Primary splenic histiocytic sarcoma associated with hemophagocytic lymphohistiocytosis: A case report and review of literature of next-generation sequencing involving FLT3, NOTCH2, and KMT2A mutations.

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.

Locally advanced breast cancer: Tumor-infiltrating lymphocytes as a predictive factor of response to neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the pathologic response after neoadjuvant chemotherapy in patients with breast cancer according to the stromal tumor-infiltrating lymphocytes (TILs) as well as the evaluation of overall and disease-free survival according to TILs. METHODS: A six years (2008-2013) review was done including patients with locally advanced breast cancer that received neoadjuvant therapy and then surgery. An evaluation of the percentage of TILs was done in the pretreatment biopsies and a correlation analysis and survival curves were done. RESULTS: 187 patients were evaluated. The pathological complete response (pCR) in patients with TILs ≥30% was 58.5%, and in patients with TILs < 30% was 11% (p <0.001). An Odds Ratio of 8.85 was obtained in patients with TILs ≥30% to achieve a pCR. This relationship was seen in patients with HER2-enriched and triple-negative subtypes. No correlation between TILs and survival was obtained (OS: log-rank; p = 0.834; DFS: log-rank; p = 0.937). CONCLUSIONS: The study of TILs is important because they represent an additional tool to predict the response to neoadjuvant treatment mostly in HER2-enriched and triple-negative subtypes of breast cancer.

Aggressive breast fibromatosis following augmentation mastoplasty: a series of case reports.

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.

Colecistectomía laparoscópica: impacto de la implementación de una lista de chequeo en la adecuada preparación del quirófano / Laparoscopic cholecystectomy: impact of the implementation of a checklist in the adequate preparation of the operating room

Evaluar el impacto de la implementación de una lista de chequeo en la adecuada preparación del quirófano para realización de colecistectomía laparoscópica. Métodos: Se trata de un estudio prospectivo, controlado, no aleatorio, donde se estudió el impacto del uso de una lista de chequeo en la incidencia de eventos adversos relacionados con la preparación del quirófano para realización de colecistectomía laparoscópica. Se compararon dos grupos, grupo A, en el cual se utilizó lista de chequeo y grupo B (control) donde la preparación del quirófano se llevó a cabo sin el uso de la lista. Para el estudio, los eventos adversos se clasificaron según su naturaleza en "ausencia y/o posición" y "defecto y/o configuración". El análisis estadístico se llevó a cabo utilizando el test exacto de Fisher considerando diferencia significativa p<0,05. Resultados: Se estudiaron un total de 40 procedimientos, (grupo A: 20, grupo B: 20). La incidencia de eventos adversos relacionados con la preparación del quirófano fue de 45 %, en contraste con el grupo control, en el cual en el 100 % de los procedimientos se documentaron eventos (p<0,001). La mayoría de los eventos documentados estuvo en relación con equipo o instrumental de hemostasia. La lista de chequeo fue útil en reducir significativamente los eventos adversos relacionados con "ausencia y/o posición" (70 % vs 5 %, p<0,001) pero no los relacionados "defecto y/o configuración" (70 % vs 40 %; p=0,057). Conclusiones: La lista de chequeo es una herramienta útil para la reducción de eventos adversos relacionados con la preparación de quirófano para colecistectomía laparoscópica, pero no elimina completamente el riesgo de su aparición(AU)

to evaluate the impact of the implementation of a checklist to obtain an optimal setting of the operating room for laparoscopic cholecystectomy surgeries. Methods: it's a prospective, controlled, non-randomized study. The usefulness of checklist implementation was studied to know the incidence of adverse events related to operating room preparation for laparoscopic cholecystectomy. Two groups, group A (checklist group), and group B (control, without the implementation of a checklist) were compared. For statistical purposes, adverse events were classified according to their nature in "Absence and/or position" and "defect and/or configuration". Statistical analysis was carried out using Fisher's exact test considering significant difference a p value<0.05. Results: A total of 40 procedures were studied (group A: 20, group B: 20). The incidence of adverse events related to operating room preparation was 45 %, in contrast to the control group, in which events were documented in 100 % of the procedures (p<0.001). Most of the documented events were related to hemostasis equipment or instruments. The checklist was useful in reducing adverse events related to "absence and/or position" (70 % vs. 5 %, p<0.001) but not related to "defect and/or configuration" (70 % vs. 40 %; p=0.057). Conclusions: The checklist is a useful tool in order to reduce adverse events related to the preparation of an operating room for laparoscopic cholecystectomy, but does not completely eliminate the risk of its occurrence(AU)

Frozen section evaluation of sentinel lymph nodes in breast carcinoma: a retrospective analysis.

OBJECTIVE: To 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. METHODS: We 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. RESULTS: A 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). CONCLUSION: Frozen 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.

In vitro identification and characterization of CD133(pos) cancer stem-like cells in anaplastic thyroid carcinoma cell lines.

BACKGROUND: Recent 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 FINDINGS: ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos) 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/CD133(pos) cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg). Furthermore, ARO/CD133(pos) showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg) was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos) in comparison to ARO/CD133(neg) 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/CD133(pos) when compared with ARO/CD133(neg) cells. CONCLUSIONS/SIGNIFICANCE: We describe CD133(pos) cells in ATC cell lines. ARO/CD133(pos) 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.

Fine-needle aspiration molecular analysis for the diagnosis of papillary thyroid carcinoma through BRAF V600E mutation and RET/PTC rearrangement.

OBJECTIVE: To evaluate BRAF(V600E) mutation on consecutive fine-needle aspiration biopsy (FNAB) specimens in order to assess FNAB's usefulness in preoperative papillary thyroid carcinoma (PTC) diagnosis with the contemporaneous analysis of RET/PTC1 and RET/PTC3 rearrangements obtained from ex vivo thyroid nodules. DESIGN: Thyroid FNABs from 156 subjects with nodules and 49 corresponding surgical samples were examined for the presence of BRAF mutation by real-time allele-specific polymerase chain reaction, confirmed with the use of a laser pressure catapulting system. Samples were also examined for RET/PTC rearrangements. The results were compared with the cytological diagnosis and histopathology. MAIN OUTCOMES: 13/156 cytological examinations were diagnostic for PTC and 19/156 showed suspicious/indeterminate FNAB (12.2%). FNAB-BRAF(V600E) mutation was detected in 11/16 (69%) cases with histological confirmation of PTC. In our series, RET/PTC rearrangement was detected in only one case of PTC, whereas it was not present in any case of adenoma, goiter, or Hashimoto's thyroiditis. No PTC case was found positive at the same time for BRAF mutation and RET/PTC rearrangements. CONCLUSION: 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.