A case of dermatofibrosarcoma protuberans with neurofibromatous change.

A 31-year-old man with posterior neck mass visited a hospital. The mass recurred four times on the same location during the past 6 years. Needle biopsy diagnosis was suspicious for benign stromal tumor. Tumor excision was performed 3 months after the biopsy. The tumor size was 8.3 × 4.5 cm and was located at subcutaneous tissue. Histologically, main tumor cells showed comma-shaped nuclei, which are same as neurofibroma. Immunohistochemically, tumor cells were positive for vimentin, CD34, but were negative for S-100. Fluorescence in situ hybridization analysis disclosed a split signal of PDGFB gene. Reverse transcriptase-polymerase chain reaction clarified COL1A1 exon 47/PDGFB exon 2 chimeric gene. Final diagnosis was dermatofibrosarcoma protuberans (DFSP) with neurofibromatous change. DFSP with neurofibromatous change is rare and could be misdiagnosed as benign tumor, especially in a biopsy specimen. Molecular diagnosis is a promising aid in a challenging case and in biopsy specimens.

Disseminated carcinomatosis of the bone marrow from rectal cancer: A case report.

A 66-year-old man presented with worsening dyspnea. A colonoscopy revealed an elevated lesion at the rectosigmoid junction. The biopsy specimen and bone marrow aspiration demonstrated adenocarcinoma, leading to a diagnosis of disseminated carcinomatosis of the bone marrow. Because chemotherapy proved effective, he survived until 333 days after admission.

Increased Oxidative Stress Underlies Abnormal Pain Threshold in a Normoglycemic Japanese Population.

Normal-high HbA1c levels are a risk factor for attenuated pain sensation in normoglycemic subjects. It is unclear, however, what mechanisms underlie the pathogenesis of attenuated pain sensation in such a population. We, therefore, explored the relationship between oxidative stress (OS) and pain sensation in a rural Japanese population. A population-based study of 894 individuals (average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold induced by intraepidermal electrical stimulation (PINT) and clinico-hematological parameters associated with OS were evaluated. Univariate linear regression analyses revealed age, BMI, HbA1c, the OS biomarker urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), systolic blood pressure, and decreased Achilles tendon reflex on the PINT scores. Adjustments for age, gender, and multiple clinical measures confirmed a positive correlation between PINT scores and urine 8-OHdG (ß = 0.09, p < 0.01). Urine 8-OHdG correlated positively with higher HbA1c levels and age in the normoglycemic population. Unlike in the normoglycemic population, both inflammation and OS were correlated with elevated PINT scores in IFG subjects. OS may be a major contributing factor to elevated PINT scores in a healthy Japanese population.

Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population.

INTRODUCTION: Small fiber neuropathy (SFN) is an early manifestation in diabetic polyneuropathy (DPN); however, the mechanisms are not fully understood. In diabetes, SFN is presumed to be common in individuals with overt DPN, enhancing activation of polyol pathway, oxidative stress, advanced glycation end products (AGEs), and inflammation. We explored the relationship between clinicohematological factors related to DPN and pain sensation in the Japanese population. RESEARCH DESIGN AND METHODS: We conducted a population-based study, recruiting 1030 individuals (average age 54.4±0.5 years), in 2017, to participate in our Iwaki project. After initial screening by fasting blood glucose and glycohemoglobin A1c (HbA1c) measurements, the subjects were categorized into control (n=894), type 2 diabetes (n=81), and impaired fasting glucose (n=55) groups. Clinical data were gathered, and relationships between pain threshold from intraepidermal electrical stimulation (PINT) and DPN were examined by analysis of variance, post hoc test, and χ2 tests to study correlations among and between groups of the clinical data and DPN. RESULTS: Univariate linear regression analyses showed significant correlations between PINT and serum lipopolysaccharide-binding protein (LBP) level (ß=0.1025, p=0.001). Adjustments for the clinical measurements confirmed a positive correlation (ß=0.070, p=0.034). Logistic regression analysis revealed high LBP value (>6.7 mg/dL) as a significant risk factor toward abnormal PINT (≥0.35 mA). LBP significantly correlated with the high-sensitivity C reactive protein, inflammation marker, elevated similarly in both pre-diabetic and overt-diabetic groups, compared with controls, but it did not correlate with a decreased Achilles tendon reflex. In contrast, urine 8-hydroxy-2'-deoxyguanosine, oxidative stress marker, and pentosidine, AGEs, markedly increased in individuals with type 2 diabetes with high HbA1c. CONCLUSIONS: Individuals with high LBP exhibited an elevated PINT in the Japanese population. Low level of inflammation evoked by metabolic endotoxemia is possibly implicated in the pathophysiology of SFN from pre-diabetic stage.

Corrigendum: Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

[This corrects the article DOI: 10.3389/fendo.2019.00651.].

Diabetes, an independent poor prognostic factor of non-B non-C hepatocellular carcinoma, correlates with dihydropyrimidinase-like 3 promoter methylation.

A concurrent increase in the prevalence of hepatocellular carcinoma (HCC) with that of type 2 diabetes (T2D) and obesity has been reported in the absence of hepatitis B virus surface antigen-negative/hepatitis C virus antibody-negative HCC (NBNC-HCC). However, the prognostic relevance of this association remains unclear. Promoter methylation (PM) of the dihydropyrimidinase-like 3 gene (DPYSL3) has been implicated in virus-related HCC. However, it remains unclear whether T2D influences PM in NBNC-HCC. We determined the influence of T2D on clinicopathological profile and PM of DPYSL3 and CDK2NA in patients with NBNC-HCC who were divided into two groups: non-diabetes (non-DM; n = 46) and diabetes (DM; n = 47). DM was associated with a higher Union for International Cancer Control grade, marginal vascular invasion and tumour cell proliferation irrespective of the duration of T2D as well as higher rates of PM of DPYSL3 than non-DM; however, PM of CDK2NA was similar between both groups. PM of DPYSL3 reduced its expression which inversely correlated with reduced patient survival. In conclusion, T2D is associated with poor prognosis of NBNC-HCC in which a high frequency of PM of DPYSL3 may play a pivotal role in its pathogenesis.

Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

Purpose: Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population. Methods: A population-based study of 894 individuals (352 men, 542 women; average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) in the 2017 Iwaki project were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold for intraepidermal electrical stimulation (P-IES) and parameters associated with metabolic syndrome were examined. Results: P-IES was elevated with increasing of age in women but not in men. Average P-IES (mA) was increased in IFG subjects (n = 55, 0.20 ± 0.03) compared with normoglycemic/non-IFG individuals (n = 894, 0.15 ± 0.11) (p < 0.01). It was comparable between IFG and a group of normal high HbA1c (5.9-6.4%). Univariate linear regression analyses showed no influence of sex, triglyceride, or cholesterol on the value of P-IES. In contrast, there were significant correlations between P-IES and serum HbA1c level (ß = 0.120, p < 0.001) Adjustments for the multiple clinical measurements confirmed positive correlation of P-IES with HbA1c (ß = 0.077, p = 0.046). Conclusion: Individuals with normal high HbA1c exhibited an elevated P-IES in a healthy Japanese population which may be useful for the screening of subclinical DPN.

Signet-ring Cell Carcinoma in Hyperplastic Polyp of the Stomach.

Signet-ring cell carcinoma rarely occurs in gastric hyperplastic polyps, with only a few such cases reported. We treated a 76-year-old woman with a signet-ring cell carcinoma arising from a hyperplastic polyp. She had been diagnosed with a gastric hyperplastic polyp four years previously. A follow-up endoscopic examination revealed the lesion in the polyp. A biopsy showed signet-ring cell carcinoma. Hybrid endoscopic submucosal dissection with snaring and a histological examination revealed signet-ring cell carcinoma in a hyperplastic polyp. The polyp was completely excised, with no evidence of recurrence one year later. A hyperplastic polyp of the stomach may transform into adenocarcinoma of an undifferentiated type.

Investigation of Paraffin-embedded Basal Cell Carcinoma Using Electron Paramagnetic Resonance.

Basal cell carcinoma (BCC) in paraffin-embedded specimens was investigated by nondestructively electron paramagnetic resonance (EPR) and X-band (9.45 GHz) EPR imaging (EPRI). A histopathological examination of specimens showed the melanin contents and revealed that they were predominantly of the nodular types. A single-line EPR pattern was observed in the BCC specimens, and the spectra of the samples were analyzed using linewidth and spectral pattern parameters. The eumelanin-related radical was observed in paraffin-embedded BCC specimens. The stability of the radical was supported by sepia pigment experiments. The g-value and peak-to-peak linewidths (ΔHpp) were 2.0046 and 0.61 ± 0.02 mT (mean ± SEM), respectively. Strong EPRI signals correspond to areas of strong pigmentation in the samples. Thus, histopathological examination, EPR, and EPRI of BCC specimens showed that the radical distribution reflects on the spatial distribution of pigments in the samples.

Worsened outcome in patients with pancreatic ductal carcinoma on long-term diabetes: association with E-cadherin1 (CDH1) promoter methylation.

Prevalence of pancreatic ductal carcinoma (PDC) is nearly twice in patients with diabetes mellitus, but the reason for this close association remains obscure. Recently promoter methylation of E-cadherin1 (CDH1) and CDKN2A genes, encoding E-cadherin and P16 respectively, are invoked in development of PDC. It is still unclear whether diabetes affects such epigenetic changes and malignant behavior in PDC. In this study, we studied whether diabetes influences the clinico-pathological profile and methylation status of CDH1 and CDKN2A genes in patients with PDC. PDC subjects were divided into 3 groups; 59 cases without diabetes (non-DM), 17 cases with short-term diabetes (short-DM)(diabetes duration 3 yrs>) and 33 cases with long-term diabetes (long-DM)(≧3 yrs). Compared to non-DM or short-DM, long-DM was associated with a higher histological grade of malignancy and a higher tumor stage. Promoter methylation of both CDH1 and CDKN2A was encountered more frequently in PDC patients with long-DM than non-DM or short DM. Cases with CDH1 promoter methylation showed reduced E-cadherin expression and worsened survival. We consider that the presence of long-DM has a negative impact on the prognosis of PDC patients which may be relevant to a high frequency of promoter methylation of CDH1.

Skin hamartoma on the hand of a newborn infant.

Skin hamartoma is an extremely rare disease on the hand in newborn infants. Reported herein is the case of a newborn infant who presented with a skin hamartoma on the hand. The patient was a girl born at 37 weeks of gestational age. The mass was seen on her proximal left thumb at birth. The mass had a spherical diameter of 4 cm and was pedunculated. One the day after birth, the stalk on the mass was ligated in the neonatal intensive care unit. The mass was diagnosed as skin hamartoma on histopathology. At 1 year of age, the child had good hand function, and no recurrence of the neoplasia was evident.

Neuropathy induced by exogenously administered advanced glycation end-products in rats.

UNLABELLED: Aims/Introduction: Advanced glycation end-products (AGE) have been implicated in the development of diabetic neuropathy. It still remains unknown, however, how AGE cause functional and structural changes of the peripheral nerve in diabetes. To explore the role of AGE in diabetic neuropathy, we examined the peripheral nerve by injecting AGE into normal Wistar rats. MATERIALS AND METHODS: Young, normal male Wistar rats were injected intraperitoneally (i.p.) daily for 12 weeks with purified AGE prepared by incubating D-glucose with bovine serum albumin (BSA). A control group received BSA alone. A group of rats given AGE were co-treated with aminoguanidine (50 mg/kg/day, i.p.). Peripheral nerve function and structure, as well as nerve Na(+),K(+)-ATPase activity, were examined in these rats. Immunohistochemical expressions of 8-hydroxy-2'-deoxyguanosine (8OHdG) and nuclear factor-κB (NF-κB)p65 were also examined. RESULTS: Serum AGE levels were increased two to threefold in the AGE-treated group compared with those in the BSA-treated control group. AGE-treated rats showed a marked slowing of motor nerve conduction velocity (MNCV) and decreased nerve Na(+),K(+)-ATPase activity compared with those in the BSA-treated group. These changes were accompanied by intensified expressions of 8OHdG and NF-κBp65 in endothelial cells and Schwann cells. Aminoguanidine treatment corrected MNCV delay, Na(+),K(+)-ATPase activity, and suppressed the expression of 8OHdG and NF-κB, despite there being no influence on serum AGE levels. CONCLUSIONS: The results suggest that an elevated concentration of blood AGE might be one of the contributing factors to the development of neuropathic changes in diabetes.

[A case of brain nocardiosis successfully treated with minocycline].

A 60-year-old man with surgically treated nocardia pyothorax was referred to our hospital since he became drowsy. Brain MRI revealed multiple brain abscesses. His cerebrospinal fluid (CSF) showed increase in polymorphonuclear cells and decrease in glucose. Since he was allergic to sulfamethoxazole * trimethoprim, ceftriaxone and then minocycline were given. Minocycline resulted in dramatic improvement of neurological symtoms, MRI findings and CSF cell count. PCR analysis of 16S ribosomal DNA using his resected thoracic wall revealed that nocardia from his tissue was strain IFM0860. Strain IFM0860 nocardia was found to be sensitive to minocycline but not to sulfamethoxazole * trimethoprim and ceftriaxone. Intravenous administration of minocycline was followed by three-year per os administration of minocycline during which he had no recurrence of brain abscess. Thus, brain nocardiosis could be successfully treated with appropriate antibiotics. The lesson from the present case is that identification of the type of nocardia by PCR analysis of 16S ribosomal DNA could help accomplish tailor-made antibiotic therapy.

Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix.

Epithelial neoplasms of appendix are infrequent, and their pathological features are not fully characterized. We collected 33 cases of appendiceal tumors and examined immunohistochemically the expression of cytokeratins (CK, CK7, and CK20), mucin core protein (MUC1, MUC2, MUC5AC, and MUC6), E-cadherin, chromogranin A, and p53 protein. Gene analysis of TP53 was also conducted on exons 5 to 8. Clinically, mucinous tumors were predominant in females. Immunohistochemically, all the tumors expressed CK20, whereas CK7 was positive in one third of the cases. Similarly, MUC2 was expressed in all the tumors, whereas MUC1 and MUC5AC were detected in about a half of the cases. Although chromogranin A-positive cells are generally sparse in normal appendix, they were more common in mucinous tumors than in nonmucinous tumors. Contrary to the previous data reported (Mod Pathol 2002;15:599-605), mucinous carcinoma exhibited a higher frequency of p53-positive cells (mean 29%) compared with mucinous adenoma (2.8%) (P < .001), whereas nonmucinous tumors showed high levels of p53-positive cells to similar extent (51%-67%) in both adenoma and carcinoma. The high expression of p53 protein coincided with the presence of mutations in multiple sites of TP53 gene in mucinous tumors. This is the first report that characterized the immunophenotypic profile of appendiceal epithelial neoplasms with an emphasis of a higher frequency of p53 positivity in mucinous carcinoma cases compared with mucinous adenoma in the appendix.