Metastatic renal interstitial cell tumor in a dog

Abstract

Renal interstitial cell tumor (RICT) is a rare renal sarcoma of dogs that arises from renal interstitial cells. Herein we describe a RICT in an 8-y-old female Labrador Retriever dog that died after a 2-d history of lethargy and disorientation. Grossly, soft white nodules of 1–10 mm diameter were present in the renal cortex and corticomedullary junction of both kidneys, left cardiac ventricular wall, and right cerebral hemisphere. A pale-white to yellow, firm, irregular mass effaced 80% of the right pulmonary parenchyma, involving mainly the cranial and middle lobes, and the adjacent tracheobronchial lymph nodes. Histologically, the renal, myocardial, and cerebral neoplasm consisted of interlacing bundles of stellate-to-spindle cells with eosinophilic vacuolated cytoplasm and round-to-oval nuclei with finely stippled chromatin. The mitotic count was 28 per 2.37 mm². Alcian blue stain revealed an extracellular myxomatous matrix throughout the neoplasm. Neoplastic cells had cytoplasmic immunolabeling for vimentin and cyclooxygenase 2. The pulmonary and tracheobronchial neoplasm consisted of infiltrative nodules of cuboidal epithelial cells that had a moderate amount of eosinophilic cytoplasm and round nuclei with coarsely stippled chromatin. There were 5 mitoses per 2.37 mm². Neoplastic cells had cytoplasmic and nuclear immunolabeling for cytokeratin AE1/AE3 and thyroid transcription factor 1, respectively. Morphologic and immunohistochemical findings were consistent with a RICT with cardiac and cerebral metastases, and a pulmonary carcinoma with tracheobronchial lymph node metastasis.

Primary renal neoplasms are uncommonly diagnosed in dogs,⁴ comprising <2% of all reported canine neoplasms diagnosed during autopsy.^1,5 The most common primary renal neoplasm in dogs is renal cell carcinoma, a malignant tumor arising from epithelial cells of the nephron.⁷ Less frequent neoplasms include multiple types of renal sarcoma and nephroblastoma, which arise from renal mesenchymal cells and from the primitive metanephric blastema, respectively.⁴ Regardless of the tumor type, these malignant neoplasms affect mainly adult dogs and are usually unilateral, with metastases reported mainly to the lungs and abdominal organs.^4,7 Nephroblastoma is also commonly diagnosed in young dogs, in which it can also occur in the kidney or intradural space of the thoracic and lumbar spinal cord.³ Renal adenomas are rare and typically an incidental finding during autopsy.⁹

Renal interstitial cell tumor (RICT) is a renal neoplasm that arises from renal interstitial cells.^5,6,8 Renal interstitial cells are rich in prostaglandin, arachidonic acid, and antihypertensive lipids, and have an important role in water and salt absorption and regulation of blood flow and arterial blood pressure through the synthesis of cyclooxygenases.^5,8 In humans, these neoplasms are referred to as renomedullary interstitial cell tumors and are the most common renal neoplasm of adults.⁸ However, RICTs are exceedingly rare in dogs, occurring as single or multiple nodules within the cortex or corticomedullary junction of one or both kidneys.^5,6 Most canine RICTs are clinically benign,^5,6 with a single RICT case that had morphologic features of malignancy.⁵ To our knowledge, no metastatic RICT has been reported in dogs to date.^5,6 Herein we describe a metastatic RICT in a dog.

An 8-y-old female Labrador Retriever dog was autopsied after a 2-d history of lethargy and disorientation. The patient died spontaneously following cardiorespiratory arrest. Gross anatomic changes consisted of multiple soft white nodules of 1–10 mm diameter in the renal cortex and corticomedullary junction of both kidneys (Fig. 1). Similar nodules were observed in the left cardiac ventricular wall and right cerebral hemisphere at the level of the basal nuclei (Fig. 2). There was a left midline shift of the brain as a result of compression by the neoplasm. In addition, an extensive, pale-white to yellow, irregular, firm mass effaced and expanded 80% of the right pulmonary parenchyma, involving mainly the cranial and middle lung lobes (Suppl. Figs. 1, 2). The adjacent tracheobronchial lymph nodes were enlarged and firm. No other gross changes were observed.

Figures 1–6.

Metastatic renal interstitial cell tumor in a dog. Figure 1. A well-demarcated, white to pale-yellow nodule expands the cortex and corticomedullary junction of the left kidney. Figure 2. A well-demarcated, white to dark-red nodule expands the right basal nuclei. There is a left midline shift as a result of compression by the neoplasm. Figure 3. The renal neoplasm consists of interlacing bundles of spindle cells with indistinct cytoplasmic borders. H&E. Figure 4. An extracellular alcian blue–positive matrix is present throughout the renal neoplasm. Figure 5. Neoplastic cells exhibit widespread immunolabeling for vimentin. Figure 6. Neoplastic cells exhibit immunolabeling for COX-2.

Representative routine samples of multiple tissues were fixed in 10% neutral-buffered formalin, processed routinely, and stained with hematoxylin and eosin. Histologically, the renal neoplasm was fairly well demarcated and consisted of interlacing bundles of stellate-to-spindle cells with a moderate amount of eosinophilic, often-vacuolated cytoplasm with indistinct cell borders (Fig. 3). Nuclei were round-to-oval and had finely stippled chromatin with 1 or 2 nucleoli. Anisocytosis and anisokaryosis were moderate, and the mitotic count was 28 per 2.37 mm² (equivalent to 10 FN22/400× fields). The cardiac and cerebral nodules consisted of morphologically similar neoplasms.

The pulmonary neoplasm consisted of multiple infiltrative nodules composed of epithelial cells forming papillary projections supported by a fine fibrovascular stroma (Suppl. Fig. 3). Neoplastic cells were cuboidal-to-columnar and had a moderate amount of eosinophilic cytoplasm with distinct cell borders. Nuclei were round and had coarsely stippled chromatin with no distinct nucleolus. There were 5 mitoses per 2.37 mm². Areas of necrosis were distributed throughout the neoplasm. A similar neoplasm partially effaced the nodal architecture of the tracheobronchial lymph nodes.

Alcian blue (AB) staining of sections of kidney and brain revealed a faintly basophilic myxomatous matrix throughout the neoplasm (Fig. 4). Immunohistochemistry (IHC) was performed on tissue sections of kidney, heart, brain, and lung, and included vimentin (mouse monoclonal, 1 in 3,000 dilution for 60 min; Biogen), cytokeratin AE1/AE3 (mouse monoclonal, 1 in 100 dilution for 90 min; Biocare Medical), cyclooxygenase 2 (COX-2; mouse monoclonal, 1 in 100 dilution for 60 min; BD Biosciences), thyroid transcription factor 1 (TFF-1; mouse monoclonal antibody, ready-to-use dilution for 60 min; Cell Marque), ionized calcium-binding adapter molecule 1 (Iba1; rabbit polyclonal antibody, 1 in 8,000 dilution for 60 min; Wako), glial fibrillary acidic protein (GFAP; mouse monoclonal, 1 in 4,000 dilution for 60 min; Biogen), oligodendrocyte lineage transcription factor 2 (Olig2; rabbit monoclonal, 1 in 400 dilution for 60 min; GeneTex), neurofilament (NF; mouse monoclonal, 1 in 2,000 dilution for 60 min; Zymed), and factor 8–related antigen (rabbit polyclonal, ready-to-use dilution for 60 min; Cell Marque). Neoplastic cells in the kidney, myocardium, and brain exhibited cytoplasmic immunolabeling for vimentin (Fig. 5) and COX-2 (Fig. 6). Neoplastic cells in the pulmonary neoplasm had cytoplasmic immunolabeling for AE1/AE3 (Suppl. Fig. 4) and nuclear immunolabeling for TTF-1 (Suppl. Fig. 5). All other IHCs were negative.

A diagnosis of RICT was achieved based on the morphologic and IHC features of the mesenchymal neoplasm in the kidney, myocardium, and brain.^5,6,8 Similar to descriptions of RICTs in dogs, tumors were bilateral and multiple.⁶ Histologically, RICTs need to be distinguished from renal fibromas and other renal sarcomas.⁵ First, the neoplasm in our case had overt morphologic features of malignancy, including high cellularity, cell and nuclear pleomorphism, brisk mitotic activity, and multiple metastases to the myocardium and brain, characteristics that promptly ruled out a fibroma. Second, the presence of an extracellular AB-positive myxomatous matrix is a typical feature described in RICTs but not in renal fibromas.⁵ Third, cytoplasmic immunolabeling for both vimentin and COX-2 is highly supportive of a diagnosis of RICT and a useful finding to rule out a fibrosarcoma (which should be negative for COX-2), as described in RICTs in dogs and humans.^5,8 A vascular neoplasm was ruled out based on the lack of immunolabeling for factor 8–related antigen.⁵ Although sarcomatoid differentiation can occur rarely within canine and human RCCs, no evidence of an epithelial component was observed in the multiple tissue sections of kidney, myocardium, and brain in our case.⁷

In humans, RICTs are typically incidental findings detected during autopsy.⁸ Canine RICTs are also typically benign and only rarely exhibit morphologic evidence of malignancy as seen in our case.^5,6 Further, to our knowledge, the cardiac and cerebral metastases present in our case have not been reported in canine cases.^5,6 The dog also had a pulmonary carcinoma, which was confirmed by IHC for AE1/AE3 and TTF-1.² The pulmonary neoplasm occupied an extensive area of the right lung and likely contributed to the clinical signs and death in our case. Interestingly, a case of RICT was described in a dog with a concurrent pulmonary carcinoma, but all of the cases in that study died or were euthanized because of other comorbidities or old age, corroborating the benign nature of most RICTs in dogs.⁶