Head and Neck Tumors at the Interface of Benign and Malignant
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1 Head and Neck Tumors at the Interface of Benign and Malignant Jennifer L. Hunt, M.D., M.Ed. Associate Chief of Pathology Director of Quality and Safety Massachusetts General Hospital Harvard Medical School Jennifer Hunt, MD 1 The Interface of Benign and Malignant Keratinizing dysplasia Superficially invasive squamous cell carcinoma In situ and low grade salivary gland carcinomas Keratinizing Squamous Lesions Keratin in mucosal surfaces = abnormal Surface keratinization Dyskeratosis Pink Cell Change Jennifer Hunt, MD (3) Jennifer Hunt, MD (4) 1
2 Keratinizing Lesions Clinical terminology: Leukoplakia Pathology terminology: Keratosis Reaction to irritation Denture rub Bite lines Tobacco Jennifer Hunt, MD (5) Keratosis Dyskeratosis Pink cell change 2
3 Diagnosing Keratosis with Dysplasia Dysplasia Continuum Keratosis with dysplasia Early lesions may be reversible Try to grade the dysplasia But, recognize the inexactness Keratinizing dysplasia is acceptable! Jennifer Hunt, MD (9) Normal Mild Dysplasia Moderate Dysplasia Severe Dysplasia Keratosis without dysplasia (reactive atypia) Keratosis with dysplasia 3
4 Keratosis with dysplasia Keratosis without dysplasia (reactive atypia) Keratosis with moderate to severe dysplasia Keratosis with severe dysplasia 4
5 The Problem with Keratinizing Dysplasia Drop-off carcinoma: A carcinoma that does not go through the usual dysplasia pathway Invasive carcinoma No high grade dysplasia But, often keratinizing dysplasia Jennifer Hunt, MD (17) Drop-off Squamous Carcinoma Drop-off Squamous Carcinoma Drop-off Carcinoma 5
6 The Interface of Benign and Malignant Keratinizing dysplasia Superficially invasive squamous cell carcinoma In situ and low grade salivary gland carcinomas Superficial Invasion Nomenclature Superficially invasive squamous cell carcinoma Microinvasive squamous cell carcinoma Jennifer Hunt, MD (21) Jennifer Hunt, MD (22) Superficial Invasion: Definition Clues to Identifying Superficial Invasion 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) Deep keratinization Keratin pearls Dyskeratosis Breach of basement membrane Single dropping off cells Islands of epithelium in the stroma Ragged borders & desmoplasia Reaction around stromal tumor cells Jennifer Hunt, MD (23) Jennifer Hunt, MD (24) 6
7 Deep dyskeratosis: Suspicious for superficial invasion Deep keratin pearls: Superficial invasion Islands and single cells in the stroma Islands and single cells in the stroma 7
8 SCC with invasion (not superficial) Tumors at the Interface Keratinizing squamous dysplasia Superficially invasive squamous cell carcinoma In situ and low grade salivary gland carcinomas Jennifer Hunt, MD (30) Low Grade Cribriform Cystadenocarcinoma Other names that have been used Low grade salivary duct carcinoma Low grade cribriform cystadenocarcinoma Clinical Excellent prognosis Unknown relationship to salivary duct carcinoma Rare tumor Low Grade Cribriform Cystadenocarcinoma Histology Smooth cysts with micropapillae Cribriform, roman arches Cytoplasmic microvacuoles Refractile yellow pigment Apocrine, with snouts Intraductal pattern Maintenance of myoepithelial cells Jennifer Hunt, MD (31) Jennifer Hunt, MD (32) 8
9 Low grade cribriform cystadenocarcinoma Low grade cribriform cystadenocarcinoma Low grade cribriform cystadenocarcinoma Low grade cribriform cystadenocarcinoma 9
10 Low Grade Cribriform Cystadenocarcinoma Immunohistochemistry Cytokeratin positive S100 positive Her-2 and AR negative Myoepithelial layer preserved Jennifer Hunt, MD (37) Low grade cribriform cystadenocarcinoma, S100 In Situ Salivary Duct Carcinoma Clinical Extremely rare, poorly understood Histology In situ or minimally invasive High grade features Necrosis, pleomorphism, mitotic figures Low grade cribriform cystadenocarcinoma, CK5/6 Jennifer Hunt, MD (40) 10
11 In Situ Salivary duct carcinoma In Situ Salivary duct carcinoma In Situ Salivary Duct Carcinoma Immunohistochemistry Myoepithelial cells should be present Invasive component loses myoepithelial cells Androgen receptor and HER2/neu positive Jennifer Hunt, MD (43) In situ salivary duct carcinoma, CK5/6 (with focal invasion) 11
12 Mammary Analogue Secretory Carcinoma Clinical Rare tumor, but not well described yet Mean age 46 (M:F approximately equal) Parotid 13/16 cases 3/15 developed recurrence, one died of disease HER2/NEU Androgen Jennifer Hunt, MD (46) Mammary Analogue Secretory Carcinoma Histology Circumscribed, but not encapsulated Lobulated mass divided by fibrous septae Microcystic, tubular, solid structures Low grade vesicular nuclei with nucleoli Bubbly secretion in microcysts (PAS +) Jennifer Hunt, MD (47) Mammary Analogue Secretory Carcinoma 12
13 Mammary Analogue Secretory Carcinoma Mammary Analogue Secretory Carcinoma, PAS Mammary Analogue Secretory Carcinoma Immunohistochemistry Strong cytokeratin (7, 8, 18) Strong diffuse S100 GCDFP (70%) and mammoglobin (100%) Molecular ETV6-NTRK3 t(12;15) Jennifer Hunt, MD (51) Mammary Analogue Secretory Carcinoma, S100 13
14 Carcinoma Ex Pleormorphic Adenoma In situ carcinoma ex PA Intracapsular carcinoma ex PA Minimally invasive carcinoma ex PA Invasive (high grade) carcinoma ex PA Carcinoma ex Pleomorphic Adenoma In situ carcinoma ex pleomorphic adenoma Histologically malignant Myoepithelial cells present No invasion Jennifer Hunt, MD (53) Di Palma, Histopath 46, 2005 Brandwein, Oral and Max Path, 81, 1996 Jennifer Hunt, MD (54) In situ carcinoma ex pleomorphic adenoma In situ carcinoma ex pleomorphic adenoma 14
15 Carcinoma ex Pleomorphic Adenoma Intracapsular carcinoma ex pleomorphic adenoma Histologically malignant No myoepithelial cells present No invasion Di Palma, Histopath 46, 2005 Brandwein, Oral and Max Path, 81, 1996 Jennifer Hunt, MD (57) Intracapsular carcinoma ex pleomorphic adenoma Carcinoma ex Pleomorphic Adenoma Minimally invasive carcinoma ex pleomorphic adenoma Histologically malignant No myoepithelial cells present Invasion is present, but is not extensive <1.5 mm <5 mm <8 mm Excellent prognosis Intracapsular carcinoma ex pleomorphic adenoma, androgen Di Palma, Histopath 46, 2005 Jennifer Hunt, MD (60) Brandwein, Oral and Max Path, 81,
16 Carcinoma ex Pleomorphic Adenoma Invasive carcinoma ex PA Relatively rare Clinical Long standing mass with recent rapid enlargement History of PA Resected incompletely Recurrent Invasive Carcinoma ex PA Histology Residual pleomorphic adenoma Carcinoma component Specific salivary carcinoma (any type) Adenocarcinoma, NOS IHC Specific to type of carcinoma Jennifer Hunt, MD (61) Jennifer Hunt, MD (62) Carcinoma ex pleomorphic adenoma Carcinoma ex pleomorphic adenoma 16
17 Tumors at the Interface Keratinizing squamous dysplasia Superficially invasive squamous cell carcinoma In situ and low grade salivary gland carcinomas Jennifer Hunt, MD (65) 17
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