Three Synchronous Head and Neck Cancers: A Multidisciplinary and Surgical Challenge.

Second primary cancer (SPC) is a term used to describe a new primary cancer occurring in patients who had formerly been diagnosed with tumor. Even though SPCs appear to be related to primary cancers, they are actually entities that have arisen independently and not as a result of recurrence. This report is of the first case in literature of a patient hospitalized for the surgical treatment of 3 synchronous Head and Neck Cancers. A 66-year-old male was admitted to our hospital (Ospedale Degli Infermi-Biella, Italy) complaining about pharyngodynia. Three different lesions were identified through endoscopic examination and narrow band imaging: the first one on left tonsil, the second one on epiglottis, and the third one on right aryepiglottic fold. The case was subject to a multidisciplinary team analysis due to its complexity, then the surgery consisted in (1) CO2 laser left tonsillectomy, associated with (2) CO2 laser excision of the lesion on epiglottis free edge, and (3) CO2 laser excision of right aryepiglottic fold lesion. Synchronous tumors are among the most defiant challenges for surgeons since no international guideline specifies differentiated strategies to be adopted in patients affected by synchronous Head and Neck Cancers, therefore surgical planning must be tailored differently from patient to patient, and many unsolved questions still concern clinical treatments to be adopted.

Identification of a minimum number of genes to predict triple-negative breast cancer subgroups from gene expression profiles.

BACKGROUND: Triple-negative breast cancer (TNBC) is a very heterogeneous disease. Several gene expression and mutation profiling approaches were used to classify it, and all converged to the identification of distinct molecular subtypes, with some overlapping across different approaches. However, a standardised tool to routinely classify TNBC in the clinics and guide personalised treatment is lacking. We aimed at defining a specific gene signature for each of the six TNBC subtypes proposed by Lehman et al. in 2011 (basal-like 1 (BL1); basal-like 2 (BL2); mesenchymal (M); immunomodulatory (IM); mesenchymal stem-like (MSL); and luminal androgen receptor (LAR)), to be able to accurately predict them. METHODS: Lehman's TNBCtype subtyping tool was applied to RNA-sequencing data from 482 TNBC (GSE164458), and a minimal subtype-specific gene signature was defined by combining two class comparison techniques with seven attribute selection methods. Several machine learning algorithms for subtype prediction were used, and the best classifier was applied on microarray data from 72 Italian TNBC and on the TNBC subset of the BRCA-TCGA data set. RESULTS: We identified two signatures with the 120 and 81 top up- and downregulated genes that define the six TNBC subtypes, with prediction accuracy ranging from 88.6 to 89.4%, and even improving after removal of the least important genes. Network analysis was used to identify highly interconnected genes within each subgroup. Two druggable matrix metalloproteinases were found in the BL1 and BL2 subsets, and several druggable targets were complementary to androgen receptor or aromatase in the LAR subset. Several secondary drug-target interactions were found among the upregulated genes in the M, IM and MSL subsets. CONCLUSIONS: Our study took full advantage of available TNBC data sets to stratify samples and genes into distinct subtypes, according to gene expression profiles. The development of a data mining approach to acquire a large amount of information from several data sets has allowed us to identify a well-determined minimal number of genes that may help in the recognition of TNBC subtypes. These genes, most of which have been previously found to be associated with breast cancer, have the potential to become novel diagnostic markers and/or therapeutic targets for specific TNBC subsets.

Isolated tumour cells in a sentinel lymph node of apparent early-stage ovarian cancer: Ultrastaging of all other 27 lymph nodes.

Sentinel lymph node (SLN) biopsy in apparent early-stage ovarian cancer may spare the surgical staging with extensive retroperitoneal dissection and its associated morbidity. However, SLN biopsy in ovarian cancer is still experimental and under investigation. A 46-year-old post-menopausal woman with bilateral apparent stage IC1 endometrioid ovarian cancer underwent surgical staging by SLN biopsy and subsequent comprehensive laparoscopic pelvic and para-aortic lymphadenectomy. Out of 4 SLNs submitted to ultrastaging, one was positive for isolated tumour cells (ITCs). We submitted to ultra-staging all the other 24 pelvic and para-aortic non-SLNs, which were reported negative for disease. This is the first reported case of comprehensive lymphadenectomy after SLN biopsy with universal ultrastaging of all non-SLNs in ovarian cancer. The presence of ITCs in only one SLN, with all other 27 lymph nodes negative at ultrastaging, is consistent with the SLN concept and the assumption of a reliable lymphatic pathway in ovarian cancer.

Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations.

PURPOSE: Struma ovarii (SO) is a highly specialized ovarian teratoma, consisting of thyroid tissue. Rarely, carcinomas histologically identical to their thyroid counterparts may occur, and are comprehensively defined as malignant struma ovarii (MSO). Their optimal management is controversial, and the molecular profile of the malignant counterpart in the ovary is incompletely known. In this study, the clinicopathological and molecular features of six MSO from different Italian Institutions were analysed, to explore genetic profiles of potential therapeutic interest. METHODS: The histopathological features and immunoprofile (according to the known markers Galectin-3, HBME1, cytokeratin 19 and CD56) were reviewed. In addition, all cases underwent genetic analysis with a next-generation sequencing (NGS) hot spot cancer panel detecting mutations in 50 genes involved in cancerogenesis. RET/PTC rearrangements and TERT promoter alterations were also evaluated. RESULTS: Papillary carcinoma in all similar to its thyroid counterpart was found in five of six cases, including classical (two tumors) and follicular variant (three tumors) types. The last case was a poorly differentiated carcinoma. An activating gene mutation, was detected in five of six cases, including two NRAS, two BRAF, and one JAK3 oncogene mutations. No alterations were found in the other panel genes, nor in TERT promoter, or in RET chromosomal regions. CONCLUSIONS: MSO is a rare condition. Papillary carcinoma is the predominant malignant type, sharing both histomorphological and molecular features of its thyroid counterpart. Interestingly, the single case of poorly differentiated carcinoma displayed a JAK3 mutation. The presence of such driving mutation could be of potential interest in guiding postoperative treatment.

Correction to: Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.