A forming primitive glomeruloid structures and cellular stroma.
3-year-old male white-handed gibbon (Hylobates
lar) was admitted to the University Veterinary Hospital, Universiti Putra
Malaysia with the complaint of chronic abdominal distention. At necropsy, there was a unilateral mass of polycystic
renal neoplasm resembling an
oversized kidney. On cut surface, the mass was heterogenous with whitish admixed
with some brownish structures, possibly remnants of the left kidney and composed of cystic spaces separated by delicate septa
with some parts contained cartilaginous structures. There were no
sign of metastasis. Detailed
histopathologic investigation revealed heterogeneous mass
consisted of highly pleomorphic cells, which in most parts resembled primitive
nephrogenic cells forming primitive glomeruloid structures and cellular stroma.
The tumor is made up of a disorganized mixture of three distinct cell elements:
the epithelial, mesenchymal and blastemal cells. In
consideration of the macroscopic and histological findings, the tumor was
classified as nephroblastoma or the so-called Wilms’ tumor, a malignant
embryonic renal tumor frequently observed in humans, especially in young children.
This tumor is rarely been documented in non-human primates thus, little is
known about the natural behavior of this tumor in non-human primate.
Keywords: Hylobateslar, nephroblastoma,
cysts, renal neoplasm, Wilms’ tumor
Wilms tumor or nephroblastoma
is the most common renal malignancy in childhood
(~8% of all cancers of the child). It is an embryonal neoplasm composed of
three cell population: blastema, epithelium, and stroma. This tumour is usually
unilateral but can be bilateral (5%). The highest incidence occurred at age 2-3
year (rarely above 10 years) and 70% of cases were diagnosed before the age of
5 years 5. Only 10% -20% of all Wilms tumor cases were diagnosed during the
first year of life. The prevalence of this tumour is 1 in 10,000 children.
Wilms tumor can affect men as well as women of equal comparability, and a
higher incidence has been reported in African American races compare to the
Asian race or Caucasian. These tumors are related with certain congenital
abnormalities and malformations syndrome.
Most cases are
sporadic, about 1% are familial inherited derived autosomally dominant 5, 11.
The aetiology is multifactorial, but it is believed due to the involvement of
the WT1 gene (Wilms Tumor Suppressor Gene 1). This gene lies on chromosome
11p13 and regulates transcription factors that are essential for normal kidney
development. WT1 gene are produced by the metanephric mesenchyme, this gene activates
growth factors that play a crucial role in inducing ureteric bud growth. (metanephric
mesenchyme and ureteric bud are adult renal and ureteric candidates). WT1 gene
is a tumour suppressor gene and if there is a defect in the gene, there will be
no control of cell growth. These
tumors are pale gray (resembling the brain) and the cells in them are composed
of metanephric mesenchyme cells, primitive renal epithelial cells, and
connective tissue. Deletions on chromosome 11p13, 11p15, and 16q have been
reported in some cases of Wilms tumor patients and it has been associated with
the increased risk of developing the tumor. Gen 11p13 was named after the
Wilms’ tumor 1 (WT1) gene while genes 11p15 was named after Wilms’ tumor 2
(WT2) genes and the 16q gene was named after genes Wilms’ tumor 3 (WT3).
animals, primary nephroblastoma most commonly found in chickens and pigs 7, 11.
Few cases has been reported in dogs,
cats, horses and cattle and rarely have been reported in nonhuman primates 7,
11. An extrarenal manifestation of nephroblastoma has been observed in bovine
foetus, which consist of several types of tissue with cartilage the predominant
The most common
renal neoplasms in nonhuman primates include carcinomas and adenomas. Only a
few reports have been documented about nephroblastomas in Old World and New
World monkeys; among them 1 case in a cynomolgus macaque (Macaca fascicularis), 2 recent cases in baboons (Papio sp.), and 1
case in a cotton-top tamarin (Saguinus oedipus). Most of the cases were
incidental findings at necropsy after the animals had died spontaneously or had
been euthanatized because of an unspecific debilitated or moribund condition. To
the knowledge of the authors, this report documents the first description of a
cystic variant of malignant nephroblastoma in a white-handed
gibbon (Hylobates lar).
male white-handed gibbon (Hylobates lar)
was admitted to the University Veterinary Hospital, Universiti Putra Malaysia
with the complaint of chronic abdominal distention. Abdominal x-ray investigation reveals a
large soft tissue opacity displacing bowel. A complete necropsy
was performed and representative tissue samples of various organs, including
the kidneys, were fixed in 10% phosphate-buffered formaldehyde for histologic investigations.
Following fixation in 10% phosphate-buffered formaldehyde for at least 24
hours, tissue samples were automatically paraffin-embedded, sectioned at 3 mm, and
stained with hematoxylin and eosin (HE) for light microscopy.
necropsy, there was a unilateral mass of polycystic renal neoplasm resembling
an oversized kidney. On cut surface, the mass was heterogenous with whitish
admixed with some brownish structures, possibly remnants of the left kidney and
composed of cystic spaces separated by delicate septa with some parts contained
cartilaginous structures. Metastasis was not observed. Detailed histopathologic
investigation revealed heterogeneous mass consisted of highly pleomorphic
cells, which in most parts resembled primitive nephrogenic cells forming
primitive glomeruloid structures and cellular stroma. The neoplasm was composed
of a disorganized mixture of three distinct cell populations: the epithelial,
mesenchymal and blastemal cells. In consideration of the macroscopic and
histological findings, the tumor was classified as nephroblastoma closely
resembling the so-called Wilms’ tumor, a malignant embryonic renal tumor
frequently observed in humans, especially in young children.
This tumor growth
in a healthy kidney tissue and form a pseudo-capsule. It has a macroscopic
boundaries which is clearly covered by kidney tissue. Following infiltration of
the tumor into the kidney tissue, it then spread into perirenal tissue before
metastasize to distant organs. Wilms’ tumour can spread through connective
tissue, hematogenous and lymphogenous route. For connective tissue, it start
from the perirenal fat tissue then spread to the peritoneum and abdominal
organs (contralateral kidney, liver, etc.). For hematogenous route, it occurs
after tumor had growth and invade into the renal vein before metastasize to the
lungs (85%) and liver (10%) and then to the brain and bones. Through lymphogenous
route, the spreading occurs in the regional glands around abdominal aorta or in
mediastinum. Congenital abnormalities occur in 12% -15% of cases. The most
common congenital abnormalities are aniridia, hemihipertrophy,
Beckwith-Wiedemann Syndrome, and genitourinary tract abnormalities, including
WAGR syndrome, and Denys-Drash syndrome.
tumor is composed of persistent blastema, dysplasia tubules (epithelium), and
supporting mesenchymal tissue (stroma). The presence of epithelial cells,
blastema, and stroma in one histological picture is called triphasic and is a
characteristic of classic Wilms tumor. Each type of cell can display spectrum
of differentiation, generally replicating the variable stage of renal
embryogenesis. The proportion of each cell type can also vary between one
tumors from another 11. Some Wilms tumors are biphasic or even monomorphic.
Wilms’ tumor are divided into well differentiated (favorable) and poorly
differentiated (unfavorable or anaplastic). The histologic picture of well
differentiated tumor is often found (89%) and is characterized by the presence
of three components as already stated previously epithelial cells, blastema,
and stroma. Histologic features of poorly differentiated are less common (less
than 10%) and illustrated by the presence of anaplasia. Anaplasia is
characterized by the presence of a giant polypoid nucleus in tumor samples. Few
criteria must be meet to determine the presence of anaplasia. First, the
nucleus must have a primary diameter of at least three times of adjacent cells,
with increased chromatin. Second, it must have multipolar features or other
identifiable polypoid mitotic features.
Anaplasia can be
focal or diffuse. Criteria for differentiating focal and diffuse anaplasia
depending on the spread of anaplasia. Focal anaplasia is indicated by changes
in anaplastic nucleus which are limited in primary tumors. This definition
limits focal anaplasia to one or several separate loci in primary and tumor
without anaplasia or other atypical nuclei. The diagnosis of diffuse anaplasia
must meet a few the criteria. First is extra renal anaplasia, including blood vessels
in the renal sinuses, extracapsular infiltration, gland metastases or distant
metastases. Second is anaplasia on randomized biopsy of the specimen. Third, acute
anaplasia in one region of the tumor, but with the pleomorphism of the nucleus
extreme approach to other naplasia criteria on lesions. Lastly is anaplasia in
more than one tumor preparation, except it is known that each preparation shows
anaplasia originating from the same region on the tumor and the focus of
anaplasia on some amounts of preparations little and surrounded entirely by
Wilms tumor is a
primary renal tumor most commonly found in childhood. Clinical symptoms can be
found between another belly bulge due to mass abdomen, hematuria, hypertension,
anemia, pain stomach, fever, and signs of a channel infection urine. Abdominal
ultrasound is an imaging technique the most often done to enforce the diagnosis
of Wilms tumor. Management including surgery, radiotherapy and chemotherapy.