Cases Of Adenoid Cystic Carcinoma Research Articles

PATH-42. METASTATIC ADENOID CYSTIC CARCINOMA OF BREAST WITH BRAIN METASTASES AND LEPTOMENINGEAL DISEASE

Abstract INTRODUCTION Adenoid cystic carcinoma (ACC) of the breast rarely metastasizes to the brain and leptomeninges. ACC is a rare type of breast cancer, accounting for less than 0.1% of cases. It is usually triple negative, but has a good prognosis when it is confined to the breast. Lymph node involvement is uncommon, occurring in less than 2% of cases, and distant metastases to the brain are extremely rare. Leptomeningeal disease has not been reported yet. Case: In this case, we describe a 57-year-old woman diagnosed with triple-negative ACC of the right breast, which had spread to the axillary lymph nodes and distant metastases to the lung. The diagnosis was confirmed by biopsies of both metastatic sites. The patient received vinorelbine and cisplatin treatment for 11 cycles followed by right needle localized lumpectomy. While awaiting for the next steps in treatment she was admitted to the hospital for altered mental status, saddle anesthesia, and urinary incontinence. Neuraxis MRI revealed numerous hemorrhagic and non-hemorrhagic brain metastasis with diffuse leptomeningeal disease. Cerebrospinal fluid analysis confirmed leptomeningeal disease with positive cytology for atypical epithelioid malignant cells. The patient underwent whole brain radiation and focal radiation treatment to specific areas of leptomeningeal disease. Although she initially improved after the first month of radiation, her condition deteriorated rapidly, preventing the initiation of the next line of treatment with high-dose methotrexate or capecitabine. DISCUSSION Adenoid cystic carcinoma of the breast is exceedingly rare however with a very good overall prognosis. It is uncommon for ACC to spread to regional lymph nodes, and even rarer for distant metastasis. Brain metastasis is also infrequently reported. There are no documented cases of metastatic ACC with leptomeningeal disease, so there is no consensus on the best course of treatment.

Stroma-and Tumor-Associated Predictive Features inSalivary Gland Adenoid Cystic Carcinoma of the Headand Neck.

There is lack of knowledge on the utility of prognostic histopathologic characteristics in adenoid cystic carcinoma (ACC) of the head and neck. We evaluated the prognostic value of tumor and stroma-related histopathologic features in ACC. A total of 65 cases of ACC from minor and major salivary glands were included in this study. We evaluated tumor budding, tumor-infiltrating lymphocytes (TILs), and tumor-stroma ratio (TSR) in hematoxylin and eosin (HE) stained sections. Stroma-rich ACCs recurred more frequently (p = 0.029) during follow-up and associated with distant metastasis (p = 0.038). In multivariable analysis, stroma-rich tumors associated with poorer disease-specific survival with a hazard ratio of 3.76 (95% CI 1.10-12.83, p = 0.034). ACCs commonly showed a low infiltration of TILs as 89% of the tumors was characterized by an immune desert pattern. Low infiltration of TILs associated significantly with increased tumor budding (p = 0.039). Adverse features of TSR and tumor budding are widely expressed in ACC, and stroma-rich tumors are associated with poor prognosis. Low number of TILs in ACC tissue indicates a weak immune response by the host and illustrates the nature of ACC as a relentless malignancy.

Comparative Analysis of MYB Expression by Immunohistochemistry and RNA Sequencing in Clinical Gene Fusion Detection in Adenoid Cystic Carcinoma.

MYB has been shown to play a central role in oncogenesis in a majority of adenoid cystic carcinomas (ACC). Testing for MYB expression via immunohistochemistry (IHC) or testing for the MYB gene fusion by next-generation sequencing(NGS) have become useful tools for the diagnosis of ACC. In addition, detection of MYB expression may have implications for patient management. A cohort of 35 ACC cases was identified from the archival pathology files of the Massachusetts General Hospital. Cases were tested for MYB expression using a panel of 4 different commercially available MYB antibodies and scored using a modified Allred system. RNA-based NGS for MYB gene fusion detection was also performed. Among 4 different MYB antibodies, the sensitivity for MYB detection ranged from 26 to 97%. When a 30% threshold for determination of MYB immunohistochemical positivity was used, the AB_10900735 IHC clone showed the maximum sensitivity (97%). RNA sequencing revealed 19 (54%) cases positive for MYB fusions, and expression analysis derived from the sequencing data confirmed a significant association between MYB expression and fusion status (p = 0.036). Although less sensitive, the AB_778878 MYB clone showed a significant positive association between IHC staining and MYB RNA expression (R2 = 0.15, p = 0.023). The detection of MYB expression using immunohistochemistry varies significantly depending on the antibody used. Comparison with MYB fusion and transcription levels, as determined by NGS, reveals that MYB has a complex relationship between genetic alterations, transcript levels, and protein abundance.

Outcome-oriented clinicopathological reappraisal of sinonasal adenoid cystic carcinoma with broad morphological spectrum and high MYB::NFIB prevalence

Adenoid cystic carcinoma (AdCC) is a salivary gland neoplasm that infrequently appears in the sinonasal region. The aim of this study was to evaluate the outcome and clinicopathological parameters of sinonasal AdCC. A retrospective analysis was conducted on all cases of AdCC affecting the nasal cavity or paranasal sinuses between 2000 and 2018 at the University Hospital Zurich. Tumor material was examined for morphological features and analyzed for molecular alterations. A total of 14 patients were included. Mean age at presentation was 57.7 years. Sequencing revealed MYB::NFIB gene fusion in 11/12 analyzable cases. Poor prognostic factors were solid variant (p < 0.001), histopathological high-grade transformation (p < 0.001), and tumor involvement of the sphenoid sinus (p = 0.02). The median recurrence-free survival (RFS) and OS were 5.2 years and 11.3 years. The RFS rates at 1-, 5-, and 10-year were 100%, 53.8%, and 23.1%. The OS rates at 1-, 5-, and 10- years were 100%, 91.7%, and 62.9%, respectively. In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases.

MYB expression by immunohistochemistry is highly specific and sensitive for detection of solid variant of adenoid cystic carcinoma of the breast among all triple-negative breast cancers.

Adenoid cystic carcinoma is a rare subtype of triple-negative breast carcinoma. These low-grade tumours, which are treated by simple mastectomy and have an excellent prognosis compared to other triple-negative breast carcinomas. Solid-variant adenoid cystic carcinomas have basaloid features and are difficult to distinguish morphologically from other triple-negative breast cancers. Breast adenoid cystic carcinoma exhibits MYB protein overexpression, which can be detected by immunohistochemistry (IHC). We compared the IHC expression of MYB in solid-variant adenoid cystic carcinoma with that in other triple-negative breast cancers. We conducted IHC staining of 210 samples of triple-negative breast cancers, including solid-variant adenoid cystic carcinoma (n = 17), metaplastic breast carcinoma (n = 44), basaloid triple-negative breast cancer (n = 21), and other triple-negative invasive ductal carcinoma (n = 128). We classified nuclear staining of MYB as diffuse/strong (3+), focal moderate (2+), focal weak (1+), or none (0). All 17 solid/basaloid adenoid cystic carcinoma cases exhibited 3+ MYB expression. Of the 21 solid/basaloid triple-negative breast cancers, one (5%) had 2+ expression, seven (33%) 1+ expression, and 13 (62%) 0 expression. Of the 44 metaplastic carcinoma cases, 39 cases (89%) had no (0) staining, and the other five cases had focal weak (1+) or moderate (2+) staining. Among the 128 triple-negative invasive ductal carcinoma cases, 92 cases (72%) had no (0) staining, 36 cases (28%) exhibited focal weak (1+) or moderate (2+) staining. Our study revealed diffuse/strong MYB staining (3+) only in solid/basaloid adenoid cystic carcinomas. Thus, we recommend routine MYB IHC staining in triple-negative breast carcinoma with solid/basaloid morphology to improve diagnostic accuracy.

Exploring the uncharted: adenoid cystic carcinoma nestled in temporal bone

BackgroundAdenoid cystic carcinoma is an uncommon malignancy primarily arising from salivary glands. An extremely rare site for adenoid cystic carcinoma is the skull base. We report a case of adenoid cystic carcinoma of skull base who presented with common complaints of pain and right ear discharge. The discussion is made with emphasis on imaging evaluation simulating infective etiology with adjacent skull base osteomyelitis. Careful observation of the imaging findings and further evaluation of the patient revealed the neoplastic nature of the lesion with the final diagnosis being adenoid cystic carcinoma.Case presentationA 40-year-old female presented to our department with complaints of pain and right ear discharge since 6 months with progressive, extensive facial swelling and facial nerve palsy. The patient had undergone modified radical mastoidectomy thrice, but the details were not available. On imaging, there was a heterogenous extensive lesion extending from scalp till upper cervical region with extensive destruction of skull base and intra-cranial extension. The possibilities of temporal bone squamous cell carcinoma and extensive skull base osteomyelitis were considered. Further the biopsy of the lesion revealed adenoid cystic carcinoma.ConclusionsExtensive lesions of the skull base can be of infective, neoplastic and inflammatory etiology. Distinguishing between these conditions is crucial, as they have similar imaging characteristics but require different management approaches. The presence of a lesion that displaces or destroys fascial planes, accompanied by solid mass-like enhancement, indicates a higher probability of a neoplastic origin rather than an infectious etiology. With squamous cell carcinoma being the most common neoplasm, adenoid cystic carcinoma of the skull base also needs to be understood due to its propensity for perineural spread and a high likelihood of recurrence.

Clinical analysis of resection and dura skull base reconstruction of cranionasal communication tumor in 31 cases

Objective:To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Methods:Data of 31 patients with cranionasal communication tumor who underwent dura and skull base reconstruction after tumor resection from 2018 to 2022 were collected. Follow-up lasted for 3 to 41 months. Results:A total of 31 patients were enrolled, including 20 males and 11 females. The ages ranged from 19 to 74 years, with a median age of 57 years old. There were 17 benign lesions（one case of hemangioma, one case of Rathke cyst, one case of squamous papilloma, one case of craniopharyngioma, two cases of meningocele, two cases of varus papilloma, two cases of meningioma of grade Ⅰ, three cases of schwannoma, four cases of pituitary tumor） and 14 malignant lesions（one case of osteosarcoma, one case of poorly differentiated carcinoma, two cases of varus papilloma malignancy, two cases of olfactory neuroblastoma, two cases of adenocarcinoma, two cases of adenoid cystic carcinoma, four cases of squamous cell carcinoma） . Sixteen cases underwent nasal endoscopy combined with craniofacial incision and 15 cases underwent nasal endoscopy surgery alone. Complete resection of the mass and dura and skull base reconstruction were performed in all 31 patients, and free graft repair was performed in 8 cases（fascia lata in 5 cases and nasal mucosa in 3 cases）. Twenty-three cases were repaired with pedicled flaps（septal mucosal flap alone in 11 cases, septal mucosal flap combined with free graft in 6 cases, and cap aponeurosis combined with free graft in 6 cases）. Eight out of 31 patients underwent skull base bone repair. Postoperative cerebral hemorrhage occurred in 1 case, cerebrospinal fluid leakage in 1 case, intracranial infection in 2 cases. All patients were successfully treated without severe sequelae. Cerebrospinal fluid leakage and intracranial infection occurred in one patient after radiotherapy, who recovered after conservative treatment. All 17 patients with benign lesions survived. Thirteen out of 14 patients with malignant lesions received radiotherapy after surgery, nine survived without recurrence, five cases recurred, of which 2 survived with tumor, one underwent reoperation and 2 died. Conclusion:Cranionasal communication tumors are high-risk diseases of anterior and middle skull base, and various surgical repair methods could be selected after complete resection of the tumor. Successful reconstruction and multidisciplinary cooperation are crucial for treatment outcome.

Abstract PO3-20-11: Among the &amp;lt; 0.1 percent of breast cancers: A case of adenoid cystic carcinoma

Abstract Among the &amp;lt; 0.1 percent of breast cancers: A case of adenoid cystic carcinoma Sera Choi, B.A., Sarah Keshwani, M.D., Andrea Madrigrano, M.D. Introduction: Adenoid cystic carcinoma in the breast (ACCB) is a rare subtype of breast cancer that accounts for &amp;lt; 0.1% of all breast-related malignancies. The majority of ACCB cases in existing literature are comprised of estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative, abbreviated as triple-negative breast cancer. Although most triple negative breast cancers are aggressive in nature and prognosis, ACCB is reported to be more indolent with a favorable outcome. This disparity raises the question of whether the treatment approach for ACCB should follow the well-established treatment plan for other triple negative breast cancers given its atypical characteristics. Furthermore, while adenoid cystic carcinoma of the salivary glands is a well-known type of head and neck cancer with established treatment guidelines, there is limited data for recommendations regarding treatment for ACCB. We report a pathologically confirmed case of ACCB and review the existing literature regarding treatment strategy and prognosis. Case: This case is of a 69-year-old female who presented with an abnormal screening mammogram with a core needle biopsy confirming ACCB in the left lower outer quadrant. The patient was asymptomatic with no palpable masses, nipple discharge, or skin changes of the breast. Biopsy revealed adenoid cystic carcinoma grade 2, classic type, with immunochemistry confirming estrogen-receptor negative, progesterone-receptor negative, and human epidermal growth factor-receptor negative. After a thorough discussion of the options, the patient elected for breast conserving therapy and sentinel lymph node biopsy. Tumor was resected with negative margins and two out of two lymph nodes were negative for metastasis. The patient was recommended whole breast adjuvant radiation therapy given the large tumor size of 4.8cm. Chemotherapy was not recommended due to data that largely supports local targeted therapy over systemic treatment in patients without metastatic ACCB. The patient is continuing with routine follow-up evaluations. Discussion: Currently, mainstay treatment comprises of surgical resection with lumpectomy or mastectomy, with or without nodal evaluation. Radiation therapy is seen as beneficial in reducing recurrence and prolonging disease-free survival in ACCB. There is ongoing debate regarding the role of chemotherapy in ACCB patients, as triple-negative breast cancers are typically treated with a systemic chemotherapy regimen. However, since ACCB has a more favorable prognosis, the role of chemotherapy remains uncertain. With lack of data on ACCB, treatment modalities should be evaluated on a case-by-case basis. Moreover, considering the scarcity of information concerning this particular subtype of breast cancer, it is advisable to discuss these patients within a multi-disciplinary tumor board setting to ensure patients receive the maximum benefit. Citation Format: Sera Choi, Sarah Keshwani, Andrea Madrigrano. Among the &amp;lt; 0.1 percent of breast cancers: A case of adenoid cystic carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-11.

Immunohistochemical marker profiles for the differentiation of collagenous spherulosis from adenoid cystic carcinoma of the breast

Collagenous spherulosis (CS) is a rare breast lesion of unknown histogenesis. Adenoid cystic carcinoma (ACC) is a rare basal-like breast carcinoma with low histological grade. CS is a benign lesion but resembles ACC. Both lesions show a similar histomorphology and feature bilineage differentiation. This study compared immunohistochemical markers in CS and ACC.We compiled n = 13 CS cases and n = 18 mammary ACCs. Fourteen marker proteins (ER, PR, HER2, GATA3, CK7, E-cadherin, CD117, CK5/14, p40, p63, SMA, CD10, calponin, P-cadherin) were evaluated by immunohistochemistry (IHC). MYB rearrangement, a common alteration in ACC, was assessed by fluorescence in situ hybridization.Patient age ranged between 40-60 years for CS lesions and 30–90 years for ACCs. 7/13 (54%) CS cases harbored a lobular carcinoma in situ (LCIS) in the luminal component. One CS/LCIS lesion occurred in a carrier of a pathogenic germline variant in CDH1/E-cadherin. MYB rearrangement was detected in 0/11 (0%) CS and 6/16 (37%) ACC cases (P = 0.054). CS was associated with expression of ER in the luminal component (P < 0.001), E-cadherin loss in the luminal component (P = 0.045), and expression of CD10 and calponin in the basal component (P < 0.001). Furthermore, CS was associated with GATA3 expression in the luminal component (12/13 [92%] versus 5/18 [27%], P < 0.001).In summary, IHC for GATA3 and E-cadherin may contribute to the differential diagnosis between CS and ACC, although these markers are not exclusively expressed in either lesion. Histologic evaluation has to take into account that CS is frequently colonized by LCIS, requiring thorough correlation of histomorphology and immunohistochemical features.

The Fundamental Role of Multidisciplinary Approach in Complex Head and Neck Pathology: A Case Report of Maxillary Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare tumor, with a documented annual incidence ranging from 3 to 4.5 cases per million. It constitutes approximately 1% of all head and neck malignancies and around 10% of salivary gland tumors. It is imperative to adopt a multidisciplinary approach to ensure the most appropriate therapeutic outcome. Treatment strategies usually involve a multidisciplinary approach and may include surgery, radiotherapy, chemotherapy, or various combinations of these. In this context, we present a clinical case of ACC originating in the palate of a woman. Throughout this article, we will detail the diagnostic challenges and multidisciplinary treatment strategies implemented, emphasizing the importance of a comprehensive approach in cases of palatal ACC. In addition, we will discuss the rehabilitation process and the outcomes observed during the follow-up of this case.

TGFβ signaling pathway in salivary gland tumors

ObjectivePleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are the most prevalent salivary gland tumors. Their pathogenesis has been recently associated with complex molecular cascades, including the TGFβ signaling pathway. The aim of this study was to evaluate the expression of genes associated with the TGFβ signaling pathway (TGFB1, ITGB6, SMAD2, SMAD4, FBN1, LTBP1, and c-MYC) to map possible downstream alterations in the TGFβ cascade. DesignThirteen PA, 17 MEC, 13 ACC, and 10 non-neoplastic salivary gland samples were analyzed by real-time RT-PCR. ResultsCases of PA presented increased TGFB1, LTPB1, c-MYC, and FBN1 expressions, whereas SMAD2 expression was decreased when compared to non-neoplastic tissue. MEC patients displayed increased expressions of TGFB1, ITGB6, FBN1, and c-MYC and decreased expressions of SMAD2 and SMAD4. ACC cases exhibited elevated expressions of the investigated genes except TGFB1. The present results suggest that decreased expression of SMAD2 and SMAD4 does not impede the transcriptional regulation of c-MYC, especially in PA and MEC. Increased expressions of ITGB6, TGFB1, LTBP1, and FBN1 appear to be related to the regulation of the TGFβ signaling pathway in these tumors. Additionally, we observed a higher expression of SMAD4 in ACC and a raised expression of ITGB6 and lowered expression of SMAD2 in MEC. ConclusionsOur study demonstrated the differential expression of TGFβ cascade members in salivary gland tumors such as SMAD2/SMAD4 and c-MYC as well as the participation of ITGB6, TGFB1, LTBP1, and FBN1, contributing to the understanding of the mechanisms involved in tumor progression.

SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree

IntroductionPrimary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway. Methods and resultsWe retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6–78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067). ConclusionIt is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST contribute to epithelial-mesenchymal transition in salivary gland tumors.

Transcription factors are important in the epithelial-mesenchymal transition process and are possibly related to the development of a more invasive tumor phenotype. Thus, the objective of this study was to analyze the expression and identify the localization of cellular markers related to the epithelial-mesenchymal transition process in salivary gland tumors. The expression and localization of E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST were evaluated, using immunohistochemistry, in 48 salivary gland tumors, being 17 pleomorphic adenomas (PA), 14 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). these proteins were compared to clinical and histopathologic parameters. normal gland tissues were included for immunohistochemical comparisons. ACC and MEC cases showed higher expression of SNAIL compared to PA. MEC showed high expression of SLUG and TWIST. Low expression of N-CADHERIN, SNAIL, and TWIST in ACC was frequent in T3 and T4. High expression of TWIST in MEC was more frequent at age ≥ 40 years A positive correlation was only observed between N-cadherin/SNAIL in ACC, between SNAIL/TWIST in MEC, and between SLUG/TWIST in PA. This study provided insight into EMT-related proteins (E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST) and their contribution to the maintenance of morphogenesis and the development of the salivary gland tumors and showed a positive correlation among N-CADHERIN/SNAIL in ACC and SNAIL/TWIST in MEC.

Correlation of MYB/NFIB gene fusion with the grade and prognosis of head and neck adenoid cystic carcinoma and the concordance of two detection methods

Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.

Wnt/β-catenin-C-kit axis may play a role in adenoid cystic carcinoma prognostication

Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. ACC is composed of myoepithelial and epithelial neoplastic cells which grow slowly and have a tendency for neural invasion. The long term prognosis is still relatively poor. Although several gene abnormalities, such as fusions involving MYB or MYBL1 oncogenes and the transcription factor gene NFIB, and overexpression of KIT have been reported in ACC, their precise functions in the pathogenesis of ACC remain unclear. We recently demonstrated that the elevated expression of Semaphorin 3A (SEMA3A), specifically expressed in myoepithelial neoplastic cells, might function as a novel oncogene-related molecule to enhance cell proliferation through activated AKT signaling in 9/10 (90%) ACC cases. In the current study, the patient with ACC whose tumor was negative for SEMA3A in the previous study, revisited our hospital with late metastasis of ACC to the cervical lymph node eight years after surgical resection of the primary tumor. We characterized this recurrent ACC, and compared it with the primary ACC using immunohistochemical methods. In the recurrent ACC, the duct lining epithelial cells, not myoepithelial neoplastic cells, showed an elevated Ki-67 index and increased cell membrane expression of C-kit, along with the expression of phosphorylated ERK. Late metastasis ACC specimens were not positive for β-catenin and lymphocyte enhancer binding factor 1 (LEF1), which were detected in the nuclei of perineural infiltrating cells in primary ACC cells. In addition, experiments with the GSK-3 inhibitor revealed that β-catenin pathway suppressed not only KIT expression but also proliferation of ACC cells. Moreover, stem cell factor (SCF; also known as KIT ligand, KITL) induced ERK activation in ACC cells. These results suggest that inactivation of Wnt/β-catenin signaling may promote C-kit-ERK signaling and cell proliferation of in metastatic ACC.

Evaluation of Immunohistochemical Expression of P53 and Pcna in Pleomorphic Adenoma, Mucoepidermoid and Adenoid Cystic Carcinomas of Salivary Glands

Salivary gland tumours are uncommon with a broad heterogeneity. The most common benign tumour is the pleomorphic adenoma, whereas mucoepider moid carcinoma and adenoid cystic carcinoma predominate among the malignancies. The aim of this study was to describe the tissue expression of p53 and PCNA protein in pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma and to compare their expression among the studied tumors. The study enrolled (45)formalin –fixed, paraffin- embedded tissue blocks of salivary gland tumors, diagnosed as pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma (15 cases for each ) and evaluated the immunohistochemical expression of P53 and PCNA proteins. The study revealed positive p53 protein expression in (60%) of muocoepidermoid carcinoma cases and (20%) of adenoid cystic carcinoma cases, while only one case (6.7%) of pleomorphic adenoma was P53 posi tive. The immunopositivity of PCNA protein expression was f ound in (100%) of both mucoepidermoid carcinoma and adenoid cystic carcinoma cases and (66.7%) of pleomorphic adenoma c ases.The results of this study demonstrated that inactivation of p53 protein may play an im portant role in the activation of PCNA with increasing the proliferati on activity of MEC and ACC.

Adenoid Cystic Carcinoma of the Minor Salivary Glands: A Systematic Review and Meta-Analysis of Clinical Characteristics and Management Strategies.

Intraoral adenoid cystic carcinoma (ACC) arising from minor salivary glands (MSG) is a rare malignancy associated with delayed diagnosis and unfavorable outcomes. This study aimed to comprehensively review ACC of MSGs, focusing on clinical characteristics, imaging modalities, treatment approaches, and long-term outcomes. A systematic search was conducted in PubMed, Web of Science, and MEDLINE databases to identify relevant articles reporting cases of ACC of MSGs between January 1997 and March 2023. The study was registered in PROSPERO (ID: CRD42023449478). A total of 10 studies that met the inclusion criteria were selected for critical review. In total, 902 patients were diagnosed with ACC of MSGs with an age range of 44.3 to 63 years, and an average age of 56.6 years. The female to male ratio ranges from 1:1 to 2.4:1. Regarding the primary site of ACC, the palate was the most common location, accounting for 30.5% to 83.3%, followed by the buccal mucosa, floor of the mouth, and lip and the retromolar area. For histology, the solid mass pattern was the most prevalent, seen in 95.2% of patients, followed by the cribriform pattern. Regarding treatment modalities, surgery was the most common approach, applied in 76.3% of cases, with a combination of surgery and radiotherapy used in 29.0% of cases. A smaller fraction, 3.2%, received a combination of surgery, chemotherapy, and radiotherapy, and 8.3% underwent radiotherapy alone. Local recurrence rates varied between 1% and 28.5%, and distant metastasis occurred in 18.2% to 33.3% of cases, predominantly to lymph nodes (14.5%). An analysis of overall survival across various stages and patient numbers indicated a 5-year survival rate of 68.0%. The findings of this study provide valuable insights for physicians in making treatment decisions and emphasize the need for ongoing research and collaborative clinical efforts to improve the management and outcomes of this challenging disease. ACC of MSGs is a multifaceted condition typically manifesting as asymptomatic enlargement and ulceration. This disease is marked by distinct histopathological patterns and perineural invasion (PNI). Recognizing these distinctive aspects is key in shaping the treatment plan, which can range from surgical procedures to radiation therapy, chemotherapy, and evolving targeted treatments. Continuous research and collaborative clinical efforts remain critical for ongoing progress in the treatment and management of this challenging condition.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features.

The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

An Uncommon Case of Sinonasal Adenoid Cystic Carcinoma Metastatic to the Kidney Treated with Metastasectomy.

Adenoid cystic carcinoma (ACC) is a rare tumor, accounting for 1% of all head and neck cancers, with an aggressive nature characterized by local recurrence, delayed metastasis, and survival of less than 50% at 10 years. This is a case of biopsy-proven ACC to the kidney, 1 of 29 known occurrences, managed by metastasectomy by robotic-assisted nephrectomy, with plans for resection of lung metastasis. Thirteen years after diagnosis of sinonasal ACC treated with resection, the patient presented with shortness of breath. This prompted a CT scan of the chest, which led to the incidental finding of left renal mass and pulmonary lesion. Literature suggests improved disease-specific survival in locoregional recurrence treated with surgery versus radiation; in patients with metastasis to the lung, metastasectomy offers greater survival benefit than supportive therapy. But, this is not significantly better than chemotherapy or radiation alone. While the optimal therapeutic approach remains to be identified in distant metastatic ACC, metastasectomy remains a viable option for patients who have potentially completely resectable metastatic tumors, appropriate performance status, and adequate affected-organ function. Preoperative counseling should include discussion on partial nephrectomy with prioritization of nephron-sparing but potential for increased perioperative risk versus radical nephrectomy to ensure negative margins and expedite timeline to systemic therapy.

Usefulness of combined ultrasonography and MRI to distinguish the diagnosis of Adenoid Cystic Carcinoma of the floor of the mouth

Background/Aim: Adenoid cystic carcinoma (ACC) is a rare type of cancer that most often occurs in the salivary glands. The aim of this report was to describe a very rare case of ACC in the floor of the mouth referring to the usefulness of combined imaging methodology for the detection of the exact origin and extension of the tumor. Case Report: A 70-year-old female patient was referred to the private practice of one of the authors (D.A., Thessaloniki, Greece). Before the examination, the patient provided written informed consent in accordance with the Helsinki Declaration for research and patient's ethics. Subsequently, the patient was examined thoroughly. She exhibited a swelling on the floor of the mouth (left side). The swelling was painless, firm-solid upon palpation, non-movable and attached to adjacent tissues with normal covering oral mucosa. The patient was referred for an ultrasonography and MRI examination and afterwards an incisional biopsy was performed. The surgical removal of ACC and the involved sublingual but also the adjacent submandibular (for safety reasons) salivary glands were performed under general nasopharyngeal anesthesia with bilateral, both external and intraoral access. In addition, post-surgical radiotherapy was performed. Conclusions: Due to the aggressiveness of the lesion and the fact that in most cases adjacent tissues are affected, surgeons tend to be rather aggressive in their interventions. The imaging techniques may vary in their interpretation of the lesions. Ultrasonography and MRI examinations may assist the surgeon by depicting borders of the lesion under investigation, much more accurately, supporting the establishment of the diagnosis and avoiding the unnecessary loss of healthy neighboring tissue.