A splenic mast cell tumor in an 11-year old Siamese cat: Clinical pathology perspective
Dr. Lisa Viesselmann provides the clinical pathology perspective on this challenging oncology case.
Dr. Lisa ViesselmannSplenic mast cell tumors can often be readily diagnosed via evaluation of a high-quality, highly cellular fine-needle aspirate or impression smear of splenic tissue. Normal feline splenic tissue is composed of a heterogeneous population of cells, including a mixture of lymphoid cells (in similar proportions to a normal lymph node), aggregates of stromal tissue (myofibroblasts, fibrohistiocytes and reticular fibers), and occasional hematopoietic cells (erythroid, myeloid and megakaryocytic). Rare individual mast cells may be found in association with splenic stroma in healthy dogs and cats.1 Since the spleen functions in blood storage and filtration, aspirates from the spleen also often contain large amounts of blood, although this can be minimized with the use of a nonaspiration sampling technique.2
In contrast to the heterogeneous appearance of a normal splenic aspirate, splenic mast cell neoplasia is characterized by a large, nearly pure population of highly granulated mast cells that typically comprise the predominant nucleated cell population (Figure 1).2
Figure 1. A representative high-power (500x) field from a splenic aspirate from the cat in this case (methanolic Wright's stain). Mast cells, most of which are highly granulated, make up the predominant nucleated cell population. An occasional plasma cell (long arrow) and small lymphocyte (short arrow) are also seen, although no splenic stromal tissue was present.
The presence of other normal splenic components such as stromal aggregates depends on the degree of neoplastic involvement of the organ (infiltration of the tissue vs. effacement of all normal architecture), assuming that the cytologic sample is of adequate cellularity. In the case of a splenic mast cell tumor, the mast cells will not only be found individually in association with splenic stroma, but also individually and in aggregates throughout the background of the smear (Figure 2).
Figure 2. The splenic aspirate from the patient in this case contained several aggregates of mast cells, such as the one shown here that resembles a cluster of grapes (500x, methanolic Wright's stain). Normal or reactive tissue mast cells tend to be present as scattered, individual cells, and finding aggregates helps to establish the diagnosis of a neoplastic population.
Neoplastic mast cells in the spleen are often moderately to highly granular, but mild variability in the degree of cytoplasmic granulation may be seen, as well as mild to moderate anisocytosis and anisokaryosis, and variability in the nuclear to cytoplasmic ratio (Figure 3).3
Figure 3. Neoplastic mast cells in the splenic aspirate from this patient exhibited mild anisocytosis and anisokaryosis (500x, methanolic Wright's stain). The long arrows indicate two cells with similar nuclear diameters, but different nuclear to cytoplasmic ratios. These cells also exhibit variable cytoplasmic granulation. Note that mast cell granules may not take up aqueous Romanowsky stains as well as they do methanolic stain, which may result in the mast cells appearing poorly granular or possibly unidentifiable as mast cells. There were occasional hematopoietic precursor cells present in this cat's spleen, such as the rubricyte in the lower left corner (short arrow).
Neoplastic mast cells in the spleen may occasionally exhibit erythrophagia, or phagocytosis of mature red blood cells, and in some cases more than 10% of the neoplastic cells may display this feature (Figure 4).2,4 Although erythrophagia is seen in other types of neoplasia, it is not seen in normal mast cells, and this process may contribute to the anemia that is commonly seen in cats with splenic mast cell tumors.5
Figure 4. Occasional mast cells in the splenic aspirate from this cat exhibited erythrophagia (1000x, methanolic Wright's stain).
Detection of mast cell tumor metastasis to distant organs such as the liver and internal lymph nodes is possible cytologically and relies on the same criteria used to diagnose the primary splenic tumor. When a liver or lymph node aspirate contains a monomorphic population of mast cells, metastasis can easily be diagnosed. However, since these tissues can contain occasional mast cells in healthy animals and in animals with nonneoplastic inflammatory disease, it can be difficult to interpret the finding of low numbers of individual mast cells.6 Based on studies involving staging of dogs with cutaneous mast cell tumors, cytologists usually rely on finding multiple aggregates of mast cells to indicate an increased probability of metastasis.7 Pleomorphic features such as marked anisokaryosis, anisocytosis and a high proportion of variably or poorly granular cells are considered atypical and more suggestive of a poorly differentiated malignant tumor8; however, there is no established cytologic (or histopathologic) grading scheme for feline mast cell tumors in any anatomic location.
Detection of mast cells in the peripheral blood is highly specific for mast cell neoplasia in cats, since, in contrast to dogs, mast cell tumors tend to be the primary condition associated with feline mastocytemia.9 Mastocytemia can be detected on either a direct smear or a buffy coat preparation of peripheral blood. Buffy coat smears are typically used as a screening tool for patients without previously diagnosed mastocytemia, since low numbers of mast cells are more likely to be detected in this concentrated sample. They are also used to monitor disease progression and response to treatment in cats with splenic tumors, as was done in this case (Figure 5).10 Evaluation of a direct blood smear is most useful for quantifying mast cells in cats with known mastocytemia.10
Figure 5. A representative 200x field from a negative buffy coat preparation from this patient (five months after splenectomy; methanolic Wright's stain). A standard blood smear technique was used to create a monolayer of concentrated leukocytes and platelets. One to two buffy coat smears are typically examined in their entirety at this magnification, and potential mast cells are evaluated more closely at higher power. Mast cells are counted on positive buffy coat smears, and the quantity of cells can be monitored over time to assess progression of disease and response to treatment.
In one study, no mast cells were found on buffy coat preparations from 40 cats that were clinically healthy or had non-mast cell tumor related illness,11 while in another study all cats with either cutaneous or visceral mast cell tumors had mast cell-positive buffy coats.9 However, the sensitivity of this method is certainly less than 100%, and a negative buffy coat does not definitively exclude the possibility of mastocytemia.10 Studies defining the prognostic implications of mastocytemia in cats with splenic mast cell tumors are lacking.
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