Renal extramedullary plasmacytoma in a dog

Abstract

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.

Case description

A 10-year-old, intact male Siberian husky dog weighing 36.5 kg was presented to the VCA Canada Calgary Animal Referral and Emergency (CARE) Centre (Calgary, Alberta), for further evaluation of a suspected left renal cyst. Prior to presentation, the dog had a 3-day history of lethargy, anorexia, polyuria, and polydipsia. Over the last year, his owner had noted that the dog’s energy levels had been steadily declining, and that for the past several months, he had appeared painful when lying down on his left side. He was evaluated by his family veterinarian 1 day before presentation. Physical examination revealed pain on abdominal palpation and a small puncture wound on the dog’s left tarsus. Vital parameters were within normal limits. Complete blood (cell) count (CBC) showed a mild nonregenerative anemia [hematocrit 35.8%; reference range (RR): 37.3 to 61.7%] but was otherwise within normal limits. A serum biochemistry panel was unremarkable, including normal blood urea nitrogen (4.8 mmol/L; RR: 2.5 to 9.6 mmol/L) and creatinine (77 μmol/L; RR: 44 to 159 μmol/L). Abdominal radiographs showed a mass effect in the left dorsal abdomen displacing intestines ventrally, with decreased serosal detail in that area. The dog was sedated with butorphanol (Torbugesic; Zoetis, Kalamazoo, Michigan, USA) intravenously (IV) for an abdominal ultrasound which revealed a large anechoic structure associated with the cranial pole of the left kidney. The dog was administered one dose of gabapentin (Neurontin; Pfizer, Kirkland, Quebec) to be given before transport to the CARE Centre the next morning.

On presentation to the CARE Centre, vital parameters showed elevated body temperature (rectal temperature: 40.2°C; RR: 37.5 to 39.5°C), tachycardia (heart rate: 148 beats/min) and hypertension (oscillometric blood pressure: 190/111 mmHg). On physical examination he was bright, alert, and estimated to be 5 to 6% dehydrated based on the presence of tacky mucous membranes. The dog had a small puncture wound on the medial side of his left tarsus that had been previously clipped and cleaned. He was tense and was extremely reactive on palpation of the region of kidneys/retroperitoneum and bladder. The dog had a stiff pelvic limb gait with delayed proprioception and decreased withdrawal reflexes on his left pelvic limb. His testicles palpated normally, and rectal examination revealed an enlarged and painful prostate.

Venous blood gas and electrolyte analysis showed a mixed disturbance with metabolic acidosis (base excess −7) and respiratory alkalosis [pH 7.47 (RR: 7.35 to 7.45), pCO₂: 23.1 mmHg (RR: 35 to 45 mmHg)]. The presence of a mild anemia was confirmed [packed cell volume (PCV): 35%; RR: 38 to 55%] with normal total solids (6.8 g/dL; RR 5.5 to 8.2g/dL). A urine sample was collected via cystocentesis for urinalysis and urine culture. Urine specific gravity before administration of fluid therapy was 1.030. An IV catheter was placed, and the dog was started on isotonic crystalloid therapy at 50 mL/kg body weight (BW) per day plus correction for 6% dehydration over 24 h. He was given maropitant (Cerenia; Zoetis), 1 mg/kg BW, IV and trazodone (Trazodone hydrochloride; Teva, Toronto, Ontario), 150 mg, PO once.

Contrast-enhanced multidetector computed tomography (MDCT) of the thorax and abdomen was performed with a 3rd generation multi-slice helical CT scanner (Toshiba Aquilion 16; Toshiba Medical Systems, Ōtawara, Japan) under sedation with fentanyl (Fentanyl; Sandoz, Boucherville, Quebec), 3 μg/kg BW, IV and dexmedetomidine (Dexdomitor; Zoetis), 4 μg/kg BW, IV. The dog was placed in dorsal recumbency and was monitored with electrocardiography, pulse oximetry, and oscillometric blood pressure while flow-by oxygen was provided. Pre- and post-contrast sequences using iodixanol Visipaque 320, (GE Healthcare Canada, Mississauga, Ontario), 800 mg/kg BW, iodine IV were acquired in lung and soft tissue algorithms. Post-contrast sequences were acquired at 30 and 90 s post-injection.

The thorax showed mild dorsal pulmonary atelectasis secondary to positioning but was otherwise unremarkable. The abdomen showed a hypoattenuating, heterogenous, moderately contrast-enhancing spherical mass-like lesion measuring 66 × 53 mm, located over the craniomedial aspect of the left kidney, ablating approximately 50% of the cranial pole of the left kidney. The margin of this lesion was well-perfused except for the caudal and medial aspect, which was disrupted. The mass bulged medially into the retroperitoneal space. Extensive wispy retroperitoneal infiltrate was present bilaterally; with an irregular, heterogenous, fluid-attenuating, amorphous, non-contrast-enhancing mass-like lesion caudal to the left kidney measuring 53 × 105 mm in diameter. This lesion enveloped the caudal lobe of the left kidney, displacing it laterally and resulted in marked enlargement of the mid and caudal retroperitoneal space. These changes were consistent with a bleeding left renal mass on the medial aspect of the cranial pole, with organized hemorrhage and hematoma formation into the retroperitoneum bilaterally. The top differential diagnosis was a primary renal neoplasia, such as renal carcinoma, hemangiosarcoma, and lymphoma. Granulomatous diseases such as fungal and bacterial conditions, or a migrating foreign body, were considered less likely.

Other CT findings included marked prostatomegaly with moderate contrast enhancement, most consistent with benign prostatic hyperplasia or prostatitis. A mild right-sided perineal hernia with pelvic fat was present, as well as testicular asymmetry. A chronic disc herniation at L2–3 was noted with moderate extradural cord compression.

A targeted ultrasound examination of the left kidney was performed in conjunction with the CT scan. Color-flow Doppler using a Philips Affiniti 70 (Philips Healthcare, Markham, Ontario) with a curvilinear high frequency transducer showed a hypoechoic homogenous renal mass with peripheral perfusion (Figure 1A).

Figure 1.

Sagittal sonogram with color-flow Doppler (A) versus axial (B) and dorsal planar (C) computed tomographic images in a dog with a left renal plasmacytoma. A — The hypoechoic mass (white arrows) arises from the left craniomedial pole of the left kidney and shows strong peripheral perfusion on color-flow Doppler. Subcapsular effusion is seen over the ventral aspect of the kidney (white arrowheads); the margins of the normal renal cortices are denoted by the white triangles. Cranial is to the left of the image. B and C — Subcapsular left renal effusion (hollow white arrowheads in B) is present with wispy retroperitoneal effusion (white arrows) on B. The left renal mass exhibited slightly heterogeneous but mild diffuse contrast enhancement with strong rim-enhancement (solid white arrowheads on C). A larger volume of mildly hyperattenuating retroperitoneal effusion (RPE) is seen caudal to the left kidney on C, consistent with an organizing hematoma. Ao — Aorta; RK — Right kidney; LK — Left kidney; CVC — Caudal vena cava. Cranial is to the top of image C, left is to the right of images B and C.

Exploratory laparotomy with left-sided nephrectomy was recommended based on imaging results. Prothrombin (PT) and partial thromboplastin time (PTT) were taken before surgery and results were within normal limits. The dog was blood-typed as DEA 1 positive. The dog was given one dose of enrofloxacin (Baytril; Bayer Healthcare, Shawnee Mission, Kansas, USA) 10 mg/kg BW, IV to treat for suspected prostatitis. He was transferred to VCA Canada Western Veterinary Specialist and Emergency Center (WVSEC, Calgary, Alberta) for surgery, at request of the on-call surgeon.

On arrival to WVSEC, the dog was in stable condition with normal vital parameters. He was anesthetized in a routine manner for an exploratory laparotomy. Surgical exploration revealed several small tan nodules on the surface of the liver ranging from 3 to 5 mm and he had an enlarged and firm prostate. A large mass on the cranial aspect of the left kidney was present as was a large blood clot in the retroperitoneal space with hemorrhagic staining extending across the dorsal midline. Blood clots were also noted in the omentum. A left nephrectomy and ureterectomy were performed. The renal vessels were ligated with polydioxanone (3-0 PDSII; Ethicon, Somerville, New Jersey, USA) and sealed with a 5-mm bipolar vessel sealing device (Ligasure Dolphin Tip; Covidien, Dublin, Ireland) before transection. The distal aspect of the ureter was also ligated with circumferential polydioxanone sutures before being transected. A liver biopsy was obtained from the left lateral lobe containing the tan nodules using a guillotine method with polydioxanone. A prostatic biopsy was taken from the right prostatic lobe using a 4-mm biopsy punch (Integra Miltex; Integra York, Princeton, New Jersey, USA). The abdomen was lavaged with warm saline and closed in 3 layers. An open castration was then performed in a routine fashion, and the testicles were submitted for histopathology. The perineal hernia was not corrected as the dog was asymptomatic at that time and repair was not considered necessary. Recovery from surgery was uneventful.

The dog was maintained on isotonic crystalloid fluids, methadone (Methadone hydrochloride; AAIPharma Services, Charleston, South Carolina, USA), 0.2 mg/kg BW, q6h, IV, enrofloxacin (Baytril), 10 mg/kg BW, IV, q24h, maropitant (Cerenia), 1 mg/kg BW, IV q24h, and dexmedetomidine (Dexdomitor) constant rate infusion as needed postoperatively. Urinalysis revealed bacteriuria [> 100 rods/high power field (hpf )], pyuria (11 to 20 WBC/hpf ), 2+ hematuria and 2+ proteinuria on urine dipstick evaluation. Urine culture showed growth of Escherichia coli sensitive to all antibiotics with the exception of cephalexin and cefadroxil. The dog was discharged on day 3 after surgery with oxycodone/acetaminophen (Percocet; Endo Pharmaceuticals, Malvern, Pennsylvania, USA), 5 mg tablets, PO, q8 to 12h, and enrofloxacin (Baytril), 300 mg, PO, q24h to treat the urinary tract infection and suspected concurrent prostatitis.

Histopathology of the right testicle was consistent with a seminoma. Prostatic biopsy was inconclusive, as the section consisted entirely of smooth muscle. Hepatic biopsy demonstrated benign nodular hyperplasia. The left kidney was effaced by a mass composed of sheets of neoplastic round cells supported by scant fibrovascular stroma. Marked anisocytosis and anisokaryosis were present with frequent binucleated, multinucleated, and karyomegalic cells. The mitotic count was 23 per 10 hpf. These findings were most consistent with a renal plasma cell tumor (Figure 2). This result was verified by 4 Board-certified veterinary pathologists, as primary extramedullary plasmacytoma had not previously been reported in the canine kidney. Immunostaining for Multiple Myeloma oncogene 1/Interferon Regulatory Factor 4 (MUM1/IRF4) was performed and was negative. Further staining to rule out a mast cell tumor (Giemsa and toluidine blue) was also negative. Light chain lambda immunohistochemistry staining was positive, confirming a plasmacytoma (Figure 2).

Figure 2.

Images at 200× magnification. A — Histopathology of renal plasmacytoma composed of sheets of neoplastic round cells exhibiting marked anisocytosis and anisokaryosis, with binucleated, multinucleated, and karyomegalic cells. Frequent mitoses are present. B — Lambda light chain immunostain with large numbers of neoplastic cells showing strong positive membranous ± cytoplasmic staining.

Following histopathology results, serum and urine protein electrophoresis were performed to screen for monoclonal gammopathy and Bence-Jones proteinuria. Urine protein electrophoresis revealed a small amount of protein in the urine (12.7 mg/dL), interpreted to be negligible. Serum protein electrophoresis showed normal total protein levels (70 g/dL; RR: 55 to 75 g/dL) with no evidence of monoclonal gammopathy. These results indicate the renal plasma cell tumor was not associated with multiple myeloma.

An oncology consultation was offered to the owner to discuss possible follow-up radiation and/or prophylactic chemotherapy, as excision with wide margins was likely not achieved due to the location of the mass. This leaves potential for tumor recurrence and/or metastasis, as the behavior of a plasma cell tumor in this location is unknown. The oncology consultation was declined. Upon a follow-up interview by telephone 2 mo after surgery, the owner indicated no concerns. The dog was euthanized 11 mo after surgery by the family veterinarian for undisclosed reasons. A necropsy was not performed.

Discussion

Extramedullary plasmacytomas (EMPs) occur as a result of clonal expansion of malignant plasma cells in soft tissues. These EMPs may appear as solitary tumors or develop to show symptoms secondary to systemic multiple myeloma. Extramedullary plasmacytomas comprise approximately 2.4% of all canine tumors, with the most common sites being skin (86%), the oral cavity (9%), and the colorectal area (4%). The skin around the limbs and head, including ears, are most affected (1,2). Extramedullary plasmacytomas arising from other sites are rare, and include the gastrointestinal tract, genitalia, eye, uterus, lung, liver, spleen, brainstem, spinal cord, trachea larynx, and third eyelid gland (1,3–8). Clinical signs associated with EMPs vary depending on tumor location (e.g., skin versus colorectal), as does biological behavior. Cutaneous, oral, and non-gastrointestinal EMPs are usually benign and local excision is often curative (2,9,10). Metastasis to lymph nodes or distant sites is uncommon, noted in one study to be < 4% (11). Gastrointestinal EMP appears to be more aggressive, with metastasis to local lymph nodes and intra-abdominal sites occurring more commonly. However, bone marrow involvement and monoclonal gammopathies are uncommon (12,13). Thus, staging recommendations differ based on location. For oral and cutaneous EMPs, CBC, serum biochemistry, and local lymph node aspiration is likely adequate for presumptive diagnosis before pursuing surgical excision. Further staging for non-oral and non-cutaneous sites, including thoracic radiographs, abdominal ultrasound, or CT may be elected for surgical planning and to screen for metastasis (10). For EMPs in atypical locations (e.g., non-cutaneous, non-oral), serum and urine protein electrophoresis are recommended to rule out multiple myeloma before pursuing surgical therapy. Bone marrow aspiration and cytology can be considered on a case-by-case basis; however, it is not always required if other screening tests for multiple myeloma are negative.

Diagnosis of EMPs is made via fine-needle aspiration and cytology, or biopsy with histopathology. Additional immunohistochemical staining of biopsy samples for MUM1/IRF4 can be useful for verification of plasma cell neoplasia. MUM1/IRF4 is a transcription factor involved in lymphoid cell differentiation and production of plasma cells (14,15), and has been used to characterize human B-cell neoplasms (16). One study showed that > 94% of canine plasmacytomas were positive for MUM1/IRF4, and this marker shows higher sensitivity and specificity than other markers for plasma cell tumors (CD70a and CD20) (16). In this case, MUM1/IRF4 staining was negative. This is similar to a previous case report in 2014 involving a strongly suspected plasmacytoma of the lung that demonstrated a negative MUM1 immunostain (8). Giemsa and toluidine blue stains were negative, ruling out a mast cell tumor. Light chain lambda staining was positive, confirming a renal plasmacytoma.

Surgical excision for oral and cutaneous EMPs is curative in 90 to 95% of cases, with local recurrence rates of 5 to 8% (2,10–12). In one study, 89% of the EMPs showing recurrence had neoplastic cells extending to the margins on histopathology (17). Due to the relative scarcity of EMPs in other locations, survival data are mostly limited to individual case reports. Although non-cutaneous and non-oral sites are thought to be more aggressive, median survival times of 15 mo have been noted following excision in dogs with colorectal EMP (1,13). Plasmacytomas with incomplete excision, or those not amenable to surgical therapy, have shown the potential for long-term survival when given radiation or systemic chemotherapy (18). Unlike solitary osseous plasmacytomas (SOP), EMPs are not thought to progress to multiple myeloma. A single case report did demonstrate a perianal mass progressing to multiple myeloma in a dog (19); although this is considered uncharacteristic.

The kidney is an atypical location for EMP in a dog. Kidney involvement in cases of plasma cell neoplasia have only been documented with renal infiltration secondary to multiple myeloma. Primary renal tumors themselves are uncommon in dogs and make up < 2% of canine cancers. Most primary renal tumors are malignant, and prevalence of tumor type varies depending on the study. Carcinomas dominate the distribution (60 to 85%), whereas mesenchymal neoplasia (e.g., sarcomas), nephroblastomas, and lymphoma characterize approximately 15 to 40% of cases (2,20,21). Tumors tend to be unilateral, but bilateral disease has been reported with carcinomas, lymphoma, and metastasis to the contralateral kidney from the primary tumor. Benign renal tumors occur but are much less common (22). Clinical signs associated with renal tumors include inappetence, lethargy, weight loss, hematuria, abdominal discomfort, or a palpable abdominal mass. This dog was also febrile, which could be secondary to inflammation, urinary infection, paraneoplastic effects, or a combination thereof.

Treatment of choice for unilateral renal tumors amenable to surgical excision is nephrectomy. Prior to surgery, full staging should be performed to determine renal function, extent of local disease, and to determine if metastasis is present. Tests include CBC, biochemistry, urinalysis, thoracic radiographs, and abdominal ultrasound. Common abnormalities include hematuria and pyuria (> 50% of cases) and neutrophilia. Azotemia may be present depending on how much of the kidney is affected (21). Thoracic and abdominal CT have been adopted in many hospitals for surgical planning and as a more sensitive way to identify metastatic disease (23). A recent study of 15 dogs demonstrated that no relevant CT differences were identified to differentiate tumor type, although this study was limited to only 3 tumor types (24). Large amounts of retroperitoneal hemorrhage were present in this patient. This is a reported occurrence in human renal tumors (25).

Pulmonary metastasis is a common feature of primary renal tumors, identified in 16 to 34% of dogs at time of diagnosis. Metastasis is seen at time of death in 77% of cases (20,21). Median survival time with primary renal tumors varies; 16 mo for carcinomas, 9 mo for sarcomas, and 6 mo for nephroblastomas. If nephrectomy is not pursued, median survival time is < 1 mo (21).

To the authors’ knowledge, this is the first report of renal EMP in a dog. In the human literature, renal EMP without associated multiple myeloma is extremely rare, with < 30 cases reported (26). Renal EMPs are often solitary, with only 2 human cases showing multiple organ involvement. Five cases of human renal EMPs are thought to be recurrence of EMPs that had been treated at a different anatomic site (25). Due to the low incidence of this condition, treatment guidelines for human medicine are not well-established, and thus cannot be extrapolated for use in veterinary patients.

Although initial screening tests for this first case of canine renal EMP were consistent with benign characteristics, long-term effects cannot be definitively determined. It is unclear whether this dog was euthanized due to complications related to his renal EMP, as a necropsy was not performed, and details of the euthanasia were not disclosed. Further studies into the role of chemotherapy and radiation for renal EMP are needed in both human and veterinary medicine to determine further treatment recommendations. CVJ