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CGH analysis of DCIS has demonstrated a large number of alterations, including gains of 1q, 5p, 6q, 8q, 17q, 19q, 20p, 20q, and Xq, and losses of 2q, 5q, 6q, 8p, 9p, 11q, 13q, 14q, 16q, 17p, 17q, and 22q [35, 41, 42]. Some AI are more frequent and constitute hot spots: loss in 11q, 16q, 17p and 17q. |
Rosenberg et al. [43] studied a series of 15 microsatellite loci in ADH and found monoclonal microsatellite alterations in 40% of cases in more than one locus, suggesting that a genetic instability plays an early role in cancer progression. |
Wiechmann and Kuerer [44] characterize the differences between LG-DCIS and HG-DCIS and their risk of progression in IDC by means of the expression of steroid receptor (LG-DCIS is frequently ER/PgR positive), growth characteristics (Ki67 is lower in LG-DCIS than in HG-DCIS), expression of c-erbB2 (frequent in HG-DCIS, r... |
In Table 2 are reported the more frequent alterations in IPLs and IDC. |
[TABLE] “hot spots” in IPLs—more frequent allelic imbalances reported. |
| Gains | Losses |
UDH | rare | rare |
ADH | 1q, 16p | 11p, 11q, 16q, 17p |
FEA | — | 3p, 11q, 16q |
DCIS | 1q (LG-DCIS), 5p, 6q, 8q, 17q, 19q, 20p, 20q (HG-DCIS), Xq | 2q, 5q, 6q, 8p, 9q, 11q (HG-DCIS),13q (HG-DCIS), 14q, 16q (LG-DCIS), 17p, 17q (HG-DCIS), 22q |
## 5. Discussion |
One of the most controversial topics about breast pathology concerns IPL, with a wide range of phenotypic manifestations from epitheliosis to DCIS. Page et al. [9, 10] have suggested that there is a continuum between these two extremes, with an intermediate condition called ADH. Azzopardi [3], on the other hand, draws ... |
High interobserver variability among experienced pathologists in ADH interpretation is reported [2], mainly related to different proposed criteria. WHO book [4] suggests the use of dimensional criteria of Tavassoli [1]: ADH is a lesion with cytological and architectural pattern of LG-DCIS measuring in aggregate less th... |
The various IPLs have different risk of progression: UDC has two folds, ADH four folds, and LG-DCIS ten folds compared to normal breast [9, 10]. At the molecular level, rarely UDH shows allelic imbalance (AI) for one gene, whereas ADH, FEA, and LG-DCIS show frequent AIs for many genes [34–39]. Expression of high-molecu... |
Several data support the concept that different types of DCIS show different genetic alterations [41, 42]. Alterations at 16q are much more frequent in LG-DCIS than in HG-DCIS, in which alterations at 13q, 17q, and 20q are more frequent [4, 6, 7, 10]. Similar findings are in invasive carcinomas of low and high grade [4... |
[TABLE] Cancerogenesis models. |
For this reason, the DIN system is not a progression through different grades, like the intraepithelial neoplasia in other tissue (e.g., the CIN system of cervical cancer), but a classification of different intraductal neoplastic conditions, each of these are not an obligate precursor of IDC. |
The DCIS classification of Wiechmann and Kuerer [44], based on biological potential to progress into IDC, shows two parallel pathways of progression with different histologic characteristics and molecular markers. Between these two pathways, there is a presumptive common progenitor, a dysplastic cell, not better charac... |
[TABLE] Classification of DCIS based on biologic potential [44]. |
In IDC, recent studies have led to a molecular classification based on the biological characteristics of the tumor rather than limited to morphological analysis. Perou [23] and Sotiriou et al. [24] identified molecular subtypes of invasive breast cancer based on an intrinsic gene signature. Many studies have aimed to i... |
## 6. Conclusions |
Diagnosis and reproducibility of proposed criteria of IPLs are complex. This is testified by terminological confusion, with a large number of designations for the same entity. To render the issue even more controversial, it is not clear whether some of these entities really occur in practice. Interobserver agreement in... |
Morphological complexity is reflected by the large variety of molecular findings described by a number of studies in the last twenty years. Some of these alterations are confirmed by different studies, and their comparison with different clinical entities provides much information about their nature and propensity for ... |
## References |
7a5da9c479f0f9c4686ad3ded650f7b25b9e6e70db2cfa81df269886bf9253f9 pmc3357964.txt |
PMCID: PMC4071798 |
TITLE: Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast |
LICENSE: https://creativecommons.org/licenses/by/2.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( |
http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( |
http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
ABSTRACT: BackgroundThis study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast.Me... |
## Background |
Despite advances in the understanding of the molecular biology of breast cancer progression and new molecular markers, the histopathological analysis remains the most widely used diagnostic method of precursor and intraductal proliferative lesions of the breast [1]. |
Currently, increasing number of breast lesions are discovered during the pre-clinical phase due to the more widespread use of mammography screening and the incorporation of new imaging technologies for the diagnosis of breast cancer. There has also been an increase in the diagnosis of intraductal proliferative and prec... |
Reproducibility studies are useful when evaluating the applicability of histological criteria for the classification of breast lesions and when determining the level of agreement amongst pathologists regarding morphological diagnoses. Studies conducted by our group have revealed significant inter-observer variability b... |
Our study aimed to assess the frequency of detection rate of precursor lesions and intraductal proliferative lesions, primarily CCL and LN, in breast biopsies sent for consultation as well as the inter-observer variability in the diagnoses made during the original report and a later review by a specialist consultant in... |
## Methods |
A retrospective, observational, cross-sectional study was conducted. Files from the Breast Pathology Laboratory at the School of Medicine of Federal University of Minas Gerais (UFMG), Brazil, were reviewed between January 2005 and December 2010, and 673 cases of breast lesions were identified as having been formally se... |
Data were collected through the use of a structured form, and the following items were analysed in both the original report and the review: type of specimen, specialty of the referring physician, and presence of intraductal proliferative lesions (columnar cell lesions [CCL], ADH, and DCIS) and the LN (atypical lobular ... |
The histological classification of LN originally reported by Page et al. and adopted by the 2012 World Health Organization (WHO) Classification of Breast Tumours was used [1]. Lobular neoplasia refers to the entire spectrum of atypical epithelial lesions originating in the terminal-duct lobular unit (TDLU) and characte... |
CCLs are a group of lesions of the terminal ductal-lobular units that are characterized by variably enlarged dilated acini lined by columnar epithelial cells without cytological or architectural atipia [1]. Flat epithelial atypia (FEA), the term adopted by the WHO Classification of Breast Tumours, since 2003, refers to... |
[TABLE] Diagnostic criteria for columnar cell lesions used in the present study |
| Columnar cell change | Columnar cell hyperplasia | Columnar cell change with atypia | Columnar cell hyperplasia with atypia |
| Flat epithelial atypia |
Topography | Terminal duct-lobular unit with variable dilation | Terminal duct-lobular unit with variable dilation | Terminal duct-lobular unit with variable dilation | Terminal duct-lobular unit with variable dilation |
Architecture | 1 or 2 cell layers | Cell stratification greater than 2 layers, complex cellular configurations are not present | 1 or 2 cell layers | Cellular stratification of more than 2 layers, complex cell configurations are not present |
Cytology | Columnar cells with ovoid to elongated nuclei orientated perpendicular to the basal membrane; nucleolus absent or inconspicuous. | Columnar cells with ovoid to elongated nuclei orientated perpendicular to the basal membrane; “hobnail” cells might appear with absent or inconspicuous nuclei. | Cytological atyp... |
Apical decapitation | Often present, not usually prominent. | Often present, might be exaggerated. | Often present, might be exaggerated. | Often present, might be exaggerated. |
Intraluminal secretions | Might be present but are not usually prominent. | Might be present and prominent. | Might be present and prominent. | Might be present and prominent. |
Calcifications | Might be present | Usually present, might be psammomatous. | Usually present, might be psammomatous. | Usually present, might be psammomatous. |
ADH was defined as a proliferation of regularly distributed monomorphic cells to form regular, uniform, and circular secondary lumens. These lesions are small, and the cells have 2 partial ducts or “spaces” involved, and are less than 2 mm in size. DCIS is characterised as an epithelial proliferation of atypical cells ... |
To tabulate the data, cases with more than one type of breast lesion were classified according to the lesion with the greatest risk or potential to develop into a carcinoma. For LN, the risk classification was as follows: pleomorphic LCIS > LCIS > ALH; for CCL: CCH atypia > CCC atypia > CCH > CCC; and for DCIS: microin... |
The SPSS program (version 17.0; SPSS Inc., Chicago, IL, USA) was used to analyse the inter-observer variability between the original diagnosis and the histopathological review conducted by the consultant pathologist, using the Kappa index. This index was interpreted according to the following values proposed by Landis ... |
## Results |
A total of 610 cases of breast lesions that had been referred for second opinion and satisfied the inclusion criteria were analysed; of these, 56.9% were breast specimens from segmental mastectomies or quadrantectomies, 29.8% from core-biopsies, 5.9% from mastectomies, and 7.4% were other specimen types. The referring ... |
LN was present in 11.0% (67/610) of the original reports and 11.8% (72/610) of the later reviews. Of 67 cases from the original reports, ALH was present in 25.4%, LCIS in 67.2%, and pleomorphic LCIS in 7.5%. Of the 72 LN cases from the later reviews, ALH was present in 30.6%, LCIS in 63.9%, and pleomorphic LCIS in 5.6%... |
[TABLE] Diagnostic agreement between the original report and later review of lobular neoplasia |
| LN report review |
Original LN report | Absent | ALH | LCIS | Pleomorphic LCIS | Total |
Absent | 521 | 10 | 11 | 1 | 543 |
ALH | 7 | 8 | 2 | 0 | 17 |
LCIS | 8 | 4 | 31 | 2 | 45 |
Pleomorphic LCIS | 2 | 0 | 2 | 1 | 5 |
Total | 538 | 22 | 46 | 4 | 610 |
CCL were present in 14.4% (88/610) of the original reports and 25.1% (153/610) of the reviews. Of 88 cases from the original reports, CCC were present in 64.8%, CCH in 12.5%, CCC with atypia in 8.0%, and CCH with atypia in 14.8% of the cases. Of the 153 cases from the reviews, CCC were present in 74.5%, CCH in 9.8%, CC... |
[TABLE] Diagnostic agreement between the original report and later review of columnar cell lesions |
| CCL report review |
Original CCL report | Absent | CCC | CCH | CCC with atypia | CCH with atypia | Total |
Absent | 437 | 66 | 10 | 2 | 7 | 522 |
CCC | 16 | 36 | 1 | 3 | 1 | 57 |
CCH | 2 | 5 | 3 | 1 | 0 | 11 |
CCC with atypia | 1 | 3 | 1 | 2 | 0 | 7 |
CCH with atypia | 1 | 4 | 0 | 2 | 6 | 13 |
Total | 457 | 114 | 15 | 10 | 14 | 610 |
ADH was present in 12.1% (74/610) of the original reports and 8.4% (51/610) of the later reviews (Table 4; Figure 2B and Figure 3). There was a moderate agreement between the original reports and later reviews regarding the diagnosis of ADH (Kappa index = 0.44; [p < 0,05]). Of the 74 cases of ADH present in the origina... |
[TABLE] Diagnostic agreement between the original diagnosis of atypical ductal hyperplasia and the reviewer´s diagnosis |
| Reviewer´s diagnosis of ADH |
Original diagnosis of ADH | Absent | ADH | Total |
Absent | 516 | 20 | 536 |
ADH | 43 | 31 | 74 |
Total | 559 | 51 | 610 |
The DCIS frequencies in the original reports and later reviews were 37.7% (230/610) and 39.0% (238/610), respectively. Of 230 DCIS cases from the original reports, low-grade DCIS was present in 25.6%, intermediate-grade DCIS in 23.0%, high-grade DCIS in 39.1%, DCIS-US in 10.9%, and microinvasive DCIS in 1.3%. Of the 23... |
[TABLE] Diagnostic agreement between the original report and later review of DCIS |
| DCIS report review |
Original DCIS report | Absent | LG DCIS | IG DCIS | HG DCIS | US DCIS | MIC DCIS | Total |
Absent | 333 | 16 | 9 | 19 | 3 | 0 | 380 |
LG DCIS | 16 | 32 | 9 | 0 | 2 | 0 | 59 |
IG DCIS | 8 | 7 | 23 | 12 | 1 | 1 | 53 |
HG DCIS | 6 | 3 | 5 | 72 | 2 | 2 | 90 |
US DCIS | 8 | 5 | 3 | 3 | 6 | 0 | 25 |
MIC DCIS | 0 | 0 | 0 | 1 | 0 | 2 | 3 |
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