An Unusual Malignant Spindle Cell Lesion to Involve the Breast - HSCP 2016.pdf · – Sensitivity and specificity of 86.7% and 99.4%, respectively • More recently, Cimino-Mathews

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:



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???



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



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


Cytokeratin positive- broad panel

p63 positive

Nuclear β catenin+/-




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



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



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

21

2.5 cm breast mass in 15 year old female with no past medical history

MyogeninCourtesy of Dr. David Hicks



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



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



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

Documents

An Unusual Malignant Spindle Cell Lesion to Involve the Breast - HSCP 2016.pdf · – Sensitivity and specificity of 86.7% and 99.4%, respectively • More recently, Cimino-Mathews