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Pulmonary lymphangioleiomyomatosis in Korea

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Pulmonary lymphangioleiomyomatosis in Korea
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  Pulmonary lymphangioleiomyomatosis in Korea Yeon-Mok Oh, Eun Kyung Mo, Seung Hoon Jang, Chul Gyu Yoo, Young Whan Kim, Jeong-Wook Seo, Sung Koo Han, Jung-Gi Im, Young-Soo Shim Abstract  Background   —Pulmonary lymphangio-leiomyomatosis (LAM) is a rare diseaseoccurring in women of reproductive ageand leading to progressive respiratoryfailure in spite of treatment. In Korea thefirst case was reported in 1984 and by 1997a total of 23 cases had been reported. Theclinical findings of these Korean cases arereviewed.  Methods  —The details of 10 cases of LAMon file at Seoul National University Hospi-tal were reviewed together with those of 13cases previously reported from otherKorean institutes. Two, including the onlyone to be reported in a man, wereexcluded after reviewing the clinical, ra-diological,andpathologicalfindings,leav-ing a total of 21 cases in the present study.  Results  —All 21 patients were women andin all cases the disease was proven patho-logically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The mostcommon symptoms were dyspnoea andpneumothorax which were seen in 19(90%) and 13 (76%) patients, respectively.Pulmonary function tests showed de-creased transfer factor (T LCO ) (100%) andairflow limitation (67%). All the cases hadcharacteristic cysts on high resolutioncomputed tomographic (HRCT) scan-ning. The overall severity score based onHRCT scans correlated with the percent-age predicted T LCO /V A  (p = 0.03) andFEV 1 /FVC (p = 0.02).The patients were alltreated with medroxyprogesterone and/ortamoxifen. Follow up was possible in 10cases. Two of these patients appeared tostabilise with no appreciable change clini-cally or in lung function on medroxypro-gesterone and/or tamoxifen, but theremaining patients all deteriorated withtwo dying of respiratory insu Y ciency andone of infection following lung transplan-tation. Conclusions  —As in other countries, inKorea LAM occurs exclusively in womenand progresses despite hormonal treat-ment. ( Thorax  1999; 54 :618–621)Keywords: lymphangioleiomyomatosis; Korea; lungtransplantation Lymphangioleiomyomatosis (LAM) is a rarehamartomatousproliferationofsmoothmusclein the lungs, mediastinum, and abdomen. 1–5 Inthe lungs the abnormal proliferation of smoothmuscle is seen around airways, blood vessels,and lymphatics. It extends into the alveolarinterstitium causing cystic change and intopulmonary veins causing lung haemorrhage.Lymph node involvement leads to chylouse V  usion. 2 It a V  ects women of reproductive ageand is characterised by dyspnoea, recurrentpneumothorax, chylothorax, and haemoptysis.Chest radiographs show di V  use interstitialinfiltrates and cysts of uniform size.Pulmonaryfunction tests often show airflow limitationwithanincreaseinresidualvolume.PulmonaryLAM occurs alone or associated with tuberoussclerosis. It is thought that pulmonary LAM isa forme fruste of tuberous sclerosis. 6 It usuallyprogresses to death from respiratory insu Y -ciency. LAM was first reported in Korea in1984, since when a total of 18 Korean caseshave been published, including one in aman. 7–21 To understand the clinical characteris-tics of LAM better we reviewed the publishedKorean cases together with five previouslyunreported patients from our own institute. Methods The records of 10 cases of pulmonary LAM(including five cases published previously)were retrieved from our institute (SeoulNational University Hospital) together with 13other Korean cases from a review of the litera-ture. The pathological specimens of seven of these 23 patients were reviewed at the AsianCongress on Lymphangioleiomyomatosis heldin Kyoto,Japan in February 1993. 4 During thatmeeting two cases—the first to be reportedfrom Korea 7 and a man 8  —were excluded afterreviewing the pathology. For this study weincluded only the remaining 21 cases, all of which were proven pathologically by open lungbiopsy (19 cases), video-assisted thoracoscopiclung biopsy (one case), or examination of lungresected at transplantation (one case). Wereviewed the clinical, radiological, and patho-logical findings. To correlate the clinical andradiological findings, pulmonary function testswere compared with disease severity based onobservation by HRCT scanning. The severityof disease based on the HRCT scan wasdefined by dividing each patient’s lung intothree zones:upper,middle,and lower.The sizeof the cysts was then scored from 1 to 4 in eachlung zone with 1 = cysts of <0.5 cm diameter,2 = 0.5–1 cm,3 = 1–2 cm,and 4 = >2 cm.Theamount of cystic change as a proportion of cystic change in each lung zone was also scoredfrom 1 to 4 with 1 = change of <25%, 2 =25–50%, 3 = 51–75%, and 4 = >75%. Thesummation of the size score and the proportionscore in every zone of the lung was used toquantify the disease severity on the HRCTscan.The relationship between disease severity Thorax  1999; 54 :618–621618 Department of Internal Medicine Y-M OhE K MoS H JangC G YooY W KimS K HanY-S Shim Department of Pathology  J-W Seo Department of Radiology  J-G Im Seoul NationalUniversity College of Medicine and LungInstitute, MedicalResearch Center,Seoul NationalUniversity, Seoul110-744, Korea Correspondence to:Dr Y-S Shim.Received 1 October 1998Returned to author8 December 1998Revised manuscript received17 February 1999Accepted for publication4 March 1999 group.bmj.comon October 7, 2016 - Published by http://thorax.bmj.com/ Downloaded from   on the HRCT scan and the results of pulmonary function tests was examined. Results CLINICAL FEATURES The clinical features of the 21 cases of LAMare summarised in table 1. The age at onset of symptoms ranged from 20 to 48 years with amean (SD) age of 32 (8.6) years. All thepatients were women. The main clinical mani-festations at presentation or during follow upwere dyspnoea (19 patients), spontaneouspneumothorax (13 patients), chest pain (6patients), haemoptysis (4 patients), and cough(4 patients). No patients had chylothorax orchylous ascites. Three patients had episodes of pneumothorax during pregnancy (cases 7, 17,and 19) and case 7 had two abortions, onespontaneous and the other artificial after pneu-mothorax. In one patient the dyspnoea wasmore severe during clomiphene therapy givento induce ovulation (case 15). Six cases wereaccompanied by other features of tuberoussclerosis. One had only a renal angiomyo-lipoma (case 4),but cases 8,12,14,18,and 21had many other features of tuberous sclerosissuch as facial angiofibroma,ungual fibroma,orsubependymal nodule. PULMONARY FUNCTION TESTS The pulmonary function tests (table 2) showedan increase in the ratio of residual volume (RV)to total lung capacity (TLC) but a decreaseoccurred in the ratio of forced expiratoryvolume in one second (FEV 1 ) to forced vitalcapacity (FVC) and in the carbon monoxidetransfer factor (T LCO ). RADIOLOGICAL FINDINGS In all cases the simple chest radiograph showeddi V  use reticulonodular or reticular infiltrationthat was more marked in the lower lung zones(fig 1A). Other findings included pneumotho-rax(10patients),cysticlesions(threepatients),hyperinflation (six patients), and pleural e V  u-sion (one patient, case 13). HRCT scansshowed thin walled cysts throughout the wholelung zones (fig 1B). Severity scores based onHRCT findings of cases 1–5 were 18, 20, 16,21, and 8, respectively. The overall severityscore correlated with the percentage of measured carbon monoxide transfer factor(T LCO ) per alveolar volume (V A ) to predictedvalue ( r   = –0.90,p = 0.03) and FEV 1 /FVC ( r   = –0.95, p = 0.02). There was no significant cor-relation with the other pulmonary function testresults. Case 5 had serial CT scans available.No di V  erence was noted between two CTscans and her symptoms were also unchangedover this period. PATHOLOGICAL FINDINGS All 21 patients were proved pathologically tohave LAM. The diagnostic features werenodular proliferation of smooth muscle cells,dilated pulmonary lymphatic vessels, and theformation of air cysts. The smooth musclenodules were in the wall of the a V  ectedlymphatic vessels and cellularity was higher in Table 1 Clinical features of 21 patients with pulmonary lymphangioleiomyomatosis Case*  Age at onset† Sex Initial manifestations Later manifestationsTuberoussclerosis Associated conditions 1 9 34 F Dyspnoea Cough, haemoptysis No Mimic tuberculosis‡2 10 40 F Pneumothorax (6)§ None No Uterine myoma3 10 48 F Pneumothorax (1) Chest pain, dyspnoea No None4 10 20 F Dyspnoea Haemoptysis, pneumothorax (4) Yes None5 10 32 F Pneumothorax (1) Cough, chest pain, dyspnoea No Active tuberculosis { 6 35 F Dyspnoea Haemoptysis No None7 26 F Pneumothorax (3) Dyspnoea No Pregnancy8 22 F Dyspnoea Pneumothorax (4) Yes Transplantation¶9 (55) F Dyspnoea Cough No None10 42 F Dyspnoea None No None11 11 29 F Dyspnoea None No None12 12 38 F Pneumothorax (2) Chest pain, dyspnoea Yes None13 13 20 F Pneumothorax (1) Chest pain, dyspnoea No None14 14 27 F Dyspnoea None Yes Mimic tuberculosis‡15 15 29 F Dyspnoea Haemoptysis No Clomiphene therapy16 16 47 F Dyspnoea Cough, pneumothorax (1) No None17 17 26 F Pneumothorax (3) Chest pain, dyspnoea No Pregnancy18 18 37 F Pneumothorax (3) Chest pain, dyspnoea Yes None19 19 26 F Pneumothorax (5) None No Pregnancy20 20 (34) F Dyspnoea None No None21 21 23 F Pneumothorax (2) Dyspnoea Yes None*Superscript numbers following case numbers refer to references.†Age at onset means the age at the onset of symptoms,but where the age is in parentheses this is the age on her first visit to the phy-sician.‡They were erroneously diagnosed as miliary tuberculosis at first.§Number in parentheses following pneumothorax indicates frequency of pneumothorax. { She had concurrent pulmonary tuberculosis and was given anti-tuberculous medications. ¶She underwent bilateral sequential lung transplantation. Table 2 Pulmonary function test results  FEV  1 (% pred) FVC (% pred) FEV  1 /FVC (%)RV (% pred)TLC (% pred)RV/TLC (%)T  LCO (% pred)Pa CO 2 (kPa)Pa O 2 (kPa) Mean 50 74 55 132 105 39 34 5.07 10.53Standard deviation 25 26 24 33 31 7.8 19 0.64 2.0FEV 1  = forced expiratory volume in one second; FVC = forced vital capacity; RV = residual volume; TLC = total lung capacity;T LCO  = carbon monoxide lung transfer factor; Pa CO 2 , Pa O 2  = arterial carbon dioxide and oxygen tension. Pulmonary lymphangioleiomyomatosis in Korea  619 group.bmj.comon October 7, 2016 - Published by http://thorax.bmj.com/ Downloaded from   those nodules than in those in the bronchialsmooth muscle. Cystic changes in the lungwere not associated with pulmonary parenchy-mal fibrosis nor with activation of alveolar epi-thelial cells. Some cases (cases 1, 4 and 17)showed papilliferous proliferation of smoothmuscle nodules, protruding into the lumen.Othercases(cases2,3and5)hadsmall slendersmooth muscle bundles in the vicinity of thelung cysts. Receptor assay using immunohisto-chemistry could be performed in seven cases:the oestrogen receptor was negative in all sevencases while the progesterone receptor waspositive in three out of five cases. TREATMENT AND OUTCOME All patients were treated with medroxyproges-terone and/or tamoxifen. No patient under-went oophorectomy. Pleurodesis was per-formed in the cases with recurrentpneumothorax. One patient underwent lungtransplantation. It was possible to evaluate theoutcomesin10casesfollowedupforatleast12months (table 3). In eight of the 10 cases(80%) the disease progressed and threeeventually died, two from respiratory insu Y -ciency and one from infection after lung trans-plantation (case 8). Discussion LAM is a progressive and generally fataldisease that a V  ects women of childbearing age.The cause of death is usually respiratory insuf-ficiency. Some patients survive for many yearsbut others follow a much shorter course. Theoptimal treatment and prognostic factors arecontroversial.In 1974 Silverstein  et al   reviewed32 cases 1 and in 1975 Corrin  et al   reported 28cases of LAM,focusing on clinical,radiologicaland pathological features. 2 In 1990 Taylor  et al  reported on the diagnosis, response to treat-ment, and survival of 32 cases. 5 In Korea 18cases have been reported since 1984 and wehave diagnosed another five new cases, makinga total of 23 Korean cases.However,only 21 of the cases are reported in this study as the firstreported Korean case has been excluded aswell as a male case where the diagnosis wasconsidered to be doubtful after review of thepathological features at the Asian Congress onLymphangioleiomyomatosis held in Kyoto, Japan in February 1993. That review, pub-lished in 1995, 4 was a clinicopathological studyand included five of the 21 cases included inthis paper. We can therefore confirm thatpulmonary LAM occurs exclusively in women.The Korean cases do not di V  er very greatlyin their clinical, functional, radiological orpathological features or in their outcome fromthose reported elsewhere, except that noKorean patients have experienced chylothoraxor chylous ascites.  Figure 1 (A) Simple chest radiograph of patient 3showing di   V  use reticular infiltration that is more marked inthe lower lung zones.Note also bilateral pneumothoraceswith chest tube in the right.(B) High resolution chest CT scan of patient 3 showing thin walled cysts throughout thewhole lung zones.Note bilateral pneumothoraces with chest tube in the right.Table 3 Treatment and clinical course CaseDiagnosticdelay* Treatment Duration of  follow up(months)Symptomaticchange FEV  1 change(%)† T  LCO change(%)‡ Final result  2 2 years MP + tamoxifen 13 Deterioration −17.9 −2 Progression3 12 months MP + tamoxifen 43 Deterioration −59.7 −47 Progression4 3 years MP + tamoxifen 29 Deterioration −59.3 −2 Progression5 2 years MP + tamoxifen 44 No change 20.8 −18 Stable6 3 years MP 54 Deterioration −46.2 −20 Death from respiratory insu Y ciency8 9 years MP + tamoxifen 25 Deterioration −29.5 9 Death from infection following transplantation15 3 years MP 15 Deterioration −34.9 −4 Progression17 4 years Tamoxifen 12 Deterioration§ NE NE Death from respiratory insu Y ciency20 2 months MP 12 No change 3.0 NE Stable21 7 years MP 12 No change −8.3 −3 ProgressionMP = medroxyprogesterone; FEV 1  = forced expiratory volume in one second; T LCO  = carbon monoxide lung transfer factor; NE = not examined.*The time between symptom onset and diagnosis.†FEV 1  change (%) = percentage of (final FEV 1  — initial FEV 1 )/initial FEV 1 .‡T LCO  change (%) = final T LCO  (% predicted) — initial T LCO  (% predicted).§She experienced three pneumothoraces, two of which were during pregnancy. 620  Oh,Mo,Jang,et al  group.bmj.comon October 7, 2016 - Published by http://thorax.bmj.com/ Downloaded from   The radiographic abnormalities observedwere similar to those already reported, consist-ing of interstitial infiltrates and thin walledcysts. On simple chest radiography the infil-trates were more marked in the lower lungzones, but the cystic change identified on theCT scans showed no remarkable di V  erencesbetween upper, middle and lower lung zonesexcept in case 5 where the upper lung zoneswere less severely a V  ected. However, in case 2there were larger cysts in the upper zone thanin the lower lung zones. This patient su V  eredfrom frequent pneumothoraces. The overallseverityscorebasedonHRCTscanscorrelatedwith the percentage predicted T LCO /V A  (p =0.03) and FEV 1 /FVC (p = 0.02), but not withFEV 1 . From these observations it appears thatfunctional impairment is worse when the cystsare larger and more numerous. It was not pos-sible to determine whether small cysts becomelarger as the disease progresses because serialfollow up CT scans were not available.In reviewing the pathological findings of sixcases we found a variable degree of pulmonarydestruction but the overall degree of pulmo-nary parenchymal damage could not beassessed because the biopsy samples were toosmall. We could not find any relationshipbetween the pathological findings and theclinical course of the disease. The pathologicalstatus of the other 15 patients could not bereviewed as their data were collected retrospec-tively.Because LAM is a rare disease, trueexamples of which have only been reportedsince 1990 in Korea, and pulmonary tubercu-losis is still prevalent in our country, 22 somephysicians erroneously diagnose pulmonaryLAM as miliary tuberculosis (see cases 1 and14). In Korea the di V  erential diagnosis be-tween the two should therefore be kept inmind. Di V  erences include fever and miliaryrather than reticulonodular density in miliarytuberculosis. However, concurrent pulmonarytuberculosis and LAM were detected in onecase (case 5).One patient (case 15) su V  ered increasingdyspnoea during treatment with clomiphene, afeature of LAM that has not previously beenreported. This might be a chance finding in apatient who was at the right age to be takingclomiphene or it might be that clomiphene,which has both oestrogenic and anti-oestrogenic properties, 23 24 may aggravateLAM.All the Korean patients were treated withmedroxyprogesterone and/or tamoxifen but,apart from two patients who stabilised, all theothers whose outcome could be evaluated pro-gressed despite treatment. No patient under-went oophorectomy. Lung transplantation canbe valuable for patients with end stagelymphangioleiomyomatosis 25 but the only Ko-rean patient who underwent lung transplanta-tion died of post-transplantation infection. The authors are grateful to Professor Bryan Corrin for helpfuldiscussion and for proofreading this manuscript.1 Silverstein EF, Ellis K, Wol V   M,  et al  . Pulmonarylymphangiomyomatosis.  Am J Roentgenol Radium Ther Nucl  Med   1974; 120 :832–50.2 Corrin B,Liebow AA,Friedman PJ.Pulmonary lymphangi-omyomatosis.  Am J Pathol   1975; 79 :347–67.3 Carrington CB, Cugell DW, Gaensler EA,  et al  .Lymphangioleiomyomatosis: physiologic-pathologic-radiologic correlations.  Am Rev Respir Dis  1977; 116 :977–5.4 Kitaichi M, Nishimura K, Hok H,  et al  . Pulmonarylymphangioleiomyomatosis:report of 46 patients includinga clinicopathologic study of prognostic factors.  Am J Respir Crit Care Med   1995; 151 :527–33.5 Taylor J, Ryu J, Colby T,  et al  . Lymphangioleiomyomatosis:clinical course in 32 patients.  N Engl J Med   1990; 323 :1254–8.6 Alensi QJ.Pulmonary lymphangiomyoma,a probable formefruste of tuberous sclerosis.  Am Rev Respir Dis  1973; 108 :1411–5.7 Gee MK,Yang KW,Kim BK, et al  .Pulmonary lymphangio-leiomyomatosis (in Korean).  Korean J Pathol   1984; 18 :437– 41.8 Kang HW,Kim CJ,Kang SK, et al.  Pulmonary lymphangio-leiomyomatosis in a male.  J Korean Med Sci   1991; 6 :83–5.9 Lee KY,Kim YW,Han SK, et al  .Di V  use reticular interstitialinfiltration associated with hyperinflation (in Korean). Tuberculosis Respir Dis  1993; 40 :79–83.10 Mo EK,Jung MP,Yoo CG, et al  .Lymphangioleiomyomato-sis in Korea (in Korean).  Tuberculosis Respir Dis  1993; 40 :519–31.11 Kang SY,Yoon KH,Yoo JH, et al  .A case of pulmonary lym-phangioleiomyomatosis (in Korean).  Tuberculosis Respir Dis 1992; 39 :266–70.12 Ahn JC,Joh WY,In KH, et al  .Two cases of pulmonary lym-phangioleiomyomatosis with tuberous sclerosis (in Ko-rean).  Tuberculosis Respir Dis  1992; 39 :542–7.13 Lim JN, Park JH, Hae JJ. Pulmonary lymph-angioleiomyomatosis:a case report (in Korean).  Kon-Kuk J  Med Sci   1994; 4 :189–92.14 Won KS,Park KU,Park HJ, et al  .A case of lymphangioleio-myomatosis looking like miliary tuberculosis (in Korean). Tuberculosis Respir Dis  1995; 42 :244–9.15 Park HC, Kim YS, Kim SG,  et al  . A patient with di V  usereticular interstitial infiltration during clomiphene therapy(in Korean).  Tuberculosis Respir Dis  1995; 42 :624–7.16 Lee OJ, Lim DK, Oh GS,  et al  . Pulmonary lymph-angioleiomyomatosis: a case report (in Korean).  Inje Med J  1995; 16 :115–9.17 Bae IH, Ko KS, Cho IS,  et al  . Pulmonary lymph-angioleiomyomatosis: a case report (in Korean).  Korean J Int Med   1990; 39 :259–62.18 Jo WB, Won NH, Paik SU,  et al  . Pulmonary lymph-angioleiomyomatosis: a case report (in Korean).  Korean J Pathol   1991; 25 :269–74.19 Moon WK, Im JG, Han MC. Pulmonary lymph-angioleiomyomatosis: high-resolution CT findings (inKorean).  Korean J Radiol   1991; 27 :543–6.20 Lee KS, Choi EW, Lee BH,  et al  . Pulmonary lymph-angioleiomyomatosis: case reports (in Korean).  Korean J Radiol   1991; 28 :240–4.21 Jung SS, Park BR, Lee JS,  et al  . Pulmonary lymph-angioleiomyomatosis: a case report (in Korean).  Korean J Thoracic Cardiovas Surg   1993; 26 :160–3.22 Korean National Tuberculosis Association. The report of national-wide survey of tuberculosis (in Korean).1995:15.23 McEvoy GK, Litvak K, Welsh, et al  .  AHFS drug information. 1995 edn. Bethesda: American Society of Health-SystemPharmacists, 1995: 2562.24 Murad F,Kuret JA.Estrogens and progestins.In:GoodmanGilman A, Rall TW, Nice AS,  et al  .  Goodman and Gilman’sthe pharmacological basis of therapeutics . 8th edn. New York:Pergamon Press. 1991: 1395–725 Boehler A, Speich R, Russi EW,  et al  . Lung transplantationfor lymphangioleiomyomatosis.  N Engl J Med   1996; 335 :1275–80. Pulmonary lymphangioleiomyomatosis in Korea  621 group.bmj.comon October 7, 2016 - Published by http://thorax.bmj.com/ Downloaded from   Pulmonary lymphangioleiomyomatosis in Korea ShimWhan Kim, Jeong-Wook Seo, Sung Koo Han, Jung-Gi Im and Young-Soo Yeon-Mok Oh, Eun Kyung Mo, Seung Hoon Jang, Chul Gyu Yoo, Young doi: 10.1136/thx.54.7.618 1999 54: 618-621 Thorax http://thorax.bmj.com/content/54/7/618 Updated information and services can be found at: These include:  References  #BIBL http://thorax.bmj.com/content/54/7/618 This article cites 19 articles, 0 of which you can access for free at: serviceEmail alerting box at the top right corner of the online article. Receive free email alerts when new articles cite this article. Sign up in the CollectionsTopic Articles on similar topics can be found in the following collections (172)Transplantation (638)Cardiothoracic surgery Notes http://group.bmj.com/group/rights-licensing/permissions To request permissions go to: http://journals.bmj.com/cgi/reprintform To order reprints go to: http://group.bmj.com/subscribe/ To subscribe to BMJ go to: group.bmj.comon October 7, 2016 - Published by http://thorax.bmj.com/ Downloaded from 
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