(Kidney tumors-1)

1. DR NOOPUR S. PATIL
JR1 PATHOLOGY
MIMSR,LATUR
RENAL PEDIATRIC
TUMORS

2. Kidney tumors in infants and children (WHO):
Nephroblastic tumors:
• Nephroblastoma
• Nephrogenic rests and nephroblastomatosis
• Cystic nephroma and cystic partially differentiated nephroblastoma
• Metanephric tumors
• Metanephric adenoma
• Metanephric adenofibroma
• Metanephric stromal tumor
•Mesoblastic nephroma:
•Clear cell sarcoma
•Rhabdoid tumor of kidney
•Renal epithelial tumors of childhood:
• Papillary renal cell carcinoma
• Renal medullary carcinoma
• Translocation associated RCC (Xp11.2 / t(6;11) translocations)
•Rare tumors:
• Ossifying renal tumor of infancy
• Angiomyolipoma

3. Wilms’ tumor (nephroblastoma)
• Comprises > 80% of renal tumors of childhood.
• More common in children of 2 – 4 years.
• Slight predominance in females.
• Tumors are bilateral in 4.4 % of cases.
• Deletion or suppression of WTI Or WTII locus on
chromosome 11 leads to various syndromes

4. Increased association with four syndromes:-
1. WAGR syndrome : aniridia, genital anomalies, mental retardation;
deletions of 11p13 (WT1 gene)
2. Denys-Drash syndrome- higher risk for Wilm's tumor (∼90%); gonadal
dysgenesis (male pseudohermaphroditism) and early-onset nephropathy;
dominant-negative missense mutation in the zinc-finger region of the WT1
gene and increased risk for gonadoblastomas (WT1- critical for normal renal
and gonadal development)
3. Beckwith-Wiedemann syndrome (BWS) -"WT2”gene ,genomic
imprinting ; overexpression of IGF-2 (embryonal growth factor) is critical ;
Organomegaly, macroglossia, hemi-hypertrophy, omphalocele, adrenal
Cytomegaly(due to growth of abnormal cells),renal medullary cysts.
4. β-catenin associated Wilms tumors - belong to WNT (wingless) signaling
pathway; 10% of sporadic cases, gain-of-function mutations.

5. GROSS:-
 Tumor is large >5 cm in diameter
 1/3 or more are > 10 cm
 Weighs >500 gm
CUT SURFACE:-
- Solid, soft, grey or pink, resembling brain tissue.
- foci of haemorrhage & necrosis are present and cysts
are common.
-enclosed by a prominent pseudocapsule composed of
compressed renal & perirenal tissues. This gives
appearance of true encapsulation.

7. G/E– Soft, homogenous, tan to grey in color.
Areas of hemorrhages ,cyst formation & necrosis.

8. Microscopy :
• Wilms tumors are composed of variable
mixtures of blastema, epithelium and stroma.
• Blastema consists of densely packed small
cells arranged in sheets.
• These cells have darkly stained nuclei and
inconspicuous cytoplasm resembling other
small blue cell tumors of childhood.
• Frequent mitotic figures are seen.

9. 1)Stromal-Usually fibrotic or myxoid in nature with Paler type of cells.
2)Blastemal-Bunch of less differentiated.
3)Epithelial-Form of abortive tubules or glomeruli as epithelial rosettes

10. • Epithelial component: consists of small tubules or cysts
lined by primitive columnar or cuboidal cells.
• Their nuclei are elongated and wedge shaped.
• Stromal component:
Loose myxoid fibroblastic spindle cell stroma are most
common.
- fetal rhabdomyomatous nephroblastoma.
• Positive stains:
•Blastema: WT1, desmin but not other muscle markers ,
focal vimentin
•Epithelium: WT1, keratin and EMA; tubules are CD57+
•Stroma: weak WT1; other stains consistent with morphologic
appearance (myogenin if rhabdomyoblastomatous, S100 if
neural, etc.)

13. Predominantly cystic Wilms tumors contain blastemal &
other wilms tumor tissues in their septa & have been
designated as :
“CYSTIC PARTIALLY DIFFERENTIATED NEPHROBLASTOMA”.

14. Favorable Histology (85%):
• Triphasic composition
– Metanephric blastema
– Immature stroma
– Tubular elements
• Good prognosis if triphasic.
Unfavorable” Histology (15%):
• Anaplastic changes
– Nuclear enlargement > 3x size
–Hyperchromatic nuclei
– Atypical mitotic figures
 Implies poor prognosis & resistance to
conventional therapy

15. Anaplasia:
• marker of unfavorable histology; associated with poor treatment response;
defined as hyperchromatic, pleomorphic nuclei that are 3× larger than adjacent cells
and have abnormal mitotic figures
•Focal anaplasia: all conditions must be met:
• (a) no anaplasia in tumor within renal vessels or outside kidney;
• (b) random biopsies are free of anaplasia;
• (c) anaplasia confined to sharply localized regions within primary intrarenal
tumor site; and
• (d) each focus of anaplasia must be surrounded on all sides by nonanaplastic
tissue, which does not show severe nuclear unrest
•Diffuse anaplasia: any conditions met:
• (a) anaplasia in tumor in any extrarenal site, including vessels of renal sinus,
extracapsular infiltrates, metastases or intrarenal vessels;
• (b) anaplasia in random biopsy; or
• (c) anaplasia unequivocally present in 1 region of tumor with extreme nuclear
unrest elsewhere

16. Clinical features —
Hematuria,Pain,fever(15-30%)
Large abdominal mass(90%)
Intestinal obstruction
Hypertension
Pulmonary metastasis
90 % long term survival .
Even metastasis can well treated with latest treatment

17. Childrens oncology group staging of pediatric renal neoplasms:
•Stage I (43%):Tumor limited to kidney and completely resected
•Renal capsule intact, tumor not ruptured or biopsied prior to removal, no residual
tumor beyond margins of resection, no tumor within renal vein and no nodal
involvement or distant metastases
Stage II (23%):Tumor extends beyond kidney but is completely resected
•Regional extension of tumor (vascular invasion outside of renal parenchyma or within
the renal sinus or capsular penetration but with negative surgical margin), no nodal or
distant metastases
Stage III (23%):Residual tumor or nonhematogenous metastases confined to
abdomen
•Metastases may be to regional lymph nodes, peritoneal tumor contamination and / or
implants
•Gross or microscopic tumor present postoperatively (i.e. positive resection margins),
tumor spill before or during surgery, presurgical biopsy (including FNA) and removal of
tumor in > 1 piece
Stage IV (10%):Hematogenous metastases or spread beyond abdomen
Stage V (5%):Bilateral renal involvement (substage each tumor separately according
to above criteria)

18. Wilms Tumor: Treatment:
• En bloc resection of affected kidney
 Excision of nodes and lung nodules
 Postop chemotherapy
 Preoperative chemotherapy for invasive disease or
bilateral Wilms, then surgery
 For all stages 2-year survival of 90%

19. DIFFERENTIAL DIAGNOSIS:
•Neuroblastoma: no triphasic patterns; has rosettes with no
lumen, > 1 cell layer, no distinct basal lamina; Wilms immature
tubules have a lumen, a single cell layer, distinct basal lamina
and surrounding fibromyxoid stroma.
•Perilobar nephrogenic rest: no fibrous capsule.
•Renal cell carcinoma: may resemble epithelial predominant
Wilms.
•Other small blue cell tumors: if blastema predominates

20. Mesoblastic nephroma
• Congenital myofibroblastic tumor that resembles infantile
fibromatosis / leiomyoma (classic) or fibrosarcoma
(cellular)
• Also called FETAL MESENCHYMAL /
LEIOMYOMATOUS HAMARTOMA
• Most common pediatric renal tumor in infancy
• 5% of all pediatric renal tumors.
• Age at presentation varies with type (classic, 16 days;
cellular, 5 months; mixed, 2 months)
• Rarely occurs in children older than 2 years of age
• Frequency: 66% cellular, 24% classic and 10% mixed
 Associated with polyhydramnios and prematurity.

21. Gross:-
• Large. External surface is smooth and bossellated.
• Renal capsule and calyceal systems are stretched over
the tumor.
• Cut surface : Firm, whorled, yellow tan. Resemble
Leiomyoma.
• Extension into the surrounding tissue is seen.

22. Tan fleshy masses with hemorrhage, necrosis and cystic degeneration

23. Whorled, myomatous appearance with prominent medial
extension (arrow) and an ill-defined margin. Very little normal
kidney remains visible.

24. Microscopic features
• Classical pattern: Moderately cellular proliferation of thick
interlacing bundles of spindle shaped cells with elongated nuclei.
• Entrapment of glomeruli and renal tubules is common.
• Mitotic figures in the range of 0-1/hpf.
 Cellular pattern: consists of densely cellular proliferation of
polygonal cells.
 Mitotic figure: 8 – 30 / hpf.
 Cysts are more common.
Positive stains:-
• Smooth muscle actin, vimentin
• Also renin (within tumor vessels or vessels in trapped cortex)
• Occasionally WT1 , INI1

25. This intermediate power view shows intersecting bundles of spindle cells creating an
appearance reminiscent of fibromatosis. Entrapped glomeruli and tubules can also
be seen.

26. Differential diagnosis:-
•Adult mixed epithelial and stromal tumor: mean age in 50s, usually
women, similar morphology and staining pattern, also positive for estrogen
and progesterone receptors
•Clear cell sarcoma: similar age but has clear cells and chicken wire
vasculature, tumor cells isolate single nephrons, fine nuclear chromatin
and low mitotic rate; negative for smooth muscle markers
•Metanephric stromal tumor: older age, nodular low power pattern, onion
skin cuffing around entrapped renal tubules, heterologous differentiation
and vascular changes, CD34+
•Rhabdoid tumor: more invasive margins, usually epithelioid cells with
cytoplasmic inclusions and prominent nucleoli, usually presents with
metastases, INI1-ve
•Wilms tumor: older age, also has blastema and nephrogenic rests;
previously treated tumors may have well differentiated spindle cell stroma

27. Clear cell sarcoma:-
• Bone metastasizing renal tumor.
• Comprises 6% of paediatric renal tumors.
• Most common between 12 – 36 months.
• More common in males ( 66% ).
• Also known as melanoma of soft parts
• Deep soft tissues of extremities, trunk or limb
girdles, tends to occur near tendon, fascia or
aponeuroses- extra renal sites.
• Slow progression, frequent local recurrences;
eventually nodal and distant metastases
• 5 year overall survival is 63%
• Size is most significant prognostic factor

28. Gross features:-
• Well circumsribed, weighing > 500 gms.
• Grey tan, large, soft , focally cystic and
necrotic.
• Occasionally the tumor produce abundant
mucin- glistening appearance.
• Bilaterality has not been reported.

30. Microscopic features:-
• Monotonous sheets of cells with light staining or
vacuolated cytoplasm, with indistinct cell borders.
• Nuclei contain dispersed chromatin and small
nucleoli.
• Cells arranged in chords, separated by septa;
composed of spindle shaped cells with dark nuclei
and branching pattern of small blood vessels.
• Infiltrative border- characteristic.
• Mean 4 MF / 10 HPF
Positive stains:-
• S100, HMB45, microphthalmic transcription
factor 75%, melanoma cell adhesion
molecule, MelanA (43%), iron (intra- and
extracellular), Leu7 / CD57, vimentin, keratin

33. Rhabdoid tumor of kidney:-
• Most commonly – 11 months of age. Rare
after 3 years.
• More common in boys.
• Metastases widely and causes death within 12
months of diagnosis.
• Very aggressive; 82% present with metastases;
90% die in 2 years
• Usually stage 2 or higher; 9% are bilateral

34. Gross:-
• Yellow grey fragmented tumor with indistinct
borders.
• Located medially in the kidney and renal sinus
and pelvis are infiltrated.
• It is unencapsulated.
• Necrosis & hemorrhage are common.

37. Microscopic features:-
• Diffuse, monotonous, medium or large polygonal
cells, with abundant eosinophilic cytoplasm &
round nuclei with thick nuclear membrane and
large nucleoli.
• Often cytoplasm contains large eosinophilic
globular inclusions that displaces the nuclei.
• Chromatin is clear / vesicular with central, large
nucleoli
• Occasionally cells are spindled; variable necrosis
and mitoses

38. Discohesive rhabdoid cells with eccentrically placed nuclei, prominent
nucleoli and densely eosinophilic cytoplasm

39. The rhabdoid appearance refers to large polygonal epithelioid
cells with eccentric vesicular nuclei, prominent nucleoli, and
abundant eosinophilic cytoplasm with paranuclear PAS+ve hyaline inclusion or
globule.

40. Differential diagnosis:-
• Wilms tumor.
• Congenital mesoblastic nephroma.
• Renal cell carcinoma.
• Oncocytoma.
• Rhabdomyosarcoma.

41. Ossifying Renal Tumor of Infancy
 Rare tumor of uncertain histogenesis.
 Common in < 6 months of age.
 Haematuria is the presenting symptom.
 X ray – calcified mass in the renal collecting
system or pelvis.
 Clinical course is benign though there is an
irregular infiltrative border.

42. Gross:-
• Tumor- stony hard, projects into the lumen of renal pelvis.
Microscopic features:-
 Spicules of osteoid are separated by chords of epitheloid
cells with abundant pale cytoplasm and small vesicular
nuclei.
 Mitotic figures are uncommon.

43. osteoid core (O) with a peripheral tubule (T) and
mesenchyme or fibrous connective tissue.

45. Angiomyolipoma:-
• Benign neoplasm composed of fat, smooth muscle, thick
walled blood vessels.
• Most of the patients are adults. Half are associated with
tuberous sclerosis and half occur sporadically.
• 80 % of patients with tuberous sclerosis have renal
angiomyolipomas.
 Positive for actin, HMB 45, Melanin 1, GP-100,
tyrosinase, CD 117, and hormone receptors like
estrogen and progesteron.

46. Gross
 Less than 1 cm upto 20 cm.
 Tumor depends on relative amounts of various
components with admixture of yellow areas and
haemorrhagic areas.
 Capsular invasion may be present and also
extension into peri renal soft tissues can be seen.
 Tumors are multiple in 1/3 rd of cases and
bilateral in 15 % of cases.

48. Microscopy
 Mature adipose tissue, tortuous thick walled blood
vessels and bundles of smooth muscle that seem to
emanate from the vessel wall.
 The smooth muscle cells occasionally have epitheloid
features with abundant eosinophilic cytoplasm and
hyperchromatic bizarre nucleus, currently known as
PEC ( Perivascular epitheloid cell).
 Nuclear pleomorphism and mitotic figures may be
present.

49. Angiomyolipomas are composed of variable amounts of adipose
tissue, smooth muscle, and thick-walled blood vessels.

50. HMB-45