Pitfalls and Problems in Breast Pathology
Section 2 -
Diagnostic Problems in Breast Pathology
How to avoid the pitfalls, new entities and controversial lesions
Ian O. Ellis and Sarah Pinder
Almost any breast lesion may produce diagnostic difficulty and a degree of selectivity is therefore
necessary in a seminar such as this. This has been achieved by reference to two main sources: data on
consistency of diagnosis from External Quality Assessment schemes in the United Kingdom organised by the
National Co-ordinating Group for Breast Screening Pathology and in Europe organised by the European
Breast Screening Pathology Group;
an informed audit of cases sent for second opinion from
other departments. It is, perhaps, not surprising that both routes produce similar problem cases which
fit into a relatively restricted group of diagnostic categories which can be considered under the
headings shown in Table 1:
Table 1 - Main categories of lesion that lead to diagnostic pitfalls in breast
|Effects of previous therapy|
|Pathological prognostic factors|
In practice the pitfalls described below may be avoided or reduced by the application of sound
general histopathological principles. These include the application of strict diagnostic protocols and
in this respect there is good world-wide agreement for most lesions. Participants in the symposium are
referred to the standard breast pathology texts in the reference list, including UK and European breast
screening pathology guidelines.
It is interesting to note that many diagnostic
difficulties arise with those lesions where complete agreement on diagnostic criteria has not yet been
reached. The aim in this presentation is to emphasise practical points of distinction rather than to
provide a comprehensive description of each lesion.
One further general point is pertinent. Experience has shown that in many cases difficulty in
diagnosis is related to sub-optimal specimen preparation, mostly poor fixation or tissue processing. A
comparatively minor investment of time and effort in improving the technical aspects of the diagnostic
process will be rewarded by considerably better quality of preparations and a consequent decrease in
unnecessary problem cases.
Some benign breast processes are characterised by a combination of epithelial proliferation, with or
without a myoepithelial component, and stromal fibrosis and sclerosis that may result in formation of a
mass lesion. The entities that can be placed within the umbrella of sclerosing lesions are sclerosing
adenosis (SA), microglandular adenosis (MGA) and radial scar/complex sclerosing lesion (RS/CSL). They
have many overlapping features and may all give rise to diagnostic problems clinically, on imaging
(ultrasound and mammography) and histopathologically. Although they are frequently impalpable, both
sclerosing adenosis and complex sclerosing lesion may produce palpable masses that can easily be mistaken
for invasive carcinoma. Fine microcalcification is a common feature of all three entities and the
appearances on mammography may be closely similar to those of low grade ductal carcinoma in situ
(DCIS).  In addition both SA and RS/CSL may be identified on mammography or ultrasound as an
architectural distortion or spiculate mass, which cannot be distinguished with confidence from
carcinoma. In all these situations a tissue diagnosis must be established and increasingly this is
obtained pre-operatively through needle core biopsy using one of the new spring loaded
Diagnostic difficulty may be experienced histopathologically in interpreting such
samples, and indeed in some circumstances excision biopsy specimens may also cause problems, the main
differential diagnosis being invasive carcinoma, especially of tubular type.
The main morphological features of the sclerosing lesions and tubular carcinoma are shown in Table
Table 2 - Differential diagnosis of sclerosing lesions
|Tubular carcinoma ||Sclerosing adenosis ||Microglandular adenosis ||Radial scar|
|Infiltrative, often stellate architecture ||Lobulocentric architecture ||Infiltrative, disorderly architecture ||Complex, stellate architecture|
|Desmoplastic stroma. Central elastosis frequent ||Often central cellularity with sclerotic periphery ||Fibrotic stroma ||Variable stromal cellularity|
|Well formed angulated tubules ||Distorted, compressed tubules. Frequent obliterated lumina ||Uniform round tubules ||Distorted tubules|
|Abundant eosinophilic cytoplasm often with apical snouts ||Infrequent apical snouts ||Clear, vacuolated or granular epithelial cytoplasm. No apical snouts ||No apical snouts|
|Absent myoepithelial cells ||Prominent admixed myoepithelial cells ||Occasional myoepithelial cells described ||Myoepithelial cells seen|
|Patchy, incomplete basement membrane ||Uniform basement membrane ||Prominent basement membrane ||Basement membrane seen|
|Intraluminal secretion or microcalcification may be seen ||Intraluminal microcalcification may be seen ||Intraluminal colloid-like material which may be calcified ||Intraluminal secretion uncommon.Microcalcification may be seen|
|Frequent associated low grade cribriform or micropapillary DCIS ||May be associated apocrine metaplasia. Associated DCIS and lobular neoplasia rare but described ||Atypical features rarely described (see text) ||Associated cysts, sclerosing adenosis, epithelial hyperplasia and rarely in situ or invasive carcinoma|
Reproduced with permission from Elston CW, Ellis IO. Systemic Pathology 3rd Ed - The Breast.
London: Churchill Livingstone, 1998
Sclerosing adenosis is characterised by a disorderly proliferation of
acinar and ductular epithelial cells, myoepithelial cells and intralobular stroma which results in
expansion and distortion of lobules and an overall whorled appearance. Despite the apparent
disorganisation of the cellular proliferation, a lobulocentric architecture is maintained. The
epithelial component may form microtubular structures but the compressed acini frequently show
obliteration of their lumina. Nuclei are small and regular without atypia and mitotic figures are
infrequent. Fine foci of microcalcification are frequently found within the lumina of epithelial
In microglandular adenosis there is a disorderly proliferation of small
round acinar structures, apparently infiltrating between normal ducts and lobules and extending into
adipose tissue. There is no spindle cell proliferation and the growth pattern is not lobulocentric. The
acini appear to be lined by a single layer of epithelial cells and the lumina often contain PAS positive,
diastase-resistant, eosinophilic material which may, rarely, be calcified.
Classically radial scar/complex sclerosing lesions are composed of a
radial arrangement of ductular structures around a central fibroelastotic core. In early lesions the
central connective tissue is cellular and includes numerous myofibroblasts. The entrapped ductular or
tubular structures are lined by a two-layered epithelium although epithelial proliferation is commonly
present. Atypical ductal hyperplasia or lobular neoplasia may also be seen. 
As noted above the most important differential diagnosis for all these lesions is invasive carcinoma,
especially the tubular type. In excision specimens sclerosing adenosis can usually be distinguished by
its circumscribed lobulocentric low power morphology in contrast with the infiltrative pattern and
desmoplastic stroma of tubular carcinoma, but care should be taken with needle core and frozen section
specimens in which this feature may not be apparent. Furthermore, the architectural distortion produced
in both these techniques may result in a mistaken diagnosis of infiltrating lobular carcinoma due to
compression of the epithelial structures. In rare cases of sclerosing adenosis extension of the
glandular components into perineural and vascular spaces is seen, a finding that must not be regarded as
indicative of malignancy in the absence of confirmatory features. The presence of apocrine atypia may
also raise the question of malignancy  and this should be avoided by recognition of the
benign features described above. Both ductal carcinoma in situ and lobular neoplasia have been recorded
in the nodular form of sclerosing adenosis and may be mistaken for invasive carcinoma if the presence of
myoepithelial cells is not recognised.  If the diagnosis is in doubt immunostaining with
anti-smooth muscle actin will readily demonstrate their presence, thus excluding the diagnosis of
Microglandular adenosis can usually be distinguished from tubular carcinoma by its diffuse pattern
and lack of central elastosis and desmoplastic stroma, although the sclerosing type of tubular carcinoma
may provide a close mimic. A useful distinguishing feature is the fact that the glandular structures in
MGA are usually uniform and rounded in contrast with the less regular, often angulated appearance in
tubular carcinoma. Immunostaining for anti-smooth muscle actin is less helpful in MGA because in most
recorded cases myoepithelial cells are said to be absent.
MGA may also be confused with
the tubulo-lobular variant of infiltrating lobular carcinoma. However, careful examination in the latter
always reveals cords of cells typical of the classical lobular type in addition to microtubular
In the great majority of cases of RS/CSL the distinction from tubular carcinoma is relatively
straightforward. The dense, sclerotic, poorly cellular stroma and elongated flattened tubules are quite
different from the desmoplastic stroma and well formed oval structures in tubular carcinoma. However,
more complex lesions with an admixture of sclerosing adenosis and epithelial hyperplasia may cause
problems; it must also be remembered that both in situ and invasive carcinoma may be encountered in
association with RS/CSL.  If there is any doubt about the correct diagnosis immunostaining
with anti-smooth muscle actin will help to clarify both these problems.
Great care should be taken in the interpretation of sclerosing lesions found on needle core biopsy
because of the sampling problem. For example, the finding of part of a benign RS/CSL on core biopsy does
not exclude the possibility of associated malignancy; it is, therefore, still our policy to excise all
parenchymal distortions or architectural deformities.
These lesions cause diagnostic problems because papillary structures are found in benign and
malignant processes and the differences between the two are often subtle and difficult to assess; the
entities concerned are shown in Table 3.
Table 3 - Spectrum of papillary lesions of the breast
|Single intraduct papilloma|
|Multiple duct papillomas|
|Complex sclerosing papillary lesion|
|Encysted papillary carcinoma (papillary carcinoma in situ)|
|Invasive papillary carcinoma|
In practice few problems should be encountered with small
single benign intraduct papillomas that are usually centrally placed under the nipple and removed by
microdochectomy. However, potential pitfalls will be encountered with all of these processes on needle
core biopsy, partly because of sampling error and partly related to architectural distortion due to crush
artefact. Our early experience with pre-operative use of needle core biopsy, based on the manual Tru-Cut
needle lead us to advice caution when benign papillary structures were identified, because of the risk of
a false negative diagnosis. It is undoubtedly true that some invasive papillary carcinomas arise in a
pre-existing benign papilloma, almost always of the multiple type. The finding of benign papillary
structures on needle core biopsy does not necessarily mean, therefore, that malignant change is not
present elsewhere in the lesion. It is our practice to issue a report with a non-specific conclusion of
'papillary lesion present', and local excision is advised. This would come into the B3 category - lesion
of uncertain malignant potential - in the revised United Kingdom National Health Service Breast Screening
Service (NHSBSP) Guidelines for Pathologists. It should also be noted that multiple duct papillomas are
usually peripheral and often associated with florid epithelial proliferations, including usual and
atypical ductal hyperplasia. In excision specimens, adequate sampling is required to exclude the
presence of associated ductal carcinoma in situ (see also below borderline lesions).
Some benign papillary lesions form relatively well defined solid masses with a dominantly sclerosed
architecture. In the past the term ductal adenoma was applied to such lesions, but they are now believed
to arise from sclerosis of duct papillomas and we prefer to use the term complex sclerosing papillary lesion. Epithelial proliferation is
relatively common and a minor degree of nuclear atypia may be seen, especially if there is apocrine
change. They are, in fact, entirely benign and care must be taken not to overdiagnose malignancy,
especially if entrapped tubular structures are found. There is considerable morphological overlap with
sclerosing adenosis and radial scar/complex sclerosing lesion and in some cases it may be impossible to
make a firm distinction.
Encysted papillary carcinoma (papillary carcinoma in situ) may be confused
with invasive papillary carcinoma, especially on needle core biopsy. This relatively uncommon lesion is
now being detected with increasing frequency in mammographic screening. Because of their soft, cystic
structure encysted papillary carcinomas are rarely palpable clinically, but are seen on mammography in
older women as well circumscribed mass lesions. Astute radiologists quickly develop a suspicion of the
correct diagnosis when they encounter an unusual degree of haemorrhage on needling the lesion. Using a
multi-disciplinary team approach this information enables the pathologist to assess the papillary
structures seen on needle core biopsy more accurately. The presence of multi-layering and genuine
cytological atypia point towards a diagnosis of encysted papillary carcinoma rather than a benign
intracystic papilloma but care must be taken not to overinterpret the presence of entrapped tubules as
evidence of invasion. In any event all such circumscribed impalpable papillary lesions should be managed
by complete local excision rather than mastectomy in the first instance. Attention must be paid to
excision margins, since local recurrence is related both to the presence of ductal carcinoma in situ in
adjacent ductal structures and completeness of excision.  As with needle core biopsy areas
of possible invasion around the periphery of the excised lesion should be assessed with caution. There
is usually a broad fibrous 'capsule' and 'pseudoinvasion' due to the presence of entrapped tubules is a
frequent finding. Invasive carcinoma may, rarely, be associated with encysted papillary carcinoma, but
should only be diagnosed when epithelial structures extend into adjacent breast or adipose tissue.
Encysted papillary carcinoma has a good prognosis and complete excision appears to be
The language used in medicine is fascinating and it is interesting to observe how insidiously words
such as 'borderline' creep into our vocabulary without due thought to their impact on clinical practice.
It is difficult to establish when the term was first applied to breast lesions but it appears to have
been in use for at least 25 years to encompass those lesions characterised by epithelial proliferation.
The main problem with the term is that it implies a sharp division between entities and this is usually
interpreted as providing a separation between benign and malignant lesions with a consequent effect on
clinical management protocols. In reality such sharp distinctions rarely occur and certainly where
breast epithelial lesions are concerned we are dealing with a spectrum of changes. This has been
emphasised in recent years by molecular genetic studies which have shown loss of heterozygosity in usual
epithelial hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ (DCIS); this data
implies that even usual epithelial hyperplasia, in some cases, is a clonal, and therefore neoplastic,
Nevertheless, from the practical viewpoint stratification is required so that
individual patients receive appropriate treatment. The entities concerned are the epithelial
hyperplasias of usual and atypical subtypes, in situ carcinoma and so-called 'minimal' invasive
carcinoma. In my view it is more appropriate to regard these lesions as occupying a borderland between
entities that are definitely benign and those that are unequivocally malignant. This concept now needs
to be re-evaluated for two main reasons; there are definite problems in reproducibility of diagnosis of
such entities as atypical ductal hyperplasia (ADH) and more appropriate cut-off points are required to
stratify patients for clinical and therapeutic management. In addition there is mounting evidence that
borderline lesions of the breast encompass a number of genetically different lesions that appear to have
distinct lineage pathways to invasive carcinoma
. These observations question the relevance
of umbrella systems for classification such as MIN
The debate concerning the utility of the term atypical ductal hyperplasia has continued for the past
20 years. Page and colleagues have promoted the view that epithelial proliferations which closely
resemble DCIS of low grade type, but which do not exhibit all the precise morphological characteristics
to make that diagnosis with confidence should be designated as ADH.
concept has received wide acceptance doubts remain. Some,
but not all, 
reproducibility studies have shown poor agreement for the entity suggesting that there is a lack of
agreement on the diagnostic criteria. It is therefore worth emphasising some key distinguishing
features, as set out below:
|a ||DCIS of low grade type has a population of evenly spaced, uniform cells with uniformly oval to rounded nuclear features, comprising without doubt the entire population of cells throughout at least two membrane-bound spaces (a measure of the extent of the lesion). Secondary spaces have smooth rounded 'punched out' borders of geometrical structure (cribriform architecture - cribrum - sieve - Latin) and rigid non-tapering bars can be found. Micropapillary structures are bulbous and regularly placed around the space.|
|NB|| Epithelial proliferations of high grade cytology, with or without comedo necrosis qualify as DCIS, regardless of lesional size.|
|b ||ADH exhibits partial involvement of the basement membrane-bound space by a cell population of the type defined above for DCIS of low grade type. A second cell population is usually present, consisting of columnar, polarised cells of the type seen in the ductal lamina positions immediately above the basement membrane. There is general agreement that lesions with these features, which measure more than 2-3 mm in diameter, are more likely to represent DCIS than ADH. ADH is, therefore, almost without exception, a tiny lesion.|
In summary, we use the following rules of thumb.
|1|| We do not entertain a diagnosis of ADH unless low grade DCIS has been considered seriously in the differential diagnosis.|
|2|| ADH is a very small, microfocal, process; the larger the lesion the more likely it is to be DCIS.|
|3|| It follows that if there is any doubt about the differential diagnosis further levels and blocks should be examined. In our experience this usually resolves the problem, almost always by revealing evidence of low grade DCIS.|
|4|| If changes resembling ADH are found in a needle core biopsy they should be regarded as either indicative of uncertain malignant potential or suspicious of malignancy. Excision biopsy is mandatory and usually reveals unequivocal low grade DCIS.
In recent years there has been a proliferation of classifications for ductal carcinoma in situ.
Despite differences in terminology all identify an aggressive comedo, poorly
differentiated, high grade subtype and a relatively indolent subtype - non-comedo, well differentiated,
low grade. In the United Kingdom it has been recommended that to avoid problems with the definitions of
comedo necrosis and architectural pattern a simpler nuclear grading system is adopted for use in the
National Health Service Breast Screening Programme (NHSBSP), and the same classification has been
accepted by the European Commission Working Party on Breast Screening Pathology.
However, problems with reproducibility still exist and only average agreement has been obtained in
studies to date.
We are still left with the dilemma of correlating the morphology of these epithelial proliferative
lesions and their management. Table 4 provides a somewhat speculative personal attempt to achieve this:
Table 4 - Current outline protocol for 'borderland' epithelial proliferative
lesions, which correlates morphological structure with clinical management
|Lesion ||Clinical significance|
|Epithelial hyperplasia Usual type ||Follow up not appropriate|
Atypical ductal hyperplasia Low grade < 3 mm
|Risk factor - follow-up only required - no|
|Ductal carcinoma in situ ||Excellent prognosis lesions - complete excision required|
|Low grade > 3 mm|
|High grade (Microinvasive carcinoma)|
'Small' invasive carcinomas <15 mm special type grade 1
ħlocal irradiation no systemic therapy
|Invasive carcinoma ||Local and systemic therapy based on evaluation of prognostic factors|
Epithelial hyperplasia of usual type, with its low relative risk factor of x2, needs no treatment or
follow-up. The size rule should still be applied to define atypical ductal hyperplasia but, in my view,
both ADH and low grade DCIS measuring less than 3 mm can be managed in the same way, by follow-up alone.
There is no doubt that the prognosis for all types of ductal carcinoma in situ is excellent, provided
that complete local excision is achieved. The same is true for so-called 'microinvasive carcinoma'
(which will be referred to further below) and small invasive carcinomas. Note that the definition of
"small" invasive tumour size has been raised to 15 mm from 10 mm because no difference in prognosis
between the two was found in the Nottingham Tenovus Primary Breast Cancer Study.  This group
of patients can therefore be treated by complete local excision, with or without axillary dissection.
Local irradiation may be appropriate, but systemic therapy is not indicated.
Experience from both anecdotal consultation cases and early data from the UK NHSBSP indicate that
microinvasion in DCIS is over-diagnosed by many general histopathologists. Because of this perception
and the lack of consensus throughout the world on diagnostic criteria the definition recommended for use
in the NHSBSP is very restrictive.  The lesion is composed predominantly of DCIS (almost
always of high grade type), but with foci of definite invasion outside the specialised lobular stroma
measuring not more than 1 mm in maximum diameter. There is no limit on the number of such foci. Care
must be taken not to confuse as microinvasion extension of DCIS into lobules, branching of ducts
containing DCIS, tangential cutting, crush and cautery artefact. Particular difficulty may be
encountered in cases with marked periductal fibrosis and inflammation. In general terms the diagnosis of
microinvasion should not be made unless there is convincing invasive carcinoma extending into
interlobular stroma or adipose tissue. Multiple levels should be examined in suspicious cases and we
have found in our laboratory that immunostaining for anti-smooth muscle actin may be helpful in
distinguishing in situ from invasive elements. Immunostaining for basement membrane components (type IV
collagen, laminin) is of less value. Pathologists are taught in general that when in doubt over a
'borderline' diagnosis to give the more malignant interpretation in order to avoid under treatment. It
should always be borne in mind when considering a diagnosis of microinvasive carcinoma that some surgeons
will carry out an axillary dissection or clearance in such cases but not, of course, for DCIS, and
overdiagnosis therefore leads to unnecessary surgery. Furthermore, there is no evidence to date that has
demonstrated that microinvasive carcinoma has a different prognosis from that of high grade DCIS. In my
view, therefore, the diagnosis should only be made in those rare cases with unequivocal evidence of
Fibroepithelial lesions may give rise to a number of diagnostic problems but the most important
concern phyllodes tumour. At the benign end of the diagnostic spectrum difficulty is occasionally
encountered in distinguishing a cellular fibroadenoma from a benign phyllodes tumour. At the malignant
end the criteria for the separation of benign and malignant phyllodes tumour are often misinterpreted
with consequent overdiagnosis of malignant phyllodes tumour.
Classically fibroadenomas are usually encountered in women under the age of 30 years whilst phyllodes
tumours are seen much more frequently in middle aged or older women. However, there is considerable
overlap between the two entities at both ends of the age range and a significant minority of phyllodes
tumours occurs in adolescents and young women.  Size alone is of no value as a
distinguishing feature; although most fibroadenomas are small, measuring less then 20 mm in diameter and
phyllodes tumours tend to be larger than this, there is marked variation in the size of both lesions. We
have certainly encountered a number of phyllodes tumours measuring no more than 10 mm in diameter.
Nevertheless, most problems are encountered with relatively large fibroadenomas in younger women when the
presence of an intracanalicular pattern with leaf-like foci and cellular stroma raise the possibility of
benign phyllodes tumour. Relative uniformity of stromal nuclei and a lack of mitoses favour a diagnosis
of fibroadenoma. Further blocks should always be examined but it may be very difficult to make a clear
distinction in some cases. It may be prudent to issue a cautious report in such cases, especially if the
lesion extends to resection margins, since risk of local recurrence in phyllodes tumour is related to
In the past phyllodes tumour gained an unwarranted aggressive reputation largely based on data from
tertiary referral centres that, by their very nature, tend to acquire the more difficult cases for
treatment. In addition there has been a general lack of agreement on the morphological criteria that
should be used to designate malignancy in an individual tumour. As a result some pathologists, in an
understandable attempt to avoid under-diagnosis, are inclined to err on the malignant side in assessing
the histological appearances. It is now accepted that the majority of phyllodes tumours are, in fact,
entirely benign; in our own community based study in Nottingham two thirds of the cases were classified
as benign on morphological grounds and only 16 per cent had malignant features.  We therefore
prefer to use the term 'phyllodes tumour' rather than cystosarcoma phyllodes and believe that the latter,
with its innate implication of malignancy, should be abandoned.
Based on semiquantitative criteria
we divide phyllodes tumour into three categories,
benign, borderline and malignant.  Benign tumours have a pushing margin, minimal stromal
overgrowth, cellularity and nuclear pleomorphism with stromal mitotic counts less than 10 per 10 fields
(field diameter 0.152 mm2). In malignant lesions the margin is infiltrative, there is marked
stromal overgrowth, cellularity and nuclear pleomorphism and mitotic counts are greater than 10 per 10
fields. Cases are placed in the borderline category if they fulfil some, but not all, of the criteria
for malignancy, e.g., a pushing margin, but moderate nuclear pleomorphism and an intermediate mitotic
count. Interestingly we found that none of these morphological features was useful in predicting local
recurrence, which was strongly related to completeness of local excision. Metastasis is very uncommon in
phyllodes tumour and only occurs in tumours with a malignant phenotype. It is our policy to excise
benign phyllodes tumours with a clear margin of at least 10 mm; re-excision may be appropriate in some
cases if completeness of excision is not achieved at the first operation. Mastectomy is advisable for
patients with malignant phyllodes tumours and is also offered to women with very large benign lesions to
avoid a poor cosmetic result. The borderline category is useful in preventing over-diagnosis of
malignancy and therefore potential over-treatment. Optimum local therapy depends on the size of the
tumour. Local excision is imperative, but only if this cannot be achieved with a satisfactory cosmetic
result need mastectomy be considered.
Controversial Lesions / New Entities
The distinction between benign apocrine hyperplasia and low grade forms of apocrine DCIS is
problematic and no simple solutions apply . In addition forms of atypical apocrine proliferation can
occur in association with sclerosing adenosis and in sclerosing lesions which can mimic invasive high
. Recognition of the problem in an individual case is key to avoiding error. We
currently apply simple rules to these problems, adopting Pages groups stance on apocrine proliferation
which uses cytomorphology and extent of lesion as the main arbiters between hyperplasia and DCIS. Use of
immunocytochemical staining for myoepithelial cells is useful to recognise involvement of a sclerosing
Columnar cell alteration and Atypia
In recent years following introduction of mammographic screening and use of needle core biopsy
to sample areas of microcalcification, forms of columnar cell alteration and atypia have been recognised
. These are often associated with mucin hypersecretion, microcyst formation and calcification.
More exaggerated forms exhibit atypia merging with or indistinguishable from micropapillary types of
DCIS. Coexisting invasive carcinoma of tubular or mucinous type have been described. We now consider
these lesions to form a spectrum of epithelial proliferations analogous to the more conventional
epithelial hyperplasia - ADH - low grade DCIS spectrum described above.
Low grade adenosquamous carcinoma and Sclerosing Lesions
We have recently recognised an association between radial scars/sclerosing lesions and a rare form of
invasive tumour "low grade adenosquamous carcinoma" . The significance of this observation
remains uncertain at present.
- Sloane JP, National Co-ordinating Group for Breast Screening Pathology. Consistency of histopathological reporting of breast lesions detected by screening: findings of the UK National External Quality Assessment (EQA) Scheme. Eur J Cancer 1994; 30: 1414-1419.
- Sloane JP, European Commission Working Group on Breast Screening Pathology. Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. Hum Pathol 1998; 29: 1056-1062.
- Sloane JP, European Commission Working Group on Breast Screening Pathology. Consistency achieved by 23 European pathologists for 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. Virchows Arch (A) Pathol Anat 1999; 434: 3-10.
- Elston CW, Ellis IO. Systemic Pathology 3E The Breast; vol 13. London: Churchill Livingstone, 1998.
- Elston CW. Breast Cancer Screening. In: Anthony PP, ed. Diagnostic Pitfalls in Histopathology and Cytopathology Practice. London: Greenwich Medical Media, 1998: vol, 39-53.
- European Commission. European Guidelines for Quality Assurance in Mammography Screening. de Wolf CJM, Perry NM, eds. 2nd ed; Luxembourg: Office for Official Publications of the European Communities, 1996.
- Royal College of Pathologists Working Group for Breast Screening Pathology. Pathology Reporting in Breast Cancer Screening. 2nd ed; NHS BSP Publications No 3, 1995.
- Royal College of Pathologists Working Group for Breast Screening Pathology. Guidelines for Pathologists. 2nd ed; NHS BSP Publications No 3, 1997.
- Spencer NJB, Evans AJ, Galea M, et al. Pathological-radiological correlations in benign lesions excised during a breast screening programme. Clin Radiol 1994; 49: 853-856.
- Dahlstrom JE, Jain S, Sutton T, Sutton S. Diagnostic accuracy of stereotactic core biopsy in a mammographic breast cancer screening programme. Histopathol 1996; 28: 421-427.
- Nguyen M, McCombs ME, Ghandehari S, et al. An update on core needle biopsy for radiologically detected breast lesions. Cancer 1996; 78: 2340-2345.
- Litherland JC, Evans AJ, Wilson ARM. The impact of core biopsy on pre-operative diagnosis rate of screen detected cancers. Clin Radiol 1996; 51: 562-565.
- Sloane JP, Mayers MM. Carcinoma and atypical hyperplasia in radial scars and complex sclerosing lesions: importance of lesion size and patient age. Histopathol 1993; 23: 225-231.
- Simpson JF, Page DL, Dupont WD. Apocrine adenosis - a mimic of mammary carcinoma. Am J Surg Pathol 1990; 3: 289-299.
- Rasbridge SA, Millis RR. Carcinoma in situ involving sclerosing adenosis: a mimic of invasive breast carcinoma. Histopathol 1995; 27: 269-273.
- Eusebi V, Foschini MP, Betts CM, et al. Microglandular adenosis, apocrine adenosis and tubular carcinoma of the breast. Am J Surg Pathol 1993; 17: 99-109.
- Millis RR, Eusebi V. Microglandular adenosis of the breast. Adv in Anat Pathol 1995; 2: 10-18.
- Carter D, Orr SL, Merino MJ. Intracystic papillary carcinoma of the breast. After mastectomy, radiotherapy or excisional biopsy alone. Cancer 1983; 52: 14-19.
- Lakhani SR, Collins N, Stratton MR, Sloane JP. Atypical ductal hyperplasia of the breast: clonal proliferation with loss of heterozygosity on chromosomes 16q and 17p. J Clin Pathol 1995; 48: 611-615.
- Lakhani SR, Slack DN, Hamoudi RA, et al. Detection of allelic imbalance indicates that a proportion of mammary hyperplasia of usual type are clonal neoplastic proliferations. Lab Invest 1996; 74: 129-135.
- Stratton MR, Collins N, Lakhani SR, Sloane JP. Loss of heterozygosity in ductal carcinoma in situ of the breast. J Pathol 1995; 175: 195-201.
- Lakhani SR. The transition from hyperplasia to invasive carcinoma of the breast. J Pathol 1999; 187: 272-278.
- Buerger H, Otterbach F, Simon R, Poremba C, Diallo R, Decker T, et al. Comparative genomic hybridization of ductal carcinoma in situ of the breast - evidence of multiple genetic pathways. J Pathol 1999;187:396-402.
- Ellis IO, Pinder SE, Lee AHS, Elston CW. A critical appraisal of existing classification systems of epithelial hyperplasia and in situ neoplasia of the breast with proposals for future methods of categorization. Where are we going? Seminars in Diagnostic Pathology. Vol 16 (3) (pp 202-208), 1999.
- Tavassoli FA. Ductal carcinoma in situ: Introduction of the concept of ductal intraepithelial neoplasia. Modern Pathology 1998;11:140-54.
- Tavassoli FA. Mammary intraepithelial neoplasia: A translational classification system for the intraductal proliferations. The Breast Journal 1997;3:48-58.
- Page DL, Dupont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985; 55: 2698-2708.
- Page DL, Rogers LW. Combined histologic and cytologic criteria for the diagnosis of mammary atypical hyperplasia. Hum Pathol 1992; 23: 1095-1097.
- Rosai J. Borderline epithelial lesions of the breast. Am J Surg Pathol 1991; 15: 209-221.
- Schnitt SJ, Connolly JL, Tavassoli FA, et al. Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardised criteria. Am J Surg Pathol 1992; 16: 1133-1143.
- Liberman L, Cohen MA, Dershaw DD, et al. Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy. Ajr Am J Roentgenol 1995; 164: 1111-1113.
- Holland R, Peterse JL, Millis RR, et al. Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol 1994; 11: 167-207.
- Poller DN, Silverstein MJ, Galea M, et al. Ductal carcinoma in situ of the breast. A proposal for a new simplified histological classification. Association between cellular proliferation and c-erbB-2 protein expression. Mod Pathol 1994; 7: 257-262.
- Silverstein MJ, Poller DN, Waisman JR, et al. Prognostic classification of breast ductal carcinoma-in-situ. Lancet 1995; 345: 1154-1157.
- Ellis, I.O.; Lee, A.H.; Elston, C.W.; Pinder, S.E.; Microinvasive carcinoma of the breast: diagnostic criteria and clinical relevance, Histopathology, 35(5), pp 470-2. 1999
- Rajan PB, Cranor ML, Rosen PP. Cystosarcoma phyllodes in adolescents and young women: a study of 45 cases. Mod Pathol 1997; 10: 24A.
- Moffat CJC, Pinder SE, Dixon AR, et al. Phyllodes tumours of the breast: a clinicopathological review of 32 cases. Histopathol 1995; 27: 205-218.
- Pietruska M, Barnes L. Cystosarcoma phyllodes. A clinico-pathologic analysis of 42 cases. Cancer 1978; 41: 1974-1983.
- Ward RM, Evans HL. Cystosarcoma phyllodes. A clinicopathologic study of 26 cases. Cancer 1986; 58: 2282-2289.
- O'Malley FP, Page DL, Nelson EH, Dupont WD. Ductal carcinoma insitu of the Breast with Apocrine cytology. Human Pathol 1994, 25: 164-168
- Simpson JF Page DL Dupont WD. Apocrine adenosis - a mimic of mammary carcinoma. Surgical Pathology 1990, 3, 289-299
- Wells CA McGregor IL, Makunura CN, Yeomans P, Davis JD. Apocrine adenosis: a precursor of aggressive breast cancer? J Clin Path 1995, 48: 737-742.
- Chinyama CN, Davis JD. Mammary mucinous lesions: congeners, prevalence and important pathological associations. Histopathology 1996,29; 533-539
- Fraser JL, Raza S, Chorny K, Connolly JL and Schnitt SJ. Columnar alteration with prominent apical snouts and secretions. A spectrum of changes frequently present in breast biopsies performed for microcalcifications. Am J Surg Path 1998, 22 1521-1527
- Oyama T, Maluf H, Koerner F. Atypical cystic lobules: an early stage in the formation of low grade ductal carcinoma in situ. Virchow Arch 1999, 435; 413-421
- Denley H. Pinder SE. Tan PH. Sim CS. Brown R. Barker T. Gearty J. Elston CW. Ellis IO. Metaplastic carcinoma of the breast arising within complex sclerosing lesion: A report of five cases. Histopathology. Vol 36(3) (pp 203-209), 2000.