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Asymptomatic Mediastinal Lymph Node Hyperplasia of Eighteen Years Duration
Asymptomatic Mediastinal Lymph Node Hyperplasia of Eighteen Years Duration* Report of a Case SOL01\lON
R.
IkRSACK, 1\1 .0. AND JOHN
S. HOWE,
1\1.0 .
Washingt on , D. C.
I
1956, CASTLEMAN, IVERSO;\l AND Menderez' described the entity of localized mediastinal lymph node hyperplasia resembling thymoma. They studied 13 cases and concluded that the lymph node mass is neither of thymic origin nor neoplastic, hut rather represents a nonspecific inflammatory proces.<;. We have encountered a case of mediastinal lymph node hyperplasia which lacked the feature of resemblance to thymoma. The patient was followed for 18 years and the large lymph node mass remained unchanged in size and asymptomatic.
of March 27, 1952 showed enlargement of the heart, especially in its left ventricular component. The semi-oval mass was clearly depicted ( Fig. 2) contiguous with the posterior aspe ct of the right cardiac silhouette. In retrospect, one can faintly discern stippled and curvilinear calcifications within it, but these were not appreciated a t that time. Angiocardiography showed enlargement of the cardiac chambers, but no opacification of the right paracardiac shadow. The previous diagnosis of aortic aneurysm was therefore discarded and was substituted by a provisional diagnosis of pericardia] cyst or benign mediastinal tumor. Thorough physical examination failed to disclose any palpable abdominal organ or superficial lymphadenopathy.
N
In September, 1955 and July, 1956 he suffered two more bouts of bronchopneumonia with good response to antibiotic therapy. His final admission occurred on October 23, 1956 because of
CASE REPORT
The patient (C.R .C . ) , a Negro veteran, was 48 years old upon his admission to the 1\11. Alto Veterans Hospital on January 6, 1941. Hi s chief complaints were chills , fever and hemoptysis of two days' duration. A diagnosis of pneumonia was made and he was successfully treated. The roentgenograms of the chest taken on January 6, 1941 and on January IS, 1941 (Fig. I) visualized the pneumonic consolidation in the left hmg and in addition revealed a curved hand-shaped density adjacent to the right border of the heart. It measured 15 x 7 em . In view of a history of a previously positive blood Wassermann test, this opacity was interpreted as the visible portion of an aneurysm arising from the descending aorta . A similar interpretation of this density was made during hospitalization for pneumonia at 'Valter Reed Army Hospital in October, 1938. He denied any knowledge of having had a primary syphilitic lesion and no positive serologic findings were ever established henceforth. The past history included furunculosis, an occasional boil and three previous episodes of pneumonia. On March 10, 1952, he was readmitted for bronchopneumonia of the left lower lobe, which readily cleared on penicillin therapy. Electrocardiograms revealed left ventricular hypertrophy and frequent auricular and occasional ventricular premature beats. The roentgenogram of the chest
FIGURE I : Roentgenogram of the chest of January IS , 1941 showing a large band -shaped density protruding along the right border of the heart. Pneumonic patch in left mid-lung field.
*From the Radiology and Pathology Departments, Mt. Alto Veterans Hospital.
443
444
BERSACK AND HOWE
Diseases of the Chest
choscopic biops y yielded a diagnosis of squamous cell car cinoma of the left lung. The patient's general condition precluded surgical intervention. He expired on November 8, 1956. Necropsy report : the pertinent postmortem finding was an oval firm mass (15 x 7 x 2 cm .) which occupied the right posteri or mediastinum and extended anteriorly to its junction with the middle mediastinum. It was loosely attached to the external surface of the right main bronchus. It showed no connection or adherence to the heart, aorta or posterior parietal pleura. Sections of this mass reveal ed a dark brownish surface resembling lymphoid tissue. There were a few focal hemorrhages and moderately large areas of calcification and bone formation (Fig. 3B) . The
2 : Right anterior oblique view depict ing the posterior mediastinal mass extending anteriorly in contiguity with the enlarged cardiac silhouette.
FIGURE
chills, fever and left pleuritic pain of one week's duration. The roentgenogram of October 30, 1956 (Fig. 3A) disclosed the new finding of complete atelectasis of the left upper lobe. Bron-
FIGURE 3B : Roentgenogram of a portion of the mediastinal mass obtained at necropsy showing stippled and whorled calcification.
FIGURE 3A : Roentgenogram of the chest of October 30, 1956 showing atelectasis of the left upper lobe due to bronchogenic carcinoma. The right lower mediastinal mass is retracted to the left and thus partly hidden behind the heart.
other positive necropsy findings whi ch were not related to the right mediastinal ma ss included : 1. squamous cell carcinoma of the left stem bronchus; 2. chronic emphysema ; 3. coronary atherosclerosis; 4. left ventricular hypertrophy, moderate with marked focal myocardial fibrosis; 5. hypertrophy and dilatation of the right heart. Mi croscopic examination (Fig. 4A and B) shows the medi astinal tumor to consist of a mass of lymphoid tissue in which individual lymph node structure cannot be made out. There
Volume 43. No.4 April 1963
MEDIASTINAL LYMPH NODE HYPERPLASIA
FIGURE 4 : Microphotographs. A. (upper ) (x 70 ). Showing the lymphoid stru cture with small follicles lacking prominent germinal cent ers. B. ( lower) (x200) . Section depi ctin g the follicular stru ctu re, the increased vascula rity and the interve ning hyaline material.
is a large a mou nt o f pink -staining h yal ine materi al sca tte red th rou ghout th e sectio n; th is te nds to foll ow th e reti cul a r patt ern of th e stroma of th e nod e or to surro und vessels. Occasiona l calci fic dep osits ar e pr esent in th e hyaline a rea s. The inte rve ning lym ph oid tissue shows num erou s sma ll foll icles with increa sed vasc ula rity. Most of the ce lls are mature lym ph ocytes, hut co llections of pl asm a ce lls a rc frequent a nd occas iona l eosi nophi ls a rc not ed . Also prese nt a rc a few la rge ret icu lum ce lls with promine nt n ucleoli, a nd ra rely a mu lti nuc lea ted re tic ulum cell is seen. N o m edulla ry sinuses arc d iscern ibl e. No epi the lia l ma sses, no conce n tric nests o f ce lls and nothing resembling H assal l's corp uscles a rc seen. DI S C USSIO:-I
From a radiologic viewp oint, one has to consider many disease ent ities wh ich ma y produce a mass adjace nt to the posterior aspect of the middle mediastinum. Lyrn-
445
phoma and mediastinal granuloma, due to tuberculosis or histoplasmosis, represent the more common causes of a unilateral med iastin al mass. In most of the mediastinal granulomas the mass is small, although Karlson and Timmes' described a 4 x 6 cm. cystic granuloma at the left heart border. The long duration would be unusual for Hodgkin's disease, although several cases of over 20 years survi val have been reported. However, there is no case on record of a large mediastinal mass later proved to be Hodgkin's disease or localized plasmacytoma, which remained unchanged in size and asymptomatic over such a long period of observation. Angiocardiography ruled out an aneurysm of the descending aorta protruding to the right of the cardiac silhouette. The presence of irregular deposits of calcium within the opa city would speak aga inst a pericardial or an enterogenous cyst. The differ ential diagnosis would still include teratoma, hamartoma, amyloid tumor, ectopic myelopoietic mass, myelolipoma or benign neoplasm of th ymic or vascular origin and localized lymph node hyperplasia. Castleman et at.,' in defining the entity of localized lymph node hyperpl asia of the med iastinum, emphasized the two histologic features ; namely, (a ) hyperplasia of lymphoid follicles, with or with out germinal center formation , and (b) marked capillary proliferation with end othelial hyperplasia. When these int rafollicular capillaries with hyperplasti c end othelium had thick hyalinized walls, the y often assumed a concentric arra ngement which was accentuated when the capillary lumina were obliterated - thus prod ucing a resemblance to Hassalls' corpuscles of the thymus. The presence of plasma cells and eosinophil s further stre ngthened their interpretation of the lesion as a chronic nonspe cific inflammatory pr ocess. As in our case, Castleman et at. also found in some sections large reticulum cells, some with prominent nucle i that faintl y resembled Reed - Sternberg cells. However, these were not sufficiently diagnostic to consider the lesion the earliest
Diseases of the Chest
BERSACK AND HOWE
benign form of Hodgkin's paragranuloma. Recently, Lattes and Pachter" challenged the inflammatory hyperplastic origin interpretation of these lymphoid masses. They argued that "the complete absence of a regular sinusoidal architecture would be against any theory that would suggest that these masses are just hyperplastic lymph nodes. Further, these masses occurred in regions such as muscles and other soft tissues of the extremities in which lymph nodes are not normally present." They made the suggestion that these masses of lymphoid tissue were hamartomas or in the case of the intramuscular and subcutaneous tumors, choristomas. Katz and Dziadiw" described a case which roentgenographically simulated posterior mediastinal neurofibroma. The mass was extrapleural, appeared to arise from the third and fourth intervertebral foramina and was adherent to a segment of the sympathetic chain. Inada et al? reported a patient with giant (16 x 9 x 5.5 em.) lymph node hyperplasia of the mediastinum and summarized four additional cases from the Japanese literature. They noted the interesting finding that histologically no typical lymphoid follicles with prominent germinal centers were found in the two cases of focal calcification, while they were pronl-
inent features in the other three cases. The lymphoid mass of our patient had focal calcifications and even ossification, but lacked the features of prominent germinal centers or configurations resembling HassaIl's corpuscles. Whether one considers these lymphoid masses as hamartomas or of inflammatory hyperplastic origin, it remains to be seen, as more cases are studied, whether two distinct subgroups will emerge; namely, those with prominent germinal centers (and resemblance to Hassall's corpuscles) but no focal calcification, and those exhibiting focal calcification, but lacking prominent germinal centers. REFERENCES CASTLEMAN, B., IVERSON, L. AND MENDEREZ, v. P.: "Localized Mediastinal Lymph Node Hyperplasia Resembling Thymoma," Cancer, 9:822, 1956.
2 KARLSON, K. E. AND TIMMES, J. J.: "Granulomata of the Mediastinum Surgically Treated and Followed Up to Nine Yaers," ]. Thor. Surg., 35: 617, 1958. 3 LATTES, R. AND PACHTER, M. R.: "Benign Lymphoid Masses of Probable Hamartomatous Nature, Analysis of 12 Cases," Cancer, 15: 197, 1962. 4 KATZ, I. AND DZIADIW, R.: "Localized Mediastinal Lymph Node Hyperplasia," Am. ]. Roentgenol., 84: 206, 1960. 5 INADA, K., KAWAI, K., KATSUMURA, T. AND NAKANO, A.: "Giant Lymph Node Hyperplasia of the Mediastinum," Am. Rev. Tuberc., 79: 232, 1959.
INTERNAL MAMMARY ARTERY IMPLANTATION Eleven patients operated upon by Internal mammary artery Implantation one to eight years ago have been studied. They showed unexpectedly good cllnlcal Improvement, with necropsy and cineangiographic evidence of patency of the implanted artery; In one case, this was eight years after operation. This report is not a plea for the widespread adoption of the operation of internal mammary artery implantation. Even in the most carefully selected group of patients represented, the results are good
but not dramatic. Extending the indications to a larger group of patients may make these results less acceptable. The remarkable feature, however, is the radiographic confirmation that an open and bleeding artery implanted into the heart will remain patent and apparently provide a source of blood supply to the heart. W. G., BASIAN, H. AND GRUSLER, G. A.: "Internal Mammary Artery Implantation for Coronary Heart Disease," l- Thor. and Cardiovas, Surg», 4~ :67, 1963.
BIGELOW,
R.
IkRSACK, 1\1 .0. AND JOHN
S. HOWE,
1\1.0 .
Washingt on , D. C.
I
1956, CASTLEMAN, IVERSO;\l AND Menderez' described the entity of localized mediastinal lymph node hyperplasia resembling thymoma. They studied 13 cases and concluded that the lymph node mass is neither of thymic origin nor neoplastic, hut rather represents a nonspecific inflammatory proces.<;. We have encountered a case of mediastinal lymph node hyperplasia which lacked the feature of resemblance to thymoma. The patient was followed for 18 years and the large lymph node mass remained unchanged in size and asymptomatic.
of March 27, 1952 showed enlargement of the heart, especially in its left ventricular component. The semi-oval mass was clearly depicted ( Fig. 2) contiguous with the posterior aspe ct of the right cardiac silhouette. In retrospect, one can faintly discern stippled and curvilinear calcifications within it, but these were not appreciated a t that time. Angiocardiography showed enlargement of the cardiac chambers, but no opacification of the right paracardiac shadow. The previous diagnosis of aortic aneurysm was therefore discarded and was substituted by a provisional diagnosis of pericardia] cyst or benign mediastinal tumor. Thorough physical examination failed to disclose any palpable abdominal organ or superficial lymphadenopathy.
N
In September, 1955 and July, 1956 he suffered two more bouts of bronchopneumonia with good response to antibiotic therapy. His final admission occurred on October 23, 1956 because of
CASE REPORT
The patient (C.R .C . ) , a Negro veteran, was 48 years old upon his admission to the 1\11. Alto Veterans Hospital on January 6, 1941. Hi s chief complaints were chills , fever and hemoptysis of two days' duration. A diagnosis of pneumonia was made and he was successfully treated. The roentgenograms of the chest taken on January 6, 1941 and on January IS, 1941 (Fig. I) visualized the pneumonic consolidation in the left hmg and in addition revealed a curved hand-shaped density adjacent to the right border of the heart. It measured 15 x 7 em . In view of a history of a previously positive blood Wassermann test, this opacity was interpreted as the visible portion of an aneurysm arising from the descending aorta . A similar interpretation of this density was made during hospitalization for pneumonia at 'Valter Reed Army Hospital in October, 1938. He denied any knowledge of having had a primary syphilitic lesion and no positive serologic findings were ever established henceforth. The past history included furunculosis, an occasional boil and three previous episodes of pneumonia. On March 10, 1952, he was readmitted for bronchopneumonia of the left lower lobe, which readily cleared on penicillin therapy. Electrocardiograms revealed left ventricular hypertrophy and frequent auricular and occasional ventricular premature beats. The roentgenogram of the chest
FIGURE I : Roentgenogram of the chest of January IS , 1941 showing a large band -shaped density protruding along the right border of the heart. Pneumonic patch in left mid-lung field.
*From the Radiology and Pathology Departments, Mt. Alto Veterans Hospital.
443
444
BERSACK AND HOWE
Diseases of the Chest
choscopic biops y yielded a diagnosis of squamous cell car cinoma of the left lung. The patient's general condition precluded surgical intervention. He expired on November 8, 1956. Necropsy report : the pertinent postmortem finding was an oval firm mass (15 x 7 x 2 cm .) which occupied the right posteri or mediastinum and extended anteriorly to its junction with the middle mediastinum. It was loosely attached to the external surface of the right main bronchus. It showed no connection or adherence to the heart, aorta or posterior parietal pleura. Sections of this mass reveal ed a dark brownish surface resembling lymphoid tissue. There were a few focal hemorrhages and moderately large areas of calcification and bone formation (Fig. 3B) . The
2 : Right anterior oblique view depict ing the posterior mediastinal mass extending anteriorly in contiguity with the enlarged cardiac silhouette.
FIGURE
chills, fever and left pleuritic pain of one week's duration. The roentgenogram of October 30, 1956 (Fig. 3A) disclosed the new finding of complete atelectasis of the left upper lobe. Bron-
FIGURE 3B : Roentgenogram of a portion of the mediastinal mass obtained at necropsy showing stippled and whorled calcification.
FIGURE 3A : Roentgenogram of the chest of October 30, 1956 showing atelectasis of the left upper lobe due to bronchogenic carcinoma. The right lower mediastinal mass is retracted to the left and thus partly hidden behind the heart.
other positive necropsy findings whi ch were not related to the right mediastinal ma ss included : 1. squamous cell carcinoma of the left stem bronchus; 2. chronic emphysema ; 3. coronary atherosclerosis; 4. left ventricular hypertrophy, moderate with marked focal myocardial fibrosis; 5. hypertrophy and dilatation of the right heart. Mi croscopic examination (Fig. 4A and B) shows the medi astinal tumor to consist of a mass of lymphoid tissue in which individual lymph node structure cannot be made out. There
Volume 43. No.4 April 1963
MEDIASTINAL LYMPH NODE HYPERPLASIA
FIGURE 4 : Microphotographs. A. (upper ) (x 70 ). Showing the lymphoid stru cture with small follicles lacking prominent germinal cent ers. B. ( lower) (x200) . Section depi ctin g the follicular stru ctu re, the increased vascula rity and the interve ning hyaline material.
is a large a mou nt o f pink -staining h yal ine materi al sca tte red th rou ghout th e sectio n; th is te nds to foll ow th e reti cul a r patt ern of th e stroma of th e nod e or to surro und vessels. Occasiona l calci fic dep osits ar e pr esent in th e hyaline a rea s. The inte rve ning lym ph oid tissue shows num erou s sma ll foll icles with increa sed vasc ula rity. Most of the ce lls are mature lym ph ocytes, hut co llections of pl asm a ce lls a rc frequent a nd occas iona l eosi nophi ls a rc not ed . Also prese nt a rc a few la rge ret icu lum ce lls with promine nt n ucleoli, a nd ra rely a mu lti nuc lea ted re tic ulum cell is seen. N o m edulla ry sinuses arc d iscern ibl e. No epi the lia l ma sses, no conce n tric nests o f ce lls and nothing resembling H assal l's corp uscles a rc seen. DI S C USSIO:-I
From a radiologic viewp oint, one has to consider many disease ent ities wh ich ma y produce a mass adjace nt to the posterior aspect of the middle mediastinum. Lyrn-
445
phoma and mediastinal granuloma, due to tuberculosis or histoplasmosis, represent the more common causes of a unilateral med iastin al mass. In most of the mediastinal granulomas the mass is small, although Karlson and Timmes' described a 4 x 6 cm. cystic granuloma at the left heart border. The long duration would be unusual for Hodgkin's disease, although several cases of over 20 years survi val have been reported. However, there is no case on record of a large mediastinal mass later proved to be Hodgkin's disease or localized plasmacytoma, which remained unchanged in size and asymptomatic over such a long period of observation. Angiocardiography ruled out an aneurysm of the descending aorta protruding to the right of the cardiac silhouette. The presence of irregular deposits of calcium within the opa city would speak aga inst a pericardial or an enterogenous cyst. The differ ential diagnosis would still include teratoma, hamartoma, amyloid tumor, ectopic myelopoietic mass, myelolipoma or benign neoplasm of th ymic or vascular origin and localized lymph node hyperplasia. Castleman et at.,' in defining the entity of localized lymph node hyperpl asia of the med iastinum, emphasized the two histologic features ; namely, (a ) hyperplasia of lymphoid follicles, with or with out germinal center formation , and (b) marked capillary proliferation with end othelial hyperplasia. When these int rafollicular capillaries with hyperplasti c end othelium had thick hyalinized walls, the y often assumed a concentric arra ngement which was accentuated when the capillary lumina were obliterated - thus prod ucing a resemblance to Hassalls' corpuscles of the thymus. The presence of plasma cells and eosinophil s further stre ngthened their interpretation of the lesion as a chronic nonspe cific inflammatory pr ocess. As in our case, Castleman et at. also found in some sections large reticulum cells, some with prominent nucle i that faintl y resembled Reed - Sternberg cells. However, these were not sufficiently diagnostic to consider the lesion the earliest
Diseases of the Chest
BERSACK AND HOWE
benign form of Hodgkin's paragranuloma. Recently, Lattes and Pachter" challenged the inflammatory hyperplastic origin interpretation of these lymphoid masses. They argued that "the complete absence of a regular sinusoidal architecture would be against any theory that would suggest that these masses are just hyperplastic lymph nodes. Further, these masses occurred in regions such as muscles and other soft tissues of the extremities in which lymph nodes are not normally present." They made the suggestion that these masses of lymphoid tissue were hamartomas or in the case of the intramuscular and subcutaneous tumors, choristomas. Katz and Dziadiw" described a case which roentgenographically simulated posterior mediastinal neurofibroma. The mass was extrapleural, appeared to arise from the third and fourth intervertebral foramina and was adherent to a segment of the sympathetic chain. Inada et al? reported a patient with giant (16 x 9 x 5.5 em.) lymph node hyperplasia of the mediastinum and summarized four additional cases from the Japanese literature. They noted the interesting finding that histologically no typical lymphoid follicles with prominent germinal centers were found in the two cases of focal calcification, while they were pronl-
inent features in the other three cases. The lymphoid mass of our patient had focal calcifications and even ossification, but lacked the features of prominent germinal centers or configurations resembling HassaIl's corpuscles. Whether one considers these lymphoid masses as hamartomas or of inflammatory hyperplastic origin, it remains to be seen, as more cases are studied, whether two distinct subgroups will emerge; namely, those with prominent germinal centers (and resemblance to Hassall's corpuscles) but no focal calcification, and those exhibiting focal calcification, but lacking prominent germinal centers. REFERENCES CASTLEMAN, B., IVERSON, L. AND MENDEREZ, v. P.: "Localized Mediastinal Lymph Node Hyperplasia Resembling Thymoma," Cancer, 9:822, 1956.
2 KARLSON, K. E. AND TIMMES, J. J.: "Granulomata of the Mediastinum Surgically Treated and Followed Up to Nine Yaers," ]. Thor. Surg., 35: 617, 1958. 3 LATTES, R. AND PACHTER, M. R.: "Benign Lymphoid Masses of Probable Hamartomatous Nature, Analysis of 12 Cases," Cancer, 15: 197, 1962. 4 KATZ, I. AND DZIADIW, R.: "Localized Mediastinal Lymph Node Hyperplasia," Am. ]. Roentgenol., 84: 206, 1960. 5 INADA, K., KAWAI, K., KATSUMURA, T. AND NAKANO, A.: "Giant Lymph Node Hyperplasia of the Mediastinum," Am. Rev. Tuberc., 79: 232, 1959.
INTERNAL MAMMARY ARTERY IMPLANTATION Eleven patients operated upon by Internal mammary artery Implantation one to eight years ago have been studied. They showed unexpectedly good cllnlcal Improvement, with necropsy and cineangiographic evidence of patency of the implanted artery; In one case, this was eight years after operation. This report is not a plea for the widespread adoption of the operation of internal mammary artery implantation. Even in the most carefully selected group of patients represented, the results are good
but not dramatic. Extending the indications to a larger group of patients may make these results less acceptable. The remarkable feature, however, is the radiographic confirmation that an open and bleeding artery implanted into the heart will remain patent and apparently provide a source of blood supply to the heart. W. G., BASIAN, H. AND GRUSLER, G. A.: "Internal Mammary Artery Implantation for Coronary Heart Disease," l- Thor. and Cardiovas, Surg», 4~ :67, 1963.
BIGELOW,