New insights in lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis

Abstract

Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH) are rare diseases that lead to progressive cystic destruction of the lungs. Despite their distinctive characteristics, these diseases share several features. Patients affected by LAM or PLCH have similar radiological cystic patterns, a similar age of onset, and the possibility of extrapulmonary involvement. In this review, the recent advances in the understanding of the molecular pathogenesis, as well as the current and most promising biomarkers and therapeutic approaches, are described.

Pleura revisited: From histology and pathophysiology to pathology and molecular biology

“…Briefly and not exhaustively, features that should be looked for are malignancy primary or metastatic, granulomatous inflammation (see below), features of LCH like stellate nodules around small airways and Langerhans cells, large cells with grooved nuclei CD1a+, S100+ surrounded by prominent eosinophilic and plasmocytic infiltrate‐ as well as cystic spaces at the periphery of the nodules. LCH often harbours the BRAF V600E mutation . It is worth reiterating that a very frequent and non‐specific finding in pneumothorax is a rich eosinophilic and histiocytic/giant cells infiltrate mostly of pleural localization not be confounded with LCH.…”

“…Furthermore, cystic spaces, especially in a young female patient should prompt searching for nodules of Actin+, HMB45+ cells around airways or vessels, features of LAM. LAM can be sporadic or associated with the tuberous sclerosis complex (TSC); in both forms, inactivating mutations of TSC1 and TSC2 genes result in activation of the mammalian target of rapamycin pathway . Finally, cysts lined by pneumocytes are found in the BHD syndrome, an autosomal dominant disorder characterized by facial fibrofolliculomas, renal tumours and pulmonary cysts with recurrent pneumothorax…”

Rare pulmonary diseases: a common fight

“…RUBBO and LUCAS [3] offer a comprehensive and thorough overview of primary ciliary dyskinesia and the related diagnostic and therapeutic aspects. TORRE et al [4] explore the latest novelties in LAM and PLCH, both in terms of research, genetics and therapy. MILANI et al [5] tackle the subject of a little known but clinically relevant condition, lung involvement in amyloidosis, with regards to the possible clinical consequences for the affected patients.…”

Avaliação dos mecanismos determinantes de limitação ao esforço e da capacidade de exercício em pacientes com histiocitose pulmonar de células de Langerhans

“…Nesses casos, o envolvimento dos pulmões é raro e reservado a casos graves (3,4,6) . Em adultos, a histiocitose pulmonar de células de Langerhans (HPCL) é mais frequente como sítio único ou predominante (2,6) .…”

“…A primeira hipótese é suportada pela abundância de células e mediadores imunes e inflamatórios nos granulomas da HPCL, ausência de alterações mitóticas clássicas e a possibilidade de remissão após cessação do tabagismo. Este, por sua vez, induz reação policlonal e alterações no epitélio bronquiolar distal através de recrutamento e acúmulo de células CD1a positivo (6,14) .…”