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The article describes the case of a 14-year-old boy with a two-month history of back pain and progressive gait disturbance. The boy developed paresthesia and complete palsy of both legs one week before his admission. The clinical examination showed an isolated spastic paraplegia, and magnetic resonance imaging (MRI) of the spine showed a T7-T12 intramedullary mass. The need to perform complete resection to give the patient a possible cure and better prognosis is stressed.

Signal transducer and activator of transcription (STAT) proteins are cytoplasmic transcription factors known to play key roles in numerous physiological and pathological processes, from pathogen response to cancer modulation. However, the roles of some STAT family members, particularly STAT1 and STAT4, in the initiation and progression of bladder cancer (BC) have not been comprehensively studied. The present study investigated the expression pattern of STAT1 and STAT4 in the prognosis and survival of BC taking advantage of patients' specimens and cell lines. In our cohort, high mRNA expression of STAT1 was significantly associated with tumor invasiveness, recurrence and progression, and was shown to increase according to tumor stage in BC cell lines. However, it did not affect patient survival. By contrast, STAT4 exhibited its highest expression in early-stage tumors, without a significant link to the tumor stage. Moreover, it was found that increased STAT4 mRNA expression was associated with improved disease-free survival and overall survival in our cohort. Collectively, these findings suggest that STAT1 and STAT4 could be promising prognostic markers to enhance BC management., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2025 El Ahanidi et al.)

Background: This review article aims to investigate the prevalence and spectrum of rat sarcoma (RAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations, and their connection with geographical location, clinicopathological features, and other relevant factors in colorectal cancer (CRC) patients in the Middle East., Methods: A systematic literature review, employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, was conducted to investigate the association between the frequency of relevant mutations and the descriptive clinicopathological characteristics of CRC patients. Multiple electronic databases, including PubMed, Science Direct, Web of Science, Scopus, and Google Scholar, were searched to analyze the relevant literature., Results: A total of 19 eligible studies comprising 2960 patients with CRC were included in this review. A comprehensive analysis of the collected literature data as well as descriptive and methodological insights is provided. Men were predominant in reviewed studies for the region, accounting for 58.6%. Overall, RAS mutation prevalence was 38.1%. Kirsten RAS Viral Oncogene Homolog (KRAS) mutations were the most common, accounting for 37.1% of cases and distributed among different exons, with the G12D mutation being the most frequent in exon 2 (23.2%) followed by G12V (13.7%), G13D (10.1%), G12C (5.1%), G12A (5.04%), and G12S (3.6%). Neuroblastoma RAS Viral Oncogene Homolog (NRAS) mutations were identified in 3.3% of tumor samples, with the most common mutation site located in exons 2, 3, and 4, and codon 61 being the most common location for the region. The total mutation frequency in the BRAF gene was 2.6%, with the V600E mutation being the most common., Conclusion: The distribution patterns of RAS and BRAF mutations among CRC patients exhibit notable variations across diverse ethnic groups. Our study sheds light on this phenomenon by demonstrating a higher prevalence of KRAS mutations in CRC patients from the Middle East, as compared with those from other regions. The identification of these mutations and geographical differences is important for personalized treatment planning and could potentially aid in the development of novel targeted therapies. The distinct distribution patterns of RAS and BRAF mutations among CRC patients across different ethnic groups, as well as the regional variability in mutation prevalence, highlight the need for further research in this area., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objectives: The present study aimed to evaluate the frequencies of KRAS , NRAS, and BRAF mutations and their possible associations with clinicopathological features in 249 Moroccan patients with colorectal cancer (CRC)., Methods: A retrospective investigation of a cohort of formalin-fixed paraffin-embedded tissues of 249 patients with CRC was screened for KRAS / NRAS / BRAF mutations using Idylla™ technology and pyrosequencing., Results: KRAS , NRAS, and BRAF mutations were revealed in 46.6% (116/249), 5.6% (14/249), and 2.4% (6/249) of patients. KRAS exon 2 mutations were identified in 87.9% of patients (102/116). KRAS G12D and G12 C were the most frequent, at 32.8% and 12.93%, respectively. Among the patients with KRAS exon 2 wild-type (wt), 27.6% (32/116) harbored additional KRAS mutations. Concurrent KRAS mutations were identified in 9.5% (11/116); including six in codon 146 (A146P/T/V), three in codon 61 (Q61H/L/R), one in codon 12 (G12 A and Q61H), and one in codon 13 (G13D and Q61 L). Among the NRAS exon 2 wt patients, 64.3% (9/14) harbored additional NRAS mutations. Concurrent NRAS mutations were identified in 28.6% (4/14) of NRAS -mutant patients. Since 3.2% wt KRAS were identified with NRAS mutations, concomitant KRAS and NRAS mutations were identified in 2.4% (6/249) of patients. KRAS mutations were higher in the >50-year-old age-group ( P = .031), and the tumor location was revealed to be significantly associated with KRAS mutations ( P = .028) predominantly in left colon (27.5%) and colon (42.2%) locations. NRAS mutations were most prevalent in the left colon (42.8%) and in well-differentiated tumors (64.2%)., Conclusion: Detection of KRAS mutations, particularly the G12 C subtype, may be significant for patients with CRC and has possible therapeutic implications. However, rare KRAS concomitant mutations in CRC patients suggest that each individual may present distinct therapeutic responses. KRAS testing alongside the identification of other affected genes in the same patient will make the treatments even more personalized by contributing more accurately to the clinical decision process. Overall, early diagnosis using novel molecular techniques may improve the management of CRC by providing the most efficient therapies for Moroccan patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells' survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses. Glucose transporters (GLUTs), which play a pivotal role as the rate-limiting step in glycolysis, are frequently overexpressed in a variety of tumors, including ovarian cancer. Multiple oncoproteins can regulate GLUT proteins, promoting tumor proliferation, migration, and metastasis, either dependent or independent of glycolysis. This review examines the alteration of GLUT proteins, particularly GLUT1, in ovarian cancer and its impact on cancer initiation, progression, and resistance to treatment. Additionally, it highlights the role of these proteins as biomarkers for diagnosis and prognosis in ovarian cancer, and delves into novel therapeutic strategies currently under development that target GLUT isoforms., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2024.)

The hypermethylation status of the promoter region of the breast cancer 1 ( BRCA1) , a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of BRCA1 promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs). The results showed that BRCA1 promoter hypermethylation was higher in MBTs (20/48; 41.67%) and NATs (7/15; 46.67%) compared to BBLs (4/21; 19.05%). The high percentage of BRCA1 hypermethylation in the histologically normal adjacent tissues to the tumors (NATs) suggests the involvement of this epigenetic silencing as a potential biomarker of the early genomic instability in NATs surrounding the tumors. The detection of BRCA1 promoter hypermethylation in BBLs reinforces this suggestion, knowing that a non-negligible rate of benign breast lesions was reported to evolve into cancer. Moreover, our results indicated that the BRCA1 promoter hypermethylated group of MBTs exhibited higher rates of aggressive features, as indicated by the SBR III grade (14/19; 73.68%), elevated Ki67 levels (13/16; 81.25%), and Her2 receptor overexpression (5/20; 25%). Finally, we observed a concordance (60%) in BRCA1 promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs.

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF V600E tumors compared to PTC-BRAF wt tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves' disease, ten goiters, and 20 hyperplasias). We detected the BRAF V600E mutation by Sanger sequencing and digital droplet PCR. The results show that NOX4 was found to be higher (score ≥ 2) in C-PTC (92.9%) compared to F-PTC (52.9%) and ATC (33.3%) concerning malignant tumors. Interestingly, all C-PTC-BRAF V600E expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAF V600E mutation and NOX4 expression. In addition, independent of the mutational status of BRAF, we observed that 90% of C-PTC infiltrating tumors showed high NOX4 expression, suggesting that NOX4 may be considered a complementary biomarker in PTC aggressiveness. Interestingly, NOX4 was highly expressed in non-malignant thyroid diseases with different subcellular localizations.

Purpose: The primary aim of this study is to determine the relationship between tumor-stroma ratio (TSR) and traditional prognostic factors in luminal early breast cancer in women treated at the medical oncology department of the military hospital of Rabat in Morocco., Methods: A retrospective study was performed on primary invasive ER+/HER2- breast cancer in the period from January 1st, 2019 to December 31st, 2019. Prognostic factors included age, tumour size, lymph nodes status, Scarff-Bloom-Richardson grading, lymphovascular invasion (LVI), Ki67 and the stage of the disease. The type of Adjuvant systemic therapy was also reported .Two independent pathologists have assessed TSR by microscopic evaluation of haematoxylin and eosin tumor slides .Patients with less than 50% stroma were classified as low-stroma, the others are classified as high-stroma., Results: Of 53 ER+/HER2- operable breast cancer, 41.5% patients had low-stroma and 58.5% patients had high stroma-tumour. High stroma was significantly associated with more stage III (p=0.041), more LVI (0.034), high Ki-67 (p=0.002) and more luminal B disease (p=0.001). Also, high stroma received more adjuvant chemotherapy (p=0.005). The results are maintained in univariate analysis., Conclusions: Data suggest that TSR can be used to guide decisions on adjuvant systemic therapy for ER+/HER2- breast cancer. The integration in routine of this simple and reproducible parameter requires a homogenization of the techniques as well as a prospective validation.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2) are the most important tissue factors involved in tumor growth and angiogenesis. The aim of this study was to evaluate the promoter mutational status of VEGFA and the expression levels of VEGFA, VEGFR1, and VEGFR2 in bladder cancer (BC) tissues and to correlate the results with the clinical-pathological parameters of BC patients. A total of 70 BC patients were recruited at the Urology Department of the Mohammed V Military Training Hospital in Rabat, Morocco. Sanger sequencing was performed to investigate the mutational status of VEGFA, and RT-QPCR was used to evaluate the expression levels of VEGFA, VEGFR1, and VEGFR2. Sequencing of the VEGFA gene promoter revealed the presence of -460T/C, -2578C/A, and -2549I/D polymorphisms, and statistical analyses showed a significant correlation between -460T/C SNP and smoking ( p = 0.02). VEGFA and VEGFR2 expressions were significantly up-regulated in patients with NMIBC ( p = 0.003) and MIBC ( p = 0.03), respectively. Kaplan-Meier analyses showed that patients with high VEGFA expression had significantly longer disease-free survival ( p = 0.014) and overall survival ( p = 0.009). This study was very informative, showing the implication of VEGF alterations in BC, suggesting that VEGFA and VEGFR2 expressions could be promising biomarkers for the better management of BC.

Background: Epidermal growth factor receptor (EGFR) mutation status is of a major clinical significance in non-small cell lung cancer (NSCLC) management, as it guides therapeutic decision making to target patients for a better response to therapy. This implicates the introduction of EGFR mutation analysis as the standard of care for Moroccan NSCLC patients, which in itself entails the implementation of targeted methods for routine EGFR mutation analysis in our laboratories. In this study, we aimed to present 2 targeted methods for EGFR mutation identification and to determine the prevalence and spectrum of EGFR mutations in NSCLC Moroccan patients., Methods: A retrospective investigation of a cohort of 340 patients was undertaken to analyze somatic EGFR mutations in exons 18 to 21 using pyrosequencing and the Idylla TM system., Results: Of the enrolled patients, 70.9% were males and 29.1% were females. Predominately, 92% of cases had adenocarcinoma, and 53.7% of patients self-reported a history of smoking. Overall, 73 patients (21.7%) harbored an EGFR mutation, the most prevalent of which were the exon 19 deletions (53.4%) followed by exon 21 substitutions (31%). Exon 18 mutations and exon 20 alterations occurred in 8.1% and 6.7% of the positive EGFR mutation cases, respectively. Of the analyzed cases, all of the EGFR-mutated patients had adenocarcinoma. EGFR mutation prevalence was significantly higher in females (females vs males: 38.4% vs 14.5%, P < .001) and non-smokers (non-smokers vs non-smokers: 36% vs 10.3%, P < .001). The featured pyrosequencing and the Idylla TM system are targeted methods endowed with high sensitivity and specificity as well as other compelling characteristics which make them great options for routine EGFR mutation testing for advanced NSCLC patients., Conclusion: These findings underline the imperious need for implementing quick and efficient targeted methods for routine EGFR mutation testing among NSCLC patients, which is particularly useful in determining patients who are more likely to benefit from targeted therapy.

Background: Mutations in RAS (KRAS, NRAS) and BRAF genes are the main biomarker predicting response to anti-EGFR monoclonal antibodies in targeted therapy in colorectal cancer (CRC)., Objective: Our study aims to evaluate the frequencies of KRAS, NRAS and BRAF mutations and their possible associations with clinico-pathological features in CRC patients from Morocco., Methods: DNA was extracted from 80 FFPE samples using the QIAamp DNA FFPE-kit. RAS and BRAF mutations were assessed by pyrosequencing assays using Qiagen, KRAS Pyro®kit 24.V1, Ras-Extension Pyro®kit 24.V1 and BRAF Pyro®Kit 24.V1, respectively, and carried out in the PyroMark-Q24., Results: RAS mutations were identified in 57.5% (56.2% in KRAS, 8.8% in NRAS). In KRAS gene, exon 2 mutations accounted for 93.3% (68.9% in codon 12, 24.4% in codon 13). Within codon 12, G12D was the most prevalent mutation (37.7%), followed by G12C (13.4%), G12S (8.9%) and G12V (6.6%). Within codon 13, the most frequently observed mutation was G13D (22.3%). The mutation rates of exon 3 and 4 were 15.6% and 13.3%, respectively. In exon 3 codon 61, 2.3% patients were detected with two concurrent mutations (Q61R, Q61H), and 4.4% with three concurrent mutations (Q61R, Q61H, Q61L). In NRAS gene, the mutation rates of exon 2, 3 and 4 were 57.1%, 28.6%, and 14.3%, respectively. G13A and Q61H were the most common mutations, accounting for 42.9% and 28.5%, respectively. There were 13% patients with concurrent KRAS/NRAS mutation and 4.3% wt KRAS with NRAS mutations. No mutations were identified in BRAF gene. In both sexes, KRAS codon 12 mutations were associated with higher stage III/IV tumors. Moreover, Patients whose tumor is in the proximal colon (56.3%) are more likely to harbor KRAS mutations than those tumor located in rectum (25%)., Conclusion: RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.

Dermal nonneural granular cell tumor is a rare neoplasm of uncertain histogenesis that Le Boit and colleagues originally described in 1991. It arises commonly from the back, extremities and head and neck. To the best of our knowledge, only 50 cases have been reported in adults in the English literature. A 42-year-old man presented with a polypoid skin nodule of the front side of the chest wall, measuring 1,8 × 1,5 cm. The lesion was removed completely with tumor-free margins. Microscopically, the tumor was composed of a diffuse infiltrate of polygonal cells, S 100 negatives, with abundant granular cytoplasm and vesicular nuclei. The diagnosis of dermal nonneural granular cell tumor was retained. No recurrence was noted during follow up of 6 months. The prognosis is good., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2022.)

Teratocarcinosarcoma is a rare and aggressive malignant tumor of uncertain histogenesis. It presents <1% of all cancers and ~3% of malignant tumors of the head and neck. It arises commonly from the nasal cavity and paranasal sinuses. To the best of our knowledge, only one case has been reported in the oral cavity. A 46-year-old woman presented with 3-week history of a rapidly growing tumor in the inner side of the left cheek. Physical examination revealed an ulcerating mass measuring 4 × 3.5 cm. An excisional biopsy was performed. Histological analysis revealed a teratocarcinosrcoma. The patient was treated by combined chemotherapy and radiation therapy. No recurrence was noted 6 months after treatment. The prognosis is poor., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2022.)

Background: Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations., Methods: To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia., Results: Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68&#95;69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T>G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798&#95;799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310&#95;1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798&#95;799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310&#95;1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈3:1., Conclusions: Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy., (© 2022. The Author(s).)

Introduction: The clinical manifestations of Hodgkin lymphoma (HL) can closely mimic spine and lymph node tuberculosis (TB). Case Description . A 48-year-old man was initially treated for retroperitoneal lymph nodes TB, and this diagnosis was made without bacteriological and histopathological confirmation. After four months of regular therapy for TB, he did not improve and was admitted to our department for lumbar spine pain. We first made diagnosis of tuberculous spondylodiscitis, and anti-TB treatment was strengthened. But, after three weeks of hospitalization, his condition worsened clinically with onset of swelling of the left supraclavicular lymph node. So, after surgical excision and anatomopathological examination of the lymph node, the diagnosis of nodular sclerosis classic Hodgkin lymphoma was made. He was treated by chemotherapy, and his condition improved significantly after the first 2 cycles of chemotherapy., Conclusion: Repeated investigations may be helpful in establishing a correct diagnosis and starting an effective treatment in this highly curable disease., Competing Interests: The authors declare conflicts of interest., (Copyright © 2022 H. Julien Djossou et al.)

Background: Tumor recurrence and progression in non-muscle invasive bladder cancer (NMIBC), therapy failure, and severe side effects in muscle invasive bladder cancer (MIBC) are the major challenges in the clinical management of bladder cancer (BC). Here, we identify new molecular targetable signatures to improve BC patients' stratification and the outcome of current immunotherapies., Material and Methods: In a prospective cohort of 70 BC patients, we assessed the genetic and molecular regulation of TERT in maintaining telomere length in parallel to immune checkpoint and microRNA expression., Results: TERT was undetectable in healthy bladder tissues but upregulated in invasive BC stages and high tumor grade. Its expression was linked with the combined effect of the C250T mutation and THOR hypermethylation, associated with progressing tumors and maintaining of telomere length. In the same cohort, PD-L1 scored highest in NMIBC, while PD-L2 was upregulated in MIBC. We also show that miR-100-5p and 138-5p were highly expressed in healthy bladder specimens and cell line, while expression decreased in the BC tissues and BC cell lines. In line with the binding prediction for these miRNAs on target genes, miRs 100-5p and 138-5p expression strongly inverse correlated with TERT, PD-L1, and PD-L2 expression, but not PD1., Conclusion: We identify a loop involving TERT, PD1-ligands, and miR-138-5p in BC, that might represent not only a useful biomarker for improved diagnosis and patients' stratification but also as a promising axis that might be therapeutically targeted in situ ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 El Ahanidi, El Azzouzi, Hafidi Alaoui, Tetou, Bensaid, Chaoui, Benbacer, Hassan, Oukabli, Michaud, Ameur, Al Bouzidi, El Mzibri, Jandus and Attaleb.)

Introduction: in cancer cells, activating mutations in PIK3CA and AKT1 genes, major players of PI3K-AKT-mTOR signalling pathway, are widely reported in many cancers and present attractive targets for the identification of new therapeutics and better cancer management. The present study was planned to evaluate the mutational status of PIK3CA and AKT1 genes in bladder cancer patients and to assess the association between these mutations and patients´ clinico-pathological features., Methods: in this prospective study, bladder cancer biopsies and matched urine sediments samples were collected form 70 patients. Mutations were assessed by deoxyribonucleic acid (DNA) sequencing and correlation with clinico-pathological data was performed using SPSS software., Results: AKT1 alterations were poorly detected. Only one patient with pT1 stage and high-grade tumour carried the E17K mutation. In PIK3CA exon 9, 2 point mutations, E545K and Q546E, and a SNP (E547E) were reported, whereas in exon 20, 2 point mutations (L989V and H1047R) and 2 SNPs (I1022I and T1025T) were detected. PIK3CA mutations were mainly observed in early stages and high-grade tumours. Statistical analysis showed no significant association between the studied AKT1 and PIK3CA mutations and patients´ clinico-pathological parameters (p > 0.05). Detection of these mutations in voided urine samples showed a high specificity (100%) for both genes and a moderate sensitivity: 100% for AKT1 and 66.7% for PIK3CA genes., Conclusion: this study shows clearly that mutations in AKT1 and PIK3CA are rare events and could not be considered as valuable biomarkers for bladder cancer management., Competing Interests: The authors declare no competing interests., (Copyright: Hajar El Ahanidi et al.)

Competing Interests: The authors report no conflict of interest.

Pathogenic variants (PVs) in BRCA genes have been mainly associated with an increasing risk of triple negative breast cancer (TNBC). The contribution of PVs in non-BRCA genes to TNBC seems likely since the processing of homologous recombination repair of double-strand DNA breaks involves several genes. Here, we investigate the susceptibility of genetic variation of the BRCA and non- BRCA genes in 30 early-onset Moroccan women with TNBC. Methods: Targeted capture-based next generation sequencing (NGS) method was performed with a multigene panel testing (MGPT) for variant screening. Panel sequencing was performed with genes involved in hereditary predisposition to cancer and candidate genes whose involvement remains unclear using Illumina MiSeq platform. Interpretation was conducted by following the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) criteria. Results: PVs were identified in 20% (6/30) of patients with TNBC. Of these, 16.7% (5/30) carried a BRCA PV [10% (3/30) in BRCA1 , 6.7% (2/30) in BRCA2 ] and 6.6% (2/30) carried a non- BRCA PV. The identified PVs in BRCA genes ( BRCA1 c.798&#95;799delTT, BRCA1 c.3279delC, BRCA2 c.1310&#95;1313del, and BRCA2 c.1658T>G) have been reported before and were classified as pathogenic. The identified founder PVs BRCA1 c.798&#95;799del and BRCA2 c.1310&#95;1313delAAGA represented 10% (3/30). Our MGPT allowed identification of several sequence variations in most investigated genes, among which we found novel truncating variations in PALB2 and BARD1 genes. The PALB2 c.3290dup and BARD1 c.1333G>T variants are classified as pathogenic. We also identified 42 variants of unknown/uncertain significance (VUS) in 70% (21/30) of patients with TNBC, including 50% (21/42) missense variants. The highest VUS rate was observed in ATM (13%, 4/30). Additionally, 35.7% (15/42) variants initially well-known as benign, likely benign or conflicting interpretations of pathogenicity have been reclassified as VUS according to ACMG-AMP. Conclusions: PALB2 and BARD1 along with BRCA genetic screening could be helpful for a larger proportion of early-onset TNBC in Morocco., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Lipoma is the most common of soft tissue tumours. It rarely occurs in the head and neck. Patients with fast-growing large sized lesion (> 10cm) should be suspected to have a cancer. We here report the case of a patient presenting with unusual cervical lipoma (size: approximately 46cm), diagnosed based on imaging tests, including computed tomography (CT) scan. Patient´s management was based on surgery., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Mohammed Elakhiri et al.)

Background: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAF V600E mutation is described to be associated with a worse prognostic of thyroid carcinomas, as well as extrathyroidal invasion and increased mortality., Objective: To our knowledge, there are no reported studies neither from Morocco nor from other Maghreb countries regarding the prevalence of BRAF V600E mutation in thyroid carcinomas. Here we aim to evaluate the frequency of BRAF V600E oncogene in Moroccan thyroid carcinomas., Methods: In this Single-Institution retrospective study realized in the Anatomic Pathology and Histology Service in the Military Hospital of Instruction Mohammed V 'HMIMV' in Rabat, we report, using direct genomic sequencing, the assessment of BRAF V600E in 37 thyroid tumors., Results: We detected BRAF V600E mutation exclusively in Papillary Thyroid Carcinomas 'PTC' with a prevalence of 28% (8 PTC out 29 PTC). Like international trends, Papillary Thyroid Carcinomas 'PTC' is more frequent than Follicular Thyroid Carcinomas 'FTC' and Anaplastic Thyroid Carcinomas 'ATC' (29 PTC, 7 FTC and 1 ATC)., Conclusion: Our finding gives to the international community the first estimated incidence of this oncogene in Morocco showing that this prevalence falls within the range of international trends (30% to 90%) reported in distinct worldwide geographic regions., (© 2020 Kaabouch M et al.)

Gastric schwannoma (GS) is a rare neoplasm of the stomach deriving from Schwann cells of the peripheral nerves in the stomach. It accounts for 0.2% of all gastric tumors and is mostly benign, slow-growing and asymptomatic. Due to its rarity, GS is not widely recognized by clinicians. Preoperatively, GSs are difficult to differentiate from other mesenchymal tumors, such as gastrointestinal stromal tumor (GIST) or leiomyoma, which develop from mesenchymal stem cells. The optimal management of GS is based on the symptoms of the patient, tumor size and histologic grading. Here, we report the case of a GS in a 73-year-old female who underwent a wedge gastric resection following a clinical diagnosis of GIST. A histological and immunohistochemical study was performed excluding the misdiagnosis of GIST. The histomorphological features of the lesion and absence of c-Kit and strong positivity of S100 indicated the diagnosis of GS., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2020.)

Primary angiosarcoma of the pleura is an extremely rare tumour arising from arterial or venous pulmonary vessels of various size. It is characterized by an aggressive course and a poor prognosis. The early diagnosis is challenging due to diverse clinical and radiological manifestations. We report a case of a 70 year old male with primary right pleural epitheloid angiosarcoma. The patient had a history of a two week's progressive dyspnea. CT-scan showed a prominent thikening of the right pleura associated with pleural effusion and atelectasis. CT-scan guided by biopsy was performed and histological examination showed a tumor proliferation consisting of sheets of polygonal and epitheloid cells showing rudimentary vascular differentiation. Immunohistochemically, tumor cells were strongly positive for CD31 and Factor VIII-related antigen, negative for CD34, weakly and focally positive for EMA and Cytokeratine. The overall pathological and immunohistochemical features of the pleural specimens supported the diagnosis of epitheloid angiosarcma. The patient died after a week of discharge by pulsless ventricular tachycardia arrest. In addition, we also present a brief litterature review on pleural angiosarcoma. Our experience with this case suggests that comprehensive and sufficient sample collection and meticulous histological examination aided with immunohistochemical stains, particulary the endothelial markers, are required for accurate diagnosis of this rare malignancy., Competing Interests: The authors declare no competing interests., (© Mustapha Azzakhmam et al.)

Chondrosarcoma is a rare malignant bone tumor. It can arise de novo or secondary to a malignant transformation of a benign underlying cartilage tumor. Secondary chondrosarcoma arising from solitary benign osteochondroma is extremely rare and data show that the reported incidence of osteochondroma of the pelvis is very low. We here report the case of a 20-year old patient with chondrosarcoma secondary to malignant transformation of an osteochondroma of the right wing of ilium, adjacent to the sacroiliac joint., Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts.

Background: Urinary schistosomiasis is a common parasitic disease in endemic countries., Case Presentation: We report the case of a patient who was on a working trip to Mauritania. This parasitosis, suspected in the presence of hematuria and the notion of stay in an endemic zone, was confirmed by the presence of Schistosoma heamatobium eggs during the histological examination of the bladder biopsy performed after cystoscopy, highlighting a bilharzial granuloma and of course, the diagnosis was confirmed by the presence of eggs during the direct examination of the freshly collected urine., Conclusions: It should be pointed out that the diagnosis of schistosomiasis must be evoked with the association of hematuria and the particular inflammatory aspect of the vesical mucosa and, of course, the notion of stay in an endemic zone., Competing Interests: Not applicable.Written informed consent was obtained from the patient for publication of this Case Report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

We present a case of a papillary tumour at the cerebellopontine angle in a 54-year-old man. He presented with right-sided ear pain associated with dizziness and hearing loss. The radiological diagnosis was in favor of acoustic neurinoma. Surgical excision was performed and the diagnosis of the endolymphatic sac tumour was made. Endolymphatic tumour is a low grade adenocarcinoma that originates from the endolymphatic sac. The definitive diagnosis requires a combination of clinical features, radiological finding and pathological correlation., Competing Interests: The authors declare no competing interests.

Background: Glutathione S-transferase pi 1 (GSTP1) is a cytosolic detoxifying enzyme that protects cells against deleterious effects of oxidative stress. Deregulated expression of GSTP1 protein and aberrant promoter methylation of GSTP1 gene were reported in various human tumors and were shown to be involved in the molecular pathway for cancer development., Aims and Methods: In this study, we aimed to determine the expression status of GSTP1 in relation to its gene promoter methylation in Moroccan population of 30 bladder cancer (BC) patients and in two noncancerous bladder tissues used as controls. GSTP1 expression was assessed by immunohistochemistry and GSTP1 gene promoter methylation status was studied by methylation-specific PCR (MS-PCR)., Results: Glutathione S-transferase pi 1 was expressed in the two normal tissues. In BC cases, GSTP1 expression was strong in 23.33% (7/30), moderate in 60% (18/30), and weak in 13.33% (4/30) of cases, while GSTP1 was not expressed in one cancer case (3.33%). Variability of GSTP1 expression does not correlate with high-grade cancer or invasive-stage (p > 0.05). No GSTP1 gene promoter methylation was detected in all control and cancer cases., Conclusion: Our data suggest that GSTP1 expression is not associated with BC development, limiting its use as a biomarker for BC management in Morocco. Moreover, difference in GSTP1 expression among BC cases is not due to GSTP1 promoter methylation., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

We here report the case of a 46-year old female patient with a history of total hysterectomy performed in 2011 due to uterine leiomyosarcoma followed by sessions of radiotherapy, who presented with right hemicorporal sensorimotor deficit of acute onset. Clinical examination showed right pyramidal syndrome. Brain magnetic resonance imaging (MRI) revealed a left frontoparietal extra-axial aggressive tumor (A). The patient underwent surgical resection of the cerebral lesion. Anatomo-pathological examination showed fusocellular tumor proliferation (B). Tumor cells looked like discreetly atypical muscle cells and showed few mitotic figures as well focal necrosis. Tumor proliferation infiltrated the bone, the soft tisuues and the dura-mater. Immunohistochemical examination was performed which showed anti h-caldesmon-positive cells (C) and smooth muscle anti-actin-positive cells. The diagnosis of brain metastasis from leiomyosarcoma was retained. The patient underwent radiotherapy sessions with improvement of the motor deficit.

Primary hyperoxaluria is a rare disease whose incidence is estimated at less than 1 cases/million inhabitants/year. This is a congenital abnormality of hepatic metabolism leading to an endogenous overproduction of oxalate with excess urinary excretion. We report the case of a 43-year-old patient, was followed to end-stage renal disease hemodialysis, consulting for anemic syndrome with mucocutaneous pallor. Laboratory tests found pancytopenia with aplastic anemia. Bone marrow was difficult to achieve, bringing medullary blood hyperdilué and uninterpretable . Radiographs showed a homogeneous splenomegaly and small dedifferentiated a kidney marrow biopsy was performed. Histological examination revealed a myelofibrosis and birefringent crystals in polarized light, diagnosis retained: spinal oxalosis.

Granular cell tumors (GCT) are uncommon tumors. They mainly occur at the level of the skin and the subcutaneous tissues. Gastric tumor is rare. We here report a new case of gastric Abrikossoff tumor as well as a brief literature review. This study aims to examine the clinical, endoscopic and therapeutic features of this rare disease.

Soft tissue melanoma was first described by Enzinger in 1965 under the name of clear cell sarcoma. In 1983, Chung and Enzinger renamed it soft tissue melanoma due to its immunohistochemical similarities with melanoma. We here report the case of a 22-year old young man with this rare type of melanoma, presenting with molluscoid lesion on his ankle without any clinical sign of malignancy. Histology examination confirmed the diagnosis of soft tissue melanoma.

Background: Inflammatory myofibroblastic tumour (IMT) is a mesenchymal neoplasm of intermediate biological potential that may affect a wide range of anatomic sites but has a particular predilection for the lung and intra-abdominal soft tissues., Case Presentation: We report here an exceptional case of inflammatory myofibroblastic tumor arising in the lacrimal gland and presenting as an orbital mass in a 24-year-old male., Conclusion: This report aims to discuss the importance of histopathological and immunohistochemical findings in arriving at the diagnosis, which helps dictate the management, treatment and prognosis of the patient.

Gliosarcoma is a very rare brain tumor accounting for 1.8 -8% of all glial tumors. It has been classified by the World Health Organization as a variant of glioblastoma. It is a tumor with double glial and sarcomatous component. Patient's clinical picture is polymorphic, imaging data are evocative, diagnosis is based on histology. Treatment is always surgical. Prognosis is closely linked to the quality of resection. We here report two clinical cases with the aim of assessing the diagnostic, therapeutic and prognostic features of this rare entity.

Background: Urothelial bladder carcinoma (UBC) is one of the most prevalent cancers in men worldwide. Human epidermal growth factor receptor 2 (HER2) expression has been detected in a wide range of urothelial carcinoma. Despite many reports in the literature, the prognostic significance of this overexpression remains unclear. The aim of this study was to assess the expression of HER2 in urothelial bladder carcinomas and its association with clinical and pathological parameters., Methods: 103 cases of UBC were diagnosed in our department between January 2014 and December 2015. The tumor specimens obtained by transurethral resection or cystectomy were evaluated by immunohistochemistry using HER2 antibody., Results: HER2 protein overexpression was present in 11.7% of cases and associated with tumor grade ( p  = 0.003) and pathological stage ( p  = 0.015). In multivariate analysis, HER2 overexpression was associated only with tumor grade ( P  = 0.04)., Conclusion: HER2 protein overexpression is noted in patients with high grade cancer. This expression may select patients for anti HER2 targeted therapy. Future larger and prospective studies will verify the frequency of HER2 alteration and the role of HER2 in the aggressive behavior.

Background: Survival is increasing after early breast cancer revealing frequent relapses and possibility of developing secondary malignancies. The concomitant occurrence of these two events is exceptionally disastrous and lethal. We report a case of a Moroccan woman who was successfully managed for synchronous recurrent breast carcinoma and chronic myelogenous leukemia., Case Presentation: A 42-year-old Moroccan woman was diagnosed with localized breast carcinoma in 2008. She received six cycles of an adjuvant chemotherapy regimen, radiation therapy and hormonal therapy by tamoxifen. After completion of 5 years of tamoxifen our patient reported asthenia; a physical examination found hepatomegaly, massive splenomegaly measuring 21 cm and supraclavicular lymphadenopathy. The staging showed lung and liver metastases. Morphology and immunohistochemical profile of this metastasis identified an adenocarcinoma of mammary origin. In parallel, the diagnosis of chronic myeloid leukemia was suspected because of the presence of a leukocytosis at 355 × 10 9 /L, with circulating blasts of 4%. Chronic myeloid leukemia was confirmed by a bone marrow biopsy with the presence of Ph chromosome on cytogenetical analysis. Daily imatinib was ordered concurrently with chemotherapy-type docetaxel. The metastases were stable after nine courses of chemotherapy. Due to breast cancer progression 4 months later, bevacizumab and capecitabine were introduced. A major molecular response was achieved after 12 and 18 months. She has now completed 2 years of follow-up, still on a major molecular response, and is undergoing imatinib and capecitabine treatment., Conclusions: Leukocytosis in breast cancer patients can reveal chronic myeloid leukemia. It may warrant a workup to find the underlying etiology, which could include a secondary hematological malignancy.

Inflammatory fibroid polyps are uncommon benign lesions that originate in the submucosa of the gastrointestinal tract. The stomach and the ileum are the most commonly affected sites. Although inflammatory fibroid polyp is one of the rare conditions leading to intestinal obstruction in adults, it should be considered as a possible diagnosis in obstructive tumors of the small bowel causing intussusceptions. We present one case of inflammatory fibroid polyp as a rare cause of intussusception in a young adult patient.

Background: Pulmonary sarcomas are uncommon accounting for 0.5 % of all primary lung cancers. Undifferentiated sarcomas account for up to 20 % of soft tissue sarcomas. A lung tumor revealed to be an undifferentiated sarcoma with epithelioid features has never been reported in the literature., Case Presentation: A 61-year-old white Moroccan man presented with 2 months' history of hemoptysis and dyspnea. Chest computed tomography showed a cystic mass involving the lower field of his right lung evoking first a hydatid cyst. Abdominal computed tomography revealed bilateral adrenal nodules. Surgical resection of the lung mass was performed. On pathological examination, the tumor was cystic containing necrotic material. A histological diagnosis of undifferentiated sarcoma with epithelioid features was made. A positron emission tomography scan showed involvement of his pleura, left colon, adrenal glands, left thigh muscle, and leptomeninges., Conclusions: Undifferentiated sarcoma with epithelioid features is a rare malignant mesenchymal tumor. Clinical and radiological features are not specific. A differential diagnosis includes sarcomatoid carcinoma, malignant mesothelioma, melanoma, and other epithelioid sarcomas.

Paraneoplastic syndromes are a heterogeneous group of clinical and biological manifestations caused by underling neoplasms. They can reveal ovarian teratoma which express neuroendocrine proteins, or contain mature or immature neural tissue inducing an autoimmune response. The etiological investigation is then crucial to early identification of the tumor in order to optimize the prognosis and to limit neurological sequelae. In case of ovarian teratoma, management is essentially based on surgical resection sometimes associated with immunotherapie. We report two new cases of ovarian teratoma revealed by paraneoplastic syndromes in young and menopausal woman., Competing Interests: The authors declare no competing interest.

Background: Primary thyroid lymphoma is an uncommon pathological entity that accounts for only 1 to 5 % of all thyroid malignancies. Primary Burkitt lymphoma of the thyroid gland is very rare. This article presents the first Moroccan case of a primary BL of the thyroid to be reported in the literature to date., Case Presentation: We describe here a case of a 70-year-old male who developed a rapidly enlarging thyroid gland with progressive symptoms of compression. Core biopsy confirmed the diagnosis of Burkitt lymphoma. The patient died of septic shock, 2 weeks after the first cycle of appropriate therapeutic chemotherapy., Conclusions: This presentation emphasizes the importance of considering lymphoma when dealing with a thyroid mass, as its management is different from that of other thyroid pathologies, and affords an opportunity to review a very rare type of primary thyroid lymphoma.

Background: Phyllodes tumors are rare fibroepithelial tumors accounting for less than 1 % of all breast neoplasms. They are malignant in 20 % of cases. Only a few cases of malignant phyllodes tumors metastatic to bone have been reported., Case Presentation: Case 1: A 40 year-old white woman presented with three-week history of pain and functional impairment of the left lower limb. Her clinical past was remarkable for previous left mastectomy and radiotherapy for malignant phyllodes tumor performed one year ago. Computed tomography revealed a moth-eaten appearance of the left femoral head. The patient underwent computed guided femoral head biopsy. Pathological findings were consistent with metastatic malignant phyllodes tumor. The patient received ifosfamide and adriamycin chemotherapy. She is doing well without any evidence of progression on her imaging follow- up after 8 months. Case 2: A 48 year-old white woman, with history of bilateral mastectomy and radiotherapy for malignant phyllodes tumor performed one and two year ago, presented with four-week left lower quadrant abdominal pain. Computed tomography and magnetic resonance imaging revealed a solid aggressive osteolytic mass of the left iliac bone with extensive soft tissue invasion. Biopsy of the tumor was performed and showed a sarcomatous proliferation consistent with metastatic malignant phyllodes tumor. The patient received the same chemotherapy regimen as in the first case but without any response on her imaging follow up after 6 months., Conclusion: Malignant phyllodes tumor is a rare and aggressive fibroepithelial neoplasm. An accurate diagnosis of metastases should be based on clinicopathological correlation allowing exclusion of differential diagnoses. The goal of successful managing this tumor is early detection and complete resection prior to dissemination.