Update in Salivary Gland Pathology - PDF Document

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  1. Update in Salivary Gland Pathology Benjamin L. Witt University of Utah/ARUP Laboratories February 9, 2016

  2. Objectives • Review the different appearances of a selection of salivary gland tumor types • Establish an immunohistochemical staining pattern to aid in distinguishing between certain tumors • Discuss some newer concepts in salivary gland pathology

  3. Acinic Cell Carcinoma • Originally this was considered a benign neoplasm until its malignant potential was described in the 1950s • Later regarded as in between adenoma and carcinoma (acinic cell tumor; WHO 1972) • Finally classified as acinic cell carcinoma in 1991 WHO classification • Diagnosis can be rendered in absence of invasive growth

  4. Acinic Cell Carcinoma • Third most common malignancy of major salivary gland (15%) • Most non-parotid ACC (11/14; 80%) actually represent misclassified mammary analogue secretory carcinoma (MASC) - Based upon positivity for S100, mammaglobin - Confirmatory ETV6 t(12;15) translocation by FISH Bishop et al. Am J Surg Pathol. 2013;37(7): 1053-57

  5. Acinic Cell Carcinoma • Neoplasm of cells differentiated towards serous acinar cells • Aside from the zymogen granule rich cells (pathognomonic acinar cells) other cell types frequent these tumors: - Vacuolated cells - Clear cells (non-mucinous, PAS negative) - Nonspecific glandular cells • No grading system exists although high grade transformation is reported

  6. Lesion 1: Parotid Mass in 68 year old female

  7. Lesion 1: Note clear and vacuolated cells

  8. Lesion 2: Parotid mass (3 cm) in 15 year old female

  9. PAS-D on Lesion 2

  10. Lesion 3: From parotid mass of 55 year old male

  11. PAS-D from Lesion 3

  12. Lesion 4: 67 year old female (least common follicular pattern)

  13. Lesion 4: DOG 1

  14. Lesion 5: 76 year old female with parotid mass

  15. Lesion 5: Microcystic with clear/vacuolated cells

  16. Lesion 5

  17. Lesion 5: Nonspecific glandular cells

  18. Mammary Analogue Secretory Carcinoma (MASC) • Recently described (2010) salivary gland tumor with morphologic resemblance to secretory carcinoma of the breast • Known ETV6-NTRK3 t(12;15) gene rearrangement • Uniform/bland cell proliferation • Eosinophilic vacuolated cytoplasm • Mostly solid, microcystic pattern with abundant PAS/D + secretions

  19. MASC • In prior years the majority would have been classified as secretory poor (or intercalated duct predominant) acinic cell carcinomas or low grade adenocarcinomas NOS • No significant prognostic difference between MASC and Acinic cell carcinoma • MASC does have slight male predilection • MASC more common to extraparotid sites • MASC have greater potential to develop nodal metastases Alena Skalova. Head and Neck Pathol. 2013;7:S30-36.

  20. 36 year old male with 3 cm parotid mass

  21. PASD DOG 1 S100 MASC

  22. Suggested IHC Panel for Acinic Cell Carcinoma versus MASC Acinic Cell Carcinoma Mammary Analogue Secretory Carcinoma S-100 Mostly - Strongly + Mammaglobin - + DOG-1 + (diffuse Usually - apical/membranous staining) GATA3 - Diffuse + PAS-D + (zymogen granules) - (NO zymogen granules) Both Acinic Cell Carcinoma and MASC lack significant p63 positivity to help distinguish from low grade mucoepidermoid carcinoma Chenevert et al. Modern Pathology (2012) 25:919-29 Schwartz et al. Head and Neck Pathol (2013) 7:311-315

  23. Image adapted from Chenevert et al. Modern Pathology (2012) 25,919-29

  24. 55 year old female with parotid mass and mediastinal/abdominal adenopathy

  25. Interface with surrounding ducts

  26. More poorly differentiated area. Apocrine starts to resemble squamoid.

  27. An Immunohistochemical Panel for Reliable Differentiation of Salivary Duct Carcinoma and Mucoepidermoid Carcinoma • SDC is often mistakenly diagnosed as high grade MEC - Apocrine features of SDC can mimic squamoid of MEC - Vacuolated cells of SDC can mimic mucocytes of MEC • Given emerging evidence that biologic therapies may have a role in the management of SDC it is an important distinction Butler RT et al. Head and Neck Pathol. 2014; 8:133-140

  28. An Immunohistochemical Panel for Reliable Differentiation of Salivary Duct Carcinoma and Mucoepidermoid Carcinoma SDC MEC p63 - (87% had no staining) + CK 5/6 - (63% had no staining) + AR + (67-100%) - (100%) Her2/Neu +/- - (100% 0 to 1+) GATA 3 + (100%, 25/25 typically strong) -/+ (41%, 11/27 variable) Schwartz et al. Head and Neck Pathol. 2013;7:311-315 Butler RT et al. Head and Neck Pathol. 2014; 8:133- 140

  29. p63 Her2 GATA 3 Our case from above

  30. Our Case • Overall morphology most consistent with SDC - ductal interface - apocrine features predominate • IHC pattern supports SDC - convincing GATA 3 nuclear staining - equivocal HER2 result - negative p63

  31. Expected result for p63 in a MEC (Intermediate to epidermoid cells)

  32. High Grade Transformation (Dedifferentiation) in Salivary Gland Carcinomas • Has been described in several of the common salivary gland carcinomas • This is distinct from hybrid carcinomas (2 distinct tumor entities) • Abrupt transition of a well-differentiated tumor into a high-grade appearance • In general the transformed component shows different growth pattern, as well as increased pleomorphism, mitoses and necrosis • Poor prognosis regardless of original tumor type

  33. Parotid mass in 74 year old male with recent increase in size

  34. Adenoid Cystic Carcinoma with High Grade Transformation • Distinct from the solid pattern that is used to grade conventional adenoid cystic carcinoma • The HGT component exhibits: - large pleomorphic nuclei - more cytoplasm than ACC - spans between poorly differentiated adenocarcinoma to solid nests with squamous eddies • Worse prognosis than solid ACC; with mean survival of 3 years (in 24 patients) Toshitaka Nagao. Head and Neck Pathol. 2013;7:S37- S47.

  35. Pleomorphic Adenoma • One of the devil’s cruelest tricks is the mimicry of PAs - More cellular/generally not encapsulated in minor salivary gland sites - Multilobular growth with irregular interface at periphery - Metaplasia (squamous, lipomatous, mucinous) - Varied growth patterns (can resemble adenoid cystic carcinoma) • 70% of PAs have either PLAG1 or HMGA2 gene rearrangement

  36. Ductules/Tubules with Matrix Stroma

  37. 48 year old male with 3.5 cm parotid mass, Cystic change

  38. PA with Hyalinization

  39. PA with Intracapsular Growth PA with Intracapsular Growth PA with Capsular Extension

  40. PA with Benign Vascular Invasion Image adapted from: Ethunandan et al. Int. J. Oral Maxillofac. Surg. 2006;35:608-12.

  41. Squamous Metaplasia in PA

  42. PA with mucinous metaplasia

  43. PA with Many Faces: Myoepithelial Heavy Area

  44. PA with Many Faces: Schwannoma-like Area

  45. PA with Many Faces: Adenoid Cystic-Like Area