1 Head and Neck Squamous Subtypes Adel K. El-Naggar, M.D., Ph.D. The University of Texas MD Anderson Cancer Center, Houston, Texas HNSCC 5 th -6 th most common cancer 400,000/year 50% mortality Considerable morbidity Nasal sinuses (4%) Nasopharynx (1%) Oral cavity (55%) Oropharynx (10%) Larynx (5%) Hypopharynx (5%)
2 Variants of Squamous Carcinoma Non-viral Conventional Verrucous Papillary Sarcomatoid Basaloid Adenoid SCC? Viral associated Lymphoepithelial Ca Oropharyngeal Ca Conventional
3 Verrucus Carcinoma
4 Clinicopathologic Features of Verrucous Carcinoma Feature Site: Age and sex: Risk: hygiene, HPV? Grade: Metastatic potential: Gross appearance: fungating Description Oral, Larynx Males over 50 years Tobacco, poor oral Low grade None in pure cases Exophytic or
5 D.D. Verrucous Carcinoma Verrucous hyperplasia Pseudoepitheliomatous hyperplasia Papillary Carcinoma
6
7 Papillary Squamous Carcinoma Sinonasal Tract 18 (%) Larynx 15 (%) Oral Cavity 6 (%) Total 39 M.D. Anderson Cancer Center 1950-1980 D.D. Papillary Carcinoma Squamous papilloma Verrucous hyperplasia
8 Basaloid Squamous Differential Diagnosis of Basaloid SCC Solid adenoid cystic carcinoma Basal cell adenocarcinoma Basal cell carcinoma Viral associated indifferentiated Ca
9 Sarcomatoid Squamous
10 Sarcomatoid Carcinoma of the Head & Neck Lower Lip 28 (25%) Oral Cavity 24 (22%) Larynx 20 (18%) Paranasal Sinuses 8 ( 7%) Others 30 (27%) Total 110 M.D.Anderson Cancer Center 1950-1980 D.D of Sarcomatoid Carcinoma: melanoma (desmoplastic, neurotrophic) sarcomas (neurogenic, fibrosarcoma) benign/reactive (post XRT changes, pseudosarcoma etc.)
11 Comparative Genomics Region 1 Region 2
12 Viral Associated Carcinomas Nasopharyngeal Carcinoma Nasal sinuses (4%) Nasopharynx (1%) Oral cavity (55%) Oropharynx (10%) Larynx (5%) Hypopharynx (5%)
13 Rare Sites: Salivary glands Lung Thymus Bladder Distinctive Features: Geographic distribution Etiology Histopathology Response to therapy Distant spread Geographic Distribution: 0.25% Caucasians 18% Asian
14 Affected Population: Native and foreign born Chinese Southeast Asians North Africans Natives of Arctic regions Origin Within Nasopharynx Spenoid sinus Opening of auditory tube Body of sphenoid Nasopharyngeal meatus Pharyngeal tonsil Soft palate Palatine tonsil Epiglottis Pharyngoepiglottic fold
15 Clinical Presentation: Nasal bleeding Hearing loss/ tinnitus Cervical lymph node mass (bilateral) Jugular Spinal accessory Retropharyngeal 12 th cranial nerve involvement: Hoarseness Diplodia Men/Women: 2-4:1 Bimodal distribution (non-endemic): 15-25 / 46-60 year Etiology EBV: B-lymphotropic Herpes Virus 172 kb double stranded DNA Linear with variable homologous tandem repeats at termini Prevalence 90%
16 Other Diseases Caused by EBV: A) Lymphocytic: Infectious Mononucleosis Hodgkin s Disease Burkitt s Lymphoma B) Epithelial: Hairy Leukoplakia Undifferentiated Gastric Carcinoma Contributing Etiologic Factors: Environmental: salted food / nitrosamine Hereditary: HLA Locus A&B HLA B17 HLABw 46 NPC Tumorigenesis: Interplay between EBV and other factors
17 Diagnosis: I Serology/molecular: a) IgA VCA (viral capsid antigen) b) IgG/IgA EA (early antigens) Incidence: 69-93% c) Recombinant antibody to: EBNA (nuclear antigen) EBMA (membrane antigen) d) Molecular-based (QT-RT-PCR): EBV DNA/RNA II - Histopathology Keratinizing Squamous Carcinoma WHO-I Non-Keratinizing Differentiated (Transitional) WHO-II Undifferentiated WHO-III Differentiated Squamous Carcinoma WHO-I
18 Non-Keratinizing (Transitional) WHO-II
19 Undifferentiated (WHO-III) Lymphoepithelial UNPC Variants:
20 Basaloid Sarcomatoid EBV - In-Situ
21 Prognostic Markers I - Serum/plasma EBV-DNA (EBNA-1): advanced disease with XRT response with recurrence II - LMP-1: Only in NPC advanced disease Differential Diagnosis: Large cell lymphoma Hodgkin s disease Sinonasal UC (SNUC) Solid adenoid cystic carcinoma Oropharyngeal carcinoma Oropharyngeal Carcinoma
22 Characteristics; HPV-association Undifferentiated histology Young adults Caucasian Good response to XRT Nasal sinuses (4%) Nasopharynx (1%) Oral cavity (55%) Oropharynx (10%) Larynx (5%) Hypopharynx (5%)
23 Diagnosis: Bx Waldeyer s ring Neck metastasis HPV-16 Genes E7 + Rb E2F p16 E6 + p53 E2F proliferation HPV: In-situ RT-PCR Markers: P16 IHC
24 p16 p16 Guidelines for p16 Expression in OPC:
25 Primary Strong/Homogenous staining Oropharyngeal site undifferentiated histology can substitute for FISH. Metastasis Neck metastasis of undifferentiated histology appropriate clinical setting may substitute for ISH Primary Negative Staining in Undifferentiated Oropharyngeal site Need ISH or PCR
26 Primary: non-hpv related Variable staining in conventional squamous carcinoma require ISH testing Thank You