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It is well known that the cell nucleus is organized in structural and functional compartments involved in transcription, RNA processing and protein modifications such as conjugation with SUMO-1 and proteolysis. Promyelocytic leukaemia (PML) bodies are dynamic nuclear structures that concentrate PML protein, SUMO-1 and several sumoylated and non-sumoylated protein regulators of nuclear functions. PML bodies and their associated CBP has been involved in neuronal survival. By light and electron microscopy immunocytochemistry and in situ hybridization we reported the presence, in non-pathological conditions, of a large PML-nuclear inclusion (PML-NI) in human supraoptic neurons. This inclusion appears as a single nuclear structure composed of a capsule enriched in PML, SUMO-1 and CBP proteins and a central lattice of filaments immunoreactive for class III β-tubulin, ubiquitinated proteins and proteasomes. Furthermore, the PML-NI concentrates the SUMO-conjugating enzyme E2 (UBC9). The PML-NI may be considered a nuclear factory involved in sumoylation and proteolysis via ubiquitin-proteasome system, two nuclear pathways engaged in the control of the nucleoplasmic concentration of active transcriptional regulators. Interestingly, the structural and molecular organization of the PML-NI is related to the Marinesco bodies, age-associated ubiquitinated intranuclear inclusions, and to the intranuclear rodlets enriched in class III β-tubulin, which are nuclear structures markedly decreased in Alzheimer's disease. © 2005 Elsevier Inc. All rights reserved., This study was supported by “Dirección General de Investigación Científica” from Spain (BFI2002-0454; BFU2005-01030), “Fondo de Investigación Sanitaria” from Spain (Red CIEN C03-C06) and Fundación Marqués de Valdecilla from Santander (API/05/04).

Valvular epithelioid hemangioendotheliomas (EHE) are exceptional. To the authors' knowledge only four cases have been reported. Herein is described an EHE incidentally detected in the mitral valve of a 69-year-old woman with chronic rheumatic valvular heart disease. The 0.4 cm lesion was situated in the anterior leaflet and was discovered in the pathological study after mitral valve replacement. The patient was alive and well 6 months after operation. Review of the literature including the present report, revealed that the mean age was 60.2 years (range, 49-69 years). Symptomatic patients had clinical features of valvular disease or embolism. Each of the four cardiac valves can be affected. Mean tumor size was 2.4 cm (range, 0.4-8 cm). In 40% of cases the EHE was an incidental finding at autopsy or in a removed valve. In two cases the involved cusp was affected by chronic rheumatic disease. In conclusion, EHE is a rare lesion that can be an incidental finding and it should be considered in the differential diagnosis of valve tumors. Although EHE can present a histologically benign appearance, the correct pathological diagnosis is clinically important because the lesion can be potentially malignant. Regular follow up is suggested due to this potential.

Bronchioloalveolar carcinoma is a distinctive subtype of pulmonary adenocarcinoma, without effective therapy, although there have recently been some attempts to use lung transplantation. However, a high post-transplantation local recurrence rate is described with some controversy regarding the possible involved mechanisms, the main possibilities being the lymphatic spread and aerosolization. Presented herein is a case of a bilateral lung transplantation for a bilateral and pneumonic form of non-mucinous bronchioloalveolar carcinoma in a 43-year-old woman. The histological analysis of mediastinal lymph nodes during surgery did not show neoplastic cells. Thirty-five months after transplantation several nodular opacities in donor lungs were detected. Three pulmonary wedge resections were performed showing a non-mucinous bronchioloalveolar carcinoma with the same histological characteristics as the primary. Again, the mediastinal lymph nodes were tumor free. A complete microsatellites molecular analysis was performed to compare the primary and recurrent carcinoma using capillary electrophoresis, showing that the recurrent tumor was generated in a recipient cellular clone. The absence of lymph node metastasis and the molecular evidence of the recipient origin of the neoplasm supports the contamination of the new lungs at the time of implantation as being the reason for the high incidence of recurrence after lung transplantation in this kind of disease.

Background: There are numerous variants of cutaneous neurofibroma reflecting its manner of growth and histologic composition. Lipomatous neurofibroma is the latest described variant with only eight cases reported. Methods: A systematic study based on 320 consecutive specimens diagnosed of cutaneous neurofibroma was carried out. Conventional microscopy, immunohistochemistry, and statistical methods were used to determine the presence of fat cells, their amount, distribution, and frequency. Results: Intratumoral fat was observed in 22 (6.9%) neurofibromas. All these were dermal neurofibromas. Intraneoplastic fat was divided into two groups: focal and diffuse (regularly interspersed). Eighteen tumors (5.6%) presented adipocytes focally intermingled with the spindle cells. There were four (1.3%) neurofibromas showing spindle cell proliferation with regularly scattered adipocytes. Lipomatous neurofibroma was more frequent located on head and neck than non-lipomatous neurofibroma ( p = 0.04). Neurofibromas without mature adipocytes were more frequently immunoreactive for CD34 compared with tumors showing intratumoral fat ( p = 0.02). Conclusions: We suggest that both metaplasia and aberrant adipose differentiation from multipotential cells may result in lipomatous neurofibroma. Focal presence of adipose cells may be attributable to metaplasia as the pathogenic mechanism. The fatty tissue being intrinsic to the tumor structure in its diffuse form, the lesion represents a distinctive tumor of the peripheral nerve sheath.

Although a decrease in bone mass is a well-known side effect of hormone therapy for prostate carcinoma, its clinical significance is unclear, as there is only scanty information about the incidence of fractures. Therefore, the aim of this study was to determine the risk of non-metastatic fractures in patients with prostate cancer undergoing androgen deprivation therapy. We performed a retrospective cohort study that comprised 288 patients with cancer who were subjected to androgen deprivation therapy (ADT). All were given LHRH agonists, and most of them also received peripheral androgen receptor blockers. The results were compared with a control group of 300 men that were not receiving ADT. The incidence rates of peripheral and vertebral fractures in the group of men on ADT were 1.9 and 0.8 per 100 patient-years, respectively. Incidence rates in the control group were 0.5 and 0.2, respectively. In the whole study group, 35 patients had at least one fracture during follow-up (25 on ADT, ten controls). Thus, the number of patients with at least one fracture was significantly higher in the group on ADT (P = 0.001 by the log-rank test). The unadjusted risk ratio was 4.2 (CI 2.0-8.9). A similar value (risk ratio 3.6; CI 1.6-7.7, P = 0.001) was found after it was adjusted for other factors, such as age or prior fractures. Therefore, ADT is associated with a fourfold increase in the incidence rate of both peripheral and vertebral fractures. Although the absolute incidence remains relatively small, preventive measures should be considered for high-risk patients.

Myxomas are uncommon soft-tissue neoplasms, which are extremely rare in the kidney, with only five cases documented in the intraparenchymal location. However, renal capsular myxoma has not yet been reported. We describe a unique case of a clinically detected renal myxoma arising in the capsule. A 37-year-old man receiving treatment for epididymitis sought medical assistance for infertility. A radiological examination incidentally discovered a right renal tumor. The mass intruded into the perirenal tissue and measured 6 cm in major diameter. The resected kidney contained a well-circumscribed gelatinous capsular tumor. It was composed of sparse, bland, slender, spindle-shaped cells scattered in large amounts of basophilic interstitial mucoid material. The tumor cells showed diffuse immunoreactivity for vimentin. Occasional cells stained for alpha-smooth muscle actin and calponin. Reactivity was negative for S100 protein, epithelial membrane antigen, pancytokeratin, neurofilament protein, and h-caldesmon antibodies. Ultrastructural examination revealed fibroblast-like cells with long thin cytoplasmic processes, prominent rough endoplasmic reticulum, a well-developed Golgi complex, and secretory vesicles. No basal lamina was identified around the tumor cells. The differential diagnosis includes many other benign and malignant soft-tissue lesions exhibiting prominent secondary myxoid features. It is important to consider a renal capsular myxoma when examining lesions at this anatomic site to avoid misdiagnoses and to ensure that the patient receives appropriate treatment and prognostic information.

Malignant tumors at the site of implantation of a pacemaker generator, although rare, have been reported in the literature. We present a case of an 89-year-old man with atypical fibroxanthoma in a pacemaker pocket. The device had been implanted for more than 4 years. An exophytic tumor had developed in this place and was clinically interpreted as a pyogenic granuloma. An excisional biopsy revealed the nature of the tumor. To our knowledge, the association of atypical fibroxanthoma arising from a pacemaker pocket has not been previously reported. A review of the literature has revealed four malignant soft tissue tumors previously reported at the pacemaker site. Routine examination in all patients with implanted pacemaker generators should be practiced at follow-up visits. This would allow an early diagnosis of a malignant associated neoplasm. Pathologists should become familiar with this type of devices and their potential neoplastic complications.

Introduction: Pleomorphic liposarcoma (PLPS) is a high-grade pleomorphic sarcoma, containing multivacuolated lipoblasts, which usually develops during late adult life. It usually occurs in the deep soft tissues and uncommonly arises in the subcutis, the dermis representing an exceedingly rare site of occurrence. Methods: We describe a case of PLPS arising in the dorsal aspect of the nose of a 75-year-old woman. Preoperative duration was 9 months. Results: The lesion was intradermal well-circumscribed, dome-shaped, measuring 1.2 cm. It fulfilled the histologic criteria for inclusion in the PLPS category. The tumor cells focally expressed calretinin. A review of the literature yielded four cases documented, to which we add the present report. All the patients were adults with a mean age of 67 (range 39–95) years, and three of five cases arose on the scalp. Local recurrence occurred in one patient, but no distant metastases or disease-related deaths were observed. Conclusion: PLPS very rarely arises in the dermis. In spite of high-grade morphology, the intradermal tumor shows a relatively favorable prognosis. Diagnostic consideration includes pleomorphic lipoma, clear cell atypical fibroxanthoma, balloon cell melanoma, and metastatic clear cell carcinoma of renal origin. Recognition of this distinctive and rare type of liposarcoma is essential to avoid under- or misdiagnosis and inappropriate treatment.

Purpose: This study was performed to identify morphologic features of cardiac myxomas related to embolism and to provide a better understanding of the biology of these tumors, mainly in relation to their interleukin (IL)-6 expression and DNA content. Patients and methods: A total of 37 cardiac myxomas were reviewed retrospectively in a clinicopathologic study that included the correlation of echocardiographic and pathologic findings in 25 cases, together with immunohistochemical evaluation of IL-6 expression and flow cytometric DNA analysis of 35 tumors. Results: There were 24 female patients and 13 male patients. The mean (± SD) age was 52 ± 15 years. Fifty-four percent of patients presented with dyspnea, 51% presented with increased erythrocyte sedimentation rate (ESR), and 27% presented with embolic episodes, which were significantly associated with villous surface tumors. Atrial fibrillation was registered in 19% of patients and was significantly associated with large left atrial myxomas. Echocardiography proved to be a reliable method for preoperative diagnosis and for predicting tumor size and morphology. There was no perioperative mortality or long-term recurrences. The frequency of early surgical complications was associated with a longer mean ischemic time. Seventeen percent of tumors had abnormal DNA content, and 74% of tumors showed immunohistochemical expression of IL-6. Neither of these factors showed a significant association with embolism or constitutional illness. Conclusions: Villous surface myxomas are related to embolism, and large left atrial tumors are related to atrial fibrillation. Echocardiography is a reliable method with which to predict tumor size and morphology. Myxoma cells usually express IL-6, and some tumors have abnormal cellular DNA content. Surgical excision of the tumor is a safe and effective treatment.

Degradation of the wall of human ascending thoracic aorta has been assessed through Optical Coherence Tomography (OCT). OCT images of the media layer of the aortic wall exhibit micro-structure degradation in case of diseased aortas from aneurysmal vessels or in aortas prone to aortic dissections. The degeneration in vessel walls appears as low-reflectivity areas due to the invasive appearance of acidic polysaccharides and mucopolysaccharides within a typical ordered microstructure of parallel lamellae of smooth muscle cells, elastin and collagen fibers. An OCT indicator of wall degradation can be generated upon the spatial quantification of the extension of degraded areas in a similar way as conventional histopathology. This proposed OCT marker offers a real-time clinical insight of the vessel status to help cardiovascular surgeons in vessel repair interventions. However, the delineation of degraded areas on the B-scan image from OCT is sometimes difficult due to presence of speckle noise, variable SNR conditions on the measurement process, etc. Degraded areas could be outlined by basic thresholding techniques taking advantage of disorders evidences in B-scan images, but this delineation is not always optimum and requires complex additional processing stages. This work proposes an optimized delineation of degraded spots in vessel walls, robust to noisy environments, based on the analysis of the second order variation of image intensity of backreflection to determine the type of local structure. Results improve the delineation of wall anomalies providing a deeper physiological perception of the vessel wall conditions. Achievements could be also transferred to other clinical scenarios: carotid arteries, aorto-iliac or ilio-femoral sections, intracranial, etc. This work has been supported by the Spanish Government through the CYCIT projects DA2TOI (FIS2010-19860) and FOS4 (TEC2013-47264-C2-1-R).

A case of fibroepithelioma of Pinkus with pleomorphic epithelial giant cells is reported. The lesion was an ovoid polypoid nodule measuring 4 mm x 3 mm x 2 mm and was located close to the right axilla in an 86-year-old woman. The immunohistochemical features of the epithelial giant cells indicate that most of these cells are not cycling. We suggest that these cellular changes may represent a senescent event. Giant cells showed a mean nuclear major diameter more than twice that of small cells. Flow cytometric study of the tumor showed a hypodiploid DNA content and an intermediate grade S-phase fraction of the aneuploid component. To the best of our knowledge, a pleomorphic variant of Pinkus fibroepithelioma has not been reported to date. In fibroepithelioma of Pinkus, the correct diagnosis depends primarily on the architectural pattern of the tumor rather than on its cytologic features.

We report a cutaneous lipomatous neurofibroma on the skin of the left-side parietal area of approximately 9 months' duration in a 67-year-old woman. The regular distribution of adipose tissue throughout the lesion suggested that fat was an integral part of the tumor, not a metaplastic or degenerative process. To our knowledge, this type of lesion has not been documented. The main differential diagnosis embraces neurocristic cutaneous hamartoma, lipoma and its variants, cutaneous meningioma, and neural nevus with fat replacement. We propose that lipomatous neurofibroma of the skin is caused by aberrant development of adipose tissue in a neurofibroma. The lesion originated as pluripotential neural crest cells after migration. This acquired lesion could arise from local stem cells. The old suggestion that neuroectoderm is capable of mesenchymal differentiation may be relevant to the histogenesis of this neoplasm.

Primary mesotheliomas of the pericardium are rare tumors. They may occur in diffuse, multiple, and localized forms. Most of the pericardial mesotheliomas are multiple or diffuse growths encasing the heart, localized forms being distinctly uncommon. We report a localized mesothelioma of the pericardium found incidentally at the autopsy of a 76-year-old woman. The neoplasm measured 3.6 x 2.4 x 2.5 cm., was well circumscribed, and affected the entire thickness of the myocardium extending from the epicardium to the endocardium of the anterior wall of the right ventricle. The tumor was epithelial in type, showed an immunohistochemical profile compatible with mesothelioma, and was DNA aneuploid. A review of the literature yielded four cases of localized pericardial mesothelioma, including the present. Most cases are seen in women and are of the epithelial variant. There is a wide age range at presentation. Localized mesotheliomas are capable of aggressive behavior. Nevertheless, in contrast to diffuse tumors, complete surgical excision may be curative. Differential diagnosis includes solitary fibrous tumor, synovial sarcoma, epithelioid angiosarcoma, and adenomatoid tumor of the pericardium.

Resumen —El liquen aureo o purpurico es una dermatosis asintomatica de etiologia desconocida que se clasifica como una variante infrecuente de dermatosis purpurica pigmentaria. Suele presentarse como lesiones de color marron dorado o purpurico, unicas o en escaso numero, y raramente adopta un patron zosteriforme. Predomina en extremidades inferiores en varones adultos. En el presente trabajo se realiza un estudio clinicopatologico e inmunohistoquimico de 6 casos de liquen aureo, tres de ellos con presentacion zosteriforme. En nuestros casos se afectaban por igual ambos sexos, todos eran adultos, excepto una nina de 12 anos, siendo la localizacion de las lesiones muy variable. El estudio inmunohistoquimico revelo un aumento de las celulas de Langerhans y un claro predominio de linfocitos T con abundantes celulas CD4+ y la presencia de macrofagos en el infiltrado dermico. Estos hallazgos sugieren un mecanismo de hipersensibilidad retardada (tipo IV) en la patogenia de la lesion. Es posible que la ausencia de sintomas, las lesiones unicas o en escaso numero, el predominio en varones y la localizacion en extremidades inferiores contribuyan a que no se consulten muchos casos, y se sugiere que la lesion es mas frecuente de lo establecido. La presentacion zosteriforme del liquen aureo debe tenerse en cuenta en el diagnostico diferencial con otros procesos con distribucion lineal o segmentaria.

Objetivos Describir la distribucion celular y el grado de expresion de diversas hormonas y receptores de opioides en el desarrollo embrionario y en el pulmon sano del adulto Metodo Seleccionamos tejido pulmonar de las tres etapas del desarrollo fetal (seudoglandular, canalicular y sacular, tres muestras por etapa), de recien nacidos (tres), ninos de 10 meses (dos) y adultos (tres) fallecidos sin afeccion pulmonar. Practicamos tincion inmunohistoquimica para hormonas especificas (calcitonina, parathormona, serotonina y hormona adrenocorticotropa [ACTH]) y receptores de opioides tipo delta y mu. Valoramos el porcentaje de celulas positivas asi como el tipo celular reactivo en cada caso Resultados La serotonina es la primera en aparecer (estadio seudoglandular en celulas neuroendocrinas aisladas) para posteriormente desaparecer. La calcitonina aparece en el estadio canalicular en celulas neuroendocrinas y neumocitos. Su expresion maxima es al nacimiento y disminuye en el pulmon adulto. No hemos encontrado produccion de ACTH ni de parathormona. Los receptores de opioides aparecen en la fase canalicular y alcanzan el maximo grado en el nacimiento. En el adulto solo existen receptores para opioides tipo delta en neumocitos, celulas musculares bronquiolares y mesoteliales Conclusiones La hormonosecrecion pulmonar es importante durante el desarrollo fetal y alcanza su maxima expresion en el nacimiento. La principal hormona que produce el pulmon fetal es la calcitonina. Existen receptores opioides durante el desarrollo fetal en diferentes tipos celulares y alcanzan su maxima expresion al nacimiento. El conocimiento de la expresion de sustancias activas podria tener consecuencias terapeuticas en determinados procesos patologicos como el sindrome de distres respiratorio en el nino o el asma bronquial

Kidney sarcomas are rare, representing only 1% of malignant renal tumors. We herein report the case of a 70-year-old woman that was admitted for an episode of confusion in relation to hypertensive encephalopathy. Imaging investigations revealed a large mass in the right kidney with extension to the renal hilum. The patient underwent right open radical nephrectomy. The histopathologic study disclosed a 15-cm, myxoid and cellular, pleomorphic tumor with elongated, curvilinear, thin-walled vessels, and focal necrosis that involved the upper and middle segments of the kidney. Immunohistochemically, the tumor cells showed strong positivity for vimentin, bcl2 protein (nuclear staining pattern), CD34, CD99, and alpha-methylacyl coenzyme A racemase. The tumor was diagnosed as myxofibrosarcoma (MFS) grade 2 according to the FNCLCC system. To the best of our knowledge, this is the first report of an MFS arising from the kidney. Thus, MFS is an uncommon soft tissue tumor that can exceptionally arise from the kidney. The differential diagnosis with other myxoid tumors is of vital importance because it includes lesions with subtle differences and extremely variable biological behavior. Radical surgery is the treatment of choice. Long-term follow-up is recommended because of the tumor's capability for local recurrence and distant metastasis.

In the 1950s, the strategy of adding chloroquine to food salt as a prophylaxis against malaria was considered to be a successful tool. However, with the development of Plasmodium resistance in the Brazilian Amazon, this control strategy was abandoned. More than 50 years later, asexual stage resistance can be avoided by screening for antimalarial drugs that have a selective action against gametocytes, thus old prophylactic measures can be revisited. The efficacy of the old methods should be tested as complementary tools for the elimination of malaria.

Solitary fibrous tumors (SFTs) represent an uncommon entity most frequently manifested in the pleura. We describe herein two new cases located in the jejunal and sigmoid mesentery incidentally found in patients aged 61 and 32 years. In a review of the literature, we have compiled 15 mesenteric SFTs including our two cases. The mean age of the patients at presentation was 51.7 years (range, 26-83 years). Most patients were males (males:females 4:1). Although occasionally these tumors were an incidental finding, the majority have been symptomatic. Tumors varied greatly in size (3 to 25 cm), but most of them were large (mean 14.8 cm). Most cases (60%) were located in the small intestine mesentery. The hemangiopericytomatous (cellular) variant was the most common. All patients were treated by surgery and no other therapeutic approaches (chemo-/radiotherapy) were used. Follow-up data were available in 11 cases and ranged from six days to 21 years, with a mean follow-up period of 36.2 months. None recurred or metastasized. Two (13.3%) of the 15 cases showed atypical histological features concordant with histological, but not clinical malignancy. The main differential diagnosis includes gastrointestinal stromal tumor, synovial sarcoma and reactive nodular fibrous pseudotumor of the mesentery. In one third of the cases, tumor excision did not require intestinal resection. To our knowledge, our Case No. 1 is the first reported that has been removed through laparoscopic surgery. Radical surgery remains the treatment of choice. The unpredictable behavior of SFTs requires a careful, close, long-term follow-up.

A renal vein aneurysm is rarely secondary to an arteriovenous fistula. A symptomatic 4.7-cm aneurysm of the right renal vein arising from an idiopathic arteriovenous fistula in a 41-year-old woman is described. Imaging techniques have a critical role in planning the treatment. The 4.7-cm aneurysm showed a venous wall with uneven thickening of the intima, irregular atrophy and architectural disarray of the media, and partial loss of elastic fibers. Potential for rupture supports surgical intervention in a selected patient with a macroaneurysm.

Prichard’s structures of the fossa ovalis are not histogenetically related to cardiac myxoma Aims: Cardiac myxomas are neoplasms of unknown histogenesis. They are thought to arise from hypothetical subendothelial vasoformative reserve cells or from primitive cells which reside in the fossa ovalis and surrounding endocardium. In 1951 Prichard described a kind of microscopic endocardial structure with a predilection for the interatrial septum, which were suggested to be related to cardiac myxomas. To confirm the existence of Prichard’s structures and to clarify their role in the genesis of cardiac myxomas, we examined histologically the fossa ovalis and we performed an immunohistochemical study of the endocardial abnormalities that were found. Methods and results: A prospective histological study of 100 interatrial septa and an immunohistochemical study of three out of the 12 endocardial abnormalities that were detected, as well as of four conventional cardiac myxomas were accomplished. Antibodies were used to vimentin, CD31, CD34, α-smooth muscle actin, S100 protein, thrombomodulin, calretinin and c-kit (CD117), a tyrosine kinase growth factor receptor for stem cell factor usually expressed by embryonic/fetal endothelium. Structures similar to the ones described by Prichard were found in 12% of septa, most of them in the left side of the fossa ovalis. The hearts with these structures were from patients 10 years older than the ones without them (72 ± 10 versus 62 ± 16 years, P=0.006). Immunohistochemically the cells comprising Prichard’s structures were positive for vimentin, CD31, CD34 and thrombomodulin, and negative for α-smooth muscle actin, S100 protein, calretinin and c-kit. Therefore these cells seem to be mature endothelial cells, but not primitive multipotential mesenchymal cells. Furthermore, these cells were not found in the atrial tissue from the bases of any of the conventional cardiac myxomas. Conclusions: Our study suggests that there is no apparent relation between Prichard’s structures and cardiac myxomas, and that Prichard’s minute endocardial deformities are age-related phenomena.

The synchronous occurrence of three different types of renal tumor in a patient is rare. We report a case of conventional (clear cell) renal cell carcinoma harboring metastatic foci of mammary carcinoma associated with two angiomyolipomas in the left kidney incidentally discovered at the autopsy. The patient was a 75-year-old woman, without the tuberous sclerosis complex, who had undergone left radical mastectomy and radiotherapy for an infiltrating duct carcinoma of breast 30 years before. This tumor was widely disseminated at autopsy, but the nontumorous renal parenchyma was free of metastases. To the best of our knowledge this combination of neoplasms has not been described before. This case shows the important role played by autopsy in the accurate investigation of interrelations among coexisting tumors. Ann Diagn Pathol 5:293-299, 2001.

Pagetoid dyskeratosis is an incidental finding in a variety of lesions of the skin and squamous mucosa. The lesion is considered a selective keratinocytic response in which a small part of the normal population of keratinocytes is induced to proliferate in response to friction. As far as we know, pagetoid dyskeratosis has not been reported in the lips. In this article, we describe the location of the lesion in the lips and its incidence in a group of 90 unselected patients who underwent biopsy or were surgically treated for diverse labial lesions. Histochemical staining and immunohistochemical studies were performed in selected cases. Pagetoid dyskeratosis was found in 38 cases (42.2%) but only in 6 cases (6.7%) the lesion was conspicuous. There was no significant difference between the upper and the lower lip in terms of incidence of the lesion. Labial pagetoid dyskeratosis was more frequent in younger patients (46.7 +/- 25.0 versus 58.5 +/- 20.5; p0.05) and in women (chi(2) = 3.89; p0.05). Pagetoid cells were more common in suprabasal location and in the labial mucosa. These cells showed positivity for high-molecular weight cytokeratin and negative reaction for low-molecular weight cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and human papilloma virus. The immunohistochemical profile is different from the surrounding keratinocytes, indicating premature keratinization. The main differential diagnoses include white sponge nevus, leukoedema, oral koilocytoses, hairy leukoplakia, pagetoid squamous cell carcinoma in situ, and extramammary Paget's disease of the oral mucosa. The morphologic features of dyskeratotic pagetoid cells are distinctive and easily recognized as an incidental finding, thus preventing confusion with other important entities including an intraepidermal tumor.

Background: Cardiac angiosarcoma is a rare tumor that has a predilection for middle-aged males and a marked predominance in the right atrium. The tumor may present abruptly with a fulminant clinical course. Initial presentation with metastatic disease is rare. Only one case has been reported of a patient who presented with cutaneous metastases. Methods and results: We here report the case of a 51-year-old man who initially presented with cutaneous metastases in the absence of cardiac symptoms. The skin biopsy was diagnosed as metastatic undifferentiated sarcoma. The patient died 26 days later with widely disseminated disease. At autopsy a tumor arising in the wall of the left atrium and in the interatrial septum was found. After an immunohistochemical study including CD31 and CD34 stains the diagnosis of cardiac pure epithelioid angiosarcoma was made. To the best of our knowledge this tumor variant has not been documented in the heart until now. Conclusion: Although cardiac angiosarcoma is a rare neoplasm, its presence should be suspected in patients with cutaneous metastatic angiosarcoma without an evident source of the tumor, even in absence of cardiac symptoms.

Pagetoid dyskeratosis, is considered a reactive process in which a small part of the normal population of keratinocytes is induced to proliferate. The lesion is characterized by pale cells resembling those of Paget's disease within the epidermis. These cells have been seen as an incidental finding in a variety of benign papules most commonly located in intertriginous areas. Among the inductors of the lesion, friction is suspected. To the best of our knowledge, these pale cells have not been reported in the cervix. We describe the location of the lesion in the ectocervix and the incidence of this lesion in a group of 100 unselected patients surgically treated for uterine prolapse. Another group of 100 unselected patients treated for uterine leiomyoma was used as a control. Pagetoid dyskeratosis was found in 37 cases (37%) of uterine prolapse and in five cases (5%) of uterine leiomyomas. The lesion is more common in uterine prolapse (p

Metastases of chondrosarcoma to the skin are uncommon. We report a case of dedifferentiated chondrosarcoma that manifested as cutaneous metastases and had an outcome of three weeks. A 69-year-old male presented with two cutaneous nodules, one in the chest and other in the inguinal area. The punch biopsy of the latter showed a poorly differentiated mesenchymal metastatic tumor. Shortly before death, an X-ray revealed a proximal epiphyseal lesion in the right humerus, radiographically interpreted as chondrosarcoma. The autopsy showed this lesion to be a dedifferentiated chondrosarcoma whose nonchondroid mesenchymal part was akin, histologically and immunohistochemically, to the cutaneous metastases. While ten previous reports of chondrosarcoma metastatic to the skin are known, we believe that this is the first case to report the cutaneous metastases of the dedifferentiated variety. Furthermore, skin metastasis preceding the diagnosis of chondrosarcoma has not been previously reported. The fact that one part of this kind of tumor can be highly undifferentiated or, else, differentiated along lines not usually reminiscent of bone tumors, can make the diagnosis of such cases extremely difficult. Most chondrosarcomas metastatic to the skin arise in bones of the extremities, including the hand. The most common type of tumor is conventional chondrosarcoma. These metastases can be either single or multiple with a slight predilection for the head and neck region. Most patients die in a mean time of 6 months after the appearance of cutaneous metastases.

In a retrospective study of 738 consecutive autopsies of adult males with solid malignant neoplasms, five (0.68%) were shown to have metastatic deposits within the testis. These were metastases from bronchial carcinoma (three cases), melanoma (one case), and pancreatic endocrine carcinoma (one case). The mean age of the patients with solid tumors metastatic to the testis was 60 years (range, 32 to 83 years). The metastases from the solid tumors presented two patterns: destructive and/or focal interstitial. The destructive pattern was characterized by sheets of malignant cells that destroyed and replaced the seminiferous tubules. The interstitial pattern was characterized by tumor cells within the interstitium without involvement of the seminiferous tubules. All metastases showing the destructive pattern were macroscopically evident. Approximately 40% of the metastatic deposits were microscopic and showed a focal interstitial pattern. These cases are not easily identified unless a sufficient number of tissue blocks are sampled and carefully scrutinized. In 20% of the cases the metastatic deposits were bilateral. Improved diagnostic skills and treatment protocols in the last 11 years apparently have not significantly affected incidence, distribution, or the pattern of metastatic spread of solid tumors to the testis.

Benign mucinous metaplasia in the surface epithelium of the genital area is rare and has only been reported once in the vulva. A unique case of benign mucinous metaplasia of the prepuce in a 65-year-old man is reported here. The lesion measured 0.6 cm, was located in the mucous surface of the foreskin, and showed acid mucin containing cells. We regard benign mucinous metaplasia as a reactive rather than a neoplastic process. The main lesions to be considered in the differential diagnosis are mucinous syringometaplasia, extramammary Paget's disease, cutaneous squamous cell carcinoma in situ with mucinous metaplasia, superficial spreading malignant melanoma, and epidermotropic metastasis. The confinement of mucin-containing cells to the epidermis, the absence of nuclear atypia, the basal orientation of the nuclei, the predominant location of the cells in the upper layers of the epithelium, and the fact that the mucinous cells are replacing the squamous epithelium rather that infiltrating it, all assist in recognizing mucinous metaplasia of the penis as a specific and benign entity.

Renal vein aneurysms are very uncommon. Those located in the right side are exceptional. A symptomatic, solitary, voluminous aneurysm of the right renal vein in a 33-year-old man is reported. The lesion was diagnosed preoperatively as a renal tumor. The pathologic study of the nephrectomy specimen disclosed a thrombosed saccular aneurism measuring 5.5 cm with marked medial atrophy of its wall. Recognition that a mass like this reported is of vascular origin is very important to avoid percutaneous biopsy which could be potentially hazardous; and for undertaking conservative prophylactic surgery. Renal venography is indicated for the diagnosis of these lesions.

Objective.—To describe one case of symptomatic skin and pleural Kaposi sarcoma (KS) associated with kidney transplantation. Diagnosis was supported by morphologic study and human herpesvirus 8 (HHV-8) detection in both tissues. Pulmonary involvement was not present. Design.—The presence of HHV-8 DNA sequences was proved using polymerase chain reaction (PCR), Southern blot hybridization, and in situ hybridization. Setting.—Human herpesvirus 8 is found in most KS from patients with and without the acquired immunodeficiency syndrome. Clinically significant pulmonary infiltration by KS is diagnosed uncommonly antemortem, and pleural disease is exceptional. Patient.—A 49-year-old man who had renal transplant with immunosuppressive therapy (tacrolimus and prednisone) and developed a cutaneous KS. A pleural effusion appeared without pulmonary involvement. Both lesions disappeared when immunosuppressive drugs were suspended. Later, the pleural effusion and the cutaneous lesions reappeared. Pleural biopsy specimens showed KS infiltration. Outcome.—The patient refused treatment and was lost to follow-up. Results.—The skin and pleural biopsies showed a proliferation of spindle-shaped cells positive for CD34. The HHV-8 sequences were detected by nested PCR. No amplification was detected in uninvolved skin from the patient or in peripheral blood mononuclear cells from 10 healthy individuals used as controls. The Southern blot hybridization confirmed these results. Conclusions.—To our knowledge, this is the first report of HHV-8 in symptomatic pleural KS, which was probably associated with immunosuppression after kidney transplantation. The demonstration of HHV-8 DNA in biopsy material in the appropriate cells could be diagnostic when the morphologic setting is consistent with KS.

The synchronous or metachronous occurrence of 2 tumors of the salivary glands in a patient is rare. These tumors are usually benign and of the same histologic type. Here we report a 78-year-old woman who developed a sebaceous lymphadenoma and an acinic cell adenocarcinoma simultaneously in the left parotid gland. To our knowledge, this combination of neoplasms has not been reported before.

Lymphangioma is a rare benign lesion of the gastrointestinal tract, in which the large intestine is the least commonly involved site. To the authors' knowledge a lymphangioma of the anal canal has not been reported. Described herein is a case of pedunculated polypoid lymphangioma of the right lateral wall on the transitional zone of the anal canal measuring 1.7 x 1.3 x 1 cm in a 40-year-old woman. A pedicle does not exclude the endoscopic diagnosis of lymphangioma. Lymphangioma must be included in the differential diagnosis of polypoid lesions of the anal canal.

Aims To determinate the relationship between tumoral angiogenesis and cathepsin D (CD) expression in tumour and host stromal cells of invasive breast carcinoma, and to examine its association with classical prognostic factors such as lymph node status, histological grade, tumour size, mitotic rate, peritumoral lymphovascular invasion and oestrogen receptor (ER) status. Methods and results Sections from 102 invasive breast carcinoma were cut from the archival formalin-fixed, paraffin-embedded tissue blocks and stained using immunohistochemistry for the endothelial cell adhesion molecule (CD31) and CD. Microvessel density was assessed by counting vessels in the three most vascular areas at × 400 field. The counts were expressed as the highest counts within any × 400 field. The evaluation of immunostaining for CD was performed separately in both the parenchymal and stromal cells. Microvessel density was correlated positively with histological grade and peritumoral lymphovascular invasion, and correlated inversely with ER status. Positive CD staining of tumour cells was more frequent in positive ER tumours and was not significantly associated with the other classical prognostic factors. However, moderate to strong staining of host cells was correlated with higher histological grade, higher mitotic index and lack of ER protein. There was a statistically significant association between CD expression of host stromal cells and higher vessel count. Conclusions CD in host stromal cells is associated with more aggressive tumours and with a higher intratumoral microvessel density. Evaluation of CD in combination with angiogenic activity may be of some help in more accurately predicting the biological behaviour of breast carcinoma.

Summary The presence of axillary lymph node metastases (ALNMs) is the most important prognostic factor in breast carcinoma. If ALNMs were predictable without performing axillary lymph node dissection (ALND), this procedure would not be necessary in selected patients. Using a combination of some of the new biological markers with the classical ones, our objective was I) to identify the best set of predictors of ALNMs, and II) to define predictive models with either high or low probability of ALNMs. We studied 102 patients with invasive breast carcinoma. All patients underwent ALND, and at least 10 axillary lymph nodes per case were obtained. In the primary tumour we evaluated size, histological subtype and grade, lymphatic/vascular invasion and margin. Hormone receptor status, MIB 1 index, microvessel density, c-erbB-2 and cathepsin D expression were assessed by immunohistochemistry, and DNA ploidy and S-phase by flow cytometry. Risk factors for ALNMs were estimated by nonlinear logistic regression analysis. The best predictors of ALNMs were: tumour size > 2 em [OR 6.45, 95% confidence interval (CI) 21.74 to 1.91], presence oflymphatic/ vascular invasion [OR 4.95, CI (14.50 to 1.69)], infiltrative margin [OR 9.87 CI (37.44 to 2.60)] and high MIB-1 index [OR 8.39, CI (33.47 to 2.10)]. Two subsets had a very high risk of ALNMs: I) tumour size > 2 em, with lymphatic/vascular invasion and infiltrative margin; 26 (89 .66%) of 29 patients of this subgroup had ALNMs, and (II) tumour size > 2 em, with lymphatic/vascular and high MIB1 index.; eight of the nine (89%) patients of this subgroup had ALNMs. We could also identify a twovariable model with a very low risk of ALNMs constituted by tumour with circumscribed margin and low MIB-1 index. Of the 19 patients showing these features, only 1 (5.26%) had ALNMs. Therefore, pathological features of the primary tumour can help to assess the risk for ALNM in invasive breast carcinoma. Such risk assessment might avoid regional surgical overtreatment.

Vasculitis involving the prostate is uncommon and usually reflects systemic disease. Isolated prostatic vasculitis is very rare. Most of these cases are morphologically categorized as polyarteritis nodosa. We describe a 72-year-old man with idiopathic granulomatous vasculitis limited to the prostate. The vasculitis was identified incidentally upon microscopic examination of the suprapubic prostatectomy specimen removed for nodular hyperplasia. The transmural inflammation was centered on muscular arteries and veins and it was accompanied by narrowing of the lumen. Vasculitis was not associated with any secondary changes such as infarct or postinfarct fibrosis. Immunophenotyping of the vascular inflammatory infiltrate disclosed abundant macrophages and T-lymphocytes and virtual absence of B-lymphocytes. The patient is alive and well on no treatment for a follow-up period of 14 months. To our knowledge this is the second case report of prostatic involvement in localized idiopathic granulomatous vasculitis. It is important to distinguish cases of isolated granulomatous vasculitis in the prostate from systemic disease, because the latter implies a poor prognosis and requires an aggressive treatment.