Peds Flashcards

Question

Primary ciliary dyskinesia AKA immotile cilia syndrome is associated in ~50% of patients with ___ syndrome.

Answer 1

Primary ciliary dyskinesia AKA immotile cilia syndrome is associated in ~50% of patients with Kartagener syndrome AKA situs inversus totalis. Chronic bronchitis, recurrent pneumonia, and atelectasis is virtually pathognomonic for Kartagener syndrome, and in this situation, cilia evaluation is not required for diagnosis.

Answer 2

Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause. Transmission is direct contact, usually oral-fecal route.

Answer 3

Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause, but other coxsackie viruses usually associated include A1 to A6, A8, A10, or A22.

Answer 4

A common viral illness of infants and children, which causes fever and blister eruptions of mouth and/or skin. Caused by virus belonging to Enterovirus group. Transmission is by direct contact. Virus is found in secretions, including saliva, nose and throat secretions, blister fluid, and stools.

Answer 5

AKA focal epithelial hyperplasia AKA multifocal epithelial hyperplasia. A benign, virus-induced epithelial proliferation of oral mucosa associated with HPV types 13 and 32. Majority of cases are in children. Micro: Prominent acanthosis and elongated broad rete ridges (since the thickened epithelium extends upward, elongated rete are at same depth as adjacent normal rete ridges). May see papillary surface. Mitosoid cells (represents ballooning and nuclear degeneration; represents an altered nucleus resembling a mitosis in an otherwise normal stratified squamous epithelium; can be seen throughout epithelium); do not misinterpret mitosoid cells as atypia. Koilocytic change in superficial keratinocytes can be seen. No dyskeratosis and/or atypia. DDx: Papilloma. Condyloma acuminatum. Oral verruca vulgaris.

Answer 6

HPV types 13 and 32.

Answer 7

AKA traumatic ulcer, traumatic ulcer with stromal eosinophilia, eosinophilic granuloma of tongue, traumatic granuloma, atypical histiocytic granuloma. It is a chronic traumatic ulceration of oral mucosa with unique histopathologic features. Riga-Fede disease specifically refers to trauma to the soft tissue (ventral tongue or inner lower lip) in newborns or infants from natal or neonatal teeth. In children, traumatic ulcer is often due to thermal or electrical burns or parafunctional habits. In adults, traumatic ulcer is often due to fractured and/or malposed teeth or parafunctional habits. Micro: Ulcer bed composed of granulation tissue with mixed inflammatory cell infiltrate of lymphocytes, histiocytes, neutrophils, and occasionally plasma cells. Inflammation including scattered eosinophils extends into underlying muscle.

Answer 8

A teratoma that arises in the oral cavity. Most common sites are palate and tongue.

Answer 9

AKA epignathus. Rare; 1 in 4000 live births have teratoma, and 1-2% of those involve head and neck. Most common sites of teratoma of the oral cavity are palate and tongue. Prenatally, can have polyhydramnios due to impaired fetal swallowing, and AFP concentrations are increased. At birth, can have significant respiratory distress. Top DDx: dermoid cyst or encephalocele.

Answer 10

Embryonal rhabdomyosarcoma is the most common type (65% of RMS cases) and usually occurs in children ages 3-10 in the head and neck (nasal and oral cavities, orbit, ear), prostate or paratesticular regions. Subtypes of embryonal rhabdomyosarcoma include embryonal NOS, anaplastic, botryoid, and spindle cell, with embryonal NOS being the most common subtype (75%).

Answer 11

Embryonal rhabdomyosarcoma is the most common type of rhabdomyosarcoma (65% of RMS cases) and usually occurs in children ages 3-10 in the head and neck (nasal and oral cavities, orbit, ear), prostate or paratesticular regions. Subtypes of embryonal rhabdomyosarcoma include embryonal NOS, anaplastic, botryoid, and spindle cell, with embryonal NOS being the most common subtype (75%).

Answer 12

AKA dysgenetic polycystic parotid gland disease. Marked dilation and cystic change within intercalated ducts of parotid gland; striated and excretory ducts unaffected. Rare developmental anomaly not associated with polycystic disease of other organ systems. Typically becomes evident in childhood. F>>>M. No malignant transformation.

Answer 13

All histologic variants of hemangioma occur in salivary glands, but capillary (juvenile) hemangioma is most common. Hemangiomas account for 90% of parotid gland tumors in infants <1 yo are hemangioma. Capillary (juvenile) hemangiomas have M:F = 1:3, while cavernous hemangiomas tends to be seen more frequently in older males. Parotid gland involved in 90%, and up to 25% are bilateral. Pediatric tumors initially grow rapidly, but 75-95% spontaneously involute before 7 yo, and many earlier. Pharmacological therapy (corticosteroids and interferon) yields a response in up to 98% of cases. IHC: Endothelial cells pos for CD31, CD34, FVIIIRAg. Residual salivary ducts are keratin pos. GLUT1 pos in juvenile hemangiomas.

Answer 14

A malignant epithelial tumor with variable components of mucous, epidermoid, and intermediate cells. Environmental exposure: ioning radiation (latent period varies, and long-term f/u is required). Most common malignant salivary gland tumor, ~16% of all salivary gland tumors, most common salivary gland tumor to arise in gnathic bones. Wide age range. Most common malignant salivary gland tumor in children. M

Answer 15

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 16

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 17

Age of the patient has an effect on serum constituents. In the newborn, much of the Hb is Hb F, not Hb A, as seen in the adult. Bilirubin concentration rises after birth and peaks at about 5 days. In cases of hemolytic disease of the fetus and newborn (HDFN), bilirubin levels continue to rise. This often causes difficulty in distinguishing between physiologic jaundice and HDFN. Infants have a lower glucose level than adults because of their low glycogen reserve. With skeletal growth and muscle development, serum alkaline phosphatase and creatinine levels, respectively, also increase. The high uric acid level seen in a newborn decreases for the first 10 years of life, then increases, especially in boys, until the age of 16.

Answer 18

Spindle cell rhabdomyosarcoma is a rare variant of embryonal rhabdomyosarcoma that has a predilection for young males and most commonly involves the paratesticular region followed by head and neck. Histopathology demonstrates elongated spindle cells with fusiform to cigar-shaped nuclei and indistinct eosinophilic cytoplasm arranged in fascicles or whorls. Although the tumor demonstrates increased cellularity and moderate atypia, the microscopic and architectural patterns can allow this tumor to be confused with multiple entities, such as leiomyosarcoma, spindle cell carcinoma, desmoplastic melanoma, or fibrosarcoma, with important therapeutic implications. IHC workup demonstrates sarcomeric differentiation with reactivity for desmin, myogenin, and MyoD1 markers. Compared with other subtypes, the spindle cell variant in children is associated with a favorable outcome; however, in the adult population there does not appear to be any prognostic advantage.

Answer 19

Histopathology is dominated by a uniform cellular proliferation of elongated, spindle cells arrayed in fascicles or whorls demonstrating a herringbone growth pattern reminiscent of leiomyosarcoma. The cells have centrally located nuclei with blunted or fusiform ends, small to inconspicuous or prominent nucleoli, and eosinophilic fibrillar cytoplasm. Mitotic figures are easily appreciated, including atypical forms. Admixed with this population can be a second cell type of immature rhabdomyoblasts, usually comprising a small percentage of the total tumor. These cells exhibit eccentric nuclei and bright cytoplasmic eosinophilia; on occasion, cytoplasmic cross-striations can be observed. The presence of these cells should be an intimation of the diagnosis. Collagen fibers are frequently intermingled between the spindle cells; however, the degree is highly variable. The extent of collagen production has led some authors to subclassify SC-RMS into collagen-rich and collagen-poor forms. The subclassification does not appear to affect clinical outcome.

Answer 20

An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection.

Answer 21

An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection. In PCH, autoanti-P is an IgG, biphasic hemolysin capable of binding RBCs at colder temperatures, followed by intravascular hemolysis at body temperature. This characteristic can be demonstrated in vitro in the Donath-Landsteiner test.

Answer 22

Malignancy. Transplantation/transfusion (including intrauterine fetal transfusion). Neonates. Excessive soluble blood group substances.

Answer 23

Chimera (transplantation chimera; genetic chimera (twin); transfusion chimera). Fetomaternal hemorrhage. Some subgroups of A (e.g. A3 and Aend).

Answer 24

Neonates. Elderly. Severe immunosuppression. Transplantation. Hypogammaglobulinemia. Subgroup of a major blood type.

Answer 25

HDFN secondary to maternal anti-Kell antibodies is often characterized by reticulocytopenia, with little or no bilirubinemia. It is now known that maternal anti-Kell (anti-KEL1 or K1) directly suppresses erythroid progenitors, leading to a severe reticulocytopenic anemia in the fetus with up to 30% of affected infants presenting with fetal hydrops. Anti-K1 is present in approximately 1% of pregnancies, with HDFN affecting 40% of K1-positive infants.

Answer 26

The Le (a+b+) phenotype is only rarely observed, usually on RBCs of very young children and some individuals of Polynesian, Japanese, or Taiwanese ancestry.

Answer 27

The Le (a-b-) phenotype is 5 times more common in blacks than whites. The Le (a−b−) phenotype is also increased in neonates owing to developmentally delayed expression of the Lewis and Secretor genes. By 5 years of age, most children will express adult levels of Lewis antigens on their RBCs.

Answer 28

The Le (a−b−) phenotype is increased in neonates owing to developmentally delayed expression of the Lewis and Secretor genes. By 5 years of age, most children will express adult levels of Lewis antigens on their RBCs.

Answer 29

They are not associated with HDFN and are only rarely associated with hemolytic transfusion reactions. For transfusion, patients with anti-Lewis antibodies reactive only at room temperature may be safely transfused with crossmatch–compatible RBCs.

Answer 30

Antibodies against Fya, Fyb, and other Duffy antigens are clinically significant. They are associated with HDFN and both immediate and delayed hemolytic transfusion reactions. They are usually of IgG isotype, reactive at 37° C, and are detected only in the IAT.

Answer 31

Anti-Xga is not associated with hemolytic transfusion reactions or HDFN. Anti-Xga may be immune stimulated or naturally occurring. Most examples are of IgG isotype, including some capable of activating complement.

Answer 32

Acute (onset/duration of <24 hours): Pyogenic bacteria. Subacute (onset/duration of 1-7 days): Enteroviruses, pyogenic bacteria. Chronic (persisting at least 4 weeks): M. tuberculosis, T. pallidum, Brucella sp., L. interrogans, B. burgdorferi, C. neoformans, C. immitis, H. capsulatum.

Answer 33

Neonates-3 months: Group B streptococcus, E. coli, L. monocytogenes (Listeria can cause meningitis in immunocompromised individuals in all age groups). 4 months-6 years (Incidence of meningitis due to HIB in the US has declined dramatically due to vaccination): S. pneumoniae. 6-45 years: N. meningitidis. >45 years: S. pneumoniae, L. monocytogenes, Group B streptococcus.

Answer 34

Although uncommon, anti-Jk can cause a mild HDFN.

Answer 35

Anti-Dombrock antibodies can be clinically significant, although many examples are benign. Anti-Dombrock antibodies are capable of causing shortened RBC survival and acute and delayed hemolytic transfusion reactions. Anti-Dombrock is not associated with HDFN. Antibodies against Dombrock antigens are usually of IgG isotype, arising from immune stimulation by transfusion or pregnancy.

Answer 36

Anti-Colton antibodies can be clinically significant: They can be associated with shortened RBC survival, hemolytic transfusion reactions, and HDFN. Antibodies to Coa and Cob are usually of the IgG isotype, resulting from immune stimulation by transfusion or pregnancy. Some examples of anti-Coa and anti-Cob are reported to bind complement.

Answer 37

Clinically benign, anti-LW antibodies are rarely a cause of hemolytic transfusion reactions or HDFN. They usually are of IgG isotype and are detected in the IAT.

Answer 38

Antibodies against Ch/Rg antigens do not cause hemolytic transfusion reactions or HDFN. Rare reports have described anaphylaxis following transfusion of plasma and platelets. Anti-Ch/Rg antibodies are of IgG isotype and are usually detected with AHG.

Answer 39

HDFN is the destruction of fetal or newborn RBCs by maternal alloantibodies specific for inherited paternal RBC antigen(s). The maternal IgG is transported across the placenta into the fetal circulation where it binds to the corresponding RBC antigen, targeting the antibody-coated RBCs for destruction by macrophages in the fetal spleen. The fetal marrow initially responds by increasing erythropoiesis and releases many of the newly produced RBCs into the circulation prematurely as nucleated precursors, leading to the term "erythroblastosis fetalis." With worsening anemia, erythropoiesis expands to the liver and spleen, causing organ enlargement and portal hypertension. A resulting decrease in liver production of albumin leads to reduced plasma colloid osmotic pressure, generalized edema, ascites, and effusions known as "hydrops fetalis."

Answer 40

A rare benign cartilaginous bone tumor arising in young adults aged 15-25 years that often occurs in the metaphysis of long tubular bones or in the small bones of the feet. Grossly: well circumscribed, solid and glistening. It is often lobulated with zonation. Older tumors are more hyalinized. Microscopic: well circumscribed, hypocellular lobules of poorly formed hyaline cartilage composed of chondroblasts with abundant pink cytoplasm, and myxoid tissue with fibrous septae containing spindle cells and osteoclasts. Atypia is common, including large, hyperchromatic nuclei. Scattered calcification and osteoclast-like giant cells are present. At the periphery, the tumor is more cellular and vascular. No/rare mitotic activity. Tumors often have 6q13 rearrangements, with recurrent 6p25 and 6q25 anomalies.

Answer 41

Rosette test. If there is insufficient or no washing before adding the indicator red blood cells, there can be a false positive result because excess unbound anti-D reagent is still present. If the mother is a weak D phenotype, there can be a false positive result because she may type as negative even though she is actually positive, and the test needs to have a D- mother and a D+ fetus to work as it should. If the fetus is weak D phenotype, there can be a false negative result because the weak D may not be enough to bind the anti-D reagent. In this last situation, if a baby initially types as D-, weak D testing is done, and if weak D is positive, go straight to a Kleihauer-Betke test instead of doing a rosette test.

Answer 42

The rosette test can detect a fetomaternal hemorrhage of approximately 10 mL or more.

Answer 43

(Fetal cells x Maternal blood volume) / Total cells counted = Fetal hemorrhage in mL. Maternal blood volume is calculated from 70 mL/kg or assumed to be 5000 mL if weight is not known. Total cells counted is always 2000. The result is divided by 30 (b/c one dose of RhIG (30 ug) covers 30 mL of whole blood). The resulting number is then rounded down if the number to the right of the decimal point is less than 5, then 1 is added to give the total vials/doses of RhIG. The resulting number is rounded up if the number to the right of the decimal point is 5 or more, then 1 is added to give the total vials/doses of RhIG.

Answer 44

Prevention of recurrent severe allergic/anaphylactic transfusion reactions. Neonatal alloimmune thrombocytopenia. Large-volume or rapid transfusion into neonates and small children. Irradiated RBC products. Patients with T-activation. Washing of RBC products for patients with paroxysmal nocturnal hemoglobinuria used to be advocated, but is no longer recommended.

Answer 45

Neonatal alloimmune thrombocytopenia (NAIT) is secondary to maternal alloantibodies, usually anti-HPA-1a, against the platelet antigen in the fetus or neonate.

Answer 46

Prior to transfusion the maternal platelets must be washed to remove the antibody against the fetal/neonatal platelet antigen contained within the maternal plasma, and irradiated to prevent TA-GVHD.

Answer 47

Washing may be used to remove potassium, anticoagulant-preservative solution (particularly additive solutions) and other substances in the supernatant in RBC products. This decreases the risk of hyperkalemia and cardiac arrhythmias. Volume reduction can achieve the same goal.

Answer 48

Unlike HDFN caused by anti-D, HDFN caused by anti-K uniquely produces suppression of fetal erythropoiesis, in addition to hemolysis.

Answer 49

IgG1 is associated with more severe disease because it is transported across the placenta earlier and in larger amounts than IgG3.

Answer 50

Before the development of color Doppler US, the severity of HDFN was usually monitored by amniocentesis, typically performed with US guidance, to follow the level of bilirubin in amniotic fluid. The aspirated amniotic fluid is protected from light and tested by a scanning spectrophhotometer for the change in fluid optical density at 450 nm, which is proportional to the bilirubin concentration. The delta OD 450 is then plotted on a graph according to gestational age. The graph is divided into zones that correspond to severity disease.

Answer 51

Amniotic fluid analysis for bilirubin does not correlate well with the degree of fetal anemia in HDFN in mothers with Kell system antibodies. For these patients, middle cerebral artery peak systolic velocity and/or cordocentesis is indicated.

Answer 52

With the widespread use of RhIG, ABO incompatibility has become the most common cause of HDFN. D incompatibility is more severe, though.

Answer 53

HPA-1a, formerly known as P1 A1, accounts for ~80% of cases. HPA-5b accounts for ~10%, HPA-1b accounts for ~4%, HPA-3a accounts for 2%, and 6% is by other antibodies.

Answer 54

The clinical significance of anti-Cromer antibodies is variable. In some individuals, anti-Cromer antibodies are associated with decreased RBC survival and HTRs. Cromer antibodies do not cause HDFN owing to adsorption of antibodies by DAF (Cromer antigens are present on DAF (CD55)) on trophoblast epithelium.

Answer 55

The Indian (IN) blood group contains 2 autosomal codominant antigens: In^a (IN1) and In^b (IN2). Three additional high-incidence antigens are known: IN3, IN4, and AnWj. The Indian antigens are present on CD44, a ubiquitous glycoprotein on many cell membranes. Antibodies against the Indian antigens can be clinically significant, with shortened RBC survival and transfusion reactions. They are not associated with HDFN.

Answer 56

The JMH (John Milton Hagen) system contains 6 high-incidence antigens and can vary in strength between individuals. JMH is carried on CD108 (SEMA-L), a semaphorin glycoprotein. Anti-JMH antibodies are of IgG isotype and can be naturally occurring. They do not cause HTRs or HDFN.

Answer 57

The I blood group system contains two biosynthetically related antigens: I and i. The biosynthetic precursor to I antigen, the i antigen, is strongly expressed on cord cells because of developmental delays in the enzyme responsible for I antigen synthesis. By 3 months of age, there is a perceptible decrease in i antigen, accompanied by increased I antigen, with an adult I+i− phenotype by 18–24 months of age. Both I and i antigens are ubiquitously expressed on glycolipids and glycoproteins on red cells and other tissues.

Answer 58

The iadult phenotype is a rare, autosomal recessive phenotype found in <1/10,000 donors. In Asia, the iadult phenotype can be associated with congenital cataracts. i antigen is also observed on cord RBCs and reticulocytes and in megaloblastic anemia, leukemia, and chronic hemolytic states as a sign of stressed erythropoiesis. Elevated i antigen is also observed in HEMPAS (hereditary erythroblastic multinuclearity with positive acidified-serum test), a congenital dyserythropoietic anemia.

Answer 59

It is hypothesized that the developmental delay in I antigen synthesis may play a protective role against HDFN-ABO by minimizing the number of ABH antigens expressed on fetal red cells. This is supported by parallel increases in I and ABH during the first 2 years of life.

Answer 60

The GIL blood group system contains one high-incidence antigen, GIL (100% donors). GIL is carried by aquaglyceroporin (AQP-3), a member of the major intrinsic protein family of water channels. Anti-GIL is associated with hemolytic transfusion reactions. No reports have described clinical HDFN due to anti-GIL despite a positive DAT. Anti-GIL is usually of IgG isotype, reactive at 37° C and enhanced with AHG.

Answer 61

The presence of hyaluronic acid and albumin in cord blood is responsible for the nonspecific agglutination that can be seen in cord blood samples contaminated with Wharton's jelly.

Answer 62

Isolated lymphopenia is uncommon but may be seen in SLE, HIV, SARS, anti-CD20 (rituxan) therapy, steroid therapy, and certain congenital immunodeficiencies (Bruton, SCID, DiGeorge, CVI).

Answer 63

Pancreatoblastoma has a bimodal distribution, with tumors presenting in both children (mean age 2.4 yrs) and adults (mean age 40 yrs), although the incidence (or perhaps simply its diagnosis) is more common in the young.

Answer 64

A rare, often cystic lesion that typically fills the nasal cavity and extends into the ethmoid sinuses. It is considered an upper respiratory tract analogue of chest wall mesenchymal hamartoma. Although benign, it may erode the cribriform plate, and have an intracranial component. It is more common in males (2/3), and typically affects children, with a mean age of 14 months. Histologically, there is well demarcated mature cartilage, myxoid stroma and spindle cells. There may also be focal osteoclast-like giant cells, aneurysmal bone cyst-like formations, and collagen fibers. DDx: aneurysmal bone cyst, chondroblastoma, chondromyxoid fibroma, fibrous dysplasia, osteochondromyxoma.

Answer 65

Bile ducts, bone, placenta, intestine.

Answer 66

Anodal mobility 1 = biliary. Anodal mobility 2 = bone. Anodal mobility 3 = placenta. Anodal mobility 4 = intestinal.

Answer 67

Biliary: -, +. Bone: -/+++. Placenta: +++/-. Intestinal: +++/+. For sensitivity to heat/urea, think "bone burns, placenta persists."

Answer 68

AKA carcino-placental alkaline phosphatase. Appears to be mostly identical to placental alk phos (same anodal mobility, same degree of inhibition by L-phenylalanine, slightly less degree of heat/urea inhibition). The Regan isoenzyme is observed in ~5% of individuals with carcinoma.

Answer 69

Hyperammonemia is nearly always due to liver failure. However, particularly in children, it should raise suspicion for an inborn error of metabolism (especially urea cycle enzyme deficiencies).

Answer 70

Physiologic jaundice. Breast milk jaundice. Polycythemia. Hemolysis (HDN, hemoglobinopathies, inherited membrane or enzyme defects). Bowel obstruction (Hirschprung disease, cystic fibrosis, ileal atresia). Inherited disorders of bilirubin metabolism (Gilbert syndrome, Crigler-Najjar syndrome).

Answer 71

Biliary obstruction (extrahepatic biliary atresia). Sepsis or TORCH infection. Neonatal hepatitis (idiopathic, Wilson disease, alpha-1 antitrypsin deficiency). Metabolic disorders (galactosemia, hereditary fructose intolerance, glycogen storage disease). Inherited disorders of bilirubin transport (Dubin-Johnson syndrome, Rotor syndrome). Parenteral alimentation.

Answer 72

Bilirubin has a special affinity for the globus pallidus, the hippocampus, and the subthalamic nucleus. Many other structures, including the striatum, thalamus, cranial nerve nuclei, inferior olives and dentate nuclei of the cerebellum are less frequently affected.

Answer 73

Unconjugated hyperbilirubinemia. Phototherapy converts unconjugated bilirubin into a molecule that can be excreted without conjugation; phototherapy is not useful for conjugated hyperbilirubinemia.

Answer 74

Usually noted between days 2-3 of neonatal life and rarely rises at a rate greater than 5 mg/dL/day. Usually peaks by days 4-5 and rarely exceeds 5-6 mg/dL.

Answer 75

In a healthy term infant, phototherapy should be considered when bilirubin exceeds 10 mg/dL before 12 hours of age, 12 mg/dL before 18 hours of age, and 14 mg/dL before 24 hours of age.

Answer 76

Alkaptonuria, an autosomal recessive disorder of amino acid metabolism. Increased homogentisic acid is secreted in urine and polymerized homogentisic acid deposits accumulate in connective tissue. The pigment is Fontana-Masson positive and Prussian blue negative.

Answer 77

Although more than 70 Legionella serogroups have been identified among 50 species, L pneumophila causes most legionellosis. L pneumophila serogroup 1 alone is responsible for 70-90% of cases in adults. In a pediatric series, L pneumophila serogroup 1 accounted for only 48% of cases, serogroup 6 accounted for 33%, and the remaining cases involved other serotypes and species. Legionella micdadei and L dumoffii are the second and third most common species to cause Legionnaires disease in children, respectively,

Answer 78

Endemic form: peak age 4-7, M:F = 2:1. Sporadic form: peak incidence in children is age 11 and median age in adults is age 30, M:F = 3-4:1.

Answer 79

GBS, GN aerobic bacilli (E. coli, Klebsiellae), L. monocytogenes.

Answer 80

In adults, S. pneumoniae, followed by N. meningitidis. In elderly adults, S. pneumoniae, followed by L. monocytogenes, followed by GN aerobic bacilli.

Answer 81

HHV-6, the virus that causes exanthem subitum, is a common cause of viral encephalitis in children, and is thought to contribute to many cases of febrile seizures in children.

Answer 82

Extremes of age (70 yo), corticosteroid therapy, transplant, DM, HIV, iron overload.

Answer 83

Monoarticular in children and adults: S. aureus. Polyarticular in young adults: N. gonorrhea.

Answer 84

Parainfluenza virus, serotypes 1-3.

Answer 85

Infants/children: RSV. Adults: Influenza A (orthomyxovirus).

Answer 86

H. influenzae type B.

Answer 87

Bordatella pertussis.

Answer 88

Measles: Rubeola virus. German measles: Rubella virus.

Answer 89

Parvovirus B19.

Answer 90

S. pyogenes (GAS).

Answer 91

Congenital varicella is diagnosed when there is evidence of maternal varicella infection during pregnancy, skin lesions on the newborn that have a dermatomal distribution, and serologic evidence of infection in the newborn (either IgM or persistent IgG beyond 7 months). Perinatal varicella arises when maternal infection occurs within a few days of delivery.

Answer 92

When a woman is infected during pregnancy, the overall incidence of congenital varicella is 1-5%. The incidence is lowest when maternal infection occurs in the 1st trimester and highest in the 3rd. In contrast, the likelihood of perinatal varicella is 50-60%.

Answer 93

CMV. Congenital CMV results from transplacental infection and is most likely to occur when a pregnant woman experiences primary CMV infection during gestation. 30-40% of pregnancies with primary CMV infection result in congenital CMV. In contrast, reactivation infection during pregnancy results in <1% incidence of transplacental transmission.

Answer 94

Sensorineural hearing loss is detected in ~70%of newborns with symptomatic congenital CMV infection and in ~15% with asymptomatic infection. This hearing loss almost always is progressive, eventually producing severe to profound hearing loss in the affected ear(s).

Answer 95

Maceration may be seen at delivery in as early as 6 hours and almost always by 12 hours.

Answer 96

Although the definition includes infants up to 1 year of age, one should be hesitant to certify a death as due to SIDS before 1 month of age or after 6 months of age.

Answer 97

SIDS is a sporadic, nonheritable syndrome. A prior SIDS death in the same family should raise the suspicion of a genetic disorder (such as metabolic disease) or homicide.

Answer 98

Extreme prematurity, very low birth weight, Beckwith-Weidemann syndrome, family history of APC gene mutations, and congenital hepatic fibrosis associated with autosomal recessive poly cystic kidney disease.

Answer 99

GSD type 1a, hereditary tyrosinemia, HBV infection, and chronic cholestasis disorders including biliary atresia, progressive familial hepatic cholestasis type 2 (ABCB11 disease), and Alagille syndrome.

Answer 100

Type I (cystic). Type II (cystic and solid). Type III (solid).

Answer 101

Type 0 CPAM to type 4 CPAM. Type 4 is now thought to represent a regressed or undersampled form of type I (cystic) pleuropulmonary blastoma.

Answer 102

FLIT is a congenital pulmonary mass typically identified prenatally or within the first 3 months of life. Histologically, the tumor has immature airspace structures separated by widened cellular septa giving the tumor a microcystic appearance. The spaces are lined by flat to cuboidal non-ciliated epithelium with clear cytoplasm. The septa contain a monotonous population of immature, round to ovoid mesenchymal cells in the interstitium. The interstitial cells are PAS positive diastase sensitive, positive for vimentin, and there is variable positivity for SMA and desmin in cases with myofibroblastic morphology.

Answer 103

LGFMS are often seen in young adult males with a median age in the third decade. But they are not uncommon in children, with up to a third of cases in those <18. LGFMS is typically a slow growing, painless deep soft tissue tumor of the extremities and trunk, superficial and visceral lesions can also be seen.

Answer 104

FT is a highly developed and organized mature teratoma resembling a malformed fetus. FIF is a parasitic monozygotic twin usually found inside the body of a neonate or infant (essentially, a form of monozygotic monochorionic diamnionic twin gestation in which the parasitic twin grows inside the body of its partner). Classically, the distinguishing feature of FIF has been the presence of an axial skeleton, but this is now controversial, and it is thought that FT and FIF lie along a continuum.

Answer 105

The cysts in MHL do not communicate with the biliary tree, whereas the latter 2 entities by definition do communicate with the biliary tree.

Answer 106

Rarely, UES has arisen either in a preexisting MHL or following incomplete excision of MHL.

Answer 107

Aneuploidy in some, as well as balanced translocation involving a common breakpoint on the long arm of chromosome 19 (band 19q13.4) with alternative partners on chromosomes 11 and 15.

Answer 108

Fibroblast growth factor receptor 3, encoded by the FGFR3 gene on chromosome 4p16.3. 75% of cases are caused by sporadic new mutations.

Answer 109

Most common form of skeletal dysplasia: achondroplasia (1 per 10-30,000 live births). Most common lethal form of skeletal dysplasia: thanatophoric dysplasia (1 per 35-50,000 births).

Answer 110

Lipoblastomas are characterized by rearrangements of 8q11-13 involving the PLAG1 gene.

Answer 111

The most common genotype of complete moles is 46,XX; a small number are 46,XY. Triploid and tetraploid complete moles are much less common. Triploid conceptions which have duplication of paternal chromosomes are partial moles, typically with a 69,XXX or 69,XXY genotype. Triploid conception resulting from a duplication of maternal chromosomal material (also 69,XXX or 69,XXY genotype) represent non-molar triploidy and lack the trophoblastic proliferation which is the hallmark of a molar pregnancy.

Answer 112

Triploid conceptions which have duplication of paternal chromosomes are partial moles, typically with a 69,XXX or 69,XXY genotype. Triploid conception resulting from a duplication of maternal chromosomal material (also 69,XXX or 69,XXY genotype) represent non-molar triploidy and lack the trophoblastic proliferation which is the hallmark of a molar pregnancy.

Answer 113

IHC cannot distinguish HA (biparental diploidy) from PHM (diandric triploidy). Short tandem repeat genotyping, which determines the parental source of polymorphic alleles, is useful.

Answer 114

Both. It is seen in association with normal pregnancy or Beckwith-Wiedemann syndrome.

Answer 115

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 116

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 117

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 118

Astrocytomas (40-60%, with low grade fibrillary astrocytomas (WHO grade II) being more common than pilocytic astrocytomas (WHO grade I)). Ependymomas (20-30%). Gangliogliomas (15-27%).

Answer 119

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 120

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 121

AKA fibrinoid leukodystrophy, is a rare leukodystrophy with 3 clinical phenotypes: infantile (63%), juvenile (24%), and adult (13%). The majority of infantile and juvenile types are caused by a heterozygous (dominant) gain of function mutation in the gene encoding GFAP, located on chromosome 17q21.

Answer 122

The disease is characterized by dysmyelination and widespread accumulation of Rosenthal fibers in a subpial, subependymal, and perivascular distribution. Early in the disease process, Rosenthal fibers are noted in astrocyte cell bodies, but later accumulate in the astrocyte processes and end-feet in the subpial and perivascular locations. These findings are accompanied by gliosis and myelin disintegration, but no macrophages, as in multiple sclerosis or subacute infarcts. The areas of Rosenthal fiber accumulation do not correlate necessarily with areas of dysmyelination.

Answer 123

Rosenthal fibers are eosinophilic intracellular rod, beaded, or corkscrew-shaped inclusions. Measurements range from 0.5-25 μm in width and 30 μm in length, to 10–40 μm in width and 100 μm in length. By EM, the fibers correspond to intracellular non-membrane bound protein deposits associated with groups of intermediate filaments including GFAP, associated with chaperone proteins. They have been described in reactive tissue (such as the highly gliotic tissue surrounding cysts and vascular malformations), in neoplasms (such as juvenile pilocytic astrocytomas), and in Alexander disease.

Answer 124

Alexander disease has 3 clinical phenotypes: infantile (63%), juvenile (24%), and adult (13%). The majority of infantile and juvenile types are caused by a heterozygous (dominant) gain of function mutation in the gene encoding GFAP, located on chromosome 17q21. These mutations are typically sporadic and de novo. In Alexander disease, a heterozygous missense mutation in the GFAP gene appears to interfere with polymerization of the protein, and results in abnormal protein folding with overexpression and accumulation of the abnormal GFAP protein within Rosenthal fibers.

Answer 125

Alexander disease AKA fibrinoid leukodystrophy.

Answer 126

AGS is a multisystem disorder with AD inheritance and variable penetrance and expressivity. The traditional diagnostic criteria have consisted of paucity of the interlobular bile ducts in association with 3 of 5 major findings, including chronic cholestasis, cardiac disease (most frequently peripheral pulmonary artery stenosis), skeletal manifestations (short stature, butterfly vertebrae), ocular abnormalities (most commonly posterior embryotoxon, a circular opacity of the posterior peripheral cornea), and characteristic facial features (triangular face with a prominent forehead, deep-set eyes, a pointed chin, and a straight nose with a bulbous tip). Mutations are in the JAGGED1 (JAG1) gene.

Answer 127

Mutations are in the JAGGED1 (JAG1) gene, which encodes a cell surface protein that functions as a ligand in the Notch signaling pathway regulating cell proliferation and differentiation. The precise mechanisms by which JAG1 mutations cause AGS is still incompletely understood. JAG1 mutations have been identified in >90% of clinically diagnosed probands; additionally, NOTCH2 mutations have been detected in the small minority of AGS patients lacking JAG1 mutations.

Answer 128

Hepatic complications do contribute significantly to the morbidity of AGS but it is the cardiovascular sequelae that are most directly responsible for the early mortality. Specifically, intracardiac anomalies, which affect ~25% of AGS patients (most commonly tetralogy of Fallot).

Answer 129

Turcot syndrome/APC gene mutations: medulloblastoma, rarely ependymoma. Tuberous sclerosis: subependymal giant cell astrocytoma. Von Hippel Lindau disease: hemangioblastoma. Li-Fraumeni syndrome (with germline TP53 mutations): medulloblastoma, astrocytic tumors, meningioma, schwannoma, choroid plexus tumors, and central PNET. NF type 1: optic glioma, astrocytoma, glioblastoma multiforme. NF type 2: multiple meningiomas, bilateral vestibular schwannomas, spinal ependymomas. Gorlin syndrome: desmoplastic/nodular variant of medulloblastoma.

Answer 130

Uncommon fibrocollagenous lesion classically arising in cervicodorsal region. However, it is not restricted to the nuchal region so the term nuchal-type fibroma can be used. Some cases are linked to FAP/Gardner syndrome. The sporadic lesions are often nuchal, seen in 3rd-5th decades, and have striking male predominance. The Gardner-associated cases mostly involve trunk, head and neck, and extremities, are seen in infants to adolescents, and have no gender predominance.

Answer 131

Rare fibroblastic/myofibroblastic neoplasm consisting of a benign proliferation of fibroblasts and myofibroblasts containing scattered eosinophilic inclusion bodies that occur on the digits of children.

Answer 132

Increased fibrofatty tissue infiltrating and surrounding nerves. Seen predominantly in children. Affects palmar surface of hand, wrist, or forearm, with median nerve and branches most commonly affected. Histologic appearance: Adipose tissue and fibrous tissue infiltrating around and between nerve branches and along perineurium. Epineurial and perineurial fibrous thickening. Perineurium can become hyperplastic (concentric layers, "onion bulb" intraneural hyperplasia). Nerve bundles become separated, atrophic in longstanding cases. DDx: Lipoma of nerve (circumscribed and confined within nerve). Neurofibroma (proliferation of neural elements with no fatty component). Neuroma (increased number of nerve bundles with no fatty component). Lipomatosis (usually affects skin and subcutis and spares nerves).

Answer 133

Peutz-Jeghers syndrome is an autosomal dominant condition caused by inactivating mutations in the serine-threonine protein kinase 11 (STK11) gene, also called LKB1, on chromosome 19p13.3. Mutations in STK11 are found in ~70% of familial cases and ~30-70% of sporadic cases.

Answer 134

In Peutz-Jeghers syndrome, hamartomatous intestinal polyps can be present throughout the GI tract, but the most common site is small intestine (jejunum > ileum > duodenum). Median age for development of polyps is 11-13 yo. The lifetime risk of small intestinal polyps in PJS is 90%, and the risk of intussusception in PJS is 50%. Colon polyps occur in 53%, stomach polyps in 49%, and rectal polyps in 32%.

Answer 135

PJS is diagnosed clinically by the presence of 2 or more of the following three criteria: 2 or more PJS-type hamartomatous polyps. Mucocutaneous pigmentation. Familial history of PJS.

Answer 136

Peutz-Jeghers syndrome patients are at increased risk of cancer (85-93% of patients by age 70), including GI cancer (50x relative risk), pancreatic cancer, lung cancer, and breast cancer (20x relative risk, affecting 8% of patients by age 40, and 31% of patients by age 60).

Answer 137

Polyposis syndromes include Peutz-Jeghers syndrome, juvenile polyposis, PTEN hamartoma syndromes (Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome), and familial adenomatous polyposis. Intestinal polyps may also be seen in MEN type 2B, Gorlin syndrome, and NF type 1.

Answer 138

Although most juvenile polyps in children are sporadic, a subset of these patients develop numerous polyps (juvenile polyposis) due gene to mutations in SMAD4 or BMPR1A. In this syndrome, juvenile polyps may develop dysplasia and eventually carcinoma.

Answer 139

>5 juvenile polyps in the colorectum OR multiple JP throughout the GI tract OR one or more JP and a positive family history of JP syndrome.

Answer 140

The PTEN hamartoma syndromes include Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, both resulting from mutations in the tumor suppressor gene phosphatase and tensin homolog (PTEN) on chromosome 10q23.3. These syndromes are associated with increased risk of breast and thyroid carcinomas.

Answer 141

ATRTs are highly malignant (WHO grade IV) CNS neoplasms seen in very young children. INI1 is a ubiquitously expressed protein encoded by the hSNF5/INI1 gene on chromosome 22q11.2. Mutations in this gene are seen in ATRT. Cytogenetic studies often show monosomy or deletion of chromosome 22; however, this is not as specific or sensitive as IHC, since other tumors with complex karyotypes may show loss of 22 in addition to other events, and the INI1 gene may be mutated by a mechanism other than deletion (i.e. point mutations) not detectable by FISH or LOH studies. The presence of an hSNF5/INI1 gene mutation or loss of the INI1 protein expression by IHC is sufficient to confer a diagnosis of ATRT.

Answer 142

Yolk sac tumor.

Answer 143

In addition to colorectal polyps, ~90% of patients with FAP also develop gastric and duodenal polyps. Other systemic manifestations of FAP include osteomas (80%), congenital hypertrophy of the retinal pigment epithelium (70-80%), desmoid-type fibromatosis (15%), and dental abnormalities. Risk of malignancy is increased relative to the general population for hepatoblastoma (847x), duodenal carcinoma (330x), ampullary carcinoma (123x), nasopharyngeal adenofibroma (25x), thyroid carcinoma (7.6x) (specifically, the cribriform morular variant of papillary thyroid carcinoma is strongly associated with APC gene mutations), brain tumors (7x), and pancreatic carcinoma (4x).

Answer 144

Many women of reproductive age are parvovirus B19 seronegative and are thus susceptible to a primary infection during pregnancy. The rate of vertical transmission from mother or fetus is ~33%. The risk of fetal demise is greatest in the early second trimester, when fetal immunity is sluggish. The most commonly recognized clinical manifestation of severe parvovirus B19 induced anemia is non-immune hydrops fetalis. Parvovirus is thought to cause ~10% of non-immune fetal hydrops cases.

Answer 145

All except for Fabry disease.

Answer 146

All except for Gaucher disease type II.

Answer 147

Beta-galactosidase deficiency is seen in GM1 gangliosidosis (mutation in the GLB1 gene). Morquio disease type B (mutation in the GLB1 gene), and galactosialidosis (partial beta-galactosidase deficiency and neuraminidase deficiency due to a defect in the protective protein/cathepsin A, which stabilizes the beta-galactosidase/neuraminidase complex).

Answer 148

An AR lysosomal storage disorder caused by deficiency of the beta-galactosidase enzyme due to mutations in the GLB1 gene on chromosome 3p. The function of the enzyme is to hydrolyze the terminal beta-galactosyl residues from GM1 ganglioside, glycoproteins, and glycosaminoglycans. Without the enzyme function, GM1 gangliosides accumulate in lysosomes of various tissues, particularly the CNS. The 3 clinical phenotypes are: type 1 (infantile), type 2 (late infantile or juvenile), and type 3 (adult or chronic).

Answer 149

~66% of MPNSTs arise from neurofibromas, often of the plexiform type. ~25-75% of MPNSTs arise in the setting of neurofibromatosis type 1.

Answer 150

Epithelioid variant, glandular variant, and malignant triton tumor (MTT)/MPNST with rhabdomyosarcomatous differentiation. The epithelioid variant is rare and not associated with NF1. The glandular variant contains foci of gland-forming epithelium that resembles intestine and may be keratin- and/or CEA-positive, often with intra- or extracellular mucin. Scattered NE cells immunoreactive for chromogranin, somatostatin, and serotonin are also a common finding. ~75% are associated with NF1. The MTT is 3-4x more common than the glandular variant and is often characterized by divergent mesenchymal differentiation with areas of chondrosarcoma, osteosarcoma, or epithelial glands. ~60% are associated with NF1.

Answer 151

Both typically have complex karyotypic abnormalities that are both numerical and structural, but no consistent karyotypic pattern has been identified. On a molecular level, homozygous deletions of the CDKN2A gene, which encodes the p16 cell cycle inhibitory molecule, occurs in the progression of neurofibromas to MPNST, being identified in ~50% of MPNST but not in neurofibromas.

Answer 152

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 153

Congenital FXIII-A deficiency may be a quantitative defect (type I deficiency) or a qualitative defect (type II deficiency). Untreated, severe congenital FXIII-A deficiency causes critical bleeding events in most cases, with intracranial hemorrhage being the major cause of death. Typically, delayed-type umbilical stump bleeding represents the first classic clinical sign of congenital FXIII-A deficiency. Muscle and subcutaneous soft tissues are also preferred sites of severe bleeding complications. The FXIII-A deficiency is frequently associated with impaired wound healing and leads to abortion. Severe FXIII-B deficiency has been rarely reported.

Answer 154

Bilirubin levels normally peak at 23-25 weeks' gestation in unaffected fetuses.

Answer 155

It predicts the severity of hemolytic disease of the newborn based on amniotic fluid bilirubin levels. On semilog paper, absorbances are plotted against wavelength. A straight line is drawn from the point at 350 nm to the point at 550 nm. This line reflects the theoretical plot if there were no pigments in the fluid. The difference between the line and the actual absorbance at 450 nm is the delta OD450, which reflects the bilirubin concentration. The delta OD450 is plotted against the EGA on a Liley chart, and results fall into zones I, II, or III.

Answer 156

A result in Zone I indicates mild or no disease. Fetuses in zone I are usually followed with amniocentesis every 3 weeks. A result in zone II indicates intermediate disease. Fetuses in low Zone II are usually followed by amniocentesis every 1-2 weeks. A result above the middle of Zone II may require transfusion or delivery. Patients with results in zone I or low zone II can be allowed to proceed to term, at which point labor should be induced. In most cases, patients in the middle of zone II can progress to 36-38 weeks of gestation. If results are in zone III or rising in zone II, deliver immediately for EGA >36 wks, and consider intrauterine transfusion otherwise.

Answer 157

Triple screen - 70%, Quad test - 80%. Integrated screen - 85%. Integrated screen combined with US nuchal fold thickness - >90%.

Answer 158

Triple screen: hCG, AFP, unconjugated estriol. Quad test: the components of the triple screen plus dimeric inhibin A. Integrated screen: PAPP-A and hCG are measured in the 1st trimester; AFP, unconjugated estriol, and dimeric inhibin A are measured in the 2nd trimester; then the data are combined.

Answer 159

The improved performance of the Quad test comes mainly from amelioration of the effects of inaccurate gestational age which plague the triple screen.

Answer 160

All 3 components (uE, hCG, AFP) are decreased.

Answer 161

hCG increased, AFP and uE decreased. Also, dimeric inhibin A is increased.

Answer 162

AFP increased, uE decreased, hCG normal. With increased AFP, if an US confirms gestational age and excludes overt anatomic abnormalities, multiple gestations, or fetal demise, then amniocentesis is performed to obtain amniotic fluid for AFP and AChE.

Answer 163

2-3% of maternal serum AFPs are elevated on prenatal screening; of these, 10% are due to an actual NTD. The sensitivity of MSAFP screening is 90% - the sensitivity is worse for multiple gestations (30%).

Answer 164

MSAFP rises progressively during the 1st and 2nd trimesters. Adjustments to the MSAFP interpretation are made for maternal weight, race, number of fetuses, and maternal diabetes. Increased maternal weight can have a dilutional effect on the AFP, providing a falsely low value. Levels are much higher in multiple gestations, and much lower in maternal diabetes.

Answer 165

>2.0 MOM is considered abnormal in maternal diabetes, and >4.5 MOM is considered abnormal in twin gestations.

Answer 166

NTDs. Omphalocele and gastroschisis. Renal anomalies. Sacrococcygeal teratoma. Cystic hygroma. Hydrops fetalis. Turner syndrome. Bowel obstruction. Twins. Wrong gestational age. Fetal demise. Fetal-maternal hemorrhage.

Answer 167

Maternal serum hCG is ~2x higher than normal in Down syndrome.

Answer 168

Trisomy 18 (Edward syndrome). Smith-Lemli-Optiz syndrome. Inherited (fetal) deficiencies of steroid sulfatase.

Answer 169

Dimeric inhibin A is a glycoprotein produced by the placenta. In a Down syndrome fetus, DIA is increased to an average of 1.9 MOM.

Answer 170

Fetal fibronectin is a protein found normally at the placental fetomaternal interface. Cervicovaginal fluid contains fetal fibronectin briefly during early gestation, after which time it is absent until just before labor. The absence of fetal fibronectin has very high NPV and can exclude impending preterm birth. A positive result suggests the onset of preterm labor, but the overall PPV is low.

Answer 171

Mature type II pneumocytes produce a mixture of phospholipids composed predominantly of lecithin. The vast majority of lecithin is disaturated phosphatidylcholine (DSPC). Lesser amounts of phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and sphingomyelin also comprise lecithin.

Answer 172

It is an issue for gestation between 34 to 37 weeks. Prior to 34 weeks, fetal lung maturity is unlikely, and the risk of RDS is very high. After 37 weeks the risk of RDS is exceedingly low, and fetal lung maturity testing is generally not indicated, except in the presence of poorly controlled maternal diabetes.

Answer 173

Lecithin/sphingomyelin ratio. Phosphatidylglycerol concentration. Foam stability. Lamellar body number density. Disaturated phosphatidylcholine concentration. Fluorescence polarization assay.

Answer 174

Lecithin increases with gestational age, while sphingomyelin remains at a relatively constant 2% of total surfactant phospholipid. Until 26 wks, the ratio is 1:1. After that, the L:S ratio increases until 2:1 is reached around 35 wks. This ratio is generally taken to indicate fetal lung maturity. Above 2:1, 2% of premature infants will develop RDS. Below 2:1, nearly 60% will.

Answer 175

In DM, a ratio of 2:1 does not ensure FLM. The phosphatidylglycerol concentration is more reliable in this senario. The presence of meconium falsely decreases the L:S ratio. The presence of blood normalizes the L:S ratio to ~1.5. The CV of the L:S ratio is high.

Answer 176

Phosphatidylglycerol concentration.

Answer 177

PG is first detected around 36 wks and its presence is indicative of FLM. Neither blood nor meconium interfere with PG determinations, making it the test of choice when the only available specimen is a contaminated one. PG can be measured by TLC or agglutination.

Answer 178

When pulmonary surfactant is present in amniotic fluid in sufficient concentration, the fluid is able to form a highly stable film that can support the structure of a foam. The amniotic fluid is serially diluted with ethanol, and the highest concentration of ethanol at which a complete ring of bubbles is seen is the foam stability index (FSI). An FSI greater than 0.47 is considered indicative of fetal lung maturity.

Answer 179

Surfactant lamellar bodies are about the size of platelets, and the platelet channel of a cell counter can be used to quantify them. An LBND greater than 50,000/mL is predictive of maturity.

Answer 180

An alternative to the L/S ratio is to determine the DSPC concentration, the major component of lecithin, directly. Since it doesn't rely on a ratio with sphingomyelin, it is unaffected by meconium and blood contamination.

Answer 181

This is now the most commonly used method; it is rapid and at least as predictive of FLM as the L/S, with considerably lower CV. A fluorescence polarization value less than 260 is considered mature. Values greater than 290 are considered immature. If these is less than 0.5% blood, results are unaffected. Greater amounts tend to lower high values and raise low values. Even in the presence of blood, values less than 230 are considered mature.

Answer 182

Antibodies to SS-A and SS-B (Ro and La) are thought to mediate this complication.

Answer 183

Normal adults score in the range of 40-120. Low LAP scores are seen in PNH, some MDSs, congenital hypophosphatasia, CML (LAP score is 0-15), and neonatal septicemia (LAP paradoxically decreased). Elevated levels (>180) are seen in leukemoid reactions, non-CML MPDs, glucocorticoid administration and 3rd trimester of pregnancy.

Answer 184

Lead absorption is inversely proportional to chronologic age. In general, approximately 30-50% of lead ingested by children is absorbed, compared with approximately 10% of that ingested by adults. The elimination half-life of lead in adult human blood has been estimated to be 1 month, whereas in children it may be as high as 10 months.

Answer 185

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 186

The CDC recommendation, made in 1978 and still upheld today, is that a blood lead level greater than or equal to 10 ug/dL should be considered elevated.

Answer 187

Their advantage is they can be performed on capillary blood samples and they easily detect moderate to severe lead toxicity. One further advantage is that blood lead levels tend to misleadingly "rebound" during treatment, so that the FEP and ZPP can be used to distinguish this phenomenon from a true increase in lead toxicity.

Answer 188

Atomic absorption spectrophotometry is the preferred method for screening for lead toxicity. It is capable of detecting lead levels below the 10 ug/dL threshold. A venous sample is necessary for this determination, as capillary blood obtained from heel- or finger-sticks can give erroneous results. Furthermore, a repeat for confirmation of any abnormal screening test is advised.

Answer 189

CaNa-EDTA test is designed to assess the degree to which lead will be mobilized by chelation therapy. An IV dose of CaNa-EDTA is given, followed by an 8-hour urine collection, and the amount of lead excreted in the urine is determined. This test is sometimes administered prior to initiation of chelation therapy.

Answer 190

At low levels (10-20 ug/dL), environmental interventions may be all that is indicated. Beyond that, both environmental intervention and chelation are indicated. A level >70 ug/dL is considered an indication for inpatient monitoring and treatment. Chelators include dimercaprol (also known as British antilewisite or BAL), CaNa-EDTA, D-penicillamine, and succimer.

Answer 191

The CDAs include types I, II, III, and IV, and are a rare group of disorders that result in anemia caused by ineffective erythropoiesis and multinuclear erythroblasts. These disorders have pathognomonic cytopathologic findings consisting of nuclear abnormalities in bone marrow erythroid precursors. Type II is also called HEMPAS and is the only one out of the 4 types to have a positive acidified serum test and increased i antigen (the others have normal levels of i antigen). It is also the most common subtype.

Answer 192

HEMPAS (Hereditary Erythroblastic Multinuclearity with Positive Acidified Serum test).

Answer 193

The mean age at presentation is 5 yrs (range 1 mo to 25 yrs), but the mean age at time of correct diagnosis is 16 yrs (range 4 mos to 65 yrs).

Answer 194

Congenital sideroblastic anemia: X-linked sideroblastic anemia. Mitochondrial transporter SLC25A38 defects. Glutaredoxin 5 (GLRX5) deficiency. Erythropoietic protoporphyria. Congenital sideroblastic anemia without identified molecular defects. Sideroblastic anemia as a component of genetic syndromes (X-linked sideroblastic anemia with ataxia. Myopathy, lactic acidosis, and sideroblastic anemia. Sideroblastic anemia, B cell immunodeficiency, periodic fevers, and developmental delay. Pearson marrow-pancreas syndrome. Thiamine-responsive megaloblastic anemia syndrome). Acquired reversible/metabolic sideroblastic anemia: Alcohol. Drugs (Isoniazid. Chloramphenicol. Linezolid.). Copper deficiency/Zinc toxicity (excess zinc ingestion leads to copper deficiency). Hypothermia.

Answer 195

X-linked sideroblastic anemia (XLSA). One-third of patients are women, who express the disorder because of highly skewed inactivation of their X chromosomes in hematopoietic tissue, favoring expression of the mutant allele. Numerous distinct mutations in the ALAS2 (the erythroid-specific form of 5-aminolevulinate synthase) gene have been identified. This type of sideroblastic anemia may be responsive to high doses of pyridoxine (B6).

Answer 196

One-third of patients are women, who express the disorder because of highly skewed inactivation of their X chromosomes in hematopoietic tissue, favoring expression of the mutant allele.

Answer 197

Diamond-Blackfan anemia. Aase syndrome has been described as another congenital pure red cell aplasia, but is not thought to probably be a variant of DBA rather than a distinct clinical entity.

Answer 198

Progressive normochromic, usually macrocytic anemia in infancy or early childhood. Reticulocytopenia. Normal cellularity of the bone marrow with markedly decreased or absent erythroid precursors. WBC count is generally normal; platelet counts are generally normal but can be increased or decreased. Congenital malformations (50 percent of patients). Increased risk of malignancies.

Answer 199

In Blackfan-Diamond anemia, i antigen ifs often over-expressed on red cells, and the HbF is increased, whereas in TEC, both are normal.

Answer 200

Fanconi anemia. Dyskeratosis congenita. Shwachman-Diamond syndrome. Amegakaryocytic thrombocytopenia. Other inherited causes include reticular dysgenesis and Down syndrome.

Answer 201

SCN due to ELANE (neutrophil elastase gene) mutations have autosomal dominant inheritance and occurs in 60 percent of patients. SCN due to HAX1 (HCLS1-associated X1) mutations have autosomal recessive inheritance. SCN due to WASP (Wiskott-Aldrich Syndrome Protein) gene mutations have X-linked inheritance.

Answer 202

It is an autosomal recessive or X-linked chromosomal breakage syndrome that occurs in all races and ethnic groups.

Answer 203

Characteristic congenital malformations are present in up to 60-70% of children affected with Fanconi anemia, including short stature, hypopigmentation and cafe-au-lait spots, hypoplastic thumbs, microcephaly or hydrocephaly, renal abnormalities such as horseshoe kidney, and developmental delay.

Answer 204

Cytopenia develops at a median age of 7 (often mild to moderate thrombocytopenia, but mild leukopenia may also may seen as an initial presentation; anemia, when detected, is typically mild on presentation). 70% of patients have bone marrow failure by age 10.

Answer 205

Patients with FA are at high risk for developing malignancy, particularly MDS, AML (predominant type is with monocytic differentiation - M4 or M5), squamous cell carcinoma of the head and neck or vulva, as well as HCC and gastric carcinoma.

Answer 206

The diagnosis is made by the presence of increased chromosomal breakage in lymphocytes cultured in the presence of DNA cross-linking agents such as mitomycin C (MMC) or diepoxybutane (DEB).

Answer 207

S-beta-thalasssemia, S-C, S-D, C Harlem.

Answer 208

HbA - 0%. HbA2 - 1-4%. HbF - 1-20%. HbS - >80%.

Answer 209

HbF, present at birth, has an inhibitory effect on HbS polymerization; thus, the manifestations of sickle cell disease are not apparent until HbS levels increase beyond 50%, which is usually about 6 months of age.

Answer 210

Major early fetal Hb: Hb Gower1. Minor early fetal Hb: Hb Gower2. Major late fetal Hb: HbF. Major adult Hb: HbA. Minor adult Hb: HbA2.

Answer 211

HbA: alpha2-beta2. HbA2: alpha2-delta2. HbF: alpha2-gamma2. Hb Gower1: zeta2-episilon2. Hb Gower2: alpha2-epsilon2.

Answer 212

HbA: alpha2-beta2. HbA2: alpha2-delta2. HbF: alpha2-gamma2. Hb Gower1: zeta2-episilon2. Hb Gower2: alpha2-epsilon2.

Answer 213

Acute episodes of anemia: Aplastic crisis (Parvovirus B19 accounts for nearly 70% of aplastic crises in children). Splenic sequestration (these episodes often occur during a viral illness). Hyperhemolytic crisis (this complication has been associated in many patients with concomitant G6PD deficiency). Slowly progressive worsening of anemia: Progressive renal insufficiency (with decreasing erythropoietin) or supervening iron/folate/B12 deficiency.

Answer 214

Acute pain crisis is thought to be due to a vasoocclusive event within bone. Acute chest syndrome is thought to be related to either vasoocclusive events or bacterial PNA.

Answer 215

S. pneumoniae infections, including pneumococcal sepsis, pneumonia, meningitis, and arthritis, are the most common overall. Other common infections include Salmonella, Haemophilus (HITB), and M. pneumoniae.

Answer 216

Neurologic complications are frequent in sickle cell disease, manifesting as TIA, cerebral infarcts, cerebral hemorrhage, cord infarction, sensorineural hearing loss, and meningitis. About 1 in 3 patients will have an angiographic appearance of moyamoya disease (segmental arterial stenoses with "puff of smoke" collaterals).

Answer 217

Acute sickle hepatic crisis presents with acute RUQ pain, jaundice, elevated LFTs (but not to the level seen in viral hepatitis). The pathogenesis is likely related to ischemia caused by sinusoidal obstruction, and histology may show sickle cell thrombi within sinusoidal spaces with engorgement by RBCs. Patients with SCD may acutely sequester large numbers of RBCs in the spleen, the pulmonary vasculature, and less commonly the liver. Patients with hepatic sequestration usually present with RUQ pain, rapidly increasing hepatomegaly, and a falling Hgb/Hct. The pathophysiology is believed to be obstruction of sinusoidal flow by the masses of sickled RBCs, with trapping of RBCs within the liver.

Answer 218

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

Answer 219

Sickle cell-beta thalassemia is divided into S-beta0 thalassemia and S-beta+ thalassemia, based upon the complete absence of beta globin or the presence of reduced amounts of beta globin, respectively, which in turn determines the level of HbA. The percentage of HbA produced in individuals with beta+ thalassemia varies from 5 to 30 percent, depending upon the molecular defect of the mutation. Compound heterozygous beta0 thalassemia, results in the production of no normal beta chains and therefore no HbA.

Answer 220

Most beta thalassemia mutations among African-Americans result in beta+ thalassemia.

Answer 221

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

Answer 222

HbA - 50-55%. HbA2 - 1-3%. HbF - <1%. HbS - 35-45%.

Answer 223

First disease (Measles, Hard measles, 14-day measles, Rubeola, Morbilli) - Measles virus. Second disease (Scarlet fever, Scarlatina) - Streptococcus pyogenes. Third disease (Rubella, German measles, 3-day measles) - Rubella virus. Fourth disease (Staphylococcal scalded skin syndrome, Ritter's disease, Filatow-Dukes' disease) - Staphylococcus aureus. Fifth disease (Erythema infectiosum, slapped cheek disease) - Parvovirus (Erythrovirus) B19. Sixth disease (Roseola infantum, Exanthem subitum, 3-day fever, rose rash of infants, "sudden rash") - HHV6B or HHV7.

Answer 224

SS: HbA - 0%. HbA2 - 1-4%. HbF - 1-20%. HbS - >80%. SA: HbA - 50-55%. HbA2 - 1-3%. HbF - <1%. HbS - 35-45%.

Answer 225

The hemoglobin electrophoresis in SA shows HbA - 50-55%. HbA2 - 1-3%. HbF -

Answer 226

As with all individuals with HbS, the 2 tests are positive.

Answer 227

HHV6 is the etiologic agent of roseola infantum (sixth disease, exanthem subitum, 3-day fever, rose rash of infants, "sudden rash"). Fully-developed roseola manifests in 10% of those with acute HHV6 infection, with the remaining children displaying a nonspecific febrile illness. HHV6 is highly neurotropic and is one of the causes of viral encephalitis. Due to its combined propensity to produce fever and CNS infection, HHV6 is responsible for a significant proportion of childhood febrile seizures.

Answer 228

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 229

Conditions that result from chronic exposure to mercury. Other names for acrodynia are hydrargyria, mercurialism, erythredema, erythredema polyneuropathy, Pink's disease, Bilderbeck's disease, Selter's disease, Swift's disease, Swift-Feer disease, and Feer syndrome. Another name for erethism is erethism mercurialis.

Answer 230

Acrodynia results from chronic exposure to mercury and occurs most often in infants and young children. Symptoms include irritability, photophobia, polyneuritis, autonomic manifestations (sweating, hemodynamic instability), and a desquamative erythematous rash on the palms and soles. It is associated with increased urinary catecholamines and can in many ways mimic pheochromocytoma. The presentation may also be similar to Kawasaki disease.

Answer 231

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 232

Clinical manifestations include paresthesias around the mouth, peripheral neuropathy, tremor, malaise, constriction of the visual field, deafness, and ataxia. The fetus is particularly vulnerable (organic mercury crosses the placenta readily), even if the pregnant mother shows no signs of toxicity.

Answer 233

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 234

AKA dilantin embryopathy or fetal dilantin syndrome. A congenital syndrome resulting from in utero phenytoin exposure. It occurs in <10% of exposed fetuses. It is characterized by IUGR, microcephaly, mental retardation, nail and distal phalanx hypoplasia, midfacial hypoplasia, hypertelorism, flattened philtrum, and shortened nose.

Answer 235

AChE testing is performed on all amniotic fluids having elevated AFP concentrations. The odds of having a fetus with a NTD are considerably greater if both the AFP is elevated and the AChE is positive.

Answer 236

Juvenile-onset form (presents at 2-4 years of age), in which HPV is thought to be acquired during passage through the birth canal and is more aggressive. Adult form (presents at 20-40 years of age), thought to be sexually transmitted, in which papillomas are fewer.

Answer 237

The papillomas arise most often on the true vocal cords. Malignant transformation is rare, but the lesions can be life-threatening because of airway obstruction, particularly in children. An HPV subtype is sometimes requested as HPV 11 is associated with more aggressive disease than HPV 6.

Answer 238

HBV chronicity develops in 5% of healthy adults, 10% of immunocompromised adults, and 90% of neonates who have become infected transplacentally.

Answer 239

Unlike the more common flu strains, H5N1 affects predominantly children and young adults, with a median age of 15 yrs. Lymphopenia is characteristic, without significant changes in the neutrophil, RBC, or platelet counts. The virus has tropism for non-ciliated epithelial cells of the lower respiratory tract, leading to an ARDS/DAD-like clinicopathologic picture and may explain the low rate of human-to-human transmission.

Answer 240

Parainfluenza viruses 1 and 2 cause the most cases of croup in children between the ages of 2 and 6. RSV is the most common cause of respiratory bronchiolitis ("viral pneumonia") in infants under age 2.

Answer 241

Classic measles infection in immunocompetent patients. Modified measles (an attenuated infection in patients with preexisting, but incompletely protective, anti-measles antibody). Atypical measles (in patients immunized with the killed virus vaccine and subsequently exposed to wild-type measles virus; is rare since the killed virus vaccine was used in the US from 1963-67). Neurologic syndromes following measles infection, including acute disseminated encephalomyelitis (ADEM) and subacute sclerosing panencephalitis (SSPE). Severe measles. Complications of measles including secondary infection, giant cell pneumonia, and measles inclusion body encephalitis.

Answer 242

Mumps infection is frequently accompanied by a nonspecific prodrome consisting of low-grade fever, malaise, HA, myalgias, and anorexia. These symptoms are generally followed within 48 hrs by the development of parotitis, a classic feature of mumps infection seen in 95% of symptomatic cases. The parotitis is due to direct infection of ductal epithelium and local inflammation. Symptomatic infection in adults is usually more severe than in children.

Answer 243

RSV causes 90% of respiratory bronchiolitis in infants and almost 50% of lower respiratory tract infections in children. Immunity to RSV is short-lived, and recurrence throughout childhood is the rule, although infections are progressively less severe with bronchiolitis uncommon after 12 mos.

Answer 244

First trimester infections have the most serious fetal implications. Defects in neonates infected in the first trimester include hearing impairment (60%), heart defects (45%) (PDA in 20% and peripheral pulmonic stenosis in 12%), microcephaly (27%), cataracts (25%), low birth weight (<2500 g) (23%), hepatosplenomegaly (19%).

Answer 245

PVL refers to injury of cerebral white matter that occurs in a characteristic distribution and consists of periventricular focal necrosis, with subsequent cystic formation, and more diffuse cerebral white matter injury. It can be caused by ischemia or infection. It is the major form of brain white matter injury that affects premature infants, and is associated with the subsequent development of cerebral palsy, intellectual impairment, and visual disturbances.

Answer 246

Pathogenesis is twofold: Germinal matrix fragility from the lack of structural support of rete of immature blood vessels due to immaturity. Disturbances of cerebral blood flow, particularly ischemia-reperfusion, increased arterial flow, or increased venous pressure.

Answer 247

In preterm infants, the site of origin of bleeding is generally the subependymal germinal matrix, which is located between the caudate nucleus and the thalamus at the level of the foramen of Monro ("subventricular zones at the angles of the lateral ventricles at the coronal level of the head of the caudate nucleus"). In term infants, the locations may be more variable.

Answer 248

Recurrent bacterial sinopulmonary infections due to staphylococci, streptococci, and hemophilus. Also, recalcitrant intestinal infection with G. lamblia. Opportunistic fungal and viral infections are not a particular problem.

Answer 249

Absence of plasma cells in lamina propria of intestinal mucosa. Lymph nodes lack germinal centers, and plasma cells are absent. Tonsils are rudimentary. Serum IgG levels are markedly reduced as are circulating mature B cells. Pre-B cells are found in lymph nodes and bone marrow where they do not mature normally into B cells.

Answer 250

Polio, hepatitis, and enteroviruses.

Answer 251

A gene on the X chromosome encoding a tyrosine kinase called Atk (agammaglobulinemia tyrosine kinase) or Btk (Bruton's tyrosine kinase).

Answer 252

CVID is a group of approximately 150 primary immunodeficiencies characterized by hypogammaglobulinemia (low IgG, IgA, and IgM) but which have different underlying causes. In CVID, the B cells are normal in numbers but they lack the capacity to differentiate into plasma cells, so the pts do not make an effective amount of Ig. The clinical severity and age of onset are somewhat variable; the typical onset is around the 2nd or 3rd decade.

Answer 253

Germinal centers are hyperplastic; the typical small bowel morphology includes pronounced reactive follicular lymphoid hyperplasia in the face of a distinctly low number of plasma cells.

Answer 254

Most pts suffer from recurrent upper and lower respiratory tract infections (S. pneumonia, H. influenza, and Mycoplasma), intestinal bacterial overgrowth, and intestinal G. lamblia infection. The development of bronchiectasis is extremely common.

Answer 255

They have high levels of specific IgE anti-staphylococcal antibody, exquisite susceptibility to staphylococcal infection, eosinophilia and eczema. These appear to result from a defect in granulocyte chemotaxis.

Answer 256

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 257

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 258

Rh negative mother with her newborn testing anti-D negative by the immediate spin D testing. Do the weak D testing (incubation period at 37 C for 15-30 min, and includes antiglobulin reagent) to make sure the baby isn't actually a weak D instead of a true D negative.

Answer 259

These look like CML but don't have the Philadelphia chromosome. JMML, aCML, and CMML.

Answer 260

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 261

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 262

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 263

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 264

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 265

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

Answer 266

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.