Yoshiaki Kinoshita

Renal cell carcinoma with rhabdoid features: an aggressive neoplasm

Aims:  Only a few reports on renal cell carcinoma with rhabdoid features have been published. This study was performed to investigate the clinicopathological characteristics of renal cell carcinomas with rhabdoid features.

Cytokeratin subunits of inclusion bodies in rhabdoid cells : Immunohistochemical and clinicopathological study of malignant rhabdoid tumor and epithelioid sarcoma

Extrarenal malignant rhabdoid tumor (MRT), which is recognized as being histologically similar to renal MRT, is characterized by the presence of “rhabdoid cell” (RC) and a highly aggressive biological behavior. Recently it has been proposed that “proximal variant” of epithelioid sarcoma (ES), whose morphology is similar to that of MRT, actually has a more aggressive clinical course than classical type ES. Detailed immunohistochemical analysis of cytokeratin (CK) subunits was performed in 3 cases of extrarenal MRT, 3 cases of renal MRT, and 11 cases of ES comprising 2 “proximal variants” and 9 classical types. Renal and extrarenal MRTs showed positive immunoreactivity for both CK8 and CK18. Classical type ESs were diffusely positive, not only for CK8 and CK18, but also for other cytokeratin subunits including CK4, 6, 10, 13, 16, 17, and “high-molecular-weight” CKs (CK1, 5, 10, and 14). On the other hand, proximal ES revealed limited immunohistochemical reactivity for cytokeratins, compared with classical ES. In conclusion, the inclusion bodies of RCs show immunoreactivity confined to CK8, CK18, and vimentin. Furthermore, ES has additional CK expressions, while proximal ES possesses characteristics intermediate between those of classical ES and those of external MRT.

Long-lasting response to crizotinib in brain metastases due to EML4-ALK-rearranged non-small-cell lung cancer

Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib, an oral ATP-competitive selective inhibitor of ALK. However, crizotinib exhibits extremely poor blood–brain barrier penetration; therefore, it is considered to play a limited role in the treatment of brain metastases. We present a case of a 50-year-old man with a diagnosis of ALK-rearranged NSCLC with brain metastasis and malignant pleural effusion. Despite the several systemic chemotherapy regimens and whole brain radiotherapy, brain metastasis was refractory; therefore, crizotinib was initiated. A CT scan showed a slight reduction in the brain metastasis and no change in intrathoracic disease 17 weeks after initiating crizotinib. Moreover, CT obtained 12 months after crizotinib treatment revealed brain metastasis without progression. To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.

A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1‐associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues. In the current study, the authors investigated whether a combination of MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in cell blocks obtained from pleural effusions.

Organizing Pneumonia Preceding Rheumatoid Arthritis

Rheumatoid arthritis patients are susceptible to interstitial lung disease, and joint manifestations of rheumatoid arthritis usually precede lung involvements by several years. Organizing pneumonia, as the first manifestation of rheumatoid arthritis, is extremely rare, and its clinical features remain currently unknown. We present a case and a literature review of patients who were pathologically diagnosed with organizing pneumonia first and met the diagnostic criteria of rheumatoid arthritis later. In this review, we observed the following: (1) patients with organizing pneumonia preceding rheumatoid arthritis have a high prevalence of rheumatoid factor or anticyclic citrullinated peptide antibodies; (2) almost all patients developed rheumatoid arthritis within one year after the diagnosis of organizing pneumonia. We suggest that patients with organizing pneumonia and positive for either rheumatoid factor or anticyclic citrullinated peptide antibody should be cautiously followed up regarding the development of rheumatoid arthritis, particularly during the first year after the diagnosis of organizing pneumonia.

Proliferation of elastic fibres in idiopathic pulmonary fibrosis: a whole-slide image analysis and comparison with pleuroparenchymal fibroelastosis

We occasionally encounter patients with idiopathic pulmonary fibrosis (IPF) who have similar imaging patterns to those of pleuroparenchymal fibroelastosis (PPFE) in the upper lung fields but are not diagnosed as having PPFE clinically. The aim of this study is to identify the clinicopathological features and intrapulmonary distribution of elastic fibres and collagen fibres in these patients.

Diagnostic application of BAP1 immunohistochemistry to differentiate pleural mesothelioma from metastatic pleural tumours

Unit, University of Padua, Unit of Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto IOV-IRCCS, Department of Surgical Oncology and Gastroenterology (DiSCOG), Surgical Clinic, University of Padua, Nanoinspired Biomedicine Laboratory, Institute of Paediatric Research, Padua, Italy, Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA, and ARC International Association of Cancer Registries, Veneto Tumor Registry, Padua, Italy

Two cases of pleuroparenchymal fibroelastosis diagnosed with transbronchial lung biopsy

Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare subset of idiopathic interstitial pneumonias (IIPs). Here we present two patients with PPFE in which the histology was confirmed with transbronchial lung biopsy (TBLB). The 25-year-old and 64-year-old men were both slender with a long history of pulmonary upper lobe fibrosis and a marked restrictive impairment. Although the imaging findings supported the diagnosis of PPFE, surgical lung biopsy (SLB) seemed to be needed to identify fibroelastosis for the definite diagnosis. However, we selected TBLB instead of SLB because of their general condition and the risk such as prolonged pneumothorax after TBLB. TBLB specimens in both patients showed aggregates of elastic fibers in the submucosa that were essential clues for the histological diagnosis of PPFE. TBLB may be an alternative tool for the histological diagnosis of PPFE, although a multidisciplinary discussion is necessary for the final diagnosis of PPFE as a clinicopathological entity.

Recovery of chylous pulmonary congestion in tuberous sclerosis complex-associated lymphangioleiomyomatosis

Chyloptysis and chylous pulmonary congestion are extremely rare complications of lymphangioleiomyomatosis (LAM). We report a case of a 50-year-old woman with tuberous sclerosis complex-associated LAM, who presented with expectorating milky-white bronchial casts. She was diagnosed with chyloptysis and chylous pulmonary congestion by sputum analysis. Her symptoms and lung infiltration were improved by oral sirolimus therapy; moreover, serum Krebs von den Lungen-6 (KL-6) levels paralleled the symptoms and lung infiltration of these complications. We suggest that serum KL-6 may be a useful monitoring biomarker of chyloptysis and chylous pulmonary congestion in LAM.

Significant increases in the density and number of lymphatic vessels in pleuroparenchymal fibroelastosis

Some investigators have detected fibrinous exudate or immature organisation in the alveolar spaces prior to the development of subpleural elastofibrosis in patients with pleuroparenchymal fibroelastosis (PPFE). We hypothesised that PPFE progress is associated with an impaired lymphatic drainage system, resulting in the failed resolution of intra‐alveolar exudate. The aim of this study is to investigate the pulmonary lymphatic vessels in PPFE, histologically.