Breast Pathology: Differential Diagnostic Dilemmas
Dr. Christopher Elston
Case 1 -
Ductal Carcinoma In Situ, Solid and Cribriform Pattern
Dr. Jean F. Simpson
A 58 year old woman underwent a stereotactic needle biopsy after suspicious calcifications were
identified on a screening mammogram. She had no previous history of abnormal mammograms.
Case 1 - Slide 1
The section shows several cores of breast tissue that contain a proliferation of monomorphic cells
filling and expanding lobular units, and true ducts. Individual cells have round, regular nuclei with
inconspicuous nucleoli, and homogenous pale cytoplasm. The cells are arranged into microglandular
structures or rosettes, some of which are subtle. In areas where the micro-rosette lumina are not
evident, the cells appear to be overlapping, and not evenly placed. Some of the spaces have punctate
necrosis and associated microcalcification. The overall size of the lesion based on the microscope
slide is 6 mm.
The distinction of atypical ductal hyperplasia and low grade ductal carcinoma in situ (DCIS) is based
on the extent of the lesion. Both of these entities are characterised by a uniform, monomorphic
population of cells. In this example, the extent of the lesion (6 mm) is sufficient to qualify as DCIS.
Moreover, the involvement of several adjacent lobular units in continuity with true ducts cements the
diagnosis of DCIS. In areas where the lumens of the rosettes are not evident, the back-to-back
arrangement of the rosettes can be mistaken for the pattern of cellular overlap that is defining for
florid hyperplasia without atypia. Another diagnostic consideration is lobular neoplasia, but careful
scrutiny will identify distinct cell borders and the formation of microglandular structures.
Immunohistochemical studies were not felt to be necessary, but this example of DCIS would be expected to
- Florid hyperplasia without atypia
- Atypical ductal hyperplasia
- Ductal carcinoma in situ, solid and cribriform pattern, low grade, with focal necrosis
- Lobular carcinoma in situ
An image-guided wire localisation biopsy was performed. The previous biopsy site was
identified, and no residual lesion was present. The patient underwent brachytherapy.
Ductal carcinoma in situ, solid and cribriform pattern, low grade with punctate necrosis, and
determinant calcifications, 6 mm.
Discussion and Clinical Implications
There is a wide recent acceptance of the heterogeneity of DCIS.
accept that cytology and histologic pattern (Table 1) can be used together to make assignment into
categories more precise, reproducible, and clinically useful.
|Histology ||Cytology ||Necrosis ||Calcification|
|Comedo* ||High grade ||Extensive ||Linear, branched|
|Intermediate ||Intermediate ||Limited ||Focal, punctate|
|Low grade ||Absent ||Microscopic foci|
* Although different terms are used for this high-grade category, the presence of both advanced nuclear atypia and extensive necrosis are necessary criteria.
# Some of these are high grade and may be considered comedo type. When present in pure form, they may be extensive.
It is evident that the lower grade, non-comedo lesions are likely to be smaller and also may be
amenable to treatment with very low recurrence rates (Table 2).
|Study ||Follow-up (mo) ||Recurrence rate (high grade/ comedo) (%) ||Recurrence rate (low-intermediate grade/ non-comedo) (%)|
|Lagios||100||11/36 (30.5) ||1/42*|
|Bellamy || 60||10/25 (40) ||0/6 (0)|
|Ottesen ||63||23/76 (30.6) ||3/36 (8.3)|
|Schwartz ||47||10/21 (47.6) ||1/51 (2)|
* The single recurrence was from a patient whose biopsy contained intermediate-grade DCIS, no
low-grade DCIS cases recurred.
Several studies have assessed the risk of subsequent invasive carcinoma for patients in whom the
diagnosis of DCIS was not made at the initial biopsy for small, non-comedo lesions. Approximately one
third of these patients developed invasive breast cancer in the same region of the same breast within
1018 years. Thus, it would appear that small examples of non-comedo DCIS are non-obligate precursor
lesions. If one accepts the fact that some of the lesions in the 1978 
and 1982 
articles were completely removed, it is likely that the progression rate of non-comedo DCIS to invasive
cancer over a prolonged period of time approaches 50%.
Developing evidence strongly supports the idea that adequate excision of DCIS lesions without
radiotherapy (Table 2) may lead to cure.  Smaller non-comedo examples of DCIS are regularly
treated successfully at least with follow-up extending to 7 or 8 years.
Role of radiation
What is the role of radiotherapy in reducing local recurrence after wide excision of a localised area
of DCIS? Preliminary data (with follow-up of <4 years) from a study in the United States 
suggests that radiotherapy may reduce the rate of disease recurrence within the breast following an
adequate excision of a localised area of DCIS. It is not clear from this study whether the benefits of
radiotherapy relate to all types of DCIS or whether the benefits will be demonstrable beyond 43 months of
follow-up. To determine the optimum treatment for DCIS detected in screening programs, a number of
clinical trials are underway. It is widely accepted that the mammographically detected DCIS lesion
should be considered separately from the regularly larger lesions presenting with palpable masses and
nipple discharge. 
Complete embedding of the lesion with accounting for the three-dimensional extent of the disease
within the breast is critical for conservative treatment of DCIS. Almost any case of DCIS excised with a
1 cm margin should not recur locally.  What has not been established is that all cases of
DCIS that are amenable to local excision for cure require a 1 cm margin. An Eastern Oncology Cooperative
Group Trial (ECOG 5194) is currently accruing patients to determine which DCIS lesions may be cured by
local excision alone. Entry criteria include complete submission of the lesion by sequential sectioning,
margins clear of DCIS by at least 3 mm, and size of the DCIS <=1 cm for high-grade and <=2.5 cm for
intermediate- or low-grade DCIS. Patients are accepted into this trial after central review of their
In summary, there is strong evidence that small size and low histologic grade interact to produce
lesions easily cured by local excision without radiation therapy. This is certainly true of lesions that
are <1 cm in largest diameter. Thus, the best estimate of size of a DCIS lesion should be stated even
for core biopsy specimens to facilitate clinical management. The greatest extent of a lesion is assessed
most easily by careful pathologicmammographic correlation, which is mandatory in most instances. It is
also clear that extensive high-grade, comedo lesions are not easily cured and that recurrences are common
even after radiation therapy.  Precisely which concurrence of histologic grade, size, and
margin clearance is to be the determinant of therapeutic decision-making is an area under investigation
currently. However, it should be understood that local recurrence in the setting of a low-grade lesion
is very unlikely to be a life-threatening event and that a woman's desire for breast conservation with a
willingness to accept the possibility of local recurrence may be as important with regard to therapeutic
decision-making as any other consideration. In contrast, local recurrence in the setting of a high-grade
DCIS lesion is much more likely to be associated with invasion, high-grade histology, and distant
Thus, careful pathologic assessment of DCIS lesions that includes histologic
pattern, grade, size, and margin status is essential for optimal clinical management, and we owe our
clinical colleagues and, more importantly, our patients nothing less.
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