Introduction 25 30 28 4 30 45 57 41 20 4 50 The main aim of this study was to assess the risk of invasive carcinoma and DCIS at the site of classical lobular neoplasia diagnosed on breast needle core biopsies. In view of the clear morphological differences, pleomorphic LCIS was considered separately. A second aim was to investigate the localisation of calcification in core biopsies containing lobular neoplasia. Materials and methods 35 44 Patients were excluded if they had synchronous or previous invasive carcinoma or DCIS in the same breast. Two patients with contralateral invasive carcinoma were included. Core biopsies containing invasive carcinoma, DCIS or an area suspicious of either diagnosis were excluded. Cores containing pleomorphic LCIS, an atypical intraductal epithelial proliferation (including atypical ductal hyperplasia), radial scar or a papillary lesion were considered separately. Thus, the main group of core biopsies studied contained classical lobular neoplasia with no other risk lesions: we termed this group “simple” classical lobular neoplasia. The core biopsies were reviewed for the following features: location of any calcification and presence of columnar cell change. Six cores were not available, so could not be reviewed. The frequency of columnar cell change was compared with 87 consecutive core biopsies reported by one observer (AHSL) as normal or benign. Results Simple classical lobular neoplasia on core biopsy Forty-nine core biopsies with lobular neoplasia from 47 women satisfied the entry criteria (0.3% of the 14,597 diagnostic core biopsies performed during this period). Two patients had two core biopsies from the same area of the breast containing lobular neoplasia: both are only counted once in the following results. The median age was 52 years (range 33 to 81). Twenty-six patients presented with mammographic screening abnormalities: 20 with calcification, 3 with a mass, 2 with calcification and distortion and 1 with a mass and calcification. Nineteen patients presented symptomatically: ten with a mass, seven with a thickening and two with a thickening and calcification. Two women had calcification identified by mammography performed in one patient as part of the investigation of a contralateral carcinoma and, in the other, as follow-up of a contralateral carcinoma. Eight core biopsies were freehand, 14 were ultrasound guided and 25 were performed under stereotactic guidance. 1 Table 1 Extent of columnar cell change in cores with lobular neoplasia and controls Columnar cell change Core biopsy with lobular neoplasia Controls (normal or benign core biopsy) None 12 (29%) 58 (67%) One lobule or duct 9 (22%) 14 (16%) At least two lobules or ducts 20 (49%) 15 (17%) χ 2 P 2 Table 2 Details of patients with invasive carcinoma, DCIS or pleomorphic LCIS at the site of the core biopsy showing simple lobular neoplasia Age Presentation Core pathology Time to excision/months Final diagnosis (surgical procedure) Pathology–radiology correlation 60 Screen-detected mass ALH, CCCh, calcs 1 13 mm IDC, G3, LN 0/4 (Mx) Core missed mass 75 Symptomatic mass LCIS, UEH, CCCh 2 6 mm IDC, G2, LN not examined (Mx) Core missed mass 63 Screen-detected distortion and calcification. Mass on US ALH 1 14 mm ILC, G2, LN 0/5 (WLE) Core missed mass 54 Screen-detected calcification ALH 1 4 mm tubulobular carcinoma G1 + 50 mm DCIS, LN 0/6 (Mx) Core missed calcs 43 Symptomatic mass LCIS 1 9 mm IDLC, G2, LN 0/7 (Mx) Core missed mass 68 Screen-detected mass ALH 1 12 mm ILC, G2, LN 0/6 (Mx) Core missed mass 64 Symptomatic mass, no mass on US. Mammographic calcification ALH, cyst, calcs 1 7 mm DCIS (WLE) Calcs sampled by core 54 Screen-detected calcification ALH 1 12 mm tubular carcinoma + 35 mm DCIS, LN 0/4 (WLE) Core missed calcs 45 Symptomatic cysts. Mammographic calcification LCIS, calcs 1 5 mm pleomorphic LCIS (WLE) Calcs sampled by core 52 Screen-detected calcification ALH, UEH, CCCh, calcs 31 9 mm ILC, G2, LN 1/6 (Mx) Mammographically occult mass 70 Screen-detected calcification ALH, calcs 29 36 mm IDC, G3, LN 6/16 (Mx) Dense original mammogram 51 Screen-detected calcification ALH, CCCh, calcs 26 30 mm DCIS + extensive LCIS (Mx) Calcs sampled by core 55 Screen-detected calcification ALH, CCCh, calcs 29 IDC 8 mm, G3, 45 mm DCIS, LN 1/4 (Mx) Calcs sampled by core US ALH LCIS UEH CCCh calcs IDC ILC IDLC DCIS G LN Mx WLE 2 No significant relationships were found between the diagnosis of malignancy (DCIS, pleomorphic LCIS or invasive carcinoma) at the site of the core biopsy and the following features: age of the woman, diagnosis of ALH or LCIS on the core biopsy, whether core biopsy or vacuum-assisted biopsy was performed and the method of guidance (freehand, ultrasound or stereotactic). Pleomorphic LCIS on core biopsy Both patients with pleomorphic LCIS on core biopsy presented with calcification detected by mammographic screening. In both, calcification was seen histologically in association with the pleomorphic LCIS. Both had a diagnostic surgical excision, which showed cribriform DCIS in one and further LCIS in the other. Atypical intraductal epithelial proliferation/radial scar/papillary lesion Eight patients had atypical intraductal epithelial proliferation, radial scar or a papillary lesion in addition to lobular neoplasia on the core biopsy. All eight presented with abnormalities detected by mammographic screening: calcification in five, calcification and distortion in one, mass in one and distortion in one. Seven patients had a diagnostic surgical excision, and one patient had her lesion removed with vacuum-assisted mammotomy. DCIS was found in one of three women with core diagnosis of atypical intraductal epithelial atypia and in one of two with core diagnosis of radial scar. Papillary DCIS with a 3-mm focus of invasion was found after a core diagnosis of papillary lesion with atypical intraductal epithelial proliferation. One patient with a core diagnosis of radial scar with atypical intraductal epithelial proliferation and one with a papillary lesion had benign findings at excision. Discussion Relation between lobular neoplasia and calcification 4 4 11 24 55 1 3 14 20 41 52 49 8 41 30 27 48 Relationship between simple classical lobular neoplasia and carcinoma In this study, 44 women with simple classical lobular neoplasia on core biopsy had surgical excision or follow-up of at least 2 years. Twenty-five women had immediate surgical excision, which showed invasive carcinoma, DCIS or pleomorphic LCIS in nine (36%). In the majority, the core biopsy was judged to have missed the clinical/radiological lesion. This emphasises the importance of clinico-pathological review and further investigation of any discordance. Most of the missed lesions occurred in the early part of the study, suggesting that the accuracy of radiological localisation of core biopsies may have improved later in the series. A smaller number of carcinomas occurred after lobular neoplasia on core biopsy apparently incidental to the clinical or radiological lesion. This raises the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia. The frequency of malignancy if the patients with radiological–pathological discordance are excluded is 11% (2/18). Four of 19 patients with at least 2 years follow-up developed carcinoma at the site of the core biopsy. In one, the carcinoma was mammographically occult, although it was clinically palpable, in one the original mammogram was dense and two women had calcification apparently adequately sampled by the core biopsy. Definite comment cannot be made, but the clinical histories suggest that it is possible that the carcinoma may have been identified earlier in some of these patients if they had had an immediate surgical biopsy. If these women are added to those without radiological–pathological discordance in the above paragraph, the frequency of malignancy is 16% (6/37). 1 3 6 9 10 12 14 16 18 20 21 23 25 26 31 33 36 37 39 41 43 46 47 51 54 58 59 15 One hundred four patients who did not have immediate surgical excision had reported follow-up. The only four patients (4%) with invasive carcinoma or DCIS on follow-up at the site of core biopsy are the four patients described in the present study. The absence of subsequent malignancy in other studies is very surprising given that lobular neoplasia is a well-established risk factor for later carcinoma. Nevertheless, the low rate suggests that the chance of invasive carcinoma or DCIS is lower in those not having immediate surgical excision. It is difficult to estimate the chance of finding invasive carcinoma or DCIS if all patients had an excision biopsy. The 15% rate found in the subset of patients who had immediate excision biopsy is probably an overestimate. If the cases with radiological–pathological discordance are excluded, the risk is probably about half of this, approximately 8%. If one assumes that half of the patients who did not have an immediate excision did not have invasive carcinoma or DCIS at the core site, this gives an estimate of about 4%. This represents an estimate of the lower limit of risk. 13 It is clearly appropriate to investigate patients with simple classical lobular neoplasia on core biopsy that does not explain the clinical or radiological abnormality. If a definitive diagnosis cannot be made with further core biopsy, then an excision biopsy is indicated. 7 34 35 40 53 19 There is a need for prospective studies with surgical excision of all lesions so that an unbiased assessment of the risk of simple classical lobular neoplasia on core biopsy can be made. Careful radiology–pathology correlation is essential. It may be possible to stratify the risk within this group using clinical, radiological or pathological features. Lobular neoplasia associated with radial scars, papillary lesions and atypical intraductal epithelial proliferations Most centres excise radial scars, papillary lesions and atypical intraductal epithelial proliferations diagnosed on core biopsy. In the present study, carcinoma was found on excision of three of the eight lesions with these lesions in combination with lobular neoplasia. This supports the practice of excising such lesions. Pleomorphic LCIS 29 50 5 20 37 32 38 22 56 Discordance of clinical or radiological findings with the pathological changes (this includes mass-forming lobular neoplasia) Lobular neoplasia with atypical histological features including pleomorphic LCIS, lobular neoplasia with necrosis, and when it is not possible to exclude DCIS despite E-cadherin immunohistochemistry If there is an associated risk lesion, such as atypical intraductal epithelial proliferation, radial scar or papillary lesion. We suggest that further studies are needed to guide the management of simple classical lobular neoplasia, as the data on the risk of associated carcinoma remain unclear in this group of patients.