Annals of Surgical Oncology Sign the Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9170-1
Annals of Surgical Oncology 14:1009-1013 (2007)
© 2007 Society of Surgical Oncology
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Valdes, E. K.
Right arrow Articles by Boolbol, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Valdes, E. K.
Right arrow Articles by Boolbol, S. K.

Original Article

Papillary Lesions: A Review of the Literature

Edna K. Valdes, MD, Sheldon M. Feldman, MD, FACS and Susan K. Boolbol, MD

Louis Venet Comprehensive Breast Service, Beth Israel Medical Center, 10 East Union Square, Suite 4E, New York NY 10003, USA

Correspondence: Address correspondence and reprint requests to: Edna K. Valdes, MD; E-mail: edvaldes{at}chpnet.org


   INTRODUCTION
TOP
 INTRODUCTION
BACKGROUND
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Papillary lesions of the mammary glands are relatively uncommon. These lesions account for less than 10% of benign breast neoplasms, 0.5–2% of all breast malignancies,1 and up to 5% of all the lesions undergoing biopsy.2 They comprise a broad spectrum of entities such as papilloma, papillomatosis, sclerosing papilloma, atypical papilloma, papilloma with atypical ductal hyperplasia, intraductal papillary carcinoma and invasive papillary carcinoma.2–8 Distinguishing benign from malignant lesions can be quite challenging without surgical excision because of the lack of distinctive clinical and radiological signs. Overall, clear management guidelines regarding papillary lesions have not yet been established.


   BACKGROUND
TOP
 INTRODUCTION
 BACKGROUND
DISCUSSION
 CONCLUSION
 REFERENCES
 
Hoda and Rosen9 stated that papillomas may harbor focal papillary carcinoma or be contiguous to carcinoma that was not included in the core biopsy sample. They therefore suggested that all papillary lesions, regardless of the presence or the degree of architectural and cytologic atypia, diagnosed with core biopsy should be excised surgically due to potential sampling errors of core biopsy. In two independent reviews on the role of core biopsy, Philpotts10 and Liberman et al.11–13 suggested that imaging and histopathological concordance and the pathologist’s judgement should be the determining criteria used for deciding whether the lesions need to be surgically removed. Liberman et al.11 reported their experience on 26 papillary lesions in which surgical correlation was available in 22 and minimum 2 years mammographic follow-up in the remaining four. The number of benign papillomas was small in this study (seven); although none proved to be carcinoma at surgery or imaging follow up, larger series with longer follow-up was recommended to assess the clinical course of benign papillary neoplasms that are not surgically excised.

Puglisi et al.3 reported their experience on 51 papillary lesions in 49 women, diagnosed by core biopsies, using 14-gauge needles. The lesions were excised in 49 cases. The authors reported 38.7% (19/49) rate of malignancy. They reported 5/19 (26% of all malignant cases) false-negative results that would have been missed without surgical excision. Mammographic findings included masses, architectural distortions, calcifications and masses with calcifications. Sonographic findings included intraluminal or extraductal masses, purely solid masses, mixed types and margins were categorized as ‘well defined’ or ‘poorly defined’. A dismal agreement was found between the gold standard surgical excision and suspicion based on preoperative imaging. Furthermore, the authors concluded that radiological findings are not useful in distinguishing benign from malignant papillary lesions. Similar results are noted in studies by Agoff et al. Soo et al. and Woods and colleagues,4 who found that papillary carcinoma and benign papillomas can have similar features and are challenging to distinguish radiologically.

Gomez-Aracil et al.14 reported that fine needle aspiration biopsy (FNAB) could be diagnostic in differentiating benign from malignant papillary lesions. Their study showed that in the case of papillary carcinomas, diagnosis is based on the presence of papillae covered by multilayered cells without fibrovascular stalks, the abundance of isolated columnar cells and naked tomour nuclei, the presence of haemosiderin-laden macrophages, and a lack of apocrine metaplasia or bipolar naked nuclei. The diagnosis of papilloma depends on the presence of more prominent fibrovascular stalk, less isolated columnar cells, the presence of bipolar naked nuclei and apocrine metaplasia. Nuclear atypia was not helpful in establishing a diagnosis.

In 2003, Masood et al.1 reported their experience in reliability of fine needle aspiration biopsy (FNAB) versus core needle biopsy in differentiating benign from malignant papillary lesions. They found malignany in 3 of 21 (14%) benign papillary lesions and in three of ten (30%) atypical papillary lesions diagnosed by FNAB. When these patients underwent surgical excision, malignant lesions were found in one of six (17%) benign papillomas and in two of four (50%) atypical papillary lesions initially diagnosed by core needle biopsy. They concluded that both FNAB and CNB share similar diagnostic challenges. Masood et al. conclude that concordance between breast image findings and the histopathological results along with the use of immunohistochemical staining to highlight the myoepithelial cells is important in differentiating between atypical and malignant papillary lesions. Since FNAB is lower in cost and is less invasive, it should be used preferentially over CNB in preliminary diagnosis of papillary lesions, however, a follow-up surgical excision is recommended.

The largest series by Gendler et al.15 in 2004, reported on 153 papillary lesions of which 87 underwent subsequent excisional biopsy. Of these 87 patients, 53 (61%) underwent FNAB with a 22-gauge or smaller needle, and 34 patients (39%) underwent biopsies with large-bore CNB (11- or 14-gauge). Carcinoma was found in 15 (17%), and ADH was found in 16 (18%) of patients who had papillary lesions in their original biopsies. Among the patients with cancer, 12 patients had DCIS, two patients had infiltrating papillary carcinoma, and one patient had infiltrating ductal carcinoma. Thirteen of 53 FNAB specimens (25%) and 18 of 34 CNB specimens (53%) diagnosed as papillary lesions had breast cancer or ADH identified at excisional biopsy. Therefore, the diagnostic accuracy for identifying carcinoma or ADH in a papillary lesion was not improved by the use of large-bore CNB compared with FNAB. The authors therefore concluded that surgical excision of all papillary lesions is prudent.

The most recent data by Valdes et al.16 earlier this year, reported on 120 papillary lesions of which 80 underwent surgical excision. Of these 80 lesions, 30 (37.5%) underwent FNAB with a 20 to 22-gauge needle, 17 lesions (21.2%) underwent core needle biopsy with a 14-gauge needle, and 33 lesions (41.3%) underwent stereotactic vacuum-assisted biopsy with an 11-gauge probe. Nineteen lesions (23.8%) had cancer present in the surgical specimen. Among the cancerous lesions, 12 lesions were DCIS, four lesions were infiltrating ductal carcinoma, one lesion was intracystic papillary carcinoma, and two lesions were invasive papillary carcinoma. Nine of 30 FNAB specimens (30%), 6 of 17 CNB specimens (35.3), and 4 of 33 mammotome specimens (12%) initially diagnosed as papillary lesions were diagnosed as cancer at surgical excision. Among the 19 malignant lesions, cytological diagnosis was papilloma/papillomatosis in six lesions (31.6%), atypical papilloma/papilloma with ADH in two lesions (10.5%), and papillary neoplasm in nine lesions (47.4%), and papillary neoplasm with atypia in two lesions (10.5%). The authors concluded that there are no distinctive clinical, radiological or cytological signs that can distinguish between a papillary lesion and carcinoma. Therefore surgical excision of all papillary lesions discovered by percutaneous needle biopsy was recommended.

Jeffrey and Ljung17 performed FNAB in 11 papillary lesions using 23-gauge needle. The correlation between cytology and histology was accurate in 2/5 (40%) malignant and 2/6 (33%) benign papillary lesions. The authors concluded that surgical biopsy is prudent in all cases of papillary lesions to determine the presence or absence of malignancy.

Simsir et al.6 reported their experience with 70 cases classified as papillary lesions using FNAB, all of which underwent surgical excision. At the time of excision, 29/70 (41%) were papillomas, 11/70 (15.7%) fibrocystic change, 6/70 (8.6%) fibroadenomas, 24/70 (34%) were malignant. Four of the 24 malignant cases (17%), three carcinomas and one phyllodes tumor, were categorized as benign papillary lesions on FNAB and therefore there were four false negative diagnoses. Furthermore 25% of the lesions categorized as papillary on FNAB were fibroadenomas and fibrocystic changes. Despite these results the authors believe that the majority of papillary lesions can be categorized accurately as benign or atypical by FNAB. The authors justify their conclusion due to two of the three missed carcinoma cases were sampling errors, and therefore there was only one carcinoma case that was a true under diagnosis. The fourth case which was a low-grade phyllodes lacked the classic features of phyllodes tumors such as hypercellular stroma and atypical spindled cells in the background.

Renshaw et al.18 reported their experience with 62 papillary lesions, 40 (65%) of which had histological follow up. The histology was classified into benign papilloma with florid hyperplasia and no or minimal atypia (18 cases), papilloma with separate foci of atypical ductal hyperplasia (7 cases), and severely atypical papillomas "suspicious" for papillary carcinoma (13 cases). Carcinoma was diagnosed in the surgical pathology in 0, 2 (29%), and 12 (92%) cases, respectively. The authors concluded that atypical papillary lesions and papillomas associated with ADH are associated with a risk of carcinoma, however, benign papillomas or papillomas with no or minimal atypia are benign and do not need to be excised. Rosen et al.2 and Liberman et al.11 in two independent studies came to the same conclusion, 38% (3/8) and 30% (3/10) of the atypical cases, respectively, were shown to be papillary carcinoma in situ after excisional biopsy. Whereas 0% (0/7) and 0% (0/4) of the benign papillomas, respectively, were shown to be benign on excisional biopsy.

In a similar study reported by Agoff et al.,4 48% (12/25) of papillary lesions with ADH were proven to be carcinoma on surgical excision. Only 11/25 benign papillomas underwent surgical excision, which revealed benign findings. The authors concluded that the presence of ADH correlated significantly with the presence of invasive or preinvasive mammary carcinoma. These findings are similar to those of Ivan and colleagues,7 who found that surgical excision revealed a rate of 63% (5/8) carcinoma in situ in the papillary lesions with ADH diagnosed on core biopsy.

Conflicting data in relation to benign papillary lesions, was then reported across three series by Jacobs et al.,8 Hermann et al.,19 and Berg et al.,20 6/51 (12%), 3/24 (12.5%), and 1/12 (8%) benign papillary lesions on core biopsy proved to be malignant on excision, respectively. Therefore, these authors concluded that recognizing the subtlety of atypical features in papillary lesions, excision seems reasonable for all papillary lesions.

Mercado et al.5 used stereotactic directional 11-gauge vacuum assisted biopsy (SDVAB) for diagnosing papillary lesions of the breast. Eighteen patients were diagnosed with papillary lesions, 12 benign, and six atypical. Surgical excision was performed in 12 patients, six benign cases and six atypical cases. The remaining six patients had long-term imaging follow-up, which comprised of mammograms at six months intervals for 2 years. Mammographic follow-up demonstrated that five lesions decreased in size after SDVAB; and no residual lesion was seen in one case, with no evidence of recurrence. One out of six (17%) benign cases excised surgically proved to be malignant. All of the atypical lesions that underwent surgical excision were found to be benign. Overall discrepancy between SDVAB and surgical excision was noted in 1/12 (8.3%). The negative predictive value for this study was 92%. The authors concluded that benign and malignant papillary lesions can be differentiated reliably using this technique when the results correlate with the mammographic findings.

In an interesting report by Saddik et al.,21 expression of CD44s detected by immunohistochemistry was studied in 11 intraductal papillomas and ten papillary carcinomas. The epithelial cells’ positivity for CD44s was scored and categorized as <10, 10–70, or >70%. Normal breast epithelial cells and all intraductal papillomas (11/11) expressed CD44s in a high proportion of cells (>70%). However, most of papillary carcinoma cases (8/10) expressed this marker in <10% of the cells. In the remaining two papillary carcinoma cases, positivity was seen in >10% but still <70% of the cells. Although the findings were encouraging, there were some limitations associated with this study, namely the small number of cases and that the borderline papillary lesions were not evaluated.

Mosunjac and colleagues22 stated that the presence or absence of myoepithelial cells is one of the most diagnostically valuable criteria to distinguish papillomas from papillary carcinomas. Antismooth muscle actin, commonly used as a marker of myoepithelial cells, also identifies stromal myofibroblasts, which makes the interpretation very difficult. Calponin is a new marker with its expression being limited to smooth muscle tissue. The authors reported that calponin is a highly specific smooth muscle marker that stains myoepithelial cells without nonspecific nuclear or background staining and it proved especially useful in delineating papillary lesions with atypical features. They concluded that a cell block should be obtained and immunohistochemistry for calponin should be performed in papillary lesions to improve accuracy of diagnosis.


   DISCUSSION
TOP
 INTRODUCTION
 BACKGROUND
 DISCUSSION
CONCLUSION
 REFERENCES
 
Over the last decade, the field of breast imaging has evolved from one of screening and detection to one of primary breast care including diagnosis and management. Percutaneous image-guided breast biopsy is well tolerated by patients and accurate for most breast lesions.23 Percutaneous biopsy is faster, less invasive, and less expensive than surgical biopsy. Less tissue is removed at percutaneous biopsy, resulting in minimal to no deformity and scarring on subsequent breast imaging. It can eliminate the need for surgical excision in patients with benign lesions and can minimize the number of surgical procedures in patients with breast cancer.12

Papillary lesions of the breast account for less than 10% of benign breast neoplasms that undergo biopsy and 0.5–2% of all breast malignancies.1,11–13 Approximately 50% of the papillary lesions arise in a central location. They present with bloody nipple discharge in 30% of patients. The average size for these lesions is 2–3 cm in diameter.1 Multiple papillomas are more likely to be associated with breast cancer compared with solitary papillomas on final surgical pathology.15

Papillary lesions develop as tufts of epithelium with a fibrovascular core that arborize into branching papillae and protrude into the duct lumen. Intraductal papilloma is the most common cause of serosanguinous or sanguinous nipple discharge.5 Papillomas may be present as solitary central lesions within large ducts in the subareolar region or as multiple lesions within the smaller ducts in the peripheral regions of the breast.5,24 It has been suggested that there may be an increased risk for development of breast cancer in women with multiple papillomas.5

Histologically, papillomas have arborizing fronds of two-cell-layered epithelium supported by a fibrovascular stalk. A layer of myoepithelial cells is present in between the luminal cells and the basement membrane. Atypical papillomas have epithelial proliferations in their papillary projections similar to presentation in atypical ductal hyperplasia.1,5,7,22,24,25 A papillary carcinoma has one layer of cells surrounding the central stalk and the myoepithelial cell layer is absent.1,22,24 Papillomatosis is a term applied to papillary hyperplasia involving the epithelium of ≥1 duct and sparse supporting fibrovascular stroma.15

Across multiple series (Table 1Go) by Valdes et al.,16 Gendler et al.,15 Jacobs et al.,8 Hermann et al.,19 and Berg et al.,23 a significant number of benign papillary lesions on core biopsy proved to be malignant on excision. Although Mercado et al.5 concluded that benign and malignant papillary lesions could be differentiated reliably using SDVAB when the results correlate with the mammographic findings; the limitation of the study was the small number of cases. Therefore larger patient population and longer follow-up period (>2 years) are needed to confirm their findings.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Results of surgical excision of papillary lesions diagnosed on percutaneous needle biopsy
 
Valdes et al.,16 Masood et al.,1 and Gendler et al.15 in three independent studies showed that FNAB and CNB share similar diagnostic challenges in diagnosing and differentiating benign from malignant papillary lesions and therefore recommended subsequent surgical excision of all these lesions.

The results of a small study reported by Saddik et al.21 that the use of CD44s may be useful in differentiating benign papillomas from papillary carcinoma, is encouraging. However, additional studies are needed to evaluate the expression of this marker in a larger number of cases, including the borderline papillary lesions.


   CONCLUSION
TOP
 INTRODUCTION
 BACKGROUND
 DISCUSSION
 CONCLUSION
REFERENCES
 
Although papillary lesions account for a small percentage of lesions undergoing percutaneous needle biopsy, they are clinically significant. Management of papillary lesions has evolved over time. However, clear guidelines have not yet been established.

There is no long-term follow up data available for partially removed papillary lesions sampled by needle biopsies. Mammography and sonography cannot reliably distinguish benign from malignant papillary breast lesions. There is no doubt that atypical papillary lesions or those associated with atypia require surgical excision because the histology can be underestimated using percutaneous needle biopsy. Based on our review of the literature we conclude that recognizing the subtlety of atypical features in papillary lesions, all papillary lesions diagnosed by percutaneous needle biopsy should be excised surgically to rule out associated ADH or malignancy. The surgical pathology may have an impact on the treatment plan, risk assessment and reduction, and/or surveillance for a significant number of patients diagnosed with papillary lesions on percutaneous biopsy.

Received for publication January 20, 2006. Accepted for publication May 2, 2006.


   REFERENCES
TOP
 INTRODUCTION
 BACKGROUND
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Masood S, Loya A, Khalbuss W. Is core needle biopsy superior to fine-needle aspiration biopsy in the diagnosis of papillary breast lesions? Diagn Cytopathol 2003; 28(6):329–34.[CrossRef][Medline]
  2. Rosen EL, Bentley RC, Baker JA, Soo MS. Imaging-guided core needle biopsy of papillary lesions of the breast. AJR Am J Roentgenol 2002; 179:1185–92.[Abstract/Free Full Text]
  3. Puglisi F, Zuiani C, Bazzocchi M, et al. Role of mammography, ultrasound and large core biopsy in the diagnostic evaluation of papillary breast lesions. Oncology 2003; 65:311–5.[CrossRef][Medline]
  4. Agoff SN, Lawton TJ. Papillary lesions of the breast with and without atypical ductal hyperplasia. Can we accurately predict benign behavior from core needle biopsy? Am J Clin Pathol 2004; 122:440–3.[CrossRef][Medline]
  5. Mercado CL, Hamele-Bena D, Singer C, Koenigsberg T, Pile-Spellman E, Higgins H, Smith SJ. Papillary lesions of the breast: Evaluation with stereotactic directional vacuum-assisted biopsy. Radiology 2001; 221:650–5.[Abstract/Free Full Text]
  6. Simsir A, Waisman J, Thorner K, Cangiarella J. Mammary lesions diagnosed as "papillary" by aspiration biopsy. 70 cases with follow-up. Cancer 2003; 99:156–65.[CrossRef][Medline]
  7. Ivan D, Selinko V, Sahin AA, Sneige N, Middleton LP. Accuracy of core needle biopsy diagnosis in assessing papillary breast lesions: Histologic predictors of malignancy. Mod Pathol 2004; 17:165–71.[CrossRef][Medline]
  8. Jacobs TW, Connolly JL. Nonmalignant lesions in breast core needle biopsies. To excise or not to excise? Am J Surg Pathol 2002; 26(9):1095–110.[CrossRef][Medline]
  9. Hoda SA, Rosen PP. Practical considerations in the pathologic diagnosis of needle core biopsies of breast. Am J Clin Pathol 2002; 118:101–8.[Abstract/Free Full Text]
  10. Philpotts LE. Controversies in core-needle breast biopsy. Semin Roentgenol 2001; 36(3):270–83.[CrossRef][Medline]
  11. Liberman L, Bracero N, Vuolo MA, Dershaw DD, Morris EA, Abramson AF, Rosen PP. Percutaneous large-core biopsy of papillary breast lesions. AJR Am J Roentgenol 1999; 172:331–7.[Abstract/Free Full Text]
  12. Liberman L. Clinical management issues in percutaneous core breast biopsy. Radiol Clin N Am 2000; 38(4):791–807.[CrossRef][Medline]
  13. Liberman L. Percutaneous image-guided core breast biopsy. Radiol clin N Am 2002; 40:483–500.[CrossRef][Medline]
  14. Gomez-Aracil V, Mayayo E, Azua J, Arraiza A. Papillary neoplasms of the breast: Clues in fine needle aspiration cytology. Cytopathology 2002; 13:22–30.[CrossRef][Medline]
  15. Gendler LS, Feldman SM, Balassanian R, et al. Association of breast cancer with papillary lesions identified at percutaneous image-guided breast biopsy. Am J Surg 2004; 188:365–70.[CrossRef][Medline]
  16. Valdes EK, Tartter PI, Genelus-Dominique E, Guilbaud DA, Rosenbaum-Smith S, Estabrook A. The significance of papillary lesions at percutaneous breast biopsy. Ann Surg Oncol 2006; 13(4):480–2.[Abstract/Free Full Text]
  17. Jeffrey PB, Ljung BM. Benign and malignant papillary lesions of the breast. A cytomorphologic study. Am J Clin Pathol 1994; 101:500–7.[Medline]
  18. Renshaw AA, Derhagopian RP, Tizol-Blanco DM, Gould EW. Papillomas and atypical papillomas in breast core needle biopsy specimens. Risk of carcinoma in subsequent excision. Am J Clin Pathol 2004; 122:217–21.[CrossRef][Medline]
  19. Hermann G, Mester J, Drossman SR, Jaffer S, Bleiweiss IJ, Feig SA. The role of core biopsy in the evaluation of intraductal papilloma of the breast: Radiologic-pathologic correlation (abstract). Radiology 2002; 225:460.
  20. Berg WA, Berg AP, Ioffe OB. Initial success and frequency of rebiopsy after ultrasound-guided 14-gauge core breast biopsy (abstract). AJR Am J Roentgenol 2003; 180:10.
  21. Saddik M, Lai R. CD44s as a surrogate marker for distinguishing intraductal papilloma from papillary carcinoma of the breast. J Clin Pathol 1999; 52:862–4.[Abstract]
  22. Mosunjac MB, Lewis MM, Lawson D, Cohen C. Use of a novel marker, calponin, for myoepithelial cells in fine needle aspirates of papillary breast lesions. Diagn Cytopathol 2000; 23:151–5.[CrossRef][Medline]
  23. Berg WA. Image-guided breast biopsy and management of high-risk lesions. Radiol Clin N Am 2004; 42:935–46.[CrossRef][Medline]
  24. Philpotts LE, Shaheen NA, Jain KS, Carter D, Lee CH. Uncommon high-risk lesions of the breast diagnosed at stereotactic core-needle biopsy: Clinical importance. Radiology 2000; 216:831–7.[Abstract/Free Full Text]
  25. Michael CW, Buschmann B. Can true papillary neoplasms of breast and their mimickers be accurately classified by cytology? Cancer 2002; 96(2):92–100.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
A. R. Skandarajah, L. Field, A. Y. L. Mou, M. Buchanan, J. Evans, S. Hart, and G. B. Mann
Benign Papilloma on Core Biopsy Requires Surgical Excision
Ann. Surg. Oncol., August 1, 2008; 15(8): 2272 - 2277.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Valdes, E. K.
Right arrow Articles by Boolbol, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Valdes, E. K.
Right arrow Articles by Boolbol, S. K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS