Smith, Maxwell L.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) remains a poorly understood clinical entity. It is currently classified as a premalignant condition by the World Health Organization (WHO). Symptoms are similar to those associated with obstructive lung disease, including breathlessness and cough. The presentation is often initially ascribed to other diseases such as asthma or chronic obstructive pulmonary disease. Here, we present what we believe is the first described case of DIPNECH diagnosed by transbronchoscopic cryoprobe biopsy. The patient presented with chronic cough, dyspnoea, pulmonary function tests consistent with obstruction, and a computed tomography (CT) scan of chest with multiple nodules. The patient went on to have transbronchoscopic cryoprobe biopsies of the lung, which confirmed the diagnosis of DIPNECH.

Context.— The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR. Objective.— To describe the perspective of members of the Pulmonary Pathology Society (PPS) on the workup of lung allograft transbronchial biopsy and the diagnosis of acute cellular rejection and AMR in lung transplant. Data Sources.— Reports by the International Society for Heart and Lung Transplantation (ISHLT), experience of members of PPS who routinely review lung allograft biopsies, and search of literature database (PubMed). Conclusions.— Acute cellular rejection should be assessed and graded according to the 2007 working formulation of the ISHLT. As currently no specific features are known for AMR in lung allografts, the triple test (clinical allograft dysfunction, donor-specific antibodies, pathologic findings) should be used for its diagnosis. C4d staining might be performed when morphologic, clinical, and/or serologic features suggestive of AMR are identified.

Background and objectives Delayed graft function is a form of AKI resulting from ischemia-reperfusion injury. Our aim was to study the effect of delayed graft function on the progression of interstitial fibrosis after deceased donor kidney transplantation. Design, setting, participants, & measurements Our study is a retrospective study of all patients transplanted at our center between July of 2003 and September of 2014 using a kidney from a deceased donor. The primary outcome was the progression of interstitial fibrosis on serial protocol biopsies done during the first year post-transplant. We analyzed the distribution of the change in the Banff interstitial fibrosis (ci) score between the delayed graft function and nondelayed graft function groups for all of the paired biopsies done at time 0 and 12 months post-transplant ( Δ fibrosis). We also performed a linear mixed model analyzing the difference in the slopes for the progression of mean Banff ci score for all of the biopsies done at time 0 and 1, 4, and 12 months post-transplant. Results There were 343 (36.7%) in the delayed graft function group and 591 in the control group. The biopsy rates for the delayed graft function and nondelayed graft function groups at time 0 were 65.3% ( n =224) and 67.0% ( n =396), respectively, and at 12 months, they were 64.4% ( n =221) and 68.4% ( n =404), respectively. Paired biopsies were available for 155 in the delayed graft function group and 283 in the control group. In a risk-adjusted model, Banff ci score >0 on the time 0 biopsy had a higher odds of delayed graft function (odds ratio, 1.70; 95% confidence interval, 1.03 to 2.82). The distribution of the Δ fibrosis between 0 and 12 months was similar in delayed graft function and control groups ( P =0.91). The slopes representing the progression of fibrosis were also similar between the groups ( P =0.66). Conclusions Donor-derived fibrosis may increase the odds of delayed graft function; however, delayed graft function does not seem to increase the progression of fibrosis during the first year after transplantation.

Context.— Idiopathic pulmonary fibrosis (IPF) is a distinctive clinicopathologic entity and the most common form of progressive diffuse lung scarring in older adults. Idiopathic pulmonary fibrosis manifests histopathologically as the usual interstitial pneumonia pattern. The usual interstitial pneumonia pattern is distinguished by geographically and temporally heterogeneous fibrosis that is peripherally accentuated, often with honeycombing and traction bronchiectasis. Idiopathic pulmonary fibrosis is not the only disease that leads to end-stage lung fibrosis, however, and several other entities may also cause advanced fibrosis. Surgical lung biopsies often present a diagnostic dilemma when they show clear evidence of advanced fibrosis, but the clinical, imaging, and/or histopathologic subcharacteristics suggest something other than IPF. Objective.— To address this dilemma, we review several other fibrotic lung diseases, including connective tissue disease–associated interstitial lung disease, chronic hypersensitivity pneumonitis, advanced pulmonary Langerhans cell histiocytosis, end-stage pulmonary sarcoidosis, Erdheim-Chester disease, Hermansky-Pudlak syndrome, and others, detailing their clinical, radiologic, and histopathologic attributes and emphasizing similarities to and differences from IPF. Data Sources.— Data sources comprised published peer-reviewed literature and personal experience of the authors. Conclusions.— Often, clues in the lung biopsy may offer the first suggestion of a fibrotic lung disease other than IPF, and accurate classification is important for prognosis, treatment, and the development of future therapies.

Context Three distinct patterns of pulmonary fibrosis, including usual interstitial pneumonia, fibrotic nonspecific interstitial pneumonia, and airway-centered fibrosis, can be identified on surgical lung biopsies. Objectives To compare the pathologic definitions, clinical and radiographic presentations, etiologies and differential diagnoses, treatments, and prognoses of usual interstitial pneumonia, fibrotic nonspecific interstitial pneumonia, and airway-centered fibrosis patterns, and to address the challenges and controversies related to pulmonary fibrosis. Data Sources Data were derived from published literature and clinical experience. Conclusions Although there may be overlap, identification of the dominant form of fibrosis in a particular case can provide a general category of disease and assist in identifying an etiology.

Aims We wanted to improve the quality of histopathology addenda and amendments by introducing standardised nomenclature and procedures. Methods We standardised amendment and addenda definitions, implemented a pathologist visual work tool, and evaluated and quantitated all amendments and addenda for 3 months prior to implementation and 17 months after. Results In the 3-month pre-intervention period, 32 of 979 addenda (3.3%) were misused and 18 of 98 amendments (18.4%) were incorrectly classified. In the 17-month post-intervention period, 57 of 5906 addenda (1.0%) were misused and 54 of 752 amendments (7.2%) were incorrectly classified. These differences were statistically significant (p<0.0001). Conclusions The introduction of standardised nomenclature and a visual work tool significantly improved the quality of histopathology addenda and amendments.

Intravesical instillation of Bacillus Calmette-Guérin (BCG) is a mainstay of adjunctive therapy for superficial bladder cancer. Disseminated BCG infection (“BCG-osis”) after this therapy is rare and potentially life-threatening; only isolated case reports detail the histopathologic findings thereof, few of which had a diagnosis confirmed by molecular testing. We report 3 additional cases of BCG-osis complicating BCG therapy, all confirmed by cultures and molecular assays, including the first cases of wedge biopsy-confirmed BCG pneumonia and BCG olecranon bursitis. When suggested by a relevant clinical history, recognition of randomly distributed granulomas in any organ should prompt consideration of BCG-osis and liberal performance of AFB stains, aided by targeted molecular assays. Physicians should maintain a high index of suspicion when miliary infiltrates arise after intravesical BCG instillation, and close multidisciplinary communication is essential. Pathologist awareness of this rare cause of granulomatous inflammation aids recognition of BCG-osis and facilitates prompt initiation of antimycobacterial therapy.

BACKGROUNDThe cytological diagnosis of malignant mesothelioma (MM) on serous effusion is challenging due to significant morphologic overlap with reactive mesothelial cells and adenocarcinoma. One of the morphologic features of MM in effusion cytology, small orangiophilic squamous‐like cells (SOSLC), has received little attention. To the best of the authors' knowledge, the current study is the first to assess the sensitivity and specificity of SOSLC in serous effusion specimens from histology‐proven MM cases along with those of reactive mesothelial and adenocarcinoma cases.METHODSA total of 130 cases of pleural (86 cases) and peritoneal (44 cases) effusion cytology cases (30 with histology‐proven MM, 41 with adenocarcinoma, and 59 with reactive mesothelial cells) were studied. The presence or absence of SOSLC was recorded in each case.RESULTSThe cytological diagnoses of the 30 histology‐proven MM cases included 1) atypical mesothelial cells, favor reactive (4 cases); 2) atypical mesothelial cells, suspicious for or cannot exclude mesothelioma (18 cases); and 3) positive for MM (8 cases). SOSLC were found in 10 of the 30 MM effusion cases (33.3%), 1 of the 41 adenocarcinoma cases (2.4%), and 5 of the 59 reactive mesothelial cell cases (8.5%). SOSLC were more likely to be present in MM effusions compared with either adenocarcinoma (P < .0001) or reactive mesothelial cell (P < .02) effusions. All 10 cases of MM with SOSLC were from pleural fluids. One case of peritoneal serous adenocarcinoma had SOSLC and 5 cases of reactive mesothelial cells in peritoneal fluid were found to have SOSLC.CONCLUSIONSAlthough not sensitive, the presence of SOSLC is quite specific for MM in pleural fluid cytology specimens. Finding this morphological feature in pleural fluid should alert the pathologist to a possible diagnosis of MM.Cancer (Cancer Cytopathol) 2014;122:70–75. © 2013 American Cancer Society.

AbstractBackgroundIn a recent clinical trial in kidney transplant recipients, induction with alemtuzumab and rabbit‐antithymocyte globulin (r‐ATG) was equally effective in preventing rejection during the first post‐transplant year; however, this study did not include protocol biopsies.MethodsThe aim of this study was to analyze the impact of alemtuzumab induction on rejection and subclinical inflammation during the first post‐transplant year compared with a historic control group receiving induction with r‐ATG. All patients received tacrolimus and mycophenolate mofetil (MMF).ResultsThere were 361 in the alemtuzumab group and 478 in the r‐ATG groups. Rejection (excluding Banff borderline), during the first year, occurred in 14% of the alemtuzumab group and 9% of the r‐ATG group (p = 0.03). Estimated glomerular filtration rate (GFR) (chronic kidney disease (CKD)‐EPI formula) at one yr and graft survival at three yr were similar. On the protocol biopsies, interstitial inflammation (Banff i scores) and tubulitis (Banff t scores) were more likely in the r‐ATG group at one month, but at four and 12 months, both inflammation and tubulitis were more likely in the alemtuzumab group.ConclusionsWe conclude that alemtuzumab induction is associated with delayed inflammation at four and 12 months, but this inflammation did not appear to negatively impact the GFR or graft survival.