Breast Pathology: Differential Diagnostic Dilemmas
Dr. Christopher Elston
Case 4 -
Dr. Laura C. Collins
A 47 year old woman was noted to have microcalcifications on a screening mammogram. The patient
underwent a wire-localised excisional biopsy. The case was sent in for consultation with a question of
atypical ductal hyperplasia. Area in the images is an incidental finding.
Case 4 - Slide 1
Diagnosis: Microglandular adenosis
Microglandular adenosis is an uncommon form of adenosis and is considered to be a benign
proliferative lesion. Clinically, microglandular adenosis may present as a mass or an area of
thickening. On mammographic examination, it can appear as an area of radiologic density or an area of
microcalcifications and may be suspicious for malignancy. Grossly, microglandular adenosis appears as an
ill-defined lesion. The age range at presentation is broad (28-82 years).
Microglandular adenosis is the one benign lesion in which the 'two cell type' rule is
that is the proliferating tubules are lined by a single layer of epithelial cells
and lack an outer myoepithelial cell layer. The arrangement of the tubules is haphazard; they are small,
regular, and rounded without angulation. Eosinophilic, periodic acid-Schiff (PAS)–positive,
diastase-resistant material is frequently seen within the lumina, as are calcium deposits. The
epithelial cells are cuboidal or flattened without apical snouting and are cytologically benign. The
cells are occasionally vacuolated and contain cytoplasmic PAS-positive material. Staining for basement
membrane by the PAS method is usually negative, but complete reticulin rings can be demonstrated around
the tubules by silver impregnation techniques. Immunohistochemistry with basement membrane markers such
as laminin and collagen IV, as well as electron microscopy, confirm the presence of an intact basement
membrane around the epithelial structures and the absence of myoepithelial cells. The epithelial cells
are strongly reactive to S100 and cathepsin D in addition to their reactivity to cytokeratin stains.
Microglandular adenosis is negative for epithelial membrane antigen (EMA) and gross cystic disease fluid
protein (GCDFP) as well as estrogen and progesterone receptors. 
Most reports on microglandular adenosis indicate that it is entirely benign.
atypical forms of this lesion have been described ('atypical microglandular adenosis') arising in
association with more typical examples of microglandular adenosis.  In atypical microglandular
adenosis, the glands become more complex with interconnecting of glands, formation of luminal bridges and
microcribriform nests. Cells begin to stratify obliterating the lumens of the glands. Cytologic atypia
is often also present and there is loss of luminal secretions.
Carcinoma can arise in or in conjunction with microglandular adenosis
progressing through atypical microglandular adenosis and/or DCIS. The invasive carcinomas tend to retain
some of the features of the underlying microglandular adenosis, such as an alveolar growth pattern and
clear cytoplasm and retention of the immunophenotypic profile (S100 and cathepsin D positive, and ER/PR
negative).  Unusual features, including a propensity to basaloid and adenoid cystic
carcinomas and even cartilaginous differentiation, may be seen.
The differential diagnosis of microglandular adenosis includes tubular carcinoma and other types of
Tubular carcinoma is an extremely well-differentiated carcinoma consisting of irregularly arranged
tubules lined by a single layer of epithelial cells that have little pleomorphism and a low mitotic
rate. Cytoplasmic apical snouting is frequently seen. The glandular lumina are open, and in contrast to
the rounded glands of microglandular adenosis, the tubules are characteristically angulated.
Occasionally, trabecular bars are present, although branching and anastomosis of tubules are not
features. The stroma is abundant and usually cellular. Elastosis may be prominent. Unlike
microglandular adenosis, tubular carcinomas are typically estrogen-receptor and progesterone-receptor
positive. Flat epithelial atypia and ductal carcinoma in situ (DCIS) are a frequently associated
finding. DCIS, when present, is usually of well-differentiated, low-grade type with a cribriform or
Features helpful in the differential diagnosis are listed in the table below.
|Feature ||MGA ||Tubular Carcinoma|
|Gland distribution ||random ||stellate|
|Gland shape ||round ||angular|
|Apical snouts ||no ||yes|
|Luminal secretions ||yes ||no|
|Basement membrane ||yes ||no|
|Desmoplasia ||no ||yes|
|Assoc DCIS ||no ||yes|
|ER/PR status ||negative ||positive|
Sclerosing adenosis is less likely to be confused with microglandular adenosis because the low-power
examination generally reveals multiple nodular areas with retention of the overall lobular architecture.
Unlike the haphazard growth pattern seen in microglandular adenosis, these nodules are usually rounded
and well defined. The numerous tubules, although frequently compressed and distorted, retain their two
cell (epithelial and myoepithelial) layers, but this feature may not be visible in each individual
tubule. Like microglandular adenosis, microcalcification is frequently seen within the glandular
lumina. The fibrous stroma is usually dense and is often hyalinized, and elastic tissue may be
prominent. Compression of the tubules occludes their lumina in many areas, resulting in an infiltrative
Secretory adenosis is a term that has been used to describe a lesion architecturally similar to
microglandular adenosis but in which myoepithelial cells are evident around the tubular
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- Tavassoli FA, Norris HJ. Microglandular adenosis of the breast. A clinicopathologic study of 11 cases with ultrastructural observations. Am J Surg Pathol 1983; 7(8): 731-737.
- Clement PB, Azzopardi JG. Microglandular adenosis of the breast--a lesion simulating tubular carcinoma. Histopathol 1983; 7(2): 169-180.
- James BA, Cranor ML, Rosen PP. Carcinoma of the breast arising in microglandular adenosis. Am J Clin Pathol 1993; 100(5): 507-513.
- Acs G, Simpson JF, Bleiweiss IJ et al. Microglandular adenosis with transition into adenoid cystic carcinoma of the breast. Am J Surg Pathol 2003; 27(8): 1052-1060.
- Harmon M, Fuller B, Cooper K. Carcinoma arising in microglandular adenosis of the breast. Int J Surg Pathol 2001; 9(4): 344.
- Tavassoli FA. Benign Lesions. In: Pathology of the breast. 2nd ed. Stamford, CT: Appleton and Lange; 1999.