Diagnosis of Fibroepithelial and Mesenchymal Lesions on Core Needle Biopsy

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1 Diagnosis of Fibroepithelial and Mesenchymal Lesions on Core Needle Biopsy Emmanuel Agosto-Arroyo, MD Assistant Member Department of Anatomic Pathology 3/3/2018

2 Disclosure There are no conflicts of interest.

3 Objectives Describe the pathologic characteristics of the most common fibroepithelial lesions diagnosed on core needle biopsy (CNB). Describe the pathologic characteristics of the most common mesenchymal lesions diagnosed on CNB. Discuss possible diagnostic challenges.

4 Agenda Fibroadenoma Phyllodes Tumors Pseudoangiomatous stromal hyperplasia Hamartomas Myofibroblastoma Fibromatosis Vascular Lesions

5 Fibroadenoma Benign tumors arising from the terminal duct lobular unit (TDLU) Most common breast tumors in adolescent and young women Childhood -> 70 years Painless, firm or rubbery Well-circumscribed

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7 Fibroadenoma Several terms have been used to subclassify FAs >90% of FAs are of the adult/usual type Immunohistochemistry (IHC): ER-α + epithelium ER-B stroma PR + stroma Actin & CD34 +/- B-catenin positivity has been reported

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10 Fibroadenoma Rarely poses a challenge on CNB diagnosis.

11 Phyllodes Tumor 6-86 (41.7) years Solitary, unilateral masses Coexistent FAs are found histologically in ~40% of cases Isolated examples described in men Diagnosis of PT favored if: > 4 cm Rapid growth

12 Phyllodes Tumor Heterogeneous histology Elongated epitheliallined clefts is a defining feature Geographic peninsula Expansion and increased stromal cellularity

13 Phyllodes Tumor Stromal overgrowth Absence of an epithelial component in at least one microscopic field at 40 total magnification Stromal expansion Absence of epithelium in at least one microscopic field at final 100 magnification Use of these parameters has intrinsic limitations Provides a useful and practical tool for evaluation

14 Histological Feature Fibroadenoma Benign PT Borderline PT Malignant PT Tumor border Well defined Well defined Well defined, may be focally permeative Permeative Stromal cellularity Variable, scanty to variably cellular, usually uniform Cellular, usually mild, may be non-uniform or diffuse Cellular, usually moderate, may be non-uniform or diffuse Cellular, usually marked and diffuse Stromal atypia None Mild or none Mild or moderate Marked Mitotic activity Usually none, rarely low Usually few (<5/10HPF) Usually frequent (5-9/10HPF) Usually few ( 10/10HPF) Stromal overgrowth Malignant heterologous elements Distribution relative to all breast tumors Relative proportion of all PTs Absent Absent Absent or very focal Often present Absent Absent Absent May be present Common Uncommon Rare Rare % 15-20% 10-20%

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19 Phyllodes Tumor Epithelial nuclear atypia is marked in 9% PTs ADH~ 1.5% ALH, DCIS & LCIS ~ 0.03% Invasive carcinoma in PTs is infrequent

20 Actin & desmin +/- CD34+ CKs focally + p53 + P63 & p40 ER/PR HER2 AR < 5% CD117 ~6% Phyllodes Tumor Benign (%) Borderline (%) Malignant (%) CD ER epithelial p

21 CNB diagnosis? 100 X

22 Fibroepithelial Lesions on CNB Excision should be recommended when features are suggestive of PT: > 2 mitosis/ 10 HPF stromal cellularity Stromal overgrowth Infiltrative borders Tissue fragmentation

23 Pseudoangiomatous Stromal Hyperplasia Myofibroblastic proliferation Driven by hormonal imbalances Contraceptives use Well circumscribed, nonencapsulated nodules

24 Pseudoangiomatous Stromal Hyperplasia No necrosis or fat infiltration PR, actin, desmin and calponin +/ % recurrence rate

25 Hamartoma 4.8% breast tumors Well demarcated, encapsulated Difficult to distinguish on CNB

26 Women and men years Wide morphological spectrum Metaplasias can be observed Desmin & CD34 + SMA, BCL2, CD99, CD10, ER, PR and AR +/- Myofibroblastoma

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28 Fibromatosis Locally infiltrative lesion Fibroblasts/myofibroblasts Pectoral fascia & breast parenchyma Previous trauma and surgery (implants) Poorly circumscribed

29 Fibromatosis

30 Fibromatosis B-Catenin + CK CD34 - Myofibroblastoma CD34 + Phyllodes Tumor B-Catenin +/- CK +/ CD34 +/- p63 +/- Metaplastic Carcinoma B-Catenin +/- CK +/ P63 +/-

31 Vascular Lesions Entity Size (cm) Borders Intralobular Distribution Papillary Endothelial Proliferation Anastomosis Hyperchromatic Nuclei Mitosis Perilobular Hemangioma Circumscribed Possible Absent Absent Rare No Hemangioma Circumscribed Absent Present Rare Rare No Angiomatosis 9-11 Irregular Absent Absent Rare Absent No Angiosarcoma Irregular Present Present Present Present Present Hoda SA, et al. Rosen s Breast Pathology. (4 th Ed).

32 Angiosarcoma Angiosarcoma Sporadic Secondary 2 nd most common mesenchymal neoplasm in breast 0.05% breast malignancies (median: 40) years Latent interval (mean 84) months 0.1% incidence (median: 70) years MYC Amplification

33 Angiosarcoma Histologic Features Grade Low Intermediate High Breast Parenchyma Involvement Present Present Present Anastomosing Channels Present Present Present Hyperchromatic Nuclei Present Present Present Endothelial Tufting Minimal Present Prominent Papillary Hyperplasia Focally Present Focally present Present Solid/Spindle cell foci Absent Absent/minimal Present Mitosis Absent/rare Present Present Blood Lakes Absent Absent Present Necrosis Absent Absent Present Hoda SA, et al. Rosen s Breast Pathology. (4 th Ed).

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35 References 1. Ashutosh N, Virendra K, Attri PC, Arati S. Giant male fibroadenoma: A rare benign lesion. Indian J Surg 2013;75: Bae SY, Choi MY, Cho DH, et al. Large clinical experience of primary angiosarcoma of the breast in a single Korean medical institute. World J Surg 2011;35: Dabbs DJ. (2012). Breast Pathology. Philadelphia, PA. Elsevier-Saunders. 4. Hoda SA, Brogi E, Koerner FC & Rosen PP. (2014). Rosen s Breast Pathology (4 th Ed.). Philadelphia, PA. Wolters Kluwer. 5. Hoda SA, Brogi E, Koerner FC & Rosen PP. (2017). Rosen s Diagnosis of Breast Pathology by Needle Core Biopsy (4 th Ed.). Philadelphia, PA. Wolters Kluwer. 6. Hodgson NC, Bowen-Wells C, Moffat F, et al. Angiosarcomas of the breast: a review of 70 cases. Am J Clin Oncol 2007;30: Hui A, Henderson M, Speakman D, et al. Angiosarcoma of the breast: a difficult surgical challenge. Breast 2012;21: Kalyani R, Srinivas V, Veda P. Vulval fibroadenoma- A report of two cases with review of literature. Int J Biomed Sci;10(2): Lakhani SR, Ellis IO, Schnitt SJ, et al. (2012). WHO Classification of Tumours of the Breast (4 th Ed.). Lyon, France. IARC Press. 10. Morgan PB, Chundru S, Hatch SS, et al. Uncommon malignancies: case 1. Low-grade myofibroblastic sarcoma of the breast. J Clin Oncol 2005;23: Oi RH, Dobbs M. Lactating breast tissue in benign cystic teratoma. Am J Obstet Gynecol 1978;130: Rosen PP, Kimmel M, Ernsberger D. Mammary angiosarcoma. The prog-nostic significance of tumor differentiation. Cancer 1988;62: Scow JS, Reynolds CA, Degnim AC, et al. Primary and secondary angiosarcoma of the breast: the Mayo Clinic experience. J Surg Oncol 2010;101: Wijnmaalen A, van Ooijen B, van Geel BN, et al. Angiosarcoma of the breast following lumpectomy, axillary lymph node dissection, and radiotherapy for primary breast cancer: three case reports and a review of the literature. Int J Radiat Oncol Biol Phys 1993;26: Wiratkapun C, Piyapan P, Lertsithichai, et al. Fibroadenoma versus phyllodes tumor: distinguishing factors in patients diagnosed with fibroepithelial lesions after a core needle biopsy. Diagn Interv Radiol. 2014;20(1):27-33.