[Pulmonary veno-occlusive disease]. / La maladie veino-occlusive pulmonaire.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterized by preferential remodelling of pulmonary venules and angioproliferation. PVOD term includes idiopathic, heritable (biallelic mutations of EIF2AK4 gene), drugs and toxins induced (alkylating agents, organic solvents) and connectivite-associated forms (especially systemic-sclerosis associated form). PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation. Lung biopsy is contraindicated in PVOD due to high risk of life-threatening bleeding. A noninvasive diagnostic approach, including oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest, is used to support a diagnosis of PVOD. PVOD prognosis is worse than other forms of PAH. There is no evidence-based medical therapy for PVOD and life-threatening pulmonary edema may occur following PAH targeted therapy in PVOD. Lung transplantation remains the preferred definitive therapy for eligible patients.

Bronchial Paraganglioma with SDHB Deficiency.

Though most paragangliomas arise as sporadic tumors, the recent advantages in the genetic screening revealed that about 30 % of paragangliomas are linked to hereditary mutations, such as those involving SDH genes. A 22-year-old woman carrying a left main bronchus tumor underwent surgery in our institution. Her past medical history included a GIST without KIT or PDGFRA mutation. The histological examination revealed a nested proliferation of medium-sized cells expressing neuroendocrine markers (chromogranin A and synaptophysin). The neoplastic cells failed to express SDHB gene product. These findings led us to the final diagnosis of bronchial paraganglioma in the setting of Carney-Stratakis syndrome. Bronchial paragangliomas are exceedingly rare tumors with polymorphous clinical presentation, and usually benign clinical course. Though most paragangliomas are sporadic, some tumors are associated with specific hereditary disease, especially those occurring in young patients or in combination with other neoplasms.

Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats.

Pulmonary arterial hypertension (PAH) is associated with dysregulated bone morphogenetic protein receptor (BMPR)-II signaling and pulmonary vascular inflammation. We evaluated the effects of dexamethasone on monocrotaline (MCT)-induced PAH in rats for potential reversal of PAH at late time-points. Saline-treated control, MCT-exposed, MCT-exposed and dexamethasone-treated rats (5 mg·kg⁻¹·day⁻¹, 1.25 mg·kg⁻¹ and 2.5 mg·kg⁻¹·48 h⁻¹) were evaluated at day 28 and day 35 following MCT for haemodynamic parameters, right ventricular hypertrophy, morphometry, immunohistochemistry, and IL6 and BMPR2 expression. Dexamethasone improved haemodynamics and pulmonary vascular remodelling, preventing PAH development at early (day 1-14 and 1-28) and reversing PAH at late (day 14-28 and 21-35) time-points following MCT, as well as improving survival in MCT-exposed rats compared with controls. Both MCT-induced pulmonary IL6 overexpression and interleukin (IL)-6-expressing adventitial inflammatory cell infiltration were reduced with dexamethasone. This was associated with pulmonary BMPR2 downregulation following MCT, which was increased with dexamethasone, in whole lung and control pulmonary artery smooth muscle cells. Dexamethasone also reduced proliferation of rat pulmonary artery smooth muscle cells in vitro. Experimental PAH can be prevented and reversed by dexamethasone, and survival is improved. In this model, mechanisms may involve reduction of IL-6-expressing inflammatory cells, restoration of pulmonary BMPR2 expression and reduced proliferation of vascular smooth muscle cells.

Pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is currently classified as a subgroup of pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially considered to be idiopathic PAH. PVOD has been described as idiopathic or complicating other conditions, including connective tissue diseases, HIV infection, bone marrow transplantation, sarcoidosis and pulmonary Langerhans cell granulomatosis. PVOD shares broadly similar clinical presentation, genetic background and haemodynamic characteristics with PAH. Compared to PAH, PVOD is characterised by a higher male/female ratio, higher tobacco exposure, lower arterial oxygen tension at rest, lower diffusing capacity of the lung for carbon monoxide, and lower oxygen saturation nadir during the 6-min walk test. High-resolution computed tomography (HRCT) of the chest can be suggestive of PVOD in the presence of centrilobular ground-glass opacities, septal lines and lymph node enlargement. Similarly, occult alveolar haemorrhage is associated with PVOD. A noninvasive diagnostic approach using HRCT of the chest, arterial blood gases, pulmonary function tests and bronchoalveolar lavage could be helpful for the detection of PVOD patients and in avoiding high-risk surgical lung biopsy for histological confirmation. PVOD is characterised by a poor prognosis and the possibility of developing severe pulmonary oedema with specific PAH therapy. Lung transplantation is the treatment of choice. Cautious use of specific PAH therapy can, however, be helpful in some patients.

[Pulmonary arterial hypertension due to tumor emboli]. / Hypertension artérielle pulmonaire postembolique tumorale.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is rare in the presence of malignancy and tumour embolisation is one of several possible pathological mechanisms. CASE REPORTS: We report our experience of 5 clinical cases and undertake a literature revue of the pathophysiological mechanisms and of the possible diagnostic and therapeutic approaches. CONCLUSIONS: Neoplastic PAH due to tumour micro-emboli is rare and the diagnosis difficult to establish. Cytological examination of pulmonary arterial blood could allow early institution of appropriate chemotherapy and lead to an improvement in the grave prognosis of this condition.

Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension.

In the present study, the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH) was tested. The phenotype and localisation of DCs were characterised by immunohistochemistry and double-labelling immunofluorescence in lung samples from controls, human IPAH patients and an experimental pulmonary hypertension model (monocrotaline-exposed rats). As compared with controls, morphometric analysis demonstrated increased numbers of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN)-positive cells in muscular pulmonary arteries in IPAH and OX-62-positive DCs in monocrotaline-induced pulmonary hypertension. In human samples, the mean+/-SEM number of DC-SIGN-positive cells.artery(-1) of 100-300 microm diameter was 1.4+/-0.4 in controls versus 26.4+/-2.7 in IPAH. In rats, the number of OX-62-positive cells.artery(-1) of 50-150 microm diameter was 0.5+/-0.2 in controls, and 0.7+/-0.5, 3.1+/-0.5 and 8.4+/-0.6 at day 7, 14 and 28 after monocrotaline exposure, respectively. Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension. The results support the concept that immature dendritic cells accumulate in remodelled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.

[Update on the pathomorphological assessment of vasculopathies in pulmonary arterial hypertension]. / Vaskulopathien bei pulmonal-arterieller Hypertonie Update zur pathomorphologischen Beurteilung.

Pulmonary arterial hypertension (PAH) is a term which has recently been redefined and includes idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension PAH related to specific pathological conditions (e.g. connective tissue diseases), as well as PAH caused by veno-occlusive disease or capillary hemangiomatosis. The clinical manifestation seems to be related to a peculiar pathological anatomy involving small, muscular pulmonary arteries, capillaries and veins. In addition to common hypertrophy of the tunica media, other vascular compartments may also be affected by intimal thickening or adventitial fibrosis. Moreover, complex lesions, such as so called plexiform lesions and arteritis can be present in certain forms of the disease. While the recent identification of responsible gene mutations in subgroups of patients have shed some light on disease evolution, therapeutic strategies must currently rely on vasodilative and antimitogenic drugs acting on the intimal and medial level of the affected pulmonary vessels. The clinical outcome of patients suffering from PAH remains poor, underlining our need for a better comprehension of disease pathophysiology, and thus for the characterization of specific histomorphological patterns.

[Mesotheliomas with leucocytic infiltration]. / Mesotheliome mit leukozytärem Infiltrat. Differenzialdiagnostische Aspekte.

Malignant mesotheliomas are rare tumors which can affect pleura, peritoneum, pericardium, or tunica vaginalis testis. Histomorphologically, predominant epitheloid, sarcomatoid and biphasic types can be distinguished. In some cases, leucocytic infiltrations can be observed adjacent to the tumor. Here, mesotheliomas presenting inflammatory reactions to tumor growth have to be differentiated from occasional cases with parasynchronic development of neoplastic lymphatic diseases. Moreover, so called lymphohistiocytoid mesotheliomas, a sporadically observed variant of malignant mesotheliomas, have been reported to imitate inflammatory patterns. These different forms of malignant mesotheliomas are difficult to distinguish and may lead to diagnostic misinterpretations and consequently therapeutic mismanagement. The purpose of this study was to differentiate morphological and immunohistochemical characteristics of the above mentioned diagnoses. We therefore studied two rare cases, a mesothelioma with parallel lymphoma and a lymphohistiocytoid mesothelioma, and compared them to a third more common case of mesothelioma with inflammatory tissue-reaction.

[The interdisciplinary aspects of notalgia paraesthetica]. / Interdisziplinäre Aspekte der Notalgia paraesthetica.

For 3 years a 75-year-old man with type II diabetes had been suffering from paroxysmal pruritus in a circumscribed area of brown discoloration of the skin over the left should blade. This condition, also known as notalgia paraesthetica, is a rare, but perhaps underdiagnosed, neurocutaneous entity, a largely sensory neuropathy due to a muscular compression phenomenon. In this case histological examination of a biopsy specimen showed focal acanthosis, obvious basal hyperpigmentation and discrete perivascular lymphocytic infiltration with numerous melanophages. At first, glucocorticoids were administered unsuccessfully against the distressing pruritus. Purely symptomatic local capsaicin treatment decreased the pruritus temporarily. Endocrinological diagnosis failed to demonstrate multiple endocrine neoplasia (MEN) syndrome 2A, which has been frequently described in association with notalgia paraesthetica.