Subclassification into type 1 and type 2 is no longer recommended. PRCC has classic morphology historically in type 1 category. Criteria of foamy histiocytes and psammoma bodies is not required. Many tumors previously diagnosed as type 2 PRCC now constitute independent entities

1. KIDNEY TUMORS

2. PAPILLARY RCC
Subclassification into type 1 and type 2 is no longer recommended.
PRCC has classic morphology historically in type 1 category.
Criteria of foamy histiocytes and psammoma bodies is not required.
Many tumors previously diagnosed as type 2 PRCC now constitute independent entities

3. PAPILLARY RCC
Arising from Renal cortex
Low grade tumors RET mutation
High grade tumors CDKN2A
Prognosis favorable
Positive for AMACR, Vimentin, CD10

5. PAPILLARY NEOPLASMS WITH REVERSE POLARITY
• Another pattern of PRCC is characterized by thinly branching papillae and low-
grade oncocytic tumour cells with nuclei aligned towards the apex of the cell.
• They appear to be consistently positive for GATA3 and negative for vimentin,
with labelling for AMACR being less extensive

11. MULTILOCULAR CYSTIC RENAL NEOPLASM OF LOW MALIGNANT
POTENTIAL
• Unilateral solitary tumors
• Asymtomatic and 90%tumors are detected incidentally
• Associated with VHL gene mutations
• Variable sized cysts filled with clear, gelatinous,serous or haemorrhagic fluid
• Cysts lined by optically clear bland looking cells.
• Presence of necrosis, frequent or atypical mitosis, lymphovascular invasion is incompatible with
this entity.

14. CLASSIFICATION OF PAEDIATRIC RENAL TUMORS

16. WILMS TUMOR
• Nephroblastoma is a malignant embryonal neoplasm derived from nephrogenic blastemal cells that
replicates the histology of developing kidneys and often shows divergent patterns of
differentiation.

17. WILMS TUMOR
• MC primary renal tumor of childhood.
• Peak age 2-5yrs.
• Clinical features abdominal mass, pain, hypertension
• 90% sporadic and 10% bilateral or multicentric(germline mutation)

18. CONDITIONS ASSOCIATED WITH NEPHROBLASTOMA

20. WILMS TUMOR
• Chromosome 11p13(WT1 gene)
WAGR syndrome(gene deletions)
Deny Drash syndrome(point mutations)
• Chromosome 11q15(WT2 gene)
Beckwith Weidman syndrome(gene deletions)

21. GROSS
• Large tumor compressing the normal renal parenchyma.
• Yellowish tumors with heterogenous appearance.

22. MICROSCOPY
• Triphasic combination
Blastemal- serpentine, nodular and diffuse WT1, Desmin
Stromal
Epithelial type- CK, EMA, WT1

23. HISTOLOGICAL CRITERIA FOR ANAPLASIA

24. Journal Indian Association Pediatric Surgeon. 2009 Jan-Mar; 14(1): 6–14

25. CLEAR CELL SARCOMA KIDNEY
A/K/A Bone metastasizing renal tumor of childhood.
BCOR mutations or YWHAE:NUTM2 gene fusion.
Centred in the renal medulla.
MC age group is less than 3yrs.
Despite their name clear cytoplasm should not be relied upon establishing the diagnosis.

26. CLEAR CELL SARCOMA KIDNEY
Gross- Homogenous, lobular with light pink soft areas.
Many histological patterns. Ovoid tumour cells with nuclear and/or cytoplasmic clearing at least
focally, distinctive arborizing fibrovascular septa

27. MIXED EPITHELIAL AND STROMAL FAMILY TUMORS
• MEST family of tumors show morphological spectrum ranging from variably solid to
predominantly cystic tumors(adult cystic nephroma) containing biphasic epithelial and stromal
components.
• Cystic nephroma and MEST are two different manifestations of the same basic process.

28. ADULT CYSTIC NEPHROMA
A/K/A Multilocular cystic nephroma.
Benign neoplasm in adult
Women> Men
Hormonal imbalance i.e. long term estrogen replacement in females and sex steroid exposure in
males.

29. ADULT CYSTIC NEPHROMA
Well circumscribed globular mass with fibrous capsule often close to renal hilum.
Multiple non communicating cysts without any solid areas.
M/E cyst wall lined by cuboidal or flattened epithelium with clear cytoplasm resembling ovarian
stroma.

32. PAEDIATRIC CYSTIC NEPHROMA
Almost exclusively occurs in children with higher prevalence in males
Similar macroscopic and microscopic findings
Septa contain fibrous tissue with focal hypercellularity and well differentiated tubules.
Most harbor DICER1 mutations.

33. XANTHOGRANULOMATOUS PYELONEPHRITIS
• Rare form of chronic pyelonephritis
• Associated with gram negative bacteria, obstruction,calculi and recurrent urinary
tract infections.
• Proteus and E.coli infection being most common.
• Presents with fever, flank or abdominal pain and gross hematuria.

34. XANTHOGRANULOMATOUS PYELONEPHRITIS
• Grossly enlarged kidney with dilated and pus filled calyces
• Irregular ill defined yellow masses is seen in the cortex.
• M/E foamy histiocytes with abundant clear cytoplasm admixed with inflammatory
infiltrate with variable number of multinucleated giant cells and microabcesses

35. XANTHOGRANULOMATOUS PYELONEPHRITIS
PAS + and Oil Red O +

36. • Malakoplakia kidney with PAS+ eosinophilic foamy
histiocytes(Von Hanseman histiocytes)
• Michalis gutmann bodies (PAS, Prussian blue and von kossa
stain positive)

38. AMYLOID KIDNEY
• Disorder characterized by extracellular deposit of misfolded proteins that
aggregate to form insoluble fibrils.
• Three forms are-
Amyloid light chain(AL)
Amyloid associated protein(AA)
β amyloid protein(Aβ)

42. AMYLOID KIDNEY
• Congo red- Apple green birefringence
• PAS- Schiff poor
• Trichrome- Blue gray
• Jones silver- negative

43. SITES OF BIOPSY
• Abdominal fat
• Rectal
• Gingiva
• Kidney

44. STAINS FOR AMYLOID
• Congo red- Pink or red, Apple green birefringence under polarizing microscope
• Van Gieson stain- Khaki color
• Alcian blue- Blue color
• Periodic acid Schiff-Pink
• Methyl violet and cresyl violet- Rose pink
• Thioflavin T- Yellow color

47. PUNLMP
• Papillary urothelial tumor, which resembles exophytic urothelial papilloma, but with increased
thickness &/or cell density of lining urothelium.
• Male predominance
• Gross or microscopic hematuria
• Urine cytology is usually negative
• Small and single exophytic papillary tumor

48. PUNLMP
• Mutations of the TERT promoter and FGFR3 have been reported
• The presence of TERT promoter mutation in PUNLMP may be associated with a
higher recurrence rate.

49. PUNLMP
• PUNLMP represents a urothelial neoplasm with branching papillary structures lined by thickened
urothelium.
• Difference is the cells are monotonous, with mild cellular and nuclear enlargement and without
variation in nuclear size, shape, or chromatin pattern in PUNLMP

50. NEW SUBTYPE OF PUNLMP
• An inverted growth pattern has been increasingly recognized and "inverted PUNLMP" is
considered an acceptable diagnostic category for tumours that do not meet the architectural criteria
of inverted papilloma yet have insufficient cytological atypia to warrant a diagnosis of inverted
urothelial carcinoma.

51. SQUAMOUS CELL CARCINOMA
• Pure squamous carcinoma is the second most common histological type of bladder cancer, but it is
rare, making up about 5% of bladder cancers in high-income countries.
• M=F
• MC in 6th decade
• Hematuria, dysuria

52. SCC ETIOLOGY
• Developmental Anomaly- Bladder exstrophy
• Environmental Exposure
Tobacco smoking (5x ↑ risk over nonsmokers)
Chronic inflammatory conditions with squamous metaplasia are risk factors
 Bladder stones, chronic indwelling catheters, neurogenic bladder, prolonged cyclophosphamide
treatment

53. SCC
• Infectious Agents
Strongly associated with schistosomal infection
Includes S. haematobium and S. mansoni (common in Egypt and other parts of Africa)
Verrucous carcinoma is more in this setting
HPV association is very rare
May be seen in cases associated with condyloma or in association with chronic injury

54. SCC

55. SCC
• Prognostic indicators include TNM stage, age at diagnosis, surgical approach, tumour size,
lymphovascular invasion, perineural invasion, and margin status

56. UPDATES IN RENAL TUMORS

58. CLEAR CELL PAPILLARY RENAL CELL TUMOR (CCPRCT)
• Renamed from carcinoma to tumor due to uniformly indolent behavior.
• Low-stage, low-grade tumor with tubulopapillary and cystic architecture composed of clear cells with
linearly aligned luminally oriented nuclei.
• Co-express CK7 and CAIX (cup-like), often positive for HMWCK, but negative for cd10, and lack
recurrent cytogenetic abnormalities or VHL gene alterations.

59. NEW CATEGORY OF MOLECULARLY DEFINED
RENAL TUMORS

60. TFE3-rearranged RCC (Formerly Named MiTF Family Xp11
Translocation RCC)
• Heterogeneous tumors in younger patients with mixed papillary and solid architecture, psammoma bodies
and clear to eosinophilic cytoplasm.
• It expresses nuclear TFE3 and variably melanocytic markers and cathepsin K.
• TFE3 rearrangement with >20 different gene partners creates fusion subtypes with variable tumor
morphology, immunoprofile and clinical behavior.

61. TFEB-REARRANGED RCC
• Tumor has either translocation or amplification of TFEB on t(6;11).
• TFEB-translocation RCC is a low-stage indolent biphasic neoplasm with nests of large clear cells
and smaller cells clustered around basement membrane material.
• TFEB-amplified RCC is an often high-grade and high-stage tumor with frequent oncocytic and
papillary morphology affecting older patients.

62. ELOC (FORMERLY TCEB1)-MUTATED RCC (NOVEL ENTITY)
• Uncommon indolent clear cell tumor with solid and papillary growth patterns and nodular
appearance due to traversing fibromuscular bands and septa.
• Morphologically, it mimics conventional clear cell and tuberous sclerosis-associated RCCs.
Consistently immunoreactive for CK7 and can be focally positive for HMWCK.
• Develops due to biallelic inactivation of TCEB1 (ELOC) on chromosome 8 encoding for elongin
C of the VHL complex with intact VHL and mTOR pathway genes.

63. FUMARATE HYDRATASE (FH)-DEFICIENT RCC
• Renamed from hereditary leiomyomatosis associated RCC. Aggressive tumor with mixed
papillary, solid, tubulocystic and cribriform architecture, composed of high-grade cells with
cherry-red macronucleoli.
• Germline (majority of cases) or somatic FH gene mutations should be suspected with
immunostaining demonstrating FH protein loss and/ or 2-succinocysteine (2SC) gain.

64. SUCCINATE DEHYDROGENASE (SDH)-DEFICIENT RCC
• Rare tumor with distinct solid morphology of bland eosinophilic cells with bubbly inclusions with
loss of SDHB protein expression and germline mutation in SDH gene complex.

65. ALK-REARRANGED RCC (NOVEL ENTITY)
• Very rare group of extremely heterogeneous eosinophilic tumors which develop due to fusions of
anaplastic lymphoma kinase gene (ALK) at 2p23 resulting in ALK protein overexpression.
• May show cytoplasmic vacuolization; solid, papillary or cribriform architecture with mucin
production; psammoma bodies; metanephric like, rhabdoid or spindle cell morphology.

66. SMARCB1-DEFICIENT RENAL MEDULLARY CARCINOMA
• Renamed from renal medullary carcinoma.
• Highly aggressive medulla-centered adenocarcinoma predominantly affecting patients with sickle
cell trait (hemoglobinopathy) and of african ancestry.
• Presents as locally advanced or metastatic disease with high grade tumor morphology
• Loss of SMARCB1 (INI1, SNF5, BAF47) protein expression on immunostaining reflects
inactivation of SMARCB1 at 22q11.23 by chromosome translocations or deletions.

67. EOSINOPHILIC SOLID AND CYSTIC RCC
• Novel distinct entity in “OTHER RENAL TUMORS” category.
• Originally described in patients with tuberous sclerosis complex, but can occur sporadically due to
TSC1 or TSC2 mutations. Indolent tumor disproportionately affecting women, with only rare
reported metastases.
• Solid and cystic architecture, voluminous eosinophilic cytoplasm and coarse basophilic
granularity. CK20 and cathepsin K are positive and there is a lack of CK7/CKIT expression.

70. UPDATES IN BLADDER

72. MOLECULAR CLASSIFICATION
• The recent molecular classification of , muscle-invasive bladder cancer has identified six molecular
clusters with different prognostic outcomes:
 Luminal-papillary (identified in 24% of cases of muscle-invasive bladder cancer)
Luminal non-specified (8%),
Luminal-unstable (15%,)
Stroma-rich (15%)
Basal-squamous (35%)
Neuroendocrine-like (3%).

73. • The neuroendocrine- like, basal-squamous, and luminal-unstable subtypes were associated with
worse overall survival.
• TP53 mutations were frequent in the neuroendocrine-like (100%), basal-squamous (61%), and
luminal-unstable (76%) groups.
• FGFR3 mutations were most notable in the luminal-papillary subtype (33%).
• In addition to prognosis, the role of molecular subtypes as predictors of therapeutic response is
under active investigation

75. THANK YOU