Prepared by Kurt Schaberg
Kidney Tumors
Eosinophilic
Oncocytoma
CK7
CD117
CA-IX
Vimentin
AMACR
Racemase
SDH
FH
-
+
-
-
-
+
+
(rare)
Chromophobe RCC
+
+
-
-
-
+
+
Papillary RCC
(Type 2)
+/-
-
+/-
+
+
+
+
HLRCC-associated
RCC
-
-
-
-
-
+
-!
SDH-deficient RCC
-
-
-
-
+/-
-!
+
Acquired Cystic
Disease-associated
RCC
-
+
+
+
Clear Cell RCC
(sometimes pinkish)
-
-
+
+
-
++
+
Oncocytoma
Benign
Abundant eosinophilic, mitochondria-rich cytoplasm
Round, regular nuclei throughout
Tight nests and alveoli surrounded by myxoid or hyalinized
hypocellular stroma. Some solid areas acceptable.
Grossly: Circumscribed, mahogany brown
NOT allowed: Necrosis, Sheet-like or papillary growth, clear
or sarcomatoid cells
Stains: Only rare CK7 + cells
(Most CK7 Negative!)
Chromophobe Renal Cell Carcinoma
Clear to Eosinophilic cytoplasm
Prominent “Plant-like” cell membranes
Perinuclear clearing
Round to Koilocytic nuclei
(hyperchromatic, crinkled, and/or binucleated)
Stains: CK7+, Hale’s colloidal iron +
Better prognosis than clear cell RCC.
No need to grade.
Chromophobe/oncocytoma hybrid tumors may be seen
in Birt-Hogg-Dubé syndrome
Papillary RCC (Type 2)
Predominantly papillary architecture
Type 2 is lined by large cells with
abundant eosinophilic cytoplasm
Higher nuclear grade→ Prominent
Nucleoli (consider HLRCC though!)
Macrophages, edema, psammoma
bodies
Hereditary Leiomyomatosis and Renal Cell Carcinoma-associated RCC
Abbreviated: HLRCC-associated RCC
Prominent, eosinophilic, inclusion-like nucleoli with
perinucleolar clearing
Usu. Papillary to tubular architecture
Loss of Fumarate Hydratatse (FH) expression
(Germline FH mutations)
Usually younger patients. Cutaneous and uterine leiomyomas.
Aggressive tumors!
Succinate Dehydrogenase Deficient RCC
Eosinophilic cytoplasm with “flocculent”
cytoplasm/inclusions (see arrows)
Neuroendocrine-like nuclei (round, evenly
dispersed chromatin
Solid to nested architecture
Defined by loss of Succinate Dehydrogenase B
(SDH-B)→ Majority of patients have germline
mutations.
Young age, good prognosis
SDH-deficient tumor syndrome: SDH-deficient
RCC, paraganglioma/pheochromocytoma, SDHdeficient GISTs
Acquired Cystic Disease-associated RCC
Occurs only in patients with ESRD with cystic disease
Abundant granular eosinophilic cytoplasm
Microcribriform appearance due to frequent
intracytoplasmic and intercellular microlumens
Large nuclei with prominent nucleoli
Frequent oxalate crystals and calcifications
Clear Cell RCC
Although it is called “Clear Cell” RCC, some cases
can have relatively eosinophilic cytoplasm.
More common with higher grades
Can have “Rhabdoid” areas
Look for classic clear cell areas as a clue
Clear
Clear Cell RCC
CK7
CD10
CA-IX
Keratins/
EMA
Melanocytic
Markers
TFEB/
TPF3
-
+
+
+
-
-
+ (basal +
-
-
(diffuse)
Clear Cell Papillary
RCC
+
Multilocular cystic
renal cell neoplasm
of LMP
-
+
+
+
-
-
MiTF translocationassociated RCC
-
+
-
- (weak to neg)
+/-
+
-
cup-like)
Clear Cell RCC
Predominantly clear cells (contains lipid and glycogen)
with sharp cell borders
Sheets and nests of cells surrounded by extensive
capillary network
Frequent alveolar lumens
Grossly: Yellow, with frequent hemorrhage and
necrosis
Associated with von Hippel Lindau Syndrome (VHL
gene)—Along with: Hemangioblastomas,
pheochromocytoma, pancreatic serous cystadenomas,
and endolymphatic sac tumor
WHO/ISUP grading system for clear cell and papillary renal cell carcinomas
Grade
Findings
1
Nucleoli are absent or inconspicuous and basophilic at 400x magnification
2
Nucleoli are conspicuous and eosinophilic at 400x and visible but not prominent at 100x
3
Nucleoli are conspicuous and eosinophilic at 100x
4
Extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or
sarcomatoid differentiation
Multilocular Renal Cell Neoplasm of Low Malignant Potential
Cysts lined by single layer of low-grade clear cells
(grade 1-2 only)
Groups of low-grade clear cells are permitted within the
septa, but must not be expansile nodules or show
infiltrative growth
Features not allowed: Necrosis, Vascular invasion,
Sarcomatous differentiation
NOTE: No longer called a carcinoma as act so indolently
Clear Cell Papillary RCC
Mixture of tubular, cystic, acinar and papillary patterns
Lined by a single layer of cuboidal to low columnar cells
Scant eosinophilic to clear cytoplasm
Nuclei apical to mid-cytoplasmic orientation
(“pseudoendometrial” appearance)
Low-grade and Low-stage
Unique immunophenotype
(CK7 +, CA-IX basolateral cuplike)
Very indolent (no reported metastases!)
MiT Family Translocation RCC
Gene fusions in MiT family transcription factors TFE3 or TFEB
(Demonstrate with cytogenetics, FISH, or IHC)
Composed of cells with abundant to voluminous cytoplasm
Clear to granular eosinophilic cytoplasm
Sharp cell borders
Frequent papillary, pseudopapillary, alveolar and nested
patterns
Vesicular nuclei with prominent nucleoli
Most often recognized in younger patients
Variable outcomes
Basaloid
Papillary RCC (Type 1)
CK7
CD10
CA-IX
AMACR
Racemase
WT-1
CD57
+
+
-/+
+
-
-
-
-
+
+
-
-
+
-
(luminal)
Metanephric Adenoma
-
Wilms Tumor
-/+ (in
+
epithelium)
(diffuse)
Mucinous Tubular and
Spindle Cell RCC
+
-/+
-
+
-
-
Tubulocystic RCC
+/-
+
-/+
+
-
-
Papillary RCC (Type 1)
Predominantly papillary architecture
Often some tubular or solid growth also
Type 1 is lined by small cells with scant
amphophilic cytoplasm
Lower nuclear grade than type 2
Macrophages, edema, psammoma bodies
Papillary Adenoma
Same thing, but < 1.5 cm
Nuclear grade 1 or 2
Benign
Metanephric Adenoma
Benign
Composed of small, primitive tubules.
Cells have minimal cytoplasm with uniform, small nuclei
Minimal mitoses.
Grossly: well-circumscribed, unencapsulated, tan nodule.
Very cellular with minimal stroma.
May appear papillary or glomeruloid
Often incidental, but associated with polycythemia
Tubulocystic RCC
Closely packed variably sized tubules and cysts
No solid component→ Grossly looks like a sponge
Lined by cuboidal to flattened and hobnail cells
High grade nuclear features with prominent round nucleoli
Good Prognosis
Grossly
looks like a
sponge
Wilms Tumor (Nephroblastoma)
1
Vast majority in Children
Triphasic (recapitulating nephrogenesis):
1) Blastema
(small, undifferentiated, overlapping cells)
2) Epithelium
(Tubules, rosette-like to well-formed)
3) Stroma
(Nondescript spindled cells, occasional
heterologous elements)
2
3
Special reporting (amount of Anaplasia, etc…)
Anaplasia = increased nuclear size (>3x size), hyperchromasia, and mitotic figures → Chemo resistant
Malignant, but often good survival
Mucinous Tubular and Spindle Cell Carcinoma
Like the name says:
1) Elongate tubules that blend into 2)
Bland spindle cells, set in 3) Mucinous
stroma
2
Cytologically bland with small oval nuclei
Very indolent/benign course
1
3
Spindled (Adult)
Angiomyolipoma
Benign
Member of “PEComa” family
(Perivascular Epithelioid Cell)
Generally 3 components (like the name):
1) Blood vessels (“Angio”)
2) Smooth muscle (“Myo”)—often blending with vessels
3) Fat (“Lipoma”)—often seen radiographically
Stains with Melanocytic Markers:
HMB45 +, MelanA +/-, Desmin + (in muscle)
Associated with Tuberous sclerosis
Renomedullary Interstitial Cell Tumor
Benign
Usually incidental, small, well-circumscribed
Located in renal medulla
Composed of bland stellate cells set in loose to
dense fibrocollagenous stroma with entrapped
tubules at the periphery
Sarcomatoid RCC
Renal cell carcinoma of any type exhibiting at least
focal sarcomatoid/spindle cell differentiation
Represents a form of high-grade transformation,
not a distinct subtype of renal cell carcinoma
Requires evidence of epithelial differentiation
(either conventional component or CK expression)
Automatically WHO/ISUP grade 4
Poor prognosis
Other Spindled Tumors
Mixed-Epithelial Stromal Tumor—Benign tumor. Cystic and solid. Ovarian-type stroma and smooth
muscle with bland epithelial cysts (conceptually sort of like a mucinous cystic neoplasm of the
pancreas, but epithelium is hobnailed and bland). Stroma stains with desmin and ER.
Juxtaglomeurlar Cell Tumor—Benign tumor that originates from smooth muscle cells in the walls of
the glomerular afferent arteriole (juxtaglomerular apparatus)→ secretes renin→ Hypertension,
Hyperaldosteronism, hypokalemia! Monotonous eosinophilic spindled to epithelioid cells with oval
nuclei.
Mucinous tubular and spindle cell carcinoma
Sarcomatoid clear cell RCC
Renomedullary interstitial cell tumor
(And any other sarcoma pretty much)
High-Grade
Collecting Duct Carcinoma
High-grade renal carcinoma arising in medulla of the
kidney, with a predominantly invasive tubular growth
pattern.
Diagnosis of exclusion. Requires:
1) No other RCC, Urothelial carcinoma, or Metastasis
2) Predominantly tubular growth
3) Firm mass centered in Medulla
4) Prominent stromal desmoplasia
5) Infiltrative growth
6) High nuclear grade
Poor Prognosis
Urothelial carcinoma
Always consider as a possibility if doesn’t fit well into
one of the RCC diagnoses.
Sample and examine the renal pelvis for urothelial CIS
Stains: GATA-3 +, p63+, HMWCK+, CK7+, CK20+,
Pitfalls: PAX8+, CA-IX +
Other
Renal Medullary Carcinoma—Like collecting duct carcinoma, but associated with
sickle cell disease, INI-1 loss
Sarcomatoid clear cell RCC, RCC NOS, Metastases, Sarcomas
Papillary
Papillary adenoma
Papillary RCC
Clear cell papillary RCC
MiTF translocation-associated RCC
Urothelial carcinoma
HLRCC-associated RCC
Spindled (Kids)
Clear Cell Sarcoma
Aggressive→ Old name “bone metastasizing renal tumor
of childhood”
Nests or cords of uniform cells with clear cytoplasm and
fine chromatin and a delicate vascular network
Some areas may be sarcomatous/anaplastic
No good stains
Rhabdoid Tumor
Aggressive
Sheets and trabeculae of cells with:
Eccentric nuclei with vesicular chromatin and prominent
nucleoli
Eosinophilic cytoplasm with pink hyaline inclusions (looks
“rhabdoid”)
Stains: CK+, INI-1 loss, Myogenin/MyoD1 -
Congenital Mesoblastic Nephroma
Classic Variant
Fibromatosis-like: intersecting bundles of bland spindled cells, infrequent mitoses
Infiltrates adjacent kidney and structures
Cellular Variant
Recurrent ETV6-NTRK3 fusions (Same as infantile fibrosarcoma, secretory carcinoma)
Pushing border, dense cellularity, numerous mitoses
Biopsy/FNA Algorithm