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1.
Arkh Patol ; 86(3): 30-37, 2024.
Article Ru | MEDLINE | ID: mdl-38881003

OBJECTIVE: The purpose of this work was to evaluate c-MYC gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor. MATERIAL AND METHODS: The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe. RESULTS: In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (p<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (p<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (p<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (p<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (p<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (p<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (p<0.05). CONCLUSION: Amplification of the c-MYC gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the c-MYC gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.


Gene Amplification , Prostatic Neoplasms , Proto-Oncogene Proteins c-myc , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-myc/genetics , Middle Aged , Aged , Genes, myc/genetics , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/pathology
2.
Head Neck Pathol ; 18(1): 44, 2024 May 22.
Article En | MEDLINE | ID: mdl-38775845

While acinic cell carcinoma (AciCC) can undergo high-grade transformation (HGT) to high-grade adenocarcinoma or poorly differentiated carcinoma, other morphologies such as spindle cell/sarcomatoid carcinoma are rare and not well-characterized. We herein report a novel case of AciCC with squamoglandular and chondrosarcomatous HGT mimicking a so-called 'carcinosarcoma ex-pleomorphic adenoma'. The patient is an 81-year-old male with a two-month history of neck swelling and referred otalgia who presented with a left parapharyngeal space mass extending into retropharyngeal space and pterygoid muscles. On resection, the tumor showed considerable morphologic diversity with high-grade serous and mucous acinar components as well as cribriform to solid apocrine-like components with comedonecrosis and squamous differentiation, all of which were embedded in a chondromyxoid background ranging from paucicellular and bland to a high-grade chondrosarcoma/pleomorphic sarcoma-like appearance. Only a minor conventional AciCC component was noted. Immunostains were negative for AR and only focally positive for GCDFP-15 arguing against a true apocrine phenotype, while PLAG1 and HMGA2 were negative arguing against an antecedent pleomorphic adenoma. On the other hand, SOX-10, DOG-1 and PAS after diastase highlighted serous acinar differentiation, and mucicarmine, and NKX3.1 highlighted mucous acinar differentiation. NR4A3 immunohistochemical staining and NR4A3 fluorescence in situ hybridization were positive in the carcinomatous and sarcomatoid components while sequencing analysis of both components revealed identical alterations involving TP53, PIK3CB, ARID1A, and STK11. This unique case warrants caution in designating all salivary sarcomatoid carcinomas with heterologous elements as part of the 'carcinoma ex-pleomorphic adenoma' family.


Adenoma, Pleomorphic , Carcinoma, Acinar Cell , Salivary Gland Neoplasms , Humans , Male , Aged, 80 and over , Diagnosis, Differential , Carcinoma, Acinar Cell/pathology , Carcinoma, Acinar Cell/diagnosis , Adenoma, Pleomorphic/pathology , Adenoma, Pleomorphic/diagnosis , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/diagnosis , Carcinosarcoma/pathology , Cell Transformation, Neoplastic/pathology , Terminology as Topic , Chondrosarcoma/pathology , Chondrosarcoma/diagnosis
3.
BMJ Case Rep ; 17(5)2024 May 24.
Article En | MEDLINE | ID: mdl-38789271

Cancer-associated stroke is an evolving subgroup of embolic strokes of undetermined source. A man in his mid-20s with progressive follicular variant acinic cell carcinoma of the parotid was admitted because of new onset left-sided weakness. Neuroimaging confirmed a right middle cerebral artery infarction. After extensive diagnostics, stroke aetiology was deemed from cancer-induced hypercoagulability. Questions which arose regarding his management included (1) What was the best antithrombotic for secondary stroke prevention? (2) What was his risk for intracranial or tumorous bleeding once antithrombotics had been started? (3) How many days post-stroke could the antithrombotic be initiated? and (4) When could he be cleared for palliative chemotherapy and whole brain irradiation? The approach to address the abovementioned questions in the management of a rare cancer complicated by stroke is presented. Although treatments are guided by known pathomechanisms, additional studies are needed to further support current treatment strategies for this subgroup of patients.


Carcinoma, Acinar Cell , Parotid Neoplasms , Humans , Male , Carcinoma, Acinar Cell/complications , Parotid Neoplasms/complications , Adult , Infarction, Middle Cerebral Artery/etiology , Infarction, Middle Cerebral Artery/diagnostic imaging , Fibrinolytic Agents/therapeutic use
6.
Am J Surg Pathol ; 48(6): 681-690, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38682454

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.


Biomarkers, Tumor , Carcinoma, Acinar Cell , Nuclear Receptor Subfamily 4, Group A, Member 2 , Salivary Gland Neoplasms , Humans , Male , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/pathology , Female , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/chemistry , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Adult , Aged , Nuclear Receptor Subfamily 4, Group A, Member 2/genetics , Nuclear Receptor Subfamily 4, Group A, Member 2/analysis , Receptors, Steroid/genetics , Receptors, Steroid/metabolism , Receptors, Thyroid Hormone/genetics , Receptors, Thyroid Hormone/analysis , Receptors, Thyroid Hormone/metabolism , Young Adult , Gene Fusion , Aged, 80 and over , DNA-Binding Proteins/genetics , Oncogene Proteins, Fusion/genetics , Immunohistochemistry
7.
Head Neck Pathol ; 18(1): 20, 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38502259

BACKGROUND: Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options. METHODS: We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options. RESULTS: In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases. CONCLUSION: Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.


Adenolymphoma , Adenoma, Oxyphilic , Breast Neoplasms , Carcinoma, Acinar Cell , Carcinoma, Ductal , Carcinoma, Intraductal, Noninfiltrating , Carcinoma , Prostatic Neoplasms , Salivary Gland Neoplasms , Male , Humans , Adenoma, Oxyphilic/pathology , Adenolymphoma/pathology , Immunohistochemistry , Diagnosis, Differential , Androgen Antagonists , Biomarkers, Tumor/genetics , Prostatic Neoplasms/diagnosis , Salivary Gland Neoplasms/pathology , Carcinoma, Acinar Cell/pathology , Carcinoma, Ductal/diagnosis
8.
Zhonghua Yi Xue Za Zhi ; 104(12): 950-955, 2024 Mar 26.
Article Zh | MEDLINE | ID: mdl-38514344

Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.


Carcinoma, Acinar Cell , Laparoscopy , Liver Neoplasms , Pancreatic Neoplasms , Male , Female , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Carcinoma, Acinar Cell/surgery , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Minimally Invasive Surgical Procedures , Liver Neoplasms/surgery
9.
Int J Clin Oncol ; 29(6): 755-763, 2024 Jun.
Article En | MEDLINE | ID: mdl-38492066

BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.


Carcinoma, Adenoid Cystic , Carcinoma, Mucoepidermoid , Salivary Gland Neoplasms , Humans , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/epidemiology , Salivary Gland Neoplasms/therapy , Female , Male , Middle Aged , Retrospective Studies , Aged , Adult , Carcinoma, Mucoepidermoid/pathology , Carcinoma, Mucoepidermoid/epidemiology , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Adenoid Cystic/therapy , Aged, 80 and over , Carcinoma, Acinar Cell/pathology , Carcinoma, Acinar Cell/epidemiology , Young Adult , Adolescent , Adenocarcinoma/pathology , Salivary Glands/pathology
10.
Curr Oncol ; 31(3): 1556-1561, 2024 03 19.
Article En | MEDLINE | ID: mdl-38534951

Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).


Carcinoma, Acinar Cell , Carcinoma, Ductal , Prostatic Neoplasms , Male , Humans , Prostate/pathology , Carcinoma, Ductal/genetics , Carcinoma, Ductal/pathology , Prostatic Neoplasms/therapy , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/pathology , High-Throughput Nucleotide Sequencing
11.
Breast Cancer ; 31(3): 496-506, 2024 May.
Article En | MEDLINE | ID: mdl-38546966

BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST). METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST. RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p < 0.05). Nonetheless, tumor grade 3 and higher AJCC stage groups remained as significant independent prognostic factors in multivariate analysis (p < 0.05). The apparent better breast cancer-specific survival of salivary gland-type carcinoma as compared to that of invasive carcinoma, NST, was diminished following adjustment for differences in baseline clinicopathological features and treatment-related variables. CONCLUSIONS: This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.


Breast Neoplasms , Propensity Score , SEER Program , Salivary Gland Neoplasms , Humans , Female , Middle Aged , Prognosis , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/therapy , Aged , Male , Adult , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Adenoid Cystic/mortality , Carcinoma, Adenoid Cystic/therapy , Carcinoma, Adenoid Cystic/epidemiology , Neoplasm Staging , Carcinoma, Acinar Cell/pathology , Carcinoma, Acinar Cell/mortality , Carcinoma, Acinar Cell/epidemiology , Neoplasm Grading , Receptor, ErbB-2/metabolism
13.
Medicine (Baltimore) ; 103(6): e37033, 2024 Feb 09.
Article En | MEDLINE | ID: mdl-38335397

INTRODUCTION: Primary tracheal acinic cell carcinoma (ACC) is an exceptionally rare malignancy, posing challenges in understanding its clinical behavior and optimal management. Surgical resection has traditionally been the primary treatment modality, but we present a compelling case of tracheal ACC managed with endotracheal intervention, challenging conventional approaches. PATIENT CONCERNS: A 53-year-old woman presented with shortness of breath, cough, and hemoptysis. Enhanced computed tomography revealed an obstructive tracheal lesion, leading to her referral for further assessment. DIAGNOSIS: Microscopic evaluation, immunohistochemistry, and clinical assessments confirmed primary tracheal ACC, an exceedingly rare condition with limited clinical insights. INTERVENTIONS: We utilized rigid bronchoscopy to perform endotracheal intervention, successfully resecting the tumor and restoring tracheal patency. Postoperatively, the patient received no radiotherapy or chemotherapy. OUTCOMES: The patient achieved complete recovery, with 24-month follow-up examinations indicating no recurrence or metastatic disease. Only minimal scar tissue remained at the resection site. CONCLUSION: This case demonstrates the potential of endotracheal intervention as a curative approach for primary tracheal ACC, minimizing invasiveness and preserving tracheal function. Collaborative research efforts and extensive case reporting are crucial for advancing our understanding of this rare malignancy and optimizing treatment strategies for improved patient outcomes.


Carcinoma, Acinar Cell , Tracheal Neoplasms , Humans , Female , Middle Aged , Tracheal Neoplasms/surgery , Tracheal Neoplasms/pathology , Carcinoma, Acinar Cell/surgery , Carcinoma, Acinar Cell/pathology , Trachea/surgery , Trachea/pathology , Bronchoscopy/methods , Tomography, X-Ray Computed
14.
Genes Chromosomes Cancer ; 63(2): e23222, 2024 02.
Article En | MEDLINE | ID: mdl-38340027

INTRODUCTION: Pancreatic acinar cell carcinomas are rare malignant neoplasms. High-quality evidence about the best treatment strategy is lacking. We present the case of a 52-year-old male with a BRAFV600E -mutated PACC who experienced a complete remission after chemotherapy with BRAF-/MEK-inhibitors. CASE: The patient presented with upper abdomen pain, night sweat, and weight loss. CT scan showed a pancreatic tumor extending from the pancreas head to body. Histological workup identified an acinar cell carcinoma. As the tumor was inoperable, chemotherapy with FOFIRNIOX was initiated and initially showed a slight regression of disease. The regimen had to be discontinued due to severe side effects. Molecular analysis identified a BRAFV600E mutation, so the patient was started on BRAF- and MEK-inhibitors (dabrafenib/trametinib). After 16 months, CT scans showed a near complete remission with a markedly improved overall health. DISCUSSION: Studies suggest that up to one-fourth of PACCs carry a BRAF mutation and might therefore be susceptible to a BRAF-/MEK-inhibitor therapy. This offers a new therapeutic pathway to treat this rare but malignant neoplasm.


Carcinoma, Acinar Cell , Pancreatic Neoplasms , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Acinar Cell/drug therapy , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/chemically induced , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mutation , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Pyridones/pharmacology , Pyrimidinones/pharmacology
15.
Anticancer Drugs ; 35(3): 263-270, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38194502

Pancreatic cancer is a highly malignant tumor, and most patients are diagnosed at an advanced stage. Unfortunately, due to the immunosuppressive tumor microenvironment of pancreatic cancer, the benefits of immunotherapy for patients with advanced pancreatic cancer are still unclear. Here, we present two cases of advanced pancreatic cancer being controlled by immunotherapy, with pathological diagnoses of ductal adenocarcinoma and acinar cell carcinoma, respectively. Next-generation sequencing (NGS) of both patients is high tumor mutation burden (tumor mutation burden-High) and microsatellite stable. The patient with pancreatic ductal adenocarcinoma was diagnosed as a locally advanced disease (stage III). She received irreversible electroporation, used the programmed death receptor-1 (PD-1) inhibitor (pembrolizumab) combined with chemotherapy (S-1), and then used only the PD-1 inhibitor as a maintenance treatment. As a result, the patient's lesion was significantly reduced, with a partial response time of up to 31 months. The patient with acinar cell carcinoma was diagnosed as a metastatic disease (stage IV), next-generation sequencing revealed mutations in SMAD4 and KMT2D, and two chemotherapy regimens were used unsuccessfully. Then, the combination of chemotherapy with PD-1 (tislelizumab) and vascular endothelial growth factor/vascular endothelial growth factor receptor (anlotinib) inhibitors were used, and the lesions of the patient were significantly reduced, and the progression-free survival after immunotherapy was 19 months. In advanced pancreatic cancer, a prognosis of this magnitude is rare. Our cases reveal the potential of immunotherapy as a cornerstone treatment in the management of advanced pancreatic cancer.


Carcinoma, Acinar Cell , Pancreatic Neoplasms , Female , Humans , Programmed Cell Death 1 Receptor , Vascular Endothelial Growth Factor A , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Immunotherapy , Tumor Microenvironment
16.
Hum Pathol ; 145: 42-47, 2024 Mar.
Article En | MEDLINE | ID: mdl-38262580

GATA3 is the most used marker to determine tumors' breast origin, but its diagnostic value in triple-negative breast cancer (TNBC) is limited. The newly identified TRPS1 is highly sensitive and specific for breast carcinoma, especially TNBC. Here, we compared the utility of TRPS1 and GATA3 expression in a subset of salivary gland-type breast tumors (including adenoid cystic, acinic cell, and secretory carcinomas [AdCC, ACC, and SC, respectively]), and we compared TRPS1 and GATA3 expression of such tumors with head and neck (H&N) and AdCC of upper respiratory tumors. TRPS1 was strongly expressed in basaloid TNBC and AdCCs with solid components, including 100 % of mixed and solid breast AdCCs. However, TRPS1 was positive in only 50 % cribriform AdCCs. Expression patterns of TRPS1 in H&N and upper respiratory AdCC were similar. TRPS1 was positive in 30 % of H&N cribriform AdCCs but was strongly expressed in mixed AdCC (67 %) and solid AdCC (100 %). In the upper respiratory AdCCs, TRPS1 was positive in 58.4 % of cribriform AdCCs and positive in 100 % of AdCCs with solid components. On the contrary, GATA3 was negative in predominant AdCCs of the breast, H&N, and upper respiratory tract. These data show that GATA3 and TRPS1 expression varies AdCCs. In addition, TRPS1 and GATA3 expression patterns were similar SC and ACC of breast and H&N. Both markers were positive in SC and negative in ACC. Therefore, TRPS1 and GATA3 cannot be used to differentiate salivary gland-type carcinomas of breast origin from those of upper respiratory or H&N origin.


Adenoids , Breast Neoplasms , Carcinoma, Acinar Cell , Carcinoma, Adenoid Cystic , Carcinoma , Fingers , Hair Diseases , Langer-Giedion Syndrome , Nose , Salivary Gland Neoplasms , Triple Negative Breast Neoplasms , Female , Humans , Adenoids/metabolism , Adenoids/pathology , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Adenoid Cystic/pathology , Fingers/abnormalities , GATA3 Transcription Factor , Nose/abnormalities , Repressor Proteins , Salivary Gland Neoplasms/pathology , Salivary Glands/metabolism , Salivary Glands/pathology , Triple Negative Breast Neoplasms/pathology
18.
Int J Cancer ; 154(8): 1492-1503, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-37971144

Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin. By single nucleus RNA-seq, salivary gland cells were stratified into four clusters: acinar cells, ductal cells 1, ductal cells 2 and myoepithelial cells/stromal cells. The localization of each cell group was verified by IHC of each cluster marker gene, and one group of ductal cells was found to represent intercalated ductal cells labeled with HES1. Furthermore, in comparison with SGC RNA-seq data, acinar cell markers were upregulated in AciCC, but downregulated in ACC and ductal cell markers were upregulated in SDC but downregulated in MECA, suggesting that markers of origin are highly expressed in some SGC. Cell type expressions in specific SGC histology are similar to those found in normal salivary gland populations, indicating a potential etiologic relationship.


Carcinoma, Acinar Cell , Carcinoma, Adenoid Cystic , Carcinoma , Salivary Gland Neoplasms , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Salivary Glands/pathology , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Carcinoma, Adenoid Cystic/pathology , Carcinoma/pathology , Carcinoma, Acinar Cell/metabolism , RNA/metabolism
19.
Mod Pathol ; 37(1): 100371, 2024 Jan.
Article En | MEDLINE | ID: mdl-38015043

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.


Breast Neoplasms , Carcinoma, Acinar Cell , Carcinoma, Adenoid Cystic , Carcinoma, Mucoepidermoid , Carcinoma , Salivary Gland Neoplasms , Humans , Female , Carcinoma, Adenoid Cystic/pathology , Prognosis , Carcinoma, Acinar Cell/pathology , Salivary Gland Neoplasms/pathology , Carcinoma, Mucoepidermoid/pathology , Carcinoma/pathology , Salivary Glands/chemistry , Salivary Glands/metabolism , Salivary Glands/pathology , Biomarkers, Tumor/analysis
20.
Histopathology ; 84(1): 102-123, 2024 Jan.
Article En | MEDLINE | ID: mdl-37694812

Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.


Adenoma, Pleomorphic , Carcinoma, Acinar Cell , Carcinoma, Adenoid Cystic , Carcinoma, Mucoepidermoid , Carcinoma , Lung Neoplasms , Salivary Gland Neoplasms , Humans , Salivary Gland Neoplasms/pathology , Carcinoma, Adenoid Cystic/pathology , Adenoma, Pleomorphic/pathology , Carcinoma/pathology , Carcinoma, Mucoepidermoid/diagnosis , Carcinoma, Mucoepidermoid/pathology , Carcinoma, Acinar Cell/pathology , Salivary Glands/pathology , Lung/pathology , Lung Neoplasms/pathology , Biomarkers, Tumor/metabolism
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