Vol. 93 • No. 6
SINGLE CASE REPORTS
17. Masson P. Le constituant nerveux des tumeurs de Wilms'. Annales D'anatomie Pathologique 1957;2:133-149. 18. McCauley RGK, Safau H, Crowley CA, Pinn VW. Extrarenal Wilms' tumor. Am J Dis Child 1979; 1333:1174-1177. 19. Movassaghi N, Leikin S, Chandra R. Wilms' tumor metastasis to uncommon sites. J Pediatr 1974;84:416-417. 20. Moyson F, Maurus-Desmarez R, Gompel C. Tumeur de Wilms' mediastinale. Acta Chir Belg 1961 ;60(Suppl 2): 118-128. 21. Orlowski JP, Levin HS, Dyment PG. Intrascrotal Wilms' tumor developing in a heterotopic renal anlage of probable mesonephric origin. J Pediatr Surg 1980;15:679-682. 22. Taylor WF, Myers M, Taylor WR. Extrarenal Wilms' tumour in an infant exposed to intrauterine phenytoin. Lancet 1980;2:481-482. 23. Thompson MR, Emmanuel IG, Campbell MS, Zachary RB. Extrarenal Wilms' tumors. J Pediatr Surg 1973;8:37-41. 24. Ward SP, Dehner LP. Sacrococcygeal teratoma with nephroblastoma (Wilms' tumor): a variant of extragonadal teratoma in childhood. A histologic and ultrastructural study. Cancer 1974;33:1355-1363. 25. Willis RA. pathology of tumours. London: Butterworths, 1962;442466. 26. Wilms M. Die Mischgschwulsteder Niere, vol 1. Leipzig: Georgi, 1899:214.
Cartilaginous Metaplasia in Calcific Aortic Valve Disease DEBRA A. GROOM, M.D. AND WILLIAM R. STARKE, M.D.
In a 49-year-old man, symptoms of aortic valve stenosis developed that required surgical intervention with valve replacement. Pathologic examination of the valve showed severe calcific aortic sclerosis and foci of hyaline cartilage. The authors believe that these foci are secondary to cartilaginous transformation of mesenchymal valvular tissue. This represents abnormal repair of valvular tissue damaged, in this case, by the nodular calcific process of calcific aortic stenosis. (Key words: Aortic valve; Cartilage; Aortic stenosis; Metaplasia) Am J Clin Pathol 1990;93:
809-812 THE USE of surgical aortic valve replacement for symptomatic aortic stenosis has increased the number of valves available for surgical pathology evaluation. The pathologic diagnosis in most of these specimens is calcific sclerosis of the aortic valve. It has been more than 60 years since cartilaginous transformation in Monckeberg's calcific stenosis has been described.6 On the other hand, bone and fatty marrow formation in the calcific aortic valve is well recognized. Karsner and Koletsky10 described the formation of bone containing fatty marrow in 9 of 200 cases of severe aortic
Department of Pathology, Los Angeles County-University of Southern California Medical Center and Hospital of the Good Samaritan, Los Angeles, California
valvular disease. In our experience at The Hospital of the Good Samaritan, we have seen 1 aortic valve with osseous transformation in 101 studied from valvular replacement surgery. We recently had the opportunity to study an aortic valve that had foci of hyaline cartilage as well as severe calcific sclerosis. A description of this case, a review of the literature, and an attempt to explain the mechanism for cartilage transformation are provided. Materials and Methods Four-micron sections were prepared from formalinfixed and decalcified, paraffin-embedded tissue blocks. They were stained with hematoxylin and eosin (H and E) and Alcian blue. Report of a Case
Received July 19, 1989; accepted for publication August 23, 1989. Address reprint requests to Dr. Starke: The Hospital of the Good Samaritan, Department of Pathology, 616 South Witmer Street, Los Angeles, California 90017-2395.
The patient was a 49-year-old white male who complained of increasing exertional dyspnea, orthopnea, dry cough, and chest pain for one month before admission. He said that for 10-15 years he had been aware that he had a heart murmur and he had been told that he might need aortic valve replacement in 1984 when he was hospitalized for alcoholism.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
8. Bittencourt AL, Britto JF, Fonseca LE. Wilms' tumor of the uterus: the first report of the literature. Cancer 1981;47:2496-2499. 9. Cozzutto C, Stracca-Pansa V, Salano F. Renal dysplasia of the sacral region: metanephric hamartoma dysplastic hamartoma of the sacral region. Virchows Arch [A] 1983;402:163. 10. Dehner LP. Gonadal and extragonadal germ cell neoplasms-teratomas in childhood. In: Finegold MJ, ed. Pathology of neoplasia in children and adolescents. Philadelphia: WB Saunders, 1986;300-301. 11. Grimes MM, Wolff M, Wolff JA, Jaretzki A III, Blanc WA. Ganglion cells in metastatic Wilms' tumor. Am J Surg Pathol 1982;6:565571. 12. Hardwick DF, Stowens D. Wilms' tumors. J Urol 1961 ;85:903-910. 13. Ho J, Ma L, Wong KC. An extrarenal Wilms' tumour arising from an undescended testis. Pathology 1981;13:619-624. 14. Johnson F, Luttenton C, Limbert D. Extrarenal and urothelial Wilms' tumor. Urology 1980;15:370-373. 15. Langman J. Medical embryology. 5th ed. Baltimore: Williams and Wilkins, 1985:260. 16. Llombart-Bosch A, Peydro-Olaya A, Cerda-Nicolas M. Presence of ganglion cells in Wilms' tumours: a review of the possible neuroepithelial origin of nephroblastoma. Histopathology 1980;4: 321-330.
809
A.J.C.P.-June 1990
GROOM AND STARKE
810
V* -
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
vol.93-No.6
SINGLE CASE REPORTS
81 1
FIG. 1. Aortic valve with cartilaginous metaplastic focus. Hematoxylin and eosin (X4). FIG. 2. Cartilaginous foci. Hematoxylin and eosin (X40). FIG. 3. Separate cartilaginous focus adjacent tofibrousand calcific nodular tissue. Alcian blue (X40). FIG. 4. Area of transformation from cartilage tofibroustissue. Hematoxylin and eosin (X40).
< At admission, the patient was in congestive heart failure that partially responded to diuresis. He had cardiac catheterization and echocardiography, which showed an aortic valve area of 0.7 cm2 with a mean systolic gradient of 35 mmHg, a left ventricular ejection fracture of 20%, and normal coronary arteries. Thesefindingswere believed to be consistent with severe calcific aortic stenosis, considered best treated with aortic valve replacement. At surgery, it was noted that the aortic valve was heavily calcified and appeared to be bicuspid.
Gross Examination The specimen was submitted as 12 fragments of heavily calcified valve tissue ranging from 2 to 10 mm in size. The external surfaces of the valve were nodular but otherwise smooth and white. The number of cusps could not be evaluated because of the fragmentation and distortion of the valve. No thrombi or vegetations were apparent. Microscopic Examination Sections of the aortic valve revealed multiple large nodular intramural calcific deposits. These calcific areas showed focal eruption through the endocardial surface. The surrounding valvular stroma demonstrated hyalinized fibrous tissue and small focal collections of mononuclear inflammatory cells. On H and E-stained sections, one of the valve fragments demonstrated a 3.0-mm round focus of mature hyaline cartilage (Fig. 1). The cartilage was composed of uninuclear chondrocytes (Fig. 2). The nuclei were found within lacunae and surrounded by a basophilic matrix, which stained strongly with Alcian blue. The margins were irregular and showed focal calcification, although no well-defined bone formation could be found. Alcian blue stain revealed two other microscopic foci of cartilage on another section of valve (Fig. 3). These other foci had not been identified on H and E-stained sections because of heavy mineralization. The cartilaginous foci were surrounded by nodular calcifications and hyalinized fibrous tissue. In areas, there appeared to be a gradual transformation from fibrous tissue to cartilage, with cells that appeared intermediate between fibroblasts and chondrocytes in the transformation zone (Fig. 4). Discussion Cartilaginous foci in the heart, although well described in other mammals, rarely occur in humans. Cartilage is
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Results
found in the aortic ring of some white rats and mice.7,8 The os cordis, composed of cartilage or bone, occurs in the trigonum fibrosum of ruminants. 2 A cartilaginous bar has been described at the base of the semilunar valve of R-Amsterdam rats and Syrian hamsters.711 Tne functional significance of these findings is not known, but they appear to be related to aging in some cases and to cartilaginous transformation secondary to mechanical forces in other cases. In the literature, only two described pediatric cases of cartilage in the heart were found.5 Small amounts of fibrocartilage were found in the central fibrous body, in close approximation to the conducting tissue in two children, ages six months and two years. These children had sudden unexpected deaths, which were believed to be related to this finding. These cartilaginous foci probably resulted from congenital defects, however, the possibility of reactive metaplasia must still be considered. The only description of cartilaginous foci of the aortic valve associated with calcific aortic or Monckeberg's stenosis was described by Henke and Labarsh in 1924, as previously mentioned. A more recent description of hyaline cartilage seen in the aortic valve of a 22-year-old male who had endocarditis was described in 1973 by Seemayer and colleagues.14 This patient presented with migratory arthritis and severe aortic insufficiency. He was treated with antibiotics and then had successful aortic valve replacement surgery. Pathologic examination of the heart valve showed mature hyaline cartilage with focal calcification and osseous transformation. The author postulated that the endocarditis caused destruction of the normal valve, which led to repair by cartilaginous transformation of the primitive mesenchymal spongiosa rather than fibrous replacement. Induction of chondrogenesis has been performed experimentally in myocardium and other nonskeletal tissue. Devitalized tissue, otocyst implantation, compression and rotational stress, and carrageenan (connective tissue growth stimulant) have all been used to induce cartilaginous metaplasia. 3 ' 41213 The injection of carrageenan into myocardium favored cartilage formation if the tissue was rendered ischemic by coronary artery ligation. The formation of both cartilage and bone in the myocardium has been described with the use of both biologic and synthetic materials as intracardiac grafts in the atrium of dogs.9 It is theorized that chondrogenesis in all these cases
812
GROOM AND STARKE
with time and additional pathologic examination that more foci of cartilage will be seen in valves involved with endocarditis, calcific sclerosis, and other entities, as well as explanted bioprosthetic valves. References 1. Arbustini E, Jones M, Ferrans VJ. Formation of cartilage in bioprosthetic cardiac valves implanted in sheep: a morphologic study. Am J Cardiol 1983;52:632-636. 2. Benninghoff A. In: Bolk L, Goppert G, Kallius E, and Lubosch W, eds. Lehrbuch der Anatomie des Menschen, vol 2. Berlin: Urban and Schuarzenberg, 1952:433-444. 3. Benoid JA. Induction de cartilage in-vitro par l'extrait d'otocystes d'embryons de poulet. J Embryol Exp Morphol 1960;8:33-38. 4. Bridges JB, Prithard JJ. Bone and cartilage induction in the rabbit. J Anat 1958;92:28-38. 5. Ferris J, Aherne WA. Cartilage in relation to the conducting tissue of the heart in sudden death. Lancet 1971;1:64-66. 6. Henke F, Labarsh O. Herz and gesasse. In: Handbuch Der Speziellen Pathologischen Anatomie und Histologic, vol 2. Berlin: Verlag von Julius Springer, 1924:196. 7. Hollander CF. Cartilaginous foci at the base of the noncoronary semilunar valve of the aorta in rats of different ages. Exp Gerontol 1968;3:303-307. 8. Hueper WC. Cartilaginous foci in the heart of white rats and mice. Arch Pathol 1938;27:466-468. 9. Kadowaki MH, Levett JM, Manjoney DL, Grina NM, Glagov S. Comparison of prosthetic graft materials as intracardiac right atrial patches. J Surg Res 1986;41:65-74. 10. Karsner HT, Koletsky S. Calcific disease of the aortic valve. Philadelphia: JB Lippincott, 1947:43. 11. Kelsall MA. Aortic cartilage in the heart of Syrian hamsters. Anat Rec 1970;66:627-634. 12. Lehoczky-Mona J, McCandless EL. Ischemic induction of chondrogenesis in myocardium. Arch Pathol 1964;78:37. 13. Scapinelli R, Little K. Observations on the mechanically induced differentiation of cartilage fromfibrousconnective tissue. J Pathol 1970;101:85. 14. Seemayer TA, Thelmo WL, Morin J. Cartilaginous transformation of the aortic valve. Am J Clin Pathol 1973;60:616-620.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
occurs as a result of the release of a specific inductor substance, which leads to cartilaginous metaplasia of the tissue or proliferation of a stem cell into cartilage differentiation. A recent study by Arbustini and colleagues' described the cartilaginous transformation of bioprosthetic cardiac valves implanted in the mitral or tricuspid positions in sheep. Foci of cartilage associated with varying degrees of calcification were seen in 12 of 120 bioprostheses that were of porcine aortic valvular or bovine pericardial origin. Cells that appeared intermediate betweenfibroblastsand chondrocytes were seen at the periphery of cartilaginous foci, similar to that seen in our case. One foci of osseous transformation was also seen. These changes were only seen in valves explanted "late" (greater than 13 weeks). The cartilage was considered to be formed by metaplasia of devitalized connective tissue of host origin. It is unlikely that the cartilaginous foci seen in our patient have an embryonic origin, although, if the valve was indeed bicuspid, a congenital defect must be considered. Findings that would suggest acquired cartilaginous transformation of mesenchymal valvular tissue include the late age of presentation and the multiplicity of foci. The apparent transformation zones seen between thefibrousand cartilaginous tissue also suggests an ongoing metaplastic process. We theorize that the aortic valve has become damaged by the nodular calcific process involved in calcific aortic stenosis. This has led to "abnormal" repair of devitalized tissue by metaplastic cartilage from mesenchymal origin, perhaps as a response to some unknown inductor substance. The same mechanism is probably responsible for osseous transformation seen in the aortic valve. It would be expected that any type of valvular damage could lead to cartilage or osseous metaplasia and that
A.J.C.P. • June 1990
SINGLE CASE REPORTS
17. Masson P. Le constituant nerveux des tumeurs de Wilms'. Annales D'anatomie Pathologique 1957;2:133-149. 18. McCauley RGK, Safau H, Crowley CA, Pinn VW. Extrarenal Wilms' tumor. Am J Dis Child 1979; 1333:1174-1177. 19. Movassaghi N, Leikin S, Chandra R. Wilms' tumor metastasis to uncommon sites. J Pediatr 1974;84:416-417. 20. Moyson F, Maurus-Desmarez R, Gompel C. Tumeur de Wilms' mediastinale. Acta Chir Belg 1961 ;60(Suppl 2): 118-128. 21. Orlowski JP, Levin HS, Dyment PG. Intrascrotal Wilms' tumor developing in a heterotopic renal anlage of probable mesonephric origin. J Pediatr Surg 1980;15:679-682. 22. Taylor WF, Myers M, Taylor WR. Extrarenal Wilms' tumour in an infant exposed to intrauterine phenytoin. Lancet 1980;2:481-482. 23. Thompson MR, Emmanuel IG, Campbell MS, Zachary RB. Extrarenal Wilms' tumors. J Pediatr Surg 1973;8:37-41. 24. Ward SP, Dehner LP. Sacrococcygeal teratoma with nephroblastoma (Wilms' tumor): a variant of extragonadal teratoma in childhood. A histologic and ultrastructural study. Cancer 1974;33:1355-1363. 25. Willis RA. pathology of tumours. London: Butterworths, 1962;442466. 26. Wilms M. Die Mischgschwulsteder Niere, vol 1. Leipzig: Georgi, 1899:214.
Cartilaginous Metaplasia in Calcific Aortic Valve Disease DEBRA A. GROOM, M.D. AND WILLIAM R. STARKE, M.D.
In a 49-year-old man, symptoms of aortic valve stenosis developed that required surgical intervention with valve replacement. Pathologic examination of the valve showed severe calcific aortic sclerosis and foci of hyaline cartilage. The authors believe that these foci are secondary to cartilaginous transformation of mesenchymal valvular tissue. This represents abnormal repair of valvular tissue damaged, in this case, by the nodular calcific process of calcific aortic stenosis. (Key words: Aortic valve; Cartilage; Aortic stenosis; Metaplasia) Am J Clin Pathol 1990;93:
809-812 THE USE of surgical aortic valve replacement for symptomatic aortic stenosis has increased the number of valves available for surgical pathology evaluation. The pathologic diagnosis in most of these specimens is calcific sclerosis of the aortic valve. It has been more than 60 years since cartilaginous transformation in Monckeberg's calcific stenosis has been described.6 On the other hand, bone and fatty marrow formation in the calcific aortic valve is well recognized. Karsner and Koletsky10 described the formation of bone containing fatty marrow in 9 of 200 cases of severe aortic
Department of Pathology, Los Angeles County-University of Southern California Medical Center and Hospital of the Good Samaritan, Los Angeles, California
valvular disease. In our experience at The Hospital of the Good Samaritan, we have seen 1 aortic valve with osseous transformation in 101 studied from valvular replacement surgery. We recently had the opportunity to study an aortic valve that had foci of hyaline cartilage as well as severe calcific sclerosis. A description of this case, a review of the literature, and an attempt to explain the mechanism for cartilage transformation are provided. Materials and Methods Four-micron sections were prepared from formalinfixed and decalcified, paraffin-embedded tissue blocks. They were stained with hematoxylin and eosin (H and E) and Alcian blue. Report of a Case
Received July 19, 1989; accepted for publication August 23, 1989. Address reprint requests to Dr. Starke: The Hospital of the Good Samaritan, Department of Pathology, 616 South Witmer Street, Los Angeles, California 90017-2395.
The patient was a 49-year-old white male who complained of increasing exertional dyspnea, orthopnea, dry cough, and chest pain for one month before admission. He said that for 10-15 years he had been aware that he had a heart murmur and he had been told that he might need aortic valve replacement in 1984 when he was hospitalized for alcoholism.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
8. Bittencourt AL, Britto JF, Fonseca LE. Wilms' tumor of the uterus: the first report of the literature. Cancer 1981;47:2496-2499. 9. Cozzutto C, Stracca-Pansa V, Salano F. Renal dysplasia of the sacral region: metanephric hamartoma dysplastic hamartoma of the sacral region. Virchows Arch [A] 1983;402:163. 10. Dehner LP. Gonadal and extragonadal germ cell neoplasms-teratomas in childhood. In: Finegold MJ, ed. Pathology of neoplasia in children and adolescents. Philadelphia: WB Saunders, 1986;300-301. 11. Grimes MM, Wolff M, Wolff JA, Jaretzki A III, Blanc WA. Ganglion cells in metastatic Wilms' tumor. Am J Surg Pathol 1982;6:565571. 12. Hardwick DF, Stowens D. Wilms' tumors. J Urol 1961 ;85:903-910. 13. Ho J, Ma L, Wong KC. An extrarenal Wilms' tumour arising from an undescended testis. Pathology 1981;13:619-624. 14. Johnson F, Luttenton C, Limbert D. Extrarenal and urothelial Wilms' tumor. Urology 1980;15:370-373. 15. Langman J. Medical embryology. 5th ed. Baltimore: Williams and Wilkins, 1985:260. 16. Llombart-Bosch A, Peydro-Olaya A, Cerda-Nicolas M. Presence of ganglion cells in Wilms' tumours: a review of the possible neuroepithelial origin of nephroblastoma. Histopathology 1980;4: 321-330.
809
A.J.C.P.-June 1990
GROOM AND STARKE
810
V* -
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
vol.93-No.6
SINGLE CASE REPORTS
81 1
FIG. 1. Aortic valve with cartilaginous metaplastic focus. Hematoxylin and eosin (X4). FIG. 2. Cartilaginous foci. Hematoxylin and eosin (X40). FIG. 3. Separate cartilaginous focus adjacent tofibrousand calcific nodular tissue. Alcian blue (X40). FIG. 4. Area of transformation from cartilage tofibroustissue. Hematoxylin and eosin (X40).
< At admission, the patient was in congestive heart failure that partially responded to diuresis. He had cardiac catheterization and echocardiography, which showed an aortic valve area of 0.7 cm2 with a mean systolic gradient of 35 mmHg, a left ventricular ejection fracture of 20%, and normal coronary arteries. Thesefindingswere believed to be consistent with severe calcific aortic stenosis, considered best treated with aortic valve replacement. At surgery, it was noted that the aortic valve was heavily calcified and appeared to be bicuspid.
Gross Examination The specimen was submitted as 12 fragments of heavily calcified valve tissue ranging from 2 to 10 mm in size. The external surfaces of the valve were nodular but otherwise smooth and white. The number of cusps could not be evaluated because of the fragmentation and distortion of the valve. No thrombi or vegetations were apparent. Microscopic Examination Sections of the aortic valve revealed multiple large nodular intramural calcific deposits. These calcific areas showed focal eruption through the endocardial surface. The surrounding valvular stroma demonstrated hyalinized fibrous tissue and small focal collections of mononuclear inflammatory cells. On H and E-stained sections, one of the valve fragments demonstrated a 3.0-mm round focus of mature hyaline cartilage (Fig. 1). The cartilage was composed of uninuclear chondrocytes (Fig. 2). The nuclei were found within lacunae and surrounded by a basophilic matrix, which stained strongly with Alcian blue. The margins were irregular and showed focal calcification, although no well-defined bone formation could be found. Alcian blue stain revealed two other microscopic foci of cartilage on another section of valve (Fig. 3). These other foci had not been identified on H and E-stained sections because of heavy mineralization. The cartilaginous foci were surrounded by nodular calcifications and hyalinized fibrous tissue. In areas, there appeared to be a gradual transformation from fibrous tissue to cartilage, with cells that appeared intermediate between fibroblasts and chondrocytes in the transformation zone (Fig. 4). Discussion Cartilaginous foci in the heart, although well described in other mammals, rarely occur in humans. Cartilage is
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Results
found in the aortic ring of some white rats and mice.7,8 The os cordis, composed of cartilage or bone, occurs in the trigonum fibrosum of ruminants. 2 A cartilaginous bar has been described at the base of the semilunar valve of R-Amsterdam rats and Syrian hamsters.711 Tne functional significance of these findings is not known, but they appear to be related to aging in some cases and to cartilaginous transformation secondary to mechanical forces in other cases. In the literature, only two described pediatric cases of cartilage in the heart were found.5 Small amounts of fibrocartilage were found in the central fibrous body, in close approximation to the conducting tissue in two children, ages six months and two years. These children had sudden unexpected deaths, which were believed to be related to this finding. These cartilaginous foci probably resulted from congenital defects, however, the possibility of reactive metaplasia must still be considered. The only description of cartilaginous foci of the aortic valve associated with calcific aortic or Monckeberg's stenosis was described by Henke and Labarsh in 1924, as previously mentioned. A more recent description of hyaline cartilage seen in the aortic valve of a 22-year-old male who had endocarditis was described in 1973 by Seemayer and colleagues.14 This patient presented with migratory arthritis and severe aortic insufficiency. He was treated with antibiotics and then had successful aortic valve replacement surgery. Pathologic examination of the heart valve showed mature hyaline cartilage with focal calcification and osseous transformation. The author postulated that the endocarditis caused destruction of the normal valve, which led to repair by cartilaginous transformation of the primitive mesenchymal spongiosa rather than fibrous replacement. Induction of chondrogenesis has been performed experimentally in myocardium and other nonskeletal tissue. Devitalized tissue, otocyst implantation, compression and rotational stress, and carrageenan (connective tissue growth stimulant) have all been used to induce cartilaginous metaplasia. 3 ' 41213 The injection of carrageenan into myocardium favored cartilage formation if the tissue was rendered ischemic by coronary artery ligation. The formation of both cartilage and bone in the myocardium has been described with the use of both biologic and synthetic materials as intracardiac grafts in the atrium of dogs.9 It is theorized that chondrogenesis in all these cases
812
GROOM AND STARKE
with time and additional pathologic examination that more foci of cartilage will be seen in valves involved with endocarditis, calcific sclerosis, and other entities, as well as explanted bioprosthetic valves. References 1. Arbustini E, Jones M, Ferrans VJ. Formation of cartilage in bioprosthetic cardiac valves implanted in sheep: a morphologic study. Am J Cardiol 1983;52:632-636. 2. Benninghoff A. In: Bolk L, Goppert G, Kallius E, and Lubosch W, eds. Lehrbuch der Anatomie des Menschen, vol 2. Berlin: Urban and Schuarzenberg, 1952:433-444. 3. Benoid JA. Induction de cartilage in-vitro par l'extrait d'otocystes d'embryons de poulet. J Embryol Exp Morphol 1960;8:33-38. 4. Bridges JB, Prithard JJ. Bone and cartilage induction in the rabbit. J Anat 1958;92:28-38. 5. Ferris J, Aherne WA. Cartilage in relation to the conducting tissue of the heart in sudden death. Lancet 1971;1:64-66. 6. Henke F, Labarsh O. Herz and gesasse. In: Handbuch Der Speziellen Pathologischen Anatomie und Histologic, vol 2. Berlin: Verlag von Julius Springer, 1924:196. 7. Hollander CF. Cartilaginous foci at the base of the noncoronary semilunar valve of the aorta in rats of different ages. Exp Gerontol 1968;3:303-307. 8. Hueper WC. Cartilaginous foci in the heart of white rats and mice. Arch Pathol 1938;27:466-468. 9. Kadowaki MH, Levett JM, Manjoney DL, Grina NM, Glagov S. Comparison of prosthetic graft materials as intracardiac right atrial patches. J Surg Res 1986;41:65-74. 10. Karsner HT, Koletsky S. Calcific disease of the aortic valve. Philadelphia: JB Lippincott, 1947:43. 11. Kelsall MA. Aortic cartilage in the heart of Syrian hamsters. Anat Rec 1970;66:627-634. 12. Lehoczky-Mona J, McCandless EL. Ischemic induction of chondrogenesis in myocardium. Arch Pathol 1964;78:37. 13. Scapinelli R, Little K. Observations on the mechanically induced differentiation of cartilage fromfibrousconnective tissue. J Pathol 1970;101:85. 14. Seemayer TA, Thelmo WL, Morin J. Cartilaginous transformation of the aortic valve. Am J Clin Pathol 1973;60:616-620.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
occurs as a result of the release of a specific inductor substance, which leads to cartilaginous metaplasia of the tissue or proliferation of a stem cell into cartilage differentiation. A recent study by Arbustini and colleagues' described the cartilaginous transformation of bioprosthetic cardiac valves implanted in the mitral or tricuspid positions in sheep. Foci of cartilage associated with varying degrees of calcification were seen in 12 of 120 bioprostheses that were of porcine aortic valvular or bovine pericardial origin. Cells that appeared intermediate betweenfibroblastsand chondrocytes were seen at the periphery of cartilaginous foci, similar to that seen in our case. One foci of osseous transformation was also seen. These changes were only seen in valves explanted "late" (greater than 13 weeks). The cartilage was considered to be formed by metaplasia of devitalized connective tissue of host origin. It is unlikely that the cartilaginous foci seen in our patient have an embryonic origin, although, if the valve was indeed bicuspid, a congenital defect must be considered. Findings that would suggest acquired cartilaginous transformation of mesenchymal valvular tissue include the late age of presentation and the multiplicity of foci. The apparent transformation zones seen between thefibrousand cartilaginous tissue also suggests an ongoing metaplastic process. We theorize that the aortic valve has become damaged by the nodular calcific process involved in calcific aortic stenosis. This has led to "abnormal" repair of devitalized tissue by metaplastic cartilage from mesenchymal origin, perhaps as a response to some unknown inductor substance. The same mechanism is probably responsible for osseous transformation seen in the aortic valve. It would be expected that any type of valvular damage could lead to cartilage or osseous metaplasia and that
A.J.C.P. • June 1990
