A case of BRCA1-mutated giant pancreatic acinar cell carcinoma successfully treated with modified FOLFIRINOX therapy and radical resection.

Pancreatic acinar cell carcinoma (PACC) is a rare type of pancreatic cancer; further, its pathogenesis and treatment strategies remain unclear. We report the case of a 70-year-old man who presented with a chief complaint of abdominal distention. Computed tomography scans revealed a large lobulated mass (tumor diameter: 150 mm) in the pancreatic body tail, which was diagnosed as a PACC through endoscopic ultrasonography fine needle aspiration. The other imaging modalities did not reveal distant metastases, and the tumor was classified as resectable. Neoadjuvant chemotherapy was planned after staging laparoscopy ruled out microscopic distant metastasis. First-line chemotherapy with gemcitabine + nab-paclitaxel failed due to tumor growth and worsening abdominal distention. Evaluation using the BRACAnalysis® device indicated that the patient was positive for BRCA1 mutation. Second-line modified FOLFIRINOX (mFFX) resulted in a marked decrease in elastase 1 levels; moreover, a partial antitumor response was observed, which prompted radical resection. After distal pancreatectomy, the patient has survived for 3.5 years without recurrence. BRCA-mutated pancreatic cancer is more likely to respond to mFFX, including platinum, and BRCA mutations have been reported to be highly prevalent in PACC. It is important to evaluate the presence of BRCA mutations in patients with PACC prior to treatment.

Thoracoscopic enucleation of an esophageal glomus tumor in the prone position: a case report and literature review.

BACKGROUND: Glomus tumors (GT) generally occur in the skin. However, esophageal GT, an extremely rare condition, has no established standardized treatment guidelines. Herein, we report the case of an esophageal GT successfully removed by thoracoscopic enucleation in the prone position using intra-esophageal balloon compression. CASE PRESENTATION: A 45-year-old man underwent an annual endoscopic examination and was found to have a submucosal tumor in the lower esophagus. Endoscopic ultrasound (EUS) revealed a hyperechoic mass originating from the muscular layer. Contrast-enhanced computed tomography identified a 2 cm mass lesion with high contrast enhancement in the right side of the lower esophagus. Pathologic findings of EUS-guided fine needle aspiration biopsy (EUS-FNA) revealed round to spindle shaped atypical cells without mitotic activity. Immunohistochemically, the tumor was positive for alpha-smooth muscle actin, but negative for CD34, desmin, keratin 18, S-100 protein, melan A, c-kit, and STAT6. He was diagnosed with an esophageal GT and a thoracoscopic approach to tumor resection was planned. Under general anesthesia, a Sengstaken-Blakemore (SB) tube was inserted into the esophagus. The patient was placed in the prone position and a right thoracoscopic approach was achieved. The esophagus around the tumor was mobilized and the SB tube balloon inflated to compress the tumor toward the thoracic cavity. The muscle layer was divided and the tumor was successfully enucleated without mucosal penetration. Oral intake was initiated on postoperative day (POD) 3 and the patient discharged on POD 9. No surgical complications or tumor metastasis were observed during the 1-year postoperative follow-up. CONCLUSIONS: As malignancy criteria for esophageal GT are not yet established, the least invasive procedure for complete resection should be selected on a case-by-case basis. Thoracoscopic enucleation in the prone position using intra-esophageal balloon compression is useful to treat esophageal GT on the right side of the esophagus.

Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer.

Introduction: The efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells. Methods: Patients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared. Results: Among 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32-0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00-2.87) and systemic progression (HR, 3.09, 95%CI, 1.95-4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04-8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different. Conclusion: The new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells.

PDGF receptor signal mediates the contribution of Nestin-positive cell lineage to subcutaneous fat development.

The beiging of white adipose tissue (WAT) is expected to improve systemic metabolic conditions; however, the regulation and developmental origin of this process remain insufficiently understood. In the present study, the implication of platelet-derived growth factor receptor alpha (PDGFRα) was examined in the beiging of inguinal WAT (ingWAT) of neonatal mice. Using in vivo Nestin expressing cell (Nestin+) lineage tracing and deletion mouse models, we found that, in the mice with Pdgfra gene inactivation in Nestin+ lineage (N-PRα-KO mice), the growth of inguinal WAT (ingWAT) was suppressed during neonatal periods as compared with control wild-type mice. In the ingWAT of N-PRα-KO mice, the beige adipocytes appeared earlier that were accompanied by the increased expressions of both adipogenic and beiging markers compared to control wild-type mice. In the perivascular adipocyte progenitor cell (APC) niche of ingWAT, many PDGFRα+ cells of Nestin+ lineage were recruited in Pdgfra-preserving control mice, but were largely decreased in N-PRα-KO mice. This PDGFRα+ cell depletion was replenished by PDGFRα+ cells of non-Nestin+ lineage, unexpectedly resulting in an increase of total PDGFRα+ cell number in APC niche of N-PRα-KO mice over that of control mice. These represented a potent homeostatic control of PDGFRα+ cells between Nestin+ and non-Nestin+ lineages that was accompanied by the active adipogenesis and beiging as well as small WAT depot. This highly plastic nature of PDGFRα+ cells in APC niche may contribute to the WAT remodeling for the therapeutic purpose against metabolic diseases.

Hypothalamic orexin prevents non-alcoholic steatohepatitis and hepatocellular carcinoma in obesity.

Non-alcoholic steatohepatitis (NASH) occasionally occurs under obesity; however, factors modulating the natural history of fatty liver disease remain unknown. Since hypothalamic orexin that regulates physical activity and autonomic balance prevents obesity, we investigate its role in NASH development. Male orexin-deficient mice fed a high-fat diet (HFD) show severe obesity and progression of NASH with fibrosis in the liver. Hepatic fibrosis also develops in ovariectomized orexin-deficient females fed an HFD but not ovariectomized wild-type controls. Moreover, long-term HFD feeding causes hepatocellular carcinoma (HCC) in orexin-deficient mice. Intracerebroventricular injection of orexin A or pharmacogenetic activation of orexin neurons acutely activates hepatic mTOR-sXbp1 pathway to prevent endoplasmic reticulum (ER) stress, a NASH-causing factor. Daily supplementation of orexin A attenuates hepatic ER stress and inflammation in orexin-deficient mice fed an HFD, and autonomic ganglionic blocker suppresses the orexin actions. These results suggest that hypothalamic orexin is an essential factor for preventing NASH and associated HCC under obesity.

A 47-Year-Old Man with Advanced Distal Pancreatic Carcinoma and an Initial Partial Response to Chemotherapy Requiring Celiac Axis Reconstruction of the Common Hepatic Artery and Left Gastric Artery.

BACKGROUND Distal pancreatectomy with en bloc celiac artery resection (DP-CAR) is a curative surgical method for locally advanced pancreatic body cancer; however, arterial reconstruction remains controversial in this procedure. This report presents the case of a 47-year-old man with advanced distal pancreatic carcinoma and initial partial response to chemotherapy who required celiac axis reconstruction of the common hepatic artery and left gastric artery. CASE REPORT A 47-year-old man had loss of appetite. He had a 40-mm hypovascular tumor extending from the pancreatic body to the tail, invading around the celiac artery, common hepatic artery, left gastric artery, and splenic artery. We initiated chemotherapy concurrent with chemo-radiotherapy with S-1 administration. After chemo-radiotherapy, computed tomography (CT) showed tumor shrinkage, indicating partial response, but soft tissue CT density surrounding the celiac axis arteries persisted. We conducted conversion surgery. When the common hepatic artery was clamped during surgery, the intrahepatic arterial blood flow reduced; thus, we reconstructed the middle hepatic artery to the common hepatic artery. The left gastric artery was also reconstructed using the second jejunal artery to prevent ischemic gastropathy. Histopathologic examination showed no tumor cells in the specimen; thus, R0 resection was achieved. CONCLUSIONS Arterial reconstruction can be an option for R0 resection in DP-CAR when hepatic arterial blood flow is reduced due to an intraoperative common hepatic artery clamping test.

Intrahepatic Bile Duct Injury as a Hepatic Immune-Related Adverse Event after Immune-Checkpoint Inhibitor Treatment.

The increased use of immune-checkpoint inhibitors to treat various types of cancer has increased the incidence of immune-related adverse events (irAEs). Hepatic irAEs are frequent and can lead to serious conditions. Among the various types of hepatic irAEs reported to date, bile duct injury has been shown refractory to steroid treatment. This study describes 2 patients with hepatic irAEs manifesting as intrahepatic bile duct injury. Immunostaining with antibodies to both CD8 and cytokeratin-7 was useful for the diagnosis, and both patients were refractory to steroid treatment. Prompt diagnosis and active immunosuppressive therapies are required in such cases.

Dysregulation of Amphiregulin stimulates the pathogenesis of cystic lymphangioma.

Along with blood vessels, lymphatic vessels play an important role in the circulation of body fluid and recruitment of immune cells. Postnatal lymphangiogenesis commonly occurs from preexisting lymphatic vessels by sprouting, which is induced by lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C). However, the key signals and cell types that stimulate pathological lymphangiogenesis, such as human cystic lymphangioma, are less well known. Here, we found that mouse dermal fibroblasts that infiltrate to sponges subcutaneously implanted express VEGF-D and sushi, Von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) in response to PDGFRß signal. In vitro, Pdgfrb knockout (ß-KO) fibroblasts had reduced expression of VEGF-D and SVEP1 and overproduced Amphiregulin. Dysregulation of these three factors was involved in the cyst-like and uneven distribution of lymphatic vessels observed in the ß-KO mice. Similarly, in human cystic lymphangioma, which is one of the intractable diseases and mostly occurs in childhood, fibroblasts surrounding cystic lymphatics highly expressed Amphiregulin. Moreover, fibroblast-derived Amphiregulin could induce the expression of Amphiregulin in lymphatic endothelial cells. The dual source of Amphiregulin activated EGFR expressed on the lymphatic endothelial cells. This exacerbation cascade induced proliferation of lymphatic endothelial cells to form cystic lymphangioma. Ultimately, excessive Amphiregulin produced by fibroblasts surrounding lymphatics and by lymphatic endothelial cells per se results in pathogenesis of cystic lymphangioma and will be a fascinating therapeutic target of cystic lymphangioma.

Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice.

Blood-brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFRα) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction. In the present study, we examined the role of PDGF signaling in the process of tissue remodeling after middle cerebral arterial occlusion (MCAO) in mice. Firstly, we found that imatinib increased lesion size after permanent MCAO in wild-type mice. Moreover, imatinib-induced HT only when administrated in the subacute phase of MCAO, but not in the acute phase. Secondly, we generated genetically mutated mice (C-KO mice) that showed decreased expression of perivascular PDGFRα. Additionally, transient MCAO experiments were performed in these mice. We found that the ischemic lesion size was not affected; however, the recruitment of PDGFRα/type I collagen-expressing perivascular cells was significantly downregulated, and HT and IgG leakage was augmented only in the subacute phase of stroke in C-KO mice. In both experiments, we found that the expression of tight junction proteins and PDGFRß-expressing pericyte coverage was not significantly affected in imatinib-treated mice and in C-KO mice. The specific implication of PDGFRα signaling was suggestive of protective effects against BBB dysfunction during the subacute phase of stroke. Vascular TGF-ß1 expression was downregulated in both imatinib-treated and C-KO mice, along with sustained levels of MMP9. Therefore, PDGFRα effects may be mediated by TGF-ß1 which exerts potent protective effects in the BBB.

Clinicopathological Features of Thyroid-Like Low-Grade Nasopharyngeal Papillary Adenocarcinoma: A Case Report and Review of the Literature.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare neoplasm of the nasopharynx. Accordingly, its clinical and pathological characteristics are not well-known. We report a case of TL-LGNPPA and review the relevant literature on TL-LGNPPA. A 38-year-old Japanese woman presented with a history of nasal obstruction that had persisted for 1 month after symptoms of a common cold (e.g., low-grade fever, sore throat, and fatigue). A pedunculated tumor of ~20 mm in diameter was found on the posterior edge of the nasal septum. The tumor was endoscopically resected. Based on careful histopathological and immunohistochemical examinations, it was diagnosed as TL-LGNPPA. At 5 years after surgery, the patient remained disease-free. TL-LGNPPA has a very good prognosis, and complete resection with a sufficient safety margin is recommended as the first-line treatment. The morphological characteristics and immunohistochemical findings, especially TTF-1 positivity and thyroglobulin negativity, are important for the diagnosis.

Critical role of platelet-derived growth factor-α in angiogenesis after indirect bypass in a murine moyamoya disease model.

OBJECTIVE: This study aimed to clarify the underlying mechanism of pathognomonic angiogenesis between the temporal muscle and neocortex after indirect bypass for moyamoya disease by shedding light on the role of platelet-derived growth factor receptor-α (PDGFRα) in angiogenesis. METHODS: The gene for PDGFRα was systemically inactivated in adult mice (α-KO mice). The Pdgfra-preserving mice (Flox mice) and α-KO mice were exposed to bilateral common carotid artery stenosis (BCAS) by using microcoils. One week later the animals underwent encephalomyosynangiosis (EMS) on the right side. Cerebral blood flow (CBF) was serially measured using a laser Doppler flowmeter. Histological analysis was performed on the distribution of CD31-positive vessels and collagen deposit at 28 days after BCAS. Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of collagen mRNA in the skin fibroblasts derived from Flox and α-KO mice. RESULTS: BCAS significantly reduced CBF up to approximately 70% of the control level at 28 days after the onset. There was no significant difference in CBF between Flox and α-KO mice. EMS significantly enhanced the improvement of CBF on the ipsilateral side of Flox mice, but not α-KO mice. EMS significantly induced the development of CD31-positive vessels in both the neocortex and temporal muscle on the ipsilateral side of Flox mice, but not α-KO mice. Deposition of collagen was distinctly observed between them in Flox mice, but not α-KO mice. Expression of mRNA of collagen type 1 alpha 1 (Col1a1) and collagen type 3 alpha 1 (Col3a1) was significantly downregulated in the skin fibroblasts from α-KO mice. CONCLUSIONS: This is the first study that denotes the role of a specific growth factor in angiogenesis after EMS for moyamoya disease by inactivating its gene in mice. The findings strongly suggest that PDGFRα signal may play an important role in developing spontaneous angiogenesis between the temporal muscle and neocortex after EMS in moyamoya disease.

Oligodendrogenesis and Myelin Formation in the Forebrain Require Platelet-derived Growth Factor Receptor-alpha.

The platelet-derived growth factor receptor-α (PDGFRα) principally mediates growth factor signals in oligodendroglial progenitors and is involved in oligodendrogenesis and myelinogenesis in the developing spinal cord. However, the role of PDGFRα in the developing forebrain remains relatively unknown. We established a conditional knockout mouse for the Pdgfra gene (N-PRα-KO) using a Nestin promoter/enhancer-driven Cre recombinase and examined forebrain development. The expression of PDGFRα was efficiently suppressed in the Olig2+ cells in N-PRα-KO mice. In these mice, Olig2+ cells were slightly decreased during embryonic periods. The decrease was particularly striking during the postnatal period. The commitment of Pdgfra-inactivated Olig2+ cells to Sox10+ oligodendroglial-lineage was largely suppressed. Surviving Olig2+ cells and Sox10+ cells were distributed widely in the N-PRα-KO mouse brain, similarly to those in control mice until the early neonatal period. After that, these cells were drastically depleted in the forebrain during the second postnatal week. The brains of N-PRα-KO mice were severely hypomyelinated, and these mice died on approximately P17 with motor disturbances. Disturbed axonal fibers and extensively aberrant vascular formations appeared in the postnatal N-PRα-KO mouse brains. After the defective PDGFRα signal in the forebrain, these phenotypes were clearly different from those in the spinal cord that showed defective populations expansion and migration of oligodendroglial lineage and premature myelination, as previously described. In contrast, areas of severe hypomyelination were common to both anatomical sites. PDGFRα was critically involved in the myelination of the forebrain and may differently regulate oligodendroglial lineage between the forebrain and spinal cord.

Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain.

Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin+ immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.

PDGFR-ß restores blood-brain barrier functions in a mouse model of focal cerebral ischemia.

Although platelet-derived growth factor receptor beta (PDGFR-ß) mediates the recruitment of vascular pericytes into ischemic lesion to restore the blood-brain barrier (BBB) dysfunction, its mechanisms still remain elusive. Compared with control PDGFR-ßfloxed/floxed mice (Floxed), postnatally induced systemic PDGFR-ß knockout mice (Esr-KO) not only showed severe brain edema, neurologic functional deficits, decreased expression of tight junction (TJ) proteins, abundant endothelial transcytosis, and deformed TJs in the BBB, but also showed reduced expression of transforming growth factor-ß (TGF-ß) protein after photothrombotic middle cerebral artery occlusion (MCAO). In endothelial-pericyte co-culture, an in vitro model of BBB, the increment in the barrier function of endothelial monolayer induced by pericyte co-culture was completely cancelled by silencing PDGFR-ß gene expression in pericytes, and was additively improved by PDGFR-ß and TGF-ß receptor signals under hypoxia condition. Exogenous PDGF-BB increased the expression of p-Smad2/3, while anti-TGF-ß1 antibody at least partially inhibited the phosphorylation of Smad2/3 after PDGF-BB treatment in vitro. Furthermore, pre-administration of TGF-ß1 partially alleviated edema formation, neurologic dysfunction, and TJs reduction in Esr-KO mice after MCAO. Accordingly, PDGFR-ß signalling, via TGF-ß signalling, may be crucial for restoration of BBB integrity after cerebral ischemia and therefore represents a novel potential therapeutic target.

Different PDGF Receptor Dimers Drive Distinct Migration Modes of the Mouse Skin Fibroblast.

BACKGROUND/AIMS: The migration of mesenchymal cells is a fundamental cellular process that has been implicated in many pathophysiological conditions and is induced by chemoattractants such as platelet-derived growth factors (PDGFs). However, the regulatory mechanisms shaping this migration remain to be elucidated. METHODS: Here, we prepared mouse skin fibroblasts inactivated for different PDGF receptor genes and systematically measured their chemotactic responses within a gradient of different chemoattractants. RESULTS: We found that PDGFRαß and PDGFRßß dimers were strong inducers of random and directionally-persistent migration, respectively, that was sustained for up to 24 h. MAPK and PI3K were necessary to mediate random and directional migration, respectively. Directional migration was accompanied by abundant ventral stress fiber formation and consistent cell shape with less frequent formation of branch-like processes. CONCLUSION: This is the first systematic study that characterized the chemotaxis mediated by three-different types of PDGFR dimers in mesenchymal cell migration. Our data demonstrate that PDGFR dimer formation is the critical step to determine the specific mode of fibroblast chemotaxis, while the accompanying cytoskeletal remodeling might contribute to migration persistence.

The Novel Pathogenesis of Retinopathy Mediated by Multiple RTK Signals is Uncovered in Newly Developed Mouse Model.

Pericyte desorption from retinal blood vessels and subsequent vascular abnormalities are the pathogenesis of diabetic retinopathy (DR). Although the involvement of abnormal signals including platelet-derived growth factor receptor-ß (PDGFRß) and vascular endothelial growth factor-A (VEGF-A) have been hypothesized in DR, the mechanisms that underlie this processes are largely unknown. Here, novel retinopathy mouse model (N-PRß-KO) was developed with conditional Pdgfrb gene deletion by Nestin promoter-driven Cre recombinase (Nestin-Cre) that consistently reproduced through early non-proliferative to late proliferative DR pathologies. Depletion of Nestin-Cre-sensitive PDGFRß+NG2+αSMA- pericytes suppressed pericyte-coverages and induced severe vascular lesion and hemorrhage. Nestin-Cre-insensitive PDGFRß+NG2+αSMA+ pericytes detached from the vascular wall, and subsequently changed into myofibroblasts in proliferative membrane to cause retinal traction. PDGFRα+ astrogliosis was seen in degenerated retina. Expressions of placental growth factor (PlGF), VEGF-A and PDGF-BB were significantly increased in the retina of N-PRß-KO. PDGF-BB may contribute to the pericyte-fibroblast transition and glial scar formation. Since VEGFR1 signal blockade significantly ameliorated the vascular phenotype in N-PRß-KO mice, the augmented VEGFR1 signal by PlGF and VEGF-A was indicated to mediate vascular lesions. In addition to PDGF-BB, PlGF and VEGF-A with their intracellular signals may be the relevant therapeutic targets to protect eyes from DR.

Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor.

Platelet-derived growth factor (PDGF) is one of the major mitogens and chemoattractants for mesenchymal and glial cells. Nowadays, the expression of PDGFs are recognized widely in our body, and emerging data indicate the relevance of PDGFs in the homeostatic control of systemic connective tissue as well as parenchymal cells such as neurons. Aberrant PDGF signal is primarily tumorigenic, and also regulates tumor microenvironments. The roles of the PDGF signal in tumorigenesis are diverse depending on the type of cancer, and anti-PDGF therapy needs to be carefully designed based on the information of each tumor cell type and the surrounding microenvironment. PDGFs and receptors (PDGFRs) are abundant in neurons and glial cells, and are neuroprotective through the regulation of neurovascular unit. PDGF signal is functionally correlated with neurotransmission, and can be pathogenetically correlated with psychosomatic neurological diseases. Growing genetic information has been unraveling novel connective tissue diseases and vascular abnormalities in which aberrant PDGF signaling is etiologically correlated. Novel therapeutic approaches targeting PDGF signal are beginning to emerge in various diseases.

Successful multimodal treatment of intraoral salivary duct carcinoma in a patient with multiple lymph node metastases: a case report.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade salivary gland malignancy that is associated with an aggressive clinical behavior and poor prognosis. Herein, we report on a long surviving case of SDC of the minor salivary gland with multiple lymph node metastases (LNMs). CASE PRESENTATION: An 83-year-old woman presented with a history of lymphadenopathy in the right side of the neck and recent onset and rapid growth of a mass in the right buccal region. Clinical examinations and biopsy findings were suggestive of a salivary gland malignant tumor with regional LNMs. The patient was treated with neoadjuvant chemotherapy. Tumor excision and ipsilateral radical neck dissection were performed, followed by adjuvant chemoradiotherapy. Postoperative histological examination revealed a tumor with irregular nests of atypical ductal epithelial cells, a cribriform growth pattern, and comedo-like central necrosis that lead to a final diagnosis of SDC. LNMs were observed in six lymph nodes of the right side of the neck. The patient underwent postoperative chemotherapy using single-agent cisplatin that was administered concurrently with radiotherapy (total, 65 Gy). There was no evidence of local recurrence or distant metastasis for >6 years. CONCLUSIONS: Although available data on treatment modalities for SDC remain limited, multimodal therapy may contribute to improved clinical outcomes in patients with advanced intraoral SDC.