QA CONFERENCE #2, May 30, 2012

1. QA CONFERENCE#2, May 30, 2012 Dr. Esther Ravinsky

2. Case 1 • 60 year old female • Ultrasound guided right breast core biopsy • Palpable nodule, UOQ • Query reactive lymph node • R/O carcinoma • Magnification x 2

3. Case 1 • Magnification x 20

4. Case 1 • Magnification x 20

5. Case 1 • Magnification x 10

6. Case 1 • Magnification x 20

7. Case 1

8. Case 1 • Immunohistochemical stain for desmin

9. Case 1 • The answer is: • Neoplasm with stromal differentiation • Differential diagnosis includes: • Myofibroblastoma with epithelioid features • Metaplastic carcinoma • Sarcoma (e.g. leiomyosarcoma)

10. Case 1 • Mastectomy was performed • The nodule which had been biopsied was described as a pinkish-grey encapsulated nodule ?lymph node ?tumour nodule, 1.8 cm in dimension

11. Excision specimen • Magnification x 1

12. Excision specimen • Magnification x 20

13. Excision specimen • Magnification x 20

14. Myofibroblastoma • Rare benign breast tumour arising from myofibroblasts • Radiologically, the tumours are homogeneous, lobulated, well circumscribed and lack microcalcifications • The excised mass is firm and rubbery with a lobulated external surface • The cut surface consists of homogeneous, bulging, gray to pink whorled tissue

15. Myofibroblastoma • Microscopically, the classic type of myofibroblastoma is devoid of mammary ducts and lobules, with compressed breast parenchyma forming a peripheral pseudocapsule • The tumour consists of bundles of slender bipolar uniform spindle shaped cells typically arranged in clusters which are separated by broad bands of hyalinized collagen distributed throughout the tumour • In a minority of cases, fat cells are present in the tumour, reflecting invasion of the surrounding tissue

16. Myofibroblastoma, variant forms • The epithelioid variant features polygonal or epithelioid cells arranged in alveolar groups • Epithelioid cells may be mixed with more classical variants or they can constitute the predominant growth pattern • Because of the epithelioid growth pattern, the tumour may be mistaken for an infiltrating lobular carcinoma, especially in the limited material of a needle core biopsy • Other variants which may be mistaken for malignancy are the cellular variant, the infiltrative variant and the deciduoid variant

17. Myofibroblastoma, variant forms • By immunohistochemistry, myofibroblastomas stain positive for actin and desmin and negative for cytokeratin • Noticing a spindle cell component can raise a red flag for the pathologist considering a diagnosis of carcinoma and result in the ordering of appropriate immunohistochemistry • The absence of mitotic figures should raise a red flag if the diagnosis of metaplastic carcinoma or sarcoma is considered

18. Infiltrating myofibroblastoma

19. Myofibroblastoma • No recurrences have been reported after follow-up of 3 to 126 months • Excision with wide margins is recommended when myofibroblastoma is identified in a needle core biopsy

20. Case 2 • 65 year old female • Endometrial biopsy • History of post menopausal bleeding • Magnification x 4

21. Case 2 • Magnification x 4

22. Case 2 • Magnification x 10

23. Case 2 • Magnification x 20

24. Case 2 • Magnification x 10

25. Case 2 • Magnification x 20

26. Case 2

27. Case 2 • Immunohistochemical stain for p53

28. Case 2 • The answer is: • Serous carcinoma of endometrium

29. Case 3 • 76 year old female • Endometrial curettage performed at diagnostic hysteroscopy • Post menopausal bleeding • Atypical glandular cells on Pap • Magnification x 2

30. Case 3 • Magnification x 10

31. Case 3 • Magnification x 20

32. Case 3 • Magnification x 4

33. Case 3 • Magnification x 10

34. Case 3 • Magnification x 20

35. Case 3 • Immunohistochemical stain for p53

36. Case 3

37. Case 3 • Immunohistochemical stain for ER

38. Case 3 • The answer is: • Endometrioid adenocarcinoma, FIGO grade 2

39. Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium • Serous carcinoma • It is defined by a discordance between its architecture which appears well differentiated; papillary or glandular and its nuclear morphology which is high grade • Papillary architecture is complex with short thick papillae though thin papillae may also be present. • The cells covering the papillae and lining the glands form small papillary tufts, many of which are detached and float freely in spaces between the papillae and in the gland lumens

40. Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium • The cells are cuboidal or hobnail shaped and contain abundant epsinophilic cytoplasm • The cells tend to be loosely cohesive • The cells show marked cytologic atypia with marked nuclear pleomorphism, hyperchromasia and macronucleoli • Multonucleated cells, giant nuclei and bizarre forms can occur • Mitotic activity is high and abnormal mitotic figures are easily identified

41. Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium • Villoglandular carcinoma is characterized by the presence of long delicate papillary fronds that do not show papillary tufting • The cells are columnar, resembling the cells in endometrioid adenocarcinoma • The glands in endometrioid adenocarcinoma have a smooth luminal border and are lined by columnar cells with nuclei which are grade 1 or 2. • Endometrioid adenocarcinomas with grade 3 nuclei are almost always solid

42. Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium • Immunohistochemical findings: • Serous carcinoma • 75% of serous carcinomas are strongly and diffusely positive for p53 • The typical serous carcinoma lacks diffuse ER and PR expression. • Carcinomas with hybrid endometrioid/serous features and admixtures of endometrioid and serous components can express ER • Diffuse strong p16 staining is characteristic of serous carcinomas • The Ki67 labelling index is extremely high (50%-75% of tumour nuclei)

43. Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium • Immunohistochemical findings: • Villoglandular/endometrioid carcinoma • The preponderance of grades 1 + 2 and half of the grade 3 endometrioid carcinomas strongly express ER and PR • P53 expression is not identified in FIGO 1 carcinomas. It is identified in a minority of FIGO 2 carcinomas and in a significant number of FIGO 3 carcinomas • However, when p53 staining is prominent, serous carcinoma, clear cell carcinoma or undifferentiated carcinoma should be considered • Overexpression characteristic of serous carcinoma is defined as diffuse and strong expression in more than 50-75% of tumour cells • Low-grade expression of p53 in less than 50% of tumour cells is commonly found in endometrioid carcinomas • Endometrioid carcinoma can show patchy expression of p16

44. Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium

45. Case 4 • 74 year old female • Open cholecystectomy • Calculi identified • Magnification x 2

46. Case 4 • Magnification x 4

47. Case 4 • Magnification x 10

48. Case 4 • Magnification x 20

49. Case 4 • Magnification x 4

50. Case 4 • Magnification x 20