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Minimally invasive carcinoma ex pleomorphic adenoma. The pleomorphic adenoma component with sclerosis is seen on the right, and the minor low grade carcinoma component infiltrates the surrounding adipose tissue. This carcinoma was immunophenotypically a myoepithelial carcinoma (stains not shown)
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Histologic grade is a significant predictor of outcome in salivary gland carcinomas. However, the sheer variety of tumor type and the rarity of these tumors pose challenges to devising highly predictive grading schemes. As our knowledge base has evolved, it is clear that carcinoma ex pleomorphic adenoma is not automatically a high grade tumor as is...
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Abstract
Benign and malignant tumors are rare conditions; it was
not uncommonly occurs in salivary glands and usually presented as
a painless mass. The presence of pain and facial nerve palsy may
indicate malignant transformation. Diagnosis is made by imaging and
biopsies.
Objectives: This study aims to know the pattern of Benign and
malignant tumo...
Citations
... It s hould be quick and time efficient. 6 Currently, for MEC, four histological grading system were proposed which includes AFIP, Brandwein system, Modified Healey system and MSKCC. 7 For the quantitative analysis, AFIP and Brandwein systems were recommended and for qualitative analysis Modified Haely and MSKCC systems. ...
... Raja Seethala (2005) suggested that all grading system are somewhat cumbersome, ambiguous but evidence suggests that using a system consistently shows greater reproducibility than using intuitive approach. 6 Histological grading is the most important tool for the clinicians in determining the appropriate management and prognostication in patients presenting with salivary gland MEC. With this aim, in the present retrospective study, histological slides were reviewed meticulously and all the cases were graded as per the histological grading systems -AFIP, Brandwein, Modified Healey system, and MSKCC. ...
: Salivary gland carcinomas comprise of only 3-5% of all head and neck malignancies. Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. The morphologic diversity of MEC can pose diagnostic challenges hence, various histological grading systems have been proposed based on the quantitative and qualitative analysis. This proves to be greatly consequential in the management and prognosis of patients with MEC.
To compare histologic grading methods in MEC of major & minor salivary glands.
20 histopathologically diagnosed cases of MEC (10 each major & minor salivary gland) will be analysed using following methods: Qualitative Method: 1) Modified Healey 2) Memorial Sloan-Kettering Cancer Center method. Quantitative method: 1) Armed force Institute of Pathology (AFIP) 2) Brandwein method Histological findings were evaluated.
In our study AFIP grading system, 50% Cases were classified as low grade, 35% as intermediate grade and 15% as high graded. According to Brandwein grading system20% of cases were categorized as low, 35% cases as intermediate, 45% cases as high grade MEC. Modified Healey grading system of MEC showed 50%, 40%, 10% cases as low, intermediate and high grade MEC respectively. MSKCC grading system revealed as 55%, 30% and 15% cases as low, intermediate and high grade MEC respectively. Our finding indicated that MSKCC grading system was the most favourable histological grading system as percentage of agreement found to be 85%.
Careful microscopic examination is the most important parameter in the grading of MEC. This meticulous microscopic examination emerges as the cornerstone in grading MEC. Both MSKCC and Modified Healey grading methods exhibits effectiveness in evaluating MEC. Our finding indicated that Memorial Slon Kettering Cancer Center (MSKCC) was the most favourable histological grading system as percentage of agreement found to be 85%. However, further longer studies are imperative to substantiate this finding and for establish of universally accepted grading system for Mucoepidermoid carcinoma.
... The grading of MEC remained for low, intermediate and high-grade tumors, but the grading criteria and specific scheme are still lacking [17,20]. Grading systems for ACCs, based upon their morphological appearances, were proposed [19][20][21]. However, these grading schemes are considered useful for assessing prognosis and not in therapeutic management. ...
... However, these grading schemes are considered useful for assessing prognosis and not in therapeutic management. CEPA are to be graded according to the malignant component [21]. ...
Salivary glands tumors are uncommon neoplasms with variable incidence, heterogenous histologies and unpredictable biological behaviour. Most tumors are located in the parotid gland. Benign salivary tumors represent 54–79% of cases and pleomorphic adenoma is frequently diagnosed in this group. Salivary glands malignant tumors that are more commonly diagnosed are adenoid cystic carcinomas and mucoepidermoid carcinomas. Because of their diversity and overlapping features, these tumors require complex methods of evaluation. Diagnostic procedures include imaging techniques combined with clinical examination, fine needle aspiration and histopathological investigation of the excised specimens. This narrative review describes the advances in the diagnosis methods of these unusual tumors—from histomorphology to artificial intelligence algorithms.
... This phenomenon can be explained from the following aspects. high-grade MSGC are more often associated with the risk of occult neck metastasis than low-grade tumors (18)(19)(20). ...
Objective
This population-based study aims to assess the survival benefits of selective neck dissection (SND) compared to neck observation in patients with T1/T2N0M0 major salivary gland malignancy (MSGC).
Methods
We conducted a retrospective review of T1/T2N0M0 MSGC patients who underwent primary tumor surgical extirpation with or without elective neck dissection in the Surveillance, Epidemiology, and End Results database (SEER) from 2004-2015. The impact of SND and clinical variables on overall survival (OS) and disease-specific survival (DSS) was evaluated using Univariate and Multivariate Cox proportional hazards regression models. Kaplan-Meier survival curves were generated, and survival rates were assessed via the log-rank test.
Results
Of 3778 post-operative T1-T2N0M0 MSGC patients, 2305 underwent elective neck dissection, while 1473 did not. Median follow-up was 106 months. Univariate and Multivariate analysis identified SND as a prognostic factor for OS in all the study population. After stratified analysis, we found that in the poorly high-grade (differentiated and undifferentiated) patients, the survival showed a significant OS and DSS benefit after receiving SND compared with the neck observations [HR for OS (95%CI): 0.571(0.446-0.731), P<0.001] and [HR for DSS (95%CI): 0.564(0.385-0.826), P=0.003], other than in the well differentiated or moderately differentiated subgroup. Especially, when the pathological is squamous cell carcinoma, the results show that the people underwent SND had better prognosis, not only in OS [HR (95%CI): 0.532(0.322-0.876), P=0.013], but also in DSS [HR (95%CI): 0.330(0.136-0.797), P=0.014]. The multivariate analysis also yielded encouraging results, compared with neck observation, receiving SND bought about a significant independent OS (adjusted HR, 0.555; 95% CI, 0.328-0.941; P=0.029) and DSS (adjusted HR, 0.349; 95% CI, 0.142-0.858; P=0.022) advantage in high grade squamous cell carcinoma MSGC patients. The Kaplan-Meier survival curves also demonstrated that adjusted SND still had significantly better OS(P=0.029) and DSS(P=0.022) than the observation group in patients with high-grade squamous cell carcinoma of MSGC.
Conclusion
Poorly differentiated and undifferentiated T1/T2N0M0 major salivary gland malignancy treated with selective neck dissection demonstrated superior survival compared to neck observation, especially in the pathological subtype of squamous cell carcinoma. These findings suggest the potential benefits of multimodal therapy for appropriately selected patients, emphasizing significant clinical implications.
... The composition of MEC comprises three distinct cell types: epidermoid cells, intermediate cells, and mucous cells, and variable amount of mucin [37], shown in Figures 4A-4C. These tumors are categorized into three histological grades-low, intermediate, and high-based on factors such as cystic component proportion, perineural invasion presence, necrosis, mitotic activity, and nuclear atypia [1,42]. MEC is defined by rearrangements of the MAML2 gene, often with various fusion partners, with CTRC1 being the most frequent partner [43]. ...
Background: Salivary gland lesions possess diagnostic challenges on fine needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis. Summary: There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117 , DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion , rearrangements of the MAML2 gene, ,and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.
... ACC primarily affects individuals aged 40 to 60 years, with a slight female predominance [3,4]. The most common sites within the oral cavity include the palate, tongue, and floor of the mouth, with additional occurrences in the lips, buccal mucosa, retromolar trigone, and tonsillar area [4][5][6]. ...
Background:
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.
Methods:
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.
Conclusion:
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.
... Cases that had insufficient or inoperable biopsy specimens, or missing medical, clinical, or follow-up records were excluded from the study. The current work included 16 cases of MEC cases which were categorized into three histologic grades (low, intermediate, and high grade) following the criteria of Modified Healey classification [18]. ...
... Mucoepidermoid carcinoma of the current work was characterized by the presence of variable proportions of three types of cells; mucoussecreting cells, epidermoid cells, and intermediate cells. This group was classified into three histologic grades (low, intermediate, and high) following the criteria of Modified Healey classification [18]. The greater number of MEC cases was represented in the high grade (10 cases, 62.4%), while the low and intermediate grades of MECs were represented in three cases for each grade (18.8%). ...
Objective: The X-linked inhibitor of apoptosis protein (XIAP) immunohistochemical expression was employed to assess the anti-apoptotic activity of mucoepidermoid carcinoma (MEC) in relation to different clinicopathological variables to understand if XIAP immunoexpression could reflect the histologic grade and the biologic activity and prognosis in MEC patients. Materials and Methods: A retrospective study was accomplished on 16 MEC cases. The worked MEC cases involved the three histologic grades, low, intermediate, and high. Assessement of XIAP immunoexpression was made in relation to different clinicopathological parameters. The analysis of data was done by Pearson`s Chi-square test. Pearson correlation co-efficiency test was used to test the association between the different variables. The P‐value <0.05 was considered to be statistically significant. Results: There were statistically significant differences in XIAP immunoexpression in relation to the following parameters; the TNM clinical stage (P=0.036), and the histologic grade (P=0.008). Conversely, the immunoexpression of XIAP was not significantly correlated with patients’ age (P=0.141), patients` gender (P= 0.471), and the anatomical site of the tumor (P=0.827) in MEC cases. Conclusion: The immunoexpression of XIAP correlates with histologic grading of MEC. Additionally, XIAP immunoexpression reflects the clinical and biological behavior of MEC.
... Based on histological features and cellular arrangement, PACC can be classified into three types, including tubular tumor (grade I), sieve-shaped tumor (grade II), and solid-type mass (grade III). 5,6 The cytological examination revealed cells of uniform size and morphology. The samples were characterized by sparse cytoplasm, small nuclei, and deep staining. ...
Background
This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC).
Methods
Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years.
Results
Immunohistochemical staining showed that the tumors expressed CK7, S‐100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively.
Conclusion
Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.
... Microscopically, AdCC is an infiltrative biphasic tumor composed of ductal and myoepithelial cells arranged in cribriform, tubular, and/or solid patterns [3]. The tubular pattern is characterized by well-formed ducts and tubules lined by luminal ductal cells having eosinophilic cytoplasm and uniform round nuclei, surrounded by abluminal myoepithelial cells with scant clear cytoplasm and angulated hyperchromatic nuclei [4]. ...
Adenoid cystic carcinoma (AdCC), associated with MYB/MYBL1 gene rearrangements, shows epithelial and basaloid myoepithelial cells arranged in tubular, cribriform and solid patterns. Variations from this classic morphology make diagnosis challenging, necessitating molecular testing. AdCC with striking tubular hypereosinophilia (AdCC-STE) is one such recently described histological subtype.
A 52-year-old female presented with a floor of mouth swelling for two months, diagnosed elsewhere as polymorphous adenocarcinoma (PAC). A biopsy was obtained. With a diagnosis of oncocytic neoplasm, wide excision of the tumor was undertaken. Histological examination, fluorescence in situ hybridization (FISH) and ultrastructural examination were performed. Archival cases of PAC and epithelial myoepithelial carcinoma (EMC) were reviewed, and MYB immunostaining and FISH were performed to identify potential AdCC-STE cases.
The excised tumor from the index patient showed bilayered tubules, micropapillae and cribriform pattern. Luminal cells with hypereosinophilic to clear cytoplasm were surrounded by flattened abluminal cells. Focally, basophilic matrix was seen within sharply demarcated pseudocystic spaces. FISH revealed MYB and EWSR1 gene rearrangements, confirmatory of AdCC-STE. Electron microscopy showed features consistent with AdCC; however, mitochondria were not prominent. Among 14 archival PACs, two showed MYB immunopositivity; one showed MYB rearrangement but was classical AdCC. Among 35 EMC, one case showed MYB immunoreactivity and eosinophilia of luminal cells but lacked MYB/MYBL1 rearrangement.
Awareness of unusual histological subtypes of AdCC, such as AdCC-STE, is imperative, as it may be misdiagnosed as PAC and EMC, among others. Presence of basophilic matrix and squamoid morules in a biphasic tumor even with hypereosinophilic rather than basaloid myoepithelial appearance should raise suspicion for AdCC-STE, and prompt molecular testing for confirmation. With wider accessibility, lower cost and significantly shorter turn-around-time when compared to RNA sequencing, FISH can be employed for confirmation of diagnosis, especially in low- and middle-income countries.
... The patients were divided into low-and high-risk groups based on the risk stratification criteria formulated by the World Health Organization. 16 Tumor size was determined based on collaborative stage tumor size (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015), EOD 10-size (1988EOD 10-size ( -2003, and EOD 4-size (1983EOD 4-size ( -1987. Baseline neck status was analyzed in accordance with the derived EOD classification, the derived AJCC classification, the derived SEER combined classification, regional nodes examined (1988þ), regional nodes positive (1988þ), and the scope of regional lymph node surgery (2003þ). ...
Objective
To identify the clinical features and prognostic factors for sublingual gland carcinoma.
Methods
This was a case–control study. Patients with surgically treated sublingual gland carcinoma were retrospectively included in the Surveillance, Epidemiology and End Results database and divided into adenoid cystic carcinoma (ACC) and non-ACC groups. Primary outcome variables were disease-specific survival (DSS) and overall survival (OS). Prognostic factors for each group were analyzed using Cox models.
Results
We included 251 patients (115 men and 136 women). Compared with the non-ACC group, the ACC group had a larger average tumor size and received more adjuvant radiotherapy. In patients with ACC, the pathologic grade had an independent impact on DSS and OS, and patients who were undergoing adjuvant chemotherapy had worse DSS than those who were not receiving chemotherapy. In the non-ACC group, pathologic grade IV, lymph node metastasis, and adjuvant chemotherapy were associated with poor DSS and OS, and tumor extension predicted worsening DSS.
Conclusions
In sublingual gland carcinoma, the pathologic grade and adjuvant chemotherapy were the most important prognostic factors, whereas lymph node metastasis had a negative impact in non-ACC patients but not in ACC patients.
... The histology of SGC was classified and graded based on the 2005 World Health Organization guidelines [20,21]. Based on Seethala's risk stratification criteria, the histological entities were categorized into high and low grades [22]. ...
Background:
The aim of this study was to interrogate if the use of postoperative chemoradiotherapy (POCRT) correlated with superior oncological outcomes for certain subgroups of patients with high-risk salivary gland carcinoma (SGC), compared with postoperative radiotherapy (PORT) alone.
Methods:
This multicenter retrospective study included 411 patients with surgically resected SGC who underwent PORT (n = 263) or POCRT (n = 148) between 2000 and 2015. Possible correlations of clinical parameters with outcomes were examined using the Kaplan-Meier analysis and Cox proportional-hazards regression model.
Results:
The median follow-up of survivors is 10.9 years. For the entire cohort, adding concurrent chemotherapy to PORT was not associated with OS, PFS, or LRC improvement. However, patients with nodal metastasis who underwent POCRT had significantly higher 10-year OS (46.2% vs. 18.2%, P=0.009) and PFS (38.7% vs. 10.0%, P=0.009) rates than those treated with PORT alone. The presence of postoperative macroscopic residual tumor (R2 resection) was identified as an independent prognosticator for inferior OS (P=0.032), PFS (P=0.001), and LRC (P=0.007). Importantly, POCRT significantly correlated with higher 10-year LRC rates in patients with R2 resection (74.2% vs. 40.7%, P=0.032) or adenoid cystic carcinoma (AdCC, 97.6% vs. 83.6%, P=0.036). On multivariate analyses, the use of POCRT significantly predicted superior OS (P=0.037) and PFS (P=0.013) for node-positive patients and LRC for patients with R2 resection (P=0.041) or AdCC (P=0.005).
Conclusions:
For surgically resected SGC, POCRT was associated with improved long-term OS and PFS for patients with nodal metastasis and superior LRC for patients with R2 resection or AdCC.
