Clinicopathological analysis of hybrid carcinomas of the salivary glands: A systematic review.

Hybrid carcinomas (HC) are the association of two or more malignant neoplasms arising within the same topographical area. The present study is a systematic review of HC of the salivary glands. This study aimed to assess HC clinicopathological features and molecular profile. Observational studies, case series, and case reports were included. PubMed, Scopus, EMBASE, Lilacs, Web of Science, and gray literature were searched until June 2024. A total of 18 articles including 34 patients were included. HC of the salivary glands is presented as a painless mass affecting mainly the parotid gland of adults with a preference for male patients. Histologically, adenoid cystic carcinoma and epithelial-myoepithelial carcinoma were the most prevalent association, being surgical excision with radiotherapy the most common treatment. It's seen that the most aggressive component might guide the patient's treatment and prognosis. Further molecular studies are necessary to determine if HC are distinct entities or biologically identical to the individual neoplasms. In conclusion, this systematic review may contribute to a better understanding of this rare lesion, their biological behavior, treatments employed, and the outcome of these patients.

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.

Distinct copy number signatures between residual benign and transformed areas of carcinoma ex pleomorphic adenoma.

The mechanisms involved with the pathogenesis of carcinoma ex pleomorphic adenoma (CXPA) seem to be associated with the accumulation of molecular alterations in the pleomorphic adenoma (PA). In this sense, using array-based comparative genomic hybridization (aCGH) a rare series of 27 cases of CXPA and 14 residual PA (rPA) adjacent to the transformation area, we investigated the profile of the copy number alterations (CNAs) comparing benign residual and transformed areas. The main findings were correlated with the histopathological classification by histologic subtype and degree of invasion. The distribution of losses (p = 0.187) and amplifications (p = 0.172) was not statistically different between rPA and CXPA. The number of gains was increased in the transformed areas compared to the benign residual areas (p = 0.005). PLAG1 gain was maintained along the malignant transformation, as it was observed in both residual PA and CXPA samples, likely being an earlier event during transformation. The amplification of GRB7 and ERBB2 may also be an initial step in the malignant transformation of PA to CXPA (salivary duct carcinoma subtype). Furthermore, the amplification of HMGA2 and RPSAP52 were the most prevalent alterations among the studied samples. It was noteworthy that amplified genes in the transformed areas of the tumors were enriched for biological processes related to immune signaling. In conclusion, our results underscored for the first-time crucial CNAs in CXPA, some of them shared with the residual benign area adjacent to the transformation site. These CNAs included PLAG1 gain, as well as amplification of GRB7, ERBB2, HMGA2, and RPSAP52.

Expanding the Molecular Spectrum of Carcinoma Ex Pleomorphic Adenoma: An Analysis of 84 Cases With a Novel HMGA2::LINC02389 Fusion.

Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive epithelial and/or myoepithelial neoplasm that arises in association with a pleomorphic adenoma (PA). Its etiopathogenesis remains poorly understood, but it is believed that the development of this tumor is due to the accumulation of genetic, protein, metabolic, and epigenetic alterations in a PA. A retrospective review of the Salivary Gland Tumor Registry in Pilsen yielded 84 CXPA, namely 25/84 salivary duct carcinoma (SDC), 15/84 myoepithelial carcinoma (MC), 1/84 epithelial-myoepithelial carcinoma (EMC), and 1/84 adenoid cystic carcinoma (AdCC). All 84 CXPA cases were analyzed by next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH). Forty-three tumors originally diagnosed as CXPA (43/84, 51.2%) showed some molecular alteration. Fusion transcripts were identified in 12/16 (75%) CXPA, including LIFR::PLAG1, CTNNB1::PLAG1, FGFR1::PLAG1, and a novel fusion, HMGA2::LINC02389. Most of the fusions were confirmed by FISH using PLAG1 (6/11) and HMGA2 (1/1) gene break probes. Split signals indicating gene break were identified by FISH for PLAG1 (12/17), HMGA2 (3/4), EWSR1 (7/22), and MYB (2/7). Concerning pathogenic mutations, only CXPA with epithelial differentiation (SDC) presented these alterations, including HRAS mutation (2/4), TP53 (1/4), PTEN (1/4), and ATK1 (1/4). In addition, amplifications in ERBB2 (17/35), MDM2 (1/4), and EWSR1 (1/7) were detected. A novel finding was the discovery of an HMGA2::LINC02389 fusion in 1 patient with EMC ex-PA. The present results indicate that molecular profiling of CXPA with myoepithelial differentiation (MC) tends to reveal chromosomal fusion events, whereas CXPA with epithelial differentiation (SDC) tends to have a higher frequency of pathogenic mutations and gene amplifications.

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.

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.

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.

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.

Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

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.

Exploring diagnosis and therapeutic complexities of an aggressive Merkel cell carcinoma: A case report and review of the literature.

Merkel cell carcinoma (MCC) is an aggressive and rare cutaneous neuroendocrine carcinoma that predominantly affects the sun-damaged skin of the head and neck region, extremities, and trunk of older white individuals. Microscopically, MCC is characterized by nests or sheets of uniform small round blue cells with scant cytoplasm, granular nuclei with a salt-and-pepper chromatin pattern, high proliferative activity, and occasional necrosis. They are usually positive for epithelial and neuroendocrine markers, particularly for cytokeratin 20 and AE1/AE3 in a paranuclear dot-like staining. We herein contribute by reporting a case of MCC affecting the auricular pavilion of a 66-year-old female patient from Campinas, Brazil. Additionally, a review of the current literature is also included to analyze all the cases that have been reported in the English-language literature, totalizing 27 cases of MCC on the external ear. The 5-year overall survival rate for individuals with localized MCC is 50% and the most common treatment choice is the combination of surgery with adjuvant radiotherapy and sentinel lymph node biopsy.

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.