Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast, and its prognostic implications

Pedersen, Lise; Holck, Susanne; Schiødt, Torben; Zedeler, Karin; Mouridsen, Henning T.

doi:10.1007/bf01805979

Cited by 49 publications

(34 citation statements)

References 12 publications

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“…Moreover, when the coassociation of individual histologic features was analyzed, the medullary subtype was most highly associated with circumscribed margins, followed by syncytial growth and lymphocytic infiltration (data not shown). These findings are similar to those of Gaffey et al 23 and contrast with Pedersen et al, 22 who found that interobserver agreement was lowest for circumscription, although the latter authors used a three-tiered scoring system for circumscription and lymphocytic infiltrate.…”

Section: Discussionsupporting

confidence: 88%

“…These results are similar to that achieved by others. 21,22 In our study, the range in interobserver agreement was greatest for lymphocytic infiltrate, followed by margin status and syncytial growth pattern. Moreover, when the coassociation of individual histologic features was analyzed, the medullary subtype was most highly associated with circumscribed margins, followed by syncytial growth and lymphocytic infiltration (data not shown).…”

Section: Discussionsupporting

confidence: 45%

“…20 The moderate degree of interobserver agreement for medullary carcinoma has been the subject of prior studies. [21][22][23] Utilizing the criteria of Ridolfi et al, 24 consensus diagnoses were achieved in 56.3% of cases in the current study. These results are similar to that achieved by others.…”

Section: Discussionmentioning

confidence: 92%

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Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study

et al. 2006

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Registry of this type; over 37 724 individuals have been enrolled to date. One activity of this Registry is the semicentralized pathologic review of tumors from all probands. Given the semicentralized nature of the review, this study was undertaken to determine the reproducibility, source(s) of classification discrepancies and stratagems to circumvent discrepancies for histologic subtyping and grading of invasive breast cancer among the reviewing pathologists. A total of 13 pathologists reviewed 35 invasive breast cancers and classified them by primary and secondary histologic type, Nottingham grade and score. Lymph-vascular space invasion, circumscribed margins, syncytial growth and lymphocytic infiltrate were also evaluated. A training session using a separate set of slides was conducted prior to the study. General agreement, in terms of categoryspecific j's and percent agreement, and accuracy of classification relative to a reference standard were determined. Classification of histologic subtype was most consistent (and accurate) for mucinous carcinoma (j ¼ 1.0), followed by tubular (j ¼ 0.8) and lobular subtypes (j ¼ 0.8). Classification of medullary subtype was moderate (j ¼ 0.4), but additional evaluation of degree of lymphocytic infiltrate, syncytial growth and circumscribed margins identified most cases. Category-specific j's were moderate to good for Nottingham grade (j ¼ 0.5-0.7), with the greatest agreement obtained in categorizing grade I (j ¼ 0.7), and grade III tumors (j ¼ 0.7). A flexible classification strategy that employs individual and combined criteria provides good interobserver agreement for invasive breast cancers with uniform, unambiguous histology and compensates for classification discrepancies in the more histologically ambiguous or heterogeneous cancers. Keywords: interobserver reproducibility; invasive breast cancer; familial breast cancer; breast/ovarian cancer family registryThe reproducibility of the classification and grading of invasive breast cancer and the cause(s) of interobserver disagreement among pathologists have not been adequately evaluated. Prior studies evaluating interobserver concordance in categorizing breast lesions have documented improved diagnostic agreement when the pathologists involved used agreed-upon criteria, 1 but other potential sources of poor interobserver agreement, such as the difficulties in the application of the individual histologic criteria, the individual pathologist's variation in use of these criteria, and most importantly, the ambiguous or borderline and heterogeneous nature of the

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 45%

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Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study

et al. 2006

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“…In addition, the histologic diagnosis of medullary carcinoma is fraught with interobserver variability and the disease entity is frequently overdiagnosed. [23][24][25] None of the studies that compared histopathologic observations and race mentioned the diagnostic criteria used to make the diagnosis of medullary carcinoma and most studies did not include a central pathology review.…”

Section: Medullary Carcinomamentioning

confidence: 99%

Histopathology of breast cancer among African-American women

Middleton

Chen

Perkins

et al. 2002

Cancer

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Although the overall incidence of breast cancer in African-American women is lower than in white women, African-American women younger than 50 years old have a higher incidence of breast cancer than white women. African-American women with breast cancer have a poorer survival rate than white women and are more likely to die of breast cancer in almost every age group. To explain this disparity, we studied a substantial body of literature that reported a biologic difference in the tumors found in African-American and white women. Specifically, more aggressive histopathologic patterns have been described among AfricanAmerican patients with breast cancer when compared with white women. In addition, there are data that support an ethnicity-related variation in the expression of breast tumor hormonal markers. The objective of this study was to critically evaluate the existing published data on the histologic features of breast cancer to determine whether breast cancer in African-American women is a histologically more aggressive disease than in white women. We conclude that the aggressive tumor histology reported in African-American women has not been analyzed carefully with respect to the age of the patient at the time of diagnosis and the stage of disease at presentation. Furthermore, there is a need for central pathology review using accepted, published criteria for diagnosis of uncommon and contro- Age of OnsetAlthough the overall incidence of breast cancer is lower among African-American women than among white women, the incidence rates among African-American women younger than 50 years old are higher than among white women.1 In general, African-American women develop breast cancer 5-10 years earlier than white women. 2,3In the Surveillance, Epidemiology, and End Results program, the median age at diagnosis of breast cancer for African-American women was 57.0 compared with 64.0 for white women.1 Newman and Alfonso 4 evaluated breast cancer in women younger than 50 years old and found that significantly more African-American patients than white patients were diagnosed at a young age. Similarly, Kovi et al. 5 reported that a higher percentage of African-American women (68%) younger than 54 years old were diagnosed with breast cancer compared with white women of the same age (53%). Their observation was based on data compiled by the Armed Forces Institute of Pathology experience with breast cancer from 1980 to 1983. 253

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“…However there is difficulty in reproducibly making this diagnosis. [11][12][13] Also, if the Ridolfi criteria are strictly applied then less than 1% of carcinomas are of this type. 14 In addition, medullary carcinomas also share histological and immunophenotypic features with tumours that arise in carriers of BRCA1 germ-line mutations, which have a poor prognosis.…”

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confidence: 99%

Histological features of medullary carcinoma and prognosis in triple-negative basal-like carcinomas of the breast

Marginean

Rakha

et al. 2010

Modern Pathology

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Medullary carcinomas have a better prognosis than other grade 3 mammary carcinomas, but they typically show basal-like biological features, which are associated with a poor prognosis. In this study we examined the associations and prognostic relevance of medullary histological features in a series of 165 invasive carcinomas with a basal-like phenotype: triple-negative (oestrogen receptor, progesterone receptor, HER2) and expressing at least one basal marker (CK5/6, CK14, CK17 or EGFR). The following histological features were associated with each other: prominent inflammation, anastomosing sheets, absence of fibrosis, absence of infiltrative margin and absence of gland formation. Prominent inflammation and anastomosing sheets in at least 30% of the tumour were associated with a better prognosis on univariate analysis. The combination of these two features (a simplified definition of medullary-like type) was present in 17% of tumours and was an independent prognostic factor on multivariate analysis. This simplified definition had good inter-observer reproducibility (j ¼ 0.61) and is worthy of more detailed assessment in an unselected group of mammary carcinomas. A fibrotic focus was present in 36% of carcinomas. Only 3% of tumours with a fibrotic focus had features of medullary-like carcinomas. Fibrotic focus of greater than 30% of the tumour was associated with a poor prognosis. This study emphasizes the heterogeneity of morphology and behaviour of triple-negative basal-like carcinomas.

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Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast, and its prognostic implications

Cited by 49 publications

References 12 publications

Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study

Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study

Histopathology of breast cancer among African-American women

Histological features of medullary carcinoma and prognosis in triple-negative basal-like carcinomas of the breast

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