Abstract
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.
Keywords: 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.
Figure 1.
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.
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).
Table I.
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.
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.
Table II.
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.
Table III.
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.
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.
Table IV.
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.
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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