Measurement of extracapsular extension in sentinel lymph node as a possible predictor of residual axillary disease in breast cancer.

BACKGROUND: The presence of Extracapsular Extension (ECE) in the Sentinel Lymph Node Biopsy (SLNB) is still a doubt in the literature. Some studies suggest that the presence of ECE may be related to a greater number of positive axillary lymph nodes which could impact Disease Free Survival (DFS) and Overall Survival (OS). This study searches for the clinical significance of the ECE. METHODS: Retrospective cohort comparing the presence or absence of ECE in T1-2 invasive breast cancer with positive SLNB. All cases treated surgically at the Cancer Institute of the State of São Paulo (ICESP) between 2009 and 2013 were analyzed. All patients with axillary disease in SLNB underwent AD. OUTCOMES: Identify the association between the presence and length of ECE and additional axillary positive lymph nodes, OS and DFS between both groups. RESULTS: 128 patients with positive SLNB were included, and 65 had ECE. The mean metastasis size of 0.62 (SD = 0.59) mm at SLNB was related to the presence of ECE (p < 0.008). The presence of ECE was related to a higher mean of positive sentinel lymph nodes, 3.9 (± 4.8) vs. 2.0 (± 2.1), p = 0.001. The median length of follow-up was 115 months. The OS and DFS rates had no differences between the groups. CONCLUSION: The presence of ECE was associated with additional positive axillary lymph nodes in this study. Therefore, the OS and DFS were similar in both groups after 10 years of follow-up. It is necessary for additional studies to define the importance of AD when SLNB with ECE.

Rectal leiomyosarcoma as the initial phenotypic manifestation of Li-Fraumeni-like syndrome: a case report and review of the literature.

BACKGROUND: Leiomyosarcoma is a rare malignant tumor of smooth muscle origin and represents 10-20% of all soft tissue sarcomas. Primary colon and rectal sarcomas constitute < 0.1% of all large bowel malignancies. In Li-Fraumeni syndrome, sarcomas are the second most frequent cancer (25%). Li-Fraumeni syndrome is a genetic disease with a familial predisposition to multiple malignant neoplasms. This syndrome has an autosomal dominant pattern of inheritance and high penetrance characterized by germline TP53 mutations. Patients with a history of cancer who do not meet all the "classic" criteria for Li-Fraumeni syndrome are considered to have Li-Fraumeni-like syndrome. To the best of our knowledge, this article is the first report of a patient with rectal leiomyosarcoma as the initial phenotypic manifestation of Li-Fraumeni-like syndrome. The authors also present a literature review. CASE PRESENTATION: A 67-year-old Brazilian woman underwent anterior rectosigmoidectomy and panhysterectomy secondary to rectal leiomyosarcoma. She subsequently developed carcinomatosis and died 2 years after the operation. Her family medical history consisted of a daughter who died at 32 years of age from breast cancer, a granddaughter diagnosed with adrenocortical carcinoma at 6 years of age and two siblings who died from prostate cancer. A genetic study was carried out to identify a pathogenic variant of Li-Fraumeni syndrome. In the DNA extracted from the peripheral blood leukocyte, restriction fragment length polymorphism was analyzed to search for mutations in the TP53 gene. The DNA sequencing identified the germline pathogenic variant p. R337H heterozygous in exon 10 of TP53. The patient was classified as having Li-Fraumeni-like syndrome. CONCLUSION: In patients with rectal leiomyosarcoma, it is advisable to investigate the family history of cancer and perform genetic studies to screen for Li-Fraumeni syndrome.

Doege-Potter syndrome associated to metastatic solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal neoplasm with an estimated annual incidence of 0.35 per 100,000 individuals. Doege-Potter syndrome is a paraneoplastic syndrome related to solitary fibrous tumor clinically characterized by hypoglycemia, occurring in less than 5% of cases. Herein, we report a case of metastatic SFT associated with recurrent severe hypoglycemia. A 43-year-old male with a noncontributory medical history presented with a painless and progressive growing mass in the right thigh. The histological evaluation rendered the diagnosis of SFT, and tumor resection was performed. One year after the operation, on the oncological follow-up, he was admitted to the emergency unit, manifesting an early-morning seizure associated with a severe hypoglycemia. The laboratory findings of non-islet cell tumor hypoglycemia (NICTH) in the background of a relapsed metastatic solitary fibrous tumor were consistent with the diagnosis of Doege-Potter syndrome. Hepatic embolization associated with oral glucocorticoid was an efficient palliative treatment to control the hypoglycemic crisis and allow hospital discharge.

High dose image-guided, intensity modulated radiation therapy (IG-IMRT) for chordomas of the sacrum, mobile spine and skull base: preliminary outcomes.

PURPOSE: To report preliminary outcomes of high dose image-guided intensity modulated radiotherapy (IG-IMRT) in the treatment of chordomas of the sacrum, mobile spine and skull base. METHODS: Retrospective analysis of chordoma patients treated with surgery and/or radiotherapy (RT) in a single tertiary cancer center. Initial treatment was categorized as (A) Adjuvant or definitive high-dose RT (78 Gy/39fx or 24 Gy/1fx) vs (B) surgery-only or low dose RT. The primary endpoint was the cumulative incidence of local failure. RESULTS: A total of 31 patients were treated from 2010 through 2020. Median age was 55 years, tumor location was 64% sacrum, 13% lumbar, 16% cervical and 6% clivus. Median tumor volume was 148 cc (8.3 cm in largest diameter), 42% of patients received curative-intent surgery and 65% received primary RT (adjuvant or definitive). 5-year cumulative incidence of local failure was 48% in group A vs 83% in group B (p = 0.041). Tumor size > 330 cc was associated with local failure (SHR 2.2, 95% CI 1.12 to 7.45; p = 0.028). Eight patients developed distant metastases, with a median metastases-free survival of 56.1 months. 5-year survival for patients that received high dose RT was 72% vs 76% in patients that received no or low dose RT (p = 0.63). CONCLUSION: Our study suggests high-dose photon IG-IMRT improves local control in the initial management of chordomas. Health systems should promote reference centers with clinical expertise and technical capabilities to improve outcomes for this complex disease.

Tumor Reduction with Pazopanib in a Patient with Recurrent Lumbar Chordoma.

INTRODUCTION: Chordomas are rare malignancies of bone origin that occur in the axial skeleton, typically the skull base and lumbar/sacral regions. Although often classified as low-grade neoplasms, its locally infiltrative behavior may result in significant morbidity and mortality. Optimal surgical resection may be curative, but up to 50% of the cases relapse within 5 years, and currently there are no systemic treatments approved in this setting. A large proportion of these tumors express stem-cell factor receptor (c-KIT) and platelet-derived growth factor receptors (PDGFRs), providing a rationale for the use of tyrosine-kinase inhibitors (TKIs). CASE REPORT: A 27-year-old male presented with recurrent chordoma of the lumbar spine 4 years after initial diagnosis. Salvage therapies in the interval included repeat resections and radiation therapy. He ultimately developed multifocal recurrence not amenable to complete excision or reirradiation. A comprehensive genomic profiling assay was performed and revealed nondrugable alterations. Decision was made to proceed with systemic treatment with pazopanib 800 mg/day, resulting in tumor reduction (-23.1% reduction in size) and prolonged disease control. CONCLUSION: For this patient with a multiple recurrent chordoma and limited treatment options, pazopanib resulted in sustained clinical benefit following initial tumor reduction.

KRAS insertions in colorectal cancer: what do we know about unusual KRAS mutations?

INTRODUCTION: KRAS mutations are negative predictors of the response to anti-EGFR therapy in colorectal carcinomas (CRCs). Point mutations in codons 12, 13, and 61 are the most common KRAS mutations in CRC. There are few reports on insertions in KRAS, and little is known about its ability to activate the RAS pathway. The scarcity of data regarding insertion frequencies and nucleotide additions in KRAS impedes the management of patients with such mutations. We present data on KRAS insertions in CRC and discuss a case. MATERIALS AND METHODS: Pyrosequencing and Sanger sequencing were performed to identify KRAS and BRAF mutations in paraffin-embedded samples of CRC. Expression of mismatch repair proteins was examined by immunohistochemistry. RESULTS: We detected a GGT insertion between codons 12 and 13 (c.36_37insGGT;p.G12_G13insG) in a CRC patient. We found that insertions in KRAS is very rare in CRC and that the most frequent type of insertion is c.36_37insGGT. CONCLUSIONS: KRAS gene insertions represent a diagnostic and clinical challenge due to the difficult and unusual pyrosequencing findings and the lack of information regarding its clinical impact.

Results of a control quality strategy in cervical cytology.

OBJECTIVE: To determine the efficacy of a quality control strategy in cervical cytology in the detection of high-grade squamous intraepithelial lesions. METHODS: Forty-two patients were selected who underwent a Pap smear and cervical uterine biopsy between April 2008 and December 2009, with evidence of a high-grade squamous intraepithelial lesion in one or both tests. The statistical parameters of the smear test were calculated before and after systematic meetings for review of the archived test results (6 years), in which the following was done: interobserver diagnostic consensus; cytohistological correlation, with the latter as gold standard; and evaluation of the therapeutic status of each patient. RESULTS: Once these controls were applied, it was noted that sensitivity and positive likelihood ratio of the test for high-grade squamous intraepithelial lesion increased 9.5% (34.5 to 44%) and 0.45% (1.64 to 2.09%), respectively, while specificity remained at 79%. Reduction in interference of false-negative results associated with errors in the analytical phase of the cytological productive process gave an estimate of failures in collection of the specimens (pre-analytical phase). CONCLUSION: In addition to improving the performance of the cytological diagnosis of the high-grade squamous intraepithelial lesion, the proposed quality control strategy allows a reflection on the causes of incorrect or conflicting scrutiny.

Differentially expressed genes in giant cell tumor of bone.

Giant cells tumors of bone (GCTB) are benign in nature but cause osteolytic destruction with a number of particular characteristics. These tumors can have uncertain biological behavior often contain a significant proportion of highly multinucleated cells, and may show aggressive behavior. We have studied differential gene expression in GCTB that may give a better understanding of their physiopathology, and might be helpful in prognosis and treatment. Rapid subtractive hybridization (RaSH) was used to identify and measure novel genes that appear to be differentially expressed, including KTN1, NEB, ROCK1, and ZAK using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry in the samples of GCTBs compared to normal bone tissue. Normal bone was used in the methodology RaSH for comparison with the GCTB in identification of differentially expressed genes. Functional annotation indicated that these genes are involved in cellular processes related to their tumor phenotype. The differential expression of KTN1, ROCK1, and ZAK was independently confirmed by qRT-PCR and immunohistochemistry. The expression of the KTN1 and ROCK1 genes were increased in samples by qRT-PCR and immunohistochemistry, and ZAK had reduced expression. Since ZAK have CpG islands in their promoter region and low expression in tumor tissue, their methylation pattern was analyzed by MSP-PCR. The genes identified KTN1, ROCK1, and ZAK may be responsible for loss of cellular homeostasis in GCTB since they are responsible for various functions related to tumorigenesis such as cell migration, cytoskeletal organization, apoptosis, and cell cycle control and thus may contribute at some stage in the process of formation and development of GCTB.