miRViz: a novel webserver application to visualize and interpret microRNA datasets.

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the regulation of major pathways in eukaryotic cells through their binding to and repression of multiple mRNAs. With high-throughput methodologies, various outcomes can be measured that produce long lists of miRNAs that are often difficult to interpret. A common question is: after differential expression or phenotypic screening of miRNA mimics, which miRNA should be chosen for further investigation? Here, we present miRViz (http://mirviz.prabi.fr/), a webserver application designed to visualize and interpret large miRNA datasets, with no need for programming skills. MiRViz has two main goals: (i) to help biologists to raise data-driven hypotheses and (ii) to share miRNA datasets in a straightforward way through publishable quality data representation, with emphasis on relevant groups of miRNAs. MiRViz can currently handle datasets from 11 eukaryotic species. We present real-case applications of miRViz, and provide both datasets and procedures to reproduce the corresponding figures. MiRViz offers rapid identification of miRNA families, as demonstrated here for the miRNA-320 family, which is significantly exported in exosomes of colon cancer cells. We also visually highlight a group of miRNAs associated with pluripotency that is particularly active in control of a breast cancer stem-cell population in culture.

MiR-483-5p and miR-139-5p promote aggressiveness by targeting N-myc downstream-regulated gene family members in adrenocortical cancer.

Adrenocortical carcinoma (ACC) is a tumor with poor prognosis in which overexpression of a panel of microRNAs has been associated with malignancy but a very limited number of investigations on their role in ACC pathogenesis have been conducted. We examined the involvement of miR-483-5p and miR-139-5p in adrenocortical cancer aggressiveness. Using bioinformatics predictions and mRNA/miRNA expression profiles, we performed an integrated analysis to identify inversely correlated miRNA-mRNA pairs in ACC. We identified N-myc downstream-regulated gene family members 2 and 4 (NDRG2 and NDRG4) as targets of miR-483-5p and miR-139-5p, respectively. NDRG2 and NDRG4 expressions were inversely correlated respectively with miR-483-5p and miR-139-5p levels in aggressive ACC samples from two independent cohorts of 20 and 44 ACC. Moreover, upregulation of miR-139-5p and downregulation of NDRG4 demonstrated a striking prognostic value. A direct interaction between miR-483-5p or miR-139-5p and their targets was demonstrated in reporter assays. Downregulation of miR-483-5p or miR-139-5p in the ACC cell lines NCI-H295R and SW13 increased NDRG2 or NDRG4 mRNA and protein expression, compromised adrenocortical cancer cell invasiveness and anchorage-independent growth. MiR-483-5p or miR-139-5p overexpression and NDRG2 or NDRG4 inhibition produce similar changes, which are rescued by NDRG2 or NDRG4 ectopic expression. We established that key factors mediating epithelial-to-mesenchymal transition are downstream effectors of miR-483-5p/NDRG2 and miR-139-5p/NDRG4 pathways. Collectively, our data show for the first time that miR-483-5p/NDRG2 and miR-139-5p/NDRG4 axes promote ACC aggressiveness, with potential implications for prognosis and therapeutic interventions in adrenocortical malignancies.

RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity.

Mineralocorticoid receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron. Herein, we decipher mechanisms by which hypotonicity increases MR expression in renal principal cells. We identify HuR (human antigen R), an mRNA-stabilizing protein, as an important posttranscriptional regulator of MR expression. Hypotonicity triggers a rapid and reversible nuclear export of HuR in renal KC3AC1 cells, as quantified by high-throughput microscopy. We also identify a key hairpin motif in the 3'-untranslated region of MR transcript, pivotal for the interaction with HuR and its stabilizing function. Next, we show that hypotonicity increases MR recruitment onto Sgk1 promoter, a well-known MR target gene, thereby enhancing aldosterone responsiveness. Our data shed new light on the crucial role of HuR as a stabilizing factor for the MR transcript and provide evidence for a short autoregulatory loop in which expression of a nuclear receptor transcriptionally regulating water and sodium balance is controlled by osmotic tone.

Diagnostic pitfall: primary myoepithelial carcinoma of the lacrimal gland, case report and literature review.

BACKGROUND: In lacrimal gland, lymphomas and inflammatory lesions predominate. Primary epithelial tumours represent less than 30% of lacrimal gland lesions. Myoepithelial carcinoma of lacrimal gland is rare. To the best of our knowledge, only nine cases have been reported in the literature. This lesion presents diagnostic difficulties: non-specific clinical and radiological findings and histological polymorphism. This is well illustrated by the diagnostic pathology errors described in the literature.We report a new case of lacrimal myoepithelial carcinoma with a review of others published cases to try to assess clinico-pathological features and outcome whenever possible of this rare tumour. CASE PRESENTATION: An 80-year-old Arabian female presented with a 2-month history of swelling over the right eyebrow, pain, proptosis of the right eye and diplopia. Computed tomography demonstrated an ill-defined, homogeneous, contrast-enhancing mass attached to the medial rectus. A biopsy was performed. Microscopic examination showed malignant spindle cells tumour, most consistently to sarcoma or sarcomatoid carcinoma. Immunohistochemical study was not possible because neoplastic material has been exhausted. Subsequently, total exenteration of the right orbit was performed. Immunohistochemical study revealed diffuse positive staining for pancytokeratin AE1/AE3, epithelial membrane antigen (EMA) and smooth muscle actin (SMA) and focal positivity for S100 protein. The lesion was immunonegative for desmin, h-cladesmon, CD34, Melan-A and HMB-45. The tumour was extending to the surgical margins. The patient was lost to follow-up until she developed local tumour progression 3 months after removal. The patient was again lost to follow-up and therefore did not receive any other treatment in our hospital. CONCLUSION: We present this rare tumour with an unusual location. The use of a complete immunohistochemical panel with epithelial and myoepithelial markers positivity helped us for classification of this poorly differentiated tumour.

Solitary fibrous tumor occurring in the parotid gland: a case report.

BACKGROUND: Solitary fibrous tumor is an uncommon spindle cell neoplasm of unknown origin. It has been reported in many anatomic sites, with a rare occurrence in the head and neck region. Solitary fibrous tumors of the parotid gland are exceptional; their clinical and radiologic features are non specific, often mimicking more common salivary gland tumors. Pathologic examination and immunohistochemistry are required to make the correct diagnosis. The prognosis is favorable, with most tumors being benign, and complete surgical resection is the treatment of choice. CASE PRESENTATION: We report the case of a 42-year-old man who presented with a painless mass involving the parotid gland. A parotidectomy was performed, and follow up was unremarkable. Gross examination showed a well circumscribed, firm tumor measuring 3,4 cm. Histologically, the tumor was composed of a spindle cell proliferation of variable cellularity, with staghorn vessels. A panel of immunohistochemical stains was performed, and confirmed the diagnosis of parotid gland solitary fibrous tumor. CONCLUSION: In this report we aim to increase awareness of this rare entity among clinicians and pathologists, and to emphasize the role of immunohistochemistry in confirming the diagnosis.

Parotid gland, an exceptional localization of sebaceous carcinoma: case report.

BACKGROUND: Sebaceous carcinoma (SC) is a rare malignancy, occurring predominantly in eyelids. Till date, only 25 cases of sebaceous carcinoma (SC) of the parotid gland have been reported in world literature. CASE PRESENTATION: A 33 year-old male presented with left sided laterocervical mass. Clinical examination showed enlargement of the left parotid gland, with cervical lymphadenopathy. No skin lesions were found. A resection of the gland was performed. Pathological findings were consistent with primary sebaceous carcinoma of the parotid gland. CONCLUSION: Sebaceous carcinoma of the parotid gland is extremely uncommon. Clinical and radiological features are not specific. The aim of this report, is to describe histopathological, and immunohistochemical findings of this rare entity, and discuss differential diagnosis.

Hypertonicity compromises renal mineralocorticoid receptor signaling through Tis11b-mediated post-transcriptional control.

The mineralocorticoid receptor (MR) mediates the Na(+)-retaining action of aldosterone. MR is highly expressed in the distal nephron, which is submitted to intense variations in extracellular fluid tonicity generated by the corticopapillary gradient. We previously showed that post-transcriptional events control renal MR abundance. Here, we report that hypertonicity increases expression of the mRNA-destabilizing protein Tis11b, a member of the tristetraprolin/ZFP36 family, and thereby, decreases MR expression in renal KC3AC1 cells. The 3'-untranslated regions (3'-UTRs) of human and mouse MR mRNA, containing several highly conserved adenylate/uridylate-rich elements (AREs), were cloned downstream of a reporter gene. Luciferase activities of full-length or truncated MR Luc-3'-UTR mutants decreased drastically when cotransfected with Tis11b plasmid, correlating with an approximately 50% shorter half-life of ARE-containing transcripts. Using site-directed mutagenesis and RNA immunoprecipitation, we identified a crucial ARE motif within the MR 3'-UTR, to which Tis11b must bind for destabilizing activity. Coimmunoprecipitation experiments suggested that endogenous Tis11b physically interacts with MR mRNA in KC3AC1 cells, and Tis11b knockdown prevented hypertonicity-elicited repression of MR. Moreover, hypertonicity blunted aldosterone-stimulated expression of glucocorticoid-induced leucine-zipper protein and the α-subunit of the epithelial Na(+) channel, supporting impaired MR signaling. Challenging the renal osmotic gradient by submitting mice to water deprivation, diuretic administration, or high-Na(+) diet increased renal Tis11b and decreased MR expression, particularly in the cortex, thus establishing a mechanistic pathway for osmotic regulation of MR expression in vivo. Altogether, we uncovered a mechanism by which renal MR expression is regulated through mRNA turnover, a post-transcriptional control that seems physiologically relevant.

Multiple functions of tristetraprolin/TIS11 RNA-binding proteins in the regulation of mRNA biogenesis and degradation.

Members of the tristetraprolin (TTP/TIS11) family are important RNA-binding proteins initially characterized as mediators of mRNA degradation. They act via their interaction with AU-rich elements present in the 3'UTR of regulated transcripts. However, it is progressively appearing that the different steps of mRNA processing and fate including transcription, splicing, polyadenylation, translation, and degradation are coordinately regulated by multifunctional integrator proteins that possess a larger panel of functions than originally anticipated. Tristetraprolin and related proteins are very good examples of such integrators. This review gathers the present knowledge on the functions of this family of RNA-binding proteins, including their role in AU-rich element-mediated mRNA decay and focuses on recent advances that support the concept of their broader involvement in distinct steps of mRNA biogenesis and degradation.

Primary mismatch repair-deficient IDH-mutant astrocytoma in child: Unusual entity.

INTRODUCTION: "Primary Mismatch Repair-Deficient IDH-mutant Astrocytoma" (PMMRDIA) is a newly identified high-grade glioma with a poor prognosis. It has not been officially recognized as a distinct entity in the 5th edition of the WHO Classification of Central Nervous System Tumors 2021, making its diagnosis challenging. CASE PRESENTATION: To highlight this entity, we present the case of a 7-year-old boy with a family history of cerebral tumor among the father's relatives and first-degree parental consanguinity. He experienced increased intracranial hypertension and inguinal café-au-lait macules. Brain imaging revealed a cystic and solid mass with irregular enhancement in the left parietal lobe, indicating a possible Pilocytic astrocytoma. The final diagnosis of PMMRDIA was confirmed through histological, immunohistochemical, and molecular analysis. CLINICAL DISCUSSION: This tumor is mainly observed in children and is characterized by microsatellite instability (MSI) and high tumor mutational burden (TMB). MSI is known to occur in recurrent IDH-mutant gliomas as a resistance mechanism towards alkylating chemotherapy. CONCLUSION: In PMMRDIA, MSI can be a good predictive biomarker for responding to immunotherapy, which could improve the outcome of these children.

A giant peripheral ossifying fibroma of the mandible: A rare case report.

INTRODUCTION: Peripheral ossifying fibroma (POF) is an unusual localized, reactive benign gingival growth. POF is usually small in size, it's measure <2 cm in diameter, but rarely reaches important sizes. The aim of this work was to present a rare case report of a giant peripheral ossifying fibroma of the mandible measuring >2 cm in diameter, misdiagnosed as peripheral myxoma. CASE PRESENTATION: We present the case of a 42-year-old woman with a large peripheral ossifying fibroma in the oral cavity measuring 6 × 4 cm in diameter. The patient presented with an asymptomatic, slowly growing gingival mass in the left anterior and posterior region of the mandible. It gradually increased in size for more than two years. The patient had a mild mental deficit; however, we performed biopsy surgery, which revealed a peripheral myxoma, and then treated the tumor by excision under local anesthesia. The final histopathological examination revealed a peripheral ossifying fibroma. CLINICAL DISCUSSION: This case report shows that POF can grow and reach unusual dimensions that may contribute to occlusal problems. The diagnosis of POF is based on clinical and radiographic features. The histopathological examination of the biopsy specimen can misdiagnose the lesion; therefore, the final diagnosis is based on the histopathological examination of the complete excised lesion. CONCLUSION: POF is usually small, but can reach a larger size. The histopathological examination of the entire lesion is of paramount importance to make a final diagnosis.

Dermoid cyst, unusual location of the pterion: About a case and review of literature.

Intracranial dermoid cysts are benign tumors of congenital origin. The intradiploic forms are rare, exceptional at the pterional level. We report the case of a 10-year-old girl who presented with a cutaneous fistula in the left frontotemporal region. The blind end of the fistula was an intradiploic dermoid cyst in the rare location of the pterion confirmed by imaging and histopathology. Once this lesion is suspected, it is important to identify its location and morphology using imaging techniques and to complete excision of the cyst to avoid complications associated with infection and to mitigate the risk of subtotal resection.

Pathologic features of head and neck adult rhabdomyosarcoma: Case series.

INTRODUCTION: Adult Head and neck Rhabdomyosarcomas (HNRMS) are exceedingly rare and remain challenging for pathologists. CASES PRESENTATION: Five cases of adult HNRMS (≥19 years) were retrieved from the archives of the Department of Pathology of Hospital of Specialities in Rabat (HSR) in Morocco, over 5 years. Clinical and pathologic findings from hematoxylin and eosin slides and immunohistochemistry for Desmin and Myogenin were reviewed. CLINICAL DISCUSSION: The median age was 33, with a men's predominance (3 M/2F). Histological analysis revealed three cases of Alveolar Rhabdomyosarcoma (RMS), one Pleomorphic RMS, and one spindle cell/sclerosing RMS. In addition to the typical histology observed in each RMS, we found tricky growth patterns that could be a source of misdiagnosis. All five cases demonstrated variable positivity for Desmin and Myogenin. CONCLUSION: HNRMS cases have different pathological features than pediatric RMS cases. We identified rare subtypes such as pleomorphic and spindle cell/sclerotic RMS, which exhibit unusual morphological patterns.

Pseudomyogenic Hemangioendothelioma Arising in the Maxillary Sinus, an Uncommon and Misdiagnosed Tumor: A Case Report.

Pseudomyogenic hemangioendothelioma (PMHE) is a rare vascular neoplasm with an intermediate to low-grade malignant potential. Only 5% of PMHEs occur in the head and neck. This tumor exhibits different histological patterns and mimics other vascular tumors, myoid tumors, or carcinomas. The distinction between these tumors can be a very challenging situation for pathologists. In this article, we report the first case, to our knowledge, of PMHE arising in the maxillary sinus, to highlight this uncommon entity and discuss differential diagnoses.

Primary epithelioid angiosarcoma of the mandibular gingiva: diagnostic pitfalls, about an unusual entity.

Primary angiosarcoma of the oral cavity is a rare malignant vascular neoplasm variably recapitulating endothelial cells and is generally associated with a worse prognosis. The epithelioid subtype is even uncommon in this localization. To our knowledge, only seven cases of primary oral epithelioid angiosarcoma have been reported until 2021. This histopathological variant is characterized by solid and sheet-like growth patterns that may be misinterpreted as other lesions with epithelioid cells. Herein, we present a new case of primary epithelioid angiosarcoma of the mandibular gingiva to discuss histopathological differential diagnoses and potential diagnostic pitfalls.

Unusual clinical presentation of a giant parathyroid adenoma: A case report from Morocco highlighting the rare entity and atypical symptoms.

Primary hyperparathyroidism (PHPT), an endocrine disorder most commonly caused by parathyroid adenoma (PTA), manifests with a diverse array of symptoms, reflecting the multisystem impact of parathyroid hormone: nephrolithiasis, peptic ulcer disease, psychiatric disorders, muscle weakness, constipation, polyuria, pancreatitis, myalgia, and arthralgia. Rarely do these PTA attain a significant size. PHPT is usually diagnosed through biochemical tests, and radiological imaging characterizes the adenoma. Serum 25-hydroxyvitamin D levels are useful in explaining the large adenoma size. Here, we report a rare case of a 60-year-old female from Morocco who presented with marked dyspnea due to a giant PTA.

Primary malignant melanoma of the parotid gland: A case report.

The primary malignant melanoma of the parotid is a rare and complex clinical entity, posing numerous diagnostic challenges due to the absence of melanin in the tumor and its histological similarities with other poorly differentiated lesions. Accurate diagnosis often requires advanced imaging techniques and immunohistochemical procedures to identify specific melanoma markers. Therapeutically, total parotidectomy with simultaneous cervical dissection is frequently recommended, although approaches combining surgery, chemotherapy, radiotherapy, or even immunotherapy are also being explored. Despite these advancements, malignant parotid melanoma continues to be associated with a grim prognosis, emphasizing the importance of ongoing research to improve therapeutic options and understanding of this rare pathology.

Chondroblastic osteosarcoma of the nasal cavity: an exceptional and misdiagnosed presentation.

Chondroblastic osteosarcoma of the nasal cavity is a rare and aggressive tumor that presents diagnostic challenges due to its variable clinical and radiological features. Histological analysis is crucial for an accurate diagnosis, despite morphological similarities with chondrosarcoma. We present a case of primary craniofacial chondroblastic osteosarcoma originating from the nasal cavity in a 17-year-old adolescent. The tumor was characterized by cartilaginous lobules and spindle cell proliferation with osteoid matrix deposition. Immunohistochemical analysis supported the diagnosis. This case highlights the rarity of this particular presentation and emphasizes the significance of accurate diagnosis through histopathological evaluation to achieve optimal management.

Intramasseteric Solitary Myofibroma: A Case Report.

Solitary myofibroma or infantile myofibroma is a rare spindle cell neoplasm that generally affects infants before the age of 2 years but cases in young children and adults have been described. Although the location of infantile myofibroma in the oral and maxillofacial region has been described, the intramasseteric location of the lesion is very uncommon. A thorough assessment of histopathological and immunohistochemical characteristics is necessary to have a correct diagnosis. Treatment relies on surgical resection. In this article, we present a rare clinical case of a 15-year-old patient with a myofibroma of the masseteric muscle and its management.

Exploring a rare case of juvenile psammomatoid ossifying fibroma in the ethmoid: a case study and review.

Juvenile ossifying fibroma (JOF) and its variants, including juvenile psammomatoid ossifying fibroma (JPOF), represent rare yet clinically significant benign fibro-osseous lesions that primarily occur in children and young adolescents. They can be found in diverse anatomical sites such as the jaw, nasal cavity, paranasal sinuses, and orbit. JOF exhibits an aggressive nature, necessitating early radiological detection and surgical intervention. Similarly, JPOF, with a locally malignant potential, requires surgical removal, typically conducted through endoscopic approaches. We report a case of a 5-year-old girl with JPOF arising in the ethmoid, revealed by recurrent epistaxis and proptosis. The text emphasizes the importance of early diagnosis through histopathology as a diagnostic tool and underscores the need for appropriate management.

Numb chin syndrome revealing a mandibular metastasis: Case report.

INTRODUCTION AND IMPORTANCE: Numb chin syndrome (NCS), although rare, is an important clinical finding. It may be a metastatic neurologic manifestation of malignancy, often with no clinically visible pathologic finding. CASE PRESENTATION: A 40-year-old female, with prior history of breast cancer, presented to our service with complaint of pain and left mandibular hypoesthesia for four months. Panoramic showed several irregular osteolytic lesions of the mandibular body. CT-scan images showed a large irregular hypodense lesion and a tissue infiltration of the left mandibular body blowing the buccal cortex. Histopathology showed a neoplastic proliferation of carcinomatous cells positive for the cytokeratin AE1/AE3. A diagnosis of breast carcinoma mandibular metastasis was made. The patient was referred sent to the oncology committee. She was treated with Palbociclib and hormone therapy. CLINICAL DISCUSSION: In the oral cavity, the mandible is the most common site for metastasis. Metastatic tumors of the oral cavity may be asymptomatic or present different non-pathognomonic. Numb chin syndrome which is considered as an important presentation of oral metastases. The consideration of malignancy as a differential diagnosis may help in early diagnosis and intervention that may affect disease prognosis. CONCLUSION: Dentists and other oral health care providers must be aware of this condition to consider metastatic cancer in patients with unexplained facial hypoesthesia.