Clinico-etiological Characteristics of Cystic Lung Disease: A Retrospective Study

Introduction: Diffuse cystic lung diseases (CLDs) are a heterogeneous group of uncommon disorders with characteristic imaging appearance. Cystic lung disease is a significant cause of mortality and morbidity with a wide spectrum of radiological presentations and etiological differentials. Though the literature is widely available on radiological approaches to CLD, a knowledge gap exists on the etiological spectrum, especially in the Indian scenario, as it is an orphan group of lung disorders. The interest and experience among pulmonologists regarding CLD are growing with the widespread use of CT scans. Clinical, radiographic, and histological findings are often essential for proper diagnosis, and multidisciplinary approach is required for optimal management of such cases. In our study, through real-world cases, we have highlighted the clinical manifestations and diverse etiological spectrum of CLD. Since these disorders are rare, incurable, and have variable disease progression, the authors have tried to address the holistic approach of this relatively less-understood group of disorders. Aims and objectives: The aim of the study was to identify clinical characteristics and etiological spectrum of patients manifesting with diffuse cystic lung disease radiologically. Materials and methods: In this retrospective analysis, the hospital electronic database was screened with Boolean operations and keywords for cysts OR pneumothorax. Among a total of 4,479 patients admitted to the respiratory ward /ICU during the period of January 2020–September 2022 at a tertiary care center in northern India, 14 patients with radiological diagnosis of CLD matched the relevant search. All relevant data of these patients were retrieved from the records. Results: Our patients presented predominantly with symptoms of cough and breathlessness. About 4 patients had pneumothorax as the first presentation. The mean age of presentation was 42.14 (standard deviation 12.6, age range 16–62 years). About 64% (n = 9/15) patients were females. The various etiologies identified were lymphangioleiomyomatosis (LAM), lymphocytic interstitial pneumonia, Birt–Hogg–Dube syndrome, hypersensitivity pneumonitis, Pneumocystis jirovecii pneumonia, and cystic metastasis, and in one patient, no definite cause was found despite detailed evaluation. Conclusion: Cystic lung disorders are a less commonly diagnosed entity with rare etiologies. In our study, we found a female preponderance and LAM as the commonest CLD. Pneumothorax is a sentinel event and commonly the presenting complaint in CLD. Identification of the etiology can help in institution of definite therapy when available. In view of unpredictable disease progression and outcome, these diseases warrant follow-up and imaging surveillance.

Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion / Linfangioleiomiomatose: níveis circulantes de FGF23 e difusão pulmonar

ABSTRACT Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. Methods: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. Results: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Conclusions: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.

RESUMO Objetivo: A linfangioleiomiomatose (LAM) é uma doença rara e destrutiva dos pulmões com um número limitado de determinantes da atividade da doença, que são uma necessidade crítica para ensaios clínicos. O FGF23 já foi implicado em várias doenças pulmonares crônicas. O nosso objetivo foi determinar a associação entre os níveis séricos de FGF23 e a função pulmonar em uma coorte de pacientes com LAM. Métodos: Estudo descritivo unicêntrico no qual foram recrutados indivíduos com LAM e controles com doenças pulmonares não declaradas. Os níveis séricos de FGF23 foram medidos em todos os indivíduos. Os dados clínicos, incluindo testes de função pulmonar, foram obtidos retrospectivamente a partir dos prontuários eletrônicos dos indivíduos com LAM. As associações entre os níveis de FGF23 e as características clínicas da LAM foram exploradas por meio do teste de hipóteses não paramétrico. Resultados: A amostra incluiu 37 indivíduos com LAM e 16 controles. Os níveis de FGF23 foram mais altos no grupo LAM do que no grupo controle. No grupo LAM, níveis de FGF23 acima do ponto de corte ideal distinguiram 33% dos indivíduos com níveis não diagnósticos de VEGF-D. Níveis mais baixos de FGF23 estavam associados à DLCO comprometida (p = 0,04), particularmente naqueles com comprometimento isolado da difusão e sem outras alterações espirométricas (p = 0,04). Conclusões: Nossos resultados sugerem que o FGF23 está associado a alterações na difusão pulmonar em pacientes com LAM e potencialmente indicam novos mecanismos de patogênese da LAM. O FGF23 isoladamente ou em combinação com outras moléculas precisa ser validado como um biomarcador da atividade da LAM em futuras pesquisas clínicas.

Diagnostic performance of VEGF-D for lymphangioleiomyomatosis: a meta-analysis / Desempenho diagnóstico do VEGF-D para linfangioleiomiomatose: meta-análise

ABSTRACT Objective: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. Methods: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. Results: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. Conclusions: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.

RESUMO Objetivo: O VEGF-D é um potencial biomarcador para linfangioleiomiomatose (LAM); entretanto, seu desempenho diagnóstico ainda não foi sistematicamente estudado. Métodos: Foram realizadas buscas nos bancos de dados PubMed, EMBASE, Scopus, Web of Science e Cochrane Library para identificar estudos primários sobre o VEGF-D com relação ao diagnóstico de LAM. A qualidade dos estudos foi avaliada por meio da ferramenta Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). As estimativas sumárias de acurácia diagnóstica foram combinadas utilizando um modelo bivariado de efeitos aleatórios. Análises de subgrupo e de sensibilidade foram realizadas para explorar possíveis heterogeneidades. O sistema Grading of Recommendations Assessment, Development, and Evaluation (GRADE) foi aplicado para avaliar a qualidade das evidências e indicar a força das recomendações. Resultados: Dez estudos envolvendo 945 pacientes eram de alto risco em qualidade, segundo a ferramenta QUADAS-2. Os parâmetros diagnósticos combinados foram indicados da seguinte forma: sensibilidade = 0,82 (IC95%: 0,71-0,90); especificidade = 0,98 (IC95%: 0,94-0,99); e OR diagnóstica = 197 (IC95%: 66-587). A ASC da análise summary ROC foi de 0,98. As análises de subgrupo e de sensibilidade revelaram que o desempenho global não foi substancialmente afetado pela composição do grupo controle, valor de corte pré-especificado, país de origem ou diferentes valores de corte (p > 0,05 para todos). Uma forte recomendação para a dosagem de VEGF-D sérico para auxiliar no diagnóstico de LAM foi feita de acordo com o sistema GRADE. Conclusões: O VEGF-D parece ter grandes implicações potenciais para o diagnóstico de LAM na prática clínica em virtude da excelente especificidade e sensibilidade subótima.

Advances in the Diagnosis, Treatment and Prognosis of Lymphangioleiomyomatosis / 罕见病研究

Lymphangioleiomyomatosis (LAM) is a rare, multisystemic, low-grade neoplasm character-ized by diffuse cystic lesions in the lung.In recent years, emerging imaging examination such as 68Ga-NEB PET-CT scan provides efficient and precise non-invasive diagnostic methods to detect lymphatic circulation abnormalities in LAM patients. The long-term efficacy and safety of sirolimus for LAM has accumulated further evidence, and genetic profiling studies have unveiled more information of genetic mechanisms. Prognosis of LAM has been much improved. We briefly reviewed the research advances of LAM in China and other countires.

Linfangioleiomiomatosis pulmonar / Pulmonary lymphangioleiomyomatosis

Introducción: La linfangioleiomiomatosis pulmonar constituye un desafío, tanto en su manejo diagnóstico como en la atención de sus complicaciones. Es una enfermedad rara que se caracteriza por la proliferación del músculo liso alrededor de las estructuras bronco-vasculares, linfáticos y en el intersticio pulmonar, unido a la dilatación quística de los espacios aéreos terminales. Objetivo: Describir la evolución clínica y el tratamiento de un paciente con linfangioleiomiomatosis pulmonar. Presentación de caso: Se presenta un caso de linfangioleiomiomatosis pulmonar que desde el punto de vista clínico se manifestó por neumotórax a repetición. Se llegó a diagnóstico definitivo mediante la realización de una biopsia de pulmón. Desarrollo: La linfangioleiomiomatosis es una entidad rara que afecta fundamentalmente a mujeres en edad fértil y que se caracteriza por la presencia de un patrón quístico difuso. Su prevalencia e incidencia es desconocida. Conclusiones: Se puede concluir que la presencia de neumotórax espontáneo o recidivante en una mujer en edad fértil, o embarazada, debe sospecharse linfangioleiomiomatosis(AU)

Introduction: Pulmonary lymphangioleiomyomatosis constitutes a challenge, both in its diagnostic management and in the care of complications. It is a rare disease characterized by the proliferation of smooth muscle around the bronchovascular and lymphatic structures and in the pulmonary interstitium, together with cystic dilation of the terminal air spaces. Objective: To describe a diagnosed case of pulmonary lymphangioleiomyomatosis. Case report: A case of pulmonary lymphangioleiomyomatosis is reported, which was clinically showed as recurrent pneumothorax. A definitive diagnosis was reached by performing a lung biopsy. Discussion: Lymphangioleiomyomatosis is a rare entity that mainly affects women of childbearing age and is characterized by the presence of a diffuse cystic pattern. Its prevalence and incidence is unknown. Conclusions: It can be concluded that the presence of spontaneous or recurrent pneumothorax in a woman of childbearing age, or pregnant, should be suspected lymphangioleiomyomatosis(AU)

Neumotórax espontaneo en paciente gestante / Spontaneous Pneumothorax in a Pregnant Woman

RESUMEN Introducción: El neumotórax es una de las enfermedades pleurales más frecuentes en la práctica médica, siendo excepcional su asociación con el embarazo, existiendo pocos casos reportados en la literatura mundial. La linfangioleiomiomatosis es una enfermedad multisistémica poco frecuente, que afecta predominante al sexo femenino en edad fértil y puede verse exacerbada por el embarazo. Objetivo: Realizar el reporte de un caso y la revisión del tema que permitan un diagnóstico precoz y una conducta de forma temprana. Caso clínico: Paciente gestante de 15 semanas, de 36 años de edad, con antecedentes de salud anterior, que debuta súbitamente con disnea a los medianos esfuerzos, tos, dolor torácico y neumotórax derecho espontáneo, recurrente en su evolución y posteriormente bilateral. Su curso fue tórpido requiriendo tratamiento en Unidad de Cuidados Intensivos por fallo respiratorio agudo, falleciendo luego de 3 meses del inicio del cuadro. Se le realizó, Radiografía de tórax: patrón reticular de tipo panal de abejas, tomografía de tórax: imágenes quísticas múltiples en todo parénquima pulmonar de predominio basal. Biopsia pulmonar compatible con linfangioleiomiomatosis. Conclusiones: La aparición de disnea súbita, dolor pleurítico y neumotórax en una gestante, deben ser siempre suficientes para tener en cuenta la presencia de una linfangioleiomiomatosis. Su inespecificidad sintomática inicial se traduce en un diagnóstico tardío, lo que empobrece su pronóstico(AU)

ABSTRACT Introduction: Pneumothorax is one of the pleural diseases most frequent in medical practice. Its association with pregnancy is essential. Few cases are reported in worldwide medical literature. Lymphangioleiomyomatosis is a rare multisystem disease that predominantly affects individuals of the female sex and at fertile age; it can be aggravated by pregnancy. Objective: To present a case report and a topic review that allow early diagnosis and early management. Clinical case: A 15-week-pregnant patient aged 36 years and with a previous health history suddenly presented dyspnea for average efforts, cough, chest pain, and spontaneous right pneumothorax, recurrent in its evolution and, later, bilateral. Its evolution was slow, a reason why it required intensive care for acute respiratory failure. The patient died three months after the onset of symptoms. The patient was performed chest x-ray, which showed honeycomb-type reticular pattern; and chest tomography, which showed multiple cystic images throughout pulmonary parenchyma, predominantly at baseline. Lung biopsy consistent with lymphangioleiomyomatosis was performed. Conclusions: Onset of sudden dyspnea, pleuritic pain and pneumothorax in a pregnant woman should always be sufficiently indicative of lymphangioleiomyomatosis. Its initial symptomatic non-specificity is determined by late diagnosis, which impoverishes prognosis(AU)

Caso Clínico: Linfangioleiomiomatosis en una Paciente Joven con Síndrome de Bourneville

INTRODUCCIÓN: El síndrome de Bourneville o esclerosis tuberosa es una alteración innata del desarrollo que se transmite de forma autosómica dominante, es causada por mutación en los genes TSC1 y TSC2. Se presenta en 1 de cada 6 000 habitantes; se considera una forma rara de facomatosis susceptible de originar tumores benignos en diversas zonas del cuerpo, entre los que se cita: angiomiolipomas renales, tumores del sistema nervioso, retina, corazón, piel y linfangioleiomiomatosis pulmonar; siendo la última una patología pulmonar quística, progresiva, que afecta a las mujeres en edad fértil y puede ser potencialmente mortal. CASO CLÍNICO: Se trata de una paciente de sexo femenino de 23 años de edad, mestiza, con antecedentes de esclerosis tuberosa, hipotiroidismo y nefrectomía izquierda por angiomiolipoma; que presentó un neumotórax espontáneo secundario a linfangioleiomiomatosis pulmonar. EVOLUCIÓN: En base a los antecedentes patológicos, cuadro clínico y estudios de imagen se diagnosticó de linfangioleiomiomatosis pulmonar. Se realizó una pleurodesis y se inició tratamiento con Sirolimus; la respuesta fue satisfactoria, se mantuvieron controles médicos periódicos evaluando la posibilidad de trasplante pulmonar a futuro. CONCLUSIÓN: El neumotórax espontáneo en una mujer joven con esclerosis tuberosa se asocia a linfangioleiomiomatosis pulmonar; en la actualidad esta patología es manejada con Sirolimus, los resultados han sido favorables en la función pulmonar y calidad de vida del paciente; el trasplante pulmonar sigue siendo el tratamiento de elección en la enfermedad avanzada.(au)

BACKGROUND: Bourneville syndrome or tuberous sclerosis is an innate development alteration transmitted by autosomal dominant inheritance. It is caused by TSC1 and TSC2 gene mutations and occurs in 1 of every 6 000 people. It is considered a rare form of phacomatosis that can cause multiple benign tumors including renal angiomyolipomas and tumors of the central nervous system, retina, heart and skin; pulmonary lymphangioleiomyomatosis can be part of the clinical presentation, affects women of childbearing age and can be life-threatening. CASE REPORT: 23 year-old female patient with history of tuberous sclerosis, hypothyroidism and left nephrectomy for angiomyolipoma, who presented a spontaneous pneumothorax secondary to pulmonary lymphangioleiomyomatosis. EVOLUTION: Based on the history, clinical picture and imaging studies; the diagnosis of pulmonary lymphangioleiomyomatosis was made. A pleurodesis was performed and a treatment with Sirolimus was started; the response was satisfactory, periodic controls were maintained evaluating the possibility of lung transplant in the future. CONCLUSION: Spontaneous pneumothorax in a young woman with tuberous sclerosis is associated with pulmonary lymphangioleiomyomatosis. Currently this pathology is managed with Sirolimus, the results have been favorable , improving pulmonary function and quality of life; lung transplantation remains the treatment of choice in advanced disease.(au)

Linfangioleiomiomatosis pulmonar, una rara enfermedad pulmonar: presentación de un caso clínico / Pulmonary lymphangioleiomyomatosis, a rare lung disease: presentation of a clinical case

Introducción: La linfangioleiomiomatosis Pulmonar (LAM) es una rara y progresiva enfermedad; caracterizada por proliferación excesiva de células musculares lisas a partir de vasos linfáticos, sanguíneos y vías aéreas. En conjunto al anormal crecimiento celular descrito, se aprecia degeneración quística difusa del parénquima pulmonar, lo que puede reflejarse desde cuadros completamente asintomáticos hasta el deterioro severo del intercambio gaseoso con insuficiencia respiratoria fulminante. Descripción del caso: Paciente femenino de 41 años de edad, con cuadro clínico consistente en tos seca ocasional, asociada a dolor leve de características pleuríticas en 'puntada de costado ' derecha. Ante la no mejoría clínica, se indica estudio imagenológico donde se demuestra neumotorax espontáneo derecho. En estudio tomográfico se aprecian además lesiones pulmonares quísticas. El estudio anátomo-patológico demuestra cambios estructurales que se reportan compatibles con LAM. Conclusión: Dada la simplicidad de los síntomas con que la LAM puede debutar, su confirmación diagnóstica se genera en fases avanzadas de la enfermedad, cuando el daño pulmonar importante conlleva a la aparición de factores clínicos con mayor repercusión sobre el estado general de los pacientes por lo que la realización de estudios imagenológicos tempranos gana vital importancia.

Introduction: Pulmonary lymphangioleiomyomatosis (LAM) is a rare and progressive disease; characterized by airway, lymphatic and blood vessels-smooth muscle cells excessive proliferation. Added to the abnormal cell growth, parenchymal cystic degeneration is present, which can be reflected initially as a asymptomatic course and can progress to severe gaseous exchange deterioration and fulminating respiratory insufficiency. Case description: A 41-year-old female patient with a clinical course consisting of occasional dry cough, associated with mild pleuritic pain on the right side of thorax. As no improvement was achieved, thoracic imaging study was performed, where a right pneumothorax was found. Tomography images showed multiple lung cystic lesions. Anatomopathological study reports structural changes compatible with LAM. Conclusion: Given the simplicity of the symptoms that LAM can debut with, its diagnostic confirmation is generated in advanced stages of the disease, when the important pulmonary damage leads to the appearance of clinical factors with greater impact on the general state of patients so early thoracic imaging studies gain vital importance.

A Stepwise Diagnostic Approach to Cystic Lung Diseases for Radiologists

Lung cysts are commonly seen on computed tomography (CT), and cystic lung diseases show a wide disease spectrum. Thus, correct diagnosis of cystic lung diseases is a challenge for radiologists. As the first diagnostic step, cysts should be distinguished from cavities, bullae, pneumatocele, emphysema, honeycombing, and cystic bronchiectasis. Second, cysts can be categorized as single/localized versus multiple/diffuse. Solitary/localized cysts include incidental cysts and congenital cystic diseases. Multiple/diffuse cysts can be further categorized according to the presence or absence of associated radiologic findings. Multiple/diffuse cysts without associated findings include lymphangioleiomyomatosis and Birt-Hogg-Dubé syndrome. Multiple/diffuse cysts may be associated with ground-glass opacity or small nodules. Multiple/diffuse cysts with nodules include Langerhans cell histiocytosis, cystic metastasis, and amyloidosis. Multiple/diffuse cysts with ground-glass opacity include pneumocystis pneumonia, desquamative interstitial pneumonia, and lymphocytic interstitial pneumonia. This stepwise radiologic diagnostic approach can be helpful in reaching a correct diagnosis for various cystic lung diseases.

Clinical characteristics in lymphangioleiomyomatosis-related pulmonary hypertension: an observation on 50 patients / 医学前沿

Lymphangioleiomyomatosis (LAM) is a rare diffuse cystic lung disease. Knowledge on LAM-related pulmonary hypertension (PH) is limited. This study aimed to analyze the clinical characteristics of LAM with elevated pulmonary artery pressure (PAP) and evaluate the potential efficacy of sirolimus. The study involved 50 LAM patients who underwent echocardiography. According to the tricuspid regurgitation velocity (TRV), these patients were divided into the TRV ⩽ 2.8 m/s group and TRV > 2.8 m/s group. Both groups comprised 25 females with an average age of 38.6 ± 8.1 and 41.5 ± 8.9 years. In the TRV > 2.8 m/s group, the estimated systolic PAP (SPAP) was significantly elevated (52.08 ± 12.45 mmHg vs. 30.24 ± 5.25 mmHg, P < 0.01). Linear analysis showed that SPAP was correlated with forced expiratory volume in 1 s (FEV), diffusing capacity of the lungs for carbon monoxide, alveolar arterial oxygen gradient (PO), and 6 min walking distance (r =-0.392, -0.351, 0.450, and -0.591, respectively; P < 0.05), in which PO was a risk factor for SPAP elevation (β = 0.064, OR = 1.066, P < 0.05). Moreover, in 10 patients who received sirolimus therapy, SPAP decreased from 57.0 12.6 mmHg to 35.2 ± 11.1 mmHg. The study showed that LAM patients with PH exhibit poor pulmonary function and hypoxemia and may benefit from sirolimus treatment.

Lung transplantation for pulmonary lymphangioleiomyomatosis:a report of 9 cases / 中华胸心血管外科杂志

Objective To investigate the selection of recipients,operative technique, and perioperative management of lung transplantation.Methods From June 2013 to September 2016, 9 patients with pulmonary lymphangioleiomyomatosis un-derwent lung transplantation at Affiliated Wuxi People's Hospital.There were 9 females aged from 23 to 52 years.Chest en-hancement of CT in 9 patients prior to transplantation suggests multiple different sized thin-walled cystic shadows in whole lung. Nine patients received bilateral sequence lung transplantation ( BSLT) .The pathological findings after the operation indicated that cells of the abnormal proliferation of smooth muscle diffused around the bronchi , vessels and lymphatics , and widened the alveolar septum, which was consistent with the pathological changes in the patients with PLAM .We analyzed the differences of oxygenation index, forcedexpiratory volume at 1 sec(FEV1), and DLCO％ pred.Using paired t test to compare these indica-tors, P<0.05 was considered statistically significant.Results The oxygenation index was increased from(210 ±55) mmHg (1 mmHg=0.133 kPa) to(400 ±80)mmHg after treatment, the difference was statistically significant(P<0.05).The FEV1 was increased from(1.0 ±0.2)L to(2.8 ±0.4)L, and the difference was statistically significant(P<0.05).The DLCO％pred was increased from(27.5 ±2.5)％ to(75.0 ±10.0)％, and the difference was statistically significant(P<0.05).Fi-nally, 8 patients were discharged from the hospital, and the pulmonary function was good.1 patients died of infection and acute rejection on the 13 day after operation.Conclusion Lung transplantation is effective in the treatment of chronic thromboem-bolic pulmonary hypertension , and long-term survival requires further investigations .Lung transplantation is the only effective means for the treatment of end-stage pulmonary lymphangioleiomyomatosis .Bilateral sequence lung transplantation is the first choice.

Sporadic lymphangioleiomyomatosis with multiple atypical features: A case report and literature review

Lymphangioleiomyomatosis (LAM) is a rare, genetically determined, progressive interstitial lung disease, which almost exclusively affects women, especially at the childbearing age. The initial symptoms and radiographic changes in a patient with LAM are always associated with the respiratory system. Here, we present a case of mediastinal and abdominal LAM of a 22-year-old male, where LAM cells are negative for human melanoma black-45 ( HMB-45). The report of this uncharacterized LAM case will make a significant contribution to the realization of LAM associated clinical features, diagnostic approaches, and its afterward treatments.

Linfagioleomiomatose pulmonar em paciente pediátrico: relato de caso / Pulmonar lymphagioleiomatosis in a pediatric patient: a case report

A linfangioleiomiomatose pulmonar (LAM) é considerada uma doença rara, com predileção de acometimento em mulheres durante período reprodutivo, principalmente entre a terceira e quarta década de vida. A doença é atualmente reconhecida como uma neoplasia de baixo grau e se caracteriza por proliferação de células musculares lisas atípicas no parênquima pulmonar. Dispneia, pneumotórax recorrente e tosse seca são as manifestações clínicas mais comuns. Em exames de imagem, é notada comumente a existência de hiperinsuflação, infiltrado intersticial reticulonodular e cistos de diferentes tamanhos em topografia pulmonar. A presença concomitante de angiomiolipomas pode ser verificada em alguns pacientes. Tais achados radiológicos, quando associados ao quadro clínico característico , falam a favor do diagnóstico de LAM, sendo possível a confirmação pela histopatologia. A despeito das diferentes formas de tratamento existentes para a LAM, ainda não existe medida curativa para a doença. Em geral, os pacientes evoluem com contínua deterioração da função pulmonar, com predomínio de um distúrbio ventilatório obstrutivo que deve ser diferenciado de outras afecções mais prevalentes, como asma e doença pulmonar obstrutiva crônica. Neste trabalho, relata-se um caso de paciente em idade pediátrica, com presença de achados clínicos e radiológicos compatíveis com o diagnóstico de LAM, ainda que fora da faixa etária usual de acometimento da doença.

Pulmonary Lymphangioleiomyomatosis (LAM) is a rare disease which affects women during reproductive age mainly between thirdies and forties. Currently the disease is recognized with a low grade neoplasm and it is characterized by proliferation of atypical smooth muscle cells in the lung parenchyma. Dyspnea, recurrent pneumothorax and dry cough are the most common clinical manifestations. On imaging studies, the presence of hyperinsuflation, interstitial infiltrates reticulonodular and cysts of different sizes in lung topography is common. The concomitant presence of angiomyolipoma can be recorded in some patients. When associated with the usual clinical condition, the radiological findings suggest the diagnosis of LAM and it can be confirmed by histopathology. Despite of different forms of treatment for LAM, there is still no curative method for it. In general, the patients develop continuous deterioration of lung function with a predominance of obstructive lung disorder which must be distinguished from other more prevalent diseases, such as asthma and chronic obstructive pulmonary disease. In this paper, we report a case of a child with the presence of clinical and radiological findings compatible with the diagnosis of LAM although it is outside the usual age of onset of the disease.

Sjogren syndrome appeared as diffuse pulmonary cystic lesion accompanied with hemoptysis: A case report and literature review / 吉林大学学报(医学版)

Objective: To analyze the clinical features of Sjogren syndrome (SS) patient by investigating the diagnosis and treatment of one SS patient and perform the review of relative literatures, and to improve the understanding of the clinicians for the rare clinical symptoms and imaging features of SS. Methods: The patient was a 23-year-old woman with dyspnea associated with cough and expectoration for 1 month, and went to the hospital after hemoptysis for 3 d. The physical examination results showed pale conjunctiva and there were no other obvious positive signs. The chest CT results showed there were multiple cystic changes in both lungs. Further bronchoscopic biopsy, labial gland biopsy and rheumatism examinations and other assistant examinations were performed. The patient received related treatment. Results: The patient was initially diagnosed as lymphangioleiomyomatosis (LAM) and eventually diagnosed as SS by related examinations. The patient was treated with oral glucocorticoids and immunosuppressive agents. The symptoms of the patient were improved after treatment. The dyspnea was relieved, hemoptysis was not found, and the lung diffusion function was improved significantly. There were no significant changes in chest CT examination of the patient 2 months after treatment. Conclusion: There is rarely patients with hemoptysis and multiple cystic lesions in both lungs simultaneously among the SS patients, SS mainly occur in the women with childbearing age and it should be differentiated from LAM.

CT features of pulmonary lymphangioleiomyomatosis / 实用放射学杂志

Objective To explore the CT features of pulmonary lymphangiomyomatosis (PLAM).Methods Clinical and high resolution CT (HRCT)data of 14 patients with pathologically proved PLAM were analyzed retrospectively.The clinical and CT features were summarized by combining the literatures.Results All 14 cases were female.They all presented with dyspnea in different degree after the activity. Scattered or widely distributed translucent and cystic lesions with indistinct walls in bilateral lungs were seen on routine CT images. HRCT showed homogeneous clear thin-walled cysts with diameter ranging from several millimeters to 25 mm,wall thickness of 1-2 mm,and surrounded by normal lung tissue.Meanwhile,blood vessels were found around the cysts,and there were no central lobular cores.The cysts were different sizes and irregular distribution.6 patients had extra-pulmonary CT manifestations:1 case with intracranial multiple sclerosis, hepatic and renal angiomyolipomas,and hepatic multiple hemangiomas,3 cases with mediastinal,hepatic and renal angiomyolipomas, and 2 cases with retroperitonea lymphangioleiomyomatosis.Conclusion The CT of PLAM is characterized by the diffuse distribution of thin-walled cystic cavities and the wall thickness is generally uniform.The typical manifestations of HRCT combined with clinical data have great values in the early diagnosis and differential diagnosis.

Complejo linfangioleiomiomatosis-esclerosis tuberosa, ¿contraindicación para el trasplante pulmonar? Presentación de un caso / Lymphangioleiomyomatosis-Tuberous Sclerosis Complex. Contraindication For Lung Transplantation? A Case Report

El complejo linfangioleiomiomatosis (LAM)-esclerosis tuberosa (ET) es una enfermedad rara, con compromiso multisistémico que afecta principalmente pulmón y cerebro. Se presenta el caso de una paciente de 25 años con LAM pulmonar que ingresa a la institución para protocolo de trasplante pulmonar. Durante los estudios de extensión se documenta compromiso extrapulmonar sistémico del complejo LAM-ET. A partir de este caso, se realizó una revisión de la literatura de las manifestaciones radiológicas sistémicas de la enfermedad y las recomendaciones de diagnóstico y manejo de estos pacientes; en especial, las indicaciones y contraindicaciones del trasplante pulmonar.

The lymphangioleiomyomatosis (LAM) - Tuberous Sclerosis (TS) Complex is a rare disease with multisystem involvement affecting mainly lung and brain. We present the case of a 25-year-old female patient with pulmonary LAM. During the work-up studies for the lung transplantation protocol, the systemic extrapulmonary involvement of the LAM-TS complex is documented. From this case, a literature review of the systemic radiological manifestations of the disease and of the diagnosis and management recommendations of these patients was made. Special focus was made on the indications and contraindications of lung transplantation.

Lymphangioleiomyomatosis: From molecular research to target therapy / 国际药学研究杂志

Lymphangioleiomyomatosis (LAM), which primarily affects women, is a rare lung disease characterized by diffuse cystic lesion and abdominal tumor(angiomyolipoma or lymphangioleiomyomas). It has two forms, sporadic LAM (sLAM) and tuberous sclerosis complex associated LAM (TSC-LAM). The mutations in the TSC genes on LAM cells lead to inappropriate activation of mam-malian target of sirolimns (Rapamycin) kinase (mTOR), which causes the development of LAM. The important role of mTOR pathway in the mechanism of LAM promotes the clinical use of mTOR inhibitors (such as sirolimns) in LAM patients. This article summarizes the mechanisms of LAM and reviews the clinical trials with mTOR inhibitors in LAM patients.

Value of imaging examinations in treatment of lymphangioleiomyomatosis with chylothorax by thoracic duct extremity exploration / 中国医学影像技术

Objective To evaluate the value of imaging examinations in the treatment of lymphangioleiomyomatosis (LAM) with chylothorax by thoracic duct extremity exploration.Methods Data of 34 LAM with chylothorax confirmed by pathology and clinical diagnosis were retrospectively analyzed.All patients underwent 99Tcm-DX lymphoscintigraphy and CT lymphangiography (CTL).Thoracic duct lesion types of 99Tcm-DX lymphoscintigraphy were type Ⅰ (abnormal concentration pattern),type Ⅱ (ectopic drainage pattern),and type Ⅲ (without image or transient image pattern).The type Ⅰ and type Ⅱ were diagnosed as thoracic duct abnormalities.Thoracic duct lesion types of CTL were type Ⅰ (dilatation pattern),type Ⅱ (distal obstruction pattern),type l (truck constriction pattern),type Ⅳ (ectopic drainage pattern),and type Ⅴ (no-display pattern).Type Ⅰ-Ⅳ were diagnosed as thoracic duct abnormalities.Consistency of displaying thoracic duct abnormalities between 99Tcm-DX lymphoscintigraphy and CTL was evaluated.Results The thoracic duct abnormalities in 99Tcm-DX lymphoscintigraphy were 58.82％ (20/34;type Ⅰ in 17,type Ⅱ in 3,type Ⅲ in 14),and in CTL were 73.53％ (25/34;type Ⅰ in 15,type Ⅱ in 3,type Ⅲ in 5,type Ⅳ in 2,type Ⅴ in 9).The consistency of CTL and 99Tcm-DX lymphoscintigraphy for detecting thoracic duct abnormalities was good (Kappa=0.679).In CTL thoracic duct types,type Ⅰ and Ⅱ were operated by thoracic duct-venous anastomosis or thoracic duct extremity release operation,type Ⅲ was operated by thoracic duct adhesion or compression band release operation,operative approach and method were chosen according to the abnormal thoracic duct flow path in type Ⅳ,type Ⅴ was took conservative treatment.Conclusion CTL is superior to 99Tcm-DX lymphoscintigraphy,which can clearly display the type of thoracic duct lesion and provide imaging informations to choose operation methods in thoracic duct exploration treatment for LAM with chylothorax.

Value of imaging examinations in treatment of lymphangioleiomyomatosis with chylothorax by thoracic duct extremity exploration / 中国医学影像技术

Objective To evaluate the value of imaging examinations in the treatment of lymphangioleiomyomatosis (LAM) with chylothorax by thoracic duct extremity exploration.Methods Data of 34 LAM with chylothorax confirmed by pathology and clinical diagnosis were retrospectively analyzed.All patients underwent 99Tcm-DX lymphoscintigraphy and CT lymphangiography (CTL).Thoracic duct lesion types of 99Tcm-DX lymphoscintigraphy were type Ⅰ (abnormal concentration pattern),type Ⅱ (ectopic drainage pattern),and type Ⅲ (without image or transient image pattern).The type Ⅰ and type Ⅱ were diagnosed as thoracic duct abnormalities.Thoracic duct lesion types of CTL were type Ⅰ (dilatation pattern),type Ⅱ (distal obstruction pattern),type l (truck constriction pattern),type Ⅳ (ectopic drainage pattern),and type Ⅴ (no-display pattern).Type Ⅰ-Ⅳ were diagnosed as thoracic duct abnormalities.Consistency of displaying thoracic duct abnormalities between 99Tcm-DX lymphoscintigraphy and CTL was evaluated.Results The thoracic duct abnormalities in 99Tcm-DX lymphoscintigraphy were 58.82％ (20/34;type Ⅰ in 17,type Ⅱ in 3,type Ⅲ in 14),and in CTL were 73.53％ (25/34;type Ⅰ in 15,type Ⅱ in 3,type Ⅲ in 5,type Ⅳ in 2,type Ⅴ in 9).The consistency of CTL and 99Tcm-DX lymphoscintigraphy for detecting thoracic duct abnormalities was good (Kappa=0.679).In CTL thoracic duct types,type Ⅰ and Ⅱ were operated by thoracic duct-venous anastomosis or thoracic duct extremity release operation,type Ⅲ was operated by thoracic duct adhesion or compression band release operation,operative approach and method were chosen according to the abnormal thoracic duct flow path in type Ⅳ,type Ⅴ was took conservative treatment.Conclusion CTL is superior to 99Tcm-DX lymphoscintigraphy,which can clearly display the type of thoracic duct lesion and provide imaging informations to choose operation methods in thoracic duct exploration treatment for LAM with chylothorax.

Diagnosis and treatment of cystic lung disease

Cystic lung disease (CLD) is a group of lung disorders characterized by the presence of multiple cysts, defined as air-filled lucencies or low-attenuating areas, bordered by a thin wall (usually < 2 mm). The recognition of CLDs has increased with the widespread use of computed tomography. This article addresses the mechanisms of cyst formation and the diagnostic approaches to CLDs. A number of assessment methods that can be used to confirm CLDs are discussed, including high-resolution computed tomography, pathologic approaches, and genetic/serologic markers, together with treatment modalities, including new therapeutic drugs currently being evaluated. The CLDs covered by this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonia/follicular bronchiolitis, and amyloidosis.