Salivary Gland Cytology Diagnostic challenges and potential pitfalls Tarik M. Elsheikh, MD Professor and Medical Director Anatomic Pathology Cleveland Clinic
FNA Salivary Gland Lesions Indications Distinguish inflammatory from neoplastic Modify management according to neoplasm type B9 and Low grade malignancy - save nerve High grade malignancy - radical excision, node sampling Warthin Tumor Distinguish SG tumors from enlarged lymph nodes (mets, lymphoma, hyperplasia) Document recurrence of neoplasm
FNA Salivary Gland Lesions Diagnostic Accuracy Sensitivity = 58-96% (81-98%) Specificity = 71-99% False negative rate < 10% - sampling error False positive rate 0-4.7% (not include suspicious) Diagnostic accuracy improves with experience
Diagnostic Challenges and Problems Cystic lesions Low grade malignancies Cellular benign neoplasms Atypical inflammatory changes Atypical lymphoid infiltrates Unusual cytologic presentation of common neoplasms Rare unusual lesions
Lesions Causing Salivary Gland Enlargement Non-Neoplastic Neoplastic
Benign Neoplasms Pleomorphic adenoma Basal cell adenoma Warthin tumor
Malignant Neoplasms Primary Mucoepidermoid carcinoma Acinic cell carcinoma Adenoid cystic carcinoma Undifferentiated carcinoma Metastatic Other Squamous cell carcinoma Malignant melanoma Malignant lymphoma
FNA of Salivary gland Tumors A Diagnostic approach Cell size Amount of cytoplasm Degree of cytologic atypia Background
FNA of Salivary Glands A Diagnostic Approach 2 1. Basaloid cell features 2. Intermediate size cells with bland cytology 3. Large cells with abundant cytoplasm 4. Many cytologic faces of pleomorphic adenoma 5. Lymphoid containing lesions
1. Salivary Gland Lesions with Basaloid Cell Features Small sized cells Scant cytoplasm Clusters and single cells
Basal Cell Adenoma 2% of SG tumors Tightly cohesive clusters Background naked nuclei Minimal cytoplasm Round to oval nuclei Fine-coarse chromatin Occasional small nucleoli
Membranous BCA Amorphous extracellular hyaline material may be seen at periphery of cell clusters
Adenoid Cystic Carcinoma Cytology Cribriform (Well Differentiated) Clusters and branching multilayered groups of basaloid cells surrounding globules of homogenous acellular material (reduplicated basal lamina PAS+) Solid (Poorly Differentiated) Loosely cohesive groups of cells with increased nuclear atypia and prominent nucleoli Acellular material (globules) lacking
Solid AdCC It may be difficult to distinguish from BCA
Basaloid Squamous CA
Cytology Basaloid Cells Shadow cells singly and in clusters (ghost squamous cells) Mononuclear and multinucleated histiocytes Non cellular debris Pilomatrixoma
Small Cell / Neuroendocrine CA 1-2 % of all SG tumors Better overall survival than bronchogenic SCC
Salivary Gland Neoplasms with Basaloid Cell Features Architectural features are most important Cribriform AdCC can be accurately diagnosed, when presents in classic pattern Solid BCA and solid AdCC are indistinguishable Never make a definitive Dx of BCA Basal cell adenocarcinoma: indistinguishable cytologically from BCA and AdCC
Differential DX of Basaloid Neoplasms With significant cytologic atypia* Adenoid cystic carcinoma, cribriform and solid Basal cell adenocarcinoma Basaloid squamous cell carcinoma Poorly differentiated carcinoma, NOS Small cell carcinoma Pilomatrixoma Metastatic carcinoma including cutaneous basal carcinoma, thyroid, breast, lung *Atypia: moderate-severe pleomorphism and/or large prominent nucleoli
Differential DX of Basaloid Neoplasms Without significant cytologic atypia Adenoid cystic carcinoma, cribriform and solid Basal cell adenoma Basal cell adenocarcinoma Cellular pleomorphic adenoma Pilomatrixoma Metastatic carcinoma LBP and Cytospins
Case Study 65 year old man presented with a parotid gland mass
Cytologic Diagnosis DX: Cellular neoplasm with basaloid cell features, see comment Comment: Differential diagnosis includes basal cell adenoma and adenoid cystic carcinoma (Ki- 67). Basal cell adenoma is favored/suggested. Histologic confirmation is needed for a definitive diagnosis.
2. Salivary Gland Lesions with Bland Cytology Intermediate size cells Moderate amount of cytoplasm Include cystic and squamous lesions
Mucus producing cells - resemble macrophages Intermediate cells Squamous cells - cohesive clusters of cells resembling metaplastic squames. LG Mucoepidermoid Carcinoma Most common malignancy in SG Occurs in all ages, peak age 20-40 Cytology
Flat sheets and 3D clusters Variable stringy mucin
-Mucous and intermediate cells LG MEC
-No fully keratinized epidermoid cells LG MEC
LG Mucoepidermoid Carcinoma Differential Diagnosis Chronic sialadenitis with squamous and mucous metaplasia Retention cyst Cystic neoplasms PA, WT LG MEC, AcCC Metastatic keratinizing squamous ca
Usually result of stones or post surgical scarring More common in SM gland Chronic inflammation with fibrosis and loss of acini Chronic Sialadenitis
Chronic sialadenitis Squamous and mucous metaplasia
Retention Cyst Most common benign cyst 2 to duct obstruction Watery mucoid aspirate Cytology Histiocytes & inflam cells Degenerated ductal or squamous cells Disappearance of mass after aspiration Descriptive diagnosis and clinical follow up
Most common cystic lesion of lateral neck Ant. border of sternocleidomastoid Occasionally in and around parotid gland Any age, more common in early adult life Branchial Cleft Cyst Cytology: Anucleated and nucleated squamous cells and neutrophils. Lymphocytes not commonly seen
Metastatic Cystic SqCC
Metastatic Cystic Squamous CA Markedly atypical squamous cells (Single cells and/or clusters) Potential 1 sites: tonsils, nasopharynx, base of tongue
3. Salivary Gland Lesions with Abundant Cytoplasm Large cells Include oncocytic and clear cell lesions Without atypia (Benign vs. Malignant) With atypia (Malignant NOS)
Salivary Gland Tumors Characterized by Large Cells and Abundant Cytoplasm Without Atypia Acinic Cell Carcinoma Warthin tumor Oncocytoma With Atypia Salivary Duct Carcinoma HG Mucoepidermoid Carcinoma Poorly differentiated carcinoma, NOS Metastatic Carcinoma
Acinic Cell CA Low grade malignancy Parotid, F>M Any age- peak 60-70y Flat sheets Thin capillaries Papillary formation Large cells Naked nuclei
AcCC - Vacuolated cytoplasm, zymogen granules - Eccentric nuclei
AcCC B9 acini
Warthin Tumor Almost always arises in parotid gland 5-10% of parotid tumors Male, 60 years Thin watery mucoid aspirate
Oncocytic-rich WT/ Oncocytoma
Oncocytic Tumors Centrally placed nuclei Dense granular cytoplasm Large prominent nucleoli
Salivary Gland Tumors Characterized by Large Cells and Abundant Cytoplasm Without Atypia Acinic Cell Carcinoma Oncocytoma Warthin tumor With Atypia HG Mucoepidermoid Carcinoma Salivary Duct Carcinoma Poorly differentiated carcinoma, NOS Metastatic Carcinoma
Cytology Large pleomorphic cells with epidermoid or undifferentiated features Glandular cells difficult to identify High Grade Mucoepidermoid Carcinoma
HG MEC
Salivary Duct CA High grade malig Poor prognosis Most aggressive Parotid Males Resembles DCIS and invasive breast ca - Cribriform, mircropapillary, comedo
Large cells, abundant cytoplasm-oncocytic Large prominent nucleoli Marked atypia- sporadic Abundant necrosis SDC
SDC vs. Undiff CA
Metastatic Malignancies Intra/peri-parotid LNs Scalp, face, ENT Most common: squamous CA and melanoma Infraclavicular primaries Lung, kidney, breast are most common Must exclude kidney if prominent clear cell features Melanoma RCC
4. The Many Cytologic Faces of Pleomorphic Adenoma The Great Pretender
Pleomorphic Adenoma 75% of major salivary gland tumors Female, 30-40 years Mixture of epithelial & mesenchymal elements
Stroma in PA
Cellular PA
Hyaline PA/myoepithelio ma Plasmacytoid cells Abundant dense cytoplasm and eccentric nuclei Minor salivary glands
Challenges in Cytologic Dx of PA Biphasic Cellular/Epithelial If epithelial cells predominate (CPA) suspect BCA or AdCC Mesenchymal May be confused with mucin in MEC
BCA/AdCC CPA
BCA/AdCC PA
MEC Mucin vs. Stroma PA
5. Salivary Gland Aspirates Containing Malignant lymphoma Lymphocytes Reactive lymphoid hyperplasia- Intra/peri-salivary gland lymph nodes Lymphoepithelial lesion Chronic sialadenitis Warthin tumor Acinic cell carcinoma LG Mucoepidermoid carcinoma
2-5% of SG neoplasms Primary, associated with Benign LEL Warthin tumor Intraparotid lymph node Secondary, part of generalized disease or leukemia Large B cell (35%), follicular (35%), low grade/malt (30%) IHC, FCM, GR Malignant Lymphoma
Lymphoepithelial sialadenitis (Benign LEL) Associated Autoimmune disorders (SS) Parotid, Female, 5th - 6th decade 44X risk of lymphoma (MALT) Difficult to differentiate from RLH Polymorphic lymphoid cells Rare ductal epithelial cells (lymphoepithelial islands)
LG MEC associated with dense chronic inflammation
Summary Most important indications for salivary FNA : Inflammatory vs. neoplastic: observation vs. surgery High grade malignancy vs. benign or low grade malignancy: extent of surgery Familiar with variable FNA appearances of SG tumors Aware of limitations and potential pitfalls that may lead to false positive and negative diagnoses
Neoplasms with Basaloid Features With significant atypia Adenoid cystic carcinoma, cribriform and solid Basal cell adenocarcinoma Basaloid squamous CA Poorly differentiated carcinoma, NOS Small cell carcinoma Metastatic CA including cutaneous basal carcinoma, thyroid, breast, lung Pilomatrixoma Without significant atypia Adenoid cystic carcinoma, cribriform and solid Basal cell adenoma Basal cell adenocarcinoma Cellular pleomorphic adenoma Metastatic carcinoma Pilomatrixoma
Salivary Gland Tumors with Intermediate Size Cells and Bland Cytology LG Mucoepidermoid Carcinoma Pleomorphic adenoma PLGA Neoplasms with a cystic component Retention Cyst and Branchial Cleft Cyst Metastatic Squamous cell CA Squamous and glandular metaplasia in chronic Sialadenitis, Warthin s tumor and PA
Salivary Gland Tumors Characterized by Large Cells and Abundant Cytoplasm With Atypia Salivary Duct Carcinoma HG Mucoepidermoid Carcinoma Adenocarcinoma, NOS Metastatic Carcinoma Without Atypia Acinic Cell Carcinoma Oncocytoma Warthin tumor
The Many Cytologic Faces of Pleomorphic Adenoma Basal Cell Adenoma Adenoid Cystic Carcinoma LG Mucoepidermoid Carcinoma Oncocytoma, Warthin tumor Acinic Cell Carcinoma
Salivary Gland Aspirates Containing Lymphocytes Chronic sialadenitis Warthin tumor Lymphoepithelial sialadenitis Reactive lymphoid hyperplasia Malignant lymphoma Acinic cell carcinoma LG Mucoepidermoid carcinoma
Summary 2 Strict cytologic criteria accurate Dx in most instances Cellular neoplasm NOS FNA diagnosis should be interpreted in context of clinical and radiologic findings
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