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Original Article |

Are Solitary Breast Papillomas Entirely Benign? FREE

Haim Gutman, MD; Jacob Schachter, MD; Nir Wasserberg, MD; Itzchak Shechtman, MD; Franklin Greiff, MD
[+] Author Affiliations

From the Departments of Surgery (Drs Gutman, Wasserberg, and Greiff), Oncology (Dr Schachter), and Pathology (Dr Shechtman), Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel, and Sackler School of Medicine, Tel Aviv University (Drs Gutman, Schachter, Shechtman, and Greiff), Tel Aviv, Israel.


Arch Surg. 2003;138(12):1330-1333. doi:10.1001/archsurg.138.12.1330.
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Hypothesis  Solitary breast papillomas are potentially malignant and are associated with a higher risk of breast cancer.

Design  Retrospective review of all pathological reports containing breast papilloma (1983-2000) and review of selected specimens.

Setting  Tertiary, referral, university-affiliated medical center.

Participants  Ninety-five women with a breast specimen containing a papilloma or papillomatosis. Patients with overt papillary carcinoma without papilloma were excluded.

Intervention  All histopathological characteristics of the papilloma and the surrounding tissue were noted. The incidence of malignant and other proliferative histopathological findings were analyzed, comparing solitary ductal papilloma cases to multiple papilloma cases. The Fisher exact test and χ2 test were applied for statistical analysis.

Main Outcome Measures  Surgical removal of solitary ductal papillomas should include margins wide enough to secure removal of any proliferative tissue within or around the papilloma and to enable thorough evaluation of the risk for future breast cancer.

Results  Solitary papillomas were associated with breast carcinoma in 7 patients (10%) in this series. An additional 9% (n = 6) presented with invasive or noninvasive carcinoma within the papilloma. Atypical papilloma was noted in 6% of patients (n = 4). The risk of associated malignancy was not significantly different between solitary ductal papilloma and multiple papilloma.

Conclusion  Increased risk of breast cancer is associated with all forms of papilloma.

Figures in this Article

PAPILLOMA IS identified in approximately 1% to 3% of all breast biopsy specimens.1 Despite this relatively low occurrence rate, the significance of papilloma of the breast should not be underestimated. Although papillomas are generally perceived as a benign disorder, diverse findings in the literature have raised the possibility of a considerable potential for malignancy.

There are 2 major variants of papillomas of the breast: solitary ductal papilloma (SDP), which originates in the large ducts and is located centrally beneath the nipple, and multiple intraductal papilloma (MP), which is located in the terminal ducts at the periphery of the breast. Originally, SDP was considered benign and MP was considered to be potentially malignant.2 However, Tavassoli and Norris3 showed that SDP and MP may be a single aspect of the larger clinical picture of atypical ductal hyperplasia (ADH), which is itself a variant of low-grade ductal carcinoma in situ (DCIS). More recently, researchers showed that some forms of both SDP and MP increase the risk of invasive breast cancer.4

To determine whether papillomas are associated with a higher risk of developing breast cancer, we reviewed the pathological reports of all women with a diagnosis of papilloma of the breast in our institution during the past 20 years. We particularly sought those pathological findings that are known to increase the risk of breast cancer.

We reviewed the computerized archives of the Department of Pathology, Rabin Medical Center, Petah Tiqva, Israel, a major tertiary care referral facility, for all breast biopsies conducted from January 1983 to October 2000 in which papilloma was either an isolated or an incidental finding. Overt papillary carcinomas without papillomas were excluded. The pathological reports were then carefully reviewed for morphological and pathological details of the papillary lesion and the surrounding tissue.

We paid special attention to the presence, relation, and location of proliferative and invasive disorders in either the papilloma itself or its close vicinity. The diagnosis of ADH was assigned to any proliferative lesion that fulfilled some but not all criteria for the diagnosis of DCIS. In addition, quantitative criteria were used extensively; a low-grade DCIS limited to a single duct or to a few neighboring ducts in an area of 2 mm or less was considered ADH as well.5 A diagnosis of carcinoma within a papilloma was assigned to carcinoma that arises in papillomas that retain areas of papilloma and that have foci of more cellular proliferation.6 Demonstrative cases are depicted in Figure 1. All specimens defined as carcinoma within papilloma were reviewed, and in any case of doubt, blocks were resectioned, stained, and evaluated.

Place holder to copy figure label and caption

Demonstrative cases of atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and carcinoma within a papilloma. A, Carcinoma in papilloma (left; hematoxylin-eosin, original magnification ×40; right; immunostain smooth muscle actin, original magnification ×100). B, Atypical ductal carcinoma (hematoxylin-eosin, original magnification ×200). C, Low-grade DCIS (hematoxylin-eosin, original magnification ×200).

Graphic Jump Location

The Fisher exact test and χ2 test were used where applicable. P≤.05 was considered statistically significant.

Ninety-five women with a breast specimen containing a papilloma or papillomatosis were identified. Ages ranged from 29 to 82 years (median age, 56 years). Twenty-six patients were younger than 50 years, and the rest were nearly equally divided in each of the sixth to ninth decades. Indications for surgery were as follows.

Solitary ductal papilloma was diagnosed in 68 patients (72%). In 6 of them (9%), the papilloma was contained within a single cyst. Multiple intraductal papilloma was found in 27 patients (28%).

Papillomas (either SDP or MP) were associated with benign, hyperplastic, atypical, and carcinomatous histologic features (Table 1, Figure 1). Invasive carcinoma was detected in 7 patients (10%) with SDP. In 6 of them, the tumor was located close to the papilloma, and in 1, it was in the other breast. Another 6 patients (9%) had an invasive or noninvasive carcinoma that originated within the papilloma. Four solitary papillomas were defined as atypical. In 2, atypical papilloma was the only finding, 1 was a part of a DCIS specimen, and 1 was part of an invasive carcinoma. In the MP group, invasive carcinoma was found in 5 patients (18%); 3 of the lesions were papillary and 2 were ductal.

Table Graphic Jump LocationAssociated Pathological Findings by Type of Papilloma

Purcell and Norris7 claimed that ADH is a point in time when proliferating hyperplastic mammary epithelium begins to acquire histological and biological characteristics of DCIS. Therefore, its presence increases the risk of future development of invasive breast cancer by 4- to 5-fold. Accordingly, Tavassoli and Norris,3 in their characterization of the histological changes in papilloma, defined lesions smaller than 3 mm as ADH and atypia larger than 3 mm as small DCIS. In 1985, Page et al8 and Dupont and Page9 showed that some proliferative disorders of the breast, including SDP, increase the risk of breast cancer by 2-fold. In a more recent study,4 the same group demonstrated a 4-fold risk of invasive carcinoma in women with atypical SDP either in the papilloma itself or in the neighboring tissue. In patients without atypia, the risk remained relatively low. Ciatto et al10 followed up 339 women with benign intraductal papillomas of the breast for an average of 6.6 years. Invasive breast cancer developed in 10 patients, which was more than expected on the basis of age-specific incidence rates. There were no differences in the rate of invasive breast cancer between women with SDP and those with MP.

In our series, as in others, intraductal papillomas seemed to be associated with other proliferative breast pathological features in 44% to 63% of cases. The pattern of association, however, differed somewhat between SDP and MP. Multiple intraductal papilloma was more frequently found in close vicinity to other proliferative disorders (or vice versa), but no malignant changes were detected in the papilloma itself. By contrast, SDP presented with neoplastic changes within the papilloma in 6 cases and with atypia in an additional 4. There were no statistically significant differences in the frequencies of the various proliferative disorders between SDP and MP.

These findings indicate that both MP and SDP are part of the spectrum of proliferative breast disorders and may be considered markers of higher risk. Patients with MP more frequently have associated histological features that predict an increased risk. In addition, SDP itself carries a potential for malignant transformation. There is also a group of patients in whom either SDP or MP is associated with only fibrocystic changes or benign hyperplasia and no atypia. This group is probably not at higher risk of developing cancer.

Our data and those of Page et al8 and Dupont and Page9 differ from those of Haagensen,11 who approached SDP as a basically benign breast disease that requires minimal excision limited to the affected duct and MP as a potentially malignant entity that requires close follow-up. Of a series of 172 patients with SDP followed up for an average of 15 years, Haagensen12 found only 8 patients who developed carcinoma of the breast (5 in the opposite breast and 3 in the same breast) within 6 to 11 years. By contrast, 6 of the 52 patients with MP developed ipsilateral invasive breast cancer after an average of 17 years, a rate 3.7 times higher than expected by life tables.12 Similar findings were also reported by others,1315 including some surgical textbooks.16,17

There are 2 possible explanations for the discrepancies among the earlier and later studies. In the past, patients with large areas of atypia were considered to have either papillary carcinoma or DCIS and were treated with mastectomy.18,19 Furthermore, during the 1970s and 1980s, screening mammograms were not performed as frequently,20 and their resolution was poorer than today. This may have led to underdiagnosis of papilloma, ADH, and DCIS. Accordingly, some of Haagensen's patients might have been a selected group with SDP without atypia within the papilloma or neighboring tissue. These patients are at low risk of invasive cancer, according to our data as well.

The results of the present retrospective, histopathological study are weakened by the absence of clinical follow-up. Nevertheless, the analysis of all the papilloma specimens of a tertiary referral center throughout a 20-year period makes it possible to better define specific subgroups of patients and the cancer risk associated with each, as well as to further characterize papillomatous lesions.

We failed to find any statistically significant differences between MP and SDP with regard to the associated pathological conditions (Table 1). In both cases, the lesions that were associated only with fibrocystic changes or benign hyperplasia seemed to be at lower risk of cancer. This situation was more common for the SDPs (P = .10).

Approximately 35% of the patients with papillomatous lesions presented with concurrent cancer. The distribution of SDPs and MPs within this subgroup was not significantly different. It is noteworthy that ADH occurred more often in patients with MP and malignancy (7/12) than in patients with SDP with malignancy (4/21). Carcinoma within a papilloma was seen only in the patients with SDP.

In conclusion, our data indicate that papilloma of the breast, either solitary ductal or multiple, should be considered a risk factor for breast cancer. The risk is more prominent in the presence of atypical ductal or papillomatous hyperplasia. Solitary ductal papilloma is not an entirely benign entity and may undergo malignant transformation or be associated with atypia in or around it. Thus, surgeons must be careful to obtain a large enough sample of tissue around a papilloma or duct to eradicate the lesion and to estimate the risk in the individual patient of the presence or future development of invasive breast cancer. Close postbiopsy follow-up should be recommended.

Corresponding author: Haim Gutman, MD, Department of Surgery B, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel (e-mail: hgutman@post.tau.ac.il).

Accepted for publication May 3, 2002.

Liberman  LBracero  NVuolo  MA  et al.  Percutaneous large core biopsy of papillary breast lesions. AJR Am J Roentgenol. 1999;172331- 337
PubMed
Kraus  FTNeubecker  RD The differential diagnosis of papillary tumours of the breast. Cancer. 1962;15444- 455
Tavassoli  FANorris  TJ A comparison of the results of long term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast. Cancer. 1990;65518- 529
PubMed
Page  DLSalhany  KEJensen  RADupont  WD Subsequent breast carcinoma risk after biopsy with atypia in breast papilloma. Cancer. 1996;78258- 266
PubMed
Rosen  PP Ductal hyperplasia. Rosen  PPed.Rosen's Breast Pathology 2nd ed. Baltimore, Md Lippincott Williams & Wilkins2001;213
Rosen  PP Papillary carcinoma. Rosen  PPed.Rosen's Breast Pathology 2nd ed. Baltimore, Md Lippincott Williams & Wilkins2001;391
Purcell  CANorris  HJ Intraductal proliferation of the breast: a review of histologic criteria for atypical intraductal hyperplasia and ductal carcinoma in situ, including apocrine and papillary lesions. Ann Diagn Pathol. 1998;2135- 145
PubMed
Page  DLDupont  WDRogers  LWRados  MS Atypical hyperplastic lesions of the female breast: a long term follow-up study. Cancer. 1985;552698- 2708
PubMed
Dupont  WDPage  DL Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. 1985;312146- 151
PubMed
Ciatto  SAndreoli  CCirillo  A  et al.  The risk of breast cancer subsequent to histologic diagnosis of benign intraductal papilloma follow-up study of 339 cases. Tumori. 1991;7741- 43
PubMed
Haagensen  CD Solitary intraductal papilloma. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;138- 175
Haagensen  CD Multiple intraductal papilloma. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;176- 191
Carter  D Intraductal papillary tumors of the breast: a study of 78 cases. Cancer. 1977;391689- 1692
PubMed
Murad  TMSwaid  SPrichett  P Malignant and benign papillary lesions of the breast. Hum Pathol. 1977;8379- 390
PubMed
Ohuchi  NAbe  RKasai  M Possible cancerous changes of intraductal papillomas of the breast: a 3-D reconstruction study of 25 cases. Cancer. 1984;54605- 611
PubMed
Iglehart  DJKaelin  CM Diseases of the breast. Townsend  CMBeauchamp  DREvers  MBMattox  KLeds.Sabiston Textbook of Surgery. 16th ed. Philadelphia, Pa WB Saunders Co2001;555- 590
Greenall  MJ Benign conditions of the breast. Morris  PJMalt  RAeds.Oxford Text Book of Surgery, 1994. Oxford, England Oxford University Press1994;789- 808
Haagensen  CD Papillary breast carcinoma. Haagensen  CDed.Disease of the Breast. 3rd ed. Philadelphia, Pa WB Saunders Co1986;729- 757
Haagensen  CD Intraductal breast carcinoma. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;782- 789
Asch  THaagensen  CD Mammography. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;577- 605

Figures

Place holder to copy figure label and caption

Demonstrative cases of atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and carcinoma within a papilloma. A, Carcinoma in papilloma (left; hematoxylin-eosin, original magnification ×40; right; immunostain smooth muscle actin, original magnification ×100). B, Atypical ductal carcinoma (hematoxylin-eosin, original magnification ×200). C, Low-grade DCIS (hematoxylin-eosin, original magnification ×200).

Graphic Jump Location

References

Liberman  LBracero  NVuolo  MA  et al.  Percutaneous large core biopsy of papillary breast lesions. AJR Am J Roentgenol. 1999;172331- 337
PubMed
Kraus  FTNeubecker  RD The differential diagnosis of papillary tumours of the breast. Cancer. 1962;15444- 455
Tavassoli  FANorris  TJ A comparison of the results of long term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast. Cancer. 1990;65518- 529
PubMed
Page  DLSalhany  KEJensen  RADupont  WD Subsequent breast carcinoma risk after biopsy with atypia in breast papilloma. Cancer. 1996;78258- 266
PubMed
Rosen  PP Ductal hyperplasia. Rosen  PPed.Rosen's Breast Pathology 2nd ed. Baltimore, Md Lippincott Williams & Wilkins2001;213
Rosen  PP Papillary carcinoma. Rosen  PPed.Rosen's Breast Pathology 2nd ed. Baltimore, Md Lippincott Williams & Wilkins2001;391
Purcell  CANorris  HJ Intraductal proliferation of the breast: a review of histologic criteria for atypical intraductal hyperplasia and ductal carcinoma in situ, including apocrine and papillary lesions. Ann Diagn Pathol. 1998;2135- 145
PubMed
Page  DLDupont  WDRogers  LWRados  MS Atypical hyperplastic lesions of the female breast: a long term follow-up study. Cancer. 1985;552698- 2708
PubMed
Dupont  WDPage  DL Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. 1985;312146- 151
PubMed
Ciatto  SAndreoli  CCirillo  A  et al.  The risk of breast cancer subsequent to histologic diagnosis of benign intraductal papilloma follow-up study of 339 cases. Tumori. 1991;7741- 43
PubMed
Haagensen  CD Solitary intraductal papilloma. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;138- 175
Haagensen  CD Multiple intraductal papilloma. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;176- 191
Carter  D Intraductal papillary tumors of the breast: a study of 78 cases. Cancer. 1977;391689- 1692
PubMed
Murad  TMSwaid  SPrichett  P Malignant and benign papillary lesions of the breast. Hum Pathol. 1977;8379- 390
PubMed
Ohuchi  NAbe  RKasai  M Possible cancerous changes of intraductal papillomas of the breast: a 3-D reconstruction study of 25 cases. Cancer. 1984;54605- 611
PubMed
Iglehart  DJKaelin  CM Diseases of the breast. Townsend  CMBeauchamp  DREvers  MBMattox  KLeds.Sabiston Textbook of Surgery. 16th ed. Philadelphia, Pa WB Saunders Co2001;555- 590
Greenall  MJ Benign conditions of the breast. Morris  PJMalt  RAeds.Oxford Text Book of Surgery, 1994. Oxford, England Oxford University Press1994;789- 808
Haagensen  CD Papillary breast carcinoma. Haagensen  CDed.Disease of the Breast. 3rd ed. Philadelphia, Pa WB Saunders Co1986;729- 757
Haagensen  CD Intraductal breast carcinoma. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;782- 789
Asch  THaagensen  CD Mammography. Haagensen  CDed.Disease of the Breast 3rd ed. Philadelphia, Pa WB Saunders Co1986;577- 605

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