Cytopathology Case Presentation #8

Emily E. Volk, MDWilliam Beaumont Hospital, Troy, MI

Jonathan H. Hughes, MDLaboratory Medicine Consultants, Las Vegas, Nevada

Clinical History

• 44 year old woman presents with new onset shortness of breath

Slide 1Pleural Effusion

200x magnification

Slide 2Pleural 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 adenocarcinoma200x magnification; Pap stain

Cannonball pattern of adenocarcinoma400x 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 adenocarcinoma400x 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 adenocarcinoma400x 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, secretoryvacuoles or intracytoplasmic lumen.

• Mucicarmine stain may be helpful to discern nature of vacuoles as the excretion of epithelial mucin indicates malignancy.

Mesothelial pattern of adenocarcinoma400x 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 ascitesBreast and lung: usually pleural effusions

Immunocytochemistry

• The use of Ber-EP4, B72.3 and CEA to identify antigens native to adenocarcinomacells 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 cytopathologicdiagnoses 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 mesothelialcells in serous effusions. Comparison with CEA, B72.3 and Leu-M1. ActaCytol. 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. DiagnCytopathol. 14; 1996: 155-161.