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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