Clinical Evidence of Parasternal Lymph Node Involvement in Neoplastic Disease

Acta Radiologica ISSN: 0001-6926 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/iaro20 Clinical Evidence of Parasternal Lymph Node Involvement in Neoplastic Disease D. W. Smithers & P. Rigby-Jones To cite this article: D. W. Smithers & P. Rigby-Jones (1959) Clinical Evidence of Parasternal Lymph Node Involvement in Neoplastic Disease, Acta Radiologica, 51:sup188, 235-247, DOI: 10.3109/00016925909177092 To link to this article: https://doi.org/10.3109/00016925909177092 Published online: 14 Dec 2010. Submit your article to this journal Article views: 797 View related articles Citing articles: 4 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalinformation?journalcode=iaro20

FROM THE RADIOTHERAPY DEPARTMENT, ROYAL MARSDEN HOSPITAL AND INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (DIRECTOR: PROF. D. w. SMITHERS), LONDON, ENGLAND CLINICAL EVIDENCE OF PARASTERNAL LYMPH NODE INVOLVEMENT IN NEOPLASTIC DISEASE by D. W. Smithers and P. Rigby-Jones INTRODUCTION... It is the fact that in more than half my recurrent cases, before I began the prophylactic use of radium, the return of the disease manifested itself either by an enlargement of the gland at the lower and inner angle of the posterior triangle, or by the appearance of nodules, later merging in sternal recurrence, upon the deep fascia at the inner end of the first, second, or third intercostal spaces. The position of these recurrences accurately along the line of the internal mammary artery shows I think beyond doubt that they are due to invasion of the lymphatic glands which lie along its course. - W. SAMPSON HANDLEY, 1927 (b). Sampson Handley was of course speaking of carcinoma of the breast. Through the work of his son, Richard Handley, the frequency of involvement of parasternal nodes in this disease has at last been recognised and a great deal of interesting histological work has been done. Little, however, even now, has appeared in support of SAMPSON HANDLEY s original clinical observation of parasternal lymph node involvement from breast tumours, and nothing, that we know of, about metastatic involvement of these nodes from primary tumours elsewhere. Our interest in this subject was aroused in 1943 when one of us saw a patient aged 75 with a recurrence to one side of the sternum, whose breast had been removed by Mr. Sampson Handley twenty-five years before and for whom he had done a parasternal radium implant for a recurrence seven years later. He had published an account of this case (HAND- LEY, 1927 (a)) as one showing clinical evidence of involvement of these nodes, having drawn attention to their histological involvement in other cases five years before (HANDLEY, 1922). When we advised this patient to go back to see Mr. Sampson Handley in 1943, he wrote in his reply:... I have not been able to persuade the profession that the int. mammary chain of glands is infected in breast cancer just as soon as the axillary chain, and that a carcinoma operation is consequently incomplete until radium tubes have been introduced above the first rib & at the inner ends of the intercostal spaces....

236 D. W. SMITHERS AND P. RIGBY-JONES Fig. 1. Sclerosis in sternum following radium implant to parasternal node recurrence. 24 years previously. He reported this patient again at a meeting of the Royal Society of Medicine (HANDLEY, 1950), and for good measure Fig. 1 is an X-ray of the sclerosis which occurred in the sternum in this patient 24 years after Sampson Handley s radium implant. As a result of this experience in 1943 we began both to collect clinical evidence of parasternal lymph node involvement and also to give radiotherapy to the parasternal region in a group of patients with upper and inner quadrant breast tumours. For this purpose special triangular shaped applicators, one for each side, were made (Fig. 2), to include the intercostal spaces in the X-ray field. The post-operative X-ray fields used at that time are illustrated in Fig. 3 and consisted of a direct parasternal triangular field, two tangential chest wall fields, a central scar field treated to a low dose and at low voltage (since abandoned), an anterior supraclaviculo-axillary field, and a posterior axillary field. The parasternal field was at first used only for upper and inner quadrant tumours and not for all of these.

PARASTERNAL LYMPH NODE INVOLVEMENT IN NEOPLASTIC DISEASE 237 Fig. 2. Triangular shaped applicators used for irradiation of intercostal spaces in 1944. Fig. 3. Old arrangement of fields for 'postoperative treatment in carcinoma of the breast. Following the publication of Richard Handley's work (HANDLEY and THACK- RAY, 1947), the frequency of involvement of nodes at this site was at last appreciated, and the irradiation of the parasternal node regions then became a routine for patients with inner half tumours in our hospital and was also employed for patients with outer half tumours who were known to have or suspected of having axillary node involvement. Evidence that recurrence in this region was less common when parasternal X-ray fields had been used, was first reported by us six years ago (RIGBY- JONES, 1953), and a summary of what was recorded then is given in Table 1. Tumours arising in the inner half of the breast have a relatively poor prognosis compared to those in the outer half in Stage I but not in later stages. This is due to the difficulty of detecting early parasternal lymph node enlargement clinically, with the result that more patients with inner half than with outer half tumours placed in Stage I do in fact have lymph node involvement (SMITHERS, 1958). During these last fifteen years our clinical examples of metastatic involvement of parasternal lymph nodes have been accumulating. These have naturally resulted predominantly from primary breast carcinomas, but a variety of neoplasms of other primary sites may metastasise to these nodes. In this paper we propose to discuss the evidence for the frequency with which lymph node metastases occur at this site from carcinoma of the breast and to give some information on cases in which we have been able to observe such involvement clinically; we shall also give a brief

238 D. W. SMITHERS AND P. RIGBY-JONES Table 1 The effectiveness of parasternal irradiation in preventing early parasternal recurrence Site of primary tumour in the breast Inner half.... Outer half..... Central... Diffuse.... Unspecified.... (from RIGBY-JONES, 1953) I First treatment including 1 First treatment not including Darasternal irradiation I parasternal irradiation Total first Parasternal 1 Total first Parasternal I recurrences I recurrences I I 21 7 3 1 6 Total.... 1-38 I 0 I 302 I 16 account of those cases in which we have detected metastases in these nodes from other primary tumours. 40 143 30 35 54 Frequency of Involvement of Parasternal Lymph Nodes in Patients with Breast Carcinoma It was the anatomical work of STIBBE (1918) on the internal mammary lymph nodes, first suggested by Sampson Handley, that led to an investigation into their involvement in neoplastic disease of the breast. Stibbe examined 60 subjects, a bilateral dissection of each intercostal space being carried out. The average number of these nodes that he was able to find at all ages and on both sides was 8.5. The nodes were found more frequently in young than in old people, the average number found in infants being 11.4, and in those over seventy years of age 6.6. Nodes were most frequently located in the first and second spaces, the third space came a good third, but other spaces contained nodes more rarely. Stibbe quoted an interesting observation from Halsted, who had described how his house surgeon, in 1898, had dissected the parasternal lymph nodes from three patients with recurrent breast tumours. HALSTED S interest had lain more with axillary and supraclavicular node involvement and he gave an account in 1907 of 101 cases in which he had done a supraclavicular node dissection. It was the work of Sampson Handley which called attention to the frequency of involvement of parasternal lymph nodes in carcinoma of the breast. This work was referred to in his book published in 1922 when he described the use of radium tubes in the treatment of these nodes. He had himself been using this radium technique since 1920, inserting tubes near the sternum in the first, second and third intercostal

PARASTERNAL LYMPH NODE INVOLVEMENT IN NEOPLASTIC DISEASE 239 spaces following radical mastectomy. In 1947 RICHARD HANDLEY and A. C. THACK- RAY published an account of their first four cases of parasternal lymph node dissection in patients with carcinoma of the breast, in which they demonstrated lymph node involvement histologically. There followed a more detailed account of the internal mammary lymph node chain metastases in carcinoma of the breast by HANDLEY and THACKRAY in 1949. In 1948 MARGOTTINI was the first to develop a routine operative procedure for the removal of the internal mammary lymphatic chain en bloc as part of a radical mastectomy. His 1952 report on 227 patients operated on showed that internal mammary lymph node involvement had occurred without axillary metastases and with small tumours in 5%, with outer half tumours and axillary lymph node involvement in 27.7%, with inner half tumours with nodes involved in the axilla in 40.5%, and with tumours occupying most of the breast in over 50%. DAHL-IVERSEN had been writing about lymph node metastases from Table 2 Frequency of internal mammary lymph nodes STIBBE (1918) examined 60 subjects post-mortem. Average number per subject of parasternal nodes, right and left sides.... 8.5 SOERENSEN (1951) examined 39 subjects post-mortem. Average number per subject of parasternal nodes, right and left sides.... 7.0 URBAN (1959) dissected 150 parasternal regions in patients with breast tumours and found nodes in 1st intercostal space in 91 per cent. 2nd - - 89- - 3rd - - 75- - 4th - - 53- - 5th - - 13- - breast carcinoma - particularly in the supraclavicular fossa - since 1927, and in 1951 he and SOERENSEN published the results of their work on the frequency with which lymph nodes could be found in the parasternal region and on their involvement in tumour spread from the breast. SOERENSEN reported 39 post-mortem examinations in which he observed an average of 7 nodes per subject, 3.5 on each side, rather less than that found by STIBBE in 1918 (Table 2). Since then much surgical evidence has been produced to show the frequency with which the parasternal and axillary nodes are involved from tumours of the inner or outer half of the breast. This evidence is summarised in Fig. 4.

~ 40 240 D. W. SMITHERS AND P. RIGBY-JONES No nodes tnvolved Pararlernal and nd arillary nodes 1 INNER HALF OF BREAST including CENTRAL k%%ly HUTCHINSON (1953 ANDREASSEN el a1 HAAGENSEN and OKlD URBAN \I959 HANDLEY and THACKRAY (19541 119591 11954, Masleoomy Mastectomy BlOpSy Martertomy Mastectomy 81 carer. 20 inner hall 100 carer. 37 inner hall 100 cases, 45 inner hall 300 cases, 239 inner hall 150 carer, 61 inner hall 70 60-50 30 20 10 OUTER HALF OF BREAST HAAGENYN and OBElD ANDREASSEN el al HUTCHINSON (19531 HANDLEY and THACKRAY URBAN 119591 119591 i19541,1954' Blopry Mailectomy Mastectomy Marlectomy Marteaorny 100 Case$, 100 carer. 81 cases. 150 cases. 300 <ares. 55 outer hall 63 ouler hall 61 outer hall 89 outer hall 61 outer hall 70 60 50 S 40 F.. 30 20 10 Fig. 4. Frequency of internal mammary node involvement in selected series of carcinoma of breast. Parasternal Lymph Nodes Observed Clinically This anatomical and histological demonstration of parasternal lymph nodes and their involvement in tumour spread has not been matched by clinical demonstration of visible or palpable nodes in this region. When small these nodes are not easily detected clinically, and if seen they may be dismissed as subcutaneous or sternal deposits. Since 1937 we have records of 65 patients with breast cancer in whom were detected visible or palpable parasternal lymph nodes, over half of these being prominent enough to photograph. This does not represent the total incidence of palpable nodes in this situation occurring in all patients attending this hospital; all we have done is to record these findings when we have ourselves observed them in the patients we have examined. The point we wish to make here is that clinical evidence of metastatic involvement of these nodes can frequently be found if it is looked for (Fig. 5).

PARASTERNAL LYMPH NODE INVOLVEMENT IN NEOPLASTIC DISEASE 24 1 Fig. 5. Parasternal node involvement in 3rd left intercostal space in a patient with an outer half tumour. The majority of these parasternal metastases were observed as the first sign of recurrence following radical mastectomy in patients who had not been irradiated. In our series only 4 out of 65 had clinical evidence of parasternal recurrence after receiving parasternal irradiation. These recurrences may be small and single (Fig. 6), large and single (Fig. 7), or multiple. In these 65 patients the primary tumour was situated in the inner half of the breast in 58 % and in the outer half in 23 %; in the other 19 % the site of the original tumour before operation was not clearly stated. In 45% of our cases there was microscopical evidence of involvement of the axillary nodes at the time of mastectomy; in 29 % there was none; and in 26 % no information concerning the state of the axillary lymph nodes was available. Table 3 shows the frequency with which the parasternal nodes were seen clinically to be involved in each intercostal space in the Royal Marsden Hospital series. The internal mammary lymph node chain on the opposite side to the primary tumour was involved in a few instances. The reasons for believing without histological confirmation that these swellings were due to deposits in lymph nodes and not to subcutaneous metastases are that they appeared without evidence of subcutaneous spread elsewhere, were found at the known lymph node sites, and responded well to treatment without further local signs of spread in most cases, although many patients died of distant metastases. The

242 D. W. SMITHERS AND P. RIGBY-JONES Fig. 6. Small right post-operative parasternal recurrence in an unirradiated patient. Fig. 7. Large left parasternal recurrence; (a) before treatment; (b) after treatment. Patient lived for 2 years after treatment and died with distant metastases.

PARASTERNAL LYMPH NODE INVOLVEMENT IN NEOPLASTIC DISEASE 243 Table 3 Instances of parasternal lymph node metastases from carcinom of the breast observed clinically at the Royal Marsden Hospital 1937-1959 (Total number of patients: 65) Site of primary tumour: Inner half of breast: 38 (58%); Outer half of breast: 15 (23%); Not stated: 12 (19%) Parasternal Lymph Node Involvement I Intercostal Same side as Opposite side to space primary tumour primary tumour 1st 2nd 3rd 4th 5th Average duration from first treatment to parasternal recurrence: 3 years 7 months. Average duration from pasternal recurrence to death: 1 year 11 months. Number of patients still alive: 14. Longest survival since parasternal recurrence: 15 years. Among these 65 patients the axillary nodes were involved microscopically in 29 (45 %); axillary nodes were not involved microscopically in 19 (29 %); there was no information about axillary nodes in 17' (27 %). * 3 of these patients were not operated on. I main reasons for thinking that patients presenting with a metastasis in the sternum from carcinoma of the breast really have direct invasion from an involved parasternal node is that the erosion is regularly on the same side as the primary, occurs at levels at which parasternal nodes are commonly found (Fig. 8), and is more frequent and has a much better prognosis than solitary bony metastases elsewhere. One of our patients with clinically advanced carcinoma of the breast, extensive bilateral lymph node involvement and a large mass in the sternum has remained alive and well for 14 years following radiotherapy (SMITHERS, 1958). Of the 65 patients reported, 14 are still alive and well, having lived for periods varying from 15 years to a few months since the appearance of the parasternal recurrence; 42 % of the cases survived for more than two years after treatment for these recurrences. Parasternal lymph node metastases from primary carcinomas other than in the breast are not very often observed clinically. In view of the frequency with which epitrochlear nodes, for example, may be felt in cases of lymphoma, this is perhaps rather surprising. Nevertheless, these nodes are sometimes enlarged in Hodgkin's

244 D. W. SMITHERS AND P. RIGBY-JONES Fig. 8. Radiograph of sternum showing erosion by enlarged parasternal lymph node. Fig. 9. Right parasternal lymph node enlargement in a patient with Hodgkin s disease. Fig. 10. Parasternal lymph node metastasis in a patient with a hypernephroma.

PARASTERNAL LYMPH NODE INVOLVEMENT IN NEOPLASTIC DISEASE 245 Fig. 12. Left parasternal lymph node metastasis in a patient with carcinoma of the thymus (infra-red photograph). Fig. 1 I. (left) Parasternal lymph node metastasis in a patient with carcinoma of the bronchus. Fig. 13. Parasternal and infraclavicular lymph node metastases in a patient with carcinoma of the cervix uteri. Fig. 14. Parasternal lymph node metastasis in a patient with carcinoma of the parotid gland.

246 D. W. SMITHERS AND P. RIGBY-JONES disease (Fig. 9)*, though they may be inconspicuous and difficult to photograph. We have a Is0 observed them to be involved in patients with, respectively, a hypernephroma (Fig. lo), a carcinoma of the bronchus (Fig. 1 I), a carcinoma of the thymus (Fig. 12). a carcinoma of the cervix uteri (Fig. 13), and a carcinoma of the parotid gland (Fig. 14). SUMMARY Little mention has been made of clinically detectable metastatic involvement of parasternal lymph nodes since Sampson Handley s observations published in 1927, though much work has been done in confirming his findings histologically. An account of clinical involvement of parasternal lymph nodes in patients with carcinoma of the breast is given. It is suggested that a number of deposits in the sternum are due to direct extension to the bone from metastases in parasternal lymph nodes. The importance of parasternal lymph node irradiation in the treatment of breast neoplasms is stressed. A few cases are reported with involvement of parasternal lymph nodes from primary tumours at other sites than the breast. REFERENCES ANDREASSEN, M., DAHL-IVERSEN, E., and SBRENSEN, B.: Glandular Metastases in Carcinoma of the Breast. Results of a More Radical Operation. Lancet 1 (1954), 176. DAHL-IVERSEN, E. : Recherches sur les mttastases microscopiques des ganglions lymphatiques parasternaux dans le cancer du sein. (Recherches histologiques de 57 cas optres radicalement). J. internat. Chir. 11 (1951), 492. HAAGENSEN, C. D., and OBEID, S. J.: Biopsy of the Apex of the Axilla in Carcinoma of the Breast. Ann. Surg. 149 (1959), 149. HALSTED, W. S.: The Results of Radical Operations for the Cure of Cancer of the Breast. Ann. Surg. 46 (1907), 1. HANDLEY, W. S.: Cancer of the Breast and Its Treatment, pp. 272-281. London: John Murray for The Middlesex Hospital Press, 1922. HANDLEY, W. S.: (a) The Radium Treatment of Sternal Recurrences in Cancer of the Breast. Clinical J. 56 (1927), 73. (b) Parasternal Invasion of the Thorax in Breast Cancer and Its Suppression by the Use of Radium Tubes as an Operative Precaution. Surg. Gynec. & Obst. 45 (1927), 721. HANDLEY, W. S.: Sternal Secondary Deposit of Breast Cancer Treated by Radium Implantation. Patient Well Twenty-fours Years Later. Proc. R. SOC. Med. 43 (1950), 83. HANDLEY, R. S., and THACKRAY, A. C.: Invasion of the Internal Mammary Lymph Glands in Carcinoma of the Breast. Brit. J. Cancer 1 (1947), 15. HANDLEY, R. S., and THACKRAY, A. C.: The Internal Mammary Lymph Chain in Carcinoma of the Breast. Study of 50 Cases. Lancet 2 (1949), 276. HANDLEY, R. S., and THACKRAY, A. C.: Invasion of Internal Mammary Lymph Nodes in Carcinoma of the Breast. Brit. med. J. 1 (1954), 61. HUTCHINSON, W. B.: Intercostal Dissection and Radical Mastectomy. Arch. Surg. 66 (1953), 440. MARGOTTINI, M.: R&nt Developments in the Surgical Treatment of Breast Carcinoma. Acta Unio internat. contra Cancrum 8 (1952), 176. RIGBY-JONES, P. : The Influence of Various Factors on Metastases in Carcinoma of the Breast. Brit. J. Cancer 7 (1953), 43 1. * We have recently seen another patient with parasternal lymph node involvement in Hodgkin s disease.

PARASTERNAL LYMPH NODE INVOLVEMENT IN NEOPLASTIC DISEASE 247 SMITHERS, D. W.: Cancer of the Breast. A Study of Short Survival in Early Cases and of Long Survival in Advanced Cases. Amer. J. Roentgenol. 80 (1958), 740. SOERENSEN, B. : Recherches sur la localisation des ganglions lymphatiques parasternaux par rapport aux espaces intercostaux. J. internat. Chir. 11 (1951), 501. STIBBE, E. P.: The Internal Mammary Lymphatic Glands. J. Anat. 52 (1918), 257. URBAN, J. A.: Clinical Experience and Results of Excision of the Internal Mammary Lymph Node Chain in Primary Operable Breast Cancer. Cancer 12 (1959), 14.