How Many Specialists Does It Take to Diagnose a Mass?

Patient information:

Age: 3 years
Gender: Female (suspected Spayed per rDVM)
Breed: Golden Retriever
Species: Canine

History:

Sandy was evaluated at her RDVM for weight loss, inappetance and urinary incontinence on 5/11/2023. Exam revealed a large palpable mass on right dorsocranial abdomen.

Ultrasonographic findings:

Kidneys: Only the left kidney was readily visible. Enlarged size (Lt = 9.4 cm) and normal shape with normal corticomedullary dimensions. Moderate pyelectasia visualized (7.5 mm).

The right kidney appears severely hydronephrotic with minimally discernible septum creating a kidney- reminiscent shape, measured approximately 12.9 cm.

There is a heterogenous, hyperechoic, peripherally vascular mass which appears to protrude into the area of the renal pelvis from the proximal ureter. Mass width exceeded the scope of the ultrasound probe (at least 9.4 cm), mass depth is at least 8.7 cm.

Intestines: There is a focally mildly thickened segment of small intestine (max thickness 5.0 mm) with no sign of infiltrative disease.

Abdominal ultrasound interpretation:

Right hydronephrosis- the findings are severe- secondary to ureteral obstruction

Right ureteral mass- the findings are severe- Ddx: carcinoma (TCC/UC, other), soft tissue sarcoma, less likely granuloma Left Kidney

Pyelectasia DDX:
a) IV fluid administration
b) Pyelonephritis and ureteritis
c) Increased diuresis caused by renal insufficiency or other condition
d) Toxin
e) Infectious (leptospira, etc)
f) Post-renal obstruction / Bladder distention
g) Diuresis

Images:

Image 1: Significant pyelectasia noted in the left renal pelvis.

Image 2: Hydrodronephrosis of the right kidney with soft tissue mass in the caudal pole suspected to be causing right ureter obstruction.

Image 3: Right caudolateral mass effect which extends beyond the scope of ultrasound probe, located between the abnormal right kidney and cranial aspect of the urinary bladder.

Recommendations:

Referral to a veterinary surgeon for further diagnostics (CT scan, chest and abdomen) and therapy is highly recommended.

Additional tests:

CT scan:
- Variable but small volume fluid is noted in the peritoneal space
- In the region of the right kidney there is a large fluid-filled structure identified with a more soft tissue rim, thought to represent the renal capsule. It has a tubular extension medially and slightly caudally, through to be the right ureter which cannot be followed to the urinary bladder. This is followed caudally towards an at least 11 cm x 8.5 cm, irregularly marginated, soft tissue attenuating and heterogeneously enhancing, mildly complex mass located in the caudal abdomen to the right of midline, questionably retroperitoneal in location.
- Moderate left renal pelvic dilation also identified, tracing into a dilated left ureter which is mildly tortuous and also cannot be traced to the level of the urinary bladder due to the large mass-effect. This mass is also noted to be displacing the caudal vena cava and associated more caudal branches dorsally with at least compression although invasion cannot be entirely excluded, especially caudal to the level of the renal parenchyma.
- The right renal vein is not specifically outlined. The aortic and additional sublumbar including the medial ilial lymph nodes bilaterally, are variably enlarged although somewhat summetrically.
- Both adrenal glands are difficult to specifically distinguish although thought to be seen separate from this mass-like change and both at least mildly enlarged.
- Conclusions: Large, more right-sided, complex soft tissue mass with regional peritoneal and retroperitoneal effusion. It is unclear as to whether this is a more caudally positioned right kidney mass (less likely) over a caudal retroperitoneal cavitary mass with chronic obstruction of the ureters, more severe on the right with resulting hydronephrosis and lack of renal parenchyma. More moderate to marked left pyelectasia to early hydronephrosis identified with chronic at least partial obstruction from this mass. Neoplasia is thought most likely and given the location hemangiosarcoma may be the primary differential over round cell neoplasia or carcinoma. Right ureteral origin mass not excluded although would be difficult to confirm with the size of this mass and expansile appearance. It is unclear as to whether guided FNA would provide additional information and biopsy may be indicated. Given the appearance surgical removal could be attempted although invasion into the caudal aspect of the caudal vena cava and involvement of the ureters cannot be specifically determined tomographically.

Photo: CT scanned image displaying the enormity of the mass prior used for surgical planning.

Surgery report:

Multiple firm, small, non-movable masses were present within the internal rectus sheath, within the abdominal cavity.
An extremely large, extensive, firm and complex mass was present in the right mid to caudal abdomen, extending past midline adjacent to the pelvic brin. Upon further evaluation, and wafter careful dissection of some of the surrounding omental adhesions to the mass, the mass was extremely complex and firm, with multiple organs adhered to or into the mass, including the mid to distal duodenunum, the descending colon, the right kidney, the right ureter, the uterine stump, the apex of the urinary bladder, the caudal vena cava, aorta, and femoral arteries.
The right kidney was markedly distended, soft, and fluid filled, resembling a large water balloon (it measured approximately 12 cm in length, and the mass was another 9-10 cm in length, 8 cm wide.
The segment of mid to distal duodenum, including the caudal duodenal flexure, were noted to be completely embedded within the mass and were visually blocking the ability to discern the dorsal margin of the mass.
Once the embedded duodenal segment "removed," the dorsal and medial margins of the mass could be visualized; the caudal vena cava and aorta were noted cranially to the mass, and then lost into the mass caudal to the left kidney. The mass appeared to have both a peritoneal and retroperitoneal component.
A partial cystectomy was performed as the apical aspect of the urinary bladder and the distal aspect of the uterine stump were completely embedded within the mass.
The distal aspect of the right ureter was noted to be entering into the urinary bladder, but the remaining proximal portion was completely embedded and lost into the mass. The mass also seemed to be firmly adhered to underlying epaxial musculature at the level of the mid ureter.
An additional extension of the mass was noted immediately dorsal to a segment of descending colon, which was deviated dorsally (due to the mass). The sacral lymph node could be visualized and was enlarged and firm.
Cytoreductive surgical removal of the most ventral aspect of the mass (the inside of the mass was caseous and gritty in appearance, with a brown to white exudate) was performed, and approximately 3/4 of the mass was removed.

Photo 1: The excised bulk portion of the right abdominal mass which includes the right kidney, small intestines, colon, ureters and indiscriminate mesentery.

Photo 2: The excised bulk portion of the right abdominal mass which includes the right kidney, small intestines, colon, ureters and indiscriminate mesentery (slightly different angle).

Histopathology report:

Pathological Findings, Diagnosis

Omental nodules: Severe, chronic, pyogranulomatous omentitis with suspected intralesional yeast or algae
Right retroperitoneal mass: Severe, chronic, pyogranulomatous retroperitonitis and nephritis with intralesional yeast or algae

Comments

Both the omental nodules and the retroperitoneal mass were caused by severe, chronic, pyogranulomatous inflammation, and the nodular inflammation often surrounded groups of suspected yeast or possibly algae (i.e. Prototheca). The inflammation and suspected organisms also infiltrated and disrupted much of the kidney in the retroperitoneal sample. Due to the negative staining of the suspected organisms, further differentiation could not be performed with routine staining.

Microscopic Description

Omental nodules (slide A) - Sections of omental fat are examined in which the fat is infiltrated by inflammatory nodules that are composed of coalescing dense groups of macrophages that surround and are mixed with large numbers of neutrophils. At the center of some nodular groups of inflammation were region of necrosis containing vague, negatively staining, round, possible fungal yeast or algal organisms that are 10 -30um in diameter. Mature, dense fibrosis dissects through and surrounds the regions of inflammation. Small numbers of lymphocytes and plasma cells are also throughout, and there are some regions of edema and hemorrhage.
Right retroperitoneal mass (slides B1 – B3) – The retroperitoneal fat and much of the kidney are infiltrated by severe, nodular pyogranulomatous inflammation with similar features to the inflammation described above in the omentum. At the center of many nodular regions of inflammation are regions of necrosis that also contain suspected, negatively staining, yeast or algal organisms. Many multinucleated cells surround the regions of necrosis, and the suspected organisms are also within the cytoplasm of many macrophages. Multiple small to moderately sized aggregates of lymphocytes and plasma cells are within the kidney.

Discussion:

The genus Prototheca entails species of achlorophyllous, unicellular, saprophytic, aerobic algae closely related to Chlorella spp. These algae are ubiquitous in the environment and may be isolated from fresh and marine water, soil, mud, tree sap, and sewage. Prototheca reproduce asexually by internal cleavage (endosporulation), resulting in the formation of 2 to 20 small endospores within the sporangium, which expand until they are released when the sporangium ruptures.

In human patients, protothecosis has 3 manifestations: i) dermatitis (comprising more than half of reported human cases), ii) olecranon bursitis, and iii) disseminated or systemic infection. Most lesions of the skin and olecranon bursa result from local traumatic inoculation. Human systemic infections are almost uniformly associated with immune compromise, occurring most commonly with anticancer therapy, organ transplantation, or clinical AIDS, and most commonly affect the skin and subcutis, alimentary tract, peritoneum, blood, and spleen.

Canine cases of protothecosis are uncommon but are increasingly recognized worldwide. A recent review of canine protothecosis identified 31 canine cases in the primary literature, largely arising from the United States.

In contrast to the human disease,canine protothecosis typically involves a broadly disseminated infection, particularly involving the colon, nervous system, and eyes, as well as the heart, kidneys, skeletal muscle, and liver. Frequent involvement of the colon makes colitis (with or without hematochezia) a common presenting complaint; other common presenting complaints include neurologic disease, blindness, and less frequently, polyuria and polydipsia.

Little is known regarding the pathogenesis of canine protothecosis. In human cases the predominance of uncomplicated cutaneous lesions suggests that direct traumatic inoculation is most likely; however, the paucity of cutaneous lesions in canine patients with disseminated disease suggests this is less likely. Most sources suggest the colon as the most likely principle site of infection, resulting in chronic granulomatous colitis and eventual dissemination of the alga to other sites of predilection. Immune dysfunction is often posited as a contributor to this pathogenesis in order to account for its sporadic occurrence, as well as to explain the possible predisposition of collies and boxers.

Protothecosis carries a grave prognosis in the canine patient. Stenner et al identified only 2 cases of canine protothecosis that survived the infection out of 31 cases reviewed. In contrast, the same review found only 2 human cases in which death was attributable to protothecosis. Stenner et al also described 17 cases of protothecosis in dogs from Australia, including 6 cases that underwent treatment. Two dogs that were presented with colitis without any indication of disseminated infection were treated with amphotericin B, with survival times noted as 12 and 17 mo and no indication of dissemination of infection (specific causes of death were not indicated). One dog presenting with colitis and later developing nervous and ocular disease was treated with amphotericin B and itraconazole, and survived to the time of publication. Three dogs were treated with ketaconazole; 2 of these animals failed to improve with therapy and were euthanatized, and 1 was euthanatized before adequate time had elapsed to assess therapeutic efficacy.

Arguments may be made that the poor prognosis associated with protothecosis could be related to the late stage of diagnosis in the progression of disease and that early detection of infection might permit earlier and more effective treatment before extensive dissemination. However, early differential diagnosis of protothecosis is complicated by the numerous other causes of chronic diarrhea and by the very small likelihood of Prototheca infection. Unfortunately, Prototheca frequently is not considered as a differential diagnosis until seen by referral specialists, or until the development of secondary lesions of dissemination to the brain or eye. Even with the development of granulomatous endophthalmitis there are numerous more likely differential diagnoses in the dog, including Blastomyces dermatitidis and Cryptococcus neoformans, more rarely Coccidiodes immitis or Histoplasma capsulatum infection. It is usually the development of ocular and/or nervous dysfunction in the face of chronic colitis that directs the clinician toward a diagnosis of disseminated protothecosis. A better understanding of the factors that contribute to the development of this disease might provide early indicators of Prototheca spp. infection.

The idiosyncracies of canine protothecosis, including methods of transmission, the tendency towards broad systemic dissemination, predilection for specific organs, and possible differential susceptibility of boxers and collies provide many questions to be answered on this disease.
Considering that many human cases arise in North America, it is important to consider protothecosis as a rare but important differential diagnosis for cases of hemorrhagic colitis with onset of multisystemic disease in the canine patient.

Vince AR, Pinard C, Ogilvie AT, Tan EO, Abrams-Ogg AC. Protothecosis in a dog. Can Vet J. 2014 Oct;55(10):950-4. Erratum in: Can Vet J. 2021 Jun;62(6):590. PMID: 25320382; PMCID: PMC4187369.

Patient outcome:

Immediate post-operative condition was significantly improved, the patient demonstrated increased activity levels, appetite and overall improved comfort. She did experience moderate regurgitation which resolved with administration of prokinetic therapy and a nasogastric tube to remove excess fluid from the stomach. She was released to her owners care approximately 48 hours after surgery.

At the time of her 2-week recheck, the owners reported a significant improvement in her comfort, activity, and demeanor.
Approximately 4 months post-op, the owners were contacted for follow up and reported that Sandy had been humanely euthanized. No specific cause for her decline was discussed. It is suspected that due to the diagnosis of Prototheca and the inability to safely remove all abnormal tissue at the time of surgery, that her growth returned and negatively affected her quality of life.

A very special thanks to Four County Animal Hospital for sharing patient details and allowing for an in-depth discussion of their patient.

A special thank you to Dr. Raphael Repellin for collaborating on this case with advanced imaging details and surgical expertise.