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INTRODUCTION: Lipomas are the most common benign mesenchymal tumors which can be found in any part of the body. Nevertheless, their etiology and pathogenesis remain unknown. It is hypothesized that some of these lesions could result from an acute or chronic trauma. PATIENTS AND METHODS: We report a case of a 54-year-old man presenting a perineal lipoma which volume grew rapidly after he fell on his buttock, in the context of inaugural epileptic seizure. Pelvic MRI showed a voluminous fatty mass, measuring 6.6 × 5 × 9 cm without any signs of local invasion. Furthermore, we review the latest research on lipomas originating from traumatic lesion. RESULTS: The mass was completely excised in one block under general anesthaesia, using an elliptical incision and a deep dissection. We did not close the skin incision in view of the cutaneous defect. Post-operative recovery was uneventful and the patient was discharged from hospital two days after the operation. Histopathology indicated a reorganised lipoma with no evidence of malignancy. CONCLUSION: Perineal lipomas are extremely rare, pathological examination of imaging guided biopsies are needed to exclude malignancy especially a well-differentiated liposarcoma. MRI remains the first option and radical surgical excision is the gold standard treatment.

There is a lack of well-characterized models for pancreatic ductal adenocarcinoma (PDAC). PDAC itself is unique because of its pronounced tumor microenvironment that influences tumor progression, behavior and therapeutic resistance. Here we investigated, in patient-derived tumor xenograft (PDTX) models developed from fine needle biopsies, the cancer cells behavior, Epithelial-to-Mesenchymal Transition (EMT) and drug response. For this, we studied two behaviorally distinct PDTX models. Tumor volume measurement, histology, immuno-histochemical staining, RT-qPCR, RNA sequencing and Western blotting were used to further characterize these models and investigate the effect of two classes of drugs (gemcitabine and acriflavine (HIF-inhibitor)). The models recapitulated the corresponding primary tumors. The growth-rate of the poorly differentiated tumor (PAC010) was faster than that of the moderately differentiated tumor (PAC006) (P<0.05). The PAC010 model showed increased cell proliferation (Ki-67 staining) and markers indicating survival (increased p-AKT, p-ERK and p-NF-kB65 and suppressin of cleaved PARP). Gene and protein analysis showed higher expression of mesenchymal markers in PAC010 model (e.g. VIM, SNAI2). Pathway analysis demonstrated activation of processes related to EMT, tumor progression and aggressiveness in PAC010. Gemcitabine treatment resulted in shrinking of the tumor volume and reduced proliferation in both models. Importantly, gemcitabine treatment significantly enhanced the expression of mesenchymal marker supportive of metastatic behavior and of survival pathways, particularly in the non-aggressive PAC006 model. Acriflavine had little effect on tumor growth in both models. In conclusion, we observed in this unique model of PDAC, a clear link between EMT and poor tumor differentiation and found that gemcitabine can increase EMT.

It has recently been shown that duodenal foveolar gastric metaplasia (FGM) sometimes presents as a polyp. The mechanism by which FGM develops into a polypoid lesion is unknown and it is unclear whether this form of FGM is indistinguishable from other polypoid lesions or whether endoscopists do not recognize it because they are unfamiliar with it. We identified and retrieved archival cases of FGM endoscopically suspicious for adenomatous polyp and examined their pathological, clinical and endoscopic features. Endoscopic features of the 13 identified FGMs presenting as polyps were heterogeneous and overlapping with those of adenomatous polyps. FGM was frequently associated with mucosal and submucosal Brunner's glands, but defining and recognizing hyperplasia of these glands remains difficult. Other pathological features could not explain the development of a polypoid lesion. The endoscopic features of FGM polyps are non-specific, overlapping with those of adenomatous polyps. FGM polyps probably acquire their polypoid aspect due to association with Brunner's gland hyperplasia (BGH), which also arises due to chronic inflammation and damage. Because BGH is ill-defined and difficult to recognize, while FGM is diagnosed easily, this type of polypoid lesions has until now only been recognized based on the presence of FGM, although FGM is most likely a secondary phenomenon and not the primary cause of the polyp.

BACKGROUND: Intramuscular myxoma is a soft tissue myxoid tumor with a broad morphological differential diagnosis and recent developments have led to the identification of markers that can exclude some, but not all, differential diagnostic entities. However, a sensitive confirmatory marker for intramuscular myxoma has not been clearly identified. Since there is some evidence that mutations in the GNAS gene could be such a marker, we evaluated our results of next-generation sequencing testing for GNAS mutations performed in recent years on our series of intramuscular myxoma. MATERIALS AND METHODS: Next-generation sequencing was performed on 10 cases of intramuscular myxoma diagnosed between 2015 and 2019, using either the TruSight Tumor 26 panel or an in-house developed 97 cancer gene panel. Additionally, immunohistochemistry for CD34 was performed on all cases. RESULTS: All intramuscular myxomas showed a diffuse and strong expression of CD34 and a GNAS mutation was found in 88% of cases, making this a very sensitive positive test for the diagnosis of intramuscular myxoma. CONCLUSIONS: Under the condition that contemporary next-generation sequencing is applied as testing method, searching for GNAS mutations is a very sensitive confirmatory test for the diagnosis of intramuscular myxoma, obviating the necessity to perform tests that exclude other entities by the virtue of their negative result. The molecular tests results also identified strong and diffuse CD34 expression as a sensitive, albeit non-specific, marker for intramuscular myxoma.

A 31-year-old patient underwent a left orchiectomy in 2012 for a pT1 mixed germ cell tumor, mainly consisting of seminoma, associated with extensive germ cell neoplasia in situ (GCNIS) in the residual surrounding parenchyma. In view of these findings, surveillance of the right testis by ultrasound was performed, which showed in October 2018 a lesion of 11 mm in the inferior and a lesion of 7 mm in the superior part of the testicular parenchyma. Intraoperative frozen section was performed on the lesions, showing that both consisted of pure seminoma. [...]

IMPORTANCE: Myofibroma is the most frequent fibrous tumor in children. Multicentric myofibroma (referred to as infantile myofibromatosis) is a life-threatening disease. OBJECTIVE: To determine the frequency, spectrum, and clinical implications of mutations in the PDGFRB receptor tyrosine kinase found in sporadic myofibroma and myofibromatosis. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study of 69 patients with sporadic myofibroma or myofibromatosis, 85 tumor samples were obtained and analyzed by targeted deep sequencing of PDGFRB. Mutations were confirmed by an alternative method of sequencing and were experimentally characterized to confirm gain of function and sensitivity to the tyrosine kinase inhibitor imatinib. MAIN OUTCOMES AND MEASURES: Frequency of gain-of-function PDGFRB mutations in sporadic myofibroma and myofibromatosis. Sensitivity to imatinib, as assessed experimentally. RESULTS: Of the 69 patients with tumor samples (mean [SD] age, 7.8 [12.7] years), 60 were children (87%; 29 girls [48%]) and 9 were adults (13%; 4 women [44%]). Gain-of-function PDGFRB mutations were found in samples from 25 children, with no mutation found in samples from adults. Mutations were particularly associated with severe multicentric disease (13 of 19 myofibromatosis cases [68%]). Although patients had no familial history, 3 of 25 mutations (12%) were likely to be germline, suggesting de novo heritable alterations. All of the PDGFRB mutations were associated with ligand-independent receptor activation, and all but one were sensitive to imatinib at clinically relevant concentrations. CONCLUSIONS AND RELEVANCE: Gain-of-function mutations of PDGFRB in myofibromas may affect only children and be more frequent in the multicentric form of disease, albeit present in solitary pediatric myofibromas. These alterations may be sensitive to tyrosine kinase inhibitors. The PDGFRB sequencing appears to have a high value for diagnosis, prognosis, and therapy of soft-tissue tum

INTRODUCTION: Acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick Type A and Type B disease) is a rare, inherited metabolic disorder. Liver-related issues, including cirrhosis and variceal haemorrhage, are a leading cause of early mortality in individuals with chronic forms of ASMD. Due to the rarity of this lysosomal storage disorder, there can be a lack of awareness that adults with chronic ASMD disease are at significant risk of cirrhosis, portal hypertension, and variceal bleeding. This case highlights an unusual presentation of recurrent variceal bleeding in an adult with cirrhosis and portal hypertension due to chronic visceral ASMD. CASE PRESENTATION: A patient with severe splenomegaly was diagnosed with ASMD at age of 25. At age 64 they had multiple hospital admissions for hematochezia (originally diagnosed as ischemic colitis) accompanied by hypotension (blood pressure 91/45 mmHg), anemia (hemoglobin 8.5g/dL, ref 12-16; INR 1.4, ref ≤1.2), and mild renal insufficiency (creatinine 1.33mg/dL, ref 0.51-0.95). Colonoscopy did not reveal a source of bleeding. Computerized tomography scanning imaging showed diffuse venous collaterals and ascites. Arteriographies during subsequent episodes of bleeding were negative for active arterial intestinal bleeding. Recurrent gastrointestinal bleeding was found to originate from a varicose vein cluster connected to the right iliac vein and the superior mesenteric vein, located in the submucosa of a small intestinal loop. Multiple varices were secondary to portal hypertension in the context of cirrhosis. The patient died from recurrent variceal bleeding that exacerbated liver failure worsened by pneumonia and hypovolemic and septic shock. CONCLUSIONS: The variceal bleeding in this patient was atypical in that it originated from venous collaterals bleeding into the small intestine rather than the more typical gastroesophageal varices observed in ASMD. With long standing liver dysfunction and gradual development

Rearrangement of the ALK gene and overexpression of ALK seems to occur very rarely in neuroendocrine lung tumors, with only 3 cases of atypical carcinoid and 1 large cell neuroendocrine carcinoma (LCNEC) reported in detail until now.(1,2,3,4) Here, we report a case of an ALK-positive neuroendocrine lung tumor showing a variable phenotype during the course of treatment. A pulmonary lesion with mediastinal adenopathies was detected in a 69-year-old, non-smoking female of Turkish origin during work-up for back pain. A very small amount of tumoral tissue was obtained through fine needle aspiration of a lymph node and stainings performed on paraffin-embedded tissue showed a very limited amount of tumoral tissue with a well-differentiated cytological aspect with regular nuclei. This article is protected by copyright. All rights reserved.

Evaluation of molecular tumour heterogeneity relies on the tumorous nuclei percentage (TNP) assessment by a pathologist, which has been criticised for being inaccurate and suffering from interobserver variability. Based on the 'Big Bang theory' which states that KRAS mutation in colorectal cancer is mostly homogeneous, we investigated this issue by performing a critical analysis of the correlation of the KRAS mutant allele fraction with the TNP in 99 colorectal tumour samples with a positive KRAS mutation status as determined by next-generation sequencing. Our results yield indirect evidence that the KRAS zygosity status influences the correlation between these parameters and we show that a well-trained pathologist is indeed capable of accurately assessing TNP. Our findings indicate that tumour zygosity, a feature which has largely been neglected until now, should be taken into account in future studies on (colorectal) molecular tumour heterogeneity

Drug-induced injury of the colon is a relatively frequent though underestimated event. The histological manifestations are very variable and frequently mimic other disease entities with different etiologies. The pathologist should try to give to the clinician indications concerning a possible drug-related etiology of the injury, with a specification of the drug involved, if feasible. Careful clinicopatho-logical confrontation is important to distinguish drug-related injury from other diseases of the colon. The following section provides an overview of the different patterns that can be encountered in drug-induced colon injury, their relation to specific medications, and the possible differential diagnosis.

To the Editor: Heterogeneity of tumors is a topic that has received much attention in recent years. First, studies that applied sequencing and other molecular techniques on different tumoral areas, like the landmark paper by the group of Swanton,1 have shown that mutations and other molecular alterations can be heterogenously present within a tumor and it metastases, thereby possibly hindering biomarker and targeted therapy development [...]

Endoscopic submucosal dissection (ESD) allows en-bloc resection of superficial gastrointestinal tumors, providing specimens on which lateral margin analysis can be performed reliably. Positive lateral margins have been linked to higher rates of recurrence/residual tumor. There are no guidelines for macroscopic processing of lateral margins. Currently, most institutions use parallel lateral sections, which are difficult to interpret. We use perpendicular lateral sections, hypothesizing that it decreases potential artifactually positive lateral margins. We analyzed positive lateral margin rates in colorectal ESD specimens according to sectioning method. We also looked at morphological factors associated with margin positivity as a function of technique used. We studied 166 ESD specimens, on which parallel sectioning practiced from 2006 to 2011 (n = 75). Perpendicular sectioning was used from 2010 to 2015 (n = 91). We recorded the number of positive margins, along with grade of dysplasia/carcinoma. Other information such as histopathological type, specimen size, lesion location, and patient follow-up was also recorded for evaluation. Forty of seventy-five (63%) margins were positive for parallel sections. In contrast, perpendicularly cut margins were significantly less frequently positive: 22/91 (24%) (p = 0.0001). Positive margins were found significantly more frequently in tubulo-villous lesions compared to tubular lesions in both the parallel and perpendicular groups (p = 0.03 and p = 0.02, respectively). Specimen size was not significantly associated with positive margins. Using perpendicular sectioning of colorectal ESD specimens, the proportion of cases with a positive lateral margin was significantly lower than when parallel sectioning was used. We suggest perpendicular sectioning to improve accuracy in histopathological analysis. This method is particularly important to use in future studies, as it may prevent authors from making conjectures based on overestima

Sclerosing epithelioid fibrosarcoma (SEF) is a rare, malignant fibroblastic neoplasm, morphologically composed of cords, nests or sheets of monotonous epithelioid cells within a collagenous matrix. It has been recently characterized by recurrent pathogenic EWS-CREB3L1/2 or FUS-CREB3L2 fusions and common MUC4 protein expression by immunohistochemistry. Typically SEF occur in middle-aged adults and rarely have been reported within the abdominal cavity. Here we report an 18-year-old man with intraabdominal tumor and multiple disseminated liver metastases, presenting pure SEF histologic and immunophenotypic features. Fluorescence in situ hybridization analysis showed unbalanced rearrangement of Ewing sarcoma breakpoint region 1 (EWSR1) gene. Genomic profiling by array CGH, followed by RT-PCR and sequencing analysis, revealed a previously not reported EWSR1 translocation partner, cAMP-responsive element-binding protein 3-like 3 (CREB3L3). The novel EWSR1-CREB3L3 fusion further extends the range of fusion types involving EWSR1 that are characteristic for SEF

Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.