Renal Pathology (Pathelective) Flashcards
How do you differentiate proximal and distal convoluted tubules on histology?
PCTs are narrow and have more granular pink cytoplasm – they have no visible lumen on histology. They are mostly cytoplasm.
DCTs are wide – they have a readily visible lumen and thinner walls, with nuclei coming into closer contact with the luminal space.
What’s going on where this mouse is pointing?
This is the juxtaglomerular apparatus – where the DCT loops back and comes into contact with the glomerulus.
Clear cell renal cell carcinoma
~65-70% of renal cancers.
Gross: yellow-tan mass, cortically based, well-circumscribed
Architecture: solid or alveolar (nested) pattern with surrounding capillary vessels.
Cytology: Clear cells (usually), may range from clear to granular/eosinophilic.
Stains: PAX8 +, CA-9+ (diffuse, membranous, “box-like”), CD10+, vimentin +, CK7 neg, AMACR neg
Genetics: Promoter methylation and inactivation of VHL, leading to HIF1a upregulation. This leads to increased VEGF, PDGF, GLUT1. (This is what attracts the vessels that make the nests!)
Prognosis: Worse prognosis than chromophobe or papillary. Metastasize hematogenously – can really metastasize anywhere.
Note: CA-9 is a surrogate marker for VHL dysregulation.
Clear cell papillary renal cell carcinoma
Architecture: Papillary, often cystic (tubules, acinar, solid) with fibrous septae. Papillae are usually short and stubby. Around 25% have multifocal disease.
Cytology: Abundant clear cytoplasm, low nuclear grade (ISUP grade 1-2). Bland, low cuboidal cells with nuclei oriented towards the luminal side. Linear arrangement makes them look like “piano keys”
Stains: PAX8+. CA-9 showing cup-like positivity (stains basolateral and lateral sides only). CK7 diffusely positive. AMACR negative, CD10 negative.
Genetics: Lacks the 3p loss and VHL gene alterations seen in clear cell RCC.
Prognosis: Indolent neoplasm. No local recurrence or distant metastasis ever reported to date. Associated with ESRD.
What is the most specific marker for clear cell RCC?
CA-9
Hemangioblastoma
Very rare, benign tumor. RCC mimic, but not of true renal origin.
Stains: PAX8 neg, inhibin +, keratin neg
Papillary adenoma
Architecture: Unencapsulated, low-grade tumor with papillary or tubular architecture. Diameter less-than or equal-to 15 mm. If >15 mm, this automatically makes it a papillary RCC. (therefore, beware diagnosing on needle biopsy)
Cytology: Low-grade nuclei. If nuclear grade >1-2, it is not an adenoma.
Very common with age. Identified in ~40% of 70+-year-olds on autopsy.
Associations: tobacco use, kidney disease, hemodialysis, more likely to occur if concomittant papillary RCC
Papillary Renal Cell Carcinoma, Type 1
2nd most common renal neoplasm (15% of cases)
Architecture: Papillary with a true fibrovascular core, sometimes tubular or solid.
Cytology:
* Type 1: Low cuboidal epithelium, scant cytoplasm, low nuclear grade, accompanying foamy macrophages with hemosiderin stuffing the fibrovascular core. True intra-tumor cell hemosiderin may also be seen in type 1 or type 2, and helps make the categorical diagnosis of papillary RCC.
Stains: PAX8+, diffusely CK7+, AMACR+, WT-1 -, CD57 -
Papillary Renal Cell Carcinoma, Type 2
THIS IS A RETIRED DIAGNOSIS – THIS CATEGORY WAS COMPOSED OF MANY GENETICALLY DISTINCT TUMORS THAT ARE NOW RECOGNIZED AS SUCH.
Architecture: Papillary with a true fibrovascular core, sometimes tubular or solid.
Cytology:
* Type 2: Abundant eosinophilic cytoplasm, nuclear pseudostratification, often higher grade nuclear features. True intra-tumor cell hemosiderin may also be seen in type 1 or type 2, and helps make the categorical diagnosis of papillary RCC.
Stains: PAX8+, diffusely CK7+, AMACR+, WT-1 -, CD57 -
Beware! Hereditary Leiomyomatosis-associated RCC (loss of FH staining, then confirm by germline testing) and Translocation RCC (TFE3 FISH, also often melanocytic marker positive, keratin negative) can look similar to Type 2. You will have to rule them out to make the diagnosis.
Metanephric adenoma
Benign tumors that recapitulate the metanephros. May represent a well-differentiated Wilm’s tumor.
Architecture: Well-circumscribed, more tubular than papillary architecture, sometimes with stubby abortive papillae. Tumors abutt and push, but don’t invade, the renal parenchyma. Psamomma bodies often present.
Cytology: Small, uniform, bland cells with high N/C ratio.
Stains: PAX8+, WT-1+, CD57+, CK7 -, AMACR -
Genetics: Often BRAF V600E positive.
Oncocytoma
Benign renal epithelial tumor derived from PCT cells.
Gross: Classic “mahogany brown with central scar” appearance on gross.
Architecture: Tend to be nested, but may be solid or cystic. Myxoid or loose stroma in “scar” region. Tendency to scallop into fat, but not true invasion.
Cytology: Round cells with abundant granular eosinophilic cytoplasm, central round nucleus with prominent nucleolus (ie, oncocytic). Binucleation is common. Degenerative atypia may be seen, with some pleomorphic cells with dark/smudgy chromatin.
Stains: CK7 negative most places, but foci of positivity and a positive central scar. Hale’s cholloidal iron staining negative, sometimes positive only in luminal aspect.
Consider oncocytosis! Numerous oncocytomas, oncocytic tubular cells, and cysts lined by oncocytic cells.
“Mahogany brown with a central scar”
Classic gross appearance of a renal oncocytoma.
Chromophobe renal cell carcinoma
4-5% of all RCCs.
Architecture: Solid sheets to nested with intervening fibrous septa. Not neat nests like oncocytoma – more jigsaw with the ability to follow a nest border out far from the nest.
Cytology: Large cells with abundant clear-to-granular cytoplasm. Often the two are intermixed (clear and granular/oncocytoma-like). Prominent cell membranes (vegetable cells). Nuclear features are key to differentiating – Crinkled, rasinoid nuclei with a perinuclear halo (koilocytic atypia), sometimes binucleated.
* In these tumors, there is usually a high degree of cell-to-cell nuclear variation.
Stains: CK7 diffusely positive, Hale’s cholloidal iron diffusely positive in cytoplasm
DDx for oncocytic renal cancer
- Oncocytoma
- Oncocytic-variant clear cell RCC
- Oncocytic-variant papillary RCC
- Chromophobe RCC
- SDHB-deficient RCC
- Hereditary Leiyomyomatosis-associated RCC
- Eosinophilic Solid and Cystic RCC
- Perivascular epithelioid cell tumor (PEComa)
“Simple” Renal Cyst
Renal cyst that is unilocular. Usually from the cortex.
Lined by cuboidal or flat cells
Multilocular cystic renal neoplasm of low malignant potential (MCRN-LMP)
(recently renamed from cystic RCC because there have never been any reported metastases!)
Multicystic mass with thin septa and clear, serous or gelatinous fluid. No grossly identified nodules.
Lined by uniform, bland cells with ample clear cytoplasm. May have nests of similar cells, but no expansile tumefactive nests.
Any necrosis, invasion, or sarcomatoid features are incompatible with this diagnosis.
Adult Cystic Nephroma
Benign.
More on the cystic side of the MEST-ACN spectrum. Hormonally responsive with an ER/PR+ ovarian-like stroma, often found in perimenopausal women.
Can have hobnail/apocrine or flat epithelium.
Mixed Epithelial and Stromal Tumor
More on the solid of the MEST<->ACN spectrum. More readily identifiable ovarian-like stroma.
What’s going on in this image?
Beware! It might look like invasive urothelial carcinoma, but actually that is a tubule and not a vessel!
This is a form of urothelial carcinoma-in-situ within the renal ducts.
Collecting Duct Carcinoma
A rare renal carcinoma with poor prognosis – more than 80% of patients develop metastatic disease.
Grossly: Infiltrative gray-white tumors arising in the medulla, with satellite nodules in the cortex.
Architecturally: Tubular, tubulopapillary, or tubulocystic with a desmoplastic stroma.
Cytologically: High-grade with irregular, pleomorphic nuclei. Look kind of like an adenocarcinoma with intraluminal or intracellular mucin. Often cribriform. May have rhabdoid or sarcomatoid features.
IHC: PAX8+, usually p63 neg. May have loss of INI-1, mimicing the medullary carcinoma immunophenotype. FH retained.
Significant morphologic and prognostic overlap with medullary carcinoma! These are the main DDx for one another!
WHO criteria:
1. Medullary involvement
2. Predominant tubular morphology
3. Desmoplastic stroma
4. Cytologically high-grade
5. Infiltrative growth pattern
6. Absence of other renal cell carcinoma subtypes or urothelial carcinoma (it’s not something else)
SMARCB1 deficient renal medullary carcinoma
Very aggressive tumor, centered in the medulla.
Associated with sickle cell trait or similar hemoglobinopathies. In fact, it arises almost EXCLUSIVELY in these patients. Also, weirdly, about 80% happen in the RIGHT kidney.
Pathophysiology: Chronic hypoxia (hemoglobinopathy) suppresses the RAD51 and BRCA1 pathways, induces NHEJ and thus predisposes to translocations. A translocation then results in SMARCB1 inactivation.
Architecture: Infiltrative, poorly circumscribed tumor with cribriform, reticular, and nested growth pattern with intervening desmoplasia. Often with a brisk acute inflammatory infiltrate. Nuclei are always high-grade with prominent nucleoli.
Cytology: High-grade nuclei, intracytoplasmic mucin. Sometimes rhabdoid features.
IHC: Loss of INI-1 staining. PAX8+.
Significant morphologic and prognostic overlap with collecting duct carcinoma! These are the main DDx for one another!
Multilocular renal cystic neoplasm of low malignant potential
Histologically, has a pure, multiloculated cystic architecture with low grade (ISUP grade 1-2) clear cells. Should NOT have any solid growth >1 mm. No papillary architecture, apical nuclei, necrosis, atypical mitoses, LVI, rhabdoid/sarcomatoid features are allowed.
Can happen at basically any age. Usually unilateral, solitary. Often displays VHL gene alterations and may be associated with VHL syndrome.
IHC: PAX8+, CA9 + (diffuse, membranous), CD10+, CK7 negative, CD117 negative, AMACR negative
Molecular: Loss of 3p in 80%
Excellent prognosis irrespsective of stage.
Mucinous tubular and spindle cell carcinoma
Rare tumor more frequent in females.
Tightly packed, anastamosing tubules lined by low-grade (ISUP 1-2) cuboidal cells, merged with spindled cells and a myxoid matrix.
High-grade transformation occurs in a subset with high-grade nuclei, necrosis, and mitoses. Sarcomatoid transformation may occur.
IHC: PAX8+, CK7+, AMACR+, CD10 may be +
Molecular: Multiple chromosomal losses (1,4,6,8,9,13,14,15,22).
Nephroblastoma (Wilm’s tumor)
Tumor consists of blastemal, epithelial and stromal elements (triphasic) which can be present in variable amounts. Biphasic and monophasic tumors are not uncommon. Epithelial and stromal elements may show different lines and degrees of differentiation. 5-10% are bilateral. Frequently syndrome associated (see below).
Arises from nephrogenic rests, however the pathway of progression is unclear.
Histologic risk classification:
* Low risk - cystic, partially differentiated nephroblastoma or completely necrotic
* Intermediate risk - epithelial, stromal, mixed, and regressive types. Focal anaplasia allowed in SIOP system, not in COG system.
* High risk - diffuse anaplasia, blastemal type
IHC:
* Blastema: Diffuse WT1+, PAX8+, vimentin+
* Epithelium: Keratin+, CD56+, variable PAX8 and WT1
* Stroma: Vimentin+, variable BCL2 and CD34, WT1 weak or absent
Treatment includes surgery +/- neoadjuvant chemotherapy with follow-up chemoradiation. The survival rate is approximately 90%. If low risk (cystic partially differentiated), it will be treated with simple resection only.
