Breast Pathology: Differential Diagnostic Dilemmas
Dr. Christopher Elston
Case 12 -
Adenoid Cystic Carcinoma of Breast, Solid/Basaloid Subtype
Dr. Christopher Elston
A female aged 73 years was referred to the Breast Clinic with a three-week history of a lump in the
right breast. Clinical examination and mammography revealed a mass lesion, suspicious of malignancy in
the upper inner quadrant. Following needle core biopsy a right mastectomy and axillary dissection were
carried out. The section is from the lesion.
Case 12 - Slide 1
A simple mastectomy specimen weighing 866 gm. In the upper inner quadrant 35 mm from the
nipple there is a moderately defined firm mass lesion measuring 13 mm in maximum diameter.
The section, which is representative of the whole lesion, shows a well-circumscribed tumour composed
of islands of dark staining ovoid to spindle shaped epithelial cells with little cytoplasm. The islands
are surrounded by a thin eosinophilic membrane. Occasional glandular lumina containing eosinophilic
secretions are present but the epithelial structures are mainly solid. There is moderate nuclear
pleomorphism but mitotic figures are scanty. No in situ component is seen. Focal areas of fibrosis are
noted centrally. Vascular invasion is absent.
The two distinguishing histological features of this tumour are the 'basaloid' appearance of the
epithelial cells and the presence of a stromal eosinophilic membrane around tumour cell islands. This
morphological pattern is similar to that seen in the solid type of adenoid cystic tumours (ACC) of
salivary gland but must also be distinguished from small cell carcinoma, primary or metastatic and ductal
carcinoma of no special type (ductal/NST). The presence of cystic spaces raises the possibility of
invasive cribriform carcinoma but the typical 'punched-out' glandular pattern is lacking. Whilst these
distinctions are difficult to make with certainty on the morphological appearances alone the correct
diagnosis may be achieved with ease by means of immunohistology.
In ACC the eosinophilic membrane is composed of basement lamina and this can be confirmed by
immunostaining with laminin and collagen 1V which also decorate secretions in pseudo-cystic spaces; this
feature is lacking in ductal/NST and small cell carcinomas. The tumour cells are uniformly positive with
cytokeratins (eg, MNF 116, AE1/AE3 and CK7); they are usually of two types, basaloid and luminal which
can be demonstrated by positive immunoreactivity with CK 14, CK5/6 and E-cadherin respectively.
Assessment of hormone receptor status may also be helpful; oestrogen receptor (ER) and progesterone
receptor (PR) are virtually always absent in ACC compared with 80% positivity in other epithelial breast
tumours. It has recently been suggested that c-kit, a transmembrane tyrosine kinase receptor protein
(cd117) is positive in most cases of ACC of salivary glands and that the same pattern is also present in
over 90% of cases in the breast. P63, a gene involved in embryonal development and cell differentiation
and which is expressed in the basal and myoepithelial components of breast epithelium is also expressed
in a high percentage of breast ACC (>80%). In contrast, c-kit and p63 are negative in most other
breast carcinomas although p63 may be expressed in the 'basal' subtype of ductal/NST carcinomas.
In view of this a panel of immunohistochemical markers was applied to the present case; the results
are shown in Table 1 below.
Table 1. Pattern of Immunoreactivity.
|Collagen IV ||+|
|CK 5/6 ||focally +|
|CK 14 ||focally +|
|CK 7 ||+|
|c-kit ||focally +|
|Smooth muscle myosin (SMM) ||basal cells +|
|Smooth muscle actin (SMA) ||basal cells +|
|HER 2 ||-|
These immunostaining characteristics are confirmatory of the histological diagnosis of adenoid cystic
carcinoma (ACC) of the breast, solid/basaloid subtype.
Adenoid cystic carcinoma is a rare special type, accounting for 0.1 – 1% of all malignant epithelial
tumours of the breast. Morphologically this subset of breast carcinoma is indistinguishable from ACC
arising in other sites, particularly salivary gland. The constituent neoplastic cells are of two types,
luminal and basal/myoepithelial, arranged in a wide spectrum of histological patterns, all of which may
be present in the same tumour. Three basic morphological subtypes are recognised, tubular-trabecular,
cribriform and solid. The relative proportions of each pattern have been used in salivary ACC to produce
a grading system and this can also be applied to the breast, as follows:
Grade I – glandular/cystic, no solid areas
Grade II – glandular/cystic with solid areas constituting <30%
Grade III – solid component >30% of the mass
As shown above, immunohistochemistry is helpful in confirming the diagnosis of ACC. The basal cells
are positive for CK5/6, CK14 and, usually focally, for myoepithelial markers such as SMM, SMA, calponin
and p63, although the latter, perhaps surprisingly, may be negative in basaloid cases. The luminal cells
are usually positive for CK7. C-kit has emerged as the most useful antibody, being positive in over 90%
of cases, although interestingly the exceptions seem to be of the solid/basaloid subtype, which was not
the case here. The polarity of the different cell types may also be demonstrated by immunostaining;
basaloid cells usually express laminin, fibronectin and collagen IV, whereas luminal cells express
proteins related to cell polarisation and epithelial differentiation such as E-cadherin and B-catenin.
Overall ACC of the breast carries an excellent prognosis with a low rate of axillary node involvement
(<10%). Local recurrence is uncommon and probably related to inadequate resection. Only rare
examples of distant metastasis have been recorded and long-term survival is close to 100%. It has been
suggested that the solid subtype (grade III), especially the basaloid variant, is more aggressive with a
greater propensity to develop lymph node and distant metastasis but the number of cases reported is very
small. A search of the recent world literature found a total of 15 cases of solid/basaloid ACC with
appropriate follow-up. Axillary node metastases were found in six (40%, one micrometastatic) and distant
metastases in two (13%). There was only one death (7%). These data should be interpreted with care
(some are based on single case reports) and need confirmation from larger studies, but they do indicate
that the solid/basaloid may be more likely to develop lymph node metastases and have a slightly worse
prognosis than the tubular/trabecular and cribriform sub-types. Nevertheless, it is worth emphasising
that the reported long-term survival for this type is still in excess of 90%.
The tumour was shown to have the following histopathological characteristics:
Tumour size – 13 mm
Type – adenoid cystic carcinoma
Grade – 2
Lymph node stage – 1 (0/8)
Vascular invasion – none
Nottingham Prognostic (NPI) – 3.26 (Good Prognostic Group [GPG], 92% 10- year survival chance)
The NPI was based on data from common types of invasive breast carcinoma rather than rare subtypes
such as adenoid cystic carcinoma and the predicted long-term survival for the GPG of 92% is a slight
underestimate for ACC overall; as noted above the true figure is close to 100%. However, this figure may
not be inappropriate for the solid sub-type.
The patient was not given adjuvant systemic therapy for her breast tumour. However, a complication
in the present case was the finding of follicular lymphoma in axillary lymph nodes. Further
investigation revealed bone marrow and splenic involvement by lymphoma – stage IV disease. She was
therefore treated with chlorambucil, nizatidine and prednisolone for her lymphoma. She remains well and
tumour free after four years follow-up.
Adenoid cystic carcinoma of breast, solid/basaloid subtype
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