNUC, H&E 57

58 SNUC, H&E 58

59 SNUC, CAM5.2 59

60 Differential Diagnosis Melanoma Ewings/PNET Rhabdomyosarcoma NUT midline carcinoma Lymphoepithelial carcinoma Lymphoma Neuroendocrine carcinoma 60

61 Work-Up of High Grade Tumor Cytokeratin stains Neuroendocrine stains S100 HMB45 CD99 Myogenin Desmin Lymphoma markers 61

62 Summary Inflammatory Conditions Fungal sinus disease Mid-line destructive diseases Epithelial proliferations Low and high grade carcinomas 62

63 Head and Neck Lesions Every Pathologist Should Know 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 63

64 Agenda Differential diagnosis for cysts in the neck Differential diagnosis for neuroendocrine tumors (sinonasal and beyond) 64

65 Neck Cysts Differential diagnosis for cysts in the neck Benign developmental cysts Metastatic cystic squamous cell carcinoma 65

66 Clinical Branchial Cleft Cyst Relatively common Usually in children and young adults Asymptomatic mass lesion Draining sinus Variable location 66

67 Auditory canal Palatine tonsil II I 1 External auditory meatus Parathyroid (inferior) Thymus Parathyroid (superior) Ultimobranchial body IV III Branchial pouches Pharyngeal grooves (clefts) 67

68 Branchial Cleft Cysts Type Location Lining Special features First Arch (type 1 and type 2) Second Arch Third and Fourth Arches Near the ear Tract in supratonsillar fossa Cyst in the low anterolateral neck Tract in pyriform sinus Cyst at anterior border of SCM Keratinized squamous Squamous and/or respiratory Lymphoid stroma Squamous and/or respiratory Lymphoid stroma Cartilage can be seen in type 2 95% are this type <1% Can present with suppurative thyroiditis 68

69 Branchial Cleft 69

70 Branchial Cleft 70

71 Branchial Cleft 71

72 Differential Diagnosis Thyroglossal duct cyst Thymic cyst Metastatic cystic squamous cell carcinoma 72

73 Thyroglossal duct cyst 73

74 Thymic cyst 74

75 Clinical Cystic Metastasis Mass lesion in upper to mid-level neck 3.9 cm average size Male >> Female Average age: 54 75

76 Gross Cystic Metastasis Well circumscribed Thick capsule Multilocular Thick purulent or gumous material 76

77 Histology Cystic Metastasis Ribbon like epithelium Thickness of tonsillar type epithelium Can have endophytic or exophytic areas Cytology Moderate N:C ratio No maturation Bland appearance 77

78 Cystic Metastatic Squamous Carcinoma

79 Cystic Metastatic Squamous Carcinoma

80 Cystic Metastatic Squamous Carcinoma 80

81 Controversies Branchiogenic carcinoma vs. metastatic squamous carcinoma Bland metastasis vs. branchial cleft cyst 81

82 Differentiating Features Feature Metastasis Branchial cleft cyst Gross Cyst contents Unilocular Keratin Debris Multilocular Clear fluid Lining Dysplastic Respiratory & squamous Age Older Younger 82

83 Carcinoma in Branchial Cleft Cyst Diagnostic Criteria Anatomy Anterior to the sternocleidomastoid Between the tragus and the clavicle Association with sinus tract Histology Benign branchial cleft tissue Carcinoma with transition from benign to dysplastic and malignant epithelium Clinical course No primary tumor identified Minimum of five-year follow-up period 83

84 Clinical Metastatic Cystic Carcinoma May be first presenting symptom Primary tumor may be extremely small 64% come from the tonsil or tongue base Other sites include larynx and nasopharynx 84

85 Tonsil and Tongue Base SCC Oropharynx: >50% of tumors are positive for HPV HPV in cystic lymph node metastases Between 50 and 80% will be positive when originating from an oropharyngeal site Desai PC, Exp Mol Pathol, 87:94, 2009 Goldenberg D, Head Neck, 30:898,

86 HPV and Tumor Characteristics HPV Positive Demographics 5 years younger Non-smokers/non-drinkers HPV Negative Typical ages Tobacco and alcohol Site Tonsil & Tongue base All locations Histology Genetics Non-keratinizing, basaloid, and lymphoepithelial p53 inactivated by E6 Rb inactivated by E7 p16 over-expressed Keratinizing SCC p53 inactivated by mutation Rb inactivated by cyclin D1 amplification Inactivation of p16 86

87 HPV Detection Methods In situ hybridization DNA based either multiplexed or single type probes RNA based transcriptionally active virus Polymerase chain reaction Other methods Hybrid capture (cytology samples) p16 immunohistochemistry 87

88 H&E HPV ISH p16 IHC

89 p16 Immunohistochemistry Excellent surrogate marker for HPV p16 staining should be strong and diffuse 89

90 Why test for HPV? Diagnostic marker (cystic metastases) Prognostic marker To select therapeutic approaches De-escalation therapy 90

91 Agenda Differential diagnosis for cysts in the neck Differential diagnosis for neuroendocrine tumors in the sinonasal cavity Olfactory neuroblastoma Neuroendocrine carcinoma Paraganglioma Ectopic pituitary lesions 91

92 Olfactory Neuroblastoma 92

93 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) 93

94 Olfactory Neuroblastoma Histopathology Small to medium sized cells in nests Minimal pleomorphism Rosettes Homer Wright: Central fibrillary material Up to 50% Flexner-Wintersteiner: True lumen Rare Neuropil Grading: Hyam s Grading system 94

95 Olfactory neuroblastoma 95

96 Olfactory neuroblastoma, Homer Wright rosettes 96

97 Olfactory neuroblastoma, Flexner-Wintersteiner rosettes 97

98 Olfactory Neuroblastoma Immunohistochemistry Synpatophysin, chromogranin positive S100 with sustentacular pattern CAM5.2 occasionally positive 98

99 Olfactory neuroblastoma, Synaptophysin 99

100 Olfactory neuroblastoma, S100 stain 100

101 Olfactory neuroblastoma with divergent differentiation

102 Olfactory neuroblastoma with divergent differentiation, S100

103 Olfactory neuroblastoma with divergent differentiation Synaptophysin Cytokeratin

104 Neuroendocrine Carcinomas Nomenclature Carcinoid Atypical carcinoid Neuroendocrine carcinoma, small cell type Neuroendocrine carcinoma, large cell type 104

105 Neuroendocrine Carcinoma, large cell type Incidence Rare tumor Locations: Throughout the head and neck Histology Solid sheets, ribbons, or trabeculae Large cells with coarse chromatin and nucleoli Necrosis and mitoses IHC Chromogranin, syaptophysin, NSE Cytokeratin 105

106 Neuroendocrine carcinoma 106

107 Neuroendocrine carcinoma 107

108 Neuroendocrine carcinoma, synaptophysin

109 Incidence Paraganglioma Adrenal (pheochromocytoma) >> extra-adrenal Head and Neck Clinical Originate from carotid body (most), middle ear, and vagal body Mass lesion, pulsatile Usually not functional in the head and neck 109

110 Histology Paraganglioma Neuroendocrine chromaffin cells Supporting sustentacular cells 110

111 Paraganglioma 111

112 Paraganglioma Immunohistochemistry Neuroendocrine chromaffin cells Chromogranin, Synaptophysin Negative for cytokeratins Supporting sustentacular cells S100 positive 112

113 Paraganglioma S

114 Paraganglioma Hereditary Von Hippel Lindau MEN syndromes Neurofibromatosis Familial paragangliomatosis 114

115 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 115

116 Pathology Ectopic Pituitary Bland appearing neuroendocrine lesion Hormones: FSH, LH, GH, TSH, ACTH, PRL, Calcitonin 116

117 Ectopic pituitary adenoma

118 Ectopic pituitary adenoma, ACTH

119 Summary Cystic lesions in the neck Branchial cleft cyst Thyroglossal duct and thymic cysts Cystic metastasis from squamous carcinoma HPV associated SCC Neuroendocrine tumors Olfactory neuroblastoma Neuroendocrine carcinoma, large cell type Paraganglioma Ectopic pituitary 119

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

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