Original Article
Clinical Outcomes of Pulmonary Langerhans'-Cell Histiocytosis in Adults
N Engl J Med 2002; 346:484-490February 14, 2002
- Abstract
Background
Pulmonary Langerhans'-cell histiocytosis is an uncommon interstitial lung disease in adults. It has an unpredictable course and may be associated with an increased susceptibility to the development of malignant neoplasms.
Methods
We reviewed the records of 102 adults with histopathologically confirmed pulmonary Langerhans'-cell histiocytosis to ascertain their vital status and whether cancer had been diagnosed. The health status of surviving patients was quantified with the use of the 36-Item Short-Form General Health Survey. Factors potentially associated with survival after the diagnosis of pulmonary Langerhans'-cell histiocytosis were analyzed with the Cox proportional-hazards model.
Results
The median follow-up period was 4 years (range, 0 to 23). There were 33 deaths, 15 of which were attributable to respiratory failure. Six hematologic cancers were diagnosed. The overall median survival was 12.5 years, which was significantly shorter than that expected for persons of the same sex and calendar year of birth (P<0.001). In a univariate analysis, variables predictive of shorter survival included an older age (P=0.003), a lower forced expiratory volume in one second (FEV1) (P=0.004), a higher residual volume (P=0.007), a lower ratio of FEV1 to forced vital capacity (P=0.03), and a reduced carbon monoxide diffusing capacity (P=0.001).
Conclusions
The survival of adults with pulmonary Langerhans'-cell histiocytosis is shorter than that in the general population, and respiratory failure accounts for a substantial proportion of deaths among such patients.
Media in This Article
Figure 1
Kaplan–Meier Analysis of Expected and Observed Survival among 102 Adults with Pulmonary Langerhans'-Cell Histiocytosis.Table 1
Characteristics at the Time of the Diagnosis of Pulmonary Langerhans'-Cell Histiocytosis in 102 Adults.Article Activity
- Article
Pulmonary Langerhans'-cell histiocytosis is an uncommon interstitial lung disease that is part of the spectrum of disorders called Langerhans'-cell histiocytoses. These disorders are thought to result from the proliferation of specific histiocytic cells, known as Langerhans' cells, and their infiltration of organ systems.1-6 The course of pulmonary Langerhans'-cell histiocytosis in adults is variable and unpredictable, ranging from an asymptomatic course to progressive disease that leads to respiratory failure and death over a period of months. Although little is known about the natural course of this disease or the long-term prognosis for affected adults, retrospective studies of case series have suggested that several factors are predictive of an adverse outcome.5,7 These factors include extremes of age; multiorgan involvement; extensive cysts and honeycombing on chest radiographs; reduced carbon monoxide diffusing capacity; physiological obstruction, as indicated by a low ratio of the forced expiratory volume in one second (FEV1) to the forced vital capacity; prolonged corticosteroid therapy; and evidence of air trapping, as indicated by a high ratio of residual volume to total lung capacity.5,7 These data have been confounded by the inclusion in the studies of patients who were children at the onset of disease and by the inclusion of patients in whom the diagnosis was not confirmed by tissue biopsy. Data from several case reports and series also suggest that patients with Langerhans'-cell histiocytosis are at increased risk for cancer,8-12 although the association between the two disorders has not been clearly defined.
We reviewed the medical records of adults (18 years or older) with histologically confirmed pulmonary Langerhans'-cell histiocytosis who were seen at our institution over a 22-year period. We compared the survival of these persons with that expected for the general population. We also identified predictors of an adverse outcome, estimated the effect of Langerhans'-cell histiocytosis on the quality of life, and estimated the risk of malignant neoplasms in our cohort of patients.
Methods
Patients
We reviewed the medical records of 102 adults with pulmonary Langerhans'-cell histiocytosis who were seen at the Mayo Clinic between January 1, 1976, and December 31, 1998. Patients were eligible for inclusion in the study if they had pulmonary Langerhans'-cell histiocytosis with histopathological confirmation on the basis of surgical lung biopsy (94 patients), transbronchoscopic lung biopsy (6 patients), or biopsy of an organ other than the lung together with findings on a high-resolution computed tomographic (CT) scan of the chest that were consistent with the diagnosis (2 patients). Patients less than 18 years of age at the time of the diagnosis were excluded. The study was approved by the institutional review board for medical research. Written informed consent was obtained from the patients who participated in the follow-up survey.
Data Collection
The following clinical data were abstracted from the patients' medical records: symptoms and age at presentation, sex, presence or absence of a history of smoking, results of physical examination and laboratory tests, treatment at the time of the initial diagnosis, coexisting medical conditions, and the results of pulmonary-function studies, which were performed in our laboratory with the use of standard techniques.13 Pulmonary-function data that were collected included plethysmographically determined total lung capacity, forced vital capacity, FEV1, the ratio of FEV1 to forced vital capacity, and the carbon monoxide diffusing capacity. A restrictive pattern was defined as a total lung capacity that was less than 80 percent of the predicted value and a normal or high ratio of FEV1 to forced vital capacity. An obstructive pattern was defined as an FEV1 that was less than 80 percent of the predicted value and a ratio of FEV1 to forced vital capacity that was less than 0.75.14,15
We determined the vital status of patients by reviewing medical records and available death certificates. Follow-up data, including symptoms, were obtained from a questionnaire sent to all surviving patients included in the study, with follow-up by telephone for patients who did not return the questionnaire.
Survival
Survival was determined from the date of the diagnosis of pulmonary Langerhans'-cell histiocytosis to the date of death or the date on which the patient responded to the survey. Cumulative survival probabilities were estimated with the use of the Kaplan–Meier method and were compared with the life expectancy for white persons of the same sex and calendar year of birth in the general U.S. population.16 The one-sample log-rank test was used to compare actual and expected survival. Factors potentially associated with survival were analyzed with the use of the Cox proportional-hazards model. The expected probability of survival at 10 years was determined for each patient on the basis of sex and calendar year of birth, with the use of life tables for white persons in the U.S. population.16 In the Cox proportional-hazards model, the association of each potential predictor with survival was adjusted for the expected probability of survival at 10 years.
Malignant Neoplasms
The relative risks of hematologic cancers (International Classification of Diseases for Oncology, 2nd Revision codes 9590 to 9595, 9650 to 9667, 9670 to 9717, 9731, 9732, 9861, 9868, 9950, and 9962) were estimated with the use of age- and sex-specific incidence rates for cancer, based on data from the Surveillance, Epidemiology, and End Results program for the period from 1973 to 1998.17 To minimize the potential influence of referral bias on the results, the analysis was performed with person-years defined as the number of years that patients were observed from the diagnosis of pulmonary Langerhans'-cell histiocytosis to the diagnosis of cancer or the last contact. For each type of cancer, the expected number of cases was computed by multiplying the number of age- and sex-specific person-years by the incidence. The risk ratio was calculated as the ratio of the total number of observed cases of cancer to the total number of expected cases, and the 95 percent confidence interval was calculated with the assumption of a Poisson distribution for the number of observed cases.
Health Status
We measured health status with the use of the 36-Item Short-Form General Health Survey (SF-36), which was part of the questionnaire sent to the patients. Responses to the SF-36 portion of the survey were scored according to published guidelines.18 Standardized T scores, scaled so that the mean score was 50 with a standard deviation of 10 for the reference population, were calculated with the use of age- and sex-specific mean scores and standard deviations for the SF-36 scales in the general U.S. population.18 For each of the eight scales, the one-sample t-test was used to compare the mean T score with a score of 50. In all cases, two-sided tests were used, with a P value less than or equal to 0.05 considered to indicate statistical significance.
Results
The clinical characteristics of 102 patients (40 men and 62 women) at the time that pulmonary Langerhans'-cell histiocytosis was diagnosed are summarized in Table 1Table 1
Characteristics at the Time of the Diagnosis of Pulmonary Langerhans'-Cell Histiocytosis in 102 Adults.. In 94 patients (92 percent), the diagnosis was established by surgical lung biopsy. Of the 102 patients in the study, 29 underwent transbronchoscopic lung biopsy, but the findings were diagnostic in only 6 of the 29, confirming prior reports that transbronchoscopic biopsy has a limited role in the diagnostic workup for pulmonary Langerhans'-cell histiocytosis.19 Staining for the S-100 and CD1a antigens was used in three of the six positive biopsy specimens to facilitate identification of Langerhans' cells.20,21 The diagnosis in the remaining 23 patients (who had a nondiagnostic transbronchoscopic lung biopsy) was established by surgical lung biopsy. Pulmonary-function data, which were available for 82 patients, are summarized in Table 2Table 2
Pulmonary Function at Diagnosis..High-resolution CT studies of the chest were performed in 29 patients at the time of the diagnosis. The most common abnormality was the presence of nodules, which were seen in 20 patients; in 5 of these patients, the nodules were described as cavitating. Lung cysts were identified in 11 patients. Four patients had a combination of lung cysts and nodules. The abnormalities were present predominantly in the upper and middle lung fields in 18 patients. Other reported abnormalities were ground-glass attenuation in three patients (reported in association with lung nodules in two patients and as the sole abnormality in one), patchy consolidating infiltrates in one patient, and mediastinal adenopathy in two patients (associated with lung nodules in both).
In 16 cases, the radiologist reported that the CT findings were highly suggestive of pulmonary Langerhans'-cell histiocytosis. In the other 13 cases, the radiologist's report indicated that the findings were not typical of pulmonary Langerhans'-cell histiocytosis, and in 9 of these cases, the report suggested an alternative diagnosis. Only three deaths occurred in the subgroup of patients who underwent high-resolution CT studies of the chest at the time of the diagnosis; the number was too small to allow a meaningful statistical analysis of the findings in this subgroup.
At the time of the diagnosis, all current smokers were advised to stop smoking. For patients with minimal symptoms or none, there were no interventions except for those involving smoking cessation. Prednisone, alone or in combination with other immunosuppressive agents, was prescribed for 54 patients (53 percent) within six months after the diagnosis; 39 of these patients (72 percent) were treated with prednisone alone or, in the case of patients with multisystem disease, prednisone in combination with another drug (vinblastine in 7 patients, methotrexate in 2, cyclophosphamide in 2, etoposide in 2, and cladribine [2-chlorodeoxyadenosine] in 2). Two patients underwent surgical pleurodesis shortly after the diagnosis, and one patient underwent lung transplantation at the time of follow-up.
Survival
The median follow-up period after the diagnosis of pulmonary Langerhans'-cell histiocytosis was 4 years (range, 0 to 23). There were 33 deaths, 15 of which were attributable to respiratory failure. Survival was significantly shorter than that expected for healthy persons of the same sex and calendar year of birth (P<0.001) (Figure 1Figure 1
Kaplan–Meier Analysis of Expected and Observed Survival among 102 Adults with Pulmonary Langerhans'-Cell Histiocytosis.). The estimated rate of survival 5 years after the diagnosis of pulmonary Langerhans'-cell histiocytosis was 74 percent (95 percent confidence interval, 56 to 85 percent), and the rate of survival at 10 years was 64 percent (95 percent confidence interval, 52 to 77 percent). The estimated median survival (from the time of diagnosis) was 12.5 years. Characteristics at the time of diagnosis that were associated with survival are summarized in Table 3Table 3
Characteristics at Diagnosis Associated with Survival.. The univariate analysis showed that shorter survival was associated with an older age (P=0.003), a lower carbon monoxide diffusing capacity (P=0.001), a lower FEV1 (P=0.004), a higher residual volume (P=0.007), and a lower ratio of FEV1 to forced vital capacity (P=0.03). After adjustment for expected survival at 10 years, based on life expectancy in the general population, survival was associated with a lower carbon monoxide diffusing capacity (P<0.001), a lower FEV1 (P=0.004), a higher residual volume (P=0.005), and former smoking (as opposed to current smoking at diagnosis) (P=0.03).Malignant Neoplasms
A total of 16 noncutaneous malignant neoplasms were identified in 14 patients in the study population (Table 4Table 4
Diagnosed Cancers in the Study Group.). All patients with neoplasms were current or former smokers at the time of the diagnosis of cancer, and a substantial proportion had a very long history of cumulative exposure to cigarette smoke. Seven cancers were diagnosed before the pulmonary Langerhans'-cell histiocytosis, six were diagnosed concurrently or in the same year, and three were detected after the diagnosis of pulmonary Langerhans'-cell histiocytosis. Hematologic cancers occurred in six patients, and five had primary lung cancers. There were 628 person-years of follow-up for hematologic cancers, with 2 observed cases and 0.172 expected (risk ratio, 11.6; 95 percent confidence interval, 1.4 to 41.9).Health Status
A follow-up survey that included the SF-36 was sent to 88 patients not known to be deceased on the basis of the chart review. Of these 88 patients, 42 returned the survey, 19 had died, 5 refused to complete the survey, and there was no response from 22 patients. Of the 42 patients who returned the survey, 35 completed the SF-36; in this group, the median period of follow-up from the diagnosis of pulmonary Langerhans'-cell histiocytosis was 6.9 years (range, 0.7 to 23.3). Analysis of the SF-36 data indicated that pulmonary Langerhans'-cell histiocytosis had a substantial effect on the health of these patients. As compared with persons of the same age and sex in the general U.S. population, the patients with pulmonary Langerhans'-cell histiocytosis had significantly lower scores for physical functioning (P<0.001), ability to perform role-related activities (physical role) (P=0.004), general health (P<0.001), and vitality (P<0.001), as well as for overall physical well-being (a composite score) (P<0.001).
Discussion
Our study shows that adults with pulmonary Langerhans'-cell histiocytosis have a shorter survival than members of the general population. A substantial proportion of the patients in our study died from respiratory failure. Evidence of obstruction, air trapping, and reduced carbon monoxide diffusing capacity on pulmonary-function testing appears to be helpful in identifying patients with a poor prognosis. Our study also shows that the health of persons with pulmonary Langerhans'-cell histiocytosis is impaired in several ways.
In 628 person-years of follow-up, 33 deaths occurred in our cohort of patients with pulmonary Langerhans'-cell histiocytosis, 15 of which were attributed to progressive respiratory failure. Some of these deaths may have resulted from associated severe chronic obstructive pulmonary disease due to concomitant cigarette smoking, although it is impossible to determine the contribution of this disease to the deaths. Three patients died as a consequence of an associated pulmonary neoplasm. The median survival in our study, 12.5 years, is almost identical to that previously reported in a European multicenter study involving 45 patients.7
Our findings confirm prior reports that in patients with pulmonary Langerhans'-cell histiocytosis, physiological evidence of impaired pulmonary function, especially evidence of an obstructive ventilatory defect, is a predictor of an adverse outcome and may be helpful in identifying patients who will benefit from aggressive treatment early in the course of disease.7 Although no specific interventions have been shown to prolong survival, vigorous efforts to help patients stop smoking seem reasonable, particularly for patients with clinical findings that point to a poor prognosis.22 The role of immunosuppressive therapy in the care of patients with adverse prognostic indicators is not clear, since such treatment has not been objectively demonstrated to improve lung function or reduce long-term mortality.
Disseminated Langerhans'-cell histiocytosis is thought to be associated with a worse prognosis than isolated organ involvement. Although we anticipated that extrapulmonary involvement would be predictive of an adverse outcome, it was not. However, firm conclusions cannot be drawn in view of the small number of patients included.
Most of the patients in our study were current or former cigarette smokers at the time of the diagnosis. The high prevalence of cigarette smoking among adults with pulmonary Langerhans'-cell histiocytosis has also been reported in several other studies, and this finding suggests that the disease may be causally related to smoking.1,2,6,22-25 Although almost all adults with pulmonary Langerhans'-cell histiocytosis are cigarette smokers, only approximately 60 percent of adults with systemic forms of the disorder have a history of exposure to cigarette smoke (unpublished data). We speculate that pulmonary Langerhans'-cell histiocytosis represents a reactive polyclonal process in the lungs that is induced by antigens in cigarette smoke and is thus different from the other systemic forms of Langerhans'-cell histiocytosis, which have been shown to be the result of a monoclonal proliferation of Langerhans' cells, much like a neoplasm.25
Although high-resolution CT scans showing nodular abnormalities accompanied by cystic changes, predominantly in the upper and middle lung fields, are virtually pathognomonic of pulmonary Langerhans'-cell histiocytosis,1,26-29 these findings were reported in only four of our patients with biopsy-confirmed disease; the majority had either cystic abnormalities or lung nodules alone. Whether the findings on high-resolution CT have any prognostic importance could not be determined by our retrospective analysis because of the small sample.
A number of investigators have reported the diagnosis of lymphoma,11,30 multiple myeloma,12,31 adenocarcinoma of the lung,32 and other solid tumors before, after, or at the same time as the diagnosis of Langerhans'-cell histiocytosis.8,9,33,34 Our study showed that a variety of neoplasms were associated with pulmonary Langerhans'-cell histiocytosis. Because of the small numbers of patients and the retrospective nature of the study, a definitive conclusion about the relative risks of various cancers, especially myeloproliferative disorders, in adults with pulmonary Langerhans'-cell histiocytosis cannot be drawn, but the association should be recognized by clinicians treating such patients. Cigarette smoking, prior treatment with chemotherapeutic agents, and chromosomal or genetic abnormalities are factors that may confer a predisposition to the development of malignant neoplasms in patients with pulmonary Langerhans'-cell histiocytosis.
Although there are no published data on measures of health status in patients with Langerhans'-cell histiocytosis, the SF-36 is a sensitive instrument for evaluating health status in patients with other interstitial lung diseases, such as sarcoidosis.35 In patients with pulmonary Langerhans'-cell histiocytosis, respiratory and constitutional symptoms, side effects of treatment, and functional limitations due to progressive respiratory impairment caused by the disease are likely to affect health.
There are several limitations of our study. We enrolled only patients with histologically confirmed disease and thus introduced a potential selection bias by excluding 15 persons with probable pulmonary Langerhans'-cell histiocytosis on the basis of the clinical history and high-resolution CT findings. These patients had minimally symptomatic disease for which a definitive diagnosis was not deemed necessary. Although their exclusion may have contributed to our data showing a poor outcome, Delobbe et al.7 reported a median survival that was almost identical to that in our study, even though their inclusion criteria were less stringent (with the diagnosis established by bronchoalveolar lavage in 20 of the 45 patients in their study).
Another limitation of our study was the use of death certificates to determine causes of death. The magnitude of the bias introduced into the analysis as a result of this approach is difficult to determine with certainty, but the number of deaths from respiratory failure may have been overestimated.
Our retrospective analysis shows that among adults with pulmonary Langerhans'-cell histiocytosis, long-term survival is shorter than that in the general population, health is substantially affected, and death is frequently due to respiratory complications. In addition, these patients appear to have an increased frequency of hematologic cancers. Poor physiological function at the time of the diagnosis of pulmonary Langerhans'-cell histiocytosis portends a poor prognosis. Although the condition is rare, our data provide a basis for designing prospective studies to elucidate these issues.
Supported by grants from the Mayo Clinic and the Robert N. Brewer Family Foundation.
We are indebted to Ms. Ann Harris for help with the preparation of the questionnaire and to the staff of the Biostatistics Unit at the Mayo Clinic for assistance with follow-up and data collection.
Source Information
From the Thoracic Diseases Research Unit, Division of Pulmonary, Critical Care, and Internal Medicine (R.V., J.H.R., A.H.L.), and the Departments of Health Sciences Research (D.R.S., P.A.D.) and Biochemistry and Molecular Biology (A.H.L.), Mayo Clinic and Foundation, Rochester, Minn.
Address reprint requests to Dr. Vassallo at the Mayo Clinic, Stabile Bldg. 8-54, 200 First St. SW, Rochester, MN 55905, or at vassallo.robert@mayo.edu.
- References
References
1
Vassallo R ,Ryu JH ,Colby TV ,Hartman T ,Limper AH . Pulmonary Langerhans'-cell histiocytosis. N Engl J Med 2000;342:1969-1978
Full Text | Web of Science | Medline2
Colby TV ,Lombard C . Histiocytosis X in the lung. Hum Pathol 1983;14:847-856
CrossRef | Web of Science | Medline3
Travis WD ,Borok Z ,Roum JH , et al. Pulmonary Langerhans cell granulomatosis (histiocytosis X): a clinicopathologic study of 48 cases. Am J Surg Pathol 1993;17:971-986
CrossRef | Web of Science | Medline4
Malpas JS ,Norton AJ . Langerhans cell histiocytosis in the adult. Med Pediatr Oncol 1996;27:540-546
CrossRef | Medline5
Basset F ,Corrin B ,Spencer H , et al. Pulmonary histiocytosis X. Am Rev Respir Dis 1978;118:811-820
Web of Science | Medline6
Friedman PJ ,Liebow AA ,Sokoloff J . Eosinophilic granuloma of lung: clinical aspects of primary histiocytosis in the adult. Medicine (Baltimore) 1981;60:385-396
CrossRef | Web of Science | Medline7
Delobbe A ,Durieu J ,Duhamel A ,Wallaert B . Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Eur Respir J 1996;9:2002-2006
CrossRef | Web of Science | Medline8
Egeler RM ,Neglia JP ,Puccetti DM ,Brennan CA ,Nesbit ME . Association of Langerhans cell histiocytosis with malignant neoplasms. Cancer 1993;71:865-873
CrossRef | Web of Science | Medline9
Egeler RM ,Neglia JP ,Arico M ,Favara BE ,Heitger A ,Nesbit ME . Acute leukemia in association with Langerhans cell histiocytosis. Med Pediatr Oncol 1994;23:81-85
CrossRef | Medline10
Ben-Ezra JM ,Koo CH . Langerhans' cell histiocytosis and malignancies of the M-PIRE system. Am J Clin Pathol 1993;99:464-471
Web of Science | Medline11
Burns BF ,Colby TV ,Dorfman RF . Langerhans' cell granulomatosis (histiocytosis X) associated with malignant lymphomas. Am J Surg Pathol 1983;7:529-533
CrossRef | Web of Science | Medline12
Ibarrola de Andres C ,Toscano R ,Lahuerta JJ ,Martinez-Gonzalez MA . Simultaneous occurrence of Hodgkin's disease, nodal Langerhans' cell histiocytosis and multiple myeloma IgA(kappa). Virchows Arch 1999;434:259-262
CrossRef | Web of Science | Medline13
Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis 1991;144:1202-1218
CrossRef | Web of Science | Medline14
Miller A ,Thornton JC ,Warshaw R ,Bernstein J ,Selikoff IJ ,Teirstein AS . Mean and instantaneous expiratory flows, FVC and FEV1: prediction equations from a probability sample of Michigan, a large industrial state. Bull Eur Physiopathol Respir 1986;22:589-597
Medline15
Miller A ,Thornton JC ,Warshaw R ,Anderson H ,Teirstein AS ,Selikoff IJ . Single breath diffusing capacity in a representative sample of the population of Michigan, a large industrial state: predicted values, lower limits of normal, and frequencies of abnormality by smoking history. Am Rev Respir Dis 1983;127:270-277
Web of Science | Medline16
Therneau TM, Sicks JD, Bergstralh EJ, Offord JR. Expected survival based on hazard rates. Technical report series no. 52. Rochester, Minn.: Section of Biostatistics, Mayo Clinic, 1994.
17
Surveillance, Epidemiology, and End Results (SEER) program public-use data (1973–1998). Bethesda, Md.: National Cancer Institute, DCCPS, Surveillance Research Program, April 2000. (Also available at http://seer.cancer.gov/Publications/.)
18
Ware JE. SF-36 Physical and mental health summary scales: a user's manual. Boston: Health Institute, New England Medical Center, 1994.
19
Housini I ,Tomashefski JF Jr ,Cohen A ,Crass J ,Kleinerman J . Transbronchial biopsy in patients with pulmonary eosinophilic granuloma: comparison with findings on open lung biopsy. Arch Pathol Lab Med 1994;118:523-530
Web of Science | Medline20
Krenacs L ,Tiszalvicz L ,Krenacs T ,Boumsell L . Immunohistochemical detection of CD1A antigen in formalin-fixed and paraffin-embedded tissue sections with monoclonal antibody 010. J Pathol 1993;171:99-104
CrossRef | Web of Science | Medline21
Emile JF ,Wechsler J ,Brousse N , et al. Langerhans' cell histiocytosis: definitive diagnosis with the use of monoclonal antibody O10 on routinely paraffin-embedded samples. Am J Surg Pathol 1995;19:636-641
CrossRef | Web of Science | Medline22
Ryu JH ,Colby TV ,Hartman TE ,Vassallo R . Smoking-related interstitial lung diseases: a concise review. Eur Respir J 2001;17:122-132
CrossRef | Web of Science | Medline23
Bernstrand C ,Cederlund K ,Ashtrom L ,Henter JI . Smoking preceded pulmonary involvement in adults with Langerhans cell histiocytosis diagnosed in childhood. Acta Paediatr 2000;89:1389-1392
CrossRef | Web of Science | Medline24
Nagai S ,Hoshino Y ,Hayashi M ,Ito I . Smoking-related interstitial lung diseases. Curr Opin Pulm Med 2000;6:415-419
CrossRef | Medline25
Yousem SA ,Colby TV ,Chen YY ,Chen WG ,Weiss LM . Pulmonary Langerhans' cell histiocytosis: molecular analysis of clonality. Am J Surg Pathol 2001;25:630-636
CrossRef | Web of Science | Medline26
Brauner MW ,Grenier P ,Tijani K ,Battesti JP ,Valeyre D . Pulmonary Langerhans cell histiocytosis: evolution of lesions on CT scans. Radiology 1997;204:497-502
Web of Science | Medline27
Brauner MW ,Grenier P ,Mouelhi MM ,Mompoint D ,Lenoir S . Pulmonary histiocytosis X: evaluation with high-resolution CT. Radiology 1989;172:255-258
Web of Science | Medline28
Collins J . CT signs and patterns of lung disease. Radiol Clin North Am 2001;39:1115-1135
CrossRef | Web of Science | Medline29
Bonelli FS ,Hartman TE ,Swensen SJ ,Sherrick A . Accuracy of high-resolution CT in diagnosing lung diseases. AJR Am J Roentgenol 1998;170:1507-1512
Web of Science | Medline30
Michetti G ,Cottini M ,Scelsi L , et al. Langerhans' cell granulomatosis and Hodgkin's lymphoma: report of a case. Minerva Med 1996;87:243-247
Medline31
Yamashita H ,Nagayama M ,Kawashima M ,Hidano A ,Yamada O ,Mizoguchi H . Langerhans-cell histiocytosis in an adult patient with multiple myeloma. Clin Exp Dermatol 1992;17:275-278
CrossRef | Web of Science | Medline32
Lombard CM ,Medeiros LJ ,Colby TV . Pulmonary histiocytosis X and carcinoma. Arch Pathol Lab Med 1987;111:339-341
Web of Science | Medline33
Egeler RM ,Neglia JP ,Arico M , et al. The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and other solid tumors. Hematol Oncol Clin North Am 1998;12:369-378
CrossRef | Web of Science | Medline34
de Camargo B ,Alves AC ,Gorender EF ,Bianchi A . Association of malignancy and Langerhans' cell histiocytosis: report of three cases. Med Pediatr Oncol 1993;21:451-453
CrossRef | Medline35
Chang JA ,Curtis JR ,Patrick DL ,Raghu G . Assessment of health-related quality of life in patients with interstitial lung disease. Chest 1999;116:1175-1182
CrossRef | Web of Science | Medline
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Chul Kim, Sung Hwan Jeong, Jae Jeong Shim, Seung-Ick Cha, Choonhee Son, Man Pyo Chung, Hye Yoon Park, Young Whan Kim, Jong Sun Park, Soo-Taek Uh, Choon Sik Park, Dong Soon Kim, Kyung Wook Cho, Jin Woo Song, Yang Jin Jegal, Moo Suk Park, Byung Hoon Park, Jin Hwa Lee, Jin-Won Hur, Ho-Kee Yum, Hong-Lyeol Lee, Yong Bum Park. (2009) Clinical Features of Pulmonary Langerhans Cell Histiocytosis in Korea. Tuberculosis and Respiratory Diseases 66:2, 98
CrossRef16
Bahadir T. Uskul, Hatice Turker, Ozge Unal Bayraktar, Meliha Onemli. (2009) Bronchogenic Carcinoma Developing during a Long-Term Course of Pulmonary Langerhans' Cell Histiocytosis. Internal Medicine 48:5, 359-362
CrossRef17
Michelle R. Aerni, Marie Christine Aubry, Jeffery L. Myers, Robert Vassallo. (2008) Complete remission of nodular pulmonary Langerhans cell histiocytosis lesions induced by 2-chlorodeoxyadenosine in a non-smoker. Respiratory Medicine 102:2, 316-319
CrossRef18
Steven E. Weinberger, Barbara A. Cockrill, Jess Mandel. 2008. Diffuse Parenchymal Lung Diseases of Unknown Etiology. , 154-171.
CrossRef19
Béla Nagy, Györgyike Soós, Kálmán Nagy, Balázs Dezső. (2008) Natural Course of Isolated Pulmonary Langerhans’ Cell Histiocytosis in a Toddler. Respiration 75:2, 215-220
CrossRef20
Eric J. Olson, Jeffrey L. Myers, Jay H. Ryu. 2008. LAM and Other Diffuse Lung Diseases. , 695-705.
CrossRef21
M. Prediger, J. Kluge, T. Laube, U. Wetzel, T. Erler, I. Gastinger. (2008) 18-Jähriger mit rezidivierendem Pneumothorax und Osteolysen. Der Pneumologe 5:1, 42-44
CrossRef22
Rajesh R Patel, Jay H Ryu, Robert Vassallo. (2008) Cigarette Smoking and Diffuse Lung Disease. Drugs 68:11, 1511-1527
CrossRef23
WH Ibrahim, A Al-Muzrkchi. (2008) A Young Man with Multiple Pulmonary Cysts. Libyan Journal of Medicine 3:3, 160-162
CrossRef24
Polyzois Makras, Georgios Piaditis, Gregory A Kaltsas. (2007) Systemic and endocrine manifestations of Langerhans’ cell histiocytosis: current concepts in diagnosis and management. Expert Review of Endocrinology & Metabolism 2:6, 773-783
CrossRef25
Christian A Merlo, Jonathan B Orens. (2007) Selection of candidates for lung transplantation. Current Opinion in Organ Transplantation 12:5, 479-484
CrossRef26
Cecilia Bernstrand, Kerstin Cederlund, Jan-Inge Henter. (2007) Pulmonary function testing and pulmonary Langerhans cell histiocytosis. Pediatric Blood & Cancer 49:3, 323-328
CrossRef27
Kristian T. Schafernak, Krishna Thavarajah, Ravi Kalhan, Pauline M. Chou, Anjana V. Yeldandi. (2007) Pulmonary Langerhans Cell Histiocytosis. Clinical Pulmonary Medicine 14:5, 265-277
CrossRef28
Chih-wei Wang, Thomas V. Colby. (2007) Histiocytic lesions and proliferations in the lung. Seminars in Diagnostic Pathology 24:3, 162-182
CrossRef29
Polyzois Makras, Krystallenia I. Alexandraki, George P. Chrousos, Ashley B. Grossman, Gregory A. Kaltsas. (2007) Endocrine manifestations in Langerhans cell histiocytosis. Trends in Endocrinology & Metabolism 18:6, 252-257
CrossRef30
G. Burça Aydin, Esin Kibar, Ünsal Han, Yusuf Kale, Ayse Aslan, Gulsen Kose. (2007) Pulmonary Langerhans cell histiocytosis in an infant: Can passive smoking accelerate the disease progress?. Pediatric Pulmonology 42:6, 565-567
CrossRef31
Lynette M. Sholl, Jason L. Hornick, Jack L. Pinkus, Geraldine S. Pinkus, Robert F. Padera. (2007) Immunohistochemical Analysis of Langerin in Langerhans Cell Histiocytosis and Pulmonary Inflammatory and Infectious Diseases. The American Journal of Surgical Pathology 31:6, 947-952
CrossRef32
Anastasia Oikonomou, Panos Prassopoulos, Prodromos Hytiroglou, Fotios V. Kirvassilis, John N. Tsanakas. (2007) Atypical CT Findings of Isolated Pulmonary Langerhans Cell Histiocytosis in a 4-year-old Boy. Journal of Thoracic Imaging 22:2, 176-179
CrossRef33
Tohru Takahashi, Mitsuru Yoshimoto, Nobuo Kondoh. (2007) Spontaneously Regressed Langerhans Cell Histiocytosis of Lymph Nodes in an Elderly Patient. Internal Medicine 46:20, 1757-1760
CrossRef34
Matthieu Canuet, Romain Kessler, Mi-Young Jeung, Anne-Cécile Métivier, Ari Chaouat, Emmanuel Weitzenblum. (2007) Correlation between High-Resolution Computed Tomography Findings and Lung Function in Pulmonary Langerhans Cell Histiocytosis. Respiration 74:6, 640-646
CrossRef35
Tamer Gunes, Esad Koklu, Mehmet Adnan Ozturk, Turkan Patiroglu, Tahir Patiroglu, Musa Karakukcu. (2007) A Case of Langerhans Cell Histiocytosis Presented With Pneumothorax. Journal of Pediatric Hematology/Oncology 29:1, 60-62
CrossRef36
Jonathan B. Orens, Marc Estenne, Selim Arcasoy, John V. Conte, Paul Corris, Jim J. Egan, Thomas Egan, Shaf Keshavjee, Christiane Knoop, Robert Kotloff, Fernando J. Martinez, Steven Nathan, Scott Palmer, Alec Patterson, Lianne Singer, Gregory Snell, Sean Studer, J.L. Vachiery, Allan R. Glanville. (2006) International Guidelines for the Selection of Lung Transplant Candidates: 2006 Update—A Consensus Report From the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. The Journal of Heart and Lung Transplantation 25:7, 745-755
CrossRef37
W Ingram, S R Desai, J S R Gibbs, G Mufti. (2006) Reduced-intensity conditioned allogeneic haematopoietic transplantation in an adult with Langerhans’ cell histiocytosis and thrombocytopenia with absent radii. Bone Marrow Transplantation 37:7, 713-715
CrossRef38
Ga??lle Dauriat, Herv?? Mal, Gabriel Thabut, Jean-Fran??ois Mornex, Michelle Bertocchi, Fran??ois Tronc, Fran??ois Leroy-Ladurie, Philippe Dartevelle, Martine Reynaud-Gaubert, Pascal Thomas, Christophe Pison, Dominique Blin, Marc Stern, Pierre Bonnette, Claire Dromer, Jean-Fran??ois Velly, Olivier Brugi??re, Guy Les??che, Michel Fournier. (2006) Lung Transplantation for Pulmonary Langerhans?? Cell Histiocytosis: A Multicenter Analysis. Transplantation 81:5, 746-750
CrossRef39
Robert Vassallo. (2005) The Pulmonary Dendritic/Langerhans Cell in Immunity and Disease. Clinical Pulmonary Medicine 12:2, 84-89
CrossRef40
Cynthia O. Townsend, Christopher D. Sletten, Barbara K. Bruce, Jeffrey D. Rome, Connie A. Luedtke, John E. Hodgson. (2005) Physical and emotional functioning of adult patients with chronic abdominal pain: Comparison with patients with chronic back pain. The Journal of Pain 6:2, 75-83
CrossRef41
Gregory B. Diette, John C. Scatarige, Edward F. Haponik, Barry Merriman, Elliot K. Fishman. (2005) Do High-Resolution CT Findings of Usual Interstitial Pneumonitis Obviate Lung Biopsy?. Respiration 72:2, 134-141
CrossRef42
N. Chaowalit, P. A. Pellikka, P. A. Decker, M.-C. Aubry, M. J. Krowka, J. H. Ryu, R. Vassallo. (2004) Echocardiographic and Clinical Characteristics of Pulmonary Hypertension Complicating Pulmonary Langerhans Cell Histiocytosis. Mayo Clinic Proceedings 79:10, 1269-1275
CrossRef43
Kristin B Highland, John E Heffner. (2004) Pleural effusion in interstitial lung disease. Current Opinion in Pulmonary Medicine 10:5, 390-396
CrossRef44
Remzi Bag, Nizar Suleman, Kalpalatha K Guntupalli. (2004) Respiratory failure in interstitial lung disease. Current Opinion in Pulmonary Medicine 10:5, 412-418
CrossRef45
Vibha N. Lama, Fernando J. Martinez. (2004) Resting and exercise physiology in interstitial lung diseases. Clinics in Chest Medicine 25:3, 435-453
CrossRef46
Robert Vassallo, Jay H. Ryu. (2004) Pulmonary Langerhans' cell histiocytosis. Clinics in Chest Medicine 25:3, 561-571
CrossRef47
Masaru SUZUKI, Tomoko BETSUYAKU, Masayuki SUGA, Akihiro ISHIZU, Masaharu NISHIMURA, Mitsuru OGURI. (2004) Pulmonary Langerhans' Cell Histiocytosis Presenting with an Endobronchial Lesion. Internal Medicine 43:3, 227-230
CrossRef48
S Dacic, C Trusky, A Bakker, S.D Finkelstein, S.A Yousem. (2003) Genotypic analysis of pulmonary Langerhans cell histiocytosis. Human Pathology 34:12, 1345-1349
CrossRef49
J. H. Ryu, S. J. Swensen. (2003) Cystic and Cavitary Lung Diseases: Focal and Diffuse. Mayo Clinic Proceedings 78:6, 744-752
CrossRef50
P Soler, D Valeyre. (2003) L’histiocytose langerhansienne pulmonaire de l’adulte. La Revue de Médecine Interne 24:4, 230-236
CrossRef51
A. Pardanani, R. L. Phyliky, C.-Y. Li, A. Tefferi. (2003) 2-Chlorodeoxyadenosine Therapy for Disseminated Langerhans Cell Histiocytosis. Mayo Clinic Proceedings 78:3, 301-306
CrossRef52
Cabot, Richard C.Harris, Nancy Lee, McNeely, William F., Shepard, Jo-Anne O., Ebeling, Sally H.Ellender, Stacey M.Peters, Christine C., Rajagopol, JayarajMark, Eugene J.. (2002) Case 32-2002. New England Journal of Medicine 347:16, 1262-1268
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