PET metabolic tumor volume as a new prognostic factor in childhood rhabdomyosarcoma

Purpose Childhood RMS is a rare malignant disease in which evaluation of tumour spread at diagnosis is essential for therapeutic management. F-18 FDG-PET imaging is currently used for initial RMS disease staging. Materials and methods This multicentre retrospective study in six French university hospitals was designed to analyse the prognostic accuracy of MTV at diagnosis for patients with RMS between 1 January 2007 and 31 October 2017, for overall (OS) and progression-free survival (PFS). MTV was defined as the sum of the primitive tumour and the largest metastasis, where relevant, with a 40% threshold of the primary tumour SUVmax. Additional aims were to define the prognostic value of SUVmax, SUVpeak, and bone lysis at diagnosis. Results Participants were 101 patients with a median age of 7.4 years (IQR [4.0-12.5], 62 boys), with localized disease (35 cases), regional nodal spread (43 cases), or distant metastases (23). 44 patients had alveolar subtypes. In a univariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 3.47 [1.79;6.74], p<0.001) and PFS (HR = 3.03 [1.51;6.07], p = 0.002). SUVmax, SUVpeak, and bone lysis also influenced OS (respectively p = 0.005, p = 0.004 and p = 0.007) and PFS (p = 0.029, p = 0.019 and p = 0.015). In a multivariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 2.642 [1.272;5.486], p = 0.009) and PFS (HR = 2.707 [1.322;5.547], p = 0.006) after adjustment for confounding factors, including SUVmax, SUVpeak, and bone lysis. Conclusion A metabolic tumor volume greater than 200 cm3, SUVmax, SUVpeak, and bone lysis in the pre-treatment assessment were unfavourable for outcome.

The Simultaneous Presence of Isolated Tumour Cells and Bone Marrow Micrometastases in Stage I and II Colon Cancer—Challenging the Theory of a Chronological Pathway of Tumour Cell Dissemination

Background According to the common tenet, tumour progression is a chronological process starting with lymphatic invasion. In this respect, the meaning of bone marrow micrometastases (BMM) in patients with lymph node negative colon cancer (CC) is unclear. This study examines the relationship of isolated tumour cells (ITC) in sentinel lymph nodes (SLN) and BMM in patients in early CC. Methods BM aspirates were taken from both pelvic crests and in vivo SLN mapping was done during open oncologic colon resection in patients with stage I and II CC. Stainings were performed with the pancytokeratin markers A45-B/B3 and AE1/AE3 as well as H&E. The correlation between the occurrence of ITC+ and BMM+ and their effects on survival was examined using Cox regression analysis. Results In a total of 78 patients with stage I and II CC, 11 patients (14%) were ITC+, 29 patients (37%) BMM+. Of these patients, only two demonstrated simultaneous ITC+ /BMM+. The occurrence of BMM+ was neither associated with ITC+ in standard correlation (kappa = − 0.13 [95% confidence interval [CI] = − 0.4–0.14], p = 0.342) nor univariate (odds ratio [OR] = 0.39, 95%CI:0.07–1.50, p = 0.180) or multivariate (OR = 0.58, 95%CI: 0.09–2.95, p = 0.519) analyses. Combined detection of ITC+ /BMM+ demonstrated the poorest overall (HR = 61.60, 95%CI:17.69–214.52, p = 0.032) and recurrence free survival (HR = 61.60, 95%CI: 17.69–214.5, p = 0.032). Conclusions These results indicate that simultaneous and not interdependent presence of very early lymphatic and haematologic tumour spread may be considered as a relevant prognostic risk factor for patients with stage I and II CC, thereby suggesting the possible need to reconsider the common assumptions on tumour spread proposed by the prevalent theory of sequential tumour progression.

Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity.

Assessment and management of metastatic neck disease

Tumour spread to the neck can occur from any primary sites that can harbour squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) mucosa. This can also happen with other histological subtypes and from primary sites in the parotid and thyroid gland. Thus, the assessment of the neck should form an integral part of the clinical examination, imaging, and decision-making process prior to deciding treatment of the primary tumour. Given the propensity of these tumours to spread to the lymph nodes and given that the treatment algorithms used to manage lymph nodes in the neck are similar to those options available for the primary site, neck status often influences the choice of treatment. This chapter outlines the assessment and management of the metastatic neck node from an SCC of the UADT. To ensure uniformity in describing and communicating information about neck disease, the neck is divided into six levels, as recommended by the American Head and Neck Society and the American Academy of Otolaryngology–Head and Neck Surgery.

Diagnostic Dilemma of a Pelvic-Abdominal Mass in a Teenage Girl

The differential diagnosis of an abdominal mass in young teenage girls include pelvic inflammatory disease, pelvic abdominal Koch’s, endometriosis, pedunculated uterine leiomyomata, colonic mass, and germ cell tumour. There is a strong possibility of benign, borderline, or malignant ovarian carcinoma to be diagnosed in young girls with abdominal mass. Preoperative diagnosis depends on age, menopausal status, serum cancer antigen (CA) level of 125, ultrasound and radiological imaging of the mass. For better diagnosis of benign borderline serous tumours, borderline ovarian tumours (BOTs) and invasive cancers, magnetic resonance imaging (MRI) and positron emission tomography has to be done. However, among patients with benign cysts, BOTs and invasive cancers, CA-125 levels can be same. Likewise, the imaging results are not unique to BOTs. The diagnosis of BOTs can therefore be not established before surgery and intraoperative decisions regarding the extent of surgical management are based on the results of frozen section examination. In BOTs, an effective frozen section diagnosis is of considerable significance. Women of reproductive age always want traditional fertility-sparing surgery. Benign cysts should be distinguished from BOTs. Inadequate surgical staging of BOT may result in misdiagnosis of BOT as a benign tumour, leading to more vigorous treatment and possible tumour spread.1

Oesophageal squamous cell carcinoma mimicking submucosal tumour

Background Oesophageal submucosal tumours are usually benign. We report a rare case of esophageal squamous cell carcinoma presenting as a submucosal tumour. Case presentation A 58-year-old man undergoing screening oesophago-gastroduodenoscopy was found to have a smooth-surfaced 0.6-cm sized submucosal tumour in the oesophagus 30 cm from the incisor. Endoscopic ultrasonography showed the tumour to be located in the muscularis mucosa; the lesion was heterogeneously hypoechoic and had a clear boundary. With a provisional diagnosis of leiomyoma, the tumour was removed by endoscopic submucosal dissection. Pathological examination showed it to be a moderately differentiated infiltrating squamous cell carcinoma, with normal overlying squamous epithelium. Immunohistochemistry indicated that it was caused by malignant transformation in mucosal glandular duct epithelium. Positron emission tomography–computer tomography showed no tumour spread to any other site. The patient was treated by oesophageal resection. Conclusion The clinician should be aware that oesophageal submucosal tumours with smooth overlying mucosa may not always be benign; malignancy must be ruled out.