Breast Pathology: Differential Diagnostic Dilemmas
Dr. Christopher Elston
Cases 5 & 6-
Metaplastic Carcinoma of the Breast
Dr. Gary Tse
Clinical History - Case 5
A 49 year old woman with a history of thyrotoxicosis for two years, presented with an incidental
finding of a left axillary mass. Palpation showed a large axillary mass about 5 cm, and in the left
breast, a firm to hard nodule is present in the 6 o'clock position. Mammography showed a 3 cm mass with
partially lobulated margin. No calcification was noted. Sonography showed two enlarged lymph nodes in
the axilla, measuring about 4 cm each.
Case 5 - Slide 1
Biopsy, and subsequent mastectomy with axillary dissection was done. 17 of 17 lymph nodes showed
Clinical History - Case 6
A 74 year old Chinese woman with a hard right breast lump.
Case 6 - Slide 1
Metaplastic carcinoma of the breast
Metaplastic carcinoma of the breast denotes a heterogeneous group of uncommon malignant entities.
This term is used by many to denote tumours with mixed epithelial and sarcomatoid components, as well as
primary squamous or mixed adenocarcinoma and squamous carcinoma. In those cases with a sarcomatoid
component, they can be classified into monophasic, composed of spindle cells only; or biphasic, being
admixed witha carcinomatous (either ductal carcinoma or squamous cell carcinoma)
component.  Other authors have systematically grouped the tumours into various diagnostic
labels, based on the presence of heterologous elements or osteoclastic giant cells, or whether the tumour
cells are monophasic, biphasic or squamoid.
Metaplastic carcinoma is generally
considered high grade, and the clinical features are similar to infiltrating duct carcinoma, although it
may rarely present as inflammatory carcinoma.  Recently a low grade variant, the fibromatosis
like group, has been reported, with a better outcome with mostly local recurrences but not distant
Biphasic metaplastic carcinoma can be defined as an intraduct or infiltrating carcinoma being
contiguous or subtly merged with a highly cellular, mitotically active pleomorphic spindle cell stroma,
which appears sarcomatous, and accounts for a significant proportion of the tumour.  Within
the tumour, the carcinomatous component can either be invasive only or invasive and in situ, each
constituting about 40-45% of the cases. In about 20% of the cases, squamous differentiation or squamous
cell carcinoma is noted in the carcinomatous component. In the sarcomatous component, most of the cases
show polymorphous tumour cells or spindle cells, and are usually of high cellularity and highly
pleomorphic with giant cells. In about 17% of the cases, heterologous components including bone or
cartilage or both can be seen.
Monophasic metaplastic carcinomas are composed predominately of spindle cells or a
sarcomatoid tumour cell component. They can have a variable range of nuclear features, from high grade
to low grade, where the latter is reminiscent of fibromatosis.  Most of the monophasic
metaplastic carcinomas are high grade, and a significant proportion shows lymph node  or
extranodal  metastasis at the time of presentation. The fibromatosis like metaplastic
carcinoma is a low grade variant that behaves in a much less aggressive manner, characterised by local
recurrence but not metastasis.  Differential diagnoses for this group of tumours include
phyllodes tumours, especially in cases with prominent stromal overgrowth, and other breast sarcomas.
Immunohistochemistry is helpful in the diagnosis of metaplastic carcinoma. In biphasic tumours, the
carcinomatous component will be positive for cytokeratins, and for the sarcomatous component, most of the
tumour cells express vimentin, and with variable degree of positivity for actin, cytokeratin and
embryonal membrane antigen (EMA). p63 has also been reported to be positive for the sarcomatous tumour
and this is reputed to be quite specific, being negative in phyllodes tumours and
other sarcomas of the breast. For the monophasic tumour, the malignant cells are positive to a variable
extent for cytokeratins with PanK (MNF116) and CK14 being more commonly positive than others like AE1/3,
CAM5.2 or EMA. p63 positivity ranges from 57 to 100%.
The histogenesis of metaplastic remains elusive. It is now accepted that despite the variable
histology of the different components, they are clonal
in origin. The observation that
many metaplastic carcinomas tend to be negative for HER2/neu and positive for EGFR may have important
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