Synchronous Lesions Research Articles

Primary Oro-Facial Manifestations of Langerhans Cell Histiocytosis in Pediatric Age: A Bi-Institutional Retrospective Study on 45 Cases.

Aims: Langerhans Cell Histiocytosis is a rare hematologic disorder usually affecting children and most commonly involving the head and neck region. Primary oro-facial manifestations are rare, and their diagnosis is often challenging as they are numerous and often resemble common pathologies, refractory to conventional medical and/or instrumental treatments. For such reasons, the diagnosis is frequently delayed, as is the following staging and therapy onset. We retrospectively studied 45 pediatric patients affected by Langerhans Cell Histiocytosis with onset in the head and neck, to examine their clinical and radiological features at the early stage. Materials and Methods: The study was a retrospective bi-institutional analysis (Department of Pediatric Dentistry and Pediatric Oncology of “Sapienza” University of Rome, Department of Interdisciplinary Medicine of the University of Bari “Aldo Moro”), which enrolled 45 patients (age range 0–18 year-old) affected by Langerhans Cell Histiocytosis with oro-facial onset. Data regarding clinical appearance, number, site, synchronous or metachronous occurrence, involved tissues/organs, radiographic features and clinical outcomes were collected, listed and overall differentiated by two age ranges (0–10-year-olds and 10–18-year-olds). Results: Patients were 26 males and 19 females, with an average age at the time of diagnosis of 4.8 ± 3.8 years (median = 3.9 years). The most common findings were inflamed, hyperplastic, painful and often ulcerated gingival lesions (22 cases), associated with deciduous tooth mobility and/or dislocation with bone loss in 18 cases, followed by nine single eosinophilic granulomas of the mandible and two of the maxilla. Lesions of the palatal mucosa were observed in six patients; nine patients showed on radiograms the characteristic “floating teeth” appearance in the mandible with synchronous lesions of the maxilla in six. Paresthesia was relatively un-frequent (three cases) and the pathological fracture of the mandible occurred in six. Head/neck lymph nodes involvement was associated with oral lesions in 12 cases and skull lesions in 14. Otitis (media or externa) was detected in four instances, exophthalmia in two, cutaneous rush in nine, contextual presence or subsequent onset of insipidus diabetes in eight. As for therapy, single or multiple small jaw lesions were all surgically removed; chemotherapy with vinblastine alone or associated with corticosteroids was the principal treatment in almost the 80% of cases; more than 50% of patients received corticosteroids, while only three patients received adjunctive radiotherapy. The overall mortality account for less than 9% (four of 45 cases) and recurrence observed in eight patients after therapy. Conclusions: Langerhans Cell Histiocytosis may mimic several oro-facial inflammatory and neoplastic diseases. Considering the potential disabling sequela following head and neck localization of Langerhans Cell Histiocytosis in children, especially at the periodontal tissues with teeth and alveolar bone loss, lesion recognition along with the histological examination of suspicious tissues is mandatory to achieve an early diagnosis and to prevent further organ involvement.

Abstract 2333: Mutational landscape of multiple primary lung cancers and its correlation with environmental factors

Abstract Background: Multiple primary lung cancers (MPLC) are reported to occur in 0.2-20 % of all primary lung cancer cases. MPLC are considered to harbor various genetic profiling patterns among the tumors even within the same individuals, though they developed from the same occupational and environmental exposure. In this study, we performed paired mutational analyses to clarify genetic mutations in MPLC and its relationship with environmental factors. Materials and methods: We obtained 38 surgical specimens from 17 patients who were pathologically diagnosed as MPLC and underwent surgery at Osaka City University Hospital between October 2007 and March 2019. In addition to the clinicopathological features, the patients' age, sex, smoking history, body mass index, radiologic features and surgical procedures were reviewed. Four of the 17 MPLC patients had metachronous lesions, whereas 13 patients only had synchronous lesions. For genetic profiling of MPLC patients, the extracted DNAs were deep-sequenced on Ion S5 sequencer (Thermo Fisher) for somatic mutations in 409 cancer-associated genes (Ion AmpliSeq Comprehensive Cancer Panel). The study was approved by institutional review board of Osaka City University Hospital and written informed consent was obtained from all of the patients. For statistically analyses, we assumed genetic mutations occurred by chance and calculated the frequency of concomitant mutations in multiple tumors within the same individuals based on a previous study (JME study; Kawaguchi T et al, J Clin Oncol 2016). Comparing the assumed frequency of mutations with the actual data, statistically analyses whether mutations would occur concomitantly or randomly were performed using an exact test. Results: Deep sequencing was successfully performed in all of the specimens with the mean coverage of 823. Results from comprehensive genetic analyses suggested that the mutation profiles differed among the tumors within the same individuals, whereas EGFR, KRAS, TP53, and PARP1 mutations were concomitantly detected in multiple tumors within the same individuals. In this study, the frequency of EGFR mutations was significantly higher in never or light -smokers and females. The occurrence of concomitant EGFR or KRAS mutations in multiple tumors within the same individuals was significantly more frequent than expected by chance (EGFR, P = .0023; KRAS, P = .0049), suggesting environmental factors play more role in EGFR and KRAS mutations than the other mutations including TP53 which occurred more randomly in individual tumors. Concomitant EGFR or KRAS mutations were particularly prominent in never or light-smokers and males. Conclusions: Results from our MPLC study confirmed that the development of EGFR or KRAS-mutated tumors were strongly related to environmental factors such as sex and smoking history, and suggested that the other mutations may occur randomly. Citation Format: Motohiro Izumi, Jun Oyanagi, Kenji Sawa, Mitsuru Fukui, Koichi Ogawa, Yoshiya Matsumoto, Yoko Tani, Tomohiro Suzumura, Tetsuya Watanabe, Hiroyasu Kaneda, Shigeki Mitsuoka, Kazuhisa Asai, Tatsuo Kimura, Nobuyuki Yamamoto, Tomoya Kawaguchi, Yasuhiro Koh. Mutational landscape of multiple primary lung cancers and its correlation with environmental factors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2333.

Abstract 2498: miFISH single cell analysis as a potential tool to stratify the progression risk in patients with Atypical Ductal Hyperplasia (ADH)

Abstract We previously studied synchronous ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC) using our novel approach of multiplex interphase Fluorescence in situ Hybridization (miFISH) that allows simultaneous enumeration of copy numbers of up to 20 gene loci per single cell, providing new insights into tumor clonality and intratumor heterogeneity (ITH). A high degree of chromosomal instability was present in DCIS, and we frequently observed a direct clonal evolution from DCIS to IDC. We now ask whether this degree of instability is also present in even earlier potential precursor lesions like atypical ductal hyperplasias (ADH). We are therefore conducting a retrospective study analyzing ADH lesions from patients without synchronous DCIS or IDC (pure ADH) and from patients with ADH adjacent to higher-grade lesions. Using our miFISH assay, we simultaneously assess copy number changes of six oncogenes (COX2 (1q), PIK3CA (3q), MET (7q), MYC (8q), CCND1 (11q), HER2 (17q), ZNF217 (20q)) and six tumor suppressor genes (FHIT (3p), DBC2 (8p), RB1 (13q), CDH1 (16q), TP53 (17q), NF2 (22q), typical for breast tumorigenesis. So far, we have analyzed fifteen pure ADH and five ADH with synchronous DCIS or IDC. The miFISH analysis showed that the majority of all pure ADH displayed a stable diploid genome without any copy number changes observed for the genes tested while only 3/15 (20%) showed changes, namely (i) a COX2 and HER2 gain in a diploid genome, (ii) a CDH1and MET loss in a tetraploid genome and (iii) a COX2 gain in a diploid genome. In the group of ADH with adjacent higher-grade lesions (n=5), all DCIS and IDC lesions analyzed displayed breast cancer specific copy number changes corroborating our previous results. Of note, two of the ADH lesions adjacent to these aberrant DCIS or IDC lesions had normal diploid genomes. Of the remaining three synchronous ADH lesions, one showed a complex gain and loss pattern similar to its adjacent DCIS, the second one was characterized by a simple COX2 gain which was maintained in the adjacent DCIS in addition to a DBC2 loss and MYC gain. The third ADH displayed a tetraploid clone without any gains or losses, while the adjacent IDC revealed a complex gain and loss pattern in its tetraploid genome. Our preliminary data indicate that the majority of pure ADH does not harbor copy number changes. However, there is a small subset of pure ADH revealing gain and loss patterns typical for DCIS and IDC often involving COX2 gain indicating it as an early event. Of note, ADH lesions adjacent to DCIS or IDC tend to display similar changes as their adjacent higher-grade lesions suggesting them as direct precursor lesions. We are currently analyzing more ADH samples and plan to add material from an ADH patient cohort with long-term follow-up to explore whether miFISH can stratify ADH patients into different risk groups. Citation Format: Kiara Whitaker, Jausheng Tzeng, Daniela Hirsch, Irianna Torres, Steven Brower, Gert Auer, Miguel Sanchez, Thomas Ried, Kerstin Heselmeyer-Haddad. miFISH single cell analysis as a potential tool to stratify the progression risk in patients with Atypical Ductal Hyperplasia (ADH) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2498.

Fluorodeoxyglucose positron emission tomography/computed tomography findings after percutaneous cryoablation of early breast cancer

BackgroundTo document 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) findings after percutaneous cryoablation for early breast cancer.MethodsData of 193 consecutive patients who had undergone cryoablation for invasive ductal carcinoma or ductal carcinoma in situ ≤ 15 mm without a history of ipsilateral breast cancer, synchronous ipsilateral lesion, and with estrogen receptor positive/human epidermal growth factor 2 negative were enrolled. The imaging characteristics of the treated areas were evaluated and classified on CT images as one of two types: fatty mass or non-fatty mass type. The maximum standardized uptake value (SUVmax) of the initial post-cryoablation PET/CT, the CT type of the treated area and selected clinical factors (age, menopausal status, lesion area, breast density, timing of PET/CT) were retrospectively evaluated.ResultsThe median interval between cryoablation and the initial post-cryoablation PET/CT was 12 months. The median SUVmax of the treated area was 1.36. The CT findings of the treated area were classified as fatty mass type (n = 137, 71.0%) or non-fatty mass type (n = 56, 29.0%). The treated areas of patients with lower breast density, of older age, post-menopausal status, and lower radiation dose were significantly more likely to be of fatty mass type (P < 0.001). Non-fatty mass type averaged a significantly higher SUVmax than did fatty mass type.ConclusionsPost-cryoablation PET/CT findings are of fatty or non-fatty mass type. A non-fatty appearance, which can show higher SUVmax, does not necessarily denote recurrence.

Renal Cell Carcinoma Metastasis to the Pancreas: the Aggressive Nature of Synchronous Presentation—Case Report and Comprehensive Review of the Literature

Typically presenting as local disease, renal cell carcinoma (RCC) is metastatic in 16% of cases, typically spreading to the lungs, brain, bones, or liver. Less common are pancreatic metastases from RCC with isolated metastasis comprising 60% of cases. We report RCC with a synchronous solitary pancreatic lesion resected leaving the patient disease free. At 3.5 years, the patient presented with recurrent multiple pancreatic lesions, suggesting an aggressive biology and an altered treatment paradigm.

Personalised mapping of tumour development in synchronous colorectal cancer patients

Synchronous colorectal cancers (syCRCs) are two or more primary tumours identified simultaneously in a patient. Previous studies report high inter-tumour heterogeneity between syCRCs, suggesting independent origin and different treatment response, making their management particularly challenging, with no specific guidelines currently in place. Here, we performed in-depth bioinformatic analyses of genomic and transcriptomic data of a total of eleven syCRCs and one metachronous CRC collected from three patients. We found mixed microsatellite status between and within patients. Overlap of mutations between synchronous tumours was consistently low (<0.5%) and heterogeneity of driver events across syCRCs was high in all patients. Microbial analysis revealed the presence of Fusobacterium nucleatum species in patients with MSI tumours, while quantification of tumour immune infiltration showed varying immune responses between syCRCs. Our results suggest high heterogeneity of syCRCs within patients but find clinically actionable biomarkers that help predict responses to currently available targeted therapies. Our study highlights the importance of personalised genome and transcriptome sequencing of all synchronous lesions to aid therapy decision and improve management of syCRC patients.

Increased incidence of metachronous gastric neoplasm after endoscopic resection in patients with synchronous gastric neoplasm

BackgroundRecurrence risk is a major concern after endoscopic resection (ER) of gastric neoplasms. This study was to compare metachronous risk in patients with and without synchronous neoplasms after complete ER.MethodsAfter ER for gastric neoplasms, patients were divided into those with and without synchronous neoplasm. The metachronous risk of gastric neoplasms was compared between the two groups.ResultsAfter ER of 678 cancers and 891 adenomas, synchronous neoplasm was found in 11.8% of cancers and 11.4% of adenomas. In the multiple (n = 182) and the single group (n = 1387), metachronous neoplasms occurred in 18.1 and 8.6%, respectively (HR 2.40; 95% CI, 1.62–3.34). When the pathology of the recurred lesion was limited to cancer, metachronous risk was also significantly higher in the multiple than in the single group (HR, 2.2; 95% CI, 1.17–3.85). In the recurred pathology of the multiple group, cancer development was frequently observed in patients with cancer compared to those with only adenomas in the synchronous lesion (67.0% vs. 13.0%, respectively; P = 0.023).ConclusionsThis study demonstrated that metachronous risk was significantly higher in patients with synchronous gastric neoplasms after ER. Therefore, meticulous examination is important in patients with synchronous neoplasm.

Comparative postoperative outcomes of GGN-dominant vs single lesion lung adenocarcinomas

BackgroundMultiple synchronous ground glass nodules (GGNs) are known to be malignant, however, they tend to progress slowly. Multiple synchronous lesions in the same patient which show different characteristics must be treated individually.MethodsThis was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison purposes. The follow-up period was 5 years for all patients.ResultsThe 5-year overall survival (OS) patients with multiple lesions did not differ from that of the patients with single lesions to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P = 0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, while a progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P = 0.3870; DFS: 80% vs. 100%, P = 0.0977).ConclusionsThe outcomes were best predicted by the stage of the DT. After surgery patients require a careful follow-up because unresected GGNs may show progression. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management of such patients should be determined according to the DT with the worst prognosis.

On the use of single‐isocenter VMAT plans for SBRT treatment of synchronous multiple lung lesions: Plan quality, treatment efficiency, and early clinical outcomes

Cone‐beam computed tomography (CT)‐guided volumetric‐modulated arc therapy (VMAT) plans for stereotactic body radiotherapy (SBRT) treatment of synchronous multiple lung lesions with a flattening filter‐free (FFF) beam is a safe and highly effective treatment option for oligometastases lung cancer patients. Fourteen patients with metastatic non–small‐cell lung cancer (NSCLC) lesions (two to five) received a single‐isocenter VMAT SBRT treatment in our clinic. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB‐based dose calculation algorithm using heterogeneity corrections with a single isocenter placed between/among the lesions. Compared to 10X‐FFF and traditional flattened 6X (6X‐FF) beams, 6X‐FFF beam produced highly conformal radiosurgical dose distribution to each target volume, reduced dose to adjacent organs at risk (OAR), and significantly reduced the lung SBRT fraction duration to < 3.5 min/fraction for 54/50 Gy treatments in 3/5 fractions — significantly improving patient convenience and clinic workflow. Early follow‐up CT imaging (mean, 9 months) results show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow up in a larger patient cohort is ongoing to further validate the outcomes of this treatment approach.

Effectiveness of planned surveillance for detecting second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma.

Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients' outcomes and the quality of life; however, an adequate surveillance schedule remains unclear. We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3-6months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12months intervals thereafter. During the median follow-up period of 49.4months (1.3-81.2months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows: 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function. Surveillance by gastrointestinal endoscopy every 6months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.

A rare family case study of multiple siblings with multiple synchronous primary lung cancers.

e21028 Background: Familial lung cancer is rare, let alone inherited lung cancer with multiple synchronous primary lung cancer lesions. Study of inherited lung cancer may facilitate the understanding of the molecular mechanism of the tumorigenesis. Methods: We identified an extremely rare family of five siblings, four with multiple primary lung adenocarcinomas by pathological examination. DNA samples were extracted from the patient tumor tissues and libraries were prepared for next-generation sequencing (NGS) analysis using a custom 500-gene cancer panel. Results: EGFR L858R or 19DEL mutations were identified in at least one lesion in all of the four lung cancer patients. Interestingly, lung cancer patient L1 had EGFR 19DEL in one lesion and L858R in the other, lung cancer patient L2 had EGFR L858R and KRAS G12C mutation in lesion 1 and lesion 2, respectively. The mutation statuses of EGFR and KRAS were confirmed by ARMS-PCR. The mutational spectrum of the two lesions from the same patient distinguished significantly based on the 500-gene NGS panel analysis, further demonstrating the heterogeneity of cancer mutations. Taken together, these results indicate that patients L1 and L2 both had synchronous primary lung cancers. Due to the small lesions, the two lesions for patient L3 were mixed together; the concurrent EGFR L858R and 19DEL mutations in the tissue sample implicated different drivers in the two different lesions since co-occurring of these two mutations was very rare. For patient L4, EGFR L858R was identified in one lesion and uncommon mutations with low frequencies were observed in the other lesion, consistent with different driving mechanisms for the two lesions. Conclusions: To our knowledge, this is the first study identifying a family of multiple siblings with multiple synchronous primary lung cancers and using NGS to reveal the genetics. Together with germline mutation analysis, this study may shed light on the tumorigenesis of familial lung cancer.

V10-02 ROBOTIC BILATERAL PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA

You have accessJournal of UrologyAdrenal Surgery & Kidney Cancer II (Advanced Kidney Cancer & Vascular Reconstruction) (V10)1 Apr 2020V10-02 ROBOTIC BILATERAL PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA Jeremy Archer*, Jonathan Pavlinec, Shavano Stedman, Tejal Patel, Sara Falzarano, and Li-Ming Su Jeremy Archer*Jeremy Archer* More articles by this author , Jonathan PavlinecJonathan Pavlinec More articles by this author , Shavano StedmanShavano Stedman More articles by this author , Tejal PatelTejal Patel More articles by this author , Sara FalzaranoSara Falzarano More articles by this author , and Li-Ming SuLi-Ming Su More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000935.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with multiple endocrine neoplasia type 2 (MEN2) and von Hippel-Lindau disease (VHL) are risk of bilateral adrenal pheochromocytomas. Total adrenalectomy was historically the standard of care for patients with hereditary syndromes, but this leads to lifelong steroid supplementation. Adrenal-sparing surgery has been described in the treatment of adrenal incidentaloma, aldosteronoma, isolated metastasis, and the hereditary pheochromocytomas of MEN2 and VHL. Synchronous bilateral laparoscopic partial adrenalectomy with intraoperative ultrasonography has been described for pheochromocytomas as safe and technically feasible, but the majority of bilateral lesions have been treated by staged operations. We report our experience of synchronous bilateral robotic partial adrenalectomy for multifocal bilateral adrenal pheochromocytomas. METHODS: A 36-year-old female with marfanoid habitus and biopsy-proven medullary thyroid cancer was found to have bilateral adrenal masses on staging workup. Laboratory results showed elevated serum metanephrines, and she was started on alpha blockade with phenoxybenzamine. Imaging revealed a 3 cm right adrenal mass with a separate area of 1 cm irregularity and a 2 cm left adrenal lesion. Bilateral robotic partial adrenalectomies were successfully performed using a 4-arm technique with the daVinci Xi robotic platform (Intuitive, Sunnyvale CA) and a 12mm assistant trocar at the umbilicus. The patient was positioned in full-flank positioning for each side with docking from the same side of the room. The midline subxiphoid robotic 8mm and the 12mm assistant trocars were used for both portions of the operation. RESULTS: Enucleation of the tumors was performed with a total operative time of 330 minutes and estimated blood loss of 50mL. Pathology revealed three pheochromocytomas, and the patient was started post-operatively on a steroid taper. She was referred for genetic counseling given suspicion for MEN2B syndrome. CONCLUSIONS: Bilateral adrenal-sparing surgery for pheochromocytoma is safe and feasible and may be achieved using a robotic 4-arm technique with linear trocar configuration with repositioning. This approach in patients with genetic predisposition to synchronous adrenal lesions may preclude or delay the need for lifelong steroid supplementation. Source of Funding: N/A © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e931-e931 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeremy Archer* More articles by this author Jonathan Pavlinec More articles by this author Shavano Stedman More articles by this author Tejal Patel More articles by this author Sara Falzarano More articles by this author Li-Ming Su More articles by this author Expand All Advertisement PDF downloadLoading ...

Clinical histopathological features and CDKN2A/CDK4/MITF mutational status of patients with multiple primary melanomas from Bologna: Italy is a fascinating but complex mosaic

The incidence of cutaneous melanoma (cM) has increased in the last decades. Germline mutations in the high-penetrance melanoma susceptibility gene CDKN2A (Cyclin-dependent kinase inhibitor 2A) are associated with a younger age at diagnosis and an increased risk to develop pancreatic cancer. We retrospectively analyzed the data of patients with prior diagnosis of cM referring to our service from January 2005 to May 2017. The aim was to investigate the rate of multiple cMs (MPM), assessing their clinical/pathological features. Moreover, the genetic tests of patients who had undergone CDKN2A/CDKN2B, CDK4 and MITF screening were evaluated. One hundred fifteen patients (9.26%) were diagnosed with MPMs: 70 males (60.87%) and 45 women (39.13%). 75 patients (43 males and 32 females) underwent genetic screening for germline mutations. The screening revealed that 4/75 patients (5.33%) were carriers of the non-synonymous missense variation c.442G>A (p.Ala148Thr) in CDKN2A exon 2 in heterozygosis, 3 of whom had at least one in-situ melanoma. In 1 patient (1.33%) we detected the variation c.249C>A, p.His83Gln in CDKN2A exon 2 in heterozygosis and in 1 patient (1.33%) the mutation c.952G>A (p.Glu318Lys) in MITF gene was found. This study confirms the need for a full body skin examination and a prolonged surveillance in patients affected by cM, as MPMs were detected in up to 10% of total cases in our series and synchronous lesions in 1/5. Moreover, it reflects the great variability of cM high-susceptibility genes mutational status within the Italian territory. Patients carrying c.952G>A (p.Glu318Lys) MITF mutation have a higher risk to develop a nodular cM.

Preoperative CT Colonography in Partially Obstructed Colon Cancer, and its Benefit in Surgical Management

Background and aims Stenotic colorectal carcinoma impending obstruction (SCRCIO) is a frequently encountered situation complicating 10% to 19% of colorectal cancers. This group of patients cannot undergo complete colonoscopic assessment. The aim of this study is to examine the accuracy of computed tomographic colonography (CTC) as preoperative assessment of the colon of patients with SCRCIO and to measure the effect on the surgical decision. Materials and methods This was a prospective study, from September 2009 through December 2012, on a cohort of symptomatic adult patients with SCRCIO. Patients underwent CTC evaluation after failed conventional colonoscopy (CC), followed by a follow-up endoscopic examination 3–6 months after surgical treatment. Results Twenty-nine patients with an average age of 55 were included in this study; the majority of stenotic masses were located in the sigmoid colon. Preoperative CTC matched the colonoscopy location of the stenotic masses (17 patients). CTC sensitivity per stenotic lesion detection was 100% and 92.5% for the location. Sensitivity was 100% for synchronous lesions, and CTC changed surgical plan in 17% of the patients. Conclusion CTC presented high sensitivity, specificity and accuracy for the identification of colonic lesions of any size. Preoperative CTC may possibly become the diagnostic procedure of choice for SCRCIO patients. It enables surgeons to evaluate the entire colon, minimizing the possibility of surgical re-intervention if there is a finding of synchronous neoplastic lesions at postoperative follow-up endoscopy.

Clinicopathological features, risk of lymph node metastasis and survival outcome of synchronous multiple early gastric cancer

To determine clinicopathological features, risk of lymph node metastasis (LNM) and survival outcome in synchronous multiple early gastric cancer (MEGC) patients. A total of 338solitary early gastric cancer (SEGC) and 26 MEGC patients who underwent surgical resection were retrospectively reviewed. The clinicopathological features and predictive factors for MEGC patients were evaluated. Also, we analyzed risk factors for LNM and compared survival difference between SEGC and MEGC patients. The frequency of multiple synchronous lesions was 7.1% in early gastric cancer (EGC) patients. The main and minor lesions were mostly confined to the same third of the stomach (84.6%, 22/26), and the most common location was the lower third of the stomach. With regard to the number of coexisting lesions, most of the patients had two lesions and more than three lesions were not common. Tumor size≤2cm (OR:2.684, 95%CI:1.131-6.368, P<0.05) and the presence of atrophic gastritis (OR:2.418, 95%CI:1.052-5.555, P<0.05) were independent risk factors for synchronous MEGC. There was no significant statistical difference between SEGC and MEGC for LNM (17.5% vs 23.1%, P=0.311). The number of coexisting lesions was not associated with the risk of LNM in EGC. In addition, the survival outcome of MEGC patients was similar to that of SEGC (5-year RFS rate, 96.0% vs 93.7%, P=0.329;5-year OS rate, 96.0% vs 88.3%, P=0.479). Meticulous endoscopic examination at the initial diagnosis of MEGC was very important, especially for those with precancerous lesions such as atrophic gastritis. In terms of treatment methods, endoscopic resection may be equally suitable for synchronous MEGC if the lesions fulfilled its indication criteria.

Potential biomarkers of ductal carcinoma in situ progression

BackgroundDuctal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.MethodsIn this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies.ResultsThe results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.ConclusionsWe propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.

Definitive Management of Presumed Synchronous Early Stage Non-Small Cell Lung Cancers: Outcomes and Utility of Stereotactic Ablative Radiation Therapy

Management of synchronous early-stage non-small cell lung cancer (NSCLC) remains controversial because resection is not always feasible. This study evaluates efficacy and patterns of failure after SABR for synchronous early-stage NSCLC. From 2005 to 2015, patients presenting with ≥2 synchronous NSCLC tumors (T1a-T2b) and receiving SABR to ≥1 lesion were reviewed. The most common prescriptions were 50 Gy in 4 or 70 Gy in 10 fractions. Patients underwent multidisciplinary management with workup including chest computed tomography and positron emission tomography/computed tomography, plus brain imaging and endoscopic bronchial ultrasound for most patients to rule out mediastinal and distant disease. Synchronous lesions were defined as multiple ipsilateral or contralateral intrapulmonary lesions diagnosed within 6 months. Of 912 patients treated with SABR for early-stage NSCLC at our institution, 82 (9%) presented with synchronous disease, with a total of 169 lesions. SABR was delivered to 142 lesions (84%), with 57 patients (69.5%) receiving SABR for all sites. Median overall survival (OS) and progression-free survival (PFS) were 5.1 and 2.7 years, respectively. At a median follow-up of 58 months, OS was 67% and 52% at 3 and 5 years, and corresponding PFS was 47% and 29%. Thirty-nine patients (48%) had progression, with 21 (26%) experiencing distant failure, and intralobar recurrence was among the first failure for 15 patients (18%). Of the 142 SABR-treated sites, these included 6 in-field (4%) and 4 marginal (3%) recurrences. There were no grade ≥3 adverse events. Among patients receiving SABR for all sites, there were no differences in OS (P = .946), PFS (P = .980), local control (P = .683), regional and distant control (P = .656), or toxicity (P = .791). On multivariable analysis, ipsilateral synchronous disease was associated with greater regional and distant failure (hazard ratio, 2.691; P = .025). Synchronous NSCLC can be managed with definitive local therapy. With high control rates and favorable outcomes, SABR is an effective and feasible treatment for synchronous early-stage NSCLC.

Diagnostic accuracy of brush biopsy-based cytology for the early detection of oral cancer and precursors in Fanconi anemia.

Individuals with Fanconi anemia (FA) have a 500-fold to 700-fold elevated risk, much earlier onset, and limited therapeutic options for oral squamous cell carcinoma (SCC) compared with the general population. The early detection of SCC, or preferably its precursors, is mandatory to retain curative therapeutic options. Due to frequent synchronic and metachronic oral lesions, tissue biopsies, as usually recommended by guidelines, often are not feasible. In the current study, an alternative strategy for early detection using oral brush biopsy-based cytology was validated regarding its diagnostic accuracy. Over a 12-year period, the oral cavities of a large cohort of 713 individuals with FA were inspected systematically and brush biopsy-based cytology of 1233 visible oral lesions was performed. In cases of inconclusive cytology, analysis of DNA ploidy was performed whenever possible. The results were correlated to a long-term clinicopathological follow-up reference standard. A total of 737 lesions were suitable for statistical analysis, including 86 lesions with at least high-grade oral epithelial dysplasia in 30 patients. For cytology, the sensitivity and specificity were 97.7% and 84.5%, respectively. Additional analysis of DNA ploidy increased the sensitivity and specificity to 100% and 92.2%, respectively. Careful inspection of the oral cavity of individuals with FA followed by brush biopsy-based cytology appears to identify visible oral, potentially malignant and malignant lesions that warrant treatment. Approximately 63% of SCC and precursor lesions are detected at a noninvasive or early stage. Negative cytology or a lack of DNA aneuploidy can exclude high-grade oral epithelial dysplasia or SCC with high accuracy and thus reduce the need for invasive diagnostic biopsies.

Adrenal gland as a target of synchronous and metacronous metastasis from renal cell carcinoma: results of surgical treatment in a single institution

Background. Surgical treatment of solitary and oligometastatic metastases in renal cell carcinoma (RCC) is one of the treatment options for modern oncology.The objective of study to compare surgical outcomes in treatment of synchronous and metachronous solitary metastatic adrenal tumors in RCC.Materials and methods. The study included 93 patients with kidney cancer, from 1997 till 2018, who underwent surgical treatment in the urological oncology department of the P.A. Hertzen Moscow Oncology Research Institute. The 1st group is represented by 58 patients with RCC and synchronous secondary adrenal gland lesion, who underwent simultaneous surgery, consist of radical nephrectomy and adrenalectomy without subsequent adjuvant therapy. The 2nd group included 35 patients with metachronous solitary metastatic adrenal gland lesion who underwent surgical treatment.Results. The progression of disease to left adrenal gland was observed in 40 (43.0 %) cases, to the right – in 39 (41.9 %), both adrenal glands — 14 (15.1 %) cases. The median diameter of the adrenal tumors was 44 (4—170) mm, the most common in both groups were tumors less than 5 cm (58.1 %). The sensitivity of ultrasound in the diagnosis of adrenal tumors was 80.6 %, computed tomography – 93.5 %, adrenal biopsy – 73.9 %. The median of the observation time was 42 months (1st group — 24 months, 2nd group – the median was not achieved). The one-year survival of patients with a metachronous lesion of adrenal was 82.3 ± 76.6 % versus 52.8 ± 7.1 % in the synchronous lesion group, three-year survival was 79.2 ± 7.0 % versus 32.3 ± 7.6 % and five-year – 57.0 ± 10.0 % versus 16.2 ± 12.0 %, respectively. In multivariate analysis, only a metachronous lesion is a factor of favorable prognosis (p = 0.002).Conclusion. Surgical treatment for metachronous adrenal gland metastatic lesions is appropriate intervention and provides better patient survival rates compared to synchronous lesions.

Upper Tract Transitional Carcinoma: An Array of Imaging Conundrum

Case report: We report a 38-year-old gentleman who presented with painless haematuria for 6-months duration. Contrast-enhanced CT renal revealed a large, calcified intrapelvic mass with calyceal extension confined within the right kidney with moderate pelvicalyceal dilatation but no evidence of synchronous lesion elsewhere. Histopathological analysis showed high grade urothelial carcinoma of the renal pelvis with invasion of the renal parenchyma. Upper tract urothelial carcinoma (UTUC) which was once thought similar to urothelial carcinoma of the bladder (UCB), is increasingly being recognized as a different entity. However, heterogenous array of imaging manifestations of UTUC is also increasingly being encountered and pose diagnostic challenges though UTUC is not as prevalent as UCB which is easier to diagnose. Despite distinctive features against renal cell carcinoma (RCC), UTUC may mimic numerous other renal pathology especially the benign ones hence imaging plays a pivotal role to ascertain the diagnosis. This disease is usually treated with radical nephroureterectomy with superadded neoadjuvant chemotherapy for high risk cases. Less invasive endoscopic resection is also offered in certain cases but stringent surveillance of the whole urinary tract as well as post-operative follow-up are mandatory.