3. Mesenchymal tumours
occurring mainly in children
Clear cell sarcoma
Rhabdoid tumour
Congenital mesoblastic nephroma
Ossifying renal tumour of infancy
4. CLEAR CELL SARCOMA (BONE –
METASTASIZING RENAL TUMOUR OF
CHILDHOOD)
Clear cell sarcoma of the kidney (CCSK) is an uncommon
renal sarcoma of uncertain histogenesis, occurring in children
CCSK constitutes approximately 3% of all malignant renal
tumours in childhood
Macroscopy
CCSKs are typically large (with a mean diameter of 11.3
cm) and centred in the renal medulla.
Tumours are unencapsulated but circumscribed, tan,
soft, and mucoid, and usually focally cystic.
5. Microscopy
The classic pattern of CCSK is characterized by
nests or cords of cells separated by regularly spaced,
arborizing fibrovascular septa.
The cord cells may be epithelioid or spindled, and
are loosely separated by extracellular myxoid material
that resembles clear cytoplasm.
The nuclei are round to oval shaped , have fine
chromatin, and lack prominent nucleoli
CCSKs are grossly circumscribed , but they
characteristically have subtly infiltrative borders,
entrapping isolated native nephrons.
6.
7. Bone metastases were once the most common mode of recurrence,
but brain metastases are now more common, likely because the
blood-brain barrier impedes effective chemotherapy
Perirenal lymph node metastasis is present in almost 30% of cases at
diagnosis.
8. RHABDOID TUMOURS
Rhabdoid tumour of the kidney is a highly invasive and
highly lethal neoplasm of young children.
It is composed of cells with vesicular chromatin, prominent
nucleoli, and hyaline intracytoplasmic inclusions.
Rhabdoid tumours account for approximately 2% of all renal
neoplasms in children. The mean patient age at diagnosis is
approximately 1 year.
Macroscopy
The tumours are typically large, haemorrhagic, and
necrotic, with poorly defined borders that reflect their
highly invasive nature.
9. Histopathology
These tumours are unencapsulated.
Sheets of relatively uniform malignant round cells
aggressively overrun native nephrons.
Vascular invasion is usually extensive.
Rhabdoid tumour cells characteristically display the
cytological triad of vesicular chromatin, prominent cherry
red nucleoli, and hyaline pink cytoplasmic inclusions.
10. The presence of characteristic hyaline inclusions is often accentuated on
vimentin or cytokeratin immuno stains. Loss of SMARCBI (also known as I Nll,
hSNF5, or BAF47) on immunohistochemistry is a sensitive and specific marker
of these . neoplasms
11. Genetic profile
•Biallelic inactivation of the SMARCB1 tumour suppressor gene,
which resides on the long arm of chromosome 22, is the
molecular hallmark of rhabdoid tumour of the kidney
Prognosis and predictive factors
Outcome is typically dismal; with > 80% of patients dying of
tumour within 2 years of diagnosis
12. CONGENITAL MESOBLASTIC
NEPHROMA
Congenital mesoblastic nephromas (CMNs) are low-grade
fibroblastic neoplasms of the infantile renal sinus. They are
subclassified into classic and cellular types
CMN constitutes 2-4% of all paediatric renal tumours . It is
the most common congenital renal neoplasm, and 90% of
cases occur in the first year of life.
Macroscopy
All CMNs arise in the medial renal sinus. Classic CMN has
a firm, whorled texture, whereas cellular CMNs are more
typically soft, cystic, and haemorrhagic.
13. Histopathology
Classic CMN (accounting for 24% of cases) is
morphologically identical to infantile fibromatosis of the
renal sinus .
Tumours are composed of interlacing fascicles of
fibroblastic cells with thin, tapered nuclei, pink cytoplasm,
low mitotic activity, and abundant collagen deposition .
tumour dissects and entraps islands of renal parenchyma.
Cellular CMN (accounting for 66% of cases) is
morphologically identical to infantile fibrosarcoma. These
tumours have a pushing border and are composed of
poorly formed fascicles that give way to sheet like growth
patterns. The tumour shows a high mitotic rate and often
features necrosis
These tumours are often immunoreactive for actin and
uncommonly for desmin. They are non-reactive for CD34.
Ultrastructural ly, the tumours have features of
myofibroblasts or fibroblasts.
14. Genetic profile
Classic CMNs are typically diploid, but cellular CMNs often demonstrate
aneuploidy of chromosomes 11, 8, and 17
Unlike classic CMN, cellular CMN has a specific chromosomal translocation,
t(1 2; 1 5)(p1 3;q25), which results in a fusion of the ETV6 and NTRK3 genes
ETV6 is an ETS transcription factor previously implicated in
translocations in paediatric B-cell acute lymphoblastic leukaemia.
NTRK3 is a tyrosine kinase receptor that responds to extracellular
signals. The fusion product is a constitutively active tyrosine kinase that
promotes cellular growth via multiple downstream pathways
Prognosis and predictive factors
When completely excised, CMN is associated with an excellent prognosis.
15.
16.
17. OSSIFYING RENAL TUMOUR
OF INFANCY
Ossifying renal tumour of infancy (ORTI) is an intracalyceal
mass composed of osteoid trabeculae, osteoblast-like cells,
and a spindle cell component The tumours arise from and are
attached to the medullary pyramid.
ORTI is extremely rare
Male predominance, and patient age at presentation ranges
from 6 days to 2 years.
18. Macroscopy
ORTI is grossly well circumscribed and typically
1-6 cm in diameter
Histopathology
ORTI has three major components: an osteoid core,
osteoblastic cells within and at the periphery of the
osteoid, and bland spindle cells.
Prognosis and predictive factors
The outcome have been uniformly favourable, and
conservative surgical management is the treatment of choice.
19.
20. Mesenchymal tumours
occurring main ly in adults
Leiomyosarcoma (including renal vein lelomyosarcoma)
Renal leiomyosarcoma is rare, accounting for < 1 % of all renal malignancies
There is no sex predilection and no known predisposing conditions.
Macroscopy
This tumour arises from the renal capsule, renal parenchyma, pelvic muscular
wall, or main renal vein
Large, solid, greyish white, soft to firm, and variably necrotic
Histopathology
The morphological features of renal leiomyosarcoma are identical to those of
leiomyosarcoma arising at other sites and include a fascicular, plexiform, or
haphazard growth pattern of spindle, epithelioid, and pleomorphic cells.
Low-grade tumours resemble differentiated smooth muscle cells but with
increased cellularity, cytological atypia, and mitotic activity.
High-grade tumours are pleomorphic, requiring immunohistochemical stains
and adequate sampling to distinguish from other malignancies such as
sarcomatoid carcinoma with leiomyosarcomatous differentiation and other
pleomorphic sarcoma
.
21. Prognosis and predictive factors
Renal leiomyosarcoma is aggressive, with a 5-year survival rate of < 36%.
Most patients die of disease within 1 year of diagnosis, with metastasis to
lung, liver, and bone
22. Angiosarcoma
Macroscopy
Renal angiosarcomas are typically large necrotic tumours, ranging from 10
to 30 cm in greatest dimension
Histopathology
Features identical to those of angiosarcoma at other locations. The tumours are
composed of mitotically active malignant endothelial cells that are at least
focally vasoformative.
In most tumours, spindled endothelial cells predominate, but tumours may be a
mixture of spindled and epithelioid cells or entirely epithelioid
Necrosis is a common finding
Renal angiosarcoma is a poorly differentiated malignancy requiring
immunostains to differentiate from highgrade renal cell carcinoma, epithelioid
angiomyol ipoma, and other sarcomas.
Tumours are immunoreactive for at least one endothelial marker, such as CD3 1
, CD34, ERG, or FLl 1 . Angiosarcoma, particularly epithelioid angiosarcoma, may
stain for cytokeratin
24. Rhabdomyosarcoma
Rhabdomyosarcoma is a malignant tumour composed of cells
with various degrees of skeletal muscle differentiation
Embryonal rhabdomyosarcoma Alveolar
rhabdomyosarcomaPleomorphic rhabdomyosarcoma
Spindle cell /sclerosing rhabdomyosarcoma
Most cases are of embryonal type, often with anaplasia.In a
paediatric renal tumour, it is far more likely that well-
differentiated rhabdomyoblasts with prominent eosinophilic
cytoplasm represent heterologous differentiation in a
nephroblastoma rather than rhabdomyosarcoma. Isolated cases
in adults are usually of pleomorphic type and thorough
sampling is necessary to exclude sarcomatoid carcinoma with
heterologous differentiation.
25. Osteosarcoma
Osteosarcoma is a neoplasm composed of malignant cells forming
osteoid or bone.
It occurs in adults > 40 years of age, with a male-to-female ratio of
1. 7: 1. Early local recurrence and metastatic spread (particularly to
the lung) are common
Macroscopy
The tumour is firm and whitish, with areas of calcification, haemorrhage,
or necrosis. Osteosarcoma is mainly cortical , commonly with extension
to the perinephric/hilar fat.
Histopathology
The morphological features of primary osteosarcoma of the kidney are
the same as those of osteosarcomas in more common osseous sites.
26. Prognosis is poor, with a mean survival of 15 months despite aggressive
triple combination therapy
27. Synovial sarcoma
Renal synovial sarcoma is a malignant mesenchymal tumour that
rarely displays epithelial differentiation
Patient age ranges from 13 to 78 years. There are no known
predisposing conditions and no sex predilection
Macroscopy
Tumours are unilateral , solid, and 2-19 cm in size. They variably show
haemorrhage, necrosis, and cyst formation.
Histopathology
Most synovial sarcomas are monophasic; composed entirely of infiltrative small
hyperchromatic spindle cells with scant cytoplasm and indistinct cell borders
arranged in short, intersecting fascicles or in sheets.
Tumours can entrap native renal tubules, some of which become cystically
dilated. Renal synovial sarcoma showing epithelial differentiation (the biphasic
type) is rare, and poorly differentiated synovial sarcoma
29. Ewing sarcoma
Peripheral neuroectodermal tumour and Ewing sarcoma are
closely related small round cell sarcomas, defined in almost
all cases by EWSR1 fusion with a member of the ETS gene
family
Ewing sarcoma is rare in the kidney. The median patient age
is 20 years and the male-to-female ratio is 3: 1
Histopathology
Renal Ewing sarcoma is morphologically
indistinguishable from its counterparts in bone and soft
tissue.
In rare cases, poorly formed rosette-like structures are
present.
Mitoses and necrosis are common.
Diffuse membranous CD99 positivity in almost all
tumour cells is characteristic.
30.
31. Angiomyolipoma
Angiomyolipoma is a benign mesenchymal tumour
composed of variable proportions of adipose tissue,
spindle cells, epithelioid smooth muscle cells, and
abnormal thick-walled blood vessels. It belongs to a family
of lesions called perivascular epithelioid cell tumours
(PEComas)
Angiomyolipoma can occur sporadically or in patients with
tuberous sclerosis.
Angiomyolipomas constitute approximately 1 % of
surgically removed renal tumours
Localization
Angiomyolipomas may arise in the cortex or medulla of
the kidney, as well as in the retroperitoneal soft tissue, with
or without renal attachment. The lesions may be multifocal
Simultaneous occurrence of angiomyolipoma with renal
cell carcinoma and oncocytoma in the same kidney has
also been reported
32. Macroscopy
Well demarcated from the adjacent kidney, but not encapsulated
The colour varies from yellow to pinkish tan, depending on the relative proportions of the various
tissue components.
A tumour composed of all three components may resemble a clear cell renal cell carcinoma,
whereas a smooth muscle-predominant angiomyolipoma may resemble a leiomyoma
Histopathology..
Most angiomyolipomas are composed of a variable mixture of mature fat, thickwalled poorly
organized blood vessels, and smooth muscle (the classic triphasic histology).
Smooth muscle cells appear to emanate from blood vessel walls in a radial pattern.
Component composed of cells associated with thin-walled, branching vessels with a pattern
similar to lymphangioleiomyoma
Lipomatous component typically consists of mature adipose tissue but may contain
adipocytes suggesting lipoblasts, resembling a liposarcoma
Oncocytoma-like angiomyolipomas are rare tumours consisting of a homogeneous population
of polygonal cells with strongly eosinophilic cytoplasm. They have been described in patients
with and without tuberous sclerosis
Small nodules with some features of angiomyolipoma (so-called microhamartomas) are often
present in kidneys bearing angiomyolipomas, suggesting that these lesions may be the source
angiomyolipomas.
The smallest nodules are often composed predominantly of epithelioid smooth muscle cells,
and the proportions of spindle cells and adipocytes increase as the lesions grow Iaege
33.
34. Lmmunophenotype
Angiomyolipomas are characterized by coexpression of melanocytic markers
(HMB45, melan A, and microphthalmia transcription factor) and smooth muscle
markers (smooth muscle actin and calponin).
CD68, S100 protein, estrogen and progesterone receptors, and desmin may also
positive, whereas epithel ial markers are always negative
Cathepsin K, a papain-like cysteine protease, is the target of the microphthalmia-
associated transcription factor family, and has recently been found to be highly
expressed in the entire spectrum of perivascular epithelioid cell lesions of the
kidney, including all the morphological variants of angiomyolipoma
Genetic profile
The alterations of two genes are known to cause tuberous sclerosis. The TSC1 gene is located
on chromosome 9q34, consists of 23 exons, and encodes hamartin, a 130 kDa protein . The
TSC2 gene is located on chromosome 16p13, consists of 41 exons, and encodes tuberin, a 1 80
kDa GTPase-activating protein for RAS-related protein 1 and Rab protein 5 . Tuberin and
hamartin interact with each other, forming a cytoplasmic complex
Prognosis and predictive factors
Classic angiomyolipomas are benign. A very small minority are associated with
complications and morbidity and mortality
35. Epithelioid angiomyolipoma
Epithelioid angiomyolipoma is a rare variant of angiomyolipoma that consists of at
least 80% epithelioid cells
Macroscopy
The tumours are usually large, with infiltrative growth and a greyish-tan , white, brown,
or haemorrhagic appearance.
Necrosis may be present.
Extrarenal extension or involvement of the renal veins or venae cavae may occur
Histopathology
Epithelioid angiomyolipoma can show two different morphological patterns.
Some tumours are characterized by the presence of large polygonal cells with dense,
deeply eosinophilic cytoplasm and atypical nuclei with prominent nucleoli arranged in
cohesive nests and compartmentalized sheets separated by thin vascular-rich septa.
Some of these tumours have >2 mitoses per 50 high-power fields, but the majority
have no mitoses or only 1 mitotic figure per 50 high-power fields.
The other pattern of epithelioid angiomyolipoma consists of epithelioid and plump
spindled cells arranged in diffuse and densely packed sheets
These neoplasms usually have no mitotic activity.
36.
37. Leiomyoma
Leiomyoma is a benign smooth muscle tumour.
Clinical features Two thirds of the cases occur in females, and patient age at
presentation ranges from second to sixth decades
Macroscopy
Most tumours are small and are incidentally detected
Histopathology
The gross and microscopic features are similar to those of the tumours'
counter parts in soft tissues and other organs
38. Haemangioma
Macroscopy
Renal haemangiomas are unencapsulated and
circumscribed , with a spongy red appearance.
They have mean size of 2 cm, but tumours as large as 18
cm have been reported
Histopathology
Both the capillary and cavernous types of haemangiomas
have been reported in the kidney, but most of these
tumours are capillary haemangiomas, which are
characterized by a circumscribed proliferation of
capillary-sized blood vessels that often entrap renal
tubules
40. Lymphangioma
Lymphangioma is a rare benign renal tumour that arises from
lymphatic channels or is the result of developmental malformations
of the lymphatic system
Epidemiology and clinical features
One third of renal lymphangiomas occur in children and two thirds occur in adults.
Unilateral or bilateral multiple lymphangiomas can occur, and are referred to as
lymphangiomatosis
Macroscopy
Lymphangiomas are encapsulated unilocular to complex multilocular thin walled
cystic tumours ranging from 0 a few centimetres in size up to 19 cm and replacing the
kidney
Histopathology
The tumours are composed of thin walled cysts lined by flattened endothelial cells
and divided by fibrous septa.
The lining cells are immunoreactive for CD31 , CD34, podoplanin, and other
endothelial markers, and are negative for cytokeratin.
41. Haemangioblastoma
Haemangioblastoma is a tumour similar in morphology to capillary
haemangioblastoma of the central nervous system. It consists of stromal cells and
abundant capillaries.
Haemangioblastoma is most commonly seen in the cerebellum. Rarely, tumours
are extracranial
Macroscopy
The tumours range in size from 1.2 to 6.8 cm (with a mean diameter of 4.1
cm) and are well circumscribed and often encapsulated.
Histopathology
The tumours are well demarcated and cellular, consisting of sheets and
occasionally lobulated nodules of ovoid cells. Most tumours show mild
pleomorphism, although occasional bizarre nuclei are present. The cytoplasm
is pale to eosinophilic.
The tumour cells are set in an arborizing network of thin-walled vessels,
which may be ectatic.
lmmunohistochemistry shows positive expression of neuron-specific enolase,
S100 protein, GLUT1 , and vimentin
43. Juxtaglomerular cell tumour
Juxtaglomerular cell tumour is a rare renin-secreting
neoplasm arising from the specialized smooth muscle of
the glomerular afferent arteriole in the juxtaglomerular
apparatus of the kidney.
Macroscopy
Juxtaglomerular cell tumour is a circumscribed
yellowish-tan mass fully or partially surrounded by a
fibrous capsule.
Histopathology
These tumours are composed of relatively uniform
polygonal to spindle cells with central round uniform
nuclei and variable amounts of eosinophilic cytoplasm.
The tumours contain a prominent vasculature that
consists of numerous small thin walled vessels and
clustered thick-walled vessels that are often hyalinized.
Cytological atypia and necrosis can be seen, but are
not associated with malignant behaviour
The tumours are immunoreactive for renin, vimentin,
45. Renomedullary interstitial cell tumour
Etiology
These tumours arise from renomedullary interstitial cells, which play a role
in the release of renin and regulate sodium excretion
Macroscopy
Most renomedullary interstitial cell tumours are 1-10 mm in diameter
Typically appear as white or pale-grey nodules within the renal medulla
Histopathology
Microscopically, the tumour cells are small, stellate, or spindled cells,
embedded in a faintly basophilic stroma reminiscent of renal medullary
stroma.
Occasionally, the stroma can be densely collagenized.
Some renomedullary interstitial cell tumours contain deposits of amyloid.
Normal renal tubules can be entrapped , particularly at the periphery of the
lesion
47. Schwannoma
Schwannomas are uncommon benign tumours that arise from the neural sheath
of peripheral and cranial nerves
Rare in kidney.Within the kidney, cases have been described involving the renal
parenchyma, hilum, renal pelvis, and renal capsule.
Haematuria may also be present
Macroscopy
well-circumscribed , sometimes lobulated , rounded masses. They are 4-16
cm in diameter (with a mean diameter of 9.7 cm) and vary in colour from tan
to yellow
Microscopy
Microscopically, renal schwannoma is composed of spindle cells, often
arranged in a palisading pattern (called Antoni A pattern) along with less-cel l
ular, loosely textured tumour areas with ectatic vessels and surrounding
hyalinization (called Antoni B pattern)
All cases express S100 protein by immunohistochemistry and lack markers of
epithelial differentiation.
48. Solitary fibrous tumour
Intrarenal solitary fibrous tumour is a rare neoplasm, with only about 40
cases reported
Most tumours follow a benign clinical course
Macroscopy
Patients usually present with large tumours, having a mean
diameter of 8.75 cm
Histopathology
The histological appearance of intrarenal solitary fibrous tumour is
the same as that of solitary fibrous tumours at more common soft
tissue locations.
Fibroblast-like cells with variable cellularity in collagenous, keloid-
like stroma, reticulin fibers, hemangiopericytoma-like vessels
The tumours are usually positive for STAT6, CD34, CD99, and Bcl2.
