GU Flashcards

Question

What are PAX2 and PAX8 and what can they be used for?

Answer 1

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.

Answer 2

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.

Answer 3

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.

Answer 4

Uroplakin III, p63, thrombomodulin, and GATA3.

Answer 5

CD57 (an immunostain) is a useful marker for the diagnosis of metanephric adenoma.

Answer 6

A specific feature that is seen in most cases of acquired cystic disease-associated RCC in the ACDK setting is intratumoral oxalate crystals.

Answer 7

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.

Answer 8

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.

Answer 9

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).

Answer 10

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.

Answer 11

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.

Answer 12

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.

Answer 13

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.

Answer 14

Sulfadiazine, acyclovir, and indinavir.

Answer 15

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.

Answer 16

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.

Answer 17

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.

Answer 18

Clear cell -3p; papillary +7, +17, -Y; chromophobe -1, -Y; oncocytoma t(11q13).

Answer 19

Carcinomas are equal to or greater than 5 mm in size.

Answer 20

Hemorrhagic cystitis due to adenoviruses, especially type 11, is most often seen in bone marrow transplant recipients.

Answer 21

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.

Answer 22

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.

Answer 23

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.

Answer 24

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.

Answer 25

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.

Answer 26

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.

Answer 27

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%.

Answer 28

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.

Answer 29

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.

Answer 30

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.

Answer 31

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.

Answer 32

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.

Answer 33

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.

Answer 34

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.

Answer 35

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.

Answer 36

The diffuse cytoplasmic positivity of chromophobe renal cell carcinoma with Hale's colloidal iron stain is due to staining of acid mucopolysaccharides.

Answer 37

The granularity of oncocytes is due to an excessive amount of mitochondria, resulting in an abundant acidophilic, granular cytoplasm.

Answer 38

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.

Answer 39

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.

Answer 40

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.

Answer 41

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.

Answer 42

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).

Answer 43

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.

Answer 44

Residual tissues from the embryonic allantoic stalk connecting the umbilicus and bladder.

Answer 45

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.

Answer 46

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.

Answer 47

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.

Answer 48

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.

Answer 49

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.

Answer 50

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).

Answer 51

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.

Answer 52

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.

Answer 53

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).

Answer 54

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.

Answer 55

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.

Answer 56

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.

Answer 57

Type IV. Type I and type II are associated with hypokalemia.

Answer 58

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).

Answer 59

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.

Answer 60

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.

Answer 61

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.

Answer 62

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.

Answer 63

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.

Answer 64

Proximal convoluted tubule.

Answer 65

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.

Answer 66

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.

Answer 67

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.

Answer 68

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.

Answer 69

1. 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.

Answer 70

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.

Answer 71

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.

Answer 72

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.

Answer 73

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).

Answer 74

Spontaneous bacterial peritonitis.

Answer 75

Secondary hyperparathyroidism is due to increased physiological PTH as a response to increased resistance to PTH activity, most commonly in end-stage renal disease.

Answer 76

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).

Answer 77

Spontaneous bacterial peritonitis.

Answer 78

Bilirubinuria indicates conjugated hyperbilirubinemia, because unconjugated bilirubin, even when quite elevated, does not appear in urine.

Answer 79

Amylase is primarily cleared by glomerular filtration.

Answer 80

Diabetic ketoacidosis, peptic ulcer disease, acute cholecystitis, ectopic pregnancy, salpingitis, bowel ischemia, intestinal obstruction, renal insufficiency, salivary gland pathology, and macroamylasemia. Amylase may also be raised somewhat by the administration of opioid analgesics, due presumably to contracture of the sphincter of Oddi.

Answer 81

Stomach, bladder, and prostate.

Answer 82

ANP is synthesized mainly by atrial myocytes (but synthesis of ANP also takes place in the ventricles, brain, kidney, and adrenals). ANP is stored in granules and stimulation results in a rapid response. BNP is synthesized by ventricular myocytes (predominantly) and brain, as well as atrial myocytes under some conditions. BNP is secreted by a constitutive mechanism; only small amounts are stored and cells are dependent upon activation of the BNP gene when secretion is needed. CNP is synthesized by brain and endothelium.

Answer 83

They are somewhat more indolent than sporadic tumors (metastasize only when quite large).

Answer 84

Hemangioblastomas (CNS and retinal), pheochromocytoma, clear cell RCC, pancreatic cysts, islet cell tumors, epididymal and ovarian cystadenomas, endolymphatic sac tumors.

Answer 85

Type 1 often has deletion or nonsense mutations. This group manifests mostly as hemangioblastomas whereas clear cell RCC and pheos are rare. Type 2 is subdivided into types 2A, 2B, and 2C, and are characterized mostly by missense mutations. Type 2A is at risk of hemangioblastomas and pheos, but not clear cell RCC. Type 2B is at risk of all 3 tumors, with a higher risk of clear cell RCC. Type 2C is at risk for only pheos. Type 3 has a risk of Chuvash polycythemia.

Answer 86

Facial angiofibromas (adenoma sebaceum) or forehead plaque. Nontraumatic ungual or periungual fibroma. >3 hypomelanotic macules. Shagreen patch (connective tissue nevus). Multiple retinal nodular hamartomas. Cortical tuber. Subependymal nodule. SEGA. Cardiac rhabdomyoma, single or multiple. LAM. Renal AML. Definite TSC is either 2 major features or one major plus 2 minor features.

Answer 87

Cutaneous lentigenes (simple lentigos). Blue nevi, particularly the cellular blue nevus. Cardiac myxomas (as well as myxomas of breast, female genital tract, and skin (especially on eyelid and external ear)). Endocrine tumors including thyroid follicular adenomas, pituitary adenomas (GH-secreting), and the so-called primary pigmented nodular adrenocortical disease (a form of multinodular hyperplasia of the adrenal cortex that causes Cushing syndrome). Large-cell calcifying Sertoli cell tumor. Psammomatous melanotic schwannoma.

Answer 88

Acute interstitial nephritis, not UTI.

Answer 89

Noninflammatory bacterial diarrhea: Vibrio spp, E. coli (especially ETEC and EPEC), C. perfringens, S. aureus, and B. cereus. Inflammatory bacterial diarrhea: C. difficile, Salmonella, Shigella, Campylobacter.

Answer 90

Haemophilus ducreyi.

Answer 91

C. trachomatis.

Answer 92

Hepatic synthetic function is poorly reflected in the albumin, since only in end-stage liver disease is serum albumin noticeably decreased. The greatest decrements in serum albumin are seen in protein-losing conditions such as protein-losing enteropathy and nephrotic syndrome.

Answer 93

Alcohol use, renal dysfunction and drugs (corticosteroids and other hormones, high-dose NSAIDs). .

Answer 94

In nephrotic syndrome due to minimal change disease, there is an especially selective loss of albumin (selective proteinuria). In other forms of nephrotic syndrome, nearly all proteins are lost, including gamma globulins. However, in all types of nephrotic syndrome, larger protein molecules are retained. The result is dimming of all the electrophoretic bands, most prominently the albumin band, with the conspicuous exception of the alpha-2 band which contains the large protein alpha-2 macroglobulin.

Answer 95

Schistosomiasis is caused by digenetic blood trematodes. The three main species infecting humans are Schistosoma haematobium, S. japonicum, and S. mansoni. Two other species, more localized geographically, are S. mekongi and S. intercalatum. In addition, other species of schistosomes, which parasitize birds and mammals, can cause cercarial dermatitis in humans.

Answer 96

S. mansoni is found in parts of South America and the Caribbean, Africa, and the Middle East; S. haematobium in Africa and the Middle East; and S. japonicum in the Far East. S. mekongi and S. intercalatum are found focally in Southeast Asia and central West Africa, respectively.

Answer 97

There is no vector; there is direct penetration of skin by free-swimming cercaria. Infection occurs when skin comes in contact with contaminated freshwater in which certain types of snails that carry the parasite are living. The parasite leaves the snail and enters the water where it can survive for about 48 hours.

Answer 98

Glomerular proteinuria is due to increased filtration of macromolecules (such as albumin) across the glomerular capillary wall. On UPEP there are strong albumin, alpha-1 and beta bands. Very large proteins, due to the persistence of some filtering function, and very small proteins due to tubular absorption, do not make their way into urine. This leaves the protein in between these, most notably albumin, AAT, and transferrin.

Answer 99

Weak albumin band and strong alpha-1 and beta bands. This pattern results from the impaired tubular reabsorption of low molecular weight proteins normally filtered freely by the glomerulus and almost completely reabsorbed in the proximal tubules, such as alpha-2-macroglobulin, beta-2-microglobulin, and Ig light chains.

Answer 100

Increased excretion of LMW proteins can occur with marked overproduction of a particular protein, leading to increased glomerular filtration and excretion. This is almost always due to immunoglobulin light chains in multiple myeloma but may also be due to lysozyme (in acute myelomonocytic leukemia), myoglobin (in rhabdomyolysis), or free hemoglobin (in intravascular hemolysis) that is not bound to haptoglobin. In these settings, the filtered load is increased to a level that exceeds the normal proximal reabsorptive capacity.

Answer 101

Pseudohyponatremia (from hyperglycemia, hyperlipidemia, hyperproteinemia). True hyponatremia with hypovolemia: renal losses (diuretics, medullary renal disease, Addison's disease, RTA type I) or extrarenal losses (GI losses, third spacing). True hyponatremia with euvolemia: SIADH, psychogenic polydipsia, drugs with ADH-like effect. True hyponatremia with hypervolemia: CHF, cirrhosis, nephrotic syndrome.

Answer 102

Inadequate potassium intake. Increased potassium excretion (mineralocorticoid excess (endogenous or exogenous), hyperreninism (renal artery stenosis), osmotic diuresis (mannitol, hyperglycemia), increased gastrointestinal losses, drugs, genetic disorders). Transcellular shifts (alkalosis, correction of DKA, refeeding, hypothermia).

Answer 103

The most common cause for metabolic acidosis with hypokalemia is GI loss (eg, diarrhea, laxative use). Other less common etiologies include renal loss of potassium secondary to renal tubular acidosis (types I and II?) or salt-wasting nephropathy.

Answer 104

~20% of the population has HSV-2 seropositivity, but only ~2% of the population has genital herpes.

Answer 105

MSTs are a group of benign tumors of the kidney, distinct from congenital mesoblastic nephroma with which they were previously grouped. They are now thought to be related more closely to Wilms tumor rather than mesenchymal tumors of the kidney. They were first recognized and referred to as nephrogenic adenofibroma, but were subsequently renamed as MST. They are considered to be part of the spectrum of metanephric tumors ranging from metanephric adenoma to metanephric adenofibroma to MST, all considered to represent the benign end of Wilms tumor.

Answer 106

Loose spindle cell proliferation with uniform hyperchromatic nuclei and thin indistinct cytoplasm. No capsule. Subtle infiltration into adjacent renal parenchyma. The spindle cells surround entrapped renal tubules and show condensation around them with a myxoid background giving it a characteristic "onion skin" pattern. There may be areas of prominent cellularity or epithelioid morphology. Prominent vascularity with changes of angiodysplasia. Another feature is the presence of heterologous elements, usually glial or cartilaginous.

Answer 107

Congenital mesoblastic nephroma and clear cell sarcoma of kidney. CMN: Unencapsulated like MST but more infiltrative. Entraps tubules only at the periphery and usually does not have mesenchymal collars like MST. Cellular CMN have the classic cytogenetic abnormality t(12;15). CMN lacks the heterologous elements and angiodysplasia as seen in MST. Are frequently desmin and/or actin positive, reflecting their myofibroblastic nature. CCSK: Is extremely cellular, although some may be composed of large areas of bland spindle cells mimicking MST. Lacks onion-skinning around tubules or heterologous elements. Has a characteristic branching vascular pattern not seen in MST.

Answer 108

Clear cell sarcoma of the kidney metastasizes frequently to bone (which is unlike Wilms tumor). Bony mets often precede mets to organs, and affected children may be hypercalcemic at presentation. In fact, CCSK was initially referred to as "bone matastasizing renal tumor of childhood".

Answer 109

Nests or cords of cells separated by regularly spaced, arborizing fibrovascular septa. Regularly spaced small blood vessels give a "chicken wire" pattern. Slightly variable ovoid nuclei with finely granular chromatin. Frequent empty nuclei. Mitoses are uncommon.

Answer 110

IgA nephropathy. Accounts for 1-3% of patients with ESRD in USA and Europe.

Answer 111

Wide age spectrum (1 to >65), peak 20-30 yo. M:F = 2:1. Ethnicity: Asians > Whites > Blacks.

Answer 112

Recurs in transplants in 30%. Graft loss due to recurrence in 5%.

Answer 113

Glomerulonephritis with predominantly IgA deposits in mesangium in absence of systemic disease.

Answer 114

IgA mesangial deposits (100%). Mesangial C3 (90%). Fibrinogen/fibrin usually present in mesangium. Lambda often more prominent than kappa (64%). Mesangial IgG, IgM (50%). Mesangial C1q (10%).

Answer 115

Yes. Bowman capsule is the layer of basement membrane surrounding Bowman space on which parietal epithelial cells rest; continuous with GBM at base of glomerulus.

Answer 116

Extracapillary proliferation of >2 cell layers occupying 25% or more of glomerular capsular circumference or >10%. The 3 types of crescents are cellular, fibrocellular, and fibrous.

Answer 117

Focal: minority of glomeruli (50% in lupus).

Answer 118

Mesangial cells are normal residents of mesangium that have contractile and phagocytic properties. Mesangial hypercellularity: 3 or 4 mesangial nuclei or more in 1 mesangial area in a 3 micron section; lupus classification uses 3; IgA classification uses 4. Mesangial hypercellularity is subdivided into mild (4-5), moderate (6-7), and severe (8 or more).

Answer 119

Mesangial matrix is the extracellular component of normal mesangium, which includes collagen III, fibronectin, and a variety of glycosaminoglycans. Mesangial matrix expansion is defined as width of mesangial interspace exceeding 2 mesangial cell nuclei in at least 2 glomerular lobules (IgA). Mesangiolysis is defined as loss of integrity of the mesangium so that glomerular capillary forms aneurysmal dilation.

Answer 120

For bone tumors, metastases are far more common than primary bone tumors in a ratio of 25:1. The 5 most common primary sites are lung, breast, prostate, kidney, and thyroid. After lungs and liver, skeleton is 3rd most frequent site of metastatic disease.

Answer 121

The effect of PTH on renal tubules causes increased calciium reabsorption and increased phosphate excretion.

Answer 122

This is because PTH has a dual effect on renal tubules, where there is increased calciium reabsorption and increased phosphate excretion.

Answer 123

An increased nephrogenous cAMP in the presence of normal PTH is highly suggestive of humoral hypercalcemia of malignancy.

Answer 124

PTH causes increased calcium reabsorption and increased phosphate excretion. Vitamin D causes increased calcium reabsorption and increased phosphate reabsorption.

Answer 125

Osteolytic metastases: breast cancer, multiple myeloma, lymphoma, leukemia. Humoral hypercalcemia (PTHrP): squamous cell carcinoma, RCC, breast cancer, bladder carcinoma, ovarian carcinoma, non-Hodgkin lymphoma, CML, leukemia, lymphoma. Tumor production of calcitriol: lymphoma (Hodgkin, non-Hodgkin, lymphomatosis/granulomatosis), ovarian dysgerminoma.

Answer 126

The equation used to measure corrected calcium in cases of hypo/hyperalbuminemia is: Corrected (Ca) = Measured total (Ca) + (0.8 x [4.5 - (alb)]). Or, 0.8 mg/dL Ca per 1g/dL protein. While this formula often provides a good estimate of the ionized calcium, its use should be avoided in patients with acid-base disturbances, renal insufficiency, liver disease, and neonates.

Answer 127

PTH-mediated: primary hyperparathyroidism, familial (MEN-I and -IIa, familial isolated hyperparathyroidism, familial hypocalciuric hypercalcemia), tertiary hyperparathyroidism. PTH-independent: hypercalcemia of malignancy, vitamin D intoxication, chronic granulomatous disorders, medications (thiazide diuretics, lithium, teriparatide, theophylline toxicity, excessive vitamin A), miscellaneous (hyperthyroidism, acromegaly, pheochromocytoma, adrenal insufficiency, immobilization, parenteral nutrition, milk-alkali syndrome).

Answer 128

Renal failure (impaired calcitriol production, hyperphosphatemia). Decreased calcium intake. Calcium malabsorption (vitamin D deficiency, bariatric surgery, celiac disease, pancreatic disease (fat malabsorption)). Renal calcium loss (idiopathic hypercalciuria, loop diuretics). Inhibiton of bone resorption (bisphosphonates, hungry bone syndrome).

Answer 129

Low PTH (hypoparathyroidism): genetic disorders, post-surgical (thyroidectomy, parathyroidectomy, radical neck dissection), autoimmune, infiltration of the parathyroid gland (granulomatous, iron overload, metastases), radiation-induced destruction of parathyroid glands, hungry bone syndrome, HIV infection. High PTH (secondary hyperparathyroidism in response to hypocalcemia): vitamin D deficiency or resistance, parathyroid hormone resistance, renal disease, loss of calcium from the circulation (hyperphosphatemia, tumor lysis, acute pancreatitis, osteoblastic metastases, acute respiratory alkalosis, sepsis or acute severe illness. Drugs. Disorders of magnesium metabolism.

Answer 130

Renal medullary carcinoma is very rare, with less than 100 reported cases. Age range 5 – 39 yo, average age 21 – 24 yo. Much more common in the right kidney than the left. Occurs predominantly in males (>75% of cases) and almost exclusively in African-Americans due to its relationship with sickle cell trait. Almost all reported cases have occurred in the setting of sickle cell trait or sickle cell disease. Most patients have sickle cell trait with Hemoglobin-AS (Hb-AS), however cases have been reported in patients with hemoglobin SC disease (Hb-SC) and sickle cell disease (Hb-SS). In fact, chronic medullary hypoxia due to hemoglobinopathy with subsequent chronic regenerative proliferation of the damaged epithelium has been implicated in the pathogenesis of renal medullary carcinoma.

Answer 131

Renal medullary carcinoma shows loss of INI1, while the other two retain INI1 expression.

Answer 132

With increased AG (>12): ketoacidosis (diabetic, starvation, EtOH-associated), lactic acidosis, D-lactic acidosis, ingestions (methanol, ethylene glycol, diethylene glycol, propylene glycol, salicylate, toluene (if early or if kidney function is impaired)), pyroglutamic acid (5-oxoproline), CKD/uremia. With normal AG (<12): diarrhea or other intestinal losses, ureteral diversion, ketoacidosis posttreatment, carbonic anhydrase inhibitors, type 1 (distal) RTA, type 2 (proximal) RTA, type 4 RTA (hypoaldosteronism), toluene ingestion (if late and if renal function is preserved - dut to excretion of sodium and potassium hippurate in the urine), CKD and tubular dysfunction (but relatively preserved GFR).

Answer 133

Toluene ingestion causes increased AG if early after ingestion or if kidney function is impaired. It causes normal AG if late after ingestion and if renal function is preserved - due to excretion of sodium and potassium hippurate in the urine.

Answer 134

With anion gap metabolic acidosis: ingestion (ethylene glycol, methanol, formaldehyde, paraldehyde); lactic acidosis; diabetic ketoacidosis; alcoholic ketoacidosis; end-stage CKD (GFR <10 mL/min) without regular dialysis. Without metabolic acidosis: ingestion (ethanol, isopropyl alcohol, diethyl ether); infusion of nonconductive glycine, sorbitol, or mannitol solutions; severe hyperproteinemia; severe hyperlipidemia.

Answer 135

Chloride responsive: diuretic therapy, vomiting, NGT suction, villous adenoma, carbenicillin, contraction alkalosis. Chloride resistant: hyperaldosteronism, Cushing syndrome, exogenous steroids, licorice (glyccrhizic acid), Bartter syndrome, milk-alkali syndrome.

Answer 136

It secretes hormones that participate in the regulation of systemic and renal hemodynamics (renin, prostaglandins, and bradykinin), red blood cell production (erythropoietin), and calcium, phosphorus, and bone metabolism (1,25-dihydroxyvitamin D3 or calcitriol).

Answer 137

Urea is freely filtered and partially reabsorbed by the nephron; this reabsorption has the consequence that BUN always slightly underestimates GFR.

Answer 138

Reabsorption increases with hypovolemia; thus BUN underestimates GFR even more in hypovolemic states.

Answer 139

The creatinine concentration was classically determined, and is still often determined, by the Jaffe reaction - alkaline picrate forms a colored complex with creatinine. Alternative enzymatic (using creatinase) and colorimetric assays are available.

Answer 140

Creatinine is derived from the metabolism of creatine in skeletal muscle and from dietary meat intake. It is released into the circulation at a relatively constant rate. Creatinine is freely filtered across the glomerulus and is neither reabsorbed nor metabolized by the kidney. However, approximately 10 to 40 percent of urinary creatinine is derived from tubular secretion by the organic cation secretory pathways in the proximal tubule, with the quantity secreted increasing with increasing serum creatinine concentration. At all serum concentrations, creatinine slightly overestimates GFR.

Answer 141

BUN underestimates GFR. Cr overestimates GFR.

Answer 142

Classic/NOS. Collapsing. Cellular. Perihilar. Tip (AKA glomerular tip lesion).

Answer 143

The strongest prognostic indicator of outcome is the initial response to therapy regardless of the type of histology. However, some do report an association between histologic variant and prognosis: The collapsing variant has the highest rate of progression to ESRD, while the tip variant has the lowest rate of progression to ESRD.

Answer 144

ClCr = UCr x VUr / PCr. Where UCr is urine creatinine in mg/dL, VUr is volume of urine in mL/24 hrs, and PCr is plasma creatinine in mg/dL. But this formula is overly simplistic and the MDRD study equation is the most widely recommended formula now.

Answer 145

Nonlinearity and nonglomerular influences upon creatinine. Nonlinearity: The inverse relationship between GFR and Cr is nonlinear. Mild to moderate degrees of GFR impairment do not cause appreciable increases in Cr concentration; only when GFR is about half of normal does creatinine rise precipitously and begin to linearly reflect changes in GFR. Nonglomerular influences upon creatinine: The serum Cr concentration is increased by muscle mass/activity/injury and protein intake; it is decreased by age; it is influences by race, age, sex, and numerous medications.

Answer 146

The MDRD equation has been studied and validated in adult Caucasian and African American populations with impaired kidney function (GFR

Answer 147

4, based on if the lab reports serum Cr in mg/dL (conventional units) or umol/L (SI units), and whether the lab uses a Cr assay that has been (traceable) or has not been (original (non-traceable)) calibrated to be traceable to an isotope dilution mass spectometry (IDMS) method.

Answer 148

The result given by the Modification of Diet in Renal Disease Study equation is multiplied by 0.742 if the patient is female and by 1.210 is the patient is African American.

Answer 149

mL/min/1.73m^2.

Answer 150

When BUN and Cr are elevated but the ratio is maintained, it is suggestive of intra-renal disease (GN and TIN) - renal azotemia. When the ratio is elevated, is suggests prerenal azotemia (poor renal perfusion) or postrenal azotemia (renal obstruction). A decreased BUN/Cr is rare and may result from dietary protein insufficiency or severe liver disease.

Answer 151

Cystatin C is a cysteine protease inhibitor produced by nearly all cells in the body that is freely filtered by the glomerulus, not reabsorbed, and is metabolized by the proximal tubular epithelium.

Answer 152

Normal proteinuria does not exceed 150 mg/day and consists mainly of Tamm-Horsfall protein and minute amounts of albumin.

Answer 153

The urine protein assay is sensitive to all kinds of protein (albumin, globulins, Bence-Jones), and its lower limit of detection is about 3 mg/dL.

Answer 154

The urine dipstick test is most sensitive to albumin (but not enough to detect microalbuminuria); it is not sensitive to globulins or even to very high levels of Bence-Jones protein. The lower limit of detection of the urine dipstick test for albumin is 18 mg/dL.

Answer 155

3 mg/dL, 18 mg/dL, and 0.3 mg/dL, respectively.

Answer 156

The albumin:creatinine ratio is reported in mg/g, and the protein:creatinine ratio is reported in mg/mg.

Answer 157

Bence-Jones protein and hook effect (a false negative result with certain immunoassays due to very high concentrations of a particular analyte).

Answer 158

Tubular dysfunction, since these proteins are freely filtered by the glomerulus then completely reabsorbed by the normally functioning proximal convoluted tubule.

Answer 159

CKD is defined as the presence of kidney damage (usually detected as urinary albumin excretion of ≥30 mg/day, or equivalent) OR decreased kidney function (defined as eGFR <60 mL/min per 1.73 m^2) for three or more months, irrespective of the cause. The persistence of the damage or decreased function for at least three months is necessary to distinguish CKD from acute kidney disease/injury.

Answer 160

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines stage according to: cause of disease, 6 categories of eGFR (G stages), and 3 categories of albuminuria (A stages).

Answer 161

Prerenal: >20:1, high (>1.020), high (>500 mmol/kg), 2%, >35%.

Answer 162

Prerenal - As an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons. Renal/Intrinsic - In response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage. Postrenal - From obstruction to the passage of urine. While this classification is useful in establishing a differential diagnosis, many pathophysiologic features are shared among the different categories.

Answer 163

The most common cause of renal/intrinsic acute kidney injury is ATN, the most common causes of which are ischemia and nephrotoxins.

Answer 164

In these patients, fractional excretion of urea can be a useful alternative.

Answer 165

Prerenal ARF: A lack of findings or isolated hyaline casts. GN: Dysmorphic RBCs and RBC casts. ATN: Pigmented casts. TIN: Leukocytes (in the absence of infection - sterile pyuria), WBC casts, and/or eosinophils.

Answer 166

HRS is one of many potential causes of AKI in patients with acute or chronic liver disease. Affected patients usually have portal hypertension due to cirrhosis, severe alcoholic hepatitis, or (less often) metastatic tumors, but can also have fulminant hepatic failure from any cause. The HRS represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. It is a diagnosis of exclusion and is associated with a poor prognosis.

Answer 167

Spontaneous bacterial peritonitis.

Answer 168

The renal biopsy is essentially normal in HRS, but an abnormal bx must be interpreted cautiously - many patients with cirrhosis due to hepatitis viruses have an associated GN, and cirrhosis can by itself lead to an IgA-like nephropathy.

Answer 169

Arterial vasodilatation in the splanchnic circulation, which is triggered by portal hypertension, appears to play a central role in the hemodynamic changes and the decline in renal function in cirrhosis. The presumed mechanism is increased production or activity of vasodilators, mainly in the splanchnic circulation, with nitric oxide thought to be most important. As the hepatic disease becomes more severe, there is a progressive rise in cardiac output and fall in systemic vascular resistance; the latter change occurs despite local increases in renal and femoral vascular resistance that result in part from hypotension-induced activation of the renin-angiotensin and sympathetic nervous systems. Thus, the reduction in total vascular resistance results from decreased vascular resistance in the splanchnic circulation. The decline in renal perfusion in this setting is associated with reductions in GFR and sodium excretion and a fall in mean arterial pressure, despite the intense renal vasoconstriction.

Answer 170

Brain, kidney, liver, and skin.

Answer 171

Ethylene glycol is metabolized to glycolate, glyoxylate, and oxalate. The parent alcohol (ethylene glycol itself) is relatively nontoxic. The glycolate is responsible for the CNS manifestations and for the anion gap acidosis. Oxalate binds calcium to produce calcium oxalate, which is deposited in tissues, with the process often resulting in hypocalcemia. ARF is primarily due to glycolate-induced damage to tubules, although tubule obstruction from precipitated oxalate crystals may contribute.

Answer 172

Lead enters the body through inhalation and ingestion. About 95% of ingested lead is distributed in erythrocytes and bone. Some also goes to the kidney where it is toxic to renal tubular cells.

Answer 173

Mitochondrial toxicity leads to reduced ATP available to drive the numerous ATP-dependent channels involved in renal tubular epithelial function. Then end-result is aminoaciduria, glycosuria, and phosphaturia (similar to Fanconi renal syndrome). Leads inclusions are detectable ultrastructurally as highly electron-dense founded intracellular bodies.

Answer 174

Amoebic colitis. Antibiotic-associated (pseudomembranous) colitis. Chemotherapy-induced colitis. Colitis complicating obstruction. Heavy metal toxicity (gold salt therapy). Hemolytic uremic syndrome. Ischemic colitis. Neutropenic enterocolitis (typhilitis). Shigellosis.

Answer 175

Goodpasture disease refers to the triad of pulmonary (alveolar) hemorrhage, glomerulonephritis of any severity, and serum anti-GBM production. The treatment of choice is plasmapheresis.

Answer 176

The NC1 domain of collagen IV in glomerular and alveolar basement membranes.

Answer 177

Anti-GBM disease, ANCA disease, and immune complex-mediated diseases (such as SLE).

Answer 178

The combination of acute glomerulonephritis and pulmonary hemorrhage. Causes: ANCA-positive vasculitis (granulomatosis with polyangiitis/Wegener's, microscopic polyangiitis). Anti-GBM disease (Goodpasture's). Pulmonary hemorrhage is a rare finding in lupus, HSP (IgAV), and infective endocarditis. Acute glomerulonephritis complicated by pulmonary edema due to fluid overload, as can occur in poststreptococcal glomerulonephritis.

Answer 179

Calcineurin inhibitors include cyclosporin A and tacrolimus. The afferent arterioles show nodular, PAS-positive, protein (hyaline) deposits deep in the medial smooth muscle layers replacing individual (necrotic) myocytes. Hyaline nodules are often seen in a necklace-like pattern along the adventitial aspect of afferent arterioles. The most serious toxic side effect is a fully developed thrombotic microangiopathy.

Answer 180

Gross hematuria, papillary necrosis, nephrotic syndrome, renal infarction, isosthenuria, pyelonephritis, renal medullary carcinoma.

Answer 181

They may manifest mild isosthenuria, are at risk for splenic infarcts at high altitudes, and have a risk for renal medullary carcinoma.

Answer 182

Adenoviruses are grouped into over 40 serotypes. Most of the respiratory infections are caused by serotypes 1-14, with types 4 and 7 associated with epidemic outbreaks of respiratory disease. Types 11 and 21 are associated with hemorrhagic cystitis. Types 40 and 41 are associated with childhood gastroenteritis.

Answer 183

The gaseous form -arsine gas- is the most toxic form of arsenic, capable of producing acute renal failure, hemolysis, and death within 24-48 hrs.

Answer 184

Ingested arsenic is excreted in urine, with most of the remainder distributed into skin, nails, and hair.

Answer 185

Arsenic inhibits the oxidative production of ATP. Thus, initial toxicity is manifested in dividing tissue such as GI mucosa, with nausea, vomiting, bloody diarrhea, and abdominal pain. The marrow is affected, causing cytopenias (with erythrocyte basophilic stippling similar to that seen in lead toxicity). Chronic toxicity results in peripheral neuropathy, nephropathy, skin hyperpigmentation and hyperkeratosis (particularly palms and soles) and transverse Mees lines in the nails.

Answer 186

Since mercury blocks the degradation pathway of catecholamines (it is suggested to inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-o-methyl transferase), epinephrine excess causes profuse sweating, tachycardia, salivation and elevated blood pressure. There are increased amounts of vanillylmandelic and homovanillic acid in urine.

Answer 187

Pulmonary absorption of mercury vapor (elemental form) is high; however, this form of mercury is only poorly absorbed from the GI tract and across the skin. The kidney is the major site of deposition for mercury derived from inhalation exposure of mercury vapor. A significant fraction of the mercury vapor taken into the lung is eliminated via exhalation; most of the absorbed mercury is eliminated in the feces. GI absorption of inorganic mercury is on the order of 15 percent. The kidney is the major site of deposition for inorganic mercury compounds. Organic mercury compounds such as methylmercury are highly absorbed from the GI tract and later de-alkylated. The kidney, hair, and CNS are major sites of deposition. Organic mercury readily crosses the placenta, causing severe neurologic impairments in the fetus.

Answer 188

When there is a change in dose, a change in the patient's renal function, or a change in concomitantly administered medications.

Answer 189

Digoxin is primarily excreted by the kidneys and has a long half-life of around 36 hours.

Answer 190

Elevated DLIS concentrations are encountered in patients with volume-expanded conditions such as uremia, essential hypertension, liver disease, and preeclampsia. They are also seen in neonates, pregnant women, and renal failure.

Answer 191

Procainamide is cleared predominantly by the liver. Procainamide is metabolized by hepatic acetyltransferase to N-acetylprocainamide (NAPA), which has pharmacologic activity of its own (in making dosing decisions, the sum of procainamide and NAPA is considered). NAPA is cleared predominantly by the kidneys.

Answer 192

Pocainamide (hepatic clearance) is metabolized to N-acetylprocainamide (NAPA) (renal clearance), which is also biologically active. The rate of conversion to NAPA is determined by the concentration of hepatic acetyltransferase, which is genetically determined. So-called fast acetylators, who have genetically high levels of acetyltransferase, have higher levels of NAPA.

Answer 193

Mainly by the kidneys.

Answer 194

Arterioles.

Answer 195

Transplant endarteritis shows infiltration of lymphocytes through an activated endothelial cell layer into the subendothelial compartment/intima. The media of the vessels is unaltered. Transplant endarteritis is a common type of acute allograft rejection. Patients usually do not benefit from conventional anti-rejection therapy with bolus steroids, but rather require potent treatment with anti-lymphocytic preparations (ATG or OKT3).

Answer 196

A rejection-induced arterial intimal thickening due to de novo deposition of collagens I and III without associated intimal elastosis. During intimal remodeling, myofibroblasts may occasionally form a new rudimentary media under the endothelial layer; Such a (so-called) neo-media formation is almost pathognomonic for "chronic vascular rejection."

Answer 197

ANCA disease accounts for ~55% of cases, anti-GBM for 7%, and both ANCA and anti-GBM present in 8% of cases.

Answer 198

Intimal fibroplasia - <1%. There are 3 types of medial dysplasia: Medial fibroplasia - 75-80%. Perimedial fibroplasia - 10-15%. Medial hyperplasia - 1-2%.

Answer 199

Clinical features. Patient's lacking signs of asthma, lung and sinus inflammation, or peripheral blood eosinophilia are best classified as having microscopic polyangiitis. Necrotizing inflammatory lesions involving the lungs, nasal sinuses and kidneys are typically seen in cases of Wegener's granulomatosis. Peripheral blood eosinophilia and asthma are defining features of Churg-Strauss syndrome.

Answer 200

The kidney (either native or transplanted).

Answer 201

Urothelial cells with BK virus. Oligodendroglial cells with JC virus.

Answer 202

Hematologic diseases such as essential mixed cryoglobulinemia, lymphoma, and aplastic anemia. Renal disease, particularly membranoproliferative glomerulonephritis. Autoimmune disorders such as thyroiditis and the presence of autoantibodies. Dermatologic conditions such as porphyria cutanea tarda and lichen planus. Diabetes mellitus.

Answer 203

Bunyaviruses, and specifically, the hantaviruses.

Answer 204

Hypothyroidism, DM, nephrotic syndrome, cholestasis, cyclosporine, thiazide diuretics, or loop diuretics.

Answer 205

Heavy alcohol consumption, obesity, DM, hepatitis, pregnancy, renal failure, beta blockers, isotretinion, corticosteroids, nephrotic syndrome, and gout.

Answer 206

Severe examples of DM, hypothyroidism, or nephrotic syndrome. Also, type III hyperlipidemia, thiazides, loop diuretics, and beta blockers.

Answer 207

Kidneys. Therefore, C-peptide is raised in renal impairment.

Answer 208

SLE causes low C3 and C4. MPGN causes low C3, but normal C4. Terminal complement deficiency is an inherited autosomal co-dominant condition with low C5, C6, C7, C8, C9 levels that causes susceptibility to infections by Neisseria. Properdin deficiency is an X-linked disorder that also causes susceptibility to neisserial infections. C1-inhibitor deficiency/hereditary angioedema will have low C4 with normal C1 and C3 levels.

Answer 209

Direct immunofluorescence (DIF) involves incubating cryostat sections of patient tissue with fluorescein-labeled AHG. Positive DIF tests confirm the in vivo presence of bound autoantibodies in the patient's tissues. Examples include skin IF and renal IF. Indirect immunofluorescence (IIF) involves incubating patient serum with cells/tissue known to contain specific antigens, then adding fluorescein-labeled AHG. Positive IIF tests confirm the presence of circulating autoantibodies.

Answer 210

SS-A (Ro) is present in 70% of patients with Sjogren syndrome and 30% of patients with SLE. SS-B (La) is present in 50% of patients with Sjogren syndrome and 15% of patients with SLE. Anti-SS-A/SS-B are found in children with neonatal lupus. Patients who are ANA+, SS-A+ but SS-B neg are very likely to have lupus nephpritis.

Answer 211

Goodpasture syndrome; the epitope is the M2 subunit of type IV collagen.

Answer 212

Type I (allergic, immediate-type): IgE; atopy, asthma, anaphylaxis. Type II (antibody-dependent, cytotoxic, antibody-mediated cellular cytotoxicity): IgM or IgG, complement, MAC; Goodpasture syndrome, autoimmune hemolytic anemia, erythroblastosis fetalis, rheumatic heart disease (also Graves disease and myasthenia gravis, but some classify these as type V). Type III (immune complex): IgG, complement, neutrophils; SLE, serum sickness, Arthus reaction, PSGN. Type IV (delayed-type, cell-mediated immune memory response, antibody-independent): T cells; tuberculin skin test, contact dermatitis, MS. Type V (an additional subtype sometimes used as a distinction from type II) (receptor mediated autoimmune disease): IgM or IgG, complement; Graves disease, myasthenia gravis.

Answer 213

ANA, anti-nucleolar, anti-Scl-70 (anti-topoisomeraseI). IIF on C. luciliae or HEp-2 cells; ELISA.

Answer 214

Blastema is present in almost all Wilms' tumors and is characterized by small blue cells with fine chromatin, inconspicuous nucleoli and very scanty cytoplasm. Occasionally, the blastema cells may form rosettes, which may suggest an erroneous diagnosis of neuroblastoma. The cells in the epithelial component are larger and have more abundant cytoplasm than blastema cells. They can form nests, glands, tubules, and glomeruloid bodies. Stroma is present in only one-third of cases and appears as metachromatic, myxoid material with spindle cells. Uncommonly, stromal elements such as muscle, fat, bone, or cartilage may be present.

Answer 215

Birt-Hogg-Dube syndrome, renal oncocytosis, and as a sporadic neoplasm.

Answer 216

CD136 in 100%. S100 in 93%. CK8 in 92%. PAX-8 in 91%. CD117 in 90%. Parvalbumin in 79%. CK18 in 77%. EMA/MUC1 in 74%. PAX-2 in 62%. Vimentin in 56%.

Answer 217

CK7+ and CK20+/-. 92% are CK7 positive, and 63% are CK20 positive.

Answer 218

CD31 in 100%, HMB-45 in 95%, SMA in 88%, melan-A in 86%, mart-1 in 75%, vimentin in 69%, MITF in 65%, desmin in 55%, tyrosinase in 31%, S100 in 29%, panCK in 0%.

Answer 219

Intralobar rests have an increased rate of progression to Wilm tumor, and are more commonly associated with WT1 mutations, Denys-Drash syndrome and WAGR syndrome. Perilobar rests are seen in sporadic tumors and are associated with idiopathic hemihypertrophy and Beckwith-Wiedemann syndrome.

Answer 220

The primary cilium is an antenna-like, nonmotile structure that extends from the surface of most mammalian cell types and is critical for chemosensing and mechanosensing in a variety of tissues including cartilage, bone, and kidney.

Answer 221

Microtubular axoneme organization in motile cilia follows a 9+2 assembly, where 9 doublets of microtubules surround a central pair; this arrangement allows specific movement patterns that can lead fluids toward a single direction in vivo by the interacting sliding of the different constitutive parts of doublets. Immotile cilia lack the microtubule central pair, thus cannot be motile.

Answer 222

85-90% of autosomal dominant polycystic kidney disease is due to mutations in the PKD1 gene on 16p13.3, while 10-15% are due to mutations in the PKD2 gene on 4q22.

Answer 223

Autosomal recessive polycystic kidney disease is due to mutations in the PKHD1 gene. The high phenotypic variability of this disease is due to alternative splicing of 86 exons assembling a variable number of transcripts with the longest being fibrocystin/polyductin.

Answer 224

PKD1 gene --> polycystin-1 (PC-1) protein. PKD2 gene --> polycystin-2 (PC-2) protein.

Answer 225

Renal dysplasia is an aberrant developmental disease usually diagnosed during the perinatal and childhood years. It is defined as abnormal metanephric differentiation diagnosed histopathologically, which can be diffuse, segmental, or focal. Renal dysplasia may be combined with abnormalities in the collecting system, or associated with complex syndromes.

Answer 226

Meckel syndrome, VATER association, renal-coloboma syndrome, Herlyn-Werner-Wunderlich syndrome, pruce belly syndrome, branchio-oto-renal dysplasia, renal-hepatic-pancreatic dysplasia, and MEN 2A.

Answer 227

Renal dysplasia is characterized principally by primitive ducts with a fibromuscular collar and lobar disorganization. Primitive ducts, which may be cystic, are considered as altered collecting ducts lined by undifferentiated or columnar-to-cuboidal epithelium. The fibromuscular collar is comprised of spindle cells arranged circumferentially around the primitive ducts. Incomplete and abnormal corticomedullary relationships and rudimentary medullary development constitute lobar disorganization. The cysts derived from primitive ducts may be large or small and numerous or scarce, and eventually lead to divergent macroscopic features of multicystic, hypoplastic, or aplastic renal dysplasia. The other pathologic findings include metaplastic cartilage, bone, basement membrane thickening of the primitive ducts, nodular renal blastema, and proliferating nerves.

Answer 228

Polycystic kidney disease, fetal kidney, renal hypoplasia, and renal atrophy.

Answer 229

The dysplastic kidney contains primitive ducts with or without dilated cysts. The kidney with concomitant multiple cysts and dysplasia is diagnosed as multicystic renal dysplasia, although it grossly resembles polycystic kidney disease. Additionally, these cysts in multicystic renal dysplasia are usually smaller than those in PCKD. The fetal kidney contains poorly differentiated tissues that are compatible with gestational development. The hypoplastic kidney has fewer nephrons than the normal kidney, but no dysplastic elements. The atrophic kidney exhibits segmental loss of parenchyma due to renal scarring, and compensatory hypertrophy in the remnant parenchyma.

Answer 230

(1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made.

Answer 231

(1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5.

Answer 232

Grade Group 1 (Gleason score 6 or less) – Only individual discrete well-formed glands. Grade Group 2 (Gleason score 3+4=7) – Predominantly well-formed glands with lesser component of poorly-formed/fused/cribriform glands. Grade Group 3 (Gleason score 4+3=7) – Predominantly poorly-formed/ fused/cribriform glands with lesser component of well-formed glands*. Grade Group 4 (Gleason score 4+4=8; 3+5=8; 5+3=8) - Only poorly-formed/fused/cribriform glands OR Predominantly well-formed glands and lesser component lacking glands** OR Predominantly lacking glands and lesser component of well-formed glands**. Grade Group 5 (Gleason scores 9-10) – Lacks gland formation (or with necrosis) with or w/o poorly formed/fused/cribriform glands*. *For cases with>95% poorly-formed/fused/cribriform glands or lack of glands on a core or at RP, the component of

Answer 233

A condition caused by biallelic pathogenic germline variants in MUTYH characterized by a greatly increased lifetime risk of colorectal cancer (43% to almost 100% in the absence of timely surveillance). Although typically associated with ten to a few hundred colonic adenomatous polyps that are evident at a mean age of about 50 years, colonic cancer develops in some individuals in the absence of polyposis. The colonic phenotype is similar to AFAP but the terminology "FAP/AFAP caused by MYH mutations" is not correct. Extracolonic manifestations include duodenal adenomas/carcinomas, ovarian CA, bladder CA, skin CA.

Answer 234

The diagnosis is suspected in otherwise healthy males with abnormal sperm counts ranging from azoospermia to mild oligozoospermia and/or abnormal sperm morphology/motility for whom other causes of infertility have been eliminated. Chromosomal microarray or routine cytogenetic testing reveals chromosome abnormalities in 5%-10% of these men. Molecular testing reveals microdeletions of the long arm of the Y chromosome in another 5%-13% of these males. Pregnancies may be achieved by in vitro fertilization using ICSI (intracytoplasmic sperm injection), but retrieval of sperm has been successful mainly for most males with deletions of AZFc, and rarely for males with deletions of AZFb or AZFa.

Answer 235

Wilms' tumor and neuroendocrine tumors/carcinoids. The relative risk of urothelial carcinoma is increased as well, due to chronic obstruction, stones or infection. However, the incidence of renal cell carcinoma is not increased.