Allen Burke

Fudan University, Shanghai, Shanghai Shi, China

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Publications (289)1398.45 Total impact

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    ABSTRACT: Background The histopathologic distinction between typical carcinoid (TC) and atypical carcinoid (AC) of the lung is based largely on mitotic index. Ki-67 may aid in separation of these tumors, as well as the distinction from large cell neuroendocrine carcinoma (LCNEC).Methods We identified 55 surgically resected primary neuroendocrine lung tumors (39 TC, 7 AC, 9 LCNEC) based on mitotic rate and histologic features. Ki-67 proliferative index based on automated image analysis, tumor necrosis, nodal metastases, local or distant recurrence, and survival were compared across groups.ResultsThe mean mitotic count and Ki-67 index for TC, AC, and LCNEC were 0.1 and 2.3%, 3.4 and 16.8%, and 56.1 and 81.3% respectively. The Ki-67 index did not overlap among groups, with ranges of 0¿6.7% for TC, 9.9-25.7% for AC, and 63.2-91.9% for LCNEC. Nodal metastases were identified in 4/39 (10%) TC, 2/7 (22%) AC, and 2/8 (25%) LCNEC. There was no survival difference between TC and AC, but there was a significant survival difference between LCNEC and TC and AC combined (p¿<¿0.001). There was a step-wise increase in disease free survival with tumor grade: no TC recurred, 2/7 AC recurred or progressed (median interval 35.5 months), and all LCNEC recurred or progressed (median interval 10.1 months). No patient with TC or AC died of disease, compared to 7/8 LCNEC with follow-up data.Conclusions We conclude that Ki-67 index is a useful diagnostic marker for neuroendocrine tumors, with 7% a divider between AC and TC, and 50% a divider between LCNEC and AC. LCNEC is biologically different from AC and TC, with a much more aggressive course, and a high Ki-67 index.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_174.
    Diagnostic pathology. 10/2014; 9(1):174.
  • The American journal of surgical pathology. 06/2014;
  • Lauren Xu, Jonathon Heath, Allen Burke
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    ABSTRACT: There are few single-institution clinicopathological series of aortitis. In this study, all ascending aneurysms were prospectively evaluated pathologically with ≥6 aortic sections over a 6-year period.Of 300 ascending aortic resections, there were 21 cases of aortitis (7%), in 11 women and 10 men (mean 67, range 41-88 years). There were 19 patients with aneurysms, and two patients with sclerosing periaortitis, clinically suspected to have intramural haematoma.Of the 19 patients with aneurysms (11 women), two had prior temporal arteritis, one ankylosing spondylitis, one IgA nephropathy, one undifferentiated autoimmune disease, one Lyme disease, and one fibromyalgia. In only two patients was aortitis suspected before surgery as the cause of aneurysm. Four patients developed distal aortic aneurysm requiring repeat surgery. Valve replacement or repair was necessary in nine patients, and two patients died after surgery. There were no significant differences between patients with and without autoimmune disease. The histological features were necrotising aortitis in 18 of 19 patients with aneurysmal aortitis, and there was one case of non-necrotising aortitis. One valve showed autoimmune valvulitis, congenitally bicuspid associated with ankylosing spondylitis. Necrotising aortitis was classified as acute (n = 5), healing (n = 9), and healed (n = 4). Acute necrotising aortitis was associated with need for valve replacement (p = 0.01) and younger age (p = 0.01). The healed phase had subtle histological features, sparse medial inflammation, marked medial attenuation, and chronic adventitial inflammation.Two patients with periaortitis demonstrated marked fibroinflammatory thickening of the adventitia with histological features typical of IgG4-related disease; neither had systemic symptoms.Ascending aortitis is histologically diverse, most frequently of the medial necrotising type, and is usually not suspected pre-operatively. Awareness of the histological spectrum is necessary for pathological diagnosis.
    Pathology 05/2014; · 2.66 Impact Factor
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    ABSTRACT: Restenosis after stenting occurs secondary to the neointima formation. Neovessels have been found in the neointima within stents. However, there are few studies correlating neointimal angiogenesis and in-stent restenosis in humans. We analyzed 65 post-mortem stented arteries from 33 patients with duration >3 months. Cause of death was determined incidental to the coronary findings in every case. Stented segments were embedded in paraffin and stained immunohistochemically for CD68 (macrophages), and endothelial marker PECAM-1 (CD31). Computerized morphometry was performed to quantitate neovessel density for CD31, macrophage infiltrates, as well as plaque and neointimal area. In-stent restenosis was defined as luminal narrowing ≥75% cross-section of the stented area. Underlying plaque morphology was classified as fibrous or atheromatous. Neovessels were present in the neointima of 57 stented segments (88%). Mean neovessel density was greater in restenotic vs. non-restenotic neointimas (p=0.009) and macrophage density was also greater (p=0.006). Neointimal area correlated positively with density of neointimal vessels (p=0.002), as well as neointimal macrophage density (p=0.006), but not type of stent, underlying plaque type, or underlying plaque macrophage score. We conclude that in-stent restenosis is associated with neointimal angiogenesis which is accompanied by macrophage inflammation. The relevance of these findings to treatment and prevention of in-stent restenosis needs to be further explored.
    Pathology - Research and Practice 04/2014; · 1.21 Impact Factor
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    ABSTRACT: Antibody mediated rejection (AMR) is characterized histologically by intracapillary macrophages. Macrophage density may be an alternative method of determining inflammatory changes in AMR. We identified 118 heart transplant patients with serologic testing for HLA alloantibodies. Macrophage density was graded as 1+ (< 45 / mm(2) ), 2+ (46-90 / mm(2) ), and 3+ (>90 / mm(2) ). Maximal macrophage density and complement staining over multiple biopsies were correlated with peak panel reactive antibodies (PRA), donor specific antibodies (DSA) and the clinical diagnosis of AMR. The presence of PRA correlated with macrophage score (p=.001). Macrophage density correlated with any DSA (p<.0001), class I DSA (p<.0001), class II DSA (p<.0001), and class II DQ (p<.0001). Nine patients had clinical AMR. Among patients with AMR, 89% had a biopsy over the period of AMR with ≥ 3+ macrophage density (89% sensitivity); among patients without AMR, 93% of patients had no biopsy at any time with ≥ 3+ macrophage density (specificity). There was perfect concordance between the scores of C4d positivity and macrophage density in 61% and only partial concordance in 20%, with complete discordance in 19% in biopsies taken during clinical episodes of AMR. Macrophage density in allograft endomyocardial biopsies is frequently elevated during clinical episodes of AMR and correlates well with alloantibodies. This article is protected by copyright. All rights reserved.
    Clinical Transplantation 03/2014; · 1.63 Impact Factor
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    ABSTRACT: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor with relatively indolent behavior. Non-classic morphological variants have not been well studied and rarely been reported. We report a challenging case MTSCC with a peculiar morphology in a 42-year-old man, arising in a background of end-stage renal disease (ESRD). Predominant areas with extensive papillary architecture, psammoma bodies and stromal macrophageal aggregates, reminiscent of a papillary renal cell carcinoma (papillary RCC), were intermixed with foci that transitioned into a MTSCC-like morphology exhibiting elongated tubules and a low grade spindle cell component in a background of mucinous stroma. Immunuhostochemistry demonstrated diffuse positivity for P504s/AMACR and vimentin in tumor cells. Focal positivity for RCC, CD10 and CK7 was also noted. Kidney-specific cadherin, cytokeratin 34betaE12 and TFE3 stains were negative in the tumor. The major differential diagnostic considerations were papillary RCC, clear cell papillary RCC, and Xp11.2 translocation carcinoma. Negative FISH studies for trisomy 7 and 17 in both papillary and spindled components supported the diagnosis of MTSCC. The ultrastructrural profile was not entirely indicative of the cellular origin of the tumor. Cytogenetic analysis should be performed in atypical cases of MTSCC for precise diagnosis.
    Pathology - Research and Practice 01/2014; · 1.21 Impact Factor
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    ABSTRACT: Background There are few studies on the histologic findings in native infective endocarditis, especially regarding mimics of autoimmune valvulitis. Methods We prospectively studied 106 surgical specimens from 95 patients with a clinical diagnosis of infective endocarditis on native valves, and compared gross and histologic findings with culture results, underlying valve disease, risk factors and time interval from symptom onset to surgical intervention. Results There were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(.9%) pulmonic and 11 (10%) multiple valve replacements. Underlying valve disease was present in 26 (27%) patients (non-calcified bicuspid aortic valve, 10 (38%) cases; mitral valve prolapse, 5 (19%) cases; calcified trileaflet aortic valve, 5 (19%) cases; calcified bicuspid aortic valve, 2 (8%) cases; post-rheumatic mitral valve disease, 2 (8%) cases; hypertrophic cardiomyopathy-related mitral valve disease, 1 (4%) case, trileaflet aortic insufficiency 1 (4%) case) and associated with streptococcal infection (p=.001). Absence of underlying valve disease was associated with intravenous drug abuse (p=.01) and dialysis dependent renal disease (p=.006). Intravenous drug abuse was associated with staphylococcal infection (p=.03). Vegetations were present in 80 (75%) of cases, and on the nonflow surface of the valve in 65 (81%) of these. Gram-stain positivity and neutrophilic microabscesses were associated with staphylococcal infection (p=.03). Epithelioid macrophages with palisading features mimicking necrobiotic granulomas were seen in 42 (40%) valves and more frequently associated with streptococcal infection (p=.03). As expected, the presence of valve necrosis and acute inflammation decreased with an increase in time with respect to symptomatic onset. Conclusion Histologic findings mimicking autoimmune inflammation is frequent in infective endocarditis and associated with streptococcal infection. Risk factors for infective endocarditis include calcific valve disease.
    Pathology - Research and Practice 01/2014; · 1.21 Impact Factor
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    ABSTRACT: Restenosis after stenting occurs secondary to the neointima formation. Neovessels have been found in the neointima within stents. However, there are few studies correlating neointimal angiogenesis and in-stent restenosis in humans.We analyzed 65 post-mortem stented arteries from 33 patients with duration > 3 months. Cause of death was determined incidental to the coronary findings in every case. Stented segments were embedded in paraffin and stained immunohistochemically for CD68 (macrophages), and endothelial marker PECAM-1(CD31). Computerized morphometry was performed to quantitate neovessel density for CD31, macrophage infiltrates, as well as plaque and neointimal area. In-stent restenosis was defined as luminal narrowing ≥ 75% cross-section of the stented area. Underlying plaque morphology was classified as fibrous or atheromatous. Neovessels were present in the neointima of 57 stented segments (88%). Mean neovessel density was greater in restenotic vs. non-restenotic neointimas (p = 0.009). and macrophage density was also greater (p = 0.006). Neointimal area correlated positively with density of neointimal vessels (p = 0.002), as well as neointimal macrophage density (p = 0.006), but not type of stent, underlying plaque type, or underlying plaque macrophage score. We conclude that in-stent restenosis is associated with neointimal angiogenesis which is accompanied by macrophage inflammation. The relevance of these findings to treatment and prevention of in-stent restenosis needs to be further explored.
    Pathology - Research and Practice 01/2014; · 1.21 Impact Factor
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    ABSTRACT: Objectives Three intravascular ultrasound (IVUS) signatures have been associated with coronary artery disease instability: echo-attenuation, intraplaque echolucent zone, and spotty calcification. We sought to investigate the substrates responsible for these IVUS signatures in a relatively large series of postmortem human coronary samples. Background The exact mechanisms and pathologic correlates underlying echo-attenuation, an intraplaque echolucent zone, and spotty calcification remain poorly understood. Methods IVUS was compared to near-infrared spectroscopy (NIRS) detection of lipid core plaque (LCP) and histopathology in 2294 vessel segments from 151 coronary specimens from 62 patients at necropsy using the modified American Heart Association classification. Results IVUS detected echo-attenuated plaques in 18.3% segments, echolucent plaques in 10.5% segments, and spotty calcification in 14.4% segments. Histopathologically, 91.4% echo-attenuated plaques corresponded to either a fibroatheroma with a necrotic core or pathologic intimal thickening with a lipid pool; almost all segments with superficial echo-attenuation indicated the presence of a fibroatheroma with an advanced necrotic core. Echolucent plaques indicated the presence of a relatively smaller lipid/necrotic core compared to echo-attenuated plaques (thickness: 0.51 [interquartile range (IQR): 0.35-0.64] vs. 0.70 [IQR: 0.54-0.92] mm, p<0.001; arc: 74.5° [IQR: 59.0°-101.0°] vs. 90° [IQR: 70.0°-112.0°], p<0.001), although 82.8% of superficial echolucent zones indicated a necrotic core-containing fibroatheroma. IVUS spotty calcification, especially superficial in location (72.6%), was often associated with a fibroatheroma with calcium deposits and had smaller arcs of calcium in the setting of fibroatheroma versus fibrocalcific plaques (37.5° [IQR, 23.0°-53.0°] vs. 59.0° [IQR, 46.0°-69.0°], p<0.001). Comparisons between IVUS and NIRS revealed that echo-attenuated plaques contained the highest probability of NIRS-derived LCP followed by echolucent plaques and spotty calcifications. Conclusions This study demonstrated that echo-attenuated plaque, especially superficial echo-attenuation, was the most reliable IVUS signature for identifying a high-risk plaque, ie, a fibroatheroma containing a large necrotic core.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
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    ABSTRACT: There are few histologic studies of intracoronary stents found at autopsy. We studied histologic findings of 87 intracoronary stents from 45 autopsy hearts. There were 40 patients with chronically implanted stents and five shorter than 30 days. Of five patients with recent stent placement, the cause of death was related to the stent (in-stent thrombosis) in one case. Of the 40 patients with chronic stents, there were 16 sudden coronary deaths and 24 noncoronary deaths (controls). There were no late stent thromboses in the coronary deaths. In the coronary deaths, 26% of stents showed restenosis versus 11% in controls (p = 0.1). The rate of healed infarcts and cardiomegaly was similar in the coronary and noncoronary groups, and acute thrombi in native arteries were seen only in three hearts in the coronary group. We conclude that the cause of death is rarely impacted by in-stent findings at autopsy, especially in chronically implanted stents.
    Journal of Forensic Sciences 11/2013; 58(6):1542-8. · 1.24 Impact Factor
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    ABSTRACT: We report a case of a 30-year-old woman who suddenly collapsed after having a physical altercation with her husband. Despite immediate resuscitation, she died on arrival at the hospital. The victim's parents requested an autopsy because they believed that their daughter was killed by her husband. Postmortem examination revealed that the victim had a diffusely enlarged thyroid gland and cardiomegaly with left ventricular hypertrophy. There was no evidence of significant trauma on the body. Further postmortem thyroid function tests and review of her medical history indicated that her death was due to Graves' disease. To the best of our knowledge, this is the first case reported of sudden death due to cardiac arrhythmia from Graves' disease induced by physical and emotional stress associated with the criminal activity of another person. The autopsy findings are described. In addition, the literature is reviewed and the significance of postmortem evaluation of thyroid hormones in the cases of sudden death is discussed.
    Journal of Forensic Sciences 08/2013; · 1.24 Impact Factor
  • The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 08/2013; · 1.04 Impact Factor
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    ABSTRACT: There are few autopsy studies of patients dying suddenly with obstructive sleep apnea (OSA). Twenty-five forensic autopsies of unexpected sudden death in individuals with OSA were reviewed. The causes of death were as follows: cardiomyopathy (n = 11); sudden unexpected death without morphologic findings (SUDNA, n = 6); and other cardiovascular diseases not related to OSA (n = 8). The cardiomyopathy group comprised five hearts with concentric left ventricular hypertrophy without dilatation and six with left ventricular diameter >4 cm (dilated cardiomyopathy). Four of six hearts in the SUDNA group showed right ventricular dilatation compared with seven of 11 showed cardiomyopathy and one of eight miscellaneous. The degree of obesity was greatest in the dilated cardiomyopathy group (10 of 11 obese) followed by the SUDNA group (four of six obese). The cardiac findings in patients dying suddenly and unexpectedly with OSA include nonspecific cardiomyopathy, other cardiac conditions, and hearts without a morphologic cause of death, which show frequent right ventricular dilatation as the only finding.
    Journal of Forensic Sciences 07/2013; · 1.24 Impact Factor
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    ABSTRACT: The mechanisms of interstitial lung disease (ILD) remain incompletely understood, though recent observations have suggested an important contribution by interleukin (IL)-33. Substantial elevation in IL-33 expression was found in the lungs of patients with idiopathic pulmonary fibrosis and scleroderma lung disease as well as in the bleomycin injury mouse model. Most of the observed IL-33 expression was intracellular and intranuclear, suggesting involvement of the full-length (fl) protein but not the proteolytically processed mature IL-33 cytokine. The effects of flIL-33 on mouse lungs were assessed independently and in combination with bleomycin injury using recombinant adenovirus-mediated gene delivery. Bleomycin-induced changes were not affected by gene deficiency of the IL-33 receptor T1/ST2. Combined flIL-33 expression and bleomycin injury had a synergistic effect on pulmonary lymphocyte and collagen accumulation, which could be explained by synergistic regulation of the cytokines TGF-β, IL-6, MCP-1, MIP-1α, and TNF-α. By contrast, there was no increase in the levels of the Th2 cytokines IL-4, IL-5, or IL-13. Also, flIL-33 was found to significantly increase expression of several heat shock proteins, particularly HSP70, which is known to be associated with ILD. Thus, full-length IL-33 is a synergistic proinflammatory and profibrotic regulator that acts by stimulating expression of several non-Th2 cytokines and activates expression of HSP70.
    American Journal of Respiratory Cell and Molecular Biology 07/2013; · 4.15 Impact Factor
  • Lauren Xu, Allen Burke
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    ABSTRACT: BACKGROUND:: The histologic reaction in the adventitia to aortic dissections may be relevant to dating the onset of symptoms and to providing insight into pathogenesis. DESIGN:: We prospectively studied 43 surgically excised acute ascending aortic dissections before false-lumen rupture, with emphasis on inflammatory reaction in the false-lumen wall in relation to duration of symptoms. RESULTS:: A total of 31 men and 13 women were included in the study. Duration of symptoms was <12 hours (n=9), 12 to 24 hours (n=12), 1 to 2 days (n=8), 2 to 7 days (n=11), and >1 week (n=3). Medial inflammation was predominantly lymphohistiocytic and was marked in 3 cases but limited to the region adjacent to the dissection plane, unlike aortitis. Adventitial neutrophils occurred before 12 hours, peaked between 12 and 24 hours, and were rare after 2 days. Eosinophils occurred after 1 day, peaked between 2 and 7 days, and were predominant between 2 and 4 days. Macrophages were present after 1 day and peaked between 2 and 7 days. Mesothelial reaction occurred only after 1 day. Apoptosis and mitotic figures involving stromal cells occurred after 12 hours and peaked between 1 and 2 days; mitotic figures persisted up to 7 days. CONCLUSIONS:: Adventitial inflammation is prominent soon after intimal injury in aortic dissections before rupture of the false lumen. The pattern of inflammation is distinct from aortitis and can be used to date early aortic dissections.
    The American journal of surgical pathology 06/2013; · 4.06 Impact Factor
  • Lauren Xu, Fabio Tavora, Allen Burke
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    ABSTRACT: INTRODUCTION:: The International Association for the Study of Lung Cancer (IASLC) recently reclassified adenocarcinomas of the lung on the basis of histologic patterns. However, there is lack of consensus about a grading system for these tumors. We studied a series of invasive lung adenocarcinomas and correlated histologic features with lymph node and distant metastases. A series of invasive lung carcinomas resected over a 5-year period were retrospectively reviewed and classified by the IASLC system. The proportion of each histologic subtype was estimated at 5% increments, and cytologic features were blindly recorded and subsequently correlated with lymph node and distant metastases. The 125 tumors were classified on the basis of the predominant pattern as lepidic predominant (LPA) (n=9), acinar (n=71), solid (n=23), papillary (n=11), and mucinous (n=11). The acinar pattern was heterogenous, in that a cribriform subgroup (n=34) was significantly more likely to demonstrate lymph node metastases compared with a tubular subgroup (n=37) and had a higher mitotic rate, rate of necrosis, vascular invasion, and prominent nucleoli. Mucinous tumors were LPA (n=3), tubular (n=4), and cribriform predominant (n=4). The rate of lymph node metastasis was greatest in the solid type (P=0.02). The rate of distant metastasis was greatest in the mucinous and solid groups (P<0.02). Mitotic activity (≥1/HPF), desmoplasia >20% of the tumor, prominent nucleoli, and vascular invasion, along with a solid growth pattern ≥20%, were independently associated with metastatic potential and considered poor prognostic histologic features. A 3-tiered grading system separated tumors into well differentiated (predominantly LPA, papillary, and tubular patterns), moderately differentiated (predominantly cribriform tumors), and poorly differentiated (≥20% solid growth pattern). Tumors in the well-differentiated group were elevated to moderately differentiated if there were poor prognostic histologic features. Using this system, there was a stepwise increase in the rate of lymph node metastasis (P<0.0001) and distant metastasis (P=0.0004) from well-differentiated, moderately differentiated, to poorly differentiated tumors, the rate being 40, 46, and 39, respectively. Application of the IASLC classification in this series resulted in a predominance of acinar adenocarcinomas. To stratify tumors into clinically relevant grades, grading by pattern (tubular, cribriform, solid), mitotic activity, and nuclear features is useful.
    The American journal of surgical pathology 05/2013; · 4.06 Impact Factor
  • Lauren Xu, Seth Kligerman, Allen Burke
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    ABSTRACT: Sarcoid lung disease may result in progressive lung failure, necessitating transplant. There is a debate on whether the scarring is similar to or distinct from that seen in other fibrotic lung disease such as usual interstitial pneumonia (UIP). We prospectively evaluated histologic sections from 9 lung explants with end-stage sarcoid lung disease diagnosed clinically and by chest computed tomographic scans. The study included 7 women and 2 men. Four lungs showed active granulomatous disease, with nonfibrotic nodular granulomas in the interstitium; the other 5 were predominantly fibrotic, of which 3 had areas of honeycombing (cysts lined by respiratory epithelium with surrounding scar). Chest computed tomographs of 8 cases were all read as either probable or definite sarcoid. Patients in the fibrotic phase were significantly older (P=0.016). All cases showed dense acellular collagen, which was more extensive in the fibrotic phase. Granulomas were present in a lymphatic distribution (along bronchi, the lobular septa, and the pleura) and were predominantly small clusters of macrophages or giant cells embedded in scar in the fibrotic phase. Granulomas were not identified in 2 lungs in the fibrotic phase. In contrast to the honeycombing of UIP, the honeycombing was predominantly central, with prominent bronchiectasis. These end-stage sarcoid lungs were characterized by a fibrotic and active granulomatous pattern, both of which are very distinct from that seen in UIP.
    The American journal of surgical pathology 02/2013; · 4.06 Impact Factor
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    ABSTRACT: The histopathologic features of pulmonary graft-versus-host disease (GVHD) status post-bone marrow transplant are not well described. Lung biopsies from patients with clinically suspected GVHD were studied. There were 17 biopsies from 9 men and 5 women. Alveolar changes were classified as acute lung injury with intra-alveolar fibrin, organizing pneumonia (OP), and chronic interstitial pneumonia (CIP). Intraepithelial bronchiolar T cells were increased in 16 of 17 biopsies within bronchiolar mucosa (56 ± 30 per 100 epithelial cells). Atypical pneumocytes were present in 10 biopsies, and atypia was marked in 2 biopsies. Reactive bronchiolar cells were also seen in all 3 groups and showed mild atypia in 5 and marked atypia in 1, mimicking viral cytopathic effect. Apoptosis of bronchiolar epithelium and interstitium was seen in all but 1 case and was most marked in the acute injury and OP patterns. Perivenular cuffing was present in 11 of 17 biopsies. All 3 patients with acute injury died of acute respiratory distress syndrome; 1 patient with OP died of systemic GVHD; and 1 patient with CIP pattern died of opportunistic infection. Obstructive lung disease with obliterative bronchiolitis developed in 3 patients, all of whom stabilized with treatment and were alive at last follow-up (mean, 25 months). All 3 histologic patterns of pulmonary GVHD are characterized by intrabronchiolar T cells, apoptosis, and perivenulitis, which help to distinguish GVHD from infections. The acute lung injury pattern has a poor prognosis, and bronchiolitis obliterans syndrome develops in a subset of patients with CIP histologic pattern.
    Human pathology 01/2013; · 3.03 Impact Factor
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    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB) was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively), and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013). Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte) and CD20+ (B lymphocyte) cells, but not CD68+ (macrophage) cells, within the aggregates. Contrary to the frequent assumption, lymphocyte aggregates were present in greater numbers in advanced disease (explant tissue) compared to early disease (surgical lung biopsy). This finding suggests that active cellular inflammation continues in IPF even in severe end stage disease.
    Journal of Inflammation Research 01/2013; 6:63-70.
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    ABSTRACT: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder related to mutations in desmosomal proteins. The current study tests the hypothesis that immunohistochemical staining for desmosomal proteins is of diagnostic utility by studying autopsy-confirmed cases of ARVC. We studied 23 hearts from patients dying suddenly with ARVC. Control subject tissues were 21 hearts from people dying from non-cardiac causes (n=15), dilated cardiomyopathy (n=3) and coronary artery disease (n=3). Areas free of fibrofatty change or scarring were assessed on 50 sections from ARVC (24 left ventricle, 26 right ventricle) and 28 sections from controls. Immunohistochemical stains against plakoglobin, plakophilin, desmoplakin, connexin-43, and N-cadherin were applied and area expression analyzed by computerized morphometry. Desmin was stained as a control for fixation and similarly analyzed. The mean area of desmin expression was similar in controls and ARVC (86% vs. 85%, p=0.6). Plakoglobin expression was 4.9% ± 0.3% in controls, vs. 4.6% ± 0.3% in ARVC (p=0.3). Plakophilin staining was 4.8% ± 0.3% in controls vs. 4.4% ± 03% in ARVC (p=0.3). Desmoplakin staining was 3.4% in controls vs. 3.2 ± 0.2% in ARVC (p=0.6). There were no significant differences when staining was compared between right and left ventricles (all p > 0.1). For non-desmosomal proteins, the mean area of connexin-43 staining showed no significant difference by presence of disease. The small and insignificant decrease in junction protein expression in ARVC suggests that immunohistochemistry is not a useful tool for the diagnosis.
    The Open Cardiovascular Medicine Journal 01/2013; 7:28-35.

Publication Stats

15k Citations
1,398.45 Total Impact Points

Institutions

  • 2011–2014
    • Fudan University
      • Department of Forensic Medicine
      Shanghai, Shanghai Shi, China
  • 2007–2014
    • University of Maryland Medical Center
      • Department of Pathology
      Baltimore, Maryland, United States
  • 2005–2014
    • University of Maryland, Baltimore
      • Department of Pathology
      Baltimore, Maryland, United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 2012
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
    • American Institute for Radiologic Pathology
      Silver Spring, Maryland, United States
  • 1989–2010
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan
    • Uniformed Services University of the Health Sciences
      • Department of Radiobiology
      Maryland, United States
  • 2009
    • Minneapolis Heart Institute
      Minneapolis, Minnesota, United States
  • 2008
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Shady Grove Adventist Hospital
      Maryland, United States
    • Infraredx, Inc.
      Burlington, Massachusetts, United States
  • 2006–2008
    • CVPath Institute
      Maryland, United States
  • 2002
    • University of South Alabama
      • Department of Pathology
      Mobile, AL, United States
  • 2000
    • New England Baptist Hospital
      Boston, Massachusetts, United States
    • Walter Reed National Military Medical Center
      Washington, Washington, D.C., United States
  • 1999
    • Walter Reed Army Institute of Research
      Silver Spring, Maryland, United States
    • Policlinico San Matteo Pavia Fondazione IRCCS
      Ticinum, Lombardy, Italy