Roden, Anja C.

Context Pulmonary Langerhans cell histiocytosis (PLCH) is a rare histiocytic disorder that almost exclusively affects the lungs of smokers. PLCH is characterized by bronchiolocentric nodules and/or cysts in an upper and mid lung distribution with sparing of the costophrenic angles. The diagnosis can be challenging and often requires transbronchial biopsy or surgical lung biopsy. Pulmonary hypertension is a relatively common and sometimes severe complication of PLCH. The pathogenesis of PLCH is still debated. Recently, BRAF V600E mutation and BRAF expression have been identified in some patients with PLCH, suggesting that at least a subset of PLCH has a clonal proliferation. While smoking cessation is the first-line treatment of PLCH, some patients might require additional treatment and eventually transplant. Given that the lesional cells of PLCH express BRAF in some patients, MAPKinase pathway–targeted treatment might be useful for therapy-resistant patients. Objective —To present the more recently recognized clinical and pathologic aspects of PLCH, including pulmonary hypertension in PLCH, pathogenesis, and treatment, as well as the basic diagnostic approach to PLCH. Data Sources Authors' own research, and search of literature database (PubMed) and UpToDate. Conclusions —Despite the recent progress, more studies are needed to elucidate the biology of PLCH for identification of prognostic factors and appropriate treatment options, especially for therapy-refractory PLCH cases.

AbstractBackground and objectivePulmonary capillaritis is generally secondary to a systemic autoimmune process. Little is known regarding other causes of pulmonary capillaritis, particularly isolated pulmonary capillaritis (IPC). IPC is defined as pulmonary capillaritis in the absence of evidence of a systemic disease. We aim to describe the aetiology of biopsy‐proven pulmonary capillaritis to add to the existing knowledge on aetiologies of pulmonary capillaritis and provide a more detailed description of IPC cases.MethodsA retrospective cohort of biopsy‐proven pulmonary capillaritis was conducted at the Mayo Clinic, Rochester over a 17‐year period. Histologic slides were re‐reviewed by a lung pathologist. Medical records were reviewed to identify a possible aetiology of the pulmonary capillaritis. A subset analysis of patients identified with IPC was then performed.ResultsThirty‐six cases of biopsy‐proven pulmonary capillaritis were identified. The majority of cases were secondary to a systemic autoimmune disease, most commonly granulomatosis with polyangiitis. There were four cases of IPC in this cohort. Median follow‐up was 116.5 months with no evidence of systemic disease development. No risk factors for IPC were identified. All patients presented sub‐acutely with haemoptysis and diffuse alveolar haemorrhage with a delay in diagnosis. After initiation of immunosuppression, most patients obtained remission with a benign clinical course.ConclusionPulmonary capillaritis is most commonly secondary to systemic autoimmune disorders, predominantly ANCA‐associated vasculitis. IPC is a rare form of pulmonary capillaritis with very few cases described in the literature, the availability of effective treatment makes this rare disease important to recognize.

Transbronchial cryobiopsy technique yields larger biopsies with enhanced quality. The benefits and safety of cryobiopsies have not been thoroughly studied in lung allografts.Context.— To compare size, quality, reproducibility of interpretation of rejection and complications of cryobiopsies with those of conventional biopsies from lung allografts.Objective.— All cryobiopsies (March 2014–January 2015) of lung allografts performed at Mayo Clinic, Rochester, and medical records were reviewed. For comparison, conventional biopsies from the same patient or, if unavailable, from a random patient, were selected. Two pathologists blinded to outcome reviewed all biopsies. Specimen volume, number of alveoli, small airways, and pulmonary vessels were counted and statistically compared.Design.— Fifty-four biopsies (27 cryobiopsies) from 18 patients (11 men) were reviewed. A median of 3 (range, 2–5) and 10 (range, 6–12) specimens were obtained with cryobiopsies and conventional biopsies, respectively. Cryobiopsies were larger and contained more alveoli (P < .001, both) and small airways (P = .04). Conventional biopsies showed more fresh alveolar hemorrhage (procedural) and crush artifact/atelectasis (P < .001, both). Cryobiopsies contained more pulmonary veins and venules (P < .001). There was no significant difference between the types of biopsies with respect to the reviewers' agreement on grades of rejection. Complications were more frequent in the cryobiopsy group, though the difference was not statistically significant.Results.— Cryobiopsies of lung allografts are larger and have less artifact. However, complications occur and should be considered. Three cryobiopsy specimens appear sufficient for histopathologic evaluation of lung allografts.Conclusions.—

Usual interstitial pneumonia (UIP) is the most common idiopathic interstitial pneumonia (IIP) and is associated with a poor prognosis and poor responsiveness to immunosuppressive therapy. We present a case of a woman with steroid-responsive biopsy-proven UIP with significant and sustained improvement in pulmonary function. A female in her 40s presented following a one-year history of progressive dyspnea, a 20 lb weight loss, and fatigue. Imaging of the chest with computed tomography (CT) showed bibasilar subpleural reticular opacities and minimal peripheral honeycombing. Comprehensive connective tissue disease (CTD) antibody testing was negative. Pulmonary function testing showed moderate impairment with reduction in forced vital capacity (FVC, 69% predicted), forced expiratory volume in one second (FEV 1 73% predicted), and diffusing capacity for carbon monoxide (DLCO, 52% predicted). Surgical lung biopsy showed UIP with prominent inflammatory infiltrates. Following treatment with prednisone and azathioprine, the patient's symptoms resolved, while objective pulmonary function testing showed normalization of lung function, which is sustained at >4 years of follow-up. Improvement in lung function following immunosuppressive therapy is distinctly uncommon in either idiopathic or secondary UIP. This report suggests that occasionally, patients with secondary UIP occurring in the context of otherwise undefinable autoimmune clinical syndromes may be responsive to immunosuppressive therapy.

ABSTRACT We present a case of disseminated Neosartorya pseudofischeri infection in a bilateral lung transplant patient with cystic fibrosis. The organism was originally misidentified from respiratory specimens as Aspergillus fumigatus using colonial and microscopic morphology. DNA sequencing subsequently identified the organism correctly as N. pseudofischeri .

Abstract Androgen has been implicated as a negative regulator of host immune function and a factor contributing to the gender dimorphism of autoimmunity. Conversely, androgen deprivation has been suggested to potentiate male host immunity. Studies have shown that removal of androgen in postpubertal male mice produces an increase in size and cellularity of primary and peripheral lymphoid organs, and enhances a variety of immune responses. Yet, few details are known about the effect of androgen removal on T cell-mediated immunity. In this study, we demonstrate two pronounced and independent alterations in T cell immunity that occur in response to androgen deprivation, provided by castration, in postpubertal male mice. First, we show that levels of T cells in peripheral lymphoid tissues of mice are increased by androgen deprivation. Second, T cells from these mice transiently proliferate more vigorously to TCR- and CD28-mediated costimulation as well as to Ag-specific activation. In addition, androgen deprivation accelerates normalization of host T and B cell levels following chemotherapy-induced lymphocyte depletion. Such alterations induced by androgen deprivation may have implications for enhancing immune responses to immunotherapy and for accelerating the recovery of the immune system following chemotherapy.

A patient presenting with acute carpal tunnel syndrome and swelling and pain in the wrist and thumb is presented. An open carpal tunnel release and tenosynovectomy were performed with biopsy specimen revealing infection with Histoplasma capsulatum. The case is discussed in context of the prior scant literature of tenosynovitis of the wrist and hand caused by histoplasmosis.