Lesions Mimicking Adenoid Cystic Carcinoma. Diagnostic Problems in Salivary Gland Pathology An Update 5/29/2009
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1 Diagnostic Problems in Salivary Gland Pathology An Update Lesions Mimicking Adenoid Cystic Carcinoma Stacey E. Mills, M.D. W.S. Royster Professor of Pathology Director of Surgical and Cytopathology University of Virginia Medical Center Charlottesville, VA Basal cell adenoma Basal cell adenocarcinoma Mixed tumor Polymorphous low-grade adenocarcinoma Solid carcinoma Basaloid squamous cell carcinoma Adenoid Cystic Ca. Cribriform Pattern Adenoid Cystic Ca. Tubular Pattern 1
2 Adenoid Cystic Ca. Solid Pattern Reticular Pattern Adenoid Cystic Ca. v. Mixed Tumor Sclerotic Pattern Adenoid Cystic Ca. v. Mixed Tumor Lesions Mimicking Adenoid Cystic Carcinoma Basal cell adenoma Basal cell adenocarcinoma Mixed tumor Polymorphous low-grade adenocarcinoma Solid carcinoma Basaloid squamous cell carcinoma 2
3 Basal Cell Adenoma Basal Cell Adenoma Basal Cell Adenoma v. Adenoid Cystic Carcinoma Lesions Mimicking Adenoid Cystic Carcinoma BCA Adenoid Cystic CA Basaloid cells Yes Yes Hyaline cylinders Yes Yes Cribriform pattern Rare Common Palisading Common Rare Stromal mucin Rare Common Margin Capsule Infiltrating Perineural invas. Absent Common Favored location Parotid, lip Any salivary gland Basal cell adenoma Basal cell adenocarcinoma Mixed tumor Polymorphous low-grade adenocarcinoma Solid carcinoma Basaloid squamous cell carcinoma 3
4 Basal Cell Adenocarcinoma Basal Cell Adenocarcinoma Basal Cell Adenocarcinoma Basal Cell Adenocarcinoma 4
5 Basal Cell Adenocarcinoma Lesions Mimicking Adenoid Cystic Carcinoma Basal cell adenoma Basal cell adenocarcinoma Mixed tumor Polymorphous low-grade adenocarcinoma Solid carcinoma Basaloid squamous cell carcinoma Mixed Tumor Mixed Tumor 5
6 Adenoid Cystic Ca. Mixed Tumor Mixed Tumor Adenoid Cystic Mixed Tumor Mixed Tumor v. Adenoid Cystic Carcinoma Mixed Tumor Adenoid Cystic Hyaline cylinders Yes Yes Cribriform pattern Rare Yes S-E junction Blurred sharp Cell type Polygonal Basaloid Typical MT pattern Common Absent Margin Focal invasion Diffuse invasion Perineural invasion Absent Common MisDx. as MT --- Uncommon MisDx. as ACC Common --- 6
7 Lesions Mimicking Adenoid Cystic Carcinoma Polymorphous Low-Grade Adenoca. Basal cell adenoma Basal cell adenocarcinoma Mixed tumor Polymorphous low-grade adenocarcinoma Solid carcinoma Basaloid squamous cell carcinoma Polymorphous Low-Grade Adenoca. Polymorphous Low-grade Adenoca. Adenoid Cystic Carcinoma 7
8 Polymorphous Low-Grade Adenocarcinoma v. Adenoid Cystic Carcinoma Immunohistochemical Features PLGA Adenoid Cystic Margin Infiltrating Infiltrating Perineural invasion Prominent Prominent Cribriform pattern Yes Yes Solid areas Yes Yes Tubules Yes Yes Myxoid stroma Minor Major Cell type Polygonal Basaloid Location Oral cavity Any seromucinous Prognosis Very good Guarded Adenoid cystic PLGA/LPASO S100 Weak, variable Strong CD-117 Strong/all Focal/minority EMA Luminal cells All cells CEA Luminal cells Focal or negative MSA Focal, non-luminal Usually negative Polymorphous Low-grade Adenoca. Adenoid Cystic Ca CD117 PLGA S100 CD117 8
9 Polymorphous Low-Grade Adenocarcinoma Clinical Features Lesions Mimicking Adenoid Cystic Carcinoma Frequency: most common oral cavity adenoca. Location: de novo in oral cavity or as component of malignant mixed tumor Age/Sex: 26 to 77 yrs, most in 6 th to 7 th decade, female predominance Clinical Course: indolent, recurrences uncommon, may be after many yrs. Non-papillary = no mets, may undergo de-differentiation. Basal cell adenoma Basal cell adenocarcinoma Mixed tumor Polymorphous low-grade adenocarcinoma Solid carcinoma Basaloid squamous cell carcinoma Solid Carcinoma Adenoid Cystic Carcinoma Solid Carcinoma 9
10 Solid Carcinoma v. Adenoid Cystic Ca Solid Carcinoma Adenoid Cystic Solid cell nests Yes Yes Comedonecrosis Prominent Rare/absent Pleomorphism Prominent Minimal Cell type Variable Basaloid Mitotic figures Numerous Sparse L.N. mets Common?never Prognosis Rapid, poor Protracted/guarded Lesions Mimicking Adenoid Cystic Carcinoma Basaloid Squamous Cell Ca. Basal cell adenoma Basal cell adenocarcinoma Mixed tumor Polymorphous low-grade adenocarcinoma Solid carcinoma Basaloid squamous cell carcinoma 10
11 Basaloid Squamous Cell Ca. Basaloid Squamous Cell Ca. Basaloid Squamous Cell Carcinoma Light Microscopic Features Basaloid Squamous Cell Carcinoma. v. Adenoid Cystic Carcinoma Sharply defined cell nests close to surface mucosa Basaloid cells Hyperchromatic to vesicular nuclei, no nucleoli Cystic spaces with mucin Assoc. with squamous cell ca., often CIS Comedonecrosis Stromal hyalinosis BSCC Adenoid Cystic Hyaline cylinders Common Common Cribriform pattern Focal Common Cell type Basaloid/pleomorphic Basaloid/uniform Comedonecrosis Prominent Rare Mitotic figures Numerous Sparse Squamous diff. Always Rare Origin Mucosa Salivary L.N. mets Common Rare Course/prognosis Rapid/poor** Protracted/guarded 11
12 Clear Cell Salivary Lesions Hyalinizing clear cell carcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Sebaceous neoplasia Acinic cell carcinoma Clear cell oncocytoma Metastatic carcinoma 12
13 Hyalinizing Clear Cell Carcinoma Pathologic Features Size: 0.5 to 3.5 cm. Microscopic: trabecula, cords, nests, sheets of cells. Infiltrating margins, hyalinizing stroma Round, clear cells with PAS+ cytoplasm Focal eosinophilic cells Rare mitotic figures,?correlation with l.n. mets Perineural invasion common Hyalinizing Clear Cell Carcinoma Immunohistochemcial Features Cytokeratins + EMA + Myoepithelial markers S100 protein PAS 13
14 CK MSA Hyalinizing Clear Cell Carcinoma Clinical Features Sites: base of tongue >> palate > larynx > salivary Sex: female to male = 2 : 1 Age: 4 th to 8 th decades Regional nodes: ~15% Prognosis:?no deaths from disease S100 14
15 Clear Cell Salivary Lesions Hyalinizing clear cell carcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Sebaceous neoplasia Acinic cell carcinoma Clear cell oncocytoma Metastatic carcinoma CK 15
16 SMA 16
17 Epithelial-Myoepithelial Carcinoma Light Microscopic Features Epithelial-Myoepithelial Carcinoma Clinical Features Often lobulated growth pattern Distinct, bilayered ducts/glands Inner epithelial layer with cuboidal, eosinophilic cells, round nuclei Outer myoepithelial layer with polygonal, clear cells, often vesicular nuclei Clear cell component may overgrow lesion May be associated with adenoid cystic carcinoma Frequency: ~1% of all salivary tumors, ~11% of minor salivary gland tumors Location: both major and minor salivary glands, parotid favored, also intraoral Age/Sex: broad age, peak in 7 th decade, occasional pediatric cases, 60% female Prognosis: low-grade malignancy, 30-40% local recurrence, 18% l.n. mets, 8% distant mets. ENT Clear Cell Tumors Differential Diagnosis Clear Cell Salivary Lesions Hyalinizing Clear Cell Ca. Epithelial- Myoepithelial Ca. Biphasic No Yes Densely sclerotic Yes No S100 Protein No Yes (myoepith.) SMA No Yes (myoepith). Glycogen Yes? Prognosis good guarded Hyalinizing clear cell carcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Sebaceous neoplasia Acinic cell carcinoma Clear cell oncocytoma Metastatic carcinoma 17
18 18
19 Clear Cell Salivary Lesions Hyalinizing clear cell carcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Sebaceous neoplasia Acinic cell carcinoma Clear cell oncocytoma Metastatic carcinoma 19
20 Clear Cell Salivary Lesions Hyalinizing clear cell carcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Sebaceous neoplasia Acinic cell carcinoma Polymorphous low-grade adenoca. Metastatic carcinoma 20
21 Clear Cell Salivary Lesions Hyalinizing clear cell carcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Sebaceous neoplasia Acinic cell carcinoma Clear cell oncocytoma Metastatic carcinoma 21
22 Clear Cell Oncocytoma Clear Cell Salivary Lesions A diagnosis to be approached with caution! Current case was CD10-, RCC-, CEA-, SMA-, S100-, CK20+ Surrounding oncocytosis is highly supportive Radiologic exclusion of renal cell may still be warranted Hyalinizing clear cell carcinoma Epithelial-myoepithelial carcinoma Mucoepidermoid carcinoma Sebaceous neoplasia Acinic cell carcinoma Clear cell oncocytoma Metastatic carcinoma 22
23 Lesions Mimicking Mucoepidermoid Carcinoma Necrotizing sialometaplasia RCC CD10 23
24 Necrotizing Sialometaplasia Necrotizing Sialometaplasia Necrotizing Sialometaplasia Necrotizing Sialometaplasia Mucoepidermoid Carcinoma 24
25 Necrotizing Sialometaplasia v. Mucoepidermoid Carcinoma Lesions Mimicking Mucoepidermoid Carcinoma Nec. Sialometaplasia Mucoepidermoid Adenosquamous Yes Yes Necrotizing sialometaplasia Adenosquamous carcinoma Pleomorphism Focal, mild Mild/moderate Lobular pattern Yes Variable Lobular infarction Yes No Inflammation Frequent Occasional Adenosquamous Carcinoma Adenosquamous v. Mucoepidermoid Carcinoma Adenosquamous Mucoepidermoid Adenosq. Pattern Yes Yes Pleomorphism Marked Mild/moderate Mitotic figures Numerous Variable Necrosis Frequent Uncommon Non-salivary Yes No Course/prognosis Rapid/poor Protracted/variable 25
26 Lesions Mimicking Mucoepidermoid Carcinoma Salivary Duct Carcinoma Necrotizing sialometaplasia Adenosquamous carcinoma Salivary duct carcinoma Salivary Duct Carcinoma Salivary Duct Carcinoma 26
27 5/29/2009 Salivary Duct Carcinoma Salivary Duct Carcinoma Location: 86% parotid, 12% submandibular Age/Sex: yrs, 71% male, 29% female Prognosis: poor, 53% 6-year mortality; high rate of local, regional & distant spread Lesions Mimicking Benign Lymphoepithelial Lesion Benign Lymphoepithelial Lesion Lymphoma Malignant lymphoepithelial lesion Metastatic undifferentiated carcinoma 27
28 Benign Lymphoepithelial Lesion Lesions Mimicking Benign Lymphoepithelial Lesion Lymphoma Malignant lymphoepithelial lesion Metastatic undifferentiated carcinoma Nodular B-Cell Lymphoma B-cell Lymphoma with Epi-myoepithelial Island 28
29 Salivary Maltoma Salivary Maltoma Salivary Maltoma Benign Lymphoepithelial Lesion Caveats K L Epi-myoepithelial islands are NOT diagnostic BLL is a diagnosis of exclusion. It may be associated with lymphoma or undifferentiated carcinoma. Patients with BLL have an increased risk of lymphoma. An increased risk of carcinoma is doubtful BLL may be monoclonal* 29
30 Lesions Mimicking Benign Lymphoepithelial Lesion Lymphoepithelioma-like Carcinoma Malignant Lymphoepithelial Lesion Lymphoma Malignant lymphoepithelial lesion Metastatic undifferentiated carcinoma Lymphoepithelioma-like Carcinoma Malignant Lymphoepithelial Lesion Malignant Lymphoepithelial Lesion Undifferentiated Carcinoma of Salivary Gland Incidence: highly regional, uncommon in the west Ethnic: strong predilection for Eskimos and Chinese Location: 90% parotid, 10% submandibular Age & Sex: range: yrs.; mean age: 40 yrs; no male/female predilection Prognosis: 30% mortality, >50% lived >4yrs. 30
31 Malignant Lymphoepithelial Lesion Age Distribution No. Pts Decade of Life 31
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