The apparent diffusion coefficient (ADC) values with diffusion-weighted MRI (DWI) can be used to differentiate and characterize benign and malignant head and neck lesions. We described two cases of glandular odontogenic cyst with DWI: Case 1: glandular odontogenic cyst of the left side of the maxilla in a 73-year-old male; Case 2: glandular odontogenic cyst of the left side of the mandible in a 57-year-old female. The two cases of glandular odontogenic cysts were defined as a well-defined unilocular lesion on panoramic radiography, and T1-weighted image, T2-weighted image, and DWI of the lesions showed high-, high-, and high-signal intensity area than surrounding muscle, respectively. The ADC values of Case 1 and Case 2 were 1.61 x 10(-3) and 2.40 x 10(-3) mm(2) s(-1), respectively. The ADC values with DWI can be an effective technique for the quantitative evaluation of the glandular odontogenic cyst.

Background/Aim:Hyalinizing clear-cell carcinoma (HCCC) is a rare malignant tumor of the minor salivary glands characterized by nests of clear cells within a hyalinized stroma. Its diagnosis remains challenging due to its histological similarity to other neoplasms, and the recent recognition of distinct molecular features, such as Ewing sarcoma breakpoint region 1 (EWSR1)-activating transcription factor 1 (ATF1) fusion. This report describes a rare case of HCCC arising from the tongue with confirmed EWSR1-ATF1 fusion. Case Report:A 54-year-old man presented with a painless mass on the right lateral border of the tongue. Clinical examination revealed an elastic hard tumor measuring 18×15×8 mm. Biopsy under local anesthesia revealed a malignant clear-cell neoplasm. The lesion was completely excised under general anesthesia 2 weeks later. Histopathology showed nests of clear cells with polygonal nuclei in a hyalinized stroma. Immunohistochemistry demonstrated positivity for cytokeratin AE1/AE3, p63 protein and cytokeratin 7, and negativity for cytokeratin 20, α-smooth muscle actin, S-100 protein, vimentin, and cluster of differentiation 10. Periodic acid-Schiff staining was positive, with no diastase sensitivity. Fluorescence in situ hybridization revealed EWSR1 rearrangement, confirmed by reverse transcription-polymerase chain reaction as an EWSR1-ATF1 fusion. Perifocal stroma showed marked hyalinization. These findings support a diagnosis of HCCC with hyalinization. The patient remained disease-free 5 years after surgery. Conclusion:This case highlights the diagnostic importance of integrating histopathology, immunoprofiling, and molecular analysis in patients with rare salivary gland tumors and underscores the favorable outcomes of complete surgical resection for HCCC of the tongue.

This study aimed to compare the clinicopathological features of stage I–II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC. Forty-eight AYA patients aged 15–39 years and 69 older patients aged ≥ 65 years with surgically treated stage I–II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed. Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7

The aim of this study was performed to investigate the salivary gland SPECT/CT of parotid glands in patients with lymphoepithelial sialadenitis including preliminary study on clinical and pathological features. The study was performed in 5 patients with lymphoepithelial sialadenitis who underwent salivary gland SPECT/CT. Correlation between maximum standardized uptake value (SUV) at ratio of pre- to post-stimulation and clinicopathological parameters in lymphoepithelial sialadenitis were performed by Pearson correlation coefficient. The maximum SUV of 10 parotid glands in 5 patients with lymphoepithelial sialadenitis using salivary gland SPECT/CT was 23.8 ± 16.9 at pre-stimulation, 10.5 ± 5.1 at post-stimulation, and 2.06 ± 0.66 at ratio of pre- to post-stimulation. Furthermore, the maximum SUV at ratio of pre- to post-stimulation was significantly correlated with Saxon test score (r = 0.637, p = 0.048). The salivary gland SPECT/CT can be useful in clinical practice for the quantitative management of parotids in patients with lymphoepithelial sialadenitis.

Most oral malignant tumors are primary, and the incidence of oral metastatic tumors is low at 1

Sialolithiasis-a condition that most commonly affects the salivary glands, especially the submandibular gland-arises from the formation of calcified masses (sialoliths) within the salivary ducts. Although the morphology of sialoliths is diverse, reports of those containing bone are exceedingly rare, with only one documented case to date. Herein, we describe an unusual case of submandibular sialolithiasis with histologically confirmed bone formation. A 50-year-old Japanese woman presented with swelling and pain in the right submandibular region. Computed tomography showed a well-defined calcified lesion, and T2-weighted magnetic resonance imaging revealed a high-signal-intensity area posterior to the calcification within the gland. Under a clinical diagnosis of submandibular sialolithiasis with sialadenitis, surgical excision of the submandibular gland was performed. Gross examination of the excised gland revealed a 20 & times; 13 mm sialolith with a pale brown core surrounded by concentric lamellar structures. Histopathological assessment confirmed bone formation within the lamellar portions of the sialolith and lamellar calcification deposited around the bone tissues. The bone mass consisted of various morphologies and maturation stages, including mature bone with osteocytes, immature woven bone, bone lacking osteocytes, and bone becoming acellular during ossification. These bone tissues were not in contact with the ductal epithelium or fibrous connective tissue. The surrounding submandibular gland exhibited chronic obstructive sialadenitis with lymphoplasmacytic infiltration. Pathological ossification may occur as degenerative or necrotic tissue transforms into bone, potentially involving local mesenchymal stromal cells; however, the exact process leading to bone formation in these rare cases cannot be confirmed until more material becomes available.

Glandular odontogenic cysts (GOC) are relatively rare, and require differentiation from radicular cysts, dentigerous cysts, and central mucoepidermoid carcinoma of jawbone. We conducted clinical, histopathological, and immunohistochemical analysis to elucidate the relationship between the clinical behavior and histopathological features, as well as the origin of tissues and factors related to the development of GOC. Thirty specimens from 29 patients (19 males, 11 females; mean age 51.8, range 18–85 years) diagnosed histopathologically with GOC were studied. By location site, mandibular molar region was most common (17 cysts), followed by maxillary anterior region (5), maxillary molar region (4), and mandibular anterior region (4). All cases were clinically asymptomatic and were detected incidentally on X-ray examination. In the X-ray findings, all cases showed unilocular, well-defined radiolucencies, with a long diameter ranging from 9 to 36 mm. Histopathologically, eosinophilic cuboidal cells and microcysts were found in all cases, apocrine snouting was observed in 27 (90

Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy based on a monoclonal antibody (mAb) conjugated to a photosensitizer (IR700Dye). The conjugate can be activated by near-infrared light irradiation, causing necrotic cell death with high selectivity. In this study, we investigated NIR-PIT using a small protein mimetic (6-7 kDa, Affibody) which has more rapid clearance and better tissue penetration than mAbs for epidermal growth factor receptor (EGFR)-positive salivary gland cancer (SGC). The level of EGFR expression was examined in vitro using immunocytochemistry and Western blotting. Cell viability was analyzed using the alamarBlue assay. In vivo, the volume of EGFR-positive tumors treated with NIR-PIT using the EGFR Affibody-IR700Dye conjugate was followed for 43 days. It was found that NIR-PIT using the EGFR Affibody-IR700Dye conjugate induced the selective destruction of EGFR-positive SGC cells and restricted the progression of EGFR-positive tumors. We expect that NIR-PIT using the EGFR Affibody-IR700Dye conjugate can efficiently treat EGFR-positive SGC and preserve normal salivary function.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign non-neoplastic lesion histopathologically characterized by papillary proliferation of endothelial cells in dilated vascular lumen, and occurrence in the oral region is relatively rare. In this study, we performed clinical, histopathological, and immunohistochemical evaluations in 13 cases of oral IPEH, and examined the pathogenetic mechanism, pathophysiology, and differentiation from other vascular anomalies. The upper lip was the most common lesion site (5 cases), followed by the lower lip (3 cases) and the tongue (2 cases). The most common clinical diagnosis was hemangioma in 7 cases, followed by benign tumor in 4 cases. On gross examination, the tumor was dark red or mucosal color, similar to a hemangioma, and the surface was smooth, elastic and soft. Histological classification was mixed form in 11 cases and pure form in 2 cases. In immunohistochemical staining, CD31 was expressed in the cytoplasm and on cell membrane of vascular endothelial cells in all 13 cases; ERG was expressed in the nuclei of vascular endothelial cells in all 13 cases; alpha-SMA was expressed on cell membrane of smooth muscle cells in the blood vessel wall in all 13 cases; CD105 was expressed in the cytoplasm of vascular endothelial cells in 10 of 13 cases; and VEGF-A was expressed in the cytoplasm of vascular endothelial cells in all 13 cases. D2-40 was expressed in the cytoplasm and on cell membrane of endothelial cells within the papillary structures in only 2 cases, but Glut-1 expression was not detected in any of the cases. IPEH was easily differentiated from angiosarcoma, Kaposi's sarcoma, mucous cyst, and pyogenic granuloma. The pathogenetic mechanism of this disease suggested by this study is that thrombus formation induces a hypoxia and low glucose state at the lesion site, and VEGF produced by endothelial cells stimulates reactive proliferation of the endothelial cells to form IPEH.

Papillary thyroid carcinoma is the most common pathological type of thyroid cancer. Lymph node metastasis in patients with papillary thyroid carcinoma is common. We report a case of cervical lymph node metastasis of papillary thyroid carcinoma in a patient with maxillary gingival squamous cell carcinoma. A 77-year-old man presented with swelling and pain on the left side of the maxilla. Maxillary gingival squamous cell carcinoma without cervical lymph node metastasis was suspected from the CT images of the lesion in addition to panoramic radiography. A partial biopsy of the maxillary region was performed. Histopathological diagnosis was well to moderately differentiated squamous cell carcinoma. Chemoradiotherapy (CDDP: 400 mg and external radiation: 60 Gy) was performed for the maxillary tumor, and post-chemoradiotherapy outcomes were good for the maxillary tumor. However, contrast-enhanced CT taken 4 months after the primary treatment showed increase of the superior internal jugular node with heterogeneous enhancement and the mid internal jugular node with homogeneous enhancement and flecks of calcification on the left side of the neck. Cervical lymph node metastasis of the left maxillary gingival carcinoma after chemoradiotherapy was suspected from the CT images. Neck dissection was performed. Histopathological diagnosis was cervical lymph node metastasis of the left maxillary gingival squamous cell carcinoma and papillary carcinoma of the thyroid.

In recent years, bacterial DNA in formalin-fixed paraffin-embedded (FFPE) samples has been recognized as a valuable bioresource for microbiota studies. This study aimed to examine the effect of the FFPE process on microbiota profiling to evaluate whether FFPE samples could serve as an alternative bioresource to fresh samples in oral microbiota studies. Fresh saliva was collected from nine subjects. The pellets obtained by centrifuging the collected saliva were fixed in formalin, then dehydrated and embedded in paraffin to prepare FFPE samples. The abundance of the hypervariable regions V1-9, V1-2, and V3-4 of the 16S rRNA gene in fresh and FFPE samples was relatively compared. In addition, microbiota profiling was performed to compare the results between the two sample types. The results showed that the FFPE process resulted in a certain degree of fragmentation of the 16S rRNA gene. However, the V1-2 region was relatively well-preserved compared to the V1-9 and V3-4 regions, suggesting that short regions are suitable targets for oral microbiota analysis. Importantly, there were no significant differences in alpha and beta diversity of microbiota between fresh and FFPE samples, and microbiota profiles were similar between the two sample types, suggesting that FFPE samples could be a valuable bioresource for oral microbiota studies.

Background SPECT/CT has been applied for preoperative planning of MRONJ. Furthermore, the SUV using bone SPECT/CT has enabled quantitative analysis of jaw lesions. This study aimed to evaluate the role of preoperative SPECT/CT SUVs in MRONJ, especially SPECT/CT in relation to CBCT and histopathological findings of the resected bone of mandibulectomy. The preliminary study was conducted on five MRONJ patients who underwent mandibulectomy after SPECT/CT. Results The SUVmax and SUVmean of MRONJ in all cases (19.5 ± 5.6 and 5.5 ± 0.8) were significantly higher than those of right side of the MRONJ (8.5 ± 2.0 and 2.7 ± 0.5) and left side of the MRONJ (7.2 ± 1.6 and 2.7 ± 0.4), respectively. The CBCT of all cases showed osteolytic and sclerotic internal texture and sequestrum. The histopathological characteristics of all cases showed necrotic bone and granulation tissue with the bone circumference surrounded by inflammatory cells. Conclusions The preliminary results indicated a difference between MRONJ and right and left sides of the MRONJ in SPECT/CT SUVs. The SUVs has enabled quantitative analysis for surgical planning of MRONJ.

Radicular cysts are the most common cystic lesions in the oral cavity, and have a rare occurrence in the primary dentition. We report a case of radicular cyst of mandible in child by multimodal imaging including panoramic radiography, CT, and MR imaging. A 7-year-old girl presented with swelling and without pain, and hypoesthesia on the right side of the mandible. On clinical examination, an expansive lesion with undulation was found to the buccal cortex of the right side of the mandible. Panoramic radiograph showed a unilocular radiolucency with well-defined margin, displaced tooth, and root resorption in the right mandible. Regarding CT imaging, axial soft tissue algorithm CT and bone tissue algorithm CT showed a low-attenuation internal structure and expansion of the buccal cortex of the right side of the mandible. Three-dimensional-CT showed expansion of the buccal cortex of the right side of the mandible. Multiplanar reformation imaging showed displaced tooth, root resorption, and expansion of the buccal cortex of the right side of the mandible. On T1-weighted image, the expansive lesion showed low signal intensity, and T2-weighted and STIR images revealed high signal intensity. A partial biopsy of the mandibular region was performed. Histopathological diagnosis was radicular cyst caused by apical periodontitis with abscess. This case suggests that multimodal imaging, especially CT and MR imaging, could be effective for evaluating mandibular lesions in child.

Sjögren's syndrome (SS) is an autoimmune disease that occurs predominantly in middle-aged and older women. Although focus score (FS) and lesion grade are determined at pathological diagnosis, few reports have examined whether these results reflect clinical symptoms. In this study, we examined and compared the results of comprehensive immunohistochemical staining of lymphocytes and NF-κB pathway in labial gland biopsies, clinical test data, and radionuclide imaging findings. One hundred labial gland biopsy specimens obtained from 20 female patients with primary SS (5 specimens per patient) were studied. Hematoxylin–eosin-stained specimens were reviewed and FS were calculated. Immunohistochemical staining of CD4, CD8, CD20, CD25, Foxp3, NF-κB, TNFAIP3 and IκBα was performed, and the results were compared with anti-SS-A/Ro (SS-A), anti-SS-B/La (SS-B) and antinuclear antibodies (ANA), and salivary gland scintigraphy findings. FS were significantly higher in the SS-A-, SS-B- and ANA-positive groups than in the respective -negative groups (p < 0.05). Of eight SS-A-positive and SS-B-negative cases, mean FS was 1.9 (seven cases: FS ≥ 1.0) and six cases were ANA-positive. In four SS-A-positive and SS-B-positive cases, mean FS was 3.2 (all cases: FS ≥ 1.0) and all cases were ANA-positive. In immunohistochemical staining, CD4-positive T cells tended to be more abundant than CD8-positive T cells. Small numbers of Foxp3-positive cells were found in all cases. NF-κB, TNFAIP3 and IκBα were positive in the acini, ductal epithelium, and lymphocytes in all cases. The above findings indicated a relationship between FS and clinical test data, and the association of NF-κB pathway with the pathophysiology of primary SS.

Multiple myeloma is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Neoplastic plasma cells stimulated osteoclasts, and destroy bone tissue, causing bone pain, pathological fractures, paralysis due to spinal cord compression, and hypercalcemia. Bisphosphonates are used as supportive therapy in the management of multiple myeloma. Medication-related osteonecrosis of the jaw (MRONJ) is a well-known complication of treatment with bisphosphonates, denosumab, and other drugs, such as anti-angiogenic agents and novel anti-cancer drugs. We report MRONJ in a patient with multiple myeloma, especially an unusual case with tumor in the surgical specimen. A 73-year-old woman presented with pain on the left side of the mandible within 3 months. On clinical examination, an exposed bone without purulent drainage presented on the left side of the mandible. Before 2 years, she received chemotherapy of zoledronate for multiple myeloma at another hospital. Panoramic imaging showed radiopacities of bone in the left side of the mandibular molar area. Multidetector computed tomography (MDCT) with axial, multiplanar reformation (MPR) and three-dimensional (3D) images showed the sequestrum without periosteal reaction. She was diagnosed as MRONJ, and underwent surgery. Finally, the surgical specimen was diagnosed as multiple myeloma in the sequestrum. This case suggests that the evaluation of the surgical specimen of MRONJ could be essential for detection of primary tumor.

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer (IR700Dye) that is activated by near-infrared light irradiation. We previously reported on the use of NIR-PIT with a small protein mimetic, the Affibody molecule (6–7 kDa), instead of a monoclonal antibody. In this study, we investigated a combination of NIR-PIT for HER2-positive breast cancer cells (SK-BR3, MDA-MB361, and JIMT1) with HER2 Affibody-IR700Dye conjugate and trastuzumab-IR700Dye conjugate. HER2 Affibody and trastuzumab target different epitopes of the HER2 protein and do not compete. In vitro, the combination of NIR-PIT using both HER2 Affibody-IR700Dye conjugate and trastuzumab-IR700Dye conjugate induced necrotic cell death of HER2-positive breast cancer cells without damage to HER2-negative breast cancer cells (MCF7). It was more efficient than NIR-PIT using either the HER2 Affibody-IR700Dye conjugate alone or the trastuzumab-IR700Dye conjugate alone. Additionally, this combination of NIR-PIT was significantly effective against HER2 low-expressing cancer cells, trastuzumab-resistant cells (JIMT1), and brain metastatic cells of breast cancer (MDA-MB361). Furthermore, in vivo imaging exhibited the strong fluorescence intensity of both HER2 Affibody-IR700Dye conjugates and trastuzumab-Alexa488 conjugates in HER2-positive tumor, indicating that both HER2 Affibody and trastuzumab specifically bind to HER2-positive tumors without competing with each other. In conclusion, the combination of NIR-PIT using both HER2 Affibody and trastuzumab expands the targeting scope of NIR-PIT for HER2-positive breast cancer.

Clinically suspected oral lichen planus (OLP) includes histopathologically proven OLP, oral lichenoid lesion (OLL) or lichenoid stomatitis, and oral lichenoid dysplasia (OLD). Malignant transforming potential of OLD is a diagnostic issue. This study aimed to exclude OLD from OLP and OLL and examine the role of OLD in malignant transformation. Immunostaining for CK13, CK17, p53, Ki-67, Coxsackie‒adenovirus receptor (CAR) and E-Cadherin was conducted in 200 cases. CK13-positive rate was lower in OLD (33.3%) than in OLP and OLL. CK17-positive rate was slightly lower in OLP (89.2%) compared to OLL and OLD. Ki-67positive rate from basal to spinous layer was higher in OLD (30.6%) than in OLP and OLL, and p53 showed similar trend (OLD: 19.4%). Rate of attenuated CAR staining intensity from basal layer to lower one-third of spinous layer was higher in OLD (77.8%) compared to OLP and OLL, similar to rate of attenuated E-Cadherin staining (OLD: 45.8%). In conclusion, a diagnosis of OLP or OLL is indicated when the lesion is CK13 positive and CK17 positive, with no attenuation of staining intensity for CAR and E-Cadherin from the basal layer to the lower onethird of the spinous layer. On the other hand, a diagnosis of OLD is indicated when the lesion is CK13 negative and CK 17 positive, with attenuation of staining intensity for CAR and E-Cadherin from the basal layer to the lower one-third of the spinous layer. In OLD, attenuated CAR expression may participate in malignant transformation by weakening cell junction in the epithelium and inducing epithelial mesenchymal transition.

PURPOSE:The purpose of this study was to evaluate the cone-beam computed tomographic (CBCT) imaging and histopathological characteristics of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ).MATERIALS AND METHODS:Ten surgical specimens from segmental mandibulectomy (3 ORN and 7 MRONJ) were analyzed using CBCT. The CBCT parameters were as follows: high-resolution mode (tube voltage, 90.0 kV; tube current, 4.00 mA; rotation time, 16.8 s; field of view, 56 mm×56 mm; thickness, 0.099 mm). Histopathological characteristics were evaluated using histological slides of the surgical specimens. The Pearson chi-square test was used to compare ORN and MRONJ in terms of CBCT findings (internal texture, sequestrum, periosteal reaction and cortical perforation) and histopathological characteristics (necrotic bone, inflammatory cells, reactive bone formation, bacteria, Actinomyces, and osteoclasts). A P value less than 0.05 was considered to indicate statistical significance.RESULTS:MRONJ showed periosteal reaction on CBCT more frequently than ORN (7 of 7 [100%] vs. 0 of 3 [0%], P<0.05). Regarding histopathological characteristics, MRONJ showed osteoclasts more frequently than ORN (6 of 7 [85.7%] vs. 0 of 3 [0%], P<0.05).CONCLUSION:This study evaluated the CBCT imaging and histopathological characteristics of ORN and MRONJ, and the findings suggest that CBCT could be useful for the evaluation of ORN and MRONJ.

Background: Depth of invasion (DOI) in oral carcinoma has been integrated into the primary tumor categories in the current tumor-node metastasis staging, and intraoral ultrasonography provides sufficient accuracy for the measurement of tumor DOI in oral tongue carcinoma. Aims: The objectives of this study were to analyze the tongue squamous cell carcinoma (SCC) with Doppler sonography and strain elastography using intraoral ultrasonography. Materials and Methods: Six patients with tongue SCC who underwent Doppler sonography and strain elastography using intraoral ultrasonography were prospectively included. Doppler sonography and strain elastography using intraoral ultrasonography were obtained with a linear 14 MHz transducer using our protocol. The tumor thickness using ultrasonography and tumor with/without vascular signals were evaluated by the Mann–Whitney U-test. The relationship between tumor thickness using ultrasonography and pathological tumor thickness and DOI was assessed by the Pearson's rank correlation test. P values lower than 0.05 indicate statistically significant differences. Results: The tumor thickness using ultrasonography in the vascular signal's presence group (5.8 ± 1.4 mm) was larger than that of the absence group (3.1 ± 1.5 mm, P = 0.050). The strain values of tumor and control in the tongue SCC were 0% and 0.534% ± 0.236%, respectively. Tumor thickness using ultrasonography was correlated with pathological tumor thickness (r = 0.811, P = 0.050) and pathological DOI (r = 0.599, P = 0.209), respectively. Conclusions: Doppler sonography and strain elastography using intraoral ultrasonography are useful for the analysis of tongue SCC.