GU Flashcards
Stains to differentiate nephrogenic adenoma from bladder adenoCA and prostate adenoCA
Nephrogenic adenoma: AMACR+ PAX8+ NKX3.1-
Bladder adenoCA: AMACR- PAX8- NKX3.1-
Prostate adenoCA: AMACr+ PAX8- NKX3.1+
Histologic features of nephrogenic adenoma
Thick basement membrane surrounding glands
tubular/glandular pattern
can appear pseudo-infiltrative
hobnail and single lining cells
eosinophilic intraluminal secretions
Etiology of nephrogenic adenoma
Urothelial injury - infection, instrumentation, surgery, calculi
Reno-tubular seeding/metaplasia
Frequent in transplant patients
Common locations of inflammatory myofibroblastic tumor
Mesentery, omentum, retroperitoneum most common
Can also happen in H&N, lung, bladder, gyne, CNS
Most common bladder tumor of childhood
Embryonal rhabodomyosarcoma
4 criteria for urachal carcinoma
Tumor primarily located at dome or anterior wall
Epicentre of carcinoma is in muscularis propria with demarcation between tumor and overlying bladder mucosa
Lack of extensive cystitis cystica et glandularis
Absence of carcinoma of similar histology at another primary site
Risk factors for bladder SCC
Schistosomiasis hematobium
bladder diverticula
Nonfunctioning bladder
transplant patients
Squamous bladder lesions
SCC
Verrucous carcinoma
Squamous cell papilloma
Squamous metaplasia
Squamous diff in urothelial CA
High risk subtypes of Urothelial CA
Nested
Micropapillary
Signet ring/plasmacytoid
Sarcomatoid
Undifferentiated
Gene mutations associated with low grade and high grade urothelial CA
Low grade: FGFR3, HRAS
High grade: TP53, RB
T-staging for bladder CA
pTa - non-invasive papillary carcinoma
pTis - carcinoma in situ
pT1 - tumor invades LP
pT2a - invades superficial MP
pT2b - invades deep MP
pT3a - microscopically invades perivesicle soft tissue
pT3b - macroscopically invades perivesicle soft tissue
pT4a - extravesicle tumor invades prostatic stroma, uterus, vagina
pT4b - invades pelvic wall, abdominal wall
N-staging for bladder
pN1 - single LN met in true pelvis
pN2 - multiple LN mets in true pelvis
pN3 - LN mets to common iliac LNs
Morphologic features of invasion in urothelial CA
Irregularly shaped nests
Single cell infiltration
Absent basement membrane
Fingerlike projections in LP
Desmoplastic stromal response
Paradoxical differentiation
Pseudosarcomatous stroma
Myxoid stroma
Retraction artifact
Inflammation
Risk factors for urothelial CA
Smoking
Drugs (cyclophosphamide, phenacetine)
Exposures (aryl amines, radiation)
Helpful stains in diagnosing Urothelial CIS
CK20 - full thickness (normal is umbrella cells only)
p53 - strong nuclear
CD44 - absent or in basal cells only
Morphologic patterns of urothelial CIS
Pleomorphic
Small cell
Pagetoid
Clinging
Undermining
DDx inverted papilloma
Inverted papilloma
Nested urothelial CA
Florid von Brunn nests
Florid cystitis cystica
Carcinoid tumor
Spectrum of papillary urothelial lesions and how to distinguish them
Papilloma - PUNLMP - LGPUC - HGPUC
Features - thickness, mitoses, pleomorphism, disorganization, fusion/branching of papillae
Causes of ureteral obstruction
Intrinsic - calculi, strictures, tumors, clots, neurogenic
Extrinsic - pregnancy, periureteral inflammation, endometriosis, tumors
Hereditary renal tumors and their associated genes
VHL - renal cysts and CCRCC
Hereditary papillary RCC (MET oncogene) - bilateral PRCC
HLRCC (FH) - FH-deficient RCC
Birt-Hogg-Dube (BHD) - kidney oncocytoma & RCC
Tuberous Sclerosis (TSC1/2) - angiomyolipomas
Stains to differentiate PRCC from CCRCC
PRCC: CK7+ CAIX cup-shaped
CCRCC: CK7- CAIX surrounds whole cell
Grading of CCRCC
1 - nucleoli absent or inconspicuous & basophilic
2 - nucleoli conspicuous & eosinophilic at 40x but not 10x
3 - Nucleoli visible & eosinophilic at 10x
4 - extreme pleomorphism/tumor giant cells/sarcomatoid or rhabdoid diff
What is a MEST and how to ddx from cystic nephroma
Mixed epithelial and stromal tumor
MEST is unencapsulated, variable cystic and solid while cystic nephroma is entirely cystic, encapsulated, and inhibin+
Extrarenal manifestation of ARPKD
Congenital hepatic fibrosis
Extrarenal manifestations of ADPKD
Liver cysts
Pancreas cysts
Lung cysts
Berry aneurysms
Mitral valve prolapse
DIverticuli
Risk factors for penile SCC
BXO
UV exposure
Smoking
Phimosis
HPV
Most common type of testicular lymphoma and age at presentation
DLBCL, >65yo
Prognostication for mixed malignant teratoma and embryonal tumors
Clinical stage
Invasion
Proportion of components (More embryonal is worse, more mature teratoma better)
Characteristic histological finding in yolk sac tumor
Schiller-Duval body (papillae containing central blood vessel surrounded by clearing)
Variants of yolk sac tumor
Reticular/microcystic (most common)
Endodermal sinus
Papillary
Solid
Glandular
Polvesicular vitelline
Parietal
Hepatoid
DDx for high AFP
Yolk sac tumor
Pregnancy
HCC
Cirrhosis
Active hepatitis
Histologic features and staining pattern for choriocarcinoma
Blood lakes, two cell populations (large multi-nucleated syncytiotrophoblastic cells and mononuclear cytotrophoblasts)
Stains: SALL4+ Oct3/4- CD30-
Stain to differentiate embryonal from seminoma
Both OCT3/4+
CD30- in seminoma
CD30+ in embryonal
Histologic features of embryonal carcinoma
3 main growth patterns: solid, glandular, papillary
Large, cohesive, highly pleomorphic tumor cells
Indistinct cell borders
hemorrhage and necrosis common
GCNIS associated and non-associated GCTs
GCNIS-associated: Seminoma, embryonal CA, Chorio CA, yolk sac, post-pub teratoma
Non-GCNIS-associated: spermatocytic tumor, prepubertal yolk sac, prepubertal teratoma
+ stains in GCNIS
OCT3/4
PLAP
CD117
D2-40
Staining profile of seminoma
OCT3/4+
CD117+
D2-40+
PLAP+
CD30-
CK-
Inhibin-F
Features of regressed seminoma
Fibrous scar - necrosis or intratubular calcification
GCNIS
Atrophic background testicular parenchyma
Histologic features of seminoma
Fibrous septae divide sheets/nests of tumor cells
Large round polygonal tumor cells with clear cytoplasm
Distinct cell membranes
Lymphoplasmacytic infiltrate in fibrous septae
Malignant features of Leydig and Sertoli cell tumors
Size >5cm
Mits >5/hpf
Necrosis
Hemorrhage
Nuclear pleomorphism
Invasive edges
Features of Leydig cell tumor
Histology: diffuse/nodular growth of polygonal cells with eosinophilic cytoplasm, uniform round nuclei and prominent central nuceoli, may have Reinke crystals
IHC: Inhibin+ MelanA+ Calretinin+ AR+ CD99+ WT1+
Clinical: gynecomastia, decreased libido, precocious puberty
Bimodal age distribution: 5-10, 30-35
Syndromes associated with Sertoli cell tumor
Carney complex
Peutz-Jegher
FAP
Causes of testicular atrophy
Cryptorchidism
Atherosclerosis
Cachexia
Chemo/rads
Female sex hormones
Exhaustion from FSH stimulation
Kleinefelter syndrome
Mumps/inflammatory orchitis
Features of testicular atrophy
Thickening of seminiferous tubule basement membrane
Intertubular fibrosis
Increased leydig cells
Decreased sperm
Decreased gross size
DDx for paratesticular tumors
Adenomatoid tumor
Mesothelioma
Lipoma/liposarcoma
Embryonal rhabdomyosarcoma
AdenoCA of rete testes/epididymis
Papillary serous CA
Leiomyoma/leiomyosarcoma
Sites of adenomatoid tumors and cell of origin
Paratesticular
Epididymis
Spermatic cord
Uterus
Fallopian tube
Adrenal gland
Mesothelial origin
Etiology of spermatic granuloma and clinical name of nodules
Hx of vasectomy
Vasitis nodosa
Causes of granulomatous orchitis and workup
Traumatic
TB
Syphilis
Sarcoid
BCG treatment
Seminoma
PAS, ZN, GMS, Silver
Risk factors for RCC
Smoking
Obesity
HTN
Unopposed estrogen therapy
Asbestos, petroleum products, heavy metals
Chronic renal failure
Acquired cystic disease
Syndromes associated with RCC
Birt-Hogg-Dube (BHD)
Tuberous sclerosis (TSC1/2)
Von Hippel Linday (VHL)
Hereditary (Familial) clear cell carcinoma
Hereditary papillary RCC
Familial leiomyomatosis and renal cell carcinoma syndrome (FH)
Paraneoplastic syndromes associated with RCC
Polycythemia
Hypercalcemia
HTN
Hepatic dysfunction
Feminization or masculinization
Cushing syndrome
Eosinophilia
Leukemoid reactions
Amyloidosis
Critical areas to sample when grossing a kidney tumor
Margins: rein vein, ureter, renal artery, soft tissue margins
Tumor: 1 section per cm, specifically any areas that stand out to look for grade 4 features
Upstaging: Large vessel invasion, renal sinus fat invasion, collecting duct involvement, perinephric fat invasion
Background normal
Gross appearance of common renal cell tumors
Clear cell: solitary, well-circumscribed with golden yellow colour, may have cystic change, hemorrhage, necrosis, calc, fibrous areas
Sarcomatoid areas of RCC: grey-white “fish flesh”
Papillary: Well-circumscribed, fibrous pseudocapsule, necrosis, hemorrhage, more likely than the others to be bilateral or multifocal
Chromophobe: Solitary, round, well-circumscribed, unencapsulated, tan to light brown colour, may have central scar
Oncocytoma: well circumscribed, mahogany-brown to tan with central or eccentric scar
Angiomyolipoma: well-demarcated, unencapsulated, colour depends on proportions of different components
Features to include in RCC report
Histotype
Involvement of renal vein/branches, renal sinus, perinephric adipose tissue, collecting system
WHO/ISUP nuclear grade
Vascular invasion
Sarcomatoid morphology and quatity
Geographic necrosis
Margins
Any other tissue involved
Background kidney parenchyma
Grading for RCCs
I: Nucleoli not prominent even at 40x
II: Nucleoli apparent but not prominent at 10x
III:: Nucleoli prominent at 10x
IV: Rhabdoid, sarcomatoid diff, tumor giant cells/bizarre pleomorphism
Immunoprofile for clear cell RCC
CAIX +
CD10/vimentin+
CK7- (usually)
AMACR+
CD117-
Prognosis of clear cell RCC
1/3 of patients with localized disease develop local and distant recurrence. Half die of disease
Distinguish papillary adenoma vs papillary RCC
<1.5cm
Low nuclear grade
Histologic features of chromophobe RCC
Solid with occasional tubulocystic architecture
Broad fibrous septae
Nuclei are irregular, hyperchromatic, wrinkled contours and occasional multinucleation
Chromophobe cell - large poygonal with thick plantlike cell borders and finely vesicular cytoplasm
Eosinophilic cell - less abundant granular eosinophilic cytoplasm and perinuclear halo
Histologic features of oncocytoma
well circumscribed, compact nested growth
Eosinophilic cells with indistinct membrane, granular cytoplasm, round to ovoid nuclei
Small and conspicuous nucleoli may be present
May have bizarre degenerative atypia
Prognosis for chromophobe RCC
better than clear cell
Mortality <10%
5 year disease survival >90%
Genetic syndrome associated with multiple chromophobe RCCs and oncocytomas
Birt-Hogg-Dube
Cutaneous fibrofolliculomas, pulmonary cysts, multifocal renal tumors
Can have hybrid tumors (HOCTs) associated with FLCN gene
Histologic features of rhabdoid tumor of kidney
Sheets of large cells with vesicular nuclei, eosinophilic cytoplasmic inclusions, and infiltrative borders
IHC for rhabdoid tumor of kidney
Vimentin+
Focal EMA+
CK+
DDx for rhabdoid tumor of kidney
Nephroblastoma
Neuroblastoma
Mesoblastic nephroma
Medullary RCC
Clear cell sarcoma of kidney with focal rhabdoid features
Reporting of sarcomatoid features in nephrectomy specimens
Give % of sarcomatoid element
Should be classified as unclassified RCC if: pure sarcomatoid CA or sarcomatoid CA associated with epithelial elements that do not confirm to usual types of RCC
Sections to assess for microscopic tumor extension in RCC
Perinephric soft tissues
Renal sinus
Gerota Fascia
Major vein
Pelvicalyceal system
adrenal gland
other organs
Common location for underrecognized extrarenal extension
Renal sinus fat
Margins in partial and radial nephrectomy
Partial: renal parenchyma, perinephric fat
Radical: ureteric, vascular, soft tissue
T classification of RCC
pT1: <7cm limited to kidney
pT1a: <4cm, limited to kidney
pT1b: 4 cm < tumor <7 cm, limited to kidney
pT2: >7cm limited to kidney
pT2a: 7 < tumor < 10cm
pT2b: >10cm
pT3: Extends into major veins or perinephric tissues but not into adrenal gland or beyond Gerota’s
pT3a: renal vein or segmental branches, perirenal/renal sinus fat
pT3b: extends into vena cava below diaphragm
pT3c: extends into vena cava above diaphragm
pT4: beyond Gerota’s, including into adrenal gland
Risk factors for testicular germ cell tumors
Caucasian
Previous contralateral GCT
Testicular dysgenesis syndrome
Cryptorchidism
Testicular microlithiasis
FHx
Molecular abnormality in GCTs
Isochromosome 12p
Classification of testicular GCTS
Seminomatous tumors
Non-seminomatous tumors: Embryonal CA, yolk sac tumor, chorioCA, Teratoma, spermatocytic tumor
Mixed GCTs
Biomarkers for testicular GCTs
LDH
AFP
B-HCG
Precursor lesions of GCTs
GCNIS
Intratubular seminoma
Intratubular nonseminoma
IHC positive in GCNIS
PLAP
OCT3/4
CD117
D2-40
Non-GCNIS associated GCTs
Prepubertal type yolk sac tumor
Prepubertal type teratoma, including dermoid cyst, epidermoid cyst and well diff NET
Prepubertal type mixed teratoma and yolk sac tumor
Spermatocytic tumor
IHC to differentiate major GCTS
GCNIS pattern: Pos PLAP, OCT3/4, CD117, D2-40
Seminoma: GCNIS pattern, CK variable, CD30-, AFP-, BHCG-
Embryonal: GCNIS pattern, CK+, CD30+, AFP variable
Teratoma: non-GCNIS pattern, CK+, focal AFP
Yolk sac: Non-GCNIS, CK+, CD30 variable, AFP+
Chorio: CK+ PLAP+ OCT3/4- B-HCG+
Spermatocytic tumor: PLAP variable, otherwise neg
You are about to sign out a pure seminoma and check the serum markers to find the AFP is very elevated. How can this be explained? Assume the tumor is fully submitted
After ruling out other systemic causes of elevated AFP, consider if the seminoma has metastasized and acquired a yolk sac component. It’s not uncommon that seminomas will differentiate into other GCTs after metastasis.
You are about to sign out a non-chorio GCT and check the serum markers to find the B-HCG is mildly elevated. How can this be explained? Assume the tumor is fully submitted
Non-ChorioCA GCTs can have syncytiotrophoblast components, which can cause a mild increase in B-HCG. Chorios should have a much higher serum B-HCG
Recommendations for sampling a testicular tumor
SIT if </=10 blocks, if >10, 1 block/cm
Sample tumor, interface with surrounding testis and tunica albuginea (best for LVI)
All grossly unique appearing areas
testicular hilum/mediastinum testis
uninvolved testis, including tunica albuginea
epididymis
spermatic cord, including cord margin
any other lesions
all identifiable lymph nodes
Features to report for testicular GCTs
Tumor types and quantities of each
Tumor size
Involved structures
LVI
Margin status
Background parenchyma - GCNIS and spermatogenesis
Features of testicular scar
Significance of testicular scar
May represent regressed/burnt out GCT
If residual disease, partial regression may signify that one of the components has regressed
Criteria for diagnosis: Scar associated with GCNIS or intratubular calcs
Other features: lymphoplasmacytic infiltrate, hemosiderin-lade macrophages, testicular atrophy
Clinical behaviour of sertoli cell and leydig cell tumors
Most are benign
~10% are malignant
Histologic features of classic seminoma
Sheets and lobules of loosely cohesive cells divided by fibrous septa containing lymphocytes and plasma cells
Round or polygonal cells with sharp cell membrane, clear-to-eosinophilic cytoplasm
Large and vesicular nuclei with prominent nucleoli
Possible areas of necrosis, syncytiotrophoblasts
Typical presentation of pure classic seminoma
Peak incidence between 4th and 5th decade
In 75% of patients, disease confined to testis at presentation
in 20% of patients, disease involves retroperitoneum
in 5%, involvement above diaphragm, or visceral mets
Variant of seminoma associated with elevated serum B-HCG
Seminoma with syncytiotrophoblasts
Variant of classic seminoma NOT a mixed GCT
Prognosis similar to classic seminoma
Prognosis for patients with classic seminoma
Excellent
Very responsive to radiotherapy
Histologic features of spermatocytic tumor
Cells arranged in sheets in an edematous stroma
Three cell types (three bears appearance): small with smudged chromatin and scant cytoplasm, intermediate with scant cytoplasm and round nuclei with granular/filamentous chromatin, large/giant uni/multinucleate
Little or no interventing stroma and no or scant lymphocytic infiltrate
Absence of GCNIS
Prognosis for spermatocytic tymor
Excellent prognosis
Treated with resection
IHC pattern of spermatocytic tumor
PLAP: variable, rare pos
CD117: 40-50% pos
other GCT markers: neg
Keratins: neg
Cam5.2: 40% pos
Behaviour of adult vs childhood testicular teratomas
Childhood: mature teratoma considered benign, immature requires close follow up
Postpubertal males: majority regarded as malignant and capable of mets regardless of maturity of tumor elements
Common sites of teratomas in adults and children
Adults: testes and ovaries
Children: Sacrococcygeal sites
Most common types of testicular lymphoma in order of frequency
Most: DLBCL
Burkitt
Least: EBV+ extranodal NK/T cell lymphoma
Behaviour of testicular lymphomas vs lymphomas arising at different sites
Testicular lymphomas have higher propensity for CNS involvement than similar histology lymphomas at other sites
Most common benign spermatic cord tumor
Lipoma
Most common benign paratesticular tumor
Adenomatoid tumor
Most common malignant paratesticular tumor in children
Rhabdomyosarcoma
Most common malignant paratesticular tumor in adults
Liposarcoma
Margins in testicular resection
Spermatic cord margin
Parietal layer of tunica vaginalis
Scrotal skin
Staging of tumors involving rete testis, epididymis, testicular hilar soft tissue, tunica vaginalis
Rete testis: Does not upstage if limited to testis and no vascular invasion
Epididymis/hilar soft tissue/penetration of visceral mesothelial layer of tunica vaginalis: pT2
Significance of venous or lymphatic vessel invasion
LVI associated with increased risk of distant mets
Reporting criteria for lymph nodes in GCTs
Number of nodes
Size of largest involved node
Size of largest metastatic deposit
Extranodal extension
Histologic subtypes
Staging of testicular tumors
pTis - GCNIS
pT1 - tumor limited to testis without LVI
Seminoma only: pT1a: <3cm
Seminoma only: pT1b: >3cm
pT2: tumor limited to testis with LVI or invasion into hilar soft tissue or epididymis or visceral mesothelium of tunica albuginea
pT3: tumor invades spermatic cord
pT4: tumor invades scrotum
Common additional pathologic findings reported in testicular neoplasms
Leydig cell hyperplasia (may be correlated with B-HCG elevation)
Regressed tumor
Intratubular calcs
Testicular atrophy
Abnormal testicular development
Importance of differentiating metastatic residual teramtoma from nonteratomatous GCTs in the postneoadjuvant setting
Pure teratomatous mets are generally treated with surgical excision
Other residual GCTs usually need additional chemo
Nodal staging for testicular neoplasms
pN0: no regional nodal mets
pN1: Lymph node mass </=2cm and </=5 nodes positive none >2cm in max dimension
pN2: Met >2cm and </=5cm, >5 nodes positive, none >5cm or evidence of extranodal extension of tumor
pN3: mets >5cm
Types of metaplasia in the urinary bladder and their significance
Intestinal metaplasia in cystitis cystica and cystitis glandularis - w/o dysplasia has no adenoCA risk, with dysplasia has increased risk
Squamous metaplasia - nonkeratinizing usually not associated with increased SCC risk, keratinizing risk factor for SCC
Nephrogenic metaplasia/adenoma - benign process that is a malignant mimic
Pathogenesis of nephrogenic adenoma/metaplasia
Derived from renal tubular epitheluial cells and not actually metaplasia
Associated with: calculi, instrumentation, trauma, cystitis
Histologic features of nephrogenic adenoma
Tubular (most common), cystic, polypoid, papillary, and polypoid patterns
Cuboidal to low columnar epithelium to scant cytoplasm; hobnail cells
Hyalin around tubules in basement membrane
Anatomic sites where nephrogenic adenoma may be found
Urinary bladder
Ureter
Urethra
Renal pelvis
Risk factors for urothelial CA
Smoking
Aryl amine exposure
Long time analgesic use
Cyclophosphamid exposure
Irradiation
Prognosis of flat urothelial lesions
Urothelial proliferation of uncertain malignant potential - if not associated with any papillary lesions, no follow up needed
AUS - predominantly good outcomes
Urothelial dysplasia, low grade - marker of urothelial instablity denoting progression and recurrence
CIS - Mortality if 7-15% is not associated with invasion
Prognosis of papillary urothelial lesions
Urothelial proliferation of uncertain malignant potential - continued monitoring required, due to associated with papillary neoplasia
Papilloma - favourable clinical course
PUNLUMP - Excellent prognosis, lower recurrence rate that LGPUC
LGPUC - Recurrence in 50-70%, progression and death in <5%
HGPUC - Profession to invasion in 15-40% of cases
Prognosis of invasive urothelial carcinoma
5y survival ~70% in pT1
Variable survival rates in pT2-T4
Common variants of urothelial CA known to behave more aggressively
Small nested
Micropapillary
Sarcomatoid
Plasmacytoid/signet ring
Undifferentiated
Common alterations found in urothelial CA
LGPUC - FGFR3
HGUC/invasive CA - TP53, RB1
Prognostic factors to report in urothelial CA cystectomy specimens
Grade
Tumor extension/depth of invasion
Associated flat CIS
Resection margins
LVI and lymph node mets
Morphologic features that suggest invasion of urothelial CA
Irregularly shaped nests and single cell infiltration
Absent basement membrane
Fingerlike projections into LP
“Paradoxical differentiation”
Desmoplastic stromal response
Myxoid stroma
Pseudosarcomatous stroma
Retraction artifact
Inflammation
Nonurothelial carcinoma of the bladder and their risk factors
SCC - Schistosomiasis hematobium, bladder diverticuli, nonfunctioning bladder, transplant patients
AdenoCA - nonfunctioning bladder, exstrophy, intestinal metaplasia, urachal remnant
Location of urachal adenoCA
Muscular wall of bladder dome
Subtypes of urachal adenoCA
Mucinous
Enteric
Signet ring cell
NOS
Mixed
Importance of distinguishing urachal and nonurachal adenoCA in the urinary bladder
Resection of urachal adenoCA must include removal of entire urachal remnant
Urachal CAs are frequently amenable to partial cystectomy as they are usually found along the free surface of the bladder
IHC to distinguish urachal and colonic adenoCA
no reliable IHC
B-catenin typically nuclear in colonic and non-nuclear in urachal
Clinical settings of postoperative bladder spindle cell nodules
Within three months of previous resection
Nodule at surgical site
Histologic features of postoperative spindle cell nodule in the bladder
Interlacing fascicles of mitotically active spindle cells with uniform nuclei and little pleomorphism
Delicate vasculature, scattered inflammatory cells, small foci of hemorrhage, edema, focal myxoid change
Main histologic differential diagnosis of postoperative spindle cell nodule in bladder and key IHC to differentiate
Inflammatory myofibroblastic tumor
ALK
DDx not to miss for postoperative spindle cell nodule of the bladder
IMT
Sarcomatoid CA
Leiomyosarcoma
Common postoperative lesions/changes in the bladder
Spindle cell nodule
Post-surgical necrobiotic granulomata
Nephrogenic adenoma
Eosinophilic inflammation/cystitis
Required elements for reporting TURBTs and biopsy
Procedure
Tumor tyoe
Histologic type
associated epithelial lesions
Histologic grade
Adequacy of material for determining muscularis propria invasion
LVI
Microscopic tumor extension
Reporting of invasion in urothelial CA
Extent of LP invasion (eg focal, mm, relation to muscularis mucosae)
Need to denote muscularis mucosa or propria as invaded
Significance of tumor next to fat on bladder biopsy
No significance. Fat common in LP and submucosa
Can only diagnose extravesical extension on cystectomy
Margins in radical cystectomy
Ureteral
Distal urethra
Deep soft tissue
How to distinguish SCC or adenoCA from urothelial CA with aberrant squamous or glandular differentation
Requires pure SCC or adenoCA histology
If papillary, invasive, or flat CIS OR present urothelial component, best to call it urothelial
Staging considerations for neoplasms of upper urinary tract
Depth of invasion and stage most important for prognosis
In the reval pelvis, tumor type impacts staging (pT3 vs pT4)
LP is absent beneath urothelium that lines renal papillae in pelvis and thin along minor calycesRe
Regional LNs for renal pelvis and for ureter
Renal pelvis: renal hilar, paracaval, aortic, retroperitoneal
Ureter: renal hilar, iliac, paracaval, periureteral, pelvic
Residual Ureter/renal pelvis tumor classification
RX: residual tumor cannot be assessed
R0: no residual tumor
R1: microscopic residual tumor
R2: macroscopic residual tumor
How to gross segmental ureterectomy
Record length and diameter of intact ureter
Ink outer aspect
Take proximal and distal cross section margins
Open ureter longitudinally
Take sections to demonstrate deepest level of invasion
Take a section of uninvolved ureter
How to gross radical nephroureterectomy with bladder cuff
Document and sample relationship of tumor to adjacent renal parenchyma, peripelvic fat, nearest soft tissue margin, ureter
Ink outer aspect of ureter and open ureter longitudinally
Take sections to demonstrate deepest level of invasion
Submit bladder cuff margin as a shave
Submit section of unremarkable kidney, pelvis, and ureter
T staging for renal pelvis tumors
pTa: noninvasive papillary tumor
pTis: flat CIS
pT1: tumor invades LP
pT2: tumor invades MP
pT3: renal pelvis only: tumor invades beyond muscularis into peripelvic fat or into renal parenchyma
Ureter only: tumor invades beyond muscularis periureteric fat
N staging for renal pelvis and ureter tumors
pN1: met in single regional LN </=2cm in greatest dimension
pN2: met in single regional LN >2cm or multiple LNs
Impact of anatomic location on tumor type in urethral tumors
In women, SCC is most common histologic subtype (75%) and most common in anterior urethral. Urothelial CA next in frequencym followed by adenoCA (10-15% each) including clear cell adenoCA
In men, tumor tumors involve bulbomembranous urethra followed by pensile urethra and prostatic urethra. 80% of CAs of urethra are SCC, followed by urothelial. Urethral adenoCAs rare in men
Reporting of depth of invasion in urethral CAs
Surrounding anatomic structures vary by location and sex
In prostatic urethra, invasion may arise from a tumor lining urethral lumen or from CIS colonizing prostatic ducts
Invasion arising from prostatic ducts is designated at least pT2
Sections to submit in urethral tumors
Transurethral specimen - 1 section per cm or more to dx or r/o invasion
Urethrectomy: 1 section per cm focusing on areas of deepest invasion
Document tumor in relation to surrounding structures
Submit distal and proximal margins
Ink and submit radial soft tissue margins
Submit several sections or urinary bladder mucosa as urothelial CA often multifocal
Representative sections of prostate and seminal vesicles to r/o concomitant prostatic CA
T staging of urethral CA (non-prostatic urethra)
pTa: noninvasive papillary CA
pTis: CIS
pT1: tumor invades subepithelial connective tissue
pT2: tumor invades corpus spongiosum or periurethral muscle
pT3: tumor invades corpus cavernosum or anterior vagina
pT4: tumor invades adjacent organs (eg bladder wall)
T staging of urethral CA in prostatic urethra
pTa: noninvasive papillary, polypoid, or verrucous carcinoma
pTis: CIS involving prostatic urethra or periurethral or prostatic ducts without stromal invasion
pT1: tumor invades urethral subepithelial connective tissue immediately underlying the urothelium
pT2: tumor invades the prostatic stroma surrounding ducts either by direct extension or by invasion from the prostatic ducts
pT3: tumor invades the periprostatic fat
pT4: tumor invades adjacent organs
Subtypes of penile SCC with better prognosis
Verrucous CA
Warty CA
Papillary CA
Pseudohyperplastic CA
Subtypes of pensile SCC with worse prognosis
Basaloid
Sarcomatoid
Risk factors for penile SCC
Phimosis
Chronic inflammatory conditions (eg BXO)
Smoking
UV radiation
HPV
Classification of penile intraepithelial neoplasia (PeIN)
Undifferentiated PeIN - HPV-associated, p16 pos
Differentiated PeIN - non-HPV associated, p16 neg, p53 mutant usually
Reporting parameters for penile SCC
Histologic grade and type
Extent of invasion
Maximum depth measurement
LVI
PNI
Resection margin status
Associated lesions - CIS, dysplasia, BXO etc
Grossing of circumcision specimens
Measure, describe, identify and describe any abnormality
Identify and ink mucosal and cutaneous margins with different colours
Most SCCs arise from mucosal surface
Lightly stretch and pin specimen. FIx for several hours in formalin. Cut vertically through urethra in 12 to 6 o’clock plane to divide penile glans, foreskin, and shaft into left and right portions
Grossing of penectomy specimen
Measure, describe, identify and describe any abnormality
Describe foreskin, if present
Cut proximal margin en face, making sure to inlude circumference of urethra (which tends to retract)
Submit skin of shaft with dartos and fascia with corpora cavernosa
Fix remaining specimen
Cut specimen longitudinally and centrally to separate into left and right halves
Serially section
Site from which penile SCCs arise
Distal epithelium (glans, coronal sulcus, mucosal surface of prepuce)
Types of invasion in penile SCC and their significance
Infiltrating vs pushing
Infiltrating has higher risk for nodal invasion
Histologic subtypes of penile SCC and their prognostic risk groups
low-risk: verrucous, papillary, warty/condylomatous, pseudohyperplasia, carcinoma cuniculatum
Intermediate-risk: usual type SCC, mixed neoplasm, high grade variants of warty/condylomatous CA
High-risk: basaloid, sarcomatous, adenosquam, poorly differentiated SCC of usual type
Grading of penile SCC
Grade 1: extremely well differentiated
Grade 2: more disorganized growth with higher nuclear atypia
Grade 3: any proportion of anaplastic cells, solid sheets or small aggregates with little to no keratinization, more nuclear atypia
Report any proportion of grade 3
Tumor depth/thickness measurement in penile SCC
Measurement from epithelial-stromal junction of adjacent nonneoplastic epithelium to deepest point of invasion
How is DOI correlated with prognosis of penile SCC
Minimal risk for mets in tumors <5mm
Tumors invading deeoer into penile anatomical levels are usually associated with higher risk for nodal involvement
Depth usually associated with grae
tumors invading into corpus cavernosum at higher risk than those invading into corpus spongiusum
Penile resection margins
Proximal urethral and surrounding periurethral cylinder (epithelium LP, corpus spongiosum, and penile fascia)
Proximal shaft with corresponding corpora cavernosa separated and surrounded by tunica albuginea and Buck Fascia
Skin of shaft with underlying dartos and penile fascia
In circumcisions: coronal sulcus margin and cutaneous margin
Most important predictive factors of mortality in penile tumors 5-10mm thick
Histologic grade
PNI
Factors that best predict nodal mets and survival in penile
Histologic grade
DOI
PNI
T stage for penile CA
pTis: CIS (PeIN)
pTa: noninvasive localized SCC
pT1: glans: tumor invade LP
Foreskin: tumor invades dermis, LP or dartos fascia
Shaft: tumor invades connective tissue between epidermis and corpora regardless of location
pT1a: tumor is without LVI or PNI and is not high grade
pT1b: tumor has LVI or PNI or is high grade
pT2: tumor invades into corpus spongiosum with or withour urethral invasion
pT3: TUmor invades into corpora cavernosum with or withour urethral invasiion
pT4: tumor invades adjacent structures
Gleason patterns
3: discrete glands
4: Fused glands, cribriforming, glomerulations,
5: no glandular formation, comedonecrosis
Gleason grade group
GG1: 3+3 = 6
GG2: 3+4 = 7
GG3: 4+3 = 7
GG4: 4+4 or 5+3 = 8
GG5: 5+4, 4+5, 5+5 = 9-10
Define tertiary gleason pattern
<5% of a higher grade pattern in a resection specimen
Define prostatic intraductal CA
Proliferation of malignant prostatic epithelial cells within ducts and acini that have intact basal cells
Histologic criteria for prostatic intraductal CA
Expanded duct
>70% of space filed with solid/loose/cribriforming growth
Nucleomegaly (5-6x usual size)
Intact basal cell layer
May have comedonecrosis
Association of prostatic intraductal CA
High volume, high grade prostate CA
Metastatic disease
Worse prognosis
What is the diagnosis when the criteria for prostatic intraductal CA are partially but not completely met?
Atypical intraductal proliferation (AIP)
Criteria for prostatic intraductal CA
Duct 2-3x the size of adjacent gland
At least 70% full of tumor cells
Cribriforming architecture
Basal cells present
AMACR negative prostate CAs
Pseudohyperplastic (75%)
Atrophic (65%)
Foamy (65%)
Conventional (20%)
AMACR positive benign prostate lesions
Nephrogenic adenoma (60%)
Atrophy (25%)
Adenosis (10%)
IHC to help differentiate primary vesicle adenocarcinoma vs colorectal adenocarcinoma involving the bladder
Nuclear B-catenin in CRC (>90%)
Pan GCT IHC marker
SALL4
HPV-associated histotypes of penile SCC
Basaloid
Papillary-basaloid
Warty
Warty-basaloid
Clear cell
Lymphoepithelioma-like
non-HPV associated histotypes of penile SCC
Usual type
Pseudohyperplasic
Pseudoglandular
Verrucous
Papillary
Adenosquamous
Sarcomatoid
