—  SPECIALTY CONFERENCE  —

Cytopathology

Case 1 - Intracystic Papillary Carcinoma

Andrea E. Dawson
Cleveland Clinic Foundation
Cleveland, Ohio


Click on each slide thumbnail image for an enlarged view
Clinical History:
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)

Cytologic Findings:
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:
Study Case Material Papillary Cancer Papillomas
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, 12 papillomas, 8 s/0 papillary neoplasm – other Increased cellularity, Complex papillae, Mild to moderate nuclear atypia discohesion 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 myoep Didn't compare
Kumar PV 1999 9 cases Similar findings to above  

Histology and Clinical Follow-Up: Can we get any help???

  1. 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.
  2. CD44 – Saddik, et al, 11 papillomas, 10 papillary cancer, IHC.
  3. 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 Papillomas
SMA (Mosunjac) 2/7 weak positive 27/27
Calponin (Mosunjac) 0/7 27/27
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.
Ki67(Saddick) 8% 13%

Discussion:
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 carcinoma.

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.

References:

  1. 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.
  2. 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.
  3. 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-
  4. 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.
  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.
  6. 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.
  7. 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; 123(2);152-6.
  8. 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.
  9. 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.