04/09/2018. Squamous Cell Neoplasia and Precursor Lesions. Agenda. Squamous Dysplasia. Squamo-proliferative lesions. Architectural features

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1 Squamous Cell Neoplasia and Precursor Lesions 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 Agenda Squamo-proliferative lesions Squamous dysplasia Keratosis Keratinizing dysplasia Pitfalls and Mimics Lichen planus Pseudoepitheliomatous hyperplasia Identifying superficial invasion Challenging biopsies: variants of SCC 2 Squamous Dysplasia Architectural features Organization Maturation Mitotic activity 3 1

2 Normal Organization Normal Maturation Poor Organization and Maturation Reactive Dysplastic 2

3 Abnormal Mitoses Squamous Dysplasia Cytologic features Hyperchromasia Higher N:C ratio (basaloid) Nuclear membrane irregularities 8 Abnormal Cytology Reactive Atypia Dysplasia 3

4 Dysplasia Continuum Normal Mild Dysplasia Moderate Dysplasia Severe Dysplasia 10 Mild dysplasia Moderate dysplasia 4

5 Severe dysplasia Mild-moderate dysplasia Moderate to severe dysplasia 5

6 Keratinizing Squamous Lesions Keratin = abnormal (nearly always) Surface keratinization Dyskeratosis Pink Cell Change 16 Keratinizing Lesions Diagnostic terminology: Keratosis Clinical terminology: Leukoplakia Reaction to irritation Denture rub Bite lines Tobacco 17 Keratosis 6

7 Keratosis Dyskeratosis Pink cell change 7

8 Pink cell change Diagnosing Keratosis Keratosis with dysplasia If you can, grade the dysplasia If you can t, consider Keratinizing dysplasia Risk of carcinoma does not correlate with classical features of dysplasia Early lesions may be reversible Some lesions look much better than they behave 23 Keratosis without dysplasia 8

9 Keratosis with severe dysplasia Keratosis with severe dysplasia Inflammatory Atypia vs. Dysplasia Is there a reason for atypia or reactive patterns? Inflammation Ulceration or ulcer debris Organisms Metaplasia Tangential sectioning 27 9

10 Lichenoid Inflammation Hyperplastic Candidiasis Neutrophils in the epithelium 10

11 Candidiasis Squamous Metaplasia 32 Tangential sectioning 33 11

12 Normal Reactive 34 Mild dysplasia Dysplasia 35 Reactive Atypia Agenda Squamo-proliferative lesions Squamous dysplasia Keratosis Keratinizing dysplasia Pitfalls and Mimics Lichen planus Pseudoepitheliomatous hyperplasia Identifying superficial invasion 36 12

13 Oral (Mucosal) Lichen Planus Clinical 1-2% of the general population; 50-77% of lichen planus patients Often asymptomatic and bilateral Demographics Female to male = 2:1 Ages: Types Reticular Atrophic Erosive Others: plaque, papular, bullous 37 Huber MA, Clinics in Dermatology 28, 262, Courtesy of Dr. Sook-Bin Woo,

14 Oral (Mucosal) Lichen Planus Histology Hyperkeratosis Saw-tooth rete Vacuolar degeneration of the basal cells Lichenoid chronic inflammation Apoptosis of epithelial cells (civatte bodies) Secondary fungal hyphae (after steroids) 40 Lichen planus 41 Lichen planus 42 14

15 Lichen planus 43 Lichen planus 44 Pseudoepitheliomatous hyperplasia Reactive pattern Associated with granular cell tumor Fungal infections Trauma Histology Down-ward finger-like proliferation Can resemble carcinoma 45 15

16 Pseudoepitheliomatous hyperplasia 46 Granular cell tumor 47 Agenda Squamo-proliferative lesions Squamous dysplasia Keratosis Keratinizing dysplasia Pitfalls and Mimics Lichen planus Pseudoepitheliomatous hyperplasia Identifying superficial invasion 48 16

17 Superficial Invasion Nomenclature Superficially invasive squamous cell carcinoma Microinvasive squamous cell carcinoma Tumor has breached the basement membrane Access to lymphatics Potential to metastasize 49 Superficial Invasion: Definition Miller Friedman Padovan Crissman Barnes cells present just below the basement membrane Scattered tongues or discrete foci of invasion through the basement membrane 2 mm or less of invasion 1-2 mm of invasion (no angiolymphatic invasion) 0.5 mm of invasion, measured from basement membrane (no angiolymphatic invasion) 50 Identifying Superficial Invasion Deep keratinization Keratin pearls Dyskeratosis Breach of basement membrane Ragged borders Single dropping off cells Desmoplasia Reaction around tumor cells 51 17

18 In situ Carcinoma 52 Superficial invasion 53 Superficial invasion 54 18

19 Superficial invasion Suspicious for superficial invasion 56 Atypical squamoproliferative lesion 19

20 Differential Diagnosis Papillary keratosis Papillary squamous cell carcinoma Verrucous carcinoma 58 Papillary Keratosis Histology Papillary architecture Surface keratinization Grade the dysplasia Differential diagnosis Papillary squamous cell carcinoma 59 Papillary Squamous Cell Carcinoma Clinical Elderly age group Traditional risk factors Alcohol & Tobacco Papillomas are not precursors Gross appearance Frond-like filiform papillae (papillary SCC) Broad-based, cauliflower appearance (exophytic SCC) 60 20

21 Papillary Squamous Cell Carcinoma Papillary Squamous Cell Carcinoma Papillary Squamous Cell Carcinoma Histology +/- fibrovascular cores Cytologic and architectural atypia (dysplasia) +/- surface keratinization 63 21

22 Papillary Squamous Cell Carcinoma Papillary Squamous Cell Carcinoma Papillary Squamous Cell Carcinoma 22

23 Papillary Squamous Cell Carcinoma Papillary Squamous Cell Carcinoma Verrucous Carcinoma Clinical More common in elderly Most common in oral cavity and larynx Related to tobacco and poor oral hygiene 69 23

24 Verrucous Carcinoma Histology Bulbous cauliflower like surface Blunted club-shaped rete Inflammatory infiltrates Lack of cytologic atypia Can have abundant keratin 70 Verrucous Carcinoma, Frozen Verrucous Carcinoma 24

25 Verrucous Carcinoma Verrucous Carcinoma Verrucous Carcinoma Treatment Excision with clear margins Radiation Prognosis Good Extremely low risk of metastasis 75 25

26 Hybrid Carcinoma Verrucous carcinoma with component of invasive SCCA <20% of verrucous carcinoma Higher risk of recurrence Possible risk of metastasis 76 Hybrid Carcinoma Hybrid Carcinoma 26

27 Summary Squamo-proliferative lesions Squamous dysplasia Keratosis Keratinizing dysplasia Pitfalls and Mimics Lichen planus Pseudoepitheliomatous hyperplasia Identifying superficial invasion Biopsies of challenging variants 79 27