OBJECTIVE:Lung cancer is the second most common malignancy worldwide and remains a leading cause of cancer-related mortality. Identifying predictive biomarkers is essential to improve personalized treatment. This prospective six-year study investigated the correlation between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) mutations in Moroccan patients with lung adenocarcinoma. MATERIALS AND METHODS:Between 2017 and 2022, 234 patients with histologically confirmed lung adenocarcinoma were prospectively enrolled. TTF-1 expression was assessed by immunohistochemistry, and EGFR mutations were evaluated using molecular testing. Statistical analyses examined associations with clinicopathological parameters and overall survival. RESULTS:TTF-1 expression was detected in 83.8 % of cases and was more frequent among females (85.5 %) and never-smokers (88.2 %). EGFR mutations were identified in 21.36 % of patients, with exon 19 deletions (15.38 %) and exon 21 mutations (4.27 %) being the most common. A strong association was observed between TTF-1 expression and EGFR mutations (p < 0.001), particularly exon 19 deletions (p = 0.009). No significant correlation was found with exon 21 mutations or rare/dual variants. Combined exon 19 and 21 mutations were also significantly associated with TTF-1 positivity (p = 0.001). CONCLUSION:This study demonstrates a strong correlation between TTF-1 expression and common EGFR mutations, especially exon 19 deletions, in Moroccan patients with advanced lung adenocarcinoma. The association was most evident in never-smokers, supporting the role of TTF-1 and EGFR as complementary biomarkers in guiding diagnosis and treatment. Larger multicenter studies are warranted to further explore their prognostic value.
Epidermal growth factor receptor (EGFR) mutation screening in non-small cell lung cancer (NSCLC) is now used to guide treatment decisions to identify patients with EGFR positive mutations that predict response to EGFR tyrosine kinase inhibitors. This study aimed to explore with a prospective study the current testing practices and the predictive value of EGFR mutations in a series of 261 patients with NSCLC. EGFR mutation testing was conducted using 2 different assays: bidirectional Sanger sequencing of polymerase chain reaction (PCR) and real-time PCR on the Rotor-Gene Q instrument. Epidermal growth factor receptor mutation testing was performed for 261 patients with lung cancer. Exons 18 to 21 were successfully analyzed in 113 tumors by Direct sequencing and in 148 tumors by real-time PCR. The prevalence of positive EGFR-mutations in each method was 22.1% (N = 25) and 24.3% (N = 36), respectively (P = .3). In total, EGFR mutations were detected in 59 patients among 261 patients with NSCLC. A statistically significant association between female sex, nonsmoking history, nonsolid major pattern, and a higher EGFR mutation frequency. In this study, we investigated clinicopathological differences between tumors harboring exon 19del and those harboring L858R. We did not find any significant differences between the 2 mutations and gender or smoking features, interestingly, the prevalence of patients aged >60 years was significantly higher in the L858R group than in the exon 19del group (81.8% vs 55.8%, P = .05). A significant association was observed between exon 19 deletions and the papillary major pattern, but no correlation was detected between exon 21 mutation and any histological pattern. This prospective study documented the real-world clinical testing of EGFR mutation in Moroccan NSCLC patients. Our experience confirms the need to develop standards-based guidelines for the routine performance and evaluation of EGFR testing to improve clinical care for this subset of lung cancer. On the other hand, our study demonstrated that tumors with exon 19 deletions and L858R harbor specific clinicopathological features in NSCLC.
Background Non-small cell lung cancer (NSCLC) remains a significant global health concern, with EGFR mutations playing a pivotal role in guiding treatment decisions. This prospective study investigated the prevalence and clinical implications of EGFR mutations in Moroccan NSCLC patients. Methods A cohort of 302 NSCLC patients was analyzed for EGFR mutations using multiple techniques. Demographic, clinical, and pathological characteristics were assessed, and overall survival (OS) outcomes were compared among different EGFR mutation subtypes. Results EGFR mutations were present in 23.5% of patients, with common mutations (81.69%) dominating. Common mutations showed strong associations with female gender and non-smoking status, while rare mutations were associated with a positive smoking history. Patients with EGFR mutations receiving tyrosine kinase inhibitors (TKIs) had significantly improved OS compared to wild-type EGFR patients. Notably, patients with common EGFR mutations had the highest OS, while those with rare mutations had a shorter survival period, albeit not statistically significant. Conclusion This study highlights the relevance of EGFR mutation status in NSCLC patients, particularly in therapeutic decision-making. The association between smoking history and rare mutations suggests the need for tailored approaches. The survival advantage for patients with common EGFR mutations underscores the significance of personalized treatment strategies.
Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.
Background In the current treatment landscape for non-small cell lung cancers, epidermal growth factor receptor-tyrosine kinase inhibitors have emerged as a well-established treatment option for patients with advanced or metastatic disease. This is particularly true for those with commonly occurring epidermal growth factor receptor mutations. However, the therapeutic efficacy of these agents for so-called rare epidermal growth factor receptor mutations, and in particular those characterized by a high degree of complexity, such as double mutations, remains a subject of clinical uncertainty. Case presentation In this context, we present the case of a 64-year-old man of Moroccan descent, a lifelong non-smoker, diagnosed with metastatic non-small cell lung cancer characterized by a complex epidermal growth factor receptor mutation encompassing L858R and S768I. The patient subsequently underwent afatinib-based treatment, showing notable clinical results. These included a remarkable overall survival of 51 months, with a median progression-free survival of more than 39 months. Conclusions This case report is a compelling testimony to the evolving therapeutic landscape of non-small cell lung cancers, providing valuable insight into the potential therapeutic efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors in the realm of rare and complex epidermal growth factor receptor mutations.
378 Background: In Morocco, Kidney cancer is the 18th most common tumour and the 19th lethal cancer in 2020. The average age of diagnosis is 65 years and men are more affected. Molecular studies of renal cell carcinoma (RCC) allowed the detection of several genetic abnormalities in each histological subtype. These aberrations got different diagnostic value depending on their specificity, prognostic implication and for some a therapeutic utility since the development of targeted therapies. The aim of our study is to evaluate the utility of fluorescence in-situ hybridization (FISH) in the diagnostic and the prognostic categorization of patients with renal cell carcinoma. Methods: We included prospectively cases of RCC diagnosed after histological examination and immunohistochemistry analysis for some cases. The methodology consisted in highlighting by FISH molecular abnormalities for each histological subtypes using Zytolight probes. Probes were chosen depending on the histological diagnosis and their corresponding molecular abnormalities. Results: A total of 30 cases of RCC were included. Clear cell carcinoma (ccRCC) represented 56,6%(17 cases) followed by papillary RCC (pRCC) with 20% (6 cases), chromophobe RCC (chRCC) with 10% (3 cases), 2 cases (6,6%) with uncertain diagnosis clear cell carcinoma or papillary carcinoma and one case of renal oncocytoma (RO) (3,3%), tubulo-cystic RCC tcRCC (3,3%). The FISH method supported the morphological diagnosis in all cases except in one biopsy diagnosed histologically as a ccRCC and this method allowed the diagnosis correction to a pRCC by the detection of a polysomy of chromosome 17 described in this histological subtype. The FISH method can also be used in prognostic categorisation of patients by the detection of some genetic aberrations with a prognostic implication like the loss of CDKN2a located in the long arm of chromosome 9 which predict a worse diagnosis. Conclusions: FISH method got an good performance in the diagnostic approach of RCC especially in cases with non-conclusive histology and immunohistochemistry. It can also be used in the prognosis of this tumour in addition to other histo-prognostic factors. This method will lead to more precision in diagnosis and better care management personalisation in RCC.
Background: We herein report the case of a patient with advanced lung adenocarcinoma who presented a heterogeneous distribution of EGFR mutation. Case report: A 74-year-old Moroccan male former smoker was diagnosed with advanced lung adenocarcinoma, harboring S768I exon 20 substitution mutation confirmed by Real Time PCR and Pyrosequencing, but not detected by direct sequencing despite 70% of tumor cells. The present report describes a case of minor histologic intratumoral heterogeneity with heterogeneous distribution of EGFR mutation. Conclusion: Both sensitivity and specificity of molecular methods can provide evidence of intratumoral heterogeneity, which may explain the mismatch between the validation of oncology biomarkers and predicting therapeutic response to targeted therapy.
Objective: Urolithiasis disease is a severe pathology causing painful bleeding in patients and can lead to kidney failure. Current treatments are limited, expensive, invasive with side effects and requires new alternatives, especially those based on natural products. This work aimed to determine the in vivo antilithiasis effect of hydroalcoholic extract (E.PG) and infusion (I.PG) of the Punica granatum L. plant, as well as their antibacterial capacity against the strains responsible of urinary tract infection such as: E. coli, P. Mirabilis, K. pneumoniae and S. Aureus. Methods: A curative protocol was followed, which consisted of inducing calcium oxalate lithiasis in rats by ethylene glycol (75%) and ammonium chloride (1%) solutions. After 15 days of oxalocalcic lithiasis induction, plant extracts were administered to rats at two different doses (200 and 400 mg/kg/day), with potassium citrate (Cit.K) used as a positive control. Water intake, urine volume, pH and body weight were measured with crystalluria and histopathological examinations of the kidneys performed. The antibacterial activity was studied by the disk diffusion method and the minimum inhibitory concentration (MIC) method. The checkerboard technique was used to determine the interactions between the two extracts. Results: The results found show a significant effectiveness of the Punica granatum L. extracts, especially the infusion in preventing the formation, development and calcium oxalate crystals deposition. In fact, crystalluria revealed an important diuresis with the presence of a very low crystals number (<50 / mm3) of very small size in the rat's urine treated with EPG and IPG at the concentration of 400 mg/kg/day. Kidney histopathology analysis showed the absence of crystal deposition, as well as an almost normal structure. Moreover, the antimicrobial activity showed the efficiency of the plant extracts in inhibiting the growth of P. mirabilis and S. aureus where the inhibition zones (IZ) revealed by the disk diffusion method are between 14 and 16 mm. I.PG extract displayed a very low MIC of 1.875 against E. coli. Furthermore, the interaction between these two extracts showed partial synergy and an additive effect against S. Aureus and K. pneumoniae. Conclusions: Punica granatum L. plant has promising antilithiasis and antibacterial effects. Therefore, future extensive studies are needed to establish its effectiveness for clinical use.
Introduction. There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p=0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p<0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p=0.008). Conclusion. Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses.
Secretory Breast Carcinoma (SBC) is a rare subtype of breast cancer, predominantly affecting young women, and characterized by hormone receptor-negative and HER2-negative tumors with distinctive histological features, including secretory droplets within tumor cells. This article presents 2 unique cases of SBC, Case 1 involving a 42-year-old woman with triple-negative mammary carcinoma later diagnosed with triple-negative secretory carcinoma, and Case 2 featuring a 48-year-old woman with poorly differentiated adenocarcinoma subsequently identified as invasive mammary carcinoma of secretory type. Both cases received diverse treatment regimens, incorporating surgery, chemotherapy, radiotherapy, and hormone therapy. The importance of accurate diagnosis and the need for further research to optimize the management of this rare breast cancer subtype are emphasized. Raising awareness of SBC and reporting additional cases can enhance understanding and improve patient outcomes. Additionally, the integration of clinical, radiological, and histopathological findings, alongside specific molecular markers like S-100 and mammaglobin, is crucial for accurate SBC diagnosis. Given the lack of established guidelines for SBC management, collecting additional cases can aid in defining a more effective strategy for diagnosis, monitoring, and treatment, ultimately contributing to advancements in the field. Herein, we report 2 cases of this rare disease that were diagnosed and treated in our institution.
Granular Cell Tumors (GCTs) or Abrikossoffs tumors are ubiquitous lesions that are currently assumed to arise from perineural Schwan cells. Granular Cell Tumors of the Breast (GCTBs) are rare tumors, representing about 5 to 15 % of all GCTs and 6,7 out of 1000 cases of breast neoplasms. They occur usually in premenopausal African-American women and are by large benign, even though in extremely rare cases they can express malignant behavior or coexist with malignant lesions. GCTBs are of particular significance as they mimic breast malignancies both clinically and radiologically. Histological examination is mandatory for the diagnosis of GCTBs and IHC seems to be the gold standard for this diagnosis, indeed, our tumor cells show strong positivity for the S-100 protein. Wide local excision is the only treatment for GCTBs that are associated with an excellent prognosis. In this article we report a case of GCTB with a brief literature review, the aim of this work is to draw the attention of senologists and pathologists toward this misleading tumor, wich should be routinely recalled as differential diagnosis of breast malignancies in order to avoid over treatement of patients.
Trichosporon is a basidiomycete yeast of tropical origin that is also opportunistic in the immunocompromised. It is characterized by irregular nodules attached to the hair called white piedra. Trichosporon spp has been reported as the 2 nd most common agent of disseminated, potentially fatal fungemia [1]. Nevertheless, no pure cutaneous manifestation had been reported. We report a single case of Trichosporon spp causing an umbilical papulonodular rash in a newly diagnosed HIV-positive subject.
Fibroadenomas are the most common tumors in women of childbearing age, especially young women under the age of 30. The majority of biopsied ACR4A lesions correspond to adenofibromas. Usually these are solid, oval, well defined, with regular contours, lobulated (≥4 lobulations).We present the case of a 17-year-old girl, who has multiple fibroadenomas, about 36 lesions. The majority of fibroadenomas are unique, however, multiple fibroadenomas can be observed in 15-20% of cases. The average number of multiple fibroadenomas in a single breast has been reported to be 2-4. Management requires long-term follow-up.
Objective Our prospective study aims to define the correlation of EGFR (epidermal growth factor receptor) mutations with major histological subtypes of lung adenocarcinoma from resected and non-resected specimens, according to the WHO 2015 classification, in Moroccan North East Population. Methods Epidermal growth factor receptor mutations of 150 primary lung adenocarcinoma were performed using Real-Time PCR or SANGER sequencing. SPSS 21 was used to assess the relationship between histological subtypes of lung adenocarcinoma and EGFR mutation status. Results 25 mutations were detected in the series of 150 lung adenocarcinomas, most of which were found in cases with papillary, acinar, patterns than without these patterns and more frequently occurred in the cases without solid pattern than with this pattern. A significant correlation was observed between EGFR mutation and acinar (P = 0,024), papillary pattern (P = 0,003) and, negative association with a solid pattern (P < 0,001). In females, EGFR mutations were significantly correlated with the acinar pattern (P = 0,02), whereas in males with the papillary pattern (P = 0,01). Association between the histologic component and exon 19 deletions and exon 21 mutations were also evaluated and, we found a significant correlation between the papillary major pattern with exon 19 mutations (P = 0,004) and, ex21 with the acinar component (P = 0,03). Conclusion An analysis of resected and non-resected lung ADC specimens in 150 Moroccan Northeast patients, revealed that acinar and papillary patterns may predict the presence of a mutation in the EGFR gene. While the solid major pattern may indicate a low mutation rate of the EGFR gene.
Introduction:Human cytomegalovirus (HCMV) and isocitrate dehydrogenase (IDH) have been separately associated to gliomas. IDH is a molecular marker considered in the histo-molecular classification of gliomas as well as in their management and prognosis. However, even if oncomodulatory properties were attributed to HCMV, its association to gliomas remains a controversy. Most of the studies that investigated this association used the histological classification of gliomas; nevertheless, in 2016, the World Health Organization recommended the introduction of molecular characteristics to refine this classification. The aims of this study were to determine the prevalence of HCMV in glioma patients, the association between HCMV and IDH with gliomas and subsequently their associations with survival of patients in a Moroccan cohort.Methods:A series of 102 gliomas and 32 controls were analyzed by nested PCR (nPCR) to determine the HCMV status. PCR and sequencing were used to determine the IDH subtypes in tumors samples. IDH mutation and HCMV status were correlated to the characteristics of the tumors using SPSS, whereas the survival curves were obtained by the Kaplan-Meier method and the log rank test.Results:HCMV shows significant association with gliomas with a detection rate of 30.4% and no case in the control group. The IDH mutation was identified in 40.9-50% of grade II-III gliomas and in 10.9% of grade IV gliomas. A significant association was obtained between survival in patients with glioblastomas and IDH/HCMV status. Glioblastoma patients with HCMV+ and IDHwt had a poor prognostic.Conclusions:HCMV was detected exclusively in tumor cases and was significantly associated with poor prognosis in patients with gliomas and particularly with glioblastomas. The worst overall survival was significantly seen in patients with gliomas HCMV+/IDHwt. So, it will be of interest to consider HCMV and IDH status in gliomas management strategies.
Hemangioma of the facial sinuses is a rare pathology, and given the lack of clinical specificity, the differential diagnosis with a malignant lesion often arises. We report the case of a 32-year-old patient who consulted for recurrent epistaxis of moderate severity. The preoperative diagnosis of a hemangioma of the left maxillary sinus was based on computed tomography and magnetic resonance imaging data, confirmed by the anatomopathological study of the surgical specimen, preceded by an embolization that facilitated the endoscopic surgical excision.
Abstract INTRODUCTION: In Morocco, Kidney cancer is the 18th most common tumour and the 19th lethal cancer in 2020. The average age of diagnosis is 65 years and men are more affected. Molecular studies of renal cell carcinoma (RCC) allowed the detection of several genetic abnormalities in each histological subtype. These aberrations got different diagnostic value, prognostic implication and for some, therapeutic utility. The aim of our study is to evaluate the utility of fluorescence in-situ hybridization (FISH) in the diagnosis and the prognosis of renal cell carcinoma. MATERIAL AND METHODS: We included prospectively cases of RCC diagnosed after histological examination and immunohistochemistry analysis for some cases. The methodology consisted in highlighting by FISH method, molecular abnormalities for each histological subtypes using Zytolight® probes. Probes were chosen depending on the histological diagnosis. RESULTS: A total of 23 case of RCC were included. Clear cell carcinoma (ccRCC) represented 47,8% (11 cases) followed by papillary RCC (pRCC) with 26%, chromophobe RCC (chRCC) with 13%, a case with uncertain diagnosis, ccRCC or pRCC (4,3%), one case of renal oncocytoma (RO) (4,3%), and a case of tubulo-cystic RCC (4,3%). FISH method supported the morphological diagnosis in all cases except in one biopsy diagnosed histologically as a ccRCC and this method allowed the diagnosis correction to pRCC by the detection of chromosome 17 polysomy described in this histological subtype. FISH can also be used in the prognostic categorization of patients by detecting of some genetic aberrations with a prognostic implication like CDKN2a loss which predict a worse evolution. CONCLUSION: FISH method got an implication in the diagnostic approach of RCC, especially in cases with non-conclusive histology and immunohistochemistry. It can also be used in the prognosis in addition to other histo-prognostic factors. This method will lead to more precision in diagnosis and better care management personalization.
Metastatic small bowel tumors in the testes are uncommon often indicating an advanced stage of sickness with poor prognosis.The route of spread to the scrotal level has not yet been defined.The most of these tumors are diagnosed at autopsy or orchiectomy for metastatic carcinoma.The diagnosis is mainly based on histological and immunohistochemical data.In this paper, we report the case of a 36-year-old patient with a spermatic torsion secondary to a testis metastasis from an adenocarcinoma of the small intestine confirmed histologically, occurring as first clinical manifestation that was taken care in the medical oncology department of CHU Hassan II in Fès.The aim of the subject is to highlight this rare metastatic localization of gastrointestinal cancer; how to approach the diagnosis and distinguish between primary testicular cancer and testicular metastasis; by describing the different clinical, radiological and anatomopathological aspects of metastatic gastrointestinal cancer to the testis.