57th Annual HSCP Spring Symposium 4/16/2016
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1 An Unusual Malignant Spindle Cell Lesion to Involve the Breast Erinn Downs-Kelly, D.O. Associate Professor of Pathology University of Utah & ARUP Laboratories No disclosures Case 39 y/o female with no significant past medical history presented with a 1.5 cm palpable, self discovered left breast mass Admits lesion has been present for at least a year Imaging including mammography and ultrasound showed irregular shape, spiculated margins, and posterior acoustic shadowing Initial ultrasound guided core needle biopsy performed elsewhere showed the following: Erinn Downs Kelly, DO 1
2 Initial core needle biopsy CK AE1/AE3 Impressions from the core needle biopsy Cellular malignant spindle cell neoplasm with focal cytokeratin AE1/3 immunoreactivity Negative for expression of myoepithelial, muscle specific, neural or melanocytic, vascular and myofibroblastic markers Metaplastic carcinoma??? Erinn Downs Kelly, DO 2
3 Malignant spindle cell lesions of the breast Metaplastic carcinoma Low grade fibromatosis-like spindle cell carcinoma Spindle cell type (sarcomatoid carcinoma) Myoepithelial carcinoma Primary sarcomas of the breast Stromal component of a malignant phyllodes tumor Metastatic lesions Malignant melanoma Sarcomas Poorly differentiated carcinoma Metaplastic carcinoma 2012 WHO Classification of Tumours of the Breast Characterized by differentiation of neoplastic epithelium into squamous cells and/or mesenchymal appearing components Spindle, chondroid, osseous and rhabdomyoid Purely composed of metaplastic elements or admixture of identifiable carcinomatous component an metaplastic elements Low-grade (fibromatosis-like) spindle cell carcinoma Spindle cell carcinoma (sarcomatoid carcinoma) Metaplastic carcinoma with osteoclastic giant cells Squamous cell carcinoma Low grade adenosquamous carcinoma Carcinoma with mesenchymal differentiation Chondroid Osseous Other mesenchymal differentiation Myoepithelial carcinoma Metaplastic carcinoma Account for <5% of invasive breast malignancies Any spindle cell lesion of the breast raises the possibility of a metaplastic carcinoma Panel of cytokeratin AE1/3, 34βE12, Cam5.2, cytokeratins 7 and 14, MNF116 p63 Typically ER, PgR and HER2 - Well circumscribed, palpable Rapid growth Imaging can be suggestive of a benign process Yang et al compared metaplastic carcinomas and invasive ductal carcinomas via mammography and US Malignant imaging features such as irregular shape, spiculated margins, and posterior acoustic shadowing are uncommon in metaplastic carcinoma Tended to show more benign imaging features like round or oval shape with circumscribed margins Yang et al. AJR Am J Roentgenol Dec;189(6): Erinn Downs Kelly, DO 3
4 Low-grade fibromatosis-like spindle cell carcinoma Hypocellular spindle cell lesion with short fascicles and admixed dense collagen bundles Adjacent lymphoid aggregate Overall bland cytology of the spindle cells without mitotic activity Low-grade fibromatosis-like spindle cell carcinoma Low-grade fibromatosis-like spindle cell carcinoma Cytokeratin positive - broad panel p63 positive Nuclear β catenin+/- Erinn Downs Kelly, DO 4
5 Spindle cell carcinoma (Sarcomatoid carcinoma) Microscopic findings Atypical spindle cells arranged in varied patterns Fascicles with a herringbone appearance or storiform Nuclear pleomorphism is usually moderate to high Frequent mitotic figures May entrap breast epithelium at the leading edge Carter et al. Am J Surg Pathol. 2006; 30: Davis et al. Am J Surg Pathol. 2005;29: Erinn Downs Kelly, DO 5
6 Spindle cell carcinoma Focal area of glandular differentiation Metaplastic carcinoma: IHC pitfall When first evaluated in metaplastic carcinoma and phyllodes, p63 appeared sensitive and highly specific for metaplastic carcinoma Koker et al: 189 invasive breast carcinomas (15 metaplastic carcinomas, 10 phyllodes tumors and 5 sarcomas of the breast) p63 was strongly expressed in 13 of 15 metaplastic carcinomas (86.7%); phyllodes tumors and sarcomas were negative for p63 expression Sensitivity and specificity of 86.7% and 99.4%, respectively More recently, Cimino-Mathews et al identified expression of focal p63, p40, and cytokeratin (AE1/AE3, Cam5.2, 34βE12) in malignant PT but not in borderline or benign PT Koker MM and Kleer, CG. Am J Surg Pathol Nov;28(11): Cimino-Mathews, A. et al. Am J Surg Pathol 2014;38: Primary Sarcoma of the Breast Before diagnosing a primary sarcoma of the breast, consider and exclude Metaplastic carcinoma: IHC and extensive tumor sampling to exclude in situ or invasive carcinoma Heterologous sarcomatous elements in phyllodes tumor (PT) can be prominent and the epithelial components can be relatively inconspicuous Metastasis? Primary sarcomas Arise from interlobular mesenchymal elements Subclassified according to their growth patterns and histiogenesis Most common primary sarcoma of the breast is angiosarcoma, followed by liposarcoma, leiomyosarcoma, pleomorphic undifferentiated sarcoma Erinn Downs Kelly, DO 6
7 Primary sarcoma Very rare, SEER data reports the annual incidence as 4.6 cases per 1,000,000 women Previous history of radiation increases the risk for development of angiosarcoma and pleomorphic undifferentiated sarcoma Complete excision is crucial for treatment Presence of residual disease after initial treatment had a 10 year probability of local control and of disease free survival of 0% Metastases Involving Breast Clinical history is key Most common entities to metastasize to the breast: Malignant melanoma Lung and ovary Breast metastasis may be the first sign of malignancy in roughly 30% of cases Propensity for rhabdomyosarcoma, in adolescents, to metastasize to breast 2.5 cm breast mass in 15 year old female with no past medical history 21 Courtesy of Dr. David Hicks Myogenin Erinn Downs Kelly, DO 7
8 3 cm breast mass in a 58 year old female with a history of metastatic leiomyosarcoma to the lung H-caldesmon Back to our case Lumpectomy and Sentinel Lymph Node Biopsy 1.5 cm ill defined mass with marker clip Mass and surrounding tissue entirely submitted > 1 cm to all margins Two sentinel lymph nodes negative for malignancy Erinn Downs Kelly, DO 8
9 Erinn Downs Kelly, DO 9
10 Not Adding Up No recognizable in situ or conventional invasive epithelial component Entrapped benign epithelium at the leading edge Some spindle cell carcinomas may be purely spindled Lesion had been present for at least a year Imaging was not characteristic of a metaplastic carcinoma Cytomorphology is uniform IHC: p63 (-) FISH for SS18 Rearrangement SS18 (18q11) Break-Apart Probe Rearranged SS18 signal Normal fused SS18 signal Synovial Sarcoma (SS) SS account for roughly 10% of all soft tissue sarcomas t(x;18;p11;q11) translocation SS18-SSX1, SS18-SSX2, SS18-SSX4 Typically arise in the para-articular regions in adolescents and young adults Less commonly arise in the trunk, abdomen, head and neck Histologic variety: biphasic, monophasic and poorly differentiated Biphasic tumors contain both epithelioid cells arranged in glandular structures and spindle cells Monophasic types are entirely composed of spindle cells Poorly differentiated usually have a large epithelioid cell appearance Small cell variant and a high-grade spindle cell variant Erinn Downs Kelly, DO 10
11 Synovial Sarcoma (SS) Cytokeratin 7, 8/18, 19 (expressed in spindled and epithelioid components) AE1/AE3 (expressed in spindled and epithelioid components) EMA (expressed in spindled and epithelioid components) CEA, bcl-2 (expressed in spindled and epithelioid components) TLE1 (97%) Synovial Sarcoma of the Breast Primary SS: Rare case reports supported by either evidence of SS18 rearrangement or evidence of the fusion transcripts SS18-SSX1 or SS18-SSX2 Metastatic SS to breast: Rare case reports with the identification of SS in the breast leading to the identification of the primary (lung) and extremity Tormo V, et al Clin Transl Oncol 2009 Dec;11(12):854-5 Doyle VJ, et al BMJ Case Rep 2013 Jun 19;2013 Sobande F, et al Breast J Jul-Aug;17(4):418-9 Kijima Y, et al Surg Today 2007;37(3):230-3 Follow up for Our Patient Synovial Sarcoma, Monophasic pt1a FNCLCC grade 2 SS18-SSX2 transcript and SS18 rearrangement identified Work up to exclude the possibility that this was a metastasis Staging with PET/CT 1.9 years status post resection with widely negative margins No evidence of distant metastatic disease NCCN Sarcoma Guidelines Erinn Downs Kelly, DO 11
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