Paraganglioma

Aligned RNA-seq bam files were analyzed using the ISB Cancer Genomics Cloud (https://isb-cgc.appspot.com/). These 33 cancer types included in this study are adrenocortical carcinoma [ACC], bladder urothelial carcinoma [BLCA], brain lower grade glioma [LGG], breast invasive carcinoma [BRCA], cervical squamous cell carcinoma and endocervical adenocarcinoma [CESC], cholangiocarcinoma [CHOL], colon adenocarcinoma [COAD], esophageal carcinoma [ESCA], glioblastoma multiforme [GBM], head and neck squamous cell carcinoma [HNSC], kidney chromophobe [KICH], kidney renal clear cell carcinoma [KIRC], kidney renal papillary cell carcinoma [KIRP], acute myeloid leukemia [LAML], liver hepatocellular carcinoma [LIHC], lung adenocarcinoma [LUAD], lung squamous cell carcinoma [LUSC], lymphoid neoplasm diffuse large B cell lymphoma [DLBC], mesothelioma [MESO], ovarian serous cystadenocarcinoma [OV], pancreatic adenocarcinoma [PAAD], pheochromocytoma and paraganglioma [PCPG], prostate adenocarcinoma [PRAD], rectum adenocarcinoma [READ], sarcoma [SARC], skin cutaneous melanoma [SKCM], stomach adenocarcinoma [STAD], testicular germ cell tumors [TGCT], thymoma [THYM], thyroid carcinoma [THCA], uterine carcinosarcoma [UCS], uterine corpus endometrial carcinoma [UCEC], and uveal melanoma [UVM]. The sample set consists of 10,337 total TCGA samples, 9,624 tumor samples, and 713 normal samples.
Level-3 gene expression (RSEM) and segment-based copy number data were downloaded from Broad GDAC firehose (https://gdac.broadinstitute.org) (version: 2016_01_28). Gene-based copy number data were obtained by intersecting with RefSeq gene annotation bed file (version: 2013-07-27). Mutation calls were provided by the Multi-Center Mutation Calling in Multiple Cancers (MC3) working group within TCGA (Key Resources Table; Ellrott et al., 2018 ).

Continuous variables are expressed as the means ± SD and were analysed by independent t-tests for normally distributed data or Mann-Whitney tests for non-normally distributed data. For the qualitative variables, the Chi square test was used to compare the sample proportions of the two groups. Generalized estimating equations based on a binary logistic regression model were used to determine whether lesion type (retroperitoneal extra-adrenal paragangliomas or schwannomas) was associated with any of the individual binary factors. In this context, stepwise variable selection was performed to determine whether the combination of two or more of the aforementioned imaging features represented a significant independent predictor of schwannoma or paraganglioma. These tests were performed separately for each reader. Kappa coefficients were not used for this determination because the very high prevalence rates of certain imaging features for many of the binary factors was expected to produce misleadingly low values [8 (link), 10 ]. All reported p values are two-sided and considered statistically significant when less than 0.05. SPSS version 19.0 software (IBM Corporation, Armonk, NY, USA) was used for all computations.

All patients underwent a fully preoperative evaluation, including general clinical assessment, haematological, cardiovascular and pneumologic evaluations. Although MRI is generally considered the best choice in the evaluation of parapharyngeal tumors as it usually provides better information about soft tissues compared to TC scan, we performed both MRI (76 patients) and CT (51 patients) preoperative examinations in many cases, as they could be complementary in tumor characteristics evaluation, particularly in potentially malignant lesions. MRI was often more able to precisely define the relationship between tumor and surrounding great vessels, especially internal carotid artery (ICA) and to define more accurately the nature of some specific neoplasms (e.g., pleomorphic adenomas, paragangliomas). On the other hand, CT scans provided more accurate information on bony invasion, erosion or calcification within tumors. A selective angiography was preoperatively proposed for all enhancing lesions (37 patients) to favor differential diagnosis between neurogenic and vascular tumors. Ultrasound-assisted fine needle aspiration (USgFNAC) was performed when malignancy was clinically or radiologically suspected (25 patients), with the exception of vascular lesions or in case of inadequate ultrasound targeting or lesion proximity with major vessels. Moreover, in patients who received malignant diagnosis, FDG-PET has been performed as a useful method to detect distant metastasis not only in pre-operative assessment to support treatment planning, but also in mid and late post-operative follow-up. Incisional transoral or transcervical biopsy was rarely considered beneficial in our patients, thus it was performed only in patients who were not candidates for surgery, to obtain the histological diagnosis (3 patients).

We performed a monocentric, retrospective observational study, on a total of 1800 patients affected by cervical tumors, who underwent to diagnostic and therapeutic workout in our Centre between 2002 and 2021. Patients were identified considering a list of International Classification of Disease (ICD) codes that refer to neoplasms involving PPS. According to many inclusion criteria of Riffat et al., (2014) [1 (link)], we selected 98 patients, 50 males and 48 females, ranging from 20 months to 86 years of age. More specifically, only tumors located in PPS were considered eligible, while metastatic neoplasms involving PPS but originating from other anatomical regions were excluded. Among the salivary neoplasms of the parotid deep lobe, we included only those located in the retroangulomandibular neck region. Among the carotid paragangliomas, we considered eligible only those located above the posterior belly of the digastric muscle. Cases lacking an accurate description of preoperative diagnostic techniques, adequate report on the tumor characteristics, surgical approach, histological subtypes diagnosis, postoperative outcome or complications accurate report were excluded. Diagnostic workout revealed bilateral neoplasms in two patients, so a total of 100 PPS tumors, ranging from 16 to 83 mm maximum diameter and involving pre or retro stiloyd parapharingeal spaces, were studied. Compressively, 96 cases underwent surgery. One patient was exclusively treated with embolization and three more cases with an elective radio-chemiotheraphy protocol after trans cervical or endoscopic biopsy to confirm histological diagnosis. surgical planning was performed according to tumor location, histology, dimensions, imaging data, surrounding anatomic features and clinical findings.