an unusual malignant spindle cell lesion to involve the breast - hscp 2016.pdf · – sensitivity...
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 1
An Unusual Malignant Spindle Cell Lesion to Involve the Breast
Erinn Downs-Kelly, D.O.Associate Professor of PathologyUniversity 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:
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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???
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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
• 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 (sarcomatoidcarcinoma)
• 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
Metaplastic carcinoma
• Account for
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 4
Hypocellular spindle cell lesion with short fascicles and admixed dense collagen bundles
Adjacent lymphoid aggregate
Low-grade fibromatosis-like spindle cell carcinoma
Overall bland cytology of the spindle cells without mitotic activity
Low-grade fibromatosis-like spindle cell carcinoma
Cytokeratin positive- broad panel
p63 positive
Nuclear β catenin+/-
Low-grade fibromatosis-like spindle cell carcinoma
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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; 30:300-309Davis et al. Am J Surg Pathol. 2005;29:1456-1463
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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. 2004 Nov;28(11):1506-12.Cimino-Mathews, A. et al. Am J Surg Pathol 2014;38:1689–1696.
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
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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
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2.5 cm breast mass in 15 year old female with no past medical history
MyogeninCourtesy of Dr. David Hicks
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 9
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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 RearrangementSS18 (18q11) – Break-Apart Probe
Normal fused SS18 signal
Rearranged 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
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57th Annual HSCP Spring Symposium 4/16/2016
Erinn Downs‐Kelly, DO 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):854-5Doyle VJ, et al BMJ Case Rep 2013 Jun 19;2013Sobande F, et al Breast J. 2011 Jul-Aug;17(4):418-9Kijima 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