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## Discussion |
In this study, we analysed the LN, CCL, ADH and DCIS diagnostic agreements and reproducibility between general pathologists and a specialist pathologist with training and experience in breast pathology in cases received in consultation for a second opinion. |
The importance of LN morphological classification is attributed to the Page group and collaborators, who correlated lobular lesion extension with patient evolution. The risks of developing invasive carcinomas were calculated as 4–5% for ALH and 8–11% for LCIS [8,9]. Eusebi et al. described the pleomorphic variant of LC... |
In our study, a good diagnostic agreement was observed between the reports from generalist pathologists and a breast pathology specialist regarding the diagnoses of ALH (Kappa index = 0.62) and LCIS (Kappa index = 0.66). Our data are similar to those of Fitzgibbons, who analysed the responses of 2,952 pathologists to c... |
The correct diagnosis of LN cases will affect the treatment options and counseling. Patients with LN are at risk of developing invasive ipsilateral and contralateral breast carcinomas. For this reason, most patients diagnosed with LN are clinically monitored, and tamoxifen might be administered as a prophylactic therap... |
CCL and FEA are a group of breast lesions whose diagnostic criteria were defined only in recent years [12]. With the widespread use of mammography screening, CCLs have often been identified in breast biopsies and are present in as many as half of the biopsies performed for microcalcifications detected via mammography. ... |
Despite advances in genetic studies of these lesions, few studies have assessed the diagnostic reproducibility of CCL amongst pathologists. In our study, we observed weak diagnostic agreements regarding CCC and CCH between generalist pathologists and a breast pathology specialist. When we assessed FEA, the agreement wa... |
The clinical importance of a correct diagnosis of FEA is that these lesions often coexist alongside LN, ADH, low-grade DCIS, and low-grade invasive carcinomas such as tubular carcinomas [22,25]. In a recent meta-analysis, Verschuur-Maes et al. analysed 24 studies that reported the presence of carcinoma in situ after di... |
ADH and DCIS comprise 10% and 15–20%, respectively, of all breast lesions detected using mammography screening. The relative risk of developing invasive carcinoma ranges from 4 to 5-fold among patients with a diagnosis of ADH and from 8- to 10-fold among patients with DCIS [1,28]. However, the histopathological diagnos... |
In our study, the diagnostic agreements between the original reports and later reviews were moderate for ADH (Kappa index = 0.44), low-grade DCIS (Kappa index = 0.47), intermediate-grade DCIS (Kappa index = 0.45), and microinvasive DCIS (Kappa index = 0.56). Elston et al. analysed the level of inter-observer agreement ... |
Various strategies have been used in an attempt to improve the diagnoses of ADH and DCIS, including a review of the diagnostic criteria and continuing education programs [33]. Recently, Jain et al. revealed that the agreement between nine pathologists regarding the diagnosis of ADH was poor (Kappa index = 0.34) and tha... |
As our study was retrospective, it includes some limitations. Proliferative lesions may or may not be associated with invasive carcinomas, a factor that might cause the generalist pathologist to underreport a case when faced with a more aggressive diagnosis. Although our data were based on pathological reports, upon as... |
Our study was the first to assess the diagnostic agreement regarding CCL and LN in cases that were sent for consultation according to reports by generalist pathologists. Interestingly, in our series, a total of 60% of cases were sent for consultation by breast surgeons and 5.2% of cases were sent by oncologists. Only 4... |
## Conclusions |
Our findings show a low degree of inter-observer diagnostic agreement between generalist pathologists and a specialist in breast pathology with regard to CCL without atypia and pleomorphic LCIS, moderate agreement for FEA, ADH, and low-grade, intermediate, and microinvasive DCIS, and good agreement for high-grade DCIS,... |
## Abbreviations |
ADH: Atypical ductal hyperplasia; ALH: Atypical lobular hyperplasia; CCC: Columnar cell change; CCH: Columnar cell hyperplasia; CCL: Columnar cell lesions; DCIS: Ductal carcinoma in situ; FEA: Flat epithelial atypia; LCIS: Lobular carcinoma in situ; TDLU: Terminal-duct lobular unit LN: lobular neoplasia; UFMG: Federal ... |
## Competing interests |
The authors declare that they have no competing interests. |
## Authors’ contributions |
DSG conceived the study, and drafted the manuscript. SSP participated in the design of the study. DB performed the statistical analysis, and drafted the manuscript. HG participated in design and coordination of the study, participated in the histological review, and drafted and reviewed the manuscript. All authors have... |
e117dda93ac267520a171a2e5b85a008d67f5e76f5789ce4c03505dc2b32d21b pmc4071798.txt |
PMCID: PMC5932853 |
TITLE: Atypical ductal hyperplasia: update on diagnosis, management, and molecular landscape |
LICENSE: https://creativecommons.org/licenses/by/4.0/Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropr... |
ABSTRACT: BackgroundAtypical ductal hyperplasia (ADH) is a common diagnosis in the mammographic era and a significant clinical problem with wide variation in diagnosis and treatment. After a diagnosis of ADH on biopsy a proportion are upgraded to carcinoma upon excision; however, the remainder of patients are overtreat... |
## Background |
The term “benign breast disease” encompasses a heterogeneous group of non-malignant lesions (Fig. 1) [1–5]. With the introduction of population-based mammographic screening programs, there has been an increased detection of these putative precursor lesions. While the detection of invasive ductal carcinoma (IDC) by mamm... |
ADH is not only a risk factor for IDC, it is also considered to be a direct but non-obligate precursor to carcinoma [1]. Diagnosis of ADH carries a four- to fivefold increased risk of developing breast cancer within 5 years that is not limited to the ipsilateral breast [1, 10]. However, Hartmann et al. [7] pointed out ... |
Strikingly, the risk associated with ADH is doubled with family history, suggesting inherited factors are associated with ADH development. Hoogerbrugge et al. [12] showed that high risk histopathologic lesions, including ADH (39%), were detected in almost 50% of the women younger than age 40 years with a hereditary pre... |
The occurrence of ADH in the general population varies widely from 3% of benign biopsies [13] (based on 30,953 cases), to 8–10% [14, 15] (n = 3532), to 23% [16] (n = 2833).These differences could come from the total number of biopsies analyzed and/or when these biopsies have been performed (pre/post-widespread mammogra... |
In this review, we focus on the definition, diagnosis, and current management of ADH as well as its molecular alterations. We also mention the strengths and limitations of some previous studies and propose ideas for studies that need to be undertaken in order to better understand breast cancer development associated wi... |
### Definition of ADH |
ADH resembles low nuclear grade ductal carcinoma in situ (DCIS) with cytonuclear and architectural atypia but with either partial involvement of the ducts and/or small size for a diagnosis of DCIS. In ADH there are ducts partially filled with abnormally uniform evenly spaced cells with polarization [20] (Fig. 2). ADH a... |
One of the major impediments to proper management of ADH is the conflicting definitions of ADH and intra-observer variability which make a definitive diagnosis difficult [10, 23]. Ghofrani et al. [23] described instances of the inconsistencies and disagreements of ADH diagnosis among 230 pathologists. For example, one ... |
### ADH diagnosis and management |
ADH is usually first identified in a core needle biopsy (CNB), and first designated as a “B3” lesion: i.e., of uncertain malignant potential of the breast. The management of patients diagnosed with ADH on CNB varies not only because of the initial biopsy type/size but also because of the variable reported “upgrade rate... |
Some parameters may be useful to take into consideration before excision, such as the number of cores, type of needle used, type of lesion, and lesion diameter [7, 10]. It has also been suggested to take into account the number of the foci in the core and how much of the radiographic lesion was removed, with multiple f... |
### Risk prediction following ADH diagnosis |
Unfortunately, risk prediction following ADH diagnosis is controversial [7], and counseling and further screening for these women diagnosed with ADH are therefore probably not adequate. Indeed, Degnim et al. [8, 11] showed that the 25-year risk of developing cancer associated with ADH is at least 25%, and it could be a... |
Apart from the histologic variables, younger/pre-menopausal women (< 45 years) are at higher risk of developing metachronous carcinoma as found by several studies [8, 38, 39], particularly higher grade cancer [40]. The complexities of analyzing focality, calcification, and atypia in terms of how these are measured emph... |
Thus far, despite the high risk of developing cancer associated with ADH, attempts to identify clinicopathological or molecular biomarkers to predict individual risk have been unsuccessful. Risk reduction strategies remain varied, from active surveillance at one end of the spectrum to prophylactic mastectomy at the oth... |
### Molecular features of ADH |
Breast cancer is well known to be a genetic disease, with very frequent somatic copy number changes, a number of driver mutations such as in PIK3CA and TP53, and widespread transcriptional deregulation [42]. While molecular studies of benign breast disease are fewer, they suggest both similarities to and differences fr... |
### Genetic events in pure ADH |
Very few studies have described the molecular genetic features of ADH (Table 1) and these are further limited because most were carried out on small numbers of samples using low resolution methodology, such as microsatellite marker-based loss of heterozygosity (LOH) or allelic imbalance (AI) analysis and cytogenetic co... |
An LOH study of 41 ADH samples at 15 genetic loci selected based on the locations of frequently inactivated tumor suppressor genes in IDC, such as TP53, RB1, and BRCA1, reported that 42% of “pure” ADH (without synchronous DCIS/IDC) showed LOH in at least one locus, suggesting that inactivation of these tumor suppressor... |
Using alternative methods, Gao et al. [54] detected copy number aberrations in 15 pure ADH samples by array CGH and found that although there were similar genetic alterations among ADH, DCIS, and IDC, there were also alterations unique to each lesion. Firstly, they found that gain at 19p and losses at 2p, 6q, 11p, 12q,... |
These genetic studies emphasize the difficulty in analyzing small numbers of cases with varying definitions of ADH, often leading to different conclusions. Nonetheless, despite individual small sample sizes, across all LOH and CGH studies, 16q loss remained the most common cytogenetic event in pure ADH, followed by 1q ... |
### ADH as a precursor lesion |
As well as evaluating pure ADH, a common strategy has been to study “synchronous” ADH found in the same breast as carcinoma (DCIS or IDC). The goal of these studies has been to establish whether ADH could be a genetic precursor to carcinoma (and determine which type of carcinoma), and to evaluate whether genetic events... |
Early studies used LOH to investigate the clonal relationship between ADH and associated cancers; for example, Larson et al. [44] performed a microsatellite analysis of 45 ADH samples with co-existing DCIS or IDC from 16 patients. These studies found that ~ 60% of the cancer cases had a co-existing clonal ADH lesion. M... |
These genetic studies to date support a role for ADH as a precursor of carcinomas identified in the same breast, but they do not explain the risk associated with ADH for the contralateral breast. It has been noted in multiple studies that ipsilateral recurrence is most common (almost twice that of contralateral) in the... |
Early models of breast cancer development, which proposed a direct linear progression from normal epithelium to ductal hyperplasia to ADH to low-grade DCIS and then to low- or high-grade IDC, are now considered to be oversimplified [21]. Instead, distinct low- and high-grade multistep models of breast cancer progressio... |
Regarding ADH progression, a prevailing view is that ADH is only a direct precursor of LG and ER-positive carcinoma [21]; however, this is not supported entirely by the literature. On one side, Larson et al. demonstrated that clonality between ADH and synchronous carcinoma was more likely when the carcinoma was low gra... |
While genetic analysis of ADH with high-grade and/or ER− carcinomas is underrepresented in the literature, HER2 cases have been addressed through the use of FISH. Interestingly, a FISH study of synchronous cases reported that the amplitude of the amplification of ERBB2 increased from ADH to DCIS to IDC [65]. Fifty-four... |
Other studies of ADH synchronous to carcinoma have also attempted to identify genetic events associated with progression, similar to studies comparing pure DCIS to DCIS synchronous with IDC, in which it has been observed that pure DCIS have different molecular profiles to synchronous DCIS, with the latter carrying more... |
### Transcriptional changes in ADH |
As well as the genetic events described above, progression to IBC from ADH may be evaluated by gene expression differences, which can also reflect the influence of the local environment. In order to understand the key driver events in breast cancer progression, Brunner et al. [72] carried out expression analysis of mat... |
A second gene expression profiling study of ADH synchronous with cancer (DCIS/IDC) (n = 31, eight with ADH) showed that significant alterations are already present in ADH and maintained in DCIS and IDC [75]. All ADH showed a grade 1 gene expression pattern and clustered with low grade DCIS and IDC, confirming the close... |
While these studies are informative for ADH present in synchrony with carcinoma, the expression profiles of pure ADH have not been adequately assessed in a sufficiently powered study. One study did attempt to profile pure ADH in comparison to ADH associated with carcinoma; however, the tissue used was taken adjacent to... |
## Conclusions |
The increasing diagnoses of ADH as a consequence of population-based mammographic screening have created clinical dilemmas for treating physicians. Should ADH always be excised or are other options viable? Understanding the genetics of ADH might lead to effective strategies to prevent development and progression of bre... |
1b86347fe5c575a049a12bff9d6ce1fd7be64ebda1f8593ebd92de8b6043aa96 pmc5932853.txt |
PMCID: PMC7170742 |
TITLE: Gliosarcoma case report and review of the literature |
LICENSE: https://creativecommons.org/licenses/by/2.0/The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is proper... |
ABSTRACT: Gliosarcoma is an unusual subtype of glioblastoma multiforme. Its characteristic features are biphasic configuration, constituting a definite, separate glial and sarcomatous differentiation, on histological evaluation. Herein, we present a rare case of Gliosarcoma that had presented only once in our center in... |
## Introduction |
Gliosarcoma (GS) is an unusual and uncommon type of an aggressive malignancy constituting 2-8% of all primary glioblastomas [1]. It is basically a sub-type of GBM which shows a separate, divergent differentiation into a glial and a sarcomatous component. Stroebe et al initially documented this entity in 1895 [2]. It wa... |
## Patient and observation |
60 years old male, known case of hypertension and diabetes was brought to the emergency department with disturbed level of consciousness and right sided hemiplegia which was progressive over four days. There were no witness’s seizures. On examination, he was afebrile, conscious, not oriented to time, person or place an... |
## Discussion |
Gliosarcoma is an unusual morphological sub type of glioblastoma, with slight predominance in males, age ranging from the sixth to seventh decades and a predilection for the temporal lobes, although it can also affect the frontal, parietal and occipital lobes [1,5,8-10] Several studies concurred that glioblastoma and g... |
## Conclusion |
Gliosarcoma, a histological biphasic tumor showing separate glial and sarcomatous components, is a very rare clinicopathological entity that was diagnosed only once in the last 13 years in our center. It is associated with a very aggressive clinical course with patient’s rapid deterioration and poor outcome. The patien... |
ea4a16bf520b64aad239274fa3ff69084720a81fa0860d30e7be414b67a1e325 pmc7170742.txt |
PMCID: PMC7536112 |
TITLE: Gross and Histological Examination of a Large Spheno-Orbital Meningioma |
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