ETM Experimental and Therapeutic Medicine 1792-0981 1792-1015 D.A. Spandidos 10.3892/etm.2011.332 etm-02-06-1069 Articles Papillary lesions of the breast diagnosed using core needle biopsies TOKINIWAHIDEAKI1 HORIGUCHIJUN1 TAKATADAISUKE1 KIKUCHIMAMI1 ROKUTANDANANA1 NAGAOKARIN1 SATOAYAKO1 ODAWARAHIROKI1 TOZUKAKATSUNORI1 OYAMATETSUNARI2 TAKEYOSHIIZUMI1 Departments of Thoracic and Visceral Organ Surgery, and Diagnostic Pathology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan Correspondence to: Dr Hideaki Tokiniwa, Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan, E-mail: tokiniwa@med.gunma-u.ac.jp November-December 2011 11 8 2011 2 6 1069 1072 30 5 2011 4 7 2011 Copyright © 2011, Spandidos Publications 2011

Papillary lesions of the breast include a broad spectrum of lesions, from benign papillomas to papillary carcinomas. It is difficult to determine whether a lesion is benign or malignant based on the fragmented material of a core needle biopsy (CNB). This study evaluated patients with papillary lesions examined using CNB. We retrospectively reviewed 31 papillary lesions diagnosed using CNB between 2004 and 2007. The clinical findings of benign and malignant papillary lesions were compared. The average patient age was 48.9 years. Twelve patients presented with a discharge and 10 patients presented with a lump. Eight patients were asymptomatic. The initial diagnoses by CNB of the 31 lesions were 25 intraductal papillomas, 4 intracystic papillomas and 2 adenomas. After CNB, excisional biopsies were performed in 23 patients and biopsies with a Mammotome® in 2 patients. Seven patients underwent regular follow-up. Five (16%) of the 31 patients with papillary lesions were ultimately diagnosed with breast cancer. The average distance from the nipple to a tumor diagnosed as malignant was 2.46 cm, which was longer than for a tumor diagnosed as benign. Ultimately, 5 papillary lesions (16%) were diagnosed as breast cancer. To avoid overlooking a malignancy, surgical excision is advantageous for papillary lesions, particularly those located far from the nipple.

 papillary lesion of the breast core needle biopsy breast cancer Introduction

Core needle biopsy (CNB) has become widely used in diagnosing breast disease (1,2). CNB is a uncomplicated examination, which is easier for patients to accept than excisional biopsy. Papillary lesions are a heterogeneous group of breast lesions and include papilloma, papillomatosis, atypical papilloma, non-invasive ductal carcinoma and invasive ductal carcinoma. Sometimes, distinguishing malignant from benign papillary lesions using CNB can be difficult since only a small portion of the lesion is examined. This study evaluated the follow-up methods and results of excisional biopsies for patients with papillary lesions initially diagnosed using CNB.

 Patients and methods

We retrospectively reviewed 31 papillary lesions of the breast diagnosed using CNB between 2004 and 2007. All cases were reviewed regarding the follow-up methods, distance from the nipple to the tumor and final pathological diagnosis.

Patient background

The median patient age was 48.9 years (range 22–81). Twelve patients came to our hospital due to nipple discharge, 10 patients presented with a lump, 8 patients had an abnormal check-up and 1 patient presented with another complaint. Ultimately, 14 patients developed nipple discharges: 8 were bloody and 6 were serous.

 Percutaneous biopsy method

Ultrasonographically guided procedures were performed with the patient in the supine or supine oblique position. Imaging was performed with a high-resolution 8–12 MHz linear array transducer (Acuson Sequoia 512; Siemens®). The biopsy was performed using a freehand technique with a 14-gauge needle and spring-loaded biopsy gun (Bard Magnum®). The distance from the nipple to the tumor was measured using ultrasonography at the time of CNB (Fig. 1). The biopsy specimen was evaluated by an experienced breast pathologist.

 Results

The initial diagnosis was intraductal papilloma in 25 patients (80%), intracystic papilloma in 4 (13%) and adenoma in 2 (7%). After CNB, excisional biopsies were performed in 23 patients and Mammotome® biopsies in 2 patients. The CNB was repeated in 2 patients. Four patients did not undergo any further biopsy, but were followed up with ultrasonography alone at the’ request of the patients. Five (16%) of the 31 patients with papillary lesions were ultimately diagnosed with breast cancer.

Five malignant cases

The mean patient age was 48.8 years (range 37–72). All cases were diagnosed as intraductal papilloma initially. Two patients presented with a lump, 2 with abnormal check-up results and only 1 with a bloody nipple discharge. The average distance from the nipple to the tumor was 2.46 cm. To obtain the final diagnosis, 4 patients underwent excisional biopsies and 1 a repeat CNB. The final diagnosis was invasive ductal carcinoma in 4 cases and non-invasive ductal carcinoma in the others. After the final diagnosis, 4 patients underwent breast-conserving surgery and 1 underwent a total mastectomy. Sentinel lymph node biopsies were performed at the time of surgery in all cases, and there was no cases of lymph node metastasis (Table I).

 Discussion

We examined the difference between the initial diagnosis, based on CNB, and the final diagnosis, based on excisional biopsy, for papillary lesions. Comparing the distance from the nipple to the tumor, it was 2.46 cm (range 0.5–4.0) for those diagnosed as malignant and 1.76 cm (range 0.5–4.5) for those diagnosed as benign. Malignant lesions were located farther from the nipple than benign lesions (Table II), although the difference was not statistically significant. There was no significant difference in the age of the patients with benign and malignant lesions (Table III). Distinguishing malignant from benign papillary lesions can be problematic. The presence or absence of a myoepithelial cell layer in the papillary component of the lesion is the most important feature for differentiating a benign papilloma from a papillary carcinoma.

We reviewed 21 studies (including ours); 10 studies supported the need for surgical excision and 10 did not (Table IV) (3–22). There were 643 cases in these studies; 424 cases (65.9%) underwent excisional biopsies: 334 cases (78.8%) were diagnosed as benign; 27 were diagnosed as atypical ductal hyperplasia; 21 were non-invasive ductal carcinoma; and 27 were invasive ductal carcinoma. Ultimately, an excisional biopsy was required in 75 cases (11.7%). Ten studies stated that an excisional biopsy was necessary to diagnose papillary lesions, while the other 10 studies concluded that it was not necessary.

It remains controversial whether papillary lesions of the breast diagnosed using CNB need a further excisional biopsy. An excisional biopsy has some merits. The pathologist can diagnose the papillary lesion as benign or malignant from the entire lesion, the nipple discharge will stop after an excisional biopsy and no repeat CNB is necessary. Conversely, there are certain disadvantages to an excisional biopsy. Local anesthesia (e.g., allergy and toxicity) and surgery convey various risks, an excisional biopsy may alter the breast shape and an accurate sentinel lymph node biopsy may be impossible as the lymphatic flow is altered. Several reports supporting CNB alone for distinguishing benign and malignant papillary lesions are based on immunohistochemical studies, which suggest that different cell surface markers help differentiate the two. Saddik and Lai proposed that CD44 is a marker for benign papillary lesions (23). Recently, high-molecular-weight cytokeratins, particularly CK5 and 6, have been studied as markers (24). Shah et al added CK5 and 6 to calponin and p63 and investigated their effect on the accuracy of CNB (25). The overall accuracy increased from 84.5 to 92.8%. Moreover, Moriya et al suggested that certain immunohistochemical markers are quite useful in diagnosing various breast lesions, particularly for separating benign lesions and malignant neoplasms; however, the situations in which these markers are valuable are not universal, and their application and methods for evaluation are limited (26).

Ultimately, 5 papillary lesions (16%) initially diagnosed as benign papillary lesions were diagnosed as a breast cancer. The average distance from the nipple to the tumors diagnosed as malignant was longer than that for those diagnosed as benign. For papillary lesions, including intraductal papilloma, located far from the nipple, it is also necessary to consider a carcinoma which may be hidden near them. To avoid overlooking a malignancy, surgical excision is advantageous for papillary lesions, particularly those located far from the nipple.

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Distance from the nipple to the nearest tumor edge was measured using ultrasonography. In this case, the distance from the nipple to the nearest tumor edge was 3.1 cm.

Five malignant cases.

Case Age (years) Initial diagnosis Clinical presentation Discharge TND (cm) Follow-up Final diagnosis Op
1 72 Intraductal papilloma Discharge Bloody 0.50 CNB IDC Bt
2 44 Intraductal papilloma Lump No 4.00 Excisional biopsy IDC Bp
3 37 Intraductal papilloma Lump No 3.20 Excisional biopsy IDC Bp
4 41 Intraductal papilloma Asymptomatic No 1.10 Excisional biopsy DCIS Bp
5 50 Intraductal papilloma Asymptomatic No 3.50 Excisional biopsy IDC Bp
Average 48.8 2.46

TND, distance from the nipple to the tumor; Op, operation; CNB, core needle biopsy; IDC, invasive ductal carcinoma; DCIS, non-invasive ductal carcinoma; Bp, wide excision; Bt, total mastectomy.

TND of malignant lesions and benign lesions.

Lesion TND mean (range)
Benign 1.76 (0.5–4.5)
Malignant 2.46 (0.5–4.0)

TND, distance in cm from the nipple to the tumor. p=0.13.

Age of the patients with malignant and benign lesions.

Lesion Age, in years mean (range)
Benign 48.4 (22–78)
Malignant 48.8 (37–72)

p=N.S.

Papillary lesions of the breast diagnosed with core biopsy; summary of the literature.

Author/(Refs.) Year No. of cases No. of excisions Benign ADH DCIS IDC Other Conclusions
Ioffe et al (3) 2000 28 8 8 No excision
Philpotts et al (4) 2000 16 6 4 2 No excision
Liberman (5) 2000 7 4 4 No excision
Mercado et al (6) 2001 12 6 5 1 Excise
Rosen et al (7) 2002 44 14 11 2 1 No excision
Irfan and Brem (8) 2002 6 3 1 1 1 -
Ivan et al (9) 2004 30 6 6 No excision
Puglisi et al (10) 2003 31 31 29 2 Excise
Agoff and Lawton (11) 2004 25 11 11 No excision
Renshaw et al (12) 2004 8 8 8 No excision
Gendler et al (13) 2004 13 13 9 2 2 Excise
Carder et al (14) 2005 2 1 1 No excision
Liberman et al (15) 2006 50 25 20 4 1 Excise
Mercado et al (16) 2006 43 36 14 8 2 12 Excise
Valdes et al (17) 2006 36 36 30 6 Excise
Plantade et al (18) 2006 86 37 32 5 No excision
Skandarajah et al (19) 2007 80 80 54 11 8 7 Excise
Arora et al (20) 2007 18 18 18 Excise
Sydnor et al (21) 2007 38 38 37 1 No excision
Askenazi et al (22) 2007 39 20 13 3 4 Excise
Present study 31 23 19 1 3 Excise
Total 643 424 334 27 21 27 15 Ten studies recommend excision

ADH, atypical ductal hyperplasia; DCIS, non-invasive ductal carcinoma; IDC, invasive ductal carcinoma.