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Distribution of thymic tissue in the mediastinal adipose tissue
J
THORAC CARDIOVASC
SURG 1991;101:1099-1102
Distribution of thymic tissue in the mediastinal adipose tissue The distribution of thymic tissue in the anterior mediastinal, retrocarinal, and preaortic fat was examined histologically in 27 autopsy subjects. Thymic tissue was found in the anterior mediastinal fat in 12 subjects (44.4 %), in the retrocarinal fat in two (7.4 %), and in the preaortic fat in none. The finding of ectopic thymic tissue in these areas has not been reported previously, would appear to be surgically inaccessible via a median sternotomy, and may be responsible in part for some of the failures of thymectomy in the treatment of myasthenia gravis.
Ichiro Fukai, MD, Yoshihiko Funato, MD, Tsutomu Mizuno, MD, Takahiko Hashimoto, MD, and Akira Masaoka, MD, Nagoya, Japan
Lymectomy has been demonstrated to be effective in the treatment of myasthenia gravis. It is now believedthat the more complete the resection, the higher the remission rate. There are a group of patients, however, who have only a partial response or no response after what is considered to be a total thymectomy. This has led to the speculation that ectopic thymus had been overlooked. This study was undertaken to confirm the presence of microscopic foci of thymic tissue in the anterior mediastinal fat and to see if thymic tissue could be identified in other areas of the mediastinum. Materials and methods Anterior mediastinal, retrocarinal, and preaortic adipose tissue was searched for in 27 consecutive autopsies performed at the Nagoya City University Medical School from September 1987 to February 1988 (Table I). None of these subjects had myasthenia gravis, thymoma, or other thymic abnormalities. The age range was birth (neonatal) to 89 years (mean 60). Fifteen were male and 10 were female; the sex of two is not known. The anterior mediastinal adipose tissue consisted of the gross fat that was contiguous with the lower poles of the identifiable thymus; this tissue is usually excised in the en bloc extended thymectomy that we perform. The retrocarinal adipose tissue lay posterior to the carina in the region of Botallo's lymph node. The tissue removed extended from the carina to the aortic arch. From the Second Department of Surgery, Nagoya City University Medical School, Nagoya, Japan. Received for publication Jan. 31, 1990. Accepted for publication July 9, 1990. Address forreprints: IchiroFukai,MD,SecondDepartmentofSurgery, Nagoya City University Medical School, Mizuhoku, Nagoya, Japan. 12/1/24526
Thymus
Retrocarinal adipose tissue
Preaortic adipose tissue
Inferior pulmonary vein
Fig. 1. Location of anterior mediastinal, retrocarinal, and preaortic adipose tissue. The preaortic adipose tissue was located anterior to the descending aorta; tissue removed extended from the inferior pulmonary vein to the descending aorta (Fig. 1). Multiple microscopic sections were taken from each specimen, were stained with hematoxylin and eosin, and were examined microscopically to determine the presence or absence of thymic tissue. The presence of thymic remnants was determined by the identification of Hassall's corpuscles. If thymic remnants were suspected but did not contain Hassall's corpuscles, additional samples were incubated with a rabbit antikeratin antibody followed by antirabbit serum and antiperoxidase complex (DAKOPATIS PAP Kit Code K528; Dako Corporation, Santa Barbara, Calif.). Sections were then stained with an immu-
1099
1 10 0
The J ourna l of Thorac ic and Ca rdiovas cular Surg ery
Fukai et al.
"
.'
Fig. 2. Immunocytochemical stai ning for cytokeratin of a nterior mediastinal adipose tissue of 55-year-o ld woman who died of urin ar y bladd er ca ncer. Arrows indicate cytoke ratin-positive cells. (Ori ginal mag nification XSO.)
Table I. Summary of 27 autopsy subj ects Age Sex Ma le Fema le U nk nown Diagnosis Maligna ncy Pneumonia Cerebr al infa rction Dissem inated intravascular coag ulation Sepsis U nknown
0-89 (mea n 60)
15 10 2 21 2 I I I I
nocytochemical staining for cytokerat in to confirm the presence of th ymic epithelium.
Results At autopsy no adipose tissue was identified in the anterior mediastinum below the level of the thymus in 7 of the 27 subjects, and none in the retrocarinal area in 1 of the 27 subjects. Adipose tissue was found in all 27 subjects in the preaortic area. The major portion of the specimens consisted of fat. In the sections stained with hematoxylin and eosin from the anterior mediastinal fat , thymus was thought to be present in 13. Immunocytochemical staining for cytokerat in excluded one of these cases (Fig. 2). Hass all's corpuscles were observed histologically in five of the remaining 12. Accordingly, thymic tissue was identified in 12 of the 27 cases (44.4%).
Table II. Distribution of microscopic thymic tissue Position of adipose tiss ue Anterior med iastinum Ret roca rinal Preaort ic
Thymic tissue
Hassall 's corpuscle
12/ 27 (44.4%)
5/ 12 (41.7%)
2/27 (7.4%) 0/27 (0%)
2/2 (100%)
In the sections stained with hematoxylin and eosinfrom the retrocarinal adipose tissue, thymus was identified in two (7.4%) of 27. Hassall's corpuscles were present in both (Fig. 3). In the preaortic adipose tissue, thymic remnants were suspected in one specimen. However, imrnunocytologic staining was negative for cytokeratin. Accordingly , thymus was not identified in the preaortic adipose tissue in any of the 27 specimens (Table II). The ages of the individuals who were found to have microscopic foci of thymus in the anterior mediastinum were 37 to 89; in the ret rocarinal area they were 67 and 74.
Discussion It is gener ally accepted that thymectomy is the preferred treatment for patients with generalized myasthenia gravis. It is also generall y agreed that total thymectomy is the goal of operation. It is though t that the more complete the thymectomy the higher the remission rates. I. 2 However , controversy continues as to the surgical approach and the extent of the resection that is necessary
Volume 101 Number 6
Thymic tissue in mediastinal adipose tissue
June 1991
I I0 I
c: -;
,"
.'
"
,~
-.. . . ...
.., ,
.
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.,
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B Fig. 3. Retrocarinal adipose tissue in a 67-year-old man who died oflung cancer. A, Some thymic tissue can be seen. (Hematoxylin and eosin stain; original magnification XS.) B, Higher magnification of A. Hassall's corpuscles are clearly observed. (Original magnification X40.)
to achieve these results. Clearly, however, to achieve complete removal of the thymus gland it is necessary to recognize the various locations ofectopic thymus.' Jaretzki and Wol~ have demonstrated the extent of thymus in the neck and anterior mediastinum and advocate a transcervical-transsternal "maximal" thymectomy to remove en bloc all thymic tissue from these areas. Others- believe the cervical thymus is accessible by means of median sternotomy alone and does not require a separate cervical incision. This study reconfirms our previous observation that microscopic thymus is frequently found in the anterior
mediastinal fat distal to the visible thymus. Although in this study it was found in this location in only 44.4% of the specimens compared with 72.2% in our previous study," this disparity is readily explained by the fact that the subjects in the present study did not have myasthenia gravis. Accordingly, these findings confirm the desirability of the en bloc resection of the anterior mediastinal fat in performing thymectomy for myasthenia gravis. The finding of thymic tissue in the retrocarinal area in two of 27 (7.4%) of the autopsy specimens is surprising. Although this region is close to the "aortic pulmonary window" region described by Jaretzki and Wolff,4 it
The Journal, of,
1 1 0 2 Fukai et al.
appears to be separate. They found thymus in the "aortopulmonary window" in 19 of 50 (38%) surgical anatomic specimens removed at the time of "maximal" thymectomy for myasthenia gravis. The discrepancy between these two findings can be explained as follows: (1) The two areas are not identical, (2) the aortopulmonary window area is contiguous with the anterior mediastinal fat, and (3) this autopsy study contained no individuals with myasthenia gravis, thymoma, or other thymic abnormalities. In any case the possibility exists that the presence of ectopic thymic tissue in the retrocarinal area is being overlooked at the time of thymectomy for myasthenia gravis. This may explain why a small percentage of patients with myasthenia gravis do not show improvement after an operation that otherwise appears to represent a total thymectomy. Further investigation may reveal other variations. Unfortunately it seems probable that thymic tissue in this area cannot be detected preoperatively with the presently available means of study. Hentze and colleagues? noted that all attempts to detect remnants of thymus before reoperations in patients who had previouslyundergone a transcervical thymectomy for myathenia gravis (including the use of computed tomography, gallium scans, and selenium scans) were unsuccessful. In conclusion, it has generally been accepted that the more complete the thymectomy in the treatment of myasthenia gravis, the better the results. Accordingly,
Thoracic and Cardiovascular Surgery
continued attempts to perform as complete a resection as possibleare indicated. This study, however,indicates that in very occasional instances microscopic thymic tissue may not be accessible surgically via median sternotomy.
1.
2.
3.
4.
5.
6.
7.
REFERENCES Penn AS. Jaretzki A III, Wolff M. Chang HW. Tennyson V. Thymic abnormalities: antigen or antibody? Response to thymectomy in myasthenia gravis. Ann N Y Acad Sci 1981;377:786-804. Rosenberg M. Jauregui WOo Vega MED, Herrera MR. Roncoroni AJ. Recurrence of thymic hyperplasia after thymectomy in myasthenia gravis: its importance as a cause of failure of surgical treatment. Am J Med 1983;74:78-82. Rosai J, Levine GD. Tumors of the thymus. In: Atlas of tumor pathology. Fascicle 13. Washington, D.C.: Armed Forces Institute of Pathology, 1976. Jaretzki A III, Wolff M. Maximal thymectomy for myasthenia gravis: surgical anatomy and operative technique. J THORAC CARDIOVASC SURG 1988;96:711-6. Masaoka A, Monden Y. Comparison of the results of transsternal simple, transcervical simple, and extended thymectomy. Ann N Y Acad Sci 1981;377:755-65. Masaoka A, Nagaoka Y, Kotake Y. Distribution of thymic tissue at the anterior mediastinum: current procedures in thymectomy. J THORAC CARDIOVASC SURG 1975;70:74754. Henze A, Biberfeld P, Christensson B. Matell G, Pirskanen R. Failing transcervical thymectomy in myasthenia gravis: an evaluation of transsternal re-exploration, Scand J Thorae Cardiovasc Surg 1984;18:235-8.
THORAC CARDIOVASC
SURG 1991;101:1099-1102
Distribution of thymic tissue in the mediastinal adipose tissue The distribution of thymic tissue in the anterior mediastinal, retrocarinal, and preaortic fat was examined histologically in 27 autopsy subjects. Thymic tissue was found in the anterior mediastinal fat in 12 subjects (44.4 %), in the retrocarinal fat in two (7.4 %), and in the preaortic fat in none. The finding of ectopic thymic tissue in these areas has not been reported previously, would appear to be surgically inaccessible via a median sternotomy, and may be responsible in part for some of the failures of thymectomy in the treatment of myasthenia gravis.
Ichiro Fukai, MD, Yoshihiko Funato, MD, Tsutomu Mizuno, MD, Takahiko Hashimoto, MD, and Akira Masaoka, MD, Nagoya, Japan
Lymectomy has been demonstrated to be effective in the treatment of myasthenia gravis. It is now believedthat the more complete the resection, the higher the remission rate. There are a group of patients, however, who have only a partial response or no response after what is considered to be a total thymectomy. This has led to the speculation that ectopic thymus had been overlooked. This study was undertaken to confirm the presence of microscopic foci of thymic tissue in the anterior mediastinal fat and to see if thymic tissue could be identified in other areas of the mediastinum. Materials and methods Anterior mediastinal, retrocarinal, and preaortic adipose tissue was searched for in 27 consecutive autopsies performed at the Nagoya City University Medical School from September 1987 to February 1988 (Table I). None of these subjects had myasthenia gravis, thymoma, or other thymic abnormalities. The age range was birth (neonatal) to 89 years (mean 60). Fifteen were male and 10 were female; the sex of two is not known. The anterior mediastinal adipose tissue consisted of the gross fat that was contiguous with the lower poles of the identifiable thymus; this tissue is usually excised in the en bloc extended thymectomy that we perform. The retrocarinal adipose tissue lay posterior to the carina in the region of Botallo's lymph node. The tissue removed extended from the carina to the aortic arch. From the Second Department of Surgery, Nagoya City University Medical School, Nagoya, Japan. Received for publication Jan. 31, 1990. Accepted for publication July 9, 1990. Address forreprints: IchiroFukai,MD,SecondDepartmentofSurgery, Nagoya City University Medical School, Mizuhoku, Nagoya, Japan. 12/1/24526
Thymus
Retrocarinal adipose tissue
Preaortic adipose tissue
Inferior pulmonary vein
Fig. 1. Location of anterior mediastinal, retrocarinal, and preaortic adipose tissue. The preaortic adipose tissue was located anterior to the descending aorta; tissue removed extended from the inferior pulmonary vein to the descending aorta (Fig. 1). Multiple microscopic sections were taken from each specimen, were stained with hematoxylin and eosin, and were examined microscopically to determine the presence or absence of thymic tissue. The presence of thymic remnants was determined by the identification of Hassall's corpuscles. If thymic remnants were suspected but did not contain Hassall's corpuscles, additional samples were incubated with a rabbit antikeratin antibody followed by antirabbit serum and antiperoxidase complex (DAKOPATIS PAP Kit Code K528; Dako Corporation, Santa Barbara, Calif.). Sections were then stained with an immu-
1099
1 10 0
The J ourna l of Thorac ic and Ca rdiovas cular Surg ery
Fukai et al.
"
.'
Fig. 2. Immunocytochemical stai ning for cytokeratin of a nterior mediastinal adipose tissue of 55-year-o ld woman who died of urin ar y bladd er ca ncer. Arrows indicate cytoke ratin-positive cells. (Ori ginal mag nification XSO.)
Table I. Summary of 27 autopsy subj ects Age Sex Ma le Fema le U nk nown Diagnosis Maligna ncy Pneumonia Cerebr al infa rction Dissem inated intravascular coag ulation Sepsis U nknown
0-89 (mea n 60)
15 10 2 21 2 I I I I
nocytochemical staining for cytokerat in to confirm the presence of th ymic epithelium.
Results At autopsy no adipose tissue was identified in the anterior mediastinum below the level of the thymus in 7 of the 27 subjects, and none in the retrocarinal area in 1 of the 27 subjects. Adipose tissue was found in all 27 subjects in the preaortic area. The major portion of the specimens consisted of fat. In the sections stained with hematoxylin and eosin from the anterior mediastinal fat , thymus was thought to be present in 13. Immunocytochemical staining for cytokerat in excluded one of these cases (Fig. 2). Hass all's corpuscles were observed histologically in five of the remaining 12. Accordingly, thymic tissue was identified in 12 of the 27 cases (44.4%).
Table II. Distribution of microscopic thymic tissue Position of adipose tiss ue Anterior med iastinum Ret roca rinal Preaort ic
Thymic tissue
Hassall 's corpuscle
12/ 27 (44.4%)
5/ 12 (41.7%)
2/27 (7.4%) 0/27 (0%)
2/2 (100%)
In the sections stained with hematoxylin and eosinfrom the retrocarinal adipose tissue, thymus was identified in two (7.4%) of 27. Hassall's corpuscles were present in both (Fig. 3). In the preaortic adipose tissue, thymic remnants were suspected in one specimen. However, imrnunocytologic staining was negative for cytokeratin. Accordingly , thymus was not identified in the preaortic adipose tissue in any of the 27 specimens (Table II). The ages of the individuals who were found to have microscopic foci of thymus in the anterior mediastinum were 37 to 89; in the ret rocarinal area they were 67 and 74.
Discussion It is gener ally accepted that thymectomy is the preferred treatment for patients with generalized myasthenia gravis. It is also generall y agreed that total thymectomy is the goal of operation. It is though t that the more complete the thymectomy the higher the remission rates. I. 2 However , controversy continues as to the surgical approach and the extent of the resection that is necessary
Volume 101 Number 6
Thymic tissue in mediastinal adipose tissue
June 1991
I I0 I
c: -;
,"
.'
"
,~
-.. . . ...
.., ,
.
'I
: . 1
.'
.,
"' ... ..
, :
-, 'w
B Fig. 3. Retrocarinal adipose tissue in a 67-year-old man who died oflung cancer. A, Some thymic tissue can be seen. (Hematoxylin and eosin stain; original magnification XS.) B, Higher magnification of A. Hassall's corpuscles are clearly observed. (Original magnification X40.)
to achieve these results. Clearly, however, to achieve complete removal of the thymus gland it is necessary to recognize the various locations ofectopic thymus.' Jaretzki and Wol~ have demonstrated the extent of thymus in the neck and anterior mediastinum and advocate a transcervical-transsternal "maximal" thymectomy to remove en bloc all thymic tissue from these areas. Others- believe the cervical thymus is accessible by means of median sternotomy alone and does not require a separate cervical incision. This study reconfirms our previous observation that microscopic thymus is frequently found in the anterior
mediastinal fat distal to the visible thymus. Although in this study it was found in this location in only 44.4% of the specimens compared with 72.2% in our previous study," this disparity is readily explained by the fact that the subjects in the present study did not have myasthenia gravis. Accordingly, these findings confirm the desirability of the en bloc resection of the anterior mediastinal fat in performing thymectomy for myasthenia gravis. The finding of thymic tissue in the retrocarinal area in two of 27 (7.4%) of the autopsy specimens is surprising. Although this region is close to the "aortic pulmonary window" region described by Jaretzki and Wolff,4 it
The Journal, of,
1 1 0 2 Fukai et al.
appears to be separate. They found thymus in the "aortopulmonary window" in 19 of 50 (38%) surgical anatomic specimens removed at the time of "maximal" thymectomy for myasthenia gravis. The discrepancy between these two findings can be explained as follows: (1) The two areas are not identical, (2) the aortopulmonary window area is contiguous with the anterior mediastinal fat, and (3) this autopsy study contained no individuals with myasthenia gravis, thymoma, or other thymic abnormalities. In any case the possibility exists that the presence of ectopic thymic tissue in the retrocarinal area is being overlooked at the time of thymectomy for myasthenia gravis. This may explain why a small percentage of patients with myasthenia gravis do not show improvement after an operation that otherwise appears to represent a total thymectomy. Further investigation may reveal other variations. Unfortunately it seems probable that thymic tissue in this area cannot be detected preoperatively with the presently available means of study. Hentze and colleagues? noted that all attempts to detect remnants of thymus before reoperations in patients who had previouslyundergone a transcervical thymectomy for myathenia gravis (including the use of computed tomography, gallium scans, and selenium scans) were unsuccessful. In conclusion, it has generally been accepted that the more complete the thymectomy in the treatment of myasthenia gravis, the better the results. Accordingly,
Thoracic and Cardiovascular Surgery
continued attempts to perform as complete a resection as possibleare indicated. This study, however,indicates that in very occasional instances microscopic thymic tissue may not be accessible surgically via median sternotomy.
1.
2.
3.
4.
5.
6.
7.
REFERENCES Penn AS. Jaretzki A III, Wolff M. Chang HW. Tennyson V. Thymic abnormalities: antigen or antibody? Response to thymectomy in myasthenia gravis. Ann N Y Acad Sci 1981;377:786-804. Rosenberg M. Jauregui WOo Vega MED, Herrera MR. Roncoroni AJ. Recurrence of thymic hyperplasia after thymectomy in myasthenia gravis: its importance as a cause of failure of surgical treatment. Am J Med 1983;74:78-82. Rosai J, Levine GD. Tumors of the thymus. In: Atlas of tumor pathology. Fascicle 13. Washington, D.C.: Armed Forces Institute of Pathology, 1976. Jaretzki A III, Wolff M. Maximal thymectomy for myasthenia gravis: surgical anatomy and operative technique. J THORAC CARDIOVASC SURG 1988;96:711-6. Masaoka A, Monden Y. Comparison of the results of transsternal simple, transcervical simple, and extended thymectomy. Ann N Y Acad Sci 1981;377:755-65. Masaoka A, Nagaoka Y, Kotake Y. Distribution of thymic tissue at the anterior mediastinum: current procedures in thymectomy. J THORAC CARDIOVASC SURG 1975;70:74754. Henze A, Biberfeld P, Christensson B. Matell G, Pirskanen R. Failing transcervical thymectomy in myasthenia gravis: an evaluation of transsternal re-exploration, Scand J Thorae Cardiovasc Surg 1984;18:235-8.