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Lymphography in Management of Lymphoma
LYDlphography in ManageDlent of LYDlphollla JOSEPH M. KIELY, M.D.
w.
EUGENE MILLER, M.D.
PAUL W. SCANLON, M.D.
Lymphography - the roentgenographic visualization of lymph vessels and nodes opacified by a contrast medium-is a procedure which is becoming more generally available in community hospitals. Its potential usefulness and limitations should be understood by clinicians. Because it makes possible the evaluation of retroperitoneal lymph nodes, this test can be of great help in the initial staging of lymphoma and the planning of treatment for it.
PROCEDURE AND EVALUATION Technique of Application Lymph vessels on the dorsum of the feet are identified after intradermal injection of a colloidal blue dye into the webs between the first, second, and third toes. Under local anesthesia a skin incision is made on the dorsum of each foot and a suitable lymphatic channel is cannulated by use of a needle with attached plastic tubing. 13 The contrast agent, iodinated poppyseed oil (Ethiodol), is injected either manually or by an automatic pump. Because of the high viscosity of this liquid, the injection of 6 ml per leg may require 1 to 2 hours. When the injection is complete, films are taken immediately to show the lymphatic channels (Fig. lA). The more important films for evaluation of nodal architecture are taken 24 hours later, when the contrast medium has moved out of the vessels and is retained in the lymph nodes (Fig. lB). Anteroposterior, lateral, and oblique roentgenograms of the pelvis and abdomen are taken to demonstrate the groin, pelvic, and periaortic nodes. Ly,mphography of the lower extremity is not technically difficult, although it is time-consuming. With experience the procedure can be accomplished successfully in 90 to 95% of patients. This investigation was supported in part by the Jack Taylor Research Fund.
Medical Clinics of North America- Vo!. 54, No. 4, July, 1970
939
940
JOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
Figure 1 (case 1). A, Normal lymphogram made immediately after injection of contrast medium, showing lymph channels in pelvis and periaortic regions. Lymphogram made 24 hours later. Contrast medium is out of lymph channels and outlines normal-appearing lymph nodes.
B:
Interpretation of Findings Normal lymph nodes are relatively small and compact, with a granular but homogeneously opaque appearance (Fig. IB). Inflammatory nodes are enlarged but show no specific change in character. Lymphomatous nodes are usually enlarged, and though the marginal sinuses are maintained, the opacified reticulum is spread out by the infiltrating tumor cells, giving the internal architecture an appearance variously described as lacy, foamy, or reticular8 (Fig. 2). Notable in some casesespecially in Hodgkin's disease and reticulum-cell sarcoma-are irregular filling defects simulating metastatic carcinoma or nonspecific fibrolipomatous replacement. In more advanced stages, when most of the node is packed with tumor cells and only subcapsular spaces are opacified, a crescentic appearance or "brim sign" may be seen. Nodes involved by lymphoma, even though grossly infiltrated by the tumor, usually continue to transmit lymph and to take up the contrast medium; but eventually some nodes are not outlined by lymphography. These unfilled nodes may be indicated by a break in the continuity of a lymphatic chain (Fig. 3A and B). In addition, the effects of lymphatic obstruction maybe evidenced by filling of collaterallymphatics, stasis, ectasia, backflow, and occasional opening of lymphaticovenolls anastomoses.
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
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Figure 2 (case 3-lymphoblastic lymphosarcoma). Lymphogram showing lymphomatous involvement of right iliac nodes and bilateral periaortic nodes.
942
JOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
Figure 3 (Hodgkin's disease). Lymphograms made on day contrast medium was injected (A) and 24 hours later (B), showing break in continuity of lymph vessels and nodes in left iliac region. Note deformity of bladder filled with urographic contrast medium and bony changes in pelvis.
These latter signs of advanced involvement are less common with lymphoma than with metastatic carcinoma filling the nodes. 2
Complications Most of the untoward reactions to lymphography are relatively minor and require little or no therapy.6 Wound infection and cellulitis about the skin incision are more common in outpatients, probably because of the trauma of walking. Fever, myalgia, and malaise occur occasionally but usually subside in 24 to 48 hours without specific treatment. Hives and other allergic skin reactions are rare and may be due to the colloidal blue dye used for lymph-vessel identification or to the oily contrast medium. The urine may have a blue color due to systemic absorption and subsequent renal excretion of the dye, and rarely the patient's skin may have a bluish tint for 24 hours. The most important complication is the almost invariable occurrence of systemic oily emboli due to the passage of the contrast medium from the retroperitoneallymphatics up the cisterna chyli and into the venous circulation. 7 The lungs filter out most of the ethiodized oil, which initially accumulates in the pulmonary capillaries and so causes an alveolarcapillary block to diffusion of respiratory gases. 5 In most patients these
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
943
pulmonary emboli are asymptomatic. Symptoms from emboli are more likely when the retroperitoneal nodes have caused partial lymphatic obstruction and consequent early shunting of the contrast medium out of the lymph vessels into the venous system via lymphaticovenous anastomoses. In patients with preexisting reduced pulmonary reserve caused by emphysema, parenchymal involvement by lymphoma, radiation fibrosis, etc., marked respiratory insufficiency and death may result. Therefore lymphography requires great caution in patients with underlying pulmonary disease and probably is most often contraindicated, except under unusual clinical circumstances. l l Death from oil emboli in cerebral blood vessels has also been reported. 14
Comparison With Other Diagnostic Techniques Before lymphography became generally available the diagnosis of retroperitoneal involvement by lymphoma was difficult and often overlooked unless laparotomy was done. Physical examination can reveal only very large masses which are palpable through the abdominal wall. Intravenous pyelography may reveal retroperitoneal involvement by displacement of kidney or ureter, but it is considerably less reliable than lymphography, failing to show retroperitoneal lymphoma in 70% of cases. Barium studies of the gastrointestinal tract are even less reliable. 12 Since the inferior vena cava lies in close proximity to the right periaortic lymphatic chain, enlarged nodes in this region may appear on the cavogram as indentations or displacement of the vessel. However, the cavogram usually reveals only large right periaortic lymph-node masses and is generally of no value for detecting left periaortic lymphadenopathy.15 There is general agreement that lymphography is the most reliable radiographic technique for detecting retroperitoneal lymphoma below the level of the first lumbar vertebra. 1 The periaortic lymphatics drain into the cisterna chyli at about the level of the second lumbar vertebra in most persons, and retroperitoneal lymph nodes above this level are rarely visualized. Hence masses in the upper retroperitoneal space (i.e., the region of the porta hepatis) are not detected by this procedure, and inferior vena cavography is the most important method for investigation of this region.
USES FOR LYMPHANGIOGRAPHY For Staging The extent of involvement by lymphoma at the time of initial diagnosis has a direct bearing on prognosis, and accurate clinical staging of the disease is essential for sound planning of treatment. 9 When the disease arises in the lymphatic chain, a painless enlargement of peripheral nodes, most often cervical, is by far the most frequently noted initial clinical sign. Especially in reticulum-cell sarcoma and lymphosarcoma, lymphography often reveals retroperitoneal involvement in asymptomatic patients thought to have disease localized above the level of the
944
jOSEPH M. KIELY, W. EUGENE MILLER, PAUL W. SCANLON
diaphragm. Among young asymptomatic patients with cervical or mediastinal involvement by Hodgkin's disease of the lymphocyte-predominant or nodular-sclerosis types, retroperitoneal involvement is infrequent. On the other hand, in older patients with Hodgkin's disease of mixed cellularity or lymphocyte depletion types, lymphography not uncommonly shows involvement of the retroperitoneal space, especially if systemic symptoms such as fever are present. Since adequate radiotherapy of asymptomatic patients with Hodgkin's disease localized above the diaphragm produces long survival and perhaps cure in many cases, most clinicians recommend lymphography as an important step in the staging of such cases. 3 Truly localized nodal reticulum-cell sarcoma and lymphosarcoma for which radiotherapy may be curative are found considerably less often than Hodgkin's disease, but these instances too should be examined by lymphography if there is no other evidence of more widespread involvement. 1O CASE 1. Chest roentgenograms revealed a large anterior mediastinal mass in a 20-year-old college girl. Physical examination and extensive laboratory studies revealed no abnormalities. Open biopsy showed the mass to be composed of enlarged lymph nodes, and pathologic study revealed Hodgkin's disease of the nodular-sclerosis type. Lymphography disclosed normal-appearing pelvic and periaortic lymph nodes (Fig. 1). High-dose radiotherapy to the lymph nodes above the diaphragm (mantle technique) was given, and the patient remains clinically well 18 months later. CASE 2. Hodgkin's disease of the lymphocyte-predominance type (Hodgkin's paragranuloma) in a 23-year-old teacher was demonstrated by cervical lymph-node biopsy. He was asymptomatic, and-except for right-cervical lymphadenopathynormal findings resulted from physical examination, chest roentgenography, and clinical laboratory tests. The disease was thought to be of stage lA, suitable for so-called curative radiotherapy. Lymphography, however, showed lymphomatous involvement of the iliac (Fig. 4) and periaortic nodes; and the estimated clinical stage was advanced to 3A with resulting change in the treatment plan.
Figure 4 (case 2-Hodgkin's disease). ment of iliac nodes.
Lymphogram showing lymphomatous involve-
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
945
CASE 3. Lymphoblastic lymphosarcoma in an asymptomatic 46-year-old farmer was proved by cervical-node biopsy. Except for left-cervicallymphadenopathy, the physical findings were not remarkable. Routine laboratory studies and a chest roentgenogram revealed no abnormality, and the patient was thought to have stage 1 involvement; but then lymphography showed massive involvement of the retroperitoneal nodes (Fig. 2). In view of the widespread disease the treatment program was modified from the originally planned curative dose of radiation. CASE 4. Lymphocytic lymphosarcoma in an asymptomatic 3D-year-old housewife was diagnosed by left supraclavicular lymph-node biopsy. The chest roentgenogram showed left mediastinal nodal enlargement, but the results of routine clinical laboratory studies were normal. Lymphography revealed extensive involvement of the periaortic and right iliac nodes (Fig. SA). Radiotherapy was directed to the retroperitoneal and pelvic regions in addition to the treatment fields above the diaphragm. On an abdominal roentgenogram made 3 months later, the involvement of the lymph nodes appeared to have regressed (Fig. SB); and the patient remains asymptomatic 3 years after treatment.
For Assessment of Recurrence and Response to Therapy In addition to its use in the initial assessment of extent of nodal involvement in the lymphoma patient, lymphography is helpful in following the clinical course and response to therapy. The oil contrast medium remains in the lymph nodes for many months and allows repeated roentgenographic monitoring of the retroperitoneal nodes during and long after therapy.4 Objective assessment of nodal shrinkage
Figure 5 (case 4-lymphocytic lymphosarcoma). A, Lymphogram showing lymphomatous involvement of periaortic and right iliac nodes. B, Abdominal roentgenogram made 3 months after radiotherapy showing regression in the involved lymph nodes.
946
jOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
following treatment is easily made, as is determination of the occurrence or recurrence of retroperitoneal involvement. 16 CASE 5. In 1960 Hodgkin's disease in a 38-year-old housewife was demonstrated by cervical lymph-node biopsy. After radiotherapy to the neck and mediastinum, she remained well for 5 years. In 1965 anemia, lymphopenia, and a rise in the erythrocyte sedimentation rate were noted; but she was asymptomatic and the physical findings were normal. Lymphography revealed extensive retro-
c
Figure 6 (case 5-Hodgkin's disease). A and B, Lymphograms made after right-sided injection showing lymphomatous - involvement of periaortic nodes in anteroposterior and lateral views. Note cross filling of left periaortic nodes. C, Abdominal roentgenogram taken 19 months after radiotherapy, showing essentially nonnal-appearing left periaortic nodes.
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
947
Figure 7 (case 6-Hodgkin's disease). A, Normal-appearing excretory urogram. B, Lymphogram after left-sided injection, showing bilateral lymphomatous involvement of retroperitoneal nodes. Note cross filling of right-sided periaortic nodes.
peritoneal lymphoma (Fig. 6A and B). After radiotherapy to the involved region, the abnormal laboratory findings reverted to normal; and the patient has remained clinically well for 4 years. Follow-up abdominal roentgenograms showed shrinkage of the opacified lymph nodes, which remained visible because of retention of the contrast medium (Fig. 6C). CASE 6. Hodgkin's disease in an asymptomatic 23-year-old housewife was revealed by cervical lymph-node biopsy. Radiation therapy caused complete disappearance of the enlarged neck nodes. The patient returned 1 year later with back pain of several months' duration. Physical examination, barium examination of the gastrointestinal tract, and intravenous pyelography (Fig. 7A) disclosed no abnormalities. Lymphography showed involvement of the periaortic lymph nodes, however (Fig. 7B); and radiotherapy to the retroperitoneal region promptly relieved the pain. In retrospect, it seems lymphography probably would have revealed stage 3 involvement at the time of the original diagnosis. CASE 7. A 52-year-old housewife had noted fever and weight loss through 5 months. Bilateral lymphadenopathy in the cervical and axillary regions was noted on physical examination. Biopsy revealed lymphoma of mixed lymphocytic and reticulum-cell type. A chest roentgenogram and excretory urogram showed no abnormalities, but the lymphogram disclosed involvement of the retroperitoneal nodes (Fig. 8A). After therapy with nitrogen mustard and chlorambucil the patient became asymptomatic and the previously enlarged peripheral lymph nodes were no longer palpable. A follow-up abdominal roentgenogram made 7 months later showed normal-appearing lymph nodes (Fig. 8B).
948
JOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
Figure 8 (case 7 -lymphoma of mixed lymphocytic and reticulum-cell type). A, Lymphogram showing lymphomatous involvement of iliac and periaortic lymph nodes. B, Abdominal roentgenogram 7 months after alkylating-agent therapy, showing essentially normal-appearing nodes.
SUMMARY Lymphography is a relatively safe and simple, although tedious, radiographic technique for determining the status of the retroperitoneal lymph nodes. In cases of apparently localized lymphoma, tumor involvement of the retroperitoneal region must be assessed before treatment is planned. Lymphography provides the most accurate basis for this evaluation short of laparotomy. Diagnosis of recurrence of lymphoma and serial observations of response to therapy are easy to make, because of the prolonged retention of the contrast medium in the retroperitoneal lymph nodes. This technique is a valuable aid to management and should be available to all physicians caring for patients with lymphoma.
REFERENCES 1. Baum, S., Bron, K. M., Wexler, L., and Abrams, H. L.: Lymphangiography, cavography, and urography: Comparative accuracy in the diagnosis of pelvic and abdominal metastases. Radiology 81 :207-218 (Aug.) 1963. 2. Cook, P. L., Jellife, A. M., Kendall, B., and McLoughlin, M. J.: The role of lymphography in the diagnosis and management of malignant reticuloses. Brit J Radiol39:561-574 (Aug.) 1966.
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3. Davidson, J. W., Saini, M., and Peters, M. V.: Lymphography in lymphoma: With particular reference to Hodgkin's disease. Radiology 88:281-286 (Feb.) 1967. 4. Fabian, C. E., Nudelman, E. J., and Abrams, H. L.: Postlymphangiogram film as an indicator of tumor activity in lymphoma. Invest Radiol 1 :386-393 (Sept.-Oct.) 1966. 5. Fraimow, W., Wallace, S., Greening, R. R., and Cathcart, R. T.: Pulmonary function studies. Cancer Chemother Rep 52:99-105 (Jan.) 1968. 6. Fuchs, W. A.: Complications in lymphography with oily contrast media. Acta Radiol (Stockholm) 57:427-432 (Nov.) 1962. 7. Gough, J. H., Gough, M. H., and Thomas, M. L.: Pulmonary complications following lymphography: With a note on technique. Brit J RadioI37:416-421 (June) 1964. 8. Jing, B-S., and McGraw, J. P.: Lymphangiography in diagnosis and management of malignant lymphomas. Cancer 19:565-572 (Apr.) 1966. 9. Karnofsky, D. A.: The staging of Hodgkin's disease. Cancer Res 26:1090-1094 (June) 1966. 10. Kittredge, R. D., and Finby, N.: Lymphangiography in lymphoma. Amer J Roentgen 94:935-946 (Aug.) 1965. 11. Koehler, P. R.: Typical fatal reactions after lymphography. Cancer Chemother Rep 52: 113-118 (Jan.) 1968. 12. Lee, B. J., Nelson, J.H., and Schwarz, G.: Evaluation of lymphangiography, inferior venacavography and intravenous pyelography in the clinical staging and management of Hodgkin's disease and lymphosarcoma. New Eng J Med 271 :327-337 (Aug. 13) 1964. 13. Miller, W. E.: A simplified cannulation technique for lymphangiography. Amer J Roentgen 101 :978-980 (Dec.) 1967. 14. Nelson, B., Rush, Elizabeth A., Takasugi, M., and Wittenberg, J.: Lipid embolism to the brain after lymphography. New Eng J Med 273:1132-1134 (Nov. 18) 1965. 15. Sheehan, F. R., Lessmann, Ellen M., and Lessmann, F. P.: A comparative study of intraosseous cavography and intravenous pyelography in the demonstration of retroperitoneallymphoma. Radiology 77:757-762 (Nov.) 1961. 16. Sweet, E. I., Scanlon, G. T., and Kaplan, S. R.: Residual Ethiodol after lymphography in diagnosis of lymphoma. Ann Intern Med 69:53-58 (July) 1968.
w.
EUGENE MILLER, M.D.
PAUL W. SCANLON, M.D.
Lymphography - the roentgenographic visualization of lymph vessels and nodes opacified by a contrast medium-is a procedure which is becoming more generally available in community hospitals. Its potential usefulness and limitations should be understood by clinicians. Because it makes possible the evaluation of retroperitoneal lymph nodes, this test can be of great help in the initial staging of lymphoma and the planning of treatment for it.
PROCEDURE AND EVALUATION Technique of Application Lymph vessels on the dorsum of the feet are identified after intradermal injection of a colloidal blue dye into the webs between the first, second, and third toes. Under local anesthesia a skin incision is made on the dorsum of each foot and a suitable lymphatic channel is cannulated by use of a needle with attached plastic tubing. 13 The contrast agent, iodinated poppyseed oil (Ethiodol), is injected either manually or by an automatic pump. Because of the high viscosity of this liquid, the injection of 6 ml per leg may require 1 to 2 hours. When the injection is complete, films are taken immediately to show the lymphatic channels (Fig. lA). The more important films for evaluation of nodal architecture are taken 24 hours later, when the contrast medium has moved out of the vessels and is retained in the lymph nodes (Fig. lB). Anteroposterior, lateral, and oblique roentgenograms of the pelvis and abdomen are taken to demonstrate the groin, pelvic, and periaortic nodes. Ly,mphography of the lower extremity is not technically difficult, although it is time-consuming. With experience the procedure can be accomplished successfully in 90 to 95% of patients. This investigation was supported in part by the Jack Taylor Research Fund.
Medical Clinics of North America- Vo!. 54, No. 4, July, 1970
939
940
JOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
Figure 1 (case 1). A, Normal lymphogram made immediately after injection of contrast medium, showing lymph channels in pelvis and periaortic regions. Lymphogram made 24 hours later. Contrast medium is out of lymph channels and outlines normal-appearing lymph nodes.
B:
Interpretation of Findings Normal lymph nodes are relatively small and compact, with a granular but homogeneously opaque appearance (Fig. IB). Inflammatory nodes are enlarged but show no specific change in character. Lymphomatous nodes are usually enlarged, and though the marginal sinuses are maintained, the opacified reticulum is spread out by the infiltrating tumor cells, giving the internal architecture an appearance variously described as lacy, foamy, or reticular8 (Fig. 2). Notable in some casesespecially in Hodgkin's disease and reticulum-cell sarcoma-are irregular filling defects simulating metastatic carcinoma or nonspecific fibrolipomatous replacement. In more advanced stages, when most of the node is packed with tumor cells and only subcapsular spaces are opacified, a crescentic appearance or "brim sign" may be seen. Nodes involved by lymphoma, even though grossly infiltrated by the tumor, usually continue to transmit lymph and to take up the contrast medium; but eventually some nodes are not outlined by lymphography. These unfilled nodes may be indicated by a break in the continuity of a lymphatic chain (Fig. 3A and B). In addition, the effects of lymphatic obstruction maybe evidenced by filling of collaterallymphatics, stasis, ectasia, backflow, and occasional opening of lymphaticovenolls anastomoses.
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
941
Figure 2 (case 3-lymphoblastic lymphosarcoma). Lymphogram showing lymphomatous involvement of right iliac nodes and bilateral periaortic nodes.
942
JOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
Figure 3 (Hodgkin's disease). Lymphograms made on day contrast medium was injected (A) and 24 hours later (B), showing break in continuity of lymph vessels and nodes in left iliac region. Note deformity of bladder filled with urographic contrast medium and bony changes in pelvis.
These latter signs of advanced involvement are less common with lymphoma than with metastatic carcinoma filling the nodes. 2
Complications Most of the untoward reactions to lymphography are relatively minor and require little or no therapy.6 Wound infection and cellulitis about the skin incision are more common in outpatients, probably because of the trauma of walking. Fever, myalgia, and malaise occur occasionally but usually subside in 24 to 48 hours without specific treatment. Hives and other allergic skin reactions are rare and may be due to the colloidal blue dye used for lymph-vessel identification or to the oily contrast medium. The urine may have a blue color due to systemic absorption and subsequent renal excretion of the dye, and rarely the patient's skin may have a bluish tint for 24 hours. The most important complication is the almost invariable occurrence of systemic oily emboli due to the passage of the contrast medium from the retroperitoneallymphatics up the cisterna chyli and into the venous circulation. 7 The lungs filter out most of the ethiodized oil, which initially accumulates in the pulmonary capillaries and so causes an alveolarcapillary block to diffusion of respiratory gases. 5 In most patients these
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
943
pulmonary emboli are asymptomatic. Symptoms from emboli are more likely when the retroperitoneal nodes have caused partial lymphatic obstruction and consequent early shunting of the contrast medium out of the lymph vessels into the venous system via lymphaticovenous anastomoses. In patients with preexisting reduced pulmonary reserve caused by emphysema, parenchymal involvement by lymphoma, radiation fibrosis, etc., marked respiratory insufficiency and death may result. Therefore lymphography requires great caution in patients with underlying pulmonary disease and probably is most often contraindicated, except under unusual clinical circumstances. l l Death from oil emboli in cerebral blood vessels has also been reported. 14
Comparison With Other Diagnostic Techniques Before lymphography became generally available the diagnosis of retroperitoneal involvement by lymphoma was difficult and often overlooked unless laparotomy was done. Physical examination can reveal only very large masses which are palpable through the abdominal wall. Intravenous pyelography may reveal retroperitoneal involvement by displacement of kidney or ureter, but it is considerably less reliable than lymphography, failing to show retroperitoneal lymphoma in 70% of cases. Barium studies of the gastrointestinal tract are even less reliable. 12 Since the inferior vena cava lies in close proximity to the right periaortic lymphatic chain, enlarged nodes in this region may appear on the cavogram as indentations or displacement of the vessel. However, the cavogram usually reveals only large right periaortic lymph-node masses and is generally of no value for detecting left periaortic lymphadenopathy.15 There is general agreement that lymphography is the most reliable radiographic technique for detecting retroperitoneal lymphoma below the level of the first lumbar vertebra. 1 The periaortic lymphatics drain into the cisterna chyli at about the level of the second lumbar vertebra in most persons, and retroperitoneal lymph nodes above this level are rarely visualized. Hence masses in the upper retroperitoneal space (i.e., the region of the porta hepatis) are not detected by this procedure, and inferior vena cavography is the most important method for investigation of this region.
USES FOR LYMPHANGIOGRAPHY For Staging The extent of involvement by lymphoma at the time of initial diagnosis has a direct bearing on prognosis, and accurate clinical staging of the disease is essential for sound planning of treatment. 9 When the disease arises in the lymphatic chain, a painless enlargement of peripheral nodes, most often cervical, is by far the most frequently noted initial clinical sign. Especially in reticulum-cell sarcoma and lymphosarcoma, lymphography often reveals retroperitoneal involvement in asymptomatic patients thought to have disease localized above the level of the
944
jOSEPH M. KIELY, W. EUGENE MILLER, PAUL W. SCANLON
diaphragm. Among young asymptomatic patients with cervical or mediastinal involvement by Hodgkin's disease of the lymphocyte-predominant or nodular-sclerosis types, retroperitoneal involvement is infrequent. On the other hand, in older patients with Hodgkin's disease of mixed cellularity or lymphocyte depletion types, lymphography not uncommonly shows involvement of the retroperitoneal space, especially if systemic symptoms such as fever are present. Since adequate radiotherapy of asymptomatic patients with Hodgkin's disease localized above the diaphragm produces long survival and perhaps cure in many cases, most clinicians recommend lymphography as an important step in the staging of such cases. 3 Truly localized nodal reticulum-cell sarcoma and lymphosarcoma for which radiotherapy may be curative are found considerably less often than Hodgkin's disease, but these instances too should be examined by lymphography if there is no other evidence of more widespread involvement. 1O CASE 1. Chest roentgenograms revealed a large anterior mediastinal mass in a 20-year-old college girl. Physical examination and extensive laboratory studies revealed no abnormalities. Open biopsy showed the mass to be composed of enlarged lymph nodes, and pathologic study revealed Hodgkin's disease of the nodular-sclerosis type. Lymphography disclosed normal-appearing pelvic and periaortic lymph nodes (Fig. 1). High-dose radiotherapy to the lymph nodes above the diaphragm (mantle technique) was given, and the patient remains clinically well 18 months later. CASE 2. Hodgkin's disease of the lymphocyte-predominance type (Hodgkin's paragranuloma) in a 23-year-old teacher was demonstrated by cervical lymph-node biopsy. He was asymptomatic, and-except for right-cervical lymphadenopathynormal findings resulted from physical examination, chest roentgenography, and clinical laboratory tests. The disease was thought to be of stage lA, suitable for so-called curative radiotherapy. Lymphography, however, showed lymphomatous involvement of the iliac (Fig. 4) and periaortic nodes; and the estimated clinical stage was advanced to 3A with resulting change in the treatment plan.
Figure 4 (case 2-Hodgkin's disease). ment of iliac nodes.
Lymphogram showing lymphomatous involve-
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
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CASE 3. Lymphoblastic lymphosarcoma in an asymptomatic 46-year-old farmer was proved by cervical-node biopsy. Except for left-cervicallymphadenopathy, the physical findings were not remarkable. Routine laboratory studies and a chest roentgenogram revealed no abnormality, and the patient was thought to have stage 1 involvement; but then lymphography showed massive involvement of the retroperitoneal nodes (Fig. 2). In view of the widespread disease the treatment program was modified from the originally planned curative dose of radiation. CASE 4. Lymphocytic lymphosarcoma in an asymptomatic 3D-year-old housewife was diagnosed by left supraclavicular lymph-node biopsy. The chest roentgenogram showed left mediastinal nodal enlargement, but the results of routine clinical laboratory studies were normal. Lymphography revealed extensive involvement of the periaortic and right iliac nodes (Fig. SA). Radiotherapy was directed to the retroperitoneal and pelvic regions in addition to the treatment fields above the diaphragm. On an abdominal roentgenogram made 3 months later, the involvement of the lymph nodes appeared to have regressed (Fig. SB); and the patient remains asymptomatic 3 years after treatment.
For Assessment of Recurrence and Response to Therapy In addition to its use in the initial assessment of extent of nodal involvement in the lymphoma patient, lymphography is helpful in following the clinical course and response to therapy. The oil contrast medium remains in the lymph nodes for many months and allows repeated roentgenographic monitoring of the retroperitoneal nodes during and long after therapy.4 Objective assessment of nodal shrinkage
Figure 5 (case 4-lymphocytic lymphosarcoma). A, Lymphogram showing lymphomatous involvement of periaortic and right iliac nodes. B, Abdominal roentgenogram made 3 months after radiotherapy showing regression in the involved lymph nodes.
946
jOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
following treatment is easily made, as is determination of the occurrence or recurrence of retroperitoneal involvement. 16 CASE 5. In 1960 Hodgkin's disease in a 38-year-old housewife was demonstrated by cervical lymph-node biopsy. After radiotherapy to the neck and mediastinum, she remained well for 5 years. In 1965 anemia, lymphopenia, and a rise in the erythrocyte sedimentation rate were noted; but she was asymptomatic and the physical findings were normal. Lymphography revealed extensive retro-
c
Figure 6 (case 5-Hodgkin's disease). A and B, Lymphograms made after right-sided injection showing lymphomatous - involvement of periaortic nodes in anteroposterior and lateral views. Note cross filling of left periaortic nodes. C, Abdominal roentgenogram taken 19 months after radiotherapy, showing essentially nonnal-appearing left periaortic nodes.
LYMPHOGRAPHY IN MANAGEMENT OF LYMPHOMA
947
Figure 7 (case 6-Hodgkin's disease). A, Normal-appearing excretory urogram. B, Lymphogram after left-sided injection, showing bilateral lymphomatous involvement of retroperitoneal nodes. Note cross filling of right-sided periaortic nodes.
peritoneal lymphoma (Fig. 6A and B). After radiotherapy to the involved region, the abnormal laboratory findings reverted to normal; and the patient has remained clinically well for 4 years. Follow-up abdominal roentgenograms showed shrinkage of the opacified lymph nodes, which remained visible because of retention of the contrast medium (Fig. 6C). CASE 6. Hodgkin's disease in an asymptomatic 23-year-old housewife was revealed by cervical lymph-node biopsy. Radiation therapy caused complete disappearance of the enlarged neck nodes. The patient returned 1 year later with back pain of several months' duration. Physical examination, barium examination of the gastrointestinal tract, and intravenous pyelography (Fig. 7A) disclosed no abnormalities. Lymphography showed involvement of the periaortic lymph nodes, however (Fig. 7B); and radiotherapy to the retroperitoneal region promptly relieved the pain. In retrospect, it seems lymphography probably would have revealed stage 3 involvement at the time of the original diagnosis. CASE 7. A 52-year-old housewife had noted fever and weight loss through 5 months. Bilateral lymphadenopathy in the cervical and axillary regions was noted on physical examination. Biopsy revealed lymphoma of mixed lymphocytic and reticulum-cell type. A chest roentgenogram and excretory urogram showed no abnormalities, but the lymphogram disclosed involvement of the retroperitoneal nodes (Fig. 8A). After therapy with nitrogen mustard and chlorambucil the patient became asymptomatic and the previously enlarged peripheral lymph nodes were no longer palpable. A follow-up abdominal roentgenogram made 7 months later showed normal-appearing lymph nodes (Fig. 8B).
948
JOSEPH M. KIELY,
W.
EUGENE MILLER, PAUL
W.
SCANLON
Figure 8 (case 7 -lymphoma of mixed lymphocytic and reticulum-cell type). A, Lymphogram showing lymphomatous involvement of iliac and periaortic lymph nodes. B, Abdominal roentgenogram 7 months after alkylating-agent therapy, showing essentially normal-appearing nodes.
SUMMARY Lymphography is a relatively safe and simple, although tedious, radiographic technique for determining the status of the retroperitoneal lymph nodes. In cases of apparently localized lymphoma, tumor involvement of the retroperitoneal region must be assessed before treatment is planned. Lymphography provides the most accurate basis for this evaluation short of laparotomy. Diagnosis of recurrence of lymphoma and serial observations of response to therapy are easy to make, because of the prolonged retention of the contrast medium in the retroperitoneal lymph nodes. This technique is a valuable aid to management and should be available to all physicians caring for patients with lymphoma.
REFERENCES 1. Baum, S., Bron, K. M., Wexler, L., and Abrams, H. L.: Lymphangiography, cavography, and urography: Comparative accuracy in the diagnosis of pelvic and abdominal metastases. Radiology 81 :207-218 (Aug.) 1963. 2. Cook, P. L., Jellife, A. M., Kendall, B., and McLoughlin, M. J.: The role of lymphography in the diagnosis and management of malignant reticuloses. Brit J Radiol39:561-574 (Aug.) 1966.
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