Subtypes of primary breast cancer, the possibility of metastatic malignancy should be

considered. Malignant melanoma is probably the most common metastatic malignancy

seen in the breast. We have also seen metastatic tumours in the breast from squamous
carcinoma of the uterine cervix, small cell anaplastic carcinoma of lung, mucin-secreting
adenocarcinoma of stomach, ovarian adenocarcinoma and alveolar rhabdomyosarcoma.

Lymphoma
Malignant lymphoma may rarely present as a primary breast tumour. The differential
diagnosis of malignant lymphoma and reactive lymphoid tissue is described in Chapter 5.
Large cell lymphoma (centroblastic and immunoblastic) may closely resemble poorly
differentiated breast carcinoma with a completely dispersed cell population. In large cell
lymphoma, nuclear size, shape and chromatin pattern is usually more variable, many cells
have a basophilic cytoplasm, eccentric nucleus and a perinuclear halo, and nucleoli
characteristic of either centroblasts or immunoblasts are present. The presence in the
background of round basophilic cytoplasmic fragments (lymphoid globules) is a useful
indicator of the lymphoid nature of the cells.

Sarcoma
The biological behaviour of a phyllodes tumour is difficult to predict on the basis of
histologic appearances. Architectural features such as size, tumour margins and relative
lack of an epithelial component, as well as mitotic counts, have shown some correlation
with recurrence rate. The parameters can obviously not be assessed in FNA smears from
a tumour at the malignant end of the spectrum contain fragments of highly cellular
stromal tissue of spindle cells which may show nuclear atypia and pleomorphism similar
to a spindle cell sarcoma. In addition, there is a variable number of sheets of epithelial
cells. The latter may appear atypical but do not show malignant criteria. In such a case,
the cytology report should suggest a phyllodes tumour with stromal atypia suspicious of
malignancy but a definitive diagnosis of sarcoma should not be made, no matter how
atypical the spindle cell component may appear. The definitive diagnosis must await
histological examination. Smears from a tumour at the benign end of the spectrum may
suggest fibroadenoma, but contain larger numbers of spindle-shaped stromal nuclei while
epithelial component is sometimes seen in phyllodes tumours should be expressed.
Prominent squamous metaplasia of the epithelial component is sometimes seen in
phylodes tumours. It should be remembered that the histological pattern may be variable
within the same tumour, and the FNA biopsy may therefore not necessarily be
representative, particularly if the tumour is large.

In angiosarcoma of the breast, aspiration yields plenty of blood and tumour cells may be
few in numbers and difficult to find. This is particularly the case with low-grade tumours
which consist mainly of wide, anastomosing vascular channels and in which the
malignant endothelial cells show little tendency to form solid proliferations. High grade,
mainly solid tumours are more easily recognized as sarcomas cytologically. The tumour
cells are spindle-shaped, they have an attenuated basophilic cytoplasm without distinct
borders and dark pleomorphic, elongated or plump spindle nuclei. Most cells form
syncytial clusters but some are single a conspicuous component of the aspirate due to the
tendency of the neoplastic vascular channels to invade the fat tissue widely.
Diagnostic pitfalls in breast FNAC
Conditions in which there is a risk of making a false positive diagnosis
1. Pepillary lesions
The difficult distinction between intraduct papilloma, in situ papillary carcinoma
and invasive papillary carcinoma has been discussed on page 151.

2. A typical epithelial hyperplasia

The large number of epithelial cells, a proportion of which have enlarged, atypical
nuclei, may raise a suspicion of malignancy, but the presence of signle bare neclei
of benign type prevents a cancer diagnosis. Open biopsy and histological
examination should follow.

3. Fibroadenoma
Epthelial atypia can be extremely worrisome in some fibroadenomas. Agains, the
presence of single benign nuclei should prevent a false positive diagnosis. The
myxoid stroma characteristic of fibroadenoma is also a vey helpful sign.

4. Regenerative epithelial atypia

In the presence of inflammatory cells, particularly of polymorphs, epithelial
atypia should be interpreted with caution.

5. Pregnancy and lactation

The smear pattern of dispersed cells resembles cancer at low power but the
uniformly round nuclei, the bland nuclear chromatin and, above all, the lipid
secretion in the background prevent misdagnosis.

6. Atypia of ductal epithelium in cysts

Ductal epithelial cells of oxyphil type seen in cyst fluid can look very atypical. If
the fluid is not haemorrhagic, and if there is no residual lump following
evacuation of the fluid, there is paractically no probability at all of malignancy.

7. Skin adnexal tumours

The smear pattern of a syringocystaddenoma papilliferum imitates that of breast
cancer closely. The following case illustrates this rare problem.

The patient, a 60-year-old woman, presented with a subcutaneous lump in the

right axilla. She had a history of right mastectomy for cancer 4 years ago. A
FNA smear from the lump contained numerous epithelial cells, both single and in
clusters. The cells had a moderate amount of cytoplasm of a vaguely oxyphil
appearance and moderately atypical nuclei. The pattern was considered to be in
keeping with metastatic breast cancer, but histological examination of the excised
lesion showed this to be a syringocystaddenoma papilliferum.

Conditions in which there is a isk of making a false negative diagnosis

1. Tumours with central necrosis or sclerosis
 Smears are practically acellular and the distinction between scirrhous cancer
and sclerosed fibroadenoma, and between necrotic cancer and duct ectasia
may require an open biopsy.

2. A small carcinoma obscured by a dominant benign lesion

The benign lesion could be a ‘lipoma’, a cyst, or a lumpy fibroadenosis. This
problem can only be overcome by the consistent use of mammography.

3. Complex proliferative lesions

Representative sampling can never be assured in poorly defined complex
lesions with epithelial hyperplasia with and without atypia, which may include
foci of in situ or even invasive carcinoma. Close correlation with clinical and
mammographic findings is crucial.

4. Low grade carcinoma

Tubular carcinoma in particular can be a problem, since single, bare, stromal
nuclei of benign type are often present in smears from such tumours and
epithelial atypia may be minimal. In most cases the overall architectural
pattern is sufficiently atypical to suggest an open biopsy.

5. Small cell carcinoma

Cells of infiltrating lobular carcinoma often have uniformly small nuclei and
the cell yield is poor due to the extremely desmo;astic stroma. The irregular
shape of the nuclei, the tendency to form single files or clusters with nuclear
moulding and he absence of single, bare nuclei of benign type are diagnostic
features. Some ductal cancers also have uniformly small neoplastic cells.