Dmitrij Seinin

Discovery of two novel EWSR1/ATF1 transcripts in four chimerical transcripts-expressing clear cell sarcoma and their quantitative evaluation

The most common recurrent translocation in clear cell sarcoma t(12;22)(q13;q12) results in an EWSR1/ATF1 chimeric gene. We present a molecular analysis of tumor overgrowing right proximal tibia with bone destruction metastatic to two groin lymph nodes. Fluorescent in situ hybridization analysis performed on paraffin-embedded tissue sections of primary tumor sample indicated one rearranged locus of EWSR1 gene and one additional red signal. Reverse transcription-polymerase chain reaction analysis revealed the presence of four different EWSR1/ATF1 chimerical transcripts in the tumor sample as well as in both metastatic lymph nodes. Two previously described transcripts EWSR1exon7/ATF1exon5 and EWSR1exon8/ATF1exon4, and two novel transcripts EWSR1exon7/ATF1exon4 and EWSR1exon9/ATF1exon4 were identified. Both novel transcripts were out-of-frame fusions and, therefore, most likely had limited biological impact in oncogenesis of clear cell sarcoma. Quantitative evaluation demonstrated unequal distribution of these transcripts, with EWSR1exon8/ATF1exon4 type being overexpressed.

Clear cell sarcoma expressing a novel chimerical transcript EWSR1 exon 7/ATF1 exon 6

Clear cell sarcoma harbours recurrent translocation, resulting in EWSR1/ATF1 or less commonly EWSR1/CREB1 fusion. To date, six types of EWSR1/ATF1 fusion have been reported, of which three are in-frame and encode functional proteins. We present a reverse transcription - polymerase chain reaction analysis of a tumour near the hallux of the right foot. The sequencing of obtained fragments revealed the presence of a novel chimerical transcript—the in-frame fusion between EWSR1 exon 7 and ATF1 exon 6 that represents the fourth in-frame type of EWSR1/ATF1 fusion identified in clear cell sarcomas.

Asymptomatic heterotopic pancreas in Meckel’s diverticulum: a case report and review of the literature

IntroductionHeterotopic pancreas is defined as pancreatic tissue without a real anatomical or vascular connection to the pancreas. It can be found in the stomach, duodenum, jejunum, ileum, Meckel’s diverticulum, colon gall bladder, umbilicus, fallopian tube, mediastinum, spleen and liver. Complications of heterotopic pancreas are inflammation, bleeding, obstruction, malignant transformation, carcinoid syndrome, jejunojejunal intussusception and ileus, but it is usually asymptomatic and diagnosed only during examinations for other diseases.Case presentationAn 81-year-old Lithuanian woman was diagnosed with caecal cancer and had undergone elective surgery. A right hemicolectomy was performed and a Meckel’s diverticulum was observed and excised. Histological results showed a poorly differentiated G3 adenocarcinoma of her large intestine and heterotopic pancreas tissue in the Meckel’s diverticulum and mesenteric adipose tissue.ConclusionsAsymptomatic heterotopic pancreas is rarely diagnosed, and usually found incidentally during surgical or diagnostic interventions. Although it has no symptoms, heterotopic pancreas found during surgical procedures should be excised.

Small Intestinal Inflammatory Myofibroblastic Metastasis in the Left Ventricle

Inflammatory myofibroblastic tumors (IMTs) are rare and usually appear in childhood and adolescence. These tumors often take a benign course, but tend to reoccur in a quarter of cases and metastasize locally. Distant IMT metastases are extremely uncommon. To our knowledge, metastatic spread to the heart has not been reported. We present a case of a 43-year-old woman with small intestinal IMT metastatic spread to the cavity of the left ventricle, stomach, liver, vertebra, and pelvic bones. The cardiac tumor was resected, and the patient survived for 9 months. She dies because the progression of IMT at other sites.

Echinococcus multilocularis infection of the liver presenting as abdominal wall fistula

Echinococcus multilocularis causes infection where the most commonly affected organ is the liver, followed by the lung, kidney, bone and the brain. Other sites such as the heart, spleen, pancreas and soft tissues are very rarely affected. Surgical treatment combined with chemotherapy using various technical approaches remains the main therapeutic modality for echinococcal liver disease. To the best of our knowledge there are less than five clinical cases of cutaneous presentation of liver alveolar echinococcosis described. We present a unique case of liver echinococcosis presenting as recurrent abdominal wall fistula and abscess in a 29-year-old man. Diagnosis was based on CT imaging, serological analysis and histological findings from the fistula. Medical treatment with albendazole was initiated and liver resection was performed. The patient has no symptoms and signs of recurrence 1 year after operation, while still on albendazole therapy. This case description highlights the importance of early suspicion and treatment of unusual echinococcosis clinical presentations.

Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules

BACKGROUND Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules. METHODS A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility. RESULTS A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis. CONCLUSIONS Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).

Fatal pulmonary complication during induction therapy in a patient with ANCA-associated vasculitis

ANCA-associated vasculitis (AAV) is an inflammatory systemic disorder affecting small to medium sized vessels and likely leading to any organ dysfunction. Adequate treatment is important to avoid mortality or severe organ damage. In most cases initial treatment (induction therapy) allows to achieve remission. Induction therapy leads to immunosuppression and may cause severe infections. However, in vasculitis patients even an intensive immunosuppressive therapy is rarely complicated by an invasive fungal infection. We present a case in a 29-year old male patient with newly diagnosed AAV. He suffered a fatal pulmonary complication of the induction immunosuppressive treatment. Pathological (infectious) changes in the lungs were misinterpreted as progression of the vasculitis and he died due to disseminated angioinvasive aspergillosis. A clinical course, imaging and histopathology of this case are described and discussed.

Solid Pseudopapillary Neoplasm of the Pancreas: Analysis of Seven Cases

Background: The purpose of this study was to describe as well as compare our surgical treatment experiences of solid pseudopapillary neoplasms (SPN) of the pancreas and to provide a review of the literature. Methods: A retrospective analysis of data from Vilnius University Hospital Santariskiu Klinikos (VUH SK) and of the literature, which was researched using Karger Publishers, Springer Science, BioMed Central, and disserCat databases, was conducted. Results: From 2001 to 2012, seven cases were identified with pathologically confirmed SPN diagnosis. A precise preoperative diagnosis was made by computertomography and magnetic resonance imaging. The median diameter of the tumors was 6.36 cm (range 1.5-12 cm). Surgical treatment was undertaken for all patients. Results of the immunohistochemical analysis confirmed a nuclear accumulation of β-catenin. The Ki-67 level was 1-2% in all of the cases. According to our collected data, all types of histological analysis revealed decent prognostic behavior with low mitotic activity (1-2 mitoses per 50 high power fields). Besides, angioinvasion, perineural invasion, and outside capsule invasion were not detected. Conclusions: There was no correlation between more aggressive types of SPN and tumor size, localization, age, and gender.