Spindle Cell Lesions Of The Breast. Emad Rakha Professor of Breast Pathology and Consultant Pathologist
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1 Spindle Cell Lesions Of The Breast Emad Rakha Professor of Breast Pathology and Consultant Pathologist
2 * SCLs comprise a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours * Overlapping clinical and morphological features, making accurate diagnosis a challenging task, particularly in biopsies * Important to maintain a wide differential diagnosis * All SCLs occurring in the soft tissue and skin can happen in the breast in addition to breast specific SCL
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4 Spindle cell breast lesions Spindle cells of MBC Spindle cell DCIS Spindle cells SPC Spindle cells of UDH Myoepithelial cell Spindle cell adenomyoepithelioma Myoepithelial carcinoma Mesenchymal cell Fibrous scar Fibromatosis, PASH Myofibroblastoma Nodular Fasciitis SFT and SC lipoma Reactive SC nodule Neural / muscle lesions Vascular lesions Sarcoma Others: Spindle cell component of fibroepithelial lesions, DFSP, SC melanoma and metastatic Spindle cell carcinoma
5 Diagnosis of Breast SCL: Approach * Cytonuclear atypia: Low grade (bland) Vs high grade (malignant looking) * Cellularity: low, moderate, or high * Component cells: Pure spindle cells, or mixed with other cells * Growth pattern: Fascicular, storiform, diffuse, or whirling * Margins: infiltrating or well defined * Immunohistochemistry (IHC) * Other features: Such as presence of necrosis, associated lesions, entrapped normal tissue, location, patient age
6 Low grade (bland-looking) Fibrous scar Fibromatosis Myofibroblastoma PASH Reactive spindle cell nodule Nodular Fasciitis, IMT Benign neural lesions DFSP Fibromatosis-like metaplastic carcinoma Benign/borderline phyllodes tumours (stroma) Myofibroblasts High grade (malignant-looking) SC metaplastic carcinoma Malignant phyllodes tumour Sarcoma Metastases /melanoma
7 Fibrous scar More common than other SCLs of the breast Tissue injury (history of prior instrumentation biopsy, surgery) Histological appearance depends on the elapsed time between injury and microscopy Early: Granulation, fat necrosis, hemosiderin deposition some fibrosis, Late: fibrosis and sclerosis
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9 Late
10 Myofibroblastoma Benign myofibroblastic neoplasm Genetically related to spindle cell lipoma & solitary fibrous tumour (monosomy 13q, 16q) Positive expression for CD34, ER, desmin, SMA, caldesmon, vimentin, Bcl2 and CD99. Negative: CKs, S100 and p63, RB, STAT6 Hormone receptor positivity may lead to resemblance of invasive lobular carcinoma (epithelioid variant)
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13 Epithelioiid
14 Myogenic differentiation Fat component Hemangiopericytomatous pattern
15 CD34 ACTIN desmin ER
16 Pleomorphic Myofibroblastoma Histological variants Classic Collagenous Cellular Infiltrative (DD: MBC) Myxoid Epithelioid (DD: ILC)
17 25-50 years old Fibromatosis Palpable mass or suspicious mammographic lesion mimics breast malignancy Can arise within the breast or chest wall Locally aggressive but non-metastasizing lesion composed of fibroblasts and myofibroblasts. May arise in patients with familial adenomatous polyposis, Gardner s syndrome
18 Fibromatosis Average size 2 to 4 cm Entraps fat and epithelial structures Variably low cellularity, Variably scant mitoses Bland tapering nuclei and little pink cytoplasm Long fascicles, thick bands of collagen Thin-walled venules, Lymphoid infiltrates perivascular and peripheral
19 Infiltrative margins
20 Entrapped parenchyma
21 Fascicular pattern Spaced nuclei
22 Collagenised areas
23 Immunohistochemistry Beta catenin 80% (nuclear) CD 34 negative CKs, p63, S100 and desmin- negative + CTNNB1 mutations in ~70% CD34 Beta-catenin
24 Low grade spindle cell metaplastic breast carcinoma (Fibromatosis-like) Radiologically spiculated or well-defined Low grade SCL resembling fibromatosis Slender/wavy nuclei. Atypia: mild/focal. Low mitotic activity Stroma usually shows regressive changes at least focally (hyalinization, myxoid degeneration and inflammatory infiltrate). +/- Scattered epithelioid/glandular elements (cords/clusters)
25 Low-grade spindle cell metaplastic breast carcinoma (Fibromatosis-like) May disclose focal squamous differentiation Expresses epithelial diff markers: keratins (HMWCKs and to less extent LMWCKs) and p63. Triple negative phenotype, CD34 negative May be associated with papilloma and radial sclerosing lesion Diagnosis change management either on core biopsy or excision: SLN biopsy. Complete excision +/- radiotherapy
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30 CK7 CK14 p63
31 P63 MNF116
32 Low grade Fibromatosis-like MBC Excellent prognosis despite being a variant of triple negative metaplastic carcinoma (LOW GRADE) Local recurrence can occur Metastases are very infrequent Low genomic instability compared to other metaplastic carcinomas
33 Fibromatosis like MBC is not high grade
34 Translocation t(17;22) / MYH9-USP6 gene fusion Nodular fasciitis Young adults, Small (<4 cm) More often occurs in the subcutis and deeper in the chest wall. Rare in the breast parenchyma. Rapid growth, may be painful / tender Self-limited clonal proliferation of fibroblasts and myofibroblasts Spontaneous regression without recurrent potential
35 IHC: Actin Nodular fasciitis Well-defined non-encapsulated but can be infiltrative Can be cellular with mitoses (no atypical mitosis) Plump stellate myofibroblasts in small whorls or fascicles and in loose matrix (tissue culture appearance) Red cell extravasation, may be mxoid or fibrotic No significant atypia or necrosis. No entrapped parenchyma or epithelioid structures
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38 RBC Tissue culture SMA
39 MBC NF
40 Pseudoangiomatous stromal hyperplasia (PASH)
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43 CD34
44 AE1/AE3
45 Benign neural tumours Schwannoma, neurofibroma Usually encountered in the skin of the breast May present as a breast lump S100+ Schwannoma
46 Dermatofibrosarcoma protuberans Arises in dermal skin Sometimes may not manifest skin changes, presenting as a primary breast mass Translocation t(17;22), COL1A1 / PDGFB fusion gene
47 CD34
48 Benign & borderline phyllodes tumours Not usually a diagnostic problem on excision specimens as the epithelial component is visible May be a challenge on core biopsy that samples only stromal elements, or in recurrent lesions that are devoid of epithelium
49 Bland spindle cell lesion Spindle cell carcinoma: epithelioid islands, IHC+ Scar: Fat necrosis, gran tissue, haemosiderin, IHC- Fibromatosis: b-catenin Myofibroblastoma: ER, Desmin, CD34 Nodular fasciitis: Look for features, IHC (Actin) Adenomyoepithelioma and fibroepithelial lesions: Biphasic Remember other entities: Hamartoma, SFT (STAT6+), IMT (ALK1), Leiomyoma, Hemangioma, DFSP, etc
50 High grade spindle cell lesions High grade spindle cell metaplastic breast carcinoma Malignant phyllodes tumour Sarcoma Metastases /melanoma
51 High-grade Spindle cell Carcinoma Sarcoma like / sarcomatoid carcinoma Pure or often coexist with high grade conventional carcinoma (glandular or squamous) Variable pattern and architecture, includes carcinomas with pleomorphic -like appearances Typically triple negative (basal-like) Poor prognosis
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53 High-grade Spindle cell Carcinoma
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56 High-grade Spindle cell Carcinoma
57 High-grade Spindle cell Carcinoma Giant cells
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59 AE1/3 Cam 5.2 CK7 p63
60 Diagnosis of high grade SC MBC 1- Coexistence of conventional type mammary carcinoma 2- Coexistence of an in-situ component (DCIS) And in the absence of both 3- Molecular demonstration of epithelial differentiation using IHC with epithelial specific markers (ie CKs and EMA)
61 Diagnosis of MBC: Absence of phyllodes tumour architecture (CD34-) Thorough sampling Clinical / previous history, Review of the previous core biopsy
62 Department of Pathology, SGH
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64 CAM5.2
65 CD34
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67 Diagnosis of MBC: In the rare cases that lack of these feature, MBC can be considered after exclusion of: 1- Being part of a metastatic process (ie metastatic RCC) 2- Primary skin (ie SCC) or chest wall tumours 3- Specific types of soft tissue tumours such as leiomyosarcoma or myofibroblastic sarcoma
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70 High grade spindle cell breast lesions Sarcoma * Angiosarcoma (commonest) * Liposarcoma (typically part of PT) * Chondrosarcoma and osteosarcoma (typically part of MBC but metastatic and primary chest wall should be excluded) * Leiomyosracoma, MPNST, myofibrobalstic & synovial sarcoma
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74 CD34 vwf CD31 D2-40
75 Metastases to the breast Unusual histology, absence of in situ carcinoma Clinical history is crucial High index of suspicion Adjunctive immunohistochemistry
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79 S100 AE1/AE3
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81 Spindle cell lesions on core biopsy Keep a broad range of differential diagnoses Clinicoradiological findings are important Benign can look malignant and malignant can look benign IHC is helpful, but be aware of pitfalls and limitations Thorough sampling Final diagnosis can be rendered on excision Important to rule out metaplastic carcinoma.
82 Breast SCL: additional questions Best immunohistochemical marker? Panel approach Keratins broad spectrum, basal p63 Markers for specific diagnoses (CD34, Alk1, B-catenin, STAT6, S100, desmin, ER, SMA,..etc) Exercise caution when staining is focal, or on limited material Be aware of cross reactivities and pitfalls Consult a colleague with soft tissue pathology expertise
83 Spindle cells lesions of the breast
84 CD34 in breast lesions Any >10% of cells Myofibroblastoma, & DFSP 100% 100% Fibroadenoma 100% 100% Phyllodes Benign 100% 100% Borderline 92% 92% Malignant 84% 63% Spindle cell carcinoma 0% 0% Fibromatosis, NF & Scar 0% 0%
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