Male Reproductive Pathology/GU Pathology Flashcards
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
CK903
What stain is positive in Stromal Tumors of Uncertain Malignant Potential (STUMP) of the prostate but is negative in other muscle neoplasms?
CD34 STUMPs are also PR +
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?
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
What 2 stains are positive in papillary renal cell that are not positive in clear cell RCC?
CK7 and racemase
What stains are positive in chromophobe RCC?
Hale’s colloidal iron, EpCAM (new marker for chromophobe), CD117 (c-kit), CK7
What stains are positive in translocation carcinomas of the kidney?
TFE3 (Xp11 translocation)
TFEB (t(6;11) translocation)
*TFEB tumors stain with Melan-A and HMB45
Cathepsin-K (both translocations)
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?
Clear cell papillary RCC
What group of stains are positive in all non-seminoma germ cell tumors but negative in seminoma?
Epithelial markers (keratins and EMA)
What mesothelial and lymphatic marker is positive in 100% of seminomas and 30% of embryonal carcinomas?
D2-40 (podoplanin)
Seminomas are generally positive for OCT4, SALL4, PLAP and c-kit. Which one of these is the only marker positive in SPERMATOCYTIC seminomas?
SALL4
What recently described stem cell marker is positive in embryonal carcinomas (not CD30)?
SOX2
What stain is positive in seminoma and embryonal carcinomas but is negative in yolk sac?
OCT4
What stains are positive in sex cord stromal tumors (Sertoli and Leydig)?
Inhibin, Melan-A (also positive in adrenocortical tissue but not of the other melanoma markers are), CD10, CD99 and Calretinin
What is the striped pattern of renal interstitial fibrosis characteristically associated with?
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.
What is Birt-Hogg-Dube syndrome, how is it inherited and what chromosome and gene is involved?
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
What is the diagnosis of the bi-valved kidney?
Xanthogranulomatous pyelonephritis
Other than PKD, what two syndromes can have bilateral diffuse cystic kidney disease?
Tuberous sclerosis
VHL
1) What renal cancers are positive for CK7?
2) What renal cancers are positive for AMACR?
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)
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?
Seminoma!
What testicular tumor is shown and what helps make the diagnosis?
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!
What testicular tumor is shown and why is this important to recognize?
Large cell calcifying variant of Sertoli cell tumor
Significance is this is seen in association with Peutz-Jeghers and Carney’s syndrome
On average, how long does it take for prostatic adenoCA to show complete therapeutic response to radiation therapy?
30 months
*this is important to know because re-biopsy predicts prognosis
What entity is characterized by deposition of inorganic salts within injured urothelial mucosa due to the action of urea-splitting bacteria (which alkalinized urine)?
Encrusted cystitis
*histologically, this shows deposits of calcium in lamina propria along with fibrin and necrotic debris
What agents cause hemorrhagic cystitis?
Cytoxan (cyclophosphamide)
BCG cystitis shows submucosal non-necrotizing granulomas
Mitomycin C adn Thiotepa usually cause mucosal denudation
What percentage of patients is metastatic disease the initial mode of presentation in patients with clear cell RCC?
30%
What is the most common genetic abnormality encountered in patients with sporadic clear cell RCC?
Deletion of 3p
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
What genetic alterations are seen in papillary RCC?
Trisomy 7, Trisomy 17, deletion of chromosome Y–seen in sporadic papillary RCC
Germline mutation of c-met gene on Chr7–seen in hereditary papillary RCC, AD
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
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
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!
What is the most common cause of nephrotic syndrome in adults?
FSGS 20-30%
Membranous is a close second at 20-25% but if asked, the answer is FSGS
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
What EM finding is diagnostic of Alport’s syndrome?
splitting of the lamina densa
What is the most common cause of glomerulonephritis worldwide?
IgA nephropathy
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.
What two syndromes get large cell calcifying Sertoli cell tumors?
Peutz-Jeghers and Carney complex
What kidney tumor is positive for Napsin A?
Papillary RCC
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
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