Atypical proliferative lesions diagnosed on core biopsy - 6 year review Dr Angela Harris, Dr Julie Weigner & Dr Ricardo Vilain NSW Health Pathology Pathology North, Hunter Anatomical Pathology & Cytology Department
Outline Definition and characteristics of atypical proliferative lesions Risk of subsequent in situ and invasive cancer diagnosis and published rates of upgrading atypical lesions Our study parameters Results Discussion and comparison to the literature Further studies and recommendations
Atypical Proliferative Lesions Atypical proliferative lesions of the breast can be challenging Difficulties arise in both rendering an accurate histopathological diagnosis and in determining appropriate treatment and adequate follow up of such lesions Aiming to avoid the burden of overtreatment balanced with early diagnosis
Atypical Ductal Hyperplasia ADH is regarded as an intermediary entity between benign and malignant disease Non-obligate part of the hyperplasia-atypia-lg DCIS pathway
Atypical Ductal Hyperplasia Histopathological features can have similarities between both atypical ductal hyperplasia and low grade DCIS Three components to a diagnosis of ADH Architectural pattern Cytology Disease extent
RCPA ecases
RCPA ecases
RCPA ecases
Atypical Ductal Hyperplasia Due to the biological similarities between ADH and DCIS, excision is often offered The rate of upgrading ADH to DCIS or invasive carcinoma on subsequent open biopsies or excisions ranges from 17-41% 1 ADH is associated with an increased risk of future in situ or invasive malignancy with the cumulative incidence approaching 30% at 25 years follow up 2 1. Kohr et al, Risk of upgrade of ADH after stereotactic breast biopsy. Radiology 2010 2. Degnim et al. Stratification of breast cancer risk in women with atypia. J Clin Oncol 2007
Our study Audit of all breast screen core biopsies - 2012-2017 Breastscreen NSW Hunter New England Epithelial hyperplasia with atypia, including ADH, and all cases of low grade DCIS Reviewed all histology, type & size of lesions, size & type of core biopsy, radiology data available to us Examined subsequent open biopsies, WLE/mastectomies Examined rate of concordance, upgrading, downgrading
Study Demographics Total core biopsies 2012-2017: 1031 ADH 19 cases (1.65%) Low grade DCIS 16 cases (1.55%) Other atypia 3 cases (0.29%) ADH: mean age 57.84 DCIS: mean age 66.75
Results 20 18 16 14 12 10 8 6 4 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results 20 18 16 14 12 10 8 6 ADH 16% concordance (3/19) 10% no residual (2/19) 47% upgrade (9/19) 37% DCIS 10% invasive carcinoma 26% downgrade (3/19) 4 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results 20 18 16 14 12 10 8 6 4 LG DCIS 63% DCIS (10/16) 31% biopsy cavity identified, no residual (5/16) ADH 1 case 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 4 2 0 1. Stellate lesion with adjacent architectural distortion At least ADH artefactually distorted duct with a small group of atypical cells MDT decision to excise, malignant diagnosis not unexpected 2. Small focus of ADH amongst ducts with UDH Excision 8mm focus of invasive carcinoma detected Both invasive carcinoma, initial biopsy size was on the lower end of the spectrum 0.66cm 3 and 1cm 3 Biopsy detected atypical lesions small, <2mm and 5-6 cells ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 4 2 0 1. Stellate lesion with adjacent architectural distortion At least ADH artefactually distorted duct with a small group of atypical cells MDT decision to excise, malignant diagnosis not unexpected 2. Small focus of ADH amongst ducts with UDH Excision 8mm focus of invasive carcinoma detected Both invasive carcinoma, initial biopsy size was on the lower end of the spectrum 0.66cm 3 and 1cm 3 Biopsy detected atypical lesions small, <2mm and 5-6 cells ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 Imaging all cases had microcalcifications Just over half of the biopsied lesions had secretory calcifications Wide range of biopsy material volumes, 0.4-4.9cm 3, but tended towards a higher volume of material (average 2.3cm 3 ) 6 4 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 4 Concordant/no residual cases grouped together Imaging all had microcalcifications, all biopsies had calcifications one patient had a well defined lesion papilloma colonised by ADH Mid range biopsy size (mean 1.12cm 3, 0.18-3cm 3 ) 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 4 All histologically difficult cases 2mm lobule with atypical features outside consult fine microcalcs?not representative ADH favoured excision papillomatosis with UDH 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 All histologically difficult cases Complex sclerosing lesion Mass on imaging Widespread UDH 4 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 All histologically difficult cases One single atypical duct at the edge of the biopsy Imaging?fibroadenoma Fibroadenoma on excision 4 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 4 2 0 All histologically difficult cases One single atypical duct at the edge of the biopsy Imaging?fibroadenoma Fibroadenoma on excision Wide range of biopsy sizes 0.08-3.3cm 3 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 LG DCIS No mass lesions on radiology All had microcalcifications Average initial lesion size similar (3.4-3.8mm) 4 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Results and Discussion 20 18 16 14 12 10 8 6 4 LG DCIS Biopsy size, no residual 5.66cm 3 (1.6-10cm 3 ) LG DCIS 3.46 Int DCIS 1.30 2 0 ADH LG DCIS Other atypia No excision Benign No residual ADH DCIS Invasive Ca
Conclusions Our ADH upgrade rate (limited cases) 47% (9/19), published rates vary 17-41% Importance of correlating clinical, radiological & pathological findings triple test Stellate lesions, correlate microcalcifications on imaging and location in specimens Biopsy size is important Vacuum assisted and larger biopsy sizes associated with higher rates of concordance with ADH and DCIS However, increases likelihood of biopsy-excision with no residual
Conclusions Centres worldwide have similar difficulties with atypical epithelial hyperplasia, risking overtreatment or underdiagnosis of DCIS Common predictors for upgrading ADH to DCIS or invasive carcinoma Size of biopsy Mammography architectural distortion Clinical symptoms, palpable mass Initial radiological size >15mm Residual calcifications post-biopsy Multiple foci >3 Marked cytological atypia Dion et al, Atypical epithelial hyperplasia of the breast: state of the art. Exp Rev Anticancer Therapy 2016
Further directions Continue to analyse data from ongoing Breastscreen core biopsies Continued follow up of patients from this series Interested in collaborating with other Breastscreen services statewide and nationally
Acknowledgements Dr Ricardo Vilain Dr Julie Weigner Dr Zoe Barker - Designated Radiologist with Breastscreen NSW HNE Breastscreen NSW Hunter New England Anatomical Pathology & Cytology Department, Pathology North, Hunter, Pathology NSW