Post on 18-Apr-2018
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Spindle Cell Lesions
A.A. Sahin, M.D. Professor of Pathology and Translation Molecular
Pathology Section Chief of Breast Pathology
23rdAnnual Seminar in Pathology
Outline
• Morphologic features of spindle cells
lesions
• Differential diagnosis
• Case presentations
Wide Spectrum
• Bland, low grade spindle cells
•High grade, pleomorphic spindle cells
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Fibroblastic/Myofibroblastic Lesions
•Nodular fasciitis
• Fibromatosis
•Myofibroblastoma
• Scar
Other Benign Mesenchymal Spindle Cell Lesions
• Pseudoangiomatous stromal hyperplasia (PASH)
•Neurofibroma
• Schwannoma
• Leiomyoma of nipple
Case 1
• 29 yo female with palpable right breast mass
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Case 2
• 64 yo female, mammogram revealed a 2 cm mass
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β-catenin
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Fibromatosis of Breast
• Females > males
• Peak 20-50 years
• Painless, firm, slow-growing mass
• May closely mimic carcinoma – Can be stellate radiologically
• May be associated with FAP, other desmoid type tumors
• Treatment: wide local excision
• Local recurrence 15-30%
Fibromatosis of Breast
• Most cases < 5 cm
• Histologically similar to desmoids in other sites
• Long fasicles of bland spindled cells
• Entrapment of breast parenchyma
• May resemble fasciitis
• Peripheral lymphocytic infiltrate common
• Local recurrence in 27%
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Nodular Fasciitis
• Young adults
• Short duration, often tender
•Most < 5 cm
• Rare local recurrence
Nodular Fasciitis
• Circumscribed
• Plump spindled cells
• Brisk mitotic rate
• Microcystic & myxoid areas
• Inflammatory infiltrate throughout lesion
• Extravasated RBC’s
• Normal breast parenchyma not entrapped
Case 3
• 41 year-old female with right breast mass
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CK
CK
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Fibromatosis-Like Spindle Cell
Carcinoma • First described as fibromatosis like metaplastic tumor
• Non-metastasizing – Gobbi, et al. Cancer 1999
• Recent study showed to be a low grade tumor
• Potential for local recurrence and distant metastasis
• No involvement axillary nodes
• Lumpectomy with clear margins or simple mastectomy
•A variant of metaplastic ca
•Discrete nodule, infiltrative
borders
•Spindle cells in intersecting
fascicles, storiform pattern
(>90-95%)
•Collagenous stroma
Fibromatosis-Like Spindle Cell Carcinoma
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•Slender nuclei with
tapered edges
•Mild nuclear
pleomorphism
•Low mitotic rate
•Epitheloid or
squamous foci
•Focal heterologous or
in situ component
Fibromatosis-Like Spindle Cell Carcinoma
Fibromatosis
Fibromatosis-Like Spindle Cell Carcinoma
Fibromatosis-Like Spindle Cell Carcinoma
• Thorough sampling is essential to demonstrate epithelial elements and exclude aggressive components
• It is important to search for epithelial differentiation even in bland spindle cell lesions
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Fibromatosis-Like Spindle Cell Carcinoma
Immunohistochemistry
• Cytokeratin (gold standard) – Patchy
• 34ßE12 + (CK903)
• AE1/AE3 +
• CK7 –
• EMA +/-
• SMA + in CK+/- cells
• ER/PR -
• Her-2/neu -
Differential Diagnoses
• Fibromatosis
• Nodular fasciitis
• Fibromatosis like spindle cell carcinoma
Differential Diagnoses
Spindle Cell Ca Nodular Fasciitis Fibromatosis
Epitheloid Areas +/- - -
Tumor Edge Infiltrative Well defined Infiltrative
Ducts & Lobules Entrapped Push aside Entrapped
Fascicles Short Short Long broad
Mitosis
Infrequent Numerous Infrequent or
Focally numerous
Cytokeratin Positive Negative Negative
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Differential Diagnosis
CK beta-Catenin
Spindle Cell Ca + N/A
Fibromatosis - nuclear +
• 75 yo male with h/o myelodysplastic syndrome, now develops a left breast mass
Case 4
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SMA
CK
Myofibroblastoma
- Males = females
- Concurrent gynecomastia in male
- Peak 50 – 75 years
- Increasingly detected on mammogram
- Mammogram: homogeneous, lobulated, well-circumscribed and lacks microcalcifications
- Findings suggestive of fibroadenoma or hamartoma
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Myofibroblastoma
•Solitary, slow growing nodule or mass
•Located in breast parenchyma and range in size from 0.9 to 10cm
Myofibroblastoma
•Cut surface is gray-pink to tan-white
•Cysts and hemorrhage are absent
Myofibroblastoma
Histology: - Circumscribed, devoid of
mammary ducts and lobules, compressed parenchyma forms a pseudocapsule
- Moderately cellular with uniform,
ovoid to spindle cells arranged diffusely or in clusters
- Broad bands of hyalinized
collagen distributed throughout the tumor
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Myofibroblastoma
- Lack atypia, necrosis, or significant mitotic figures, 0 – 1/ 10 HPF
- Mast cells are seen in many cases - Occasionally has cartilaginous metaplasia – no
influence on clinical behavior - Variant forms: collagenized / fibrous epithelioid cellular infiltrative myxoid
Fibrous Infiltrative
Epithelioid Myxoid
Differential Diagnosis
• Metaplastic carcinoma (CK+)
• Reactive spindle cell lesion/nodular fasciitis – Plump myoid cells,
– Inflammatory reaction
– Foci of microcystic myxoid change
– RBC extravasation
– Desmin –
• Fibromatosis – Infiltrative margins w/finger-like extension of monotonous
fibroblasts
– Entrapped glands
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Differential Diagnosis
• Spindle cell lipoma
–more abundant adipose tissue and mast cells
• Solitary fibrous tumor
–Bland spindle cells admixed w/thin, or less frequently, thick collagen
–Hemangiopericytoma-like vascular pattern
–Desmin -
Case 5
• 58 yo female with 3 cm slow growing mass in the right breast over the past 3 years
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ER
Pan-CK
Desmin
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CD34
Myofibroblastomawith epithelioid and adipocytic
components
Diagnosis
Myofibroblastoma
• Resembles spindle cell lipoma
But. . .
• More cellular and fascicular
• Rare smooth muscle/cartilage metaplasia
• CD34 / desmin positive, SMA variable
• Loss of 13q and 16q
• Cytogenetic relationship to spindle cell/ pleomorphic lipoma (may be related)
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Differential Diagnosis
Myofibroblastoma Nodular fasciitis
Fibromatosis Spindle cell
lipoma
Edge Well defined Well defined Infiltrative Well defined
Ducts & lobules Not entrapped Not entrapped Entrapped Not entrapped
Mitosis Infrequent Numerous Infrequent or
focally numerous
Infrequent
Inflammatory infiltrates
Peripheral Central Peripheral N/A
SMA + + + -
Desmin + - - -
CD34 + Focal + - +
High Grade Spindle Cell Neoplams
•Metaplastic (sarcomatoid) carcinoma
• Bona fide sarcoma
•Malignant phyllodes tumor
Spindle Cell Sarcomas of the Breast
-Extremely uncommon-
• Post-radiation sarcoma, NOS
• Leiomyosarcoma
• MPNST
• Metastasis from elsewhere
*Must rule out recurrent malignant phyllodes tumor!
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Case 6
• 47 yo female with 7 cm left breast mass
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CK
Metaplastic (Sarcomatoid) Carcinoma Main Morphologic Patterns
• Spindle cell
• Pleomorphic (MFH-like) +/- giant cells
• With squamous metaplasia
• With heterologous elements (usually osteosarcoma / chondrosarcoma)
Metaplastic (Sarcomatoid) Carcinoma
Diagnostic Clues
• Adjacent DCIS/ invasive ductal carcinoma (not always present)
• Squamous metaplasia
• Plump, somewhat more epithelioid atypical spindle cells
• Always do pan-cytokeratin
– Multiple keratins may be needed
– Especially HMW keratins
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Metaplastic Carcinoma Immunophenotype
• Keratin ~100%
• SMA 70-80%
• P63 50%
• EMA 10-20% (rare cells)
• S-100 protein 10%
• ER/PR/HER2 negative
Metaplastic Carcinoma
Key Points:
• More common than primary spindle cell sarcoma in breast!
• Significant subset shows myoepithelial differentiation
• <5% lymph node metastasis in predominantly metaplastic tumors
• Frequently aggressive behavior
• Suggested to be managed as sarcoma
Case 7
• 57 yo female with 5 cm right breast mass
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Prior lesion in the same patient
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Conclusions
• Always think first about common lesions
• Carcinoma
• Phyllodes tumor
• May need to use multiple IHC markers
• Do not overcommit on needle biopsies
• Clinical history/imaging features is crucial
Take Home Messages
• Always first consider the possibility of metaplastic (spindle cell) carcinoma or phyllodes tumor
• Clinicopathologic correlation is often crucial in the diagnosis
• Accurate diagnosis on the needle biopsy may be impossible