Atypical ductal hyperplasia and the risk of underestimation: tissue sampling method, multifocality, and associated calcification significantly influence the diagnostic upgrade rate based on subsequent surgical specimens

Abstract

Background Risk assessment and therapeutic options are challenges when counselling patients with an atypical ductal hyperplasia (ADH) to undergo either open surgery or follow-up only. Methods We retrospectively analyzed a series of ADH lesions and assessed whether the morphological parameters of the biopsy materials indicated whether the patient should undergo surgery. A total of 207 breast biopsies [56 core needle biopsies (CNBs) and 151 vacuum-assisted biopsies (VABs)] histologically diagnosed as ADH were analyzed retrospectively, together with subsequently obtained surgical specimens. All histological slides were re-analyzed with regard to the presence/absence of ADH-associated calcification, other B3 lesions (lesion of uncertain malignant potential), extent of the lesion, and the presence of multifocality. Results The overall underestimation rate for the whole cohort was 39% (57% for CNB, 33% for VAB). In the univariate analysis, the method of biopsy (CNB vs VAB, p = 0.002) and presence of multifocality in VAB specimens ( p = 0.0176) were significant risk factors for the underestimation of the disease (ductal carcinoma in situ or invasive cancer detected on subsequent open biopsy). In the multivariate logistic regression model, the absence of calcification ( p = 0.0252) and the presence of multifocality (unifocal vs multifocal ADH, p = 0.0147) in VAB specimens were significant risk factors for underestimation. Conclusions Multifocal ADH without associated calcification diagnosed by CNB tends to have a higher upgrade rate. Because the upgrade rate was 16.5% even in the group with the lowest risk (VAB-diagnosed unifocal ADH with calcification), we could not identify a subgroup that would not require an open biopsy.

Atypical Ductal Hyperplasia: Risk Factors for Predicting Pathologic Upgrade on Excisional Biopsy

“…The strongest risk factor for ADH upgrade was the biopsy method (US-CNB vs. S-VAB, p < 0.001), possibly due to the different amounts of target lesion removed between CNB and VAB. This result was similar to that of Rageth et al ( 29 ). Although there was no difference according to lesion type, calcification was the most common presentation of ADH (64.1%, 91/142) in our study, and it could only be seen on mammography.…”

B3-Läsionen der Mamma: Histologische, klinische und epidemiologische Aspekte

“…Ergänzende immunhistochemische Färbungen sind hilfreich für die Diagnosebestätigung. Eine ADH exprimiert stark und diffus Östrogenrezeptoren in 100 % der Zellkerne und zeigt dabei einen Verlust der basalen Zytokeratine (CK5/6 oder CK14) [ 16 , 40 , 41 , 47 ]. Die internationale übliche Bezeichnung, die auch in der WHO-Klassifikation geführt wird, ist die „ADH“ wobei in einigen europäischen Ländern auch der Begriff „AIDEP“ („atypical intraductal epithelial proliferation“) gebraucht wird.…”

“…Als Grund wird angeführt, dass in der Regel an der Nadelbiopsie die endgültige Ausdehnung der atypischen intraduktalen Epithelproliferation nicht festgelegt werden kann und somit keine sichere Grenzziehung zwischen ADH und low-grade duktalem Carcinoma in situ (DCIS) möglich ist [ 4 , 16 , 47 , 55 ]. Zahlreiche Studien haben versucht morphologische Kriterien an den präoperativen Biopsien zu identifizieren, die voraussagen können, welche ADH-Fälle im nachfolgenden chirurgischen Präparat höhergradige Läsionen (wie DCIS, invasives Karzinom) oder andere B3-Läsionen wie klassische lobuläre Neoplasie (LN) oder flache epitheliale Atypie (FEA) enthalten [ 34 , 38 , 41 ]. Diese Kriterien (unter anderem die Assoziation zu Verkalkungen, die Zahl der betroffenen Gangstrukturen oder der Nachweis von assoziierten intraläsionalen Nekrosen) können zwar in Einzelfällen prädiktiv sein, eine signifikante Assoziation zwischen diesen Faktoren an der Stanzbiopsie und den Diagnosen im Operationspräparat konnte aber bisher nicht etabliert werden [ 34 , 38 , 41 ].…”

Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions

“…Many ABLs have mixed components, exhibiting both ADH and ALH, as well as FEA (10). Several prediction models have been proposed to determine which lesions are associated with a high risk of upgrading to cancer at surgery, and therefore may require surgical excision (11,12). However, most of them were focused on one or another kind of ABL.…”