Mantle Cell Lymphoma in the Oral Cavity: Exploring the Differential Microscopic Diagnosis of a Rare Case.

Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin's lymphoma (NHL), which generally has an aggressive course. Its pathophysiology seems to be related with the malignant transformation of B-cell mantle zone lymphocytes due to the CCND1 rearrangement. The occurrence of MCL in the oral cavity is especially rare. In this report, we present an exceptional case of oral MCL diagnosed in the palate in a 56-year-old male patient, highlighting its distinct morphological and immunohistochemical features that may assist in the accurate diagnosis.

Insights into the molecular alterations of PLAG1 and HMGA2 associated with malignant phenotype acquisition in pleomorphic adenoma.

Pleomorphic adenoma (PA) is the most common neoplasm of the salivary gland, presenting with a variety of histological features. In some cases, PA can undergo malignant transformation to carcinoma ex pleomorphic adenoma (CXPA). The transition from PA to CXPA is associated with complex molecular alterations, particularly involving the pleomorphic adenoma gene 1 (PLAG1) and high mobility group protein gene (HMGA2). This review investigates the molecular alterations of PLAG1 and HMGA2 in all domains in the malignant transformation of PA. Our analysis highlights that these markers are key alterations in the etiopathogenesis of PA and CXPA, with gene fusion and amplification being frequently reported mechanisms. Although the exact role of PLAG1 and HMGA2 in the oncogenic process remains unclear, further studies on the HMGA2 and PLAG1, are needed particularly in HMGA2-PLAG1-IGF2 which is proving to be a potential pathway for the development of clinically applicable therapies, especially for CXPA management.

HAF prevents hepatocyte apoptosis and progression to MASH and hepatocellular carcinoma through transcriptional regulation of the NF-κB pathway.

BACKGROUND: HCC incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways driving MASH-HCC are poorly understood. We have previously reported that male mice with haploinsufficiency of hypoxia-associated factor, HAF (SART1+/-) spontaneously develop MASH-HCC. However, the cell type(s) responsible for HCC associated with HAF loss are unclear. RESULTS: We generated SART1-floxed mice, which were crossed with mice expressing Cre-recombinase within hepatocytes (Alb-Cre; hepS-/-) or myeloid cells (LysM-Cre, macS-/-). HepS-/- mice (both male and female) developed HCC associated with profound inflammatory and lipid dysregulation suggesting that HAF protects against HCC primarily within hepatocytes. HAF-deficient hepatocytes showed decreased P-p65 and P-p50 and in many components of the NF-κB pathway, which was recapitulated using HAF siRNA in vitro. HAF depletion also triggered apoptosis, suggesting that HAF protects against HCC by suppressing hepatocyte apoptosis. We show that HAF regulates NF-κB activity by regulating transcription of TRADD and RIPK1. Mice fed a high-fat diet (HFD) showed marked suppression of HAF, P-p65 and TRADD within their livers after 26 weeks, but showed profound upregulation of these proteins after 40 weeks, implicating deregulation of the HAF-NF-κB axis in the progression to MASH. In humans, HAF was significantly decreased in livers with simple steatosis but significantly increased in HCC compared with normal liver. CONCLUSIONS: HAF is novel transcriptional regulator of the NF-κB pathway and is a key determinant of cell fate during progression to MASH and MASH-HCC.

Head and neck sarcomas: Thirty years of experience in a tertiary referral center in Brazil.

PURPOSE: This study analyzed the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas (HNS) diagnosed in a tertiary reference center in Brazil. MATERIALS AND METHODS: HNS cases were retrospectively retrieved from the Department of Pathological Anatomy of the School of Medical Sciences of the State University of Campinas. The medical records were examined to extract demographic, clinicopathological, and follow-up information. The Pearson chi-square test, Kaplan-Meier curve, and Cox proportional hazards regression model were employed to identify survival and potential prognostic factors. RESULTS: A total of 47 patients were included in the study. The majority were men (61.7%) with a mean age of 38.9 years. The nasal cavity (34.0%) was the most common anatomical site. The lesions are usually presented as volume increases (78.7%). The most common histological subtypes were chondrosarcoma, osteosarcoma, and alveolar rhabdomyosarcoma. Surgical excision alone was the most common treatment modality. Local recurrence was observed in 10 cases, and metastases in 3 cases. During a mean follow-up period of 71.9 months, from diagnosis to the last follow-up, 31 patients (65.9%) were alive without the disease. A total of 10 patients (21.3%) died of the HNS for a mean follow-up period of 14.3 months. The time to presentation of more than 6 months (p = 0.0309) and the presence of metastases (p = 0.0315) were identified as prognostic factors for survival, while male sex was found to be an independent prognostic factor for recurrence. CONCLUSION: In conclusion, the results of this study indicate that the occurrence of a shorter lesion time to presentation and the presence of metastases were associated with a reduction in survival rates in patients with HNS.

Solitary Angiokeratoma in the Oral Cavity: A Critical Literature Review and Report of a New Case.

This study aimed to perform an integrative review of solitary angiokeratomas cases in the oral cavity and to report a new case in a 39-year-old man. A modified PECOS strategy was used using PubMed, Embase, Scopus, Web of Science databases, and the reference lists of the selected articles. Case reports of oral solitary angiokeratoma published in English, Portuguese, and Spanish languages with histopathological diagnosis without the presence of systemic disorders were included. Of the 51 articles identified, 18 met the eligibility criteria. Solitary angiokeratomas have a slight male predilection, with a peak incidence in the fourth decade of life. The tongue was the most common localization (77.7%), followed by buccal mucosa (11.1%), labial mucosa (5.6%), and tonsillar pillar (5.6%). The granulomatous appearance was the most frequent clinical aspect. Surgical excision was implemented in 94.4% of the cases. The lesion presented a good prognosis, with no recurrence in 3 to 24 months. In summary, solitary angiokeratoma is a rare lesion in the oral cavity. The professional making the oral diagnosis should be familiar with the clinical manifestation of angiokeratoma and be prepared to consider it in the differential diagnosis of pigmented lesions since these lesions may be part of systemic disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04631-w.

Efficacy of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Treating Traumatic Brain Injury-Induced Brain Edema: A Systematic Review and Meta-analysis of Animal Studies.

Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.

Secretory carcinoma of the minor salivary gland: An in-depth case report.

A 56-year-old female was referred to our service for management of a malignant salivary gland neoplasm with compromised margins that had been biopsied previously at another service. The patient reported a twenty-year history of a lesion in the oral cavity with progressive and exuberant growth over the past two years, associated with local pain and dyspnea. Physical examination revealed an erythematous, ulcerated, and hemorrhagic lesion measuring approximately 3 cm on the left soft palate and tonsillar pillar. Computed tomography revealed an expansile lesion in the topography of the left soft palate, growing predominantly toward the lumen of the nasopharynx and partially invading the left wall of this region. The patient underwent surgery and histopathologic examination revealed an infiltrative and aggressive epithelial neoplasia with large vacuolated and eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The neoplastic cells were arranged in a solid, microcystic, tubular, and follicular pattern with eosinophilic luminal secretion. Mitotic figures were frequent and all margins were affected by the neoplasia. Morphologic and immunohistochemical features supported the diagnosis of secretory carcinoma, and the patient is currently being followed for further therapeutic intervention.

Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets.

The Eph/ephrin system regulates many developmental processes and adult tissue homeostasis. In colorectal cancer (CRC), it is involved in different processes including tumorigenesis, tumor angiogenesis, metastasis development, and cancer stem cell regeneration. However, conflicting data regarding Eph receptors in CRC, especially in its putative role as an oncogene or a suppressor gene, make the precise role of Eph-ephrin interaction confusing in CRC development. In this review, we provide an overview of the literature and highlight evidence that collaborates with these ambiguous roles of the Eph/ephrin system in CRC, as well as the molecular findings that represent promising therapeutic targets.

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

OBJECTIVE: This study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA). MATERIALS AND METHODS: We analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis. RESULTS: Across the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59 in RPA, 846 in residual PA, and 2555 in CXPA. The chromosome 8 showed higher involvement in altered miRNAs in PAs and CXPA patients. Six miRNA genes were shared among all groups. Additionally, miR-21, miR-455-3p, miR-140, miR-320a, miR-383, miR-598, and miR-486 were prominent CNAs found and is implicated in carcinogenesis of several malignant tumors. These miRNAs regulate critical signaling pathways such as aerobic glycolysis, fatty acid biosynthesis, and cancer-related pathways. CONCLUSION: This study was the first to explore CNAs in miRNA-encoding genes in the PA-CXPA sequence. The findings suggest the involvement of numerous miRNA genes in CXPA development and progression by regulating oncogenic signaling pathways.

Dynamic Role of miRNAs in Salivary Gland Carcinomas: From Biomarkers to Therapeutic Targets.

BACKGROUND: Salivary gland carcinomas (SGCs) are a rare group of malignant neoplasms of the head and neck region. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been associated with the control biological process and oncogenic mechanism by the regulation of gene expression at the post-transcriptional level. Recent evidence has suggested that miRNA expression may play a role in the tumorigenesis and carcinogenesis process in SGCs. METHODS: This review provides a comprehensive literature review of the role of miRNAs expression in SGCs focusing on the diagnostic, prognostic, and therapeutic applications. RESULTS: In this review, numerous dysregulated miRNAs have demonstrated an oncogenic and suppressor role in SGCs. CONCLUSION: In the future, these miRNAs may eventually constitute useful diagnostic and prognostic biomarkers that may lead to a better understanding of SGCs oncogenesis. Additionally, the development of therapeutic agents based on miRNAs may be a promising target in SGC treatment.

Hematopoietic colony-stimulating factors in head and neck cancers: Recent advances and therapeutic challenges.

Colony-stimulating factors (CSFs) are key cytokines responsible for the production, maturation, and mobilization of the granulocytic and macrophage lineages from the bone marrow, which have been gaining attention for playing pro- and/or anti-tumorigenic roles in cancer. Head and neck cancers (HNCs) represent a group of heterogeneous neoplasms with high morbidity and mortality worldwide. Treatment for HNCs is still limited even with the advancements in cancer immunotherapy. Novel treatments for patients with recurrent and metastatic HNCs are urgently needed. This article provides an in-depth review of the role of hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3; also known as multi-CSF) in the HNCs tumor microenvironment. We have reviewed current results from clinical trials using CSFs as adjuvant therapy to treat HNCs patients, and also clinical findings reported to date on the therapeutic application of CSFs toxicities arising from chemoradiotherapy.

A rare report of a metastatic lung large-cell neuroendocrine carcinoma in palatine tonsil.

INTRODUCTION: Neuroendocrine carcinoma is a rare form of cancer originating from neuroendocrine cells, with the lungs being the most common site of occurrence. These tumors have the potential to metastasize to the head and neck region. CASE REPORT: A 57-year-old man, with a smoking history of 74 pack-years, presented with complaints of hoarseness, dry cough, dysphagia, and significant weight loss over a two-month period. During oral examination, a submucosal nodule in the left palatine tonsil was discovered. Histological analysis confirmed a poorly differentiated tumor consisting of large cells with nuclear pleomorphism and abundant cytoplasm. The tumor tested positive for CD56, chromogranin, synaptophysin, and EMA. Further imaging revealed a substantial endobronchial lesion in the upper segment of the left lower lobe. Biopsy results from this lesion were morphologically and immunohistochemically consistent with those from the oral lesion. A diagnosis of metastatic large-cell neuroendocrine carcinoma originating from the lung and involving the oral mucosa was established. CONCLUSION: This case highlights the metastatic potential of pulmonary neuroendocrine carcinoma and its occurrence in atypical dissemination sites. Additionally, our findings underscore the importance of early detection of oral metastases to ensure accurate diagnosis and expedite appropriate treatment.

Induction chemotherapy response of HPV-related multiphenotypic sinonasal carcinoma: First-ever reported therapeutic outcome and a brief literature review.

A 54-year-old male patient complained of nasal obstruction and epistaxis for 2 years, with worsening of the symptoms in the preceding year. Physical examination revealed a friable, irregular mass, with yellowish secretion, in the left nasal fossa. Magnetic resonance imaging revealed an expansive lesion in the left nasal cavity, extending into the nasopharynx, ethmoid, right nasal cavity, and cortical bone of the hard palate. An incisional biopsy was then performed. Morphologically, a cellular malignant proliferation with a solid basaloid appearance admixed with adenoid cystic-like areas was observed. Immunohistochemistry revealed positivity for AE1/AE3, CK7, p63, and calponin, with focal labeling for CD117 and α-SMA. p16 had diffuse cytoplasmic and nuclear positivity. Ki-67 index was >80%. Given the morphological and immunohistochemical aspects, the diagnosis was conclusive for HPV-related multiphenotypic sinonasal carcinoma. The tumor was considered irresectable, and the patient was submitted to induction chemotherapy with docetaxel, cisplatin, and infusional 5-fluorouracil, with significant regression after therapy, followed by chemoradiotherapy with carboplatin, without limiting toxicities. The patient is currently under regular follow-up, with complete clinical and radiological response. To date, there are no reports in the literature of induction chemotherapy use or its complete therapeutic responsiveness related to this lesion. A brief literature review was included with the main epidemiological, clinical, therapeutic, and prognostic aspects regarding the 85 cases reported in the literature, including ours.

Clinicopathological profile of sclerosing polycystic adenoma/adenosis: A systematic review.

In this systematic review, we aimed to evaluate the clinicopathological profile of sclerosing polycystic adenoma (SPA). PubMed, Scopus, EMBASE, Lilacs, Web of Science, and gray literature were searched to access cases of SPA in salivary glands. One hundred and thirty cases of SPA were found across 61 selected articles. SPA affected mainly the parotid gland of adults with a mean age of 44.6 years old, with a slight preference for females. The lesion was usually presented as a painless firm mass with a long period of evolution. Histologically, they are well-delimitated lesions composed of acinar and ductal elements with a variety of cytomorphologic features surrounded by a densely collagenized stroma. PI3K was the most common gene mutation related to SPA. SPA is a benign condition that mainly affects the parotid gland of female patients and it is usually treated by surgical resection with a good prognosis.

Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights.

Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for 50%-60% of these neoplasms. If untreated, 6.2% of PA may undergo malignant transformation to carcinoma ex-pleomorphic adenoma (CXPA). CXPA is a rare and aggressive malignant tumor, whose prevalence represents approximately 3%-6% of all salivary gland tumors. Although the pathogenesis of the PA-CXPA transition remains unclear, CXPA development requires the participation of cellular components and the tumor microenvironment for its progression. The extracellular matrix (ECM) comprises a heterogeneous and versatile network of macromolecules synthesized and secreted by embryonic cells. In the PA-CXPA sequence, ECM is formed by a variety of components including collagen, elastin, fibronectin, laminins, glycosaminoglycans, proteoglycans, and other glycoproteins, mainly secreted by epithelial cells, myoepithelial cells, cancer-associated fibroblasts, immune cells, and endothelial cells. Like in other tumors including breast cancer, ECM changes play an important role in the PA-CXPA sequence. This review summarizes what is currently known about the role of ECM during CXPA development.

Discovery proteomics reveals potential protein signature associated with malignant phenotype acquisition in pleomorphic adenoma.

OBJECTIVE: To analyze the proteomic profile of salivary pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) samples and correlate them with the malignant transformation of the PA. MATERIALS AND METHODS: Thirty samples (10 PA, 16 CXPA, and 4 residual PA) were microdissected and submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomic data and protein identification were analyzed through LC-MS/MS spectra using the MaxQuant software. RESULTS: The proteomic analysis identified and quantified a total of 240 proteins in which 135 were found in PA, residual PA, and CXPA. The shared proteins were divided into six subgroups, and the proteins that showed statistically significant differences (p > 0.05) and fold-change > or <2.5 in one subgroup to another subgroup were included. Seven proteins (Apolipoprotein A-I-APOA1, haptoglobin-HP, protein of the synaptonemal complex 1-SYCP1, anion transport protein of band 3-SLC4A1, subunit µ1 of AP-1 complex-AP1M1, beta subunit of hemoglobin-HBB, and dermcidin-DCD) were classified as potential protein signatures, being HP, AP1M1, and HBB with higher abundance for PA to residual PA, APOA1 with higher abundance for PA to CXPA, SLC4A1 with lower abundance in the PA to CXPA, SYCP1with lower abundance for residual PA to CXPA, and DCD with higher abundance in the CXPA with epithelial differentiation to myoepithelial differentiation. CONCLUSIONS: In this work, we demonstrated the comparative proteomic profiling of PA, residual PA, and CXPA, and seven were proposed as protein signatures, some of which may be associated with the malignant phenotype acquisition.

Oral Teratoma with Hairy Polyp-Like Features: A Brief Report of a Rare Presentation.

We present a 21-day-old female child presenting with a large oral epithelialized tumor implanted at the rhinopharynx and ethmoid plate through a cleft palate, associated with feeding and respiratory difficulties. The histopathological exam showed mature central adipose tissue, hair follicles, sebaceous glands, and neurovascular structures, lined by keratinized stratified squamous epithelium. Proliferative cartilaginous, glandular, lymphatic, bony, and immature myxoid tissue was seen at the posterior region and insertion. Despite the characterization of the tumor as a teratoma containing structures derived from the three embryonic leaflets, the anterior portion presented a microscopic bigeminal pattern fully compatible with hairy polyp.