Prevalence of Molecular Alterations in a Swiss Cohort of 512 Colorectal Carcinoma Patients by Targeted Next-Generation Sequencing Analysis in Routine Diagnostics.

INTRODUCTION: Colorectal carcinoma (CRC) is among the most common carcinomas in women and men. In the advanced stage, patients are treated based on the RAS status. Recent studies indicate that in the future, in addition to KRAS and NRAS, alterations in other genes, such as PIK3CA or TP53, will be considered for therapy. Therefore, it is important to know the mutational landscape of routinely diagnosed CRC. METHOD: We report the molecular profile of 512 Swiss CRC patients analyzed by targeted next-generation sequencing as part of routine diagnostics at our institute. RESULTS: Pathogenic and likely pathogenic variants were found in 462 (90%) CRC patients. Variants were detected in TP53 (54.3%), KRAS (48.2%), PIK3CA (15.6%), BRAF (13.5%), SMAD4 (10.5%), FBXW7 (7.8%), NRAS (3.5%), PTEN (2.7%), ERBB2 (1.6%), AKT1 (1.5%), and CTNNB1 (0.9%). The remaining pathogenic alterations were found in the genes ATM(n= 1), MAP2K1(n= 1), and IDH2(n= 1). DISCUSSION/CONCLUSIONS: Our analysis revealed the prevalence of potential predictive markers in a large cohort of CRC patients obtained during routine diagnostic analysis. Furthermore, our study is the first of this size to uncover the molecular landscape of CRC in Switzerland.

Unusual Presentation of Clear Cell Odontogenic Carcinoma: Case Report and Literature Review.

Clear cell odontogenic carcinoma (CCOC) is a rare, aggressive epithelial neoplasm of the jaw first described in 1985 by Hansen and classified as an odontogenic malignant tumor in the 2005 WHO classification. To date, only 117 cases have been reported in the literature written in English. In this paper, we report the atypical presentation of a pericoronal localized tumor in the right mandibular wisdom tooth discovered during a routine radiologic examination. The patient, a 44-year-old healthy female, was referred by her general dental practitioner for examination of temporomandibular dysfunction and recurrent myofascial pain. Anamnesis and clinical examination did not suggest tumoral disease. The osteolytic lesion was removed, and histological examination revealed a clear cell odontogenic tumor (CCOT) of the right posterior lower jaw. Segmental lower jaw resection was performed, and a free iliac crest bone transplant was fixed with mandibular reconstruction plate. No cervical neck dissection was needed. A five-year follow-up examination shows excellent local and systemic recovery and no sign of tumor recurrence. The patient still suffers from bruxism and myofascial related pain, which are treated conservatively with a Michigan splint and physiotherapy. Based on this additional case, we review the literature and discuss the challenging diagnostic aspects, the unusual clinical presentation, and the treatment of CCOC.

Increasing Incidence of Microscopic Colitis in a Population-Based Cohort Study in Switzerland.

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, nonbloody watery diarrhea and only few or no endoscopic abnormalities. Histologic examination discriminates lymphocytic colitis (LyC; presence of ≥20 intraepithelial lymphocytes per 100 surface epithelial cells) and collagenous colitis (CC; colonic subepithelial collagen band >10 µm in diameter).1,2 MC not otherwise specified describes a subgroup of patients who do not fulfill the diagnostic criteria for either CC or LyC.1,2 Population-based epidemiologic data regarding MC are scarce. We aimed to evaluate the clinical presentation at diagnosis, incidence, and prevalence of MC in Cantons of Vaud and Fribourg, Switzerland.

Deadly injuries through recoilless anti-tank weapons while military shooting practice-two case studies from Germany and Switzerland.

In this casuistry, two accidents from Germany and Switzerland are presented that happened during the shot of recoilless anti-tank weapons. In both cases, the injuries led to the death of two soldiers: A 22-year-old soldier in Germany was struck by the counter mass of a so-called Davis gun which had been fired by a comrade during a firing exercise; he died from his severe injuries, especially in the abdominal part of the body. As a peculiarity of the wound morphology, it was found to be a thick-layered, metallic, gray material in the wound cavity, which corresponded to the material of the counter mass that was ejected opposite to the shooting direction. The other case took place in Switzerland, where a 24-year-old soldier was seriously injured during an exercise with portable anti-tank rockets. At the time the shot was fired, he stood behind the launcher and was hit by the propulsion jet of the rocket motor. He died as well from his severe injuries, which were located at the chest done by the gas jet and by the very high pressure. In both cases, two different causes of death were present: massive blunt violence in the first case versus a jet of hot gases of very high speed and temperature in the second case.

Molecular Profile of Gastrointestinal Stromal Tumors in Sixty-Eight Patients from a Single Swiss Institution.

INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. It has distinct molecular features and primarily affects the KIT and PDGFRA genes. OBJECTIVE: We wanted to assess the molecular profile of 68 GIST patients who were sequenced consecutively between 2014 and 2019 at our institute of pathology. METHODS: Our cohort comprised 60 primary and 8 metastatic GIST patients; 43 and 57% of the cases, respectively, were analyzed by Sanger sequencing or next-generation sequencing (NGS). RESULTS: Of the 60 primary GIST patients, 47 (78%) showed a KIT mutation; 2 cases showed a double KIT mutation, and 1 of these was a therapy-naive GIST. Nine (15%) patients harbored a PDGFRA mutation, 2 (3%) had a BRAF mutation, 1 (2%) had a PIK3CA mutation, and 1 (2%) did not show any mutation. One BRAF and the PIK3CA mutation have not been described in GIST before. All metastatic GIST harbored exclusively KIT mutations. CONCLUSION: A retrospective analysis of GIST sequenced at our institute revealed incidences of KIT and PDGFRA mutations comparable to those in other cohorts from Europe. Interestingly, we found 2 previously undescribed mutations in the BRAF and PIK3CA genes as well as 1 treatment-naive case with a double KIT mutation in exon 11.

Comparison of contemporary staging systems for oropharynx cancer in a surgically treated multi-institutional cohort.

BACKGROUND: Between the publication of the Union of International Cancer Control staging system (UICC) 7th and 8th editions, other staging algorithms for oropharyngeal squamous cell carcinoma (OPSCC) were proposed from Radiation Therapy Oncology Group (RTOG), MD Anderson Cancer Center (MDACC), and Yale University. METHODS: With C-statistics, the above-mentioned five staging algorithms were compared for overall and relapse-free survival endpoints in a multi-institutional cohort of OPSCC cases (n = 338) treated with primary surgery. RESULTS: Pathological UICC 8th ed yielded the highest C-indexes in the entire cohort and in the HPV- subset, whereas MDACC was superior for HPV+ OPSCC. RTOG was the simplest and holistic algorithm with a noninferior discriminatory power. CONCLUSION: UICC 8th ed, MDACC, and RTOG offer moderate and comparable efficacy for staging in this OPSCC patient cohort undergoing surgical treatment. Notable discrepancy between clinical and pathological UICC 8th ed algorithms poses potential concerns in diagnosis, treatment, research, and data management.

Pott's puffy tumor presenting as a frontal swelling under a Swiss army helmet.

In this report, we describe an uncommon presentation of a Pott's puffy tumor, which is defined as a subperiosteal abscess related to a chronic frontal sinusitis. This condition has become rare in our part of the world because of the widespread use of antibiotics. Clinical history, investigations, and management are presented.

Impact of human papillomavirus on outcome in patients with oropharyngeal cancer treated with primary surgery.

BACKGROUND: Knowledge about prognostic factors in surgically treated patients with oropharyngeal squamous cell carcinoma (SCC) is limited. The purpose of this study was to identify influential factors on survival in a large cohort of patients with surgically treated oropharyngeal SCC. METHODS: Retrospective analysis of survival estimates in patients with surgically treated oropharyngeal SCC using tumoral positivity for human papillomavirus (HPV) and risk-of-death categories according to a study from 2010 as stratification factors. RESULTS: The 5-year overall survival (OS) and disease-specific survival (DSS) rates after surgery alone were higher in HPV-associated oropharyngeal SCC (OS 80% vs 62%; P = .01; DSS 92% vs 76%; P = .03). Patients in the low-risk category had higher survival rates (OS 91%; DSS 99%) than patients in the intermediate-risk group (OS 63%; DSS 83%), and high-risk group (OS 61%; DSS 75%). CONCLUSION: Nonsmokers with HPV-positive oropharyngeal SCC have a better prognosis than smokers with HPV-positive oropharyngeal SCC and also than patients with HPV-negative tumors when treated by surgery alone.

A dramatic lung cancer course in a patient with a rare EGFR germline mutation exon 21 V843I: Is EGFR TKI resistance predictable?

We report on the medical history of a Caucasian smoker woman diagnosed with a stage IV NSCLC adenocarcinoma, characterized by a rare epidermal growth factor receptor (EGFR) point mutation in exon 21 codon 843 (p.V843I/c.2527G>A/COSMIC ID 85894). This genetic alteration revealed to be germline, after its presence was demonstrated in chondroblasts from the bone biopsy. While it is the first description of germline V843I mutation without concomitant additional known EGFR activating mutation, we modeled the EGFR ATP catalytic domain in complex with ATP, gefitinib and erlotinib using computer-aided approaches to estimate possible changes in affinity upon the V843I mutation.

Effect of vertebral cement augmentation with polymethylmethacrylate on intervertebral disc and bone tissue.

Vertebral cement augmentation is reported to be a safe and effective technique for providing stabilization and pain relief. However, adjacent intervertebral discs may be at risk of accelerated degeneration as a result of aggravated nutritional constraints. Therefore, we investigated the effects of injecting polymethylmethacrylate (PMMA) into three adjacent lumbar vertebrae on intervertebral disc and vertebral bone tissue in 12 skeletally mature sheep. After 6 and 12 months of augmentation, the sheep were euthanized and their spines were processes for histological evaluation. Semiquantitative histomorphological analysis of discs and endplates was conducted using published criteria. Histomorphological changes in the augmented bone were assessed qualitatively. Approximately 80% of the length of the endplates was in contact with PMMA. However, there was no significant difference between the histopathological score of the discs adjacent to augmented vertebrae and the score of the control discs. Bone tissue reaction to PMMA was characterized by a thin fibrous tissue layer and occasional foreign-body reactions. New bone formation was present in all augmented vertebrae. Concerns about aggravation of disc degeneration as a result of vertebral cement augmentation seem to be unsubstantiated. Furthermore, adverse effects of PMMA cement on bone biology do not seem to be a relevant issue.

Intrapancreatic Accessory Spleen Misdiagnosed as a Nonsecreting Endocrine Tumor: Case Report and Review of the Literature.

In a large series of nonselected autopsy investigations an accessory spleen was found in 10-30%. The second most common site is the pancreatic tail (17%). We report a case of intrapancreatic accessory spleen misdiagnosed as a nonsecreting neuroendocrine tumor of the pancreas. Nuclear scintigraphy may provide the definitive diagnosis of an intrapancreatic spleen and therefore prevent patients from unnecessary major surgery.

FDG uptake in giant cell tumor of the tendon sheath in a patient restaged for gastrointestinal stroma tumor (GIST).

A 70-year-old man known for recurrent abdominal gastrointestinal stroma tumor presented with a suspicious peritoneal mass demonstrated by an abdominal CT scan. Whole-body PET showed focal FDG uptake in the right hip, whereas the peritoneal mass was FDG negative. Histologic work-up of the PET positive lesion surprisingly revealed a giant cell tumor of the tendon sheath. The benignity of the peritoneal mass was confirmed by its disappearance in repeated CT scans. In general, focally increased FDG uptake should be subject to further investigations, especially in localizations that are not consistent with typical metastatic pathways of the former primary tumor.

Parotid tumors: fine-needle aspiration and/or frozen section.

OBJECTIVE: The purpose of this study was to analyze and compare the value of fine-needle aspiration cytology (FNAC) and frozen section (FS) analysis in the assessment of parotid gland tumors. STUDY DESIGN: Chart review and cross-sectional analysis. SUBJECTS AND METHODS: FNAC and FS analysis of 110 parotid tumors, 68 malignancies and 42 benign tumors, were analyzed and compared with the final histopathologic diagnosis. RESULTS: The accuracy, sensitivity, and specificity of FNAC in detecting malignant tumors were 79 percent, 74 percent, and 88 percent, respectively. On FS analysis, the accuracy, sensitivity, and specificity in detecting malignant tumors were 94 percent, 93 percent, and 95 percent, respectively. The histologic tumor type was correctly diagnosed by FNAC and FS in 27 of 42 (64%) and 39 of 42 (93%) benign tumors, respectively, and in 24 of 68 (35%) and 49 of 68 (72%) malignant neoplasms, respectively. CONCLUSION: The current analysis showed a superiority of FS compared with FNAC regarding the diagnosis of malignancy and tumor typing. FNAC alone is not prone to determine the surgical management of parotid malignancies.

Carcinoma ex pleomorphic adenoma: diagnostic difficulty and outcome.

OBJECTIVE: To analyze a series of carcinoma ex pleomorphic adenoma (CXPA) and to assess the diagnostic difficulties. STUDY DESIGN: The clinical presentation of 24 CXPAs was compared with 300 pleomorphic adenomas (PAs). Furthermore, pathohistological findings and follow-up results of CXPAs were evaluated. RESULTS: Eight of 24 (33%) CXPAs versus 41 of 300 (14%) PAs were localized in the deep lobe (P < 0.05). Forty-two percent of CXPAs versus 6 percent of PAs, respectively, were greater than 4 cm (P < 0.05). The sensitivity in detecting CXPA by fine-needle aspiration cytology (FNAC) was 47 percent. The tumor was known to be malignant preoperatively in 10 (42%) patients. Six of 24 (25%) patients with CXPA developed a tumor recurrence. The overall 5-year survival rate of CXPA was 76 percent. CONCLUSION: CXPAs are difficult to identify preoperatively. FNAC has a low accuracy and sensitivity. CXPAs versus PAs are significantly more frequently localized in the deep lobe and are significantly greater in size.

Pretherapeutic staging of recurrent laryngeal carcinoma: clinical findings and imaging studies compared with histopathology.

OBJECTIVE: To assess the accuracy of preoperative imaging studies and clinical and endoscopic examinations for recurrent laryngeal carcinoma evaluation. STUDY DESIGN AND SETTING: A retrospective comparative study was performed at a university department on 42 recurrent laryngeal carcinomas. Surgical specimens were cut into whole-organ slices. Histologic findings were compared with the findings of the different preoperative diagnostic modalities. RESULTS: The craniocaudal tumor spread was correctly evaluated by endoscopy and imaging studies in 52% and 24%, respectively, and the contralateral tumor spread in 50% and 52%, respectively. The sensitivity, specificity, and accuracy for detection of tumor infiltration of the thyroid was 48%, 88%, and 64% and of the cricoid 47%, 80%, and 67%. The accuracy of recurrent tumor classification (crT) was 50%; most tumors were underclassified. CONCLUSION: The inadequately evaluated tumor spread and the inadequately classified recurrent tumors were underestimated and underclassified in most cases, respectively.

Parapharyngeal abscess by Aspergillus flavus in a neutropenic patient with myelogenous leukaemia.

This is the first description of an Aspergillus infection of the parapharyngeal space. A high degree of clinical suspicion may be needed due to the non-specific signs and symptoms and repeated tissue biopsies for microbiological and histopathological work up may be warranted.

Pleomorphic adenoma of the parotid gland: histopathologic analysis of the capsular characteristics of 218 tumors.

BACKGROUND: Histopathologic features of the capsule may have an impact on the recurrence rate of pleomorphic adenomas. METHODS: Retrospective (n = 154) and prospective (n = 64) histologic analysis of the capsular characteristics such as incompleteness, tumor penetration, pseudopodia, and satellite tumors of 218 pleomorphic adenomas. RESULTS: In 160 of the 218 (73%) pleomorphic adenomas, 1 or more capsular characteristics such as incomplete capsule (33%), capsule penetration (26%), pseudopodia (40%), and satellite nodules (13%) were detected. Incomplete capsule and satellite tumors were most frequently seen in the stroma-rich (myxoid) subtype. Capsular penetration and pseudopodia were significantly more common in the prospective group than in the retrospective group (p < .05/<.05). CONCLUSION: Pseudopodia and satellite tumors were more common than reported in the literature. If left in the surrounding salivary gland tissue at surgery, they can lead to recurrences of pleomorphic adenomas of the parotid gland.

Histologic characteristics and tumor spread of recurrent glottic carcinoma: analysis on whole-organ sections and comparison with tumor spread of primary glottic carcinomas.

BACKGROUND: The assessment of the precise tumor extent of recurrent glottic carcinomas is a challenge. METHODS: The histologic characteristics of 29 recurrent glottic carcinomas after radiation failures, initially classified as T1 and T2, were analyzed on whole-organ slices. The growth patterns of 21 recurrent prT3 and prT4 and 52 primary pT3 and pT4 carcinomas were compared. RESULTS: Fifteen of 29 (52%) recurrent carcinomas were under-staged by imaging studies and endoscopy. Most recurrent carcinomas presented with multicentric tumor foci, whereas most primary carcinomas with a concentric tumor growth pattern (p < .05). Undifferentiated dissociated tumor cells were observed more often in the vicinity of recurrent tumor foci than of the primary tumor mass (p < .05). CONCLUSION: Recurrent glottic carcinomas are often under-staged and present with multiple tumor foci dispersed in different regions of the larynx. If voice-preserving salvage surgery is considered as a treatment option, these facts should be kept in mind.