Benign Mixed Tumor Research Articles

Association of histological features with potential risk factors and survival in canine mammary tumors

Veterinaria México OA ISSN: 2448-6760Cite this as:Salas Araujo YJ, Aburto E, Alonso R, Márquez Alvarado AA, Corona Monjaras H, Romero Romero L. Association of histological features with potential risk factors and survival in canine mammary tumors. Veterinaria México OA. 2016;3(1). doi: 10.21753/vmoa.3.1.359The epidemiological and clinicopathological features of canine mammary tumors may provide valuable information to facilitate analysis of the behavior of the disease and represent a potential tool for the study of breast cancer in women. The aim of this study was to associate the histological features of canine mammary tumors with potential risk factors and survival. One hundred and seventy-eight mammary tumors were collected from 80 female dogs. The statistical analyses consisted of a series of univariate studies and frequencies of the different study variables, such as a bivariate analysis with the Chi squared test (χ2), a relative risk and Kaplan Meier survival analysis, and a multiple correspondence analysis was used to correlate the tumor’s biological behavior with the dogs’ breed. Most patients were older than 8 years and had at least one malignant tumor, which was usually solitary and measured more than 6 cm; these patients had poor survival. The most frequent tumors were a complex adenoma, benign mixed tumor, carcinoma complex and mixed type carcinoma. The most commonly affected breeds were Poodle, Cocker Spaniel and Dachshund, and the breeds at the highest risk of tumor development were Cocker Spaniel, Labrador Retriever and German Shepherd. Overall, the data indicated that mammary tumors in dogs mainly affected older females with malignant tumors and that there were high mortality and short-term survival rates. However, the most commonly affected breeds were not necessarily the most susceptible. Our data do not support the hypothesis of an increased risk of canine mammary tumors in nulliparous female dogs.Figure 1. Frequency of canine mammary tumors according to their size (cm).

Chondroid Syringoma of the Hypothenar Region.

To the Editor, Chondroid syringoma (CS) is a benign adnexal tumor of eccrine/apocrine sweat glands. CS constitutes of 0.01–0.1% of primary skin tumors (1). CS is usually seen in elderly males as a painless, slowly growing, well demarcated subcutaneous/intradermal nodular lesion originating from the skin of the region of the head and neck, especially the cheek, nose and lip (2). Rare localization areas are the axillary region, abdomen, trunk, genitalia and extremities (1,2). There are a few case reports defining the cytological characteristics of CS in the English language literature (2–5). A 30 year-old female patient was admitted because of a slowly growing painless swelling in the right hypothenar region for 5 years (Figure 1). The swelling was in a character of well demarcated subcutaneous nodular lesion. Aspiration smears had moderate cellularity with mild nuclear pleomorphism. Single or small groups of tumor cells with slightly eccentric nuclei on chondromyxoid matrix were noticed (Figure 2). The cytological findings reminded benign mixed tumor of salivary glands. We reported the case as a benign tumoral lesion with chondroid matrix. The excised lesion was a well demarcated and partially capsulated nodular lesion with bright, solid gray-white colored cut-section. The lesion had dimensions of 2.5×2×1.5 cm. Microscopy showed an intradermal/subcutaneous tumoral lesion consisting of small clusters or short chords of benign epithelial or myoepithelial cells in chondromyxoid matrix. There were no findings of necrosis, atypical mitoses, meaningful nuclear pleomorphism and vascular invasion. We diagnosed CS on the basis of the histopathological findings. No recurrence was observed 3 years after the excision. Informed consent was obtained from the patient. FIG. 1. A subcutaneous nodular lesion with overlying intact skin on right hypothenar region FIG. 2. a, b. Groups of the cells with monomorphic and mildly eccentric nuclei, amphophilic staining cytoplasm in chondromyxoid stroma on aspiration smears (MGG, ×20) (a), tumor cell cords and groups intermingled with myxoid stroma (HE, ×15) (b) ... Despite CS usually being benign tumors, malignant forms have been also reported (1,2). Malignant forms usually localize on the trunk and extremities and are mostly seen in young women. They are rapidly growing masses and their diameters are larger than 3 cm. Erosion/ulceration of the overlying skin is frequent. Mortality rates are high due to metastasis to the lung in malignant forms. Histological evidences of malignancy and satellite nodules favor the diagnosis of malignant CS (1,2). Chondroid syringoma should be differentiated from other subcutaneous tumoral lesions. Some of these lesions are dermoid cysts, sebaceous cysts, peripheral nerve sheet tumors (PNST), lipoma, hemangioma, dermatofibroma and pilomatrixoma, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, myxofibrosarcoma and malignant PNST (1,2). The diagnosis is usually made by histopathological examination. However, there are only a few reports describing the cytological characteristics of CS (2–5). The presence of uniform plasmacytoid cells and myoepithelial cells in the chondromyxoid matrix favor the cytological diagnosis of CS (2). These findings may also be seen on aspiration smears obtained from mesenchymal tumors, especially chondroid tissue tumors. Cytological discrimination between malignant CS and sarcomas is very difficult. The age of our case and localization of the mass were not usual for benign CS. However, there were no histological/cytological and clinical evidences of malignancy. Some cases may be overlooked in routine practice. Hence, if aspiration smears from a subcutaneous nodular lesion show plasmacytoid cells in a chondromyxoid matrix, CS should be considered in the spectrum of differential diagnosis.

Pleomorphic adenoma of the upper lip: a case report and review of literature

<p>Pleomorphic Adenoma is a benign epithelial tumor arising from the salivary gland. It is a benign mixed tumor composed of epithelial and myoepithelial cells arranged with various morphological patterns, demarcated from surrounding tissues by fibrous capsule. In this article, we report an unusual case of 30 year, male with a single, nodular swelling evident in the upper lip which was discovered during a routine dental procedure. Fine Needle Aspiration Cytology (FNAC) was planned for the patient, where a of cytological diagnosis of Pleomorphic Adenoma was rendered, which was confirmed by biopsy. Hence, this highlights, FNAC makes up an important diagnosing tool as the first line of investigation to distinguish between benign and malignant salivary gland neoplasms.</p>

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.

Clinical Outcomes of Surgically Managed Spontaneous Tumors in 114 Client-owned Dogs

Medical records of 139 tumors from 114 dogs that underwent surgery from May 2010 through March 2015 were retrospectively reviewed. Among 114 dogs, females (64.9%) were significantly more common than males (35.1%) (p<0.05). Dogs aged 6 to 10 years were more presented than non-tumor patients, however, there was no significant difference. The mean age (±SD) was 10.3±3.0 years. Although we found no significant difference of breed predisposition, the most common breed was Maltese (19.3%), followed by Shih-Tzu (14.0%), and Yorkshire terrier (13.2%). Proportional morbidity ratios (PMRs) of mammary gland, oral cavity, and skin tumors were high in Poodles, Yorkshire terriers, and Golden retrievers, respectively. Mammary gland (36.0%) was the most common site, followed by skin and soft tissues (12.2%), oral cavity (10.8%), and digestive organs (8.6%), but there was no significant difference. The objectives of surgery were curative surgery (86.2%), biopsy (4.9%), and palliative surgery (6.5%). In this study, 123 of 139 tumors had histopathological diagnoses. Adenocarcinoma was the most common type (n=24), followed by adenoma (n=17), soft tissue sarcoma (n=13), benign mixed tumor (n=5), and others (n=64). Recurrence or suspected metastasis was identified in 26 dogs. Median survival times of malignant mammary gland tumors, skin and subcutaneous tumors, and splenic tumors were 1,563.0±1,201.7, 469, and 128 days, respectively.

B-mode Echotexture Analysis and Color Doppler Sonography in Canine Mammary Tumors

Forty-one mammary gland tumors from twenty eight bitches were used for the study. Ultrasonographic examinations of tumor masses were performed before surgical excision and a quadratic region-of-interest (ROI) was chosen randomly on B-mode tumor images for the echotexture analyses. All tumors were evaluated histopathologically after surgery. Contrast (CONT), Mean Gradient (MG), Mean Value (MV), Homogeneity (HOM), Entropy (ENTR) and Gray Value (GV) parameters were used for the texture analyses of ultrasonographic images. Ultrasonographic image characteristics were additionally evaluated by the following macroscopic patterns: tumor shape, invasion of tumor to surrounding tissue, tumor border sharpness, echogenicity of tumor, hyperechogenic artifact, anechogenic artifact, and shadow around tumor. After B-mode ultrasonographic examination, Pulsatility Index (PI), Resistive Index (RI), Peak Systolic Flow Velocity (Vmax) and Number of Color Pixel (CP) parameters were evaluated by means of color Doppler sonography. Statistical analysis of the HOM and GV parameters indicated that there was a significant difference between benign (3.10 and 1.14) and malignant tumors (1.54 and 0.57; P<0.01). Besides, a significant difference was found between images of MalignantMixed Tumors (MMT) and Benign-Mixed Tumors (BMT) with regard to CONT and HOM (p< 0.001). In addition, MV was significantly higher in malignant tumors in comparison to the benign cases (P<0.05). A significant negative correlation was found between tumor size and MV in malignant tumor and adenocarcinoma cases (-0.991/ P<0.05; -0.999/P<0.01, respectively). On the other hand, there was a positive correlation between tumor size and GV (0.961/P<0.05) in malignant tumors.

Relationship between the expression of versican and EGFR, HER-2, HER-3 and CD44 in matrix-producing tumours in the canine mammary gland.

Versican is an extracellular matrix proteoglycan that has been identified as a modulator of adhesion loss, cell motility, and tumour progression. This motility results from the interaction between versican and cell surface receptors. Studies have also demonstrated the relationship between this molecule and invasion in canine mammary tumours. Given the evidence for the participation of proteoglycans in tumour progression, this study aimed to assess versican expression and its association with cell surface receptors; human epidermal growth factor receptors 1, 2, and 3 (EGFR, HER-2, and HER-3) and CD44 through an immunohistochemical analysis of benign mixed tumours (BMTs), carcinomas in mixed tumours (CMTs), and carcinosarcomas (CSs) of the canine mammary gland. Malignant tumours were divided into low and high groups with respect to versican stromal expression. The results indicated that the BMTs showed weak stromal versican expression and correlations between the expression of stromal versican and EGFR in the epithelial membrane in benign areas (p=0.013, r=0.571). A higher stromal versican expression was observed adjacent to invasive epithelial areas compared with in situ areas in CMTs and CSs, suggesting a direct relationship between versican expression and invasiveness. Furthermore, the CSs exhibited a higher expression of HER-2, cytoplasmic HER-3, and CD44 in epithelial invasive cells in cases of higher stromal versican expression. Therefore, the cell surface receptors (HER-2, HER-3, and CD44) are more evident in CSs that overexpress versican in stroma adjacent to the invasive areas. These findings suggest that the association between these molecules may be directly related to the biological behaviour and invasiveness of these canine mammary tumours.

The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland

ObjectivesPleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors. DesignThe study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer. ResultsPleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD. ConclusionsSummarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma.

Characterization of Soft Tissue Tumors by Diffusion-Weighted Imaging.

Background:Diffusion-weighted imaging (DWI) is a noninvasive method for investigation of tumor histological content. It has been applied for some musculoskeletal tumors and reported to be useful.Objectives:The aim of the present study was to prospectively evaluate the apparent diffusion coefficient (ADC) values of benign and malignant soft tissue tumors and to determine if ADC can help differentiate these tumors.Patients and Methods:DWI was performed on 25 histologically proven soft tissue masses. It was obtained with a single-shot echo-planar imaging technique using a 1.5T magnetic resonance (MR) machine. The mean ADC values were calculated. We grouped soft tissue tumors as benign cystic, benign solid or mixed, malignant cystic and malignant solid or mixed tumors and compared mean ADC values between these groups.Results:There was only one patient with a malignant cystic tumor and was not included in the statistical analysis. The median ADC values of benign and malignant tumors were 2.31 ± 1.29 and 0.90 ± 0.70 (median ± interquartile range), respectively. The mean ADC values were different between benign and malignant tumors (P = 0.031). Benign cystic tumors had significantly higher ADC values than benign solid or mixed tumors and malignant solid or mixed tumors (p values were < 0.001 and 0.003, respectively). Malignant solid or mixed tumors had lower ADC values than benign solid or mixed tumors (P = 0.02).Conclusion:Our preliminary results have shown that although there is some overlap between benign and malignant tumors, adding DWI, MR imaging to routine soft tissue tumor protocols may improve diagnostic accuracy.

Characterization of Spontaneous Mammary Tumors in Domestic Djungarian Hamsters (Phodopus sungorus).

Mammary tumors that spontaneously occurred in domestic Djungarian hamsters (Phodopus sungorus) were histologically examined. Forty-five mammary tumors included 14 adenomas, 18 adenocarcinomas, 1 lipid-rich carcinoma, 2 adenoacanthomas, 2 malignant adenomyoepitheliomas, 1 benign mixed tumor, and 7 "balloon cell" carcinosarcomas. The latter 4 types were newly recognized neoplasms in Djungarian hamsters. The relatively high incidence of spontaneous mammary carcinosarcomas in domestic Djungarian hamsters is intriguing. Carcinosarcomas exhibited anomalous histological features made up of a mixture of glandular cells, polygonal cells (including "balloon cells"), and sarcomatous spindle cells in varying proportions. Transitional features from glandular cells to polygonal cells and subsequently to sarcomatous spindle cells were observed. Using immunohistochemistry, we observed that glandular cells exhibited an epithelial phenotype (cytokeratin(+)/vimentin(-)), spindle cells exhibited a mesenchymal phenotype (cytokeratin(-)/vimentin(+)), and polygonal cells exhibited an intermediate phenotype (cytokeratin(+)/vimentin(+)). Reduction or loss of β-catenin expression and gain of S100A4 expression were observed in polygonal and spindle cells. The polygonal cell population included a varying number of characteristic cells that were expanded by large intracytoplasmic vacuoles. Electron microscopy revealed that these "balloon cells" had large cytoplasmic lumens lined by microvilli. These observations suggest that epithelial-mesenchymal transition may account for the pathogenesis of mammary carcinosarcomas in Djungarian hamsters.

Defects of the Carney complex gene (PRKAR1A) in odontogenic tumors

The surgical treatment of some odontogenic tumors often leads to tooth and maxillary bone loss as well as to facial deformity. Therefore, the identification of genes involved in the pathogenesis of odontogenic tumors may result in alternative molecular therapies. The PRKAR1A gene displays a loss of protein expression as well as somatic mutations in odontogenic myxomas, an odontogenic ectomesenchymal neoplasm. We used a combination of quantitative RT-PCR (qRT-PCR), immunohistochemistry, loss of heterozygosity (LOH) analysis, and direct sequencing of all PRKAR1A exons to assess if this gene is altered in mixed odontogenic tumors. Thirteen tumors were included in the study: six ameloblastic fibromas, four ameloblastic fibro-odontomas, one ameloblastic fibrodentinoma, and two ameloblastic fibrosarcomas. The epithelial components of the tumors were separated from the mesenchymal by laser microdissection in most of the cases. We also searched for odontogenic pathology in Prkar1a(+) (/) (-) mice. PRKAR1A mRNA/protein expression was decreased in the benign mixed odontogenic tumors in association with LOH at markers around the PRKAR1A gene. We also detected a missense and two synonymous mutations along with two 5'-UTR and four intronic mutations in mixed odontogenic tumors. Prkar1a(+) (/) (-) mice did not show evidence of odontogenic tumor formation, which indicates that additional genes may be involved in the pathogenesis of such tumors, at least in rodents. We conclude that the PRKAR1A gene and its locus are altered in mixed odontogenic tumors. PRKAR1A expression is decreased in a subset of tumors but not in all, and Prkar1a(+) (/) (-) mice do not show abnormalities, which indicates that additional genes play a role in this tumor's pathogenesis.

Association of Immunolocalization of Ezrin and Podoplanin in Benign Epithelial and Mixed Odontogenic Tumours

Association of Immunolocalization of Ezrin and Podoplanin in Benign Epithelial and Mixed Odontogenic Tumours

The role of Nrf2 in pathology of pleomorphic adenoma in parotid gland.

BackgroundPleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, the processes involved in its carcinogenesis are not well defined. This study aimed to define the contribution of Nfr2 (nuclear factor (erythroid-derived 2)-like 2) to pleomorphic adenoma pathology. The Nrf2-controlled gene system is one of the most critical cytoprotective mechanisms, providing antioxidant responses.Material/MethodsThe study was carried out in pleomorphic adenoma and control parotid gland tissues, investigating gene expression of NFE2L2, as well as KEAP1 (Kelch-like ECH-associated protein 1) and NQO1 (quinone oxidoreductase), at mRNA and protein (immunohistochemistry) levels. Functional evaluation of Nrf2 system in the parotid gland was evaluated in HSY cells (human parotid gland adenocarcinoma cells).ResultsPleomorphic adenoma specimens showed cytoplasmic and nuclear Nfr2 expression in epithelial cells, as well as more variable lower Nrf2 level in mesenchymal cells. In the parotid gland, Nrf2 was expressed in cytoplasm of serous, mucous, and duct cells. Nuclear Nrf2 expression was predominantly seen in serous cells, whereas mucous and duct cells were mostly negative. Comparable mRNA levels of NFE2L2 and NQO1 genes and significantly higher expression of KEAP1 in pleomorphic adenoma were seen. HSY cell incubation with oltipraz demonstrated significant elevation of NFE2L2 after 24 and 48 hours of stimulation, whereas NQO1 was elevated, but significantly only after 24 hours, and KEAP1 expression remained unchanged.ConclusionsSummarizing both in vitro and in vivo observations, it can be stated that Nrf2 may play a role in the pathology of pleomorphic adenoma.

Peer review report 1 on “Rare benign mixed tumour of the upper lip: A case report”

Peer review report 1 on “Rare benign mixed tumour of the upper lip: A case report”

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.

Peer review report 2 on “Rare benign mixed tumour of the upper lip: A case report”

Peer review report 2 on “Rare benign mixed tumour of the upper lip: A case report”

Giant Parapharyngeal Space Pleomorphic Adenoma of the Deep Lobe of Parotid Presenting as Obstructive Sleep Apnoea: A Case Report & Review of the Diagnostic and Therapeutic Approaches.

Salivary gland tumours constitute about less than 4 % of all head and neck tumours. Pleomorphic adenoma, also called benign mixed tumour, is the most common tumour of the salivary glands. About 80-90 % of these tumours occur in the major salivary gland mainly parotid gland and 10 % of them occur in the minor salivary glands. Aim of this case report is to discuss the unique case of giant parotid pleomorphic adenomas arising in the deep lobe involving the parapharyngeal space and difficulty in respiration at sleep during nights repoted at this institute. The patient was undergoing treatment for obstructive sleep apnea syndrome when she reported at this institute for disturbed sleep. Diagnosis was based on computed tomography scan and magnetic resonance imaging and cytology by means of fine needle aspiration biopsy. An exhaustive pre-operative diagnostic algorithm is mandatory before approaching such lesions involving parapharyngeal space. Fine needle aspiration biopsy is, in our opinion, mandatory to avoid histological surprises. The surgical approach varies according to the location of the tumour and should provide excellent visibility with wide surgical exposure to secure local neurovascular structures.

Recurrent Pleomorphic Adenoma: a Case Report

Salivary gland tumors are rare, comprising less than 3% of all neoplasia of the head and neck region. Pleomorphic adenoma, also known as benign mixed tumor is the most common tumor of the salivary gland accounting for 60-80% of the benign variety. The tumor is almost always solitary and is usually found as a firm, mobile, painless slow growing mass. Multiple or bilateral pleomorphic adenomas are rare. After surgical resection, up to 43% of patients are at risk of recurrence, even as late as 45 years after the initial surgery. Here we report a case of recurrent pleomorphic adenoma in a 34-year-old male patient on the right side.

Fine needle aspiration cytology of a myoepithelioma presenting as a thyroid nodule

Myoepitheliomas are rare neoplasms that are typically found in the major and minor salivary glands and represent approximately 1.5% of all salivary gland neoplasms. We present a patient with an exophytic anterior midline neck mass, which was initially believed to be a thyroid isthmus nodule that underwent fine needle aspiration (FNA) biopsy. FNA cytologic evaluation reveals numerous plump spindle cells and a myxoid background, thus raising the possibility of rare benign mixed tumor of the thyroid. However, the resected specimen consists of predominately spindle cells with a minor component of chondromyxoid matrix, and no ductal epithelial cells, favoring a diagnosis of myoepithelioma. Although this lesion clinically and radiologically appeared to arise from the thyroid gland, at the time of resection, it was found to be adjacent to the thyroid isthmus and was ultimately diagnosed as a soft tissue myoepithelioma of the midneck.

The Role of Extracapsular Dissection for Benign Parotid Tumors

Surgical treatment of benign parotid tumors has been debated for decades. Extracapsular dissection (ECD) differs markedly from classic surgical approaches to the parotid neoplasm because facial nerve dissection is not performed. ECD, its advantages, disadvantages, indications, and contra-indications for benign tumors with an emphasis on benign mixed tumor will be comprehensively explored in this chapter. Factors noted to favor this approach include mobility of the tumor within the gland, a thin covering of capsule and glandular tissue, and a tumor large enough to allow digital manipulation during dissection. Imaging, fine needle aspiration cytology, and neuro-monitoring play a heightened role in ECD. Recurrence and permanent facial nerve dysfunction with ECD are not higher in high volume centers performed by experienced surgeons. Transient facial nerve dysfunction, Frey’s syndrome, sensory deficits, and sialocele are lower with ECD. Devastating adverse outcomes of permanent facial nerve dysfunction and recurrence should be considered by the occasional and inexperienced parotid surgeon.