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* From the Pulmonary-Critical Care Medicine Branch (Drs. Chu and Moss) and Pathology Section (Drs. Horiba, Usuki, and Ferrans), National Heart, Lung, and Blood Institute, and Diagnostic Radiology Department (Dr. Avila) and Department of Nuclear Medicine (Dr. Chen), Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, and Armed Forces Institute of Pathology (Dr. Travis), Washington, DC. Supported by Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
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Abstract |
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 TOP Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Design: Prospective study.
Patients: Thirty-five female subjects with LAM.
Setting: Clinical Center, National Institutes of Health.
Interventions: BAL, pulmonary function test, ventilation/perfusion lung scans, CT of the chest and abdomen, ultrasonography of abdomen, and immunohistochemical study of lung biopsy specimens.
Results: Most patients had exertional dyspnea (83%) and pneumothorax (69%). BAL did not show diagnostic changes. The most common abnormalities on pulmonary function tests were decreased diffusing capacity of carbon monoxide (83%), hypoxemia (57%), and airway obstruction (51%). Bronchodilator response was found in 26% of patients. CT, which is almost pathognomonic, showed numerous thin-walled cysts throughout both lungs in all patients. Thirty-four patients (97%) had abnormal ventilation and/or perfusion lung scans. An unusual "speckling" pattern was observed on ventilation scans of 74% of patients. Common extrapulmonary features were retroperitoneal adenopathy (77%) and renal angiomyolipomas (60%). The percentage of abnormal smooth muscle cells (LAM cells), reactive with HMB45, varied from 17 to 67% in 10 lung biopsy specimens.
Conclusions: Improved diagnostic methods have defined the abnormalities in patients with pulmonary LAM and increased the potential for early recognition and treatment of this disorder. Patients with LAM should be evaluated for bronchodilator responsiveness and may benefit from a trial of bronchodilators.
Key Words: angiomyolipoma • bronchoalveolar lavage • lymphangioleiomyomatosis • pneumothorax • smooth muscle cell proliferation
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Introduction |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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LAM is a multisystem disorder that frequently involves other organs, such as the kidneys, retroperitoneal lymph nodes, liver, uterus, and pancreas, in addition to the lungs.6 ,7 ,8 ,9 LAM is frequently complicated by the development of angiomyolipomas. These are benign tumors composed of thick-walled blood vessels, smooth muscle cells, and mature adipose tissue. They represent only about 1% of surgically excised renal tumors.10 The prevalence of renal angiomyolipomas in patients with LAM has been reported to range from 15 to 57%.6 ,7 ,8 ,9 LAM cells and the smooth muscle cells of angiomyolipomas differ from normal smooth muscle cells in that they react with monoclonal antibody HMB45, which recognizes melanocyte lineage-specific antigen(s).11 ,12 ,13 ,14 Although the histologic features of LAM cells usually are distinctive, immunohistochemical study with HMB45 is useful to distinguish LAM cells from other smooth muscle cells, especially when a biopsy specimen contains a small number of these cells (as in transbronchial biopsy specimens).11 ,12
In recent years, interest in LAM has led to the application of a number of new techniques for the study of this disorder. In this communication, we present the results of a comprehensive evaluation of the pulmonary and extrapulmonary manifestations in 35 patients with LAM, including the following: (1) clinical features and therapeutic regimen to understand better the natural course of the disease; (2) CT of chest and abdomen/pelvis and ultrasonography of abdomen to evaluate the extent of the pulmonary and extrapulmonary involvement of LAM; (3) pulmonary function tests and ventilation/perfusion scans to evaluate pulmonary physiology; (4) BAL to evaluate the changes in local milieu of distal airways in LAM lung; and (5) immunohistochemical study of LAM lung with HMB45 to evaluate the expression of gp100, a melanosomal antigen, which has been found to be valuable in making the diagnosis of LAM.
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Materials and Methods |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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All patients had clinical presentations consistent with the diagnosis of LAM, which had been confirmed by open lung biopsy specimens in 16 patients, thoracoscopic lung biopsy specimens in 10, transbronchial biopsy specimens in 3, and retroperitoneal lymph node biopsy specimens in 3. Three patients did not have a tissue diagnosis of LAM. These three patients had typical cysts on CT of the chest. In addition, one had a history of pneumothorax and renal angiomyolipoma diagnosed by total nephrectomy, another had persistent chylothorax and history of hemoptysis and recurrent pneumothorax, and a third patient had a history of recurrent pneumothorax and a transbronchial biopsy specimen that was consistent with, but not diagnostic of, LAM.
BAL
Fiberoptic bronchoscopy was used to perform BAL15
on six normal female volunteers (age, 38.2 ± 10.8 years) and 16 LAM
patients (39.4 ± 7.2 years) with FEV1 
45% of
predicted value and PaO2 65 mm Hg. All
were nonsmokers except that one volunteer and three LAM patients were
ex-smokers. Briefly, each of three subsegments (usually one subsegment
each from the right upper lobe, right middle lobe, and lingula) was
lavaged with five 20-mL portions of sterile 0.9% saline solution by
sequential instillation and aspiration. In one patient with LAM, BAL
was performed in only two lobes. The BAL fluid was filtered through
several layers of sterile gauze and pooled in a sterile plastic cup;
the cells were dispersed by repeatedly drawing into and expelling from
a 10-mL pipet. A sample was removed for the determination of cell
number, morphology, and differential cell count. For cell differential
count and morphology, the cells were sedimented (Cytospin II; Shannon
Instruments; Pittsburgh, PA) and stained (DiffQuik; Baxter Healthcare
Corporation; Miami, FL). For each sample, 1,000 intact cells were
counted to determine differential cell count; 200 macrophages were
evaluated to determine the percentage of pigment-laden macrophages. The
remaining BAL fluid was then centrifuged (600g for 15 min at
room temperature to remove the cells). The amount of epithelial lining
fluid (ELF) in BAL fluid was determined by the urea
method.16
To detect possible pneumothorax after BAL, a
chest radiograph, taken at the end of expiration, was performed on each
patient 4 to 8 h after bronchoscopy.
Pulmonary Function Tests
Pulmonary function tests were performed on all patients. The
spirometry and measurements of functional residual capacity and the
diffusing capacity of the lung for carbon monoxide (DLCO)
(corrected for hemoglobin) were performed with the patient in the
sitting position using a computerized system (Collins Gold Standard
PLUS; Warren E. Collins; Braintree, MA). The spirometry and
DLCO measurements were performed by standard techniques
recommended by the American Thoracic Society.17
,18
The
FEV1 and the FVC were measured before and after the
administration of albuterol, either 2.5 mg via nebulization or 180 µg
via a metered-dose inhaler. Functional residual capacity was measured
using the closed circuit helium equilibration technique. Expiratory
reserve volume was subtracted from the functional residual capacity to
obtain the residual volume and the vital capacity was added to residual
volume to obtain total lung capacity. The predicted values for
FEV1, FVC, and FEV1/FVC were derived from
Morris et al.19
The predicted functional residual capacity
and residual volume were obtained from the data of Goldman and
Becklake.20
The predicted total lung capacity was
calculated by adding predicted FVC to predicted residual volume. The
predicted DLCO was obtained from the data of Gaensler and
Wright.21
Arterial blood gas determinations were performed
while patients were resting, supine, and breathing room air. A
bronchodilator response was defined as a postbronchodilator increase in
FEV1 of 200 mL and 12% over the prebronchodilator
FEV1.
Ventilation/Perfusion Lung Scans
Ventilation/perfusion lung scans were performed on all patients.
Aerosol ventilation studies were performed using approximately 50 mCi
99mTc diethylenetriamine pentaacetic acid in the reservoir.
Patients were administered the aerosol in the sitting position until a
count rate of approximately 2,000/s was achieved; images of the lungs
were obtained in multiple projections. Following this, 5 to 6 mCi
99mTc macroaggregated albumin was administered IV and
images of the lungs were obtained again. Studies were interpreted
qualitatively for abnormalities in ventilation and perfusion scans. In
addition, the degree of "speckling" seen on ventilation studies was
evaluated.
CT of Chest and Abdomen
CT of the chest was performed on inspiration on all patients
using a CT unit (General Electric HiSpeed Advantage Unit; GE Medical
Systems; Milwaukee, WI). The unit was set at 140 kV (peak kilovoltage),
180 mA seconds, and 1.0-s scan time. The scans were obtained with 8- to
10-mm collimation at 1.0-cm intervals. In addition, all patients were
scanned with 1.0-mm collimation (high-resolution CT) at 3.0-cm
intervals. The scans were viewed at window levels and widths
appropriate for lung parenchyma and mediastinum.
CT of the abdomen was performed on all patients as outlined above. The studies were performed following administration of oral contrast medium, before and after IV administration of a nonionic contrast agent (Isovue; Bracco Diagnostics, Inc; Princeton, NJ). Three patients with a history of allergic reactions were not given IV contrast medium. A renal lesion was considered to be an angiomyolipoma if attenuation equivalent to that of fat was detected within the mass. Fatty tissue was considered to be present within the angiomyolipoma if a "region of interest" value of -10 Hounsfield units or lower was found within the tumor.22
Ultrasonography of Abdomen
Using an ultrasonography unit (Acuson 128 XP Unit;
Mountainview, CA), gray scale abdominal ultrasonography was
performed on 34 patients with abnormal findings on CT of the abdomen.
Immunohistochemical Study of LAM Lung Tissue With HMB45 and
Anti-
Smooth Muscle Actin Antibody
To determine the percentage of LAM cells that were positive for
HMB45, immunohistochemical studies were performed using mouse
monoclonal antibody HMB45 (DAKO Co; Carpinteria, CA) and anti-
smooth muscle actin antibody (DAKO Co) on lung biopsy specimens from 10
patients. Seven specimens were from open lung biopsies, two from
thoracoscopic biopsies, and one from a transbronchial biopsy. The
peroxidase method was used for immunostaining with both antibodies in
serial sections of formalin-fixed, paraffin-embedded tissues.
Endogenous peroxidase activity was suppressed by incubation with 0.3%
H2O2 in methanol for 30 min. Sections were then
treated with 0.4% pepsin in 0.01N HCl for 15 min at 37°C. After
washing in phosphate-buffered saline solution and blocking nonspecific
binding of the antibody with 5% normal horse serum for 30 min, either
HMB45 (diluted 1:1,000 in phosphate-buffered saline solution containing
1% bovine serum albumin) or anti- smooth muscle actin antibody
(diluted 1:200 in 1% bovine serum albumin) was applied. After
incubation overnight at 4°C and three washes with phosphate-buffered
saline solution, the sections were treated with biotinylated horse
antimouse IgG (diluted 1:200) for 30 min at room temperature. After
washing in phosphate-buffered saline solution, the sections were
incubated with ABC reagent (Vectastain Elite ABC Peroxidase Kit; Vector
Laboratories; Burlingame, CA). Finally, the peroxidase color was
developed (with the Vector VIP Substrate Kit). The sections were
counterstained with hematoxylin. For each sample, an average of
1,259 ± 796 (range, 219 to 2,486) LAM cells were rated as either
positive or negative for HMB45 staining, and the percentage of positive
cells was calculated using the number of -smooth muscle
actin-positive cells as 100%.
Statistical Analysis
Data are presented as mean ± SD. Statistical comparisons were
made using two-tailed Student's t test.
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Results |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Bronchoalveolar Lavage
The total amounts of cells recovered per BAL, the number of cells
per milliliter of lavage fluid, and the numbers of cells per microliter
of ELF were similar in both groups (p > 0.05; Table 2
).
The percentage of lavage fluid recovered was significantly lower
(p = 0.03), and the relative amounts of ELF in lavage fluid recovered
were significantly higher in LAM patients (p = 0.01). The
differential cell counts in BAL fluid were similar in LAM patients and
control subjects. Pigment-laden macrophages were present in BAL fluid
in 13 (81%) LAM patients and 2 (33%) normal subjects. The percentage
of pigment-laden macrophages in LAM patients was significantly higher
than in normal subjects (p = 0.04). No patient developed pneumothorax
after BAL, but two had fever that subsided in < 24 h without
antimicrobial therapy.
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CT and Ultrasonography of the Abdomen
CT and ultrasonography revealed solid renal masses in 22 patients
(63%) (Table 5
). Nine of these patients (26%) had multiple masses and
six (17%) had bilateral masses. A total of 51 solid renal masses were
observed, 34 in the left kidney and 17 in the right. The average size
of these masses was 1.4 ± 1.6 cm (range, 0.3 to 9 cm).
A total of 31 renal solid masses that met the CT criteria for angiomyolipoma (see "Materials and Methods" section; Fig 3 , top [A]) were detected in 18 patients (51%). Six patients (17%) had multiple angiomyolipomas and four (11%) had bilateral involvement. Two angiomyolipomas (6%) were > 4 cm in diameter. All angiomyolipomas that were visible on ultrasonography were hyperechoic (Fig 3 , bottom [B]).
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Adenopathy in the axial lymphatics was common. Retroperitoneal
adenopathy was found in 27 patients (77%). Fat attenuation in
retroperitoneal lymph nodes was observed in eight patients (23%).
Pelvic adenopathy was observed in four patients (11%). Other findings
included unilateral, single renal cysts in three patients (9%) and
ascites in four (11%). All renal cysts were 
1 cm in diameter.
Three of four patients with ascites also had chylothorax.
Variable HMB45 Reactivity of LAM Cells
All 10 lung biopsy specimens evaluated by immunohistochemical
staining contained LAM cells that were positive for HMB45. The
percentage of HMB45-positive LAM cells in these specimens ranged from
17 to 67% (mean, 41 ± 16%; Fig 4
).
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Discussion |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Clinical Characteristics
Consistent with the findings in other studies, exertional dyspnea
and pneumothorax were the major presenting complaints in our patients
with LAM.1
,2
The mean interval between the initial
symptoms attributable to the disease and diagnosis was 3.4 ± 5.7
years. These data are similar to those reported by Taylor et
al.1
The diagnosis was confirmed by identification of LAM
cells in tissue sections of lung in 29 patients. Diagnosis was made by
retroperitoneal lymph node biopsy specimens in three patients with
chylothorax and retroperitoneal adenopathy, which was initially thought
to represent malignancy. A tissue diagnosis was not obtained in three
patients who had typical clinical and laboratory findings.
Pleurodesis and pleurectomy are frequently performed in patients with LAM (54% in our series) for the control of chylothorax or recurrent pneumothorax. Not surprisingly, these procedures increase morbidity and mortality of subsequent pulmonary transplantation.6 We suggest reserving pleurodesis or pleurectomy for patients in whom persistent chylothorax or recurrent pneumothorax results in significant physiologic impairment.
Bronchoalveolar Lavage
BAL constitutes a valuable and widely used procedure for the
evaluation of a variety of pulmonary disorders, including interstitial
lung diseases, airway diseases, infections, and malignancies. However,
it has been used in only a few patients with LAM, because of the high
incidence of pneumothorax in this disease. Our data demonstrate that
BAL can be performed safely in selected LAM patients with relatively
good pulmonary function. Pneumothorax did not occur in any of our
patients after this procedure. The total and differential cell counts
in BAL fluid of LAM patients were not different from those of normal
subjects (Table 2
). However, more patients with LAM (81%) than normal
subjects (31%) had pigment-laden macrophages in BAL and the percentage
of pigment-laden macrophages was significantly higher in LAM patients
than in normal subjects. This is likely due to microscopic pulmonary
hemorrhages in LAM patients, since 11 of 13 LAM patients who had
pigment-laden macrophages in BAL were nonsmokers. Clinically, only two
of these patients had hemoptysis in the 3-month period preceding BAL.
Of note, the only normal ex-smoker had 8% pigment-laden macrophages.
This combined with the small control group (n = 6) explains the high
incidence (33%) of normal subjects who had pigment-laden macrophages
in our study. Except for the higher percentage of pigment-laden
macrophages in LAM patients, the findings of BAL fluid in this study
were similar to those previously reported in normal
subjects.24
Although no significant difference between normal subjects and LAM patients was found in the cell differential counts of BAL fluid, the possibility that BAL fluid may contain important factors that stimulate smooth muscle cell proliferation cannot be ruled out. Further studies will be required to explore this possibility.
Pulmonary Function Tests
Consistent with the data in previous reports, most patients (91%)
in the present study had abnormal results of pulmonary function
tests.1
,2
,25
The most frequent abnormality was decreased
DLCO that was found in 83% of the patients. This was
followed by hypoxemia (57% of the patients). The frequency of these
two findings was lower in our patients than in those reported by Taylor
et al1
and Kitaichi et al.2
This was likely
due to the inclusion of more patients with milder disease in the
present study. Importantly, the most common abnormality was decreased
DLCO in all three series. Restriction or combined
restriction and obstruction was found in nine (26%) patients. Among
these patients, only one (3%) did not have pleural effusion or
pneumothorax at the time of pulmonary function testing or had not had
pleurodesis or pleurectomy. In most patients with LAM, restrictive
dysfunction can be explained by causes other than parenchymal lung
cysts. Hypercapnia is uncommon in LAM and usually develops in the very
late stages of the disease. Only 12% of the patients studied by
Boehler et al6
developed hypercapnia before lung
transplantation. A significant response to bronchodilators was found in
26% of patients in this study. The significance of this response is
not clear. It will be of interest to determine whether the airway
hyperresponsiveness in LAM is associated with accelerated decline in
FEV1, as has been observed in patients with
1-antitrypsin deficiency and chronic
bronchitis.26
,27
Patients with LAM should be evaluated for
bronchodilator responsiveness and may benefit from a trial of
bronchodilator therapy.
Ventilation/Perfusion Scans
Most patients in the study (97%) had abnormal ventilation and/or
perfusion lung scans. Only one patient with normal lung function had
normal ventilation/perfusion scan. The defects on ventilation and
perfusion scans were usually grossly matched. An unusual
"speckling" pattern (Fig 1
) was observed on the ventilation scans
of 74% of the patients. This was considered to be due to the
accumulation of radioactive aerosol in distal airways or the
parenchymal cysts. It was notable that severe speckling was observed
only on ventilation scans of patients who were using supplemental
oxygen (n = 5). Although a speckling pattern is observed occasionally
in other disorders, such as COPD, it usually is less striking than that
seen in our patients. A severe speckling pattern on a ventilation scan
of a woman of childbearing age should raise the clinical suspicion of
LAM.
Intrathoracic Involvement in LAM
Consistent with the findings in earlier reports,2
,6
high-resolution CT of the chest clearly demonstrated diffusely
distributed, thin-walled parenchymal cysts in the lungs of all patients
in the present study. Although CT is a most useful method for
establishing the diagnosis of LAM, it is necessary to emphasize that
the finding of thin-walled pulmonary cysts is not pathognomonic of this
disorder. Similar cysts occur also in other diseases, including
pulmonary Langerhans' cell histiocytosis (pulmonary histiocytosis
X),28
emphysema, and various pulmonary tumors, including
cystic hamartoma,29
cystic sarcomas, and benign
metastasizing leiomyoma.30
,31
The thin-walled cysts in
pulmonary Langerhans' cell histiocytosis, which affects both male and
female patients, usually occur in the middle and upper lung zones and
spare the costophrenic angles.28
The cysts in emphysema
usually are more irregular in shape than those in LAM. Mesenchymal
cystic hamartomas can appear very similar to the LAM cysts on CT of the
chest.29
Benign metastasizing leiomyoma, thought to
represent metastases from a benign-appearing leiomyoma of the uterus,
can be confused with LAM. Although usually manifest as pulmonary
nodules on chest radiograph, they may also present with interstitial
changes and recurrent pneumothorax.30
,31
Similar to LAM,
these tumors occur primarily in women of reproductive age.
In addition to parenchymal cysts, several other abnormalities were found on CT of the chest. These included linear scars, retrocrural adenopathy, pleural effusion, dilated thoracic duct, pericardial effusion, and pneumothorax. Of note, retrocrural adenopathy was not uncommon (26%) in LAM. Among five patients with pleural effusion, four had chylous effusions; the remaining patient had a small effusion and did not undergo thoracentesis. In contrast to a previous report2 describing nodular densities on CT of the chest in 5% of LAM patients, such lung nodules were not found in our patients. This finding may be useful in differentiating LAM from pulmonary Langerhans' cell histiocytosis (pulmonary histiocytosis X),28 which is often associated with nodules and cysts in lungs.
The data reviewed above demonstrate the great value of CT in the evaluation of the intrathoracic manifestations of LAM. Although the combination of homogenously distributed thin-walled cysts on chest CT and clinical features compatible with LAM is often highly suggestive of the diagnosis, it is desirable to obtain lung tissue for the pathologic confirmation of the diagnosis.
Approximately 1 to 2.3% of patients with tuberous sclerosis, an autosomal dominant disorder with incomplete penetrance, develop parenchymal lung cysts identical to pulmonary LAM.32 ,33 In addition to parenchymal lung cysts, 23% of patients in the present study were found to have chylothorax, which is much less frequent in patients with tuberous sclerosis.
Extrathoracic Involvement in LAM
In addition to pulmonary involvement, other organs and tissues,
eg, kidney, retroperitoneal lymph nodes, liver, uterus, and
pancreas, can also be affected in LAM patients.6
,7
,8
,9
Renal
angiomyolipomas are the most important extrapulmonary complication of
LAM. These tumors have been reported to occur in 15 to 57% of patients
with this disorder.6
,7
,8
,9
In this study, 21 patients (60%)
had renal angiomyolipomas diagnosed by either CT or pathologic
examination of tumors. It has been suggested that only angiomyolipomas
will produce the combination of fat attenuation on CT and
hyperechogenicity on ultrasonography.10
In addition to
renal angiomyolipoma, fat attenuation in retroperitoneal lymph nodes,
which was present in 23% of LAM patients, should raise a suspicion of
LAM. As observed in one of our patients, some renal angiomyolipomas may
not show fat attenuation on CT. However, a renal mass that does not
meet radiographic diagnostic criteria for angiomyolipomas may need
further evaluation for potential malignancy.
The major complication of angiomyolipoma is massive bleeding. In our study, shock was the presenting sign in 9% of patients with angiomyolipomas measuring at least 4 cm.34 Among the three patients in this study who underwent total nephrectomy, one had retroperitoneal bleeding, another had intratumoral hemorrhage, and a third had chronic flank pain.
The nature of the relationship between LAM and angiomyolipomas remains very poorly understood. A common pathogenetic factor is suggested by the fact that the smooth muscle cells in both types of lesions are immunoreactive with HMB45 antibody (see below). Coincident renal cell carcinomas have been observed in 2 to 7% of patients who had renal angiomyolipomas but lacked the stigmata of tuberous sclerosis.10 The possibility of this complication must be taken into account in the evaluation of renal masses, particularly those that grow rapidly, as in some patients with LAM.
Common renal lesions in patients with tuberous sclerosis are renal angiomyolipomas and renal cysts.8 ,35 Renal angiomyolipomas, which are often multiple and bilateral, could be observed in up to 80% of patients with tuberous sclerosis. Renal cysts, which are often multiple and bilateral also, develop in approximately 20% of patients with tuberous sclerosis. In contrast, only five patients (14%) had bilateral renal angiomyolipomas and no patient had bilateral renal cysts in this study.
Variations in Reactivity of LAM Cells for HMB45
Immunostaining of lung tissue with HMB45 is a highly sensitive
method for the identification of LAM cells. However, this antibody is
also known to react with cells of melanocytic origin, including
malignant melanoma, as well as with clear cell
tumors.11
,12
,13
,36
These tumors occur in the lung and in
other organs, and their cellular origin remains uncertain. The antigen
recognized by HMB45 antibody in LAM cells, as well as in melanocytes,
is a 100-kDa glycoprotein (gp100) that is localized in premelanosomes.
The reason for the expression of gp100 protein in LAM cells and in the
smooth muscle cells of angiomyolipomas is not known. HMB45 antibody is
particularly valuable for establishing the diagnosis of LAM when only
small specimens of lung tissue are available.11
,12
Although the histochemical reactivity of LAM tissue with HMB45 has been
described in a number of previous reports,11
,12
a
quantitative assessment has not been made of the frequency of HMB45
positivity among the LAM cells in a series of lung biopsy specimens. It
is important to note that we found the percentage of HMB45-positive LAM
cells to vary considerably among patients, eg, from 17 to
67%. Unpublished observations from our laboratory suggest that there
is an inverse relationship between HMB45 positivity and cellular
proliferation, such that the less reactive or unreactive LAM cells are
more likely to be actively proliferating cells. Awareness of this
variability is necessary in the interpretation of lung biopsy
specimens, since in some of these, contrary to expectation, only a
minority of the LAM cells may show a positive reaction for HMB45.
Hormonal Therapy and Prognosis
Hormonal therapy (eg, progesterone, oophorectomy,
gonadotropin-releasing hormone agonist, tamoxifen, or radiation of the
ovaries) has been the only therapeutic option for patients with LAM. It
has been observed that most patients responsive to hormonal therapy had
chylothorax or chylous ascites.1
,2
In this study,
improvement of pulmonary function was observed in a patient with
chylothorax, ascites, and chyloptysis. Because of persistent left-sided
chylothorax and recurrent right-sided pneumothoraces, the patient
underwent bilateral pleurodeses. Several years later, chyloptysis
developed and her pulmonary function deteriorated significantly. Only
after medroxyprogesterone was increased to 1,600 mg/mo (400 mg weekly)
did chyloptysis stop and FEV1 gradually increase from its
lowest point of 1.04 to 1.58 L. We cannot exclude the possibility that
lack of a response to antiestrogen treatment may be due, at least in
some patients, to inadequate dose and duration of treatment.
The clinical course of LAM patients in recent studies is better than that in earlier reports,1 ,2 ,3 ,4 perhaps as a result of more optimal hormonal therapy. Although pulmonary function continues to decline in most patients despite therapy, it is possible that hormonal therapy does slow the progression of the disease. A better understanding of the pathogenesis of LAM at the molecular and cellular level should facilitate the design of more effective therapy.
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Acknowledgements |
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Footnotes |
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Correspondence to: Joel Moss, MD, PhD, Bldg 10, Room 6D03, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr, MSC 1590, Bethesda, MD 20892-1590; e-mail: mossj@fido.nhlbi.nih.gov
Abbreviations: DLCO = diffusing capacity of the lung for carbon monoxide; ELF = epithelial lining fluid; LAM = lymphangioleiomyomatosis
Received for publication July 7, 1998. Accepted for publication October 29, 1998.
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References |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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1-antitrypsin deficient individuals [abstract]. Am J Respir Crit Care Med 155,A592
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 A. E. Tattersfield and M. K. Glassberg Lymphangioleiomyomatosis: A National Registry for a Rare Disease Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 2 - 4. [Full Text] [PDF]
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J. H. Ryu, J. Moss, G. J. Beck, J.-C. Lee, K. K. Brown, J. T. Chapman, G. A. Finlay, E. J. Olson, S. J. Ruoss, J. R. Maurer, et al. The NHLBI Lymphangioleiomyomatosis Registry: Characteristics of 230 Patients at Enrollment Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 105 - 111. [Abstract] [Full Text] [PDF]
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U. B.S. Prakash Uncommon Causes of Cough: ACCP Evidence-Based Clinical Practice Guidelines Chest, January 1, 2006; 129(1_suppl): 206S - 219S. [Abstract] [Full Text] [PDF]
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 M M Cohen, S Pollock-BarZiv, and S R Johnson Emerging clinical picture of lymphangioleiomyomatosis Thorax, October 1, 2005; 60(10): 875 - 879. [Abstract] [Full Text] [PDF]
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 G. F. Abbott, M. L. Rosado-de-Christenson, A. A. Frazier, T. J. Franks, R. D. Pugatch, and J. R. Galvin From the Archives of the AFIP: Lymphangioleiomyomatosis: Radiologic-Pathologic Correlation RadioGraphics, May 1, 2005; 25(3): 803 - 828. [Abstract] [Full Text] [PDF]
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 N. El-Hashemite, V. Walker, and D. J. Kwiatkowski Estrogen Enhances whereas Tamoxifen Retards Development of Tsc Mouse Liver Hemangioma: A Tumor Related to Renal Angiomyolipoma and Pulmonary Lymphangioleiomyomatosis Cancer Res., March 15, 2005; 65(6): 2474 - 2481. [Abstract] [Full Text] [PDF]
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N. A. Avila, A. J. Dwyer, D. V. Murphy-Johnson, P. Brooks, and J. Moss Sonography of Lymphangioleiomyoma in Lymphangi |
