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Triple-negative tumors are characterized immunohistochemically by the absence of positivity to sex hormone receptors and to human epidermal growth factor receptor 2. Additionally, they are differentiated into basal-like and non-basal (or null) subtypes, based on the presence of basal cytokeratin expression (CK5/6, 14, and17). Triple-negative subtypes are yet to be characterized in male dogs, to our knowledge. We report herein the clinical and pathologic findings and molecular characterization of carcinoma in the mammary glands of 2 male dogs. Case 1 was diagnosed as a grade II tubulopapillary carcinoma; case 2 was diagnosed as a grade II carcinoma in a mixed tumor. The tumors were characterized phenotypically as triple-negative basal and triple-negative non-basal, respectively.

Odontoameloblastoma (OA) is a mixed odontogenic tumor that is an ameloblastoma with concurrent histologic evidence of odontoma differentiation. As a mixed tumor, OA is a tripartite lesion comprised of neoplastic odontogenic epithelium, induced dental ectomesenchyme (dental pulp), and mineralized dental matrix. Although rare, OA represents a diagnostic conundrum, as it is histologically closely related to 2 other mixed odontogenic tumors: odontoma (complex and compound) and ameloblastic fibro-odontoma. Herein we describe an OA arising from the mandible of a 4-mo-old Fischer 344 rat that had been exposed in utero to the mutagen ENU (N-ethyl-N-nitrosourea), and a naturally occurring lesion in a 2-y-old Appaloosa horse. In order to satisfy the diagnostic criteria for this lesion, mineralized dental matrix in relationship to neoplastic odontogenic epithelium must be identifiable within the OA lesion. This group of odontogenic tumors is differentiated by the degree to which the dental matrix is organized and the relative proportions of pulp ectomesenchyme, odontogenic matrix, and odontogenic epithelium.

Purpose Uterine papillary serous carcinoma (UPSC) is an atypical variant of endometrial carcinoma with a poor prognosis. It is commonly associated with an increased risk of extrauterine disease. The aim of this study was to investigate clinical and pathological characteristics, therapeutic methods, and prognostic factors in women with UPSC. Methods All patients who underwent surgery for UPSC at a single high-volume cancer center between January 1995 and December 2010 were retrospectively reviewed. Patients who did not undergo surgical staging and those with mixed tumor histology were excluded. Univariate and multivariate regression models were used to identify the risk factors for overall survival (OS) and progression-free survival (PFS). Results A total of 46 patients were included, the majority of whom having stage I disease (IA, 13 [28.2%] and IB, 12 [26.7%]). Stages II, III, and IV were identified in 5 (10.9%), 8 (17.4%), and 8 (17.4%) women, respectively. Optimal cytoreduction was obtained in 67.3% of patients. Recurrences developed in 8 (17.4%) patients. Multivariate analysis confirmed that lymphovascular space invasion (LVSI) (odds ratio [OR] 26.83, p = 0.003) was the only independent prognostic factor for OS, whereas LVSI and optimal cytoreduction were found to be independent prognostic factors for PFS (OR 6.91, p = 0.013 and OR 2.69, p = 0.037, respectively). The 5-year overall survival rate was 63%. Conclusions Our study demonstrated that LVSI is the only independent prognostic factor for OS, whereas LVSI and optimal cytoreduction are independent prognostic factors for PFS in patients with UPSC

Spindle cell epitheliomas of the vagina are rare benign tumors of uncertain histogenesis. It has been hypothesized that they originate from a pluripotent cell population. Here, we report 2 cases of spindle cell epitheliomas of the vagina. Both patients presented with a painless vaginal nodule. The resected lesions were solid, well circumscribed, and composed of a proliferation of epithelioid or epithelial cells admixed with spindle cells without atypia. The 2 cellular populations expressed epithelial and mesenchymal markers. Based on these morphologic and immunohistochemical findings, a diagnosis of spindle cell epithelioma was rendered in both cases. Furthermore, we describe for the first time the expression of WT-1 (Wilms’ tumor protein 1) and calretinin in addition to the previously defined immunohistochemical profile.

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.

The most common benign salivary gland tumor is the pleomorphic adenoma (PA). They can attain grotesque proportions and weigh several kilograms. They can cause facial disfigurement and, if untreated, could lead to airway compromise. We report a case of a large PA arising from the left submandibular salivary gland in a 20-year-old black female. The lesion measured ∼16 × 15 ×12 cm.

Background Carcinoma ex pleomorphic adenoma (CXPA) is a rare aggressive epithelial malignancy arising from a primary or recurrent benign mixed tumor. Only a few case reports describing the radiologic features of CXPA have been published. Purpose To describe and characterize the magnetic resonance (MR) imaging findings of CXPA in the parotid gland and correlate them with pathologic findings. Material and Methods The MR images of surgically proven CXPA in the parotid gland of five men and five women ranging in age from 28 to 75 years (mean 52 years) were retrospectively reviewed. All MR images were evaluated with emphasis on the size, margin characteristics, extraparotid infiltration, the presence of an encapsulated component, and signal intensity on T2-weighted or short-inversion-time inversion recovery (STIR) images. Results The average maximal diameter was 4.3 cm. All 10 tumors had ill-defined boundaries, and seven tumors showed extraparotid infiltration, reflecting invasive growth of the malignant component identified on histological examination. Eight tumors had a round encapsulated component and seven of those signal intensities were a mixture of hypo- and hyperintensity on T2-weighted or STIR images. Histological correlation of these components revealed fibrously encapsulated tumors containing hyalinization and myxoid tissue, suggesting degenerated pleomorphic adenoma. Invasive malignant components had non-specific and various signal intensities. Conclusion An invasive parotid mass co-existing with a round encapsulated component is suggestive of carcinoma ex pleomorphic adenoma.

Ameloblastic fibro-odontoma is a rare, benign, and slowly growing neoplasm of the jaw composed of proliferating odontogenic epithelium in ectomesenchymal tissue along with dental hard tissue formation. Herein, we describe a case of an ameloblastic fibro-odontoma in 12-year-old female with paresthesia of the chin and lower lip. Panoramic radiography showed a radio-opacity in the right posterior mandible near the mandibular canal and associated with the right mandibular third molar. Histologically, the lesion contained epithelial and mesenchymal odontogenic components in close proximity to odontoma-like elements. Enucleation and curettage of the affected site in the mandible resulted in resolution of the paresthesia postoperatively.

A 13-year-old female llama was presented to the referring veterinarian for swelling and firmness of the right rear mammary gland, for a duration of 2 months, which had been unresponsive to antibiotics. A formalin-fixed wedge biopsy specimen from the affected quarter was submitted to Purdue University Animal Disease Diagnostic Laboratory for histopathology. Histopathologic examination revealed tubulopapillary acinar or solid nest-like clusters of neoplastic epithelial cells surrounded by whorls and sheets of proliferative myoepithelial cells. Histologic criteria for malignancy observed in neoplastic epithelial cells included marked cellular and nuclear atypia, high mitotic index, and numerous bizarre mitoses. The presence of osseous metaplasia in the proliferative mesenchymal component justified classification as a mixed tumor. Positive immunohistochemical staining of neoplastic epithelial cells with anticytokeratin antibody, and proliferative spindloid cells with antiviemtin and antismooth muscle actin antibodies supported the histopathologic diagnosis. The llama was in good health after about 1 year of initial presentation, and metastasis to regional lymph nodes was not reported. Mammary neoplasia is rare in camelids. To the authors' knowledge, this is the first report of a carcinoma in a mixed mammary tumor in a llama.

Pleomorphic adenoma, also known as mixed tumor, is a benign tumor which typically presents as a painless and persistent mass. The majority of pleomorphic adenomas involve the salivary glands, most commonly the parotid gland. Other sites include breast and skin. It is a rare tumor in the vulva. In this article we are reporting a case of pleomorphic adenoma of labia with characteristic pathologic and clinical findings, as reminder of a common benign neoplasm occurring with rare locality.

A 4-year-old native-breed cow had a mass with wide areas of ulceration and hemorrhage at the base of the tail at the same level as the vulva. The tumor was 19 X 13 X 11 cm, appeared red-brown, and was firm to hard, with gritty areas apparent on cut surface. Histologically, the tumor mass was composed of multilayered epithelial cells forming glandular structures with occasional apical blebs and rare solidly packed cells in nests. The stroma included fibrous connective tissue, scattered or periglandular sheets of spindle-shaped cells resembling myoepithelium, several cartilaginous formations, and numerous irregular islands of mineralized osteoid, well-formed bone trabeculae lined by osteoblasts, and many osteoclast-like multinucleated giant cells among or near the neoplastic epithelium. Immunohistochemically, the neoplastic epithelium was positive for pan-cytokeratin (AE1/AE2) and cytokeratin 19 but was negative for cytokeratin 18. Spindle-shaped cells were stained with alpha smooth muscle actin (αSMA) and to a lesser extent vimentin antibodies. The cells of osteogenic lineage and spindle cells closely associated with the osteoid showed strong immunostaining for vimentin but not for αSMA. Immunostaining for neuron-specific enolase and S100 protein was not observed in any component of the tumor mass. These findings suggested that the origin of bone formation was undifferentiated mesenchymal cells with osteogenic potential.

Pleomorphic adenomas account for the majority of parotid masses, typically arising in the tail of the gland and enlarging slowly over time. The vast majority are 2 to 6 cm in size when resected. We report resection of the largest benign mixed tumor recorded in the modern English language literature. An 85-year-old reclusive woman had a 20-year history of an enlarging right periauricular mass that had begun bleeding several days prior to admission. The patient ultimately underwent resection of the mass, which measured 26 cm in diameter, weighed 6.85 kg, and proved on pathologic examination to be a benign mixed tumor without malignant degeneration. The implications of this unusual case for the management of mixed tumors are discussed, and a review of the world literature on giant pleomorphic adenomas is presented.

An interesting case of a traumatic neuroma of the greater auricular nerve provides the impetus for a discussion of head and neck neuromas. Traumatic neuromas of the head and neck are relatively rare. Division of the greater auricular nerve during parotidectomy occasionally results in a traumatic neuroma. We report a case of a 73-year-old woman who presented with a traumatic neuroma nine years after undergoing superficial parotidectomy with dissection of the facial nerve for a mixed tumor. The patient had a 1.5 cm x 1.0 cm mass located below the old surgical site over the anteromedial border of the sternocleidomastoid muscle. The patient's past history was significant for Frey's syndrome, which is the result of abnormal neurologic growth. On first impression, the tumor was thought to be a recurrence of neoplastic disease; however, because of the evaluation, traumatic neuroma was suspected. An attempt at fine-needle aspiration of the mass was too painful to be carried out. At surgery, a whitish tumor was excised which, on final pathologic examination, revealed traumatic neuroma. The surgical literature is reviewed and the subject of head and neck neuromas, including their evaluation and management, is thoroughly discussed. Knowledge of this possible diagnosis may spare the patient and the surgeon needless worry, as well as unnecessary procedures, once tumor recurrence has been ruled out.

Aims and background Various histogenetic mechanisms have been postulated to explain the biphasic carcinomatous-sarcomatous appearance of malignant mixed müllerian tumors (MMMTs), but the nature of these uncommon neoplasms is still unclear. Some evidence would suggest that MMMT displays similarities with sarcomatoid carcinoma, a tumor arising in extragenital sites that also features a mixed appearance. To gain further insight into the histogenesis of this tumor, we have studied by immunohistochemistry a case of uterine MMMT showing an extensive rhabdomyosarcomatous component. Methods A panel of antibodies including reactivity for p53, cytokeratin, vimentin, desmin, muscle actin, epithelial membrane antigen (EMA), myoglobin, type IV collagen, laminin, and tenascin was applied to paraffin tumor sections by means of the avidin-biotin complex technique. Results p53 immunoreactivity was observed in approximately the same number of cells in carcinomatous and sarcomatous tissue. The former stained for vimentin, cytokeratin and EMA, while the latter, in addition to expressing vimentin, desmin, muscle actin and myoglobin, also exhibited immunoreactivity for epithelial markers such as cytokeratin and EMA. At the borders between carcinoma and sarcoma the basement membrane pattern, as seen by staining for type IV collagen and laminin, showed interruptions in correspondence with areas of transition between the two tissues. Antibody to tenascin strongly labeled the sarcomatous tissue immediately around carcinomatous elements. Conclusions A similar immunoreactivity for p53 in both carcinomatous and sarcomatous components, expression of epithelial markers in the sarcomatous cells, and disruption of the basement membrane profile in areas of transition between carcinomatous and sarcomatous tissue, would all suggest, as has been postulated for extragenital sarcomatoid carcinomas, an origin from a common epithelial clone and an epithelial-to-mesenchymal transformation-based mechanism of development for this MMMT. In addition, these findings provide further analogies between these categories of tumors, supporting a unifying nosological concept for MMMTs and sarcomatoid carcinomas of non-genital tract origin.

Pleomorphic adenoma, or mixed tumor of the salivary glands, is a benign tumor originating from the major and minor salivary glands. Eighty-five percent of these tumors are found in the parotid gland, 10% in the minor (sublingual) salivary glands, and 5% in the submandibular gland. It is the most common type of salivary gland tumor, accounting for almost 50% of all neoplasms in these organs. In fact, after the first observation of recurrent loss of chromosome 22 in meningioma, this was the second type of benign tumor for which non-random chromosomal changes were reported. The rate of malignant change with the potential to metastasize has been reported to be only 2 to 3%, and only a few cases of metastasizing pleomorphic salivary gland adenomas have been described to date. The fact that these tumors arise in organs located in an ontogenetic transitional zone, a region where endoderm and ectoderm meet, might be one of the reasons for the often-problematic histopathological classification. This type of benign tumor has been cytogenetically very well-characterized, with several hundreds of tumors karyotyped. In addition to the cytogenetic subgroup with an apparently normal diploid stemline (making up approximately 30% of the cases), three major cytogenetic subgroups can be distinguished. In addition to a subgroup showing non-recurrent clonal abnormalities, another subgroup is composed of tumors with various translocations involving 12ql5. By far the largest cytogenetic subgroup, however, consists of tumors with chromosome 8 abnormalities, mainly showing translocations involving region 8ql2. The most frequently encountered aberration in this group is a t(3;8)(p21;q12).

A 13-year-old male Shetland Sheepdog with progressive exophthalmos had a neoplastic mass in the ocular adnexa. Histologically, this neoplasm was composed of duct-forming epithelial cells with decapitation secretion. Tumor cells invaded the globe through the tunica conjunctiva and replaced the vitreous body. The cornea, iris, ciliary body, and retina were extensively destroyed. Both the epithelial and spindle-shaped myoepithelial cells showed nuclear atypia and mitotic activity in the globe. The primary tumor was diagnosed as adenocarcinoma, probably originating from apocrine sweat glands of the eyelid, and the infiltrating intraocular neoplasm was diagnosed as a malignant mixed tumor.

Bilateral parotid tumors occur very rarely; they account for 0.5 % of 544 cases of parotid tumors recorded at the National Cancer Institute of Milan from 1945 to 1974. Three cases of bilateral tumors are described; two tumors were synchronous and one metachronous. The patients were women of 51, 46 and 52 years. The histologic type was the same on both sides in all cases, namely adenolymphoma, mucoepidermoid carcinoma and mixed tumor respectively. Surgical excision was the treatment of choice; according to the histology of the tumors partial (adenolymphoma) or total parotidectomy (mixed and malignant tumors) was performed. As to the case of mucoepidermoid cancer of both parotid glands no recurrence was observed after five years.

Two cases of lipoma of the tuber cinereum, unexpectedly discovered in the course of autopsy examination, are reported. Each case was thoroughly investigated by serial sectioning of both the diencephalic floor and the tumor. Some peculiar findings observed and a complete survey of the literature revealed that such a growth may be considered an incomplete benign mesenchymoma, i.e., a mixed tumor of mesenchymal derivates, according to Stout (14). The error in development, consisting in the inclusion of embryonal germs of primitive meninx into the nervous system, may occur early during the third month of intrauterine life, at the time of the formation of the primitive septa.

In a lifetime study, female beagle dogs in a closed colony were administered 226radium and 90strontium. An unirradiated control group was included in the study. A total of 223 of 356 dogs at risk developed 1,112 mammary proliferative growths (hyperplastic nodules and neoplasms). There was no correlation between occurrence and types of lesions in radiation and control groups. The age range for first occurrence of lesions was 10.4 to 13.9 years; hyperplastic nodule and benign mixed tumor occurred 1 to 2 years earlier than other lesions. A multiplicity of growths of similar or different morphological type were common throughout the lifetime of the dog. The female beagles, collectively, developed 244 hyperplastic nodules, 78 adenomas, 694 benign mixed tumors, 78 carcinomas, 14 malignant mixed tumors, and four myoepitheliomas. Proliferations occurred with increasing frequency from the cranial to caudal mammary glands. Metastasis was found in 77% of the dogs with carcinoma. The median time from diagnosis to metastasis was 10 months, but was shorter in dogs with infiltrative carcinoma.

Because of the variability of the histological appearance of a given mixed tumor of the salivary gland and because of “recurrences” following less than total removal, biologically benign (not capable of metastasis) mixed tumors have been considered malignant. The true malignant mixed tumor, or more commonly carcinoma, arising from preexisting mixed tumors are unusual and ill-defined in the literature. These tumors make up no more than 5% of the mixed tumor category and occur primarily in the parotid gland. In this report, we present a clinico-pathological appraisal of the malignant mixed tumor based on five cases from the University of Michigan Medical Center and relate our experience to that in the literature. The importance of recognizing the malignant mixed tumor, or “carcinoma ex-mixed tumor,” lies in the accelerated recurrence rate and surprisingly high metastatic rate manifested by this lesion. Minimal treatment is radical total excision. Wide, early excision of the primary “benign” stage of these mixed tumors should reduce the problem of ultimate “malignification.”

A case is described of the so-called mixed tumour of the breast occurred in a prostatectomized man. The pathogenesis is considered in the light of the recent endocrinological acquirements and some obscure aspects of the problem are pointed out.

Recurrence of benign neoplasms can usually be attributed to incomplete excision. Such is the case with benign mixed tumors of salivary glands. Certain histopathologic features of mixed tumors, however, appear to facilitate recurrences. These are: 1) a predominantly myxoid composition, and 2) transcapsular extension by the tumor. Multicentric origin is possible, but it must be regarded as a much lower order of probability.