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Male Reproductive Pathology/GU Pathology Flashcards

1
Q

What stain is positive in urothelial carcinoma and negative in prostate carcinoma? Also, this stain is positive in basal cells in the prostate but is absent in cancer

A

CK903

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2
Q

What stain is positive in Stromal Tumors of Uncertain Malignant Potential (STUMP) of the prostate but is negative in other muscle neoplasms?

A

CD34 STUMPs are also PR +

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3
Q

Carbonic anhydrase IX (CAIX) is the most sensitive and specific marker of clear cell RCC. This is expressed as a result of mutation of what gene?

A

VHL mutation (100% inherited and 75% of sporadic)

VHL normally regulates the degradation of HIF (hypoxia inducible factor). So VHL mutation leads to increased HIF which leads to increased expression of HIF-regulated genes (CAIX and VEGF). Targeted therapies for clear cell RCC (Sunitinib) inhibit this pathway

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4
Q

What 2 stains are positive in papillary renal cell that are not positive in clear cell RCC?

A

CK7 and racemase

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5
Q

What stains are positive in chromophobe RCC?

A

Hale’s colloidal iron, EpCAM (new marker for chromophobe), CD117 (c-kit), CK7

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6
Q

What stains are positive in translocation carcinomas of the kidney?

A

TFE3 (Xp11 translocation)

TFEB (t(6;11) translocation)

*TFEB tumors stain with Melan-A and HMB45

Cathepsin-K (both translocations)

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7
Q

What kidney tumor is recently recognized that typically occurs in the setting of end stage renal disease, it does not have genetic changes of clear cell renal cell (chromosome 3p loss), papillary RCC (trisomy 7 and 17) or Xp11 translocation RCC and it has low grade nuclei that typically show reverse polarization similar to secretory endometrium?

A

Clear cell papillary RCC

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8
Q

What group of stains are positive in all non-seminoma germ cell tumors but negative in seminoma?

A

Epithelial markers (keratins and EMA)

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9
Q

What mesothelial and lymphatic marker is positive in 100% of seminomas and 30% of embryonal carcinomas?

A

D2-40 (podoplanin)

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10
Q

Seminomas are generally positive for OCT4, SALL4, PLAP and c-kit. Which one of these is the only marker positive in SPERMATOCYTIC seminomas?

A

SALL4

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11
Q

What recently described stem cell marker is positive in embryonal carcinomas (not CD30)?

A

SOX2

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12
Q

What stain is positive in seminoma and embryonal carcinomas but is negative in yolk sac?

A

OCT4

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13
Q

What stains are positive in sex cord stromal tumors (Sertoli and Leydig)?

A

Inhibin, Melan-A (also positive in adrenocortical tissue but not of the other melanoma markers are), CD10, CD99 and Calretinin

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14
Q

What is the striped pattern of renal interstitial fibrosis characteristically associated with?

A

Cyclosporine/tacrolimus toxicity

This is an important cause of renal allograft dysfunction and can lead to acute tubular necrosis, vacuolar change of tubular epithelium, as well as microvascular injury with vascular thrombosis. Prolonged administration is manifested by a specific striped pattern of interstitial fibrosis and this pattern is associated with arteriolopathy and is therefore thought to be ischemic in origin.

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15
Q

What is Birt-Hogg-Dube syndrome, how is it inherited and what chromosome and gene is involved?

A

Birt-Hogg-Dubé syndrome is an autosomal dominant inherited disorder associated with a genetic abnormality on chromosome 17p11.2 leading to a mutation in the BHD (FLCN) gene that encodes folliculin.

Clinical manifestations include spontaneous pneumothorax, multiple benign cutaneous follicular tumors (fibrofolliculoma, trichodiscoma and acrochordon), oncocytomatosis and multifocal chromophobe renal cell tumors

*they can also get hybrid oncocytic - chromophobe tumor

(HOCT) which occurs in three settings: sporadic, in renal oncocytomatosis and BHD syndrome

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16
Q

What is the diagnosis of the bi-valved kidney?

A

Xanthogranulomatous pyelonephritis

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17
Q

Other than PKD, what two syndromes can have bilateral diffuse cystic kidney disease?

A

Tuberous sclerosis

VHL

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18
Q

1) What renal cancers are positive for CK7?
2) What renal cancers are positive for AMACR?

A

1) Chromophobe RCC, papillary RCC and mucinous tubular and spindle cell carcinoma (shown here)
2) papillary RCC and mucinous tubular and spindle cell carcinoma (shown here)

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19
Q

What testicular tumor is associated with granulomas 50-60% of the time and therefore if you are entertaining the diagnosis of granulomatous orchitis, you should consider that it’s actually this lesion run over with granulomas?

A

Seminoma!

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20
Q

What testicular tumor is shown and what helps make the diagnosis?

A

Spermatocytic seminoma

The cystic spaces help

The chromatin is filamentous as well which can be helpful (spirime (?) chromatin)

These are indolent UNLESS there is a sarcomatous component

*this will be negative for all markers!

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21
Q

What testicular tumor is shown and why is this important to recognize?

A

Large cell calcifying variant of Sertoli cell tumor

Significance is this is seen in association with Peutz-Jeghers and Carney’s syndrome

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22
Q

On average, how long does it take for prostatic adenoCA to show complete therapeutic response to radiation therapy?

A

30 months

*this is important to know because re-biopsy predicts prognosis

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23
Q

What entity is characterized by deposition of inorganic salts within injured urothelial mucosa due to the action of urea-splitting bacteria (which alkalinized urine)?

A

Encrusted cystitis

*histologically, this shows deposits of calcium in lamina propria along with fibrin and necrotic debris

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24
Q

What agents cause hemorrhagic cystitis?

A

Cytoxan (cyclophosphamide)

BCG cystitis shows submucosal non-necrotizing granulomas

Mitomycin C adn Thiotepa usually cause mucosal denudation

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25
What percentage of patients is metastatic disease the initial mode of presentation in patients with clear cell RCC?
30%
26
What is the most common genetic abnormality encountered in patients with sporadic clear cell RCC?
Deletion of 3p
27
Which part of the renal parenchyma does clear cell RCC arise? Papillary RCC? Oncocytomas/Chromophobe RCC?
Clear cell RCC arises from the proximal convoluted tubule Papillary RCC arises from the distal convoluted tubule Oncocytomas/Chromophobe RCC arise from intercalated cells of the collecting ducts
28
What genetic alterations are seen in papillary RCC?
Trisomy 7, Trisomy 17, deletion of chromosome Y--seen in sporadic papillary RCC ## Footnote **Germline mutation of *c-met* gene on Chr7--seen in hereditary papillary RCC, AD**
29
What is the mechanism behind the collapsing variant of FSGS?
Collapse of the tuft + ***_proliferation_*** of visceral epithelial cells Seen with HIVAN, Parvo B19, panidronate Under normal instances podocytes cannot proliferate Exception: HIV = exception where HIV infection induces dedifferentiation with ability to proliferate POOR prognosis
30
What are two gene mutations which encode for slit diaphragm proteins that cause hereditary FSGS/nephrotic syndrome?
NPHS1 encoding nephrin – congenital NS of the Finnish type NPHS2 encoding podocin – steroid-resistant NS of childhood onset Localization to the slit diaphragm and to adjacent podocyte cytoskeletal structures, role in maintenance of normal glomerular filtration barrier
31
If you are given stem of a bodybuilder on steroids on boards and asked about a medical kidney disease, what should you think about?
FSGS!
32
What is the most common cause of nephrotic syndrome in adults?
FSGS 20-30% ## Footnote Membranous is a close second at 20-25% but if asked, the answer is FSGS
33
What are the three types of RPGN?
**I** - autoantibodies to the glomerular basement membrane (Goodpasture's) **II** - severe circulating immune complex glomerulonephritis (severe cases of postinfectious, IgA, lupus nephritis) **III** - pauci-immune/ANCAs associated
34
What EM finding is diagnostic of Alport's syndrome?
splitting of the lamina densa
35
What is the most common cause of glomerulonephritis worldwide?
IgA nephropathy
36
What is Birt-Hogg-Dube syndrome?
An autosomal dominant condition characterized by _benign cutaneous tumors and pulmonary cysts, also predisposes to the development of multifocal and bilateral chromophobe RCC and/or oncocytoma_. BHDS is the consequence of inactivating mutations in the **folliculin** (FLCN) gene located on the **short arm of chromosome 17 at position 11.2(17p11.2),**which functions as a tumor suppressor gene. The most common renal cell tumor (50% of the cases) seen in BHDS is the oncocytic hybrid tumor, which is a hybrid between oncocytoma and chromophobe carcinoma. Chromophobe RCC and renal oncocytomas have been observed in 33% and 5% of BHDS patients, respectively.
37
What two syndromes get large cell calcifying Sertoli cell tumors?
Peutz-Jeghers and Carney complex
38
What kidney tumor is positive for Napsin A?
Papillary RCC
39
What two stains are helpful in distinguishing CIS in the bladder from reactive urothelium and what is the staining pattern?
CD44: positive in BASAL layer of REACTIVE urothelium, negative in CIS CK20: positive in ALL layers in CIS but only positive in UMBRELLA layer of reactive urothelium
40
What syndrome has Wilms tumor, gonadoblastoma and diffuse mesangial sclerosis?
Denys-Drash syndrome Not familial inherited and neither is WAGR The difference is WAGR is a deletion of the WT1 gene (which also gets the adjacent gene responsible for the aniridia) and DD is a WT1 point mutation
41
If you see a papillary RCC with macronucleoli surrounded by a clear halo, what syndrome should you think of?
Hereditary Leiomyomatosis and Renal Cell Cancer \*their LMs also show this peculiar feature
42
What syndrome should you think of with an inverted urothelial carcinoma of the renal pelvis?
Lynch syndrome
43
What syndrome should you think about if you see this tumor of the epididymis? What is the female tumor counterpart?
Papillary cystadenoma of epididymis VHL Female counterpart is adnexal papillary cystadenoma of probably mesonephric origin (ACMO)
44
BQ SLIDE! Name this testicular tumor.
Sclerosing sertoli cell tumor
45
BQ SLIDE! Name this testicular tumor.
Sertoli cell adenoma (nodule)
46
What testicular tumor is this?
Seminoma ## Footnote Classic: AFP (-), HCG (-) IHC: PLAP (+), c-kit (+), OCT3/4 15% HCG (+), syncytial giant cells LN mets Radiosensitive!
47
What germ cells tumor has: ## Footnote * deposits of extracellular basement membrane material * Intracellular PAS (+) hyaline globules * Patchy AFP (+) * Keratin (+)
Yolk sac tumor
48
What is this lesion in paratesticular tissue?
Adenomatoid tumor +calretinin (lesional cells are mesothelial cells)
49
What are the group of cells on the right from this prostate lesion?
Cowper's glands (PSA negative)
50
Name this bladder lesion.
PUNLMP ## Footnote * Resembles papilloma \>6 cell layers * Orderly maturation * Papillary tumors
51
Name this bladder lesion.
Papillary urothelial carcinoma
52
What is the T staging for urinary bladder?
pT1: Tumor invades subepithelial connective tissue (lamina propria) pT2: Tumor invades muscularis propria (detrusor muscle) pT2a: Tumor invades superficial muscularis propria (inner half) pT2b: Tumor invades deep muscularis propria (outer half) pT3: Tumor invades perivesical tissue pT3a: Microscopically pT3b: Macroscopically (extravesicular mass) pT4: Tumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall pT4a: Tumor invades prostatic stroma or uterus or vagina pT4b: Tumor invades pelvic wall or abdominal wall
53
What is this bladder lesion and what is a well known benign mimic?
Nested cell variant of urothelial carcinoma Benign mimic seen here is florid cystitis cystica
54
What bladder lesion is this?
Micropapillary urothelial carcinoma
55
What bladder lesion is this?
Lymphoepithelioma-like carcinoma (keratin positive)
56
What is the mutation in hereditary leiomyomatosis and RCC?
* **Fumarate hydratase gene** (Krebs cycle enzyme) 1q42 * Cutaneous/uterine leiomyomata * Kidney cancer: Papillary RCC type II * Solitary * 41 yo * large tumors, aggressive, microcystic
57
What renal tumor is this?
**Mucinous tubular spindle cell carcinoma** small elongated tubules separated by mucinous stroma NOT a sarcoma, prognosis favorable! (low grade) Well-circumscribed, solid AMACR, Cytokeratin 7, EMA positive
58
What are the four major subtypes of hereditary RCC?
* Clear Cell RCC -inactivated VHL gene * Papillary RCC type I – met gene * Papillary type II – fumarate hydratase gene * Chromophobe RCC – folliculin gene
59
What is this kidney tumor?
Mixed epithelial & stromal tumor of the kidney (MEST) "ovarian like stroma" and tubules +ER
60
What renal tumor is this?
Congenital mesoblastic nephroma (CMN) \>90% less than 1 yr of age * Cellular CMN represents infantile fibrosarcoma * t(12;15)(p13;q25) – fusion of the ETV6 and NTRK3 genes * Classic CMN – no consistent genetic abnormality * Surgery for both * Recurrences/mets – in cellular
61
What stain can help differentiate between a nephrogenic adenoma and prostatic adenoCA?
p63 NA are neg, PA are pos
62
Is there dysplasia in the surface epithelium adjacent to or above an inverted papilloma of the bladder?
NO! In order to establish diagnosis, there can't be dysplasia in overlying epithelium
63
The granulomatous reaction that can be seen after BCG therapy is most pronounced where?
Interestingly, it is usually more intense in the prostate than the bladder!
64
What paraneoplastic syndrome is seen in patients with rhabdoid tumors of the kidney?
Hypercalcemia apparently due to secretion of parathyroid hormone or prostaglandin E2 by the neoplastic cells
65
What type of cystic kidney disease is this?
ARPKD showing distinctive linear radiating appearance AD will look like this
66
What cystic kidney disease is this?
Medullary sponge kidney (confined to medulla) Cystic renal dysplasia has a "bunch of grapes" appearance seen here
67
What germ cell tumor can cause thyrotoxicosis and why?
Choriocarcinoma Thought to be from cross-reactivity of TSH and hCG
68
This is a gross pic of what childhood renal tumor?
Mesoblastic nephroma ## Footnote Two types: Classic and Cellular Many patients are found to have polyhydramnios prenatally Classic looks like leiomyoma grossly and cellular is more friable and hemorrhagic which looks like a fibrosarcoma microscopically but despite this, most are cured with nephrectomy
69
Embryonal carcinomas are positive for keratin, CD30, and PLAP but negative for what other epithalial marker?
**EMA** When dealing with a metastatic tumor of unknown primary and you have an epithelial malignancy that is CK positive but EMA negative then the possibility of a germ cell tumor needs to be considered so add PLAP and CD30 to profile
70
A tumor metastasizing to the penis is very rare but when it does, what is the most likely source?
Prostate
71
What is the most common malignant paratesticular tumor in children?
Spindle cell variant of embryonal rhabdomyosarcoma
72
What are the only two germ cell tumors that occur is pre-pubescent boys?
Yolk sac and teratoma (which are benign) There are NO BENIGN TERATOMAS post puberty
73
Is keratinizing and non-keratinizing squamous metaplasia in the bladder a risk for carcinoma?
Keratinizing YES Non-keratinizing NO (normal in females trigone)
74
What transcript is overexpressed (up to 70 fold) and highly specific for prostate cancer with only normal kidney showing some expression and its detection in urine following prostatic massage has been demonstrated to have a high sensitivity and specificity for prostate cancer?
DD3PCA3 ## Footnote A NASBA (nucleic acid sequence-based amplification) uPM3 which simultaneously and quantitatively detects both PSA mRNA as an indicator of the presence of prostatic cells and DD3PCA3 in urine appears to be a more specific indicator of prostatic cancer than PSA
75
What mutation is associated with a high rate of bilaterality in seminomas?
KIT
76
What mutation is seen in low grade noninvasive papillary urothelial carcinomas with a low propensity to progress and is mutually exclusive with p53 mutations?
FGFR3
77
What antigen is involved in most cases of membranous glomerulonephritis?
Podocyte phospholipase A2 receptor
78
What type of GN is this?
Membranous GN Granular IF plus subepithelial electron dense deposits
79
What are the three C3 nephropathies and which one has this very characteristic IF pattern of "linear" capillary loops and mesangial "rings"?
Dense deposits disease (IF shown) ## Footnote \*will also show dense transformation of the GBM lamina densa (shown here) Atypical HUS C3 nephropathy
80
What types of lupus nephritis are prognostically important?
Class III and IV ## Footnote 50% 2.5 yr renal failure without tx Diagnostic feature is: “endocapillary proliferation” i.e. capillary loop proliferation Class III \<50% glomeruli have endocapillary proliferative lesions Class IV \>50% glomeruli have endocapillary proliferative lesions
81
What is the diagnosis when you have a kidney biopsy that is identical to diabetic nephropathy but there is no clinical evidence of glucose intolerance?
Idiopathic Nodular Glomerulosclerosis ## Footnote Strong association with heavy smoking Elevation of advanced glycation end products
82
If you see a test question about renal vein thrombosis in a renal disease patient, what renal disease is heavily associated with this?
Membranous nephropathy
83
What entity is shown?
Minimal change disease Podocyte effacement
84
What entity is shown?
Focal segmental glomerulosclerosis
85
What entity is shown?
Membranous glomerulonephritis ## Footnote Silver stain showing spikes and EM showing subepithelial deposits
86
What entity is shown?
IgA nephropathy ## Footnote mesangial hypercellularity and IF showing mesangial immune deposits
87
What entity is shown?
Diffuse proliferative glomerulonephritis
88
What entity is shown?
Acute post streptococcal glomerulonephritis ## Footnote EM showing ‘hump-like’ subepithelial deposits
89
What entity is shown?
Membranoproliferative glomerulonephritis, type I ## Footnote EM showing subendothelial deposits
90
What entity is shown?
Diffuse proliferative lupus nephritis ## Footnote EM showing massive subendothelial and mesangial deposits
91
What entity is shown?
Dense deposit disease - EM ## Footnote * Predominately affects children/young adults * Some pts have partial lipodystrophy and retinal alterations * Clinical course: similar to MPGN with high incidence of ESRD * Etiology defective complement regulation C3 nephritic factor an IgG ab Stabilizes C3 convertase (C3bBb) Unrestricted activation
92
What entity is shown?
Crescentic glomerulonephritis showing cellular crescent
93
What entity is shown?
IF – fibrin in a crescent
94
What entity is shown?
Linear fluorescence of Goodpasture's syndrome
95
What entity is shown?
Nodular diabetic nephropathy
96
What entity is shown?
Alport syndrome ## Footnote EM showing basement membrane lamellation
97
What entity is shown?
Amyloidosis ## Footnote mesangial deposits and EM showing amyloid fibrils (8-12 nm)
98
What entity is shown?
Light chain cast nephropathy showing cellular reaction to light chain cast
99
What is this picture showing?
Tip variant of FSGS
100
What are the nephritic diseases with hypocomplementemia?
- Acute post streptococcal (post infection) glomerulonephritis - Membranoproliferative glomerulonephritis - Dense deposit disease - Cryoglobulinemic glomerulonephritis - Diffuse proliferative lupus glomerulonephritis
101
What is the molecular alteration in collecting duct carcinoma?
Del 1q Aggressive, positive for keratin, negative for CD10 and vimentin
102
What kidney tumor shown is usually in women less than 35yo and has these micro findings: ## Footnote ● Papillary and nested growth pattern with clear cells and eosinophilic cells ● Fibrous pseudocapsule, often calcified ● Polygonal tumor cells with sharp cell borders, voluminous clear to eosinophilic cytoplasm, irregular nuclei containing vesicular chromatin and small nucleoli ● Surrounded by thin walled vessels ● Also minor solid, acinar, alveolar and tubular patterns ● Foci of calcification are common ● No/rare mitotic figures
Renal CA with Xp11.2 translocation

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