Cell proliferation marker MCM2, but not Ki67, is helpful for distinguishing between minimally invasive follicular carcinoma and follicular adenoma of the thyroid.

AIMS: To compare cell proliferation markers, minichromosome maintenance protein 2 (MCM2) and Ki67, in minimally invasive follicular carcinoma (MIFC) and follicular adenoma (FA) of the thyroid and among MIFCs with different diagnostic criteria. METHODS AND RESULTS: Twenty-two MIFCs and 20 FAs were immunohistochemically stained for MCM2 and Ki67. The MIFCs were subdivided into six Group 1 tumours with both capsular and vascular invasions, seven Group 2 tumours with vascular invasion only and nine Group 3 tumours with capsular invasion only. The MCM2 and Ki67 indices were calculated, counting more than 1000 tumour cells in the most frequently positive areas. In total and Groups 1-3 MIFCs and in FAs, the average MCM2 index was 26.7 +/- 11.0, 28.4 +/- 8.6, 26.3 +/- 14.8, 25.9 +/- 8.4 and 10.7 +/- 4.5, respectively, whereas the average Ki67 index was 2.07 +/- 1.65, 1.93 +/- 2.02, 2.49 +/-1.38, 1.84 +/- 1.5 and 1.78 +/- 0.92, respectively. There was a significant difference in the MCM2 index, but not in the Ki67 index, between each category of MIFCs and FA (P < 0.01). However, neither the MCM2 index nor the Ki67 index showed a statistically significant difference among the subgroups of MIFC. CONCLUSIONS: MCM2, but not Ki67, is a helpful marker for differentiating MIFC from FA. The tumour cell proliferative activity supports the histological criteria based on diagnosing MIFC by either capsular or vascular invasion only.

Expression of matrix metalloproteinases in benign and malignant follicular thyroid lesions.

AIMS: To examine expression of matrix metalloproteinases (MMPs) and related proteins in follicular thyroid lesions (FTLs) and to determine their usefulness for differential diagnosis of FTLs, particularly between minimally invasive carcinoma and adenoma. METHODS AND RESULTS: Six widely invasive follicular carcinomas (WIFCs), 15 minimally invasive follicular carcinomas (MIFCs), 19 follicular adenomas (FAs) and 10 adenomatous goitres (AGs) were analysed immunohistochemically for MMP-1, MMP-2, MMP-7, MMP-9, membrane-type 1-MMP (MT1-MMP) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). MMP-1 was positive in all FTLs. MMP-2 and MMP-7 were positive in more than 80% of WIFC and MIFC cases, whereas they were negative in all FA and AG cases except one MMP-2+ FA (P < 0.001). MMP-9 stained positive significantly more in MIFC than FA or AG cases (P < 0.05, respectively). The positivity of MT1-MMP and TIMP-2 was different among some of the FTLs, but with no significant difference between MIFC and FA cases. In-situ hybridization of MMP-2 and MMP-7 mRNA in selected cases demonstrated the expression of these enzymes in the tumour cells as well as in some stromal cells. CONCLUSIONS: Our results confirm MMP expression mainly in malignant FTLs and suggest that MMP-2 and MMP-7 may be useful markers to distinguish MIFC from FA.

Glia maturation factor-beta is produced by thymoma and may promote intratumoral T-cell differentiation.

AIMS: To investigate whether Glia maturation factor-beta (GMFB) is expressed in thymomas and is associated with T-cell development. METHODS AND RESULTS: We investigated the expression of GMFB by immunohistochemistry in 86 cases of thymoma classified into five type A, 35 type AB, 11 type B1, 26 type B2, and nine type B3 thymomas according to the World Health Organization classification system. Immunoblotting and in situ hybridization (ISH) studies were also performed in selected cases. The results of the immunoblot analysis were in accordance with those of immunohistochemical scoring. The ISH study ascertained the tumour cells producing the protein. Immunohistochemically, GMFB expression was observed in one (20%) of type A, 32 (80%) of type AB, all (100%) of type B1 and B2, and eight (89%) of type B3 thymoma with statistically significant differences between type A and type AB, type B1, or type B2 thymoma, and between type B3 and type AB or type B2 thymoma. There was a significant correlation between GMFB expression and the amount of accompanying non-neoplastic T cells. GMFB promoted T-cell differentiation into CD4-/CD8+ cells when analysed by two-colour flow cytometry. CONCLUSIONS: The present study suggests that T-cell development in thymoma may be maintained partly by GMFB produced by the tumour cells.

Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis.

AIMS: Malignant thymic tumour histologically resembling a soft tissue sarcoma is extremely rare and defined as sarcomatoid carcinoma in the recent World Health Organization (WHO) classification. We report two such cases in which the tumour cells showed a prominent rhabdomyoblastic differentiation and analyse whether these tumours retain an epithelial nature at least in part. METHODS AND RESULTS: One tumour occurred in a 51-year-old man (Case 1) and the other in a 40-year-old woman (Case 2). Microscopically, both tumours consisted essentially of two types of tumour cells: spindle and large round cells, with no apparent epithelial components. Osteosarcomatous small foci were also found in Case 2. Immunohistochemically, desmin and muscle-specific actin were positive in the majority of both types of tumour cells, whereas myogenin was predominant in the spindle cells and myoglobin in the large round cells. Some of both types of cells expressed cytokeratin with co-expression of myoglobin in the large round cells, but with no myogenin in the spindle cells. Some cytokeratin-positive spindle cells were also negative for desmin. Ultrastructural examination of a recurrent tumour in Case 2 revealed some epithelial features among the spindle cells. Cytogenetic study of the same tumour showed a complex abnormality including der(16)t(1;16)(q12;q12.1), an identical pattern previously reported in a case of thymic squamous cell carcinoma. CONCLUSIONS: The findings support the definition in the WHO classification of sarcomatoid carcinoma that includes purely sarcomatous tumour as in the present cases. Occurrence of this type of tumour may indicate a relationship between thymic epithelial cells and myoid cells and/or a potential for divergent differentiation in thymic epithelial tumours.

FDG-PET findings in sclerosing hemangioma of the lung: a case report.

We report a case of sclerosing hemangioma of the lung that showed an intermediately increased accumulation of 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET). We suggest that FDG-PET may be useful for considering a lesion as benign or low-grade malignant.

A case of isolated esophageal cyst in the posterior mediastinum.

We report a rare case of posterior mediastinal esophageal cyst associated with pulmonary anomaly that had no connection with the proper esophagus, on either CT or MRI, and suggest including this entity in the differential diagnosis of posterior mediastinal masses.

The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia.

AIMS: A rare type of thymoma, micronodular thymoma with lymphoid B-cell hyperplasia, was recently reported by Suster and Moran. Thymic epithelial tumours with a similar pattern but with varied cytological features of the tumour cells are analysed. METHODS AND RESULTS: A total of 11 cases of thymic epithelial tumours characterized by micronodular proliferation of tumour cells separated by abundant lymphoid stroma with prominent germinal centres were reviewed clinicopathologically and examined immunohistochemically. The presence of Epstein-Barr virus (EBV) genome was also examined by in-situ hybridization. Based on the morphology of tumour epithelial cells, cases were subdivided into four groups: group 1 (two cases) having spindle epithelial cells; group 2 (two cases) showing an admixture of spindle and polygonal epithelial cells; group 3 (five cases) having polygonal epithelial cells, with mild to moderate cytological atypia in four cases, and group 4 (two cases) representing lymphoepithelioma-like carcinoma. The degree of cytological atypia and the number of tumour cells positive for MIB-1 and p53 gradually increased towards group 4. The abundant lymphoid stroma in all cases contained many CD20-positive B-cells and CD3 and CD45RO-positive T-cells. CD99-positive immature T-cells were present in all cases of groups 1 and 2 and in most cases of group 3, but not in both cases of group 4 tumours. IgG, IgM and IgD-positive plasma cells and lymphocytes were also present in all cases, more prominent in those of groups 3 and 4. The EBV genome was detected in only a few lymphocytes in five cases. CONCLUSIONS: The tumours in this series belong to a distinct category of thymic epithelial tumours and each of the above groups may constitute a spectrum in the continuum of cytological atypia. The aetiological relationship of EBV with these tumours could not be proved. The lymphoid B-cell hyperplasia may result from a host immune response and may suggest a favourable clinical course of this type of tumour.

CT and MR findings of a pleomorphic adenoma in the peripheral lung.

We report a rare case of pleomorphic adenoma in the peripheral lung and its appearance on both CT and MR. The findings correlated well with the pathological findings and corresponded to the nature of the cellular predominance type that is common in the lung but is rare in the salivary gland.

Histopathologic changes of thymoma preoperatively treated with corticosteroids.

Preoperative treatment of thymoma in advanced stages with corticosteroids may reduce the size of the tumor, but no precise histologic evaluation has been performed. We examined the histopathologic features of pretreatment biopsy and posttreatment surgical specimens of eleven cases of thymoma with such treatment to see the changes of the histologic subtypes based on Muller-Hermelink classification. All specimens were also assessed immunohistochemically for MIB-1 labeling and apoptotic cells to verify the effectiveness of this pretreatment. Seven tumors clinically diminished in size after the treatment with corticosteroids. Fungal infection occurred in three cases postoperatively. The histology of mixed thymomas (two cases) was converted to that of medullary thymoma. Predominantly cortical thymomas (four cases) and cortical thymomas (three cases) changed to show similar histologic features; both became epithelial-rich thymoma with large polygonal tumor cells having indistinct cell borders. In contrast, two well-differentiated thymic carcinomas showed at surgery more prominent squamoid appearance with distinct cell borders. The apoptotic indices of epithelial cells were increased (P = 0.001), and the MIB-1 indices tended to be decreased with corticosteroid treatment. These results suggest that there may be a histogenetic relationship between medullary and mixed thymomas and also between predominantly cortical and cortical thymomas. Corticosteroids may cause degenerative changes in the epithelial cells and lymphocytes and, in thymomas in advanced stages, corticosteroid pretreatment may be warranted, although attention should be paid to infection after surgery.

Mott cell tumor of the stomach with Helicobacter pylori infection.

A plasma cell tumor of the stomach with unusual histology is reported. Macroscopically, the tumor formed two ulcers in the gastric body, and microscopic examination revealed proliferation of plasma cells producing immunoglobulin G kappa monotypic immunoglobulin, with metastatic infiltration in some perigastric lymph nodes. Most of these plasma cells had various-sized Russell bodies in the cytoplasm; hence the tumor may be called Mott cell tumor. The Russell bodies showed a strong affinity to concanavalin A by lectin immunohistochemistry, compared with those in reactive Mott cells. In addition, Helicobacter pylori (H. pylori) infection was proved by Gimenez stain and immunohistochemistry. The mixture of some centrocyte-like cells and presence of reactive lymph follicles with follicular colonization by tumor cells suggest that this lesion may be a variant of mucosa-associated lymphoid tissue lymphoma in association with H. pylori infection. The patient has shown no evidence of recurrence of the tumor after 11 years of follow up.

Clinical and functional significance of WHO classification on human thymic epithelial neoplasms: a study of 146 consecutive tumors.

We examined the clinical and functional significance of histologic classification of thymic epithelial neoplasms proposed by the World Health Organization (WHO), based on an analysis of 146 consecutive tumors derived from 141 patients and 47 normal thymuses derived from children ranging in age from 1 to 9 years. Invasive tumors were seen in 12.5%, 38.6%, 40.0%, 69.4%, 80.0%, and 100% of type A, AB, B1, B2, B3, and C primary tumors, respectively. All of six recurrent or metastatic lesions were type B2 tumors. Myasthenia gravis was associated in 0%, 6.8%, 40.0%, 55.6%, 10.0%, and 0% in patients with type A, AB, B1, B2, B3, and C tumors, respectively. The average number (x10(6)) of tumor-associated CD4+CD8+ cells present in 1 g of tumor tissue was 1.5, 391.1, 1041.7, 333.9, 24.5, and 0.2 in type A, AB, B1, B2, B3, and C, respectively, and it was 1168.2 in the normal thymuses. Thus, type B1 tumor retained the function to induce CD4+CD8+ double-positive cells at a level comparable to that of the normal thymic cortical epithelial cells, followed by type AB and type B2 tumors. Type A and B3 tumors had this function at a barely detectable level, and type C tumor was nonfunctional. WHO histologic classification was shown to reflect the clinical features and the T-cell-inducing function of thymic epithelial tumors.

Different keratin profiles in craniopharyngioma subtypes and ameloblastomas.

Craniopharyngiomas are generally considered to arise from the remnants of Rathke's pouch or a misplaced enamel organ. We tried to refine these hypotheses, comparing the subtypes of craniopharyngioma with Rathke's cleft cyst, a known Rathke's pouch derivative, and with ameloblastoma, an enamel organ derivative. Nineteen craniopharyngiomas (14 adamantinomatous and 5 papillary type tumors) and 17 ameloblastomas were immunostained for cytokeratin (CK) 7, CK 8, CK 14, and human hair keratin (HHK). All cases of adamantinomatous craniopharyngioma were CK 7+/CK 8+/CK 14+. Two cases (40%) of papillary craniopharyngioma were CK 7+/CK 8+/CK 14+, whereas the remaining three cases (60%) were CK 7+/CK 8-/CK 14+. Fifteen cases (88%) of ameloblastoma were CK 7-/CK 8+/CK 14+. Only the shadow cells present in adamantinomatous craniopharyngiomas were positive for HHK, which may indicate their follicular differentiation. In Rathke's cleft cyst, ciliated cuboidal cells were CK 7+/CK 8+/CK 14- and metaplastic squamous cells were CK 7+/CK 8/CK 14+. These findings suggest that both subtypes of craniopharyngioma may differ from ameloblastoma in histogenesis, although cytokeratin expression patterns may change during tumor development. Adamantinomatous craniopharyngioma may be related to a heterotopic ectodermal tissue which can differentiate into hair follicles, while papillary craniopharyngioma may arise from Rathke's cleft cyst.

CT-pathologic correlation in a case of solitary plasmacytoma of the rib.

We report a case of solitary plasmacytoma of rib origin in a 46-year-old man. CT revealed a focal expanding mass in the right fifth rib. The mass showed ridging, cortical thickening, and fine erosion on the inner aspect of the cortex and had partly penetrated the bone. On both T1- and T2-weighted MR images, the mass showed low to intermediate intensity, and contrast studies showed homogeneous enhancement. Whole body bone scintigraphy revealed abnormal solitary accumulation, and therefore surgical resection was performed. Macroscopically the specimen revealed destruction of the cortex caused by tumor invasion, corresponding to the CT findings. Microscopic findings included a large number of plasma cells, leading to a histopathological diagnosis of plasmacytoma.

A case of thymic cyst associated with thymoma and intracystic dissemination.

We report a rare case of anterior mediastinal thymic cyst together with a thymoma and its intracystic dissemination. More attention should be given to intramural nodules, especially in patients with an anterior mediastinal thin wall cystic lesion.

PE-35-related antigen expression and CD1a-positive lymphocytes in thymoma subtypes based on Müller-Hermelink classification. An immunohistochemical study using catalyzed signal amplification.

PE-35 monoclonal antibody, detecting a cell-surface antigen of various types of carcinoma and normal epithelium, reacts exclusively with the medullary epithelium in the thymus; therefore, the antigen has been considered as a marker of medullary differentiation in thymomas. Using the catalyzed signal amplification method, which made it possible to apply PE-35 to routinely processed, archival tissues, we examined expression of this antigen, together with CD1a reactivity of lymphocytes, in 40 thymic epithelial tumors subclassified using the Mü1ler-Hermelink system. Medullary thymomas infiltrated with a small number of CD1a-negative lymphocytes were PE-35 positive, although many of the long spindle tumor cells were PE-35 negative. Mixed thymomas and predominantly cortical thymomas, both with prominent CD1a-positive lymphocytes, were also PE-35 positive, although some areas of the latter type were PE-35 negative. Cortical thymomas with decreased numbers of CD1a-positive lymphocytes were largely PE-35 negative. In well-differentiated thymic carcinomas with a few CD1a-positive lymphocytes, two cases were negative, but four cases were at least focally positive with PE-35. All high-grade thymic carcinomas infiltrated with some CD1a-negative lymphocytes were PE-35 positive. These results suggested that medullary thymoma generally possesses the medullary nature, although the latter tends to be lost in the long spindle tumor cells. Mixed and predominantly cortical thymomas may have mixed medullary phenotype and cortical function. Cortical thymoma and many well-differentiated thymic carcinomas may possess the cortical nature, while the large polygonal tumor cells tend to lose immature T-lymphocyte-retaining function.

Percutaneous myocardial ablation in double-chamber right ventricle.

Double-chamber right ventricle (DCRV) exhibits intracavitary outflow obstruction. We report the first case of percutaneous myocardial ablation of DCRV in a 73-year-old patient. An alcohol-induced conus branch occlusion provided the reduction of pressure gradient from 81 to 48 mm Hg and clinical improvement. This strategy may be an alternative therapy to surgery in the adult patients with DCRV. Cathet. Cardiovasc. Intervent. 49:97-101, 2000.

Mucinous tumor of the gallbladder with a separate nodule of anaplastic carcinoma.

A case of mucinous tumor of the gallbladder with a separate nodule of anaplastic carcinoma is reported. The patient was an 83-year-old Japanese man who underwent cholecystectomy under the preoperative diagnosis of a mucus-producing gallbladder tumor. A mucinous tumor was found in the neck and distal body of the gallbladder, associated with a separate nodule in the fundus. The latter nodule was initially diagnosed as a benign xanthogranulomatous lesion. However, the immunohistochemical study revealed that the atypical cells in the superficial part of the nodule were positive for cytokeratin and epithelial membrane antigen, confirming the diagnosis of anaplastic carcinoma. Although the occurrence of mural nodules in mucinous cystic tumors of the ovary and pancreas is well reported, to our knowledge, this is the first report on the occurrence of a mucinous tumor with a nodule of anaplastic carcinoma in the gallbladder.

Final results of the STent versus directional coronary Atherectomy Randomized Trial (START)

OBJECTIVES: This study was designed to compare primary stenting with optimal directional coronary atherectomy (DCA). BACKGROUND: No previous prospective randomized trial comparing stenting and DCA has been performed. METHODS: One hundred and twenty-two lesions suitable for both Palmaz-Schatz stenting and DCA were randomly assigned to stent (62 lesions) or DCA (60 lesions) arm. Single or multiple stents were implanted with high-pressure dilation in the stent arm. Aggressive debulking using intravascular ultrasound (IVUS) was performed in the DCA arm. Serial quantitative angiography and IVUS were performed preprocedure, postprocedure and at six months. The primary end point was restenosis, defined as > or =50% diameter stenosis at six months. Clinical event rates at one year were also assessed. RESULTS: Baseline characteristics were similar. Procedural success was achieved in all lesions. Although the postprocedural lumen diameter was similar (2.79 vs. 2.90 mm, stent vs. DCA), the follow-up lumen diameter was significantly smaller (1.89 vs. 2.18 mm; p = 0.023) in the stent arm. The IVUS revealed that intimal proliferation was significantly larger in the stent arm than in the DCA arm (3.1 vs. 1.1 mm ; p < 0.0001), which accounted for the significantly smaller follow-up lumen area of the stent arm (5.3 vs. 7.0 mm2; p = 0.030). Restenosis was significantly lower (32.8% vs. 15.8%; p = 0.032), and target vessel failure at one year tended to be lower in the DCA arm (33.9% vs. 18.3%; p = 0.056). CONCLUSIONS: These results suggest that aggressive DCA may provide superior angiographic and clinical outcomes to primary stenting.