Case #2 2026

Interpretation

Blood smear: Regenerative anemia with an inflammatory leukogram and likely iron deficiency

Pyloroduodenal mass: Malignant tumor with inflammation and hemorrhage; presumptive hemangiosarcoma

Explanation

Blood smear: There are moderate to many polychromatophils, a subpopulation of hypochromic mature red blood cells and a few ovalocytes (Figures 1-2, Question 1). The moderate to many polychromatophils are consistent with the strongly regenerative anemia based on the high absolute reticulocyte count from the hematology analyzer. The high MCV and low MCHC, with a high red blood cell distribution width can be attributed to the regenerative response, with alterations to bone marrow sinusoids, potentially from hypoxic injury, causing release of nucleated red blood cells. There was also a subset of mature erythrocytes with increased central pallor, supporting iron-restricted erythropoiesis, likely from iron deficiency. The latter may be contributing to the low MCHC. Polychromatophils were also hypochromic, however this could be due to their leptocytic nature (increased surface area to volume ratio) versus iron-restricted erythropoiesis. Iron-restricted erythropoiesis was supported on our automated hematology analyzer results, which showed a subpopulation of normocytic hypochromic red blood cells on the scatter plots and a high percentage of mature red blood cells showing low cellular hemoglobin concentration (CH) (18%, normal < 10%). The most common cause of iron deficiency in adult animals is chronic external blood loss and, in this case, blood loss (the mechanism of the anemia, Question 2) is likely occurring into the gastrointestinal tract from the intestinal tumor identified on cytologic assessment of the mass aspirate. Although the cat was presented with a short duration of disease, cats frequently “hide” chronic illnesses until they reach a tipping point, when they show clinical signs. Given the tumor in the intestine, chronic gastrointestinal hemorrhage was considered likely. A hemorrhagic or blood loss anemia and concurrent iron deficiency are supported by the panhypoproteinemia and low iron and percentage iron saturation, respectively, on the serum biochemical panel. The ovalocytes could be secondary to liver injury, based on the high transaminase activities (ALT, AST) with normal CK activity on the biochemical panel. The liver injury can be attributed to hypoxia given the severe anemia (which is likely worse than indicated, as is the panhypoproteinemia, because the cat was clinically dehydrated at the time the blood was sampled), although metastases of the intestinal tumor is also possible. There was also a concurrent inflammatory leukogram, based on the increased band neutrophil and monocyte counts and presence of mild toxic change in neutrophils (not obvious in the images). Inflammation may be contributing to the low iron and percentage iron saturation on the biochemistry panel. The low sodium and chloride concentrations can be attributed to blood or fluid losses into the intestinal tract, associated with the tumor. Hypokalemia could be secondary to vomiting and hyporexia, although other mechanisms could be operative in this cat. Despite the hyperlactatemia documented on point-of-care testing, the bicarbonate concentration and anion gap are only trending down and up, respectively, and are not outside established reference intervals, reflecting the insensitivity of population-based reference intervals for detecting underlying pathologic disturbances. The hypocalcemia can be attributed to the hypoalbuminemia.

Intestinal mass aspirate: One of the submitted smears was highly cellular and consisted of numerous disorganized aggregates of medium to large round to oval to spindled cells in a bloody background. Although the cells appeared somewhat cohesive, red blood cells were intercalated between the aggregates of cells, arguing against true cohesion. The cells had eccentric round to indented nuclei with finely stippled chromatin and 1-3 nucleoli, some of which were large and abnormally shaped. Binucleated cells were evident. The cells had a moderate to large amount of medium to dark blue cytoplasm, which contained variable numbers of clear discrete margined vacuoles, often at one edge of the cell. The cells displayed moderate to marked anisokaryosis and anisocytosis and mitotic figures were noted (Figures 3-5). Erythrocytes were also seen within the cells (xenocannibalistic behavior, presumptive). Individual tumor cells were undergoing cell death and necrotic cellular debris was evident in the background. Inflammatory cells were judged increased and were mostly neutrophils, which were also undergoing cell death, with fewer macrophages, including erythrophagocytic and hemosiderin-containing forms, and low numbers of small lymphocytes. Moderate numbers of differentiating erythroid precursors were also seen. (Note that all of these described features were not evident in the provided figures.) The cytologic diagnosis was a malignant tumor and based on the pattern of arrangement, with tumor cells separated by red blood cells and presence of erythroid precursors (not attributable to the metarubricytosis in blood), a hemangiosarcoma was the top differential diagnosis for tumor type (Question 3).

Outcome

Based on the cytologic results and age of the cat, humane euthanasia was selected by the owner.  A post-mortem examination was not done and the tumor type was not confirmed.

Discussion

Hemangiosarcoma is a tumor of vascular endothelial cells that is thought to arise from a hematopoietic-endothelial progenitor.¹ It is an uncommon tumor in cats, comprising 10% of 189 non-hematopoietic neoplasms identified in necropsied cats.² in one study, 77% of 53 cases of hemangiosarcoma occurred in the skin or subcutaneous tissues of the head, trunk or limbs.² Other reported sites are abdominal organs (liver, spleen, kidney), with rare tumors in the gastrointestinal tract, mesentery, lungs, mediastinum, brain and other sites.^2–7 Cutaneous and visceral tumors can occur concurrently in individual cats.⁴ Within the gastrointestinal tract, hemangiosarcoma has been identified in the rectum,⁵ small and large intestine^2,4,5 with intestinal tumors comprising 16 (62%; split between small and large intestine) of 26 cases⁴ and four (26%) of 13 cases⁷ in two studies of hemangiosarcoma affecting the viscera of cats.  

In a four-case series of intestinal hemangiosarcoma, cats displayed non-specific climical signs of weight loss, lethargy, and anorexia or hyporexia as in the report herein.  In one case, the tumor protruded from the rectum.⁵ Cats can have palpable abdominal masses and imaging can locate the lesions in the intestine.⁵ The tumors can cause partial obstruction of the lumen⁵ or result in hemorrhagic or transudative effusions.^4,8 The tumor is typically considered highly aggressive and frequently metastasizes, particularly those arising in internal organs.^4,6,7 The median survival time was 77 days in one study of visceral hemangiosarcoma.⁴ Cats are frequently humanely euthanized upon diagnosis, as in this case, or during surgical exploration.^4,5 However, long survival times (more than a year) can be seen in cats with tumors restricted to the cutaneous tissues, including the nasal planum, after palliative radiation therapy or combination treatment with surgical removal and radiation.^2,4,9

Tumor classification in previous cases of intestinal hemangiosarcoma has relied on histologic evaluation of resected tissue.^4,5,8 The tumor cells vary in shape from round to oval to spindled and classically form erythrocyte-containing vascular channels, allowing for tumor identification. Staining for the endothelial-related antigens, von Willebrand factor or CD31 (platelet-endothelial cell adhesion molecule), can be used to verify the histologic diagnosis of hemangiosarcoma and differentiate it from other neoplasms forming vascular channels, such as telangiectatic osteosarcoma and lymphangiosarcoma (positive for PROX-1).^5,10–12 There are epithelioid variants of hemangiosarcoma,¹³ which have not been described in cats to date. These variants mimic carcinomas on histologic examination, consisting of tubules, micropapillae, solid sheets, and ductular- or glandular-like clusters of polygonal to epithelioid cells, but a few vascular formations and classic knob-like projections into the lumen (so-called “hobnail-like” arrangements) are seen.¹³ Positive immunostaining for endothelial-related antigens is required for diagnosis, because 43% of these epithelioid variants concurrently expressed cytokeratin AE1/3 in one study of 30 cases in dogs.¹⁴

On cytologic examination of tissue aspirate smears, hemangiosarcomas typically consist of variably sized aggregates of spindled to stellate cells, showing prominent cytologic criteria of malignancy, such as marked anisokaryosis and macronuclei.¹⁵ They have a low to moderate nuclear to cytoplasmic ratio and contain variable numbers of discrete margined vacuoles,¹⁵ which are also seen in histologic specimens.¹³ Other cytologic findings that have been described in association with hemangiosarcoma are extracellular and intracellular matrix, signet ring-like cells with intracellular material (presumably matrix), extramedullary hematopoiesis, erythrophagia or xenocannabilism of erythrocytes, hemosiderin- and erythrocyte-containing macrophages (indicating concurrent hemorrhage, as seen in this case), and increased numbers of neutrophils (and rarely eosinophils), which may be due to margination.^15–18 Erythrocytes are also seen in single vacuoles within the cells on histologic assessment¹³  and similar cells were also seen in the aspirate from the cat in this report. Features supporting a presumptive diagnosis of hemangiosarcoma in this case were the aggregates of distinctly spindled tumor cells with intercalated erythrocytes, the medium to dark blue cytoplasm with microvesiculation, apparent xenocannabilism of erythrocytes, and evidence of erythropoiesis. However, the tumor shows substantial cytologic variability with bland spindled variants being seen in the skin (personal observations) and epithelioid forms, consisting of round to oval cells in cohesive-appearing and even acinar-like arrangements (which can surround matrix).^15,16 In sections of the cellular smear from this case, the tumor was forming sheets of mostly round tumor cells, which did mimic a carcinoma (the latter tumor would have been the top differential diagnosis for the intestinal mass). However, the spindled cells and lack of true cohesion favored a sarcoma. Unfortunately, histologic assessment of the tumor was not performed to confirm the presumptive hemangiosarcoma diagnosis in this case.

Author: T. Stokol

References

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