中華放射醫誌 Chin J Radiol 2004; 29: 93-97 93

Lymphangioleiomyomatosis (LAM) is anextremely rare disease. It most commonly involvesthe lung; however, benign angiomyolipoma of thekidney may be present. Diffuse type LAM is evenrarer. This report presents a case of lymphangi-oleiomyomatosis in bilateral lungs, kidneys, liver,retrocrural space and retroperitoneal space withoutstigmata of tuberous sclerosis.

Key words: Lung, Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a very raretumor occurring exclusively in women of reproductiveage. The most common presentations are progressiveexertional dyspnea, spontaneous pneumothorax, and,less frequently, chylothorax [1, 2, 3]. Histologically, itis characterized by an abnormal proliferation ofatypical smooth muscle in lymphatic vessels, bloodvessels and airways. LAM most commonly involvesthe lung; however, smooth muscle proliferation mayalso involve extrapulmonary sites [2, 3, 4]. High-reso-lution chest computed tomography (HRCT) scan is animportant diagnostic tool for pulmonary LAM. Itreveals numerous randomly scattered thin-walled cystsof various sizes surrounded by normal lungparenchyma and bronchovascular bundles at peripheryof cyst walls.

CASE REPORT

A 35-year-old non-smoking married womansuffered from progressive exertional dyspnea and shortof breath in recent years. The dyspnea gradually deteri-orated, aggravated by pregnancy but did not improveafter delivery. She visited local hospital and chest X-ray disclosed emphysematous change with overinfla-tion of bilateral lung fields (Fig. 1). She was referredto our hospital for further evaluation and management.During the admission, physical examination revealeddecreased breathing sound, tactile fremitus and hyper-resonant percussion of bilateral chest fields. Therewere no symptoms of mental retardation, seizure attackhistory, adenoma sebaceum, pleural effusion, chy-lothorax, pneumothorax, abdominal fullness or pain.High-resolution chest computed tomography (HRCT)scans was performed, and demonstrated diffuse finethin-walled cysts randomly distributed throughout thelungs (Fig. 2). Pulmonary function tests performed onthe same day showed obstructive ventilatory defect(FEV1 = 48%; FEV1/FVC: 24%; FVC: 1.99), severeobstructive lung disease was impressed. Exercise

Reprint requests to: Dr. Po-Pang TsaiDepartment of Radiology, China Medical UniversityHospital.No 2, Yuh Der Road, Taichung 404, Taiwan, R.O.C.

Diffuse Lymphangioleiomyomatosis with Lungand Extrapulmonary Involvement– a casereportHSIN-YI LAI

1 PO-PANG TSAI1 JEON-HOR CHEN

1 TZE-YI LIN2 WU-CHUNG SHEN

1

Department of Radiology1, Pathology2, China Medical University Hospital

pulmonary function test showed severe pulmonaryventilation and perfusion (V/Q) mismatch and inpending pulmonary hypertension. Open lung biopsyrevealed smooth muscle proliferation arounddestructed cystic alveolar spaces and along adjacentinteralveolar septa, suggestive of pulmonary lymphan-gioleiomyomatosis (LAM) (Fig. 3). The smoothmuscle nature of the cell was confirmed by positiveHMB45 immunostaining. The diagnosis of pulmonaryLAM was then established. The abdominal computedtomography (CT) scan with and without contrastenhancement showed some hypodense attenuationlesions in right lobe of liver and multiple heteroge-neously enhancing lesions with some hypodensecomponent in bilateral kidneys, retrocrural space andretroperitoneal space (Fig. 4, 5). Analysis of CTnumbers revealed negative Hounsfield unit of thesemass lesions, indicating fat content. Under the condi-tions of characteristic pathologic findings on lungbiopsy, typical cystic appearance on chest CT scan andhepatic angiomyolipoma, typical renal angiomy-olipomas with abdominal lymphadenopathy, diffuselymphangioleiomyomatosis was then diagnosed.Therefore she visited OPD for regular follow up andreceived medroxy-progesterone medication. Becausethe clinical condition did not improve after medicaltreatment, she received left single lung transplantaionseveral months later. The patient was dischargeduneventfully.

DISCUSSION

Lymphangioleiomyomatosis (LAM) is a disorderof unknown etiology which exclusively affects repro-ductive women [1, 2, 4, 5]. It is a rare lung diseasethat was first described in the medical literature byvon Stossel in 1937. The most common presentationsare progressive exertional dyspnea, spontaneous pneu-mothorax, and, less frequently, chylothorax [2, 3].Histologically, LAM is characterized by an abnormalproliferation of atypical smooth muscle cells, with noassociated inflammatory cells in lymphatic vessels,blood vessels and airways, which can lead to airtrapping, overinflation, formation of cysts, pneumoth-orax, chylothorax and alveolar hemorrhage. Althoughthese cells are not considered cancerous, they actsomewhat like cancer cells in that they grow uncon-trollably. HMB45 is a monoclonal antibody withspecific immunoreactivity for malignant melanomaand it constitute a highly specific and highly sensitivediagnostic marker for LAM [5]. It may also be usefulin patients with only minor smooth muscle prolifera-tion, in whom the diagnosis of LAM is difficult to be

confirmed by conventional histologic examination [5]. Smooth muscle proliferation may also involve

extrapulmonary sites. The most common forms ofextrapulmonary LAM include renal angiomyolipoma(20~54% of cases), enlarged abdominal lymph nodes(39%), and lymphangiomyoma (16~20%) [2, 3, 4].Less commonly, ascites (10%) and hepatic angiomy-olipoma (4%) may be present [2, 3, 4]. A few cases ofLAM with renal angiomyolipoma, multiple abdominal

Diffuse lymphangioleiomyomatosis94

Figure 1. Chest radiograph shows emphysematouschange of both lung fields and lung volume is increased.

Figure 2. High-resolution CT scan demonstrates diffusefined thin-walled cysts, which are randomly distributedthroughout the lungs.

lymphadenopathy or with hepatic angiomyolipomahave been reported [1, 2, 4]; however, in this articlewe report LAM of bilateral lungs, kidneys, liver, retro-crural space and retroperitoneal space in one patient.

The low density lesion within right lobe of liverparenchyma appeared to be like pure lipoma of liver,but hepatic lipoma is exceedingly rare and the LAMhas been proven in this patient. Therefore, the hepaticangiomyolipoma associated with LAM is morefavorable (Fig. 4). Angiomyolipomatosis of kidneyswas impressed by demonstration of intratumoral fatwith negative attenuation values in CT within thesemass lesions (Fig. 5). There are many lym-

phadenopathy with some hypodense component,which analysis of CT number revealed negative atten-uation in retrocrural space and retroperitoneal space(fig. 5). However, no definite lymphangiomyoma orascites is noted in this patient. The low attenuationareas within the enlarged lymph nodes representedchylous lymph collection, and enlarged lymph nodescould measured up to 4 cm in diameter [1].Lymphangioleiomyoma may be thick- or thin-walled,vary in size and low attenuation retroperitoneal mass,which occurs in 16~20% of patients with LAM [1, 4].

The chest radiographic findings in LAM arevariable [6]. In early stage, the chylous pleuraleffusion may dominate, or proliferation interstitialmuscle bundles may produce a micronodular ormilitary pattern [6]. Chylous pleural effusion may beunilateral or bilateral. The CT attenuation of chylouspleural effusion is usually indistinguishable from thatof other protein rich effusion. LAM induced chy-lothorax usually recur and in large amount [1]. Septallines due to the lymphatic obstruction appear,producing a coarse reticular pattern [6, 7]. In moreadvanced disease, the chest radiograph shows hyperin-flation, small cysts areas that may be superimposed ona coarse reticular pattern, and sometimes a pneumoth-orax [6]. In addition, dilatation of the thoracic ductcould be identified in 26% patients with LAM. Theclinical features and the presentation of chest radi-ograph are often nonspecific [8], so the high-resolu-tion chest CT (HRCT) scan is an important diagnostictool for pulmonary LAM. The HRCT of LAM patientreveals numerous randomly scattered thin-walled cystsof various sizes surrounded by normal lung

Diffuse lymphangioleiomyomatosis 95

Figure 3. Open lung biopsy reveals smooth muscleproliferation (�) around cystic destruction of severalalveolar spaces and along adjacent interalveolar septa(�), suggestive of pulmonary lymphangioleiomyom-atosis (LAM). (H&E, x40)

Figure 4. Precontrast CT scans of the abdomen show twoextremely low density lesions at liver parenchyma andsome low-attenuation lesions in retrocrural space.Analysis of CT numbers revealed negative attenuationwithin these lesions, a finding diagnostic of hepaticangiomyolipoma and retrocrural lymphadenopathy.

Figure 5. Precontrast and postcontrast CT scans revealsome heterogeneous enhancing mass lesions in bilateralkidneys and retroperitoneal space. Analysis of CTnumbers revealed negative attenuation within theselesions, a finding diagnostic of renal angiomyolipoma-tosis ( ) and retroperitoneal lymphadenopathy ( ).

parenchyma. Because LAM occurs almost in women of child-

bearing age and exacerbations are suspected to berelated to pregnancy, exogenous estrogens, and contra-ceptive pills, it has been suggested that hormonalfactors play an important role in the development ofLAM [8]. Hormonal therapy, if beneficial, should bestarted as soon as possible, before irreversible majorlung destruction occurs [3]. A recent paper reports thattuberous sclerosis gene mutations are a cause of lym-phyangioleiomyomatosis [1, 9]. The mutations arefound in the angiomyolipoma cells and LAM cellsfrom four women with LAM [1]. The mutations arenot present in normal lung, kidney or blood cells, indi-cating that these women with LAM do not have theinherited disease, tuberous sclerosis [1].

Other interstitial lung diseases, such asHistiocytosis X, tuberous sclerosis, idiopathicpulmonary fibrosis, acinar emphysema and bronchiec-tasis should be differentiated from LAM. HistiocytosisX of lung is more frequent in young men, and predom-inant of cysts and nodules in the upper lung fields withsparing of costophrenic angles. Pulmonary LAM andtuberous sclerosis differ in terms of their clinicalsetting. LAM usually occurs in female in whom thereis no mental deficiency and no clinical evidence ofcentral nervous system damage [7]. The autosomaldominant transmission of tuberous sclerosis shows ofneurologic or cutaneous manifestations such asseizure, mental retardation, adenoma sebaceum, orcephalic calcifications [3, 7]. Idiopathic pulmonaryfibrosis can be differentiated from LAM by the smallirregular thick-walled cysts and may distribute moreperipherally. In acinar emphysema, the bronchovas-cular bundles are usually in central position of cyst.HRCT scan is clearly a sensitive modality for thediagnosis of early pulmonary LAM, even when chestX-ray is inconclusive. It may be indicated in sponta-neous pneumothorax or renal angiomyolipoma inwomen of childbearing age [1, 2, 3, 5].

Early reports of LAM revealed most patients diedwithin 10 years. In present study, Kaplan-Meier plotshowed survival probabilities of 91% after 5 years,79% after 10 years, and 71% after 15 years of diseaseduration [3]. In a recent worldwide retrospective studyof 34 cases of lung transplantation for pulmonaryLAM, the survival rate was 69% at 1 year and 58% at2 years [3]. There are particular complications inpatients with LAM, such as excessive bleeding frompleural adhesions during surgery, pneumothorax of thenative lung, chylothorax and hemorrhage, thereforethe survival rate of post lung transplantation patientswas lower than LAM patients without transplantation

surgery. Although disease-related complications arefrequent and recurrence is possible but rare, weconsider that lung transplantation is indicated inpatients with end-stage LAM [1, 3, 4, 8].

In conclusion, LAM is a rare serious progressivedisease that predominantly affects women of child-bearing age and leads to chronic respiratory insuffi-ciency [1, 3]. The radiologist is often the first tosuggest the diagnosis of LAM because the thoracichigh-resolution CT findings are very characteristic [1,3]. Abdominal CT scan or ultrasound examinationmay be indicated in women of childbearing age pre-senting with multiple thin-walled cysts on chestHRCT scan [3, 10]. ◆

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3. Thierry U, Romain L, Jacques L, et al. PulmonaryLymphangioleiomyomatosis. Medicine 1999; 78: 321-337

4. Yuen YW, Tai KY, Winnie CWC. Atypical presentationof lymphangioleiomyomatosis as acute abdomen: CTDiagnosis. AJR 2003; 181: 284-285

5. Galen B. Toews. Interstitial lung disease. Lee Goldman,J. Claude Bennett. Cecil Textbook of Medicine, 21sted., Philadelphia: W.B. Saunders Company, 2000: 415-416

6. Marvin IS, Reuben MC, Talmadge EKJR. DiffuseAlveolar Hemorrhage and Other Rare InfiltrativeDisorders. John FM, Jay AN. Textbook of RespiratoryMedicine, 3rd ed., Philadelphia, London, New York, St.Louis, Sydney, Toronto: W.B. Saunders Company,2000: 1733-1748

7. John HJ, Janet EK. Lymphangiomyomatosis. John HJ,Andrew BC, Janet EK. Paul and Juhl’s Essentials ofRadiologic Imaging, 7th ed., Philadlephia, Baltimore,New York, London: Lippincott Williams & Wilkins,1998: 1075-1076

8. Kenneth GK, Thomas AR. Lymphangioleio-myomato-sis. John FM, Jay AN. Textbook of RespiratoryMedicine, 3rd ed., Philadelphia: W. B. SaundersCompany, 2000: 1775-1785

9. Noonan DJ, Lou D, Griffith N, Vanaman TC. Acalmodulin binding site in the tuberous sclerosis 2 geneproduct is essential for regulation of transcription eventsand is altered by mutations linked to tuberous sclerosisand lymphangioleiomyomatosis. Arch BiochemBiophys 2002; 398: 132-140

10. Shan CC, Koji H, Jiro U, et al. Clinical investigations:Comprehensive evaluation of 35 patients with lymphan-gioleiomyomatosis. Chest 1999; 115: 1041-1051

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瀰漫性淋巴血管平滑肌增生症：病例報告

賴欣宜1 蔡伯邦1 陳中和1 林智一2 沈戊忠1

中國醫藥大學附設醫院　放射線部1 病理部2

瀰漫性淋巴血管平滑肌增生症是一種罕見的疾病，大部分發生在生育年齡的婦女，最常影

響的器官是肺臟。肺臟以外的地方，例如：腎臟的血管肌肉脂肪瘤也有人報導，而瀰漫性淋巴

血管平滑肌增生症則更是少見。本文報告一例在兩側肺臟、腎臟、肝臟、橫隔膜後及後腹腔的

瀰漫性淋巴血管平滑肌增生症。

關鍵詞：肺臟；淋巴血管平滑肌增生症