Cytopathology Case Presentation #8

Cytopathology Case Presentation #8 Emily E. Volk, MD William Beaumont Hospital, Troy, MI Jonathan H. Hughes, MD Laboratory Medicine Consultants, Las Vegas, Nevada

Clinical History 44 year old woman presents with new onset shortness of breath

Slide 1 Pleural Effusion 200x magnification

Slide 2 Pleural Effusion 200x magnification

What is your diagnosis?

Diagnosis: Metastatic lobular carcinoma

The diagnosis of metastatic lobular carcinoma in effusion specimens Emily E. Volk, MD and Jonathan H. Hughes MD The illustrations in this presentation represent material collected from the authors as well as submitted material from the College of American Pathologists Non-Gynecologic Cytopathology Program. A common manifestation of metastatic breast cancer is pleural effusions. About 80% are ipsilateral to the primary lesion, while 10% are bilateral. Malignant effusions originating from breast carcinomas have several morphologic presentations that can be identified as one of four major patterns: cannonballs, Indian files, signet ring cells, and mesothelial pattern.

Cannonball pattern Cohesive, closely packed clusters of malignant cells Smooth borders around cell clusters Cells with even, homogenous cytoplasm Large cell clusters of suggestive of ductal rather than lobular carcinoma

Cannonball pattern of adenocarcinoma 200x magnification; Pap stain

Cannonball pattern of adenocarcinoma 400x magnification; Pap stain

Indian file pattern Indian file pattern or long chain pattern of adenocarcinoma is nearly diagnostic of breast origin Small cells in long chains with homogenous cytoplasm and relatively bland nuclei suggest lobular carcinoma Medium to larger cells in shorter chains is more commonly associated with ductal carcinoma Other malignancies that may present with chains of tumor cells within effusions include pancreatic carcinoma, gastric carcinoma, small cell carcinoma of lung, mesothelioma and carcinoid tumors.

Indian-file pattern of adenocarcinoma 400x magnification; Pap stain

Signet ring pattern Malignant cell population that has large cytoplasmic vacuoles Nucleus is compressed to the cell periphery Indentation of the nuclear membrane is characteristic Often associated with isolated tumor cells Differential diagnosis of intracytoplasmic vacuoles includes benign mesothelial cells with degenerative changes. Signet ring pattern adenocarcinoma is highly suggestive of breast (lobular carcinoma), and gastric origins. Other malignancies that may present with this pattern in pleural effusions include lymphoma, melanoma, sarcoma and mesothelioma.

Signet-ring pattern of adenocarcinoma 400x magnification; Pap stain

Mesothelial pattern Malignant tumor cells blend imperceptibly with the background benign mesothelial population. Extremely difficult to diagnose, but a relatively common pattern. Helpful diagnostic clues of malignancy include irregularly thickened nuclear membranes, extra Barr bodies, prominent nucleoli, secretory vacuoles or intracytoplasmic lumen. Mucicarmine stain may be helpful to discern nature of vacuoles as the excretion of epithelial mucin indicates malignancy.

Mesothelial pattern of adenocarcinoma 400x magnification; Pap stain

Most common sites of origin of malignant effusions 80% of malignant cells in effusions are adenocarcinomas or lymphomas Most common sites of origin of adenocarcinoma: Breast-25% Lung-23% Ovaries-17% Stomach-8% Other-27% Ovaries and stomach: usually ascites Breast and lung: usually pleural effusions

Immunocytochemistry The use of Ber-EP4, B72.3 and CEA to identify antigens native to adenocarcinoma cells and not found in mesothelial cells often assists in diagnosing difficult cases. The use of leukocyte common antigen and Ki-1 to identify antigens native to malignant lymphoma cells and not found in adenocarcinoma cells may also be useful.

Immunocytochemistry Cell block material can be very useful EMA positivity in metastatic adenocarcinoma in pleural fluid

References 1. Demay RM. The Art and Science of Cytopathology, Volume 1. ASCP Press, Chicago, p.272-273. 2. Johnston WW. The malignant pleural effusion. A review of cytopathologic diagnoses of 585 specimens from 472 consecutive patients. Cancer. 56; 1985: 905-909. 3. Bailey ME, Brown RW, Mody DR, Cagle P, and Ramzy I. Ber-EP4 for differentiating adenocarcinoma from reactive and neoplastic mesothelial cells in serous effusions. Comparison with CEA, B72.3 and Leu-M1. Acta Cytol. 40; 1996: 1212-1216. 4. Murphy WM, Ng APB. Determination of primary site by examination of cancer cells in body fluids. Am J Clin Pathol. 58; 1972: 479-488. 5. Zakowski MF, Feiner H, Finfer M, Thomas P, Wollner N, Flippa DA. Cytology of extranodal Ki-1 anaplastic large cell lymphoma. Diagn Cytopathol. 14; 1996: 155-161.