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Elastin and collagen are the main components of the lung connective tissue network, and together provide the lung with elasticity and tensile strength. In pulmonary pathology, elastin staining is used to variable extents in different countries. These uses include evaluation of the pleura in staging, and the distinction of invasion from collapse of alveoli after surgery (iatrogenic collapse). In the latter, elastin staining is used to highlight distorted but pre-existing alveolar architecture from true invasion. In addition to variable levels of use and experience, the interpretation of elastin staining in some adenocarcinomas leads to interpretative differences between collapsed lepidic patterns and true papillary patterns. This review aims to summarise the existing data on the use of elastin staining in pulmonary pathology, on the basis of literature data and morphological characteristics. The effect of iatrogenic collapse and the interpretation of elastin staining in pulmonary adenocarcinomas is discussed in detail, especially for the distinction between lepidic patterns and papillary carcinoma.

Ciliated muconodular papillary tumor (CMPT) is a rare type of tumor with both benign and malignant characteristics. Herein, we report the surgical case of a 65-year-old man with CMPT. Chest computed tomography revealed a solitary cavitary lesion with a maximum diameter of 11-mm in S10b of the right lower lung. A thoracoscopic lung wedge resection was subsequently performed. On microscopic examination, the tumor was composed of highly columnar cells with tubular-to-papillary and cystic growth patterns. On immunostaining, it was positive for the epidermal growth factor receptor. The tumor was diagnosed as a CMPT, exhibiting no recurrence after two years of follow-up.

To our knowledge, the in situ phase of small cell lung carcinoma (SCLC) has not been reported previously although in situ/pre-invasive lesions are commonly observed in murine models. We report a patient diagnosed with SCLC presenting mostly as carcinoma in situ after photodynamic therapy (PDT) under the diagnosis of bronchial squamous cell carcinoma (SqCC) in situ.

Pleuroparenchymal fibroelastosis (PPFE) is characterized by upper lobe-predominant subpleural fibroelastosis. Despite its characteristic uneven distribution, detailed whole-lung pathological features of PPFE have rarely been studied. We investigated PPFE in the explanted lungs from a 19-year-old male patient with a history of chemotherapy. Grossly, the explanted lungs showed upper lobe-predominant shrinkage with subpleural and central consolidation. Histologically, fibroelastosis was prominent in the perilobular areas and along the bronchovascular bundles. The other areas of the lung showed diffuse, non-specific interstitial pneumonia (NSIP)-like change with a characteristic increase of septal elastic fibers. In the digital image analysis, the ratio of elastic fibers to whole fibrosis (EF score) was lower in the subpleural areas than in the NSIP-like lesions, but the EF scores of the latter showed no significant difference between upper and middle/lower lobes. In the present case, the diffusely distributed elastic fiber-rich NSIP-like change, probably caused by the earlier chemotherapy, may have been conducive to the development of PPFE. This suggests that some unknown vulnerability of the upper lobe may exist, various primary lesions converging to the upper lobe predominance of PPFE.

Birt-Hogg-Dube (BHD) syndrome is a rare genetic disorder characterized by cutaneous fibrofolliculomas, pulmonary cysts and renal cell carcinomas. Affected individuals inherit germline mutations in the folliculin gene (FLCN). Approximately 150 pathogenic FLCN variants have been identified worldwide. Many Japanese probands of BHD syndrome were first identified by pulmonologists and/or radiologists during treatment of pneumothoraces. Lung specimens obtained through video-assisted thoracoscopic surgery (VATS) have characteristic features unique to BHD syndrome; however, pathologists often miss key findings and diagnose patients with "bullae/blebs". The pleural and subpleural cysts of BHD syndrome-associated lung diseases are often modified by tissue remodeling and can be difficult to distinguish from emphysematous bullae/blebs. Intraparenchymal unruptured cysts tend to retain distinctive features that are different from other cystic lung diseases. Here, we review the clinicopathological findings of BHD syndrome in a Japanese population based on data from 200 probands diagnosed by genetic testing and a total of 520 symptomatic family members identified through BHD-NET Japan (http://www.bhd-net.jp/). Detailed morphology of pulmonary cysts obtained from VATS and autopsied lung specimens are described, and pathological clues for differentiating miscellaneous cystic lung disorders are discussed.

Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS. ispartof: PATHOLOGY vol:53 issue:4 pages:446-453 ispartof: location:England status: published

Tumors can acquire tolerance to tumor immunity and develop enhanced proliferation. Regulatory B cells (Bregs), whose role in immune tolerance is similar to that of regulatory T cells (Tregs), appear to be involved in tumor immunity. Recently, Bregs were found to induce Tregs against tumor immunity. However, the platform for the coexistence of Bregs and Tregs in cancer patients and its clinical significance remain unclear; thus, they were evaluated in breast cancer patients. In 489 breast cancer patients, CD25- and IL10-positive Bregs and Foxp3-positive Tregs were immunohistochemically evaluated in tumor-infiltrating lymphocyte aggregates (TIL aggregates) that consisted of CD19-positive B-cell follicles and CD3-positive T-cell parafollicles. Then the correlations of the localization and existence of these cells with metastasis-free survival (MFS) were evaluated in breast cancer patients. TIL aggregates were observed in marginal regions of tumors in breast cancer patients. In the TIL aggregates, the existence of Bregs was closely related to that of Tregs (p

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by numerous colorectal adenomatous polyps with predisposition to the development of colorectal cancer (CRC). Here, we conducted genome-wide DNA methylation analysis of FAP neoplasms, including seven cancer samples and 16 adenoma samples, using an Infinium 450K BeadArray. As controls for sporadic colorectal neoplasms and mucosae, we used Infinium 450k data from 297 CRC samples, 45 colorectal adenoma samples, and 37 normal mucosa samples with reference to The Cancer Genome Atlas and other databases. Unsupervised two-way hierarchical clustering analysis of FAP and sporadic CRC/adenoma revealed that CRC was classified into four DNA methylation epigenotypes (MEs): high-ME (HME), intermediate-ME (IME), low-ME (LME), and normal-like ME (NME). Five FAP neoplasms (two cancer and three adenoma) were clustered with IME, whereas 18 FAP neoplasms (five cancer and 13 adenoma) were clustered into NME. IME FAP neoplasms significantly correlated with KRAS mutations, similar to sporadic CRC. Within IME cases, however, aberrant DNA methylation was significantly less frequent in FAP neoplasms than sporadic neoplasms, and these unmethylated genes included WNT family genes and several types of oncogenes. In summary, FAP neoplasms were classified into at least two molecular subtypes, i.e., NME in the majority of cases showing mostly no aberrant methylation and IME in some cases accompanied by KRAS mutations but less frequent aberrant DNA methylation than sporadic neoplasms, suggesting that FAP may follow a tumorigenesis pathway different from that of sporadic CRC.

STEROIDOGENESIS IN HEPATIC MUCINOUS CYSTIC NEOPLASM Aim Mucinous cystic neoplasms (MCNs) occur in the ovary, pancreas, and retroperitoneum but very rarely in the liver. Mucinous cystic neoplasms are known to harbor ovarian-like mesenchymal stroma (OLS) expressing progesterone and estrogen receptors. In this study we evaluated steroidogenesis in OLS of 25 hepatic MCNs and 24 pancreatic MCNs. Methods Both steroid receptors and steroidogenic factors were immunohistochemically evaluated using H-scores and results were compared with those in 15 ovarian MCNs and 10 normal ovaries. Results Androgen receptor (AR) H-scores in OLS were significantly higher in hepatic, pancreatic, and ovarian MCN than those in normal ovaries. H-scores of cytochrome P450 17α-hydroxylase/c17-20 lyase (P450c17) and 5α-reductase-1 (5αRED-1) in the stroma were significantly higher in OLS of hepatic and pancreatic MCN than in the stroma of ovarian MCN and normal ovary. In tumor epithelium, AR H-scores were significantly higher in hepatic and pancreatic MCN than in ovarian MCN. In both hepatic and pancreatic MCN, a significant positive correlation was detected between AR H-score in the epithelium and P450c17 H-score in OLS (hepatic MCN: Pearson's r = 0.446, P = 0.025; pancreatic MCN: r = 0.432, P = 0.035). In pancreatic MCN, a significantly positive correlation was detected between AR H-score in the tumor epithelium and 5αRED-1 H-score in OLS (Pearson's r = 0.458, P = 0.024). Conclusions These results indicated that locally produced androgens in OLS could be pivotal for tumorigenesis of both hepatic and pancreatic MCN and influence epithelial cells, possibly in a paracrine fashion, which could represent biological significance of OLS in these neoplasms.

A 27-year-old female patient had presented progressing exertional dyspnea due to pulmonary hypertension. Chest CT revealed diffusely spread patchy ground-glass opacities sparing subpleural parenchymal areas suggesting the diagnosis of pulmonary veno-occlusive disease (PVOD). Despite the diagnosis of PVOD, she was somehow managed by a repetitive escalation of the epoprostenol dose and oxygen supply during the 12-month waiting period until successful bilateral lung transplantation was performed. Pathology demonstrated capillary proliferation in alveolar septae with scarce lesions of narrowed and/or occluded postcapillary small veins, leading to the final diagnosis of pulmonary capillary hemangiomatosis (PCH), not PVOD. We herein present a case of PCH diagnosed after lung transplantation with a focus on its etiology and a key to clinical diagnosis.

Primary mucinous carcinoma of the skin (PMCS) is a rare malignant adnexal tumor with a high rate of local recurrence.1 Given its rarity, no standard of care for PMCS has been established. In general, surgical excision with a wide margin with or without regional lymph node dissection is the treatment of choice. Although distant metastases are infrequent, recurrent and metastatic PMCS are highly resistant to radiotherapy and chemotherapy,2, 3 requiring alternative treatment. In this report, we describe a case of repeated recurrences of PMCS with lymph node and lung metastases, which was successfully controlled by endocrine therapy with an aromatase inhibitor.

Background Sclerosing pneumocytoma is a rare lung tumor that is usually recognized as a solitary nodule in the lung. Surgical removal is recommended; however, its clinical diagnosis is still an issue because it is difficult to differentiate from lung adenocarcinomas using a tiny sample obtained from biopsy. Case presentation We report a case of pulmonary sclerosing pneumocytoma located in the upper lobe of the right lung of a 34-year-old woman, which was diagnosed before surgery by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). A 3-cm irregular mass was detected by chest X-ray without any symptoms. She was referred to our hospital after being followed for 10 years in her previous clinic. During this follow-up period, the tumor had grown to 5 cm. We performed the EBUS-TBNA for the diagnosis. The histological findings obtained by EBUS-TBNA consisted of alveolar type 2-like cells that were positive for napsin A and round cells that were positive for vimentin. Based on these immunostaining results, we successfully diagnosed sclerosing pneumocytoma before surgery. Right upper lobectomy was performed, and the pathological diagnosis of the surgical specimen was also confirmed as sclerosing pneumocytoma. Conclusions We herein report a case of sclerosing pneumocytoma, which was clinically diagnosed by EBUS-TBNA and resected surgically.

Background Insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3) is a valuable marker that distinguishes malignant from benign lesions and predicts prognosis. Methods First, we evaluated IMP3 expression in 77 resected specimens of pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), and chronic pancreatitis (CP). Eleven PDAC patients preoperatively underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Survival analysis of IMP3 and clinicopathological factors was performed. IMP3 and p53 expression was evaluated in another 127 EUS-FNA samples of solid pancreatic masses to compare the diagnostic value of routine and immunohistochemical staining. Results IMP3 expression was detected in 72.3%, 50%, 20%, and 0% of PDAC, malignant IPMN, benign IPMN, and CP, respectively. Evaluation of IMP3 expression in EUS-FNA specimens coincided with that in resected specimens in 10 of 11. IMP3 expression correlated with tumor differentiation in PDAC samples (p = .006) and with poor prognosis through univariate analysis (p = .045). Tumor differentiation and lymph node metastasis were significantly associated with poor prognosis through multivariate analysis. In EUS-FNA specimens, the sensitivity, specificity, and accuracy of cytohistological analysis were 80.8%, 100%, and 85.0%, respectively. IMP3 and p53 expression were detected in 80.8% and 44.9% of malignant and 0% and 5% of benign lesions. Combined with IMP3 immunostaining, the sensitivity, specificity and accuracy of cytohistological analysis significantly increased to 87.9%, 100%, and 90.8% (p = .016), respectively. Meanwhile, p53 staining had no impact on the results. Conclusions IMP3 immunohistochemical staining can improve the diagnostic accuracy of EUS-FNA for malignant pancreatic tumors.

A 68-year-old woman was referred to our hospital for the treatment of bile duct stone, pancreatic tumor, and pancreatic cysts. First, bile duct stone was removed using endoscopic retrograde cholangiopancreatography. By abdominal contrast-enhanced computed tomography, a 12-mm diameter tumor was found in the pancreatic body. The tumor was isodense compared with the surrounding pancreatic parenchyma in the non-contrast phase and poorly enhanced in the arterial phase; it exhibited gradual enhancement from the portal vein phase to the late phase. Numerous pancreatic cysts were also observed by contrast-enhanced computed tomography. By magnetic resonance imaging, the tumor was hypointense in T1-weighted images, isointense in T2-weighted images, and hyperintense in diffusion-weighted images. By magnetic resonance cholangiopancreatography, the main pancreatic duct was not dilated, and pancreatic cysts communicated with the main pancreatic duct. The pancreatic cysts were diagnosed as branch-type intraductal papillary mucinous neoplasm. Histopathologic assessment of the specimens obtained by endoscopic ultrasound-guided fine-needle aspiration revealed the tumor as benign pancreatic granular cell tumor. The patient was followed up without surgical resection. On contrast-enhanced computed tomography at 6 months after admission, the tumor did not show any changes in diameter or characteristics.

Background/Aims Eosinophilic esophagitis (EoE) is often erroneously diagnosed as gastroesophageal reflux disease (GERD). The aim of this study is to investigate the prevalence of EoE and the expression of tight junction (TJ) proteins in patients with GERD symptoms. Methods One hundred patients with GERD symptoms and 10 healthy controls were prospectively studied. Sixty-two patients had symptoms refractory to proton pump inhibitors (PPI). All patients underwent esophageal biopsy. Patients were diagnosed with EoE if the number of eosinophil granulocytes per high-power field was ≥15. Immunohistochemical analysis of TJ proteins (claudin-1, claudin-4, occludin, and zonula occludin-1 [ZO-1]) was performed. Results EoE was diagnosed in six of 100 patients (6%) with GERD symptoms and in six patients (9.7%) of 62 patients with PPI-refractory GERD. Only one had typical EoE endoscopic findings. The proportion of ZO-1-positive cells was significantly lower in the lower than in the middle esophagus (56.0%±14.0% vs 66.0%±11.5%, p

We report a case of a huge solitary non-endobronchial pulmonary tumor in a 76-year-old male smoker. The tumor measured 11 × 10 × 8 cm. It was ill-defined, and it was located periphery of the right lower lobe with the subpleural cystic spaces. He underwent right lower lobectomy with mediastinal lymph node dissection and is free from tumor 30 months after surgery. Microscopically, it was composed of a proliferation of squamous and ciliated columnar epithelial cells with a few mucous cells. These cells were arranged in a papillary growth fashion extending along the fibrously thickened alveolar septa together with metaplastic bronchiolar and squamous epithelia displaying an usual interstitial pneumonia-pattern. Although the histologic features of the tumor were that of a mixed squamous cell and glandular papilloma (MSCGP), it was peripherally located and showed a lepidic growth, and it was much larger than previously reported MSCGPs. It is possible that the tumor developed in association with bronchial metaplasia in the periphery of the lung, and then extended along the surface of the reconstructed air spaces, which resulted in its unique histologic appearance. Further investigations of respiratory papilloma are needed to clarify the pathogenesis of these lesions. Keywords: Mixed squamous cell and glandular papilloma, Non-endobronchial, Cytology, Interstitial pneumonia, Pulmonary tumor

Obtaining biopsy specimens for pathologic diagnosis of primary cardiac tumors is challenging because of their anatomic location and the risk of tumor embolization. Due to the difficulty of histologic diagnosis and limited treatment strategies, it is not uncommon for patients to be treated based on radiologic findings alone. However, a firm pathologic diagnosis may permit more appropriate treatment selection, especially for those with primary cardiac lymphoma. Endoscopic ultrasound with bronchoscope-guided fine-needle aspiration is a minimally invasive modality for sampling mediastinal lymph nodes and mediastinal lesions adjacent to the esophagus. In this case report we present 2 patients with cardiac tumors that were successfully and safely diagnosed by endoscopic ultrasound with bronchoscope-guided fine-needle aspiration.

Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a relatively rare subtype of lung malignancy. According to revised 2015 World Health Organization (WHO) criteria for the pathological diagnosis of LCNEC, neuroendocrine markers must be examined by immunohistochemistry. In this study, we reevaluated endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples of patients previously diagnosed with LCNEC using the revised WHO criteria. Methods Clinical tissue samples that had been obtained by EBUS-TBNA between January 2004 and December 2011, and that had been pathologically diagnosed as LCNEC according to the previous criteria, were reevaluated according to the revised WHO criteria. Results The records of 471 lung cancer patients with mediastinal or hilar lymph node metastasis diagnosed by EBUS-TBNA were analyzed. Thirteen patients were diagnosed with LCNEC; one of which was diagnosed based on cytology alone because the histological material was insufficient for a histological examination. Among the 12 cases in which a histological examination was performed, nine were diagnosed with possible LCNEC based on neuroendocrine marker positivity, while three were diagnosed with suspected LCNEC because they did not meet the immunostaining criteria. The patient who was cytologically diagnosed was found to have non-small cell carcinoma with neuroendocrine morphology. Conclusion LCNEC could be pathologically diagnosed based on 2015 WHO criteria using EBUS-TBNA samples.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare neoplasm originating from the nasopharyngeal surface epithelium. Histopathologically, TL-LGNPPA is characterized by cuboidal/columnar tumor cells forming papillary fronds and thyroid transcription factor-1 (TTF-1) expression resembling papillary thyroid carcinoma. To date, the recorded histological features of TL-LGNPPA have been almost uniform, and the range of histological variations in this tumor type has not been sufficiently understood. Here, we report on a 68-year-old man with TL-LGNPPA. Microscopic examination of the resected tumor revealed findings typical of papillary adenocarcinoma of this type, and moreover, this case showed scattered squamous cell foci as a hitherto unreported finding. The squamous cells showed no obvious nuclear atypia or proliferating activity, and their presence was similar to the "squamous metaplasia" of papillary thyroid carcinoma. Immunohistochemically, p40 and TTF-1 coexpression was observed in the squamous cell nuclei, indicating their origin from the glandular tumor cells of TL-LGNPPA.

This retrospective study aimed to assess the diagnostic performance of contrast-enhanced ultrasound with Sonazoid (S-CEUS) for liver metastasis. We enrolled in this study 98 patients with 148 histologically proven liver lesions, with 121 metastases and 27 non-metastases. The S-CEUS technique showed sensitivity in 95.0% (115 of 121), specificity in 44.4% (12 of 27) and accuracy in 85.8% (127 of 148) for the diagnosis of metastasis. Higher body mass index had a negative influence on the positive predictive value and accuracy, and a greater depth of the lesion had a negative influence on the accuracy. The management was changed in 8 patients (8.2%) because of S-CEUS findings. In conclusion, the addition of S-CEUS may offer a great benefit by improvement of the quality of diagnosis and management for patients with cancer who have a tentative diagnosis of liver metastasis by contrast-enhanced computed tomography.

Oropharyngeal squamous cell carcinoma (OPSCC) incidence has increased dramatically due to human papillomavirus (HPV); however, associated epigenetic alterations are not well studied. We performed genome-wide DNA methylation analysis using an Infinium 450k BeadArray for clinical OPSCC and non-cancerous samples and cancer cell lines with/without 5-aza-2′-deoxycytidine and/or trichostatin A treatment. Frequent promoter hypermethylation and methylation-associated silencing were detected in 144 genes, which included those involved in cell-cell signaling and neuron differentiation. The methylation of nine genes ( GHSR , ITGA4 , RXRG , UTF1 , CDH8 , FAN19A4 , CTNNA2 , NEFH , and CASR ) was quantitatively validated in 70 pharyngeal SCC cases by pyrosequencing. Hypermethylation significantly correlated with HPV-L1 positivity, but not with age or smoking status. p16 INK4A was generally activated in HPV-L1(+) tumors, and p16-positive cases significantly associated with better prognosis. RXRG hypermethylation strongly correlated with positivity of HPV-L1 and p16 ( P = 3 × 10 −5 and P = 5 × 10 −4 , respectively). RXRG -methylation(+) significantly associated with better prognosis when analyzing all tumor cases ( P = 0.04), and when analyzing the p16-negative poorer-outcome group ( P = 0.03). Thus, aberrant DNA methylation might be involved in HPV-associated OPSCC; in addition, DNA methylation could serve as a marker to classify subgroups based on outcome.

Hereditary renal cell carcinomas (RCCs) are life-threatening disorders not only for the patients but also for their relatives. Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). The protein product, FLCN, functions as a tumor suppressor, and the affected patients have high risks of developing multiple RCCs. The carcinogenic mechanisms stemming from FLCN dysfunction have been investigated using rodent models and human RCC tissues. However, very limited information has been available about in vitro signaling of human renal cells with genetically mutant FLCN. Herein, we established a new cell line, BHD-F59RSVT, from a BHD patient's chromophobe RCC by transfecting SV40 large T antigen. We investigated FLCN mutations, chromosome profiles, and cytopathologic characteristics of the cell line. BHD-F59RSVT reflected the patient's FLCN germline mutation, a 3-nt deletion in exon 13 (c.1528_1530delGAG). Neither somatic mutation nor loss of heterozygosity of FLCN was detectable. Chromosome 17p11.2 of the FLCN proximal region demonstrated a trimodal pattern. Genome-wide chromosomal analysis revealed a loss of chromosome 16 and mosaic segmental gains in chromosome 7. BHD-F59RSVT cells were positive when immunostained for cytokeratin 7, supporting their origin from distal convoluted tubules. Western blotting analysis demonstrated severely suppressed FLCN expression at the protein level. The collective findings indicate that the established cell line will be suitable for functional analysis of the typical phenotype of BHD-associated RCC with suppressed FLCN expression.

Although nivolumab is known to cause immune-related interstitial lung diseases (ILD), the detailed characteristics of ILD are still not fully understood. A 68-year-old man was treated with nivolumab because of unresectable sinonasal melanoma, he achieved a complete response soon after the initiation of the therapy and a complete response was thereafter maintained for 30 weeks until the patient experienced dyspnea of subacute onset. CT images revealed patchy infiltrates and ground-glass opacifications. The bronchoalveolar lavage fluid (BALF) contained elevated percentages of lymphocytes (53%) and neutrophils (30%). A transbronchial lung biopsy revealed intraalveolar fibrin balls without hyaline membranes, which was considered to be consistent with the pattern of acute fibrinous and organizing pneumonia (AFOP). This is the first report of AFOP induced by nivolumab.

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin with an aggressive clinical course. Although anthracycline- and platinum-based regimens are empirically used as first-line treatments for metastatic or unresectable cases, no salvage therapy has been established. A 73-year-old man with platinum-refractory recurrent MCC was treated with amrubicin. The symptoms improved soon, and a partial response was achieved. A total of nine cycles of amrubicin were administered in nine months with manageable adverse events until disease progression was finally observed. The present findings suggest the potential of amrubicin monotherapy as a second-line therapy for patients with advanced/recurrent MCC.

We herein report a case of Rosai-Dorfman disease (RDD) overlapping with IgG4-related disease (IgG4-RD), which presented as diffuse interstitial lung disease with a perilymphatic pattern, followed by submandibular gland and eyelid swelling. The pathological findings of the submandibular gland biopsy specimen were indicative of IgG4-RD alone. We diagnosed the patient with RDD with overlapping IgG4-RD. However, the optimal method for differentiating between these two entities is still controversial. It is important that clinicians are aware that RDD should be included in the differential diagnoses of diffuse interstitial lung disease with a perilymphatic pattern and that RDD can overlap with IgG4-RD.

Pulmonary endometriosis (PEM) is a rare disease characterized by the proliferation of ectopic endometrial tissue in the lungs, which presents as catamenial hemoptysis. A 20-year-old-woman was admitted for repeated hemoptysis. Chest CT revealed a ground-glass opacity that appeared consistently with her menstrual cycle. Our detailed inquiry revealed a history of artificial abortion, which was followed by the use of oral contraceptives and catamenial hemoptysis after the discontinuation of these medications. Surgical removal was performed and histopathological examinations confirmed PEM. This clinical course suggested hematogenous metastasis. An inquiry regarding the patient's history of uterine procedures and use of oral contraceptives was suggestive for the diagnosis of this disease.

Recurrence of an embolized pulmonary arteriovenous malformation (PAVM) is common after coil embolization. A 23-year-old woman who had undergone multiple instances of transcatheter coil embolization was admitted with hypoxia and hemoptysis. A PAVM in the left S6 was found to be recanalized by reperfusion through the pulmonary and bronchial arteries. The left S6 was partially resected; the specimen contained necrotic granulomas and non-tuberculous mycobacteria (NTM) around the PAVM. Clinicians should consider possible recurrence of PAVM after reperfusion of the pulmonary and bronchial arteries, as well as the risk of NTM infection during follow-up of patients who have undergone repeated coil embolization.