Case Studies ANOMALOUS ORIGIN OF LEFT CORONARY LEADING TO DEMISE IN A NEONATE NEVENKA S. GOULD,
ARTERY
MD, SAROJA BHARATI, MD, GERARDOFRONDA,MD,
Anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) is a relatively rare abnormality, representing 0.25% to 0.50% of all congenital cardiac malformations.’ This is a highly lethal lesion, with more than half of the patients dying between 3 and 6 months of age and 79% dying by the age of 13 months.‘,” Sudden death following exertion is well known in previously undiagnosed older children or adults. The majority of patients present clinically between 8 and 16 weeks of age with failure to thrive, and episodic dyspnea, restlessness, pallor, and perspiration usually associated with feeding.‘,J A postnatal delay in onset of symptoms is well recognized.‘,5 We report a term neonate with ALCAPA who died suddenly at 2 days of age. CASE REPORT A 3,390-g female was born at 40 weeks’ gestation via spontaneous vaginal vertex delivery to a 27-year-old gravida 7, para 1, aborta 5 woman. The woman’s previous gestations included two tubal pregnancies, three spontaneous abortions, and one midtrimester stillbirth. This pregnancy occurred following tuboplasty, and was otherwise uncomplicated. At delivery, the Apgar scores were 8 and 9 at 1 and 5 minutes. Initial examination was within normal limits, and the infant was admitted to the newborn nursery. Routine examination the following day revealed an active baby with a grade I-II/ VI systolic murmur that was to be followed expectantly; the examination was otherwise entirely normal. The nursing staff described the infant as somewhat irritable. At 2 days of age, the infant was taken to the mother for nursing, at which time she appeared well. Fifteen minutes later, the mother returned to the nursing station screaming that the infant was unresponsive; the infant was found to be in cardiorespiratory arrest and could not be resuscitated. AUTOPSY
FROM THE PULMONARY
FINDINGS
Autopsy revealed a well-formed, well-nourished female neonate with abnormal findings confined to the heart and lungs. The heart weighed 24 g (normal, 21.2 g) and the apex was made up of the left ventricle. The right atrium was acutely dilated, and the pulmonary artery (PA) was somewhat more prominent than the aorta, with mild bulging in situ of the sinuses of Valsalva. Both ventricles were somewhat thick-walled, From the Departmentsof Pathologyand Pediatrics,Michael Reese Hospital and Medical Center, Chicago. IL; and the Congenital Heart and Conduction System Center, The Heart Institute for Children, Christ Hospital and Medical Center, Palos Heights, IL. Accepted for publication December 4, 1990. Ke? words: anomalous origin of coronary artery, neonatal myocardial necrosis. Address correspondence and reprint requests to Nevenka S. Gould, MD, Department of Pathology, Michael Reese Hospital and Medical Center. Lake Shore Dr at 31st St, Chicago, IL 60618. Copyright 0 1991 by W.B. Saunders Company 0046-8177/91,‘2‘210-0013$5.00/O
1044
AND
ARTERY
CLIMENTENEJONES, MD
with the right measuring 0.5 cm and the left measuring 0.45 cm. (normal. 0.3 cm and 0.3 to 0.4 cm). The tricuspid valve showed mild nodular thickening along the line of closure. The ostium of the LCA originated slightly eccentrically from the left sinus of Valsalva of the pulmonary trunk via a large ostium that measured 1.2 cm in diameter (Fig 1). The right coronary artery (RCA) arose from the right sinus of Valsalva of the aorta, but its ostium was much smaller in comparison, measuring 0.5 mm. The LCA was the dominant vessel. Injection studies of the coronaries were not carried out. The foramen ovale and ductus arteriosus were normally patent, and no other abnormalities were found grossly. Microscopic examination revealed a recent myocardial infarct (Fig 2) involving the posterior papillary muscle of the mitral valve, characterized by cytoplasmic acidophilia, nuclear pyknosis, and mild hyperemia. No other areas of infarction and no myocardial fibrosis or calcification were present. The lungs revealed severe congestion, partial atelectasis, and patchy edema. The intrapulmonary vessels were normal. DISCUSSION Patients with ALCAPA have been classified according to manner and age of presentation. Gouley” divided the cases into infantile and adult types. The infantile variant occurs in early infancy when little or no collateral circulation exists between the normally arising RCA and the anomalous LCA. The LCA is then perfused antegrade from the PA. As the PA systolic pressure falls, perfusion and oxygen delivery fall. In the adult type. which includes older children as well as adults, rich intercoronary collaterals have developed, leading to retrograde perfusion of the LCA from the RCA. Between these two stages, Edwards” has postulated a transitional phase during which a temporary period of minimal blood flow to the myocardium in the distribution of the LCA can lead to myocardial infarction. A fourth stage has been emphasized7,8 in patients who have developed good collateral circulation, allowing a late “coronary artery steal” situation to occur; shunting of blood from the RCA into the pulmonary trunk acts like an arteriovenous malformation. In an extensive review of 140 cases of ALCAPA, Wesselhoeft et al grouped the patients into four categories according to clinical presentation.” The “infant syndrome” occurred at 2 to 4 months of age with failure to thrive, tachypnea, and angina-like episodes. The “mitral insufficiency” group included infants, children, or adults with hemodynamically significant mitral insufficiency as the main finding. The third subgroup, “continuous murmur syndrome,” was represented by a few asymptomatic small children and adults in whom the abnormality was apparent only by physical examination. Lastly, cases of sudden death were described in teenagers or adults, sometimes after exercise. A symptom-free interval following birth has been emphasized in ALCAPA and has been attributed to several factors, the most important being that the high PA pressure during fetal life continues into the postnatal period. Another factor
CASE STUDIES is a lower initial left ventricular 111~s. because in utero the systemic pre’jsure is low and because the workload is shared by both ventricles as ;I result of the patent ductus arteriosus. Only after tile left ventricular mass has sufficiently increased to outstrip the blood supply will inFarction occur. Lastly, a high hematocrit and fetal hemoglobin in the neonate increase the oxygen-carrying capacity to the myocardium, decreasing the risk of infarction.’ The case presented here is unusual in that death occurred at L’ days of age. None of the 60 “infant syndrome” cases described by Wesselhoeft et alJ presented this early: seven patients had onset between 2 and 3 weeks of age, 12 between 4 and 8 weeks, 35 between 8 and 16 weeks, and six after 6 months. In other reported series, onset of symptoms in the neonatal period (up to 28 days of age) included one of 11 patients at 3 weeks of agr.” one of 15 at 2 weeks,” and two of 10 by 2 weeks.’ Death in these cases occurred beyond the neonatal period. In review of 58 presurgery patients, half died between 3 and 6 months of age and 70% died by 13 months.’ Presentation in the immediate perinatal period was due to coexistent cardiac defects.“’ A separate review of 29 neonates’with myocardial necrosis includes two infants with ALCAPA: a l-day-old Down syndrome patient with a ventricular septal defect and multiple anomalies nnt further specified and a Il-day-old infant with a patcmt dnctuj artrriosus.” Both infants had widespread myocardial necrosis; the second patient also had myocardial calcific-ation. Major rtiologies of myocardial necrosis in neonates have been as$yxia and hypotension, coronary embolization, sepsis and shock, congenital heart diseases, and idiopathic arterial calcification of infancy.““’ The poor outcome seen in the infant reported here can be ,ittributed to srveral causes. Thr often-quoted protective high neonatal, PA pressure usually drops rather rapidly in term newborns and at 21 hours is 50% that of the aorta. with a further declirlr over the next 2 clays.” soon reaching adult \-allies. The l’rr-existing mild left ventricular hypertrophy in
FIGURE 1. A large LCA (arrow) arising from the PA (the ostium is somewhat magnified by the shadow).
FIGURE 2. Posterior mitral papillary muscle showing early necrosis with nuclear pyknosis (left) of the inner portion. (Hematoxylin-eosin stain; magnification > 160.) this infant, the cause of which is not entire11 clear, rep]-esented an increased muscle mass requiring increased oxygen deliver); thus increasing the risk of myocardial infarction. Papillary muscle infarction in this infant, which antedates the acute terminal crisis and was considered to have occurred the day prior, lends support to this hypothesis. Prognosis in patients with AI,CAPA has hren related in thr literature to vessel dominance, with a large RCA and a small I.CA lavoring sul-viva1 to adulthood.“.“.” In this inf‘ant, the converse was true; the left coronary ostiunl was LIII~~II~~~II~~ large. whereas the right was rather- small. Whether the ostial inequality could have produccd in utero interarterial coronary anastomoses is uncertain; if so, whether thrse were rxtensive rnough to lead to reversal of How cantlot IX determined. In retrospec’t, the il-ritability of the patierlt may have represented angina1 pain. The murmur heard at 1 day of age may have been clue to a coronary steal or. more likely, to a stillfunctioning duct us arteriosus. Following physiologic closure of the ductus. the PA pressure dropped rapidly. Dc,pendence on a large IKA system, which suddenly was poorly perfused, produced a sizeable mitral papillary muscle infarctl~rm as early as 1 day of age. It is felt that recurrent h)Foperfusion during nursing extended the intarction and led to the death of the infant.
HUMAN PATHOLOGY
Volume 22, No. 10 (October
10. Cottrill CM, Davis D, McMillen M. et al: Anomalous left coronaq’ artery from the pulmonary artery: Sigt%carlce of associated intracardiac defects. J Am Coil Cardioi 6:237-242, 1985 11. Esterly JR. Oppenheimer EH: Some aspects of cardiac pathology in infancy and childhood. I. Neonatal myocardial necrosis. Bull Hopkins Hospital 119:191-199, 1966 12. Donnelly WH. Bucclarelli RL, Nelson KM: Ischemir papillatry muscle necrosis in stressed newborn infattts. J Pediatr 96:295-300. 1980
ADENOSQUAMOUS
CARCINOMA
DEIRDKE M. DEVANEY. MRCPK~H,
OF THE PROSTATE:
A 70-year-old man presented with obstructive urinary symptoms in March 1980. A transurethral prostatectomy was performed and 70 g of tissue was removed. Histologic examination of the tissue revealed a prostatic adenocarcinoma (Gleason grade 3) (Fig 1). The patient had stage B disease and was treated with stilbestrol. 1 mg daily for 9 years. In March 1988, a repeat transurethral resection of the prostate was performed due to recurrence of symptoms. Biopsy specimens showed adenocarcinoma and focal squamous metaplasia of prostatic ducts (Fig 2). Serum prostatic acid phosphatase was normal and diagnostic imaging was negative for skeletal or visceral metastases. Stilbestrol therapy was continued. The patient underwent another biopsy in September 1988 for persistent obstructive urinary symptoms; specimens showed adenosquamous carcinoma (Fig 3). Stilbestrol therapy was discontinued in February 1989 following another resection, which demonstrated persistence of adenosquamous carcinoma. AND
13. Anderson KA. Burtwk JA. Fenton LJ. et al: Idiopathic arterial calcihc:ttion ,,f itlfanry in rlewbom siblings with unusual light and electron microscopic martifestations. Arch Pathol Lab Med 109:X38-840. 1985 14. Emmanouilide~ CC. Moss A,J, Duffie ER, et al: Pulmonary arterial pressure charlges irr human newborn infants from birth to 3 days of age. J Pediatr 55:327-333. 1964 1.5.Levm DC, Fellows KE, Abl-ams I-1L: Hemodynamically significant primary ;mo!nalies 01.the ~OII~IIV at-tet-iea. Circulation 58:25-34. 1978
A CASE REPORT
ANTHONY DORMAN, MB, ANI)Mary IXADEK, MD
Mixed ty!es of carcinoma of the jnostote are rure. The majority of those described (22 cases) are examples of mixed adenocarcinoma and transitional cell carcinoma. Much more unusual is the mixed adenosquamous carcinoma, of which only three cases have been described. This report presents an additional case of the rare actenosquamous carcinoma of the prostate. It discusses the cliGc@athologic features and the possible histogenesis of this tumor and suggests a role for stilbestrol in its development. HUM P.STMX 22:10461050. Copyright 0 1991 by W.H. Saunders Contpay
MATERIALS
1991)
METHODS
Pathology Light microscopy. Routinely processed paraffin blocks and hematoxylin-eosin-stained sections were available for study. The tissue specimen from 1980 showed a prostatic adenocarcinema (Gleason grade 3) with no evidence of squamous dif-
ferentiation (Fig 1). The March 1988 biopsy specimen also showed adenocarcinoma (Gleason grade 4); however, in addition, squamous metaplasia of prostatic ducts was also seen (Fig 2). In the biopsy material from September 1988 and February 1989 there was histologic evidence of an adenosquamous carcinoma (Fig 3). Both components were distinct and separate and. although closely juxtaposed, there was no obvious transition. The bulk of tumor now consisted of well-differentiated squamous carcinoma and the glandular component showed poorly differentiated adenocarcinoma (Gleason grade 4).
Immunohistochemisty The adenocarcinomatous component was positive for prostatic specific antigen (PSA; Dakopatts), prostatic acid phosphatase (PAP; Dakopatts). and the cytokeratin markers AEl/AE3 (Hybritech), and was negative for epithelial membrane antigen (EMA; Dakopatts). The malignant squamous component was positive for EMA and AEl/AEJ but negative for PSA and PAP. Squamous metaplasia showed only cytokeratin (AEl/AE3) positivity.
Electron Microscopy For ultrastructural studies, selected tissue specimens from 1989 were recovered from a paraffin wax block and sections were examined in a Jeol 1200EX transmission electron microscope. Ultrastructurally, the malignant squamous component lacked tight junctions, desmosomes, and tonofibrils and showed microvilli lining the intercellular spaces. Mucus granules were not seen.
DNA Analysis Selected areas of adenocarcinoma and squamous cell carcinoma were extracted from 1980 and 1989 blocks, respectively. Five-micrometer sections were cut and stained with Feulgen and were examined by an image analyzer (Cell Analysis System CAS 100, Becton Dickinson). Cytospin preparations of 50-Km sections were examined by image analysis (Fig 4) and by an EPICS Profile Flow Cytometer (Coulter). Diploid peaks were seen in the adenocarcinomatous component (Fig 4, top) and the malignant squamous component (Fig 4. bottom) by both methods of DNA analysis. No aneuploid stem lines were identified.
From the Departrrtent of Histopathology, Beaumont Hospital, Dublin. Ireland. and The Royal College of Surgeons in Ireland, Dublin, Ireland. Accepted for publication December 4. 1990. Key wordr: adenosquamous carcinoma, prostate, squamous metaplasia, stilbestml. Address correspondence and reprint requests to Mary Leader, MD, Department of Pathology, Beaumont Hospital, Dublin 9. Republic of Ireland. Copyright 0 1991 by W.B. Saunders Company 0046-8177/91/2210-0014$5.00/O
1046
ARTERY
MD, SAROJA BHARATI, MD, GERARDOFRONDA,MD,
Anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) is a relatively rare abnormality, representing 0.25% to 0.50% of all congenital cardiac malformations.’ This is a highly lethal lesion, with more than half of the patients dying between 3 and 6 months of age and 79% dying by the age of 13 months.‘,” Sudden death following exertion is well known in previously undiagnosed older children or adults. The majority of patients present clinically between 8 and 16 weeks of age with failure to thrive, and episodic dyspnea, restlessness, pallor, and perspiration usually associated with feeding.‘,J A postnatal delay in onset of symptoms is well recognized.‘,5 We report a term neonate with ALCAPA who died suddenly at 2 days of age. CASE REPORT A 3,390-g female was born at 40 weeks’ gestation via spontaneous vaginal vertex delivery to a 27-year-old gravida 7, para 1, aborta 5 woman. The woman’s previous gestations included two tubal pregnancies, three spontaneous abortions, and one midtrimester stillbirth. This pregnancy occurred following tuboplasty, and was otherwise uncomplicated. At delivery, the Apgar scores were 8 and 9 at 1 and 5 minutes. Initial examination was within normal limits, and the infant was admitted to the newborn nursery. Routine examination the following day revealed an active baby with a grade I-II/ VI systolic murmur that was to be followed expectantly; the examination was otherwise entirely normal. The nursing staff described the infant as somewhat irritable. At 2 days of age, the infant was taken to the mother for nursing, at which time she appeared well. Fifteen minutes later, the mother returned to the nursing station screaming that the infant was unresponsive; the infant was found to be in cardiorespiratory arrest and could not be resuscitated. AUTOPSY
FROM THE PULMONARY
FINDINGS
Autopsy revealed a well-formed, well-nourished female neonate with abnormal findings confined to the heart and lungs. The heart weighed 24 g (normal, 21.2 g) and the apex was made up of the left ventricle. The right atrium was acutely dilated, and the pulmonary artery (PA) was somewhat more prominent than the aorta, with mild bulging in situ of the sinuses of Valsalva. Both ventricles were somewhat thick-walled, From the Departmentsof Pathologyand Pediatrics,Michael Reese Hospital and Medical Center, Chicago. IL; and the Congenital Heart and Conduction System Center, The Heart Institute for Children, Christ Hospital and Medical Center, Palos Heights, IL. Accepted for publication December 4, 1990. Ke? words: anomalous origin of coronary artery, neonatal myocardial necrosis. Address correspondence and reprint requests to Nevenka S. Gould, MD, Department of Pathology, Michael Reese Hospital and Medical Center. Lake Shore Dr at 31st St, Chicago, IL 60618. Copyright 0 1991 by W.B. Saunders Company 0046-8177/91,‘2‘210-0013$5.00/O
1044
AND
ARTERY
CLIMENTENEJONES, MD
with the right measuring 0.5 cm and the left measuring 0.45 cm. (normal. 0.3 cm and 0.3 to 0.4 cm). The tricuspid valve showed mild nodular thickening along the line of closure. The ostium of the LCA originated slightly eccentrically from the left sinus of Valsalva of the pulmonary trunk via a large ostium that measured 1.2 cm in diameter (Fig 1). The right coronary artery (RCA) arose from the right sinus of Valsalva of the aorta, but its ostium was much smaller in comparison, measuring 0.5 mm. The LCA was the dominant vessel. Injection studies of the coronaries were not carried out. The foramen ovale and ductus arteriosus were normally patent, and no other abnormalities were found grossly. Microscopic examination revealed a recent myocardial infarct (Fig 2) involving the posterior papillary muscle of the mitral valve, characterized by cytoplasmic acidophilia, nuclear pyknosis, and mild hyperemia. No other areas of infarction and no myocardial fibrosis or calcification were present. The lungs revealed severe congestion, partial atelectasis, and patchy edema. The intrapulmonary vessels were normal. DISCUSSION Patients with ALCAPA have been classified according to manner and age of presentation. Gouley” divided the cases into infantile and adult types. The infantile variant occurs in early infancy when little or no collateral circulation exists between the normally arising RCA and the anomalous LCA. The LCA is then perfused antegrade from the PA. As the PA systolic pressure falls, perfusion and oxygen delivery fall. In the adult type. which includes older children as well as adults, rich intercoronary collaterals have developed, leading to retrograde perfusion of the LCA from the RCA. Between these two stages, Edwards” has postulated a transitional phase during which a temporary period of minimal blood flow to the myocardium in the distribution of the LCA can lead to myocardial infarction. A fourth stage has been emphasized7,8 in patients who have developed good collateral circulation, allowing a late “coronary artery steal” situation to occur; shunting of blood from the RCA into the pulmonary trunk acts like an arteriovenous malformation. In an extensive review of 140 cases of ALCAPA, Wesselhoeft et al grouped the patients into four categories according to clinical presentation.” The “infant syndrome” occurred at 2 to 4 months of age with failure to thrive, tachypnea, and angina-like episodes. The “mitral insufficiency” group included infants, children, or adults with hemodynamically significant mitral insufficiency as the main finding. The third subgroup, “continuous murmur syndrome,” was represented by a few asymptomatic small children and adults in whom the abnormality was apparent only by physical examination. Lastly, cases of sudden death were described in teenagers or adults, sometimes after exercise. A symptom-free interval following birth has been emphasized in ALCAPA and has been attributed to several factors, the most important being that the high PA pressure during fetal life continues into the postnatal period. Another factor
CASE STUDIES is a lower initial left ventricular 111~s. because in utero the systemic pre’jsure is low and because the workload is shared by both ventricles as ;I result of the patent ductus arteriosus. Only after tile left ventricular mass has sufficiently increased to outstrip the blood supply will inFarction occur. Lastly, a high hematocrit and fetal hemoglobin in the neonate increase the oxygen-carrying capacity to the myocardium, decreasing the risk of infarction.’ The case presented here is unusual in that death occurred at L’ days of age. None of the 60 “infant syndrome” cases described by Wesselhoeft et alJ presented this early: seven patients had onset between 2 and 3 weeks of age, 12 between 4 and 8 weeks, 35 between 8 and 16 weeks, and six after 6 months. In other reported series, onset of symptoms in the neonatal period (up to 28 days of age) included one of 11 patients at 3 weeks of agr.” one of 15 at 2 weeks,” and two of 10 by 2 weeks.’ Death in these cases occurred beyond the neonatal period. In review of 58 presurgery patients, half died between 3 and 6 months of age and 70% died by 13 months.’ Presentation in the immediate perinatal period was due to coexistent cardiac defects.“’ A separate review of 29 neonates’with myocardial necrosis includes two infants with ALCAPA: a l-day-old Down syndrome patient with a ventricular septal defect and multiple anomalies nnt further specified and a Il-day-old infant with a patcmt dnctuj artrriosus.” Both infants had widespread myocardial necrosis; the second patient also had myocardial calcific-ation. Major rtiologies of myocardial necrosis in neonates have been as$yxia and hypotension, coronary embolization, sepsis and shock, congenital heart diseases, and idiopathic arterial calcification of infancy.““’ The poor outcome seen in the infant reported here can be ,ittributed to srveral causes. Thr often-quoted protective high neonatal, PA pressure usually drops rather rapidly in term newborns and at 21 hours is 50% that of the aorta. with a further declirlr over the next 2 clays.” soon reaching adult \-allies. The l’rr-existing mild left ventricular hypertrophy in
FIGURE 1. A large LCA (arrow) arising from the PA (the ostium is somewhat magnified by the shadow).
FIGURE 2. Posterior mitral papillary muscle showing early necrosis with nuclear pyknosis (left) of the inner portion. (Hematoxylin-eosin stain; magnification > 160.) this infant, the cause of which is not entire11 clear, rep]-esented an increased muscle mass requiring increased oxygen deliver); thus increasing the risk of myocardial infarction. Papillary muscle infarction in this infant, which antedates the acute terminal crisis and was considered to have occurred the day prior, lends support to this hypothesis. Prognosis in patients with AI,CAPA has hren related in thr literature to vessel dominance, with a large RCA and a small I.CA lavoring sul-viva1 to adulthood.“.“.” In this inf‘ant, the converse was true; the left coronary ostiunl was LIII~~II~~~II~~ large. whereas the right was rather- small. Whether the ostial inequality could have produccd in utero interarterial coronary anastomoses is uncertain; if so, whether thrse were rxtensive rnough to lead to reversal of How cantlot IX determined. In retrospec’t, the il-ritability of the patierlt may have represented angina1 pain. The murmur heard at 1 day of age may have been clue to a coronary steal or. more likely, to a stillfunctioning duct us arteriosus. Following physiologic closure of the ductus. the PA pressure dropped rapidly. Dc,pendence on a large IKA system, which suddenly was poorly perfused, produced a sizeable mitral papillary muscle infarctl~rm as early as 1 day of age. It is felt that recurrent h)Foperfusion during nursing extended the intarction and led to the death of the infant.
HUMAN PATHOLOGY
Volume 22, No. 10 (October
10. Cottrill CM, Davis D, McMillen M. et al: Anomalous left coronaq’ artery from the pulmonary artery: Sigt%carlce of associated intracardiac defects. J Am Coil Cardioi 6:237-242, 1985 11. Esterly JR. Oppenheimer EH: Some aspects of cardiac pathology in infancy and childhood. I. Neonatal myocardial necrosis. Bull Hopkins Hospital 119:191-199, 1966 12. Donnelly WH. Bucclarelli RL, Nelson KM: Ischemir papillatry muscle necrosis in stressed newborn infattts. J Pediatr 96:295-300. 1980
ADENOSQUAMOUS
CARCINOMA
DEIRDKE M. DEVANEY. MRCPK~H,
OF THE PROSTATE:
A 70-year-old man presented with obstructive urinary symptoms in March 1980. A transurethral prostatectomy was performed and 70 g of tissue was removed. Histologic examination of the tissue revealed a prostatic adenocarcinoma (Gleason grade 3) (Fig 1). The patient had stage B disease and was treated with stilbestrol. 1 mg daily for 9 years. In March 1988, a repeat transurethral resection of the prostate was performed due to recurrence of symptoms. Biopsy specimens showed adenocarcinoma and focal squamous metaplasia of prostatic ducts (Fig 2). Serum prostatic acid phosphatase was normal and diagnostic imaging was negative for skeletal or visceral metastases. Stilbestrol therapy was continued. The patient underwent another biopsy in September 1988 for persistent obstructive urinary symptoms; specimens showed adenosquamous carcinoma (Fig 3). Stilbestrol therapy was discontinued in February 1989 following another resection, which demonstrated persistence of adenosquamous carcinoma. AND
13. Anderson KA. Burtwk JA. Fenton LJ. et al: Idiopathic arterial calcihc:ttion ,,f itlfanry in rlewbom siblings with unusual light and electron microscopic martifestations. Arch Pathol Lab Med 109:X38-840. 1985 14. Emmanouilide~ CC. Moss A,J, Duffie ER, et al: Pulmonary arterial pressure charlges irr human newborn infants from birth to 3 days of age. J Pediatr 55:327-333. 1964 1.5.Levm DC, Fellows KE, Abl-ams I-1L: Hemodynamically significant primary ;mo!nalies 01.the ~OII~IIV at-tet-iea. Circulation 58:25-34. 1978
A CASE REPORT
ANTHONY DORMAN, MB, ANI)Mary IXADEK, MD
Mixed ty!es of carcinoma of the jnostote are rure. The majority of those described (22 cases) are examples of mixed adenocarcinoma and transitional cell carcinoma. Much more unusual is the mixed adenosquamous carcinoma, of which only three cases have been described. This report presents an additional case of the rare actenosquamous carcinoma of the prostate. It discusses the cliGc@athologic features and the possible histogenesis of this tumor and suggests a role for stilbestrol in its development. HUM P.STMX 22:10461050. Copyright 0 1991 by W.H. Saunders Contpay
MATERIALS
1991)
METHODS
Pathology Light microscopy. Routinely processed paraffin blocks and hematoxylin-eosin-stained sections were available for study. The tissue specimen from 1980 showed a prostatic adenocarcinema (Gleason grade 3) with no evidence of squamous dif-
ferentiation (Fig 1). The March 1988 biopsy specimen also showed adenocarcinoma (Gleason grade 4); however, in addition, squamous metaplasia of prostatic ducts was also seen (Fig 2). In the biopsy material from September 1988 and February 1989 there was histologic evidence of an adenosquamous carcinoma (Fig 3). Both components were distinct and separate and. although closely juxtaposed, there was no obvious transition. The bulk of tumor now consisted of well-differentiated squamous carcinoma and the glandular component showed poorly differentiated adenocarcinoma (Gleason grade 4).
Immunohistochemisty The adenocarcinomatous component was positive for prostatic specific antigen (PSA; Dakopatts), prostatic acid phosphatase (PAP; Dakopatts). and the cytokeratin markers AEl/AE3 (Hybritech), and was negative for epithelial membrane antigen (EMA; Dakopatts). The malignant squamous component was positive for EMA and AEl/AEJ but negative for PSA and PAP. Squamous metaplasia showed only cytokeratin (AEl/AE3) positivity.
Electron Microscopy For ultrastructural studies, selected tissue specimens from 1989 were recovered from a paraffin wax block and sections were examined in a Jeol 1200EX transmission electron microscope. Ultrastructurally, the malignant squamous component lacked tight junctions, desmosomes, and tonofibrils and showed microvilli lining the intercellular spaces. Mucus granules were not seen.
DNA Analysis Selected areas of adenocarcinoma and squamous cell carcinoma were extracted from 1980 and 1989 blocks, respectively. Five-micrometer sections were cut and stained with Feulgen and were examined by an image analyzer (Cell Analysis System CAS 100, Becton Dickinson). Cytospin preparations of 50-Km sections were examined by image analysis (Fig 4) and by an EPICS Profile Flow Cytometer (Coulter). Diploid peaks were seen in the adenocarcinomatous component (Fig 4, top) and the malignant squamous component (Fig 4. bottom) by both methods of DNA analysis. No aneuploid stem lines were identified.
From the Departrrtent of Histopathology, Beaumont Hospital, Dublin. Ireland. and The Royal College of Surgeons in Ireland, Dublin, Ireland. Accepted for publication December 4. 1990. Key wordr: adenosquamous carcinoma, prostate, squamous metaplasia, stilbestml. Address correspondence and reprint requests to Mary Leader, MD, Department of Pathology, Beaumont Hospital, Dublin 9. Republic of Ireland. Copyright 0 1991 by W.B. Saunders Company 0046-8177/91/2210-0014$5.00/O
1046
