intrapulmonary lymph nodes in south african miners—an autopsy survey
TRANSCRIPT
AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 50:261–264 (2007)
Intrapulmonary Lymph Nodes in SouthAfrican Miners—An Autopsy Survey
Koichi Honma, MD,1 Gill Nelson, MSc,2 and Jill Murray, MD2,3�
Background Knowledge on intrapulmonary lymph nodes (IPLNs) is still limited.Progress in imaging techniques has enabled easier, more frequent visualization of IPLNsso that a more comprehensive understanding of these nodes is necessary.Methods Microscopic slides of lung tissue from 2,337 dust-exposed South African minersautopsied in 1975 were reviewed to identify IPLNs. The prevalence of IPLNs wascalculated and histopathological changes in IPLNs and the surrounding lung parenchymawere described. Pathological changes of IPLNs were correlated with those of thesurrounding pulmonary parenchyma.Results IPLNswere found in 86 of theminers (3.7%). Silicotic noduleswere seen in IPLNsin 32 of the 86 cases (37.2%), in themajority of which (21/32; 65.6%) the surrounding lungparenchyma was almost normal.Conclusion IPLNs are not uncommon among dust-exposed individuals. Silicotic fibrosisof IPLNs appears to precede pulmonary parenchymal disease. Am. J. Ind. Med. 50:261–264, 2007. � 2007 Wiley-Liss, Inc.
KEY WORDS: intrapulmonary lymph nodes; autopsy; miners; silicosis
INTRODUCTION
Pulmonary lymph nodes are normally found around the
main bronchi at the hilum of the lung. However, lymph nodes
may also be found anywhere within the lung parenchyma,
even as far out as the pleura [Trapnell, 1964; Kradin et al.,
1985]. Grossly, such intrapulmonary lymph nodes (IPLNs)
are identified as black spots on the pleural surface or as
palpable pigmented nodules in the lung parenchyma,
measuring up to 20 mm in diameter [Kradin et al., 1985].
Histologically, well-developed IPLNs are identical to
ordinary lymph nodes comprising both cortex and medulla,
with or without germinal centers; the peripheral capsulemay,
however, be incomplete [Kradin et al., 1985].
IPLNs are usually detected as incidental radiographic
findings in asymptomatic patients [Kradin and Mark, 1983].
With the widespread utilization of mass survey and general
health examination chest radiographs and CT scans, they
have become increasingly easier to detect, and they enter
into the differential diagnosis of coin lesions in the lung
[Fujimoto et al., 1998; Takashima et al., 2003]. Despite
recent progress in imaging technology, it is currently not
possible to distinguish IPLNs radiologically from other
benign or malignant pulmonary nodules [Bankoff et al.,
1996; Fujimoto et al., 1998; Yokomise et al., 1998;
Tsunezuka et al., 2000].
Although several case reports and small series of IPLNs
have been reported over the past decades, the prevalence of
IPLNs in the general population is unknown. Most reports of
IPLNs are based on cases referred for investigation of solitary
pulmonary nodules [Kradin et al., 1985; Bankoff et al., 1996;
Fujimoto et al., 1998; Yokomise et al., 1998]. This article
� 2007Wiley-Liss, Inc.
1Department of Pathology, Dokkyo University School of Medicine, Mibu,Tochigi, Japan2School of Public Health, University of theWitwatersrand, Johannesburg, South Africa3Pathology Section,National Institute for Occupational Health,National Health Laboratory
Service, Johannesburg, South AfricaThe workwas performed at the National Institute for Occupational Health, Johannesburg,
South Africa. Part of this study was presented at the19th European Congress of Pathology,September 6^11, 2003 in Ljubljana, Slovenia.
*Correspondence to: Jill Murray, National Institute for Occupational Health, P.O. Box 4788,Johannesburg, 2000, South Africa. E-mail: [email protected]
Accepted 2 January 2007DOI10.1002/ajim.20436. Published online inWiley InterScience
(www.interscience.wiley.com)
describes the prevalence and histologic appearances of
IPLNs in an autopsy-based study of South African miners,
and is the largest known series of IPLNs to date.
MATERIALS AND METHODS
By South African law, autopsy examination of the
cardiorespiratory organs of deceased miners and ex-miners
is required for compensation purposes, regardless of the
clinical cause of death, provided the next of kin agrees.
Autopsy rates are high, viz. 80%, for men who die in
employment. The organs are removed locally (where the
person dies), placed in formalin and sent to the National
Institute for Occupational Health (NIOH) where compre-
hensive macroscopic and microscopic examinations are
conducted according to standard procedures. The lungs are
sliced into sections of 3 mm. These sections are examined
visually and are also thoroughly palpated for detection of
nodules (the size detection limit is around 2 mm). Although
not all nodules are examined histologically as there may be
dozens of silicotic nodules in a single lung, all nodules
suspected of being IPLNs on macroscopic examination
are examined histologically to confirm the diagnosis. The
gold mining industry accounts for approximately 80% of
autopsies.
Microscopic slides of the lung tissue from all 2,337
consecutive cases autopsied in 1975 were reviewed by one of
the authors in order to identify and describe the IPLNs.
Special attention was paid to IPLNs located in the peripheral
lung tissue (lymph nodes adjoining the major bronchi were
excluded). Histological features of the IPLNswere noted and
prevalence was calculated. Size and distribution of IPLNs by
lung zones were not recorded. In these cases with IPLNs,
various secondary pathologic changes were also investi-
gated, including massive fibrosis, tuberculosis, emphysema,
diffuse interstitial fibrosis, and lung cancer, as previously
described elsewhere [Honma et al., 1997].
RESULTS
Eighty-six of the 2,337 autopsy cases had IPLNs, giving
a prevalence of 3.7%; multiple IPLNs were seen in 9 of
these cases (10.6%). The ages of the men ranged from 18 to
80 years, with a mean age of 47.4 years. The majority of men
with available exposure had worked in the gold mining
industry (66/86; 76.7%). A further 7.4% had worked in the
coal mining industry; the remaining 11.1% hadworked in the
platinum, asbestos, iron and copper mining industries.
There were silicotic nodules in 37.2% (32/86) of the
IPLNs (Table I, Fig. 1). In the majority of cases with silicotic
nodules in the IPLNs (21/32; 65.6%), the lungs were
unremarkable with only some dust-laden macrophages in
the alveoli. The surrounding lung parenchyma was frankly
silicotic in five cases with silicotic nodules in the IPLNs (5/
32; 15.6%). The remaining six cases showed dust macules,
i.e. interstitial peribronchiolar dust-laden macrophages
accompanied by a moderate increase in reticulin fibers.
Seven of the 86 cases had pulmonary tuberculosis but no
tuberculosis was seen in the IPLNs. Six cases had both
primary lung cancer and IPLNs; two of these had deposits
of metastatic carcinoma in the IPLNs. There were only
three cases of parenchymal silicosis without IPLN
silicosis. All the nodes had collections of pigment/dust-
laden macrophages.
DISCUSSION
To our knowledge no previous studies have reported
population prevalence rates of IPLNs. The prevalence in this
study, which is the largest known series of IPLNs to date, was
3.7%. This is, however, a minimum estimate as not all
nodules are examined histologically. It has been mentioned
that IPLNs develop on an acquired basis from intrapulmon-
ary lymphoid tissue associated with deposition of dust
[Trapnell, 1964; Kradin andMark, 1983; Kradin et al., 1985].
If excessive exposure to dust facilitates the conversion of
intrapulmonary lymphoid tissue into IPLNs, as has been
suggested [Trapnell, 1964; Kradin and Mark, 1983; Kradin
et al., 1985], the prevalence of IPLNs in the general
population which, unlike miners, is not exposed to dust,
would be expected to be lower than the 3.7%observed among
this group of dust-exposed workers. It is interesting to note
that this prevalence is higher than that of peripheral
pulmonary hamartomas in a similar population of miners
TABLE I. Pathology of Lung Parenchyma in 86 Cases with IntrapulmonaryLymphNodes
Pathology
Silicotic nodules inthe intrapulmonary
lymph nodes Total
Yes (n¼ 32) No (n¼ 54) n¼ 86
Silicosis 5 3 8Dustmacules 6 8 14Dust-ladenmacrophages in the alveoli 21 15 36Bronchopneumonia 13 9 22Marked emphysema 7 6 13Interstitial fibrosis 0 4 4Malignant lymphoma 1 0 1*Leukemia 0 1 1Ferruginous bodies 2 6 8Pulmonary tuberculosis 4 3 7**Lung cancer 2 4 6{
*Not present in the lymph nodes.**None with tuberculosis in the lymph nodes.{Two with metastatic deposits in the lymph nodes.
262 Honma et al.
who came to autopsy from 1975 to 1988, viz. 0.1% to 0.75%
[Murray et al., 1991a].
The histopathologic spectrum between peribronchiolar
lymphoreticular aggregates and IPLNs suggests an acquired
nature of most IPLNs [Hayek, 1970], and a reaction to
inhaled dustmay play an important role in their development,
causing hypertrophy of lymphoid tissue in the lung [Trapnell,
1964; Kradin and Mark, 1983; Kradin et al., 1985; Murray
et al., 1991b; Bankoff et al., 1996]. Several observations
support this, such as aggregates of dust-ladenmacrophages in
the IPLNs which have been identified in several case series
[Kradin and Mark, 1983; Kradin et al., 1985; Bankoff et al.,
1996; Katzenstein, 1997]. In our series, all of the IPLNs
showed dust-laden macrophages. In addition, silicotic
collagenization in IPLNs has also been reported [Kradin
and Mark, 1983; Kradin et al., 1985].
In some cases, IPLNs exhibit extensive silicotic fibrosis,
mimicking a large parenchymal silicotic nodule. If IPLN
silicosis is this advanced in an individual with a history of
occupational exposure to dust, it may mimic confluent or
large parenchymal silicotic nodules, possibly leading to an
erroneous diagnosis of pulmonary silicosis even though the
lungs may otherwise appear unremarkable.
Silicotic collagenization was present in 37.2% of the
IPLNs. In this autopsy study, unlike most other reported
studies, the macroscopic and microscopic histological
findings of the lungs were known. Seven cases had
pulmonary tuberculosis; however, no tuberculosis was seen
in the IPLNs. Six cases had primary lung cancer, two of
which had deposits of metastatic carcinoma in the IPLNs. In
none of our cases did the IPLNswith silicotic collagenization
show calcification. This is in contrast to hilar lymph nodes in
silica dust exposed people which not infrequently have
calcification (responsible for the radiographic eggshell
appearance).
In this series there was no silicosis in the lung
parenchyma in 84% of the cases with silicotic nodules in
the IPLNs. Just as hilar lymph node fibrosis appears to
precede parenchymal silicosis [Kradin et al., 1985; Baldwin
et al., 1996] and probably occurs at relatively low levels of
exposure to silica dust coupled with a superior lymphatic
clearance, so could one expect a similar sequence in cases
with IPLN collagenization.
The data presented here are from autopsies conducted in
1975. Although the severity of silicosis, and prevalence of
HIVand tuberculosis have changed in themining population,
we are not aware of any data to suggest that these changes
would affect the prevalence of IPLNs.
CONCLUSION
IPLNs are not uncommon among dust-exposed indivi-
duals (3.7%). IPLNs with silicotic fibrosis may masquerade
as parenchymal nodules, leading to an erroneous diagnosis of
pulmonary silicosis.
Silicotic fibrosis in IPLNs appears to precede pulmonary
parenchymal disease as do pulmonary hilar lymph nodes.
Ethical Issues
Consent for the use of autopsy material for research
purposes is given by the next of kin when the organs are
submitted to the NIOH. The research was reviewed and
FIGURE 1. Lungsectionshowingadust-laden intrapulmonary lymphnodewith silicoticnodules.Hematoxylin andEosin,X5.
Intrapulmonary Lymph Nodes in South African Miners 263
approved by the University of the Witwatersrand
Human Research Ethics Committee (Certificate no. R14/49
Murray).
ACKNOWLEDGMENTS
The authors thank JCantrell for technical assistance, and
the pathologists who performed the autopsies.
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