Histomorphological evaluation, cell proliferation and endothelial immunostaining in oral and maxillofacial myofibroblastic lesions.

BACKGROUND: Myofibroblasts (MF) are mesenchymal cells with features of both fibroblasts and smooth muscle cells. Although these are usually reactive cells, they can lead to myofibroblastic tumors that may share clinical and histomorphological characteristics but with different prognosis. The aim of this study is to perform a histomorphological evaluation as well as to compare and evaluate two different cell proliferation immunomarkers and two endothelial markers in a group of oral and maxillofacial myofibroblastic lesions (MFL). MATERIAL AND METHODS: Cross-sectional and retrospective study. Demographic, clinical, histomorphological and immunohistochemical characteristics of 39 cases of MFL were analyzed. Immunohistochemical reactions were performed with the Ki67, MCM2, CD34 and CD105 antibodies. Kruskal-Wallis test and Spearman correlation analysis were used. RESULTS: Four cases of nodular fasciitis (NF), 18 myofibromas (My), 6 desmoplastic fibromas (DF), 7 inflammatory myofibroblastic tumors (IMT) and 4 myofibroblastic sarcomas (MFS) were studied. There were twenty women (51.2%); the median age was 13 [Q1-Q3: 8-24] years and most cases occurred in the mandible (48.7%). A statistically significant difference with MCM2 immunostaining (p=0.0221) was observed between the MFL; furthermore, a correlation between CD34 and CD105 immunostaining in NF (p <0.0001) and IMT (p=0.0408), between MCM2 and CD34 in IMT (p=0.0362) and between MCM2 and CD105 in MFS (p <0001) were found. CONCLUSIONS: MCM2 immunostaining could assess more clearly the cell growth fraction in MFL. The correlation between MCM2 and CD34 in IMT and between MCM2 and CD105 in MFS are indicative of the high activity of these lesions. These results emphasize the importance of the studied immunohistochemistry markers as possible tools for a better characterization of some of the MFL.

SELNET clinical practice guidelines for bone sarcoma.

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.

Perineurioma versus meningioma. A multi-institutional immunohistochemical and ultrastructural studY.

The differential diagnosis between perineurioma (PN) and meningioma (MEN) can be difficult by histology and immunohistochemistry (IHC) because the perineurium and arachnoid have the same embryological origin. However, there are no comparative studies determining conclusive parameters for the differential diagnosis. The aim of this study is to compare IHC of PN and MEN and their ultra-structural characteristics to elucidate which are the useful data that allow differentiate both entities. Thirty-five MEN were analyzed, and 15 PN, (11 skin and soft tissues and four oral cavity). IHC for epithelial membrane antigen (EMA), Claudin-1, GLUT-1, somatostatin-2 receptor (SSTR-2), and progesterone receptor (RP) was performed. Ultrastructural studies were performed on 8 MEN and 15 PN. Only in PN Claudin-1 was positive in 9/11 (90%) cases and GLUT-1 in 7/11 (63%) cases. In MEN, the progesterone receptor was expressed in 21/35 (60%) cases and no case expressed Claudin-1 and GLUT-1; EMA was expressed in all MEN cases and 93% of PN. SSTR-2 was expressed weakly in six cases of MEN (17%), and it was not considered useful for differential diagnosis. On ultrastructure, PN showed thin and parallel processes, some caveolae, and lacked cell junctions. The cellular processes were surrounded by a collagenous stroma in 94% of the cases. MEN were characterized by curved cytoplasmic cell processes showing desmosomes in 75% of cases. Ultrastructural findings aid in the differential diagnosis between PN and MEN, especially if molecular studies are not available.

Prognostic factors and treatment strategies for adult head and neck soft tissue sarcoma.

Adult head and neck soft tissue sarcomas are rare and display a variety of histological types and clinical characteristics; they are also associated with a variety of mortality risks. The purpose of this study was to examine all patients treated at the Instituto Nacional de Cancerologia for head and neck sarcoma during a 5-year period. Fifty-one adult patients were examined and treated for head and neck sarcomas from 2004 to 2009. The 51 tumours were histologically re-evaluated by expert pathologists and classified as low, intermediate or high grade sarcomas. A multivariate analysis was performed to evaluate the surgical margins, histological grades, and clinical stages as prognostic factors for the disease. Adult head and neck soft tissue tumours are rare, and they are associated with poor prognosis for patients, especially at clinical stages III and IV. The average survival rate after 2 years is 45%, and most of these patients die because of disease progression and metastases.

Dilated intercellular spaces in subtypes of gastroesophagic reflux disease.

BACKGROUND: Dilatation of the intercellular spaces by electron microscopy has been considered as an early morphological marker of tissue injury in gastroesophageal reflux disease. The degree of dilatation in Barret's esophagus in currently unknown. OBJECTIVES: To determine the frequency of dilated intervellular spaces in Barrett's esophagus. MATERIAL AND METHODS: Cross-sectional and prospective analysis of consecutive patients with gastroesophageal reflux disease. We selected symptomatic patients > 18 years and both sexes. Patients with recent PPI use (< 14 days), H-2 antagonists, NSAID's or previous upper GI tract surgery were excluded. VARIABLES INCLUDED: Clinical-demographic data, Carlsson-Dent score, conventional endoscopy findings, pH-metry results (in non-erosive) and normal mucosal biopsies at 2 and 5 cm above the squamocolumnar junction. Dilation of intercellular spaces was measured by electron microscopy. STATISTICS: Chi square test with a significance level 0.05 was calculated. The following four groups were compared: a) non-erosive reflux disease (n = 14); b) erosive esophagitis (n = 5); c) Barrett's esophagus (n = 13); and d) healthy controls (n = 5). RESULTS: the dilation of intervellular spaces was increasingly greater form non-erosive revlux to Barrett's esophagus and higher in biopsies taken at 5 cm than at 2 cm of the squamous columnar junction (2.72 +/- 1.35 vs. 1.71 +/- 0.48 microg) (p = 0.001). There was no difference between biopsies at 2 and 5 cm in the order groups. CONCLUSION: dilation of intercellular spaces was greater in Barrett s esophagus than in the other groups and higher at 5 cm from the squamocolumnar junction.

Lymphoepithelioma-like anaplastic thyroid carcinoma: report of a case not related to Epstein-Barr virus.

A 68-year-old man developed a rapidly growing thyroid tumor that extended into the retropharyngeal, prevertebral, and perilaryngeal spaces, and eventually invaded the esophagus. The patient was treated with radiotherapy, obtaining a good but incomplete response. The neoplasia was composed of sinctitial sheaths of epithelial cells with large vesicular nuclei, prominent nucleoli, and high mitotic activity. There was abundant lymphoid infiltrate surrounding and invading the cell sheaths. The overall picture was of a lymphoepithelioma, but no evidence of Epstein-Barr virus infection was detected by studies of immunohistochemistry and polymerase chain reaction. We believe this case represents a morphologic variant of anaplastic carcinoma that should be separated from carcinoma showing thymus-like differentiation, a tumor that also resembles lymphoepithelioma but has an indolent course. Ann Diagn Pathol 5:21-24, 2001.

Hepatocellular carcinoma: an update.

Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and alpha1 -antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal-infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of H BV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically-induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy.

Large cell calcifying Sertoli cell tumor of the testis: a clinicopathological, immunohistochemical, and ultrastructural study of two cases.

Large cell calcifying Sertoli cell tumor of the testis (LCCSCT) is a rare tumor that is usually benign and multifocal. It may be associated with hereditary endocrine anomalies such as Carney's and Peutz-Jeghers syndromes. Malignant forms are exceptional. Two cases of LCCSCT, one malignant and one benign are described. Both were composed of cords and trabeculae of large polygonal cells embedded in a myxoid and fibrous stroma with areas of calcification. The malignant tumor showed nuclear atypia, necrosis, and abundant mitoses. The cells were positive for vimentin and S-100 protein, and the intercellular space for laminin and collagen type IV. By electron microscopy, nucleolonemas and multilayered basal lamina were seen. The benign tumor was positive for vimentin and S-100 protein, and ultrastructurally showed less basal lamina.

Germ cell tumors of the mediastinum and testis: a comparative immunohistochemical study of 120 cases.

An immunohistochemical study was performed in 120 cases of mediastinal and testicular germ cell tumors from archival, paraffin-embedded material to compare the patterns of expression between the two groups with a panel of markers, including broad-spectrum keratin, CAM 5.2 low-molecular-weight cytokeratin, placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), human beta-chorionic gonadotropin (hCG), vimentin, and CD30 (Ki-1 antigen). Significant differences were observed between mediastinal and testicular seminomas: mediastinal seminomas showed strong dot-like paranuclear positivity of the tumor cells with antibodies to CAM 5.2 low-molecular-weight keratin in 80% of cases (32 of 40), as compared with only 20% positivity (5 of 24) in testicular seminomas; placental alkaline phosphatase (PLAP) was also found to be less commonly expressed in testicular seminomas (12 of 24) than in mediastinal seminomas (37 of 40); a similar pattern of expression was also observed for vimentin, which was present in scattered tumor cells in a higher proportion of mediastinal seminomas (28 of 40) than in testicular seminomas (11 of 24). The staining pattern and distribution of these markers did not show significant differences between the two groups for the various other tumor categories studied, including yolk sac tumor, embryonal carcinoma, and choriocarcinoma. The tumor cells in both testicular and mediastinal embryonal carcinoma showed strong positivity for the CD30 antigen; however, strong positivity for this marker was also observed in 6 of 25 yolk sac tumors and in scattered individual tumor cells in 4 of 63 seminomas. The results of this study show that significant differences exist between the immunostaining patterns of mediastinal and testicular seminomas, suggesting that the former may be characterized by a more mature phenotype than their testicular counterparts. Also, CD30 expression may not be necessarily restricted to embryonal carcinomas and occasionally may be observed in yolk sac tumors and seminoma cells, supporting the close histogenetic relationship that exists among these tumor types.

Amphicrine medullary carcinoma of the thyroid with luminal differentiation: report of an immunohistochemical and ultrastructural study.

A case of amphicrine medullary carcinoma of the thyroid is presented. The patient was an 18-year-old female with nonhereditary MEN IIb, submucosal neuromas in the oral cavity, and a thyroid tumor that metastasized to regional lymph nodes. Histologically the thyroid tumor was composed of polygonal cells arranged in a solid/trabecular pattern admixed with mucus-producing goblet cells and displaying focal cytoplasmic lumen formation. Immunohistochemical stains were positive for calcitonin, carcinoembryonic antigen, and chromogranin. Electron microscopy demonstrated C-cells containing neurosecretory granules as well as intestinal-type microlumina. The presence of goblet cells and intestinal-type microlumina in medullary carcinoma of the thyroid is reminiscent of amphicrine tumors of the gastrointestinal tract and supports the hypothesis that the parafollicular C-cells of the thyroid may be of endodermal derivation.

Epithelioid angiosarcoma of the breast. Clinicopathological, immunohistochemical, and ultrastructural study of a case.

A breast tumor with features of epithelioid angiosarcoma (EAS) occurring in a 26-year-old woman is described. The lesion on lumpectomy was initially diagnosed as infiltrating ductal carcinoma and treated accordingly by radical mastectomy. The surgical specimen disclosed a high-grade tumor characterized by solid groups and sheets of atypical polygonal epithelioid cells displaying cytoplasmic microlumina alternating with anastomosing vascular channels. The endothelial nature of the epithelioid cells was demonstrated by the presence of vascular endothelium-associated markers by immunohistochemical and ultrastructural studies. The clinical features of this rare, hitherto undescribed lesion are similar to those of conventional breast angiosarcoma. The recognition of this entity is crucial because it can be confused with neoplasms displaying epithelial cytomorphology such as ductal carcinoma, pseudoangiosarcomatous carcinoma, metaplastic carcinoma, and epithelioid hemangioendothelioma. EAS should be added to the list of conditions that may present as a discrete tumor mass of the breast in young women.

Malignant meningioma of the parapharyngeal space: a case report.

A case of a malignant meningioma arising in the left parapharyngeal space in a 29-year-old woman is reported. Electron microscopic examination of the tumor was critical in establishing the diagnosis. Meningiomas of the parapharyngeal space are extremely rare. This constitutes the first malignant case documented in this location.

Ectopic poorly differentiated (insular) carcinoma of the thyroid. Report of a case presenting as an anterior mediastinal mass.

A case is presented of an anterior mediastinal mass arising in a 64-year-old woman that showed on histologic, immunopathologic, and ultra-structural examination features of a poorly differentiated (insular) thyroid carcinoma. The tumor in this patient most likely arose from ectopically displaced thyroid tissue on the basis of a developmental defect. The clinicopathologic features and differential diagnosis of the lesion in the setting of its mediastinal location are discussed. Ectopic poorly differentiated (insular) carcinoma of the thyroid should be added to the list of mediastinal tumors showing a solid or insular growth pattern.

Plasmacytoid myoepithelioma of the laryngeal region: a case report.

The first case of plasmacytoid myoepithelioma of the laryngeal region is presented. The tumor showed immunoreactivity for the S-100 protein, low molecular weight cytokeratin, and vimentin. Staining was negative with muscular actin and glial fibrillar acid protein. By electron microscopy the tumor cells showed abundant microfibrillar material, elongated densities resembling smooth muscle dense bodies, pinocytic vesicles, and replicated basal lamina. The myoepithelial nature of plasmacytoid tumors of the salivary gland has been questioned.

Dermatofibrosarcoma protuberans: ultrastructural and immunocytochemical observations.

In an attempt to elucidate the histogenesis of dermatofibrosarcoma protuberans, 38 specimens were examined by electron microscopy and immunocytochemistry. The cumulative evidence strongly favors a fibroblastic/myofibroblastic derivation.

Clinical and cellular effects of colchicine in fibromatosis.

The proliferating cells in fibromatoses are myofibroblasts that produce abundant stromal collagen and contain intracellular native and widely spaced collagen fibers. To assess the clinical and cellular effects of colchicine in such tumors, this drug was administered to three patients, one with musculoaponeurotic desmoid fibromatosis, one with Dupuytren's palmar fibromatosis, and one with Peyronie's disease. All three patients had an excellent clinical response, with reduction of tumor size and improvement of contracture. Two cases were studied ultrastructurally; the main cellular changes detected were collapse of the rough endoplasmic reticulum cisternae, reduction of myofilaments, and disappearance of intracellular widely spaced collagen. The findings from this study indicate another probable application for colchicine and support the concept that collagen fibers can be formed intracellularly.