1. Session 4. Biopsies. Professor Sarah Pinder

2. Case A - SP08-9685

17. Diagnosis - Angiosarcoma. 5 years after radiotherapy for breast carcinoma in wide local excision

18. Angiosarcoma Majority of angiosarcomas negative for CKs but epithelioid areas may stain positively in up to 35% of cases Conversely, less than 2% stain of breast carcinomas positive for CD31 and CD34 Macias-Martinez V. Am J Surg Pathol 1997;21:599-604 Meis-Kindblom JM. Am J Surg Pathol 1998;22:683-697

27. Infiltrative margins Nests, cords & strands of epithelioid tumour cells within a myxohyaline stroma Epithelioid cells show prominent intracytoplasmic vacuolisation, occasionally containing erythrocytes IHC profile may suggest carcinoma - CK 7 +ve and CK 18 +ve, but express vascular antigens (CD31, CD34 & Factor VIII) Also negative for high molecular weight cytokeratins, e.g. CK 14, characteristic feature of metaplastic breast carcinoma Epithelioid haemangioendothelioma

28. Case B - Core 08/261

45. Diagnosis - Seeding of epithelial cells after previous core biopsy of papillary lesion

46. Seeding of Malignant Cells After core biopsy Harter. Radiology. 1992;185;713-4 May be relatively common 2 out of 47 consecutive cases Grabau. Eur J Surg Oncol. 1993;19;192-4 Uncertain significance Benign and malignant epithelial displacement also noted after FNA and other needling procedures Youngson. Am J Clin Pathol 1995;103;598-602 Youngson. Am J Surg Pathol 1994;18;896-903

47. Epithelial displacement in breast lesions 53 cases of epithelial cell displacement US core (24 cases), mammotome core (16), FNAC (8), anaesthetic injection (3), suture placement (5) & wire localization (1) Displacement of epithelial cells occurred in biopsy tract (42 cases), lymphatic channels (5), both (4), breast stroma (2) Diagnoses included intraductal papilloma (6 cases), DCIS (45; 15 with invasive carcinoma), 2 pure invasive carcinoma Except in 3 cases, associated with underlying papillary lesion Nagi C. Arch Pathol Lab Med. 2005;129:1465-9

48. Malignant Cell Displacement 352 cancer excisions Tumour cell displacement in 32% patients after large- gauge needle core biopsy 76 cases displacement of 1 or 2 clusters, 38 cases displacement of multiple fragments Incidence & amount inversely related to interval between core & excision 42% of patients with interval of <15 days 31% of patients with interval of 15-28 days 15% of tumours excised >28 days after core Diaz LK. AJR Am J Roentgenol. 1999;173:1303-13

49. Case C - (1) Core biopsy - SP08-8208 (2) Excision - SP08-10287

60. Diagnosis - Phyllodes tumour with liposarcoma

62. Features of phyllodes tumours and fibroadenomas in core biopsy 12 features in previous core biopsy specimens of 36 excised phyllodes tumours & 38 excised fibroadenomas 4 features significantly more common in cores from phyllodes tumours & had a kappa statistic of > 0.6: –stromal cellularity increased in at least 50% compared with typical fibroadenoma –stromal overgrowth (x10 field with no epithelium) –fragmentation –adipose tissue within stroma Lee AHS et al. Histopathol. 2007;51:336-44

63. Needle Core Biopsy Reporting Combination of architectural & stromal features Mild increase in stromal cellularity alone insufficient for definitive diagnosis of PT Report as “fibroepithelial lesion” if cannot be certain whether represents cellular FA or benign PT on core Fibroadenoma (FA) or Phyllodes Tumour (PT)?

64. C2 = Excision

70. Case D - SP08-4462

80. ER

83. Diagnosis - Metastatic lung carcinoma

84. Metastases to Breast Usually manifestation of disseminated disease Average interval from primary to breast secondary, about 2 years Breast lesion is initial sign of tumour in about 25% Generally poor prognosis

85. Metastases to breast - common sites of origin Malignant melanoma87 Lung78 Ovary50 Prostate39 Kidney24 Stomach15 Ileum13 Alva & Shetty-Alva 1999 Lymphoma

86. Metastatic Carcinoma to the Breast 18 cases in 10 yrs at Nottingham City Hospital* – Lung: 5 – Ovary: 5 – Melanoma: 4 – Thyroid: 1 – Kidney: 1 – Oesophagus: 1 – (Prostate: 1) *Lee AHS. J Clin Pathol 2007; 60: 1333-1341

87. How to reach a correct diagnosis H & E - Unusual histological pattern (does not look like NST, lobular, tubular, mucinous, etc) No DCIS or LCIS ER negative (mostly) Clinical history & mammogram Immunohistochemistry Ck 7 and 20 TTF-1 WT1 HMB45 CD20 GCDFP-15 Chromogranin, CD10, CD56

88. Consider metastasis if morphology is not typical for primary carcinoma Compare with primary Immunohistochemistry

93. CK7

94. TTF1

95. Case E - (1) & 2 (2) SP08-9657 5cm mass in breast of 80 year old woman

103. Diagnosis? Received as second opinion. Diagnosed as grade 1 invasive breast carcinoma.

104. E2 = Excision

114. Diagnosis? IHC?

116. ER

118. Diagnosis ?

119. ?Microglandular adenosis ?Atypical microglandular adenosis ?Invasive carcinoma in microglandular adenosis ?Combination of the above

120. Atypical Microglandular Adenosis 108 cases at M.D. Anderson between 1983 and 2007 that had diagnosis of MGA 65 had available material for review Inclusion criteria were glands of MGA expressing S- 100 protein and lacking myoepithelial layer 11 out of 65 qualified to have an MGA component; myoepithelial layer detected in remaining 54 cases which were classified as adenosis 3 of 11 had uncomplicated MGA, 2 had AMGA, 6 had MGACA Khalifeh IM et al. Am J Surg Pathol. 2008;32:544-52

121. Carcinoma in AMGA Multiple invasive components in the MGACA cases All had a duct-forming component; basal-like component in 2 cases, acinic-like in 2, matrix producing in 4, sarcomatoid in 1, adenoid cystic in 1 All strong and diffuse CK8/18 & EGFR expression but no ER, PR or HER2, or CK5/6 Ki-67 and p53 labelling indices was 30% in MGACAs 2 out of 6 MGACA cases developed metastasis and died of disease Khalifeh IM et al. Am J Surg Pathol. 2008;32:544-52

122. Carcinoma in MGA Memorial Sloan-Kettering Cancer Center Breast carcinoma arose in or in conjunction with microglandular adenosis (MGA) in 14 of 60 (23%) Carcinoma in the MGA in 13 patients In situ carcinoma in expanded MGA glands composed of cells with vesicular poorly differentiated nuclei When it arose in MGA, basement membranes present in benign MGA and in situ carcinoma but tended to be disrupted in invasive foci Strong immunoreactivity for cytokeratin, S-100 & cathepsin D in carcinomas 2 PR positive, 1 ER positive, 1 HER2 positive, 4 p53 protein positive James BA, Cranor ML, Rosen PP. Am J Clin Pathol. 1993;100:507-13

125. Collagen IV

126. Diagnosis - “Typical” and atypical microglandular adenosis. No invasive carcinoma.