Anatomic Pathology: Cytopathology

• Metastatic breast carcinoma has a few characteristic patterns in fluid cytology, one of which is depicted in the photomicrograph. This photomicrograph was taken at very low power. Each of the round structures represents a large so-called morule (also called “proliferation sphere”) that also is referred to as a “cannonball” because of this low power appearance.

• Cannonballs are large, tightly cohesive balls of relatively uniform, neoplastic epithelial cells; a high power view of one of the cannonballs in the photomicrograph is shown in the inset photo. Very few single malignant epithelial cells may be present (notice the relatively very small single cells in the background in the photo).

• Although cannonballs are suggestive of breast origin, they also occasionally may be seen in carcinomas from other sites. Malignant fluids from metastatic colorectal carcinomas characteristically contain clusters of obviously malignant cells, and the presence of some cells demonstrating a palisading and/or columnar appearance provides a clue to the diagnosis.

• Small cell carcinoma cells appear as small malignant cells that may be round to spindle-shaped. Cytoplasm is scanty or absent and nuclear chromatin is coarse. Nucleoli may be more evident in fluids than in bronchial specimens. The malignant cells may be single or in small clusters, and nuclear molding is characteristic. Single file arrangements may also be present.

• Malignant lymphoma cells appear singly and nuclear membrane irregularities may be prominent. N/C ratios are often high, with scanty cytoplasm; however, large cell lymphoma cells may display more abundant cytoplasm.

• Massive karyorrhexis in a fluid displaying a single cell pattern of neoplastic cells is highly suggestive of lymphoma. On Diff Quik staining, lymphoglandular bodies, which are small blue fragments of the cytoplasm of lymphoid cells, may be evident.

• Immunocytochemistry and flow cytometry may be helpful in establishing a specific diagnosis. Mesothelioma often produces very large groups containing many neoplastic cells. In addition, single neoplastic cells are present and display a spectrum of cytologic atypia, with cells ranging from benign-appearing mesothelial cells to malignant cells, many of which retain mesothelial features.