New Histologic Finding of Amyloid Insulin Bodies at an Insulin Injection Site in a Patient With Diabetes.

Amyloidosis is a heterogeneous group of protein deposition diseases with more than 40 known clinical presentations. Localized amyloidosis occurs when the protein deposits exist in a singular location. Patients with diabetes mellitus who inject insulin at the same site can develop localized insulin-derived amyloidosis (AIns) at the injection site, which can be confused clinically with lipoma, lipohyperplasia, lipoatrophy, and fat necrosis. Histologic examination is performed to confirm localized AIns. We report a case of a patient with a long history of type 2 diabetes who presented with a subcutaneous mass in the abdomen at a preferred insulin injection site. Examination by light microscopy revealed diffuse deposition of eosinophilic material. Two of the tissue fragments contained numerous 30-40 µm spherical bodies within the eosinophilic material. The bodies had dark centers with peripheral eosinophilic material. Polarized sections stained with Congo red showed apple green birefringence, a characteristic of amyloid. Immunohistochemistry was positive for insulin antibodies in the dark spherules and the surrounding matrix. Proteomic analysis by mass spectrometry showed that the Congo red-positive material was insulin. Electron microscopy showed a background matrix consisting of nonbranching protein fibrils measuring 8.8-16.1 nm, consistent with amyloid; the spherules contained dark globular proteins in the center surrounded by nonbranching fibrillary proteins. Because these spherules were positive for insulin by immunohistochemistry and showed amyloid ultrastructurally, we refer to them as amyloid insulin bodies. The identification of AIns, specifically with amyloid insulin bodies, is important for diagnosis and treatment and may further our understanding of amyloidogenesis.

Erratum to: A case of B-cell acute lymphoblastic leukemia in a child with Down syndrome bearing a t(2;12)(p12;p13) involving ETV6 and biallelic IGH@ rearrangements.

[This corrects the article DOI: 10.1186/s40364-015-0036-1.].

A case of B-cell acute lymphoblastic leukemia in a child with Down syndrome bearing a t(2;12)(p12;p13) involving ETV6 and biallelic IGH@ rearrangements.

BACKGROUND: Rearrangements involving ETV6 (12p13) are among the most common structural abnormalities in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and involve numerous partner genes. Additionally, the t(8;14)(q11.2;q32), which can result in the placement of CEBPD (8q11.2) near the regulatory regions of IGH@ (14q32) and consequent overexpression of CEPBD, occurs at a higher frequency in individuals with Down syndrome-associated ALL (DS-ALL) compared to both the general and pediatric population. The coexistence of cytogenetically detectable ETV6 abnormalities and t(8;14)(q11.2;q32) is a rare occurrence in B-ALL and has only been reported in a single case in the literature. FINDINGS: Herein, we present a case of B-ALL in a 9-year old male with Down syndrome in which conventional cytogenetic analysis revealed two reciprocal translocations: a t(8;14)(q11.2;q32) and a t(2;12)(p12;p13). Interphase and metaphase fluorescence in situ hybridization (FISH) analysis using break apart probes confirmed the involvement of IGH@ and ETV6 in these translocations, respectively. Additionally, interphase FISH revealed a clonal subpopulation bearing biallelic IGH@ rearrangements not observed by conventional cytogenetic analysis. CONCLUSIONS: To the best of our knowledge, this is the first reported case of B-ALL bearing an ETV6 translocation with a partner gene on the short arm of chromosome 2 confirmed by FISH. Additionally, it is the second reported case of t(8;14)(q11.2;q32)-ALL bearing a concomitant, cytogenetically detectable abnormality involving ETV6. This case provides insight into a novel translocation involving ETV6 as well as potentially unique and understudied mechanisms of clonal evolution in pediatric B-ALL.

A novel method of esophageal lengthening in a large animal model of long gap esophageal atresia.

PURPOSE: Long gap esophageal atresia remains a significant treatment challenge. We aimed to create the first large animal model of long gap esophageal atresia to test a degradable esophageal lengthening device. METHODS: The distal esophagus was divided 2 cm above the gastroesophageal junction in 6 minipigs. A polycaprolactone (PCL) spring device was secured inside the distal esophageal segment, and the end was oversewn. Nonexpanding PCL tubes served as controls. An esophagogastric anastomosis was created to restore continuity. After 4 weeks, the distal esophageal pouch was analyzed. RESULTS: The distal esophageal pouch of experimental animals increased in length from 1.9 to 4.5 cm. Control animals demonstrated no change. When comparing lengthened to native esophagus, there was no difference in the thickness of muscularis mucosa or muscularis propria. Mechanically lengthened esophagus showed mild to moderate superficial inflammation and fibrosis. There were no differences in the number of myenteric or submucosal ganglia. CONCLUSION: We created the first porcine model of long gap esophageal atresia and lengthened the distal esophagus with an internally placed device. This model may be used to explore novel therapies in the management of long gap esophageal atresia.

Core needle biopsy is a safe and accurate initial diagnostic procedure for suspected lymphoma.

BACKGROUND: Excisional biopsy is currently recommended for the analysis of lymphadenopathy suspicious for lymphoma. This study aims to evaluate the efficacy and safety of image-guided core needle biopsy (IGCNB) for the diagnosis of lymphoma using a standard protocol for tissue acquisition and analysis. METHODS: All IGCNBs from 2008 to 2014 performed under the study protocol were included in analysis. Demographics, pathology results, additional studies, and follow-up information were recorded. RESULTS: Seventy-three IGCNBs were performed in 71 consecutive patients. Lymphoma was diagnosed in 37 patients (51%). All 37 patients (100%) were subtyped and treated based on IGCNB results. The remaining 36 IGCNBs in 34 patients did not have subsequent diagnosis of lymphoma in a mean follow-up of 15 months (range, 0 to 54 months). There were no complications. CONCLUSIONS: IGCNB performed under a standard protocol is effective and safe and should be considered as an initial diagnostic tool for the evaluation of lymphadenopathy suspicious for lymphoma.

Alcoholic liver disease patients treated with S-adenosyl-L-methionine: an in-depth look at liver morphologic data comparing pre and post treatment liver biopsies.

BACKGROUND: The objective of this study is to assess if there were any changes in liver biopsies after treatment with S-adenosyl-L-methionine(SAMe) in alcoholic liver disease patients. METHODS: Liver biopsies of 14 patients were randomized for SAMe treatment at week 0 (biopsy #1) and at 24 weeks (biopsy #2). Patients received 1.2g of SAMe or placebo by mouth daily and stopped alcohol intake. Biopsies were semi-quantitatively scored for: steatosis, inflammation, necrosis, fibrosis, apoptosis by TUNEL stain, percent fibrosis per square field, smooth muscle actin stain, Kupffer cells, polymorphonuclear leukocytes, lipogranules, lymphocytes, balloon cell formation, Mallory-Denk bodies, and duct metaplasia. RESULTS: Comparing treatment arm to placebo arm, no significant difference was found between biopsy #1 and biopsy #2. However, when both study arms were grouped together, there was decrease in smooth muscle actin stain, where the P-value=0.027. CONCLUSION: Treatment with SAMe did not show a statistically significant difference in the characteristics studied. However, when both the treatment and placebo arm data were grouped together to increase the n and power, there was a decrease in the smooth muscle actin stain, reflecting a decrease in stellate cells activation, likely due to the alcohol abstinence. This study suggests that it may not be beneficial to wait for more definitive treatment, like liver transplant in alcoholic liver disease patients, since the liver tissue remained largely with the same degree of pathology six months out, regardless of treatment.