Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: An Extensive Study Containing More Benign Lesions

Introduction: The Japan Lung Cancer Society (JLCS) and the Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma (JLCS-JSCC system). Prior to the proposal, the Papanicolaou Society of Cytopathology (PSC) had proposed a revised reporting system (PSC system), which comprises the “neoplastic, benign neoplasm, and low-grade carcinoma” category (N-B-LG category), in addition to the 4 categories of the JLCS-JSCC system. This study aimed to evaluate the interobserver agreement of the JLCS-JSCC system with an additional dataset with more benign lesions in comparison with the PSC system. Methods: We analyzed 167 cytological samples, which included 17 benign lesions, obtained from the respiratory system. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the JLCS-JSCC system and PSC system. Results: The interobserver agreement was moderate in the JLCS-JSCC (k = 0.499) and PSC (k = 0.485) systems. Of the 167 samples, 17 samples were benign lesions: 7 pulmonary hamartomas, 5 sclerosing pneumocytomas, 2 squamous papillomas, one solitary fibrous tumor, one meningioma, and one lymphocytic proliferation. There were diverse sample types as follows: 11 touch smears, 3 brushing smears, 2 aspirations, and one sputum sample. Fourteen samples (82.3%) were categorized into “negative” or “atypical” by more than half of the observers in the JLCS-JSCC system. Conversely, 3 samples were categorized as “suspicious” or “malignant” by more than half of the observers in the JLCS-JSCC system. On the other hand, 11 samples (64.7%) were categorized into the N-B-LG category by more than half of the observers in the PSC system. Conclusions: The concordance rate in the JLCS-JSCC system was slightly higher than that in the PSC system; however, the interobserver agreement was moderate in both the JLCS-JSCC and PSC systems. These results indicate that both the JLCS-JSCC and PSC systems are clinically useful. Therefore, both systems are expected to have clinical applications. It may be important to integrate the 2 systems and construct a universal system that can be used more widely in clinical practice

Xanthogranuloma of the intrasellar region presenting in pituitary dysfunction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Differentiation of cystic mass lesions of the sellar and parasellar regions may pose a diagnostic dilemma for physicians, neurosurgeons, radiologists and pathologists involved in treating patients with these entities. A considerable number of tumors previously identified as craniopharyngiomas may, in fact, have been xanthogranulomas. We report a case of pituitary dysfunction caused by xanthogranuloma of the intrasellar region.</p> <p>Case presentation</p> <p>A 47-year-old man of Japanese descent presented to our institution with a tumor located exclusively in the intrasellar region which manifested as severe hypopituitarism. MRI revealed a clearly defined intrasellar mass that was heterogeneously hyperintense on T1-weighted images and markedly hypointense on T2-weighted images. We preoperatively diagnosed the patient with Rathke's cleft cyst or non-functioning pituitary adenoma. Although the tumor was completely removed using a transsphenoidal approach, the improvement of the patient's endocrine function was marginal, and continued endocrine replacement therapy was needed. Postoperatively, a histological examination revealed the tumor to be a xanthogranuloma of the intrasellar region. His visual field defects and headache improved.</p> <p>Conclusion</p> <p>Because diagnosis depends on surgical intervention and xanthogranulomas of the intrasellar region are very rare, the natural history of xanthogranuloma is still unknown. Therefore, this entity is difficult to diagnose preoperatively. We suggest that xanthogranuloma should be included in the differential diagnosis, even in the case of sellar lesions, to formulate appropriate postoperative management and improve endocrine outcomes.</p

Insufficiency of Positron Emission Tomography and Magnetic Resonance Spectroscopy in the Diagnosis of Intravascular Lymphoma of the Central Nervous System

Intravascular large B-cell lymphoma (IVL) is a rare type of extranodal lymphoma with an aggressive clinical course characterized by the proliferation of lymphoma cells within the lumen of small vessels. Diagnosis is often difficult because of marked variability in clinical presentation and nonspecific laboratory and radiological findings, especially when central nervous system (CNS) symptoms are the only manifestation. Modern metabolic imaging techniques such as positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) have been reported to be useful in the diagnosis of conventional primary CNS lymphoma. We report the case of a 69-year-old man who presented with a progressive leukoencephalopathic syndrome. The patient was examined by 18F-fluorodeoxyglucose and 11C-methionine PET and MRS, but none of these examinations were able to show the presence of a tumor in the lesions or to clarify the tumor characteristics. Brain biopsy was the only way to obtain a definite diagnosis of IVL. The patient was treated intensively with standard immunochemotherapy but died 6 months after the diagnosis. Here, we discuss the insufficiency of modern metabolic imaging techniques, including PET and MRS, and recommend a rapid decision of brain biopsy in the diagnosis of IVL only involving the CNS

Prognostic significance of tumor budding in patients with pancreatic invasive ductal carcinoma who received neoadjuvant therapy

Neoadjuvant therapy is commonly used for invasive pancreatic ductal carcinoma (PDAC). Tumor budding and high podoplanin expression in cancer-associated fibroblasts (CAFs) are prognostic factors in patients with various carcinomas including PDAC who have not received neoadjuvant therapy. In this study, we investigated whether tumor budding and podoplanin-positive CAFs are associated with outcomes in Japanese PDAC patients with neoadjuvant therapy. Histopathological findings of surgically resected PDACs with neoadjuvant therapy from 2005 to 2018 were reviewed (n = 97). With reference to International Tumor Budding Consensus Conference recommendations, tumors were evaluated for budding at 20 × magnification (/0.785 mm2) and at 40 × magnification (/0.237 mm2; mean number of fields: 3) for podoplanin expression in CAFs (%). Overall survival, disease-free survival, and disease-specific survival (DSS) were analyzed using the log-rank test and Cox proportional hazards model. After adjusting for T category, N category, resection margin, and adjuvant therapy, multivariate analyses demonstrated that tumor budding at 40 × magnification was an independent prognostic factor for worse DSS (hazard ratio: 2.41, p = 0.022). Tumor budding at 20 × magnification and podoplanin-positive CAFs tended to be associated with worse DSS; however, these findings were not statistically significant. Our findings indicate that tumor budding is an independent prognostic factor in PDAC patients with neoadjuvant therapy

Verification of B-lymphocyte activating factor’s involvement in the exacerbation of insulin resistance as well as an autoimmune response in patients with nonalcoholic steatohepatitis and patients with HCV-related chronic liver disease

Abstract Background Ten to forty percent of nonalcoholic steatohepatitis (NASH) and HCV-related chronic liver disease (CLD-C) patients have antinuclear antibodies (ANAs). However, the relationship between autoimmune response and insulin resistance remains uncertain among those patients. The primary purpose of this study was to investigate whether or not ANA status was associated with the development of insulin resistance and obesity in NASH and CLD-C patients. Methods Degrees of hepatic fibrosis and steatosis were evaluated by the classification proposed by Brunt et al. Obesity and insulin resistance were estimated by calculating body mass index and the value of homeostasis model of for assessment of insulin resistance (HOMA-IR), respectively. A revised scoring system was applied to the diagnosis of autoimmune hepatitis (AIH). Serum B-lymphocyte activating factor (BAFF) levels were determined, using an ELISA technique. Results Ten of 25 (40%) NASH patients and 9 of 22 (41%) CLD-C patients had ANAs, though the titers were weak in most patients. Only one NASH patient met the category of “definite” AIH among the enrolled patients. Serum IgG levels were significantly higher in NASH and CLD-C patients with ANAs than in those without ANAs, and NASH and CLD-C patients with ANAs had significantly higher HOMA-IR values than those without ANAs (6.81 ± 3.36 vs. 4.00 ± 2.57, p = 0.0305, 3.01 ± 1.31 vs. 1.28 ± 0.50, p = 0.0011). CLD-C patients with ANAs had more advanced hepatic fibrosis and steatosis than those without ANAs, while ANA status was not associated with hepatic fibrosis or steatosis in NASH patients. Obesity was independent of ANA status in both subjects. Serum BAFF levels were significantly higher in CLD-C patients with ANAs than those in CLD-C patients without ANAs (1303 ± 268 vs. 714 ± 143 pg/ml, p = 0.0036). A close correlation between serum BAFF level and the HOMA-IR value was observed in CLD-C patients (r = 0.467, p = 0.0485). Conclusion Our data suggest that NASH and CLD-C patients with ANAs have more severe insulin resistance than those without ANAs. More advanced insulin resistance deriving from excessive BAFF production may result in severe hepatic fibrosis and steatosis in CLD-C patients with ANAs

RNF128 expression in lung adenocarcinoma is a favorable prognostic factor associated with decreased tumor‐associated macrophages

Abstract Objectives Molecular‐level research has linked RING finger (RNF) protein family members to carcinogenesis and tumor progression. Among them, RNF128 is related to tumor progression, but reports on its association with lung cancer are few. This study aimed to clarify the unknown association between RNF128 expression and clinical outcomes in patients with lung adenocarcinoma. Methods Clinical data of 545 patients with therapy‐naïve lung adenocarcinoma who underwent lobectomy with systematic lymph node dissection between 1999 and 2016 were retrospectively reviewed. Histological and immunohistochemical analyses were conducted to evaluate the relationship between RNF128 expression and prognosis. Results Among adenocarcinoma histologic types, acinar, micropapillary, and solid tumors did not express RNF128 compared with other histologic types (p < 0.001). Patients with high RNF128 expression exhibited fewer clusters of differentiated (CD) 68+ tumor‐associated macrophages (TAMs) and CD163+ TAMs. Multivariate analysis of relapse‐free survival (RFS) and overall survival (OS) revealed that the lack of RNF128 expression was an independent prognostic factor for poor RFS (hazard ratio [HR] 1.60, p = 0.029) and OS (HR 1.83, p = 0.041), suggesting that RNF128 expression is a favorable prognostic factor. Conclusion RNF128 expression may be an independent predictor of favorable outcomes in Japanese patients with untreated lung adenocarcinoma who undergo surgical resection. Further elucidation of the role of TAM‐related E3 ubiquitin ligase in immune function may facilitate the development of effective immunomodulatory therapies for lung adenocarcinoma

Incidental finding of extramammary Paget's disease during active surveillance for early‐stage prostate cancer in a prostate biopsy

Introduction Skin tissue contamination within transcutaneous visceral organ biopsies is seldom found. We encountered a rare case of extramammary Paget's disease incidentally diagnosed by prostate biopsy during active surveillance for prostate cancer. Case presentation A 71‐year‐old Japanese patient was diagnosed with prostate cancer, and active surveillance was selected. After 1 year, prostate biopsy was performed by a transperitoneal approach, and 16 biopsy cores were taken. One biopsy core contained skin tissue showing extramammary Paget's disease. Careful skin examination confirmed the presence of an extramammary Paget's disease lesion in the left perineum, and curative surgical resection was performed. Recurrence and metastasis did not occur after 6 months of follow‐up. Conclusion Although the perianal region is a common site of extramammary Paget's disease, early‐stage extramammary Paget's disease is often asymptomatic. Thus, during a transcutaneous biopsy, it is important to consider the appearance of the skin and the pathological features of migrating skin tissue