Genitourinary Flashcards
Where in the penis is this histology demonstrative of?
Corpora cavernosa
High power view of interanastamosed slit-like vascular spaces with thin muscular walls.
Complex tridimeensional network of trabeculae.
Vessel walls: thick bundles of smooth muscle. The vascular structures of the corpora cavernosa are thicker adn more complex when compared with those of the corpus spongiosum.
Why is it important to histologically separate corpus spongiosum from cavernosum?
Because tumours affecting cavernosum are a/w a higher rate of nodal metastasis.
Anatomical location?
Describe histological composition?
Describe key anatomical feature?
Litter glands (intraepithelial mucous glands) emptying into urethra.
Urethra surrounded by periurethral cylinder
Urethral epithelium (stratified with columnar celll ayer at the surface, devoid of umbrella cells) -> LP -> corpus spongiosum, albuginea and Buck fascia.
Periurethral mucinous Littre glands
Penioe lesion
Dx:
Histo features
Penile linear schlerosis -> precursor to Lichen sclerosis/
Moderate lymphcytic infiltrate in LP.
Dx:
Feature:
Lichen Sclerosis
Basal vacuolation seen just above the linear sclerosis of the basal membrane.
Dx:
Histo features:
Classic or band-like lichen sclerosis
Features: Sclerotic band replacing the LP is located between the epithelium and a dense and diffuse lymphocytic infiltrate located below.
Dx:
Key histo features:
Lichen sclerosis
Normal to atrophic epithelium covering a band of diffuse sclerosis in the lamina propia overlying a dense and continuous band of lymphocytes. Note the vacuolization of basal cells and the globular perivascular hyalinization at the epithelial-stromal interface.
Dx
LS (lymphocytic depletion subtype)
Sclerotic band replacing the lamina propria, globular and perivascular hyalinization and scarce lymphocytic infiltrate is seen. The overlying epithelium shows moderate atypia, corresponding to differentiated penile intraepithelial neoplasia.
Section from prostate bx
Dx?
Cowper’s glands
From testicular mass.
Histo features?
Dx?
Seminoma
Histo: Large cells with clear cytoplasm and squared off nuclei and prominent nucleoli admixed with inflammatory cells (lymphocytes and plasma cells in fibrous bands)
Incidental finding in bladder bx?
Dx?
Histo features?
Cause?
Dx: nephrogenic adenoma
Cause: metaplastic change of the urothelium in response to chronic infection, calculi, or prolonged catheterization. Sometimes implants.
Histo: : heterogeneous with numerous architectural patterns that are often admixed including small tubular, papillary, sheet-like with clear cytoplasm (diffuse), fibromyxoid, and flat. The lesional cells are low cuboidal and may have a hobnail arrangement in tubules or on papillae; thick BM material often surrounds the tubules. Small tubules often have an intraluminal blue myxoid material that may simulate a signet ring cell.
PCCRT is diffusely positive for CK7 and exhibits cup-like staining for CAIX with no luminal border staining. GATA3 may be positive, as are PAX2, PAX8, and 34βE12. AMACR and CD10 are negative or only patchy.
Morphology: luminal nuclei. pT1 tumour (grade 1 or 2).
ccRCC:
Inactivation of the VHL complex is the defining signature event in CCRCC, Loss of 3p .CAIX (CA9) is part of the hypoxia pathway related to VHL and shows extensive membranous immunohistochemical labelling diffusely throughout the tumour (circumferential), contrasting with the usually focal labelling associated with necrosis or ischaemia in other tumour types. CK7 usually shows negative or only focal labelling in CCRCC, but it often marks cystic areas
Bladder CIS vs reactive epithelium
IHC to differentiate?
CK20, p53, Ki67, CD44
decreased labelling for CD44 in CIS (basal only or absent, in contrast to full-thickness labelling in reactive urothelium)
Ki67 is a less established marker in WHO blue book
bladder bx. smoker.
dx?
Diagnostic features?
Urothelial carcinoma in situ.
High-grade malignant urothelial cells with markedly atypical nuclear features (recognizable at low to intermediate magnification) with no papillary formation.
In CIS, the neoplastic cells need not occupy the full thickness of the mucosa. The presence of unequivocally malignant isolated cells interspersed within benign urothelium (i.e. pagetoid spread) or of cells undermining the overlying benign urothelial layer cells is sufficient for the diagnosis.
60M bladder bx
DX?
Urothelial CIS.
Adjacent urothelium is denuded (often the case). Don’t need full-thickness atypia.
bladder bx
dx?
Key features?
Aetiology?
Cystitis cystica.
Superficial nests of urothelial mucosa with cystic change in the b/g of chronic inflammation. Often exhibit a vaguely lobular architecture, non-infiltrative growth and connection to overlying epithelium. Cells lack significant atypia, mitotic activity, stromal reaction and muscular invasion.
Aetiology: chronic irritation/local inflammatory insult
Dx?
Aetiology?
Key features?
IHC?
Nephrogenic adenoma/metaplasia.
Injury to urothelium.
Tubules lined by simple cuboidal, flattened or hobnail cells, forming an exophytic papillary or endophytic lesion
Associated acute and chronic inflammation and edema in the stroma; lack of desmoplastic reaction
multiple patterns: tubular, tubulocystic, polypoid, flat, fibromyxoid, signet ring cell-like
Hyaline rim surrounds the tubules (PAS positive thickened basement membrane)
No mitotic activity
IHC: PAX8(+), CK7(+), AMACR(+), EMA(+)
59M. Testicular mass
Dx?
Key features?
Dx: Spermatocytic tumour
Incidence peaksin the the sixth decade of life, with a mean age of 52–59 years. The tumours are rare in teenage boys and non-existent in children.
The most characteristic feature is a polymorphous cell population, often described as tripartite, consisting of three distinct cell types with distinguishing features based on cell size and chromatin: the small cells exhibit round, uniformly dense nuclei and scant cytoplasm; intermediate-sized cells have round nuclei with finely granular to filamentous (spireme) chromatin and variably prominent nucleoli; and giant cells have single or multiple nuclei with similar nuclear features to those of the intermediate-sized cells. Mitotic figures, including atypical forms, are usually frequent, as are a large number of apoptotic tumour cells. Unlike in a classic seminoma, prominent lymphocytic infiltrates are not present, and granulomatous inflammation is only rarely seen. Intratubular growth is common, but GCNIS is absent.
Essential: spermatocytic tumours typically occur in an older age group, with most patients in their fifth or sixth decade; tripartite microscopic appearance with three distinct cell types and without lymphocytic infiltrate or prominent fibrous septa; no immunoreactivity for usual embryonic germ cell tumour markers; no GCNIS.
Testicular tumour
pathological staging?
testicular mass 30M
Dx?
Key features?
IHC?
Embryonal carcinoma.
The key diagnostic feature is the cell type: large pleomorphic, epithelioid cells with vesicular nuclei containing macronucleoli (one or more), mitotic figures, and dense amphophilic cytoplasm. Nuclei frequently overlap and there is often a syncytial appearance without well-defined cell borders.
IHC: Embryonal carcinomas consistently express CD30 (membrane), OCT3/4 (nuclear), SALL4, and AE1/AE3. CD30 may be lost in metastases, but OCT3/4 is maintained in lymph node metastases after chemotherapy
Syncytiotrophoblastic giant cells frequently seen in EC (46% of cases)
Embryonal carcinoma
How can you distinguish intratubular spread from LVSI with IHC?
The distinction between intratubular spread and lymphovascular invasion may require immunohistochemistry (CD34 for basement membranes of tubules, CD31 for blood vessel endothelia, and D2-40 for lymphatic vessel endothelia).
Describe the gross anatomical layers of the testis
Embryonal ca vs chorio
46% of EC show syncytiotrophoblasts. How can you distinguish EC from chorio in this instance?
OCT3/4 staining in embryonal carcinoma, and its absence in the cytotrophoblast of choriocarcinoma, is the most useful distinguishing feature.
Embryonal ca vs seminoma
Some embryonal carcinomas (11%) show a seminoma-like pattern, how can you distinguish this from true seminoma?
AE1/AE3 and CD30 staining is diffuse/strong in embryonal carcinoma, but AE1/AE3 is patchy/weak in seminoma and CD30 should be negative or only very focally positive. PLAP, D2-40, and KIT (CD117) are diffusely positive in seminoma but should be negative (or can be patchy) in embryonal carcinoma. OCT3/4 is consistently expressed in seminoma and embryonal carcinoma and thus does not help in the distinction. SOX2 is a specific marker for embryonal carcinoma, staining 96% of embryonal carcinomas and < 1% of seminomas
Embryonal ca vs yolk sac tumour
Which IHC is useful in distinguishing these two entities?
OCT3/4 is positive in embryonal carcinoma and negative in YST, whereas glypican-3 (GPC3) and AFP are positive (diffuse/patchy) in YST and negative in embryonal carcinoma.
Embryonal ca vs teratoma
EC is (+) for Oct3/4.
Teratoma is (-) for Oct3/4 (and lacks nuclear pleomorphism)
clear cell and papillary RCC
ISUP grading?
clear cell renal cell carcinoma
IHC used to differentiate it from its ddx?
30M testicular mass
Dx?
Pattern demonstrated?
Presentation?
Other patterns?
IHC?
Yolk sac tumour, post-pubertal type.
Malignant germ cell tumour that forms structures of the embryonic yolk sac, allantois, and extraembryonic mesenchyme. Usu occurs as part of a mixed germ cell tumour. A/W GCNIS.
Glandular pattern (more common in later occurrences)
But various architectural patterns: microcystic/reticular; myxoid; endodermal sinus/perivascular; hepatoid; papillary; sarcomatoid/spindle cell; parietal pattern; polyvesciular vitelline
IHC:
AFP (+ but insensitive, can be (+) in HCC, hepatoblastoma and teratomas). Membraneous/cytoplasmic granular staiing
GPC3 is more sensitive than AFP, often with more diffuse staining (cytoplasmic/membranous).
SALL4 and pankeratins are diffusely positive (except CK7 + EMA
GATA3 + CDX2 freq (+). CD30(-), Oct3/4(-).
29M testicular mass
Dx?
Pattern?
IHC?
Yolk sac tumour, post-pubertal type.
Microcystic pattern.
IHC: AFP, GLP3, SAL4, panCK (except EMA/CK7). CDX2/GATA3 often (+) too. CD30(-), Oct3/4(-).
25M testicular mass
Yolk-sac tumour, post-pubertal type.
Pattern: Hepatoid
Most likely to be intensely AFP stain (+). Solid pattern more likely to be AFP (-).
25M testicular mass.
Dx?
Presentation?
Key features?
IHC?
Choriocarcinoma.
Malignant germ cell tumour that differentiates to resemble the trophoblastic cells of the extraembryonic chorion, including cytotrophoblasts, intermediate trophoblasts, and syncytiotrophoblasts. More often part of mixed germ cell tumour. (In men), 40% occur in the testis, can occur mediastinum, liver, lung, and gastrointestinal tract. Pts often present w/ disseminated disease which is vascular (e.g.haemoptysis from lung mets, anaemia) and raised bHCG.
Micro: haemorrhagic/necrotic lesion; mixture of mononucleated trophoblasts (cytotrophoblasts and intermediate trophoblasts) and multinucleated syncytiotrophoblasts. The cystic haemorrhagic spaces (blood lakes) are lined by aggregates of mononucleated trophoblasts capped by syncytiotrophoblasts that are often protruding into the cystic spaces, thus imparting an appearance of early placental villous growth that typically lacks stromal cores. Vasc invs is common.
IHC: bhCG & hPL expressed in syncytiotrophoblasts (some cytos do). STB also express GATA3/GLP3.
cytotrophoblasts express SALL4, GDF3, p63, and GATA3
Cytos Oct3/4(-)!!!
Haemorrhage+biphasic cells: cytotrophoblasts/ syncytiotrophoblasts
41M testicular mass
Dx?
Key features?
IHC?
Dx: Leydig cell tumour
Medium to large polygonal cells that have abundant eosinophilic cytoplasm and a single prominent nucleolus. Brownish pigmentation, globular cytoplasmic inclusions, and Reinke crystals are found in one third of cases.
IHC: (90% + for) calretinin, α-inhibin, melan-A, SF1, CD99, FOXL2, and synaptophysin.
30M
Dx?
GCNIS
Seminiferous tubules, most showing germ cell neoplasia in situ arranged as atypical gonocytes in the spermatogonial niche.
testicular tumours
Teratoma is most commonly seen with which other testicular tumours?
embryonal and yolk sac
GCNIS is also commonly seen along side teratoma
25M testis
Teratoma, post-pubertal type
A/W GCNIS
This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
25M testicular mass
Dx?
Mixed germ cell tumour
This example shows an embryonal carcinoma (centre bottom) surrounding a subtle nest of yolk sac tumour (centre top); teratoma is also present (right).
3M testicular mass
Dx?
Essential + desireable WHO criteria
Teratoma, pre-pubertal type
This example shows an embryonal carcinoma (centre bottom) surrounding a subtle nest of yolk sac tumour (centre top); teratoma is also present (right).
papule face of 50F
Dx?
DDx?
Desmoplastic trichoepithelioma
DDx: MAC, syringoma, morpheaphorm/infiltrative BCC
renal lesion bx
dx:
Features exemplified:
Essential and desireable dx criteria
IHC:
Fumarate hydratase deficiency RCC
Essential: demonstration of germline/somatic mutation of FH or immunohistochemical evidence of FH deficiency (FH loss and/or 2SC expression).
Desirable: presence of multiple admixed architectural patterns with at least focal macronucleoli; clinical and/or family history of skin and uterine leiomyomas (if associated with HLRCC syndrome).
Negative immunohistochemical staining for FH in tumour cells, in the presence of positive FH staining in internal non-neoplastic cells, is highly specific for FH-deficient RCC but typically not sensitive. In contrast, aberrant staining for 2SC is highly sensitive for FH-deficient RCC but less specific
renal lesion
dx:
Key feature displayed in image:
essential/desireable dx criteria:
SDH deficient RCC
Essential: loss of expression of SDHB in the presence of an internal positive control in non-neoplastic cells; cases associated with SDHA mutation also show loss of expression of SDHA.
Desirable: typical morphology, characterized by bland cells with eosinophilic (but not oncocytic) cytoplasm and occasional cytoplasmic inclusions, is usually present at least focally, but other morphologies are increasingly being recognized.
Image: Distinctive cytoplasmic inclusions containing eosinophilic or pale flocculent material.
Furthermore, weak diffuse cytoplasmic expression of SDHB should also be considered negative if it contrasts the strong granular mitochondrial expression in internal positive controls. Tumours associated with biallelic inactivation of SDHA also show a loss of SDHA (as well as SDHB) expression, whereas tumours driven by SDHB, SDHC, or SDHD mutation show preserved SDHA expression
chromophobe-oncocytoma hybrid tumours
Syndromic association?
Birt-Hogg-Dubé syndrome
Fumarate-deficient RCC
syndromic association?
Hereditary leiomyomatosis and RCC syndrome
(germline FH mutations and multiple leiomyomas)
Fumarate deficient RCC
IHC
demographics
loss of FD expression and gain of 2-succinocysteine (2SC) staining
Younger patients, aggressive tumours,
50M H/O PCK
Dx
Clin presentation
IHC:
Dx: acquired cystic disease RCC
Tumour occurs exclusively in patients with acquired cystic disease, usually after long-term dialysis.
Key features: Architectural variability. Eosinophilic cells. Most characteristically, the tumour cells have intracytoplasmic or intercytoplasmic lumina or holes, imparting a cribriform (sieve-like) appearance. Intratumoural oxalate crystal deposition is common
usu indolent
IHC: PAX8, CD10, RCCm, and AMACR are positive. Most ACD-RCCs are negative for GATA3, CK7, and KIT
renal papillary adenoma, dx criteria.
Essential: size ≤ 15 mm; papillary, tubular, or tubulopapillary architecture; absence of a fibrous capsule; low histological grade (grade 1–2).
50M renal lesion
Dx:
Key morpho features:
IHC:
Epithelioid angiomyolipoma
Two different patterns:
- carcinoma-like pattern: nests of atypical large eosinophilic cells, resembling ganglion cells, with prominent nucleoli and intranuclear inclusions (ganglion cell–like appearance). Separated by thin, vessel-rich septa. Few mitoses.
2) epithelioid and plump spindle cells; diffuse growth, voluminous cells and spindle cells, moderate atypia and pale cytoplasm. Mitotic activity as well as intranuclear inclusions are uncommon or lacking.
IHC: melanocytic markers (HMB45, melan-A, and MITF), cathepsin K, CD68 and (variably) smooth muscle markers. DDx: ccRCC and urothelial ca with extensive sarcomatoid differentiation. Immunolabelling for cathepsin K, HMB45, and melan-A is helpful. This immunophenotype overlaps with TFE3-rearranged or TFEB-altered renal cell carcinoma, but PAX8 and CD68 are reliable tools for distinguishing between them
In image; Note the relatively uniform epithelioid cells with clear to granular, feathery eosinophilic cytoplasm.
50M renal lesion
Dx:
IHC:
Epithelioid angiomyolipoma with carcinoma-like pattern characterized by large eosinophilic cells with atypical nuclei and prominent nucleoli arranged as nests.
IHC: melanocytic markers (HMB45, Melan-A, MIFT), CD68, cathepsin K
dx criteria
epithelioid angiomyolipoma/epithelioid Pecoma of the kidney
Essential: a carcinoma-like appearance and/or epithelioid and plump spindle cells in a diffuse growth pattern showing positivity for melanocytic markers and cathepsin K; ≥ 80% of the tumour cells should be epithelioid cells.
renal lesion
dx:
Histo features:
IHC:
Key molecular:
Eosinophlic solid and cystic RCC
Unencapsulated, can be primarily solid. polygonal and have Neoplastic cells: voluminous eosinophilic cytoplasm with basophilic cytoplasmic stippling. The cysts are typically lined by a single layer of hobnail cells that are often multinucleated. Minimal pleomorphism. +/- foamy histiocytes/lymphocytes admixed, as well as psammoma bodies.
IHC: Pax8(+); CK20 & cathepsin K patchy (+); KIT/CK7 (-). Occasional tumour cells (+) melan-A (»ddx: MiT family translocation renal cell carcinoma).
Mole: Demonstration of TSC1 or TSC2 gene alterations may be helpful .
Essential: solid and cystic architecture; voluminous eosinophilic cytoplasm with coarse basophilic stippling.
Desirable: CK20 immunoreactivity; mutations in TSC1 or TSC2.
Below: coars basophilic stippling.
renal lesion
dx?
Key features:
DDx:
IHC:
Molecular:
Metanephric adenoma (benign)
Lack pseudocapsules; well-circumscribed.
Embryonal epithelial cells with small round nuclei only slightly larger than those of lymphocytes. No prominent nucleoli and have minimal cytoplasm. Hyalinized, oedematous, paucicellular stroma. Psammoma bodies are common/often abundant. Mitotic figures absent or rare. Vascular invasion not seen.
DDx: solid subtype of low-grade papillary renal cell carcinoma and epithelial-predominant nephroblastoma.
IHC: diffuse nuclear WT1 (+); cytoplasmic/membranous CD57(+); EMA/AMACR/CK(-) ; BRAF VE1 (cytoplasmic +)
NB: pRCC: CK7 & EMA (+); WT1 (-) (glom podocyte processes = (+) internal control) + trisomy 7 and 17. Epithelial predominant nephroblastoma: younger age, Mitoses ++, BRAF (-)
In this image: More prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and lack of stromal foam cells are clues to the diagnosis of MA.
renal lesion
Dx:
essentail and desireable key features
Metonephric adenoma
Essential: a primitive-appearing but mitotically inactive renal epithelial neoplasm that is WT1-positive.
Desirable: BRAF p.V600E mutations.
Image: The stroma is oedematous and contains branching tubules and tubulopapillary structures that create a fingerprint-like appearance.
40F renal lesion
dx:
clin presentation:
Essiential and desireable dx criteria:
IHC:
Mixed epithelial and stromal tumour of the kidney.
Occur overwhelmingly in women, typically middle-aged.
Cystic nephroma
Essential: multilocular cystic tumour, cysts lined by flat, cuboidal, or hobnail-shaped cells and separated by thin septa with benign-appearing spindle-shaped cells. (sometimes resembling ovarian stroma. Stromal luteinization and nodules of hyalinized stroma with sharp contours resembling ovarian corpora albicantia can occur )
Desirable: IHC labelling for PR and/or ER and frequently for inhibin.
MEST
Essential: a complex solid and cystic tumour composed of varied epithelial elements embedded in a variably cellular heterogeneous spindle-shaped cell stroma
(Small cysts containing eosinophilic material reminiscent of thyroid follicles)
Desirable: immunohistochemical labelling for PR and/or ER but not for cathepsin K.
Image: A cyst (left) is lined by flattened epithelial cells and surrounded by spindle cell stroma (centre) resembling ovarian stroma.
35F renal lesion
Dx?
Features demonstrated?
MEST
A solid area demonstrates ovarian-like stroma containing numerous tubules with flattened lining, resembling thyroid tubules.
kidney lesion, child
Dx:
Histo features:
IHC:
nephroblastoma
Histo features: characteristically contain undifferentiated blastemal cells, as well as cells differentiating to various degrees and in different proportions towards epithelial and stromal lineages. Triphasic patterns are the most characteristic, but biphasic and monophasic lesions are often observed. Most of these components represent stages in normal or abnormal nephrogenesis, but heterologous, non-renal elements also occur.
IHC: Immunoreactivity for WT1 (seen in ~80% of cases) is typically limited to the blastema and epithelial components of nephroblastoma, with the stroma being negative.
Image: Classic triphasic growth pattern, of blastemal cells, stromal cells, and epithelial differentiation including tubules and primitive glomeruli.
nephroblastoma
ddx for monophasic patterns and how you’d work them out w/ IHC
monophasic nephroblastomas can be mistaken for a variety of neoplasms. Pure epithelial nephroblastomas can be confused with metanephric adenoma as well as type 1 papillary renal cell carcinoma. WT1 immunoreactivity helps exclude papillary renal cell carcinoma, but it is consistently found in metanephric adenoma. Pure blastemal nephroblastomas raise the broad differential diagnosis of small round cell tumours, particularly neuroblastomas and rhabdoid tumour in young patients and Ewing sarcoma in older children or young adults. The absence of membranous CD99 immunoreactivity or nuclear PHOX2B immunoreactivity, as well as intact SMARCB1 (INI1) labelling, can help exclude these possibilities. Pure stromal nephroblastomas can be confused with clear cell sarcoma of the kidney, congenital mesoblastic nephroma, or synovial sarcoma { 32204536 }. This difficulty can be magnified by preoperative chemotherapy, which often selectively kills the blastemal and epithelial cells of nephroblastoma and leaves the stromal component behind. A paediatric renal neoplasm containing skeletal muscle can be assumed to be a nephroblastoma until proved otherwise.
nephroblastoma (WT)
associated conditions
WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies, and a range of developmental delays)
Denys–Drash syndrome
renal lesion
dx:
IHC
Papillary renal cell carcinoma
Essential: variable proportions of papillary and tubular architecture lined by cuboidal to columnar cells, lacking extreme morphological pattern heterogeneity (which would suggest fumarate hydratase–deficient RCC) or the classic morphology of CCRCC.
Desirable: foamy histiocytes; psammoma bodies; diffuse strong immunohistochemical labelling for AMACR; normal positive (intact/retained) fumarate hydratase labelling.Papillary RCC
IHC: AMACR S+D (+); CK7 (+); vimentin & CCD10 (+); CAIX (-)
50M cystic lesion upper pole of kidney
Dx:
Key features
Molecular
IHC
Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP)
90% are incidentally detected radiologically
Cyst lining consists of one or a few layers of optically clear, bland-looking cells. Clear cell clusters may be present within the fibrous capsule or thin septations; however, they should not alter their contours by expansile growth or exceed a 20× (1 mm) microscopic field of view i.e. lack solid growth). The presence of necrosis, frequent or atypical mitoses, lymphovascular invasion, or rhabdoid or sarcomatoid dedifferentiation is incompatible with a diagnosis of MCNLMP. The immunoprofile is similar to that of CCRCC because of the diffuse reactivity for CAIX, EMA, CAM5.2, PAX8, and PAX2
Molecular: Loss of the entire chromosome 3 or its short arm (3p) harbouring the VHL locus is detected by FISH in 77% of MCNLMP cases { 20348877 ; 29770853 }. Inactivating VHL mutations are detected in 25–40% of cases
NB: dx cannot be made on bx alone as the features of MCNLMP overlap with those of cystic CCRCC and even solid CCRCC with a focal cystic/degenerative component.
well circumscribed corticocystic lesion upper pole
dx
key features
ddx to exclude
Px
tubulocystic RCC
Key features:
Well circumscribed
The cut surface consist of small white cysts containing clear fluid. No haemorrhage or necrosis is observed
Comprises small to intermediate-sized tubules admixed with larger cysts, which are lined by a single layer of flattened, cuboidal/columnar, and hobnail epithelium.
Nuclei are enlarged/irregular; intermediate to large and prominent nucleoli;
Abundant eosinophilic cytoplasm.
Low-grade fumarate hydratase–deficient tumours must be excluded by immunohistochemistry, but they are recognizable by their heterogeneous architecture and high-grade features
Px: indolent tumour with a good prognosis
renal lesion
dx
key diagnostic features
IHC
papillary RCC
thinly branching papillae and low-grade oncocytic tumour cells with nuclei aligned towards the apex of the cell. Tumours with this distinctive pattern have been recently recognized as papillary neoplasms with reverse polarity. They appear to be consistently positive for GATA3 and negative for vimentin, with labelling for AMACR being less extensive. CAIX (CA9) labelling is typically negative or focal, unlike in CCRCC. These tumours have recurrent mutations of KRAS, differing from typical PRCCs
Essential: variable proportions of papillary and tubular architecture lined by cuboidal to columnar cells, lacking extreme morphological pattern heterogeneity (which would suggest fumarate hydratase–deficient RCC) or the classic morphology of CCRCC.
Desirable: foamy histiocytes; psammoma bodies; diffuse strong immunohistochemical labelling for AMACR; normal positive (intact/retained) fumarate hydratase labelli
Low-grade oncocytic tumour and eosinophilic vacuolated tumor, molecular mutations
Mutations in MTOR pathway and tuberous sclerosis genes 1 and 2
Low grade oncocytic tumours of the kidney
compare IHC profile with that of oncocytoma
LOT: CK7 S/D +; CD117(-)
Oncocytoma: CK7(-); CD117(+)
renal mass
dx
IHC
Key features
Molecular
Dx: eosinophilic, vacuolated tumour
IHC: CD117+; CK7/CD20-
Key histo features: solid, entrapped renal tubules, coarse cytoplasmic vacuoles, prominent nucleoli
Molecular: Some with TSC1, TSC2, and Mtor p/w mutations
testicular mass
Dx
essential and desireable features
IHC
choriocarcinoma
Essential: a characteristic biphasic pattern containing cytotrophoblastic cells and syncytiotrophoblasts.
Desirable: trophoblastic immunohistochemical markers (e.g. hCG, hPL, GATA3, and GDF3) for the distinction of choriocarcinoma from other germ cell tumours; presence of germ cell neoplasia in situ.
IHC: hCG, GATA3, GDF3
35M testis mass
Dx:
Key features:
Dx: regressed germ cell tumour
Key features:
Intratesticular fibrous scar.
Acellular collagenous tissue with numerous small interspersed vessels
Foamy or hemosiderin laden macrophages
Lymphoplasmacytic infiltrate
May have necrosis or intratubular calcification (microlithiasis)
Residual germ cell tumor may be present if regression is incomplete
Pure seminoma most common
Testicular parenchyma:
Germ cell neoplasia in situ (50% of cases)
Remaining parenchyma may be atrophic with:
Shrunken seminiferous tubules with decreased spermatogenesis
Sertoli cell only lined tubules
Thickened peritubular basement membrane
10M testicular lump
Dx:
Key diagnostic features
DDx:
Px:
Dx: Sertoli cell tumour
Key features: a testicular mass with conspicuous or at least focal tubular differentiation in varying amounts. In this image, tubules and cords with interanastomosing growth.
DDx: adenomatoid tumour (IHC for calretinin, WT1); if brisk lymphocytic infiltrate and clear cell change, seminoma but SCT not a/w GCNIS and lacks expression of germ cell markers e.g. SALL4.
Sertoli cell nodule - has spermatogonia in the tubules
Px: good px; mets very rare and higher in malignant SCT
30M testicular mass
Dx:
essential and desireable diagnostic features.
IHC:
Px:
Sertoli cell tumour
Essential: a testicular mass with conspicuous or at least focal tubular differentiation in varying amounts.
Desirable: immunoreactivity for cytokeratins; nuclear positivity for β-catenin.
IHC: + for cytokeratins (60–80%), nuclear β-catenin (60–70%)
Px: generally benign.
45M testicular mass + gynaecomastia
Dx:
Essential and desireable features.
Feature demonstrated?
Sertoli cell tumour
Essential: a testicular mass with conspicuous or at least focal tubular differentiation in varying amounts.
Desirable: immunoreactivity for cytokeratins; nuclear positivity for β-catenin.
In this image showing prominent stromal sclerosis. Many Sertoli cell tumours show variable sclerosing features.
50M testicular mass
Dx
Key feature demonstrated
Sertoli cell tumour
The characteristic solid or hollow tubular architecture is present, at least focally, in most cases.
6M testicular mass
Dx
Sertoli cell tumour
55M testicular mass
dx?
Essential and desirable dx criteria
spermatocytic tumour
Essential: spermatocytic tumours typically occur in an older age group, with most patients in their fifth or sixth decade; tripartite microscopic appearance with three distinct cell types and without lymphocytic infiltrate or prominent fibrous septa; no immunoreactivity for usual embryonic germ cell tumour markers; no GCNIS.
Desirable: absence of 12p overrepresentation; characteristic molecular alterations including gain of chromosome 9.
In this image, Intratubular growth of tumour cells; the seminiferous tubules are expanded by variably sized tumour cells
layers of urothelium in bladder and staging
Layers of bladder wall (from inside out)
Urothelium: specialized stratified lining epithelium, impermeable barrier
Lamina propria: connective tissue containing vessels, lymphatics, nerve endings and a few elastic fibers
Muscularis propria: also called detrusor muscle; consists of 3 layers (inner longitudinal, middle circular and outer longitudinal)
Serosa / adventitia: serosa is loose connective tissue covering bladder dome; the remaining area is covered by adventitia
bladder lesion 70M routine surveillance following bcg
Dx:
Key histo features
Nephrogenic adenoma
Key features:
Tubules lined by simple cuboidal, flattened or hobnail cells, forming an exophytic papillary or endophytic lesion
Associated acute and chronic inflammation and edema in the stroma; lack of desmoplastic reaction
Morphologic variants: papillary, tubular, tubulocystic, polypoid, flat, fibromyxoid, signet ring cell-like
Hyaline rim surrounds the tubules (PAS positive thickened basement membrane)
No mitotic activity
May be associated with radiotherapy
In below image, small and cystic tubules in the context of a heavy inflamed stroma. The thickened hyalinized basement membrane is prominent (left.
bladder lesion bx
Dx?
Key features?
Papillary/polypoid cystitis
Exophytic polypoid to papillary structures characterized histologically by normal or mildly hyperplastic urothelium overlying a congested, chronically inflamed and edematous stroma
Note, terminology:
Polypoid cystitis: polypoid (broad based) structure
Papillary cystitis: papillary (slender, finger-like) papillae
Bullous cystitis: bullous contour with width greater than height
25M orchidectomy
dx
Key feature displayed
Cryptorchid testis
Image displaying sertoli only tubules, peritubular fibrosis, absent spermatogenesis.
Below imagin: high-power view showing sertoli cells and no spermatogenesis and dense pink peritubular fibrosis.
16M chronic painless left testicular mass
testicular splenic fusion
-> encapsulated splenic tissue is found adjacent ot he left testis,
60M incidental finding spermatic cord
dx?
adrenal cortical rest
testis
dx
essential dx criteria
ddx
Placental site trophoblastic tumour
Essential: mononucleated trophoblastic cells in diffuse sheets; infiltrative pattern with prominent vascular invasion; tumour cells are positive for hPL and negative for p63.
DDx: Epithelioid trophoblastic tumour (hPL -, p63+)
NB: Only 7 cases have been described!!!!
Above image: Pleomorphic trophoblastic cells in a fibrinoid background with prominent vascular invasion. The tumour shows a cohesive growth pattern with areas of cells growing in small clusters and singly.
Below image: The squamoid tumour cells are pleomorphic and often multinucleated; the nuclei contain prominent nucleoli. The cells contain hyaline globules and show prominent apoptosis and necrosis. Mitotic figures are easily identified.
teratoma, postpubertal type
diagnostic molecular alteration
Isochromosome 12p and 12p overrepresentation can be observed in the majority of tumours using cytogenetic and FISH studies
teratoma with somatic type malignancy
essential dx criteria?
Essential: expansile and infiltrative growth of epithelial or mesenchymal component measuring ≥ 5 mm.
To declare a tumour as a somatic-type malignancy, the tumours should exhibit a pure population of atypical mesenchymal or epithelial cells and occupy at least one low-power field (×4 objective, 5 mm in diameter)
postpubertal vs prepubertal teratoma
distinguishing clinical, histological and molecular features
prepubertal teratoma
essential and desireable dx features
Essential: a teratoma with no associated GCNIS and an absence of regressive changes in the non-neoplastic testicular tissue; exclusion of embryonic-type neuroectodermal tumour.
Desirable: absence of 12p alterations.
3M testicle lump
Dx
teratoma, prepubertal type
Large cell calficying sertol cell tumour
Seen in which hereditary condition?
Mode of inheritance
Carney complex
Autosomal dominant
Multiple neoplasia syndrome with myxomas and pigmented lesions of skin and mucosa, due to mutation in PRKAR1A gene
ccRCC
associated inherited cancer syndromes
von Hippel-Lindau disease: AD, clear cell RCC, hemangioblastomas of hte cerebellum and retina, pheochromocytoma, pancreatic neuroendocrine tumours and inner ear tumours. Germline mutations of hte VHL TSG on chromosome 3p25.3
Inherited cancer syndromes that affect the kidney
vHL
Hereditary papillary RCC
Birt Hogg Dube syndrome
Tuberous sclerosis syndrome
Hereditary leiomyomatosis and RCC
Hereditary paraganglioma-phaeochromocytoma syndorme
Polycystic kidney disease
mutations in AR vs AD PKD?
Broadly, what type of disorder do these diseases fall under?
ARPKD: PKHD1 gene (encodes polyductin/fibrocystin)
ADPKD: PKD1 (85%) AND PKD2 (15%) encoding polycystin-1 and polycystin-2 respectively.
Classified as ciliopathies.
Wilms tumour
conditions a/w WT
Denys-Drash (90% risk of WT)
WAGR (30% risk)
Fraiser (8%)
Mosaic-variegated aneuploid, Perlman sydnrome, and Fanconi anaemia have risk of WT in 25% to 35% of affected children.
47M right epididymal head mass
Dx:
DDx and how you’d differentiate?
Papillary cystadenoma (2nd most common tumour of the epididymus after adenomatoid tumour)
DDX: ccpRCC; serous borderline tumour and serous adenocarcinoma of the paratestis
IHC: renal antigen, AMACR? and for serous borderline/adeno ->atypia, mitotic activity, stratification and detached cell clusters
clinical, gross, microscopic and immunohistochemical features of a mixed epithelial and stromal tumor
How do they differ from adult cystic nephroma?
Typically occur in perimenopausal women, often with long term hormonal treatment.
Solitary, well circumscribed tumors, with variable solid and cystic components
Versus adult cystic nephroma - predominantly cystic tumors with no solid components
Mostly benign but rare malignant transformation of epithelial or stromal component
Stromal cells typically positive for ER / PR
Usu Located in renal medulla, with some bulging into renal pelvis
Stroma-
Wide spectrum of morphology:
Areas may show smooth muscle differentiation or ovarian type stroma with luteinization
Condensation of spindle cells around epithelial component
Epithelium:
Cysts and glands of varying size and architecture; scattered or clustered
Lining cells with broad spectrum of morphology: flat, cuboidal, columnar, hobnail, urothelial-like, clear cell, ciliated
Urothelial carcinoma - subtypes
Micropapillary
Nested
Large nested UC
Tubular and microcytic
Plasmacytoid
SArcomatoid UC
Lipid-rich
Lymphoepithelioma-like
Giant cell
Clear cell
UC, poorly differentiated
The Paris classification for urine cytology.
limitations
Acknowledges the inability of cytology to reliably detect low-grade urothelial neoplasm. In general, urine specimens with HGUC are cellular w/ numerous cells displaying a set of characteristic nuclear diagnostic features, including an N:C ratio >0.7, hyperchormasia, irregular clumpy chromatin, and irregular contours. NB: not all subtypes carries a high N:C ratio > 0.7 (e.g. plasmacytoid or micropapillary UC may contain cells with relatively bland nuclear features. Moreover, HGUC with divergent squamous differentiation will contain numerous cells with a low N:C ratio).
Birt Hogg Dubé syndrome
Gene mutation
Mode of inheritance
Features
Mutation in FLCN (follicular) gene
AD but variable penetrance.
Skin lesion (fibrofolliculoma; acrochordons)
Renal tumours (chromophobe; oncocytoma; hybrid oncocytoma chromophobe tumour; RCC unclassified)
Lung cysts - inferior to carina.
genetic alteration in pRCC
trisomy of 7 and 17
describe the gleason grading for prostate carcinoma
molecular alteration in papillary RCC
PRCCs commonly have gains of chromosomes 7 and 17, and loss of the Y chromosome
Which molecular IHC clone is using for testing metanephric adenomas?
BRAF VE1 clone
AJCC p staging criteria for prostate ca
