Genetic alterations in pulmonary epithelioid hemangioendothelioma and epithelioid angiosarcoma

Epithelioid hemangioendothelioma (EHE) is a low-to-intermediate-grade vascular tumor that occurs in many organs, and epithelioid angiosarcoma (EA) is a subtype of angiosarcoma that is associated with high-grade malignancy. These two types of tumors have different forms of biological behavior. Pulmonary epithelioid hemangioendothelioma (PEH) and epithelioid angiosarcoma (PEA) are both very rare, and genetic studies on them are extremely limited. We examined and compared the cytogenetic characteristics of these two types of lung tumors in two patients utilizing the Array-Comparative Genomic Hybridization (Array-CGH) method. Considerable differences in the cytogenetic characteristics were observed between the two types of tumors. Small fragment gains (<10 MB) were dominant in PEH, whereas large fragment gains and deletions (>10 MB) were dominant in PEA. Some large fragment alterations, such as gains in chromosomes 19q and 19p, and deletions in chromosomes 9p and 13q, involved over half of a chromosome arm. PEH and PEA showed great cytogenetic differences; therefore, further genetic studies on these two types of tumors are warranted.     

Fine needle aspiration cytology of epithelioid angiosarcoma: a case report

BACKGROUND: Malignant vascular tumors are rare. Few studies have described cytomorphologic features of hemangioendothelioma and angiosarcoma on fine needle aspiration cytology (FNAC). Malignant vascular tumor with epithelioid morphology can create diagnostic difficulty, as the cytology may simulate that in other nonvascular malignant tumors. We describe epithelioid angiosarcoma, diagnosed on FNAC, in which a differential diagnosis of histiocytosis and inflammatory granulation tissue was considered. CASE: A 20-year-old man presented with forehead and scalp swellings. The forehead lesion was radiologiocally associated with a lytic lesion in the bone. FNA resulted in high cellular yield, and smears revealed prominent vascular pattern with endothelial cell atypia and histiocytoid/epithelioid neoplastic cells, occasional mitotic figures and a few cells displaying nuclear grooving. Smear background showed a significant number of neutrophils. Epithelioid hemangioendothelioma/angiosarcoma, histiocytosis and inflammatory granulation tissue were considered. A cytologic diagnosis of epithelioid angiosarcoma/epithelioid hemangioendothelioma was suggested and confirmed on histopathologic and immunohistochemical examination. CONCLUSION: Cellular aspirates from malignant epithelioid endothelial tumors involving bone may be cytologically mistaken for histiocytosis and, rarely, inflammatory granulation tissue. However, prominent vascular pattern with striking endothelial cell atypia, presence of mitotic figures and careful search for presence of endothelial differentiation are helpful in accurate cytologic diagnosis.     

Fine needle aspiration of metastatic epithelioid angiosarcoma: a report of 2 cases

BACKGROUND: Epithelioid angiosarcomas (EAs) are uncommon mesenchymal tumors occurring in the thyroid, deep-seated soft tissues, parenchymal organs and, more rarely, superficial soft tissues of the head and neck. Due to their cytologic and immunocytochemical presentation on fine needle aspiration cytology (FNAC) samples, these neoplasms may closely mimic a number of different tumors, potentially causing an erroneous cytopathologic diagnosis unless immunophenotypical markers of vascular differentiation are sought in the cellular material. CASES: A 68-year-old man with a 1-year history of total thyroidectomy for EA presented with a suspicious right neck node and underwent FNA. A 63-year-old woman with a history of recurring multiple scalp nodules diagnosed as EA ultimately developed small multiple, bilateral lymph nodes in the neck and underwent FNA. In both cases a cytopathologic diagnosis of metastatic EA was made. CONCLUSION: The cytopathologic diagnosis of EA is a challenge. Knowledge of the clinical history is of great help in diagnosing metastatic lesions. The cytopathologicpicture of metastases is a useful way for cytopathologists to gain confidence with presentaton of this rare entity in primary sites on FNAC samples. Cytopathologic hints of vascular differentiation should be sought in the cytopathologic material when a diagnosis of EA is entertained.     

Fine needle aspiration cytology of epithelioid angiosarcoma. Report of a case with nuclear grooves and indentations

BACKGROUND: Angiosarcoma, because of its rarity and histologic diversity, has been a persistent challenge to cytopathologists. Epithelioid angiosarcomas are often confused with carcinomas, melanomas and other epithelioid sarcomas, both cytologically and histologically. Here we report the cytopathologic features of a case of epithelioid angiosarcoma with prominent nuclear grooves. CASE: A 61-year-old male visited the hospital with a neck mass. On fine needle aspiration the hypercellular smear, with a lymphocytic bloody background, showed variable-sized, round to oval, pleomorphic cells with frequent nuclear grooves, indentations and plump cytoplasm. The cells were diffusely scattered or loosely aggregated, with occasional acinar and cell-in-cell configuration. The case was diagnosed as epithelioid angiosarcoma on excisional biopsy. CONCLUSION: Whenever fine needle aspiration cytology, especially in the head and neck area, suggests malignancy composed predominantly of epithelioid cells, epithelioid angiosarcoma should be considered. The differential diagnosis should include metastatic tumors, such as carcinoma, melanoma and primary sarcoma. Nuclear grooves and indentations are 1 of the important diagnostic features of epithelioid angiosarcoma.     

Visceral leishmaniasis with cardiac involvement in a dog: a case report

A dog presented with cutaneous nodules, enlarged lymph nodes and oedema in limbs, face and abdomen. The diagnosis of visceral leishmaniasis was established by identification of Leishmania amastigotes within macrophages from skin and popliteal lymph node biopsies. At necropsy, lesions were found in different organs, but it was particularly striking to observe large areas of pallor in the myocardium. Histological examination revealed an intense chronic inflammatory reaction in many organs, and numerous macrophages were found to contain amastigote forms of Leishmania. The inflammatory reaction was especially severe in the heart, where large areas of the myocardium appeared infiltrated with huge numbers of mononuclear immune cells, causing cardiac muscle atrophy and degeneration. Despite the severe inflammation, the number of parasitized macrophages was low in the myocardium, as revealed by immunohistochemical staining of Leishmania amastigotes. Because cardiac involvement is not usually described in this condition, this dog represents a very rare case of canine visceral leishmaniasis with affection of the myocardium.     

Pulmonary metastasis of a postradiation breast epithelioid angiosarcoma mimicking adenocarcinoma. A case report

BACKGROUND: Epithelioid angiosarcoma (EAS) is a mesenchymal neoplasm that may appear indistinguishable from carcinoma, melanoma and other tumors with epithelioid/epithelial differentiation. We report a case of metastatic postradiation EAS to the lungs that was mistaken for adenocarcinoma. CASE: A 45-year-old woman who received radiotherapy for ductal carcinoma in situ (DCIS) 5 years previously had a local recurrence a year earlier and recent development of bilateral small pulmonary nodules. Fine needle aspiration biopsy of the lung lesions showed round to oval tumor cells with amphophilic cytoplasm. An interpretation of adenocarcinoma was rendered during assessment for specimen adequacy. The original breast tumor was typical of cribriform DCIS. Review of the recurrent breast tumor (initially reported as DCIS) and a prior wedge resection of the lung nodules (reported as EAS) showed an epithelial-appearing tumor exhibiting an endothelial immunophenotype CONCLUSION: The cytologic features of EAS may resemble those of other neoplasms. In evaluating tumors with epithelioid morphology, mesenchymal tumors should also be considered so that appropriate antibodies can be included in the panel for immunohistochemistry. The importance of reviewing the patient's previous biopsy materials cannot be overemphasized.     

Widespread occurrence of a domestic dog mitochondrial DNA haplotype in southeastern US coyotes

Sequence analysis of the mitochondrial DNA control region from 112 southeastern US coyotes (Canis latrans) revealed 12 individuals with a haplotype closely related to those in domestic dogs. Phylogenetic analyses grouped this new haplotype in the dog/grey wolf (Canis familiaris/Canis lupus) clade with 98% bootstrap support. These results demonstrate that a male coyote hybridized with a female dog, and female hybrid offspring successfully integrated into the coyote population. The widespread distribution of this haplotype from Florida to West Virginia suggests that the hybridization event occurred long ago before the southeastern USA was colonized by coyotes. However, it could have occurred in the southeastern USA before the main front of coyotes arrived in the area between male coyotes released for sport and a local domestic dog. The introgression of domestic dog genes into the southeastern coyote population does not appear to have substantially affected the coyote's genetic, morphological, or behavioural integrity. However, our results suggest that, contrary to previous reports, hybridization can occur between domestic and wild canids, even when the latter is relatively abundant. Therefore, hybridization may be a greater threat to the persistence of wild canid populations than previously thought.     

The co-expression of cytokeratin and p63 in epithelioid angiosarcoma of the parotid gland: a diagnostic pitfall

ABSTRACT: SUMMARY: Epithelioid angiosarcoma of the parotid gland is rare, and may pose a great diagnostic challenge. We report a case of primary epithelioid angiosarcoma in a 64-year-old male without history of radiation. The histopathological findings demonstrated a high grade epithelioid neoplasm. Immunostaining showed that the tumor was positive for the pancytokeratin, p63, cytokeratin18, Vimentin and vascular markers CD31, and was negative for CD34, cytokeratin5/6, cytokeratin7, cytokeratin20, CD68, CD30, S-100, HMB45, desmin, alpha- SMA and CD45. The tumor was diagnosed as an epithelioid angiosarcoma. To our knowledge, this is the first reported case of angiosarcoma which showed common positivity for cytokeratin and p63. In addition to cytokeratin, p63 is considered a useful marker for carcinoma. The co-expression of cytokeratin and p63 in epithelioid angiosarcoma represents a diagnostic pitfall. Thus, using a panel of antibodies is essential for distinguishing this tumor from poorly differentiated carcinoma. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6548916707504750.     

Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction (MI).Understanding the mechanisms for acute pump failure is therefore important.The aim of this study is to examine in anacute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated withpump failure.Anterior MI was produced in dogs via ligation of left anterior descending (LAD) coronary artery,thatresulted in an infract size of about 30% of the left ventricular wall.Measurements of hemodynamic status,mitochondrialfunction,free radical production and mitochondrial uncoupling protein 3 (UCP3) expression were determined over 24h period.Hemodynamic measurements revealed a>50% reduction in cardiac output at 24 h post infarction when com-pared to baseline.Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction.ADP/Oratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to theADP/O ratios within the same samples with and without palmitic acid (PA).GTP inhibition of (PA)-stimulated state 4respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarctionrespectively when compared to sham and pre-infarction samples.This would suggest that the mitochondria are uncoupledand this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsysamples.Blood samples from the coronary sinus measured by electron paramagnetic resonance (EPR) methods showedan increase in reactive oxygen species (ROS) over baseline at 6 h and 24 h post-infarction.In conclusion,mitochondrialbio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall.Mitochondria ap-pear to be energetically uncoupled and this is associated with declining pump function.Free radical production may beassociated with the induction of uncoupling proteins in the mitochondria.     

Deformation of the dog lung in the chest wall

Data on the shape of the chest wall at total lung capacity (TLC) and functional residual capacity (FRC) were used as boundary conditions in an analysis of the deformation of the dog lung. The lung was modeled as an elastic body, and the deformation of the lung from TLC to FRC caused by the change in chest wall shape and gravity were calculated. Parenchymal distortions, distributions of regional volume at FRC as a fraction of the volume at TLC, and distributions of surface pressure at FRC are reported. In the prone dog there are minor variations in fractional volume along the cephalocaudal axis. In transverse planes opposing deformations are caused by the change of shape of the transverse section and the gravitational force on the lung, and the resultant fractional volume and pleural pressure distributions are nearly uniform. In the supine dog, there is a small cephalocaudal gradient in fractional volume, with lower fractional volume caudally. In transverse sections the heart and abdomen extend farther dorsally at FRC, squeezing the lung beneath them. The gradients in fractional volume and pleural pressure caused by shape changes are in the same direction as the gradients caused by the direct gravitational force on the lung, and these two factors contribute about equally to the large resultant vertical gradients in fractional volume and pleural pressure. In the prone position the heart and upper abdomen rest on the rib cage. In the supine posture much of their weight is carried by the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

X-ray diffraction from a left ventricular wall of rat heart

We studied x-ray diffraction from the left ventricular wall of an excised, perfused whole heart of a rat using x rays from the third-generation synchrotron radiation facility, SPring-8. With the beam at right angles to the long axis of the left ventricle, well-oriented, strong equatorial reflections were observed from the epicardium surface. The reflections became vertically split arcs when the beam passed through myocardium deeper in the wall, and rings were observed when the beam passed into the inner myocardium of the wall. These diffraction patterns were explained by employing a layered-spiral model of the arrangement of muscle fibers in the heart. In a quiescent heart with an expanded left ventricle, the muscle fibers at the epicardium surface were found to have a (1,0) lattice spacing smaller than in the rest of the wall. The intensity ratio of the (1,0) and (1,1) equatorial reflections decreased on contraction with a similar time course in all parts of the wall. The results show that it is possible to assign the origin of reflections in a diffraction diagram from a whole heart. This study offers a basis for interpretation of x-ray diffraction from a beating heart under physiologically and pathologically different conditions.     

Widespread association of a Rickettsiales-like bacterium with reef-building corals

White band disease type I (WBD I) has been a major cause of the dramatic decline of Acroporid coral populations throughout the Caribbean during the last two decades, yet the aetiological agent of this disease is unknown. In this study, the bacterial communities associated with both healthy and diseased Acropora species were compared by 16S rDNA analyses. The bacterial communities of both healthy and diseased Acropora spp. were dominated by a single ribotype with 90% identity to a bacterium in the order Rickettsiales. Screening by nested PCR specific to the coral-associated Rickettsiales 1 (CAR1) bacterium showed that this microbe was widespread in both healthy and diseased A. cervicornis and A. palmata corals from 'healthy' (i.e. low WBD I incidence) and 'stressed' reefs (i.e. high WBD I incidence). These results indicate that there were no dramatic changes in the composition of the microbial community associated with WBD I. CAR1 was also associated with non-Acroporid corals of the Caribbean, as well as with two Acroporid corals native to the Pacific. CAR1 was not present in the water column. This bacterium was also absent from preserved Caribbean Acroporid samples collected between 1937 and 1980 before the outbreak of WBD I. These results suggest CAR1 is a relatively new bacterial associate of Acroporids and that a non-bacterial pathogen might be the cause of WBD I.     

Reduction in interaction between cGMP and cAMP in dog ventricular myocytes with hypertrophic failure

Baseline function and signal transduction are depressed in hearts with hypertrophic failure. We tested the hypothesis that the effects of cGMP and its interaction with cAMP would be reduced in cardiac myocytes from hypertrophic failing hearts. Ventricular myocytes were isolated from control dogs, dogs with aortic valve stenosis hypertrophy, and dogs with pacing hypertrophic failure. Myocyte function was measured using a video edge detector. Cell contraction data were obtained at baseline, with 8-bromo-cGMP (10(-7), 10(-6), and 10(-5) M), with erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA; a cAMP phosphodiesterase (PDE(2)) inhibitor] plus 8-bromo-cGMP, or milrinone (a PDE(3) inhibitor) plus 8-bromo-cGMP. Baseline percent shortening and maximal rates of shortening (R(max)) and relaxation were slightly reduced in hypertrophic myocytes and were significantly lower in failing myocytes (R(max): control dogs, 95.3 +/- 17.3; hypertrophy dogs, 88.2 +/- 5.5; failure dogs, 53.2 +/- 6.4 mum/s). 8-Bromo-cGMP dose dependently reduced myocyte function in all groups. However, EHNA (10(-6) M) and milrinone (10(-6) M) significantly reduced the negative effects of cGMP on cell contractility in control and hypertrophy but not in failing myocytes (R(max) for control dogs: cGMP, -46%; +EHNA, -21%; +milrinone, -19%; for hypertrophy dogs: cGMP, -40%; +EHNA, -13%; +milrinone, -20%; for failure dogs: cGMP, -40%; +EHNA, -29%; +milrinone, -32%). Both combinations of EHNA-cGMP and milrinone-cGMP significantly increased intracellular cAMP in control, hypertrophic, and failing myocytes. These data indicated that the cGMP signaling pathway was preserved in hypertrophic failing cardiac myocytes. However, the interaction of cGMP with the cAMP signaling pathway was impaired in these failing myocytes.     

Assessment of fatty acids in dog left ventricular myocardium

The concentration and composition of fatty acids in four lipid classes in biopsies of dog left ventricular myocardium were determined, using gas-liquid chromatography. When precautions were taken to minimize lipolysis during storage of the tissue and the homogenization process, the following results were obtained: 29 ± 10 nmol non-esterified fatty acids, 2.98 ± 2.41 μmol triacylglycerol, 149 ± 51 nmol cholesteryl esters and 23.76 ± 3.38 μmol phospholipid (expressed as fatty acid moiety per gram of wet tissue). The concentration of non-esterified fatty acids was 15 to 300 times lower than reported in literature.The main constituents of the non-esterified fatty acids were palmitic, stearic and oleic acid. Triacylglycerol consisted of approximately 40% esterified oleic acid. Linoleic acid accounted for 40% of the fatty acids in the cholesteryl-esters class. More than half of the fatty acid moiety of total phospholipids was linoleic acid and arachidonic acid.     

Widespread RNA segregation in a spiralian embryo

Asymmetric cell divisions are a crucial mode of cell fate specification in multicellular organisms, but their relative contribution to early embryonic patterning varies among taxa. In the embryo of the mollusc Ilyanassa, most of the early cell divisions are overtly asymmetric. During Ilyanassa early cleavage, mRNAs for several conserved developmental patterning genes localize to interphase centrosomes, and then during division they move to a portion of the cortex that will be inherited by one daughter cell. Here we report an unbiased survey of RNA localization in the Ilyanassa embryo, and examine the overall patterns of centrosomal localization during early development. We find that 3-4% of RNAs are specifically localized to centrosomes during early development, and the remainder are either ubiquitously distributed throughout the cytoplasm or weakly enriched on centrosomes compared with levels in the cytoplasm. We observe centrosomal localization of RNAs in all cells from zygote through the fifth cleavage cycle, and asymmetric RNA segregation in all divisions after the four-cell stage. Remarkably, each specifically localized message is found on centrosomes in a unique subset of cells during early cleavages, and most are found in unique sets of cells at the 24-cell stage. Several specifically localized RNAs are homologous to developmental regulatory proteins in other embryos. These results demonstrate that the mechanisms of localization and segregation are extraordinarily intricate in this system, and suggest that these events are involved in cell fate specification across all lineages in the early Ilyanassa embryo. We propose that greater reliance on segregation of determinants in early cleavage increases constraint on cleavage patterns in molluscs and other spiralian groups.     

Uterine epithelioid leiomyosarcoma in a pig-tailed macaque

Abstract: During ultrasonographic examination following spontaneous abortion, an approximately 6-cm diameter mass of mixed echogenicity is detected in the uterine wall of a mature pig-tailed macaque (Macaca nemestrina). Grossly, the mass is associated with the uterine fundus, multilobulate and tan with red-black mottled foci on cut surface. Microscopically, the invasive mass is composed of poorly differentiated round cells arranged in sheets and bundles supported by a fine fibrous stroma. On immunohistochemical evaluation, neoplastic cells contain vimentin, desmin, muscle actin, and smooth muscle α-actin antigens and do not react with antibodies to low and high molecular-weight cytokeratins. Cell morphology and immunohistochemical results indicate a diagnosis of epithelioid leiomyosarcoma (clear cell variant).