BackgroundRecent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown.Methodology/Principal FindingsATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133pos cells only in ARO and KAT-4 (64±9% and 57±12%, respectively). These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133pos cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133neg. Furthermore, ARO/CD133pos showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133neg was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133pos in comparison to ARO/CD133neg cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133pos when compared with ARO/CD133neg cells.Conclusions/SignificanceWe describe CD133pos cells in ATC cell lines. ARO/CD133pos cells exhibit stem cell-like features - such as high proliferation, self-renewal ability, expression of OCT-4 - and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in vitro findings might provide new insights for novel therapeutic approaches.
BRAF(V600E) mutation detected on FNAB specimens, more than RET/PTC rearrangements, is highly specific for PTC and its routine research might well be an adjunctive and integrative diagnostic tool for the preoperative diagnostic iter.
Aggressive fibromatosis comprises connective tissue tumours that represent 0.03% of all bodily neoplasms, occurring more often in the abdominal wall, mesentery, and extremities; its location in the breast constitutes a very infrequent type of lesion. Its pathogenesis is diverse and its relationship with augmentation mastoplasty is still unclear. Four cases of aggressive breast fibromatosis following augmentation mastoplasty are reported in this article.
ObjectiveTo determine the false-negative rate, sensitivity, and diagnostic accuracy of the frozen section analysis of the sentinel lymph node (SLN) biopsy in early-stage breast cancer compared to the definitive section and to identify the factors that could be associated with the appearance of false-negative cases. Secondarily, to evaluate the pathological results of cases submitted to completion axillary lymph node dissection (ALND) for positive SLN.MethodsWe performed a five-year review of cases (2011–2015), including patients with early-stage breast cancer undergoing SLN biopsy, with frozen section evaluation and subsequent definitive pathological analysis. These results were compared to calculate the false-negative rate and the factors associated with it. The histopathological findings were also evaluated in patients submitted to completion ALND.ResultsA total of 281 patients were evaluated, identifying 18 cases with frozen section results as false negative (false-negative rate: 23.7%), and 55.5% of these cases were micrometastases. The false-negative rate in SLN with macrometastasis was 13.1% and for micrometastasis cases was 66.7% (p < 0.001). True-positive patients that were submitted to completion ALND had additional axillary lymph nodes with metastases in 28% of cases, whereas the group of false negatives had additional positive axillary lymph nodes in 40% of patients (p = 0.62).ConclusionFrozen section analysis had a false-negative rate acceptable in SLN biopsy in our institution, and the micrometastasis in the SLN was the most important factor associated with the appearance of this phenomenon.
Background: Histiocytic sarcoma is a very rare monocyte/macrophage-derived hematopoietic system tumor with a poor prognosis whose diagnosis is pathologically challenging due to its extreme rarity and histological overlap with various mimicking entities in which histiocytes also predominate.Case: We report the case of a 33-year-old male patient with hemophagocytic lymphohistiocytosis, purpuric syndrome, and significant splenomegaly. The patient underwent splenectomy; subsequent macroscopic examination revealed a spleen weighing 2065 grams with hyperemic red pulp and multiple infarcts at the periphery.The histological and immunohistochemical study established a diagnosis of primary splenic histiocytic sarcoma with frequent hemophagocytosis. Next-generation sequencing demonstrated mutations in FLT3, NOTCH2, and KMT2A, microsatellite stability, and a tumor mutational burden of 2 mut/Mb. The patient's condition deteriorated clinically from the appearance of the first symptoms and he died 6 months later from multi-organ failure.
Conclusion:Primary splenic histiocytic sarcoma is one of the rarest tumors of the hematopoietic system. We report the first case with mutations in FLT3, NOTCH2, and KMT2A, and associated hemophagocytic lymphohistiocytosis.
BackgroundHistiocytic sarcoma (HS) is a very rare monocyte/macrophage-derived hematopoietic system tumor with a poor prognosis whose diagnosis is pathologically challenging due to its extreme rarity and histological overlap with various mimicking entities in which histiocytes also predominate.Case PresentationWe report the case of a 33-year-old male patient with hemophagocytic lymphohistiocytosis (HLH), purpuric syndrome, and significant splenomegaly. The patient underwent splenectomy; subsequent macroscopic examination revealed a spleen weighing 2,065 grams with hyperemic red pulp and multiple infarcts at the periphery. The histological and immunohistochemical study established a diagnosis of primary splenic histiocytic sarcoma (PSHS) with frequent hemophagocytosis. Next-generation sequencing (NGS) demonstrated mutations in FLT3, NOTCH2, and KMT2A, microsatellite stability (MSS), and a tumor mutational burden (TMB) of 2 mut/Mb. The patient's condition deteriorated clinically from the appearance of the first symptoms and he died six months later from multi-organ failure.ConclusionPrimary splenic histiocytic sarcoma (PSHS) is one of the rarest tumors of the hematopoietic system. We report the first case with mutations in FLT3, NOTCH2, and KMT2A, and associated hemophagocytic lymphohistiocytosis.
Objectives:Restore patellar anatomy and function of extensor mechanism. Reduction of surgical time, improval of rehabilitation and reduce complications of open surgery.Methods:37 patients with transverse patella fracture operated from June 2004 to April 2012. Inclusion criterion: Both sexes, age 20 to 65 years. Less than 10 days since fracture. Transverse fractures. Exclusion criterion: Comminuted , longitudinal and open fractures. More than 10 days since fracture. Fractures classified with AO and Watson Jones classifications. In all cases close reduction and percutaneous osteosynthesis with conic,canulated, compressive, full threaded screws of 3,5 and/or 5 mm diameter under fluoroscopic and arthroscopic assistance, was performed. Medium follow-up was 31 months (range 24-46) Comparative clinical evaluation of both knees was done: physical exam, X-rays and functional scales ( IKDC ; Lisholm Score, Knee Society score ).Results:Excellent results were achieved in 34 of 37 cases (91.9%). Three patients that had minor complications referred good and fair results: 1 case complain of occasional mild pain, another patient had 110 degrees of flexion compared to 145º on the normal knee and 1 patient had a 3mm step but remains asymptomatic. They were no infections and non needed screw removal.Conclusion:Percutaneous surgery under arthroscopic and fluoroscopic assistance , showed to be a simple and beneficial method for transverse patellar fractures. It takes shorter surgical and hospitalization time. Diminishes complications, morbidity, and achieves earlier range of motion.
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