A report of two long-surviving cases of pulmonary lymphangioleiomyomatosis and the response to progesterone therapy

doi:10.1016/0007-0971(85)90077-4

British Journal of Diseases of the Chest

Volume 79, 1985, Pages 400-406

https://doi.org/10.1016/0007-0971(85)90077-4 Get rights and content

Abstract

Two cases of pulmonary lymphangioleiomyomatosis, with survival between 12 and 28 years are described. Both were treated with medroxyprogesterone acetate with a slight initial improvement in both lung function and exercise tolerance, and no further deterioration during the period of follow-up of 10–20 months. The results are discussed and other reports of hormonal treatment of this rare condition are reviewed.

References (20)

J.K. Bush et al.
Diffuse lung disease due to lymphangioma
Am. J. Med.
(1969)
T.L. Svendsen et al.
Pulmonary lymphangioleiomyomatosis: a case of progesterone receptor positive lymphangioleiomyomatosis treated with medroxyprogesterone, oophorectomy and tamoxifen
Br. J. Dis. Chest
(1984)
D.J. Adams et al.
Estrogen regulation of specific proteins as a mode of hormone action in human breast cancer
Biomembranes
(1983)
A.S. Banner et al.
Efficacy of oophorectomy in lymphangioleiomyomatosis and benign metastasising leiomyoma
New Engl. J. Med.
(1981)
S.L. Bradley et al.
Pulmonary lymphangiomyomatosis
Lung
(1980)
M.M. Bretani et al.
Steroid receptors in pulmonary lymphangiomyomatosis
Chest
(1984)
C.B. Carrington et al.
Lymphangioleiomyomatosis: physiologic-pathologic-radiologic correlations
Am. Rev. resp. Dis.
(1977)
J.L. Cornog et al.
Lymphangiomyoma, a benign lesion of chyliferous lymphatics synonymous with lymphangiopericytoma
Cancer
(1966)
B. Corrin et al.
Pulmonary lymphangiomyomatosis
Am. J. Path.
(1975)
S.F. Cramer et al.
Metastasising leiomyoma of the uterus; s-phase fraction, oestrogen receptor and ultrastructure
Cancer
(1980)

There are more references available in the full text version of this article.

Cited by (30)

Effect of a gonadotrophin-releasing hormone analogue on lung function in lymphangioleiomyomatosis
2008, Chest
Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM.
Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed.
Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density.
Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density.
Pulmonary lymphangioleiomyomatosis with or without tuberous sclerosis
2007, Revue des Maladies Respiratoires
La lymphangioléiomyomatose (LAM) pulmonaire est une maladie de la jeune femme, révélée par des pneumothorax récidivants, avec ou sans dyspnée d’effort.
D’autres lésions comme un chylothorax ou un angiomyolipome rénal sont évocatrices du diagnostic. La maladie est liée à une prolifération de cellules musculaires lisses anormales reconnues par l’anticorps HMB45. Elle peut être sporadique ou associée à une sclérose tubéreuse de Bourneville dont elle partage des anomalies sur le gène suppresseur TSC2. La tomodensitométrie pulmonaire en haute résolution note des kystes pulmonaires bilatéraux à l’emporte pièce. Les explorations fonctionnelles respiratoires quantifient l’obstruction bronchique et la distension thoracique, la baisse du TCO étant l’anomalie la plus précoce.
Bien qu’il existe des formes peu évolutives, la LAM évolue le plus souvent vers une insuffisance respiratoire chronique, en quelques années ou dizaines d’années. L’hormonothérapie n’a pas démontré son efficacité en l’absence d’étude clinique contrôlée. La transplantation pulmonaire est le dernier recours thérapeutique ; de rares récidives sur poumon greffé ont été rapportées.
L’analyse des mécanismes moléculaires induits par les mutations du gène suppresseur TSC2 et la mise en évidence de propriétés migratrices des cellules musculaires lisses dont l’origine pourrait être extrathoracique font apparaître des perspectives thérapeutiques antiprolifératives spécifiques.
Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting young women and presenting with recurrent pneumothorax.
Other lesions such as chylothorax or renal angiomyolipoma may suggest the diagnosis. The condition is related to a proliferation of abnormal smooth muscle cells staining for the monoclonal antibody HMB45. LAM can appear sporadically or be associated with tuberous sclerosis with abnormalities of the TSC2 suppressor gene. High resolution thoracic CT scanning shows bilateral, thin walled pulmonary cysts. Pulmonary function tests reveal bronchial obstruction and over-inflation with a reduced DLCO being the earliest abnormality.
Although there are non-progressive forms, LAM usually leads to chronic respiratory insufficiency within a few, or ten or so years. In the absence of a controlled clinical trial hormone therapy has not been shown to be effective. Lung transplantation is the last therapeutic resort; recurrences in the transplanted lung have been occasionally reported.
Analysis of the molecular mechanisms induced by mutations of the TSC2 suppressor gene and the demonstration of the migratory properties of smooth muscle cells, whose origin may be extra-thoracic, reveal new specific antiproliferative therapeutic options.
Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone
2004, Chest
Citation Excerpt :
The efficacy of hormonal therapy with progesterone in slowing the progression of lung disease in LAM has not been established. Reports of success, based on few patients, or without objective data, are matched by reports2526272829303132333435 of therapeutic failures. In one study36 of premenopausal patients, the yearly decline in Dlco was less in 16 patients treated with progesterone than in 13 untreated patients.
Lymphangioleiomyomatosis (LAM), a disease affecting women and causing cystic lung lesions, and, in some instances, leading to respiratory failure and death, appears to be exacerbated by estrogens. Hence, hormonal therapy with progesterone is frequently employed; however, efficacy has not been demonstrated. Our aim was to determine whether progesterone administration slowed the decline in lung function in LAM.
Retrospective study.
National Institutes of Health, Bethesda, MD.
The study population comprised 348 patients with LAM participating in a longitudinal research protocol. Declines in diffusion capacity of the lung for carbon monoxide (Dlco) and FEV₁ were measured in 275 patients observed for approximately 4 years. The declines in Dlco and FEV₁ of patients treated with progesterone, po (n = 67) or IM (n = 72), were compared with those of untreated patients (n = 136).
Overall yearly rates of decline in Dlco and FEV₁ were 2.4 ≤ 0.4% predicted (0.69 ≤ 0.07 mL/min/mm Hg) and 1.7 ≤ 0.4% predicted (75 ≤ 9 mL), respectively (mean ≤ SEM). The most significant predictors of functional decline were initial lung function and age. After adjusting for initial FEV₁, age, and duration of disease, patients treated with IM progesterone tended to have lower rates of decline in FEV₁ than patients treated po (1.9 ≤ 0.6% predicted vs 3.2 ≤ 0.8% predicted, respectively; p = 0.081). However, there was no significant difference in rates of decline in FEV₁ between patients treated with IM progesterone and untreated patients (1.9 ≤ 0.6% predicted vs 0.8 ≤ 0.5% predicted, respectively; p = 0.520), and patients treated with po progesterone and untreated patients (3.2 ≤ 0.8% predicted vs 0.8 ≤ 0.5% predicted, respectively; p = 0.064). After adjusting for initial Dlco, rates of decline in Dlco were significantly higher in patients treated with po progesterone (3.6 ≤ 0.7% predicted, p = 0.002) and IM progesterone (2.8 ≤ 0.5% predicted, p = 0.022) than in untreated patients (1.6 ≤ 0.6% predicted).
Within the limitations of a retrospective study, our data suggest that progesterone therapy does not slow the decline in lung function in LAM.
Lymphangioleiomyomatosis
1998, Chest
Failure of buserelin-induced medical castration to control pulmonary lymphangiomyomatosis in two patients
1992, Chest
Two women, aged 44 and 29 years, respectively, were admitted to the hospital in early 1987 for recurrent pneumothorax, dyspnea and a diffuse reticulonodular pattern evidenced on the chest x-ray film. Lung biopsy confirmed LAM in both patients. Both were treated sequentially with medroxyprogesterone and a LHRH agonist (buserelin) to achieve reversible medical castration. Neither subjective nor objective improvement was noted after 13 and 5 months, respectively, of buserelin therapy (900 μg/day, nasal spray) despite an effective suppression of the pituitary-gonadal axis. Medroxyprogesterone also was ineffective. Buserelin thus failed to control pulmonary LAM in these two patients, in spite of effective medical castration.
Pulmonary lymphangioleiomyomatosis associated with pulmonary parenchymal, hilar, and mediastinal noncaseating granulomas
1991, Chest
A young nonsmoking woman presented with severe dyspnea, exercise desaturation, and chest discomfort. Pathologic and histochemical findings revealed pulmonary lymphangioleiomyomatosis (LAM) as the primary abnormality. In addition, there were multiple noncaseating granulomas with special stains and cultures negative for organisms. This highly unusual combination of pathologic findings might suggest the presence of coexistent sarcoidosis in our patient with LAM.

View all citing articles on Scopus

View full text

General articleA report of two long-surviving cases of pulmonary lymphangioleiomyomatosis and the response to progesterone therapy

Abstract

Am. J. Med.

Br. J. Dis. Chest

Estrogen regulation of specific proteins as a mode of hormone action in human breast cancer

Biomembranes

Efficacy of oophorectomy in lymphangioleiomyomatosis and benign metastasising leiomyoma

New Engl. J. Med.

Pulmonary lymphangiomyomatosis

Lung

Steroid receptors in pulmonary lymphangiomyomatosis

Chest

Lymphangioleiomyomatosis: physiologic-pathologic-radiologic correlations

Am. Rev. resp. Dis.

Lymphangiomyoma, a benign lesion of chyliferous lymphatics synonymous with lymphangiopericytoma

Cancer

Pulmonary lymphangiomyomatosis

Am. J. Path.

Metastasising leiomyoma of the uterus; s-phase fraction, oestrogen receptor and ultrastructure

Cancer

General article
A report of two long-surviving cases of pulmonary lymphangioleiomyomatosis and the response to progesterone therapy