Presented at the "Symposium on Quality Assurance in Breast Pathology 24/04/99, Leuven" under the tittle " Preliminary results of a Multicenter External Quality Assurance Programme. Phase 2: The Test Slides Exchange. ". A collaboration between "Le Centre de référence pour le dépistage du cancer du sein", Brussels, the "Leuvens Universitair Centrum voor Kankerpreventie", the "Laboratoire National de Santé" and the "Programme Mammographie", Grand Duchy of Luxembourg, the National Expert and Training Center for Breast Cancer Screening, Nijmegen , The Netherlands and the European Commission Working Group for Breast Cancer Screening Pathology. Faverly D, Drijkoningen R, Renard F, Scheiden R, Sloane J.

The cases of the slide seminar are illustrated on an experimental Internet site: http://www.1st1.net/forpath/ in collaboration with the Forum of Pathology.

        Education and quality assurance in pathology of mammographically detected lesions have been encouraged by the European Commission. The present project aims to evaluate the performance of the belgian and luxembourgian pathologists in diagnosing and classifying minimal breast lesions. Twenty cases were selected from the files of the reference centre of The Netherlands and prepared for a testing slide set. The cases were submitted to the 109 pathologists participating in the first phase of the programme. The diagnosis, the potential behaviour of the lesions and the suggested therapeutic attitude were collected on a formated questionnaire. The slides were also examined by 17 expert-members of the European Commission Working Group for Breast Screening Pathology, regarded as the "golden standard group".

Eighty-nine questionnaires among the 109 mailed were returned (81.7%).

1. Diagnosis analysis: The absence of diagnosis (no answer, no definite answer before special technique, request for an external consultation,…) varies from 6 to 33% in the Belux group. Special and rare lesion are less frequently diagnosed (Case 17: adenomyoepithelioma - 33.7% or Case 9: spindle cell invasive carcinoma - 30.4%). In general, the diagnosis proposed by the Belux group are confident with the golden standard. A consensus is nevertheless more common in this last group (Case 1: LCIS - 50.6% in Belux against 82.3% in Expert group). Papillary lesions seems to pose important problems. Almost 15% of the responders consider Case 19 as a benign papillary lesion although an absolute consensus on malignancy is reached by the experts. The adenoma of the nipple (Case 18) is also misleading the diagnosis in 11% of the responders.
   The lack of agreement in diagnosing ADH is a well known phenomenon also constated in this study and in both groups (Case 14: Fibrocystic changes - 21.4% and 11.8% of ADH respectively in Belux and Expert groups). ADH supposes to be a rare lesion but a mean number of 7 records (alone or associated) per case is reported in the Belux group. The classical and unresolved differential diagnosis with DCIS is illustrated by Case 5 (same proportion of ADH & Radial scar than DCIS and Radial scar in both groups!).
   An association of multiple elementary lesions is preferably reported by the expert group (Case 20: Tubular carcinoma & DCIS &/ LCIS - 82% against 29.3% respectively for Belux and Expert groups). The diagnosis consistency with which benign lesions were identified is in general better in the golden standard group (Cases 4, Case 18,…).
2. Potential behaviour analysis and therapeutic attitude: Three options are possible, Benign, Borderline lesion with unpredictable behaviour and Malignant. Lobular carcinoma in situ was regarded as Malignant in 68% of the responders, the remainders (32%) as a Borderline lesion with unpredictable behaviour. The suggested therapeutic attitude appears consistent with the diagnosis category.
   ADH was classified as Benign by 27% of the responders and Borderline in 73% of the cases. Case 2 illustrates the differential diagnosis between DCIS and ADH. Fifteen percent of the responders of the Belux group identifies DCIS. Nevertheless, 38% amongst them regard this lesion as a Borderline lesion of unpredictable behaviour!

In conclusion, the preliminary results of this first slide exchange in Belgium and Luxembourg stress on the need of a quality assurance and training programme to insure an acceptable level in diagnosis consistency. A multidisciplinary approach is essential to define a coherent clinical and therapeutic attitude facing specific minimal breast lesions.

Clinical history: A 45-year-old patient discovers a 1 cm large lump in her right breast. Fourteen years ago, she underwent breast augmentation with silicon prosthesis implant. On mammography, presence of a 1 cm mass suspicious for malignancy under the right nipple. A differential diagnosis with a silicon granuloma was suggested. The same area shows a 2 cm large spot on MRI. A lumpectomy was performed with gross margin of at least 1 cm around palpable tumor. Pathology: Invasive lobular carcinoma (ILC) 1.8 cm, totally removed. Demonstrated slide: Representative sample of the margin with inked surgical edge. Original diagnosis: Extensive lobular carcinoma in situ (LCIS) in the margin and the resection lines.

Original treatment: Prosthesis resection, right mastectomy with lymph node resection. Residual LCIS, no metastasis.

Clinical history: Fifty-year-old patient asymptomatic, follow-up of the right breast after left mastectomy for invasive tubular carcinoma and DCIS, 5 years ago. Mammography: Presence of a cluster of fine granular calcifications at 2.5 cm distance from the nipple, noted for the first time after left mastectomy. Magnification views demonstrated some smaller clusters in a total area of +/-1 cm. A biopsy is requested to exclude DCIS. Surgery: Resection biopsy for diagnosis with stereotactic localization. Demonstrated slide: Representative sample of the lesion and of the inked surgical edges. Original diagnosis: Ductal hyperplasia with some cytonuclear atypia. The lesion is not strictly defined as ADH according to Page’s definition. A moderate risk factor for the development of cancer may nevertheless be considered.

Original treatment: A single mastectomy was performed. The breast shows a similar aspect but, with some DCIS foci.

Mammography: First round of participation in screening of a 50-year-old woman. Detection of clusters of fine granular calcifications in an area of +/- 3 cm. Surgery: Resection biopsy for diagnosis with stereotactic localization of a part of the calcifications. Demonstrated slide: Representative sample of the lesions associated with the calcifications. Original diagnosis: Adenosis with columnar cell hyperplasia.

Original treatment: nihil.

Mammography: First round of participation in screening of a 50-year-old woman. Presence of a single cluster of coarse granular suspicious calcifications in an area of +/-1 cm. Magnification views demonstrated a parenchymatous density associated with the calcifications. Surgery: Stereotactic localization and complete resection for diagnosis. Demonstrated slide: Representative sample of the lesion and of the inked surgical edges. Original diagnosis: Ductal adenoma.

Original treatment: nihil.

Clinical history: Fifty-year-old patient asymptomatic, first screening round. Mammography: Detection of a 3 cm large stellate lesion in the right breast. Palpation and sonography are unable to demonstrate the abnormality. Surgery: Complete resection for diagnosis with stereotactic localization. Demonstrated slide: Representative cross section of the biopsy containing the closest surgical edge. Original diagnosis: Radial scar. No definite consensus on the foci of ductal hyperplasia. ADH or single foci of DCIS are Original.

Original treatment: No further treatment. Follow-up is Original.

Follow-up: nihil until now (6 years after the biopsy).

Mammography: Demonstration of a 3.5 cm large area of multiple clusters irregular calcifications in the breast of a 48-year-old woman. Surgery: Partial resection for diagnosis with stereotactic localization. Demonstrated slide: Representative sample of the lesion and of the surgical edges. Original diagnosis: Extensive DCIS involving the surgical resection edges. Presence of multiple foci of invasive carcinoma, from micro-invasion to 0.2 cm large IDC.

Original treatment: Modified mastectomy with axillary lymph node resection. Presence of residual DCIS foci in the breast, absence of axillary metastasis.

Mammography: Screening detected minute stellate lesion 0.5 cm large in the right breast of a 68-year-old woman. Surgery: Complete resection with ample margins (2 cm) after stereotactic localization. Demonstrated slide: Representative sample of the lesion. The surgical edges are not demonstrated in the section and are tumor-free at histology. Original diagnosis: Minute radial scar. Differential diagnosis with tubular carcinoma has been Original. Immuno-staining with actin shows an irregular staining of the borders of the tubular structures. The distribution of the tubular structures in a "soft wavy pattern" is in favour of a diagnosis of benignity.

Original treatment: nihil.

Mammography: Widespread clusters of fine granular calcifications over an area of at least 4 cm in the breast of a 55-year-old woman. Surgery: Partial resection biopsy for diagnosis with stereotactic localization. Demonstrated slide: Representative sample of the lesion, the surgical edges are not visible in this section but contains the same type of histologic lesions. Original diagnosis: Extensive DCIS with "hobnailed" cells.

Original treatment: Modified mastectomy with axillary lymph node resection. Presence of residual DCIS foci in the breast, absence of axillary metastasis.

Mammography: Well outlined round, 1 cm large mass in the left breast of a 53-year-old woman, detected at screening mammography only. Surgery: Resection biopsy in two parts with stereotactic localization. The lesion is totally removed and the surgical edges are grossly tumor-free. Demonstrated slide: Representative cross section of the lesion. Absence of inking viewing the fragmentation of the sample. Original diagnosis: Spindle cell invasive carcinoma 1.3 cm large. Cam 5.2 (+), Vimentine (-), S100 (-), SM1 actin (focally+).

Original treatment: Breast conserving therapy with axillary dissection. Absence of lymph node metastasis.

Follow-up: No recurrence or metastasis until January 98 (6 years follow-up).

Mammography: One cm large area with foci of fine granular calcifications in the breast of a 50-year-old patient. Surgery: Resection biopsy for diagnosis with stereotactic localization. Demonstrated slide: Representative sample of the lesion and of the inked surgical edges. Original diagnosis: DCIS clinging low nuclear grade with LCIS. The surgical edges seems involved.

Original treatment: Single mastectomy. The breast quadrant where the biopsy was performed contains some residual foci of DCIS and LCIS. Absence of invasive tumor.

Clinical history: Asymptomatic but anxious 29-year-old patient with a family history of breast cancer (mother and aunt). Mammography: Presence of a single cluster of fine granular calcifications of 0.5 cm. Surgery: Wide resection biopsy (7 cm) with stereotactic localization. Demonstrated slide: Representative sample of the lesion. The surgical edges are at distance from the lesion, are not visible in the section and appears free of tumor on histologic analysis. Original diagnosis: Minute foci of DCIS low nuclear grade, well differentiated.

Original treatment: A single mastectomy was performed ! Absence of malignant lesion in the breast. No contralateral disease after 8 years follow-up.

Clinical history: Palpable "tumor", 1 cm large, in the breast of a 47-year-old patient. Mammography: Irregular calcifications in a total area of +/-1 cm corresponding to the palpable lesion. Surgery: Wide resection biopsy (7 cm) with stereotactic localization. Demonstrated slide: Representative sample of the lesion and of the closest surgical edge painted with China ink. Original diagnosis: DCIS (2.5 cm diameter) with invasive foci of cribriform carcinoma.

Original treatment: Breast conserving therapy. The lymph nodes were not removed, the invasive component had been missed at the time of biopsy.

Clinical history: Nipple discharge accentuated by palpation of the UOQ of the breast of a 23-year-old patient. Mammography: Dense breast, absence of tumor or calcifications. Surgery: Tylectomy of the clinically suspicious area. Partial resection of a fibrocystic lesion. Demonstrated slide: Representative cross section of the biopsy containing the lesion. Original diagnosis: Complex papillary ductal adenoma incompletely removed.

Original treatment: nihil. Follow-up unknown.

Clinical history: Sixty-eight-year-old woman with a painful, 2 cm large, palpable "mass" in the left breast. Mammography: Absence of definite tumor but the examination is handicapped by the high density of the breast parenchyma. Surgery: Resection biopsy of the clinically suspicious area for diagnosis. Demonstrated slide: Representative cross section of the lesion. Original diagnosis: Area of fibrocystic disease with epithelial hyperplasia.

Original treatment: nihil.

Clinical history: Palpable "tumor" in the breast of a 54-year-old patient. Mammography: Presence of a 1.5 cm large mass associated with many suspicious calcifications in a total area of +/-6 cm. FNAC: Suspicion of malignancy (category C4). Surgery: Incision biopsy with frozen section for diagnosis. Demonstrated slide: Representative cross section of the entire biopsy containing the mass. Original diagnosis: Invasive carcinoma with mucinous secretion (2 cm) and DCIS.

Original treatment: Modified radical mastectomy with axillary lymph node resection. Widespread DCIS, presence of a lymph node metastasis. Adjuvant chemotherapy CMF. One year after diagnosis, development of a contralateral breast cancer treated by mastectomy. The patient if free from recurrence and distant metastasis after 6 years follow-up.

Clinical history: Fifty-year-old patient presenting with a 2 cm large palpable "mass" in the breast. No family history of breast cancer. Mammography: Widespread calcifications over an area of 6 cm with extension in direction of the nipple. Nodular aspect of the breast parenchyma. Surgery: Resection biopsy of the nodular area and of some calcifications for diagnosis. Many calcifications remains in the breast. Demonstrated slide: Representative cross section of the entire biopsy containing the lesions and of the inked surgical edges. Original diagnosis: DCIS low nuclear grade, LCIS, variant of invasive lobular carcinoma with apocrine differentiation. The resection edges are involved.

Original treatment: Modified radical mastectomy with axillary lymph node resection. Many foci of DCIS, LCIS and a second focus of ILC, presence of few lymphatic emboli. Absence of lymph node metastasis.

Clinical history: Well outlined, 1 cm large palpable nodule in the breast of a 76-year-old patient. Mammography: unknown. Surgery: Complete resection with grossly tumor-free margin. Demonstrated slide: Representative sample of the lesion. Original diagnosis: Adenomyoepithelioma benign.

Original treatment: nihil.

Clinical history: Irregular nipple with history of bleeding and discharge in a 68-year-old woman. Mammography: Absence of definite tumor and calcification in the breast. Diffuse density of the nipple. Surgery: Resection biopsy of a part of the nipple for diagnosis. Demonstrated slide: Representative sample of the lesion. Original diagnosis: Nipple adenoma.

Original treatment: nihil. Developement of an abscess one year later.

Clinical history: Seventy-two-year-old patient with previous history of bowel and lung carcinoma, presenting with a soft, 2 cm large palpable tumor under the nipple. Breast imaging: Well outlined round tumor with nipple retraction on mammography. Cystic aspect on sonography. Surgery: Complete resection of the mass with 0.5 to 1 cm large grossly tumor-free margin. Demonstrated slide: Representative cross section of the lesion. The closest surgical edge is visible (underlined) in the section. Original diagnosis: Papillary intracystic carcinoma with DCIS low nuclear grade.

Original treatment: Regarding the clinical history of the patient, all additional treatment was omitted. Seven years after surgery, the patient developed a recurrence of the tumor with the same clinical and histologic presentation.

Clinical history: Fifty-five-year-old patient asymptomatic with family history of breast cancer. Mammography: Development of minimal amount of isolated fine granular calcifications with a 1 cm large, single suspicious cluster of the same type calcifications in the right breast. Surgery: Resection biopsy for diagnosis with stereotactic localization of this cluster. Demonstrated slide: Representative sample of the lesion and of an inked surgical edge. Original diagnosis: DCIS low nuclear grade with invasive tubular carcinoma 0.8 cm.

Original treatment: Modified radical right mastectomy with axillary lymph node resection and biopsy of the left breast. Extensive DCIS, LCIS and many microscopic foci of invasive tubular carcinoma in the mastectomy specimen and in the left biopsy. A left modified radical mastectomy was performed and shows the same histologic picture. Absence of lymph node metastasis, both side.

LCIS: Lobular carcinoma in situ, DCIS: Ductal carcinoma in situ, CIS: Carcinoma in situ, type not precised, ALH: Atypical lobular hyperplasia, ADH: Atypical ductal hyperplasia, FCC: Fibrocystic changes, IC: Invasive carcinoma, type not precised, NDD: no definite diagnosis, Rscar: radial scar, TUB: Invasive tubular carcinoma, Hyperpl: Ductal hyperplasia of the usual type, Ect: ductal ectasia, IDC: Invasive ductal carcinoma, Minv: micro-invasive carcinoma, ComédoC: comédo-carcinoma, invasive or in situ not precised, MGA: micro-glandular adenosis, ICPS: invasive carcinoma pseudo-sarcomatous or spindle cell, MED(A): invasive (atypical) medullary carcinoma, ISCC: invasive small cell carcinoma, Sarcomat: sarcomatoid tumor, PapillaryCar: papillaryt carcinoma, invasive or in situ not precised, IDC Muc: invasive ductal carcinoma with mucinous differentiation, MUC: mucinous carcinoma, ILC(V): invasive lobular carcinoma (variant), APO: invasive apocrine carcinoma, IDAPO: invasive ductal carcinoma with apocrine differentiation, PapillaryCarc ICystic: Encysted, in situ papillary carcinoma, PapillaryCarc Inv: Invasive papillary carcinoma.