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ANNUAL SLIDE SEMINAR June 21-23 2007 Bratislava Slovakia

This case study presents the histopathological analysis of a sarcomatous tumor found in the breast of a 75-year-old female with a history of previous malignancies. The study highlights the tumor's macroscopic and microscopic characteristics, including cellular morphology, areas of necrosis, and extracellular matrix composition. Immunohistochemistry results for various markers are also included.

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ANNUAL SLIDE SEMINAR June 21-23 2007 Bratislava Slovakia

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  1. ANNUAL SLIDE SEMINAR June 21-23 2007 Bratislava Slovakia B. Fredrik Petersson MD, PhD Department of Pathology, Karolinska University Hospital Stockholm Sweden

  2. Case 2 History Female, age 75 years. Medical history: 2001, Mammary carcinoma, ductal NOS, N0. Partial mastectomy. 2005, Keratinizing squamous cell carcinoma of the tongue, T1. Radiation + Neck resection (N0). 2006, Oncocytic adenoma + medullary thyroid carcinoma. Thyroidectomy. 2007, Deeply seated, large tumor, right breast FNA: ”sarcomatous tumor”. Mastectomy

  3. Case 2 Macroscopy • 6 x 3,5 x 2,5 cm fairly well circumscribed tumor with somewhat glistenig relatively homogenous cut surface and central necro-cystic areas. 3 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  4. Case 2 Histology • - Relatively well circumscribed, quite cellular, non-encapsulated tumor with areas of obvious infiltration in adipose tissue and striated muscle on the deep aspect. • Areas of necrosis. • Epitheloid – polygonal but mainly spindled cell-morphology with malignant cytomorphological characteristics. • Mitotic figures easily found. • Myxoid to collagenized extracellular matrix with some ares showing more of hyaline eosinophilic material in close association to the neoplastic cells. 4 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  5. 5 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  6. 6 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  7. 7 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  8. 8 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  9. Case 2 Histology • Relatively well circumscribed, cellular non-encapsulated tumor with areas of obvious infiltration in adipose tissue and striated muscle on the deep aspect. • Areas of necrosis. • Epitheloid – polygonal but mainly spindled cell-morphology with malignant cytomorphological characteristsics. • Mitotic figures easily found. • Myxoid to collagenized extracellular matrix with some ares showing more of hyaline eosinophilic material. • . 9 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  10. 10 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  11. Case 2 Histology • Relatively well circumscribed, cellular, non-encapsulated with areas of obvious infiltration in adipose tissue and striated muscle on the deep aspect. • Areas of necrosis. • Epitheloid – polygonal but mainly spindled cell-morphology with malignant cytomorphological characteristics. • Mitotic figures easily found. • Myxoid to collagenized extracellular matrix with some areas showing more of hyaline eosinophilic material. • . 11 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  12. 12 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  13. 13 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  14. Case 2, Histology • Relatively well circumscribed, cellular, non-encapsulated with areas of obvious infiltration in adipose tissue and striated muscle on the deep aspect. • Areas of necrosis. • Epitheloid – polygonal but mainly spindled cell-morphology with malignant cytomorphological characteristics. • Mitotic figures easily found. • Myxoid to collagenized extracellular matrix with some areas showing more of hyaline eosinophilic material. • . 14 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  15. 15 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  16. 16 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  17. Case 2 Histology • Relatively well circumscribed, non-encapsulated tumor with areas of obvious infiltration in adipose tissue and striated muscle on the deep aspect. • Areas of necrosis. • Epitheloid – polygonal but mainly spindled cell-morphology with malignant cytomorphological characteristsics. • Mitotic figures easily found. • Myxoid to collagenized extracellular matrix with some areas showing more of hyaline eosinophilic material. • . 17 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  18. 18 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  19. 19 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  20. Case 2 Immunohistochemistry • Estrogen and progesteron receptors – • Her-2 neu – • Calcitonin – • CEA – • Cytokeratin 7- • Cytokeratin 8- • Cytokeratin 18- • Cytokeratin 20- 20 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  21. Case 2, Immunohistochemistry: • Weak positive focal staining for smooth muscle actin. • Strong and diffuse staining for cytokeratin 5. • Strong and diffuse staining for cytokeratin 14. • Strong and diffuse staining for p63. • Moderately strong staining for calponin. 21 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  22. CK 5 22 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  23. CK 5 23 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  24. CK 14 24 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  25. p63 25 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  26. Calponin 26 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  27. Calponin 27 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  28. DIAGNOSIS: MYOEPITHELIAL CARCINOMA

  29. MYOEPITHELIAL CARCINOMA • Rare malignant tumor in the breast with only 27 cases reported in the literature. • None in males. • First case by Cameron et al. J Pathol, 1974. 29 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  30. MYOEPITHELIAL CARCINOMA • The term was first used in by Schurch et al. 1985 (Ultrastruct Pathol). • Malignant adenomyoepitheliomas are more frequently reported. • Largest series is a British material consisting of 6 patients with a review of all other 21 published cases, in 16 papers. Behranwala KA et al. J Cancer Surg, 2004. 30 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  31. MYOEPITHELIAL CARCINOMA Clinical features • In the British series: • Median age was 60 years (40-66). • Median follow-up was 34,5 months (14-79 mo). • Three patients developed local recurrence at 15, 38 and 50 months, respectively. • Two patients developed distant metastasis at 30 and 79 moths. • Two patients have succumbed to the disease. • All were receptor negative. 31 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  32. MYOEPITHELIAL CARCINOMA,Clinical features • The pooled data of the published cases showed: • 2 year survival rate of 88% • 5 year survival rate of 55% • Size correlates with poor clinical behaviour and tumors larger than 2 cm confer a bad prognosis 32 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  33. MYOEPITHELIAL CARCINOMAHistomorphology • Monophasic with predominantly spindle cell morphology. Some epitheloid - plasmacytoid - polygonal features but without any evidence of epithelial differentiation (i.e. tubular, glandular/acinar structures or mucinous features). • Infiltrative growth. • Easily identifiable mitotic figures. 33 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  34. MYOEPITHELIAL CARCINOMA Immunohistochemistry • Positive immune-reactivity for ”basal-type” cytokeratins 5, 14, 17 but negative reaction for ”lumen-type” cytokeratins 8, 18, 19. • Varied positivity for SMA, S-100, calponin. • Positive reaction for p63. • ER and PR negative. 34 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  35. MYOEPITHELIAL CARCINOMA Differential diagnosis • Other mammary spindle cell lesions including: • Metaplastic (sarcomatoid) carcinomas. • Spindle cell sarcoma. • Poorly differentiated myoepithelial-rich carcinoma. (Damiani and Eusebi, Histopathol, 1997) • Malignant adenomyoepithelioma. • Fibromatosis and fibromatosis-like carcinoma; myofibroblastic immunephenotype 35 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  36. MYOEPITHELIAL CARCINOMA Differential diagnosis • Immunohistochemical overlap with mammary carcinoma of basal-type. • Rakha, Ellis et al. claim to have described and defined carcinomas with both basal- and myoepithelial features (n=88). J Pathol, 2006. However, no photomicrographs are presented in the paper. (These carcinomas should not be confused with myoepithelial-rich carcinoma [Damiani and Eusebi] which were CK 8 positive.) • These carcinomas were associated with extremely poor prognosis, 10-20% 5 year survival, half of that of the group with only ”basal markers”. • However, the defining features for stratifying the cases were the immunohistochemical expression of ”basal” and ”myoepithelial” markers, respectively. Not morphology. 36 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  37. Thank you for the attention. 37 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  38. 38 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  39. 39 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  40. 40 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  41. 41 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  42. 42 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  43. 43 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  44. 44 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  45. 45 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  46. 46 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  47. 47 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

  48. 48 B.F. Petersson MD, PhD. Annual Slide Seminar, Bratislava, Slovakia, 21-23 June, 2007. Case 2

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