Dendritic cell subpopulations in carcinoma ex-pleomorphic adenoma: A multicenter study.

OBJECTIVE: Carcinoma ex-pleomorphic adenoma (CEXPA) represents a malignant transformation from a recurrent or primary pleomorphic adenoma (PA), and the immune response may be essential in this process. Therefore, in this study, we aimed to identify and quantify subpopulations of dendritic cells (DCs) in CEXPA, residual PA in CEXPA (rPA), and PA. MATERIALS AND METHODS: A multicenter study was performed collecting salivary gland tumor (SGT) samples from three Oral and Maxillofacial Pathology Centers. A tissue microarray containing 41 samples of CEXPA and 22 samples of PA was included in this study and submitted to immunohistochemical reactions against CD1a, CD83, CD207, and Ki67 antibodies. RESULTS: Both PA and rPA showed a higher quantification of CD207+ and CD83+ cells when compared to CEXPA (p < 0.001 and p < 0.01, respectively). There was also a difference when comparing the cell proliferation index between PA/rPA and CEXPA using the Ki-67 marker (p = 0.043). However, there was no difference in the DC population regarding clinical parameters such as sex, anatomical location, size, and metastases (p > 0.06). CONCLUSIONS: Immunohistochemical profile of DC subpopulations and cell proliferation biomarkers in SGTs can contribute as an important tool in the differentiation of benign and malignant tumors or detection of initial areas with malignant transformation.

Clinicopathological and survival profile of patients with salivary gland myoepithelial carcinoma: A systematic review.

OBJECTIVES: In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma. MATERIALS AND METHODS: MEDLINE/PubMed, Scopus, and Embase search was performed with the keywords "myoepithelial carcinoma" "malignant myoepithelioma," and "salivary glands." Primary salivary glands myoepithelial carcinoma that fulfilled the World Health Organization diagnostic criteria were included. The Joanna Briggs Institute tool was used to assess the risk of bias. RESULTS: Forty-three studies (71 patients) met the inclusion criteria. The patients showed a mean age of 56.4 ± 19.6 years with no sex predilection. The parotid was the most affected gland (49.3%). The tumor presented as an asymptomatic (65.1%) mass (84%). The most common histological findings were the presence of clear tumor cells (39.7%) and multinodular growth patterns (60.7%). Multivariate analysis showed plasmacytoid cell type (p = 0.010) and solid growth pattern (p = 0.003) were related to decreased disease-free survival. Surgery alone was the most used treatment (53.5%). Patients with a combination of treatments showed a longer disease-free survival (p = 0.049). The 2-year and 5-year overall survival rates were 67.5% and 46.1%, respectively. CONCLUSION: Salivary gland myoepithelial carcinoma showed no sex predilection, with a higher incidence in the parotid gland. Cell type, growth pattern, and treatment type may be related to a lower disease-free survival. Overall, salivary gland myoepithelial carcinoma presented low recurrence and metastasis rates. Registration and protocol: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022311512).

Approaches to the diagnosis of secretory carcinoma of the salivary glands: a case series and review.

Secretory carcinoma (SC) is a salivary gland neoplasm included in the latest World Health Organization Classification of Head and Neck Tumours. Its morphologic and immunohistochemical characteristics resemble those of breast secretory carcinoma, and the tumors share the same fusion gene, ETV6::NTRK3. This chromosome translocation can be confirmed through reverse transcription-polymerase chain reaction or located using ETV6 fluorescent in situ hybridization. These techniques are expensive, and few laboratories can carry out molecular analysis. In addition, some of these tumors are related to non-NTRK fusion types and non-ETV6 translocation. Therefore, recognition of the typical histopathologic features of SC is the first step in considering this disease among the diagnostic hypotheses. In this case series, morphologic findings combined with immunohistochemical profiles were sufficient to make the correct diagnosis.

Severe craniofacial fibrous dysplasia associated with decreased visual acuity: a case report.

Fibrous dysplasia is a developmental abnormality characterized by the replacement of normal bone tissue by fibrous connective tissue with poorly organized bone trabeculae. This disorder rarely occurs in the craniofacial region, but in such cases it causes facial asymmetries and has severe clinical implications for the patient. This case report describes the treatment of an 18-year-old man who presented with complaints of facial deformity and decreased visual acuity. Cone beam computed tomography revealed a diffuse bone lesion affecting the region of the maxillary, frontal, and nasal bones on the left side of the face. After microscopic examination, the diagnosis of craniofacial fibrous dysplasia was made. The patient underwent a bilateral temporal craniotomy to perform decompression of the orbital apices and correct the loss of visual acuity. In addition, surgical cosmetic contouring of the facial bones was performed. The patient has been followed up by a multidisciplinary team; at his most recent examination, 18 months after the last surgical intervention, his clinical condition remained stable.

Comparison of tobacco and alcohol consumption in young and older patients with oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: To compare the proportion of young (up to 45 years of age) and older (over 45 years of age) oral squamous cell carcinoma (OSCC) patients who report tobacco and alcohol consumption. METHODS: Observational studies reporting tobacco and alcohol consumption among young and older OSCC patients were selected in a two-phase process. Search strategies were conducted on five main electronic databases and complemented by grey literature. The risk of bias was assessed using the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Synthesis of results was calculated with the software R Statistics version 4.0.2 (The R Foundation). RESULTS: From 6675 records identified, 38 studies met the eligibility criteria and were selected for qualitative synthesis and meta-analysis, encompassing 2439 young and 13,393 older patients. Tobacco smoking was reported by 39.5% (confidence interval (CI) = 31.7% to 47.9%, I2 = 78%) of the young patients and 48.4% (CI = 37.8% to 59.2%, I2 = 94%) of the older patients. Alcohol consumption was reported by 30.9% (CI = 22.7% to 40.5%, I2 = 83%) of the young and 45.8% (CI = 35.6% to 56.5%, I2 = 95%) of the older patients (P < 0.05). CONCLUSION: The comparison in the proportion of individuals reporting tobacco and alcohol consumption demonstrated that these habits were more prevalent in the older group (48.4% and 45.8% respectively) than in the young group (39.5% and 30.9%, respectively). CLINICAL RELEVANCE: As a significant proportion of patients with OSCC reported no habits, novel risk factors for OSCC need to be investigated in further research.

Solitary fibrous tumor arising from the buccal mucosa: diagnostic challenge of a rare entity.

A solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor characterized by spindle cell proliferation that rarely affects the oral cavity. The clinical and histopathologic features of an oral SFT are described for the benefit of dental practitioners who may encounter one of these rare cases. A 25-year-old man presented with a slow-growing swelling in the left buccal mucosa. A painless, exophytic, and well-circumscribed submucosal lesion was detected, and an excisional biopsy was performed. The biopsy specimen was submitted for histologic and immunohistochemical staining and subsequent microscopic analysis. The histopathologic examination revealed variable cellularity areas that included spindle- and star-shaped cell proliferation. These cells were immersed in a collagenized stroma containing branching vessels with a staghorn arrangement. According to immunohistochemical analysis, the tumor was characterized by STAT6, CD34, ß-catenin, and Bcl-2 expression. Diagnosis of oral SFTs is challenging given that their microscopic characteristics can mimic those of malignant mesenchymal neoplasms.

Prognostic significance of CD30 expression in diffuse large B-cell lymphoma: A systematic review with meta-analysis.

BACKGROUND: CD30 is variably expressed in diffuse large B-cell lymphoma (DLBCL), but its prognostic potential for the affected patients remains debatable and unclear. Therefore, we aimed to determine the frequency of CD30 expression in DLBCL and its potential for prognostic determination. METHODS: An electronic systematic review was performed using multiple databases, followed by a quantitative meta-analysis to assess the frequency of CD30 expression with positivity cut-off values of >0% and >20%, and to determine its association with clinicopathological features and patients' survival. RESULTS: Using a cut-off value >0%, we observed that 3.5%-59.1% of the cases were considered positive for CD30. There was a significant association of the protein expression with a lower number of extra-nodal sites affected by the neoplasm, with Ann Arbor advanced stage, the absence of B-symptoms, the lack of MYC and BCL2 translocations, and a lower ECOG performance. Using a cut-off value >20%, we observed that 2.5%-36.7% of the cases were considered positive for CD30, being significantly associated with a lower number of extra-nodal sites affected by the neoplasm, Ann Arbor stages III/IV, non-GCB tumours, the lack of MYC and BCL2 translocations, and a lower ECOG value. CD30 expression was significantly associated with a better survival rate, regardless of what cut-off parameter was used. CONCLUSION: Despite variations in the cut-off values used to determine CD30 positivity in DLBCL, the expression of this protein seems to be associated with a higher survival rate and better prognosis.

Gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development.

OBJECTIVE: To analyze the gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in normal salivary gland (NSG), pleomorphic adenoma (PA), and carcinoma ex pleomorphic adenoma (CXPA) samples. MATERIAL AND METHODS: The gene expression was investigated by the real-time PCR (qRT-PCR) method in 9 samples of frozen tissues of normal salivary gland, 13 PA, and 10 CXPA. We validated the reactions by immunohistochemistry on 20 samples from NSG, 85 PA, and 44 CXPA. RESULTS: Our results showed that there was no statistically significant difference in HIF-1α gene and immunohistochemistry expression among the tissues studied while FASN gene and immunohistochemistry expression increased along the carcinogenesis of the PA. GLUT-1 was significantly more expressed in tumor tissues (PA and CXPA), although protein is mainly expressed in transformed cells than in PA and NSG. In contrast, adipophilin was significantly more expressed in NSG while the expression of the protein increased in PA and CXPA. CONCLUSIONS: In summary, the data presented here suggest that neoplastic cells reprogram the expression of GLUT-1 and adipophilin to adapt to the tumor microenvironment and reinforce, through immunohistochemical results, a possible transcriptional and post-translational regulatory mechanisms that act on the expression of these genes.

A multicenter study of oral sarcomas in Brazil.

OBJECTIVES: The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil. MATERIALS AND METHODS: A cross-sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods. RESULTS: From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3-87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range <1-156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3-15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill-defined limits. CONCLUSIONS: Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi's sarcomas were the main sarcomas of the oral cavity in Brazil.

Fatty acid synthase and Ki-67 immunoexpression can be useful for the identification of malignant component in carcinoma ex-pleomorphic adenoma.

BACKGROUND: Fatty acid synthase (FASN) is the key molecule for catalyzing fatty acid synthesis and have been associated with several malignant tumors. METHODS: We analyzed the expression of FASN and Ki-67, by immunohistochemistry on 29 carcinomas ex-pleomorphic adenoma (CXPAs) and 25 pleomorphic adenomas (PAs). RESULTS: Ki-67 proliferation index and FASN expression were significantly higher in patients with CXPA than patients with PA (P < 0.001). We found intense immunoreactivity for FASN in the malignant component of CXPAs, and these malignant areas also had intense nuclear immunoreactivity for Ki-67. CONCLUSIONS: The present results suggest that overexpression of FASN in CXPAs might be associated with malignant transformation of ductal epithelial cells and/or myoepithelial cells from PA. FASN associated with Ki-67 may be useful diagnostic markers for CXPA.

Primary intraosseous carcinoma of the maxilla arising from an odontogenic keratocyst: a case report and review of the literature.

A 47-year-old man was referred for treatment of a painful lesion of 5 months' duration located on the left side of the maxilla. A small perforation in the buccal cortex was observed during the intraoral examination. Cone beam computed tomography (CBCT) showed an extensive, well-delimited radiolucent lesion extending from the alveolar ridge to the nasal cavity. An incisional biopsy was performed, and a cystic lesion consistent with an odontogenic keratocyst (OKC) was observed microscopically. The initial treatment option was decompression to be followed by enucleation. However, 3 months after decompression of the lesion, the patient returned because there was a significant increase in the size of the perforation. A destructive lytic lesion that involved the left side of the maxilla and crossed the midline was evident in the CBCT. The examination of a second incisional biopsy specimen showed epithelial neoplasia comprising islands and projections toward the surface. There was abundant keratin deposition, resulting in the formation of pearls and plugs. A diagnosis of primary intraosseous carcinoma arising from an OKC was confirmed, and the patient underwent a maxillectomy. After 1 year of follow-up, there were no signs of recurrence.

A decreased peritumoral CD1a+ cell number predicts a worse prognosis in oral squamous cell carcinoma.

AIMS: Dendritic cells (DCs) are known to play a central role in the regulation of both innate and adaptive immunological responses, including antitumour immunity. The aim of this study was to evaluate the prognostic impact of intratumoral and peritumoral DCs in oral squamous cell carcinoma (OSCC) affecting the tongue and floor of the mouth. METHODS AND RESULTS: Immunohistochemistry for CD1a and CD83 was performed in 53 patients with OSCC in the tongue and floor of the mouth. The markers were evaluated by automated examination in intratumoral and peritumoral compartments, and the results were expressed as density of cells/mm2 . Correlations between these data and clinicopathological and survival outcomes were investigated. Depletion of peritumoral CD1a+ cells was associated with lymph node metastasis (P = 0.05), whereas depletion of peritumoral CD83+ cells was correlated with smoking history (P = 0.04), lymph node metastasis (P = 0.015), and extracapsular spread of lymph nodes (P = 0.018). Peritumoral CD1a+ was correlated with recurrence (P = 0.007) and overall survival (P = 0.03). The results of the survival analysis with the Cox proportional hazard model showed that depletion of peritumoral CD1a+ cells is an independent factor associated with overall survival and disease-free survival. CONCLUSION: Our results suggest that depletion of peritumoral CD1a+ cells is a strong independent prognostic factor, predicting a higher recurrence rates and worse survival outcomes.

CD1a+ and CD83+ Langerhans cells are reduced in lower lip squamous cell carcinoma.

BACKGROUND: Actinic cheilitis (AC) is a potentially malignant lesion diagnosed in the lip of patients chronically exposed to the sun that may give rise to a fully invasive lower lip squamous cell carcinoma (LLSCC). It is known that ultraviolet radiation causes dendritic cells (DCs) depletion in the epidermis, but the role of this cellular population in lip cancer progression remains uncertain. Therefore, this study investigated the distribution of DCs in normal, dysplastic and neoplastic tissues of the lower lip. METHODS: Thirteen cases of lower lip mucocele, 42 of ACs and 21 of LLSCC were retrieved and original diagnoses confirmed by two oral pathologists, who further classified ACs as low- and high-risk lesions. Immunoreactions against CD1a and CD83 identified immature and mature DCs, respectively. RESULTS: Immature CD1a+ Langerhans cells (LCs) were significantly decreased in LLSCC when compared to morphologically normal (P < 0.009) and dysplastic epitheliums (P < 0.003), whereas mature CD83+ LCs were significantly decreased in LLSCC when compared to normal epithelium (P = 0.038). There was no significant difference between low- and high-risk ACs regarding CD1a+ and CD83+ LCs (P > 0.05), but ACs demonstrated a lower concentration of CD1a+ LCs than normal epithelium (P < 0.009). There was no significant difference in the distribution of CD1a+ and CD83+ interstitial dendritic cells (IDCs) in the connective tissue among the studied groups (P > 0.05). CONCLUSION: These results suggest that depletion of epithelial LCs, but not IDCs in the connective tissue, would represent an important step for lip cancer development.

Genomic copy number alterations of primary and secondary metastasizing pleomorphic adenomas.

AIMS: Metastasizing pleomorphic adenoma (MPA) is a rare tumour, and its mechanism of metastasis still is unknown. To date, there has been no study on MPA genomics. We analysed primary and secondary MPAs with array comparative genomic hybridization to identify somatic copy number alterations and affected genes. METHODS AND RESULTS: Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPAs were subjected to array comparative genomic hybridization investigation, and the data were analysed with NEXUS COPY NUMBER DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and 19p13.3p123, and a complex pattern of four different deletions at chromosome 6. The 3p deletion encompassed several genes: CTNNB1, SETD2, BAP1, and PBRM1, among others. The secondary MPA showed a genomic profile similar to that of the primary MPA, with acquisition of additional copy number changes affecting 9p24.3p13.1 (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain). CONCLUSION: Our findings indicated a clonal origin of the secondary MPA, as both tumours shared a common profile of genomic copy number alterations. Furthermore, we were able to detect in the primary tumour a specific pattern of copy number alterations that could explain the metastasizing characteristic, whereas the secondary MPA showed a more unbalanced genome.

Decreased CD1a(+) , CD83(+) and factor XIIIa(+) dendritic cells in cervical lymph nodes and palatine tonsils of AIDS patients.

AIMS: The purpose of this study was to quantify and compare the density of dendritic cells (DCs) in cervical lymph nodes (LNs) and palatine tonsils (PTs) of AIDS and non-AIDS patients. METHODS AND RESULTS: Factor XIIIa, CD1a and CD83 antibodies were used to identify migratory DCs by immunohistochemistry in LNs and PTs of 32 AIDS patients and 21 HIV-negative control patients. Quantification was performed by the positive pixel count analytical method. AIDS patients presented a lower density of factor XIIIa(+) cells (P < 0.001), CD1a(+) cells (P < 0.05) and CD83(+) cells (P < 0.001) in cervical LNs and PTs compared to the non-AIDS control group. CONCLUSION: Overall depletion of DCs in lymphoid tissues of AIDS patients may be predictive of the immune system's loss of disease control.

Traumatic ulcerative granuloma with stromal eosinophilia mimicking a squamous cell carcinoma.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare lesion of a traumatic-reactive nature of the oral mucosa that can clinically mimic an oral carcinoma. A 59-year-old male patient presented painful ulceration with indurated margins on the base of the tongue, extending to the floor of the mouth. The use of ill-fitting denture hurting the mucosa of the region was reported by the patient. The evolution time was 45 days. The presumptive diagnoses were oral squamous cell carcinoma and chronic ulcer. An incisional biopsy revealed an ulceration associated with an eosinophil-rich inflammatory infiltrate and a bed of proliferating histiocyte-like cells in either diffuse or fasciculate arrangement. There was diffuse immunopositivity for CD3, but focal for CD68 and α-SMA, and negativity for CD30. The final diagnosis was TUGSE. The use of the ill-fitting dental prosthesis was suspended and the lesion had complete spontaneous remission three weeks later. TUGSE is an uncommon traumatic self-limiting lesion that must be included in the differential diagnosis of ulcerative lesions resembling oral cancer. The correlation of clinical and histopathological findings is pivotal for a proper diagnosis, avoiding unnecessary aggressive surgical approaches. Key words:Oral ulcer, eosinophilia, immunohistochemical, differential 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.

Reactive post-radiotherapy bone formation in the maxilla.

OBJECTIVE: High-dose radiation therapy affects bone metabolism, and therefore post-radiotherapy bone formation is an uncommon finding. This case describes an unusual ossification in the maxillary region identified after head and neck radiotherapy. RESULTS: A 45-year-old female patient was submitted to maxillary surgical resection and orbital exenteration due to squamous cell carcinoma. Radiotherapy post-surgery was performed because of compromised surgical margins. After 4 months of the conclusion of radiotherapy, the patient presented a bone exposition at surgical site. Surprisingly, the oral examination and computed tomography revealed a new formation of the right palatine vault and bone formation filling the nasal and orbital cavity. The incisional biopsy discarded residual disease or osteoradionecrosis and showed normal tissue. CONCLUSIONS: To the best of the authors' knowledge, this is the first case of wide bone formation as an early effect of head and neck radiotherapy.

Prevalence of dental alterations in patients under bisphosphonates therapy: a systematic review.

This systematic review aimed to estimate the prevalence and describe dentoalveolar lesions associated with bisphosphonates therapy. A systematic review of the literature was conducted using the following databases: PubMed, Embase, Cochrane, CINAHL, Scopus, Web of Science, Lilacs, SciElo, and Grey Literature. Quality of individual studies analysis was performed by using Newcastle-Ottawa Scale. Certainty of cumulative evidence was achieved by applying Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. The software R Statistics version 4.0.5 (The R Foundation) was used for proportion estimations per study and corresponding confidence intervals were estimated through the Clopper-Pearson method. Four articles were included for the qualitative synthesis. Two studies were considered of good quality, one of fair, and one of poor quality. A total of 231 patients were encompassed. Widening of the periodontal ligament space (22.2-39.7%), periradicular radiolucencies (20-22.9%), and pulp calcifications (33.3-69.2%) were the most frequent alterations. Certainty of evidence was rated as very low. Based on limited evidence, this systematic review reports a variety of dentoalveolar alterations in patients under bisphosphonate therapy. These features might impact on dental clinical practice. However, the level of evidence is considered very low due to important limitations.

Impact of radiotherapy on the morphological and compositional structure of intra-radicular dentin.

Considering the side effects in the oral cavity and dental structures of radiotherapy (RDT) for head and neck cancer, this study aimed to evaluate the effects of RDT on the root dentin concerning the obliteration of dentinal tubules, the inorganic composition of intra-radicular dentin, and the integrity of collagen fibers. Thirty human canines were selected from a biobank and randomly divided into two groups (n=15). The samples were sectioned buccolingually, and a hemisection was used for structural analysis by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer (EDS). Low-vacuum SEM images were obtained at 2000-x magnification to observe the obliteration of the dentinal tubules. Moreover, compositional evaluation was performed using EDS. After RDT, the SEM and EDS analyses were repeated using the same methodology. RDT was applied fractionally at 2 Gy per day, 5 days per week, for 7 weeks, resulting in a total dose of 70 Gy. The collagen integrity of the irradiated and non-irradiated samples was analyzed using Masson's trichrome and picrosirius red staining polarization microscopy. Samples subjected to RDT exhibited dentinal tubule obliteration (p < 0.001); low integrity of type I and III collagen fibers (p < 0.05); compositional reduction of calcium (p = 0.012), phosphorus (p = 0.001), and magnesium (p < 0.001); an increased Ca/P ratio (p < 0.001). RDT affects the structure of dentinal tubules, the inorganic composition of intra-radicular dentin, and the collagen fiber integrity in the root dentin, which may interfere with the effectiveness and durability of dental procedures.