Rare adrenal incidentaloma: ganglioneuroma.

Ganglioneuroma (GN) is a rare, benign neurogenic tumor that develops from sympathetic ganglion cells. It occurs mainly in the retroperitoneal region. Adrenal localization is rare. We report a case of adrenal ganglioneuroma in a 22-year-old woman with no previous history of the disease. The tumor was discovered incidentally on an entero scan ordered as part of the etiological assessment for chronic diarrhea. The diagnosis was confirmed by pathological examination.

High expression of BTN3A1 is associated with clinical and immunological characteristics and predicts a poor prognosis in advanced human gliomas.

Introduction: Gliomas represent the most prevalent and aggressive tumors within the central nervous system. Despite the current standard treatments, the median survival time for glioblastoma patients remains dismal, hovering around 14 months. While attempts have been made to inhibit the PD-1/PD-L1 and CTLA-4/CD80-CD86 axes through immunotherapy, the outcomes have yet to demonstrate significant efficacy. The immune checkpoint Butyrophilin 3A1 (BTN3A1) can either be involved in advantageous or detrimental function depending on the cancer type. Methods: In our study, we utilized a Moroccan cohort to delve into the role of BTN3A1 in gliomas. A transcriptomic analysis was conducted on 34 patients, which was then corroborated through a protein analysis in 27 patients and validated using the TCGA database (n = 667). Results: Our results revealed an elevated expression of BTN3A1 in glioblastoma (grade 4), as evidenced in both the TCGA database and our cohort of Moroccan glioma patients. Within the TCGA cohort, BTN3A1 expression was notably higher in patients with wild-type IDH. We observed a positive correlation between BTN3A1 expression and immune infiltration of B cells, CD8+ T cells, naive CD4+ T cells, and M2 macrophages. Patients exhibiting increased BTN3A1 expression also presented elevated levels of TGF-ß, IL-10, and TIM-3 compared to those with reduced BTN3A1 expression. Notably, patients with high BTN3A1 expression were associated with a poorer prognosis than their counterparts with lower expression. Conclussion: Our findings suggest that BTN3A1 might promote the establishment of an immunosuppressive microenvironment. Consequently, targeting BTN3A1 could offer novel therapeutic avenues for the management of advanced gliomas.

Clinicopathological characteristics and tumor infiltrating immune cells associations of PD-L1 tumor expression in non-small cell lung cancer patients.

AIM: Our study aimed to perform on Moroccan patients' non-small cell lung carcinoma (NSCLC) concerning the relationship between PD-L1 tumor expression, clinicopathological features and tumor infiltrating immune cells (ICs). METHODS: This is a retrospective study (2019 to 2021) conducted on samples from Moroccan patients with NSCLC at the Pathological Anatomy Laboratory of Ibn Rochd University Hospital in Casablanca. Eligible participants for our study had to meet the following predefined criteria: age ≥18 years, histologically confirmed NSCLC, no prior therapeutic interventions, availability of clinical and pathological data, and a usable tumor sample for determining PD-L1 status. Exclusion criteria applied to patients with other types of lung cancer and unusable tumor samples. The evaluation of tumor and immune expression of PD-L1 was performed using immunohistochemistry (IHC), with the 22C3 clone on the Dako Autostainer Link 48 platform. Tumor PD-L1 expression was categorized into 3 levels: TPS <1% (negative expression), TPS 1-49% (low expression), and TPS ≥50% (high expression). ICs infiltrating the tumor expressing PD-L1 were considered positive when more than 1% of positive ICs were present. RESULTS: Among the 316 analyzed samples, 56.6% showed a negative expression of PD-L1, 16.8% displayed a low expression of PD-L1, and 26.6% exhibited a strong expression. Regarding the histological type, among patients with TPS ≥ 50%, 25.8% had adenocarcinoma. Among patients with TPS ≥ 50%, 24.81% were smokers. PD-L1 was also strongly expressed in the lung (28.2%) and bronchi (26.5%). PD-L1 expression (TPS ≥ 50%) was observed in 35.29% of early-stage patients. Concerning tumor cells (TCs), 27.5% of tumors infiltrated by ICs had TPS ≥ 50%. Furthermore, coexpression of PD-L1 on both TCs and ICs infiltrating the tumor was found in 27.8% of tumors. Statistical analysis demonstrated a significant association between tumor PD-L1 expression and smoking status (P=0.019). However, no significant difference was observed between PD-L1 expression and the presence of ICs infiltrating the tumor (P=0.652), as well as the IHC expression of PD-L1 on ICs (P=0.259). CONCLUSION: Our results demonstrate a significant association between PD-L1 expression and smoking status. However, no significant association was observed between PD-L1 expression and the presence of infiltrating ICs, nor with the IHC expression of PD-L1 on ICs. Our data underscore the importance of participating in the study of specific factors influencing PD-L1 expression in patients with NSCLC.

Visceral leishmaniasis as a rare cause of granulomatous hepatitis.

Visceral leishmaniasis (VL) is a potentially fatal infection caused by species of Leishmania. It is characterized by fever, weight loss, anemia, and enlargement of the spleen and liver. Hepatitis due to VL is one of the causes of granulomatous hepatitis rarely described in the literature. It poses a problem of differential diagnosis with other causes, notably infectious and autoimmune. Hence the need for a global clinical, biological, and histological evaluation to orientate this entity, especially in endemic countries like ours. In the present case study, a 2-year 8-month-old boy was diagnosed with VL and treated with meglumine antimoniate; the evolution was marked after 2 months by the persistence of a large liver; laboratory results showed elevated liver functions and anemia. A liver biopsy was performed, and the histological findings confirmed the diagnosis of granulomatous hepatitis.

Management of Ptosis in Kearns-Sayre Syndrome: A Case Report and Literature Review.

Kearns-Sayre syndrome (KSS) is a rare mitochondrial disease that affects young adults, due to a deletion of mitochondrial DNA and characterized by the triad: age of onset lower than 20 years, chronic progressive external ophthalmoplegia, and an atypical pigmentary retinopathy. It is also characterized by other endocrine, neurological, and especially cardiac impairment with a very high risk of cardiac complications during surgical procedures under all types of anesthesia. We report a case of KSS revealed by severe bilateral ptosis and confirmed by a muscle biopsy with "ragged red fibers." The ptosis was surgically managed by cautious Frontal suspension under local anesthesia "Frontal nerve block." Through this case, we discuss challenges in the management of KSS patients.

Prognostic Value of ATRX and p53 Status in High-Grade Glioma Patients in Morocco.

INTRODUCTION: Glioblastoma and astrocytoma, grade 4, are the most common and aggressive brain tumors. Several biomarkers, such as the isocitrate dehydrogenase mutation (IDH-1), alpha-thalassemia/mental retardation, and the X-linked mutation (ATRX), enable more accurate glioma classification and facilitate patient management. This study aimed to determine the prognostic value of clinical and molecular factors (IDH, TP53, and ATRX mutations). We also studied the relationship between these molecular markers and the overall survival (OS) of 126 patients with grade 4 glioblastoma/astrocytoma. METHODS: The immunohistochemical study was conducted using antibodies namely, IDH1, R132H, p53, and ATRX. Statistical tests were used to investigate factors that might influence overall survival using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY). RESULTS: The median age at diagnosis was 51.5 years. Patients with a Karnofsky performance score (KPS) <70 presented less favorable survival outcomes compared to those with a KPS ≥70. The median OS for patients was found to be 11.17 months. Expression of IDH1 R132H was found in 13.5% of patients, p53 overexpression was identified in 55.6% of cases, and loss of ATRX expression was detected in 11.9%. The group of patients with IDH mutant/ATRX mutant/p53 wild-type had the best prognosis (OS = 27.393 months; p = 0.015). Our results were in line with previous studies. CONCLUSION: The clinical value of IDH and ATRX mutations in prognostic assessment was confirmed (p ≤0.05). The overexpression of p53 had no significant impact on OS (p = 0.726). Therefore, p53 alone cannot predict survival in glioblastoma patients. Based on the results, these biomarkers may be a potential therapeutic target to prolong patient survival, hence the need for further investigations.

A rare clinical case of systemic AA amyloidosis with cardiac involvement complicating ankylosing spondylitis: a case report.

BACKGROUND: Ankylosing spondylitis (AS) is a type of chronic inflammation that is most prevalent in young adults and is characterized by an inflammatory enthesiopathy that gradually develops toward ossification and ankylosis. If inflammation is left unchecked, it can potentially lead to complications such as secondary amyloidosis, also known as AA amyloidosis, involving the deposition of amyloid serum A protein. Our case presents with a thyroid localization of AA amyloidosis which is secondary to this AS. Such a case has been described in only four cases in the literature. Cardiac localization of AA amyloidosis has been exceptionally described in the literature. CASE PRESENTATION: We report the case of a young patient with severe AS complicated by secondary amyloidosis with thyroid, cardiac, and probably renal localization. He was treated with anti-TNF therapy, and his condition improved significantly. CONCLUSIONS: Our case presents several localizations of AA amyloidosis secondary to this AS. Although cardiac involvement is rare in secondary AA amyloidosis, it should always be screened for, even in a cardiacly asymptomatic patient.

Exploring the multifaceted effects of Ammi visnaga: subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities.

Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.

The Clinicopathological Features and Prognostic Significance of HER2-Low in Early Breast Tumors Patients Prognostic Comparison of HER-Low and HER2-Negative Breast Cancer Stratified by Hormone Receptor Status.

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.

Epidemiological and clinical characteristics of children with peripheral neuroblastic tumors: a study on a Moroccan population.

PURPOSE: Peripheral neuroblastic tumors are the most common extracranial cancers found in children, and they are characterized by a diverse spectrum of clinical manifestations and heterogeneous behaviors. This study aimed to investigate the epidemiological and clinical characteristics of children with peripheral neuroblastic tumors admitted to the Department of Pediatric Hematology and Oncology of the Hospital August 20 in Casablanca. METHODS: The medical files of 48 children with peripheral neuroblastic tumors addressed to our department between February 2018 and February 2023 were reviewed. The clinical and demographic characteristics of patients were analyzed by the Statistical Package for the Social Sciences (SPSS), survival curves were obtained by Kaplan-Meier technique, and we assigned the tumor stage to patients based on the International Neuroblastoma Risk Group Staging System (INRGSS). RESULTS: The median age of diagnosis was 30 months (1-174), with a ratio F/M of 1.28. 93.75% of patients had neuroblastoma, and the rest had ganglioneuroma. About 64.6% of patients had at their initial presentations stage M of peripheral neuroblastic tumors. The adrenal region made up 71% of the primary tumor site. The bone was one of the most prevalent metastatic sites (54.2%). The five-year overall survival rate was 35.4%. CONCLUSION: Overall, this study revealed a high stage of peripheral neuroblastic tumors in the majority of the diagnosed patients in our Department of Pediatric Hematology and Oncology. Moreover, the heterogeneity of peripheral neuroblastic tumors makes clinical recognition difficult and, in general, too late.

The immune checkpoint VISTA is associated with prognosis in patients with malignant uveal melanoma.

Introduction: Uveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4. Methods: Evaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM. Results and discussion: Our results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients.

The immune checkpoint adenosine 2A receptor is associated with aggressive clinical outcomes and reflects an immunosuppressive tumor microenvironment in human breast cancer.

Background: The crosstalk between the immune system and cancer cells has aroused considerable interest over the past decades. To escape immune surveillance cancer cells evolve various strategies orchestrating tumor microenvironment. The discovery of the inhibitory immune checkpoints was a major breakthrough due to their crucial contribution to immune evasion. The A2AR receptor represents one of the most essential pathways within the TME. It is involved in several processes such as hypoxia, tumor progression, and chemoresistance. However, its clinical and immunological significance in human breast cancer remains elusive. Methods: The mRNA expression and protein analysis were performed by RT-qPCR and immunohistochemistry. The log-rank (Mantel-Cox) test was used to estimate Kaplan-Meier analysis for overall survival. Using large-scale microarray data (METABRIC), digital cytometry was conducted to estimate cell abundance. Analysis was performed using RStudio software (7.8 + 2023.03.0) with EPIC, CIBERSORT, and ImmuneCellAI algorithms. Tumor purity, stromal and immune scores were calculated using the ESTIMATE computational method. Finally, analysis of gene set enrichment (GSEA) and the TISCH2 scRNA-seq database were carried out. Results: Gene and protein analysis showed that A2AR was overexpressed in breast tumors and was significantly associated with high grade, elevated Ki-67, aggressive molecular and histological subtypes, as well as poor survival. On tumor infiltrating immune cells, A2AR was found to correlate positively with PD-1 and negatively with CTLA-4. On the other hand, our findings disclosed more profuse infiltration of protumoral cells such as M0 and M2 macrophages, Tregs, endothelial and exhausted CD8+ T cells within A2ARhigh tumors. According to the Single-Cell database, A2AR is expressed in malignant, stromal and immune cells. Moreover, it is related to tumor purity, stromal and immune scores. Our results also revealed that CD8+T cells from A2ARhigh patients exhibited an exhausted functional profile. Finally, GSEA analysis highlighted the association of A2AR with biological mechanisms involved in tumor escape and progression. Conclusion: The present study is the first to elucidate the clinical and immunological relevance of A2AR in breast cancer patients. In light of these findings, A2AR could be deemed a promising therapeutic target to overcome immune evasion prevailing within the TME of breast cancer patients.

Metachronous ureteral metastasis of a gastric adenocarcinoma: a case report and review of literature.

BACKGROUND: Ureteral metastasis from gastric cancers are rare and can be a cause of ureteral obstruction. There have been few published case reports in the literature. In this paper, we report an additional case and a review of the literature of all the previous reported cases. CASE PRESENTATION: A 67 years old North African women who was treated four years before for a gastric adenocarcinoma, presented with abdominal pain. Imaging and endoscopy showed a mural stenosis of the left ureter, without any other abnormality. Histopathology confirmed the gastric origin of the metastasis. A palliative chemotherapy was foreseen, but due to the deterioration of the general condition of the patient, she received palliative care. We have also reviewed the literature and reported the previously published cases of ureteral metastasis from gastric cancer. CONCLUSIONS: It is worth recalling that in a context of neoplasia and with the presence of signs of ureteral obstruction, it is important to keep in mind the possibility of a ureteral metastasis.

Cystic squamous metaplasia in a giant benign phyllodes tumor of the breast: a case report.

Phyllodes tumor is a rare tumor of the breast, which encompasses both stromal and epithelial components. In these components, metaplastic changes can be observed occasionally. We report the case of a 51-year-old woman nulligest menopaused who presented a huge mass, largely ulcerated in her right breast. The radiological examination revealed a large tumor with microcalcifications classified as Breast Imaging and Reporting Data System Category 5. The patient undergone right mastectomy and the histological analysis revealed benign phyllodes tumor with cystic squamous metaplasia. Therefore, we aim to present this uncommon event occasionally occurring in phyllodes tumor of the breast.

TMIGD2 as a potential therapeutic target in glioma patients.

Introduction: Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown. Methods: In the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software. Results: TMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients. Discussion: Taken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.

High VISTA expression is linked to a potent epithelial-mesenchymal transition and is positively correlated with PD1 in breast cancer.

Breast cancer is the most common type of tumor in women worldwide. Immune checkpoint inhibitors, particularly anti-PDL1, have shown promise as a therapeutic approach for managing this disease. However, this type of immunotherapy still fails to work for some patients, leading researchers to explore alternative immune checkpoint targets. The Ig suppressor of T cell activation domain V (VISTA) has emerged as a novel immune checkpoint that delivers inhibitory signals to T cells and has demonstrated encouraging results in various cancers. Our study investigated the association of VISTA expression with clinicopathological parameters in breast cancer patients, its involvement in the Epithelial-Mesenchymal-Transition (EMT) process, and its correlation with PD1 expression. Transcriptomic analysis revealed that VISTA was associated with lobular and metaplastic histological type, tumor size, lymph node status, ER and PR negative status, and the TNBC molecular subtype. Furthermore, VISTA expression was strongly associated with an immunosuppressive tumor microenvironment. Immunohistochemistry analysis corroborated the transcriptomic results, indicating that VISTA was expressed in most immune cells (94%) and was significantly expressed in breast cancer tumor cells compared to matched adjacent tissues. Our study also showed for the first time that VISTA overexpression in breast cancer cells could be associated with the EMT process. Additionally, we identified a positive correlation between VISTA and PD-1 expression. Together, these results highlight the immunosuppressive effect of VISTA in breast cancer patients and suggest that bi-specific targeting of VISTA and PD-1 in combination therapy could be beneficial for these patients.

Chromophobe renal cell carcinoma with liposarcomatous dedifferentiation: a case report.

Chromophobe renal cell carcinoma with liposarcomatous dedifferentiation is a very extremely rare tumor and only few cases have been reported in the literature. Here we report a case of a 37-year-old woman who presented with a pain and a palpable mass in the right flank. The abdominal computed tomography (CT) scan found a renal tumor and the patient underwent a right radical nephrectomy with adrenal gland resection. After the histological examination of the specimen completed by immunohistochemical and molecular study, a diagnosis of chromophobe renal cell carcinoma with liposarcomatous dedifferentiation was made. The patient received adjuvant chemotherapy. Afterwards, she developed bone metastasis and died 13 months after the surgery. Chromophobe renal cell carcinoma with liposarcomatous dedifferentiation is a rare tumor associated with a poor prognosis and a metastatic potential.

Unusual case of parietal metastasis from papillary thyroid carcinoma: a case report.

Parietal metastasis is a very rare secondary location of papillary thyroid carcinoma. It associated with poor prognosis. We report a case of a 61-year-old woman with parietal metastasis from papillary thyroid carcinoma. The patient presented a parietal nodule on the back. In her past history, she had been diagnosed papillary thyroid carcinoma after total thyroidectomy and also reoperated for local recurrence. The CT scan performed has revealed metastasis to the lungs, bones, lymph nodes and adrenal glands. The parietal nodule was excised and submitted for histopathological examination. The histologic and immunohistochemical findings confirmed the thyroid origin. Although papillary thyroid carcinoma is a relatively indolent tumour, it can exhibit an unusual metastatic behaviour.

Ki-67 proliferation index to further stratify invasive breast cancer molecular subtypes: Northern African comparative cohort-study with external TCGA-BRCA and METABRIC validation.

Introduction: breast cancer (BC) is a malignancy with very high incidence and mortality in Africa, especially in Western Africa, where more than 25 thousand deaths are registered every year. Not all BC have the same prognosis, and being able to personalize treatment and predict aggressiveness is of crucial importance. The purpose of our study is to explore further subdivisions associated with prognosis, beyond breast cancer molecular classification that is routinely established in pathology departments. Methods: we conducted a 5-year retrospective cohort study on 1266 invasive BC of Moroccan patients, collected at the Pathology Department of Ibn-Rochd University Hospital in Casablanca, and followed at King Mohammed VI National Centre for the Treatment of Cancers. We elaborated an Estimation-Maximization Clustering, based on the main BC biomarkers: Ki-67, HER2, estrogen and progesterone receptors, evaluated by immunohistochemistry. Two independent datasets (TCGA-BRCA and Metabric) were also analyzed to assess the external reproducibility of the results. Results: each molecular subgroup could be partitioned into two further subdivisions: Cluster1, with average Ki-67 of 16.26% (±11.9) across all molecular subgroups and higher frequency within luminal BC, and Cluster2, with average Ki-67 of 68.8%(±18) across all molecular subgroups and higher frequency in HER2 as well as in triple-negative BC. Overall survival of the two Clusters was significantly different, with 5-year rates of 52 and 37 months for Custer1 and Cluster2, respectively (p=0.000001). Moreover, mortality rates within the same molecular subgroup, especially in luminal B HER2-, varied remarkably depending on Cluster membership (6% for C1 and 18% for C2 after 1 year of follow-up). Two different algorithms to evaluate the prognostic importance, variable selection using random forests (VSURF) and Minimal depth, ranked the subdivision proposed as one of the 4 most influential features being able to predict patient survival better than several histoprognostic features, both in the Moroccan and in the external datasets. Conclusion: our results highlight a new refinement of the BC molecular classification and provide a simple and improved way to classify tumors that could be applied in low to middle-income countries. This is the first study of its kind addressed in an African context.

Osteoid osteoma of the rib: A report of an extremely rare condition.

INTRODUCTION: Osteoid osteoma (OO) is a type of benign bone tumor that usually affects long bones of the lower extremities. In this case report, we describe a successful surgical resection of an OO located in the rib which is an extremely rare location. CASE PRESENTATION: This is a 23-year-old man, referred to our thoracic surgery department for a very intense nocturnal right chest pain for over two months, the physical examination was normal without clinically palpable chest mass. The CT scan showed an osteocondensing lesion at the junction of the middle and posterior arches of the right 6th rib suggesting Ewing's sarcoma, a PET CT was then requested showed an appearance of a regular non-hypermetabolic inhomogeneous condensation at the junction of the middle and posterior arcs of the 6th right rib. After multidisciplinary concertation, a CT-guided biopsy of the lesion was performed, the histological examination of which revealed an osteoid osteoma, then a complete resection of the lesion was performed under posterolateral thoracotomy which histology confirmed a costal osteoid osteoma. The patient is currently in good health condition with complete disappearance of chest pain after one month of the operation and does not present any complications for the long-term follow-up. DISCUSSION: Osteoid osteoma (OO) is a benign primary bone tumor with unknown pathogenesis. That occurs in patients during the first two decades of life in about 60 to 75% of cases with a strong predilection for long bones, in 60 to 70% of cases. Flat bones, such as the skull, jawbones, innominate bones, and ribs are rarely described (McDermott et al., 1996 [1]). The standard treatment for OO is complete surgical excision, which is offered to the patient when the pain is chronic and not relieved by medical treatment (Osteoid osteoma: the results of surgical treatment [Internet] [2]). CONCLUSION: The osteoid osteoma of the rib is a very rare entity of bone neoplasms, this is the first case in our department that demonstrates that the OO of the rib must be suspected affront any painful rib and that complete surgical excision when it's possible, is a safe and effective treatment.