Monophasic Spindle Cell (Sarcomatous) Carcinoma
James L. Connolly
Beth Israel Deaconess Medical Center
This is a biopsy of a breast mass in a 71 year old African American woman. The patient was in an automobile accident, with breast trauma, 8 months prior to the biopsy.
Pertinent Laboratory Data:
The lesional cells were positive for actin and vimentin and negative for keratin coctail(Ae1-Ae3 & Cam 5.2)
Pure spindle cell lesions of the breast present a difficult diagnostic dilemma. The
most important lesion not to miss is a metaplastic carcinoma. Metaplastic carcinomas with areas of
traditional ductal carcinoma don't present diagnostic problems. Monophasic spindle cell (sarcomatoid)
carcinomas present a diagnostic dilemma.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
This case presented
in 1998 as a breast mass in the 71-year- old African-American female with a remote history of breast
injury following an automobile accident. The lesion was relatively acellular with keloidal like areas
and no nuclear atypicality. The spindle cells were positive for by vimentin and actin. The spindle
cells were negative for cytokeratins (ae1-3,cam5.2). Our diagnosis at the time was a reactive process.
The lesion was rebiopsied in 2000 and 2001 with similar findings. In 2003 the lesion was biopsied and
the patient had a mastectomy. At that time the lesion had a much more epitheliod appearance and was
strongly positive for pan- keratin(MNF-116 and p63.
The differential diagnosis of the lesion in 1998 includes a reactive change,
areas of fibromatosis, nodular fasciitis or a monophasic metaplastic carcinoma.
The final diagnosis for the 1998 lesion is still unclear. By the year 2003 the
breast showed a high-grade spindle cell metaplastic carcinoma that extended from the skin to the chest
wall. The patient ultimately died of metastatic carcinoma.
The limited samples that we had from 1998 through 2001 were not diagnostic with the
tools the we had available at time. It wasn't until 2003 that we were you routinely using the high
molecular weight cytokeratins and the p63 that are so useful in diagnosing this type of metaplastic
Review of the Literature/Treatment Options (if applicable):
Diagnosis: Monophasic Spindle Cell (Sarcomatous) Carcinoma
Differential Diagnosis: Nodular fasciitis
Classically this lesion presents as a rapidly enlarging, tender or painful mass. Although it is a
self limited process and will resolve spontaneously there is some evidence that there are clonal
rearrangements on chromosome 15 and 16 supporting a benign neoplasm . Most lesions are well defined
but have no capsule. The size varies but is usually less than 3 cm. Grossly they are usually well
defined and may appear fibrous, myxoid or cystic
Microscopically they are composed of
proliferating bland myofibroblasts. Mitoses are frequent but not atypical. The background is loose
collagenous stroma often with microcystic change. Inflammatory cells, particularly lymphocytes and
neutrophils are not uncommon particularly at the periphery of the lesion. Thin walled blood vessels with
associated red cell extravisation are common. In most cases the spindle cells are arranged in short
fascicles. The cellular proliferation tends to push away adjacent structures, such as breast ducts and
lobules, rather than invade them. There may be myxoid stromal change and as lesions age fibrosis or even
keloidal change. Multinucleated giant cells are not uncommon. Immunohistochemically the lesions should
be positive for actins and negative for keratins. They are usually negative for desmins .
Fibromatosis Fibromatosis of the breast is analogous to fibromatosis in other sites and is characterized
by a locally invasive, non-encapsulated proliferation of well- differentiated spindle cells
These tumors have the capacity to recur locally if inadequately excised, but they do no
metastasize.Margins of excision are difficult to evaluate. Gross disease left behind predicts for
recurrence but the microscopic margins are not predictive in some studies . Most cases of fibromatosis
have somatic beta- catenin or adenomatous polyposis coli (APC) gene mutations
. One of the main
concerns is to distinguish these lesions from well differentiated "fibromatosis like" metaplastic
carcinomas. Clinically the lesions can arise at any age but the median age is earlier than carcinoma
The lesions are usually painless and palpable as a firm or hard tumor which may be associated with
skin retraction. These features clinically suggest breast cancer. Grossly the size is quite variable.
The lesion is usually ill defined, firm, fibrous tissue. Microscopically the lesions typically are
composed of long fascicles of bland spindle cells, there is no significant cellular atypia and mitotic
figures are sparse. The stroma varies from cellular to keloidal like. A myxoid stroma is not uncommon.
The lesions tend to be centrally hyalinized and more cellular at the periphery. Lymphoid infiltrates are
frequently seen at the periphery. In contrast to nodular fasciitis, fibromatosis, is an infiltrative
lesion. At the periphery breast ducts and lobules will typically be infiltrated. Centrally especially
in large lesions parenchymal elements will be absent. Ocassionally areas of necrosis have been
Immunohistochemically the lesions should be positive for actins and negative for keratins. They are
usually negative for desmins. In contrast to other myofibroblastic proliferations these lesions often
show nuclear staining for beta-catenin
The lesions require wide excision since they are
infiltrative and can be locally aggressive. One of the main concerns is to distinguish these lesions
from well differentiated "fibromatosis like" metaplastic carcinomas. Metaplastic Carcinoma Metaplastic
carcinomas represent a morphologically heterogeneous group of invasive breast cancers in which a variable
portion of the glandular epithelial cells comprising the tumor have undergone transformation into an
alternate cell type – either a non-glandular epithelial cell type (e.g., squamous cell) or a mesenchymal
cell type (e.g., spindle cell, chondroid, osseous, myoid, etc.). There are numerous published reports
describing various aspects of metaplastic carcinomas, and numerous appellations have been applied to the
various tumors comprising this group
However, there is no uniformly agreed upon classification
scheme for these tumors. Metaplastic carcinomas are uncommon lesions, representing less than 5% of all
of breast cancers. The prognostic implications of metaplastic carcinomas are difficult to define, and
relate to the type of metaplasia present, as discussed below. There is growing evidence that epithelial
and sarcomatoid elements have a clonal origin . In addition it is likely that most metaplastic
carcinomas are of basal or myoepithelial origin
Genetic studies indicate that metaplastic breast
cancers are enriched in epithelial-to-mesenchymal transition and stem cell encoding genes.
Clinical Presentation Patients with metaplastic carcinoma are similar to patients with invasive carcinoma
of NST with regard to their age at presentation, the manner in which their tumors are detected, and the
location within the breast in which these tumors arise
Most patients present with a single
palpable lesion that often is associated with rapid growth . Gross Pathology The gross appearance of
metaplastic carcinomas is not distinctive, and these tumors can either be well- circumscribed or show an
indistinct or irregular border. Cystic degenerative changes are not infrequent, particularly in lesions
with squamous differentiation. In general, metaplastic carcinomas tend to be relatively large tumors,
compared to invasive carcinomas of NST. Histopathology Metaplastic carcinomas may arise from DCIS or may
be associated with papillary, sclerosing or adenomatous lesions
carcinomas are highly distinctive, but vary in the types and extent of metaplastic changes. Most reports
divide metaplastic carcinomas into two broad categories: those that show squamous differentiation
and those that feature heterologous elements, such as cartilage, bone, muscle, adipose tissue,
vascular elements and even melanoncytes, among others
While many patterns exist
Lesions that are primarily spindle cell in nature present the most difficult differential diagnosis .
Spindle-cell differentiation is common in metaplastic carcinomas, and is frequently seen in association
with squamous differentiation. A low-grade metaplastic breast tumor composed of spindle cells that
resemble those seen in fibromatosis is particularly difficult to diagnose
carcinomas resembling sarcomas are far more common than primary or metastatic sarcomas to the breast.
The correct diagnosis in such cases may require extensive tissue sampling in order to demonstrate
epithelial elements and immunohistochemical staining for epithelial markers, such as keratin, may be
required for proper diagnosis. In general high molecular weight cytokeratins and basal or myoepithelial
markers such as p63 and 34beta E12 are the most sensitive
There is increasing evidence that
metaplastic carcinomas are variants of basal like tumors
While this is often helpful in tumors
with spindle cell differentiation, not all metaplastic carcinomas show expression of epithelial markers,
particularly those with heterologous differentiation. The results of immunohistochemical staining for
other markers have been even more variable and this subject has been reviewed in detail
frequency of DCIS seen in association with metaplastic carcinoma varies among published reports. In
lesions characterized by a prominent mesenchymal component in which a true sarcoma is in the differential
diagnosis, the presence of DCIS or ADH argues in favor of metaplastic carcinoma. Estrogen and
progesterone receptor studies in metaplastic carcinomas are typically negative, regardless of the
histologic subtype examined
Metaplastic carcinomas are typically
aneuploid or tetraploid
A small study of metaplastic carcinomas demonstrated identical
clonality of the epithelial and mesenchymal components The conclusion was that the mesenchymal component
of these lesions arose from mutation of the epithelial component  . "Fibromatosis-like" metaplastic
carcinoma is a well differentiated variant of monophasic (sarcomatoid) metaplastic carcinoma .Similar to
fibromatosis, these lesions are composed of a monotonous proliferation of bland, elongated spindle cells
with an infiltrative pattern of growth and an invasive edge. The neoplastic cells have mild (or no)
nuclear pleomorphism, variable (but low) mitoses and are disposed within a collagenous stroma. Focal
biphasic (epithelial), heterologous (e.g. cartilage, bone) and/or in situ areas may be found in
metaplastic carcinoma, which will not be present in fibromatosis. Therefore, multiple sections of a low
grade spindle cell lesion such as this should be submitted for microscopic examination. Furthermore,
immunohistochemistry for cytokeratins and epithelial membrane antigen (EMA) are very useful if positive
as fibromatosis is negative for these markers, whereas metaplastic carcinoma usually stains positively.
Immunostaining may be focal in metaplastic carcinoma, and therefore, a negative result still does not
rule out the diagnosis. Clinical Course and Prognosis In most cases, the routes of metastatic
dissemination in biphasic metaplastic carcinomas are similar to those seen in breast cancers of no
special type, including lymphatic spread to axillary lymph nodes rather than the hematogenous spread
characteristic of mammary sarcoma. Metastatic lesions may either demonstrate an epithelial phenotype,
the metaplastic phenotype, or both. A large recent study of biphasic metaplastic carcinomas indicated
that they were aggressive(52% 5yr relapse free survival) and treatment refractory with a prognosis of
poorly differentiated, receptor negative adenocarcinomas . Tumors in which the sarcomatous elements
predominate are more likely to have metastatic spread similar to a sarcoma . In a recent study
spindle cell (sarcomatoid) carcinoma of the breast rarely involved axillary nodes(5%) and commonly spread
to the lungs(46%)
. In the same study these lesions had a dire prognosis with 42% of patients dead of
disease at a median interval of 11.5 months. . High- grade spindle cell metaplastic carcinomas have a
considerably worse prognosis than low-grade lesions . The fibromatosis like" metaplastic carcinoma
may have a more favorable prognosis
Metaplastic carcinomas resembling sarcomas are far more common than primary or metastatic sarcomas to
the breast. The correct diagnosis in such cases may require extensive tissue sampling in order to
demonstrate epithelial elements and immunohistochemical staining for epithelial markers, such as keratin,
may be required for proper diagnosis. In general high molecular weight cytokeratins and basal or
myoepithelial markers such as p63 and 34beta E12 are the most sensitive
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