Evaluation of Combined p57KIP2 Immunohistochemistry and Fluorescent in situ Hybridization Analysis for Hydatidiform Moles Compared with Genotyping Diagnosis.

Immunostaining with p57KIP2 is a widely used diagnostic technique to differentiate complete hydatidiform moles (CHMs) from partial hydatidiform moles (PHM) and non-molar hydropic abortion. However, distinguishing between PHMs and non-molar hydropic abortions using histopathology alone is often challenging. This study aimed to evaluate the technical validity and additional benefits of using fluorescence in situ hybridization (FISH) in combination with p57KIP2 immunostaining to diagnose molar and non-molar conceptuses. The study involved 80 specimens, which underwent genetic diagnosis using short tandem repeat analysis, including 44 androgenetic CHMs, 20 diandric monogynic PHMs, 14 biparental non-molar hydropic abortions, 1 monoandric digynic triploid abortion, and 1 vaginal specimen of gestational trophoblastic neoplasia. Two pathologists independently diagnosed the cases based on morphology and p57KIP2 immunostaining while the clinical information was masked. FISH analysis was performed using 3 probes (CEP17, CEPX, and CEPY), which revealed that all androgenetic CHM and biparental diploid non-molar hydropic abortion specimens were diploid. Among the 20 diandric monogynic PHM cases examined by analyzing short tandem repeat polymorphisms, 18 were triploid, and the remaining 2 were diploid. These two specimens were possibly androgenetic/biparental mosaics based on FISH analysis, where the three-signal ratios counting 50 cells were clearly within the diploid ranges. Eight of the 20 genetic PHMs and 2 of the 14 genetically confirmed non-molar hydropic abortions that were falsely diagnosed based on morphology and immunohistochemistry by at least 1 pathologist were correctly diagnosed as PHM and non-molar hydropic abortion, respectively, by FISH analysis. However, 1 monoandric digynic villus was classified as triploid by FISH analysis, leading to a false PHM diagnosis. In conclusion, the combination of FISH analysis with p57KIP2 immunostaining helps in diagnosing molar and non-molar conceptuses in numerous cases; nevertheless, exceptional cases should be considered.

Relapsing Polychondritis Complicated by Vasculitis of the Omentum.

A 78-year-old man presented with bilateral auricular and nasal chondritis and an inner ear disorder. Relapsing polychondritis (RPC) was diagnosed and corticosteroid therapy was initiated. Two years later, he developed abdominal pain and a fever. A contrast-enhanced computed tomography scan showed enhancement of the mesentery and massive ascites. The patient underwent emergency laparotomy, which revealed inflammation and thickening of the omentum. A microscopic examination of the omentum disclosed vasculitis, and corticosteroid and cyclophosphamide pulse therapies were administered. We herein report the first case of RPC complicated by pathologically proven vasculitis of the omentum, clearly indicating an association between the pathogenesis of these two conditions.

Therapeutic dose of acetaminophen as a possible risk factor for acute kidney injury: learning from two healthy young adult cases.

Acetaminophen overdose can lead to severe liver and kidney failure; however, the risk of therapeutic doses in healthy individuals causing acute kidney injury (AKI) is less clear. We herein describe the cases of two young adults with renal biopsy-proven acute tubular necrosis under a therapeutic dose of acetaminophen. The first patient exhibited mild reversible renal insufficiency, whereas, in the second case, the patient demonstrated a slightly increased serum creatinine level and enlarged kidneys and the administration of contrast media and antibiotics may have worsened the renal dysfunction, leading to the need for temporal hemodialysis. Physicians should be aware of the risk of acetaminophen causing AKI and avoid administering other nephrotoxic agents in such cases.

Severely fluctuating blood glucose levels associated with a somatostatin-producing ovarian neuroendocrine tumor.

CONTEXT: Somatostatin-producing tumors are a rare type of neuroendocrine tumor. Their effects on blood glucose levels have been variously reported, and detailed reports have been scarce. OBJECTIVE: The aim of this study was to identify the reasons for the extraordinary blood glucose fluctuations in a case with no previous history of diabetes. PATIENTS AND METHODS: A 68-yr-old nondiabetic woman with an ovarian tumor was suffering from hyper- and hypoglycemia. Based on the results of an oral glucose tolerance test and continuous glucose monitoring, we speculated that the fluctuating blood glucose level was accompanied not only by a low insulin level but also by low counter-regulatory hormones levels, and that those broad hormonal suppressions were caused by a high somatostatin level produced in the ovarian tumor. We performed an oophorectomy and assessed the pathology of the tumor and changes in the blood glucose profile as well as hormonal levels postoperatively. RESULTS: The blood glucose level was completely normalized after the oophorectomy. Insulin secretion was also normalized. Histological examination showed that the tumor comprised a mature cystic teratoma and a stromal carcinoid. Immunohistochemically, the stromal carcinoid component was positive for somatostatin. The somatostatin level was 8505 pmol/liter preoperatively, which dropped down to 71.5 pmol/liter postoperatively. We found two previous reports of somatostatin-producing ovarian neuroendocrine tumors. Somatostatin levels among cases of ovarian origin were much higher than those among cases of gastrointestinal origins, and cases of ovarian origin all experienced blood glucose fluctuations. CONCLUSION: Extremely high somatostatin levels and blood glucose fluctuations may be characteristics of somatostatin-producing ovarian neuroendocrine tumors.

Drug-induced acute interstitial nephritis mimicking acute tubular necrosis after initiation of tenofovir-containing antiretroviral therapy in patient with HIV-1 infection.

We describe a case of 68-year-old Japanese man with HIV-1 infection who developed acute kidney injury with prominent tubular dysfunction immediately after starting tenofovir-containing antiretroviral therapy. Antiretroviral therapy was discontinued in two weeks but renal function, as well as tubular function, did not shown full recovery even at a 3-year follow-up examination. Acute tubular necrosis, a rare but well-known side effect of tenofovir, was suspected, but kidney biopsy confirmed interstitial nephritis. It is important to distinguish drug-induced interstitial nephritis from acute tubular necrosis, because early steroid administration can improve renal dysfunction caused by acute interstitial nephritis.

Histological features of nodular gastritis and its endoscopic classification.

OBJECTIVES: To clarify the histological features and endoscopic classifications of nodular gastritis (NG). METHODS: Overall 40 996 patients who had undergone an upper gastrointestinal endoscopy were enrolled. NG is defined as a uniform and diffuse protrusion from the antrum to angulus, which has two types at endoscopy: nodular (N) and granular (G). Three biopsy specimens were taken from the antrum, angulus and corpus. The histological features were evaluated using the updated Sydney System (USS). The topography of gastritis (antrum-predominant, pangastritis or corpus-predominant) and the prevalence of lymphoid follicles were also investigated. RESULTS: Overall 89 patients (0.22%) were diagnosed with NG, which tended to decrease in prevalence over age and predominantly affected women. All the patients were Helicobacter pylori-positive. Among these, 65 patients underwent biopsy. Activity and inflammation were mostly moderate or severe, while intestinal metaplasia and atrophy were mostly absent at all three sites. Pangastritis was the most frequent (72%) type of gastritis. Lymphoid follicles were found in 69% at the antrum, 65% at the angulus and 51% at the corpus. There were no significant differences between N and G types in clinical features, USS scores, topography of gastritis, and prevalence of lymphoid follicles. CONCLUSIONS: Atrophy and intestinal metaplasia are rare but activity and chronic inflammation are severe at the antrum, angulus and corpus in NG. Pangastritis is the commonest type of gastritis. Lymphoid follicles affect everything up to the upper corpus, contrary to endoscopic protrusion found only at angulus. There was no correlation with pathological features between N and G types.

Diagnostic value of antigenemia assay for cytomegalovirus gastrointestinal disease in immunocompromised patients.

AIM: To investigate the utility of the cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV gastrointestinal disease (GID). METHODS: One hundred and thirty immunocompromised patients were enrolled in this study. Patients with a history of anti-CMV treatment and who had not undergone examination using the antigenemia assay were excluded. CMV-GID was defined as the detection of large cells with intranuclear inclusions alone or associated with granular cytoplasmic inclusions by biopsy. Biopsy sections were stained with hematoxylin and eosin and immunohistochemically stained with anti-CMV. We evaluated the association between CMV-GID and patient characteristics (symptoms, underlying disease, medication, leukocyte counts, and antigenemia assay). All patients were checked with an human immunodeficiency virus (HIV) antibody test before endoscopic examination. White blood cell (WBC) counts were obtained from medical records within 1 wk of endoscopy. Leukopenia was defined as a total WBC count < 5000 cells/mm(3). For HIV patients, we also checked CD4+ counts from medical records. RESULTS: A total of 99 patients were retrospectively selected for analysis. Of the immunocompromised patients, 19 had malignant disease, 18 had autoimmune disease, 19 had disorders of biochemical homeostasis, three had undergone transplantation, and 45 had HIV infection. A total of 50 patients had received immunosuppressive therapy. No patients had inflammatory bowel disease. Fifty-five patients were diagnosed as having CMV-GID. Univariate analysis indicated an association between HIV infection, leukopenia, and positive antigenemia and CMV-GID (P < 0.05). Multivariate analysis using logistic regression revealed that HIV infection and positive antigenemia were the only independent factors related to CMV-GID (P < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of antigenemia for CMV-GID were 65.4%, 93.6%, 91.9%, and 71.0%, respectively. In a subgroup analysis, patients with leukopenia displayed low sensitivity and high specificity. Minimal differences in accuracy were seen among patients with or without leukopenia. HIV-infected patients displayed low sensitivity and high specificity. Accuracy barely differed between HIV-positive and -negative patients. In HIV-infected patients, CD4 count < 50 cells/µL resulted in low sensitivity and high specificity. Differences in accuracy among patients were minor, regardless of CD4 count. In patients who had undergone both quantitative real-time polymerase chain reaction (PCR) and antigenemia assay, real-time PCR was slightly more accurate in terms of sensitivity than the antigenemia assay; however, this difference was not statistically significant (P = 0.312). CONCLUSION: If the antigenemia test is positive, endoscopic lesions are acceptable for the diagnosis of CMV-GID without biopsy. The accuracy is not affected by HIV infection and leukopenia. Either PCR or the antigenemia assay are valid.

Predictability of Gastric Intestinal Metaplasia by Mottled Patchy Erythema Seen on Endoscopy.

BACKGROUND: Intestinal metaplasia (IM) is regarded as a premalignant lesion. However, endoscopic diagnosis of IM has been considered difficult. Using endoscopy, we found a unique pattern of erythema, "Mottled Patchy Erythema (MPE)," which includes severe IM. Helicobacter pylori (Hp) infection itself can cause erythema, which reflects histologic changes in the gastric mucosa. Therefore we enrolled Hp eradication patients to validate the relation between MPE and pathologic findings. METHODS: We enrolled patients with chronic gastritis who underwent successful Hp eradication at least 6 months before the study. We defined MPE as multiple flat or depressed erythematous lesions. When encountering MPE on endoscopy, we performed biopsy on both the MPE site and non-MPE site. The non-MPE site was defined as an adjacent mucosa located within 3 cm of the MPE site. All biopsy specimens were evaluated immunohistochemically for IM subtype using MUC2, MUC5AC, MUC6, CD10, and CDX2 stains. The degree of IM was defined according to the Updated Sydney System. The diagnostic accuracy of the MPE findings for pathologic IM was calculated. The relation between MPE and IM subtype was also assessed. RESULTS: A total of 102 patients were selected for the study. Of these, 55 (54%) patients had MPE. Biopsy specimens were taken from the MPE sites and non-MPE sites from these 55 patients. The IM percentages and median scores of IM were both significantly higher at the MPE sites (P < 0.001) than at the non-MPE sites. The sensitivity and specificity for MPE in the detection of histologic IM were 72.7% and 84.1%, respectively. No significant associations were observed in the expression of MUC2, MUC5AC, MUC6, CD10, and CDX2 between the MPE sites and non-MPE sites. There were no significant differences in the ratios (complete/incomplete) of IM subtypes between the two groups. CONCLUSIONS: MPE is a useful endoscopic finding to detect histologic IM without the use of chromoendoscopy and magnifying endoscopy. However, the IM subtype is difficult to identify. In the era of Hp eradication, MPE has the potential to become a predictive finding for the risk of gastric cancer.

CD44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker.

The expression of variant isoforms of CD44 (CD44v) correlates with the metastatic potential of various carcinomas. In endometrial cancer, however, the significance of CD44v-expression as a prognostic indicator has not been fully investigated, nor has it been compared with that of p53, estrogen receptor or Ki67. Surgical material consisted of 14 atypical endometrial hyperplasias (AEH) and 163 endometrial carcinomas (EC). Expression of CD44s, v3 and v6 in carcinoma tissue, and other prognostic markers were immunohistochemically evaluated. The expression in the squamous differentiation was strictly excluded for the evaluation of immunohistochemistry, because the significance was different from that in the adenocarcinoma component. CD44s was frequently expressed in AEH and EC. On the other hand, CD44v3- and v6-positivities were rare or nonexistent in AEH, but were observed in 8 and 35% of EC, respectively. CD44v3-expression correlated significantly with histologic grade and lymph node metastasis. However, there was no correlation between CD44v6 expression and any clinicopathologic factor, nor were other prognostic markers expressed. Univariate analysis revealed that each CD44 was a prognostic determinant in the patients with EC. However, employing multivariate analysis, there were only three independent factors: p53 overexpression, CD44v6 expression and myometrial invasion. CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients with EC.