Differentiating the round cell tumors (Proceedings)


Differentiating the round cell tumors (Proceedings)

Aug 01, 2008

Round cell tumors are commonly detected as cutaneous or subcutaneous masses. However, the majority of these tumors also appear in other locations. More differentiated tumors have very unique features that help to identify the specific type of neoplasia. However, poorly differentiated round cell tumors can be very difficult to identify even by histopathology and diagnosis often requires phenotypic marking by immunocytochemistry or flow cytometry.

Mast cell tumor

Mast cell neoplasia are common in both dogs and cats. While the distribution varies somewhat between species (e.g. primary splenic mast cell neoplasia is more common in cats while cutaneous mast cell neoplasia is more common in dogs), mast cell tumors have been reported from nearly every site and organs. Cytologic features include the presence of many individualized mast cells. Well differentiated cells have abundant small blue to purple granules that often obscure the nucleus. Poorly differentiated cells can be highly pleomorphic with multiple criteria of malignancy and few to no granules or large granules. Eosinophilic inflammation often present, but is not always seen. Mesenchymal cells (sometimes with granules) may also be seen. Diff Quik may degranulate the granules of some mast cell and any diagnosis of round cell neoplasia using Diff-Quik that doesn't clearly fall into another category should be further examined by staining new slides (counterstaining previously stained slides will not work) with Wright's or Giemsa based stains.


Lymphoma may be localized or part of disseminated disease. Cells may be small to large but are uniform in appearance (vs. heterogeneous suggesting lymphoid hyperplasia or inflammation). Nuclei may be round, indented or highly convoluted, the latter being a feature of epitheliotropic lymphomas and Sezary syndrome. However, other malignant T cells and B cells may also have irregular nuclear borders. Chromatin is often fine, even in smaller to intermediate cells. Nucleoli are often seen, but may be indistinct in appearance. The amount and basophilia of the cytoplasm varies with the stage of the neoplastic lymphocytes.

Small lymphocytes are smaller in size than a neutrophil and have a round nuclei that takes up the majority of the cell. The nuclei contain densely aggregated chromatin forming large chromocenters (condensed chromatin). Nucleoli are not seen. The cytoplasm is scant (sometimes only a very thin rim is visible) and lightly basophilic in color. These are typically called 'mature lymphocytes'. However, early lymphoid progenitor cells, hematopoietic stem cells, certain stages and types of dendritic cells, and other immature precursor cells may have a very similar morphology to 'mature, well-differentiated, small, resting lymphocytes'.

Intermediate to large lymphocytes range in size from slightly larger than small lymphocytes to the size of neutrophils. The nuclei still takes up the majority of the cell, however more abundant cytoplasm is visible in these cells. Often, the nuclei is placed eccentrically within the cytoplasm. The nuclear chromatin is finely clumped to granular. Typically, nucleoli are not seen although strands of loosely clumped nuclear chromatin may be mistaken for nucleoli. The cytoplasm is lightly basophilic in color. Occasionally these cells contain azurophilic granules suggestive of a natural killer (NK) phenotype.

Lymphoblasts are as large as a neutrophil or larger. Size alone does not indicate neoplasia. Very large lymphoblasts (2-4x the size of neutrophils) may be seen in reactive and hyperplastic processes. Lymphoblasts contain round to oval nuclei with fine or stippled chromatin (loosely aggregated chromatin). One or more nucleoli may be visible. The cytoplasm is moderately to deeply basophilic. Occasionally (seen more in cats than dogs) the cytoplasm may contain punctate vacuoles.

Plasma cell neoplasia

Plasmacytomas are more common in dogs than cats and the cutaneous forms have a predilection for the oral cavity, ears, digits, and forelimbs. Extraskeletal multiple myeloma and plasmacytoma may be seen in the spleen, liver, and GI tract. In general, plasma cell neoplasias exfoliate well, however the neoplastic cells may appear as 'pockets' within tissues so obtaining several aspirates from a site may increase the likelihood of a diagnosis. Neoplastic plasma cells range from those that appear similar to mature, well-differentiated plasma cells to those that are barely recognizable as plasma cells. Well-differentiated plasma cells have eccentric nuclei, clumped "cartwheel" chromatin, deeply basophilic cytoplasm with discrete margins that is darker at the margins and paler in the perinuclear zone creating a perinuclear clear zone. Binucleated cells are commonly seen and multinucleated cells may be present. Nuclei with less clumped chromatin may be seen. These cells may be more difficult to identify. Poorly differentiated plasma cells need to be differentiated from amelanotic melanoma, osteosarcoma, and malignant histiocytosis.