GU Flashcards
Adenocarcinoma of the urinary bladder.
Adenocarcinoma of the urinary bladder arising from the urothelial lining is an uncommon malignant neoplasm, accounting for 0.5-2.0% of all malignant vesical tumors. The histologic variants show a predominant colonic (enteric) type glandular morphology with varied histologic patterns. Based on the morphology they are clasified as follows: colonic (enteric) type, adenocarcinoma NOS, mucinous, signet ring cell (SRC), clear cell type, hepatoid, and mixed forms. These tumors are also grouped as urachal and nonurachal type (the following information is about the nonurachal type). Irrespective of the various histologic patterns, there is usually evidence of cystitis cystica et glandularis or surface glandular metaplasia in the adjacent benign urothelium. Patients usually are M and in their 6th decade. The most common clinical presentation is hematuria. ~90% of the tumors arising in exstrophied bladder are adenocarcinomas. They are also more prevalent in settings of vesical schistosomiasis. In most cases, they involve the trigone and posterior bladder wall, and tend to be unifocal. Grossly, they can have a papillary, nodular, flat, or ulcerated architecture. Some variants, especially SRC, tend to present with prominent bladder wall thickening (“linitis plastica” like) without apparent growth due to diffuse infiltration of the bladder wall by tumor cells. Microscopically, these tumors show pure glandular morphology, with well to moderately differentiated colonic-type infiltrating glands with or without abundant extracellular mucin. Bladder adenocarcinomas need to be distinguished from the more common metastatic adenocarcinoma (direct spread, lymphatic, and hematogenous). The principal primary organs to be considered include colon, prostate, female genital tract, appendix, stomach, and breast. The IHC panel used to distinguish primary vesical adenocarcinoma from metastatic colonic adenocarcinoma include: CK7 and CK20 (7 and 20 are positive in >50% of primary bladder adenos; colonic adenos are typically 7 negative and 20 positive), thrombomodulin (90% of urothelial carcinomas positive, 59% of bladder adenos positive, 0% colonic adenos positive), beta-catenin (nuclear staining in 81% of colonic adenos and 0% of bladder adenos, membranous staining in 100% of colonic adenos and 88% of bladder adenos), CDX-2 is positive in both.
Aggressive angiomyxoma.
Aggressive angiomyxoma is a rare mesenchymal tumor arising primarily in the soft tissue of the pelvis and perineum of adults. The term aggressive refers to its infiltrative nature and propensity for local recurrence, but it is an indolent tumor with low metastatic potential. F:M = 6.6:1. It occurs predominantly in women of reproductive age with a peak incidence in the 4th decade and an age range of 11 to 77. In women, it arises in the vulvovaginal region, perineum, and pelvis. In men, it arises in the inguinoscrotal region and perineum. AAM is often clinically mistaken for entities such as Bartholin cyst, vaginal or labial cyst, abscess, leiomyoma, lipoma, fibroepithelial polyp, and inguinal or perineal hernia. Grossly, AAM is unencapsulated, is poorly circumscribed, and may blend imperceptively with surrounding soft tissue. The tumor is tan-pink to tan-gray, bulky, and has a rubbery consistency with a glistening, gelatinous cut surface. Microscopically, AAM is a sparsely cellular tumor composed of pale to eosinophilic stroma studded with numerous haphazardly arranged blood vessels ranging in size from thin-walled capillaries and venules to larger muscular arteries. The stroma is myxoid with intermixed wispy collagen fibrils, scattered smooth muscle bundles, and extravasated RBCs. The tumor cells are cytologically bland and have a spindled, ovoid, or stellate appearance with ill-defined cytoplasmic borders. There is minimal to no cellular atypia and mitoses are rare. IHC shows diffuse positivity for ER, PR, vimentin, and desmin. DDx for AAM includes angiomyofibroblastoma, superficial angiomyxoma, fibroepithelial stromal polyps, myxoid lipomatous tumors, and myxoid leiomyoma.
Differential diagnosis of nephrogenic adenoma.
When the NA consists of surface lesions (papillary), the DDx includes urothelial papilloma, PUNLMP, and low-grade papillary urothelial carcinoma. When the NA involves deep lamina propria and/or superficial muscle, the DDx includes prostatic adenocarcinoma and urothelial carcinoma with bland histology. When the NA has hobnail cells or a solid growth of clear cells, the DDx includes clear cell carcinoma of the urinary bladder.
Epithelioid angiomyolipoma.
Originally believed to be a hamartomatous lesion, angiomyolipoma (AML) is currently defined as a benign mesenchymal tumor composed of a variable proportion of adipose tissue, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels. AML is a member of the PEComa family. Although most AMLs arise in kidney, extrarenal AMLs are also described in various sites. The epithelioid variant of AML (EAML) is mainly characterized by a predominance of epithelioid cells. In contrast to their classical counterpart, EAMLs are now considered a potentially malignant neoplasm. EAMLs are more often associated with tuberous sclerosis complex than classical AMLs. EAMLs mimic morphologically a variety of neoplasms such as RCC, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumor, epithelioid peripheral nerve sheath tumor, epithelioid GIST, epithelioid melanoma, hepatoblastoma, and HCC. Morphologic clues to diagnosis such as islands of mature fat and abnormal vessels should be diligently searched for in surgical specimens, and prudent use of IHC may be needed.
Examples of pseudoneoplastic lesions in the genitourinary tract (male and female) and their related neoplastic mimes.
Pseudocarcinomatous epithelial hyperplasia (adenocarcinoma and urothelial carcinoma). Postoperative spindle cell nodules (sarcomas; sarcomatoid carcinoma). Drug effects (eg, cytoxan cystitis mimicking carcinoma in situ) (urothelial carcinoma). Prostatic urethral (utricular) polyp (adenocarcinoma). Paratesticular mycobacterial pseudotumor (sarcomas). Xanthogranulomatous nephritis/cystitis/orchitis/endometritis/oophoritis (sarcomatoid carcinomas). Adenomatous and basal-cell prostatic hyperplasia (adenocarcinoma). Nodular stromal prostatic hyperplasia (low-grade sarcoma). Prostatic sclerosing adenosis (adenocarcinoma). Radiation effect on prostatic epithelium (residual adenocarcinoma). Granulomatous prostatitis/orchitis (sclerosing high-grade adenocarcinoma; sclerosing seminoma). Vaginal adenosis (adenocarcinoma). Uterine cervical mesonephric remnants (adenocarcinoma). Uterine cervical microglandular adenosis (adenocarcinoma). Ovarian stromal hyperplasia/hyperthecosis (ovarian stromal neoplasms). Nephrogenic metaplasia of bladder and urethra (adenocarcinoma). Endometriosis (adenocarcinoma).
Histologic features of nephrogenic adenoma?
A metaplastic response of urothelium to injury. Also associated with renal transplantation and intravesical bCG. Histologic features are tubules (96%) composed of a single layer of cuboidal or flattened cells with clear to eosinophilic cytoplasm, round nuclei, and fine chromatin. Other features are inflammation (95%), extension into muscle (77%), structures resembling vessels (73%), presence of adjacent urothelium (69%), peritubular sheaths (65%), prominent nucleoli (54%), cords and individual cells (46%), thyroidization of tubules (38%), blue-tinged mucinous secretions (32%), papillary configurations (19%), and signet ring-like tubules (12%). The adjacent urothelium, if present, often exhibits cuboidal metaplasia (61%) or squamous metaplasia (28%). Mitotic figures are not present.
IHC for adrenal cortical carcinoma vs pheochromocytoma?
Adrenal cortical carcinoma is synaptophysin +, chromogranin -, inhibin +, Melan-A +, calretinin +, S-100 -. Pheochromocytoma is synaptophysin +, chromogranin +, inhibin -, Melan-A -, calretinin -, S-100 reactive only in nuclei of sustentacular cells.
IHC staining of nephrogenic adenoma?
Strong and diffuse granular reactivity for P504S. Rarely shows focal PSA or PAP positivity. Frequently negative (44%) or only focally positive (44%) for CK903 (AKA 34betaE12). Positive for EMA, CK7, and PAX2. Negative for CD10 and p63.
Immunostain to distinguish muscularis mucosa from muscularis propria in urothelial CA of bladder?
Smoothelin, which is a marker of terminally differentiated smooth muscle cells, stains muscularis propria but not muscularis mucosa.
Nephrogenic adenoma.
Also called nephrogenic metaplasia. An uncommon benign lesion of the urothelial tract, characterized by a circumscribed proliferation of tubules (resembling renal tubules), cysts, and papillae lined by cells with low cuboidal to columnar epithelium. M:F = 2:1. Most occur in adults, but seen in age range 4-81 years. They commonly arise in the setting of prior urothelial injury, such as past surgery (60%), calculi (14%), or trauma (9%). Additionally, 8% of patients have a previous history of renal transplantation or BCG therapy for urothelial carcinoma of the bladder. They are most commonly seen in the urinary bladder (80%); however, urethra (12%) or ureter (8%) can also be involved.
Urachal carcinoma of the urinary bladder.
Urachal carcinoma is an uncommon tumor that can present as a bladder mass. It tends to occur in the dome and anterior bladder wall and has a male predominance. Adenocarcinoma with enteric features is the most common histologic subtype and can also show mucinous and signet ring cell variants. Diagnostic criteria for urachal carcinoma include (1) tumor in the dome; (2) absence of cystitis cystica and cystitis glandularis; (3) predominant invasion of the muscularis or deeper tissues with a sharp demarcation between the tumor and surface bladder urothelium that is free of glandular or polypoid proliferation; (4) urachal remnants within the tumor; (5) extension into the bladder wall with involvement of the space of Retzius, anterior abdominal wall, or umbilicus; and (6) no evidence of a primary neoplasm elsewhere. The previous criteria help in differentiating it from primary vesical adenocarcinomas. IHC profile is similar to primary vesical adenocarcinomas and hence is of no practical utility. The management of urachal carcinoma is typically a partial cystectomy as opposed to a radical cystectomy for primary bladder adenocarcinomas.
What are renal MESTs?
Mixed Epithelial and Stromal Tumors. Other names for this entity are: leiomyomatous renal hamartomas, congenital mesoblastic nephroma in an adult, cystic hamartoma of renal pelvis, solitary multilocular cysts of the kidney, multilocular renal cyst with mullerian-like stroma, and adult metanephric stromal tumor. Is a benign renal neoplasm of adults that has a variable admixture of epithelial and mesenchymal components. M:F = 1:10. Grossly, variably solid and cystic, tan to yellow, well-circumscribed but rarely encapsulated. Microscopically, the mesenchymal component is characterized by fascicles of spindle cells showing variable degrees of smooth muscle, fibroblastic, or myofibroblastic differentiation associated with interspersed bundles of collagen. The mesenchymal component resembling that of ovarian stroma, and focal changes of the stromal cells reminiscent of ovarian stromal cell luteinization have been described. The epithelial component is dispersed throughout the neoplasm and varies from round and regular tubules to more complex tubulopapillary structures with or without cystic dilatation. These are lined by cuboidal to flattened epithelium that may show clear cell change and a hobnail appearance. Malignant transformation, recurrence, and metastasis are rare in MESTs. For pathogenesis, the female preponderance of MEST and history of long-term estrogen replacement in females or long-term sex-steroid exposure in males, combined with frequent expression of ER and PR in the mesenchymal component suggest that steroid hormones may play a role in the evolution of these tumors. The major differential diagnosis is cystic nephroma. MESTs have a higher stromal to epithelial ratio, prominent ovarian stroma, smaller cysts with phyllodes glands pattern, and stromal luteinization. CN have a low stromal to epithelial ratio, large cysts, and thin septa. DDx also includes congenital mesoblastic nephroma and primary renal synovial sarcoma.
What are the average diameters for a normal glomerulus in newborns and adults?
Newborn, 100 um. Adult, 200-250 um. Glomeruli reach normal adult size by ~8 years of age.
What are typical staining patterns for CK7, CK20, CD10, and RCC in oncocytoma, chromophobe renal cell carcinoma, and clear cell renal cell carcinoma.
Oncocytoma: CK7 neg, ~25% are CK20 pos, ~30% are CD10 pos, RCC neg. Chromophobe renal cell carcinoma: CK7 pos, CK20 neg, 0 to 45% are CD10 pos, RCC neg. Clear cell renal cell carcinoma: CK7 neg, CK20 neg, CD10 pos, RCC pos.
What does CK AE1/AE3 cocktail stain, and what are it’s uses in prostate?
CK AE1/AE3 cocktail detects acidic (CK10, CK14-16, and CK19) and basic (CK1-CK6 and CK8) cytokeratins. Is useful in the DDx of nonspecific granulomatous prostatitis, crushed or marked inflammation, or xanthoma cells versus Gleason pattern 5 prostate carcinoma. Is also useful in diagnosing small cell proliferations in the prostate, such as small cell carcinoma, lymphoma, and rhabdomyosarcoma. In the posttreatment setting, is helpful in highlighting individual atrophic prostate cancer cells and is superior to PSA, which can be suppressed by therapy and is, therefore, not detectable by IHC posttreatment.
What is the PAX-2 marker?
The PAX-2 marker is a renal-restricted nuclear transcription factor expressed in 70-80% of metastatic clear cell RCC.
What is the RCC marker?
The RCC marker is a glycoprotein found in the brush border of the proximal tubules of the kidney. It is + in 47-85% of clear cell RCC and 60-90% of papillary RCC.
Will adrenal cortical carcinomas stain positive for cytokeratins?
Adrenal cortical carcinomas are negative for CKs in formalin-fixed tissue unless antigen retrieval techniques are utilized, and even then the tumors are only focally weakly positive.
Xanthogranulomatous pyelonephritis.
XGP is a chronic destructive granulomatous process of renal parenchyma in association with long-term urinary tract obstruction and infection. The 3 forms of XGP are diffuse, segmental, and focal. Segmental XGP is characterized by segmental involvement of the disease, and focal XGP is located within the cortex with no pelvic communication. Segmental and focal XGP can be associated with normal kidney function. F>M. Mean age is ~50, with a range of 2-84. Almost all patients are symptomatic, and the most common symptoms are flank or abdominal pain, lower urinary tract symptoms, fever, palpable mass, gross hematuria, and weight loss. The common laboratory findings are leukocytosis and anemia. Urine cultures most often reveal E. coli and P. mirabilis. On CT scan, the combination of a nonfunctioning enlarged kidney, a central calculus within a contracted renal pelvis, expansion of the calices, and inflammatory changes in the perinephric fat is strongly suggestive of XGP. Grossly, the kidney has single or multiple yellow to orange nodules, and there can be central necrosis with abscess formation, involvement of perinephric fat, diffuse cortical scarring with effacement of the normal renal architecture, and cortical atrophy. Microscopically, there is a granulomatous mixed inflammatory infiltrate with fibrosis and cholesterol clefts in the background. The inflammatory infiltrate is composed of a variable number of xanthomatous histiocytes with foamy cytoplasm, neutrophils, lymphocytes, plasma cells, and multinucleated giant cells. Also, a variable degree of renal tubular atrophy, tubular dilatation and focal squamous metaplasia of the urothelium, microabscesses, lymphoid aggregates with germinal center formation, and spindle cell proliferation can be seen. The lesion shows diffuse positivity for CD68 and vimentin, and negativity for SMA, desmin, and epithelial markers. DDx includes clear cell RCC, papillary RCC, sarcomatoid RCC, leiomyosarcoma, malakoplakia, and megalocytic interstitial nephritis.
The cytoplasm of the cells in renal oncocytomas are granular and deeply eosinophilic, reflecting the abundant, packed ___ seen at the ultrastructural level.
The cytoplasm of the cells in renal oncocytomas are granular and deeply eosinophilic, reflecting the abundant, packed mitochondria seen at the ultrastructural level. In some cases, areas of the tumor are composed of oncoblasts, which are identical to the cells of the usual oncocytoma, except that the cytoplasm is not as abundant. Focal areas of cytoplasmic clearing are not uncommon but should be focal and restricted to the areas of the central scar, representing degenerative clearing of the cytoplasm because of ischemic changes.
Can renal oncocytomas show infiltration into perinephric fat and microscopic lymphovascular invasion?
Yes. But make sure it really isn’t something else. Resample and reevaluate.
The perinuclear halos seen in chromophobe renal cell carcinoma reflect the presence of ___ around the nucleus at the ultrastructural level.
The perinuclear halos seen in chromophobe renal cell carcinoma reflect the presence of microvesicles around the nucleus at the ultrastructural level. The microvesicles, which do not have affinity to H&E staining, are thought to be related to defective mitochondriogenesis. They displace cytoplasmic organelles to the periphery of the cytoplasm, leading to prominent cell membranes.
What renal neoplasms are seen in patients with Birt-Hogg-Dube syndrome?
Patients with BHD syndrome have multifocal renal tumors that include hybrid tumors (renal oncocytoma + chromophobe RCC), oncocytomas, chromophobe RCCs, clear cell RCCs, and papillary RCCs.
Clear cell RCC arises from proximal/distal tubules, and chromophobe RCC and oncocytoma arise from proximal/distal tubules.
Clear cell RCC arises from proximal tubules, and chromophobe RCC and oncocytoma arise from distal tubules.
What are PAX2 and PAX8 and what can they be used for?
PAX2 and PAX8 are transcription factors that are essential for the development of kidney, mullerian, and other organs. They are expressed in normal kidney as well as in most of the renal neoplasms. PAX2 and PAX8 have very similar expression profiles in RCC and in ovarian and endometrial carcinoma. However, PAX8 is also expressed in thyroid follicular cells and thyroid carcinoma, but PAX2 is typically negative in thyroid tumors. This makes them useful for the workup of metastatic RCC.
Alpha-methylacyl coenzyme a racemase (AMACR).
AMACR is a mitochondrial enzyme mediating the expression of fatty acids and is commonly expressed in normal hepatocytes, the bronchus, and epithelium of the proximal renal tubules. It is a positive tumor marker for prostatic adenocarcinoma. Almost all papillary RCCs are positive for AMACR, but other types of RCC are rarely positive.
TFE3, TFEB, and cathepsin-K immunostains. What renal tumors do they stain?
TFE3 is a transcription factor that is overexpressed in a group of RCCs with translocation involving Xp11.2. TFEB is a transcription factor that is overexpressed in RCCs with t(6;11)(p21;q12). Cathepsin-K is overexpressed in most TFE3 translocation carcinomas and all TFEB translocation carcinomas.
What are 4 markers that are expressed in a high percentage of urothelial carcinomas but are not usually expressed in RCCs?
Uroplakin III, p63, thrombomodulin, and GATA3.
___ (an immunostain) is a useful marker for the diagnosis of metanephric adenoma.
CD57 (an immunostain) is a useful marker for the diagnosis of metanephric adenoma.
A specific feature that is seen in most cases of acquired cystic disease-associated RCC in the ACDK setting is ___.
A specific feature that is seen in most cases of acquired cystic disease-associated RCC in the ACDK setting is intratumoral oxalate crystals.
What renal tumors can develop in patients with acquired cystic disease of the kidney?
ACDK is often, but not always, associated with a history of dialysis. The tumor types seen in ESRD and ACDK encompass (1) the 3 common subtypes of RCC: papillary RCC, clear cell RCC, and chromophobe RCC; (2) the 2 other subtypes of RCC that are either exclusively or predominantly seen in the setting of ESRD: acquired cystic disease (ACD)-associated RCC, and clear cell papillary RCC.
For the following renal cystic diseases, give the cancer risk and the most common renal tumor types: ESRD and ACD of the kidney, von Hippel-Lindau disease, tuberous sclerosis complex, autosomal-dominant polycystic kidney disease.
ESRD and ACD of the kidney; cancer risk 3-7%; ACD-associated RCC, clear cell papillary RCC, usual types of RCC (papillary, clear cell, chromophobe). von Hippel-Lindau disease; cancer risk 45-60%; clear cell RCC. Tuberous sclerosis complex; cancer risk 2-3%; angiomyolipoma, clear cell RCC, oncocytoma, RCC unclassified/TSC-related. Autosomal-dominant polycystic kidney disease; cancer risk equivocal; clear cell RCC, papillary RCC.
What immunostain and pattern is characteristic of papillary clear cell RCC?
The tumor cells express carbonic anhydrase IX (CAIX) in a diffuse, membranous distribution but staining is absent along the luminal borders of the tumor cells (cup-shaped distribution).
What determines type 1 and type 2 von Hippel-Lindau syndrome?
The absence of pheochromocytoma (type 1) or the presence of pheochromocytoma (type 2). Certain genotype-phenotype correlations have been established; Type 1 disease is associated with loss of VHL protein through large deletions or nonsense mutations, while type 2 disease is associated with germline VHL missense mutations.
Multilocular cystic RCC.
Multilocular cystic RCC is a renal cortical neoplasm with a distinct, multilocular gross appearance, and is a variant of clear cell RCC. Microscopically, the tumor consists of numerous clear cell-lined cysts with small clusters of clear cells in the tumor septa. This entity accounts for approximately 4% of all clear cell RCCs and affects middle-aged adults with M:F = 1.2-2.1:1.
How are multilocular cystic RCCs and cystic clear cell RCCs different?
Multilocular cystic RCCs have cysts with small clusters of clear cells in the tumor septa. Cystic clear cell RCCs have expansile nodular growth within the septa.
What are the casts in light chain cast nephropathy AKA myeloma cast nephropathy composed of?
The are composed predominantly of a single monoclonal light chain, which is typically admixed with Tamm-Horsfall protein secreted by the thick ascending limb of Henle.
What are the 3 most common drugs associated with drug-induced cystalline nephropathy?
Sulfadiazine, acyclovir, and indinavir.
What conditions can lead to oxalate nephropathy?
Enteric hyperoxaluria, toxic exposures (such as ethylene glycol ingestion or excessive vitamin C intake (vitamin C is metabolized to oxalate)), excessive dietary intake of oxalate, and inborn errors of metabolism.
What is enteric hyperoxaluria?
It is the most common etiology of oxalate nephropathy and is caused by fat and/or bile acid malabsorption, leading to steatorrhea. Under normal conditions, calcium and oxalate complex with each other in the colonic lumen and are excreted in the feces. In the setting of fat malabsorption, high levels of free fatty acids are present in the intestinal lumen and bind calcium, thereby reducing the amount of free calcium available to bind oxalate. This results in high intestinal levels of free oxalate, which is readily absorbed by the colonic epithelium and ultimately precipitates as calcium oxalate crystals in the kidney. In addition, the presence of high levels of free fatty acids and bile salts enhances colonic mucosal permeability to oxalate, further promoting oxalate absorption. Enteric hyperoxaluria can be seen in patients with inflammatory bowel disease, pancreatic insufficiency, following bowel surgery (including jejunoileal bypass and rou-en-Y gastric bypass), and use of gastrointestinal lipase inhibitors such as orlistat.
Acute uric acid nephropathy typically presents as oliguric or anuric acute renal failure and is most frequently seen in the setting of ___.
Acute uric acid nephropathy typically presents as oliguric or anuric acute renal failure and is most frequently seen in the setting of massive tissue destruction because of tumor lysis syndrome. Histologically, there is diffuse acute tubular injury accompanied by uric acid crystals located predominantly in the collecting tubules. In formalin-fixed tissue, urate crystals are largely dissolved in processing, leaving behind empty lacunae. If frozen sections or alcohol-fixed specimens are examined, the urate crystals stain blue with hematoxylin and are birefringent under polarized light. The crystals are typically needle-shaped or rectangular and occasionally incite an interstitial inflammatory respone.
The most frequent cytogenetic abnormalities seen in these renal cell neoplasms (clear cell, papillary, chromophobe, oncocytoma)?
Clear cell -3p; papillary +7, +17, -Y; chromophobe -1, -Y; oncocytoma t(11q13).
What makes the distinction between a renal papillary adenoma and papillary carcinoma?
Carcinomas are equal to or greater than 5 mm in size.
Hemorrhagic cystitis due to adenoviruses, especially type 11, is most often seen in (type of patient).
Hemorrhagic cystitis due to adenoviruses, especially type 11, is most often seen in bone marrow transplant recipients.
What do the terms focal, diffuse, segmental, and global refer to when classifying glomerular diseases by distribution?
Classification of disease distribution when many glomeruli are considered: Focal - disease affecting only some of the glomeruli. Diffuse - disease affecting most or all glomeruli. Classification of disease distribution when single glomeruli are considered: Segmental - a lesion involving only a part of the glomerulus. Global - a lesion involving the entire glomerulus.
Although nodular glomerulosclerosis (or nodular mesangial sclerosis) is a characteristic feature for DM, this finding is not specific and should provoke consideration of other entities, including ___.
Although nodular glomerulosclerosis (or nodular mesangial sclerosis) is a characteristic feature for DM, this finding is not specific and should provoke consideration of other entities, including renal amyloidosis, monoclonal immunoglobulin deposition disease, fibrillary GN, and immunotactoid glomerulopathy.
Arterionephrosclerosis/Hypertensive nephropathy/Nephrosclerosis. Gross and histologic features?
The gross appearance of the kidney shows granularity of the capsular surface, which corresponds to the light microscopic glomerular and tubulointerstitial scarring due to this vascular injury. Microscopic features include proliferative and fibrotic intimal thickening with narrowing of the arteries that may be accompanied by replication of the internal elastic lamina. Subendothelial hyalinosis affecting primarily the afferent but not efferent glomerular arterioles is often observed. Early glomerular changes are initiated by ischemic injury to the glomerulus with thickening and wrinkling of the basement membranes, usually in a global distribution along with thickening and fraying of Bowman capsule. Collagen gradually accumulates in the urinary space and compresses the shrunken glomerular tufts until eventually the entire glomerulus is sclerotic. Globally sclerotic glomeruli (global glomerulosclerosis) may be arranged in wedge-shaped zones of chronic ischemic injury of the outer cortex if the blood flow of larger renal arteries is compromised. Global glomerulosclerosis is associated frequently with tubular atrophy and interstitial fibrosis of the surrounding parenchyma because the blood exiting the efferent glomerular arteriole supplies the adjacent peritubular capillaries. Progressively more glomeruli are involved until the process results in ESRD with few residual intact nephrons. In advanced arterionephrosclerosis, there may be glomerular enlargement and superimposed focal segmental glomerulosclerosis, which has been postulated to be secondary to overloading the decreasing numbers of functional nephrons.
Membranoproliferative glomerulonephritis is a well-known manifestation of hepatitis ___. In the setting of malignancies, MPGN is often associated with ___, and is less common observed with solid tumors.
Membranoproliferative glomerulonephritis is a well-known manifestation of hepatitis C. In the setting of malignancies, MPGN is often associated with non-Hodgkin lymphoma, and is less common observed with solid tumors.
Idiopathic or primary FSGS is caused by ___ and characteristically manifests with ___. Secondary FSGS arises because of ___.
Idiopathic or primary FSGS is caused by injury of the glomerular podocytes and characteristically manifests with nephrotic syndrome. Secondary FSGS arises because of structural or functional renal alterations, which can be categorized into 3 broad categories: (1) a response to reduction of functional nephron mass due to primary glomerular or tubulointerstitial disease of vascular, infectious, immunologic, hereditary, or congenital origin; (2) secondary to glomerulonephritis, with the consequence of postinflammatory segmental glomerular scarring; and (3) secondary to hereditary basement membrane defects, such as Alport syndrome.
In the bladder, how do you distinguish postoperative spindle cell nodule from inflammatory myofibroblastic tumor?
IMFTs tend to reach a larger size, have greater prominence of the myxoid stroma, lesser degree of cellularity, greater pleomorphism, and lesser tendency for keratin immmunoreactivity.
What tumors are seen in the subtypes of MEN syndrome?
MEN1: Pancreatic tumors (gastrinoma 50%, insulinoma 20-30%, VIPoma 12%, glucagonoma 33%. MEN 2B: Medullary thyroid carcinoma 85%, pheochromocytoma 50%, mucosal neuroma 100%, marfanoid body habitus 80%. FMTC: Medullary thyroid carcinoma 100%.
What is encrusted cystitis?
Encrusted cystitis is caused by bacterial infections associated with alkaline urine in a predisposed immunocompromised patient. Corynebacterium is frequently involved. Histologically, it si characterized by a necrotic surface containing encrusted calcifications and underlined by necrotic tissue with inflammatory cells and bacterial colonies.
What is emphysematous cystitis?
Emphysematous cystitis is a complication of urinary tract infection, characterized by the presence of air within the bladder wall, caused by gas-forming bacteria. It occurs more commonly in women, and particularly in immunocompromised patients, including those suffering from diabetes mellitus. It is usually suspected clinically or radiologically. Histologically, it shows a mixed inflammatory infiltrate, as well as clear air spaces in the lamina propria, which can be surrounded by a foreign bdy giant cell reaction.
What are von Hansemann cells?
Are also called Hansemann macrophages. These cells are modified macrophages found in malakoplakia of the urinary tract. Malakoplakia is the result of an acquired defect in macrophage function causing impairment of bactericidal activity. These large macrophages that are present at sites of infection (von Hansemann cells) exhibit numerous secondary lysosomes containing partially digested organisms. Fusion and calcification of these lysosomes results in the formation Michaelis-Gutmann bodies, considered pathognomonic of malakoplakia. The Michaelis-Gutmann bodies are one or several round basophilic structures measuring between 1µm and 10µm, can be extracytoplasmic or intracytoplasmic, some are laminated, others appear homogeneous, and others have a dense central core with a targetoid appearance. Michaelis–Gutmann bodies demonstrate positivity with PAS stain, von Kossa stain, and sometimes Perls Prussian blue stain.
What is the etiology of biliary atresia?
Biliary atresia is though to represent the end result of intrauterine or perinatal injury to bile ducts, leading to fibrous obliteration of these structures and severe cholestatic liver disease in the neonatal period. Various parts of the extrahepatic biliary system are initially affected, but intrahepatic bile ducts are subsequently involved in a significant proportion of patients, even in those who undergo an initially successful portoenterostomy/Kasai procedure. Histologic examination of bile duct remnants supports the contention that, in most cases, the observed fibro-obliterative cholangiopathy in biliary atresia results from destruction of a presumably well-formed biliary system rather than from primary failure of normal embryologic development of these structures. To date, however, no single agent or abnormality has consistently been implicated as a cause of biliary atresia in humans. Instead, multiple etiologic factors (including immunologic, viral, genetic/metabolic, vascular insult, and environmental/miscellaneous categories) have been postulated to be part of the pathogenesis of this complex disease.
What is the differential diagnosis in high-grade carcinoma involving the renal sinus?
Renal cell carcinomas (collecting duct carcinoma, renal medullary carcinoma, clear cell renal cell carcinoma, papillary renal cell carcinoma (usually type2)) vs. Invasive high-grade urothelial carcinoma of the upper urinary tract.
What genetic abnormality do mesoblastic nephroma, infantile fibrosarcoma, and secretory carcinoma of the breast share?
t(12;15).
In the bladder, does small cell carcinoma tend to be pure, or admixed with another histologic type?
SmCC of the urinary bladder accounts for only 0.3-0.7% of all primary bladder cancers. Compared with its pulmonary counterpart, which usually exhibits pure small cell growth, bladder SmCC is more frequently admixed with another histologic subtype (~40-50% of cases). The mixed epithelial component is most commonly conventional urothelial carcinoma, including CIS, followed by squamous cell carcinoma and adenocarcinoma and, rarely, even sarcomatoid (spindle cell) carcinoma. The frequent association of bladder SmCC with otherwise conventional UC has led to a proposed common origin for both tumors, suggesting that small cell appearance may represent dedifferentiation within urothelial cell neoplasms. Mixed tumors, even with only focal smal cell histology, show dismal prognosis that is more similar to that of pure SmCC than to UC or pure tumors consisting of other components, warranting, therefore, a diagnosis as SmCC.
How does small cell carcinoma of the bladder differ from small cell carcinoma in other body sites in regard to immunohistochemical staining?
Histomorphologically, bladder SmCC resembles its counterparts elsewhere in the body. Unlike SmCC of most other organs, however, the sensitivity of conventional neuroendocrine markers (such as synaptophysin, chromogranin A, NSE, and CD56) has been relatively low in bladder SmCC cases. Therefore, the WHO diagnostic criteria allow for the diagnosis of bladder SmCC to be made on morphologic grounds alone. CD56 stains 71% of bladder SmCC, synaptophysin stains 64%, and chromogranin A stains 29%. NSE stains 80% of bladder SmCC, but the specificity of NSE is very low.
What is the Vysis UroVysion test?
Vysis UroVysion is a molecular cytology test that detects aneuploidy of chromosomes 3, 7, and 17 and deletion of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from persons with hematuria suspected of having bladder cancer.
The diffuse cytoplasmic positivity of chromophobe renal cell carcinoma with Hale’s colloidal iron stain is due to __.
The diffuse cytoplasmic positivity of chromophobe renal cell carcinoma with Hale’s colloidal iron stain is due to staining of acid mucopolysaccharides.
The granularity of oncocytes is due to __.
The granularity of oncocytes is due to an excessive amount of mitochondria, resulting in an abundant acidophilic, granular cytoplasm.
What are the PAX2 and PAX8 genes, what is their utility as immunostains?
PAX2 and PAX8 belong to the pair box gene family consisting of 9 members, PAX1 through PAX9, each of which encodes a transcription factor. These transcription factors are expressed in an orderly manner during fetal development. They play a critical role in the formation of tissues and organs during embryonic development and are also crucial for maintaining the normal function of certain cells after birth. Although these 9 transcription factors control the development of a wide range of organs, the roles of PAX2 and PAX8 in ontogenesis are distinctively similar. Both of them are known to control the development of the central nervous system, eye, kidney, thyroid gland, organs deriving from the mesonephric (wolffian) duct, and those related to the müllerian duct. Transcription factors are identified in the nuclei of the cell types that are under their developmental control during organogenesis, but they often disappear in mature tissue. These transcription factors, however, may reexpress in an organ-specific fashion during neoplastic transformation. For example, both PAX2 and PAX8 are abundantly expressed by renal blastemal cells during nephrogenesis, then are noted in only a few renal parenchymal cells in mature kidney, but are identified again in RCC. Tissue expression of transcription factor therefore has been used as a specific marker for tumor diagnosis.
Iatrogenic KS is associated with immunosuppression due to drugs or after transplantation. Kaposi sarcoma occurs mainly in ___ transplant recipients, and infrequently after other solid organ or bone marrow transplants.
Iatrogenic KS is associated with immunosuppression due to drugs or after transplantation. Kaposi sarcoma occurs mainly in renal transplant recipients, and infrequently after other solid organ or bone marrow transplants. Posttransplant KS may result from reactivation of latent HHV8 infection in recipients or from tumor cells contributed from organ donors. Transplant-associated KS has a protracted, but aggressive course. In transplant recipients, KS lesions may regress after discontinuation of immunosuppressive therapy.
What is a STUMP?
Stromal Tumor of Uncertain Malignant Potential (STUMP). STUMPs are rare prostatic tumors characterized by atypical stromal proliferation, that may resemble breast phyllodes tumors. They are characterized by hypercellular stroma or cytologic atypia, but without evidence of true sarcomatous transformation. The atypical stromal cells have enlarged nuclei with nuclear hyperchromasia and variable multinucleation. There are few/no mitotic figures, and no atypical mitotic figures. Tumors may be associated with benign prostatic glands that may including crowding, a prominent basal cell layer or prominent papillary infolding.
What entities are in the differential diagnosis of renal morphological lesions reminiscent of diabetic nephropathy?
Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without any clinical history or evidence of diabetes. The differential diagnosis includes: Monoclonal immunoglobulin deposition disease. Amyloidosis. Immunotactoid glomerulopathy (fibrillary glomerulonephritis). Fibronectin glomerulopathy. Collagen glomerulopathy. Membranoproliferative glomerulonephritis. Idiopathic nodular glomerulosclerosis. Nodular glomerulosclerosis secondary to chronic hypoxic or ischemic state. The well-formed, intercapillary, nodular mesangial lesions, along with thickened glomerular basement membranes and tubular basement membranes, and hyaline arteriolosclerosis are virtually pathognomic of diabetic nephropathy. However, the pathologist must exclude lesions reminiscent of diabetic nephropathy by performing special stains on histologic sections, IF, and EM studies.
What are common benign bladder lesions that exhibit glandular differentiation?
Cystitis cystica, cystitis glandularis, von Brunn nests, nephrogenic adenoma, intestinal metaplasia, urachal remnant, mesonephric remnant, endometriosis, and prostatic-type polyp. Also, be aware of pseudoglandular differentiation of reactive urothelium or in urothelial carcinoma; this is formation of small intraepithelial spaces due to degenerative changes rather than true glandular differentiation (there is no glandular epithelial lining).
The WHO defines primary adenocarcinoma of the bladder as ___.
The WHO defines primary adenocarcinoma of the bladder as an epithelial malignancy with pure glandular differentiation without evidence of typical urothelial carcinoma. In contrast, a tumor with both typical urothelial carcinoma and adenocarcinomatous components is classified as urothelial carcinoma with glandular differentiation.
What are urachal remnants?
Residual tissues from the embryonic allantoic stalk connecting the umbilicus and bladder.
What entities are in the differential diagnosis of HCC?
The differential diagnosis of HCC includes other hepatic lesions, such as focal nodular hyperplasia, angiomyolipoma, metastatic pancreatic or small bowel neuroendocrine tumors, and renal cell carcinoma.
What is the most common primary malignant tumor of the kidney in children?
Described by Max Wilms in 1899, Wilms tumor (nephroblastoma) is the most common primary malignant tumor of the kidney in children. While it rarely occurs in adults, the peak incidence is in young children (average age, 3-4 years). Approximately 500 cases are diagnosed annually in the United States.
Wilms tumor typically has a triphasic morphology. Describe.
Typically, Wilms tumors has a classic triphasic morphology: blastema, stroma, and epithelium, although in some cases only one or two of these components are present, for example in the “blastema-predominant” variant composed only of the primitive small round cell component, or in the “epithelial-predominant” variant mimicking metanephric adenoma. The epithelial component is typically formed by hyperchromatic primitive-appearing tubules and less commonly, small glomeruloid structures. Mesenchymal differentiation within Wilms tumors is prominent in some cases, particularly smooth muscle or skeletal muscle elements. Fat, cartilage, osteoid, squamous or glandular epithelium, and glial elements are also reported.
What are the unfavorable and favorable histologies of Wilms tumor?
Histologic classification of Wilms tumor is generally divided into two types: Unfavorable histology (tumors with focal or diffuse anaplasia) and Favorable histology (tumors with no anaplasia). Anaplasia is defined as presence of markedly enlarged hyperchromatic nuclei (3x greater in size than other tumor nuclei) and presence of atypical multipolar mitoses, both of which are changes typically seen at screening magnification. Diffuse anaplasia is defined as presence of anaplastic cells in multiple different fields of the primary tumor or in a metastatic site, whereas focal anaplasia refers to presence of anaplastic cells in one or only a few discretely localized foci. This distinction between focal and diffuse anaplasia warrants documentation or “mapping” of the site of sampling of tissue blocks in order to determine proximity of anaplastic fields submitted in separate blocks.
What are the variants of Wilms tumor?
Variants of Wilms tumor include the rhabdomyoblastic , blastemal-predominant, epithelial-predominant, teratoid, cystic variant, and cystic, partially differentiated nephroblastoma (CPDN). CPDN is characterized by microscopic foci of Wilms tumor within fibrous septations in a grossly cystic tumor. Gross identification of solid nodules within a cystic neoplasm warrants a diagnosis of cystic Wilms tumor rather than CPDN.
Approximately 90% of Wilms tumors are sporadic, while a minority are associated with syndromes and/or mutations in the tumor suppressor genes ___ or ___.
Approximately 90% of Wilms tumors are sporadic, while a minority are associated with syndromes and/or mutations in the tumor suppressor genes WT1 (chromosome 11p13) or WT2 (chromosome 11p15).
What are syndromes associated with Wilms tumor?
Syndromes associated with Wilms tumor include WAGR (Wilms tumor-Aniridia-Growth Retardation), Denys-Drash syndrome (Wilms tumor, mesangial sclerosis, gonadal dysgenesis), Beckwith-Wiedemann syndrome (Wilms tumor predilection, organomegaly, hemihypertrophy of extremities, omphalocele, and other anomalies), Simpson-Golabi-Behmel syndrome (Wilms tumor predilection, facial overgrowth, congenital anomalies), and isolated hemihypertrophy.
What are nephrogenic rests within Wilms tumors?
Nephrogenic rests are benign pre-neoplastic lesions associated with Wilms tumor in some cases. Detection of nephrogenic rests typically prompts screening and follow-up of the contralateral kidney due to the risk of multifocality and/or metachronous tumor formation. Hyperplastic nephrogenic rests are typically wedge-shaped and interdigitate microscopically with adjacent renal tubules, whereas incipient Wilms tumor nodules are typically spherical and have a capsule separating the tumor from the surrounding kidney. The difficulty in distinguishing a hyperplastic “adenomatous” nephrogenic rest from a small epithelial-predominant Wilms tumor is well-recognized. Accurate distinction requires examination of the edge of the lesion, and cannot be accurately distinguished by needle biopsy.
What entities are in the differential diagnosis of Wilms tumor?
The differential diagnosis of Wilms tumor includes other primary renal tumors of childhood, including malignant rhabdoid tumor, congenital mesoblastic nephroma (classic and cellular variants), clear cell sarcoma of the kidney, and renal cell carcinoma. Other diagnostic considerations include other small cell tumors of the kidney (synovial sarcoma, primitive neuroectodermal tumor of the kidney, desmoplastic small round cell tumor, neuroblastoma, lymphoma) and a variety of benign tumors (cystic nephroma, infantile ossifying tumor of the kidney, oncocytoma, and others).
What is clear cell oncocytosis?
Oncocytes are altered epithelial cells whose cytoplasm contains vast numbers of abnormal mitochondria. They are large, polygonal cells with well-defined borders and abundant finely granular acidophilic/eosinophilic cytoplasm. Cytoplasmic glycogen accumulation may peripheralize intracytoplasmic mitochondria, resulting in clear cytoplasm (clear cell oncocytosis). Or, it may be a fixation artifact.
Hypovolemic hyponatremia is often due to ___. Euvolemic hyponatremia is often due to ___. Hypervolemic hyponatremia is often due to ___.
Hypovolemic hyponatremia is often due to water loss either through the kidneys or GI tract. Euvolemic hyponatremia is often due to drugs. Hypervolemic hyponatremia is often due to CHF, nephrotic syndrome, or cirrhosis.
Type I renal tubular acidosis is due to ___. Type II renal tubular acidosis is due to ___. Type IV renal tubular acidosis is due to ___.
Type I, or distal renal tubular acidosis is due to the inability to produce an acid urine. Associated with hypokalemia. Type II, or proximal renal tubular acidosis is due to bicarbonate wasting. Associated with hypokalemia. Type IV renal tubular acidosis is due to aldosterone deficiency. Associated with hyperkalemia.
In which renal tubular acidosis is hyperkalemia seen?
Type IV. Type I and type II are associated with hypokalemia.
What is IMP3 gene and protein?
IMP3 protein is a member of the insulin-like growth factor II mRNA-binding proteins that consist of IMP1, IMP2, and IMP3. The IMP3 gene is located on band 7p11.2 and is identical to the KH domain–containing protein overexpressed in cancer (KOC) protein. IMP3 is an oncofetal protein involved in embryogenesis. Recent studies have shown that IMP3 is an important cancer-specific gene that is associated with many aggressive and advanced cancers and is specifically expressed in malignant tumors but is not found in benign tissues. Moreover, IMP3 promotes tumor cell proliferation, adhesion, invasion, and metastasis. IMP3 is an important prognostic biomarker for localized RCC (predicts metastasis and prognosis) and superficial urothelial carcinoma (predicts aggressive superficial UCs).
Xp11.2 translocation renal cell carcinoma is a subtype of renal cancer defined by a breakpoint at Xp11.2 with gene fusions between the transcription factor E3 (TFE3) gene and 6 other genes. The most common fusion partners are ___.
Xp11.2 translocation renal cell carcinoma is a subtype of renal cancer defined by a breakpoint at Xp11.2 with gene fusions between the transcription factor E3 (TFE3) gene and 6 other genes. The most common fusion partners are the papillary renal cell carcinoma (PRCC, 1q21) gene and alveolar soft part sarcoma chromosome region, candidate 1 (ASPSCR1, 17q25) gene. The same ASPSCR1-TFE3 gene fusion is seen in alveolar soft part sarcoma, a rare pediatric tumor. Another renal translocation carcinoma exhibits the t(6;11)(p21;q12) translocation with a gene fusion between the alpha gene and the transcription factor EB (TFEB) gene. Both TFEB and TFE3 are members of the MiTF/TFE family of transcription factors.
The only known predisposing risk factor for developing translocation RCC is ___.
The only known predisposing risk factor is cytotoxic chemotherapy treatment during childhood, which was found in about 15% of patients. The chemotherapeutic agents are thought to cause DNA damage, which then induces repair mechanisms that foster a translocation.
What are the FDA-approved criteria for a positive UroVysion FISH test result?
UroVysion is a multitarget multicolor FISH assay that examines 4 chromosomal abnormalities that commonly occur in UC. The assay is done on exfoliated urothelial cells using centromeric fluorescent denatured chromosome enumeration probes for chromosomes 3, 7, and 17, as well as a locus-specific identifier probe for 9p21. Normal cells are diploid or possess 2 copies of each chromosome. The types of genetic abnormalities observed by FISH include gains (3 or more copies) of one or more chromosomes, monosomy (1 copy), or deletions (no copies). The abnormalities that have been found to be associated with UC are polysomy (including tetrasomy), trisomy, and 9p21 deletion. The FDA-approved criteria for a positive FISH result are (1) 4 or more cells with polysomy (3 or more copies of 2 or more chromosomes), or (2) 9p21 deletion in 12 or more cells. A minimum of 25 morphologically abnormal cells need to be scanned.
What conditions is ACD associated with?
ACD appears to be due to defective iron utilization/metabolism and is associated with chronic nonhematologic disorders such as chronic infections, connective tissue disorders, malignancy, and renal, thyroid, and pituitary disorders.
How does renal failure cause anemia?
Another normocytic, hypoproliferative anemia is the anemia of chronic renal failure. Loss of the kidneys’ excretory function produces an increase in BUN and creatinine, as discussed later, as well as a buildup of metabolic byproducts. The resulting uremia appears to be responsible for changes in red cell shape, with burr cells (echinocytes) and ellipsoidal cells commonly present on peripheral blood films. Identification of burr cells on peripheral blood films during the course of illness may signal the development of renal dysfunction. In addition to decreased excretory function, the kidneys’ ability to produce erythropoietin is decreased, resulting in impaired erythropoiesis, such that the marrow’s response to hypoxia becomes inadequate. In contrast to aplastic anemia, white cell and platelet counts usually remain within normal limits.
70% of the total filtered sodium is reabsorbed in what part of the nephron?
Proximal convoluted tubule.
Epithelioid angiomyolipoma. Morphological DDx?
EAMLs mimic morphologically a variety of neoplasms such as RCC, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumor, epithelioid peripheral nerve sheath tumor, epithelioid GIST, epithelioid melanoma, hepatoblastoma, and HCC. Morphologic clues to diagnosis such as islands of mature fat and abnormal vessels should be diligently searched for in surgical specimens, and prudent use of IHC may be needed.
What is BCG? What is it used for and what is the mechanism of action?
Bacille Calmette–Guerin is a live-attenuated strain of Mycobacterium bovis developed in 1921 as a vaccine for tuberculosis. The first published reports of its use in the bladder were in 1976. Intravesical BCG therapy has been demonstrated to reduce the recurrence rate and the risk of progression to muscle-invasive disease in patients with CIS (BCG is the gold standard for treatment of urothelial CIS), as well as superficial bladder tumors. High-risk patients treated with BCG following TURBT have lower cystectomy rates. The mechanism of action is induction of a massive influx of inflammatory cells and production of cytokines in the bladder mucosa and lumen that leads to an immune response against tumor cells. An intact immune system is a necessary prerequisite to successful BCG therapy.
Brief overview of low-grade myofibroblastic proliferations of the urinary bladder.
The low-grade myofibroblastic proliferations of the urinary bladder are rare lesions affecting males more often than they do females. The most-common signs and symptoms are hematuria and dysuria. Histopathologically, they are spindle cell proliferations in a loose myxoid stroma, even though compact proliferations or hypocellular fibrous patterns can be found. Typically, there are varying amounts of acute, chronic, or mixed inflammatory infiltrates. Necrosis is rare to absent. Muscularis propria infiltration is common, while perivesical soft tissue invasion is uncommon. IHC is nonspecific, except for ALK-1 positivity (20%–89%). FISH has demonstrated clonal genetic aberrations involving the ALK gene in 50% to 60% of cases. After surgery, only 6% of patients experience local recurrence, without metastases or deaths from the disease. Malignant transformation has been reported exceptionally. These myofibroblastic proliferations are probably part of a continuum with, at one end, benign pseudosarcomatous proliferations and, at the opposite end, more-aggressive lesions.
For renal allograft biopsies, what are requirements for minimum sample adequacy and optimal sample adequacy according to the Banff classification?
For minimum sample adequacy, a minimum of 7 glomeruli and one artery are required. For optimal sample adequacy, 10 glomeruli and two arteries are required.
Distinction between benign and malignant adrenal cortical tumors may be extremely difficult, and numerous authors have utilized various parameters in order to allow differentiation of these neoplasms. Medeiros and Weiss have proposed a system which utilizes histologic criteria only. What are the 9 features commonly associated with adrenal cortical carcinoma, according to these authors?
- High nuclear grade (Fuhrman criteria). 2. Mitotic rate exceeding 5 per 50 HPFs. 3. Atypical mitoses. 4. Eosinophilic tumor cell cytoplasm (>75% of tumor cells). 5. Diffuse architecture (>33% of tumor). 6. Necrosis. 7. Venous invasion (smooth muscle in wall). 8. Sinusoidal invasion (no muscle in wall). 9. Capsular invasion. The presence of two or fewer features portends low metastatic potential, while three or more features portend metastatic potential and/or recurrence. The three most important criteria according to Weiss are mitotic activity greater than 5 per 50 high-power field, atypical mitoses, and venous invasion.
Villin IHC stain. What is the target? In what normal and disease states is there positivity? What are some uses of the stain?
Villin is an actin binding protein present in cytoskeleton of intestinal microvilli; has critical role in maintaining brush border organization. It is relatively specific for GI epithelium with brush border microvilli or adenocarcinomas derived from them. Positive staining (normal): Digestive tract epithelium, proximal renal tubules, hepatic bile ducts. Positive staining (disease): Colonic adenocarcinoma, renal cell carcinoma, pulmonary adenocarcinomas. Negative staining: Renal distal tubules, bronchiolar epithelium, pulmonary alveolar cells, bronchial gland cells. Uses: Primary bladder adenocarcinoma (villin-, CDX2-) vs. colorectal carcinoma to bladder. Ovarian adenocarcinoma (villin-) vs. colorectal adenocarcinoma.
Congenital adrenal hyperplasia is a group of autosomal recessive disorders characterized by impairment of cortisol biosynthesis, with or without impairment of aldosterone biosynthesis, and ~95% of cases are due to ___ deficiency.
Congenital adrenal hyperplasia is a group of autosomal recessive disorders characterized by impairment of cortisol biosynthesis, with or without impairment of aldosterone biosynthesis, and ~95% of cases are due to 21-hydroxylase (21-OHD) deficiency. CAH is manifested in a variety of clinical severities comprised of three subtypes: i) classic salt wasting, ii) classic simple virilizing, and iii) nonclassic (mild or late onset) forms.
What entities are in the DDx of small round cell tumors of the kidney?
The differential diagnosis of small round cell tumors of the kidney includes blastema-predominant Wilms tumors, lymphoblastic lymphoma, clear cell sarcoma, small cell carcinoma, monophasic synovial sarcoma, neuroblastoma, rhabdomyosarcoma, desmoplastic round cell tumor, rhabdoid tumor and extraskeletal Ewing sarcoma/PNET.
Which type of azotemia (prerenal, renal, or postrenal) is most likely when the BUN/Cr ratio is maintained but the levels of both are elevated?
Renal azotemia. A maintained but elevated ratio is suggestive of an intrinsic renal defect, most commonly glomerulonephritis or tubulointerstitial nephritis. Deranged ratios, such as when BUN increases more than Cr, is suggestive of impaired renal perfusion, such as prerenal (insufficient volume to the kidney) and postrenal (insufficient volume out of the kidney).
What is the most common cause of renal failure in cirrhotic patients?
Spontaneous bacterial peritonitis.
What is the most common cause of secondary hyperparathyroidism?
Secondary hyperparathyroidism is due to increased physiological PTH as a response to increased resistance to PTH activity, most commonly in end-stage renal disease.
Which type of azotemia (prerenal, renal, or postrenal) is most likely when the BUN/Cr ratio is maintained but the levels of both are elevated?
Renal azotemia. A maintained but elevated ratio is suggestive of an intrinsic renal defect, most commonly glomerulonephritis or tubulointerstitial nephritis. Deranged ratios, such as when BUN increases more than Cr, is suggestive of impaired renal perfusion, such as prerenal (insufficient volume to the kidney) and postrenal (insufficient volume out of the kidney).
What is the most common cause of renal failure in cirrhotic patients?
Spontaneous bacterial peritonitis.
Bilirubinuria indicates (conjugated/unconjugated) hyperbilirubinemia.
Bilirubinuria indicates conjugated hyperbilirubinemia, because unconjugated bilirubin, even when quite elevated, does not appear in urine.
How can renal insufficiency spuriously elevate serum amylase?
Amylase is primarily cleared by glomerular filtration.
