Intrathoracic
Lymph
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THERESA
Node
C. McLOUD,1
Metastases
LESTER
KALISHER,1’
from 2
The clinical records of 1 ,071 cases of extrathoracic malignant neoplasms seen over a 2 year period were reviewed: 163 had abnormal chest films, and 25 of these showed evidence of mediastinal and/or hilar lymph node metastases. The primary malignancies which metastasized to intrathoracic lymph nodes included eight tumors of the head and neck, 12 genitourinary malignancies, three carcinomas of the breast, and two malignant melanomas. The chest films were analyzed to determine the distribution of lymph node groups involved. Unilateral lymph node enlargement occurred in eight. The most frequently detected lymph node group was the right paratracheal chain (60%), while the subcarinal and posterior mediastinal groups were rarely affected. Of the 25 cases, 10 had radiographic evidence of hematogenous or lymphangitic metastases in addition in the lungs. Metastatic disease from extrathoracic neoplasms should always be considered in the differential diagnosis of hilar and mediastinal adenopathy.
PAUL
STARK,1
disease cause
enlargement. lymphadenopathy series
of
patients
cite
neoplasms hilar lymph
Radiographically identifiable has previously been
cell carcinoma Isolated case 8] also
from extrathoracic of mediastinal and
Of
the
strated
with
malignant
melanoma
[2, 3], and carcinoma reports [5-7] and personal primary
sources
from
[1],
nopathy.
cancer
of the
testinal tract, prostate, kidneys, and breast. took the following radiologic study to assess frequency of various types of extrathoracic
which
metastasize
describe lymph
the node
to intrathoracic distribution
groups
lymph
of
Among
films,
which
are
Materials
upper
(i.e., lung,
and
renal
metastatic
spread;
and mediastinum);
of the lymphatic
until
the
[4]. [7,
were
cases
node
address:
Am J Ro.ntg.nol © 1978 American
Department
to
expired
during
reviewed ease,
the
131:403-407,
Roentgen
September Ray Society
General
twelve
of
(table
was testicular
the
25 cases.
with
in
tumors
intrathoracic
intrathoracic
Four
pa-
demexamitwo of
lymph
available
The
h ig hest
and
on routine chest of hilar and/or was
the
1).
node
films. mediastinal
in
14
of
the
at autopsy, 1 1 had or mediastinoscopy,
25
biopsy and
period
1974-1977,
and
four
fact
node
for
that
evidence
11
of
metastases
case recsummaries (1977) and a
ture (1)
exist,
the
or
and
(3)
enous
lung
or lymphagitic
type
the
extent
codify the inin nomencla-
nodes
were
[9]:
(nodes
of
in
this
included
nodes,
posterior
of parenchymal
mdi-
classification
prevascular
bifurcation,
disthoracic
2 years
and to variations
(2) peritracheobronchial pulmonary nodes
with
within
window chain,
metastatic
finding. to determine
to use Rouviere’s
mediastinal
region);
for
of the analyzed
aorticopulmonary
group);
other patients
lymphadenopathy Although several
we chose
anterior
25
succumbed
cates the grave prognosis The chest films were of intrathoracic volved groups.
of
the
that
is, right
or subcarinal
and nodes
roots or hilar nodes (proxiwere also included in the hilar mediastinal
nodes.
metastases
of either
was
also
The
pres-
hematog-
assessed.
April 24, 1978. Hospital
5t. Barnabas 1978
the
follow-up
in detail the
lymph
malig-
The
present
after revision
of Radiology,
neck);
one had an aspiration needle biopsy of a parenchymal lung metastasis. The remaining 11 had clinical courses consistent with metastatic disease. Five of those 11
ence
Present
testis),
metastases
were analyzed by two of us (T. C. McLoud and L. Kalisher) the presence of hilar or mediastinal lymph node enlargement.
2
and
sarcomas
among
cases. Two were confirmed performed at either thoracotomy
nodes of the intrapulmonary
Massachusetts
no
(kidney,
and mal
20, 1978; accepted
because
carcinomas
metastases
were discovered corroboration
25 cases were in the pediatric age group. The chest radiographs of 163 patients were reported as abnormal at some point during their clinical course. Of these, 149 were available for review and
of Radiology,
cavity,
(21 .4%)
metastases
paratracheal
January
avail-
series
malanomas
intrathoracic
left
Department T. C. McLoud.
without
the
three
malignant
There
lymph
gastroin-
listing of all abnormal radiographic studies. A total of 1,071 cases had 1,151 malignant tumors; several patients had two or more primary tumors. The 651 females and 420 males ranged in age from 8 to 100 years (mean, 50.8); only
Aeceived
oral
carcinoma
metastases Pathologic
and reticuloen-
which
follow-up
cases
in
of the remaining six demonstrated reduction in the lymphadenopathy after irradiation or chemotherapy. Although not all clinical records of the study group were
and leukemia). of computerized
clinical
passage,
of
node
these
intrathoracic
dothelial system (i.e., lymphoma ords were available in the form included
additional
included
demon-
lymphade-
tients had hilar or mediastinal lymphadenopathy onstrated on the chest film at the time of initial nation (thyroid, kidney, testis, and larynx). In
spinal cord, and skin (except melato rarely cause any form of distant
and tumors
24
mediastinal
reports described bilateral hilar and lymph node enlargement. The primary
two
cell
(29.4%).
Methods
esophagus,
nant tumors of the brain, noma), which are known
14
was
reviewed,
and/or
malignancies;
freq uency
The clinical records of patients initially seen in the Oncology Center of our institution during 1974 and 1975 were reviewed. Excluded from the study were patients with primary intratho-
racic cancers
the
one
respiratory
breast;
involved.
and
radiographs
of hilar
genitourinary
a
and
GREENE1
malignancies which metastasized to intrathoracic lymph nodes included eight tumors of the head and neck (i.e.,
We underthe relative neoplasms
nodes
particular
REGINALD
chest
several radiologic right paratracheal
renal
of the breast observations
149
evidence
able
is an node
intrathoracic reported in
AND
Neoplasms
Results
lymph Metastatic infrequent
Extrathoracic
and Harvard Medical
Medical
Center,
403
School,
Livingston,
Boston, New Jersey
Massachusetts
02114.
Address
reprint
requests
07039.
0361 -803X/78/0900-0403
$00.00
to
McLOUD
404
TABLE Frequency
of Intrathoracic
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Head and neck: Larynx Lingual tonsil Nasopharynx
Nasal
cavity
(malignant Total
only
additional the films several
and were
lateral
performed
%
2 1 1
3.7 5.3 6.6
1
14.3
2 1
6.1 3.3
34 18 27 14 28 17 248
1 1 1 3 1 5 3
2.9 5.5 3.7 21.4 3.6 29.4 1.2
52
2
3.8
tomographic on one patient radiologic
high on
studies. could
reports
kilovoltage 15
patients;
Lymph
Anterior mediastinal Bilateral hilar Right hilar Left hilar
Bilateral
Nodes No. Cases
.
No.
25
2
of Metastatic Location
33 30
595
Posteroanterior films
Location
Cases with Adenopathy
7
melanoma)....
Anatomic
Metastases
53 19 15
Thyroid Tongue Genitourinary: Bladder Cervix uteri Corpus uteri Kidney Ovary Testis Breast
Skin
TABLE Node
No. Cases . Reviewed
Malignancy
AL.
1 Lymph
.
Sites ot Primary
ET
6 7 4 6 4 11 2 1 1
paratracheal
Aightparatracheal Left paratracheal Posterior mediastinal Subcarinal
4.2
(150 nine
kV) had
As mentioned above, not be retrieved, but
indicated
the
presence
of
lymphadenopathy. The initial chest radiograph which demonstrated the intrathoracic lymph node enlargement was evaluated. Table 2 lists the frequency of anatomic distribution of the involved lymph node groups. Unilateral lymph node enlargement was observed in eight of the 25 patients (fig. 1), and bilateral hilar nodes with or without mediastinal involvement was seen in seven (fig. 2). The right paratracheal chain was the most frequently detected lymph node group (60%) (fig. 1). The least frequently detected groups included the subcarinal region and nodes of the posterior mediastinum (one case each). However, evaluation of these areas was limited by the absence of overpenetrated posteroanterior views or mediastinal tomograms in all cases. Five cases had multiple pulmonary nodules consistent with hematogenous metastases (fig. 3) and five had a radiographic pattern indicative of either local or diffuse lymphagitic spread. Metastasis to a single lymph node group as an isolated abnormality occurred in five cases in which the primary tumors were carcinomas of the bladder, larynx, testis, thyroid, and breast.
Discussion The differential diagnosis of hilar and mediastinal lymph node enlargement includes such entities as lymphoma, local extension from bronchogenic carcinoma, noninfectious granulomatous disease (i .e. sarcoidosis), and infectious granulomas (e.g., tuberculosis and histoplasmosis) [10]. Metastasis from extrathoracic neoplasms is considered to be a rare cause of intrathoracic lymphadenopathy, particularly if bilateral hilar nodes or isolated lymph node groups are involved [3, 11]. In a large proportion of our cases (12 of 25), the intrathoracic ,
Fig. 1 .-Metastatic carcinoma (azygous) lymph node enlargement.
of breast with right Left mastectomy.
paratracheal
metastases arose from tumors of the genitourinary tract. This finding agrees with the findings of studies of renal cell carcinoma [2, 3, 7] and carcinoma of the prostate [8]. In a series of 152 patients with metastatic hypernephroma, Arkless [12] found 11 with mediastinal adenopathy involving carinal, hilar, and paratracheal areas. Lymphogenous spread is one of a variety of pathways by which kidney neoplasms can metastasize [2]; however, extension to regional and occasionally distant nodes is the primary and more common metastatic route for tumors of the ovary, uterus, testis, and prostate. Early extension to paraaortic nodes occurs frequently in testiculartumors [13]. In an autopsyseries, Barringerand Earl [1 4] reported that 27% of testicular teratomas presented with evidence of metastatic disease involving lymph nodes from the bifurcation of the aorta to the left supra-
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INTRATHORACIC
Fig. 2.-Posteroanterior nant melanoma. (Case
(A),lateral (B), and anteroposterior not from present series).
LYMPH
(C) tomograms
NODE
METASTASES
showing
bilateral
primarily
involve
405
hilar
adenopathy
the
secondary
external
iliac
to metastases
and
paraaortic
from
malig-
chains
[13]. Numerous lymphatic outlets of the cervix produce regional metastatic implants in the pelvic nodes and subsequent extension to the paraaortic group, the thoracic duct, supraclavicular nodes, and mediastinal nodes [13]. Although there were no cases of carcinoma of the prostate in our series, metastases to the mediastinum from
Fig. 3.-Anteroposterior tomogram cheal adenopathy and parenchymal from
androblastoma
showing bilateral paratrahematogenous metastases
of testis.
clavicular region. Each patient in this group with metastatic adenopathy demonstrated a continuous chain of metastatic nodes along the course of the thoracic duct. In our series, testicular tumors demonstrated the highest frequency of mediastinal metastases (29.4%). Lymphatic metastases from carcinoma of the endometrium appear late in the course of the disease and
this
tumor
has
been
observed
[8,
10].
The route and mechanism of extension of lymph node metastases into the thorax from retroperitoneal nodes secondarily involved by genitourinary neoplasms is not completely understood. The lymphatics from the pelvis and abdomen drain into the thoracic duct. No direct communication between the anterior mediastinum and the thoracic duct as it courses through the posterior mediastinum has been shown [16]. However, if incompetence or absence of valves controlling direction of flow exists, reflux of tumor emboli from the thoracic duct into the bronchomediastinal trunks will occur. Retrograde flow into the paratracheal, bronchopulmonary, and interlobular lymphatics may then ensue [15-17]. It has been shown that reflux into mediastinal nodes during lymphangiography normally occurs in 5%-14% of patients, presumably due to incompetent valves [18]. Cancer of the nasal and oral cavities and neck primarily metastasize to the regional lymphatics, often causing death by local pressure upon vital structures before hematogenous dissemination occurs [19]. One-third of the cases of mediastinal adenopathy in our series were secondary to carcinomas of this area. Drainage typically is from local lymph node groups to one of the three lymphatic chains in the neck, that is, the anterior or jugular chain, the posterior or spinal chain, and the
McLOUD
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406
transverse or supraclavicular chain. Communication between the anterior chain and anterior mediastinal lymph nodes has been described by Rouviere [9]; this route is presumed to be the course by which mediastinal lymph node metastases occur. In a series of 1 1 5 cases of operated thyroid carcinoma with clinically positive cervical nodes, Frazell and Foote [20] found six with mediastinal extension. Carcinomas of the iaryngopharynx also tend to spread toward the mediastinum through lymphatic permeation [13], and mediastinal lymph node involvement in laryngeal carcinoma often accompanies stomal recurrence after a laryngectomy [21]. Malignant melanoma accounted for two of the cases of lymph node enlargment in our series. Although melanomas are uncommon primary cancers, representing only 1% of all malignant tumors, they account for a significant percentage of lesions which metastasize to the thorax [1]. In a series of 65 patients with radiographically identifiable metastases to the thorax, Webb and Gamsu [1] reported 28 with enlargement of mediastinal or hilar lymph nodes on the chest radiograph. All but three in that series had evidence of pulmonary parenchymal metastases as well. In our series, however, neither of the two patients with metastatic melanoma to intrathoracic lymph nodes initially demonstrated pulmonary parenchymal nodules Although melanoma disseminates widely to many organs, initial spread occurs to regional lymph nodes with subsequent extension into the mediastinum. Radiographicaily visible metastases from carcinoma of the breast to mediastinal or hilar lymph nodes has been observed [4, 5]. Minor [4] reported a series of 314 cases of malignant neoplasms which had metastasized to the thorax. Of the 77 breast carcinomas, 18 exhibited mediastinal lymph node involvement on the chest radiograph. In our series the incidence of lymph node metastasis from breast carcinoma was much lower (three of 248, or 1 .2%). Since carcinoma of the breast is often a relatively slowly growing tumor, metastases may become visible several years after the primary tumor has been resected; mediastinal adenopathy is more likely to occur late in the course of the disease. Gouin et al. [5] reported three cases of mediastinal lymph node metastases which appeared on an average of 7 years after original diagnosis and treatment. Our series represented only a 3 year follow-up after initial presentation. Handley and Thackray [22] discovered that the internal mammary lymph chain was important in the treatment of carcinoma of the breast because of the drainage to that area from inner quadrant lesions. Communication between the upper parasternal and anterior mediastinal nodes has been noted, suggesting a direct route by which mediastinal metastases occur [23]. In our series there were no cases of intrathoracic lymph node metastases from carcinomas of the gastrointestinal tract. This finding differs somewhat from reports [24, 25] which describe hilar adenopathy in association with carcinoma of the stomach and (rarely) the pancreas. However, in all cases described in the literature, hilar adenopathy was invariably associated with radiologic .
ET
AL.
evidence of lymphangitic carcinomatosis Only rarely were other mediastinal lymph described as being enlarged [24, 25]. There may be several explanations for observe any intrathoracic lymphadenopathy carcinomas of the stomach and 25 primary pancreas. As Yang and Lin [25] emphasized of
the
chest
films
of
62
proven
cases
of
in the lungs. node groups our
failure to among 46 tumors in the in a review Iymphangitic
carcinoma, the most common pattern in carcinoma of the stomach is a progressive diffuse reticular pattern in both lungs with normal hila or minimal hilar enlargement. They suggested that the route of metastatic spread was via the diaphragmatic lymphatic channels to the parietal and visceral pleura with subsequent involvement of the intrapulmonary lymphatics, rather than retrograde extension from mediastinal and hilar nodes already enlarged by metastatic tumor. Hilar lymphadenopathy would then constitute a secondary site of metastatic extension. It has been postulated that hematogenous dissemination to the capillaries of the lungs, followed by invasion of the peripheral lymphatics and spread along them to the hila, occurs in lymphangitic carcinomatosis [8]. Spread by this route may occur in carcinoma of the pancreas. In any case, intrathoracic lymph node enlargement in metastatic stomach and pancreatic cancer is not an isolated phenomenon but is almost invariably associated with or follows radiologic evidence of lymphangitic spread and is usually limited to the hilar nodes. Our results indicate that individual types of primary cancers do not show any particular distributions of adenopathy in the thorax. However, the subcarinal and posterior mediastinal lymph node group are infrequently involved in metastatic disease. Unilateral lymphadenopathy, which is felt to be characteristic of bronchogenic carcinoma and infectious granulomatous disease (such as tuberculosis), occurred in almost a third of our patients. Furthermore, enlargement of a single lymph node group as an isolated abnormality was also an occasional feature of metastatic disease. Lymphadenopathy in the thorax from metastases such as testicular tumors may occur as an incidental finding on a chest radiograph before the primary lesion is recognized. In conclusion metastatic disease from extrathoracic neoplasms should always be considered in the differential diagnosis of hilar and mediastinal adenopathy. In our experience, the most common extrathoracic primary cancers to be considered are genitourinary, head and neck, breast, and malignant melanoma. ,
REFERENCES 1 . Webb
WA, Gamsu G: Thoracic metastasis melanoma. Chest 71 : 176-181 1977
in malignant
,
2. Latour A, Shulman HS: cell carcinoma. Radiology
Thoracic
manifestations
of renal
121 :43-48, 1976 3. Reinke AT, Higgens CB, Newayama G, Harris RH, Friedman PJ: Bilateral pulmonary hilar adenopathy, an unusual manifestation of renal cell carcinoma. Radiology 121 :49-50, 1976 4. Minor G: A clinical pulmonary neoplasms.
and
radiologic
J Thorac
study
Cardiovasc
of metastatic 20:34-42,
Surg
INTRATHORACIC
LYMPH
1950
5. Gouin
B, Couturier
D, Hardouin
JP, Debray
tinit#{233}sneoplasiques complications tardines sein . Nouv Press Med 1 : 1 563-1 568, 1972
Downloaded from www.ajronline.org by 117.253.240.225 on 10/19/15 from IP address 117.253.240.225. Copyright ARRS. For personal use only; all rights reserved
6. Jereb Acta
B: Metastases Radiol
7. Khan bilateral
MB,
and recurrences
12:289-304,
Khan
adenopathy
C: Les m#{233}diasdes cancers
du
FA:
Hypernephroma:
and
an example
in nephroblastoma.
tion
10. 11.
12. 13.
of
intrapulmonary
phy. Radiology A rare of the
cause
of
importance
of
Philadelphia, Saunders, 1970 Rouviere H: Anatomy of The Human Lymphatic System, translated by Tobias MJ. Ann Arbor, Mich., Edwards Brothers, 1938 Blank N, Castellino RA: Mediastinal lymphadenopathy. Semin Roentgenol 12:215-223, 1977 Winterbauer RH, Belic N, Moores, KD: A clinical interpretation of bilateral hilar adenopathy. Ann Intern Med 78:6571,1973 Arkless A: Renal carcinoma, how it metastasizes. Radiology 84:496-501, 1965 Ackerman LV, del Aegato JA: Cancer. St. Louis, Mosby, 1962
14. Barringer BS, Earl D: Teratoma testis: survey of thirty-seven autopsy records. Surg Gynecol Obstet 72:591-600, 1941 15. Baltaxe HA, Constable WC: Mediastinal lymph node visualization in the absence of intrathoracic disease. Radiology 90:94-99, 1968
407
METASTASES
16. Grant T, Levin B: Lymphangiographic visualization of pleural and pulmonary lymphatics in a patient without chylothorax. Radiology 1 1 3 : 49-50, 1974 17. Weidner WA, Steiner AM: Roentgenographic demonstra-
1973
tissue diagnosis in suspected cases of sarcoidosis. Chest 66:722-723, 1974 8. Fraser AG, Pare JAP: Diagnosis of Diseases of the Chest. 9.
NODE
18.
Rosenberger
structural,
lymphatics
during
100 : 533-539, 1971 A, Aaler 0, Abrams
HL:
lymphangiogra-
The
thoracic
duct:
functional
and radiologic aspects. CRC Crit Rev Clin Radiol NucI Med 3 : 523-541 1972 19. Cole WH: The mechanisms of spread of cancer. Surg Gynecol Obstet 1 37 : 853-871 1973 20. Frazell El, Foote FW: Papillarythyroid carcinoma: patholog,
,
ical findings
and without clinical evidence of Cancer 8:1164-1166, 1955 Sisson GA, Straekley CJ, Johnson NE: Mediastinal dissection of recurrent cancer after laryngectomy. Laryngoscopy 72:1064-1077, 1962 Handley AS, Thackray AC: The internal mammary lymph chain in carcinoma of the breast: a study of 50 cases. Lancet 2:276-278, 1949 cervical
21.
22.
node
in cases
with
involvement.
23. Anezyres N, Sawas-Dimopoulou, Dontas N, Samaras U: Thoracic lymph node scintiscan as a diagnostic test in mediastinal malignant enlargement. Chest 59:372-377, 1971 24. Mueller HP, Sniffen AC: Roentgenologic appearance and pathology of intrapulmonary lymphatic spread of metastatic cancer. Am J Roentgenol 53:109-123, 1945 25. Yang 5, Lin C: Lymphangitic carcinomatosis of the lungs. Chest
62:179-187,
1972
Lymph
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THERESA
Node
C. McLOUD,1
Metastases
LESTER
KALISHER,1’
from 2
The clinical records of 1 ,071 cases of extrathoracic malignant neoplasms seen over a 2 year period were reviewed: 163 had abnormal chest films, and 25 of these showed evidence of mediastinal and/or hilar lymph node metastases. The primary malignancies which metastasized to intrathoracic lymph nodes included eight tumors of the head and neck, 12 genitourinary malignancies, three carcinomas of the breast, and two malignant melanomas. The chest films were analyzed to determine the distribution of lymph node groups involved. Unilateral lymph node enlargement occurred in eight. The most frequently detected lymph node group was the right paratracheal chain (60%), while the subcarinal and posterior mediastinal groups were rarely affected. Of the 25 cases, 10 had radiographic evidence of hematogenous or lymphangitic metastases in addition in the lungs. Metastatic disease from extrathoracic neoplasms should always be considered in the differential diagnosis of hilar and mediastinal adenopathy.
PAUL
STARK,1
disease cause
enlargement. lymphadenopathy series
of
patients
cite
neoplasms hilar lymph
Radiographically identifiable has previously been
cell carcinoma Isolated case 8] also
from extrathoracic of mediastinal and
Of
the
strated
with
malignant
melanoma
[2, 3], and carcinoma reports [5-7] and personal primary
sources
from
[1],
nopathy.
cancer
of the
testinal tract, prostate, kidneys, and breast. took the following radiologic study to assess frequency of various types of extrathoracic
which
metastasize
describe lymph
the node
to intrathoracic distribution
groups
lymph
of
Among
films,
which
are
Materials
upper
(i.e., lung,
and
renal
metastatic
spread;
and mediastinum);
of the lymphatic
until
the
[4]. [7,
were
cases
node
address:
Am J Ro.ntg.nol © 1978 American
Department
to
expired
during
reviewed ease,
the
131:403-407,
Roentgen
September Ray Society
General
twelve
of
(table
was testicular
the
25 cases.
with
in
tumors
intrathoracic
intrathoracic
Four
pa-
demexamitwo of
lymph
available
The
h ig hest
and
on routine chest of hilar and/or was
the
1).
node
films. mediastinal
in
14
of
the
at autopsy, 1 1 had or mediastinoscopy,
25
biopsy and
period
1974-1977,
and
four
fact
node
for
that
evidence
11
of
metastases
case recsummaries (1977) and a
ture (1)
exist,
the
or
and
(3)
enous
lung
or lymphagitic
type
the
extent
codify the inin nomencla-
nodes
were
[9]:
(nodes
of
in
this
included
nodes,
posterior
of parenchymal
mdi-
classification
prevascular
bifurcation,
disthoracic
2 years
and to variations
(2) peritracheobronchial pulmonary nodes
with
within
window chain,
metastatic
finding. to determine
to use Rouviere’s
mediastinal
region);
for
of the analyzed
aorticopulmonary
group);
other patients
lymphadenopathy Although several
we chose
anterior
25
succumbed
cates the grave prognosis The chest films were of intrathoracic volved groups.
of
the
that
is, right
or subcarinal
and nodes
roots or hilar nodes (proxiwere also included in the hilar mediastinal
nodes.
metastases
of either
was
also
The
pres-
hematog-
assessed.
April 24, 1978. Hospital
5t. Barnabas 1978
the
follow-up
in detail the
lymph
malig-
The
present
after revision
of Radiology,
neck);
one had an aspiration needle biopsy of a parenchymal lung metastasis. The remaining 11 had clinical courses consistent with metastatic disease. Five of those 11
ence
Present
testis),
metastases
were analyzed by two of us (T. C. McLoud and L. Kalisher) the presence of hilar or mediastinal lymph node enlargement.
2
and
sarcomas
among
cases. Two were confirmed performed at either thoracotomy
nodes of the intrapulmonary
Massachusetts
no
(kidney,
and mal
20, 1978; accepted
because
carcinomas
metastases
were discovered corroboration
25 cases were in the pediatric age group. The chest radiographs of 163 patients were reported as abnormal at some point during their clinical course. Of these, 149 were available for review and
of Radiology,
cavity,
(21 .4%)
metastases
paratracheal
January
avail-
series
malanomas
intrathoracic
left
Department T. C. McLoud.
without
the
three
malignant
There
lymph
gastroin-
listing of all abnormal radiographic studies. A total of 1,071 cases had 1,151 malignant tumors; several patients had two or more primary tumors. The 651 females and 420 males ranged in age from 8 to 100 years (mean, 50.8); only
Aeceived
oral
carcinoma
metastases Pathologic
and reticuloen-
which
follow-up
cases
in
of the remaining six demonstrated reduction in the lymphadenopathy after irradiation or chemotherapy. Although not all clinical records of the study group were
and leukemia). of computerized
clinical
passage,
of
node
these
intrathoracic
dothelial system (i.e., lymphoma ords were available in the form included
additional
included
demon-
lymphade-
tients had hilar or mediastinal lymphadenopathy onstrated on the chest film at the time of initial nation (thyroid, kidney, testis, and larynx). In
spinal cord, and skin (except melato rarely cause any form of distant
and tumors
24
mediastinal
reports described bilateral hilar and lymph node enlargement. The primary
two
cell
(29.4%).
Methods
esophagus,
nant tumors of the brain, noma), which are known
14
was
reviewed,
and/or
malignancies;
freq uency
The clinical records of patients initially seen in the Oncology Center of our institution during 1974 and 1975 were reviewed. Excluded from the study were patients with primary intratho-
racic cancers
the
one
respiratory
breast;
involved.
and
radiographs
of hilar
genitourinary
a
and
GREENE1
malignancies which metastasized to intrathoracic lymph nodes included eight tumors of the head and neck (i.e.,
We underthe relative neoplasms
nodes
particular
REGINALD
chest
several radiologic right paratracheal
renal
of the breast observations
149
evidence
able
is an node
intrathoracic reported in
AND
Neoplasms
Results
lymph Metastatic infrequent
Extrathoracic
and Harvard Medical
Medical
Center,
403
School,
Livingston,
Boston, New Jersey
Massachusetts
02114.
Address
reprint
requests
07039.
0361 -803X/78/0900-0403
$00.00
to
McLOUD
404
TABLE Frequency
of Intrathoracic
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Head and neck: Larynx Lingual tonsil Nasopharynx
Nasal
cavity
(malignant Total
only
additional the films several
and were
lateral
performed
%
2 1 1
3.7 5.3 6.6
1
14.3
2 1
6.1 3.3
34 18 27 14 28 17 248
1 1 1 3 1 5 3
2.9 5.5 3.7 21.4 3.6 29.4 1.2
52
2
3.8
tomographic on one patient radiologic
high on
studies. could
reports
kilovoltage 15
patients;
Lymph
Anterior mediastinal Bilateral hilar Right hilar Left hilar
Bilateral
Nodes No. Cases
.
No.
25
2
of Metastatic Location
33 30
595
Posteroanterior films
Location
Cases with Adenopathy
7
melanoma)....
Anatomic
Metastases
53 19 15
Thyroid Tongue Genitourinary: Bladder Cervix uteri Corpus uteri Kidney Ovary Testis Breast
Skin
TABLE Node
No. Cases . Reviewed
Malignancy
AL.
1 Lymph
.
Sites ot Primary
ET
6 7 4 6 4 11 2 1 1
paratracheal
Aightparatracheal Left paratracheal Posterior mediastinal Subcarinal
4.2
(150 nine
kV) had
As mentioned above, not be retrieved, but
indicated
the
presence
of
lymphadenopathy. The initial chest radiograph which demonstrated the intrathoracic lymph node enlargement was evaluated. Table 2 lists the frequency of anatomic distribution of the involved lymph node groups. Unilateral lymph node enlargement was observed in eight of the 25 patients (fig. 1), and bilateral hilar nodes with or without mediastinal involvement was seen in seven (fig. 2). The right paratracheal chain was the most frequently detected lymph node group (60%) (fig. 1). The least frequently detected groups included the subcarinal region and nodes of the posterior mediastinum (one case each). However, evaluation of these areas was limited by the absence of overpenetrated posteroanterior views or mediastinal tomograms in all cases. Five cases had multiple pulmonary nodules consistent with hematogenous metastases (fig. 3) and five had a radiographic pattern indicative of either local or diffuse lymphagitic spread. Metastasis to a single lymph node group as an isolated abnormality occurred in five cases in which the primary tumors were carcinomas of the bladder, larynx, testis, thyroid, and breast.
Discussion The differential diagnosis of hilar and mediastinal lymph node enlargement includes such entities as lymphoma, local extension from bronchogenic carcinoma, noninfectious granulomatous disease (i .e. sarcoidosis), and infectious granulomas (e.g., tuberculosis and histoplasmosis) [10]. Metastasis from extrathoracic neoplasms is considered to be a rare cause of intrathoracic lymphadenopathy, particularly if bilateral hilar nodes or isolated lymph node groups are involved [3, 11]. In a large proportion of our cases (12 of 25), the intrathoracic ,
Fig. 1 .-Metastatic carcinoma (azygous) lymph node enlargement.
of breast with right Left mastectomy.
paratracheal
metastases arose from tumors of the genitourinary tract. This finding agrees with the findings of studies of renal cell carcinoma [2, 3, 7] and carcinoma of the prostate [8]. In a series of 152 patients with metastatic hypernephroma, Arkless [12] found 11 with mediastinal adenopathy involving carinal, hilar, and paratracheal areas. Lymphogenous spread is one of a variety of pathways by which kidney neoplasms can metastasize [2]; however, extension to regional and occasionally distant nodes is the primary and more common metastatic route for tumors of the ovary, uterus, testis, and prostate. Early extension to paraaortic nodes occurs frequently in testiculartumors [13]. In an autopsyseries, Barringerand Earl [1 4] reported that 27% of testicular teratomas presented with evidence of metastatic disease involving lymph nodes from the bifurcation of the aorta to the left supra-
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INTRATHORACIC
Fig. 2.-Posteroanterior nant melanoma. (Case
(A),lateral (B), and anteroposterior not from present series).
LYMPH
(C) tomograms
NODE
METASTASES
showing
bilateral
primarily
involve
405
hilar
adenopathy
the
secondary
external
iliac
to metastases
and
paraaortic
from
malig-
chains
[13]. Numerous lymphatic outlets of the cervix produce regional metastatic implants in the pelvic nodes and subsequent extension to the paraaortic group, the thoracic duct, supraclavicular nodes, and mediastinal nodes [13]. Although there were no cases of carcinoma of the prostate in our series, metastases to the mediastinum from
Fig. 3.-Anteroposterior tomogram cheal adenopathy and parenchymal from
androblastoma
showing bilateral paratrahematogenous metastases
of testis.
clavicular region. Each patient in this group with metastatic adenopathy demonstrated a continuous chain of metastatic nodes along the course of the thoracic duct. In our series, testicular tumors demonstrated the highest frequency of mediastinal metastases (29.4%). Lymphatic metastases from carcinoma of the endometrium appear late in the course of the disease and
this
tumor
has
been
observed
[8,
10].
The route and mechanism of extension of lymph node metastases into the thorax from retroperitoneal nodes secondarily involved by genitourinary neoplasms is not completely understood. The lymphatics from the pelvis and abdomen drain into the thoracic duct. No direct communication between the anterior mediastinum and the thoracic duct as it courses through the posterior mediastinum has been shown [16]. However, if incompetence or absence of valves controlling direction of flow exists, reflux of tumor emboli from the thoracic duct into the bronchomediastinal trunks will occur. Retrograde flow into the paratracheal, bronchopulmonary, and interlobular lymphatics may then ensue [15-17]. It has been shown that reflux into mediastinal nodes during lymphangiography normally occurs in 5%-14% of patients, presumably due to incompetent valves [18]. Cancer of the nasal and oral cavities and neck primarily metastasize to the regional lymphatics, often causing death by local pressure upon vital structures before hematogenous dissemination occurs [19]. One-third of the cases of mediastinal adenopathy in our series were secondary to carcinomas of this area. Drainage typically is from local lymph node groups to one of the three lymphatic chains in the neck, that is, the anterior or jugular chain, the posterior or spinal chain, and the
McLOUD
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406
transverse or supraclavicular chain. Communication between the anterior chain and anterior mediastinal lymph nodes has been described by Rouviere [9]; this route is presumed to be the course by which mediastinal lymph node metastases occur. In a series of 1 1 5 cases of operated thyroid carcinoma with clinically positive cervical nodes, Frazell and Foote [20] found six with mediastinal extension. Carcinomas of the iaryngopharynx also tend to spread toward the mediastinum through lymphatic permeation [13], and mediastinal lymph node involvement in laryngeal carcinoma often accompanies stomal recurrence after a laryngectomy [21]. Malignant melanoma accounted for two of the cases of lymph node enlargment in our series. Although melanomas are uncommon primary cancers, representing only 1% of all malignant tumors, they account for a significant percentage of lesions which metastasize to the thorax [1]. In a series of 65 patients with radiographically identifiable metastases to the thorax, Webb and Gamsu [1] reported 28 with enlargement of mediastinal or hilar lymph nodes on the chest radiograph. All but three in that series had evidence of pulmonary parenchymal metastases as well. In our series, however, neither of the two patients with metastatic melanoma to intrathoracic lymph nodes initially demonstrated pulmonary parenchymal nodules Although melanoma disseminates widely to many organs, initial spread occurs to regional lymph nodes with subsequent extension into the mediastinum. Radiographicaily visible metastases from carcinoma of the breast to mediastinal or hilar lymph nodes has been observed [4, 5]. Minor [4] reported a series of 314 cases of malignant neoplasms which had metastasized to the thorax. Of the 77 breast carcinomas, 18 exhibited mediastinal lymph node involvement on the chest radiograph. In our series the incidence of lymph node metastasis from breast carcinoma was much lower (three of 248, or 1 .2%). Since carcinoma of the breast is often a relatively slowly growing tumor, metastases may become visible several years after the primary tumor has been resected; mediastinal adenopathy is more likely to occur late in the course of the disease. Gouin et al. [5] reported three cases of mediastinal lymph node metastases which appeared on an average of 7 years after original diagnosis and treatment. Our series represented only a 3 year follow-up after initial presentation. Handley and Thackray [22] discovered that the internal mammary lymph chain was important in the treatment of carcinoma of the breast because of the drainage to that area from inner quadrant lesions. Communication between the upper parasternal and anterior mediastinal nodes has been noted, suggesting a direct route by which mediastinal metastases occur [23]. In our series there were no cases of intrathoracic lymph node metastases from carcinomas of the gastrointestinal tract. This finding differs somewhat from reports [24, 25] which describe hilar adenopathy in association with carcinoma of the stomach and (rarely) the pancreas. However, in all cases described in the literature, hilar adenopathy was invariably associated with radiologic .
ET
AL.
evidence of lymphangitic carcinomatosis Only rarely were other mediastinal lymph described as being enlarged [24, 25]. There may be several explanations for observe any intrathoracic lymphadenopathy carcinomas of the stomach and 25 primary pancreas. As Yang and Lin [25] emphasized of
the
chest
films
of
62
proven
cases
of
in the lungs. node groups our
failure to among 46 tumors in the in a review Iymphangitic
carcinoma, the most common pattern in carcinoma of the stomach is a progressive diffuse reticular pattern in both lungs with normal hila or minimal hilar enlargement. They suggested that the route of metastatic spread was via the diaphragmatic lymphatic channels to the parietal and visceral pleura with subsequent involvement of the intrapulmonary lymphatics, rather than retrograde extension from mediastinal and hilar nodes already enlarged by metastatic tumor. Hilar lymphadenopathy would then constitute a secondary site of metastatic extension. It has been postulated that hematogenous dissemination to the capillaries of the lungs, followed by invasion of the peripheral lymphatics and spread along them to the hila, occurs in lymphangitic carcinomatosis [8]. Spread by this route may occur in carcinoma of the pancreas. In any case, intrathoracic lymph node enlargement in metastatic stomach and pancreatic cancer is not an isolated phenomenon but is almost invariably associated with or follows radiologic evidence of lymphangitic spread and is usually limited to the hilar nodes. Our results indicate that individual types of primary cancers do not show any particular distributions of adenopathy in the thorax. However, the subcarinal and posterior mediastinal lymph node group are infrequently involved in metastatic disease. Unilateral lymphadenopathy, which is felt to be characteristic of bronchogenic carcinoma and infectious granulomatous disease (such as tuberculosis), occurred in almost a third of our patients. Furthermore, enlargement of a single lymph node group as an isolated abnormality was also an occasional feature of metastatic disease. Lymphadenopathy in the thorax from metastases such as testicular tumors may occur as an incidental finding on a chest radiograph before the primary lesion is recognized. In conclusion metastatic disease from extrathoracic neoplasms should always be considered in the differential diagnosis of hilar and mediastinal adenopathy. In our experience, the most common extrathoracic primary cancers to be considered are genitourinary, head and neck, breast, and malignant melanoma. ,
REFERENCES 1 . Webb
WA, Gamsu G: Thoracic metastasis melanoma. Chest 71 : 176-181 1977
in malignant
,
2. Latour A, Shulman HS: cell carcinoma. Radiology
Thoracic
manifestations
of renal
121 :43-48, 1976 3. Reinke AT, Higgens CB, Newayama G, Harris RH, Friedman PJ: Bilateral pulmonary hilar adenopathy, an unusual manifestation of renal cell carcinoma. Radiology 121 :49-50, 1976 4. Minor G: A clinical pulmonary neoplasms.
and
radiologic
J Thorac
study
Cardiovasc
of metastatic 20:34-42,
Surg
INTRATHORACIC
LYMPH
1950
5. Gouin
B, Couturier
D, Hardouin
JP, Debray
tinit#{233}sneoplasiques complications tardines sein . Nouv Press Med 1 : 1 563-1 568, 1972
Downloaded from www.ajronline.org by 117.253.240.225 on 10/19/15 from IP address 117.253.240.225. Copyright ARRS. For personal use only; all rights reserved
6. Jereb Acta
B: Metastases Radiol
7. Khan bilateral
MB,
and recurrences
12:289-304,
Khan
adenopathy
C: Les m#{233}diasdes cancers
du
FA:
Hypernephroma:
and
an example
in nephroblastoma.
tion
10. 11.
12. 13.
of
intrapulmonary
phy. Radiology A rare of the
cause
of
importance
of
Philadelphia, Saunders, 1970 Rouviere H: Anatomy of The Human Lymphatic System, translated by Tobias MJ. Ann Arbor, Mich., Edwards Brothers, 1938 Blank N, Castellino RA: Mediastinal lymphadenopathy. Semin Roentgenol 12:215-223, 1977 Winterbauer RH, Belic N, Moores, KD: A clinical interpretation of bilateral hilar adenopathy. Ann Intern Med 78:6571,1973 Arkless A: Renal carcinoma, how it metastasizes. Radiology 84:496-501, 1965 Ackerman LV, del Aegato JA: Cancer. St. Louis, Mosby, 1962
14. Barringer BS, Earl D: Teratoma testis: survey of thirty-seven autopsy records. Surg Gynecol Obstet 72:591-600, 1941 15. Baltaxe HA, Constable WC: Mediastinal lymph node visualization in the absence of intrathoracic disease. Radiology 90:94-99, 1968
407
METASTASES
16. Grant T, Levin B: Lymphangiographic visualization of pleural and pulmonary lymphatics in a patient without chylothorax. Radiology 1 1 3 : 49-50, 1974 17. Weidner WA, Steiner AM: Roentgenographic demonstra-
1973
tissue diagnosis in suspected cases of sarcoidosis. Chest 66:722-723, 1974 8. Fraser AG, Pare JAP: Diagnosis of Diseases of the Chest. 9.
NODE
18.
Rosenberger
structural,
lymphatics
during
100 : 533-539, 1971 A, Aaler 0, Abrams
HL:
lymphangiogra-
The
thoracic
duct:
functional
and radiologic aspects. CRC Crit Rev Clin Radiol NucI Med 3 : 523-541 1972 19. Cole WH: The mechanisms of spread of cancer. Surg Gynecol Obstet 1 37 : 853-871 1973 20. Frazell El, Foote FW: Papillarythyroid carcinoma: patholog,
,
ical findings
and without clinical evidence of Cancer 8:1164-1166, 1955 Sisson GA, Straekley CJ, Johnson NE: Mediastinal dissection of recurrent cancer after laryngectomy. Laryngoscopy 72:1064-1077, 1962 Handley AS, Thackray AC: The internal mammary lymph chain in carcinoma of the breast: a study of 50 cases. Lancet 2:276-278, 1949 cervical
21.
22.
node
in cases
with
involvement.
23. Anezyres N, Sawas-Dimopoulou, Dontas N, Samaras U: Thoracic lymph node scintiscan as a diagnostic test in mediastinal malignant enlargement. Chest 59:372-377, 1971 24. Mueller HP, Sniffen AC: Roentgenologic appearance and pathology of intrapulmonary lymphatic spread of metastatic cancer. Am J Roentgenol 53:109-123, 1945 25. Yang 5, Lin C: Lymphangitic carcinomatosis of the lungs. Chest
62:179-187,
1972
