Spindle Cell Lesions of the Breast

Stuart J. Schnitt, M.D.

Brigham and Women’s Hospital, Dana-Farber
Cancer Institute, and Harvard Medical School
Boston, MA
 Disclosures

• No relevant disclosures
 Spindle Cell Lesions of
the Breast
• Uncommon
• Range from reactive processes to
aggressive malignant neoplasms
• Some lesions have overlapping
histologic features
• Problematic cases require use of
immunostains for definitive dx
A Breast Pathologist’s Differential Diagnosis
of Spindle Cell Lesions of the Breast
A Breast Pathologist’s Differential Diagnosis
of Spindle Cell Lesions of the Breast
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Spindle cell (metaplastic) carcinoma
• Everything else
 Spindle Cell Lesions of the Breast
Take Home Messages

• Always consider possibility of spindle cell

(metaplastic) carcinoma
• Always consider possibility of phyllodes tumor
• Be cautious in core needle biopsies; definitive
categorization may not be possible
• Use of appropriate immunostains can be
immensely helpful
Practical Approach to Spindle Cell
Lesions of the Breast
• Bland spindle cells
– Scar
– Fibromatosis
– Myofibroblastoma
– PASH (fascicular type)
– Adenomyoepithelioma
– Spindle cell carcinoma
– Rare
• Nerve sheath tumors
• Leiomyoma
• Myxoma
• Solitary fibrous tumor
• Inflammatory myofibroblastic tumor
• Atypical spindle cells
– Spindle cell carcinoma
– Phyllodes tumor
– Nodular fasciitis
– Sarcoma (primary or
metastatic)
– Metastatic spindle cell
carcinoma
– Metastatic melanoma
Spindle Cell Carcinoma
WHO, 5th Edition

• Metaplastic carcinoma
– Low grade adenosquamous ca
– Fibromatosis-like metaplastic ca
– Spindle cell ca
– Squamous cell ca
– Metaplastic ca with
heterologous mesenchymal
differentiation
– Mixed metaplastic ca
 Spindle Cell Carcinoma
Clinical Features

• <1% of breast cancers

• Presentation similar to
conventional mammary ca
• Lymph node metastases very rare
• Typically ER, PR, HER2 negative
 Spindle Cell Carcinoma

• Spindle cells can vary from cytologically

bland to highly pleomorphic
• Fascicular, fasciitis-like, storiform,
haphazard growth patterns
• Irregular infiltration of fat
• Areas suggestive of vascular spaces
• Foci of squamous differentiation
• Foci of heterologous differentiation
(chondroid, osseous)
 Spindle Cell Carcinoma
Helpful Clues

• Associated DCIS
• Areas in which spindle cells
aggregate and assume more
epithelioid appearance
• Frank epithelial differentiation
• None may be present
 Spindle Cell Carcinoma
Cytokeratin Immunostaining

• Panel of cytokeratin stains often

needed to demonstrate tumor cell
reactivity
• Antibodies to high molecular weight
cytokeratins most sensitive
– Pankeratin MNF116
– 34βE12
– CK 5/6
– CK 14
AE1/AE3

MNF116
 Spindle Cell Carcinoma
Other Features

• p63 expression in >70%

• Muscle specific actin, SMA expression
common
• Features overlap with those of
myoepithelial carcinoma/malignant
myoepithelioma; likely represent parts of
the same spectrum; distinction largely
semantic
• Cluster in basal-like and claudin-low
groups by gene expression profiling
 How much cytokeratin or p63
staining is enough ?
• WHO 4th edition, 2012
– In a pure spindle cell lesion of the breast,
unequivocal expression of HMW-CK and/or p63
in any proportion of cells should prompt a
diagnosis of metaplastic carcinoma
• WHO 5th edition, 2019
– Unequivocal expression of high molecular
weight cytokeratins and/or p63
Cytokeratin and p63 Stains in the
Evaluation of Spindle Cell Lesions
Words of Caution

• Stromal cells of phyllodes tumors can

show focal staining for cytokeratins
and p63 (usually very focal)
• Use caution, especially in core needle
biopsies
Malignant PT with stromal overgrowth

MNF-116
 Fibromatosis-Like
Metaplastic Carcinoma

• May arise de novo or in association with

papillomas and benign sclerosing lesions
• Composed of bland spindle cells similar to
those seen in fibromatosis
• Epithelioid areas or foci of squamous
differentiation may be seen
• Cytokeratin stains may be required for
diagnosis
• High rate of local recurrence
• Metastases rare
AE1/AE3-CAM5.2
MNF116
p63
MNF116
Fibromatosis
 Fibromatosis

• Infiltrative, locally aggressive

proliferation of
fibroblasts/myofibroblasts
• Painless, slowly growing mass
• Gross features:
– Poorly-defined or stellate gray-white
to tan lesion
– May simulate carcinoma
 Fibromatosis
• Histologic features:
– Long, sweeping fascicles of bland
spindle cells in collagenous stroma
– Surround and entrap mammary ducts
and lobules; extend irregularly into fat
– Mitoses usually infrequent
– Stroma may vary from keloidal to
myxoid / fasciitis-like
– Lymphoid infiltrates common; most
prominent at edges
 Fibromatosis
Immunophenotype
• Actin positive
• Variable staining for desmin, S100
• Cytokeratin negative
• Nuclear expression of β-catenin seen in
~75%
– but, not specific for fibromatosis
• 23% of metaplastic carcinomas, 94% of benign
phyllodes tumors, 57% of malignant phyllodes
tumors show nuclear β-catenin expression
(Lacroix-Triki, 2010)
β-catenin
 Fibromatosis
Outcome

• High rate of local recurrence (20-30%)

• Most recurrences within first 3 years
after diagnosis
• Risk of local recurrence appears to be
more related to tumor biology (i.e.,
presence and type of CTNNB1
mutation, microenvironment, field
effect) than to margin status
– ? need for wide excision
 JAMA Oncol, 2019

• Active surveillance recommended

as primary strategy in most
patients
– Behavior unpredictable
– Spontaneous growth arrest and
regression can occur
JAMA Oncol, 2019
 Breast Cancer Res Treat, 2019

88% had
regression or
stabilization

Monitor by MRI to detect progressive disease

Myofibroblastoma
 Myofibroblastoma
Clinical Features

• Males = females
• Increasingly detected on
mammogram
• Peak 50-75 years
• Mobile, slowly growing
• Most < 4 cm; occasionally very
large
• Also may occur outside breast
• Benign; no recurrence
 Myofibroblastoma
Pathologic Features

• Rubbery firm, lobulated mass; cut

surface homogenous gray to pink
whorled or lobulated tissue
• Classic type-histology:
– Circumscribed, no true capsule
– Variable amounts of fat
– Short fascicles of uniform spindle-shaped
cells with round to oval nuclei
– Broad bands of hyalinized collagen
 Myofibroblastoma
Other Histologic Features

• Usually no entrapped mammary

ducts/lobules
• Perivascular lymphoplasmacytic
infiltrates
• Mast cells
• Myxoid change
• Chondroid or smooth muscle
metaplasia
 Myofibroblastoma
Immunophenotype

• Cells positive for

– Vimentin
– CD34 (epithelioid variant may be
negative)
– ER
– PR
– AR
– Actin
– Desmin
– bcl2
• Staining may be focal / variable
 Myofibroblastoma
Variants
• Collagenized/fibrous
• Cellular
• Myxoid
• Lipomatous
• Infiltrative
• Atypical
• Deciduoid
• Palisaded
• Epithelioid
Collagenized/Fibrous
Collagenized/Fibrous
Cellular
Cellular
Myxoid
Lipomatous
Lipomatous
Palisaded

Magro, Hum Pathol, 2013

Atypical
Atypical
 Epithelioid Variant of
Myofibroblastoma
• Polygonal or epithelioid cells
arranged in cords or alveolar
groups
• May constitute predominant
growth pattern or be admixed
with classic form
• Growth pattern may resemble
invasive lobular carcinoma
Myofibroblastoma Lobular Carcinoma
 Myofibroblastoma
Additional Pearls

• Similar lesions at extramammary

locations, especially inguinal
• Relationship to spindle cell lipoma
• Morphologic and immunophenotypic
overlap
• “13q/Rb family of tumors”: deletion or
rearrangement of 13q14 with loss of Rb
expression by IHC
Myofibroblastoma Spindle Cell Lipoma
A Few Other Spindle Cell
Lesions to Think About
SMA
Nodular fasciitis
Fascicular PASH
CD34
STAT 6

Solitary Fibrous Tumor

Calponin
p63

Adenomyoepithelioma
Spindle Cell Lesions in
Core Needle Biopsies
 Spindle Cell Lesions in
Core Needle Biopsies
• Almost always require work up with
immunostains
• Definitive diagnosis sometimes
possible, but often is not
– Dx: Spindle cell lesion; excision
recommended
• Don’t be a hero!
 MNF116

K903
CK5/6

p63

Dx: Spindle Cell Carcinoma

MNF116
 β-catenin

Dx: Fibromatosis
CD34

SMA

DES

ER

Rb

Dx: Myofibroblastoma
Dx: Phyllodes Tumor
 Don’t Forget About
Phyllodes Tumors!

• An apparently pure spindle cell

lesion may be a phyllodes tumor
(especially in core needle
biopsies)
• Don’t exclude the possibility of
phyllodes tumor even if no
epithelial component is seen
 Spindle Cell Lesions of the Breast
Take Home Messages

• Always consider possibility of spindle cell

(metaplastic) carcinoma
• Always consider possibility of phyllodes tumor
• Be cautious in core needle biopsies; definitive
categorization may not be possible
• Use of appropriate immunostains can be
immensely helpful