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.

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.

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.

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.

Inflammatory myofibroblastic tumor of the lacrimal gland: case report of an exceptional location.

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.

Expression of human epidermal growth factor receptor 2 in bladder urothelial carcinoma.

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.

Primary leiomyosarcoma of the submandibular gland: a case report.

BACKGROUND: Leiomyosarcoma is a rare malignant mesenchymal tumor that represents 5-7 % of all soft tissue sarcomas. The occurrence of this tumor in the salivary glands is exceptional. Only five cases are reported in the submandibular gland. CASE PRESENTATION: A 65-year-old white Moroccan woman presented with a history of progressive right submandibular swelling which had grown over a period of 8 months. Clinical examination showed a submandibular painless, mobile and hard mass without cervical lymphadenopathy. Ultrasonography and computed tomography revealed a solid and heterogeneous mass measuring 4 × 2 cm involving the submandibular gland. A resection of the gland was performed. Pathological findings were consistent with primary leiomyosarcoma of the submandibular gland. No recurrence occurred after two months of follow-up. CONCLUSION: Primary leiomyosarcoma of the submandibular gland is an extremely rare mesenchymal tumor. Clinical and radiological features are not specific. Differential diagnosis includes metastatic leiomyosarcoma and gastrointestinal stromal tumor, myoepithelioma, sarcomatoid carcinoma, melanoma and other sarcomas. Little is known about the overall biologic behavior of this tumor, but the prognosis seems to be poor.

Primary lymphoma of the cranial vault: case report and a systematic review of the literature.

BACKGROUND: Bone involvement is a common finding in many types of lymphoma. Cranial vault involvement is extremely rare, and the majority of patients are found at staging to have concurrent disease in lymph nodes. Thirty-eight cases of primary lymphoma of the cranial vault have been reported to date. METHODS: This article presents a rare case of primary cranial vault lymphoma and conducts a systematic review of the current literature. A total of 36 articles comprising 38 cases were included for analysis. The relevant demographic, clinical, and imaging characteristics, as well as the treatment and outcomes of this unique disease presentation were studied. RESULTS: The average patient age was 60 years. There was no significant difference in patient gender. The predominant patient complaint was a subcutaneous scalp mass. Of the patients, 11.7% were immunocompromised. CT scans showed signs of osteolysis in 74% of lesions and hyperostosis in 5%, and the cranial vault was observed as normal in 18% of cases. MRI was performed in 23 cases. There was a wide range of histological subtypes, with a slight predominance of diffuse large B-cell lymphoma. Treatment consisted of surgery alone, surgery followed by radiotherapy, and surgery followed by radiotherapy and chemotherapy. The follow-up periods ranged from 5 months to 6 years, with a median value of 7 months. Sixteen patients were followed up to 12 months; 13 of them were alive at 1 year from diagnosis. CONCLUSION: Primary cranial vault lymphoma is an extremely rare finding. It should be considered in the differential diagnosis of scalp masses. Although the analysis of outcome of the reported cases is difficult because of the small number of occurrences of this entity and the variability of follow-up, a combination of surgery, radiotherapy, and chemotherapy seems to offer better outcomes.

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.

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.

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.

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.

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.

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.

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.

Sacral hemangiopericytoma involving the retrorectal space: report of a case.

A primary hemangiopericytoma (HP) of the bone is rare, because the vast majority of these tumors arise in soft tissue. This report presents a case of a hemangiopericytoma in the sacrum (S1-S2) with extension to the retrorectal space. Only a few cases of osseous hemangiopericytomas in the sacrum and involving the retrorectal space have so far been reported. The difficult diagnosis of HP and the surgical strategy was chosen according to the location of the lesion in the sacrum and retrorectal space. A local excision was indicated. A sacral resection should be considered for tumors below S4. This report demonstrated the safety of this strategy. Adjuvant radiotherapy is useful in HP. The value of chemotherapy is still doubtful, although patients with high-grade tumors or metastatic spread seem to gain substantial benefit. Due to the often unpredictable behavior of this neoplasm, extended follow-up is strongly recommended.

[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.