Carcinoma Ex Pleomorphic Adenoma Research Articles

Identification of differentially expressed microRNAs as potential biomarkers for carcinoma ex pleomorphic adenoma

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignancy that transforms from PA. Early detection of the carcinoma by biopsy is difficult due to similar histopathology of the malignant and benign components. To address this, we investigated and compared the characteristic miRNA expression patterns across samples of the PA, carcinomatous portions (CA) of CXPA, as well as conventional PA. We selected 13 CXPA and 16 conventional PA FFPE samples, separated the PA and CA portions of CXPA samples and conducted miRNA profiling for each group. Among 13 transcripts that were differentially expressed between PA and CA of CXPA, eight miRNAs were up-regulated and five down-regulated in CA. Bioinformatic analysis revealed that the up-regulated miRNAs were related to cancer progression and down-regulated ones to tumor suppression. Additionally, seven miRNAs were significantly up-regulated in PA of CXPA compared to conventional PA, although they are histopathologically similar. Almost all of these transcripts interacted with TP53, a well-known tumor suppressor. In conclusion, we identified differentially expressed miRNAs in PA and CA of CXPA, which were closely associated with TP53 and various cancer-related pathways. We also identified differentially expressed miRNAs in the PA of CXPA and conventional PA which may serve as potential biomarkers.

Diagnostic Value of Nuclear Receptor Subfamily 4 Group A Member 3 in Salivary Gland Carcinomas

Salivary gland carcinomas are diagnostically challenging lesions in heterogeneous groups. However, recently described genomic alterations may be helpful and have future therapeutic implications. The molecular investigation is becoming useful tool to help diagnosis and provide prognostic information. Diagnosis of acinic cell carcinoma (AcCC) is challenging due to its rarity and similarity with other SGCs or normal acinar cells.
 Herein, the diagnostic performance of transcription factor nuclear receptor subfamily 4 group A member3 (NR4A3) was analysed immunohistochemically. This study was done on 68 cases of SCCs, including 32 of AcCC, 14 of adenoid cystic carcinoma (AdCC), 8 of mucoepidermoid carcinoma (MEC), 7 of epithelial myoepithelial carcinoma (EMC), 4 of salivary duct carcinoma (SDC), and only one case from each of carcinoma ex pleomorphic adenoma (CXPA), polymorphous adenocarcinoma (PAC) and secretory carcinoma (SC) for detecting NR4A3.
 All stained samples of AcCC (100%) responded positively to the NR4A3 antibody. However, only one case of AdCC and MEC demonstrated NR4A3 immunostaining in less than 10% of cells. On the other hand, the different types of SGCs, including EMC, SDC, CXPA, PAC, and SC, revealed negative expressions. Therefore, we can conclude that NR4A3 can be used as a potential marker for AcCC rather than other SGCs.

Increased MIB-1 expression in salivary gland pleomorphic adenoma that recurs and undergoes malignant transformation

The objective of this retrospective study was to explore possible changes in histopathological features and expression of cyclin D1 and MIB-1 in salivary gland pleomorphic adenoma (PA) that recur or undergo malignant transformation. Knowledge of these characteristics might help to guide the management of these rare tumors. The histopathology and immunohistochemical staining characteristics of such tumors were analyzed in a cohort of 65 patients constituting three different groups of tumors: PA, recurrent pleomorphic adenoma (RPA) and carcinoma ex PA (CxPA). The RPAs were divided into two subgroups: primary PA that were known to recur later (PA-prim) and recurrent tumors appearing after a primary tumor (PA-rec). RPAs and CxPAs were compared with PAs without recurrence, which served as a control group. In our study, CxPA and PA-rec, but not PA-prim, showed increased MIB-1 expression compared with the control group. Neither cyclin D1 expression nor any histopathological features showed any association in statistical analyses. CxPA showed increased mitotic activity, squamous metaplasia, and nuclear atypia. Tumor multifocality was more frequent in PA-rec and CxPA. The different MIB-1 expression in CxPA and PA-rec in comparison to PA-prim suggests that the changes in expression could develop after the primary tumor.

Risk and Lag-time for Development of Lacrimal Gland Carcinoma Expleomorphic Adenoma: Observations and Conjectural Study.

To estimate the proportion of de novo lacrimal gland pleomorphic adenomas (PAs) and carcinomas expleomorphic adenomas (CEPAs), together with age at presentation and first symptom. Conjectural models of tumor growth are considered. Retrospective review of patients with orbital lobe PA or CEPA. The presenting age was examined for conformation to a Gaussian distribution and the cumulative distribution function derived for both tumor types. The risk of CEPA with age was estimated by logistic regression. About one-sixth (27/172; 16%) of these primary orbital lobe tumors were CEPAs, with 145 PAs (76/145 male; 52%) and 27 CEPAs (12/27 male; 44%). The mean presenting age for PAs was 48.3 years (median 47.7; range 11-84 years) and 57.7 years for CEPAs (median 61.2, range 27-91 years) ( p = 0.0062), and the standard deviations for each group are almost identical (16.3 for PAs, 15.9 for CEPAs; p = 0.92). Five (3.4%) PAs and 1 (3.7%) CEPA were asymptomatic: otherwise, the median symptom duration was 24 months for both PAs and CEPAs ( U test: p = 0.65). The odds of CEPA rises significantly with age, increasing 1.04-fold annually ( p = 0.0079). The almost identical measures of dispersion for the presenting ages of PA and CEPA suggests that, once malignant transformation occurs, there might be a relatively constant period before it is evident. CEPAs present about a decade after PAs, this unexpectedly later presentation for the malignancy possibly being explained by a gradual replacement of the PA by the newly arising carcinoma within the preceding benign tumor.

Predictors of Occult Nodal Involvement in Clinically Node Negative Primary Parotid Carcinoma: An NCDB Analysis

<h3>Purpose/Objective(s)</h3> Primary Parotid Carcinomas (PPC) comprise a wide array of histologies, each with varying propensity for local invasion and cervical nodal involvement. Upfront surgical excision of the primary tumor constitutes the standard of care for PPC, but there exists little consensus regarding management of the clinically negative neck (cN0). We conducted a clinicopathologic correlative analysis of the National Cancer Database (NCDB) to identify predictors of occult nodal involvement in PPC to guide elective neck management. <h3>Materials/Methods</h3> The NCDB was queried for adults with a first malignant diagnosis of cN0M0 cancer of the parotid who underwent adequate surgical resection (defined as subtotal to radical parotidectomy with ³18 nodes examined) without pre-surgical treatment. Pathologic T-classification, tumor size, histology, grade, lymphovascular space invasion (LVSI), gender, and age at diagnosis were specified <i>a priori</i> as variables of interest. The primary outcome, occult nodal positivity (<i>i.e.</i> cN0 but pN+), was assessed by univariable (UVA) and multivariable (MVA) logistic regression analysis, depicted as odds ratios (OR) and corresponding 95% confidence intervals (95% CI) with a prespecified threshold for statistical significance of <i>p</i>£0.05. Recursive partitioning analysis (RPA) was subsequently performed to categorize patients according to their calculated risk of occult nodal disease. <h3>Results</h3> From an initial cohort of 41,445 patients with PPC 978 met inclusion criteria and were included for analysis, of whom 331 (33.8%) had occult nodal involvement. By UVA, the incidence of occult nodal positivity was significantly higher in male patients, those aged 72 and older, patients with high grade disease, pT4 classification, adenocarcinoma histology, a >4cm tumor, and those with positive LVSI. On MVA, tumor size, age, and gender were no longer significantly associated with occult nodal involvement; however, LVSI (OR 6.1, 95% CI 4.3-8.8), carcinoma ex-pleomorphic adenoma (OR 5.6, 95% CI 2.1-14.8), adenocarcinoma (OR 5.1, 95% CI 2.6-9.9), salivary duct (OR 4.0, 95% CI 1.8-8.6), or mucoepidermoid (OR 2.3, 95% CI 1.2-4.3) histology, pT3 (OR 2.0, 95% CI 1.1-3.7) or pT4 (OR 3.9, 95% CI 2.1-7.3) status, and high grade (OR 2.0, 95% CI 1.4-3.0) remained significant. LVSI, histology, pT status, and grade were further evaluated with RPA, which identified LVSI as the strongest predictor of occult nodal involvement (57.1% vs 42.9%, <i>p</i><0.01). <h3>Conclusion</h3> LVSI appears to supersede tumor histology, grade, size, and pT status as the strongest risk factor for occult nodal involvement in PPC. To our knowledge, this is the largest series to evaluate this pathologic feature. Further research into this heretofore underappreciated risk factor and its implications for management of the cN0 neck is warranted.

Progressivity analysis of pleomorphic adenoma toward carcinoma ex pleomorphic adenoma

Background: Pleomorphic adenoma (PA) is a benign salivary gland tumour with high incidence and recurrence after treatment. It may recur with the same appearance or develop toward malignancy, namely as carcinoma ex pleomorphic adenoma (CXPA). Howthis tumour can transform into a CXPA remains unclear. Purpose: The aim of this study was to analyse the possibility of pathogenesis and progressivity of PA to CXPA. Methods: Twenty-four samples of PA and three control samples of CXPA were stained with haematoxylin and eosin (HE), Mallory’s trichrome, and Periodic acid–Schiff (PAS). All of the PA cases were identified through different kinds of stroma, tumour cells types, morphologic patterns, or else through atypical appearance of the PA similar to the CXPA. Results: Twenty-four samples of PA demonstrated that the most dominant stroma was myxofibrous, and the dominant tumour cell type was plasmacytoid cells with a trabecular pattern. Additionally, in the pleomorphic histological picture of adenomas we found several patterns of malignant tumour behaviour, including pseudopodia, metaplasia and hyalinisation, and cholesterol crystals that are thought to come from fat cell necrosis derived from adipose metaplasia. Conclusions: PA displays several atypical characteristics that have the potential to develop into malignancies such as CXPA, due to capsular infiltration, necrosis, hyalinization and high mitotic activity of cells, but all these atypical characteristics that we observed still cannot be clearly classified as CXPA because they require other specific examinations.

Comparison of gene fusion detection methods in salivary gland tumors

Salivary gland neoplasms may pose diagnostic difficulties due to overlapping morphologic features. Recently, specific gene fusions have been discovered that correspond to particular tumor types, and can aid in accurate diagnosis. Gene rearrangements are commonly assessed by fluorescence in situ hybridization (FISH), although use of next-generation sequencing is increasing. However, there is no “gold standard” for fusion detection. We determined the concordance between FISH and a targeted RNA sequencing panel in gene fusion detection across twenty-two salivary gland tumors, including five mucoepidermoid carcinomas, four acinic cell carcinomas, four pleomorphic adenomas, two adenoid cystic carcinomas, two NUT carcinomas, and one each of basal cell adenoma, salivary duct carcinoma ex-pleomorphic adenoma, salivary duct carcinoma, clear cell carcinoma, and secretory carcinoma. Directed FISH testing based on the diagnosis was performed on cases that did not already have FISH conducted during clinical workup. Targeted RNA sequencing of 507 genes and their partners (using the Illumina TruSight Fusion Panel) was completed. Six of twenty-two (27.3%) cases had discordant results. In three cases, FISH results were negative while RNA sequencing results found fusion transcripts, which were all confirmed with RT-PCR and Sanger sequencing. In three cases, RNA sequencing results were negative while FISH results were positive for a gene rearrangement. Thus, if fusion analysis results are conflicting with the morphologic impression, a second mode of fusion detection may be warranted. Although both methods have advantages and drawbacks, RNA sequencing provides additional information about novel fusion partners and fusions that may not have been originally considered.

Discovery proteomics reveals potential protein signature associated with malignant phenotype acquisition in pleomorphic adenoma.

To analyze the proteomic profile of salivary pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) samples and correlate them with the malignant transformation of the PA. Thirty samples (10 PA, 16 CXPA, and 4 residual PA) were microdissected and submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomic data and protein identification were analyzed through LC-MS/MS spectra using the MaxQuant software. The proteomic analysis identified and quantified a total of 240 proteins in which 135 were found in PA, residual PA, and CXPA. The shared proteins were divided into six subgroups, and the proteins that showed statistically significant differences (p>0.05) and fold-change > or <2.5 in one subgroup to another subgroup were included. Seven proteins (Apolipoprotein A-I-APOA1, haptoglobin-HP, protein of the synaptonemal complex 1-SYCP1, anion transport protein of band 3-SLC4A1, subunit μ1 of AP-1 complex-AP1M1, beta subunit of hemoglobin-HBB, and dermcidin-DCD) were classified as potential protein signatures, being HP, AP1M1, and HBB with higher abundance for PA to residual PA, APOA1 with higher abundance for PA to CXPA, SLC4A1 with lower abundance in the PA to CXPA, SYCP1with lower abundance for residual PA to CXPA, and DCD with higher abundance in the CXPA with epithelial differentiation to myoepithelial differentiation. In this work, we demonstrated the comparative proteomic profiling of PA, residual PA, and CXPA, and seven were proposed as protein signatures, some of which may be associated with the malignant phenotype acquisition.

Histopathological and Immunohistochemical Analysis of Rare Parotid Tumours: A Case Series

Malignant salivary gland tumours are rare representing only 2% of all head and neck malignancies. The most common malignant salivary gland tumour is mucoepidermoid carcinoma followed by adenoid cystic carcinoma while parotid is the most common site. But there are presence of other rare variants with diverse biological feature of maliganacy including Salivary Duct Carcinoma (SDC), basal cell adenocarcinoma, Carcinoma ex Pleomorphic Adenoma (CXPA), polymorphous adenocarcinoma which represent 1-5% of all salivary gland neoplasm. They typically are high-grade carcinomas with presence lymph nodal metastases. Hereby, author report 5 rare cases of parotid gland malignancy detected by histopathological examination along with confirmation by immunohistochemical examination. A 60-year-old and 65-year-old male diagnosed with salivary duct carcinoma of left parotid and right parotid respectively with ipsilateral cervical lymph node involvement but peripheral resection margins were free from tumour invasion. A 50-year-old female diagnosed with basal cell adenocarcinoma of left parotid with lymph node metastasis and resection margin was involved by the tumour. A 60-year-old male presented with recurrent swelling in left parotid region, diagnosed as carcinoma ex pleomorphic adenoma with lymph node involvement in a case of pleomorphic adenoma of parotid, reported previously. A 52-year-old male presented with right-sided parotid region swelling for last six months having Fine Needle Aspiration Cytology (FNAC) report of pleomorphic adenoma. Parotidectomy revealed diagnosis of polymorphous adenocarcinoma while surgical resection margins were free. Surgery is the main mode of treatment in these tumours. Involvement of resection margins, extraparotid extension, lymphovascular and perineural invasion along with lymph node metastasis are the common indicator for postoperative radiation therapy.

Elective neck dissection in salivary gland malignancies: Systematic review and meta-analysis.

We defined the occult nodal metastasis (ONM) rate of clinical node-negative salivary gland malignancies and examined the role of elective neck dissection (END). Meta-analysis querying four databases, from inception of databases to March 25th, 2020. Fifty-one studies with 11 698 patients were included. ONM rates were 64% for salivary ductal carcinoma (SDC), 51% for undifferentiated carcinoma, 34% for carcinoma ex-pleomorphic adenoma (CXPA), 32% for adenocarcinoma not otherwise specified (ANOS), 31% for lymphoepithelial carcinoma (LE), 20% for mucoepidermoid carcinoma, 17% for acinic cell carcinoma, and 17% for adenoid cystic carcinoma. T3/T4 tumors had a 2.3 times increased risk of ONM than T1/T2 tumors. High-grade tumors had a 3.8 times increased risk of ONM than low/intermediate-grade tumors. ONM rates were exceedingly high for T3/T4, high-grade, and undifferentiated, SDC, ANOS, CXPA, and LE tumors, indicating the potential role of END.

Increase in Chymase-Positive Mast Cells in Recurrent Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland.

Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFβ1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.

Expanding the clinicopathological spectrum of TGFBR3‐PLAG1 rearranged salivary gland neoplasms with myoepithelial differentiation including evidence of high‐grade transformation

PLAG1 rearrangements have been described as a molecular hallmark of salivary gland pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), and myoepithelial carcinoma (MECA). Several fusion partners have been described, however, commonly no further assignment to the aforementioned entities or a morphological prediction can be made based on the knowledge of the fusion partner alone. In contrast, TGFBR3‐PLAG1 fusion has been specifically described and characterized as an oncogenic driver in MECA, and less common in MECA ex PA. Here, we describe the clinicopathological features of three TGFBR3‐PLAG1 fusion‐positive salivary gland neoplasms, all of which arose in the deep lobe of the parotid gland. Histopathology showed high morphological similarities, encompassing encapsulation, a polylobular growth pattern, bland basaloid and oncocytoid cells with myoepithelial differentiation, and a distinct sclerotic background. All cases showed at least limited, unusual foci of minimal invasion into adjacent salivary gland tissue, including one case with ERBB2 (Her2/neu) amplified, TP53 mutated high‐grade transformation, and lymph node metastases. Of note, all cases illustrated focal ductal differentiation. Classification remains difficult, as morphological overlaps between myoepithelial‐rich cellular PA, myoepithelioma, and MECA were observed. However, evidence of minimal invasion advocates classification as low‐grade MECA. This case series further characterizes the spectrum of uncommon cellular myoepithelial neoplasms harboring TGFBR3‐PLAG1 fusion, which show recurrent minimal invasion of the adjacent salivary gland tissue, a predilection to the deep lobe of the parotid gland, and potential high‐grade transformation.

Myoepithelial Carcinoma ex Pleomorphic Adenoma: Rare Case Report with Clinicopathologic and Immunohistochemical Features

Abstract Introduction/Objective Myoepithelial carcinoma is identified by nearly exclusive myoepithelial differentiation and evidence of malignancy. It may arise de novo or in preexisting benign tumors including pleomorphic adenoma and benign myoepithelioma. It occurs most commonly in the parotid gland followed by submandibular glands, minor salivary glands, and occasionally in the sublingual gland. Nasopharyngeal origin has been rarely reported. Methods/Case Report An afebrile 19-year-old female presented to the emergency department with persistent facial pressure, otalgia (right side greater than left side), rhinorrhea, and several episodes of epistaxis. One month before, she has been treated with Amoxicillin for three days with no relief, where Augmentin started for her for five days. About four days prior presentation, she was placed on Prednisone and Cefdinir. Over the next several days, she began having throat pain with difficulty swallowing. Routine blood work revealed a leukocytosis of 14.2 with normal differentiation. CT of the neck showed a large soft tissue mass centered at the right nasopharynx. Flexible nasal endoscopy performed bilaterally to reveal the nasopharynx is entirely obstructed with a lobulated mass filling the nasopharynx. On the right side, it extends into the posterior nasal passage filling the sphenoethmoid recess and the posterior floor of the nasal passage. Outpatient biopsy from nasopharynx mass is also performed. Results (if a Case Study enter NA) Mass biopsy reveals a mucinous and chondromyxoid background with mixed epithelial and myoepithelial differentiation. The is squamous metaplasia of myoepithelial cells and prominent mitotic activity and apoptotic activity. Immunohistochemistry was positive for CK5/6, calponin, BCL2, SMA, BerEp4, Sox10, and a proliferative index up to 40%. Based on this information Myoepithelial Carcinoma ex-pleomorphic adenoma of the nasopharynx is the diagnosis. Conclusion Carcinoma ex pleomorphic adenoma is usually a high-grade malignancy. It occurs most commonly in the parotid gland, followed by submandibular glands, minor salivary glands, and occasionally in the sublingual gland. Our case is one of the few cases of myoepithelial carcinoma arising in nasopharyngeal pleomorphic adenoma.

Identification of Salivary Gland Tumors (SGT) at Risk for Local or Distant Recurrence After Postoperative Radiation Therapy (PORT) With or Without Systemic Therapy (ST) Using Clinical Risk Grouping

To identify risk groups and patterns of recurrence after curative treatment of primary SGT treated with PORT +/- ST.We retrospectively identified consecutive pts with stage I-IVA SGT, excluding adenoid cystic carcinoma (ca), treated with curative-intent surgery and postoperative IMRT with or without radiosensitizing chemotherapy from 12/2008-02/2020 at a tertiary care center. Pts were classified into clinical risk groups based on histologic diagnoses and pathologic features: (1) low-risk = morphologically low grade (LG) tumors (e.g. acinic cell, secretory, LG mucoepidermoid (MEC), epithelial-myoepithelial, basal cell adenocarcinoma), pN0, without lymphovascular invasion (LVI) or perineural invasion (PNI), including minimally invasive/non-invasive carcinoma ex-pleomorphic adenoma (CXPA); (2) intermediate-risk = intermediate grade morphology (e.g. grade 2 MEC) or LG morphology with PNI or LVI or pN+; (3) high-risk = high grade histology (e.g. salivary duct, high-grade MEC, poorly differentiated ca including invasive CXPA). Kaplan Meier estimates were used for recurrence-free survival (RFS) and univariable predictors.72 pts were included. Median age at surgery was 59.6 years [interquartile range (IQR) 49.7,67.7 yrs]. Sites were: 86% parotid (n = 62), 8% submandibular (n = 6), 4% minor salivary (n = 3), and 1% unknown primary. SGT were classified into clinical risk groups: 26% low (n = 19), 25% intermediate (n = 18), and 49% high-risk (n = 35). Concurrent chemotherapy (CRT) was given to 3% of low-risk (n = 1), 13% of intermediate risk (n = 4), and 71% of high-risk pts (n = 25). Regimens included carboplatin + paclitaxel, cisplatin, and concurrent/adjuvant trastuzumab (in 10 pts with HER2-positive SGT). With a median follow-up of 40.5 months, 2-year OS was 95% (85-98%); there were 11 recurrences (9 distant metastasis (DM), 2 in-field local failure (LF) both in pts with gross residual after surgery), with 82% (9 of 11) having received CRT. All recurrences were in the high-risk group with 2-year RFS of 73% (54%-85%) and 2-year cumulative incidence of DM 21% and LF 6%. Factors associated with RFS included positive margins (P = 0.004) and low-neck positive lymph nodes (level III/IV/V vs. level I/II, P = 0.04). Thirteen pts (18%) had targeted genomic sequencing (4 with recurrence); common mutations included TP53 (n = 4), HRAS (n = 3), NFKBIZ (n = 3), and PIK3CA (n = 3). Mutations in NF1 (n = 3) and HNFA1 (n = 2) were observed only in pts that recurred.DM are the primary mode of recurrence in pts with resected SGT treated with PORT +/- ST and occurred only in high-risk pts. After randomized trials like RTOG 1008 determine the added benefit of chemo to PORT, DM is likely to remain an unmet need. Further studies incorporating molecular characterization of high-grade SGT may identify potentially actionable targets to prevent distant recurrence.

The presence of herpesviruses in malignant but not in benign or recurrent pleomorphic adenomas.

The etiology of salivary gland tumors is mainly unknown. The anatomical location of the salivary glands, with the mucosal pathway to the oral cavity and its rich microbiome, raises the question of potential viral background. This study focuses on the potential presence of herpes-, polyoma- and parvoviruses in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA) and carcinoma ex pleomorphic adenoma (CaxPA). Thirty different viruses were analyzed by PCR-based assays in 68 formalin-fixed paraffin-embedded salivary gland tumors (25 PA, 31 RPA and 12 CaxPA). Virus DNA was detected altogether in 19/68 (28%) tumor samples. Human herpesviruses 6B and 7 (HHV-6B and HHV-7) and Epstein-Barr virus (EBV) were frequently and almost exclusively found in CaxPA (5/12, 7/12, and 3/12, respectively). Within the 7 CaxPA that were virus-positive, 3 samples contained 3, and 1 sample even 4, different viruses. Infrequent viral positivity was shown for parvovirus B19 and cutavirus, as well as Merkel cell and Malawi polyomaviruses. Our unexpected finding of herpesvirus DNA almost exclusively in CaxPA tissues deserves further in-depth studies.

NR4A3 Immunostain Is a Highly Sensitive and Specific Marker for Acinic Cell Carcinoma in Cytologic and Surgical Specimens.

Salivary gland acinic cell carcinoma (AciCC) has recognizable cytomorphologic features that can overlap with benign and malignant entities, creating a diagnostic challenge. AciCC harbors a t(4;9) translocation increasing nuclear receptor subfamily 4 group A member 3 (NR4A3) expression, detectable by immunohistochemistry (IHC) on surgical resection (SR). NR4A3 IHC cytology data are limited. Here, we examine NR4A3 IHC on smears, cell blocks (CBs), and SRs of AciCC and its mimickers. Our cohort comprised AciCC (including high-grade transformation), secretory carcinoma, mucoepidermoid carcinoma (MEC), Warthin tumor, pleomorphic adenoma (PA), cellular PA, carcinoma ex-PA, oncocytic carcinoma, oncocytoma, and nodular oncocytosis. NR4A3 IHC (Santa Cruz Biotechnology and Origene antibodies) was positive if more than 5% tumor cells showed nuclear staining. Among CBs, 90% of AciCC cases and none of the mimickers expressed NR4A3. Among SRs, 100% of AciCC cases showed diffuse NR4A3, whereas one high-grade MEC expressed focal NR4A3. Concordance was 95% with two antibody clones. Sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 100%, 100%, and 94.7% for CBs and 100%, 98.8%, 92.3%, and 100% for SRs, respectively. NR4A3 immunostaining was demonstrable on smears from an AciCC case. NR4A3 IHC can be a robust diagnostic tool to identify AciCC, especially for cytology specimens.

Carcinoma Ex Pleomorphic Adenoma of the Uvula - Case Report

Introduction: Carcinoma Ex Pleomorphic Adenoma (CEPA) results from the malignant transformation of a benign tumor of the Salivary Glands (SG), the Pleomorphic Adenoma (PA). PA is considered the most common salivary tumor with a 5% risk of malignant transformation and its excision is recommended. CEPA is a rare tumor, corresponding to 3.6% of all salivary tumors and 11.6% of all GS carcinomas. About 18% of CEPAs affect minor SG, with the palate being the most common location. The present work serves to describe a case of a CEPA of the Uvula Minor SG (UMSG). Case Report: We present a case report of a 57-year-old patient, with no relevant medical history, referred to the ENT consultation due to the appearance and progressive growth of a painless uvula lesion. The objective ENT examination showed a 15 mm ulcerative-vegetating lesion with apparent origin on the posterior face of the uvula. The lesion was biopsied and histopathological examination identified the presence of a neoplasm of the minor SG, probably NOS adenocarcinoma. The patient underwent Computed Tomography (CT) scan that showed an irregularity of the uvula, with no signs of invasion of the remaining soft palate, without other significant pharyngo-laryngeal changes. The patient underwent partial pharyngectomy and bilateral selective cervical ganglion dissection, and the histopathology of the surgical specimen confirmed that it was an invasive CEPA, the malignant component of the tumor corresponding to a NOS adenocarcinoma of the UMSG. The patient has been followed up in the ENT consultation, with no signs so far of loco-regional recurrence. Discussion/Conclusion: In the presented case, the patient probably developed an undiagnosed PA that had become malignant over time. Given that it is a poor prognosis neoplasm, it’s essential that the ENT specialists are aware of this disease, in order to facilitate and anticipate the diagnosis and treatment as much as possible.

Pleomorphic adenoma: the great mimicker of malignancy.

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex-pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests.

Ectopic carcinoma ex-pleomorphic adenoma in the lower neck: a rare entity at a rare location

Ectopic salivary gland tissue (ESGT) is salivary tissue located outside the major, minor and accessory salivary glands. Neoplasms rarely arise from ESGT, let alone carcinoma expleomorphic adenoma (CEPA) which is a malignant tumour that arises from the epithelial component of pleomorphic adenoma. It usually occurs in the parotid gland and in lesser instances, from submandibular gland or minor salivary glands. Herein, we report a rare case of CEPA in right supraclavicular ESGT of a 67-year-old lady.She underwent complete surgical excision of the mass and is free from any recurrence to date. Brief review of pathogenesis, clinical features and treatment of ectopic CEPA are discussed. A thorough review of the English literature reveals that our patient may be the second case of ectopic CEPA in the neck region ever reported to date.&#x0D; Bangladesh Journal of Medical Science Vol.20(3) 2021 p.658-661

Carcinoma Expleomorphic Adenoma of the Lacrimal Gland.

To report the characteristics and long-term outcomes of patients presenting with carcinoma ex-pleomorphic adenoma (CXPA) or malignant mixed tumor of the lacrimal gland. A retrospective case-note review for patients with CXPA, seen at Moorfields Eye Hospital between 1985 and 2018, was performed for demographics, presentation, imaging, histopathology, management, and outcome. Twenty-six patients (11 male; 42%) presented at a mean age of 46 years (median 46.4; range 24-81), with average symptom(s) duration of 67 months (median 24 months; range 6 weeks-53 years). The commonest symptoms were proptosis (13 patients; 50%), orbital ache or pain (11/26, 42%), having noted a lump in the upper eyelid (8/26, 31%), and diplopia (7/26, 27%). About 90% of patients had nonaxial globe displacement, over a half had a palpable mass and 3-quarters had reduced motility. Adenocarcinoma was the commonest malignant component of the tumor, occurring in 16 (62%) of the patients, followed by adenoid cystic carcinoma in 5 patients (19%); 10/26 (28%) tumors showed significant invasion on histological examination. A quarter of the patients had tumor-related death at an average of 2.8 years after diagnosis (median 2.5; range 1.5-4.4 years), and the overall probability of survival for the whole cohort was 63% at both 5 years and 10 years after treatment. The prognosis for CXPA was significantly worse with a history of prior incompletely excised pleomorphic adenoma (p < 0.001), a markedly invasive malignant component (p = 0.001), evidence of perineural invasion (p = 0.042), and an American Joint Committee on Cancer tumor size of T3 or greater (p = 0.024). Intact excision of CXPAs that do not display histological evidence of extension beyond the tumor pseudocapsule have a good outcome, similar to that for intact excision of benign pleomorphic adenomas. In contrast, our patients with markedly invasive CXPA had a tendency to local recurrence or distant metastasis, and tumor-related death occurred in about two-thirds.