AJR 2005; 184:459-464
© American Roentgen Ray Society
Sonography of Lymphangioleiomyoma in Lymphangioleiomyomatosis: Demonstration of Diurnal Variation in Lesion Size
Nilo A. Avila1,
Andrew J. Dwyer1,
Diane V. Murphy-Johnson1,
Pamela Brooks2 and
Joel Moss2
1 Diagnostic Radiology Department, Warren Grant Magnuson Clinical Center,
National Institutes of Health, 10 Center Dr., MSC 1182, Bldg. 10, Rm. 1C-658,
Bethesda, MD 20892-1182.
2 Pulmonary-Critical Care Medicine Branch, National Heart, Lung and Blood
Institute, National Institutes of Health, Bethesda, MD 20892-1590.
Received March 29, 2004;
accepted after revision June 30, 2004.
Address correspondence to N. A. Avila.
Abstract
OBJECTIVE. Our aims were to define the sonographic features of
abdominal and pelvic lymphangioleiomyomas in lymphangioleiomyomatosis (LAM)
and to evaluate the utility of sonography in visualizing diurnal change in the
size of the masses.
MATERIALS AND METHODS. Forty-four patients with LAM and abdominal
and pelvic lymphangioleiomyomas found on screening CT underwent sonography.
Twenty-two patients had two studies on the same day, one in the morning and
the other late in the afternoon.
RESULTS. Forty-nine masses were scanned in the 44 patients. The
anatomic distribution of the masses was the following: retroperitoneal (29/44
patients, 66%), pelvic (10/44, 23%), and both retroperitoneal and pelvic
(5/44, 11%). Of the 49 masses, 12 (24%) were cystic, 16 (33%) were solid, and
21 (43%) were complex. Twenty-two patients underwent sonography in the morning
and afternoon. The masses increased in size between the two studies in all 21
patients in whom the masses were visualized in both studies. In three of 21
patients, the echotexture of the masses changed between the morning and
afternoon studies: In two the echotexture changed from solid to complex, and
in the other, it changed from hyperechoic to isoechoic relative to the
liver.
CONCLUSION. The sonographic characteristics of lymphangioleiomyomas
are similar to some neoplasms such as lymphoma and ovarian cancer (a
similarity that sometimes prompts biopsy). After a mass is shown in a patient
with LAM, repeat sonography in the morning and afternoon is useful to depict
diurnal variation in size and echotexture and to confirm the diagnosis of
lymphangioleiomyoma and avoid biopsy.
Introduction
Lymphangioleiomyomatosis (LAM) is a rare multisystem disorder occurring
almost exclusively in women. It is characterized by the proliferation of
abnormal smooth-muscle cells—LAM cells—in the lungs (resulting in
pulmonary cysts) and in the lymphatics of the thorax and retroperitoneum
(resulting in lymphangioleiomyomas)
[1–4].
Accumulation of LAM cells in the lymphatics may cause mural thickening,
obstruction, dilatation, and development of cystic collections of chylous
material. The resulting complex lymphatic masses are termed
"lymphangioleiomyomas" and have CT characteristics similar to
those of malignant neoplasms, sometimes prompting biopsy
[4].
One feature, which has been shown on CT, helps to differentiate
lymphangioleiomyomas from malignancy. Lymphangioleiomyomas have been shown to
increase in size during the day from morning to afternoon—whereas with
malignancy, negligible growth is expected in a single day. This diurnal
variation in the size of lymphangioleiomyomas also explains the reports of
patients of worsening abdominal and pelvic symptoms (e.g., abdominal pain,
incontinence, lymphedema, and paresthesias of the lower extremities) at the
end of the day [5].
In this report, we illustrate the spectrum and prevalence of the
sonographic features of lymphangioleiomyomas and assess the utility of
sonography in depicting diurnal change in the size of these masses.
Materials and Methods
The study protocol (95-H-0186) was approved by the National Heart, Lung and
Blood Institutional Review Board. Our institution is a referral center
currently studying the natural history of LAM. As part of the protocol, all
patients have screening CT of the chest, abdomen, and pelvis. Written informed
consent was obtained from all study participants. This study includes the
initial 255 consecutive patients (all women; age range, 23–77 years;
mean, 44 years) with pulmonary LAM evaluated at our institution between March
1996 and April 2003. The diagnosis of LAM was established by lung biopsy in
186 patients and biopsy of abdominopelvic masses in 10 patients. Fifty-nine
patients did not have tissue biopsy but had classic clinical (recurrent
spontaneous pneumothorax or pleural effusions or both) and pulmonary CT
findings (diffusely scattered thin-walled lung cysts) of LAM. This study
comprises 44 patients who had abdominal and pelvic lymphangioleiomyomas
depicted on screening CT and then had follow-up sonography of the abdomen and
pelvis.
Abdominopelvic Sonography
Twenty-nine of the 44 patients underwent abdominal sonography, 10 of 44
patients underwent pelvic sonography, and five of 44 patients underwent both
abdominal and pelvic sonography. Pelvic masses adjacent to the uterus,
bladder, or adnexa were studied with transvaginal sonography (seven patients);
those adjacent to the pelvic walls were studied using the transabdominal
approach (eight patients). The patients were scanned on ATL 4000 and 5000
(Philips Medical Systems) and Acuson 128XP, Aspen, and Sequoia (Siemens
Medical Solutions) scanners. The transducer frequency used for the abdominal
sonograms was between 3.5 and 5 MHz. The endovaginal studies were performed
with multifrequency transducers ranging between 5 and 8 MHz. We recorded the
maximum transverse, anteroposterior, and longitudinal diameters of the masses
and whether the masses were solid, cystic (simple or multiloculated cysts), or
complex (contained both cystic and solid components). Other sonographic
features recorded were echogenicity relative to the liver in abdominal solid
and complex masses, echogenicity relative to the uterus in pelvic solid and
complex masses, and wall thickness (for cystic and complex masses). We
measured the anteroposterior thickness of the walls on transverse images and
used 2 mm as the limit between thin and thick.
Diurnal Variation
In 22 patients, sonography was performed in both the morning
(8:00–10:00 am) and afternoon (2:30–5:00 pm) of the same day. The
patients were scanned by the same technologist using the same machine and the
same transducer frequency for both the morning and the afternoon studies. All
studies were checked by the same board-certified radiologist before the
patient left the department. The mass sizes were quantified using an estimated
volume index that was calculated by multiplying the transverse,
anteroposterior, and longitudinal diameters of the masses. The change in
volume of the masses during the day was assessed by comparing estimated
morning and afternoon volume indexes. The percentage difference in volume
between morning and afternoon studies was calculated using the following
formula (Table 1):
 | (1) |
Review of Clinical History
All patients were interviewed regarding abdominal and pelvic symptoms.
Medical records were reviewed to determine whether a patient had a history of
abdominopelvic biopsy.
Results
Forty-four patients had 49 masses seen on CT that were evaluated on
sonography. The anatomic distribution of the masses was retroperitoneal (29/44
patients, 66%), pelvic (10/44, 23%), and both retroperitoneal and pelvic
(5/44, 11%). Sixteen (33%) of 49 masses were solid: isoechoic to liver or
uterus in 10 (63%) of 16, hypoechoic in five (31%) of 16, and hyperechoic in
one (6%) of 16. Twelve (24%) of the 49 masses were cystic: simple cysts in
four (33%) of 12 and multiloculated cysts in eight (67%) of 12
(Fig. 1). Twenty-one (43%) of
49 masses were complex (Figs. 2
and 3). Wall thickness in the
eight patients with multiloculated masses was thin (three patients) and both
thin and thick (five patients). All 21 patients with complex masses had both
thin and thick walls.
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Fig. 1. —51-year-old woman with mild lung involvement with
lymphangioleiomyomatosis who complained of pelvic discomfort and urinary
frequency. Transabdominal longitudinal sonogram of pelvis shows large simple
cyst (arrow) adjacent to uterus (U).
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Fig. 2. —33-year-old woman with severe lung involvement with
lymphangioleiomyomatosis who complained of increased abdominal girth that
worsened during day. Transabdominal longitudinal sonogram of right pelvis
shows thick-walled complex mass (arrows) with central anechoic
space.
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Fig. 3. —42-year-old woman with mild lung involvement with
lymphangioleiomyomatosis diagnosed after biopsy of pelvic mass to exclude
ovarian cancer. Abdominal longitudinal sonogram shows large retroperitoneal
mass (arrows) isoechoic to liver, containing serpiginous central
anechoic spaces that had no flow on Doppler interrogation and were thought to
represent dilated lymphatic channels.
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Diurnal Variation
Twenty-two patients underwent sonography in the morning and afternoon. In
one patient, the mass was not well visualized and therefore not measurable on
the afternoon study. The estimated morning volume indexes of the masses ranged
from 1 to 521 cm3 (median, 38 cm3). The estimated
afternoon volume indexes of the masses ranged from 3 to 647 cm3
(median, 173 cm3). Increase in volume during the day was observed
in all 21 patients (Table 1 and
Fig. 4A,
4B,
4C,
4D). The difference between the
afternoon volume and the morning volume indexes ranged from 2 to 237
cm3 (median, 41 cm3). The percentage change in volume
ranged from 10% to 484% (median, 38%)
(Table 1).
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Fig. 4A. —25-year-old woman having severe lung involvement with
lymphangioleiomyomatosis, diagnosed after biopsy of pelvic mass to exclude
ovarian cancer. Patient complained of chronic back pain and urinary frequency
that worsened during day. Transverse sonogram obtained at 8:30 am at level of
right kidney shows complex mass (arrows) that measures 3.3 x
4.8 x 5.5 cm in anteroposterior, transverse, and longitudinal
diameters.
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Fig. 4B. —25-year-old woman having severe lung involvement with
lymphangioleiomyomatosis, diagnosed after biopsy of pelvic mass to exclude
ovarian cancer. Patient complained of chronic back pain and urinary frequency
that worsened during day. Follow-up sonogram obtained at 2:45 pm shows
interval increase in size of cystic portion of mass (arrows) that
then measured 4.8 x 5.0 x 7.0 cm in anteroposterior, transverse,
and longitudinal diameters.
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Fig. 4C. —25-year-old woman having severe lung involvement with
lymphangioleiomyomatosis, diagnosed after biopsy of pelvic mass to exclude
ovarian cancer. Patient complained of chronic back pain and urinary frequency
that worsened during day. Transabdominal longitudinal sonogram of left adnexa
obtained at 8:15 am shows complex left pelvic mass (arrows) that
measures 2.5 x 2.6 x 3.1 cm in anteroposterior, transverse, and
longitudinal diameters.
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Fig. 4D. —25-year-old woman having severe lung involvement with
lymphangioleiomyomatosis, diagnosed after biopsy of pelvic mass to exclude
ovarian cancer. Patient complained of chronic back pain and urinary frequency
that worsened during day. Follow-up transabdominal sonogram obtained at 3:00
pm shows interval increase in size of left adnexal mass (arrows) that
then measured 3.7 x 3.8 x 3.8 cm in anteroposterior, transverse,
and longitudinal diameters.
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The relation of the percentage change in size of the masses during the day
to the size of the masses in the morning was graphed
(Fig. 5). As expected, greater
percentage changes in volume were more common in smaller masses. All three
masses with changes in volume of less than 10 cm3 (2, 7, and 9
cm3) clearly showed increase in the percentage change in size
(200%, 350%, and 49%, respectively).
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Fig. 5. —Scatterplot of percentage change in volume as function of
morning volume indexes of lymphangioleiomyomas in 21 patients. Morning volume
indexes (anteroposterior x transverse x longitudinal measurements)
ranged from 1 to 521 cm3 (median, 38 cm3). Percentage
change in volume ranged from 10% to 484% (median, 38%). Greater percentage
changes in volume were more common in smaller masses.
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The echotexture of the masses changed between the morning and afternoon
studies in three patients. In two patients, solid masses on the morning
studies became complex (with both cystic and solid elements) on the afternoon
study (Fig. 6A,
6B). In one patient, a
hyperechoic mass in the morning study became isoechoic to the liver on the
afternoon study.
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Fig. 6A. —43-year-old woman having moderate involvement of lungs with
lymphangioleiomyomatosis. Endovaginal longitudinal sonogram of right adnexa
obtained at 10:00 am shows solid mass (arrows) isoechoic to uterus
and situated between right iliac vessels and right ovary.
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Fig. 6B. —43-year-old woman having moderate involvement of lungs with
lymphangioleiomyomatosis. Follow-up sonogram obtained at 2:50 pm shows
increase in size of mass (calipers), which now contains anechoic spaces in
addition to solid component. ov = ovary, v = pelvic vessel.
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Review of Clinical History
Patients described the following symptoms, which worsened during the course
of the day and were most pronounced in the evening: abdominal bloating
(n = 23), abdominal pain (n = 3), back pain (n =
1), urinary frequency (n = 1), pelvic pain (n = 1),
constipation (n = 1), lower extremity edema (n = 4), and
lower extremity paresthesia (n = 2). Ten patients who had undergone
abdominal and pelvic CT or sonography before the diagnosis of LAM had been
misdiagnosed with cancer because of masses found on the imaging studies: Six
patients were told they had ovarian cancer and four were told they had
lymphoma. Subsequent biopsies on these patients revealed no evidence of cancer
and established the diagnosis of LAM.
Discussion
The most common clinical characteristics of LAM that lead to the correct
diagnosis include exertional dyspnea (46%) and pneumothorax (43%). Patients
may undergo transbronchial biopsy that shows proliferation of immature
smooth-muscle cells (LAM cells) in the lungs and the bronchial wall lymphatics
[3]. Twenty-one percent of
patients with LAM develop complex lymphatic masses that may cause symptoms
(urinary frequency and lower extremity edema) by compressing adjacent organs
[5]. Usually when an abdominal
or pelvic mass due to LAM is discovered, the diagnosis of pulmonary LAM is
already known. However, in some cases, the diagnosis of LAM follows discovery
of the mass. In our series, this occurred in 10 of 44 patients with LAM with
masses; in these patients, the diagnosis of LAM was established by biopsy of
masses discovered on CT or sonography. Hence, the awareness of the thoracic
and abdominal imaging features of LAM in expediting diagnosis and precluding
unnecessary biopsy is important.
The sonographic characteristics of lymphangioleiomyomas are not specific
and are similar to those of malignant abdominal and pelvic masses such as
lymphoma and ovarian cancer (a similarity that sometimes prompts biopsy). One
distinctive feature of lymphangioleiomyomas is an increase in size during the
day. This phenomenon (which we have termed "diurnal variation") is
caused by accumulation of lymph within the mass (Fig.
7A,
7B). Because malignant
neoplasms commonly exhibit negligible change in size in a day, reliable
evidence of diurnal variation can differentiate a lymphangioleiomyoma from a
malignant mass. Also, diurnal variation explains the worsening of symptoms
(bloating, abdominal discomfort, lymphedema, and lower extremity paresthesias)
toward the end of the day reported by patients with lymphangioleiomyomas
[5].
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Fig. 7A. —Proposal models for effects of lymphangioleiomyomatosis (LAM)
on lymphatics. Models of effect of LAM on lymphatics show normal lymphatic
vessel with unidirectional valve and normal direction of lymph flow
(arrows) (a), proliferation of abnormal smooth-muscle cells (LAM
cells) on walls of lymphatic that causes mural thickening and luminal
narrowing (b), and obstruction of lymph flow by LAM cells that results in
dilatation of lymphatic proximal to obstruction, creating lymphangioleiomyoma
(c).
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Fig. 7B. —Proposal models for effects of lymphangioleiomyomatosis (LAM)
on lymphatics. Models show diurnal variation in size of lymphangioleiomyomas
between morning and afternoon. Normal lymphatic flow (arrows) is
shown in morning (a). By late afternoon, lymphangioleiomyoma has increased in
size (b). Phenomenon results from combination of factors: increased lymph flow
during day caused by increased lymph production after meals and increased
return of chyle from extremities after normal daily exercise.
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Diurnal variation in the size of lymphangioleiomyomas is likely the result
of several factors: first, greater lymph flow through the pelvis and abdomen
during the day (resulting from increased chyle production after meals and
increased lymphatic return from the lower extremities due to walking and other
daytime muscular activities) and second, the effect of gravity on intraluminal
pressure and its dependence on patient position. During the day—when the
patient is predominantly upright—intraluminal pressure is increased
within the abdominal and pelvic lymph collections and draining lymphatics
(which are working "uphill" against gravity to return lymph to the
thoracic duct). The increased intraluminal pressure induces dilatation of the
lymph collections and lymphatics. At night, when the patient is recumbent,
this effect of gravity on intraluminal pressure is nullified
[5]
(Fig. 7B).
Along with the measurable increase in size between the morning and
afternoon studies, the dynamic nature of lymphangioleiomyomas is further
revealed by the fact that some of the masses changed in echotexture between
the morning and afternoon studies (i.e., masses that were solid in the morning
study appeared complex or hypoechoic on the afternoon examination). We
attribute this change in sonographic appearance to the accumulation of lymph
within the lymphatic channels in the masses that have been described
histologically but are too small to be resolved as discrete structures
sonographically [6].
Patients with LAM are usually screened with CT. We propose that when an
abdominal or pelvic mass is found on CT, a repeat examination be performed to
evaluate changes in size of the mass. Visualization of diurnal variation, on
either sonography or CT, should exclude a diagnosis of malignancy and avoid
the need for biopsy. For this evaluation, we suggest that sonography, rather
than CT, be used initially. Because patients newly diagnosed with LAM are
usually premenopausal women and because lymphangioleiomyomas arise most
commonly from the abdomen and pelvis, performing sonography will avoid
radiation to the pelvic organs. If the mass is not satisfactorily visualized
on sonography or if evidence of diurnal variation is not certain, then a
repeat limited CT study should be performed at the level of the mass for
better characterization.
There are technical limitations of sonography as a diagnostic tool to
evaluate diurnal variation. Most masses arise in the abdomen and pelvis, thus
bowel artifact may obscure or preclude unequivocal identification of the
masses. Further, diurnal variation in size may be difficult to document if a
mass is small or if the change in size is small. Given the dependency of
sonographic findings on technique, the initial and follow-up sonography should
be performed by the same sonographer who can be certain that the same anatomic
area is scanned in the same cross-section on both studies. Another limitation
of the study is the absence of assessment of intraobserver variability;
unfortunately, time constraints caused by patient scheduling precluded us from
rescanning the patients multiple times to obtain this data.
The sonographic characteristics of lymphangioleiomyomas are similar to
those of malignant abdominal and pelvic masses such as lymphoma and ovarian
cancer. Sonography, repeated in the morning and afternoon, is useful in
documenting diurnal variation in size and differentiating lymphangioleiomyomas
from neoplastic masses.
References
- Kitaichi M, Nishimura K, Itoh H, Izumi T. Pulmonary
lymphangioleiomyomatosis: a report of 46 patients including a
clinicopathologic study of prognostic factors. Am J Respir Crit
Care Med 1995;151:527
–533[Abstract]
- Taylor JR, Ryu J, Colby T, Raffin T. Lymphangioleiomyomatosis:
clinical course in 32 patients. N Engl J Med1990; 323:1254
–1260[Medline]
- Chu SC, Horiba K, Usuki J, et al. Comprehensive evaluation of 35
patients with lymphangioleiomyomatosis. Chest1999; 115:1041
–1052[Abstract/Free Full Text]
- Carrington CB, Cugell DW, Gaensler EA, et al. Lymphangiomyomatosis:
physiologic-pathologic-radiologic correlations. Am Rev Respir
Dis 1977;116:977
–995[Medline]
- Avila NA, Bechtle J, Dwyer AJ, Ferrans VJ, Moss J.
Lymphangioleiomyomatosis: CT of diurnal variation of lymphangioleiomyomas.
Radiology2001; 221:415
–421[Abstract/Free Full Text]
- Matsui K, Tatsuguchi A, Valencia J, et al. Extrapulmonary
lymphangioleiomyomatosis (LAM): clinicopathologic features in 22 cases.
Hum Pathol2000; 31:1242
–1248[Medline]
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[Abstract]
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Abstract
Introduction
