Breast Pathology: Differential Diagnostic Dilemmas
Dr. Christopher Elston
Papillary Carcinoma In Situ (Complex Sclerosing Papillary Lesion with Associated DCIS)
Dr. Christopher Elston
A female aged 59 years attended for routine breast screening. A lobulated 22 mm mass was found in
the right upper outer quadrant; clinical assessment was 'probably benign'. Mammography and ultrasound
examinations were designated 'indeterminate'. Ultrasound guided mammotome biopsy was performed.
The section shows several cores of tissue from a mass lesion composed mainly of well-formed papillary
structures. These are lined by two-layered epithelium, with inner myoepithelial and outer secretory
cells surrounding fibrovascular cores. The epithelial cells are regular in appearance with no nuclear
atypia. Focally there is mild to moderate secretory cell proliferation. In addition, at the edge of the
lesion in one core there are two duct spaces which contain a monotonous epithelial proliferation with a
solid and partly cribriform architecture; some nuclear atypia is present in these cells and they exhibit
a clear eosinophilic cytoplasm.
Papillary lesions are classified under the following sub-headings:-
Benign duct (or intracystic) papilloma
Duct papilloma with epithelial atypia
Papillary carcinoma in situ (encysted papillary carcinoma)
Invasive papillary carcinoma
In Europe non-operative needle core biopsies are reported using the following convention:
B1 – normal
B2 – benign
B3 – benign of uncertain malignant potential
B4 – suspicious of malignancy
B5 – malignant
It is clear that, depending on the morphological features present; papillary lesions can be allocated
to any of the categories from B2 to B5. In this case the main lesion appears benign and it might be
thought that the B2 category would be appropriate. However, focally there is moderate epithelial
hyperplasia and the morphological features in the adjacent duct spaces raise the possibility of an
associated in situ carcinoma; the choice then lies between B3 – benign of uncertain malignant potential
and B 4 – suspicious of ductal carcinoma in situ. In most circumstances both categories would lead to
further investigation, usually in the form of an excision biopsy; the difference is that a B3 diagnosis
would result in a more limited diagnostic biopsy whilst a B4 diagnosis might be followed by a therapeutic
excision, depending on the degree of suspicion clinically and on imaging. In view of this it was
considered that the appropriate reporting category was:
B3 – benign of uncertain malignant potential.
An image-guided wire localisation biopsy was performed. The specimen weighs 56 gm and measures
85 x 40 x 35 mm. Centrally there is an ill-defined firm area approximately 15 mm in diameter with
adjacent fat necrosis.
Microscopically, the firm area consists of papillary structures, most of which show epithelial
proliferation without atypia. In addition several ducts contain a monotonous proliferation of cells with
vesicular nuclei showing moderate nuclear atypia and abundant eosinophilic cytoplasm, arranged in a
cribriform architectural pattern; mitoses are scanty. These features are those of intermediate grade
ductal carcinoma in situ (DCIS). Some papillary structures appear to have an intermediate epithelial
proliferation with atypical cells similar to those found in the ducts involved by DCIS. The histological
diagnosis is confirmed by immunostaining for basal (CK5, 14) and luminal (CK8/18) cytokeratins; a mixed
cell population is seen in the papillary areas whilst in the cribriform structures the cell proliferation
is dominantly of luminal type. A further feature is the presence of central sclerosis with entrapped
ductules. These appearances are interpreted as those of a complex sclerosing papillary lesion with
associated DCIS and are considered to be part of the spectrum of Papillary carcinoma in situ . No
invasive element is seen.
The closest excision margin was 2 mm (diagnostic excision only). Adjacent linear cellular fibrosis
indicated the site of the previous mammotome biopsy.
A cavity re-excision was performed and clear margins (>10 mm) were obtained.
No further therapy was given and the patient remains well and tumour-free after two years clinical
and imaging follow-up.
A diagnosis of papillary lesion on needle core biopsy does not necessarily mean that excision is
required. If the appearances are entirely benign (B2) and the core appears to be an adequate sample,
based on the size of the core (multiple cores increase the yield) compared with the clinical and imaging
features, there is evidence that no further surgery is required at this point. Follow-up should be
maintained and if the lesion increases in size excision may then be advisable.
Opinion is divided on the correct management of cases in which atypical features are found in a core
biopsy, short of frank malignancy (B3), partly because most studies contain very few cases. Some have
shown that the majority of lesions are subsequently shown to be papillary carcinoma in situ whilst others
have found the opposite – the majority prove to be benign or atypical papillomas.
In Nottingham it is our policy to recommend excision biopsy following a B3 diagnosis on core biopsy
unless there are good clinical reasons to avoid surgery.
Differential immunostaining with basal (CK5,14) and secretory (CK8,18) cytokeratins and myoepithelial
markers (smooth muscle myosin (SMM), p63) may help to reduce the number of B3 diagnoses by recategorising
cases as B2 or B5. Features which favour a malignant diagnosis include the following:
NB care must be taken to avoid over-interpretation of entrapped epithelial structures in the
peripheral pseudocapsule as evidence of invasion. A suspicious (B4) or malignant (B5) diagnosis on core
biopsy requires therapeutic excision with clear margins or mastectomy. The type of definitive surgery
depends on the clinical and imaging findings and patient choice.
- multi-layering of epithelial cells
- the presence of nuclear atypia and an increase in
- a deficient myoepithelial layer (demonstrated by
negative SMM and p63 immuno- staining)
- areas with a cribriform architecture
- a monomorphic epithelial growth pattern (supported by
differential cytokeratin immuno-staining)
Papillary carcinoma in situ (Encysted Papillary Carcinoma) is regarded as a specific but uncommon
variant of ductal carcinoma in situ (DCIS) occurring mainly in women over the age of 60 years. It is
rare in symptomatic practice but may present as a soft palpable mass. The main method of detection is
through mammographic screening in which it is visualised as an impalpable mass lesion, usually with
associated cystic change. The presence of haemorrhage within such a cystic structure is highly
suggestive of papillary carcinoma in situ.
The appearance is that of a soft, circumscribed, cystic mass with a thin fibrous wall and a
haemorrhagic or fleshy cut surface, approximately 10-30 mm in diameter.
Microscopically there is a fundamental papillary structure with clear fibrovascular cores and
sufficient epithelial proliferation with multilayering and cytological atypia to qualify as in situ
carcinoma. A focal cribriform architecture is often present. If the diagnosis of malignancy is in doubt
immunostaining should be carried out, as detailed above. Based on the degree of nuclear atypia and
number of mitotic figures cases can be assigned to low, intermediate or high grade, in a similar way to
DCIS. DCIS may be present in adjacent duct spaces and blocks should be selected carefully to include
surrounding breast tissue and excision margins. Occasionally invasive carcinoma may intervene and the
tumour periphery should be searched carefully for evidence of spread beyond the pseudocapsule; as noted
above, however, the presence of entrapped epithelial islands within the pseudocapsule must not be
interpreted as invasion.
The prognosis of papillary carcinoma in situ is excellent and long-term survival (>10 years) is
greater than 90%; this appears to be independent of grade. Mastectomy can be regarded as curative and
conservation surgery also gives good results, especially if there is no DCIS in adjacent ducts (about 60%
of cases). Local recurrence, both in situ and invasive, may occur if local excision is incomplete and
this risk is related to the presence of adjacent DCIS.
Papillary carcinoma in situ (complex sclerosing papillary lesion with associated DCIS)
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