Case 2 -
Solid Variant of Adenoid Cystic Carcinoma with Basaloid Features
Laura C. Collins
Beth Israel Deaconess Medical Center and Harvard Medical School
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- A 43 year old female presented with a 2.5 cm right
- Overlying skin dimpling was present
- On imaging the lesion appeared as a well
circumscribed, lobulated mass
- Due to the superficial location of the lesion an
excisional biopsy was performed
Case 2 - Figure 1
Low power view of several irregular nests of tumor cells embedded in a fibrotic stroma.
Case 2 - Figure 2
Higher power view showing a solid nest of basaloid appearing cells characterized by large cells with round to oval, hyperchromatic nuclei with scant eosinophilic cytoplasm. Nucleoli are inconspicuous.
Case 2 - Figure 3
High power view showing a cribriform area. On high power the basaloid cells show moderate to marked nuclei atypia. Around some of the lumens the cells appear to have more abundant eosinophilic cytoplasm and normochromatic nuclei. Other lumens contain homogeneous, eosinophilic material.
Case 2 - Figure 4
Low power view showing another area of the tumor which has the appearance, at this power, of having fibrotic material within the solid tumor cell nests.
Case 2 - Figure 5
Low power images of this tumor show solid, irregular nests of basaloid tumor cells infiltrating
through a fibrotic stroma. On higher power, the basaloid morphology of the tumor cells is better
appreciated. These cells have moderate to marked nuclear atypia and scant cytoplasm. In some of the
nests, areas of cribriforming architecture are appreciated. Around some of the lumens ("true lumens") in
the cribriform areas, cells with a more epithelial appearance are noted. These cells have more abundant
eosinophilic cytoplasm and the nuclei are less hyperchromatic than those in the basaloid cells. Other
lumens contain homogeneous, eosinophilic material consistent with basement membrane material.
Immunostains for estrogen and progesterone receptor (ER and PR) were negative. HER2 was not
overexpressed in this case. Neuroendocrine markers were performed and were negative. This case showed
focal expression with cytokeratin (CK) 5/6.
Differential diagnostic considerations include:
- Infiltrating ductal carcinoma
This could be an NOS infiltrating ductal carcinoma except for the very basaloid appearance of the
tumor cells and the foci that have abundant eosinophilic material within the tumor cell nests. These
features should prompt further exploration into whether this might represent a "special type" carcinoma
- IDC with
At first glance, the solid nested pattern and appearance of the tumor cells may raise the possibility
of neuroendocrine carcinoma. But high power examination will reveal the marked nuclei atypia and
hyperchromasia. As well the presence of amorphous material in some of the tumor cell nests does not fit
with infiltrating carcinoma with neuroendocrine features. The neuroendocrine markers were negative.
- Solid papillary
These tumors are composed of single or multiple circumscribed nodules of neoplastic cells with a
solid growth pattern. Often difficult to appreciate is the delicate to hyalinized fibrovascular stromal
network. Endocrine differentiation is common as is intra- and extra-cellular mucin production . These
latter features are not apparent in our case. These tumors are frequently associated with mucinous
carcinoma and IDC
- Small cell carcinoma
This tumor has the same morphology as small cell carcinoma at other locations. It may have either a
solid nested growth pattern or a more infiltrative pattern. Typically molding, crush artifact and
nuclear streaming would be seen . These latter features are not present in the current case.
- Basal-like carcinoma
Strictly speaking basal-like carcinomas are a class of tumor defined through gene expression
profiling. Histologic and immunophenotypic correlation of this class of tumors has demonstrated that
many are high grade tumors with a brisk mitotic rate; have a solid growth pattern with pushing tumor
margins and large zones of geographic necrosis or a central fibrotic focus. These tumors have a triple
negative immunophenotype and expression of basal cytokeratins and/or epidermal growth factor receptor
(EGFR). In many respects, this case may fit with this description; however, it does not have the very
brisk mitotic rate nor the "typical" morphology of a basal-like carcinoma.
- Solid variant of adenoid cystic
carcinoma with basaloid features
This is a rare tumor. It most often is a lobulated, unicentric mass and it has a >90% solid growth
pattern. The tumor cells have "basaloid" features (as described above). Ductules (or "true" lumens) may
be appreciated within the solid tumor cell nests. These ductules are surrounded by larger cells with
more eosinophilic cytoplasm. Additionally, cyst-like spaces ("pseudo" lumens) containing homogenous
eosinophilic (basement membrane-like) material can usually be
Solid variant of adenoid cystic carcinoma with basaloid features
Adenoid Cystic Carcinoma
Adenoid cystic carcinomas (ACC) are uncommon tumors, representing only ~0.1% of all breast
carcinomas . The reported age at presentation is broad age. ACC presents equally in both breasts with
approximately 50% located in the sub-periareolar region . ACC often presents as a discrete nodule,
which may be painful. Occasionally overlying skin dimpling may occur. On imaging, ACC is usually a
solid mass, with a lobulated appearance .
ACC of the breast show the distinctive biphasic pattern of these tumors in other locations. True
lumens are lined by epithelial cells that may have varying degrees of glandular, sebaceous and squamous
differentiation. These areas of glandular differentiation are thought to represent intercalated ducts
and may be subtle. More readily recognizable are the "pseudolumens" which are lined by basaloid
(myoepithelial) cells and contain acellular, eosinophilic basement membrane material.
ACC of the breast are typically estrogen and progesterone receptor negative and do not show
overexpression or amplification of HER2 .
These tumors are also c-kit and p63 positive
Cytokeratin (CK) 7 is useful as this antibody highlights the intercalated ducts which may not be readily
discernible in the solid variant of ACC.
Grading and Prognosis
Three architectural patterns have been described: cribriform, trabecular-tubular and solid . Some
reports have suggested that clinical course is correlated with growth pattern and that tumors with a
solid growth pattern exhibit a more aggressive clinical course . This observation has led to the
classification of ACC according to the proportion of solid growth (I, no solid growth; II, <30% solid
growth; III, >30% solid growth). Tumors with a solid growth pattern have been shown to be larger at
presentation and have a greater propensity for local recurrence as well as axillary lymph node
Others have shown no correlation between clinical behavior and tumor grade .
Overall, ACC of the breast have a very favorable prognosis with a low rate of axillary lymph node
Differential Diagnosis of ACC
The differential diagnosis of ACC includes other lesions with a cribriform pattern such as invasive
cribriform carcinoma and DCIS. Collagenous spherulosis may also be a differential diagnostic
Invasive cribriform carcinoma is composed of a single population of
malignant epithelial cells. Myoepithelial cells and basement membrane material are absent.
Cribriform DCIS is similarly composed of a single population of malignant
epithelial cells, but the tumor cell nests are bounded by a layer of myoepithelial cells. Basement
membrane material is absent from the lumens within the cribriform nests.
Collagenous spherulosis is a benign lesion that is frequently found in
association with other benign proliferative processes. Like ACC, collagenous spherulosis has a
population of myoepithelial cells producing basement membrane material deposited in lumens within the
lesion. However, unlike ACC, collagenous spherulosis does not exhibit an invasive growth pattern; it is
generally very limited in extent and is usually an incidental finding in a biopsy performed for another
Of interest, a number of lesions have been reported in association with ACC or even in transition to
ACC. Microglandular adenosis (MGA)
is the lesion most often reported in this scenario
have described foci of MGA to be intermingled with ACC. In some cases, the MGA shows a spectrum of
changes through atypical MGA and transitioning to ACC. Others have reported ACC in association with
tubular adenoma and adenomyoepithelioma. Whether any of these entities represents a precursor lesion (or
ACC in situ) is still a matter of debate.
There is very little data on the genetic alterations found in ACC of the breast. One case report
found low levels of genetic instability with small deletions on 16p and 17q (in the region of the BRCA1
. The authors speculate whether these findings may suggest a role for additional epigenetic
mechanisms or whether the 17q loss may explain the "basal" features of these tumors .
With respect to the issue of whether ACC are "basal-like" carcinomas, a recent study evaluating the
gene expression profiles of a variety of special-type carcinomas found ACC to localize with tumors of the
"basal-like" subtype .
The immunophenotype (ER, PR and HER2 negative and basal cytokeratin and c-kit
also supports the notion that these tumors belong to the basal-like carcinoma group .
However, in contradistinction to most invasive ductal carcinomas in among this subtype, ACC has a very
Treatment varies with each case. Many smaller well-demarcated lesions can be satisfactorily treated
with wide excision alone. Radiation therapy is often given as an adjunct though the benefit of this
modality for ACC is unknown. Axillary lymph node dissection is not indicated unless there is clinical
evidence of lymph node involvement
Sentinel lymph node sampling is recommended for high grade
ACC or for tumors in which there is a component of a second type of invasive carcinoma . Systemic
therapy is given for patients with lymph node metastasis .
In summary, solid variant of adenoid cystic carcinoma with basaloid features is an unusual tumor
composed of solid nests of basaloid appearing cells with moderate to marked nuclear atypia, rare
intercalated ducts and deposition of basement membrane material .
- Recognition of solid ACC as special type of
carcinoma with a more favorable prognosis
- Identification of pseudolumens with basement
membrane material as well as true glandular lumens will aid in diagnosis
- C-Kit and CK7 may be helpful adjuncts to diagnosis
Breast, carcinoma, adenoid cystic carcinoma, basal-like
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