Hung Chiang

Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma

Abstract Eleven atypical teratoid/rhabdoid tumors (AT/¶RT) and 121 primitive neuroectodermal tumors/medulloblastomas (PNET/MB) were included in this study for evaluation of the histopathological features of AT/RT and comparison between AT/RT and PNET/MB. Histopathological studies of AT/RT showed that in addition to the commonly recognized components, i.e., rhabdoid cells, small (PNET/MB) cells, spindle cells and epithelial components, there was a previously unrecognized component, sickle-shaped embracing cells, which were present in all cases and could be useful as a histological marker of this tumor. Immunohistochemical studies showed divergent differentiation of the tumor cells and among the 16 antibodies studied, vimentin, neuron-specific enolase, epithelial membrane antigen and glial fibrillary acidic protein were most commonly reactive. The frequency of AT/RT expressed as a ratio of AT/RT to PNET/MB was 1 : 11 in general and increased to 1 : 3.8 among patients younger than 3 years old. The AT/RT patients were younger than those with PNET/MB and had a female predominance. The MIB-1 labeling index of AT/RT was significantly higher than that of PNET/MB (mean 63.9 vs 40.1), which correlated with a shorter survival in patients with AT/¶RT than those with PNET/MB (median survival time ¶15.4 months vs 156.4 months).

The clinicopathological correlation of epithelial subtyping in thymoma: A study of 112 consecutive cases

The clinicopathological features of 112 thymomas collected from the surgical pathological files of Taipei Veterans General Hospital from 1961 to 1991 were investigated to determinate the clinical efficacy of epithelial subtyping. All thymomas were categorized based on the Müller-Hermelink system into three subtypes: cortical thymoma, mixed thymoma, and medullary thymoma. The former was further subclassified into organoid thymoma, conventional cortical thymoma, and well differentiated thymic carcinoma (WDTC) according to the systems of Pescarmona and Kirchner. The association of each subtype with sex, age at diagnosis, clinical stage, presence of myasthenia gravis, and length of survival was studied. As classified by the Müller-Hermelink system, the cortical thymomas as a whole tended to occur in younger patients and were more frequently associated with myasthenia gravis than the medullary thymomas. The cortical thymomas also showed a propensity to be invasive in nature, whereas the medullary thymomas generally behaved as benign tumors. Further subclassification of cortical thymomas into organoid thymoma, conventional thymoma, and WDTC did not provide more information about clinical behavior. By Kaplan-Meiers actuarial survival analyses none of the epithelial subtypes displayed a statistically significant influence on prognosis. It is concluded that staging remains the most important factor affecting the patients outcome. Because of the existence of many intermediate forms and the deficiency of clinical relevance, the subclassification of cortical thymomas should be interpreted as a morphological continuum rather than as distinct histological variants.

Clear cell myomelanocytic tumor of the urinary bladder.

Clear cell myomelanocytic tumors are a recently described neoplastic growth considered to be a member of the family of perivascular epithelioid cell tumor. These tumors have a predilection for falciform ligament/ligamentum teres. We report an additional case arising from the muscularis propria of the urinary bladder in a 33-year-old woman. The tumor consisted of clear to eosinophilic, epithelioid, and spindled cells arranged in fascicles or packets. A delicate vascular stroma was found among the nests. Immunohistochemically, the tumor cells were typically positive for HMB-45 and smooth muscle actin but negative for S-100 protein, Melan-A, desmin, and pan-cytokeratin. The patient has been free of the disease since the excision of the tumor 6 years ago. This case, in association with the expanding list of perivascular epithelioid cell tumor reported in different sites, suggests that this type of neoplasm may be ubiquitous.

A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma.

Optimal histologic criteria for the classification of and grading of ependymomas, including their anaplastic forms, remain elusive. This is especially true because of the poor correlation of these criteria with clinical outcome. The aim of this study was to identify the histopathologic parameters that could distinguish different prognostic groups of patients with ependymomas. Eighty-one patients with ependymal tumors, including those originally diagnosed ependymomas, anaplastic ependymomas and myxopapillary ependymomas, were enrolled in this study. Thirteen histologic parameters, including hypercellularity, nuclear pleomorphism, mitoses, endothelial proliferation, necrosis, clear cell, thrombi, dystrophic calcification, psammoma bodies, bone, cartilage, Rosenthal fibers and MIB-1 labeling index (LI), were evaluated in each patient and correlated with clinical outcome. We assigned one score for each histopathologic parameter evaluated and used a stepwise selection method with entry model based on the significance of the log-rank statistic to formulate a scoring model. Four parameters were chosen in this process, including mitoses ≥ 4/10 hpf (1.7/mm2), hypercellularity, endothelial proliferation and necrosis. The sum of these four parameters (scores) was the histopathologic score of the tumor. The progression-free survival (PFS) and overall survival (OS) of patients with histopathologic scores 0 and 1 were significantly better than those with histopathologic scores 2, 3 and 4 (p < 0.001 and p = 0.005, respectively). Because of the latter finding, we proposed that anaplastic ependymoma could be diagnosed by the presence of any two of the aforementioned four parameters. Multivariate analyses including clinical and histopathologic variables showed that histopathologic score ≥ 2 and subtotal resection were the factors related to increased risk of recurrence, while histopathologic score ≥ 2 was the only factor related to overall survival. Based on the above findings, we concluded that histopathology is an important prognostic indicator for patients with ependymomas.

Interobserver Reproducibility of Her-2/neu Protein Overexpression in Invasive Breast Carcinoma Using the DAKO HercepTest

Although there are criteria for interpretation of the staining results for Her-2/neu in the DAKO HercepTest, the determination of staining intensity and percentage of complete membrane staining is subjective. We studied 46 cases of invasive breast carcinoma to evaluate interobserver reproducibility among 5 pathologists. Complete agreement was achieved in 22 (48%) of46 cases. Generalized kappa values indicated substantial agreement (0.80). Discrepancies between negative (0, 1+) and positive (2+, 3+) results occurred in 2 cases (kappa = 0.96). One was because of a tangential cut of the basal part of the tumor that mimicked complete membranous staining, and the other was a borderline case that revealedfocal (5%-15%) complete membranous staining. Distinguishing weakly (2+) from strongly (3+) positive results showed agreement in only 13 (59%) of 22 positive cases (kappa = 0.38). If more than 50% of tumor cells revealing strong complete membrane staining were regarded as strongly positive, agreement would be improved (kappa = 0.78). While there was a high percentage (70%-80%) of negative cases during routine evaluation, the good interobserver agreement and high negative predictive value made immunohistochemical analysis an effective screening test to exclude negative cases.

Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases.

Forty-three cases of spindle cell thymoma (medullary, WHO type A) and 38 cases of mixed spindle/lymphocytic thymoma (WHO type AB) were studied for their clinicopathologic and immunohistochemical characteristics. Three histologic patterns of spindle cell thymoma were observed: short-spindled (57%), long-spindled (31%), and micronodular (12%). The short-spindled variant was composed of oval to short spindle cells commonly arranged in a hemangiopericytic or microcystic pattern. The long-spindled variant chiefly consisted of fibroblast-like epithelial cells mimicking fibrohistiocytic neoplasms. The micronodular variant was characterized by small nests of short spindle cells dispersed among a lymphoid stroma with frequent germinal centers. All kinds of spindle cell could be admixed with lymphocyte-rich “cortex”-like areas to constitute mixed spindle/lymphocytic thymomas. Immunohistochemically, the epithelial cells in up to 70% of the short-spindled and long-spindled variants of spindle cell thymoma and 90% of mixed spindle/lymphocytic thymomas were positive for CD20, whereas the epithelial cells in all micronodular spindle cell thymomas were negative. All of the spindle cell thymomas and most of the mixed spindle/lymphocytic thymomas in this study were found in stages I and II. Follow up of the patients did not disclose relapse or mortality directly resulting from the tumors. However, the prognosis of stage I and II spindle cell and mixed spindle/lymphocytic thymomas did not significantly differ from those of stage I and II thymomas of other types by a stage-matched survival analysis. Our data showed that spindle cell and mixed spindle/lymphocytic thymomas are distinctive in histologic pattern and immunohistochemical profile. When interpreted within the context of staging, spindle cell and mixed spindle/lymphocytic thymomas presenting in stages I and II most likely behave in an indolent fashion.

The clinicopathological characteristics of gonadotroph cell adenoma: a study of 118 cases.

Gonadotroph cell adenoma was the most common pituitary adenoma, constituting 35% of the pituitary adenomas in our series of 339 patients with surgically removed pituitary adenomas from June 1987 to December 1995. The average age of these patients was 53 years, with a male predominance (1.5:1). The most common neurological symptoms were visual symptoms and headache. Amenorrhea and galactorrhea were recorded in 41% and 14%, respectively, of the female patients of reproductive age. Oncocytic change of varying degrees was seen in 69% of the tumors, and the average age of these patients (56 years) was older than those who had no such change (47 years) (P < .005). Five types of gonadotroph cell adenomas were recognized; they were tumors that contained (1) betaFSH, betaLH, and alphaSU, (2) betaFSH and betaLH, (3) betaFSH and alphaSU, (4) betaFSH, and (5) alphaSU. The immunostaining of betaFSH-containing cells was usually diffuse, whereas staining of betaLH- or alphaSU-containing cells was usually focal. Double immunostaining showed the immunoreactive cells containing one or any combination of the gonadotropin subunits. Increases in serum gonadotropin levels were only seen in 35% of the patients with gonadotroph cell adenoma. There was no correlation between serum hormonal levels and immunostaining results. Of the 33 recurrent cases, significant decrease or total absence of immunoreactivity of one or more hormone subunits in subsequent biopsy specimens were seen in three cases.

An easy method for manual construction of high-density tissue arrays.

Tissue array technique is a powerful tool for high-throughput in situ analysis on a large cohort of cases. This report describes an easy and effective method for manual construction of high-density tissue array containing 88 (11 × 8) samples, each of which measures 2 mm in diameter. No extraneous device is needed except a conventional 16-gauge bone marrow biopsy trephine apparatus to puncture the paraffin blocks. The authors constructed 563 cases of epithelial neoplasm into 7 blocks. The sectioning is smooth and does not require adhesive tape. They performed immunohistochemical staining for cytokeratins 7 and 20 on these tissue array slides. The samples rarely fell off during the antigen retrieval and staining procedure. The results were generally in agreement with those in previous reports. The authors offer a satisfactory alternative method for building custom arrays for any laboratory that is unable to afford a tissue array apparatus.

Detection of Epstein-Barr virus genome within thymic epithelial tumours in Taiwanese patients by nested PCR, PCR in situ hybridization, and RNA in situ hybridization

Epstein–Barr virus (EBV) is known to be associated with a variety of tumours, including Burkitts lymphoma, nasopharyngeal carcinoma, and some carcinomas of other organs with similar lymphoepithelioma‐like features. The association between EBV and thymic epithelial tumours is inconclusive, as reports in this regard are not entirely consistent and the methods employed are of different sensitivity and specificity. This study examined 78 thymomas and 21 thymic carcinomas in Taiwanese patients, to detect the viral genome at both DNA and RNA levels. The tissue blocks were first screened by nested polymerase chain reaction (PCR) targeting on the first tandem internal repeats. The positive cases were further submitted for viral localization by in situ PCR insitu hybridization (ISH) and Epstein–Barr‐encoded RNA‐1 (EBER‐1) ISH. None of the thymomas showed a detectable EBV genome. Eight thymic carcinomas were positive for EBV by nested PCR, of which six displayed nuclear signals within the tumour cells by in situ PCR ISH and/or RNA ISH, one displayed signals within the lymphocytes, and one showed no discernible in situ signals. Most of them exhibited a lymphoepithelioma‐like morphology. These results show that nested PCR is a sensitive method for screening the EBV genome in thymic epithelial tumours. In situ PCR ISH is reliable for localization of the virus, in addition to EBER‐1 RNA ISH. Thymomas are not related to EBV, even in this endemic area. Thymic carcinomas, especially the lymphoepithelioma‐like thymic carcinomas, are more often associated with the virus. Copyright

Primary renal synovial sarcoma with inferior vena cava and right atrium invasion.

Abstract  Primary renal synovial sarcoma is an uncommon and perhaps under‐diagnosed disease. We report a case of renal tumor in a 19‐year‐old man. Clinically, the tumor mimicked renal cell carcinoma with renal vein, inferior vena cava and right atrium invasion. Histologically, the tumor consisted of monophasic, high‐grade, spindle cell components. The diagnosis was validated by fluorescence in situ hybridization and reverse transcription‐polymerase chain reaction, which demonstrated SYT‐SSX translocation: a characteristic cytogenetic finding for synovial sarcoma. Our case shows that synovial sarcoma should be considered in the differential diagnosis of renal tumors, especially in adolescents and young adults. Proper molecular analysis should be undertaken to attain a definitive diagnosis.