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Case Presentation - Winter, 2007

Ductal Carcinoma in-situ with Papillomatosis
ThinPrep® Non-gyn Cytology

NOTE: The diagnosis and analysis for this case study were provided by an independent physician. All conclusions and opinions are those of the physician and not Hologic, Inc.

History: 49 year old female

Specimen type: Right breast FNA

Tumor site: Central nipple duct

ThinPrep® cytologic diagnosis: Clusters of ductal epithelial cells, some with overlapping, crowding and cytologic atypia and some with apocrine features in a background of abundant macrophages. Findings are consistent with a papillary proliferative lesion with cytologic atypia. Further radiologic and clinical evaluation are recommended.

Biopsy diagnosis: Ductal carcinoma in-situ and papillomatosis

Case provided by: Mount Auburn Hospital, Cambridge, Massachusetts

PAPILLOMATOSIS

Discussion
Papillomatosis is a rare benign tumor that is also known as nipple adenoma, florid papillomatosis, subareolar duct papillomatosis, erosive adenomatosis or papillary adenoma. It occurs beneath the nipple and subareolar region of the breast. Papillomatosis is caused by the papillary proliferation of epithelial cells within the lactiferous ducts. It can occur in both men and woman at any age, but usually presents in the fifth decade. Clinically papillomatosis can present with a nipple discharge associated with erosion of the nipple, as well as ulceration and crusting of the nipple. A subareolar nodule may also be present. Clinically, this tumor is sometimes mistaken for Paget's disease. Histologically, papillomatosis can be mistaken for adenocarcinoma. Malignant transformation in papillomatosis is very rare. This tumor coexists with breast carcinoma in 16% of patients.

Cytology
FNA aspirates of papillomatosis are cellular and consist of epithelial cells found singly, in clusters and in papillary clusters with or without vascular cores. Epithelial cells are typically columnar shaped and may be admixed with myoepithelial cells. A moderate amount of cytoplasm is usually seen. Nuclei are typically regular and have a fine chromatin pattern and inconspicuous nucleoli. Anisonucleosis, hyperchromasia, and bare nuclei may also be noted. The background can consist of inflammatory cells, cellular debris, and hemosiderin containing macrophages.

Treatment and Prognosis
Because papillomatosis is not a precancerous lesion, the tumor is usually locally excised. Local recurrence of the tumor has been reported.

DUCTAL CARCINOMA IN SITU
Discussion
Ductal Carcinoma in situ (also referred to as intraductal carcinoma) is the abnormal growth of duct lining cells that remain confined by the basement membrane and do not invade surrounding breast tissue. DCIS is considered a precancerous condition because it is not invasive. DCIS can be subcategorized into either comedo and noncomedo types (or sometimes mixed). Comedo DCIS is the most aggressive and fastest growing type and is the most likely to progress into invasive breast cancer. The term comedo refers to the center of the duct being plugged with dead cells, or necrosis. Noncomedo type DCIS includes solid, micropapillary and cribriform DCIS. DCIS is usually detected by a mammogram and can be confirmed by a breast biopsy or FNA. DCIS is commonly detected in patients in their sixth decade. Approximately 20% of all new breast cancer cases will be ductal carcinoma in situ.

Cytology
FNA aspirates of comedo DCIS are typically highly cellular with loosely cohesive clusters of atypical cells. Individual cell necrosis and mitosis can be seen. High N/C ratios, nuclear membrane abnormalities and pleomorphism, hyperchromasia, chromatin clumping and conspicuous and/or irregularly shaped nucleoli are characteristic of comedo DCIS. The absence of myoepithelial cells is also noted.

Aspirates of noncomedo DCIS can vary in cellularity. The cell population is typically small to medium sized monomorphic epithelial cells seen singly or in loose clusters. Single cells are typically uniform with round to oval nuclei and occasional nucleoli. Minimal nuclear atypia has been noted. Clusters can vary in shape from solid to papillary to cribriform. Myoepithelial cells are typically absent, but a scant amount can be seen in the background along with foamy histiocytes and microcalcified particles. Mitotic figures, as well as single cell necrosis and small areas of necrosis may be seen.

Treatment and Prognosis
Treatment options for DCIS are dependant on the type of DCIS diagnosed (based on mammography and biopsy results). Breast conservation (also known as lumpectomy or breast sparing) is the removal of the abnormal area of the breast along with a margin of normal breast tissue surrounding the DCIS. This option is best when the tumor is not aggressive and very small. Breast conservation along with radiation therapy is another option that reduces the risk of recurrent DCIS. Lastly, for DCIS that has spread widely through the ducts of the breast, a total mastectomy is typically the treatment. Lymph nodes are not usually removed since DCIS is noninvasive. Tamoxifen is used by some patients to lower their risk of developing recurrent DCIS or invasive cancer. Patients with DCIS have a 25-50% risk of developing invasive cancer at a later date. However, studies have shown that patients that receive conservation surgery plus radiation have a 9% chance of developing invasive carcinoma, while patients that receive a mastectomy have a 1.5% chance. DCIS is almost 100% curable if correctly diagnosed and treated, with proper follow up.