Pre-existing Pleomorphic Adenoma Research Articles

A rare case report on carcinoma ex pleomorphic adenoma and mini review of histological features

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a rare malignancy that represents a transformation of a primary pleomorphic adenoma (PA), or carcinoma arising from primary (de novo) or recurrent or pre-existing pleomorphic adenoma (PA). Pleomorphic adenoma is a benign mixed common neoplasm that arises from the major salivary gland. Here we are presenting a case report of a 60-year-old female patient with a history of swelling in her right parotid region for 1 year. After a thorough clinical and histological examination it is diagnosed as carcinoma ex pleomorphic adenoma (Ca ex PA). In our case report we are more emphasizing the histological behavioral pattern of Carcinoma ex pleomorphic adenoma in preexisting pleomorphic adenoma (Ca ex PA) as distinctive histological features of this rare tumor play an essential role in the diagnosis of this tumor and thus, aid in the correct treatment plan and better prognosis.

Cytopathology of salivary gland myoepithelial carcinoma: A study of 13 cases and review of the literature

Myoepithelial carcinoma (MECA) is an infrequently recognized salivary gland (SG) neoplasm that commonly develops within a preexisting pleomorphic adenoma (MECA ex PA). Fine-needle aspiration (FNA) biopsy reports of this neoplasm are largely restricted to small series and single case reports. Our cytopathology files were searched for examples of SG MECA/MECA ex PA having confirmatory histopathologic verification. Conventional FNA biopsy smears were performed, and exfoliative specimens processed using standard techniques. Thirteen cases from 9 patients (M:F = 3.5:1; age range: 36 to 95 years, mean age = 60 years) met inclusion criteria. FNA biopsy sites included parotid gland (4), trunk (2), scalp (2), and neck (2). Exfoliative specimens included pleural fluid (1), bronchial brushing (1), and bronchoalveolar lavage (1). Most cases were metastatic deposits (8; 62%), 4 were primary neoplasms, and 1 a local recurrence. FNA diagnoses were MECA ex PA (6; 46%), myoepithelial neoplasm (2), PA (2), basaloid neoplasm (1), atypical myoepithelial cells (1), and myxoma (1). Ancillary testing in 2 cases showed positive staining for myoepithelial markers. Cytologic features were that of a low-grade neoplasm composed principally of epithelioid/polygonal cells exhibiting minimal if any cytologic atypia. Myxoid and chondromyxoid stroma was often the dominant feature in MECA ex PA aspirates. In the primary setting, a cytologic diagnosis of MECA/MECA ex PA is extremely challenging if at all possible. Due to overwhelming amounts of stroma, the diagnosis may be challenging in some cases of metastatic MECA ex PA.

Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements.

The formal pathogenesis of salivary carcinosarcoma (SCS) remained unclear, both with respect to the hypothetical development from either preexisting pleomorphic adenoma (PA) or de novo and the clonal relationship between highly heterogeneous carcinomatous and sarcomatous components. We performed clinicopathological and molecular (targeted RNA sequencing) analyses on a large series of 16 cases and combined this with a comprehensive literature search (111 cases). Extensive sampling (average 11.6 blocks), combined with immunohistochemistry and molecular studies (PA-specific translocations including PLAG1 or HMGA2 proven in 6/16 cases), enabled the morphogenetic identification of PA in 15/16 cases (93.8%), by far surpassing a reported rate of 49.6%. Furthermore, we demonstrated a multistep (intraductal/intracapsular/extracapsular) adenoma-carcinoma-sarcoma-progression, based on two alternative histogenetic pathways (intraductal, 56.3%, versus myoepithelial pathway, 37.5%). Thereby, early intracapsular stages are identical to conventional carcinoma ex PA, while later extracapsular stages are dominated by secondary, frequently heterologous sarcomatous transformation with often large tumour size (>60 mm). Our findings strongly indicate that SCS (almost) always develops from PA, with a complex multistep adenoma-carcinoma-sarcoma-sequence, based on two alternative histogenetic pathways. The findings from this novel approach strongly suggest that SCS pathogenetically is a rare (3-6%), unique, and aggressive variant of carcinoma ex PA with secondary sarcomatous overgrowth. In analogy to changes of terminology in other organs, the term "sarcomatoid carcinoma ex PA with/without heterologous elements" might be more appropriate.

CARCINOMA EX-PLEOMORPHIC ADENOMA: A CASE REPORT

A 37-year-old afrodescendant man presented a nodular lesion on the palate, with 2 years of evolution and history of pain and ulceration in the last 6 months. The provisional diagnosis was salivary gland neoplasia. An incisional biopsy revealed areas of typical pleomorphic adenoma (PA) associated with mucous, clear and atypical squamous cells, and cystic spaces. Immunohistochemical positivity for AE1/AE3, CK 7, CK14, CK19, p63, and Ki-67 (30%) was observed. The diagnosis was carcinoma ex-pleomorphic adenoma (CEPA). The tumor was resected, with a safety margin, and complementary chemo and radiotherapy were performed. No recurrence was observed after 1 year of follow-up. CEPA represents a malignant change in a pre-existing PA, which is extremely uncommon in minor salivary glands. Despite the rarity, this tumor must be considered in the differential diagnosis of intraoral salivary gland tumors with sudden changes in their clinical behavior.

The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy.

ObjectiveSalivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only de novo but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy.Materials and MethodsThe EZH2 and H3K27me3 immunohistochemical expression and EZH2 Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases).ResultsEZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. EZH2 Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups.ConclusionsA high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.

Intracapsular Carcinoma ex Pleomorphic Adenoma

This is the case of a 37-year-old female patient presenting with a 10-year history of a gradually enlarging right infra-auricular mass. A parotidectomy was performed. The surgical pathology specimen consisted of an 18 cm diameter encapsulated nodular mass with a homogenous, cream-tan solid surface. Microscopic section showed an encapsulated neoplasm with abundant chondromyxoid stroma and tubular epithelial elements characteristic of a pleomorphic adenoma. (Figure 1) Randomly scattered within the tumor were foci of haphazard and complex glands. (Figure 2) These glands exhibited nuclear pleomorphism, luminal necrosis, and mitoses compatible with an adenocarcinomatous proliferation. (Figure 3) Based on these features, the case was signed out as an intracapsular carcinoma ex pleomorphic adenoma.
 
 Carcinoma ex pleomorphic adenoma is a carcinoma arising from a pre-existing pleomorphic adenoma. The antecedent benign tumor may either be a long-standing one, often with a history measured in decades, or characterized by a protracted history of excisions and multiple recurrences.1,2 The carcinoma on the other hand is either epithelial or myoepithelial in derivation. By morphologic sub-type, the most commonly reported carcinoma arising in a pleomorphic adenoma is a salivary duct carcinoma or an adenocarcinoma that is not otherwise specified (NOS).1,3 Residual pleomorphic adenoma tissue is identifiable either in its typical morphology, a chondromyxoid stroma, or a hyalinized sclerotic nodule.1
 
 Aside from the type of carcinoma arising from the pleomorphic adenoma, another parameter that has to be reported is the extent of involvement by the carcinomatous component. A carcinoma that is entirely limited to within the parent tumor that is still enclosed by a complete capsule is termed an “intracapsular” or “non-invasive” carcinoma ex pleomorphic adenoma.1,2 Once the carcinoma breaches the capsule and infiltrates the surrounding tissue, then it is considered invasive. If the invasion is less than 4 – 6 mm beyond the capsular border, the tumor is termed “minimally invasive”. Carcinomatous elements that extend beyond this threshold is termed “widely invasive”.1 This threshold is greater than the previous threshold of 1.5 mm recommended in an earlier edition of the WHO classification although the present edition does state that this threshold is preliminary and requires further validation.1,2,4 It has to be pointed out though that quantifying invasion may not always be possible in tumors that have positive margins, those that are intrinsically unencapsulated such as minor salivary gland tumors, and those with complex multinodular growth patterns such as in recurrent pleomorphic adenoma.1 This difficulty has to be stated in the report and what conditions preclude quantifying the degree of invasion.
 
 Non-invasive carcinoma ex pleomorphic adenoma has quite a good outcome with very low reported rates of recurrence or regional metastasis. In a review of thirty cases and a report of an additional three cases, only one case showed recurrence or metastasis.3 This favorable outcome certainly contrasts with that of the widely invasive type where metastasis is reported to occur in up to 70% of cases.1 Another review of ten cases showed one case developing metastasis, and recommended that non-invasive cases should thus still be followed up closely after primary treatment because regional or distant metastasis can occur.2 
 
 To the best of our knowledge, there are no published local data on the incidence of early malignant transformation of pleomorphic adenomas in the Filipino population. Hence, we take this opportunity to report this case. Awareness of the entity and prudent liberal sampling of these tumors may help address this gap.

Epithelial myoepithelial carcinoma arising in a pleomrophic adenoma

Epithelial–myoepithelial carcinoma (EMC) is a rare and low-grade malignant tumor of the salivary gland. We present a case of a 37-year-old male with good general condition with swelling in the right preauricular region for the past 3 years measuring 3 cm × 2 cm with intact facial nerve. This patient had a history of preauricular sinus excision surgery 15 years ago. EMC mostly occurs in elderly females. Rarity of our case is in the fact that it has occurred in a middle-aged male with histologic evidence of preexisting pleomorphic adenoma.

Comprehensive Genomic Profiling and Precision Pathology for Clinically Advanced Salivary Gland Myoepithelial Carcinoma

Myoepithelial carcinomas of salivary glands (MyC) are generally low-grade malignancies that can arise de novo or in the background of a pre-existing pleomorphic adenoma (CPA). However, on occasion, MyC can present or progress into inoperable locally advanced and/or metastatic disease. DNA was extracted from 40 microns of FFPE sections from 24 cases of relapsed, refractory and metastatic MyC. Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation-based next-generation sequencing assay. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA), including base substitutions (sub), insertions and deletions (short variants), fusions, and copy number changes including amplifications (amp) and homozygous deletions. At the time of CGP, 10 (42%) MyC were stage III and 14 (58%) were stage IV. Of 22 cases where the primary site was known, 16 (73%) arose in the parotid, 1 (5%) in the submandibular SG, and 5 (22%) from accessory SG.Tabled 1Abstract 247MyC cases24Genomic alterations (GA)/case2.3Clinically Relevant GA (CRGA)RICTOR amp & PIK3CA sub (21% each) PTCH1 & PDGFRB sub (8 % each) NF1 & BRCA2 sub (4% each)Non-actionable GACDKN2A loss (25%) CDKN2B & HRAS sub (21% each) TERT, MYC, TP53 & NOTCH1 subs (13% each)TMB > 20 Mut/Mb2 (8%)TMB < 10 Mut/Mb22 *(92%)* No cases of ERBB2 GA and no cases of MSI-high status. Open table in a new tab * No cases of ERBB2 GA and no cases of MSI-high status. Clinically advanced MyC are similar to the usually less aggressive SG tumors, adenoid cystic, and acinic cell carcinomas in having a low frequency of GA, a low TP53 mutation frequency, low TMB, and general paucity of CRGA when compared to the usually more aggressive adenocarcinomas which may feature targetable driver alterations in ERBB2 and other pathways. However, the findings of potentially targetable alterations in RICTOR, PTCH1, NF1, and BRCA2 and the presence of high TMB, albeit in a relatively small percentage of MyC cases, encourage the continued use of CGP.

Epithelial-Myoepithelial Carcinoma: Frequent Morphologic and Molecular Evidence of Preexisting Pleomorphic Adenoma, Common HRAS Mutations in PLAG1-intact and HMGA2-intact Cases, and Occasional TP53, FBXW7, and SMARCB1 Alterations in High-grade Cases.

We hypothesized that there is a relationship between the preexisting pleomorphic adenoma [PA]), histologic grade of epithelial-myoepithelial carcinomas (EMCAs), and genetic alterations. EMCAs (n=39) were analyzed for morphologic and molecular evidence of preexisting PA (PLAG1, HMGA2 status by fluorescence in situ hybridization, FISH, and FGFR1-PLAG1 fusion by next-generation sequencing, NGS). Twenty-three EMCAs were further analyzed by NGS for mutations and copy number variation in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, the following subsets of EMCA emerged: (a) EMCAs with morphologic evidence of preexisting PA, but intact PLAG1 and HMGA2 (12/39, 31%), (b) Carcinomas with PLAG1 alterations (9/39, 23%), or (c) HMGA2 alterations (10/39, 26%), and (d) de novo carcinomas, without morphologic or molecular evidence of PA (8/39, 21%). Twelve high-grade EMCAs (12/39, 31%) occurred across all subsets. The median disease-free survival was 80 months (95% confidence interval, 77-84 mo). Disease-free survival and other clinicopathologic parameters did not differ by the above defined subsets. HRAS mutations were more common in EMCAs with intact PLAG1 and HMGA2 (7/9 vs. 1/14, P<0.001). Other genetic abnormalities (TP53 [n=2], FBXW7 [n=1], SMARCB1 deletion [n=1]) were seen only in high-grade EMCAs with intact PLAG1 and HMGA2. We conclude that most EMCAs arose ex PA (31/39, 80%) and the genetic profile of EMCA varies with the absence or presence of preexisting PA and its cytogenetic signature. Progression to higher grade EMCA with intact PLAG1 and HMGA2 correlates with the presence of TP53, FBXW7 mutations, or SMARCB1 deletion.

Carcinosarcoma of the submandibular gland with a rhabdomyosarcoma component: A case report and review of the literature

Carcinosarcoma of the salivary gland is a rare and aggressive malignancy with a poor prognosis. These neoplasms are composed of malignant epithelial and mesenchymal elements. This report describes a new case of carcinosarcoma arising in the submandibular gland, which had a rhabdomyosarcoma component, without clinical or histological evidence of a preexisting pleomorphic adenoma. Till date, only two case reports have described the occurrence of carcinosarcoma with a rhabdomyosarcoma component in the salivary gland, to the best of our knowledge. Histological and immunohistochemical results are presented. The literature is reviewed, and the possible histogenesis and pathogenesis of carcinosarcoma (true malignant mixed tumor) of the salivary gland are briefly discussed.

Carcinosarcoma ex Pleomorphic Adenoma of the Submandibular Gland in a 64-Year-Old Man: A Case Report

Carcinosarcoma (CS) is a rare tumor, consisting of both carcinomatous and sarcomatous components. In this paper, we present a case of CS arising from a pleomorphic adenoma (PA) of the submandibular gland. A 64-year-old Japanese man presented with a left submandibular mass that had developed for 20 years with complaints of pain for the last 3 months. Magnetic resonance imaging showed a lesion involving the left submandibular gland. The patient underwent total dissection of the left submandibular gland and left cervical lymph nodes. Upon gross examination, the mass appeared completely covered by fibroadipose tissue measuring 46×42×45 mm; sectioning revealed a solid-white nodule with central bleeding and necrosis, invading into the surrounding adipose tissue. Microscopically, the presence of carcinomatous and sarcomatous components in the fibro-myxomatous stroma was detected, suggestive of pre-existing PA. The carcinoma component was diagnostic of salivary adenocarcinoma, not otherwise specified, whereas the sarcomatous component exhibited features of osteosarcoma characterized by formation of osteoid. As the border between the carcinomatous and sarcomatous components was not evident, CS may have occurred via transformation of the carcinoma into sarcoma. Tumor metastasis was detected in the cervical lymph nodes. Immunohistochemically, AE1/AE3 expression was noted in the carcinomatous component, but not in the osteosarcoma component. Both components were diffusely positive for vimentin. Four months after the operation, the patient developed a metastatic CS lesion in the lung, suggesting tumor aggression.

Abstract 4662: Expression of PLAG1 in salivary duct carcinomas: its efficacy of the distinction of carcinoma ex pleomorphic adenoma type and de novo type

Abstract Salivary gland duct carcinoma (SDC) is one of the high-grade salivary gland carcinoma, classified into two patterns; i) carcinoma ex pleomorphic adenoma (Ca-ex-PA) type, which is derived from benign pleomorphic adenoma (PA), ii) de novo type, which is generated from normal salivary gland tissue. According to current WHO classification, Ca-ex-PA is diagnosed when pathological examination proves as follows, a) the mixture of the component of cancer cells and that of pre-existing PA cells, b) the existence of malignant cells after the resection of PA. However, current criteria cannot entirely be accurate from the viewpoint of disease onset. For example, i) if a benign component of PA is replaced completely by Ca-ex-PA, the Ca-ex-PA type can be misdiagnosed as de novo type because histopathological examination cannot clarify the existence of PA in its surgery specimen. Moreover, ii) if a de novo type SDC, arising from normal salivary tissue, is growing and infiltrate to the preexisting PA, the de novo type can be misdiagnosed as Ca-ex-PA type. Recently, Pleomorphic adenoma gene 1 (PLAG1) has been identified as the gene associated with tumorigenesis of PA. Subsequently, the overexpression of PLAG1 protein has been reported to be observed in both PAs and Ca-ex-PAs and useful for diagnosis of them. Thus, we considered that PLAG1 immunohistochemistry can enable us to distinguish Ca-ex-PA type and de novo type in SDCs more definitively. In this study, 23 SDC patients who underwent primary surgery for cancer at our institution were enrolled, including 14 Ca-ex-PA types and 9 de novo types. In each case, we had its formalin-fixed-paraffin-embedded tissue sample stained for PLAG1-antibodies (clone 3B7, Mouse mAb, 1:100, Abnova) and evaluated PLAG1 protein expression in the component of glandular-epithelial component and that of non-glandular-epithelial, respectively. PLAG1 immunostaining was scored as positive when the more than 10% nuclear staining of tumor cells are observed. In all 23 SDCs, there was no PLAG1 protein overexpression in glandular-epithelial component, irrespective of benign or malignant. In all 14 Ca-ex-PA types, positive findings of PLAG1 overexpression were observed in non-glandular-epithelial component. In all 9 de novo types, no non-glandular-epithelial component showed any signs of PLAG1 protein overexpression. There was no discrepancy of conventional criteria and the status of PLAG1, which are the cases; i) Ca-ex-PA which is misdiagnosed as de novo type, ii) de novo type which is misdiagnosed as Ca-ex-PA type. Conclusions : There is no difference between conventional criteria and PLAG1-based criteria in our cases. However, in the cases with obscure characteristics of PA morphologically, such as mucoid/myxoid or cartilaginous-like materials, findings of PLAG1-positive cells can help us to distinguish Ca-ex-PA type from de novo type more definitively. Citation Format: Takayoshi Suzuki, Satoshi Kano, Kanako Hatanaka, Yutaka Hatanaka, Tomohiro Sakashita, Takatsugu Mizumachi, Hiromitsu Hatakeyama, Akihiro Homma, Yoshihiro Matsuno, Satoshi Fukuda. Expression of PLAG1 in salivary duct carcinomas: its efficacy of the distinction of carcinoma ex pleomorphic adenoma type and de novo type [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4662. doi:10.1158/1538-7445.AM2017-4662

Carcinoma ex pleomorphic adenoma of the infratemporal fossa: a case report with magnetic resonance imaging findings

The infratemporal fossa is the deep retromaxillary space that corresponds to the inferior aspect of the middle cranial fossa. Although tumors of the infratemporal fossa are uncommon, a variety of neoplasms have been reported to involve this area. They include nasopharyngeal carcinomas, juvenile angiofibromas, and adenoid cystic carcinomas. Rarely, a pleomorphic adenoma (PA) is seen, although carcinoma ex PA, a malignant tumor of the salivary glands arising in a preexisting PA, has not been reported in the literature. Factors affecting the malignant transformation of a PA include tumor recurrence, the age of the preexisting tumor, radiation therapy, advanced age of the patient, and tumor size. Here, we present the case of a 40-year-old woman with carcinoma ex PA of the infratemporal fossa with its associated computed tomography and magnetic resonance imaging findings.

Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.

The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA). SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033). The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. © 2016 American Cancer Society.

Salivary Duct Carcinoma of the Deep Lobe of the Parotid Gland: A Rare Clinical Finding.

Salivary Duct Carcinoma of the Deep Lobe of the Parotid Gland: A Rare Clinical Finding.

Clinicopathological characteristics and cell cycle proteins as potential prognostic factors in myoepithelial carcinoma of salivary glands.

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).

Carcinoma ex-pleomorphic adenoma of the salivary glands has a high risk of progression when the tumor invades more than 2.5 mm beyond the capsule of the residual pleomorphic adenoma.

Carcinoma ex-pleomorphic adenoma (CPA) is subclassified based on the extent of penetration of the malignant component beyond the fibrous capsule of the pre-existing pleomorphic adenoma (PA). These subclasses are considered to be prognostically significant since the non-invasive/minimally invasive groups have an excellent outcome. Nevertheless, there is no consensus as to the cutoff value to distinguish between minimal and wide invasion, even though the 2005 WHO classification defines 1.5 mm as cutoff. The objective of this study is to evaluate a consecutive series of CPA, in order to establish what the effect is of the extent of extra-capsular invasion on prognosis. Fifty-eight cases of CPA were reviewed to obtain demographic and pathological information. Extent of invasion was measured. Eleven cases were non-invasive, 9 had ≤1.5 mm invasion, and for the remainder, the depth of invasion ranged between 2.5 and >10 mm. Distant metastases or death did not occur in the first two groups. In the group with ≥2.5 mm invasion, 15 patients had progressive disease and 9 of them died. The minimum extent of invasion associated with tumor progression and death was 2.5 mm. Two histologically non-invasive carcinomas had regional lymph node metastasis. CPA with ≤1.5 mm depth of invasion has good prognosis. Nevertheless, the lymph node metastases found in two cases of this group question the concept that intracapsular/minimally invasive CPA has a prognosis similar to that of PA. The minimum extent of invasion associated with death was 2.5 mm, which is at variance with findings in other recent series. Thirteen cases with depth of invasion exceeding 2.5 mm did well, confirming that additional factors should be considered in the clinical management of these patients.

Mucoepidermoid Carcinoma Associated with Osteosarcoma in a True Malignant Mixed Tumor of the Submandibular Region.

Introduction. True malignant mixed tumor, also known as carcinosarcoma, is a rare tumor of the salivary gland composed of both malignant epithelial and malignant mesenchymal elements. Frequently carcinosarcoma arises in the background of a preexisting pleomorphic adenoma; however, if no evidence of benign mixed tumor is present, the lesion is known as carcinosarcoma “de novo.” We reported the first case of true malignant mixed tumor of the submandibular gland composed of high grade mucoepidermoid carcinoma associated with osteosarcoma. Case Presentation. A 69-year-old Caucasian male came to our department complaining of the appearance of an asymptomatic left submandibular neoformation progressively increasing in size over 3 months. We opted for surgical treatment. Histological examination confirmed the diagnosis of carcinosarcoma with the coexistence of high grade mucoepidermoid carcinoma and osteosarcoma. Conclusion. To the best of our knowledge, in the true malignant mixed tumor of the submandibular gland, mucoepidermoid carcinoma associated with osteosarcoma has never been previously reported.

Carcinosarcoma of submandibular salivary gland: our experience of a rare tumour with review of literature

Carcinosarcoma arising from the submandibular gland is a very rare pathologic entity. Rarity of tumour makes the treatment recommendations difficult. We share our experience of a 76 year old gentleman who presented with a swelling in right submandibular region which was present since last fifteen years and increased over last one month. Fine needle aspiration cytology was done preoperatively which was suggestive of salivary gland carcinoma. After investigating properly a diagnosis of malignant tumour arising from submandibular gland was made and he underwent submandibular gland fossa clearance with ipsilateral modified radical neck dissection. Post-operative histopathology with immunohistochemistry correlation was suggestive of carcinosarcoma arising from pre-existing pleomorphic adenoma of submandibular gland. He received radiotherapy as adjuvant treatment.