A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors.

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)-BRAFV600E tumors compared to PTC-BRAFwt 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 BRAFV600E 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-BRAFV600E expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAFV600E 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.

Clinical Significance of Somatic Mutations in RAS/RAF/MAPK Signaling Pathway in Moroccan and North African Colorectal Cancer Patients.

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: a case report.

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.

A case report of a primary pericardial leiomyosarcoma: An extremely rare cardiac neoplasm.

Introduction and importance: Primary malignant pericardial tumors are an entity that is infrequently encountered and may be a cause of pericardial effusion. Primary pericardial leiomyosarcoma are even rarer, and highly aggressive tumors, with no more than 200 cases reported in the literature. In this case report, we are presenting a rare case of a primary pericardial leiomyosarcoma that was diagnosed at our institution. We discuss the available diagnostic modalities and also shed light on alternative therapies when patients are not ideal surgical candidates. Case presentation: A 27-year-old male patient was admitted with a gradually worsening dyspnea associated with a deterioration of general condition. Echocardiography examination showed a circumferentiel pericardial effusion with significant fibrin deposits and pericardial thickening. An open surgical biopsy of the pericardium was indicated which was in favor of the diagnosis of pericardial leiomyosarcoma. Unfortunately, the patient died during the procedure. Clinical discussion: Despite its rarity, primary pericardial leiomyosarcoma should be considered as a differential diagnosis in the assessment of a pericardial effusion of an unknown etiology. Cardiac magnetic resonance imaging is considered to be the reference standard technique for evaluation of a suspected pericardial tumor. Surgical biopsies provide the best odds for detection of the cell of origin, but it's fought with periprocedural risks depending on the site of the tumor. Conclusion: Primary pericardial leiomyosarcomas appear to have a poor prognosis. Surgical approach is the primary modality of treatment. Chemotherapy and radiotherapy should be offered to patients who are not ideal surgical candidates.

Teratocarcinosarcoma of the cheek: a case report.

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.

Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa.

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_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_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_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_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_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.

Management and positive outcome of skull-base ossifying fibroma: a case report.

The ossifying fibroma is a benign fibro-osseous tumor rarely affecting the skull base. The incidence of ossifying fibroma itself is uncommon. It is considered to be an aggressive and fast-growing bone lesion. Early detection and complete surgical removal are essential to deal with its aggressive nature and recurrence. We report a case of a 20-year-old man admitted for the management of ossifying fibroma of the orbital roof extending inside the orbit mimicking meningioma and revealed by a progressive proptosis and headache. The patient underwent surgery for the subtotal removal of the tumor with its frontal infiltration with a good outcome. All meningiomas like tumors are not meningiomas and other tumors such as ossifying fibroma might be mistaken for meningioma and even get confirmation from the pathological anatomy study. Need be for these tumors to be looked at more closely for better therapeutic decision-making.

Acquired Reactive Perforating Collagenosis: A Case Report.

Reactive perforating collagenosis (RPC) is a rare form of dermatosis. It forms with perforating folliculitis, Kyrle's disease, and serpiginous perforating elastosis, which is a group of perforating dermatosis. RPC can be hereditary with autosomal dominant transmission or it can be acquired, which is usually observed in diabetics with chronic renal failure. Here we report a new observation in a 72-year-old woman treated by phototherapy with a favorable outcome.

Typical presentation of pulmonary lepidic adenocarcinoma: a rare case report.

Bronchioloalveolar carcinoma (BAC) is a rare subtype of adenocarcinoma of lung with distinct features and distinctive characteristics. It accounts approximately for 4% of lung cancers. In the following study we report a rare observation of a 50 years old female with a clinical, radiological and histological presentation, which is typical of an invasive mucinous lepidic adenocarcinoma formerly named BAC.

BRAFV600E hot spot mutation in thyroid carcinomas: first Moroccan experience from a single-institution retrospective study.

BACKGROUND: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAFV600E 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 BRAFV600E mutation in thyroid carcinomas. Here we aim to evaluate the frequency of BRAFV600E 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 BRAFV600E in 37 thyroid tumors. RESULTS: We detected BRAFV600E 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.

[Chondrosarcoma arising in solitary osteochondroma: a case study]. / Chondrosarcome né sur un ostéochondrome solitaire: à propos d'un cas.

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.

Urinary schistosomiasis: report of case diagnosed in bladder biopsy.

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.

[Primary epidermoid carcinoma of the breast mimicking an abscess]. / Carcinome épidermoide primitif du sein mimant un abcès.

Squamous cell carcinoma of the breast is a basal-like phenotype metaplastic cancer with poor prognosis. It is often diagnosed at earlier stages based on voluminous palpable mass not detected on screening. Squamous cell carcinoma should be suspected in patients with abscess, as is the case with our 44-year old female patient presenting with a mass in the left breast diagnosed as a cyst with abscess formation measuring 5,4cm x 5cm on mammography combined with ultrasound (A). Surgical biopsy was performed. Anatomopathological examination showed tumor proliferation with large carcinomatous lobules and clear squamous differentiation greater than 90% (B). Tumor cells were very atypical and showed many mitotic figures. Immunohistochemical study showed tumor cells expressing cytokeratins 5/6 (C). Proliferation index was 85% (D). Hormone receptors and hercept test were negative. The diagnosis of metaplastic squamous cell carcinoma was retained. Our patient underwent left mastectomy with axillary dissection and adjuvant chemotherapy followed by radiotherapy. The patient didn't developed locoregional recurrence or distant metastasis during a 9-month follow-up period.

[Brain metastases from uterine leiomyosarcoma]. / Métastases cérébrales d'un léiomyosarcome utérin.

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.

Myxoid chondrosarcoma extraskeletal in pelvis location : a case report.

BACKGROUND: The extraskeletal myxoid chondrosarcoma (CME) is a rare tumor of the soft tissue, with clinically distinguishable clinical, histological, immunohistochemical, cytogenetic and evolutionary characteristics with an unfavorable long-term prognosis. CASE: We reported the case of a young patient of 18 years, accusing pelvic pain for 5 months with a poor general condition, an MRI was performed immediately, objective infiltrative mass endopelvic evoking several etiologies. The histology of the biopsy extraskeletal myxoid chondrosarcoma reveals a (CME). 's Staging came back normal. We performed an incomplete surgical resection due to the deep location of the pelvis in the tumor followed by radiotherapy. CONCLUSION: The CME is a tumor diagnosis very difficult and often delayed, despite a mostly local aggressiveness and prolonged survival, it is considered a low-grade sarcoma malignancy or intermediate malignancy. Treatment consists of complete surgical resection with a potential adjuvant radiotherapy . Chemotherapy is not very effective.

[A special form of pancytopenia]. / Une forme particulière de pancytopénie.

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.

Evaluation of glutathione S-transferase pi 1 expression and gene promoter methylation in Moroccan patients with urothelial bladder cancer.

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.

Primary Intracranial pPNET/Ewing Sarcoma: Diagnosis, Management, and Prognostic Factors Dilemma-A Systematic Review of the Literature.

BACKGROUND: Ewing sarcoma (ES) is a malignant bone tumor that is most commonly observed in the long bones, the pelvis, and the chest. Primary intracranial localization is extremely rare. OBJECTIVE: In the aim of identifying the prognostic factors of this rare localization, we conducted a systematic review of the literature for patients with primary intracranial peripheral primitive neuroectodermal tumor/ES. METHODS: A complete MEDLINE search was undertaken for all articles reporting data for primary intracranial peripheral primitive neuroectodermal tumor/ES. We divided the patient population into 2 groups: group I, patients who were free of disease; and group II, patients who died or had uncontrolled disease at the last available follow-up. We conducted a comparative statistical analysis of data between the 2 groups. RESULTS: A total of 48 patients were included in the review. There were 32 patients in group I and 12 in group II. Fifty percent of tumors in group II and only 16% of tumors in group I were infratentotorial (P = 0.03). Signs of bone involvement were observed in 19% of patients in group I and 54% in group II (P = 0.03). Total removal was accomplished in 29% of patients in group I and in no patients in group II (P = 0.03). Radiotherapy was performed in 73% of patients in group II and 81% in group I (P = 0.43). Chemotherapy was administered in 36% of patients in group II and 74% in group I (P = 0.03). CONCLUSIONS: Infratentorial localization and the presence of bone involvement were associated with poor prognosis; Surgery seems to be a predictive factor of prognosis; radiotherapy and chemotherapy must be performed whenever the tumor is not totally removed.