Immunohistochemical Characterization of a Renal Nephroblastoma in a Trp53-mutant and Prolyl Isomerase 1-deficient Mouse

A nephroblastoma is a tumor arising from metanephric blastema occurring in childhood. Among laboratory rodents, nephroblastoma has been frequently reported in rats, but it remains exceedingly rare in mice. The present work describes a nephroblastoma in a young mouse homozygous for the specific Trp53 R172H point mutation coupled with targeted deletion of the Pin1 gene. The affected kidney was effaced by a biphasic tumor with an epithelial component arranged in tubules surrounded by nests of blastemal cells. Immunohistochemically, the neoplasm was diffusely positive for Wilms’ tumor antigen. The epithelial component expressed markers of renal tubular differentiation including wide-spectrum cytokeratin, E-cadherin and folate-binding protein. Furthermore, the neoplasm exhibited a high proliferative index and diffuse nucleocytoplasmic β-catenin expression. Based on histological and immunohistochemical features, a diagnosis of nephroblastoma potentially associated with Trp53 loss and oncogenic β-catenin activation has been proposed.     

Treatment of renal nephroblastoma in an adult dog

An 8-year-old Labrador retriever was diagnosed with a unilateral malignant nephroblastoma and hypertrophic osteopathy. The histopathologically malignant tumor was confined to the renal capsule, but the sarcomatous component was anaplastic, resulting in its classification as a Stage I tumor with unfavorable histopathology. The dog was treated with unilateral nephrectomy, vincristine, and doxorubicin. This dog has remained disease free for >25 months. Reported treatments of renal nephroblastoma in the dog have not described disease-free intervals of >8 months.     

Spontaneous Nephroblastoma with Lung Metastasis in a Rat

This report describes a spontaneous nephroblastoma with lung metastasis in a 10-week-old male Crl:CD(SD) rat. Macroscopically, a white mass in the kidney and two white masses in the lung were observed. Histopathologically, the renal mass was located in the cortex of a kidney, and it caused pressure on the surrounding renal parenchyma. Three components could be distinguished in the tumor: blastemal, epithelial (primitive glomerular/tubular structures) and mesenchymal (neoplastic connective tissues) elements. Immunohistochemically, the tumor cells were positive for Wilms tumor 1 protein (WT1) and vimentin. Metastasis was found in the lung. Thus, the case was diagnosed as a nephroblastoma with lung metastasis.     

Malignant nephroblastoma in a common marmoset (Callithrix jacchus)

Necropsy of a 17-month-old male common marmoset (Callithrix jacchus) with a history of increased abdominal girth resulted in the finding of a unilateral polycystic renal neoplasm. Detailed histopathologic and immunohistochemical investigations revealed different tissue types within the tumor including stromal connective tissue and fusiform mesenchymal cell formations surrounding blastemal cells as well as different developmental stages of organ-specific epithelial cells accompanied by extensive cyst formation. Metastases were not observed. In consideration of the macroscopic, histologic, and immunohistochemical findings, the tumor was classified as a nephroblastoma closely resembling the so-called Wilms' tumor, a malignant embryonic renal tumor frequently observed in humans, especially in young children. In contrast, this tumor entity has rarely been observed in nonhuman primates. This report represents the first documented case of a cystic variant of nephroblastoma in a nonhuman primate.     

Extradural spinal,bone marrow,and renal nephroblastoma

A 1-year-old, female intact Shetland sheepdog presented with acute onset of neurological signs. Physical examination revealed a large abdominal mass. Neurological examination revealed multifocal disease with neck pain, short-strided forelimbs, and hind-limb paresis with loss of tail and anal tone. Blood work, imaging techniques, cytopathology, and histopathology led to a diagnosis of renal, bone-marrow, and extradural spinal nephroblastoma. This report documents potential clinical and pathological manifestations of canine nephroblastoma that have not been previously reported.     

Nasopharyngeal nephroblastoma in a 3-month-old Boer goat

A 3-mo-old, female Boer goat was presented because of respiratory difficulties. Tachypnea and inspiratory dyspnea were noted during physical examination. Thoracic radiographs were unremarkable; however, upper airway and nasal passage radiographs revealed a soft tissue mass within the nasal passages. The patient underwent cardiorespiratory arrest and did not respond to resuscitation efforts during endoscopy. A large, pedunculated, semi-firm mass originated from the soft palate and obstructed 90% of the nasopharynx on autopsy. Histologically, the mass was composed of primitive cells that multifocally formed tubules and glomeruloid structures intermingled with areas of fusiform and blastemal cells. The neoplastic cells were positive for cytokeratin (tubular and glomeruloid cells), vimentin (fusiform population and blastemal cells), and Wilms tumor 1 protein (glomeruloid structures) on immunohistochemistry, consistent with a triphasic nephroblastoma. To our knowledge, nasopharyngeal nephroblastoma has not been reported previously in any species.     

Renal nephroblastoma in a 3-month-old golden retriever

Nephrectomy was performed in a 3-month-old intact female golden retriever dog for a renal nephroblastoma. The dog has remained disease-free for 19 months with nephrectomy alone. The adoption of human Wilms’ tumor grading criteria may be useful in determining clinical stage, adjuvant treatment options, and prognosis in this rare disease.     

Spontaneous nephroblastoma in a Japanese giant salamander (Andrias japonicus)

An adult male Japanese giant salamander (Andrias japonicus) died accidentally, and necropsy showed a white mass (23 × 15 mm) in the left kidney and hepatorrhexis with hemoperitoneum. Histologically, the renal mass was mainly composed of immature nephroblastic tumor cells. In the tumor tissue, a trabecular pattern lined by oval to polygonal tumor cells with a rich interstitium, solid growth and a few tubular structures was observed. Nephroblastic tumor cells were strongly positive for vimentin and weakly positive, and epithelium-like tumor cells were strongly positive for cytokeratin. However, antibody for Wilms' tumor protein 1 did not react with the salamander's cells. On electron microscopy, a desmosome junction was observed between tumor cells. This is the first report of nephroblastoma in a Japanese giant salamander.     

Primary renal tumours in cats: 19 cases (1992-1998)

A search from databases of four veterinary colleges and one private referral practice between January 1992 and April 1998 provided 20 cases diagnosed with primary renal neoplasia. Review of these cases revealed 19 primary renal tumours, excluding lymphoma. Of the 20 histologically reviewed cases, the diagnosis was amended in eight. There were 13 renal carcinomas (11 tubular and two tubulopapillary), three transitional cell carcinomas, one malignant nephroblastoma, one haemangiosarcoma and one adenoma. The haemangiosarcoma is, to our knowledge, the first reported case of this tumour type as a primary renal tumour in the cat. Most cats were presented for non-specific clinical signs such as anorexia and weight loss. One cat presented with tumour-associated polycythaemia which has not, to our knowledge, been reported previously. The metastatic rate for cats with complete staging was 64%, and 100% for transitional cell carcinomas.     

Renal adenocarcinoma in a ferret

A spontaneous case of renal tumor was observed in a 7-year-old ovariectomized female pet ferret (Mustela putorius furo). Clinical signs included exhaustion, emaciation, anorexia, and stooping position. At necropsy, a solid and cystic mass replaced the left kidney and adrenal gland. The tumor was composed of pleomorphic epithelial cells with a large number of giant cells. Metastases were recognized in the lung, liver, greater omentum, right renal pelvis, and systemic lymph nodes. Immunohistochemical stains revealed that the tumor cells were positive for CD10, cytokeratin (CAM 5.2), and Ki-67 (MIB-1). On the basis of morphologic and immunohistochemical features, the tumor was diagnosed as a pleomorphic renal adenocarcinoma. This type of neoplasm is very rare in all species and has never been reported in a ferret.     

Renal pelvic rupture,intrapelvic haematoma and retroperitoneal haemorrhage associated with obstructive ureterolithiasis in a cat

A neutered female cat presented with a 9-day history of hyporexia and depression. The referring veterinarian had identified moderate non-regenerative anaemia, haematuria and suspected unilateral obstructive ureterolithiasis. Subsequent ultrasonography revealed moderate distension of the left renal pelvis with echogenic material, ureteral distension and ureterolithiasis. A partial ureteral obstruction was suspected. After 4 days of medical management, there was further distension of the renal pelvis with well-delineated echogenic material and an accumulation of perinephric fluid. A left nephroureterectomy was performed. Renal pelvic rupture with intrapelvic haematoma and retroperitoneal haemorrhage was confirmed by histopathology. Eighteen months following surgery, the cat remained clinically well with normal renal values.     

COMPUTED TOMOGRAPHIC CHARACTERISTICS OF INTRAPELVIC MASSES IN DOGS

In people, the computed tomography (CT) characteristics of intrapelvic masses can be used to distinguish a malignant from a benign mass. As prognosis varies greatly between malignant and benign intrapelvic masses, knowledge of their biological behavior can aid treatment planning before surgery. The purpose of this study was to determine if CT characteristics exist to help differentiate benign from malignant intrapelvic masses in dogs. The CT images of 14 dogs with a histopathologically confirmed intrapelvic mass were evaluated. Postcontrast internal heterogeneity of the mass was the only characteristic significantly associated with malignancy (P=0.005). Preoperative CT examination of intrapelvic masses in dogs can provide prognostic information before invasive surgical treatment.     

Expression of calbindin-D28K in sporadic nephroblastomas of the chicken

Calbindin-D28K (Ca-D28K) is a calcium-binding protein. In the kidney, Ca-D28K is present in the distal nephron, but not in the proximal nephron. This site-specific distribution in the kidney indicates that Ca-D28K is a potential marker for the differentiation of the distal nephron. In this study, we have examined the expression of Ca-D28K in 25 sporadic cases of chicken nephroblastomas. All cases of nephroblastomas were composed of atypical tubular structures, blastemal cells, and fibrous stroma in varying degrees of differentiation. Immunohistochemically in all nephroblastoma specimens, Ca-D28K was expressed in the epithelial cells of the subsets of tubular structures, but not in the blastema or the stroma. These results suggested that the tubuli in the nephroblastomas are able to differentiate into the phenotype of distal nephrons. Furthermore, Ca-D28K might develop as a novel diagnostic marker for nephroblastomas because this molecule is reported to be completely negative in other renal tumors, including renal cell carcinoma, chromophobe carcinomas, and oncocytoma.     

Renal embryonal nephroma exhibiting malignant features in a Dutch rabbit (Oryctolagus cuniculus)

BackgroundBenign embryonal nephromas have been documented in rabbits. However, only one case of nephroblastoma with concurrent metastasis (pulmonary), a postmortem incidental finding, has been published.Case presentationA 3-year-old neutered male Dutch rabbit (Oryctolagus cuniculus) was referred for assessment of a firm mass located in the mid-dorsal abdomen. Abdominal ultrasonography confirmed a large soft tissue mass of suspected renal origin. A left-sided nephrectomy was performed via a ventral midline approach. Multiple white macular lesions, hyperemia, and petechiae were observed in the mesenteric fat surrounding the spleen. Histopathological examination of the abnormal kidney and the mesenteric fat revealed microscopic findings consistent with an embryonal nephroma exhibiting distinct features of malignancy. At 6- and 12-month postsurgery, ultrasonographic evidence of tumor recurrence was not observed.Conclusion and case relevanceThis is the first report of successful treatment of an embryonal nephroma showing malignant behavior and metastasis to the surrounding adipose tissue with a minimum postoperative survival time of 12 months and no ultrasonographic evidence of local recurrence.     

Sagittal pubic osteotomy in the investigation and treatment of intrapelvic neoplasia in the dog

Sagittal pubic osteotomy was used as the surgical approach in 24 cases of intrapelvic neoplasia in the dog. Thirteen cases involved the urethra, seven cases the colorectum, one case the prostate and three cases the iliac periosteum. Surgical excision was performed in 10 cases of urethral neoplasia, four cases of rectal neoplasia, two cases of periosteal fibrosarcoma and one case of chondrosarcoma. The remaining cases were assessed as inoperable due to the extent of disease and euthanasia was carried out. Access to intrapelvic structures via a caudal midline laparotomy, perineal or dorsal routes or via an episiotomy is severely limited. The structures within the pelvic canal most likely to require surgical attention are the urethra, rectum and prostate. Procedures which require wide excision, accurate anastomotic techniques or relocation of intrapelvic organs necessitate an approach that allows generous exposure. A simple method of pubic osteotomy has been employed which has allowed resection of intrapelvic neoplasms.     

Natural occurrence of neoplastic lesions in young sprague-dawley rats

It is important for the assessment of toxicological effects of chemicals to know what kinds of neoplasms naturally occur in the early life of experimental animals. In the present study, we demonstrated spontaneous neoplasms in Sprague-Dawley rats used in 4-, 13- and 26-week toxicity studies conducted at Bozo Research Center in the last decade. The tumors, which were first observed in 19-week-old animals, included anterior adenoma of the pituitary, follicular cell adenocarcinoma and C cell adenoma of the thyroids, nephroblastoma of the kidneys, basal cell tumor of the skin and malignant lymphoma. Thereafter, hemangiosarcoma of the tongue, adenocarcinoma of the submandibular glands, histiocytic sarcoma of the spleen, oligodendroglioma of the brain and adenocarcinoma and fibroadenoma of the mammary glands were detected in 32-week-old animals. The incidences of mammary adenocarcinoma and pituitary anterior adenoma were higher than those of other tumors. The present results showed that the same tumors as reported in aged rats could also develop in younger rats.     

IMAGING OF A SPINAL NEPHROBLASTOMA IN A DOG

An 8-month-old German Shepherd dog was presented for investigation of pelvic limb gait abnormality. Neurolocalization indicated a T3-L3 spinal cord lesion. The myelographic appearance was of an intramedullary lesion at T9/10, but upon subsequent magnetic resonance imaging it was determined that the mass was extramedullary. A diagnosis of nephroblastoma was made on histological examination. The imaging features of this rare tumor and the differentiation of intradural-extramedullary and intramedullary masses are discussed.     

Proliferative potential of a spinal nephroblastoma in a young dog

The proliferative potential of a spinal nephroblastoma was studied in a young dog. A 4-month-old, female golden retriever showed developing deterioration in her gait and subsequent paralysis of her hind legs. At necropsy, a well-demarcated grayish brown tumor mass was found in the lumbar spinal cord segments between L2 and L3. Histologically, a blastemal cell tumor with a tubule- or glomeruli-like structure was found to be infiltrating intradurally. Proliferating cells at the S-phase, assessed using the bromodeoxyuridine (BrdU) labeling method, were seen occasionally in the tubular cells and glomeruli-like structures and were frequently seen in the blastemal cells. Immunohistochemically, the tubular epithelial cells were positive for cytokeratin, and the blastemal cells were positive for vimentin. The present tumor showed a high potential for growth and invasion, which suggests that it the potential to expand into the adjacent spinal cord.     

Spinal nephroblastoma in a miniature Dachshund

A 2-year-old castrated miniature Dachshund dog was presented to the Rakuno Gakuen Veterinary Teaching Hospital for diagnosis of progressive hindlimb paresis and ataxia. There was no thoracolumbar intervertebral disk hernia and magnetic resonance imaging revealed an intramedullary spinal cord lesion at the ninth and tenth thoracic vertebrae. Following surgical excision of the neoplasm, there was minor amelioration of neurological signs, but forelimb function was not recovered. The extracted tumor was histopathlogically diagnosed as spinal nephroblastoma.