Processing and characterization of canine mixed mammary tumor using transmission electron microscopy.

Canine mammary gland tumors represent the second most frequent type of neoplasm in dogs, being an important problem within veterinary medical field. Canine mixed mammary tumors are the most common; the use of a transmission electron microscope (TEM) can contribute as a tool in its diagnosis by determining the characteristics of cellular components from numerous neoplasms. The aim of this study was to characterize cytologically canine mammary mixed tumor by the use of the TEM. A biopsy collected from an 11 years old bitch Shih-Tzu and analyzed by histopathology was used for ultrastructural analysis. Specimens obtained were double stained using uranyl acetate and lead citrate prior to observation in the TEM. The protocol established to transmission electron microscopy observation allowed the identification of main cellular characteristics of canine mixed mammary tumors; however, it was not possible a detailed visualization of the organelles due to the preservation of the biopsy in formaldehyde.

Cerebellar Liponeurocytoma, an Unusual Tumor of the Central Nervous System--Ultrastructural Examination.

Cerebellar liponeurocytoma is a rare tumor of the central nervous system which shows neuronal and variable astrocytic differentiation, along with foci of lipomatous differentiation. It is usually located in the cerebellum, and may be mistaken for medulloblastoma with lipidized cells or lipomatous ependymoma. Histopathological examination, supplemented by immunohistochemistry and electron microscopy, is required to distinguish between these entities. This 35-year-old male presented with vomiting and headache for three months, followed by gait imbalance. Neurological examination showed positive cerebellar signs with ataxic gait. Magnetic resonance imaging showed a lesion measuring 4.4 cm× 4.3 cm× 3.9 cm involving the cerebellum. The patient underwent midline suboccipital craniotomy to excise the tumor. Histopathological examination showed a circumscribed, cellular tumor composed of round to polygonal cells with moderate cytoplasm and minimal pleomorphism. Clear intracytoplasmic vacuoles were seen within the tumor cells. These tumor cells were immunopositive for synaptophysin, NSE, and MAP-2, confirming their neurocytic origin. On ultrastructural examination, lipid vacuoles as well as dense-core neurosecretory granules were identified within these neurocytic cells, confirming the diagnosis of liponeurocytoma. No cilia, microvilli, or gap junctions were identified in the tumor cells, ruling out the possibility of lipomatous ependymoma. The differentiation of liponeurocytoma from its morphological mimics is imperative, as their treatment differs drastically. The role of electron microscopy is extremely important in this differential diagnosis.

Mesothelioma with signet-ring cell features: report of 23 cases.

Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum. For comparison purposes and in order to determine the value of these techniques in the differential diagnosis of these tumors, seven cases of signet-ring cell lung adenocarcinoma were also studied. All signet-ring cell mesotheliomas were positive for calretinin, keratin 5/6, keratin 7, and mesothelin, 93% for podoplanin, and 91% for WT1; whereas, none reacted for MOC-31, CEA, TAG-72, CD15, TTF-1, napsin A, or CDX2. Among signet-ring cell lung adenocarcinomas, 100% were positive for keratin 7, CEA, and napsin A, 86% each for TTF-1 and TAG-72, 71% for CD15, and 14% for mesothelin, while all were negative for calretinin, keratin 5/6, WT1, podoplanin, and CDX2. After analyzing the results, it is concluded that the panels of markers used in the differential diagnosis of this mesothelioma variant should include those markers that are usually expressed in mesotheliomas (eg, calretinin, keratin 5/6, WT1, and podoplanin), broad-spectrum carcinoma markers that are frequently expressed in adenocarcinomas regardless of their site of origin (eg, MOC-31 and CEA), and organ-associated markers (eg, TTF-1 and napsin A for lung), which allow the site of origin of a metastatic adenocarcinoma to be established. Electron microscopy can be very useful as it permits the identification of characteristic ultrastructural mesothelioma and adenocarcinoma markers, and it also allows a better understanding of the morphologic features seen on routine light microscopy. Pathologists should be aware of this mesothelioma subtype as it can potentially be confused with other tumors that exhibit signet-ring features.

Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, ultrastructural and immunohistochemical findings.

Gastroblastoma is a rare gastric epitheliomesenchymal biphasic tumour composed of spindle and epithelial cells, reported by Miettinen et al in a series of three cases in 2009. All those cases arose in stomachs of young adults. Neither the epithelial nor the mesenchymal component displayed sufficient atypia to diagnose a carcinosarcoma or other malignancy. On immunohistochemistry, the epithelial component expressed cytokeratin, and the mesenchymal component was positive for vimentin and CD10. Miettinen et al designated these neoplasms as gastroblastomas based on their similarities with other childhood blastomas such as pleuropulmonary blastoma and nephroblastoma. This report describes a probable fourth case of this unique type of neoplasm. The present case arose in the gastric antrum of a 9-year-old boy. While similarities were evident with the other cases, there were some differences. The epithelial component was more predominant and showed more mature morphology. Immunohistochemically, the epithelial component showed immunolabelling for c-KIT and CD56. The mesenchymal component was only focally positive for CD10. Ultrastructually, desmosomes and microvilli were found supporting a truly epithelial lesion.

Mixed tumors, myoepitheliomas, and oncocytomas of the soft tissues are likely members of the same family: a clinicopathologic and ultrastructural study.

Four diagnostically unusual soft tissue tumors are presented. All lesions were of consistent size and long duration. Histologically, one lesion was analogous to mixed tumors of the usual sites (i.e., salivary glands), one lesion was totally spindled, and the two other lesions both had oncocytic appearances (epithelioid and spindle biphasic pattern in a case, purely epithelioid in the other). Immunohistochemically, the mixed tumor was positive for vimentin, cytokeratins, S-100 protein, and focally for EMA. The purely spindled tumor exhibited immunoreactivity for vimentin, actins, S-100 protein, EMA (focally), and GFAP. The oncocytic biphasic tumor was positive for mitochondrial antigen, vimentin, and actins. The purely epithelioid oncocytic neoplasm was immunoreactive only for mitochondrial antigen and vimentin. Ultrastructurally, in the epithelial-like portion of the first (mixed) tumor, peripheral arrays of contractile filaments were detected along with well-developed desmosomes. In the second (spindled) case, peripheral contractile filaments and attenuated desmosomes were also seen. In the third case, a huge number of mitochondria, some desmosomes, and actin-type microfilaments were found. In the fourth case, desmosomes and punctate subplasmalemmal densities, in addition to numerous mitochondria, were documented. In all cases an external basal lamina were present, which was discontinuous in the first three cases and almost continuous in the fourth. These tumors were respectively designated as mixed tumor, myoepithelioma of the classic type, myoepithelioma of oncocytic type with biphasic cell architecture, and true oncocytoma. So far, all tumors have followed benign clinical courses (median follow up: 12 months). Comparisons with similar tumors of other sites are drawn, and suggestions for considering all of them as members of the same myoepithelial-derived tumor family are given.

Amphicrine tumor.

The term amphicrine refers to cells, and tumors, which show both exocrine and endocrine features. Author s aim was to analyse the characteristics of these neoplasms. 40 suspicious cases were reviewed. Mucin-stains (PAS, diastase-PAS, Stains-all, Alcian-blue), immunohistochemistry (antibodies against Neuron-Specific Enolase (NSE), and Chromogranin A (CGA), and electronmicroscopic studies were performed to demonstrate exocrine and/or endocrine features of the tumor cells. By means of these methods, 16 cases turned out to be amphicrine tumors. Among them, there were 4 sinonasal, 1 bronchial, 1 mediastinal, 8 gastrointestinal and 2 suprarenal gland neoplasms. In connection to the subject, a brief review is given of amphicrine tumor, regarding its etiological and pathological aspects. These tumors form a distinct clinicopathological entity and should be separated from both neuroendocrine tumors and adenocarcinomas.

Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression.

Transgenic mice which express the simian virus 40 large T-antigen (Tag) under the regulatory control of the hormone responsive rat C3(1) gene develop unusual lesions of heterotopic bone growth associated with mixed tumor formation arising from eccrine sweat glands found only in the foot pads of mice, ischiocavernosus muscle adjacent to bulbourethral glands and occasionally the salivary and mammary glands. These lesions are very similar to mixed tumors arising in several types of human cancers. Based upon electron microscopic examination and immunocytochemical analyses of cellular differentiation markers, the mixed proliferative lesions in this transgenic mouse model begin with the Tag-induced proliferation of epithelial and myoepithelial cells. The proliferation of these two types of cells results in hyperplasia and adenomatous transformation of the epithelial component, whereas the proliferating myoepithelial cells undergo metaplasia to form chondrocytes which deposit extracellular matrix, including collagen fibers. Cartilage develops focally between areas of epithelial proliferation and subsequently ossifies through a process of endochondrial bone formation. The metaplasia of myoepithelial cells to chondrocytes appears to require the inductive interaction of factors produced by the closely associated proliferating epithelial cells, including members of the TGF-beta superfamily. We demonstrate that TGF-beta1 protein accumulates in the extracellular matrix of the lesions, whereas RNA in situ hybridization reveals that BMP-2, another strong inducer of heterotopic bone formation, is overexpressed by the proliferating epithelial cells during the development of ectopic bone. The formation of sarcomatous tumors within the mixed tumors appears to be androgen-dependent and more frequent in mice lacking a normal allele of p53. This process of cartilage and bone induction may mimic epithelial-mesenchymal interactions which occur during embryonic bone formation. These transgenic mice may provide new insights into the processes of ectopic endochondrial bone formation associated with mixed tumor formation and serve as a useful model for human heterotopic bone disease.

[Thyroid neoplasm of mid follicular-medullary type; an uncommon, particular and aggressive form: report of 3 cases]. / Cáncer tiroídeo tipo intermedio folicular-medular; una forma inhabitual, particular y agresiva. Comunicación de tres casos.

Mixed medullary and follicular carcinoma of the thyroid shares secretory and immunohistochemical features of both follicular and parafollicular thyroidal cells. We report three women, aged 34, 63 and 61 old with this type of tumor. Its diagnosis must be bore in mind in patients with thyroidal tumors and a histological appearance of a medullary or undifferentiated carcinoma. An early diagnosis of a mixed medullary and follicular carcinoma of the thyroid is important, considering its special treatment and negative prognosis.