Spindle Cell CA SPINDLE CELL LESIONS OF THE BREAST. Mammary Spindle Cell Lesions 04/13/2017

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1 Melinda F. Lerwill, MD Massachusetts General Hospital Harvard Medical School SPINDLE CELL LESIONS OF THE BREAST Mammary Spindle Cell Lesions Spindle cell carcinoma Fibromatosis Nodular fasciitis PASH Myofibroblastoma Solitary fibrous tumor Sarcoma Spindle Cell CA 1

2 Spindle Cell Carcinoma Type of metaplastic carcinoma Probable basal cell / myoepithelial origin Average age 65 y Average size 4 cm (range <1 to >20 cm) 2

3 3

4 4

5 K903 p63 Keratin 5

6 6

7 CK7 7

8 Heterologous Differentiation AE1.3/Cam5.2 K903 8

9 p63 Immunohistochemistry of SpCC High rate of positivity Cytokeratin MNF116 Cytokeratin K903 (34 E12) Wide spectrum cytokeratin p63 Often positive Cytokeratins 5/6, 14, AE1/AE3, Cam5.2 Negative CD34 and ER, PR, Her-2 Immunohistochemical Work-up for Spindle Cell Carcinoma Multiple keratins, e.g.: Cytokeratin MNF116 Cytokeratin K903 (34 E12) Cytokeratin AE1.3/Cam5.2 p63? GATA3 +/- CD34 9

10 Low Intermediate Grading of SpCC No well-defined criteria Assess degree of atypia and mitotic activity High SpCC Local Recurrence LR Grade Carter et al Sneige et al Gobbi et al Wargotz et al /24 (13%) All 2/16 (13%) Low 8/30 (27%) Low 32/100 (32%) All 10

11 SpCC Clinical Behavior Carter MR et al. AJSP 2006;30: DISTANT METS DOD Low-grade 3/6 (50%) 2/6 (33%) Int-grade 2/8 (25%) 1/8 (13%) High-grade 6/10 (60%) 7/10 (70%) TOTAL 11/24 (46%) 10/24 (42%) Interval (median) m (12 m) 1 46 m (11.5 m) Low-Grade SpCC Behavior DISTANT METS DOD Carter et al Sneige et al Gobbi et al /6 (50%) 2/6 (33%) 2/16 (13%) 2/16 (13%) 0/30 (0%) 0/30 (0%) DDx of Spindle Cell Neoplasms in the Breast 1. Spindle cell carcinoma 2. Phyllodes tumor with stromal overgrowth 3. Mesenchymal neoplasms: Fibromatosis Nodular fasciitis (rare) Primary sarcoma (rare) 11

12 Fibromatosis Mammary Fibromatosis Age range y Most common y Tumor size <1-17 cm, average 3 cm Usually sporadic Minority associated with FAP Minority associated with breast implants Approximately ¼ recur locally after excision 12

13 13

14 β-catenin: Nuclear Positivity Nuclear β-catenin Mammary fibromatosis Spindle cell carcinoma 83% 23% Phyllodes tumors 72-87% Fibroadenoma % Other non-fibromatosis spindle cell lesions 5-30% Nuclear Β-catenin in mammary fibromatosis 14

15 Nodular Fasciitis Nodular fasciitis 15

16 Spindle Cell CA Top 10 Differential Diagnoses 1. Spindle cell carcinoma! 2. Spindle cell carcinoma! 3. Spindle cell carcinoma! 4. Spindle cell carcinoma! 5. Spindle cell carcinoma! 6. Spindle cell carcinoma! 7. Spindle cell carcinoma! 8. Spindle cell carcinoma! 9. Spindle cell carcinoma! 10.Spindle cell carcinoma! Keratin AE1/AE3-positive spindle cells can be seen in nodular fasciitis but only rare cells were positive 16

17 22 yo female 1.1 cm palpable breast mass Core bx: c/w nodular fasciitis Resolved 1 month after core bx D-FISH showing juxtaposition of USP6 and MYH9 loci 3 USP6: green 5 MYH9: orange Figure 3b Pseudoangiomatous Stromal Hyperplasia 17

18 18

19 Typical Fascicular Cellular Myoid 19

20 CD34 Tumoral PASH Management Recommended therapy: Wide local excision Local recurrence in ~15% Core biopsy caveats: Other neoplasms may have PASH-like areas (e.g., phyllodes tumor) PASH may be incidental and not the targeted lesion Small number of reported patients (n=80) have undergone observation after core dx of PASH 77.5% stable / 17.5% progression / 5% regression Myofibroblastoma 20

21 Myofibroblastoma M = F Mean age: 7 th decade y Only exceptionally seen in younger patients Avg size 2 cm Smaller tumors often detected on screening mammography Slow-growing solitary mass Very rare multifocal or bilateral cases 21

22 CD34 MFB Immunohistochemistry Desmin Typically + for: CD34 Vimentin Muscle Actin SMA Calponin Desmin CD10 22

23 MFB-Related Neoplasms Loss of 13q14 (RB1, FOXO1 region): Mammary myofibroblastoma Extramammary myofibroblastoma Spindle cell lipoma Cellular angiofibroma Mammary Myofibroblastoma Myofibroblastomas show frequent loss of Rb expression by immunohistochemistry Figure 2 Chen BJ et al. Loss of retinoblastoma protein expression in spindle cell/pleomorphic lipomas and cytogenetically related tumors. AJSP 2012;36: Cellular 23

24 Epithelioid 24

25 CD34 Desmin Keratin 25

26 Collagenized Myxoid Cartilaginous Metaplasia 26

27 Myofibroblastoma Variants Cellular Collagenized / Fibrous Infiltrative Epithelioid Deciduoid Myoid Myxoid Palisaded Cellular Myofibroblastoma 27

28 AE1.3 CK5/6 p63 CD34 Solitary Fibrous Tumor 28

29 NAB2-STAT6 gene fusion STAT6 nuclear localization in solitary fibrous tumor STAT6 rabbit monoclonal antibody is a robust diagnostic tool for the distinction of solitary fibrous tumour from its mimics. Cheah AL et al. Pathology 2014;46(5): STAT6 in Mammary SFT Sarcoma Post-XRT Angiosarcoma 29

30 Post-XRT Sarcoma Leiomyosarcoma Pleomorphic Liposarcoma 30

31 DDx of Mammary Sarcoma Metaplastic carcinoma Phyllodes tumor Primary sarcoma Post-XRT Angiosarcoma Other Sporadic Metastasis Post-radiation Angiosarcoma IMMUNOHISTOCHEMISTRY 31

32 SPINDLE CELL LESIONS Integral Epithelial Component or Differentiation? YES Spindle cell CA Neoplastic epithelium Phyllodes tumor Non-neoplastic epithelium NO Mesenchymal lesions Thorough sampling Immuno panel 32

33 33

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