Case Report 296
Entodermal Inclusion Cyst ofthe Tricuspid Valve G. Machens . c.-F. Vahl, R. Hofman n ' , D. Wolf", and S. Hagl
2
De part ment of Card iac Surgery Department of Patho logy Dep artm ent of Pediatric Cardiology, Univer sity of Heidelberg. Germa ny
Summary
Entode r male Zyst e der Trikuspid a lklappe
This is a rep ort on an ep ithelial inclusion cyst covering the se ptal leaflet of the tricuspid valve. The tumor was an accidental finding in a 5 ljz yea rs-o ld boy with conge nital heart disease including double-cham bered right ven tricle, ventricular a nd atrial sep tal defects a nd subvalvular a ortic ste nos is. Histological examination showed a two-layer ed ciliate d epithelium , typically presen t in the respi ra tory syste m. Embryologic tissue heterotopia arising from seques tered entodermal eleme nts from the primitive foreg ut during cardiac organogenesis is a possible explanation for the locality a nd histology of the tumo r. To our knowledge, a similar case ha s never been presen ted before.
Wir berichten von einer dem se ptalen Trikuspida lklappensegel au fgclagerten epithelialen Inklusionszyste als Zusatzbefund bei einem 5%jahr igen Jun gen , der wegen eines komplexen kcngenitalen Vitium s zu r Operation kam. Die feingewebliche Untersuchung des Tumors zeigte ein zweischichtiges Flimmcrepithel, wie es fur den Hespiration str akt typisch ist. Eine embryologische Geweb she terotopie wird als mogllcher Mechan ism us zur Deutung von Lage un d Histologie des Tumors diskutiert . Nach unser er Kenntn is ist bislan g von keinem abnliche n Fall ben chtet word en. Keywords Epithelial inclusion cyst - Cardiac tumor - Embry ologic tissue heterotopia
Introduction
Tissue displacem ent dur ing embryological development of an or ga n may le a d to b izar re m al form ation s in its n ew loca tion . A cha racte r istic exam ple of th es e h eterotopi a s in the hum an h eart is the a tr ioven tr icu la r n ode tumo r th a t h as been qu ot ed as the sm a llest tum or th a t can ca use su dden
death (17). However, histogenes is of these heter otopias
hea rt valves were described as normal in function and sha pe. During the following yea rs, the boy showed only mild symptoms or exert ion dyspnoe. All ECGs' showed sinus rh ythm. Intraope ratively, in addition to the preope ratively known cardiac abne rma lities a mas s was noted covering the septa l leaflet of the tricu spid valve. Grossly, it was a che rry-s ized, firm , yellowish cyst mea suring 2 x 1 x 1 em that protrud ed into the at rium (see Fig. 1) giving the aspect or "growing out or the septa l leaflet. Posterior and anterior
often r e m a ins co ntroversia l. Thus the atr ioventricula r node
tumor was regarded to be of endothelial (2), entodermal (11, 15), and of mesenchyma l origin (12). \ Ve re port on an epithelial cystic tumor, solely restricted to the tricuspid va lve an d ass ociated w ith com p licated con ge n ital he art dis ease .
Case report A 5 lfz yea rs-old boy suffering from complex congenital hear t disease includi ng double-cha mber ed right ventr icle, ventric ular and atrial septal defects, and subvalvular aorti c stenosis was admitted for elective ca rdiac sur gery. Card iac cat hete ris ation 3 weeks after birt h had led to the diagnosis or ventricular septum defect, patent du ct us arteriosus and elevated pr essure in the pulmona ry a rte ry. After ductal ligation adequate reduction of pulm onary artery pres sure was obs erved . A second cardiac catheterisa tion was per formed 7 months after ductal ligation , showing a dou ble-chambered right vent ricle with a 85 mmHg systolic inll ow/outfl ov..' gra dient a nd a vent ricu lar 21 % right-to -Ieft shunt. A slight su bvalvula r ao rtic ste nosis caused a small systolic gradient or 20 mmHg. All
Fig. 1
Tho rae. ca rdiovasc. Surgeon 39 (1991) 296 - 298
Re ceived for Pu hli cation : A p r il 1 5, 1991
© GeorgThieme Verlag Stuttgart - New York
Intraoperative viewofthe tricusp id valvetumor in situ
Downloaded by: University of British Columbia. Copyrighted material.
1
Entade rmu l Inclusion Cys t of the Tricusp id \lbfl'e
leaflets of the valve seemed slightly thickened . The chordae tendineae were th ickened and fibrotic. On opening the tumor , small amou nts of mucoid fluid were observed. After excision of the tumor the septal leaflet of the tricuspid valve was reconstru cted without evidence for insufficiency. The atr ial- and ventric ular septal defects were repaired and the rightventricula r outflow tract stenosis was remove d subseq uently in the same session. The patients' postope rative course was uneventful without complications. Two weeks postoperatively the boy was discharged from hospital. Detailed histological analysis revealed a single thick-walled cyst which contained a yellowish creamy fluid. The inner surface of the cyst was covered by single or two-layered columnar epithelium . Most interestingly the epitheli um was partly ciliated. It had a thick basal membrane. A subepithelial infiltration with mononuclea r inflammatory cells could also be detected. The cyst had a partly myxomato us stroma (Fig. 2-3) .
Thome. eard io/'(Jse. S urgeoll39 (1991)
297
Fig. 2 HEphotomicrographofthe cyst wall that iscove red byan epithelial celllayer. Notethesubepithelial mononuclear inflammatory cells
Various tricuspida l valve tumors have been desc ribed over more than 100 years , including myxoma, fibr oma, lipoma, fibr oelastoma , thro mbi, and blood cysts (13). However , to our knowledge, this is the first present ation of an epithelial inclusion cyst of the tricuspid valve. The ciliated epithelium found in this case strong ly suggests an entoderm al origin (1). However , the pathogenesis ofthis lesion still re main s to be clarified . Interestingly, the well known polycystic atrioventricular node tumor , first descri bed by Armstrong and Monckeberq in 191 1 (2), has a similar histological pattern. Most lesions had a columna r, cuboidal, or fiattened epithelium witho ut cilia and conta ined mucus. A ciliated epithelium was found in only one case , described by Morris and John son (14). Tbeir finding, however , had been ques tioned by Fine and Morales (7) , who studied mate rial from that case and could not confirm the presence of cilia. Meanwhile, more than 50 cases of AV-node-tumors have bee n published in the literature (6,16) . Two of those tumors reached the septal leaflet of the tricuspid valve (9, 10). Histologically these tu mors always appea red benign and well circumscribed. They becam e clinically apparent for reasons of arrhythmias as a result of their location. In a second grou p of cardiac heterotopias the inclusions were located within the superficial myocard ium. Typically, the abe rrant tiss ue was cystic or tu bular , lined with epithelial cells of cuboidal, ciliated, or mucous secreting type. Feaux de Lacroix and Hubner reviewed 12 cases of ciliated cardiac inclusion cysts of the left ventricle (one of them an own pr ese ntatio n) (5). All malformations ha d been acciden tal findings at autopsy witho ut clinical symptom s. Kindred described an epithelial cyst in the primordium of the tr icuspid vaive of an abnormal human embryo (9). The cyst meas ured 0.077 mm x 0.05 mm an d the epithe lium was pseud ostratified columnar and sim ple low columnar. Histological ana lysis refer s to a preparation of a fifty-days-old em bryo. The author believed tha t the cyst had arisen from an aberrant proliferation and sequestration ofa portion of the primitive epimyocardial mantle at a stage compa ra ble to that of the 5-somite emb ryo. During this stage a prolifer ation of the cardiagenic folds ta kes place to form the atrioventricular sulci. The possible forma tion of cysts from the perimyocardial mantle at the time when the cardiogenic folds were closing around the endothelial tubes vent ral to the foregut in a 14-som ite embryo had already
Fig. 3 PAS photomicrographrevealing clearlythe existenceof asubepithelial basal membraneand showinga }- 2 layered columnar epithelium which is partly ciliated
been me ntioned by Davis (3) an d later on by lleuser (8) who studied the same cases. In our opinion, an anomaly in the development of the emb ryo might explain both the epithe lial valvular heterotopia and the multiple cardiac malformations in this patient. During early embryogenic life, the mesocar dium dorsale separates the simple rudimentary tubular heart from the buccopharyngeal mem bra ne an d the foregut. Tbese structures are lined by endodermal epithelium and unde rgo a dilTer entiation into pharynx, thyroid paren chyma , respiratory tract, esophagus, and upper gastrointes tinal tra ct. During further differentiation the primitive heart undergoes a complicated sequenc e of rotat ions and
Downloaded by: University of British Columbia. Copyrighted material.
Discussion
G. Mach ens . c-r. vohl. R. Hofma nn, D. IFolf. and S //agl
Thom e. cardiol'asc . Su rgeon 3 9 (19 91)
involutions , which form the heart cham bers and atria. During this per iod port ions of the foregut may become pinched off into the mesocard ium dorsale, formin g a so-called epithelial keel (4). Fragments of this epithelial keel might be the source of the heterotopic cyst that we found on the se ptal tricusp id leaflet.
10
II
12
Refer ences I
2
3
4
5 6
g
9
13
Anderson. W. A D., and E. T. Dmy try k : Primary tumor of the hea rt
conta ining epith elium-like elements . Am. J. Path . 22 (194 6) 33 7-349 Armstrong. H.. un d J. G. Monckeberq . Herzblock bedingt durch prtmaren Herztumor bei einem Sja hrigen Kinde. Dtsch . Arch. Klin . Med .l 02 (1911 ) 144-1 66 Daois. C. L.: Development of the human heart from its first a ppearance to the sta ge found in emb ryos of twenty paired somites. Contrib . Embryo!. 19 (192 7) 24 5- 284 Dosc h. F.: Uber eine n Fallvon Glandula thyreoidea accessoria intraca rdialis. Beitr. pathol. Anat. 105 (1941) 244 -2 55 De La croix . F.. and G. Hubner: Ciliated epithelial inclusion cyst ofthe heart. Beitr. Path . 151 (1974) 103- 110 Duray. P. t t., E. J. M ark, K. W. Barwi ck et a i.: Congenital polycystic tumor of the atrioventricular node . Autopsy study with immunohistochemical findings suggest ing endoderma l derivation. Arch. Patho!' Lab. Med. 109 (1965) 30- 34 Fine. G.. and A. R. Mora les: Mesoth elioma of the at rioventricular node . Arch . Path. 92 (1971) 402 -408 Heus er. C. H.: A human embryo with 14 pairs of somites. Contrib. Embryo!. 22 (1930) 135- 154 Kindred. J. E.: A cyst in the primord ium of the tr icuspid valve of an abn or mal human embryo. Am. J . Path. 33 (1957) 967- 975
14 IS
16
Ii
Leigh ton, J.. J. Hur s t. and J. Cra wford: Squamo us ep ithelial cysts in
the heart of an infant with coincident cystic changes in the ovaries an d breasts . Arch . Path . 50 (1950) 632-64 3 Linder. 1.. J. D. Shelburne, and J. P. Sorge: Congenita l en dodermal heter otopia of the atr ioventricular node: evidence for the en dodermal origin of so-called mesotheliomas of th e at riovent ricular node. Hum. Patho!' 15 (1984) 1093-1 098 Maha im.l.: Le coelotheliome tawarien benin: un tum eur sui gen er is du noeud de Taware avec bloc du cceur. Card iologia 6 (1942) 57- 82 Maha im. I.: Les tumeur s et les polypes du cceur. Etude ana tomoclinique. Monogra phic de l'lnsti tute d'a natomie pathologtque de l'Universite de Lau sanne (1945) Morr is, A S ., and I. AI. John son : Epithelial inclusion cysts of the hear t. Arch. Path. 77 (196 4) 36-40 Rez ek . P.: Ober eine primare epithell ale Gesch wulst an der Gegen d des Reizleitungssystems beim Menschen. Vlrchows Arc h. 301 (1938) 305- 320 Traoers. 11. : Congenital polycystic tu mor of the atriovent ricular node. Possible familial occurre nce and critical review of rep orted cases with special emphasis on histogenesis. Hum. Path ol. 13 (1982) 25-35 Wolf. P. I.. and R. Bing: The sma llest tu mor which ca uses sudden death. JAMA 194 (196 5) 674 - 675
Dr. C.-F. Vahl Department of Cardiac Surge ry University of Ileidelberg 1m Neuenh eimer Feld 110 0 -6900 Heidelberg Germa ny
Downloaded by: University of British Columbia. Copyrighted material.
298
Entodermal Inclusion Cyst ofthe Tricuspid Valve G. Machens . c.-F. Vahl, R. Hofman n ' , D. Wolf", and S. Hagl
2
De part ment of Card iac Surgery Department of Patho logy Dep artm ent of Pediatric Cardiology, Univer sity of Heidelberg. Germa ny
Summary
Entode r male Zyst e der Trikuspid a lklappe
This is a rep ort on an ep ithelial inclusion cyst covering the se ptal leaflet of the tricuspid valve. The tumor was an accidental finding in a 5 ljz yea rs-o ld boy with conge nital heart disease including double-cham bered right ven tricle, ventricular a nd atrial sep tal defects a nd subvalvular a ortic ste nos is. Histological examination showed a two-layer ed ciliate d epithelium , typically presen t in the respi ra tory syste m. Embryologic tissue heterotopia arising from seques tered entodermal eleme nts from the primitive foreg ut during cardiac organogenesis is a possible explanation for the locality a nd histology of the tumo r. To our knowledge, a similar case ha s never been presen ted before.
Wir berichten von einer dem se ptalen Trikuspida lklappensegel au fgclagerten epithelialen Inklusionszyste als Zusatzbefund bei einem 5%jahr igen Jun gen , der wegen eines komplexen kcngenitalen Vitium s zu r Operation kam. Die feingewebliche Untersuchung des Tumors zeigte ein zweischichtiges Flimmcrepithel, wie es fur den Hespiration str akt typisch ist. Eine embryologische Geweb she terotopie wird als mogllcher Mechan ism us zur Deutung von Lage un d Histologie des Tumors diskutiert . Nach unser er Kenntn is ist bislan g von keinem abnliche n Fall ben chtet word en. Keywords Epithelial inclusion cyst - Cardiac tumor - Embry ologic tissue heterotopia
Introduction
Tissue displacem ent dur ing embryological development of an or ga n may le a d to b izar re m al form ation s in its n ew loca tion . A cha racte r istic exam ple of th es e h eterotopi a s in the hum an h eart is the a tr ioven tr icu la r n ode tumo r th a t h as been qu ot ed as the sm a llest tum or th a t can ca use su dden
death (17). However, histogenes is of these heter otopias
hea rt valves were described as normal in function and sha pe. During the following yea rs, the boy showed only mild symptoms or exert ion dyspnoe. All ECGs' showed sinus rh ythm. Intraope ratively, in addition to the preope ratively known cardiac abne rma lities a mas s was noted covering the septa l leaflet of the tricu spid valve. Grossly, it was a che rry-s ized, firm , yellowish cyst mea suring 2 x 1 x 1 em that protrud ed into the at rium (see Fig. 1) giving the aspect or "growing out or the septa l leaflet. Posterior and anterior
often r e m a ins co ntroversia l. Thus the atr ioventricula r node
tumor was regarded to be of endothelial (2), entodermal (11, 15), and of mesenchyma l origin (12). \ Ve re port on an epithelial cystic tumor, solely restricted to the tricuspid va lve an d ass ociated w ith com p licated con ge n ital he art dis ease .
Case report A 5 lfz yea rs-old boy suffering from complex congenital hear t disease includi ng double-cha mber ed right ventr icle, ventric ular and atrial septal defects, and subvalvular aorti c stenosis was admitted for elective ca rdiac sur gery. Card iac cat hete ris ation 3 weeks after birt h had led to the diagnosis or ventricular septum defect, patent du ct us arteriosus and elevated pr essure in the pulmona ry a rte ry. After ductal ligation adequate reduction of pulm onary artery pres sure was obs erved . A second cardiac catheterisa tion was per formed 7 months after ductal ligation , showing a dou ble-chambered right vent ricle with a 85 mmHg systolic inll ow/outfl ov..' gra dient a nd a vent ricu lar 21 % right-to -Ieft shunt. A slight su bvalvula r ao rtic ste nosis caused a small systolic gradient or 20 mmHg. All
Fig. 1
Tho rae. ca rdiovasc. Surgeon 39 (1991) 296 - 298
Re ceived for Pu hli cation : A p r il 1 5, 1991
© GeorgThieme Verlag Stuttgart - New York
Intraoperative viewofthe tricusp id valvetumor in situ
Downloaded by: University of British Columbia. Copyrighted material.
1
Entade rmu l Inclusion Cys t of the Tricusp id \lbfl'e
leaflets of the valve seemed slightly thickened . The chordae tendineae were th ickened and fibrotic. On opening the tumor , small amou nts of mucoid fluid were observed. After excision of the tumor the septal leaflet of the tricuspid valve was reconstru cted without evidence for insufficiency. The atr ial- and ventric ular septal defects were repaired and the rightventricula r outflow tract stenosis was remove d subseq uently in the same session. The patients' postope rative course was uneventful without complications. Two weeks postoperatively the boy was discharged from hospital. Detailed histological analysis revealed a single thick-walled cyst which contained a yellowish creamy fluid. The inner surface of the cyst was covered by single or two-layered columnar epithelium . Most interestingly the epitheli um was partly ciliated. It had a thick basal membrane. A subepithelial infiltration with mononuclea r inflammatory cells could also be detected. The cyst had a partly myxomato us stroma (Fig. 2-3) .
Thome. eard io/'(Jse. S urgeoll39 (1991)
297
Fig. 2 HEphotomicrographofthe cyst wall that iscove red byan epithelial celllayer. Notethesubepithelial mononuclear inflammatory cells
Various tricuspida l valve tumors have been desc ribed over more than 100 years , including myxoma, fibr oma, lipoma, fibr oelastoma , thro mbi, and blood cysts (13). However , to our knowledge, this is the first present ation of an epithelial inclusion cyst of the tricuspid valve. The ciliated epithelium found in this case strong ly suggests an entoderm al origin (1). However , the pathogenesis ofthis lesion still re main s to be clarified . Interestingly, the well known polycystic atrioventricular node tumor , first descri bed by Armstrong and Monckeberq in 191 1 (2), has a similar histological pattern. Most lesions had a columna r, cuboidal, or fiattened epithelium witho ut cilia and conta ined mucus. A ciliated epithelium was found in only one case , described by Morris and John son (14). Tbeir finding, however , had been ques tioned by Fine and Morales (7) , who studied mate rial from that case and could not confirm the presence of cilia. Meanwhile, more than 50 cases of AV-node-tumors have bee n published in the literature (6,16) . Two of those tumors reached the septal leaflet of the tricuspid valve (9, 10). Histologically these tu mors always appea red benign and well circumscribed. They becam e clinically apparent for reasons of arrhythmias as a result of their location. In a second grou p of cardiac heterotopias the inclusions were located within the superficial myocard ium. Typically, the abe rrant tiss ue was cystic or tu bular , lined with epithelial cells of cuboidal, ciliated, or mucous secreting type. Feaux de Lacroix and Hubner reviewed 12 cases of ciliated cardiac inclusion cysts of the left ventricle (one of them an own pr ese ntatio n) (5). All malformations ha d been acciden tal findings at autopsy witho ut clinical symptom s. Kindred described an epithelial cyst in the primordium of the tr icuspid vaive of an abnormal human embryo (9). The cyst meas ured 0.077 mm x 0.05 mm an d the epithe lium was pseud ostratified columnar and sim ple low columnar. Histological ana lysis refer s to a preparation of a fifty-days-old em bryo. The author believed tha t the cyst had arisen from an aberrant proliferation and sequestration ofa portion of the primitive epimyocardial mantle at a stage compa ra ble to that of the 5-somite emb ryo. During this stage a prolifer ation of the cardiagenic folds ta kes place to form the atrioventricular sulci. The possible forma tion of cysts from the perimyocardial mantle at the time when the cardiogenic folds were closing around the endothelial tubes vent ral to the foregut in a 14-som ite embryo had already
Fig. 3 PAS photomicrographrevealing clearlythe existenceof asubepithelial basal membraneand showinga }- 2 layered columnar epithelium which is partly ciliated
been me ntioned by Davis (3) an d later on by lleuser (8) who studied the same cases. In our opinion, an anomaly in the development of the emb ryo might explain both the epithe lial valvular heterotopia and the multiple cardiac malformations in this patient. During early embryogenic life, the mesocar dium dorsale separates the simple rudimentary tubular heart from the buccopharyngeal mem bra ne an d the foregut. Tbese structures are lined by endodermal epithelium and unde rgo a dilTer entiation into pharynx, thyroid paren chyma , respiratory tract, esophagus, and upper gastrointes tinal tra ct. During further differentiation the primitive heart undergoes a complicated sequenc e of rotat ions and
Downloaded by: University of British Columbia. Copyrighted material.
Discussion
G. Mach ens . c-r. vohl. R. Hofma nn, D. IFolf. and S //agl
Thom e. cardiol'asc . Su rgeon 3 9 (19 91)
involutions , which form the heart cham bers and atria. During this per iod port ions of the foregut may become pinched off into the mesocard ium dorsale, formin g a so-called epithelial keel (4). Fragments of this epithelial keel might be the source of the heterotopic cyst that we found on the se ptal tricusp id leaflet.
10
II
12
Refer ences I
2
3
4
5 6
g
9
13
Anderson. W. A D., and E. T. Dmy try k : Primary tumor of the hea rt
conta ining epith elium-like elements . Am. J. Path . 22 (194 6) 33 7-349 Armstrong. H.. un d J. G. Monckeberq . Herzblock bedingt durch prtmaren Herztumor bei einem Sja hrigen Kinde. Dtsch . Arch. Klin . Med .l 02 (1911 ) 144-1 66 Daois. C. L.: Development of the human heart from its first a ppearance to the sta ge found in emb ryos of twenty paired somites. Contrib . Embryo!. 19 (192 7) 24 5- 284 Dosc h. F.: Uber eine n Fallvon Glandula thyreoidea accessoria intraca rdialis. Beitr. pathol. Anat. 105 (1941) 244 -2 55 De La croix . F.. and G. Hubner: Ciliated epithelial inclusion cyst ofthe heart. Beitr. Path . 151 (1974) 103- 110 Duray. P. t t., E. J. M ark, K. W. Barwi ck et a i.: Congenital polycystic tumor of the atrioventricular node . Autopsy study with immunohistochemical findings suggest ing endoderma l derivation. Arch. Patho!' Lab. Med. 109 (1965) 30- 34 Fine. G.. and A. R. Mora les: Mesoth elioma of the at rioventricular node . Arch . Path. 92 (1971) 402 -408 Heus er. C. H.: A human embryo with 14 pairs of somites. Contrib. Embryo!. 22 (1930) 135- 154 Kindred. J. E.: A cyst in the primord ium of the tr icuspid valve of an abn or mal human embryo. Am. J . Path. 33 (1957) 967- 975
14 IS
16
Ii
Leigh ton, J.. J. Hur s t. and J. Cra wford: Squamo us ep ithelial cysts in
the heart of an infant with coincident cystic changes in the ovaries an d breasts . Arch . Path . 50 (1950) 632-64 3 Linder. 1.. J. D. Shelburne, and J. P. Sorge: Congenita l en dodermal heter otopia of the atr ioventricular node: evidence for the en dodermal origin of so-called mesotheliomas of th e at riovent ricular node. Hum. Patho!' 15 (1984) 1093-1 098 Maha im.l.: Le coelotheliome tawarien benin: un tum eur sui gen er is du noeud de Taware avec bloc du cceur. Card iologia 6 (1942) 57- 82 Maha im. I.: Les tumeur s et les polypes du cceur. Etude ana tomoclinique. Monogra phic de l'lnsti tute d'a natomie pathologtque de l'Universite de Lau sanne (1945) Morr is, A S ., and I. AI. John son : Epithelial inclusion cysts of the hear t. Arch. Path. 77 (196 4) 36-40 Rez ek . P.: Ober eine primare epithell ale Gesch wulst an der Gegen d des Reizleitungssystems beim Menschen. Vlrchows Arc h. 301 (1938) 305- 320 Traoers. 11. : Congenital polycystic tu mor of the atriovent ricular node. Possible familial occurre nce and critical review of rep orted cases with special emphasis on histogenesis. Hum. Path ol. 13 (1982) 25-35 Wolf. P. I.. and R. Bing: The sma llest tu mor which ca uses sudden death. JAMA 194 (196 5) 674 - 675
Dr. C.-F. Vahl Department of Cardiac Surge ry University of Ileidelberg 1m Neuenh eimer Feld 110 0 -6900 Heidelberg Germa ny
Downloaded by: University of British Columbia. Copyrighted material.
298
