A 75 year old woman presents with a 9 mm lobulated mass on a
screening mammogram. An ultrasound is performed that shows that the mass is partially cystic. An
ultrasound guided FNA is done and sent to cytology. (Images 1A, 1B)
The distinction between benign and malignant papillary
neoplasms is a well recognized difficult diagnostic area in FNA cytology and surgical pathology. The
difficulty in interpreting the FNA is in part a reflection of the spectrum of histologic findings seen in
benign, atypical and malignant papillary lesions. These lesions include benign intraductal papillomas,
papillomas with foci of atypical or carcinoma in situ, DCIS with a papillary growth pattern(intracystic
papillary carcinoma) and invasive papillary carcinoma.
Figure 1A - This breast FNA is moderately cellular. Large epithelial clusters with papillary architecture are present. Numerous single epithelial cells can be identified with cuboidal to columnar shape. These findings are suggestive of a papillary neoplasm. (Papanicolaou stain, low power)
Figure 1B - A higher power photomicrograph of loosely cohesive clusters of cells shows tall columnar cells with hyperchromatic nuclei. When these cells are identified in an aspirate that has papillary features a papillary carcinoma can be favored. (Papanicolaou stain, high power)
Clinical and Mammographic Findings:
- Can present as a palpable or nonpalpable mass
- Subareolar lesions can present with nipple discharge
- Mammographically – well-circumscribed, lobulated mass, partially cystic or solid
- Ductogram – isolated filling defect
Cytologic Findings of Papillary Neoplasms: Benign vs. Malignant
Several papers have described the cytologic features of papillary breast lesions. These studies are
all small retrospective series that compare the FNA cytology of benign and malignant papillary lesions
and in some studies, other lesions that may mimic papillary lesions are included. In 1994, Dawson and
Mulford compared the cytologic features of 17 benign papillomas to 13 papillary carcinomas. The
papillary carcinomas consisted of 7 intracystic papillary carcinomas and 6 invasive carcinomas. This
study found considerable overlap between benign and malignant papillary lesions. The FNA often was
hypercellular with a papillary architecture that was apparent on low power. Papillary architecture and
three-dimensional cell clusters were present in both benign and malignant lesions. Features seen more
frequently in papillary cancer were increased cellularity, single cells and mild to moderate nuclear
atypia. Hyperchromatic tall columnar cells, both singly and in clusters, were only identified in
papillary carcinomas. Intraductal papillomas tended to have decreased cellularity and single cells.
Apocrine metaplasia was seen only in benign intraductal papillomas. The conclusion of this study was
that papillary neoplasm could be identified. The presence or absence of certain features, for example
tall columnar cells, could allow you to favor a diagnosis of malignant vs. benign.
Since 1994, several other authors have looked at cytologic findings in papillary lesions. These are
summarized in the following Table.
Review of Literature: Comparison of Papillary neoplasms:
Case Material ||
Papillary Cancer ||
Gomez-Aracil, et al 2002 ||
15 papillary cancer,
15 papillomas ||
Increased cellularity, tall columnar cells, hemosiderin macrophages ||
Cohesive stalks with honeycomb sheets, apocrine met, bipolar nuclei |
Michael CW, 2002 ||
10 papillary cancer,
8 s/0 papillary neoplasm – other ||
Mild to moderate nuclear atypia
Apocrine metplasia |
Nayar R, et al 2001 ||
28 s/0 papilllary neoplasm, variety of follow up ||
Hemorrhagic background, 3D papillary clusters, columnar cells, fibro-vascular cores, inconspicuous
Didn't compare |
9 cases ||
Similar findings to above || |
Histology and Clinical Follow-Up: Can we get any help???
- Myoepithelial cells – immunohistochemical studies with smooth muscle actin (SMA) and calponin
(Mosunjac, et al), performed on cell blocks of 40 papillary breast lesions with FNA.
- CD44 – Saddik, et al, 11 papillomas, 10 papillary cancer, IHC.
- Cyclin D1 and Ki67 – Saddik, et al, 8 papillomas, 6 papillary cancers, IHC.
The results of these studies are summarized below.
Immunohistochemical Studies in Papillary Neoplasms:
Papillary Cancer ||
SMA (Mosunjac) ||
2/7 weak positive ||
Calponin (Mosunjac) ||
CD44 (Saddick) ||
8/10- <10% of cells,
2/10- >10 <70% of cells ||
11/11 >70% of cells |
Cyclin D1 (Saddick) ||
8% +/-7% cell positive ||
89% +/-18% cells pos. |
The cytologic diagnosis is: Papillary neoplasm, cannot rule out
intracystic papillary carcinoma.
A core biopsy is performed due to the equivocal FNA diagnosis and the diagnosis in surgical pathology
is: Papillary neoplasm, favor intracystic papillary carcinoma.
The lesion is excised. The histologic diagnosis is Intracystic papillary
The above review I think has demonstrated that we can in fact identify papillary neoplasms with a high
degree of confidence in FNA cytology. The question remains how far can we go in distinguishing between
benign and malignant? Before we throw our hands up and give up on FNA cytology for the evaluation of
these breast lesions, we should be aware of the issues with core biopsy, the other non-invasive method of
evaluating breast lesions. Papillary lesions are also notoriously difficult in the core biopsy and often
times we end up with a diagnosis that is similar to the FNA. So depending on the preference of the
patient, aspirator, institution and clinicians both FNA and core can be useful adjunctive tests. In a
review by Jacobs, et al discussing nonmalignant lesions in breast core needle biopsies, they suggest that
based on limited available data that in patients with benign papilloma on CNB have a small but definite
chance of atypia or malignancy on excision. Obviously, if the CNB or FNA and radiologic findings are
discrepant an excision should be performed. It is probably prudent to recommend excision of the lesion
when a papillary neoplasm is identified by FNA or CNB.
- Gomez-Aracil V, Mayayo E, Azua J, Arraiza A. Papillary Neoplasms of the Breast: Clues in fine needle
aspiration cytology. Cytopathol 2002 Feb 13(1): 22-30.
- Michael CW, Buschman B. Can true papillary neoplasms of the breast and their mimickers be accurately
classified by cytology? Cancer 2002 Apr 25, 96(2):92-100.
- Nayar R, De Frias DV, Bourtsos EP, Sutton V, Bedrossian C. Cytologic differential diagnosis of
papillary pattern: Correlation with histology. Ann Diagn Pathol 2001 Feb; 5(1):34-
- 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 Sept 23 (3):151-5.
- Saddik M, Lai R. CD44 as a surrogate marker for distinguishing intraductal papilloma from papillary
carcinoma of the breast. J Clin Pathol 1999 Nov;52(11):862-4.
- Kumar PV, Taler AR, Malikhusseim SA, Monabati A, Vasei M. Papillary carcinoma of the breast:
Cytologic study of 9 cases. Acta Cytol 1999 Sep-Oct43(5):767-70.
- Saddik M, Lai R, Medeiros L, McCourty A, Brynes RK. Differential expression of cyclin D1 in breast
papillary carcinomas and benign papillomas. An immunohistochemical study. Arch Pathol Lab Med 1999 Feb;
- Jacobs TW, Connolly JL, Schnitt SJ. Nonmalignant lesions in breast core needle biopsies: to excise
or not to excise? Am J Surg Pathol 2002 Sep 26(9):1095-110.
- Dawson AE and Mulford DK: Benign versus malignant papillary neoplasms of the breast. Diagnostic
clues in fine needle aspiration cytology. Acta Cytol 1994 Jan-Feb 38(1):23-8.