Case Of Pulmonary Langerhans Cell Histiocytosis Research Articles

Langerhans Cell Histiocytosis-Associated Pulmonary Adenocarcinoma: A Word of Caution during Molecular Determinations

Background: Smoking habit is a common cause of pulmonary Langerhans cell histiocytosis (PLCH) and lung cancer and both diseases may coexist in the lung and share genetic alterations, such as V600E BRAF mutations. We collected a small series of three cases of PLCH-associated lung adenocarcinoma in order to evaluate the molecular setup in both components and underline the critical role of careful tissue selection for predictive molecular driver testing. Methods: Three cases of PLCH-associated adenocarcinoma were collected from consultation files. Clinical data from referring physicians and clinical data were obtained. The surgical biopsies were tested by immunohistochemistry and molecular analysis after separate dissection of adenocarcinoma cells and Langerhans histiocytes. Results: There were three active smoking men with a median age at diagnosis of 60.6 years. PLCH was disclosed at imaging during work-up for suspected lung cancer. Molecular analysis revealed KRAS (G12C and G13C) mutations in two cases and V600E BRAF mutation in one case of PLCH. Immunostaining with the V600E BRAF mutation specific primary antibody VE1 correctly recognized BRAF-mutated LCH. One case was wild-type in both diseases. Two similar cases were found in the literature, one of which showed a discrepant KRAS (G12D) mutation in adenocarcinoma and a V600E BRAF mutation in LCH; Conclusions: This case series of PLCH-associated adenocarcinoma underline the possibility to disclose identical genetic alterations in co-existing benign and malignant pathologies, then potentially creating erroneous interpretation of molecular analysis leading to inadequate therapeutic options in case of incorrect diagnostic recognition and inappropriate selection of both components through microdissection.

Bronchoalveolar Lavage as a Diagnostic Tool in an Atypical Pulmonary Langerhans Cell Histiocytosis.

Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon diffuse cystic lung disease that occurs almost exclusively in young adult smokers. High-resolution computed tomography of the chest allows a confident diagnosis of PLCH in typical presentation, when nodules, cavitating nodules, and cysts coexist and show a predominance for the upper and middle lung. Atypical presentations require histology for diagnosis. Histologic diagnosis rests on the demonstration of increased numbers of Langerhans cells and/or specific histological changes. PLCH is one of the few diseases in which bronchoalveolar lavage (BAL) has a high diagnostic value and can in some circumstances replace lung biopsy. We present a case of PLCH in an elderly non-smoker. Chest imaging revealed the presence of advanced interstitial lung disease with a fibrocystic pattern. BAL cellular analyses disclosed a macrophage pattern with CD1a phenotype that strongly supports the PLCH diagnosis, even in the setting of atypical clinical presentation and a lack of smoking exposure. PLCH is extremely rare in non-smokers and could represent a distinct phenotype.

WHERE THERE IS NOT SMOKE THERE IS STILL FIRE: A CASE OF PULMONARY LANGERHANS CELL HISTOICYTOSIS IN A FORMER SMOKER WITH A HISTORY OF MULTIPLE MALIGNANCIES

SESSION TITLE: Diffuse Lung Diseases SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Pulmonary langerhans cell histiocytosis (PLCH) is a cystic interstitial lung disease (ILD) that occurs almost exclusively in smokers. We present a case of PLCH in a former smoker with a history of multiple previous non-pulmonary malignancies. CASE PRESENTATION: A 71 year old African American female presented to us for management of multiple pulmonary nodules discovered on a PET/CT scan done for malignancy monitoring. CT chest showed multiple areas of reticulo-nodular densities with few cysts in bilateral upper lobe. She noted only cough and dyspnea on moderate exertion. No other organs were noted to be PET-avid. She has a history of stage I breast cancer status post bilateral mastectomy, stage II adenocarcinoma of the colon status post right hemicolectomy, and was a previous 1 pack per day smoker quiting in 1998. This was confirmed on urine and saliva testing for nicotine and cotinine. CT-guided transthoracic fine needle aspiration was suggestive of PLCH but subsequent trans-bronchial biopsy was non diagnostic. The time since she quit smoking cast doubt on her diagnosis, so a video assisted thoracoscopic lung biopsy was performed to evaluate for malignancies. Pathology revealed langerhans cells that stained positive for S-100 and CD1a. Given her history of previous malignancies and lack of current smoking, genetic analysis was done revealing a B-RAFV600E mutation. Her symptoms and pulmonary function tests declined, and she was started on supplemental oxygen. She did not respond to oral corticosteroids. She was referred to hematology and started on Dabrafenib, a B-RAF inhibitor. At her three month follow up visit, the patient noted improvement of her dyspnea, cough, and a decrease in her supplemental oxygen requirement. DISCUSSION: PLCH occurs almost exclusively in current and former smokers and the mainstay of treatment is smoking cessation, though immunosuppression is sometimes used. The lag time between cessation and development of disease has not been quantified. Recently, B-RAFV600E mutations have been identified in LCH and in several cases of PLCH. LCH, though more common in children, can occur in adults before, during, or after other malignancies, but is rarely limited to the lungs. In patients with progressive disease despite removal of smoke exposure, cladiribine, a purine analogue cytotoxic to lymphocytes, has been used to some success. The discovery of the B-RAFV600E mutation has also opened the door to treatment with BRAF inhibitors, such as in our patient. CONCLUSIONS: This case highlights the development of PLCH in a patient who has not smoked in 10 years, but has had multiple prior malignancies putting her at risk for the development of LCH. The presence of the B-RAFV600E mutation should be evaluated in patients with PLCH and LCH, as it represents a possible treatment for those who are not smoking and those whose disease progresses despite standard therapy. Reference #1: Roden, A., Yi, E.S. Pulmonary Langerhans Cell Histiocytosis: An update from the pathologist’s perspective. Arch Pathol Lab Med. 2016 Mar;140(3):230-40. DISCLOSURES: No relevant relationships by Scott Blumhof, source=Web Response No relevant relationships by Kevin Dsouza, source=Web Response No relevant relationships by Tejaswini Kulkarni, source=Web Response No relevant relationships by Amitkumar Mehta, source=Web Response

Pulmonary Langerhans Cell Histiocytosis Presenting With Unusual Radiologic Features

SESSION TITLE: Sarcoidosis and Cystic Lung Disease SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease with characteristic features on computed tomography (CT) of nodular and cystic lesions in an upper to middle lung distribution. We present a case of PLCH with diffuse centrilobular ground glass nodularity and hemoptysis. CASE PRESENTATION: A 51 year-old Ukrainian female with a 10 pack-year smoking history presented with intermittent submassive hemoptysis over 6 months. Extensive environmental and occupational exposure history was unremarkable. Physical examination was notable for bibasilar crackles on auscultation. Vital signs showed normal saturation on room air. Laboratory data revealed Hemoglobin of 12 (Normal: 12-16), elevated c-reactive protein of 6.2 (Normal: 0-0.8), and positive Quantiferon Gold. Sputum returned with negative acid-fast bacilli smears, gram stains, and cultures. CT scan of the thorax revealed diffuse bilateral centrilobular ground glass nodularity without focal consolidation or mediastinal lymphadenopathy. Work-up for hypersensitivity pneumonitis and connective tissue diseases was negative. Video bronchoscopy with bronchoalveolar lavage yielded a predominance of alveolar macrophages (95%) with negative microbiology and cytology. Transbronchial biopsy revealed hemosiderin deposits and nonspecific inflammation. Unfortunately, she signed out against medical advice. One month later, she presented with worsening hemoptysis and repeat CT of the thorax demonstrated progression of diffuse bilateral centrilobular nodularity (fig. 1). Surgical lung biopsy was performed which revealed obliterative bronchiolitis with intraluminal blood, hemosiderin deposition, adjacent cyst formation, and nodules in various states of fibrosis and inflammation. Pathognomonic CD1-antigen stain was positive for peribronchial and intrabronchial Langerhans cells consistent with PLCH (fig. 2). Our patient’s hemoptysis and CT findings resolved with abstinence of smoking. DISCUSSION: Diffuse centrilobular nodules, as seen in our patient, have not yet been described in PLCH to the best of our knowledge. This radiologic pattern represents early changes with significant inflammatory infiltration as evidenced by biopsy. With advances in radiologic techniques and enhanced resolution new patterns may be identified. CONCLUSIONS: Further studies are needed to identify the spectrum of radiographic presentations, especially to determine if diffuse centrilobular nodular opacities represent earlier changes seen in PLCH. This will provide opportunities for early diagnosis with timely treatment and has potential prognostic implications. Reference #1: Juvet SC, Hwang D, Downey GP. Rare lung diseases III: Pulmonary Langerhans' cell histiocytosis. Candian Respiratory Journal: Journal of the Canadian Thoracic Society. 2010; 17(3):e55-62. DISCLOSURE: The following authors have nothing to disclose: Spencer Pugh, Anil Singh, Tina Dudney, Arseniy Tsapenko No Product/Research Disclosure Information

Smoking-Related Interstitial Lung Disease in a Non-Smoker

SESSION TITLE: Fellow Case Report Poster - Diffuse Lung Disease I SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon diffuse cystic lung disease that occurs almost exclusively in young adult smokers. We present a case of PLCH in a non-smoker. CASE PRESENTATION: A 23-year-old male presented with acute onset of sharp, left-sided chest pain and shortness of breath. His past medical history was significant for two episodes of left-sided pneumothoraces, which were managed with chest tube placement. He did not have a history of current or prior cigarette smoking. He did not have a significant second-hand cigarette smoke exposure. On presentation, his vitals were stable. Physical examination revealed decreased breath sounds on the left side of the chest. Chest X-ray showed left-sided pneumothorax and bilateral diffuse interstitial infiltrates. He was treated with chest tube placement. CT of the chest revealed bilateral, multiple thick and thin walled cysts in the upper and middle lung fields with relative sparing of the bases. Video-assisted thoracoscopic lung biopsy (VATS) was obtained and mechanical pleurodesis was performed to treat his recurrent pneumothorax. Immunohistochemical staining for S-100 protein was positive in the Langerhans cells, consistent with PLCH. DISCUSSION: PLCH is a rare interstitial lung disease characterized by infiltration and proliferation of Langerhans cells. It occurs mostly in young adults, 20-40 years of age. Cigarette smoking is considered to be the inciting factor. There are no direct experimental data that support the role of cigarette smoke in the pathogenesis of PLCH. But, there are several observational studies, suggesting that the disease may be causally related to smoking. A history of current or previous cigarette smoking is identified in up to 97 percent of patients. PLCH has also been described in association with malignancy especially bronchogenic carcinoma and Hodgkin’s lymphoma. It is extremely rare in non-smokers and the etiology remains unknown. CONCLUSIONS: The overwhelming majority of adult patients with PLCH smoke cigarettes or were exposed to substantial second-hand smoke. PLCH has been described under the spectrum of smoking-related interstitial lung diseases. PLCH in non-smokers is not well studied. Reference #1: Suri H, Yi E, Nowakowski G, et al. Pulmonary langerhans cell histiocytosis. Orphanet J Rare Dis. 2012; 7: 16. doi: 10.1186/1750-1172-7-16 PMCID: PMC3342091 Reference #2: Abbott G, et al. Pulmonary Langerhans cell Histiocytosis1. Archives of the AFIP. DOI: http://dx.doi.org/10.1148/rg.243045005 DISCLOSURE: The following authors have nothing to disclose: Sathish Kumar Krishnan, Kumar Shah, Gurminder Dhillon No Product/Research Disclosure Information

Pathomorphological features of pulmonary Langerhans cell histiocytosis

The paper provides the clinical and X-ray characteristics of pulmonary Langerhans cell histiocytosis (PLCH). It describes pulmonary pathohistological changes in this disease, characterizes the cellular composition of granuloma, and gives methods that can verify the diagnosis of PLCH. A case of PLCH with severe respiratory failure, for which bilateral lung transplantation and histological examination of removed lungs have been made, is described.

Intriguing bronchoalveolar lavage proteome in a case of pulmonary langerhans cell histiocytosis

Background:Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease associated with tobacco smoke exposure. New insights into its pathogenesis and how it differs from that of chronic obstructive pulmonary disease (COPD) may be provided by proteomic studies on bronchoalveolar lavage fluid (BALF).Case Report:We present the BALF proteome in a biopsy-proven case of PLCH and compare it with typical proteomes of COPD and of the healthy lung. The BALF proteins were separated by two-dimensional gel electrophoresis (2-DE) and the protein patterns were analyzed with a computerized 2-DE imaging system. As compared to the healthy subject and the COPD case, the PLCH case showed a strikingly different 2-DE pattern. There was much more IgG (heavy chain) and orosomucoid, and less α1-antitrypsin, surfactant protein-A, haptoglobin, cystatin-S, Clara cell protein 10, transthyretin and gelsolin. Moreover, no apolipoprotein-A1, pro-apolipoprotein-A1, amyloid P, calgranulin A, or calgranulin B was detected at all.Conclusions:This case of PLCH presents with an extreme BALF proteome lacking significant amounts of protective and anti-inflammatory proteins. Thus, the intriguing BALF proteome opens up new lines of research into the pathophysiology of PLCH and how its pathogenesis differs from that in COPD.

A Case of Pulmonary Langerhans' Cell Histiocytosis Mimicking Hematogenous Pulmonary Metastases

A 31-year-old man presented with a dry cough and exertional dyspnea. The chest X-ray showed multiple nodular opacities throughout the entire lung field. Chest computed tomography (CT) revealed variable-sized nodules with a peribronchiolar or centrilobular distribution, some of which revealed thick-walled cavitary change. Based on the chest CT findings, it was initially assumed that metastatic lung nodules with hematogenous spread were present; therefore, we performed an open lung biopsy. On microscopic examination, several compact cellular interstitial infiltrates composed of Langerhans' cells, eosinophils, and lymphocytes were observed. Immunochemically, the Langerhans' cells showed strong cytoplasmic staining for S-100 protein. Based on these findings, the patient was diagnosed with Langerhans' cell histiocytosis of the lung. High-resolution CT of the chest is a useful, sensitive tool in the diagnosis of pulmonary Langerhans' cell histiocytosis (PLCH). A typical radiologic finding of PLCH is irregularly shaped cysts. The radiological finding in this case of nodular opacities throughout the lung fields only without cysts is rare in PLCH. We report a case of PLCH with atypical multiple nodules mimicking hematogenous metastatic lung nodules.

Evolución clínica y radiológica de una mujer con histiocitosis pulmonar de células de Langerhans durante 18 años

The Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon pulmonary diffuse cystic disease. This review presents one case of PLCH diagnosed in a non-smoker female adolescent, who consulted for rapidly progressive dyspnea associated to left pleuritic pain that corresponded to a bilateral pneumothorax. The diagnosis was confirmed by surgical biopsy of the lung. Treatment with corticoids (prednisone) was indicated during the first year. After 18 years from diagnosis she presented an important clinical improvement, with a favourable but not complete radiological and spirometric improvement. The cases that make their debut with recurrent spontaneous pneumothorax are infrequent. The natural evolution of this disease is variable and the treatment is still controversial, been the immunosuppressive therapy, as corticoesteroids and cytotoxic agents of limited value, since are few studies that confirm their effectiveness

The Rapid Evolution of CT Findings in Pulmonary Langerhans Cell Histiocytosis: A Case Report

Imaging findings of pulmonary Langerhans cell histiocytosis (PLCH) demonstrate evolving changes over time, and the radiological transitions shown by imaging tools may allow a prediction of histopathological activity in PLCH. However, there are no reports describing how rapidly CT findings change with time. We describe a case of PLCH that showed a rapid evolutional change of the pulmonary lesions in a 48-year-old man, in which the nodular lesions showed cystic changes within two-month follow-up periods on chest CT scans.