FirstCyte Ductal Lavage History: 68 Year Old Female Gail Index: Unknown Clinical History: Negative Mammogram in 1995 6 yrs. later presents with bloody nipple discharge Subsequent suspicious mammogram Suspicious ultrasound Negative ductogram Negative core biopsy Ductal lavage and excisional biopsy of duct at same time Specimen type: Ductal Lavage Case provided by an independent physician who wishes to remain anonymous. *The images and diagnosis for this case study were provided to Cytyc by an independent physician. All conclusions and opinions on the diagnosis of this case are those of the physician and not Cytyc Corporation. Slide 1-20x
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Slide 6-20x Discussion: Slide 1: Multilayered papillary cell groups with monomorphic enlarged nuclei (12-16um), and nuclear overlap. Slide 2: Small 3D papillary cluster that is more than 2 cell layers thick and showing anisonucleosis. Slide 3: A cell group with slight irregularly distributed coarse chromatin granules, mild nuclear membrane irregularity, moderately sized nucleoli, and anisonucleosis on one end. Hemosiderin-laden macrophages (a worrisome background feature) are seen on either side of the cell group. Slide 4: Cells with enlarged nuclei wrapped around a piece of microcalcification. The cell group to the left of the microcalcification has monomorphic nuclei. Slide 5: Another microcalcification engulfed by a macrophage. Microcalcifications may be seen in malignant as well as benign breast lesions. Slide 6: Tissue section showing ductal carcinoma in situ in micropapillary formations. Adequacy: Satisfactory for Evaluation* *At least 10 epithelial cells are required for adequacy. Cytologic Diagnosis: Atypical/Marked Changes; Many papillary groups of monomorphic ductal epithelial cells with nuclear enlargement and crowding in a background of hemosiderin-laden macrophages. Consistent with atypical ductal proliferative lesion - cannot exclude low-grade ductal carcinoma in situ. Tissue Diagnosis: Right breast duct: Ductal Carcinoma in Situ, micropapillary and papillary types; Focal atypical lobular hyperplasia; Intraductal Papilloma; Apocrine Metaplasia
Ductal Carcinoma In Situ (DCIS) is divided into 2 main categories: comedo and noncomedo types. Noncomedo type is broken down further into several categories including micropapillary type. The noncomedo types cytologically show small to intermediate monomorphic cells arranged in 3D clusters and single cells. Individual cells show round to oval nuclei and may have nucleoli. Mitotic figures, histiocytes, microcalcifications and focal necrosis may be seen. It is often difficult to differentiate between DCIS and invasive carcinoma. The average decade for a patient with DCIS is in the fifties. It is associated with high risk for developing invasive breast cancer,( 25-50% or 8-10X) and it accounts for 10-20% of mammographically detected breast cancers. Atypical Lobular Hyperplasia (ALH) precedes Lobular Carcinoma In Situ (LCIS) and usually occurs premenopausally. The cytologic features are shared between ALH/LCIS. Small poorly cohesive groups of 10-30 cells and some single cells are seen. The cells are small and uniform with high N/C ratios. The nuclei are slightly hyperchromatic, round to angular, mildly pleomorphic, and have slight irregular nuclear membranes. The cytoplasm may be wispy or well defined and can have intracytoplasmic lumens. Papillary neoplasms are somewhat rare lesions in the breast. The average decade is patients in their forties but there is a wide age range. Benign papilloma is one of the most common causes of an abnormal, particularly bloody, nipple discharge. The cytologic features of benign papilloma may be similar to fibroadenoma except that the stromal component is sparse or absent. 3D papillary clusters, with bland, uniform epithelial cells characterize benign papillomas. Apocrine metaplasia may also be present. There is strong intercellular cohesion however single cells may also be seen. The multiple types of lesions seen in this case makes it a very interesting and difficult case cytologically due to some overlap in morphological criteria. However, a diagnosis of Atypical can be confidently agreed upon when considering the case in its entirety. Over 50 years ago, Dr. George Papanicolaou recognized that the detection of the earliest cellular precursors could be a significant factor in decreasing cervical cancer morbidity. Since then, deaths from cervical cancer have decreased 70%. Similarly, detection of the earliest cellular precursors of breast carcinoma in high risk women could be a significant factor in breast cancer morbidity. Breast cancer is the most common malignancy diagnosed among women in the United States and the 2nd leading cause of cancer death in women. The vast majority of breast cancers arise in the epithelium lining the ductal lobular units. Breast cancer that originates in this one cell layer thick epithelium is believed to result from progressive molecular and morphologic changes. Ductal lavage is a process by which cells representing these precursors to malignancy may be obtained for diagnosis in women that are considered at high risk. High risk is assessed by many factors, close familial history of early onset breast cancer, previous abnormalities, specific genetic mutation in a gene such as BRCA1 or BRCA2, or a high Gail index. The Gail model is used to quantify an individual woman s risk of developing breast cancer. It uses five significant predictors of a woman s lifetime breast cancer risk: current age, age at menarche, number of breast biopsies, age at first live birth, and number of first-degree relatives with breast cancer. References: 1) Demay, Richard. The Art and Science of Cytopathology. 1996:875-876;883-885 2) Breast Ductal Fluid Cytology training manual; published by Pro-Duct Health, Inc. prior to Cytyc acquisition. 3) Cytyc Health Corporation website: www.ductallavage.com 4) In Touch Website: www.intouchlive.com