Keishi Sugino

Immunoglobulin G4-related lung disease: Clinicoradiological and pathological features

Immunoglobulin G4 (IgG4)‐related disease is a multi‐organ disorder that can include the lungs. IgG4‐related lung disease can present in various forms; the clinical, radiological and pathological features of patients with this disease have been assessed.

Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone

The results of studies examining the outcome and the factors predicting prognosis in combined pulmonary fibrosis and emphysema (CPFE) have so far been contradictory. Our objective was to determine prognosis and the prognostic factors for CPFE.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

Background: Germline alterations in the proapoptotic protein Bcl-2–like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non–small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. Methods: We studied 70 patients with EGFR mutation-positive non–small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. Results: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864–8.547; p < 0.001). Conclusions: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

Recombinant human soluble thrombomodulin treatment for acute exacerbation of idiopathic pulmonary fibrosis: a retrospective study.

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) can be fatal, and abnormalities in the coagulation system of patients with AE-IPF have been reported. Recombinant human soluble thrombomodulin (rhTM) forms a complex with thrombin to inactivate coagulation. It also inhibits high-mobility group box protein 1 (HMGB-1), which results in the suppression of inflammation. Objectives: We aimed to evaluate the effectiveness of rhTM for the treatment of AE-IPF. Methods: We retrospectively reviewed the medical records of 41 patients with AE-IPF who were admitted to our institution during the period 2006-2013. The clinical features and outcomes of 16 patients treated with rhTM (rhTM group) were compared with those of 25 patients treated with conventional therapy (control group). Patients were treated with corticosteroid (CS) pulse therapy for 3 days, followed by maintenance treatment with a tapered dose of CS. Patients in the rhTM group also received rhTM (0.06 mg/kg/day) for 6 days as an initial treatment, in combination with CS. Results: Except for D-dimer level, there were no significant differences in the baseline characteristics of the 2 groups. When compared with the control group, the rhTM group had a significantly higher survival rate at 3 months (40 vs. 69%, p = 0.048). A univariate Cox proportional hazards regression model showed that the predictive factors for survival were lactate dehydrogenase level and rhTM treatment. Regarding adverse events, 1 patient in the rhTM group developed mild bleeding events. Conclusion: rhTM as an add-on to conventional treatment may improve survival in patients with AE-IPF.

Primary pulmonary adenocarcinoma with enteric differentiation resembling metastatic colorectal carcinoma: a report of the second case negative for cytokeratin 7.

We report the case of a 51-year-old woman with pulmonary adenocarcinoma with enteric differentiation (PAED) that is indistinguishable from metastatic colorectal carcinoma by immunohistochemistry as well as histology. A chest computed tomography scan revealed a 1cm nodule in the right upper lobe and a 3cm mass in the left lower lobe. Initial examination showed no evidence of any other tumor. She underwent partial resection of the right upper lobe and left lower lobectomy. Histopathological examination revealed that both tumors were composed of medium to large complex glands with central necrosis. The tumor cells were cuboidal to tall columnar with eosinophilc cytoplasm, oval nuclei, and brush-border. Immunohistochemical study yielded the following results: tumor cells were diffusely positive for cytokeratin (CK) 20 and CDX-2, and negative for CK7, thyroid transcription factor-1, and Napsin A. MUC2 was partially observed, while MUC5AC was not detected. These findings were strongly indicative of metastatic colorectal carcinoma. However, no primary colorectal cancer was detected in any clinical examination, including fluorine 18-labeled fluorodeoxyglucose-positron emission tomography scan and video capsule endoscopy, and she has not presented with any characteristic symptoms at any follow-up to date, approximately 4 years after operation. From all features, the final diagnosis was primary PAED, suggestive of multifocal primary lung cancer. So far, only 1 case of CK7-negative PAED has been reported. This is the second case of primary PAED resembling metastatic colorectal cancer morphologically and immunohistologically.

Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study.

Treatment with pirfenidone may slow the decline in vital capacity and increase progression‐free survival (PFS) in idiopathic pulmonary fibrosis (IPF). The effects of combination therapy with inhaled N‐acetylcysteine (NAC) and pirfenidone are unclear. We assessed the effects of this combination therapy in patients with advanced IPF.

The usefulness of a disease severity staging classification system for IPF in Japan: 20 years of experience from empirical evidence to randomized control trial enrollment

Since 1991, the severity of idiopathic pulmonary fibrosis (IPF) has been classified into 4 stages-stage I (characterized by a resting PaO2 ≥ 80 Torr), stage II (70-79 Torr), stage III (60-69 Torr), or stage IV (<60 Torr)-to aid decisions on medical care subsidization in Japan. Among patients with stage II/III IPF, the severity should be increased by one stage if the lowest oxygen saturation on pulse oximetry (SpO2) is <90% during a 6-min walk test. Patients with stage III/IV IPF receive Japanese government subsidies for incurable diseases. This classification system highly correlates with serial changes in the percentage of vital capacity (%VC), the diffusing capacity for carbon monoxide, the incidence of acute exacerbation, and survival. A phase III trial of pirfenidone showed that IPF patients with an SpO2 on exertion of <90% and either a %VC ≥ 70% or a PaO2 ≥ 70 Torr (which includes most patients with stage III disease) at baseline would benefit from pirfenidone treatment. Recent post-marketing surveillance of 1370 patients--67.3% of whom had stage III/IV IPF--showed that pirfenidone was well-tolerated among those treated for longer than 6 months (63% of patients). A Japanese randomized controlled trial (RCT) demonstrated that inhaled N-acetylcysteine monotherapy benefitted patients with early IPF (stage I/II, with no desaturation on exertion). Thus, N-acetylcysteine monotherapy is suitable for early IPF, and pirfenidone is indicated for advanced disease. The classification of IPF severity is important in identifying clinically responsive patients and those suitable for RCT enrollment.

Plasmablastic lymphoma of the cecum: report of a case with cytologic findings.

Plasmablastic lymphoma (PBL) is a rare lymphoma that is characterized by a diffuse proliferation of large neoplastic cells resembling B immunoblasts, but shows the immunophenotype of plasma cells. PBL is most commonly seen in the oral cavity of human immunodeficiency virus (HIV)‐positive patients. Epstein‐Barr virus (EBV) may be closely related the pathogenesis of PBL. We report a case of HIV‐negative PBL in a 75‐year‐old man without EBV infection. Histologic examination of the cecal tumor following right hemicolectomy and cytologic examination of ascitic fluid were performed. Cytologic specimens were hypercellular and composed of single cells and loosely formed clusters. Large tumor cells showed plasmacytoid features with basophilic cytoplasm, large nuclei, prominent nucleoli, and focal perinuclear halos. Abnormal mitotic figures were easily identified. On immnohistologic study, the tumor cells were positive for CD138 (plasma cell marker) and kappa, but negative for CD45, CD3, CD20, CD79a, CD56, and cyclin D1. The proliferation index (Ki‐67) was high. This is a very rare case of PBL without HIV and EBV infection, involving the cecum. Diagn. Cytopathol. 2011;39:297–300.

Histopathological bronchial reconstruction of human bronchiolitis obliterans

To clarify the morphological mechanisms of airway obliteration in bronchiolitis obliterans (BO) associated with various causes, we conducted a retrospective study of 9 patients with a histological diagnosis of BO. The morphological characteristics were analyzed by histopathological bronchial reconstruction. BO was classified into two major morphologic subtypes: constrictive BO (CoB) and cellular/destructive BO (CDB). CoB is characterized by concentric narrowing of the airway lumen due to submucosal fibrosis. In contrast, in CDB the narrowing of the airway lumen is due to intraluminal, mural, and peribronchiolar infiltration of inflammatory cells as well as proliferation of granulation tissue. The histopathological diagnosis was CoB in 6 patients and CDB in 3 patients. Macroscopic bronchial reconstruction in CoB demonstrated that the beginnings of bronchial obliterations were in the 4th to 7th branches, numbering from each segmental bronchus and the lesions were distributed intermittently. Histopathologically, the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal obliteration in CoB, whereas the primary lesions in CDB revealed more continuous obliteration of the bronchiolar lumen than observed in CoB. In conclusion, this bronchial reconstruction study demonstrated marked morphological differences in the mechanisms of airway obliteration between two major morphologic subtypes of BO.

Bronchiolitis obliterans associated with Stevens-Johnson Syndrome: histopathological bronchial reconstruction of the whole lung and immunohistochemical study

This study presents an extremely rare case of constrictive bronchiolitis obliterans (BO) associated with Stevens-Johnson Syndrome (SJS) provides the morphological and immunohistochemical features using histopathological bronchial reconstruction technique. A 27-year-old female developed progressive dyspnea after SJS induced by taking amoxicillin at the age of 10. Finally, she died of exacerbation of type II respiratory failure after 17 years from clinically diagnosed as having BO. Macroscopic bronchial reconstruction of the whole lungs at autopsy showed the beginning of bronchial obliterations was in the 4th to 5th branches, numbering from each segmental bronchus. Once they were obliterated, the distal and proximal bronchi were dilated. Microscopic bronchial reconstruction demonstrated the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal narrowing or obliteration. Moreover, CD3-, CD20-, and CD68-positive cells were found in the BO lesions. CD34- and D2-40-positive cells were mainly distributed in the peribronchiolar lesions and bronchiolar lumens, respectively. SMA- and TGF-β-positive cells were seen in the fibrous tissue of BO lesions.The virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1071703140102601.