Myocardial plasma cell tumor with intratumoral amyloidosis in a dog.

A 12-year-old mixed breed dog was evaluated for marked hypercalcemia that was identified during assessment for acute polydipsia and polyuria. Physical examination identified a new grade II/VI left apical systolic murmur. A mass involving the left ventricular posterior wall and left atrium was identified by echocardiography, suggesting neoplastic invasion into the myocardium. The patient was euthanized, and post-mortem cardiac evaluation identified an intramyocardial amyloid-producing plasma cell tumor. Multiple myeloma was suspected but could not be confirmed due to the limited post-mortem evaluation. This case is the first report of myocardial amyloidosis in a dog with a myeloma-related disorder (MRD). Dogs with MRD and myocardial involvement may not exhibit clinical signs that localize to the cardiovascular system; therefore, echocardiography should be considered during the staging process.

MUM1/IRF4 immunolabeling of neoplastic Langerhans histiocytes in a putative case of canine Langerhans cell histiocytosis.

Langerhans cell histiocytosis is a systemic histiocytic proliferative disease with cutaneous manifestations which is well described in human medical literature and has relatively recently been reclassified as a neoplastic disorder. The diagnosis of canine Langerhans cell histiocytosis has been proposed in the veterinary literature to refer to a histiocytic proliferative disease in the dog with clinical and histopathologic features that mirror the human disease. However, reports that invoke this diagnosis are rare and often lack complete diagnostic characterization. This case report presents an extensive diagnostic investigation of a putative case of Langerhans cell histiocytosis in a 3-year-old male castrated Golden Retriever dog, including gross, cytologic, histopathologic, and immunohistochemical findings. Furthermore, we document that canine LCH may have positive immunolabeling for the transcription factor multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4), which is classically used for the diagnosis of canine plasma cell neoplasms.

Multiple myeloma presenting as blepharitis in a horse.

Myeloma-related disorders, including multiple myeloma, extramedullary plasmacytoma, and solid osseous plasmacytoma, are rare in horses. Clinical complaints for myeloma-related disorders are nonspecific, and when present, M-protein location is more variable on protein electrophoresis in horses relative to dogs and cats. Here, we describe a case of a 15-year-old Thoroughbred mare who presented with recurrent blepharitis. Marked hyperglobulinemia was an incidental finding on routine hematologic and biochemical testing. Bone marrow aspiration consisted of >30% plasma cells, and serum protein electrophoresis demonstrated a monoclonal gammopathy in the alpha 2 fraction leading to a diagnosis of multiple myeloma. Immunofixation and radial immunodiffusion confirmed the presence of an IgG M-protein. Based on a restricted peak in the alpha 2 location, the specific M-protein is suspected to be IgG(T), an IgG isotype unique to horses. M-protein migration in horses is variable relative to dogs and cats, yet immunofixation can still be used to identify equine IgG M-protein isotypes. The unique clinical presentation in this case also serves as a reminder to consider neoplasia in horses with unusual or nonspecific clinical signs.

Extramedullary plasmacytoma of the oral cavity metastasising to both kidneys in a dog.

BACKGROUND: Most extramedullary plasmacytomas (EMPs) aresolitary and located in the head and neck region. They may also occur in the visceral parts of the body. OBJECTIVES: Here, we report a case of oral EMP followed by neoplastic plasma cell metastasis to both kidneys in a neutered male Pomeranian. METHODS: Oral plasmacytoma recurred 11 months aftersurgical removal of an oral mass and partial maxillectomy was performed. Eighteen months after partial maxillectomy, neoplastic masses were detected in both kidneys on computed tomography. The dog died 12 months after detection of bilateral kidney neoplasms. The resected neoplastic masses were routinely processed for histopathological observation and immunohistochemistry against pan-cytokeratin, desmin, CD3, and MUM-1. RESULTS: The recurred mass mainly consisted of well-differentiated plasma cells and contained a small portion of aggressive cells with malignant features. Monoclonal gammopathy was not observed on serumelectrophoresis performed to exclude multiple myeloma. The mass was composed of plasma cells with high nuclear pleomorphism and abundant mitotic figures. The neoplasm stained positive for MUM-1 with a more aggressive morphology than in oral EMP. CONCLUSION: Based on serum biomarker and pathological observations, a diagnosis of recurrence and metastasis of oral-to-renal EMP was established. To the best of our knowledge, metastasis of oral EMP into the bilateral kidneys, as described in the current case, has not been previously reported in dogs.

A retrospective study of canine oral extramedullary plasmacytoma over a 15-year period (July 2004-July 2019): Treatment, histologic parameters and clinical outcomes.

A total of 45 cases of canine oral extramedullary plasmacytomas (EMPs) presented to a tertiary referral institution over a 15-year period were examined. Histologic sections of 33 of these cases were examined for histopathologic prognostic indicators. Patients underwent variable treatment including surgical intervention, chemotherapy and/or radiation therapy. Long term survival was observed in the majority of dogs with a median survival time of 973 days (2-4315 days). However, almost 1/3 of dogs had progression of plasma cell disease, including two cases with myeloma-like progression. Histologic characterization of these tumours did not reveal criteria to predict tumour malignancy. However, cases without tumour progression did not exceed 28 mitotic figures in ten 400× fields (2.37 mm2 ). All cases with tumour related death showed at least moderate nuclear atypia. Oral EMPs may represent a local manifestation of systemic plasma cell disease or singular focal neoplasia.

Oral Extramedullary Plasmacytoma Treatment Using a Combination of Marginal Excision and Strontium-90 Therapy in Five Dogs.

Extramedullary plasmacytoma (EMP) is a benign round cell tumor that is most commonly found in cutaneous locations in dogs and occurs less frequently in the oral cavity. They are highly radiosensitive, are distinct from systemic multiple myeloma syndrome and wide surgical excision is typically curative. This report describes five cases of non-invasive oral EMP in dogs treated with a combination of marginal excision and strontium-90 plesiotherapy. All five cases had narrow or incomplete margins on histopathologic evaluation but experienced no recurrence after combination therapy. Plesiotherapy radiation may offer a potential adjunct treatment for non-invasive oral EMP by providing a superficial dose of radiation that complements a less invasive surgical removal. The combination of plesiotherapy and marginal excision may offer an alternative to wide surgical excision for non-invasive oral EMPs.

Diagnosing Multiple Myeloma and Related Disorders.

This review provides current information on myeloma-related disorders, a group of plasma cell or immunoglobulin (Ig) secreting neoplasms including multiple myeloma, extramedullary plasmacytoma (both cutaneous and noncutaneous variants), solitary osseous plasmacytoma, Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, Ig-secretory B-cell lymphoma, plasma cell leukemia, and monoclonal gammopathy of undetermined significance. The diagnostic procedures commonly used to characterize myeloma-related disorders, including cytopathology, histopathology, polymerase chain reaction for antigen receptor rearrangement, flow cytometry, and electrophoretic techniques are outlined and discussed.

A series of heterogeneous lymphoproliferative diseases with CD3 and MUM1 co-expressed in cats and dogs.

Lymphoma diagnosis in dogs and cats is continually evolving as new subtypes and human correlates are being recognized. In humans, T-cell lymphomas with MUM1 expressed and plasma cell neoplasia or B-cell lymphomas with CD3 expressed aberrantly are reported only rarely. We report here a case series of tumors in dogs and cats with CD3 and MUM1 co-expressed as determined by immunocytochemistry or immunohistochemistry. Lineage was assigned for these tumors by 3 board-certified pathologists and a veterinary immunologist based on review of clinical and cellular features and the results of ancillary testing including PCR for antigen receptor rearrangements, flow cytometry, and serum protein electrophoresis with immunofixation. In cats, 7 of 7 tumors, and in dogs, 3 of 6 tumors with CD3 and MUM1 co-expressed had clonal rearrangement of the immunoglobulin gene or serum monoclonal immunoglobulin, consistent with a diagnosis of a plasma cell neoplasia or myeloma-related disorder with CD3 expressed aberrantly. Disease was often disseminated; notably, 3 of 7 feline cases had cutaneous and/or subcutaneous involvement in the tarsal area. In dogs, 3 of 6 cases had a clonal T-cell receptor gamma result and no clonal immunoglobulin gene rearrangement and were diagnosed as a T-cell tumor with MUM1 expressed. The use of multiple testing modalities in our series of tumors with plasma-cell and T-cell antigens in dogs and cats aided in the comprehensive identification of the lymphoproliferative disease subtype.

A clonality assay in canine B cell tumors targeting the immunoglobulin light chain lambda locus.

Clonality assays for antigen receptor rearrangement have been used as adjunct examinations of lymphoproliferative diseases. These assays have been useful for differentiation between inflammation and clonal expansion of lymphocytes. Whereas the immunoglobulin heavy chain (IGH) and immunoglobulin light chain kappa (IGK) loci have been targeted in canine clonality assays previously, the immunoglobulin light chain lambda gene (IGL) locus has not yet been investigated. This study aimed to evaluate the usefulness of clonality assays in dogs using IGL. Canine diffuse large B cell lymphomas (DLBCL), cutaneous plasmacytomas, and pathologically diagnosed lymph nodes without lymphoma, were used in this study. Genomic DNA was extracted from formalin-fixed paraffin embedded sections. Sequences of IGLV and IGLJ were obtained from the ImMunoGeneTics database. Several primers against IGLVs and IGLJs were designed in the regions showing homology, by alignment of the gene segments. Products of polymerase chain reaction were analyzed on a capillary electrophoresis. In total, 20 of 23 cases of DLBCL showed clonality (87.0 %), whereas 8 of 30 cutaneous plasmacytomas were clonal (26.7 %). One of 23 lymph nodes without lymphoma showed clonality, thus the specificity was 95.7 %. These data indicate that the IGL locus could be a target for canine clonality assays and that the sensitivity of IGL-based clonality assays in cutaneous plasmacytomas was lower than that in DLBCL.

Periarticular plasma cell tumors in cats.

This report describes periarticular plasma cell tumors with abundant amyloid in 11 cats. The tarsus was the most commonly affected joint (10/11), and the masses were often circumferential around the tarsal joint, involving the dermis and subcutis. The 2 cases in which synovium was examined had neoplastic cells expanding the synovium. Three of the 5 cases staged radiographically had bony lysis of the affected joint. Cutaneous biopsy specimens often consisted of more amyloid than plasma cells, making the diagnosis difficult on small samples. Follow-up information was available in 7 cases; in those cases, the median survival was 194 days (range 53-671 days). Four cases had confirmed metastases, most often to regional lymph nodes, liver, and spleen. Although canine cutaneous plasma cell tumors are typically benign, those with abundant amyloid surrounding the joints of cats may involve deeper tissues and have a more aggressive behavior. These tumors can be difficult to diagnose due to low cellularity and abundant amyloid.

Renal extramedullary plasmacytoma in a dog.

A 10-year-old, intact male Siberian husky dog was presented for a suspected left renal cyst. Computed tomography (CT) identified a large, left kidney mass with retroperitoneal hemorrhage. A left-sided nephrectomy was performed, and histopathology confirmed a renal plasmacytoma. Perioperative screening for multiple myeloma was negative. The dog was lost to follow-up and was euthanized 11 months after surgery. A necropsy was not performed. To the authors' knowledge, this is the first case of renal extramedullary plasmacytoma in a dog. Key clinical message: This report describes the clinical presentation, and laboratory, diagnostic imaging, and surgery findings of a case of renal extramedullary plasmacytoma in a dog.

Plasmocytome rénal extra-médullaire chez un chien. Un chien husky sibérien mâle intact de 10 ans a été présenté pour un kyste rénal gauche suspecté. La tomodensitométrie a identifié une grande masse rénale gauche avec une hémorragie rétropéritonéale. Une néphrectomie gauche a été réalisée et l'histopathologie a confirmé un plasmocytome rénal. Le dépistage péri-opératoire pour myélome multiple était négatif. Le chien n'a pas eu de suivi et a été euthanasié 11 mois après la chirurgie. Une autopsie n'a pas été réalisée. À la connaissance des auteurs, il s'agit du premier cas de plasmocytome rénal extra-médullaire chez un chien.Message clinique clé :Ce rapport décrit la présentation clinique et les résultats de laboratoire, d'imagerie diagnostique et de chirurgie d'un cas de plasmocytome rénal extra-médullaire chez un chien.(Traduit par Dr Serge Messier).

Gastric Plasmacytoma with Immunoglobulin Lambda Light Chain Deposition in a Dog.

A 12-year-old castrated male Jack Russell Terrier presented with intermittent vomiting. Abdominal ultrasonographic examination detected a thickened stomach wall with a mass measuring approximately 1.5 cm in diameter. Computed tomography revealed a solitary mass measuring approximately 2.1 cm in diameter between the submucosa and muscle layers in the greater curvature the pyloric region of the stomach, and a swelling in the hepatic lymph node. The gastric mass was composed of round neoplastic cells arranged in a diffuse pattern. The neoplastic cells had a round nucleus and a pale abundant cytoplasm. Multinucleated giant cells were often found. Hyalinized eosinophilic material, which did not stain with Congo red and had no affinity for thioflavin T, was also observed. Neoplastic cells were immunopositive for MUM1, CD79a and Ig lambda light chain but negative for CD3, CD20, BLA36, IgG and Ig kappa light chain. Stromal eosinophilic material was positive for Ig lambda light chain. The neoplasm was therefore diagnosed as a gastric plasmacytoma with non-amyloid Ig lambda light chain deposition.

Solitary osseous plasmacytomas in dogs: 13 cases (2004-2019).

OBJECTIVES: To further characterise solitary osseous plasmacytoma in dogs, an extremely rare disease. To describe diagnosis, disease progression and treatment outcomes in dogs with solitary osseous plasmacytoma. MATERIALS AND METHODS: Retrospective review of dogs with solitary osseous plasmacytomas that were diagnosed and treated at a single institution from 2005 to 2019. Kaplan-Meier single group survival analysis was used to estimate median survival time and progression-free interval. RESULTS: Thirteen dogs met the inclusion criteria for the study, and of those, 11 were treated. The median age at diagnosis was 8 years (range 4 to 11). Most solitary osseous plasmacytomas occurred in the vertebrae (n=8). Other sites included the maxilla (n=2), the mandible (n=1), the tibia (n=1) and the carpus (n=1). The median survival time for all dogs with solitary osseous plasmacytoma was 912 days (range 5 to 2179), and the progression-free interval for treated dogs was 310 days (range 22 to 2179). Most dogs were treated with radiation therapy (n=10) with nine of 10 receiving a definitive, daily fractionated protocol and with five of ten having had neoadjuvant surgery. Seven dogs received chemotherapy, which was initiated after progressive disease in five dogs. The median survival time for dogs that completed radiation therapy (n=9) was 1166 days (range 545 to 2179). While five dogs developed lesions at other sites, no dogs progressed to multiple myeloma. CLINICAL SIGNIFICANCE: Canine solitary osseous plasmacytomas can be managed long term with appropriate local therapy. This observation reflects the biologic behaviour observed in humans.

Hypoglobulinemia in a dog with disseminated plasma cell neoplasia: Case report and review of the diagnostic criteria.

This is the first reported case of hypoglobulinemia in a dog with disseminated plasma cell neoplasia. A 6-year-old male intact Rottweiler was referred to the U-Vet Animal Hospital (Werribee, Vic, Australia) for weight loss, hyporexia, lethargy, vomiting, and soft stools. Examination of a buffy coat preparation and splenic and liver aspirates revealed a monomorphic population of plasmacytoid cells, and the same cells comprised approximately 90% of bone marrow samples submitted for cytologic and histologic evaluation. Biochemistry revealed a hypoglobulinemia, and the presence of an M-protein was not supported by serum and urine protein electrophoresis or serum immunofixation. Immunohistochemistry demonstrated strong nuclear labeling for MUM-1.

Chromogenic in situ hybridization for the detection of lambda and kappa immunoglobulin light chains as a potential auxiliary diagnostic technique in canine plasmacytomas.

The heterogeneous morphologic features of canine plasmacytomas (PCTs) can make their differentiation from other round cell tumors challenging. Immunohistochemistry (IHC) for lambda (λ) and kappa (к) immunoglobulin (Ig) light chains is often equivocal because of high background staining. The chromogenic in situ hybridization (CISH) technique for light chains has shown higher sensitivity compared to IHC in human plasma cell tumors. Therefore, we aimed to validate automated CISH for light chains in canine tissues and to evaluate its diagnostic potential in canine PCTs, in conjunction with routinely used IHC markers. CISH for light chains demonstrated a clear signal in plasma cell populations of canine control tissues (lymph nodes, lymphoplasmacytic inflammation) showing a polyclonal pattern with a prevalence of λ-producing cells. CISH detected monotypic light chain expression in 33 of 53 (62%) PCTs, 31 expressing λ and 2 expressing к. CISH was more sensitive than IHC for λ light chain (58% vs. 47%, respectively) and more easily interpretable given the absence of confounding background staining. The absence of CISH staining for both λ and к in a considerable subset of tumors may be the result of lower light chain production by neoplastic cells. Multiple myeloma oncogene 1 (MUM1) was expressed by all but 2 PCTs (96%), which showed λ expression by CISH and IHC. The identification of poorly differentiated canine PCTs requires the assessment of a panel of IHC markers, with the potential support of CISH for Ig light chains.

Outcome Following Curative-Intent Electrochemotherapy for Extramedullary Plasmocytoma in Dogs - Case Reports.

Plasma cell tumors can occur as solitary collections referred as extramedullary plasmocytoma (EMP). The present report describes four cases of EMP treated with a local nonthermal ablative approach. Four dogs were diagnosed with extramedullary plasmocytomas (EMP) in different body regions (oral cavity, digits, and lip). Since surgical excision was declined by the owners (maxillectomy; amputation or lip reconstruction), a curative-intent approach was indicated as solely treatment- electrochemotherapy (ECT). All the patients received ECT under general anesthesia using bleomycin intravenously (15,000 UI/m²) or cisplatin intratumorally (1mg/cm³). All dogs developed transitory ulceration and swelling one-week after procedure that completely healed within 30 days post-ECT. Complete remission was achieved in all cases and lasted for 515 (oral case), 695 (one digit), 90 (another digit case) and 240 (lip) days. These results suggested that ECT promoted remission in EMP cases being a possibility for local control in dogs affected by this disease.

Response and outcome following radiation therapy of macroscopic canine plasma cell tumours.

Thirty dogs with macroscopic plasma cell tumours (PCTs) were treated with radiation therapy (RT). Twelve patients were treated with palliative-intent prescriptions (range, 4-10 Gy/fraction (median, 7 Gy/fraction) for a total dose of 20 to 35 Gy (median total dose 30 Gy). Eighteen patients received definitive-intent prescriptions (range, 3.0-4.2 Gy/fraction (median, 3 Gy/fraction) for a total dose of 42 to 54 Gy (median total dose 48 Gy). Involved sites included the oral cavity, skin, multiple myeloma (MM)-associated lytic bone lesions, bone (solitary osseous plasmacytoma; SOP), nasal cavity, larynx, retrobulbar space, lymph node and rectum. Ninety-five percent of evaluable dogs had a complete (CR; 16/22) or partial response (PR; 5/22). Patients with MM experienced significant analgesia. The median progression-free survival (PFS) was 611 days (range: 36-2001 days). Events in the non-MM cases included in-field progression (5/26, 19%) and disseminated disease (5/26, 19%). The median survival time (MST) for all dogs was 697 days (range: 71-2075 days), and when only non-MM cases were considered, MST was 771 days (range: 71-2075 days). Fourteen patients were alive without disease progression or had died of unrelated causes. Achievement of a PR was associated with an inferior PFS and MST as compared with CR. Palliative-intent RT was associated with inferior MST as compared with definitive-intent RT. RT is a useful therapeutic modality for PCTs and tumour responses are often complete and durable, with protracted survivals. The optimal radiation dose and schedule are yet to be defined.

Spontaneous Regression of a Mandibular Plasmacytoma in a Juvenile Dog: A Case Report.

A 4 mo old female Finnish lapphund presented for further investigation of a swelling of the right rostral mandible. A computed tomography scan showed the swelling to be an expansile and osteolytic mandibular lesion. Histopathology revealed a poorly differentiated, moderately well-demarcated, unencapsulated, highly infiltrative round cell neoplasm, and immunohistochemistry was supportive of a plasmacytoma. Performance of a rostral partial mandibulectomy was initially discussed with the owners, but the lesion improved spontaneously both clinically and on repeated computed tomography scanning before surgery could be performed. It subsequently almost completely resolved 6 mo after diagnosis. Hypotheses for spontaneous regression of the lesion are discussed and the human literature is briefly reviewed.

Plasma cell leukemia with plasmablastic morphology in a dog.

A 5-y-old female Golden Retriever was presented with a 2-wk history of hyporexia, vomiting, diarrhea, lethargy, weight loss, polyuria, and polydipsia. Clinical examination and ultrasonography revealed multiple organ enlargement with gallbladder and kidney nodules suggestive of disseminated neoplasia. Hematologic and biochemical analyses revealed pancytopenia, hypercalcemia, and monoclonal IgA gammopathy suspicious for a plasma cell neoplasm. Bone marrow and blood smear examination revealed neoplastic atypical cells highly suggestive of lymphoid origin. Autopsy confirmed the presence of homogeneous white masses and multifocal pale infiltrates in the spleen, kidney, small intestine, gallbladder, and urinary tract. Histologic features were consistent with a multicentric atypical plasma cell tumor. Tumor cells were negative for CD204, IBA-1, E-cadherin, CD3, CD5, CD79a, CD20, and PAX5, and positive for MUM1, consistent with plasma cell origin. The presence of > 20% of circulating blastic plasma cells was consistent with primary plasma cell leukemia with plasmablastic morphology, a disease rarely described in veterinary medicine.

Improved clonality analysis based on immunoglobulin kappa locus for canine cutaneous plasmacytoma.

Sensitivity of clonality analysis based on immunoglobulin heavy chain (IGH) in canine cutaneous plasmacytoma is lower than that in diffuse large B cell lymphoma (DLBCL) because of somatic hypermutation occurring at the IGH locus. Therefore, this study aimed to improve the sensitivity of clonality analysis for canine cutaneous plasmacytoma. To achieve this, clonality analysis based on the immunoglobulin kappa chain (IGK) locus was established. Sensitivity and specificity were examined in genomic DNA extracted from formalin-fixed paraffin-embedded sections of cutaneous plasmacytomas, DLBCLs, and lymph nodes without lymphoma. Forward primers were designed based on the IGKV genes, and reverse primers were designed based on the IGKJ genes and kappa deleting element (Kde). Analysis using IGKV and IGKJ primers demonstrated clonality in 24 of 29 cutaneous plasmacytomas (82.8%), while analysis with primers for IGKV and Kde showed clonality in 16 of 29 cases (55.2%). In DLBCL, the IGKV and IGKJ primer set yielded clonality in 18 of 23 cases (78.3%), and the IGKV and Kde primer set yielded 9 of 23 cases (39.1%). No clonal results were obtained from 23 lymph nodes without lymphoma. Sensitivity of the IGKV and IGKJ primer set was significantly higher than that of the IGH primers reported previously. Thus, clonality analysis based on the IGK locus can be utilized for canine B cell tumors. In conclusion, clonality testing based on IGH and IGK may be beneficial as an adjunct tool for diagnosis of canine B cell tumors including cutaneous plasmacytoma.