An Integrated Cytologic and Histologic Approach to the Diagnosis of Salivary Gland Tumors

Transcription

1 An Integrated Cytologic and Histologic Approach to the Diagnosis of Salivary Gland Tumors W.C. Faquin, M.D., Ph.D. Massachusetts General Hospital Massachusetts Eye and Ear Infirmary Boston, MA An Integrated Cytologic and Histologic Approach to the Diagnosis of Salivary Gland Tumors INTRODUCTION 8 FNA CASES WITH CORRESPONDING HISTOLOGY Celeste N. Powers, M.D., Ph.D. Medical College of Virginia Richmond, VA SALIVARY GLAND FNA Because of the wide range of non-neoplastic and neoplastic lesions, and the cytologic overlap between many benign and malignant tumors, salivary gland FNA is probably the MOST CHALLENGING area of cytopathology. Salivary Gland Lesions Non-Neoplastic Acute sialadenitis Chronic sialadenitis LESA HIV-associated lymphoepithelial lesion Reactive lymph nodes Mucocele Mucinous metaplasia Sialadenosis Lipoma Hemangioma Branchial cleft cyst Neoplastic Benign Pleomorphic adenoma Basal cell adenoma Warthin s tumor Oncocytoma Low-Grade Mucoepidermoid carcinoma, low-grade Acinic cell carcinoma Polymorphous low-grade adenocarcinoma Basal cell adenocarcinoma Epithelial-myoepithelial carcinoma MALT lymphoma High-Grade *Adenoid cystic carcinoma Salivary duct carcinoma Mucoepidermoid carcinoma, high-grade Ca-ex-pleomorphic adenoma Clear cell carcinoma Large B-cell Lymphoma SALIVARY GLAND FNA CHALLENGING DIAGNOSTIC ISSUES Matrix-containing tumors Oncocytic lesions Basaloid tumors Lymphoid lesions Cystic and mucinous lesions High-grade carcinomas Clear cell tumors Spindle cell lesions 1

2 SALIVARY GLAND FNA Rationale and Indications for FNA: Any unexplained salivary gland mass Safe, cost-effective, accurate Guide the clinical management/pre-op strategy:» Non-neoplastic» Benign tumor or low-grade carcinoma» High-grade carcinoma SALIVARY GLAND FNA Sample Preparation: Both Romanowsky and Papanicolaou stained preparations are essential! SALIVARY GLAND FNA SALIVARY GLAND FNA Accuracy: High accuracy for non- neoplastic vs neoplastic High accuracy for low-grade vs high-grade Variable accuracy for a specific entity: High for pleomorphic adenoma Low for basal cell adenocarcinoma Usually Specific Diagnosis Pleomorphic adenoma Warthin s tumor Acute and chronic sialadenitis Basal cell adenoma, membranous type Reactive lymph node Lymphoma Sometimes Specific Diagnosis Adenoid cystic carcinoma LG mucoepidermoid carcinoma Carcinoma ex PA Metastasis Small cell carcinoma Mucocele Oncocytoma LESA Usually Descriptive Diagnosis Basal cell adenoma, tubulotrabecular and solid types HG mucoepidermoid carcinoma Salivary duct carcinoma Polymorphous low-grade adenocarcinoma Basal cell adenocarcinoma Epithelial-myoepithelial carcinoma Acinic cell carcinoma SOME SALIVARY GLAND FACTS FEATURES OF THE NORMAL SALIVARY GLAND 3 Major glands (ectodermally derived): Parotid (serous) Submandibular (mixed seromucinous) Sublingual (mucinous) Minor glands: Submucosa of oral cavity Seromucinous glands of the nasal cavity, larynx, and bronchi Tumors: per 100,000 people Older adults, females, parotid gland, approx. 75% are benign Risk of malignancy is inversely proportional to the size of the gland (20% in parotid; 80-89% in oral cavity) 2

3 HISTOLOGIC FEATURES OF THE NORMAL SALIVARY GLAND HISTOLOGIC FEATURES OF THE NORMAL SALIVARY GLAND HISTOLOGIC FEATURES OF THE NORMAL SALIVARY GLAND HISTOLOGIC FEATURES OF THE NORMAL SALIVARY GLAND HISTOLOGIC FEATURES OF THE NORMAL SALIVARY GLAND FNA OF THE NORMAL SALIVARY GLAND Cytologic Features of the Normal Aspirate Serous and mucinous-type acinar cells in lobules Background naked acinar cell nuclei Few admixed small sheets and tubules of ductal epithelium Intercalated ducts Striated ducts Excretory duct Adipose tissue 3

4 FNA OF THE NORMAL SALIVARY GLAND Polarized grape-like clusters of acinar cells NORMAL SALIVARY GLAND FNA Key Pitfall of the Normal Aspirate: Misinterpreting normal acinar cells as acinic cell carcinoma FNA OF THE NORMAL SALIVARY GLAND - PITFALL SALIVARY GLAND FNA CASES Normal Salivary Gland Acinic Cell Carcinoma History: CASE 1 A 31 year old woman with a 1.5 cm nontender right parotid mass that has been slowly enlarging over the past year. 4

5 Case 1 Pleomorphic Adenoma aka Benign Mixed Tumor Diff-Quik Stain Pap Stain Matrix Tumors Pleomorphic Adenoma Adenoid Cystic Carcinoma Monomorphic Adenomas Carcinoma Ex Pleomorphic Adenoma Pleomorphic Adenoma Most common of all salivary gland tumors in both children and adults 75% of parotid tumors & 50% of all salivary tumors Superficial parotid gland is most common site esp. the tail of the parotid at jaw angle Firm, moveable, well demarcated (encapsulated), slow growing, painless 5

6 Cells Biphasic Tumor Epithelial cells arranged in cohesive, honeycomb groups Myoepithelial cells arranged singly and haphazard clusters. Cells may be plasmacytoid, epithelioid, spindled, or clear Matrix Fibrillar with frayed, indistinct margins Chrondromyxoid (Metachromatic) Embedded myoepithelial cells Infarction: Spontaneous vs Aspiration 6

7 Pitfalls Cellular lesions with sparse or absent matrix Myoepithelial predominant (myoepithelioma) Epithelial predominant (basaloid tumors) Focal adenoid cystic like areas Matrix mimics Cytologic atypia Metaplasia Squamous Mucinous Squamous Metaplasia Adenoid Cystic Carcinoma 4-10% of all salivary gland neoplasms Relatively slow growing with perineural invasion and poor long-term survival Submandibular gland, palate, and parotid 4 th to 7 th decade, women > men (3:2) FNAB is often reported as painful Cribriform, tubular, and solid forms Adenoid Cystic Carcinoma Cells Basaloid cells with dark angulated nuclei Variable atypia Matrix 3-D spheres and branching structures Acellular hyaline globules Metachromatic with sharp borders 7

8 Adenoid Cystic Carcinoma Pleomorphic Adenoma vs Adenoid Cystic Carcinoma Pleomorphic Adenoma - predominance of myoepithelial cells - atypia - matrix is fibrillar with ragged edges and myoepithelial cells embedded within Adenoid Cystic Ca - cells more basaloid in appearance - minimal atypia - unique matrix: acellular, smooth edges, homogeneous hyaline globules Pleomorphic Adenoma vs. Adenoid Cystic Carcinoma Final Comments Pleomorphic adenoma Adenoid cystic carcinoma Pleomorphic adenoma, monomorphic adenoma and adenoid cystic carcinoma can overlap significantly History: slow vs rapid growth presence or absence of pain Matrix: fibrillar arrays +/-embedded cells homogenous acellular globules CASE 2 History: A 71 year old man with a l.5 cm right nontender submandibular mass that had been slowly increasing in size for 1.5 years. 8

9 Case 2 Acinic Cell Carcinoma Acinic Cell Carcinoma Second most common salivary gland malignancy 2-6% of all salivary gland neoplasms Low-grade malignancy recapitulating growth of normal acinous cells 6.5% of neoplasms, 18% of malignant F>M, 90% parotid Acinic Cell Carcinoma Well demarcated/encapsulated, lobulated, Slow growing Growth patterns Solid & microcystic (common); papillary-cystic; follicular variants Complete surgical excision 12% local recurrence; 8% mets, 6% pts die 9

10 Acinic Cell Carcinoma Cells (high cellularity) Serous type acinar cells, predominate Intercalated duct cells Background Naked nuclei + lymphocytes Clean may be cystic Psammoma bodies (papillary) Capillary meshwork Acinic Cell Carcinoma Serous type acinar cells Sheets and dyshesive 3-D clusters Large polygonal cells with abundant finely vacuolated to granular basophilic cytoplasm PAS+D resistant cytoplasmic zymogen granules Bland nuclear cytologic features some are higher grade. Acinic Cell Carcinoma Intercalated duct cells Cohesive ductal cells with moderate to scant cytoplasm Papanicolaou stain Diff Quik stain Acinic Cell Carcinoma, papillary-papillocystic Pitfalls Misinterpreting normal acinar cells as acinic cell carcinoma Misinterpreting metastatic carcinoma as acinic cell carcinoma 10

11 Normal Salivary Gland Normal Salivary Gland vs. Acinic Cell Carcinoma Acinic Cell Carcinoma Metastatic Tumors Uncommon Intraparotid lymph nodes Clinical history in 70% of cases Skin cancers (SCC, basal cell, MM) Head and neck SCC Sebaceous carcinoma Small cell carcinoma Lymphoma Renal cell carcinoma Metastatic Renal Cell Carcinoma vs. Acinic Cell Carcinoma Renal cell carcinoma: Clinical history of cancer Evidence of lymph node involvement CD10+, RCC+, EMA+, CK7-, PAS+ Acinic cell carcinoma: Primary salivary tumor May have lymphocytes CD10-, RCC-, EMA +, CK7+, PAS + D granules Metastatic Renal Cell Carcinoma vs. Acinic Cell Carcinoma Acinic Cell Carcinoma Renal Cell Carcinoma Oncocytic Tumors Acinic Cell Carcinoma Warthin Tumor Oncocytoma Mucoepidermoid carcinoma (oncocytic variant) Metastatic Renal Cell Carcinoma Warthin Tumor Second most common salivary gland tumor 5-10% of all salivary gland neoplasms Bilateral, men> women, fluctuant mass Doughy on palpation Thick brown-green granular fluid machine oil 11

12 Warthin Tumor Cells Oncocytic, 2-D sheets Lymphocytes, germinal centers Background Mucoid, mucinous or watery Granular or dirty or machine oil Cholesterol crystals Warthin Tumor Variable cellularity Oncocytes large cells, abundant cytoplasm (squamous/glandular metaplasia eccentric nuclei, prominent nucleoli Lymphocytes heterogeneous (plasma cells, small lymphs) occasional germinal centers, DNA artifact Warthin Tumor Pitfalls Squamous metaplasia in Warthin Tumor may be mistaken for squamous cell carcinoma WT lacks overtly malignant features of SCCa Abundant oncocytes in Warthin Tumor may be mistaken for an oncocytic neoplasm Papanicolaou Stain Diff-Quik Stain 12

13 Squamous Metaplasia Oncocytoma Circumscribed nodule Fibrous capsule Parotid gland May be bilateral Cells Oncocytes 2-D and 3-D groups Homogeneous granular cytoplasm without vacuoles Background No lymphocytes Clean Acinic Cell Carcinoma vs. Oncocytoma Acinic Cell Carcinoma Vacuolated cytoplasm Delicate, slightly basophilic cytoplasm Variable atypia PAS + D granules PTAH negative Oncocytoma No cytoplasmic vacuoles Dense, granular eosinophilic cytoplasm Minimal to absent atypia No PAS + D granules PTAH positive Oncocytoma Final Comments Common problem Normal vs Warthin tumor vs Acinic cell ca Clinical information is very helpful History of primary Fluctuant, recurrent vs firm and fixed Pattern vs cytomorphology Monomorphic vs biphasic population Sheets vs papillae Granular vs vacuolated cytoplasm 13

14 CASE 3 History: A 45 yo man with a 6 month history of a 3.7 cm mildly painful, enlarging left parotid gland mass. An MRI showed a nodular, slightly irregular lesion with variable signal intensity located in the superficial parotid gland just lateral to the facial nerve. An FNA was performed. CASE 3 CYTOLOGIC DIAGNOSIS: BASALOID NEOPLASM WITH MILD ATYPIA, FAVOR BASAL CELL ADENOMA. SEE NOTE. Note: The differential diagnosis includes basal cell adenoma and basal cell adenocarcinoma; however, a more aggressive basaloid neoplasm cannot be entirely excluded. CASE 3 SURGICAL RESECTION: Superficial parotidectomy was performed. A frozen section performed at the time of surgery also favored a basal cell adenoma. 14

15 CASE 3 HISTOLOGIC DIAGNOSIS: BASAL CELL ADENOCARCINOMA, 3.7 CM, SOLID TYPE. Clinical follow-up: The patient has been free of disease for 6 years. BASAL CELL ADENOCARCINOMA Rare, low-grade salivary gland neoplasm Approximately 2% of malignant salivary gland tumors Parotid gland, rarely in submandibular gland Average age: 60 years (range: years) Good prognosis: Local recurrence (35%), infrequent metastatic disease (10%), and low mortality (3%) Complete surgical excision with disease-free margins BASAL CELL ADENOCARCINOMA Malignant counterpart of basal cell adenoma (aka monomorphic adenoma) Distinguished by histologic evidence of invasion CANNOT DISTINGUISH BY FNA! 3 Patterns: Solid, tubulotrabecular, and membranous May be associated with synchronous dermal tumors BASAL CELL ADENOMA & ADENOCARCINOMA Histologic Features: Basaloid cells - Small dark cells - usually peripheral Larger pale cells Palisading of the small dark cells Conspicuous hyaline membranes of basal lamina surround nests Intercellular hyaline droplets Small tubules lined by cuboidal cells Squamous morules BASAL CELL ADENOMA & ADENOCARCINOMA: Membranous Type 15

16 BASAL CELL ADENOMA & ADENOCARCINOMA: Membranous Type BASAL CELL ADENOMA & ADENOCARCINOMA: Synchronous Cutaneous Cylindroma BASAL CELL ADENOMA & ADENOCARCINOMA: Tubulotrabecular Type BASAL CELL ADENOMA & ADENOCARCINOMA: BASAL CELL ADENOMA & ADENOCARCINOMA: Solid Type BASAL CELL ADENOMA & ADENOCARCINOMA Peripheral palisading 16

17 BASAL CELL ADENOMA & ADENOCARCINOMA BASAL CELL ADENOMA & ADENOCARCINOMA Squamous morule BASAL CELL ADENOMA & ADENOCARCINOMA BASAL CELL ADENOMA & ADENOCARCINOMA: Myoepithelial Markers Calponin Keratin SM Actin S100 P63 BASAL CELL ADENOMA VS. ADENOCARCINOMA Malignancy is based upon finding histologic evidence of infiltrative growth into salivary gland parenchyma and soft tissue. 25% of carcinomas show perineural or lymphovascular invasion. BASAL CELL ADENOMA & ADENOCARCINOMA Cytologic Features: Two populations of basaloid cells - Small oval cells with scant cytoplasm Bland dark nuclei Haphazard arrangement in cohesive groups Absence of marked nuclear atypia Peripheral palisading Squamous morules Peripheral ribbons & intercellular droplets of dense, nonfibrillary, acellular matrix Metachromatic by Romanowsky stains, cyanophilic by Pap stain 17

18 Basal Cell Adenoma & Adenocarcinoma: 3 Subtypes - Solid, tubulotrabecular and membranous BASAL CELL ADENOMA & ADENOCARCINOMA: Membranous Type BASAL CELL ADENOMA & ADENOCARCINOMA: Solid Type Squamous Morule BASAL CELL ADENOMA & ADENOCARCINOMA DIFFERENTIAL DIAGNOSIS Adenoid cystic carcinoma Polymorphous low-grade adenocarcinoma Cellular pleomorphic adenoma Chronic sialadenitis Cutaneous basal cell carcinoma Metastatic basaloid squamous carcinoma Basal Cell Tumor vs Adenoid Cystic Carcinoma Solid Basal Cell Tumor vs Solid Adenoid Cystic Carcinoma Features favoring basal cell tumor: Peripheral bands of matrix Intercellular matrix globules Dual cell population Peripheral palisading Squamous morules Bland cytology Basal cell adenoma Adenoid cystic carcinoma 18

19 BASAL CELL ADENOMA & ADENOCARCINOMA In the final analysis, it may not always be possible to make a specific diagnosis. Rather, a diagnosis favoring a basal cell tumor with a note explaining the differential diagnosis. Polymorphous Low-Grade Adenocarcinoma Minor salivary glands, esp. palate Circumscribed subepithelial mass Resembles infiltrating lobular breast carcinoma Histologic Features: Diverse architecture: solid, trabecular, cords/single file, ductular, tubular, papillary, cystic, cribriform Concentric whorling appearance Few myoepithelial cells, minimal atypia, & absence of myxochondroid matrix Infiltrative growth Prominent neurotropism without necrosis Polymorphous Low-Grade Adenocarcinoma Polymorphous Low-Grade Adenocarcinoma Polymorphous Low-Grade Adenocarcinoma Polymorphous Low-Grade Adenocarcinoma 19

20 Polymorphous Low-Grade Adenocarcinoma Polymorphous Low-Grade Adenocarcinoma Cellular Pleomorphic Adenoma Chronic Sialadenitis: Kuttner Tumor Features favoring PA: Matrix is fibrillar and contains cells Absence of peripheral palisading Predominance of myoepithelial cells/absence of two basaloid cell populations Chronic Sialadenitis Hypocellular with small basaloid groups and background chronic inflammation. Final Comments Most difficult diagnostic problem in the salivary gland Often a descriptive diagnosis Basal cell adenocarcinoma and adenoma are cytologically indistinguishable: 2 populations of basaloid cells Peripheral matrix ribbons and intercellular globules Squamous morules Palisading The DDX includes adenoid cystic carcinoma. 20

21 CASE 4 History: A 49 year-old woman with a several year history of rheumatoid arthritis presents with a markedly enlarged left parotid gland. By clinical exam, the parotid gland was diffusely firm; however, a discrete mass was not identified. An FNA was performed. The initial working diagnosis based upon rapid interpretation included reactive lymph node, chronic sialadenitis, LESA, and lymphoma. Therefore material for flow cytometry was sent and was negative for lymphoma. CASE 4 Cytologic Diagnosis: LYMPHOEPITHELIAL SIALADENITIS (LESA) 21

22 LYMPHOEPITHELIAL SIALADENITIS (LESA) Variety of names: Benign lymphoepithelial lesion Myoepithelial sialadenitis (MESA) Mikulicz s disease Often associated with Sjogren s syndrome, rheumatoid arthritis or other autoimmune disorders Can be unilateral, bilateral, solid, or cystic Increased risk of B-cell lymphoma, esp. MALT-type LYMPHOEPITHELIAL SIALADENITIS (LESA) Histologic Features: Lymphocytic infiltration of gland with parenchymal atrophy T-lymphocytes, plasma cells, and monocytoid B-cells Variable germinal center formation Ductal hyperplasia to form lymphoepithelial lesions LYMPHOEPITHELIAL SIALADENITIS (LESA) LYMPHOEPITHELIAL SIALADENITIS (LESA) Cytologic Features: Cellular aspirate Mixed population of lymphocytes and plasma cells Germinal center fragments Tingible body macrophages Lymphoepithelial lesions Absence of acinar cells A key pitfall in the diagnosis of LESA is metastatic squamous cell carcinoma. SCC LESA Differential Diagnosis of LESA Chronic sialadenitis Reactive intraparotid lymph node Lymphoepithelial carcinoma Metastatic squamous cell carcinoma B-cell lymphoma MALT Follicular Diffuse large B-cell 22

23 Epithelial Salivary Gland Tumors with Lymphocytes Warthin tumor Mucoepidermoid carcinoma Acinic cell carcinoma Lymphoepithelial carcinoma Metastatic carcinoma LESA vs. Chronic Sialadenitis Chronic Sialadenitis differs from LESA by: Hypocellularity Fewer lymphocytes and germinal centers Smaller angulated groups rather than sheets Absence of lymphoepithelial lesions LESA vs. Lymphoma Immunophenotyping is essential for distinguishing LESA from lymphoma, especially MALT lymphoma. Salivary Gland Lymphomas 2-5% of salivary gland neoplasms Parotid is most frequently involved Most are B-cell NHL MALT is the most common DLBCL Follicular lymphoma primarily in parotid LNs MALT LYMPHOMA MALT LYMPHOMA 23

24 Salivary Gland Lymphomas MALT Follicular DLBCL Small lymphs, centrocytes, monocytoid B cells Slight nuclear atypia CD20+, 23-, 10-, 5-, cyclin D1-, bcl2+, bcl6- Mixed small & large Notched and grooved nuclei CD20+, 23-, 10+, 5-, bcl2+, bcl-6+ May be CD10- T(14:18) by FISH Large size: Immunoblasts & centroblasts Marked atypia CD20+, keratin -, S-100- Final Comments A characteristic feature of LESA is the lymphoepithelial lesion. The differential diagnosis of lymphoid lesions in the salivary gland includes non-neoplastic and benign conditions, B-cell lymphoma, and carcinoma. Without ancillary studies, LESA can be impossible to distinguish from MALT lymphoma. History: Case 5 A 58 year old man with a 2.0 cm nontender, enlarging left parotid gland mass. 24

25 Case 5 Mucoepidermoid Carcinoma Mucoepidermoid Carcinoma Low Grade Most common salivary gland in children Second only to PA in frequency in adults M=F; Age range: years Usually slow growing and painless Residual mass post aspiration Mucoepidermoid Carcinoma Low Grade Cells (variable cellularity, sheets) Mucous containing epithelial cells Epidermoid cells (squamous features) Intermediate cells (low N/C ratio) Background Mucinous often with cellular debris 25

26 Low-Grade Mucoepidermoid Carcinoma Low-Grade Mucoepidermoid Carcinoma Low-Grade Mucoepidermoid Carcinoma Intermediate cells Cystic Lesions Low grade mucoepidermoid carcinoma Branchial cleft cyst Lymphoepithelial cyst Salivary duct cyst/retention cyst Cystic squamous cell carcinoma 26

27 Mucocele/Retention Cyst Low-Grade Mucoepidermoid Carcinoma vs Mucocele Low grade mucoepidermoid carcinoma is the most common cause of false negative salivary gland diagnoses: Low cellularity due to cyst Bland cytology of cells Mucin cells resemble foamy histiocytes Branchial Cleft Cyst Branchial Cleft Cyst Usually present in young adults Lateral neck along SCM muscle, around external ear 1st branchial cleft (parotid) Type I ectodermal only Type II ectodermal and mesodermal (cartilage) Non tender fluctuant masses Pap Stain Diff-Quik Stain Final Comments Search for three cell types (mucus, intermediate, squamous) to distinguish LG MEC from Tumors with squamous or mucinous metaplasia Beware making a definitive diagnosis when aspirates are hypocellular 27

28 Case 6 History: 52 year old man presented with a rapidly enlarging right parotid gland mass. The lesion is painful, and the patient has symptoms of facial nerve involvement. Case 6 Salivary Duct Carcinoma Diff-Quik Stain Pap Stain Salivary Duct Carcinoma Uncommon Clinically aggressive Parotid in elderly men Resembles high-grade comedo-type ductal carcinoma of the breast 28

29 Salivary Duct Carcinoma Cells Overtly malignant cytomorphology Sheets, clusters, papillae, cribriform groupings Polygonal with abundant vacuolated cytoplasm Large hyperchromatic, pleomorphic nuclei Prominent nucleoli Background Necrosis Salivary Gland Duct Ca High-Grade Carcinomas High-grade carcinomas Salivary Duct Carcinoma Mucoepidermoid Carcinoma Carcinoma Ex Pleomorphic Adenoma Squamous Cell Carcinoma Salivary duct ca High-grade MEC Ca Ex PA Mucoepidermoid Carcinoma High- Grade Most common malignant salivary gland tumor (2 nd in frequency to PA) Clinically aggressive: rapidly enlarging and painful Parotid in elderly men Resembles high-grade comedo-type ductal carcinoma of the breast 29

30 Mucoepidermoid Carcinoma High- Grade Cells High cellularity, obvious malignant features Epithelial cells in clusters and singly Little distinction between squamous and glandular cells Pleomorphism, prominent nucleoli Background Variable necrosis and/or cystic component (mucinous) Malignant Mixed Tumor Rare, occurs in 5-9% of pleomorphic adenomas Pre-existent pleomorphic adenoma Sudden rapid growth in salivary gland mass present for considerable time Three types Carcinoma ex pleomorphic adenoma Carcinosarcoma Metastasizing mixed tumor Carcinoma Ex Pleomorphic Adenoma Cells High-grade carcinoma with pre-existent PA Sheets and aggregates of malignant cells Background Matrix (associated with PA) associated with HG Carcinoma Necrosis 30

31 Squamous Cell Carcinoma Rare salivary gland primary Metastases from H&N often cystic High-grade non-keratinizing squamous cell carcinoma often indistiguishable from high-grade primaries (esp. MEC) Cells Squamous Cell Carcinoma, High-Grade Sheets and aggregates of malignant cells Pleomorphic nuclei with coarse chromatin Distinct nucleoli Background Necrosis and cell debris (+/- keratin) Inflammation Squamous Cell Carcinoma, Primary Squamous Cell Carcinoma, Metastatic Final Comments The presence of matrix suggests Ca ex PA The combination of squamoid cells and rare mucin+ cells favors MEC (cell block is useful) Keratinization favors a metastasis over MEC Salivary duct carcinomas resemble high-grade breast cancers with comedo necrosis they can be mucin + 31

32 CASE 7 History: A 69 year-old woman presented with a slowly enlarging, non-tender, 2.0 cm parotid gland mass. An FNA was performed. CASE 7 Cytologic Diagnosis: LOW-GRADE BIPHASIC SALIVARY GLAND NEOPLASM WITH ABUNDANT MYOEPITHELIAL CELLS. SEE NOTE. Note: The DDX includes epithelial-myoepithelial carcinoma and cellular pleomorphic adenoma. The tumor was surgically excised by superficial parotidectomy. 32

33 CASE 7 Epithelial-Myoepithelial Carcinoma Histologic Diagnosis: EPITHELIAL-MYOEPITHELIAL CARCINOMA Rare - 1% of all salivary gland tumors Parotid gland Average age: 62 years (range: years) M:F = 1:2 Low-grade malignancy; locally aggressive Excellent prognosis Epithelial-Myoepithelial Carcinoma Epithelial-Myoepithelial Carcinoma Histologic Features: Biphasic: myoepithelial cells and intercalated duct-type cells Multinodular and hyalinized stroma Eosinophilic, PAS+ luminal material Solid, organoid, cystic, and nested patterns Infiltrative growth Variable atypia, necrosis, and mitoses Epithelial-Myoepithelial Carcinoma Epithelial-Myoepithelial Carcinoma 33

34 Epithelial-Myoepithelial Carcinoma Epithelial-Myoepithelial Carcinoma Cytologic Features: Cellular Biphasic: sheets and spheres of cells: Myoepithelial cells -Polygonal with abundant clear cytoplasm -Bland oval nucleus with pale chromatin -Small distinct nucleolus -PAS+ for glycogen Ductal cells -Cuboidal -Round nuclei with dark chromatin -Scant granular cytoplasm Background stripped myoepithelial nuclei Acellular matrix material and proteincaceous secretions In some cases, the clear myoepithelial cells predominate to the near exclusion of the ductal component. Epithelial-Myoepithelial Carcinoma Special Studies: Cell block can be used to demonstrate the biphasic features of the tumor: PAS+ to demonstrate abundant glycogen IPX for WS keratins for ductal cells IPX for smooth muscle actin, calponin, S-100 for myoepithelial cells Epithelial-Myoepithelial Carcinoma: The DDX includes other tumors with clear cells DIFFERENTIAL DIAGNOSIS: Myoepithelioma/carcinoma Acinic cell carcinoma Oncocytoma Sebaceous adenoma/carcinoma Clear cell carcinoma Lipoma Metastatic renal cell carcinoma Mucoepidermoid carcinoma, low-grade 34

35 Epithelial-Myoepithelial Carcinoma: The DDX includes other tumors with clear cells Clear Cell Tumors: Myoepithelioma/Carcinoma What is in the clear cytoplasm?: Glycogen Lipid Condensed mitochondria Mucin Monophasic pattern Less abundant glycogenrich cytoplasm May contain fibrillar matrix with embedded cells High-grade when malignant Myoepithelioma Myoepithelial carcinoma Clear Cell Tumors: Myoepithelioma/Carcinoma Myoepithelioma Myoepithelial Carcinoma Clear Cell Tumors: Sebaceous Adenoma/Lymphadenoma Very rare Clear cells and squamous cells Highly vacuolated cytoplasm Background lymphocytes Cytoplasm contains fat: oil red-o + on air-dried Fat Stain + Sebaceous Lymphadenoma Clear Cell Tumors: Acinic Cell Carcinoma Can be confused with LG MEC, but it lacks mucin. Lacks myoepithelial cells Lacks biphasic pattern Contains PAS + D zyomogen granules 35

36 Clear Cell Tumors: Clear Cell Carcinoma Usually palatal Lacks ductal structures Lacks myoepithelial differentiation Diagnosis of exclusion Final Comments Epithelial-myoepithelial carcinoma is a rare lowgrade biphasic tumor with a predominance of large clear myoepithelial cells. Histology is unique; cytology is more challenging! The DDX includes numerous other clear cell tumors, but none matches the biphasic pattern of epithelialmyoepithelial carcinoma. Ancillary studies can be helpful CASE 8 A 48 year-old female presented with a 1.5 cm tender, rapidly enlarging lesion of the left parotid. An FNA was performed. CASE 8 Cytologic Diagnosis: SPINDLE CELL LESION, FAVOR BENIGN. SEE NOTE. Note: The differential diagnosis includes nodular fasciitis, schwannoma, and pleomorphic adenoma. 36

37 The nodule was surgically excised by superficial parotidectomy. Immunohistochemistry for Vimentin Immunohistochemistry for Smooth Muscle Actin CASE 8 Summary of immunohistochemistry: Vimentin + Smooth muscle actin + S Keratin - CD34 - CASE 8 Histologic Diagnosis: NODULAR FASCIITIS 37

38 Nodular Fasciitis First reported in 1955 (Konwaler et al.) Reactive myofibroblastic lesion in young adults (20-40 year-old) Rapidly enlarging, often tender subcutaneous nodule (<3 cm) May be associated with trauma Most anatomic sites but predilection for the upper limb, especially forearm less common in the head and neck Self-limiting clinical course; recurrence is uncommon Nodular Fasciitis Histologic Features: Circumscribed but unencapsulated Short interweaving fascicles of myofibroblasts Loose collagenous or myxoid stroma Delicate capillaries with red blood cell extravasation Mild mixed inflammation Mitoses may be frequent May contain osteoclast-type giant cells Absence of atypia Nodular Fasciitis Nodular Fasciitis Nodular Fasciitis Cytology (cellular aspirate): Spindle-shaped myofibroblasts, plump nuclei, pale chromatin, vacuolated cytoplasm, wispy bipolar cytoplasmic processes Small groups often with intercellular collagen Bloody and myxoid background Chronic inflammatory cells Nodular Fasciitis The diagnosis is often suggested by the clinical presentation, and FNA serves to simply confirm the clinical suspicion. 38

39 Nodular Fasciitis: Differential Diagnosis BENIGN: Myoepithelioma/PA Schwannoma Solitary fibrous tumor Inflammatory pseudotumor Granuloma Fibrous histiocytoma Neurofibroma Leiomyoma Nodular Fasciitis: Benign Differential Diagnosis Schwannoma Wavy nuclei with pointed ends Palisading (Verocay bodies) Distinguished by IPX: Strongly S-100+ Schwannoma Nodular Fasciitis: Benign Differential Diagnosis Granuloma Solitary fibrous tumor Leiomyoma Nodular Fasciitis Immunocytochemistry: Positive:» Vimentin +» Smooth muscle actin + Negative: (Positive)» S-100 Schwannoma» Desmin Leiomyoma» Keratin Pleomorphic adenoma» CD34 Solitary fibrous tumor» CD68 Granuloma FNA of Spindle Cell Lesions of the Head and Neck Spindle cell lesions of the head and neck diagnosed by FNA between : Schwannoma (16) Myoepithelioma (10) Malignant melanoma (6) Medullary carcinoma (4) Hemangiopericytoma (2) Fibrosarcoma (2) Nodular fasciitis (3) Neurofibroma (1) Solitary fibrous tumor (1) Angiosarcoma (1) Spindle cell carcinoma (1) Leiomyosarcoma (1) 39

40 FNA of Spindle Cell Lesions of the Salivary Gland Region Evaluating these difficult lesions: Clinical history including information about the nature of the lesion (size, growth rate, site) is CRITICAL! When possible, additional material for immunocytochemical studies should be obtained, preferably as a paraffin-embedded cell block. Electron microscopy can be an extremely valuable ancillary tool. Benign versus Malignant Spindle Cell Lesions of the Salivary Gland Region It may not always be possible to give a specific diagnosis; however, distinguishing benign from malignant spindle cell lesions is often feasible. Benign versus Malignant Spindle Cell Lesions of the Salivary Gland Region Nonetheless, a note recommending close clinical follow-up and re-biopsy, should the lesion fail to resolve or should it show evidence of growth, is suggested. Benign versus Malignant Spindle Cell Lesions of the Salivary Gland Region Features associated with malignant lesions: Nuclear hyperchromasia Prominent nucleoli Irregular chromatin distribution Nuclear pleomorphism Necrosis Hemorrhage Atypical mitoses High cellularity Nodular Fasciitis: Malignant Differential Diagnosis MALIGNANT: Myoepithelial carcinoma Malignant melanoma Spindle cell carcinoma MPNST Sarcoma:» Fibrosarcoma» Synovial sarcoma» MFH Final Comments Evaluation of spindle cell lesions by FNA can be very challenging. In many cases, distinction between benign and malignant is possible based upon microscopic and clinical features. Clinical correlation and adequate material for ancillary studies are essential for making an accurate evaluation. 40

41 41