JBJS | Analysis of Lymph Nodes for Polyethylene Particles in Patients Who Have Had a Primary Joint Replacement*†

The Journal of Bone & Joint Surgery, Volume 78, Issue 4

Articles | April 01, 1996

Analysis of Lymph Nodes for Polyethylene Particles in Patients Who Have Had a Primary Joint Replacement*†

KEVIN G. SHEA, M.D.‡; ROY D. BLOEBAUM, PH.D.§; JIM M. AVENT, M.D.¶; G. TROY BIRK, M.D.‡; KENT M. SAMUELSON, M.D.¶, SALT LAKE CITY, UTAH

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Investigation performed at the Department of Orthopedics, University of Utah School of Medicine, and Latter Day Saints Hospital, Salt Lake City

The Journal of Bone & Joint Surgery. 1996; 78:497-504

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Abstract

Polarized light microscopy has been used for more than forty years to identify polyethylene particles in histological specimens; however, few investigators have assessed the specificity of this technique. We examined specimens from dissected lymph nodes for the presence of strongly birefringent particles resembling polyethylene. Twenty-seven patients had dissection of lymph nodes after a total joint replacement (Group 1), and a control group of eighteen patients had dissection of lymph nodes before a total joint replacement (Group 2). Specimens from both groups of lymph nodes were examined under plain and polarized light. The presence of strongly birefringent particulate debris was graded from 0 to 4. Twenty-one (78 per cent) of the twenty-seven patients in Group 1 and eight of the eighteen patients in Group 2 had strongly birefringent particles in the lymph nodes.Our results demonstrate that, in the assessment of the systemic dissemination of polyethylene in the lymphoreticular system, polarized light microscopy has important limitations. More refined techniques employing polarized light and other methods of physical and chemical analysis may be necessary to identify polyethylene particles accurately within the lymphoreticular system and periprosthetic tissue.

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Introduction

Introduction | Materials and Methods | Results | Discussion | References

The local and regional dissemination of particles of wear debris from total joint replacements has been well described in the literature. Numerous investigators have assessed the presence of wear debris in periprosthetic tissue obtained during revision operations for failed total joint replacements^{8,10,11,14,16,25,28,34}. Fewer investigators have analyzed such debris in association with stable primary total joint replacements⁵. The work of Charnley⁹, of Willert and Semlitsch³⁴, and of Schmalzried et al.²⁸ suggested that, in addition to the pericapsular dispersion of particles of debris, the joint fluid circulating along the bone-prosthesis interface may carry particles into the periprosthetic tissue. Distribution of particles within this interface led Schmalzried et al. to propose the concept of the so-called effective joint space, which includes all periprosthetic regions that are exposed to joint fluid and particulate debris²⁸.

It has also been proposed that particles of debris can be transported from the tissue around the joint capsule through the lymphoreticular system^14,33 and that eventually this transport system can be saturated, leading to the local accumulation of wear debris around the implant. This results in a macrophage and foreign-body giant-cell reaction³⁴, which has been implicated as a cause of osteolysis and subsequent aseptic loosening of a total joint replacement^{1,6,11,17,21,27,32,34,35}.

The dissemination of particles of wear debris from total joint replacements to regional lymph nodes has been reported in studies of humans^{3,12,14,19,31} and animals^15,23. Recent autopsy studies have demonstrated widespread distribution of particles of wear debris throughout the lymphoreticular system^5,19. The dissemination of particles to regional lymph nodes from a total joint replacement has been reported as soon as seven months after an operation, although large amounts of particles are not usually seen before eighteen months⁵. Bloebaum et al.⁴ proposed the concept of the extended joint space to account for the local and systemic spread of particles from joint replacements.

Particles from total joint replacements include polyethylene, metal, polymethylmethacrylate, and hydroxyapatite. Polyethylene particles are strongly birefringent and can be visualized with polarized light, which has been used for this purpose for more than forty years²⁶. The oil-red-O method has been reported to improve the visualization of polyethylene particles. Recent evaluation of this method demonstrated it to be as sensitive as but less specific than polarized light microscopy²⁹. This suggests that the results of the oil-red-O method should be interpreted with caution. At present, polarized light microscopy is the standard in the literature for the assessment of polyethylene particles associated with total joint replacement¹³.

For the present study, we used polarized light microscopy to examine specimens obtained from dissected lymph nodes for the presence of strongly birefringent particles similar to polyethylene. The lymph nodes had been dissected, for the treatment of various carcinomas, from patients who had had a previous primary total joint replacement and also from patients who had not. The aims of our study were to assess the dissemination of polyethylene particles throughout the lymphoreticular system in patients who had had a primary rather than a revision joint replacement and to assess the reliability of polarized light microscopy by examining a control group of patients who had not had a joint replacement for the presence of particles similar to polyethylene.

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Funds were received in total or partial support of the research or clinical study presented in this article. The funding sources were Department of Veterans Affairs Medical Research Funds, Veterans Affairs Medical Center and the Latter Day Saints Hospital, and the Department of Orthopedics of the University of Utah School of Medicine, Salt Lake City, Utah.

†Read at the Annual Meeting of the Orthopaedic Research Society, New Orleans, Louisiana, February 23, 1994.

‡Department of Orthopedics, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, Utah 84132.

§Bone and Joint Research Laboratory, Veterans Administration Medical Center, 500 North Foothill Drive, Salt Lake City, Utah 84148.

¶Department of Orthopaedic Surgery and Pathology, Latter Day Saints Hospital, 8th Avenue and C Street, Salt Lake City, Utah 84143.

†Read at the Annual Meeting of the Orthopaedic Research Society, New Orleans, Louisiana, February 23, 1994.

‡Department of Orthopedics, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, Utah 84132.

§Bone and Joint Research Laboratory, Veterans Administration Medical Center, 500 North Foothill Drive, Salt Lake City, Utah 84148.

¶Department of Orthopaedic Surgery and Pathology, Latter Day Saints Hospital, 8th Avenue and C Street, Salt Lake City, Utah 84143.

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Figs. 1-A and 1-B: Case 22. Photomicrographs of a specimen from an axillary lymph node. The patient had had a total joint replacement seven months before the lymph nodes were dissected because of breast cancer. Fig. 1-A: Under plain light (X 400).

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Under polarized light, there are strongly birefringent particles resembling polyethylene (a grade of 4).

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Figs. 2-A and 2-B: Case 31. Photomicrographs of a specimen from an axillary lymph node. Fig. 2-A: Under plain light (X 400).

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Under polarized light, there are strongly birefringent particles resembling polyethylene (a grade of 4). This patient had not had a total joint replacement before the dissection, and therefore this is an example of a false-positive result.

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TABLE I DATA ON THE PATIENTS IN GROUP 1

*0 = no birefringent particles, 1 = widely scattered birefringent particles without sinus histiocytosis, 2 = scattered aggregates of two birefringent particles or more per aggregate without sinus histiocytosis, 3 = single scattered regions of sinus histiocytosis with one birefringent particle or more, and 4 = numerous to confluent regions of sinus histiocytosis with multiple birefringent particles.

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Location of Total Joint Replacement	Time from Joint Replacement to Dissection of Lymph Nodes (Mos.)	Grade of Strongly Birefringent Particles Resembling Polyethylene*
1	M, 69	Pelvic	Prostate cancer	R knee	30	4
2	M, 72	Pelvic	Prostate cancer	L knee	2	3
3	F, 71	Pelvic, para-aortic	Endometrial adenocarcinoma	R hip	84	0
4	M, 68	Pelvic	Prostate cancer	L knee	53	3
5	F, 67	L axillary	Benign L axillary mass	L knee	1	2
6	M, 66	R axillary	Ductal cancer of R breast	L hip	6	2
7	M, 69	Pelvic	Prostate cancer	L knee	28	0
8	M, 63	Pelvic	Prostate cancer	R knee	25	2
9	F, 60	R inguinal	Vulvar cancer	L hip	17	2
10	M, 67	Pelvic	Prostate cancer	R hip	51	4
11	F, 58	Duodenal, para-aortic	Cholangiocarcinoma	Bilat. knee	192	3
12	M, 64	Pelvic	Prostate cancer	L hip	6	0
13	M, 63	Pelvic	Prostate cancer	R hip	36	3
14	M, 64	Pelvic	Prostate cancer	L knee	19	2
15	M, 68	Pelvic	Prostate cancer	L hip	88	0
16	F, 72	L axillary	Ductal cancer of L breast	R hip	113	2
17	F, 77	R axillary	Ductal cancer of R breast	L hip	12	4
18	M, 69	Pelvic	Prostate cancer	L hip	8	0
19	M, 78	R axillary	Melanoma of R side of back	L knee	19	2
20	F, 61	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	24	3
21	F, 61	L axillary	Ductal cancer of L breast	R knee	14	2
22	F, 68	R axillary	Ductal cancer of R breast	R knee	7	4
23	F, 60	Pelvic, iliac	Endometrial adenocarcinoma	R hip	26	1
24	M, 55	Pelvic	Prostate cancer	R hip	6	3
25	F, 76	R axillary	Ductal cancer of R breast	R hip	17	1
26	F, 79	R axillary	Lobular cancer of R breast	R hip	146	0
27	F, 68	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	33	4
Average and stand. dev.	67 ± 6				39 ± 47

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TABLE I DATA ON THE PATIENTS IN GROUP 1

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Location of Total Joint Replacement	Time from Joint Replacement to Dissection of Lymph Nodes (Mos.)	Grade of Strongly Birefringent Particles Resembling Polyethylene*
1	M, 69	Pelvic	Prostate cancer	R knee	30	4
2	M, 72	Pelvic	Prostate cancer	L knee	2	3
3	F, 71	Pelvic, para-aortic	Endometrial adenocarcinoma	R hip	84	0
4	M, 68	Pelvic	Prostate cancer	L knee	53	3
5	F, 67	L axillary	Benign L axillary mass	L knee	1	2
6	M, 66	R axillary	Ductal cancer of R breast	L hip	6	2
7	M, 69	Pelvic	Prostate cancer	L knee	28	0
8	M, 63	Pelvic	Prostate cancer	R knee	25	2
9	F, 60	R inguinal	Vulvar cancer	L hip	17	2
10	M, 67	Pelvic	Prostate cancer	R hip	51	4
11	F, 58	Duodenal, para-aortic	Cholangiocarcinoma	Bilat. knee	192	3
12	M, 64	Pelvic	Prostate cancer	L hip	6	0
13	M, 63	Pelvic	Prostate cancer	R hip	36	3
14	M, 64	Pelvic	Prostate cancer	L knee	19	2
15	M, 68	Pelvic	Prostate cancer	L hip	88	0
16	F, 72	L axillary	Ductal cancer of L breast	R hip	113	2
17	F, 77	R axillary	Ductal cancer of R breast	L hip	12	4
18	M, 69	Pelvic	Prostate cancer	L hip	8	0
19	M, 78	R axillary	Melanoma of R side of back	L knee	19	2
20	F, 61	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	24	3
21	F, 61	L axillary	Ductal cancer of L breast	R knee	14	2
22	F, 68	R axillary	Ductal cancer of R breast	R knee	7	4
23	F, 60	Pelvic, iliac	Endometrial adenocarcinoma	R hip	26	1
24	M, 55	Pelvic	Prostate cancer	R hip	6	3
25	F, 76	R axillary	Ductal cancer of R breast	R hip	17	1
26	F, 79	R axillary	Lobular cancer of R breast	R hip	146	0
27	F, 68	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	33	4
Average and stand. dev.	67 ± 6				39 ± 47

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TABLE II DATA ON THE PATIENTS IN GROUP 2

*0 = no birefringent particles, 1 = widely scattered single birefringent particles without sinus histiocytosis, 2 = scattered aggregates of two birefringent particles or more per aggregate without sinus histiocytosis, 3 = single scattered regions of sinus histiocytosis with one birefringent particle or more, and 4 = numerous to confluent regions of sinus histiocytosis with multiple birefringent particles.

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Grade of Strongly Birefringent Particles Resembling Polyethylene*	Prev. Op. in Patients with False-Positive Result
28	F, 62	L axillary	Ductal cancer of L breast	0
29	F, 69	L axillary	Ductal cancer of L breast	0
30	F, 65	R axillary	Ductal cancer of R breast	0
31	F, 76	L axillary	Ductal cancer of L breast	4	Appendectomy, uterine suspension
32	M, 65	Pelvic	Prostate cancer	0
33	F, 76	R axillary	Lobular cancer of R breast	0
34	F, 79	L axillary	Lobular cancer of L breast	0
35	M, 74	L axillary	Lobular cancer of L breast	0
36	F, 52	Pelvic	Ovarian cancer	4	Abdominal op.
37	F, 73	Cervical	Benign thyroid nodule	4	Appendectomy, hysterectomy, cholecystectomy
38	F, 74	R axillary	Ductal cancer of R breast	3	None
39	F, 68	Pelvic	Endometrial adenocarcinoma	3	Appendectomy, hysterectomy
40	M, 74	Pelvic	Prostate cancer	0
41	F, 59	Pelvic, para-aortic	Endometrial adenocarcinoma	2	None
42	F, 74	L axillary	Ductal cancer of L breast	3	Hysterectomy, cholecystectomy
43	M, 67	Pelvic	Prostate cancer	0
44	F, 36	R axillary	Ductal cancer of R breast	0
45	M, 73	Cervical, parotid	Parotid cancer on R	2	Appendectomy
Average and stand. dev.	68 ± 10

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TABLE II DATA ON THE PATIENTS IN GROUP 2

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Grade of Strongly Birefringent Particles Resembling Polyethylene*	Prev. Op. in Patients with False-Positive Result
28	F, 62	L axillary	Ductal cancer of L breast	0
29	F, 69	L axillary	Ductal cancer of L breast	0
30	F, 65	R axillary	Ductal cancer of R breast	0
31	F, 76	L axillary	Ductal cancer of L breast	4	Appendectomy, uterine suspension
32	M, 65	Pelvic	Prostate cancer	0
33	F, 76	R axillary	Lobular cancer of R breast	0
34	F, 79	L axillary	Lobular cancer of L breast	0
35	M, 74	L axillary	Lobular cancer of L breast	0
36	F, 52	Pelvic	Ovarian cancer	4	Abdominal op.
37	F, 73	Cervical	Benign thyroid nodule	4	Appendectomy, hysterectomy, cholecystectomy
38	F, 74	R axillary	Ductal cancer of R breast	3	None
39	F, 68	Pelvic	Endometrial adenocarcinoma	3	Appendectomy, hysterectomy
40	M, 74	Pelvic	Prostate cancer	0
41	F, 59	Pelvic, para-aortic	Endometrial adenocarcinoma	2	None
42	F, 74	L axillary	Ductal cancer of L breast	3	Hysterectomy, cholecystectomy
43	M, 67	Pelvic	Prostate cancer	0
44	F, 36	R axillary	Ductal cancer of R breast	0
45	M, 73	Cervical, parotid	Parotid cancer on R	2	Appendectomy
Average and stand. dev.	68 ± 10

Materials and Methods

Introduction | Materials and Methods | Results | Discussion | References

With use of the computerized medical records system at Latter Day Saints Hospital in Salt Lake City, fifty patients were identified as having a history of both total joint replacement and dissection of lymph nodes because of cancer between 1983 and 1993. Of these fifty patients, forty-five had adequate specimens of lymph nodes for review. Specimens that had been obliterated by cancer or for which the histological preparation had been poor were rejected. Twenty-seven of the forty-five patients had had a total joint replacement before the lymph nodes were dissected (Group 1). None had had a revision joint replacement. The remaining eighteen patients had dissection of the lymph nodes before a total joint replacement and served as a control group (Group 2).

The records of the patients were reviewed for information regarding the dates of any operations, the time from the implantation of the joint replacement to the dissection of the lymph nodes, the location of the joint replacement, the location of the dissection, and the pathological diagnosis that was made on the basis of the dissection (Tables I and II). The average age (and standard deviation) was 67 ± 6 years (range, fifty-five to seventy-nine years) for the patients in Group 1 and 68 ± 10 years (range, thirty-six to seventy-nine years) for those in Group 2. The average time from the total joint replacement to the dissection of the lymph nodes was 39 ± 47 months (range, one to 192 months) for the patients who had had the replacement before the dissection.

The specimens of the dissected lymph nodes had been fixed in formalin, embedded in paraffin, and stained with hematoxylin and eosin for histological evaluation. The specimens were blindly and randomly reviewed by a pathologist under 100, 200, and 400 times magnification with use of a light microscope (BH-2; Olympus Optical, Tokyo, Japan) and polarizing filter. These specimens were first viewed under plain light to assess their histological features, including the presence of sinus histiocytosis (Figs. 1-A and 2-A). The illumination was changed to polarized light to detect strongly birefringent particles consistent with the appearance of polyethylene (Figs. 1-B and 2-B). The criteria used for the appearance of microscopic polyethylene were those of Mirra et al.^24,25, of Charosky et al.¹⁰, and of others^16,23,33,35. Artefacts, such as starch granules from talcum powder (which appear as a Maltese cross pattern), collagen fibers, and cotton fibers, were not counted as strongly birefringent particles of debris. In order for strongly birefringent particles to be considered similar to polyethylene, they had to be (1) poorly visualized or not clearly identifiable under plain light, (2) strongly birefringent and silver-white but not exhibiting dichroism under polarized light, (3) in or surrounded by histiocytes, and (4) in the plane of focus of the cytoplasm of the cells.

The presence of strongly birefringent particles resembling polyethylene within histiocytes was graded in a semiquantitative fashion with use of a scale of 0 to 4. Grade 0 indicated no birefringent particles; grade 1, widely scattered single birefringent particles without sinus histiocytosis; grade 2, scattered aggregates with two birefringent particles or more per aggregate without sinus histiocytosis; grade 3, single scattered regions of sinus histiocytosis with at least one birefringent particle; and grade 4, numerous to confluent regions of sinus histiocytosis with multiple birefringent particles. Sinus histiocytosis was defined as aggregates of histiocytes distending the sinusoids or located within the cortex of the lymph node. The highest grade for a particular dissection specimen was recorded. Because our specimens were from lymphatic tissue, in which the particle concentration is less than that found in tissue immediately adjacent to the joint capsule, we did not use the quantitative grading system developed by Mirra et al.²⁵. That scale is used to assess periprosthetic tissues, which contain relatively high numbers of polyethylene particles.

The term false-positive was used according to the definition of Armitage². A false-positive result indicated that the test result was positive when the condition did not exist. Patients in Group 2 who had a positive result for strongly birefringent particles were considered to have a false-positive result for polyethylene particles.

Results

Introduction | Materials and Methods | Results | Discussion | References

The nodes of twenty-one (78 per cent) of the twenty-seven patients in Group 1 were positive for strongly birefringent particles resembling polyethylene (Figs. 1-A and 1-B). The presence of particles was graded as 0 in six specimens, as 1 in two, as 2 in eight, as 3 in six, and as 4 in five (Table I). Analysis of the nodes from eight of the eighteen patients in Group 2 revealed a positive result for strongly birefringent particles resembling polyethylene (Figs. 2-A and 2-B). The presence of particles was graded as 0 in ten specimens, as 2 in two, as 3 in three, and as 4 in three (Table II). Most of the particles ranged in dimension from 0.5 to 2.0 micrometers.

In Group 1, the time from the implantation of the joint replacement to the appearance of strongly birefringent particles resembling polyethylene in the lymph nodes ranged from one to 192 months (average, thirty-nine months) (Table I). Such particles appeared within six months after the total joint replacement in five of the patients (Cases 2, 5, 6, 12, and 24; Table I). Two patients (Cases 2 and 5) had strongly birefringent particles resembling polyethylene present at two and one month postoperatively, respectively. Of the specimens in Group 1 that were positive for strongly birefringent particles resembling polyethylene, eight were from the axillary nodes (Table I).

The eight positive results for strongly birefringent particles resembling polyethylene in Group 2 were classified as false-positive. It should be noted that six of these eight results were for patients who had had an operation before the dissection of the lymph nodes. None of the six patients had had a previous total joint replacement or implantation of a device containing polyethylene (Table II).

Discussion

Introduction | Materials and Methods | Results | Discussion | References

The purpose of this study was to assess the dissemination, in the lymphoreticular system, of birefringent material resembling polyethylene particles from stable primary joint replacements. Numerous studies have demonstrated local distribution of particles to tissue adjacent to a prosthetic joint retrieved at the time of a revision operation^{8,10,11,14,16,25,28,34}. It is difficult to conduct histological studies of local distribution of particles from stable primary joint replacements because they require specimens that have been obtained at autopsy⁵. By using lymph nodes instead of local tissue obtained at a revision operation, we were able to assess the dissemination of polyethylene particles throughout the lymphoreticular system of patients who had a stable primary joint replacement.

Polarized light microscopy has been used for the identification of polyethylene particles in histological specimens for more than forty years²⁶. Of the numerous studies that have relied on this technique, few have addressed the issue of specificity of detection with polarized light^2,13. By including a control group of patients who had not had a joint replacement before the dissection, we could assess the reliability of polarized light microscopy for the identification of polyethylene particles. Eight of the eighteen patients in our control group had a false-positive result.

Schmalzried et al.²⁹ as well as Guttmann et al.¹³ studied the use of polarized light microscopy for the assessment of polyethylene particles. Employing polarized light, they refined further the criteria for identification of polyethylene particles in periprosthetic tissue and demonstrated the physical limitations of light microscopy in the identification of submicrometer polyethylene particles. Even with use of their refined polarized-light technique, the larger particles (1.0 to 2.0 micrometers) identified in the present study were still classified as polyethylene. The size of many polyethylene particles is beyond the resolution limits of light microscopy, and different techniques are necessary to identify these particles in histological specimens or in digested tissue^7,13,18.

Our first hypothesis was that polarized light microscopy is a reliable method for the identification of polyethylene particles in the lymphoreticular system. This was disproved. The control group, which included patients who did not have a total joint replacement before dissection of the lymph nodes, had a false-positive rate of eight of eighteen patients.

Other particles, including silica, starch granules from talcum powder, expanded polytetrafluoroethylene or Gore-Tex (W. L. Gore and Associates, Flagstaff, Arizona), and Dacron, can exhibit birefringence under polarized light^13,22. In this review of histological specimens, well defined criteria were used for the identification of birefringent polyethylene particles under polarized light^{10,11,16,23-25,33,35} and thus the rate of false-positive results was minimized.

There are several possible reasons for the false-positive results. Six of the eight patients who had such a result had had a previous operation (Table II), although not a total joint replacement. These patients had had a major abdominal operation, and the inorganic, non-degradable sutures and clips commonly used in such procedures may have generated particles that appeared similar to polyethylene under polarized light. None of these patients had had polyethylene implanted during the previous operation. It is also possible that these false-positive results represent an artefact of tissue-processing. It is not uncommon for clean, packaged histological slides to contain particles of silica one to five micrometers in size. These or other particles may have been introduced into the histological specimens from the chemicals or embedding techniques used during tissue-processing. We attempted to limit this possibility by excluding particles that were not in the same plane of focus as that of the cytoplasm of the cells. Another possible explanation for strongly birefringent particles in the lymphoreticular system is exposure to airborne environmental particles. Studies on the pulmonary inhalation of environmental particles have shown that these particles are concentrated within the lymphoreticular system⁶.

The second hypothesis of our study was that polarized light microscopy can be used to identify systemic dissemination of polyethylene particles reliably in patients who have had a joint replacement. This was not the case. Because of the lack of specificity of polarized light microscopy in the identification of polyethylene, we were unable to state with certainty that the birefringent particles identified in the dissected lymph nodes were polyethylene wear debris. Thus, the results in Group 1 (the patients who had had a total joint replacement before dissection of the lymph nodes) must be questioned, as some of them may be false-positive.

Previous studies have demonstrated dissemination of particles resembling polyethylene through the lymphoreticular system to regional lymph nodes in subdiaphragmatic sites, including the para-iliac, inguinal, and para-aortic lymph nodes^5,23. Metal particles from total joint replacements have been demonstrated in periprosthetic tissue; throughout the lymphoreticular system; and in the liver, spleen, and lungs. Metal particles have been identified with the use of sophisticated techniques, such as laser-microprobe mass analysis⁵, electron microscope x-ray-probe microanalysis³¹, and atomic absorption spectrometry¹⁹. After a thorough review of the literature, we were unable to identify any studies that have demonstrated dissemination of polyethylene particles from a total hip or knee replacement to other supradiaphragmatic regions.

The present study demonstrated strongly birefringent particles in the axillary nodes in eight patients (Cases 5, 6, 16, 17, 19, 21, 22, and 25; Table I) who had had a total joint replacement before dissection of the lymph nodes. If the strongly birefringent particles identified in the axillary nodes were actually polyethylene, this represents an unusual finding. Particles produced from joint replacements in a lower extremity can be transported to the subdiaphragmatic lymph nodes^{3,12,14,19,31}. These lymph nodes drain into the thoracic duct, which drains all of the lymph from the body except that from the right upper extremity and the right halves of the thorax, head, and neck. The thoracic duct drains into the venous system at the confluence of the left internal jugular and subclavian veins. Retrograde flow is possible in the lymphatic system, and particles from a joint replacement could possibly flow retrograde from the thoracic duct into the left axillary node chain²⁰.

Drainage of lymph from the right upper extremity has a separate path into the central venous system that is distinct from the thoracic duct. Therefore, retrograde flow from the thoracic duct to the right axillary chain is not possible, and joint particles from the lower extremity cannot be transported directly through the lymphatic system to the right axillary nodes. Because of the isolation of the right axillary chain from the thoracic duct and from particles from joint replacements in a lower extremity, the presence of particles in the right axillary lymph chain suggests systemic distribution of joint particles through the hematological vascular system to the right upper extremity. If systemic distribution does occur, the particles could be transported to the right axillary nodes by the lymphatic drainage of that extremity²⁰. These observations suggest false-positive results and are additional evidence against the reliability of polarized light microscopy in this determination.

In conclusion, the present study casts doubt on the reliability of polarized light microscopy as a test for the presence of polyethylene particles in specimens from lymph nodes. It is well known that the lymphoreticular system can contain foreign particles from various sources, such as operative implants or inhaled particles. Osteolysis induced by particulate debris is recognized as a major threat to the long-term durability of total joint replacements¹. Attempts to define and improve the sensitivity and specificity of the existing tests for polyethylene particles are essential to avoid false-positive identification of such particles. More refined microscopy that employs polarized light¹³, in addition to other methods of physical and chemical analysis^7,18,30, may be necessary to identify polyethylene particles accurately within the lymphoreticular system and periprosthetic tissue.

References

Introduction | Materials and Methods | Results | Discussion | References

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Armitage, P.: Statistical Methods in Medical Research, p. 434. New York, Wiley, 1971.

Bauer, T. W.; Saltarelli, M.; McMahon, J. T.; and |and |Wilde, A. H.: Regional dissemination of wear debris from a total knee prosthesis. A case report. J. Bone and Joint Surg,75-A: 106-111, Jan. 1993.75-A106 1993

Bloebaum, R. D.; Beeks, D.; Dorr, L. D.; Savory, C. G.; Dupont, J. A.; and |and |Hofmann, A. A.: Complications with hydroxyapatite particulate separation in total hip arthroplasty. Clin. Orthop,298: 19-26, 1994.29819 1994 [PubMed]

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Campbell, P.; Clarke, I. C.; and Kossovsky, N.: Clinical significance of wear debris. In Hip Arthroplasty, pp. 555-570. Edited by H. C. Amstutz. New York, Churchill Livingstone, 1991.

Campbell, P. A.; Ma, S.; Schmalzried, T. P.; and |and |Amstutz, H. C.: Technical note. Tissue digestion for wear debris particle isolation. J. Biomed. Mater. Res,28: 523-526, 1994.28523 1994 [PubMed][CrossRef]

Charnley, J.: Tissue reactions to polytetrafluorethylene [letter]. Lancet,2: 1379, 1963.21379 1963 [CrossRef]

Charnley, J.: Low Friction Arthroplasty of the Hip. Theory and Practice. New York, Springer, 1979.

Charosky, C. B.; Bullough, P. G.; and |and |Wilson, P. D., Jr.: Total hip replacement failures. A histological evaluation. J. Bone and Joint Surg,55-A: 49-58, Jan. 1973.55-A49 1973

Dorr, L. D.; Bloebaum, R.; Emmanual, J.; and |and |Meldrum, R.: Histologic, biochemical, and ion analysis of tissue and fluids retrieved during total hip arthroplasty. Clin. Orthop,261: 82-95, 1990.26182 1990 [PubMed]

Gray, M. H.; Talbert, M. L.; Talbert, W. M.; Bansal, M.; and |and |Hsu, A.: Changes seen in lymph nodes draining the sites of large joint prostheses. Am. J. Surg. Pathol,13: 1050-1056, 1989.131050 1989 [PubMed][CrossRef]

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Johanson, N. A.; Bullough, P. G.; Wilson, P. D. Jr.; Salvati, E. A.; and |and |Ranawat, C. S.: The microscopic anatomy of the bone-cement interface in failed total hip arthroplasties. Clin. Orthop,218: 123-135, 1987.218123 1987 [PubMed]

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Langkamer, V. G.; Case, C. P.; Heap, P.; Taylor, A.; Collins, C.; Pearse, M.; and |and |Solomon, L.: Systemic distribution of wear debris after hip replacement. A cause for concern. J. Bone and Joint Surg,74-B(6): 831-839, 1992.74-B(6)831 1992

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Santavirta, S.; Konttinen, Y. T.; Bergroth, V.; Eskola, A.; Tallroth, K.; and |and |Lindholm, T. S.: Aggressive granulomatous lesions associated with hip arthroplasty. Immunopathological studies. Bone and Joint Surg,72-A: 252-258, Feb. 1990.72-A252 1990

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Under polarized light, there are strongly birefringent particles resembling polyethylene (a grade of 4).

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Figs. 2-A and 2-B: Case 31. Photomicrographs of a specimen from an axillary lymph node. Fig. 2-A: Under plain light (X 400).

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TABLE I DATA ON THE PATIENTS IN GROUP 1

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Location of Total Joint Replacement	Time from Joint Replacement to Dissection of Lymph Nodes (Mos.)	Grade of Strongly Birefringent Particles Resembling Polyethylene*
1	M, 69	Pelvic	Prostate cancer	R knee	30	4
2	M, 72	Pelvic	Prostate cancer	L knee	2	3
3	F, 71	Pelvic, para-aortic	Endometrial adenocarcinoma	R hip	84	0
4	M, 68	Pelvic	Prostate cancer	L knee	53	3
5	F, 67	L axillary	Benign L axillary mass	L knee	1	2
6	M, 66	R axillary	Ductal cancer of R breast	L hip	6	2
7	M, 69	Pelvic	Prostate cancer	L knee	28	0
8	M, 63	Pelvic	Prostate cancer	R knee	25	2
9	F, 60	R inguinal	Vulvar cancer	L hip	17	2
10	M, 67	Pelvic	Prostate cancer	R hip	51	4
11	F, 58	Duodenal, para-aortic	Cholangiocarcinoma	Bilat. knee	192	3
12	M, 64	Pelvic	Prostate cancer	L hip	6	0
13	M, 63	Pelvic	Prostate cancer	R hip	36	3
14	M, 64	Pelvic	Prostate cancer	L knee	19	2
15	M, 68	Pelvic	Prostate cancer	L hip	88	0
16	F, 72	L axillary	Ductal cancer of L breast	R hip	113	2
17	F, 77	R axillary	Ductal cancer of R breast	L hip	12	4
18	M, 69	Pelvic	Prostate cancer	L hip	8	0
19	M, 78	R axillary	Melanoma of R side of back	L knee	19	2
20	F, 61	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	24	3
21	F, 61	L axillary	Ductal cancer of L breast	R knee	14	2
22	F, 68	R axillary	Ductal cancer of R breast	R knee	7	4
23	F, 60	Pelvic, iliac	Endometrial adenocarcinoma	R hip	26	1
24	M, 55	Pelvic	Prostate cancer	R hip	6	3
25	F, 76	R axillary	Ductal cancer of R breast	R hip	17	1
26	F, 79	R axillary	Lobular cancer of R breast	R hip	146	0
27	F, 68	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	33	4
Average and stand. dev.	67 ± 6				39 ± 47

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TABLE I DATA ON THE PATIENTS IN GROUP 1

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Location of Total Joint Replacement	Time from Joint Replacement to Dissection of Lymph Nodes (Mos.)	Grade of Strongly Birefringent Particles Resembling Polyethylene*
1	M, 69	Pelvic	Prostate cancer	R knee	30	4
2	M, 72	Pelvic	Prostate cancer	L knee	2	3
3	F, 71	Pelvic, para-aortic	Endometrial adenocarcinoma	R hip	84	0
4	M, 68	Pelvic	Prostate cancer	L knee	53	3
5	F, 67	L axillary	Benign L axillary mass	L knee	1	2
6	M, 66	R axillary	Ductal cancer of R breast	L hip	6	2
7	M, 69	Pelvic	Prostate cancer	L knee	28	0
8	M, 63	Pelvic	Prostate cancer	R knee	25	2
9	F, 60	R inguinal	Vulvar cancer	L hip	17	2
10	M, 67	Pelvic	Prostate cancer	R hip	51	4
11	F, 58	Duodenal, para-aortic	Cholangiocarcinoma	Bilat. knee	192	3
12	M, 64	Pelvic	Prostate cancer	L hip	6	0
13	M, 63	Pelvic	Prostate cancer	R hip	36	3
14	M, 64	Pelvic	Prostate cancer	L knee	19	2
15	M, 68	Pelvic	Prostate cancer	L hip	88	0
16	F, 72	L axillary	Ductal cancer of L breast	R hip	113	2
17	F, 77	R axillary	Ductal cancer of R breast	L hip	12	4
18	M, 69	Pelvic	Prostate cancer	L hip	8	0
19	M, 78	R axillary	Melanoma of R side of back	L knee	19	2
20	F, 61	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	24	3
21	F, 61	L axillary	Ductal cancer of L breast	R knee	14	2
22	F, 68	R axillary	Ductal cancer of R breast	R knee	7	4
23	F, 60	Pelvic, iliac	Endometrial adenocarcinoma	R hip	26	1
24	M, 55	Pelvic	Prostate cancer	R hip	6	3
25	F, 76	R axillary	Ductal cancer of R breast	R hip	17	1
26	F, 79	R axillary	Lobular cancer of R breast	R hip	146	0
27	F, 68	Pelvic, para-aortic	Endometrial adenocarcinoma	R knee	33	4
Average and stand. dev.	67 ± 6				39 ± 47

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TABLE II DATA ON THE PATIENTS IN GROUP 2

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Grade of Strongly Birefringent Particles Resembling Polyethylene*	Prev. Op. in Patients with False-Positive Result
28	F, 62	L axillary	Ductal cancer of L breast	0
29	F, 69	L axillary	Ductal cancer of L breast	0
30	F, 65	R axillary	Ductal cancer of R breast	0
31	F, 76	L axillary	Ductal cancer of L breast	4	Appendectomy, uterine suspension
32	M, 65	Pelvic	Prostate cancer	0
33	F, 76	R axillary	Lobular cancer of R breast	0
34	F, 79	L axillary	Lobular cancer of L breast	0
35	M, 74	L axillary	Lobular cancer of L breast	0
36	F, 52	Pelvic	Ovarian cancer	4	Abdominal op.
37	F, 73	Cervical	Benign thyroid nodule	4	Appendectomy, hysterectomy, cholecystectomy
38	F, 74	R axillary	Ductal cancer of R breast	3	None
39	F, 68	Pelvic	Endometrial adenocarcinoma	3	Appendectomy, hysterectomy
40	M, 74	Pelvic	Prostate cancer	0
41	F, 59	Pelvic, para-aortic	Endometrial adenocarcinoma	2	None
42	F, 74	L axillary	Ductal cancer of L breast	3	Hysterectomy, cholecystectomy
43	M, 67	Pelvic	Prostate cancer	0
44	F, 36	R axillary	Ductal cancer of R breast	0
45	M, 73	Cervical, parotid	Parotid cancer on R	2	Appendectomy
Average and stand. dev.	68 ± 10

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TABLE II DATA ON THE PATIENTS IN GROUP 2

Case	Sex, Age (Yrs.)	Location of Dissection of Lymph Nodes	Diagnosis	Grade of Strongly Birefringent Particles Resembling Polyethylene*	Prev. Op. in Patients with False-Positive Result
28	F, 62	L axillary	Ductal cancer of L breast	0
29	F, 69	L axillary	Ductal cancer of L breast	0
30	F, 65	R axillary	Ductal cancer of R breast	0
31	F, 76	L axillary	Ductal cancer of L breast	4	Appendectomy, uterine suspension
32	M, 65	Pelvic	Prostate cancer	0
33	F, 76	R axillary	Lobular cancer of R breast	0
34	F, 79	L axillary	Lobular cancer of L breast	0
35	M, 74	L axillary	Lobular cancer of L breast	0
36	F, 52	Pelvic	Ovarian cancer	4	Abdominal op.
37	F, 73	Cervical	Benign thyroid nodule	4	Appendectomy, hysterectomy, cholecystectomy
38	F, 74	R axillary	Ductal cancer of R breast	3	None
39	F, 68	Pelvic	Endometrial adenocarcinoma	3	Appendectomy, hysterectomy
40	M, 74	Pelvic	Prostate cancer	0
41	F, 59	Pelvic, para-aortic	Endometrial adenocarcinoma	2	None
42	F, 74	L axillary	Ductal cancer of L breast	3	Hysterectomy, cholecystectomy
43	M, 67	Pelvic	Prostate cancer	0
44	F, 36	R axillary	Ductal cancer of R breast	0
45	M, 73	Cervical, parotid	Parotid cancer on R	2	Appendectomy
Average and stand. dev.	68 ± 10