Reproductive Pathology: Breast, Obstetrics, Pediatrics

D. Gross, microscopic, and radiologic presentation of the mass is consistent with fibroadenoma. Large and coarse calcifications should not be misleading the diagnosis. Grown of fibroadenoma accelerates with pregnancy.

34-year-old female presents with a painless breast mass incidentally discovered a few days ago. Physical examination reveals a 1.5 cm well-circumscribed, rubbery in consistency mass in the outer upper quadrant of the right breast. Mammograpic image of the mass is attached. Core-needle biopsy shows neoplastic epithelial ductal structures embedded within a fibromyxoid stroma. With of the following is the most likely effect of pregnancy on this breast lesion? A) Progressiontoinvasiveductularcarcinoma B) Progression to invasive ductular carcinoma C) Metastasis to the axillary lymph nodes D) Rapid growth E) Development of secondary changes: necrosis and calcifications

F Spontaneous abortion (miscarriage) may occur in at least a third of pregnancies, and most occur in the first trimester. Fetal problems are the most likely cause for early losses, whereas maternal problems account for most late fetal losses. Half of early abortuses have a chromosomal abnormality, many of which are incompatible with prolonged survival, such as trisomy 16. If there is recurrent early pregnancy loss, a parental germline chromosomal anomaly may be suspected. Infections, uterine anomalies, masses such as leiomyomas, and toxemia are more likely to cause fetal loss later in pregnancy. Polycystic ovarian syndrome is more likely to be a cause for infertility. Maternal smoking is most likely to affect fetal weight, and less likely to cause early fetal loss.

A 17-year-old girl missed a menstrual period, and her pregnancy test is positive. A month later, she notes suprapubic pain and passing blood clots from her vagina. She passes a small amount of tissue 3 days later. Pathologic examination of this tissue shows products of conception. Which of the following is the most likely cause for her pregnancy loss? A Bifid uterus B Group B streptococcus infection C Polycystic ovarian syndrome D Preeclampsia E Smoking cigarettes F Fetal trisomy 16

E Necrotizing enterocolitis is a complication of prematurity that is related to various factors, including intestinal ischemia, enterocyte apoptosis induced by platelet-activating factor, bacterial overgrowth, and formula feeding. If severe, the wall of the intestine becomes necrotic and perforates, necessitating surgical intervention. Duodenal atresia is an uncommon congenital anomaly most often associated with trisomy 21; it leads to upper gastrointestinal obstruction and vomiting. Hirschsprung disease is a congenital condition resulting from an aganglionic segment of distal colon; it leads to obstruction with distention, but not bloody diarrhea. A Meckel diverticulum is a common anomaly and is seen in about 2% of individuals. Typically, it is an incidental finding, although later in life it may be associated with gastrointestinal tract bleeding if ectopic gastric mucosa is present within the diverticulum. Meconium ileus is seen in the setting of cystic fibrosis and can lead to obstruction, but the infant typically does not pass stool. Pyloric stenosis manifests at 3 to 6 weeks of life with projectile vomiting.

A 17-year-old primigravida gives birth at 34 weeks' gestation to a male infant of low birth weight. The infant is given exogenous surfactant and does not develop respiratory distress. On the third day of life, physical examination reveals hypotension, abdominal distention, and absent bowel sounds, and there is bloody stool in the diaper. A radiograph shows pneumatosis intestinalis and abdominal free air. Surgical removal of the bowel is performed. Which of the following conditions is most likely to be present in this infant? A Duodenal atresia B Hirschsprung disease C Meckel diverticulum D Meconium ileus E Necrotizing enterocolitis F Pyloric stenosis

E Though a specific genetic abnormality, such as a chromosomal abnormality or single gene defect, may be sought, unknown causes still account for 40% to 60% of birth defects. This is particularly true with more common birth defects, such as those listed in this case, and when they do not fit with a recognized pattern of defects suggesting a specific syndrome. Environmental factors related to birth defects include infections, maternal disease such as diabetes mellitus (not gestational diabetes), and teratogens, accounting for up to 10% of birth defects. Multifactorial causes from the influence of multiple gene predispositions is the second most likely cause for birth defects, at 20% to 25%.

A 17-year-old primigravida gives birth at 37 weeks' gestation. Her Hgb A1C is 6%. The birth weight is 2350 g. On physical examination, the infant has multiple congenital abnormalities including single umbilical artery, cleft lip, and spina bifida occulta. Which of the following is the most likely risk factor for these findings? A Infection B Gestational diabetes C Single gene defect D Teratogen E Unknown

F Preterm premature rupture of membranes accounts for 30% to 40% of preterm deliveries, and infection is often the cause, with ascending infection often resulting in chorioamnionitis and funisitis. This organism is found in the genital tract of sexually active adults. Intrauterine infection results in release of collagenases and elastases that promote rupture of membranes and release of prostaglandins that induce smooth muscle contraction and labor. Cystic fibrosis and inborn errors of metabolism are usually not manifest until after birth. Rh incompatibility is unlikely in a primigravida, unless she received a prior incompatible blood transfusion, and results in fetal hydrops. Sudden infant death syndrome occurs in infants 1 month to 1 year of age, and there are no associated pathologic abnormalities. Maternal hypertension and convulsions should be present for a diagnosis of toxemia. Trisomy 16 can be seen with first-trimester losses, and is not associated with inflammation.

A 17-year-old primigravida has an uneventful pregnancy until 25 weeks, when she notes absence of fetal movement for a day. On examination, her temperature is 37° C, pulse is 80/min, and blood pressure is 115/80 mm Hg. No fetal heart tones are present. An ultrasound examination shows no apparent fetal anomalies. The next day she develops premature rupture of fetal membranes, and the next day a stillborn fetus is delivered. Examination of the placenta shows normal size for gestational age, but microscopic analysis shows that neutrophils have infiltrated the chorion and amnion. What is the most likely diagnosis? A Cystic fibrosis B Rh incompatibility C Sudden infant death syndrome D Toxemia of pregnancy E Trisomy 16 F Ureaplasma urealyticum infection

D The erythroid precursors exhibit large, pink, intranuclear inclusions typical of parvovirus infection. In adults, such an infection typically causes fifth disease, which is self-limiting. This is one of the "O" infections in the TORCH mnemonic, however, describing congenital infections (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus or HIV infection). Parvovirus infection in the fetus can lead to a profound fetal anemia with cardiac failure and hydrops fetalis. Results of the Coombs test are negative, because no antierythrocyte antibodies are involved. Congenital tumors are an uncommon cause of hydrops, and they would produce a mass lesion, which was not described in this case. Cystic fibrosis does not affect erythropoiesis. Although various chromosomal anomalies—monosomy X, in particular—may lead to hydrops, malformations are typical. Erythroblastosis fetalis from maternal IgG antibodies directed at fetal RBCs is unlikely to occur in a first pregnancy, and only erythroid expansion would be present, not erythroid inclusions.

A 19-year-old primigravida who has had an uncomplicated pregnancy undergoes a screening ultrasound at 16 weeks' gestation that shows no abnormalities. At 18 weeks, the woman develops a mild rash on her face. She gives birth to a stillborn, severely hydropic male infant at 33 weeks. At autopsy, there are no congenital malformations, but cardiomegaly is present. From the histologic appearance of the bone marrow shown in the figure, which of the following is the most likely cause of these findings? A Chromosomal anomaly of the fetus B Congenital neuroblastoma C Inheritance of two abnormal CFTR genes D Infection with parvovirus B19 E Maternal IgG crossing the placenta

B. A. Fibrocystic disease of the breast: lumps are bilateral, fluctuate in size with menstrual cycle; are not discrete, are not mobile and usually painful. B. Intraductal papilloma: usually found in the ages 35-55 years; made of glands and fibrous tissue c vessels, therefore not discrete; takes a long time to develop. C. Lobular carcinoma: rapidly invasive to lymph nodes and other parts; usually there is change of texture of the skin over the lump; the lump is thickened and web-like. D. Ductal carcinoma: begins in the milk ducts, then spreads through other tissue to the skin.

A 19-year-old woman went to her doctor because she noticed a painless mass in her left breast 2 weeks ago, during her monthly breast self-examination. She told her doctor that her mother died of metastatic breast cancer at the age of 40 years. Examination showed bilateral large dense breasts, a 2-cm, discrete, firm, mobile mass palpable in the upper outer quadrant of the left breast. There were no changes in the skin or nipple. The axillary lymph nodes were not palpable. Which of the following is the most likely diagnosis? A. Fibrocystic breast changes B. Fibroadenoma C. Intraductal papilloma D. Lobular carcinoma E. Ductal carcinoma

D The neonate most likely has hyaline membrane disease from fetal lung immaturity and lack of surfactant. Surfactant produced by type II pneumocytes consists predominantly of phospholipids-like lecithin contained in lamellar bodies released into alveoli. The adequacy of surfactant production can be gauged by the phospholipid content of amniotic fluid because fetal lung secretions are discharged into the amniotic fluid. Chromosomal analysis may help to predict problems after birth or the possibility of fetal loss. The Coombs test may help to determine the presence of erythroblastosis fetalis. Cystic fibrosis does not cause respiratory problems at birth. The maternal serum α-fetoprotein level is useful to predict fetal neural tube defects and chromosomal abnormalities.

A 19-year-old woman, G2, P1, has a screening fetal ultrasound at 20 weeks' gestation that shows no abnormalities. Premature labor leads to an emergent vaginal delivery at 31 weeks. Soon after birth, the neonate develops respiratory distress requiring intubation with positive pressure ventilation. Which of the following prenatal diagnostic tests could have best predicted this neonate's respiratory distress? A Chromosomal analysis with karyotyping B Coombs test on cord blood C Genetic analysis for cystic fibrosis gene D Phospholipid level in amniotic fluid E Maternal serum α-fetoprotein determination

C This infant has erythroblastosis fetalis, which results when prior sensitization to a fetal blood cell antigen leads to alloantibodies in maternal blood that can cross the placenta. The Rh blood group system is most often implicated. The maternal antibody coats fetal RBCs, causing hemolysis. The Coombs test is positive. The fetal anemia leads to congestive heart failure and hydrops. Hemolysis results in a very high bilirubin level. A high maternal serum level of α-fetoprotein suggests a fetal neural tube defect; such defects are not associated with hydrops. Viral hepatitis is not a perinatal infection. Diminished glucocerebrosidase activity causes Gaucher disease, and this condition does not lead to perinatal liver failure or anemia. Listeriosis or other congenital infections may produce fetal hydrops and anemia, although not of the severity described in this case.

A 20-year-old woman, G3, P2, has a screening ultrasound at 18 weeks' gestation that shows hydrops fetalis but no malformations. The woman's two previous pregnancies ended at term in live births. The current pregnancy results in a live birth at 36 weeks. Physical examination shows marked hydrops of the neonate and placenta. Laboratory studies show a cord blood hemoglobin level of 9.2 g/dL and total bilirubin concentration of 20.2 mg/dL. Which of the following laboratory findings is most likely to be present in this case? A Diminished glucocerebrosidase activity in fetal cells B Elevated maternal serum α-fetoprotein level C Positive Coombs test result on cord blood D Positive maternal hepatitis B surface antigen E Positive placental culture for Listeria monocytogenes

D The figure shows a hydatidiform mole, or complete mole, with enlarged, grapelike villi that form the tumor mass in the endometrial cavity. These trophoblastic tumors secrete large amounts of human chorionic gonadotropin (hCG). Molar pregnancies result from abnormal fertilization, with only paternal chromosomes present. Neural tube defects can be distinguished from other fetal defects (e.g., abdominal wall defects) by use of the acetylcholinesterase test on amniotic fluid obtained by amniocentesis. If acetylcholinesterase and maternal serum α-fetoprotein are elevated, a neural tube defect is likely. If the acetylcholinesterase is not detectable, another fetal defect is suggested. α-Fetoprotein is a marker for some germ cell tumors that contain yolk sac elements. Estrogens can be elaborated by various ovarian stromal tumors, including thecomas and granulosa cell tumors. More ominously, a decrease in maternal serum estriol suggests incipient abortion. Human placental lactogen is produced in small quantities in the developing placenta, and serum levels typically are not measured.

A 21-year-old G2, P1 woman is in the early second trimester. She has noted a small amount of vaginal bleeding for the past week and has had marked nausea and vomiting for 3 weeks. On physical examination, the uterus measures large for dates. An ultrasound examination shows intrauterine contents with a "snowstorm appearance," and no fetus is identified. The gross appearance of tissue obtained by dilation and curettage is shown in the figure. Which of the following substances is most likely to be greatly increased in her serum? A Acetylcholinesterase B α-Fetoprotein C Estradiol D Human chorionic gonadotropin E Human placental lactogen

D This is accessory breast tissue with lactational change. Prolactin secretion from the adenohypophysis increases in postpartum women to support milk production in breast lobules. Oxytocin released from the posterior pituitary stimulates myoepithelial cells to contract during nursing. The remaining hormones listed do not have a direct effect upon breast tissue. The presence of the breast tissue in the axilla represents accessory breast tissue, and can explain the origins of breast cancer in women following simple mastectomy.

A 21-year-old woman delivered a normal term infant a week ago and is now nursing the infant. She now notes a lump in her right axilla that has increased in size over the past week. On physical examination there is a rubbery, mobile, 1.5-cm mass beneath the skin at the right anterior axillary line. The mass is excised and the microscopic appearance is shown in the figure. Which of the following hormones most likely produced the greatest effect upon this tissue? A Cortisol B Growth hormone C Oxytocin D Prolactin E Testosterone

B Conditions predisposing to ectopic pregnancy include chronic salpingitis (which may be caused by gonorrhea, but a culture would be positive only with acute infection), intrauterine tumors, and endometriosis. In about half of cases, there is no identifiable cause. Gestational trophoblastic disease associated with a triploid karyotype with partial mole developing outside the uterus is rare. Candida produces cervicitis and vaginitis and is rarely invasive or extensive in immunocompetent patients. Syphilis is not likely to produce a tubal mass with acute symptoms (a gumma is a rare finding).

A 22-year-old woman experiences sudden onset of severe lower abdominal pain. Physical examination shows no masses, but there is severe tenderness in the right lower quadrant. A pelvic examination shows no lesions of the cervix or vagina. Bowel sounds are detected. An abdominal ultrasound scan shows a 4-cm focal enlargement of the proximal right fallopian tube. A dilation and curettage procedure shows only decidua from the endometrial cavity. Which of the following laboratory findings is most likely to be reported for this patient? A Cervical culture positive for Neisseria gonorrhoeae B Detection of human chorionic gonadotropin in serum C 69,XXY karyotype on decidual tissue cells D Pap smear showing pseudohyphae of Candida E Positive result of serologic testing for syphilis

B Nonimmune hydrops fetalis may be due to cardiac failure in utero, with cardiac defects leading to high-output congestive heart failure. Cardiac defects may occur in association with other anomalies and may be part of chromosomal aneuploidies (chromosomes 13, 18, 21, and XO). A mass lesion with increased blood flow, such as a hemangioma, could lead to hydrops, but a neuroblastoma is unlikely to have markedly increased flow, or lead to a paraneoplastic effect with anemia. Cerebral lesions such as leukomalacia may be related to hydrops when due to a congenital infection such as cytomegalovirus or toxoplasmosis ("C" and "T," respectively, in the TORCH mnemonic), but the TORCH titer results were negative in this case. A low-lying placenta may lead to uteroplacental insufficiency with intrauterine growth retardation, and predispose to placenta previa at the time of birth. Splenomegaly is more likely to accompany immune hydrops, with marked extramedullary hematopoiesis.

A 23-year-old woman has reduced fetal movement at 19 weeks' gestation. Fetal ultrasound scan is performed and shows marked soft tissue fluid collections. The maternal Coombs test is negative. TORCH titers are unremarkable. Which of the following additional findings is most likely to be observed with this ultrasound examination? A Congenital neuroblastoma B Endocardial cushion defect C Leukomalacia D Low-lying placenta E Splenomegaly

E Choriocarcinomas are aggressive, malignant trophoblastic tumors. Some of these tumors can arise without evidence of pregnancy. Metastases in the vaginal wall and lungs and a hemorrhagic appearance are characteristic. The large pleomorphic and hyperchromatic syncytiotrophoblastic cells produce human chorionic gonadotropin. Treatment with agents such as etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine can often lead to remission and cure. Amnionic cells do not give rise to neoplasms. Rhabdomyoblasts are present in embryonal rhabdomyosarcomas of the vagina of young girls. Serous epithelium does not give rise to gestational trophoblastic disease. Smooth muscle cells give rise to leiomyomas, and rarely leiomyosarcomas, typically arising in the uterus.

A 23-year-old woman suddenly notices a bloody, brownish vaginal discharge. The next day she has shortness of breath. On physical examination, a 3-cm, red-brown mass is seen on the lateral wall of the vagina. A chest radiograph shows numerous 2- to 5-cm nodules in both lungs. Laboratory studies show that her serum human chorionic gonadotropin levels are markedly elevated. A biopsy specimen of the vaginal mass is obtained and shown in the figure. Chromosome analysis of these cells shows a 46,XX karyotype. Which the following cells is most likely present in this mass lesion? A Amnionic B Rhabdomyoblast C Serous epithelial D Smooth muscle E Syncytiotrophoblast

E Partial hydatidiform mole develops from triploidy (69 chromosomes). In contrast to a complete mole with only 360paternal chromosomes, in which no fetus is present, a partial mole has a fetus because maternal chromosomes are present. Survival of the triploid fetus to term is rare. A partial mole may contain some grapelike villi, or none. The fetus is usually malformed, often with 3,4 syndactyly. A 46,XX karyotype could be present in a complete mole or a normal female fetus. A fetus with Turner syndrome (monosomy X) has a 45,X karyotype. Most female fetuses with loss of an X chromosome undergo spontaneous abortion, but some survive. Klinefelter syndrome has a 47,XXY karyotype, and male infants are live-born, with no placental problems. A 47,XY,+18 karyotype of trisomy 18 is associated with multiple congenital malformations, but not with a partial mole.

A 23-year-old woman, G3, P2, has a spontaneous abortion at 15 weeks' gestation. The male fetus is small for gestational age and is malformed, with syndactyly of the third and fourth digits of each hand. The placenta also is small, and shows 0.5-cm grapelike villi scattered among morphologically normal villi. Chromosomal analysis of placental tissue is most likely to show which of the following karyotypes? A 45,X B 46,XX C 47,XXY D 47,XY,+18 E 69,XXY

D Staphylococcal acute mastitis typically produces localized abscesses, whereas streptococcal infections tend to spread throughout the breast, because streptococci often produce streptolysins. Acute mastitis can be associated with the first few months of breastfeeding. Candida may cause some local skin irritation, but is likely to become invasive only in immunosuppressed patients. Lactobacillus acidophilus is the organism used to produce fermented nonhuman milk. Listeriosis can be spread by contaminated food, including milk products, not by human milk.

A 24-year-old woman is breastfeeding 3 weeks after giving birth to a normal term infant. She notices fissures in the skin around her left nipple. Over the next 3 days, a 5-cm region near the nipple becomes erythematous and tender. Purulent exudate from a small abscess drains through a fissure. Which of the following organisms is most likely to be cultured from the exudate? A Candida albicans B Lactobacillus acidophilus C Listeria monocytogenes D Staphylococcus aureus E Viridans streptococci

A Her age would suggest the lesion is probably benign, and even fibroadenomas and fibrocystic changes can have calcifications. The fibrous component of a fibroadenoma or fibrocystic changes can make it difficult to aspirate cells from them. However, the family history and the mammographic appearance of small clustered calcifications are concerning for carcinoma. A delay in diagnosis and treatment of breast cancer decreases survival. Although BRCA1 mutations are associated with HER2 and ER- and PR-negative breast cancers, the lesion must still be diagnosed. Based upon the histologic findings and molecular markers, a treatment plan can then be instituted that may include additional studies and pharmacologic therapies.

A 24-year-old woman notes a lump in her right breast for the past month. She is concerned because her sister was diagnosed with a poorly differentiated "triple negative" breast cancer at age 31. Ultrasonography of the breast shows a solid mass. Fine needle aspiration is attempted but no diagnostic cells are obtained. Mammography is performed and there is a single 1-cm density with small clustered calcifications in the right breast but no lesions of the opposite breast. Which of the following is the best course of action for this patient? A Biopsy to obtain tissue from the lesion B Continued monthly breast self-examination C Genetic testing for BRCA1 mutations D Hormonal therapy with tamoxifen E Radiologic imaging to detect metastases

A The biopsy specimen shows an invasive breast cancer. Given the young age of the patient and the strong family history of breast cancer, it is reasonable to assume that she has inherited an altered gene that predisposes to breast cancer. There are two known breast cancer susceptibility genes: BRCA1 and BRCA2. Both are cancer suppressor genes. Specific mutations of BRCA1 are common in some ethnic groups, such as Ashkenazi Jews. Estrogen receptors are expressed in 50% to 75% of breast cancers. Their presence bodes well for therapy with hormone receptor antagonists. There is no known relationship between the structure of the estrogen receptor gene and susceptibility to breast cancer. Likewise, presence of progesterone receptors in the cancer cells indicates potential response to hormonal therapy, not risk for breast cancer. HER2/neu is a growth factor receptor gene that is amplified in certain breast cancers and is a marker of poor prognosis, not susceptibility. There is alteration of TP53 in many cancers, typically acquired and not familial, including breast carcinomas, but it does not have predictive value for risk. Inheritance of RB1 mutations increases the risk for retinoblastoma and osteosarcomas, but not breast carcinomas.

A 25-year-old Jewish woman sees her physician after finding a lump in her right breast. On physical examination, a 2-cm, firm, nonmovable mass is palpated in the upper outer quadrant. No overlying skin lesions and no axillary lymphadenopathy are present. The figure shows an excisional biopsy specimen. The family history indicates that the patient's mother, maternal aunt, and maternal grandmother have had similar lesions. Her 18-year-old sister has asked a physician to determine whether she is genetically at risk of developing a similar disease. A mutated gene encoding for which of the following is most likely to be found in her sister? A BRCA1 B Estrogen receptor (ER) C HER2/neu D TP53 E Progesterone receptor (PR) F RB1

F Maternal diabetes can result in hyperplasia of the fetal islets because of the maternal hyperglycemic environment. This can occur if gestational diabetes is present, or if the mother has had diabetes mellitus before pregnancy. After birth, the hyperplastic islets continue to overfunction, resulting in neonatal hypoglycemia. Infants of diabetic mothers also tend to exhibit macrosomia because of the growth-promoting effects of increased insulin levels. The other listed findings are more characteristic of pancreatic disorders in adults. Neutrophilic infiltration with necrosis and hemorrhage are characteristic of acute pancreatitis. A mass with irregular glands and abnormal nuclear features could be an adenocarcinoma. Amyloid deposition in islets may be seen in some cases of type 2 diabetes mellitus. Extensive fibrosis and fatty replacement of the pancreas is seen in patients with cystic fibrosis surviving for decades. Infiltration of T cells into islets occurs with the insulitis that presages overt clinical type 1 diabetes mellitus.

A 25-year-old primigravida has an uncomplicated prenatal course. She gives birth to a 4500-g boy whose Apgar scores are 8 and 10 at 1 minute and 5 minutes. Shortly after birth, he develops irritability with seizure activity. On examination, the infant is normally developed with no anomalies. The lungs are clear to auscultation. Laboratory studies show serum Na+, 145 mmol/L; K+, 4.2 mmol/L; Cl-, 99 mmol/L; CO2, 25 mmol/L; urea nitrogen, 0.4 mg/dL; and glucose, 18 mg/dL. Which of the following pathologic findings is most likely to be present in the pancreas of this infant? A Acute pancreatitis B Amyloid deposition C Adenocarcinoma D Fatty replacement E Insulitis F Islet hyperplasia

B The immaturity of the fetal lungs before 35 to 36 weeks' gestation can be complicated by lack of sufficient surfactant to enable adequate ventilation after birth. This can result in hyaline membrane disease, shown in the figure. Tests on amniotic fluid before birth, including lecithin-sphingomyelin ratio, fluorescence polarization, and lamellar body counts, are useful in predicting the degree of pulmonary immaturity. Fetal anemia leads to heart failure and pulmonary congestion. Maternal toxemia and congenital infections such as toxoplasmosis may lead to hyaline membrane disease if the birth occurs prematurely as a consequence of these conditions, but they do not directly affect lung maturity. Oligohydramnios may result in neonatal respiratory distress through the mechanism of pulmonary hypoplasia.

A 25-year-old woman gives birth at 28 weeks' gestation. The newborn girl has initial Apgar scores of 5 and 6 at 1 and 5 minutes, but within 1 hour, she experiences severe respiratory distress and appears cyanotic. A chest radiograph shows a bilateral ground-glass appearance in the lungs. She is treated with assisted ventilation and nutritional support and seems to improve for 24 hours, but then becomes progressively more cyanotic, develops seizures, and dies 4 days after birth. At autopsy, the newborn's lungs have the microscopic appearance shown in the figure. Which of the following conditions initiates the development of these findings? A Congenital toxoplasmosis B Immaturity of lungs C Marked fetal anemia D Maternal toxemia of pregnancy E Oligohydramnios

C The acute inflammation suggests a bacterial infection, and group B streptococcus, which can colonize the vagina, is a common cause for congenital infection at term. The infection can develop quickly. Cytomegalovirus, syphilis, and toxoplasmosis are congenital infections that can cause stillbirth, but they are more likely to be chronic and develop earlier in gestation. Herpetic infections are most likely to be acquired by passage through the birth canal.

A 25-year-old woman, G3, P2, is in her 39th week of pregnancy. She has felt no fetal movement for 1 day. The infant is stillborn on vaginal delivery the next day. On physical examination, there are no external anomalies. Microscopic examination of the placenta shows acute chorioamnionitis. Which of the following infectious agents is most likely responsible for these events? A Cytomegalovirus B Herpes simplex virus type 2 C Streptococcus agalactiae (group B) D Toxoplasma gondii E Treponema pallidum

B Patients with the BRCA1 gene mutation have a high incidence of carcinomas with medullary features that are poorly differentiated and triple negative (do not express the HER2/neu protein, and are negative for estrogen and progesterone receptors).

A 26-year-old woman has felt a breast lump for the past month and is worried because she has a family history of early onset and bilateral breast cancers. On physical examination, there is a firm, 2-cm mass in the upper outer quadrant of her left breast. A biopsy is done, and the specimen microscopically shows carcinoma. Genetic analysis shows that she is a carrier of the BRCA1 gene mutation, as are her mother and sister. Which of the following histologic types of breast carcinoma has the highest incidence in families such as hers? A Lobular carcinoma B Medullary carcinoma C Metaplastic carcinoma D Papillary carcinoma E Tubular carcinoma

B Grossly and radiographically, this patient has a discrete mass that in a woman her age is most likely a fibroadenoma. Fat necrosis and infiltrating cancers are masses with irregular outlines. Fibrocystic changes are generally irregular lesions, not discrete masses. Mastitis has a more diffuse involvement, without mass effect. Phyllodes tumors are typically much larger and are far less common.

A 26-year-old woman has noticed a lump in her right breast for the past year. A 2-cm, firm, circumscribed, movable mass is palpated in the lower outer quadrant. The figure shows the excised mass (A) and the mammogram (B). What is the most likely diagnosis? A Fat necrosis B Fibroadenoma C Fibrocystic changes D Infiltrating ductal carcinoma E Mastitis F Phyllodes tumor

B Nonproliferative (fibrocystic) changes account for the largest category of breast lumps. These lesions are probably related to cyclic breast changes that occur during the menstrual cycle. In about 30% of cases of breast lumps, no specific pathologic diagnosis can be made. Fibrocystic changes include ductal proliferation, ductal dilation (sometimes with apocrine metaplasia), and fibrosis. A fibroadenoma is a discrete mass formed by a proliferation of fibrous stroma with compressed ductules. Carcinomas have proliferations of atypical neoplastic cells that fill ducts and can invade stroma. Inspissated duct secretions may produce duct ectasia with a surrounding lymphoplasmacytic infiltrate. Trauma with subsequent fat necrosis may produce a localized, firm lesion that mimics carcinoma, but microscopically shows macrophages and neutrophils surrounding necrotic adipocytes, and healing leaves a fibrous scar.

A 27-year-old woman feels a lump in her right breast. She has normal menstrual cycles, she is G3, P3, and her last child was born 5 years ago. On examination a 2-cm, irregular, firm area is palpated beneath the lateral edge of the areola. This lumpy area is not painful and is movable. There are no lesions of the overlying skin and no axillary lymphadenopathy. A biopsy specimen shows microscopic evidence of an increased number of dilated ducts surrounded by fibrous connective tissue. Fluid-filled ducts with apocrine metaplasia also are present. What is the most likely diagnosis? A Fibroadenoma B Fibrocystic changes C Infiltrating ductal carcinoma D Mammary duct ectasia E Traumatic fat necrosis

A Fibroadenomas are common and may enlarge during pregnancy or late in each menstrual cycle. Most intraductal 370papillomas are smaller than 1 cm and are not influenced by hormonal changes. Lobular carcinoma in situ is typically an ill-defined lesion without a mass effect. Medullary carcinomas tend to be large; they account for only about 1% of all breast carcinomas. Phyllodes tumors are uncommon and tend to be larger than 4 cm.

A 27-year-old woman in the third trimester of her third pregnancy discovers a lump in her left breast. On physical examination, a 2-cm, discrete, freely movable mass beneath the nipple is palpable. After the birth of a term infant, the mass appears to decrease in size. The infant is breastfed without difficulty. What is the most likely diagnosis? A Fibroadenoma B Intraductal papilloma C Lobular carcinoma in situ D Medullary carcinoma E Phyllodes tumor

B Fat necrosis is typically caused by trauma to the breast. The damaged, necrotic fat is phagocytosed by macrophages, which become lipid laden. The lesion resolves as a collagenous scar within weeks to months. The firm scar can mammographically and grossly resemble a carcinoma. An abscess may form a palpable but painful mass lesion, and often from Staphylococcus aureus infection when localized. A fibroadenoma is a neoplasm, and tumors are not induced by trauma. Inflammatory carcinoma refers to dermal lymphatic invasion by an underlying breast carcinoma, giving a rough red-to-orange appearance to the skin. Sclerosing adenosis is a feature of fibrocystic changes, a common cause of nontraumatic breast lumps.

A 30-year-old woman sustained a traumatic blow to her right breast. Initially, there was a 3-cm contusion beneath the skin that resolved within 3 weeks, but she then felt a firm, painless lump that persisted below the site of the bruise 1 month later. What is the most likely diagnosis for this lump? A Abscess B Fat necrosis C Fibroadenoma D Inflammatory carcinoma E Sclerosing adenosis

B The flattened face and deformed feet of this infant suggest oligohydramnios resulting from renal agenesis. Fetal kidneys produce urine that becomes the amniotic fluid. The lack of this fluid constricts the developing fetus and restricts pulmonary growth. Pulmonary hypoplasia is the rate-limiting step to survival. Congenital rubella can lead to various malformations, but not deformations. Infants born to diabetic mothers have an increased risk of congenital anomalies without a specific pattern. Fetal lung maturity is typically achieved at 34 to 35 weeks' gestation, and hyaline membrane disease is unlikely at 36 weeks. Trisomy 13 is accompanied by various malformations, including malformations affecting the kidneys. The external features are quite different from those seen in this case, however, and affected infants almost always have microcephaly and midline defects, such as cleft lip and palate.

A 31-year-old woman, G1, P0, has noticed very little fetal movement during her pregnancy. At 36 weeks' gestation, she gives birth to an infant with the facial features and positioning of extremities shown in the figure. Soon after birth, the infant develops severe respiratory distress. Which of the following conditions affecting the infant best explains these findings? A Congenital rubella infection B Bilateral renal agenesis C Maternal diabetes mellitus D Hyaline membrane disease E Trisomy 13

B This is a classic example of an embryonic disruption that leads to the appearance of congenital abnormalities. Fibrous bands and possible vascular insults may explain such findings, which fall within the spectrum of a limb-body wall complex that includes amniotic band syndrome. Various malformations may occur as a result of congenital infections, but amniotic bands are not among them. Oligohydramnios with diminished amniotic fluid leads to deformations, not disruptions. Rh incompatibility can give rise to erythroblastosis fetalis, which may manifest as hydrops fetalis. Fetuses affected by hydrops have widespread edema and intense jaundice. In trisomy 18 and other chromosomal abnormalities, an omphalocele centered on the umbilicus is the most common abdominal wall defect.

A 31-year-old woman, G3, P2, has had an uneventful pregnancy except for lack of any fetal movement. She has a spontaneous abortion at 20 weeks' gestation and delivers a stillborn boy. On examination at birth, the fetus has an abdominal wall defect lateral to the umbilical cord insertion; a short umbilical cord; marked vertebral scoliosis; and a thin, fibrous band constricting the right upper extremity. A radiograph is shown in the figure. None of the woman's other pregnancies, which ended in term births, were similarly affected. Which of the following is the most likely cause of these findings? A Congenital cytomegalovirus infection B Early amnion disruption C Oligohydramnios D Maternal fetal Rh incompatibility E Trisomy 18

A. Placental infections are most likely to ascend from the vagina, and they are not usually hematogenous. Preterm premature rupture of membranes may predispose to ascending infection, or it may be caused by prostaglandins released from acute inflammatory cells in the infection as suggested by the purulent exudate. Premature labor with delivery is likely to occur over the next 24 hours. Of the TORCH infections, the one most likely in this case is the O, including bacteria, such as group B streptococcus, whereas Listeria monocytogenes may produce more chronic inflammation.

A 36-year-old woman has had an uneventful pregnancy for the past 37 weeks. Over the past 12 hours, she has developed lower abdominal pain. On examination, there is suprapubic tenderness. Her temperature is 37.4° C. Pelvic examination reveals a purulent cervical discharge. The infant is delivered 12 hours later. Which of the following organisms is most likely responsible for her premature labor? A Group B streptococcus B Herpes simplex virus C Rubella virus D Toxoplasma gondii E Treponema pallidum

A The only increased IgM titer, indicating recent infection, is that for Toxoplasma. The fetal central nervous system findings are consistent with congenital toxoplasmosis. Her increased IgG titers for CMV and HSV type 1 suggest past infection. Her positive rubella titer is consistent with past immunization. Congenital HIV does not have significant effects on the fetus in utero. The likely route for her recent Toxoplasma infection is ingestion of poorly cooked, contaminated meat containing cysts of Toxoplasma gondii. The other routes of infection listed are not characteristic for toxoplasmosis.

A 31-year-old woman, G3, P2, is in the second trimester. Her prior pregnancies ended with delivery of normal term infants who are still living. She has an ultrasound examination because of lack of fetal movement by 18 weeks, and it shows microcephaly with periventricular leukomalacia and calcifications. Her HIV test is positive; her serologic test for syphilis is negative. TORCH titers are performed on maternal blood: Which of the following is the most likely risk factor for this fetal infection? A Ingestion of contaminated meat B Inhalation of droplet nuclei C Injection drug use D Mosquito bite E Previous blood transfusion F Sexual intercourse

D Listeriosis can be a congenital infection. Although pregnant women may have only a mild diarrheal illness, the organism can prove devastating to the fetus or neonate. Mini-epidemics of listeriosis are often linked to a contaminated food source, such as dairy products, chicken, or hot dogs. Neonatal meningitis can be caused by Listeria monocytogenes. Cytomegalovirus and toxoplasmosis are most likely to produce severe central nervous system damage. Group B streptococcal infections most often infect the fetus near term or peripartum. These organisms release a factor that inhibits the neutrophilic chemotactic factor complement C5a, inhibiting a suppurative response. Herpetic congenital infections typically are acquired via passage through the birth canal. Parvovirus infection may cause a severe fetal anemia.

A 33-year-old woman in the 32nd week of pregnancy notices lack of fetal movement for 3 days. On physical examination, no fetal heart tones can be auscultated. The fetus is stillborn. At autopsy, scattered microabscesses are seen in the liver, spleen, brain, and placenta. No congenital anomalies are present. Investigation by Centers for Disease Control (CDC) reveals that similar fetal losses have occurred in the same community for the past 3 months and food contamination is suspected. Congenital infection with which of the following organisms is most likely to produce these findings? A Cytomegalovirus B Group B streptococcus C Herpes simplex virus D Listeria monocytogenes E Parvovirus F Toxoplasma gondii

C Intraductal papillomas are usually solitary and smaller than 1 cm. They are located in large lactiferous sinuses or large ducts, and have a tendency to bleed, though they are benign. Abscesses complicating mastitis organize with a fibrous wall. Fibroadenomas contain ducts with stroma and are not highly vascular; these lesions are not located in ducts. Phyllodes tumors also arise from intralobular stroma and can be malignant, but they do not invade ducts to cause bleeding. Sclerosing adenosis, a lesion occurring with fibrocystic changes, has abundant collagen, not vascularity.

A 34-year-old woman has noticed a bloody discharge from the nipple of her left breast for the past 3 days. On physical examination, the skin of the breasts appears normal, and no masses are palpable. There is no axillary lymphadenopathy. She has regular menstrual cycles and is using oral contraceptives. Excisional biopsy is most likely to show which of the following lesions in her left breast? A Acute mastitis B Fibroadenoma C Intraductal papilloma D Phyllodes tumor E Sclerosing adenosis

E Twin-twin transfusion syndrome is the result of a vascular anastomosis between halves of a monochorionic placenta. The donor twin typically is smaller, with reduced organ function, including kidneys, and reduced amount of amniotic fluid. The recipient twin becomes plethoric with hydrops and increased amniotic fluid. The donor may also become hydropic because of high-output heart failure from the increased work of pumping blood into both twins. A chromosomal aneuploidy is likely to affect just one of fraternal twins and could lead to hydrops, but the other twin might not be affected. The other listed options should affect both twins similarly.

A 34-year-old woman, G4, P3, is large for dates at 16 weeks' gestation. Fetal ultrasound examination shows one large plethoric twin with hydrops fetalis as well as polyhydramnios and one small anemic twin with oligohydramnios. The maternal Coombs test is negative. What is the most likely explanation for these findings? A α-Thalassemia major B Chromosomal aneuploidy C Erythroblastosis fetalis D Parvovirus B19 infection E Placental vascular anastomosis

E Classic features of eclampsia are defined by hypertension, edema, and proteinuria, typically with onset in the third trimester. The addition of seizures defines eclampsia. Primigravid women are at greater risk. There is no evidence in this case that primary renal disease could cause her hypertension, and the onset was sudden. Although the precise cause of preeclampsia/eclampsia is unknown, placental ischemia is believed to be the underlying mechanism. This is associated with shallow placentation and incomplete conversion of decidual vessels into high-volume channels required to perfuse the placenta adequately. Untreated patients may go on to disseminated intravascular coagulation. Cushing syndrome with adrenal cortical hyperplasia could lead to hypertension with sodium retention, but she does not have hypokalemia or hyperglycemia. Gestational trophoblastic disease predisposes patients to preeclampsia, but hydatidiform mole is excluded by the presence of a fetus, and a partial mole would be unlikely to persist into the third trimester. Functional ovarian tumors, most commonly estrogen secreting, such as a granulosa cell tumor or thecoma, do not produce hypertension and proteinuria. Gestational diabetes may increase the risk for fetal loss, but in this case the glucose is normal.

A 35-year-old primigravid woman at 30 weeks' gestation develops worsening headaches along with a 3-kg weight gain over 1 week. This morning she had a generalized seizure. On physical examination, she is afebrile, but her blood pressure is 190/115 mm Hg (it was 120/80 mm Hg at a prenatal visit 1 month ago). She has peripheral edema involving her head and all extremities. Fetal heart tones of 140/min and fetal movement are present. Laboratory studies show hemoglobin, 12.5 g/dL; hematocrit, 37.6%; MCV, 92 μm3; platelet count, 199,000/mm3; serum creatinine, 1 mg/dL; potassium, 4.2 mmol/L; and glucose, 101 mg/dL. Urinalysis shows 2+ proteinuria, but no hematuria, RBCs, WBCs, or casts. Which of the following is the most likely underlying factor in the causation of her disease? A Adrenal cortical hyperplasia B Disseminated intravascular coagulation C Gestational trophoblastic disease D Ovarian neoplasm producing estrogen E Placental ischemia F Uncontrolled gestational diabetes

D Toxemia of pregnancy in this case is best classified as preeclampsia, because she has hypertension, proteinuria, and edema, but no seizures. The placenta tends to be small because of reduced maternal blood flow and uteroplacental insufficiency; infarcts and retroplacental hemorrhages can occur. Microscopically, the decidual arterioles may show acute atherosis and fibrinoid necrosis. Chorioamnionitis is most often due to ascending bacterial infections and leads to, or follows, premature rupture of membranes. A chronic villitis is characteristic of a congenital infection such as cytomegalovirus. Placental hydrops often accompanies fetal hydrops in conditions such as infections and fetal anemias. In a partial mole, a fetus is present, but it is malformed and rarely live-born.

A 36-year-old primigravida develops peripheral edema late in the second trimester. On physical examination, her blood pressure is 155/95 mm Hg. Urinalysis shows 2+ proteinuria, but no blood, glucose, or ketones. At 36 weeks, she gives birth to a normal viable but low-birth-weight infant. Her blood pressure returns to normal, and she no longer has proteinuria. Which of the following pathologic findings is most likely to be found on examination of the placenta? A Chorioamnionitis B Chronic villitis C Hydropic villi D Multiple infarcts E Partial mole

B The hyperinsulinism in the fetus of a diabetic mother suppresses pulmonary surfactant production. Corticosteroids stimulate surfactant production in type II pneumocytes. Infection may increase the risk of premature birth, but it does not significantly affect surfactant production. The risk for major malformations, called diabetic embryopathy, is 6% to 10% in infants born to mothers with diabetes mellitus; but there is no set pattern to the anomalies, and similar embryopathies are not seen in gestational diabetes. So the cause for anomalies here is unknown. Macrosomia is the result of growth-promoting effects of insulin in the fetus. Oligohydramnios leads to constriction in utero that culminates in pulmonary hypoplasia, not decreased surfactant. Maternal hypertension may reduce placental function and increase growth retardation, but it typically does not have a significant effect on the production of surfactant.

A 38-year-old primigravida has premature rupture of membranes at 36 weeks' gestation, necessitating delivery. At birth, the infant is noted to have a two-vessel umbilical cord, a cleft lip, a heart murmur, and spina bifida. Which of the following factors is most likely to increase the risk of hyaline membrane disease in the infant? A Chorioamnionitis B Diabetes mellitus, type 1 C Maternal corticosteroid therapy D Oligohydramnios E Pregnancy-induced hypertension

D Medullary carcinomas account for about 1% to 5% of all breast carcinomas. They tend to occur in women at 369younger ages than do most other breast cancers. Despite poor prognostic indicators (such as absence of HER2, ER, and PR), medullary carcinomas have a better prognosis than most other breast cancers. Perhaps the infiltrating lymphocytes are a helpful immune response. Colloid carcinomas occur about as frequently as medullary carcinomas, but they are often positive for ER, and the prognosis is better than average. Infiltrating ductal and infiltrating lobular carcinomas tend not to produce large, localized lesions because they are more invasive, and they lack a distinct lymphoid infiltrate. True papillary carcinomas are quite rare, although other types of breast carcinoma may have a papillary component. The phyllodes tumor is typically large, but it has stromal and glandular components.

A 39-year-old woman has noticed an enlarging mass in her left breast for the past 2 years. The physician palpates a 4-cm firm mass. Following biopsy, a simple mastectomy is performed with axillary lymph node sampling. On gross sectioning, the mass has a soft, tan, fleshy surface. Histologically, the mass is composed of large cells with vesicular nuclei and prominent nucleoli. There is a marked lymphocytic infiltrate within the tumor, and the tumor has a discrete, noninfiltrative border. No axillary node metastases are present. The tumor cells are triple negative, for HER2, estrogen receptor (ER), and progesterone receptor (PR). What is the most likely diagnosis? A Colloid carcinoma B Infiltrating ductal carcinoma C Infiltrating lobular carcinoma D Medullary carcinoma E Papillary carcinoma F Phyllodes tumor

B Fibrocystic changes without epithelial hyperplasia do not suggest a significantly increased risk of breast cancer. Moderate to florid hyperplasia increases the risk twofold, and atypical ductal or lobular hyperplasias increase the risk fivefold. The risk in this patient is not great enough to suggest radical or simple mastectomy at this time, but follow-up is needed. Breast cancers are not associated with tobacco use. The BRCA1 gene accounts for a small percentage of breast cancers, primarily in families in which cancer onset occurs at a young age, and genetic testing of all persons at risk for breast cancer is not warranted. These proliferative changes are not the result of infection.

A 47-year-old woman has a routine health examination. There are no remarkable findings except for a barely palpable mass in the right breast. A mammogram shows an irregular, 1.5-cm area of density with scattered microcalcifications in the upper outer quadrant. A biopsy specimen from this area is obtained and microscopically shows ductal hyperplasia. Which of the following is the most appropriate option for follow-up of this patient? A Cessation of smoking cigarettes B Continued screening for breast cancer C Performing a simple mastectomy D Testing for the BRCA1 oncogene E Prescribing broad-spectrum antibiotic therapy

D Phyllodes tumors, although grossly and microscopically similar to fibroadenomas, occur at an older age, are larger, and are more cellular than fibroadenomas; they can recur locally following excision, but rarely metastasize. The figure shows cellular stroma protruding into spaces lined by a single layer of cuboidal epithelium. In contrast, fibrocystic changes can produce a breast lump, but usually not as large as 6 cm, and without firm areas of cellular stroma. A lobular carcinoma has malignant-appearing epithelial cells in clusters and rows and may not even produce a significant mass effect. Tubular carcinomas of the breast are uncommon, most are less than 1 cm in diameter, and most have small tubular structures in a noncellular stroma.

A 48-year-old woman has felt a poorly defined lump in her right breast for the past year. On examination, she has a nontender, firm, 6-cm mass in the upper inner quadrant of her right breast. There are no lesions of the overlying skin and no axillary lymphadenopathy. A biopsy is performed, and microscopic examination of the specimen shows the findings in the figure. The mass is excised with a wide margin, but recurs 1 year later. After further excision, the lesion does not recur. What is the most likely diagnosis? A Fibroadenoma B Fibrocystic changes C Lobular carcinoma D Phyllodes tumor E Tubular carcinoma

E Paget cells are large cells that have clear, mucinous cytoplasm and infiltrate the skin overlying the breast. They are malignant and extend to the skin from an underlying breast carcinoma, which may be occult, so that Paget disease may be the first sign of malignancy. Apocrine metaplasia affects the cells lining the cystically dilated ducts in fibrocystic change. The macrophages in fat necrosis do not infiltrate the skin and do not have the atypical nuclei seen in the figure. Inflammatory carcinoma does not refer to a specific histologic type of breast cancer; rather, it describes the involvement of dermal lymphatics by infiltrating carcinoma, and there may be thickening and a reddish-orange appearance to the skin. In lobular carcinoma in situ, terminal ducts or acini within the breast are filled with neoplastic cells.

A 48-year-old woman has noticed a red, scaly area of skin on her left breast that has grown slightly larger over the past 4 months. On physical examination, there is a 1-cm area of eczematous skin adjacent to the areola. The figure shows the microscopic appearance of the skin biopsy specimen. What is the most likely diagnosis? A Apocrine metaplasia B Fat necrosis C Inflammatory carcinoma D Lobular carcinoma in situ E Paget disease of the breast

A. Expression of estrogen receptors is a feature of male breast cancer.

A 72-yer-old African man present with a solitary mass in his left breast. Physical examination reveals a 3-cm stone-hard mass with irregular borders. Fine needle aspiration yields malignant glandular cells. Which of the following features will most likely be identified in the aspirated cells by immunohistochemistry technique? A) Expressionofestrogenreceptors B) OverexpressionofHER2 C) Loss of estrogen receptors D) Loss of HER2 E) Lossofe-cadherin

A This irregular, infiltrative mass is an infiltrating (invasive) ductal carcinoma, the most common form of breast cancer. Breast carcinomas are most likely to metastasize to regional lymph nodes. By the time a breast cancer becomes palpable, lymph node metastases are present in more than 50% of patients. A bloody discharge from the nipple most often results from an intraductal papilloma. Pain in the chest wall could be bone metastases, but less likely local invasion, and there is a margin of adipose tissue around the mass in the specimen shown. Breast cancers are associated in rare cases with ectopic corticotropin secretion or Cushing syndrome. Lobular carcinomas are more often bilateral, but they are less common than infiltrating ductal carcinomas.

A 49-year-old woman felt a lump in her left breast 1 week ago. On examination, a firm, irregular mass is palpable in the upper outer quadrant of her left breast. There are no overlying skin lesions. The gross appearance of the excisional biopsy specimen is shown in the figure. Which of the following additional findings is she most likely to have on physical examination? A Axillary lymphadenopathy B Bloody discharge from the nipple C Chest wall tenderness D Cushingoid facies E Mass in the opposite breast

E The most likely cause of death here is sudden infant death syndrome (SIDS). Other causes of death must be excluded by careful examination and interviews with caretakers. By definition, there are no significant gross or microscopic autopsy findings. Infants with congenital anomalies or infections are unlikely to appear healthy, feed well, or gain weight normally. Though the cause for SIDS is unknown, abnormalities of serotonergic neural pathways in the medulla oblongata, and a respiratory tract stressor (sleeping prone) may put vulnerable infants at risk. Abnormalities in medullary centers that regulate responses to noxious stimuli such as hypoxia, hypercarbia, and thermal stress may lead to absence of cardiorespiratory and reflexive responses that normally maintain homeostasis. The other neurotransmitters listed are not implicated. Acetylcholine acts at all preganglionic and postganglionic parasympathetic neurons and at preganglionic sympathetic neurons. Dopaminergic neurons are found in the substantia nigra. GABAergic neurons have an inhibitory function on other neurons in the central nervous system. Noradrenergic neurons originate in the locus ceruleus, and they comprise postganglionic sympathetic neurons as well.

A 5-month-old male infant died suddenly and unexpectedly. Scene investigation reveals the infant was prone with no airway obstruction or evidence of trauma. Gross and microscopic examination at autopsy reveals only petechiae of mesothelial surfaces. Which of the following neurotransmitters that involves signaling within brainstem medullary arousal centers is most likely implicated in the pathogenesis of this infant's death? A Acetylcholine B Dopamine C γ-Aminobutyric acid D Norepinephrine E Serotonin

D The gross appearance of the skin is consistent with invasion of dermal lymphatics by carcinoma—the so-called inflammatory carcinoma, which is not a histologic type of breast cancer, but a descriptive phrase based upon the gross appearance (peau d'orange) resembling an inflammatory process. Nipple retraction and nontender axillary lymphadenopathy also suggest invasive ductal carcinoma. Atypical ductal hyperplasia may increase the risk of carcinoma, but it is not capable of invasion and does not produce visible surface skin changes. Acute mastitis may produce pain and swelling, but it is more likely to occur in association with breastfeeding, and as an inflammatory process would be more likely to produce painful lymphadenopathy. Fat necrosis on palpation can mimic that of carcinoma, but the skin is not involved. Sclerosing adenosis is a feature of benign fibrocystic changes producing breast lumps, but it has no skin involvement.

A 51-year-old woman has noticed an area of swelling with tenderness in her right breast that has worsened over the past 2 months. On physical examination, the 7-cm area of erythematous skin is tender with a rough, firm surface resembling an orange peel. There is swelling of the right breast, nipple retraction, and right axillary nontender lymphadenopathy. Excisional biopsy of skin and breast is most likely to show which of the following lesions? A Acute mastitis B Atypical epithelial hyperplasia C Fat necrosis D Infiltrating ductal carcinoma E Sclerosing adenosis

E The expression of HER2/neu, an epidermal growth factor receptor, suggests that biotherapy with trastuzumab may have some effectiveness. Drug names with the suffix -mab are monoclonal antibodies that target a specific 368biochemical component of cells. This form of biotherapy is useful because normal breast cells do not express HER2/neu. Doxorubicin is a standard chemotherapeutic agent that is part of various multiagent protocols. Hydroxyurea is a cycle-acting agent that is not useful in breast cancer. Letrozole is an aromatase inhibitor that is useful for treating ER-positive breast cancers. Raloxifene is a selective estrogen receptor modulator (SERM) that reduces risk for breast cancer and reduces osteoporosis. Tamoxifen is an antiestrogenic compound that has effectiveness in the treatment of breast cancers positive for ER/PR.

A 54-year-old woman feels a lump in her left breast. On examination there is a firm, irregular mass in the lower outer quadrant. A mammogram shows a 2-cm density with focal microcalcifications. Excisional biopsy shows intraductal and invasive carcinoma. Immunohistochemical staining is negative for estrogen receptor (ER). FISH analysis (green = HER2; red = chromosome 17 centromere) shows the findings in the figure. When combined with doxorubicin, which of the following drugs is most likely to be useful in treating this patient? A Hydroxyurea B Letrozole C Raloxifene D Tamoxifen E Trastuzumab

B Among primary malignancies of the breast, lobular carcinoma in situ (LCIS) is most likely to be bilateral. LCIS may precede invasive lesions by several years. Lobular carcinoma may be mixed with ductal carcinoma, and it may be difficult to distinguish them histologically. The other neoplasms listed are less likely to be bilateral and more likely to produce a single mass effect.

A 54-year-old woman noticed a lump in her right breast. On examination, she has an ill-defined, 1-cm mass in the upper outer quadrant. The mass is cystic on ultrasound. An excision is done, and microscopically the mass shows predominantly fibrocystic changes, but the lesion shown in the figure also is present. Fine-needle aspirates of both breasts reveal additional foci of similar cells. Which of the following breast lesions is most likely to produce these findings? A Infiltrating ductal carcinoma B Lobular carcinoma in situ C Malignant phyllodes tumor D Medullary carcinoma E Mucinous (colloid) carcinoma

E Micronodular cirrhosis is most often a consequence of chronic alcoholism and impairs hepatic estrogen metabolism, which can lead to bilateral gynecomastia. ACTH-secreting pituitary adenomas cause truncal obesity because of Cushing syndrome. Choriocarcinomas of the testis produce human chorionic gonadotropin and may cause some breast enlargement. Choriocarcinomas are highly malignant neoplasms that would not remain indolent for 2 years. Chronic renal failure is unlikely to have this consequence. Diabetes mellitus slightly increases the risk for breast cancer in women. Rheumatoid nodules can appear in various locations along with rheumatoid arthritis, but they rarely occur in the breast and are unlikely to be bilateral.

A 57-year-old man has developed bilateral breast enlargement over the past 2 years. On physical examination, the enlargement is symmetric and is not painful to palpation. There are no masses. He is not obese and is not taking any medications. Which of the following underlying conditions best accounts for his findings? A ACTH-secreting pituitary adenoma B Choriocarcinoma of the testis C Chronic glomerulonephritis D Diabetes mellitus E Micronodular cirrhosis F Rheumatoid arthritis

A In this lobular carcinoma, note the pleomorphic cells infiltrating single file through the stroma. The metastatic profile of this cancer includes the carcinomatous meningitis suggested by her leptomeningeal enhancement, as well as intra-abdominal metastases. E-cadherin is an adhesion molecule that serves as a tumor suppressor, and its loss characterizes another infiltrating carcinoma—signet ring carcinoma of the stomach. Medullary carcinomas are solid masses of cells with little desmoplasia, but prominent lymphoid infiltrates. Metaplastic carcinomas are rare in humans and have a component resembling another tissue, such as squamous carcinomas. In the setting of a malignant breast mass, any brain lesion is a suspected metastatic lesion; although glioblastoma is capable of extracranial metastases, this is rare, and there should be a bulky cerebral mass present. Phyllodes tumors can be malignant, with a stromal component, but these are typically bulky masses, and there is a microscopic leaflike pattern of cystic spaces lined by epithelium.

A 57-year-old woman has felt a lump in her left breast for 4 months. She has had new onset headaches associated with nausea for the past month. Her physician palpates a firm but irregular 2-cm mass in her left breast. CT imaging of her brain shows leptomeningeal enhancement. A lumpectomy with axillary node sampling is performed. Immunohistochemical staining of these cells shows absence of E-cadherin and HER2, but presence of estrogen receptor (ER) and progesterone receptor (PR). An H and E stained section is shown in the figure. No nodal metastases are present. Which of the following is the most likely diagnosis? A Lobular carcinoma B Medullary carcinoma C Metaplastic carcinoma D Metastatic glioblastoma E Phyllodes tumor

A Atypical lobular hyperplasia and atypical ductal hyperplasia increase the risk of breast cancer fivefold; the risk affects both breasts and is higher in premenopausal women or women who have a family history of breast cancer. Smoking and exogenous estrogen therapy are not well-established risk factors for breast cancer. The BRCA1 mutation accounts for about 10% to 20% of familial breast carcinomas and only a few percent of all breast cancers.

A 58-year-old woman sees her naturopathic health care provider for a routine health examination. There are no remarkable findings on physical examination. A screening mammogram shows a 0.5-cm irregular area of increased density with scattered microcalcifications in the upper outer quadrant of the left breast. Excisional biopsy shows atypical lobular hyperplasia. She has been on postmenopausal estrogen-progesterone therapy for the past 10 years. She has smoked 1 pack of cigarettes per day for the past 35 years. Which of the following is the most significant risk factor for the development of lobular carcinoma in patients with such lesions? A Atypical cytologic changes B History of smoking C Hormone replacement therapy D Postmenopausal age E Underlying BRCA1 gene mutation

B An intraductal carcinoma, or ductal carcinoma in situ (DCIS), may not produce a palpable mass. The figure shows ducts that contain large, atypical cells in a cribriform pattern. If grossly soft, white material is extruded from small ducts when pressure is applied, then there is necrosis of the neoplastic cells in the ducts (that leads to dystrophic calcification), and the term comedocarcinoma is applicable. Intraductal carcinomas represent about one fourth of all breast cancers. If not excised, such lesions become invasive. Intraductal carcinoma has several other histologic patterns, including noncomedo DCIS and Paget disease of the nipple, in which extension of the malignant cells to the skin of the nipple and areola produces the appearance of a seborrheic dermatitis. Colloid carcinomas occur about as frequently as medullary carcinomas, but they are often positive for estrogen receptor and progesterone receptor, and the prognosis is better than average. Infiltrating ductal carcinomas tend to produce irregular, firm, mass lesions because they are more invasive. Infiltrating lobular carcinomas can have a diffuse pattern without significant mass effect. Medullary carcinomas tend to be large masses; microscopically, they have nests of large cells with a surrounding lymphoid infiltrate. True papillary carcinomas are rare, although a papillary component may be present in other types of breast carcinoma.

A 63-year-old woman has a screening mammogram that shows an irregular density with microcalcifications. On physical examination, there are no lesions of the overlying skin, and there is no axillary lymphadenopathy. An excisional biopsy specimen shows no mass on sectioning. Microscopic examination shows the findings in the figure. What is the most likely diagnosis? A Colloid carcinoma B Ductal carcinoma in situ C Infiltrating ductal carcinoma D Infiltrating lobular carcinoma E Medullary carcinoma F Papillary carcinoma

C This luminal A form comprises over half of all invasive breast cancers, and it tends to be low grade, and lack BRCA1, BRCA2, TP53, and CHEK2 familial gene mutations. It is often responsive to antiestrogen hormonal therapy, although surgery alone can be curative. Even with metastases, the course is prolonged. This patient has multiple risks for breast cancer, including nulliparity, obesity, and hormone replacement therapy. Breast cancer at her age is less likely to be familial. Trastuzumab is useful for HER2-positive breast cancers.

A 66-year-old nulliparous woman received hormone replacement therapy for 7 years following menopause at age 53 years. Her BMI is 33. She now undergoes screening mammography, and an irregular mass is identified in the right breast. An excisional biopsy yields a 1.5-cm mass that microscopically has invasive cells that are positive for estrogen receptor but negative for HER2, with low proliferation markers and mutated PIK3CA gene. Following surgical removal of the mass, which of the following clinical courses will most likely occur over the next year? A Detection of cancer in the left breast B Need for chemotherapy C Very low likelihood of recurrence D Need for treatment with trastuzumab E Occurrence of widespread metastases

G Many factors affect the course of breast cancer. The involvement of axillary lymph nodes is the most important prognostic factor listed. If there is no spread to axillary nodes, the 10-year survival rate is almost 80%. It decreases to 35% to 40% with 1 to 3 positive nodes, and to 15% with more than 10 positive nodes. Increasing age is a risk for breast cancer, but age alone does not indicate a prognosis, and treatment of cancers in the elderly can be successful. An increased DNA content with aneuploidy and a high S-phase suggests a worse prognosis, but staging is still a more important determinant of prognosis. Estrogen receptor positivity suggests a better response to hormonal manipulation of the tumor, whereas expression of HER2/neu suggests responsiveness to biotherapy with the monoclonal antibody trastuzumab. Some histologic types of breast cancer have a better prognosis than others, but staging is a more important factor than histologic type. The expression of stromal proteases, such as cathepsin D, predicts metastases, but in this case "the horse is out of the barn," and metastasis has occurred.

A 79-year-old, previously healthy woman feels a lump in her right breast. The physician palpates a 2-cm firm mass in the upper outer quadrant. Nontender right axillary lymphadenopathy is present. A lumpectomy with axillary lymph node dissection is performed. Microscopic examination shows that the mass is an infiltrating ductal carcinoma. Two of 10 axillary nodes contain metastases. Flow cytometry on the carcinoma cells shows a small aneuploid peak and high S-phase. Immunohistochemical tests show that the tumor cells are positive for estrogen and progesterone receptor (ER/PR), negative for HER2/neu expression, and positive for cathepsin D expression. What is the most important prognostic factor for this patient? A Age at diagnosis B DNA content in the carcinoma C Estrogen receptor positivity D Expression of stromal proteases in the carcinoma E Histologic subtype of carcinoma F Lack of HER2/neu expression in the carcinoma G Presence of lymph node metastases

D These are manifestations of cystic fibrosis (CF), from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The chloride channel defect in sweat ducts leads to concentration of sodium and chloride in sweat. Note that some CFTR mutations lead to a "forme fruste" (attenuated manifestation) of CF in which azoospermia may be the only manifestation. An elevated hemoglobin A1c is a feature of hyperglycemia with diabetes mellitus, but this is a late finding in CF, because the islets of Langerhans are not affected to the same degree as exocrine pancreas. Aminoaciduria suggests galactosemia, which is most likely to become apparent as hepatic failure in infancy. Hyperphenylalaninemia is a feature of phenylketonuria (PKU) manifested by mental retardation. VMA is increased in the urine of patients with neuroblastoma.

A clinical study is performed involving male subjects with infertility. Some of these patients are found to have bilateral agenesis of the vas deferens along with a history of recurrent respiratory tract infections, steatorrhea, and biliary cirrhosis. Genetic analysis reveals polymorphisms of mannose-binding lectin 2 (MBL2) and transforming growth factor beta 1 (TGFβ1) genes. An abnormality involving which of the following laboratory tests is most likely to be found in these infertile men? A Blood hemoglobin A1c B Urinary amino acids C Serum phenylalanine D Sweat chloride E Urine vanillylmandelic acid (VMA)

C The relative risk of breast cancer increases with various factors, but family history is one of the strongest. A history of bilateral breast disease and earlier age of onset of cancer increase the risk. The earlier age of onset increases the risk of identifying a BRCA1 or BRCA2 mutation. A longer reproductive life, with early menarche (<11 years old) and late menopause (>55 years old), and nulliparity increase the risk of breast cancer, probably because of increased estrogen exposure. "Soft" risk factors include exogenous estrogens and obesity. Mastitis does not affect the risk of breast cancer.

A clinical study is performed on postmenopausal women living in Paris, France, who are between the ages of 45 and 70 years. All have been diagnosed with infiltrating ductal carcinoma positive for estrogen receptor (ER) and progesterone receptor (PR), but negative for HER2 expression, which has been confirmed by biopsy and microscopic examination of tissue. None has the BRCA1 or BRCA2 mutation. Which of the following is most likely to indicate the highest relative risk of developing the carcinomas seen in this group of women? A Age at menarche older than 16 years B Age at menopause younger than 45 years C First-degree relative with breast cancer D Multiparity E Prior diagnosis of mastitis

A About 10% of cytomegalovirus-infected neonates have extensive infection with inclusions found in many organs. Severe anemia and myocardial injury cause hydrops, and the brain is often involved. The renal tubular epithelium can be infected, and large cells with inclusions can be seen with urine microscopic examination in some cases. Cytomegalovirus manifested in neonates may have been acquired transplacentally, at birth, or in breast milk. Herpes simplex virus is usually acquired via passage through the birth canal and does not cause a periventricular leukomalacia. HIV infection in utero does not produce marked organ damage. Parvovirus infection may cause a severe fetal anemia. Congenital rubella manifests in the first trimester, often with cardiac defects.

A neonate born at 36 weeks' gestation manifests severe hydrops fetalis, hepatosplenomegaly, generalized icterus, and scattered ecchymoses of the skin. Laboratory studies show a hemoglobin concentration of 9.4 g/dL and platelet count of 67,000/mm3. Ultrasound of the head shows ventricular enlargement. Death occurs 14 days after birth. At autopsy, there is extensive subependymal necrosis, with microscopic evidence of encephalitis. Within the areas of necrosis, there are large cells containing intranuclear inclusions. Congenital infection with which of the following organisms is most likely to produce these findings? A Cytomegalovirus B Herpes simplex virus C HIV D Parvovirus E Rubella virus

B Alcohol is one of the most common environmental teratogens affecting fetuses, although the effects can be subtle. There is no threshold amount of alcohol consumption by the mother to produce fetal alcohol syndrome; no amount is safe. Children with fetal alcohol syndrome tend to be developmentally impaired throughout childhood, but the physical anomalies tend to become less apparent as the child matures. Vertebral abnormalities, including scoliosis, can be present. The liver can have fatty metamorphosis with hepatomegaly and elevated serum transaminases. The major effects of congenital rubella occur during organogenesis in the first trimester and result in more pronounced defects, including congenital heart disease. Maternal diabetes often results in a larger infant, and malformations may be present. Placenta previa, a low-lying placenta at or near the cervical os, can cause significant hemorrhage at the time of delivery or uteroplacental insufficiency with growth retardation before delivery. Placental causes of intrauterine growth retardation result in asymmetric growth retardation with sparing of the brain. The findings of trisomy 21 are subtle at birth, but typically include brachycephaly, not microcephaly.

A newborn boy delivered at 38 weeks is small for gestational age. Physical examination shows microcephaly, frontal bossing, long and narrow forehead, hypotelorism, maxillary and mandibular hypoplasia, narrow palpebral fissures, thin elongated philtrum, vermilion border of the upper lip, dental malocclusion, saddle nose, tooth enamel hypoplasia, and uvular hypoplasia. Ocular problems include microphthalmia, corneal clouding, coloboma, nystagmus, strabismus, and ptosis. A systolic murmur is heard on auscultation, and echocardiography shows a membranous ventricular septal defect. Which of the following conditions is most likely to produce these findings? A Congenital rubella B Fetal alcohol syndrome C Maternal diabetes mellitus D Placenta previa E Trisomy 21

A This is the basal-like subset of NST breast cancers that is triple negative for the usual immunohistochemical markers. Hence, lack of ER positivity predicts that antihormonal therapy with tamoxifen will not be of benefit, and lack of HER2/neu indicates that trastuzumab will be ineffective. The basal-like cancers are highly aggressive and tend to metastasize early, so containment with surgery or radiation is unlikely. However, some of them are cured by chemotherapy. This emphasizes the importance of gene expression profiling, so that treatment is individualized to each cancer patient for the best chance of success.

A study of gene expression profiling involving breast biopsies showing invasive carcinoma of no specific type (NST) is performed. A subset of these cases, comprising about 15% of all cases, has the following characteristics: estrogen receptor (ER) and progesterone receptor (PR) negative, HER2/neu negative, basal keratin positive, flow cytometry showing aneuploidy and high proliferation rate, and association with BRCA1 mutations. Which of the following therapies is most likely to be effective in women with this subset of NST breast cancer? A Chemotherapy B Radiation C Surgery alone D Tamoxifen E Trastuzumab

A Nonproliferative cysts are quite common in the breast. When they are fluid-filled, they are unlikely to contain proliferative elements. The cells lining these cysts may be flattened cuboidal to atrophic, but often have abundant pink cytoplasm resembling apocrine change. Microcalcifications may be seen in both benign and malignant breast lesions, but in the case of cysts they represent calcified secretions. If excised, the intact cysts may have a blue to brown color. Ductal carcinomas 367are likely to be solid lesions. Fat necrosis may contain many macrophages, but also connective tissue, producing a firm lesion. Papillomatosis is a proliferative feature in fibrocystic changes that tends to form a solid lesion. Sclerosing adenosis produces a firm, fibrous lesion.

A study of mammographic findings on women of reproductive years is performed. The study identifies mammograms showing 1- to 5-cm cysts with focal microcalcifications and surrounding densities. Subsequent fine-needle aspiration yielded turbid fluid with few cells. Which of the following microscopic changes is most likely to be present in these lesions? A Apocrine metaplasia B Ductal carcinoma in situ C Fat necrosis D Papillomatosis E Sclerosing adenosis

D The estrogen receptor and progesterone receptor (ER and PR) status helps predict whether chemotherapy with antiestrogen compounds such as tamoxifen would be effective; however, the correlation is not perfect. ER and PR do not affect immunogenicity and are not targets for immunotherapy. In contrast, immunotherapy targeted to the overexpressed HER2/neu gene is being used. The overall prognosis may be predicted from several factors, including histologic type, histologic grade, presence of metastases, degree of aneuploidy, and tumor stage. A family history and the presence of specific mutations such as BRCA1 or BRCA2 correlate with familial risk of breast cancer.

A study of women with breast carcinoma is done to determine the presence and amount of estrogen receptor (ER) and progesterone receptor (PR) in the carcinoma cells. Large amounts of ER and PR are found in the carcinoma cells of some patients. These receptors are not present in the cells of other patients. The patients with positivity for ER and PR are likely to exhibit which of the following traits? A Greater immunogenicity B Greater likelihood of metastases C Greater risk of familial breast cancer D Higher response to therapy E Higher tumor stage F Higher tumor grade

A Rubella infection in the first trimester, when organogenesis is occurring (3 to 9 weeks' gestation), can lead to embryopathy with cardiac, ocular, skin, central nervous system, and hepatic abnormalities. Rubella is rare with routine vaccinations. Folate deficiency is most likely to be associated with neural tube defects. Dispermy is rare and can lead to triploidy, a condition that rarely results in a live birth. Erythroblastosis fetalis leads to fetal anemia with congestive heart failure and hydrops, but not to malformations. In the past, thalidomide use was a cause of malformations (almost invariably prominent limb deformities). Nondisjunctional events during meiosis in the maternal ova account for trisomies and monosomies, many of which have associated cardiac defects, including ventricular septal defect (e.g., trisomy 21). This mechanism is unlikely in paternal sperm, however, which are constantly being produced in large numbers throughout life.

A term infant has initial Apgar scores of 8 and 10 at 1 and 5 minutes. On auscultation of the chest, a heart murmur is audible. There is hepatosplenomegaly. Cataracts of the crystalline lens are noted. The infant is at the 30th percentile for height and weight. Echocardiography shows a patent ductus arteriosus. Which of the following events is the most likely risk factor for the findings in this infant? A Congenital rubella infection B Dietary folate deficiency C Dispermy at conception D Erythroblastosis fetalis E Maternal thalidomide use F Paternal meiotic nondisjunction

A This mild hemolytic anemia is most likely due to an ABO incompatibility with maternal blood type O, which results in anti-A antibody coating fetal cells. Most anti-A and anti-B antibodies are IgM. In about 20% to 25% of pregnancies, there are also IgG antibodies, which cross the placenta in sufficient titer to produce mild hemolytic disease in most cases. The bilirubin concentration in the term infant in this case is not high enough to produce kernicterus. ABO incompatibilities are not likely to have such serious consequences for subsequent pregnancies as does Rh incompatibility. As the infant matures, the level of maternal antibody diminishes, hemolysis abates, and the infant develops normally. Respiratory distress is unlikely at term because of appropriate fetal lung maturity.

An 18-year-old woman gives birth to a term infant after an uncomplicated pregnancy and delivery. Over the first 2 days of life, the infant becomes mildly icteric. On physical examination, there are no morphologic abnormalities. Laboratory studies show a neonatal bilirubin concentration of 4.9 mg/dL. The direct Coombs test of the infant's RBCs yields a positive result. The infant's blood type is A negative, and the mother's blood type is O positive. Based on these findings, which of the following events is most likely to occur? A Complete recovery B Failure to thrive C Hemolytic anemia throughout infancy D Kernicterus E Respiratory distress syndrome

E The cause of sudden infant death syndrome (SIDS) is unknown, but certain demographic risk factors are well established. Among these is age. SIDS most often occurs between 1 month and 1 year of age, and 90% of SIDS deaths occur during the first 6 months of life. Along with age, other factors listed increase the risk of SIDS. Male sex, African American race, low socioeconomic background of parents, lack of underlying medical problems, and absence of anatomic abnormality all favor the likelihood of SIDS. The key factor that argues for SIDS in this case is the lack of autopsy findings that support another diagnosis. SIDS may relate to abnormalities of serotonergic neural pathways in the medulla oblongata, and a respiratory tract stressor (sleeping prone) may put vulnerable infants at risk.

An 4-month-old African American boy is found dead in his crib one morning. The distraught parents, both factory workers, are interviewed by the medical examiner and indicate that the child had not been ill. She finds no gross or microscopic abnormalities at autopsy, and the results of all toxicologic tests are negative. The medical examiner tells the parents she believes the cause of death is sudden infant death syndrome (SIDS). This conclusion is most likely based on which of the following factors? A Age of the child B Sex of the child C Race of the child D Parental socioeconomic status E No abnormalities at autopsy.

A Male breast cancers are rare, and they occur primarily among the elderly. Additional risk factors include first-degree relatives with breast cancer, decreased testicular function, exposure to exogenous estrogens, infertility, obesity, prior benign breast disease, exposure to ionizing radiation, and residency in Western countries. Of cases in men, 4% to 14% are attributed to germline BRCA2 mutations, less frequently for BRCA1, and ATM mutations in less than 1%. Gynecomastia does not seem to be a risk factor.

An epidemiologic study is conducted with male subjects who have been diagnosed with breast carcinoma. Their demographic data, medical histories, family histories, and laboratory data are examined to identify factors that increase the risk of cancer. Which of the following factors is most likely to be associated with the greatest number of male breast carcinomas? A Age older than 70 years B Asian ancestry C ATM gene mutation D Chronic alcoholism E Gynecomastia

B Sustained, high-dose oxygen therapy delivered with positive pressure ventilation can cause injury to immature lungs, leading to the chronic lung disease known as bronchopulmonary dysplasia. Pulmonary manifestations of cystic fibrosis are not seen at birth or in infancy. Mortality from pulmonary hypoplasia is greatest at birth. In sudden infant death syndrome, no anatomic abnormalities are found at autopsy. A ventricular septal defect eventually could lead to pulmonary hypertension from the left-to-right shunt.

An infant is born prematurely at 32 weeks' gestation to a 34-year-old woman with gestational diabetes. On physical examination, the infant is at the 50th percentile for height and weight and there are no congenital anomalies. The infant requires 3 weeks of intubation with positive pressure ventilation and dies of sepsis at 4 months of age. At autopsy, the lungs show bronchial squamous metaplasia with peribronchial fibrosis, interstitial fibrosis, and dilation of airspaces. Which of the following conditions best explains these findings? A Cystic fibrosis B Bronchopulmonary dysplasia C Pulmonary hypoplasia D Sudden infant death syndrome E Ventricular septal defect

E Surfactant is synthesized by type II pneumocytes that line the alveolar sacs. They begin to differentiate after the 26th week of gestation. These cells can be recognized on electron microscopy by the presence of lamellar bodies filled with phospholipids. Surfactant production increases greatly after 35 weeks' gestation. Other structures in the lung do not synthesize the phosphatidylcholine and phosphatidylglycerol compounds that are important in surfactant production for reducing alveolar surface tension.

In a study of lung maturation, the amount of surfactant at different gestational ages is measured. Investigators find that the amount of surfactant in the developing lung increases between 26 and 32 weeks' gestation, with progression of lung architecture to a saccular alveolar configuration. This increase in surfactant is most likely related to which of the following developmental events? A Apoptosis in interlobular mesenchymal cells B Development of ciliated epithelium in airspaces C Differentiation of alveoli from embryonic foregut D Increased density of pulmonary capillaries E Maturation of type II alveolar epithelial cells