Case #2 2025

Interpretation

Plasma cell tumor 

Explanation

The impression smear was highly cellular and consisted of individualized round cells. The cells had eccentric round nuclei with clumped chromatin and moderate amounts of smooth deep blue cytoplasm with a distinct perinuclear clear zone (Figures 1 and 2). Anisocytosis and anisokaryosis were moderate and bi- and multinucleated cells were seen (Figure 2). The cytologic features of the cells were consistent with plasma cells, leading to a diagnosis of plasma cell tumor (Question 1). The tumor could be part of the syndrome of multiple myeloma or a solitary plasmacytoma of bone (SPB, used to be called solitary myeloma of bone).

Additional tests

A section of the mass was submitted for STAT histologic section. The sample was frozen in liquid nitrogen and hematoxylin-&-eosin-stained smears were prepared from the cryosection. The smears contained sheets of round cells, resembling those seen in the impression smear of the mass. The cells were locally infiltrative and extended to all margins of the section (Figures 3-4). The morphologic diagnosis was a plasma cell tumor. To confirm this diagnosis, staining for MUM-1 was performed but was surprisingly negative, since it is considered a marker of plasma cell tumors in dogs and cats (Question 2).^1–4 Additional immunostaining for CD3 (T cells), CD20 (B cells), Pax-5 (B cells), CD45 B220 (näive B cells) and Iba-1 (dendritic cells and monocyte-derived macrophages) showed a positive reaction only for CD20 (Figure 5). CD20 has been reported to be positive in canine and feline plasma cell tumors.^1,2 Taking the morphologic features of the cells together with the case presentation, the immunostaining results were considered to be consistent with a plasma cell tumor.

The cat’s neurologic signs improved after surgery. It was placed on corticosteroid therapy for the tumor and discharged to the care of its owners. The cat was seen monthly by the referring veterinarian, who diagnosed diabetes mellitus, presumably secondary to chronic corticosteroid therapy. The corticosteroid dose was decreased and the cat was brought back by the owners to CUHA for evaluation by the oncologic service 5 months after surgery. Clinical pathologic testing at this time showed a normal hemogram and moderate hyperglycemia (399 mg/dL, reference interval, 71-182 mg/dL) and mildly increased alkaline phosphatase (78 U/L, reference interval, 11-49 U/L) on a biochemical panel. An abdominal ultrasonographic examination showed a moderately diffusely enlarged liver and mild mesenteric lymphadenopathy. The hepatopathy was attributed to the corticosteroid therapy, which may explain the increased alkaline phosphatase activity from hepatocellular swelling. Thoracic radiographs revealed mild cardiomegaly. Overall, the results supported a diagnosis of SPB versus multiple myeloma, which is a multisystemic plasma cell tumor that infiltrates the bone marrow in cats.^5–9 Even though globulin concentrations were not increased, serum was submitted for protein electrophoresis, which revealed a narrow peak in the gamma region on a polyclonal base, suggestive of a monoclonal gammopathy (Figure 6), although a restricted oligoclonal gammopathy (usually due to infectious causes) could not be ruled out. The serum was submitted to Colorado State University for immunofixation, which was interpreted as a monoclonal IgG gammopathy on a polyclonal background (Figure 7). The small size of the monoclonal peak was attributed to the prednisolone therapy.

Outcome

The corticosteroids were tapered and the cat was treated with cyclophosphamide. The cat did well clinically for another 3 months, after which time it developed thrombocytopenia, which required cessation of the chemotherapy. However, 3 months after stopping cyclophosphamide, the ataxia and hindlimb weakness recurred, necessitating re-institution of corticosteroid therapy and initiation of radiation therapy for presumed recurrence of the plasma cell tumor. A splenic aspirate done at this time did not reveal plasma cell tumor infiltrates. At the last recheck (one month after starting radiation therapy and the same month of this report), there was marked improvement in the cat’s neurologic signs. The cat continues to undergo radiation therapy and is also being treated with prednisolone and gabapentin. 

Discussion

Solitary plasmacytoma of bone is a rare form of plasma cell neoplasia consisting of a local accumulation of plasma cells within a single bone. The tumor typically occurs in thoracic followed by lumbar vertebrae in human patients, but the ribs, sternum, scapula, clavicle and skull can also be affected sites.^10,11 Together with extramedullary plasmacytomas, SPB comprise about 5-10% of human cases of plasma cell tumors,¹⁰ also known as myeloma-related disorders in veterinary medicine.^6–9,12 Multiple myeloma followed by extramedullary plasmacytoma are the more common types of plasma cell tumor in cats,^5,7–9 with a single prior report in one cat.¹³ Similar to our case, the tumor was uncovered as a lytic lesion in a thoracic vertebra on imaging  studies of a cat with neurologic signs affecting the thoracic limb.¹³ In a 13-dog case series, vertebrae were the main site for the primary tumor, with tumors also being located in the carpi, tibia, and facial bones (maxilla, mandible).¹⁴ In the case herein, the diagnosis of SPB was made on morphologic features of the cells in cytologic and histologic samples and the lack of tumor involvement in other sites based on clinical pathologic testing (no cytopenias), imaging, and cytologic aspirates of tissues (spleen). In the previously reported case, the tumor was a presumptive diagnosis based on the lytic bone lesion and a concurrent monoclonal gammopathy in serum, with plasma cells comprising <1% of a bone marrow aspirate.¹³ A bone marrow aspirate was not performed in our case to exclude the presence of plasma cell infiltrates, which would favor a diagnosis of multiple myeloma; a lack of clonal plasma cell infiltrates in the bone marrow is required to differentiate SPB from multiple myeloma in human patients.¹⁵ Different cut-offs have been used to support a diagnosis of multiple myeloma based on the percentage of plasma cells in bone marrow aspirates of cats: 1) 10%⁸ or 20%⁵ well-differentiated plasma cells; and 2) 5-10%⁸ or 10%⁵ plasma cells if there is concurrent atypia (e.g. marked anisokaryosis, multinucleation in 5% of cells⁵). Extramedullary plasma cell infiltrates, such as in the liver and spleen, are common in affected cats^5–9 and aspiration of these sites can be helpful for confirming the presence of a plasma cell tumor. However, clonality testing of plasma cell tumors is not routinely done, although one study did show clonally rearranged immunoglobulin receptors in 6/7 cats with extramedullary plasmacytomas and multiple myeloma (with “possible” clonality in the remaining cat).¹⁶

Due to the location within vertebra, SPB is usually inaccessible for aspiration cytology to facilitate a diagnosis. However, a cytologic diagnosis of a plasma cell tumor was obtained in this case via impression smears prepared from the surgically excised tissue. Plasma cells have a characteristic cytologic appearance, including eccentric round nuclei with clumped chromatin and moderate amounts of smooth dark blue cytoplasm with a perinuclear clearing. However, plasma cell tumors may not always have these features and can display marked atypia, making a morphologic diagnosis more difficult.⁶ Immunostaining for MUM-1, a plasma cell marker, was performed on a histologic section of the mass but results were unexpectedly negative. The negative reaction resulted in a larger panel of immunostains being applied, which yielded a positive reaction for CD20, a B cell marker.¹⁷ The immunostaining results highlight the advantage of running panels of immunostains versus a single immunostain that would support a morphologic diagnosis, because tumors can aberrantly drop off expression of a lineage-associated marker or express markers typically associated with other neoplasms. For instance, plasma cell tumors can aberrantly express CD3.¹⁶ In addition, markers are not 100% specific. In dogs, MUM-1 is also expressed on B cell tumors,² T cell tumors,¹⁶ and cutaneous histiocytomas;¹⁸ similar knowledge of MUM-1 specificity is not available in cats. In our hands, MUM-1 has been unreliable in confirming a plasma cell lineage for round cell tumors in cats, but CD20 can be positive in plasma cell tumors in this species, as seen in this case, and in dogs.^1,2 Like MUM-1, CD20 is not specific for B cells, being expressed in T cell tumors in dogs.^19,20 Staining reactions for the B cell marker CD79a can be positive in feline and canine plasma cell tumors,^2,3,6 but CD79a immunolabeling was not done in this case. Pax-5 immunostaining is usually negative in plasma cell tumors in dogs¹ and this antigen was not detected in the case herein nor in a previously reported of an extramedullary plasma cell tumor in a cat.²¹ In the past, plasma cell tumors were confirmed via positive immunohistochemical staining reactions for immunoglobulin heavy and light chains,^6,14 however these immunostains have fallen out of favor and been largely replaced by MUM-1. Considering the variable immunostaining results in feline and canine plasma cell tumors, a panel of stains for B and T cell markers (MUM-1, CD20, Pax-5, CD79a and CD3) taken together with morphologic features of the tumor, should be used to differentiate plasma cell tumors from other round cell neoplasms, as recommended by others¹² (Question 2).

The main differential diagnoses for cats with neurologic signs attributable to a lytic vertebral lesion are osteosarcoma,^22,23 multiple myeloma,^8,24,25 and lymphoma (which is usually extradural and intradural but can invade bone secondarily).^25,26 There are rare reports of a vertebral body chordoma²⁷ and metastatic carcinoma.^25,26 In retrospect, serum protein electrophoresis would have been worthwhile performing in this cat after initial detection of the lytic vertebral mass. The presence of a monoclonal gammopathy would have prioritized multiple myeloma or SPB as the diagnosis for a lytic vertebral lesion, although lymphoma can rarely produce monoclonal immunoglobulins in cats.²⁸ The lack of hyperglobulinemia does not preclude electrophoresis testing as monoclonal proteins can be present in animals with normo- and even hypoglobulinemia, as seen in other cases.^12,13

Cats with plasma cell neoplasms such as multiple myeloma are usually treated with chemotherapy, specifically melphalan combined with corticosteroid therapy.^7–9 The previously reported case of SPB was also treated with these drugs.¹³ Single tumors, such as the one in this case, are also amenable to radiation therapy, which was the selected treatment protocol after cyclophosphamide therapy was discontinued in lieu of thrombocytopenia. In the 13 dogs with SPB (called solitary osseous plasmacytoma by the authors), 10 animals were treated with radiation, with concurrent surgical debulking in 5 dogs. Chemotherapy was given to 7 dogs, particularly after disease progression.¹⁴ The prognosis of SPB in cats is unknown. In our case, the cat was still alive and responding clinically to therapy 16 months after onset of clinical signs. In the previous case report, the cat developed cutaneous plasmacytomas, which may reflect de novo tumors or metastases from the primary tumor, however the tumor in the spinal column and associated neurologic clinical signs did not recur for up to 3 years after diagnosis, when the cat was euthanized due to the cutaneous lesions. In human patients with SPB, relapses are more common and there is a higher probability of progression to multiple myeloma in 5 years (50-60%) compared to extramedullary plasmacytomas in other sites, leading to an overall poorer prognosis.^29,30 In the case series of 13 dogs, median survival time was 912 days, with slightly longer survival in dogs given radiation therapy (median, 1166 days). Dogs were euthanized due to morbidity associated with the primary tumor or unrelated reasons, including development of other neoplasms. None of the dogs developed multiple myeloma, but plasma cell tumors did occur at other sites, including the eye, lung, ribs, and skin. Two dogs developed widespread disease.¹⁴ Overall, these results suggest that animals can live for 3 or more years after initial diagnosis, which is a decent prognosis given their shorter lifespan versus humans.

Author: T Stokol, Katerina Wehe (Class of 2025)

Acknowledgements: The case was the subject of Katerina Wehe’s senior seminar presentation in 2025. Dr. Lopez was the clinical advisor for the seminar. Drs. Shelton and Duhamel examined the histopathologic sections and immunostain and Dr. Miller consulted on the case.

References

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