Session 4. Biopsies. Professor Sarah Pinder. Case A - SP08-9685

Session 4.

Biopsies.

Professor Sarah Pinder

Case A - SP08-9685

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Diagnosis - Angiosarcoma.

5 years after radiotherapy for breast carcinoma in wide local

excision





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





































• 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

Case B - Core 08/261





































































Diagnosis - Seeding of epithelial cells after

previous core biopsy of papillary lesion





Seeding of Malignant CellsAfter 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





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





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

Case C -(1) Core biopsy - SP08-8208

(2) Excision - SP08-10287













































Diagnosis - Phyllodes tumour with

liposarcoma









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





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)?

C2 = Excision





















Case D - SP08-4462









































ER









Diagnosis - Metastatic lung carcinoma





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





Metastases to breast - common sites of origin

• Malignant melanoma 87

• Lung 78

• Ovary 50

• Prostate 39

• Kidney 24

• Stomach 15

• Ileum 13

Alva & Shetty-Alva 1999

Lymphoma





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





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





•Consider metastasis if morphology is not typical for primary carcinoma

•Compare with primary

• Immunohistochemistry





















CK7





TTF1

Case E - (1) & 2 (2) SP08-9657

5cm mass in breast of 80 year old woman

































Diagnosis?

Received as second opinion.

Diagnosed as grade 1 invasive breast carcinoma.

E2 = Excision









































Diagnosis?

IHC?









ER









Diagnosis ?





?Microglandular adenosis

?Atypical microglandular adenosis

?Invasive carcinoma in microglandular adenosis

?Combination of the above





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





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 < 3% in all MGAs, 5% to 10% in the AMGAs and > 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





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













Collagen IV





Diagnosis - “Typical” and atypical

microglandular adenosis.No invasive carcinoma.

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Session 4. Biopsies. Professor Sarah Pinder. Case A - SP08-9685