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Introduction: Adult T-cell leukaemia/lymphoma (ATL) caused by human retrovirus, HTLV-1, is a neoplasm of mature T-cell. In Japan, more than a thousand patients with ATL die every year because this disease still remains incurable. Acute crisis is a common phenomenon of chronic leukaemia and indolent haematological malignancy, in which proliferation of leukaemic cells is accelerated following a certain term of chronic phase. Although some genetic changes are thought to be responsible for this sudden change of characteristics in leukaemic cells, it has been unclear if they are the cause or the result of crisis. Methods: We assessed the therapy and outcome of 79 newly diagnosed or referred ATL patients from 2005 to 2010. Serum sample of patient was preserved in freezer to measure the level of soluble proteins, sCD30 and sIL-2R, using ELISA. The sIL-2R concentration in serum was measureed by Cell freeN IL-2R (Kyowa Medex, Japan) and Determiner CL IL-2R (Kyowa Medex, Japan). The sCD30 concentration in serum was measured by Human sCD30 Platinum ELISA (eBioscience). In the present study, patients with ATL chronic type were investigated by monitoring changes in the serum levels of sIL-2R and sCD30. Results: Six patients showed acute crisis from chronic phase (the observed periods of chronic phase are 31–866days) and increasing sCD30 level as well as sIL-2R elevation was found as an earlier event of the acute crisis (average levels of sCD30 and sIL-2R were 2029U/ml and 14035U/ml in acute crisis; 341U/ml and 5008U/ml in chronic phase). In contrast, average of sCD30 and sIL-2R in 25 HTLV-1 carriers are 37U/ml and 428U/ml, respectively. Although the patterns and levels of soluble proteins elevation were unique to each case, serum sCD30 level predominantly elevated at the crisis. Interestingly, CD30 is not always detected on the surface of ATL cells. Chronic inflammation caused by constituvive activation of STATs may be associated with Matrix Metalloproteinase activation which sheds CD30 from the surface of ATL cells. Conclusion: Our findings suggest that soluble protein levels in sera of patients are useful biological markers for diagnosis and therapy of ATL. Furthermore, since spontaneous remission was observed during the insufficinet level of serum sCD30 by comparison to the sIL-2R level, it is conceivable that the sCD30 protects CD30+ leukaemic stem cells from CD30 ligand-mediated cell death. [Copyright &y& Elsevier]

Context.—: Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5th edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphologic criteria used for biopsy specimens in real-world practice remains undetermined., Objective.—: To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies., Design.—: We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis., Results.—: The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization., Conclusions.—: The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Aim: To assess for any additive value of hydroxychloroquine (HCQ) in Japanese patients with systemic lupus erythematosus (SLE) depending on calcineurin inhibitors (CNIs)., Methods: We retrospectively evaluated patients with SLE who visited our hospital from 2015 to 2016 and were taking prednisolone (PSL) at <20 mg/d and one immunosuppressant (IS). Patients were divided into two groups depending on HCQ use and the groups were compared for changes in SLE Disease Activity Index (SLEDAI), prednisolone (PSL) dose, and cumulative flare rate between patients who were treated and not treated with CNI., Results: Among the 103 patients evaluated, 19 (18.4%) were treated with HCQ. On analysis of all patients, SLEDAI, PSL doses, and cumulative flare rate were significantly reduced in patients who received HCQ compared to those who did not (P = 0.04, P = 0.01, and P = 0.03, respectively). Regarding IS use, we found less additive therapeutic effect in CNI users than in users of other ISs in terms of reduction in SLEDAI and PSL dose (P = 0.05 and P < 0.01, respectively)., Conclusions: The addition of HCQ reduced disease activity, PSL dose, and flares in Japanese SLE patients but conferred less additive clinical efficacy when added to CNIs., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

Accurate distinction of clear cell carcinoma (CCC) from endometrioid carcinoma (EC) has important clinical implications, but, not infrequently, EC demonstrates clear cell change (EC-CC), mimicking CCC. We examined whether a panel of immunomarkers can help distinguish between these tumors. Sixty-four CCCs (40 ovarian and 24 uterine), 34 ECs (21 ovarian and 13 uterine), and 34 EC-CCs (6 ovarian and 28 uterine) were stained for HNF1β, BAF250a, Napsin A, ER, and PR. Intensity and extent of immunoreactivity was assessed. Fifty-seven of 64 (89%) CCCs, 14/34 (41%) EC-CCs, and 16/34 (47%) ECs expressed HNF1β, and 56/64 (88%) CCCs, 4/34 (12%) EC-CCs, and 1/34 (3%) ECs stained for Napsin A. Most CCCs demonstrated at least moderate and diffuse staining for both markers, whereas only focal and weak expression was identified in most EC-CC/EC. Compared to HNF1β, Napsin A showed increased specificity (93.0% vs. 55.9%, P<0.0001) and similar sensitivity (87.5% vs. 89.1%) in distinguishing CCC from EC-CC/EC. Thirteen of 64 (20%) CCCs, 6/34 (18%) EC-CCs, and 2/34 (6%) ECs showed loss of BAF250a. ER was expressed by 10/64 (16%) CCCs, 30/34 (88%) EC-CCs, and 33/34 (97%) ECs, whereas PR positivity was identified in 9/64 (14%) CCCs, 26/34 (77%) EC-CCs, and 33/34 (97%) ECs. The majority of EC and EC-CC demonstrated diffuse staining for ER/PR, whereas most CCCs showed very focal positivity. There is a statistically significant difference in HNF1β, Napsin A, ER, and PR immunoexpression between CCC and EC/EC-CC, with Napsin A being a more specific marker for CCC than HNF1β. Overall, the immunoprofile of EC-CC is more comparable to that of EC than CCC. The use of a panel of immunostains can help distinguish EC-CC from CCC.

Background/aims: The Japanese National Hospital Organization evidence-based medicine (EBM) Study group for Adverse effects of Corticosteroid therapy (J-NHOSAC) is a Japanese hospital-based cohort study investigating the safety of the initial use of glucocorticoids (GCs) in patients with newly diagnosed autoimmune diseases. Using the J-NHOSAC registry, the purpose of this observational study is to analyse the rates, characteristics and associated risk factors of intracellular infections in patients with newly diagnosed autoimmune diseases who were initially treated with GCs., Methodology/principal Findings: A total 604 patients with newly diagnosed autoimmune diseases treated with GCs were enrolled in this registry between April 2007 and March 2009. Cox proportional-hazards regression was used to determine independent risk factors for serious intracellular infections with covariates including sex, age, co-morbidity, laboratory data, use of immunosuppressants and dose of GCs. Survival was analysed according to the Kaplan-Meier method and was assessed by the log-rank test. There were 127 serious infections, including 43 intracellular infections, during 1105.8 patient-years of follow-up. The 43 serious intracellular infections resulted in 8 deaths. After adjustment for covariates, diabetes (Odds ratio [OR]: 2.5, 95% confidence interval [95% CI] 1.1-5.9), lymphocytopenia (≦1000/μl, OR: 2.5, 95% CI 1.2-5.2) and use of high-dose (≧30 mg/day) GCs (OR: 2.4, 95% CI 1.1-5.3) increased the risk of intracellular infections. Survival curves showed lower intracellular infection-free survival rate in patients with diabetes, lymphocytopaenia and high-dose GCs treatments., Conclusions/significance: Patients with newly diagnosed autoimmune diseases were at high risk of developing intracellular infection during initial treatment with GCs. Our findings provide background data on the risk of intracellular infections of patients with autoimmune diseases. Clinicians showed remain vigilant for intracellular infections in patients with autoimmune diseases who are treated with GCs.

Aim: CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients., Material and Methods: Paraffin-embedded surgical tissue samples from 25 patients with ovarian serous and endometrioid adenocarcinoma were stained with anti-CD147 antibody (monoclonal antibody 12C3: MoAb 12C3) for immunohistochemical analysis., Results: CD147 protein was expressed in 84.0% (21 of 25 cases) of cancerous lesions, but not in normal lesions. CD147 expression by ovarian cancer cells was inversely correlated with overall survival. There was no correlation between CD147 expression and histological grade., Conclusions: These results suggest that measurement of CD147 expression may enhance the understanding of the pathophysiology of epithelial ovarian cancer., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

A subset of endocervical-type mucinous adenocarcinomas (ACs) of the uterine cervix exhibit a gastric phenotype and morphology, as reported in cases of minimal deviation AC in which the presence of human papillomavirus (HPV) has been rarely detected. To investigate the HPV-independent pathway of carcinogenesis in cases of gastric-type AC, we investigated the common high-risk HPV (hr-HPV) status in 52 nonsquamous cell carcinomas, using a PCR-based typing method and immunohistochemistry of p16INK4a (a cyclin-dependent kinase inhibitor that is overexpressed in both cancerous and precancerous cervical tissue, making it an ideal biomarker for cervical cancer cases). Using novel morphological criteria, seven of 52 (13.5%) carcinomas were designated as gastric-type ACs, all of which were negative for both hr-HPV DNA and p16INK4a. Nongastric-type ACs were frequently positive for both hr-HPV DNA (90%, 28/31) and p16INK4a (94%, 29/31) with adenosquamous and neuroendocrine carcinomas demonstrating the presence of hr-HPV DNA in 86% (6/7) and 83% (5/6) of cases, respectively. In these two types of carcinoma, 86% (6/7) and 100% (6/6) were positive for p16INK4a, respectively. Our data suggests that gastric-type AC appears to represent an oncogenic hr-HPV-independent neoplasm and therefore is a potential pitfall of HPV DNA testing and vaccination.

We examined mortality from adult T-cell leukemia/lymphoma (ATL/ATLL) and other diseases alleged to be associated with human T-lymphotropic virus type I (HTLV-I) among anti-HTLV-I antibody-positive blood donors in Kyushu, Japan. During 1984-87, a total of 3,991 blood donors aged 40 years or over were followed from the date of donation to the date of death or the end of the study. Crude mortality rates from ATL (with 95 percent confidence intervals) were 68 per 100,000 (13-202) for males and 36 per 100,000 (3-132) for females. The rates were underestimated by approximately 50 percent because of self-selection and short observation periods. Neither death rates from other cancers nor death rates from all cancers were elevated.

Plasma gonadotropin levels throughout the regular menstrual cycle in 10 Japanese women were measured daily using radioimmunoassay. At the peak of ovulation, mean FSH levels were 17.6 +/- 7.9 mlU/ml and mean LH levels were 75.2 +/- 26.0 mlU/ml. At midcycle, the mean gonadotropin levels were significantly lower in Japanese women than in Nigerian women who, as reported by Nylander (1973), had a high frequency of twinning. It is, therefore, suggested that the low frequency of dizygotic twinning in Japanese women might be related to their low output of gonadotropin.