Congenital disseminated malignant rhabdoid tumor: a distinct clinicopathologic entity demonstrating abnormalities of chromosome 22q11

The clinical, pathologic, and immunohistochemical features of a widely disseminated tumor with rhabdoid phenotype are described in nine infants < or = 3 months of age. Five neonates had tumor evident at birth, two of which had placental metastases. The average survival following diagnosis was < 6 weeks. None of the infants had an apparent primary tumor in either the kidney or brain. In four cases, the dominant mass involved the head and neck region, and in two cases, the primary mass was paraspinal. The histologic features were those of a high-grade, round cell neoplasm with abundant cytoplasm and containing cells with cytoplasmic filamentous inclusions. Immunohistochemical studies revealed polyphenotypic antigen expression. Genetic information was available from eight of nine cases. Karyotype analysis revealed abnormalities of chromosome band 22q11-12 in three of six tumors. Fluorescence in situ hybridization studies or molecular studies demonstrated 22q11.2 deletions in all five cases with available frozen tissue, two of which had translocations involving 22q by karyotype analysis. The similar clinical and pathologic findings in these rapidly fatal tumors in infants and the demonstration of abnormalities of chromosome 22q11 in a majority of the cases supports their histogenetic and nosologic relationship to the family of malignant rhabdoid tumors that typically occur in young children in several anatomic sites, including kidney, soft tissues, liver, and brain. Like neuroblastoma and rhabdomyosarcoma, malignant rhabdoid tumor can appear as disseminated disease at birth or shortly thereafter.     

Ultrastructure of capillary permeability in human brain tumor: disseminated and metastatic medulloblastoma

The ultrastructure of the tumor vessels of primary cerebellar, subarachnoidal disseminated and extraneural metastatic medulloblastomas was studied. They were compared with those in glial, nonglial and metastatic brain tumors which have been previously reported. Twelve surgical specimens were examined. Seven tumors were limited to the vermis, the floor of the fourth ventricle and the cerebellar hemispheres. Four gross nodule seedings were demonstrated in the cerebral and spinal subarachnoid space. One metastasis was demonstrated in the subclavicular lymph node. Ultrathin section of those tumors and replica specimens were studied under the transmission electron microscope. The tumor vessels of primary medulloblastoma and glial tumors had nonfenestrated capillaries and were morphologically similar to normal brain capillaries. On the other hand, the tumor vessels of disseminated and metastatic medulloblastoma, nonglial tumors, and metastatic brain tumors had fenestrated capillaries. These findings were anticipated because the arachnoid membrane and lymph nodes have fenestrated capillaries. The presence of fenestration suggests that the tumor vessels of disseminated and metastatic brain tumors resemble the blood vessels found in normal arachnoid membrane and lymph nodes.     

成人肾恶性横纹肌样瘤临床与病理学特点分析

目的探讨成人肾恶性横纹肌样瘤（MRTK）的临床及病理学特点。方法结合文献回顾性分析5例成人MRTK患者的临床和病理资料。男4例，女1例。年龄21—67岁，平均50岁。其中左侧3例，右侧2例。3例有肉眼血尿、腰痛不适和腹部包块等症状，体检发现右肾肿物1例，查体仅1例表现低热，未见萁他阳性发现。结果5例均行根治性肾切除。肿瘤平均直径6．5cm。NWTS分期Ⅱ期4例，Ⅲ期1例。病理特点：MRTK细胞有丰富的嗜酸性胞质，部分胞质内有大圆形嗜酸性包涵体，核分裂多。免疫组织化学染色波形蛋白、上皮膜抗原阳性。电镜观察：胞质内见中间丝及圆形、不规则形纤维状或轮状小体。4例获随访3—24个月，2例术后1年死于转移或并发症，2例无瘤存活6个月。结论MRTK是一种具有特殊形态的少见肾癌类型，与同期、同级其他类型肾癌比较预后较差，成人预后好于青少年。     

E, N-cadherins and beta-catenin expression in medulloblastoma and atypical teratoid/rhabdoid tumor

Cadherins are cell-surface glycoproteins that mediate Ca2+-dependent, homophilic cell-cell adhesion. The classical cadherins, E- and N-cadherins, bind to beta-catenin, the lining protein. Dysfunctional expression of these factors seems to be related to tumor invasion and metastasis. This study examined the relationship between changes in E- and N-cadherins, and catenin expression, and biological behavior in medulloblastomas and atypical teratoid/rhabdoid tumors. Specimens of 13 medulloblastomas and two atypical teratoma/rhabdoid tumors were collected and stained immunohistochemically to detect E- and N-cadherins, and beta-catenin. None of the medulloblastomas were immunoreactive for E-cadherin, but both atypical teratoma/rhabdoid tumors were immunoreactive for E-cadherin at the cell-cell borders where epithelial differentiation occurred. In contrast, N-cadherin and beta-catenin were present at the cell-cell borders in 12 of the 13 medulloblastomas and both atypical teratoma/rhabdoid tumors. Nuclear beta-catenin staining was not present in the medulloblastomas or atypical teratoma/rhabdoid tumors. There was no significant difference in the Ki-67 staining index between patients with medulloblastomas showing high and low immunoreactivity for N-cadherin and beta-catenin. Moreover, immunoreactivity for N-cadherin and beta-catenin increased with dissemination in the medulloblastomas. Low immunoreactivity in medulloblastomas tended to be associated with a better prognosis. These results suggest that expression of E-cadherin is useful for the differential diagnosis of atypical teratoma/rhabdoid tumor and medulloblastoma, and the expression of N-cadherin or beta-catenin may be related to the biological behavior of medulloblastomas.     

Suprasellar primary malignant rhabdoid tumor in an adult: a case report

Malignant rhabdoid tumor (MRT), described for the first time in 1978 in the kidney, has rarely been reported in other organs including the brain and has involved adults in only 3 cases. We described a case of MRT in a 32-year-old woman who presented with severe headache, nausea and sudden onset of visual disturbance. MRI showed a well-enhanced mass at the suprasellar region. Subtotal removal of the tumor was performed. However, tumor regrowth occurred after the operation (doubling time, 8.36 days) and spinal dissemination was detected. Therefore, chemotherapy and radiotherapy were administered focusing on the suprasellar lesion and the spinal cord. Pathologically, light micrographs showed rhabdoid cells with large, round, single or double nuclei with one prominent nucleolus and eosinophilic cytoplasmic inclusions. Electron micrographs were made of typical rhabdoid cells displaying bundles of intermediate filaments within the perikaryon. In immunohistochemical studies, EMA, vimentin, cytokeratin and SMA were positive. Pathological findings were consistent with those of MRT. Optimal treatment for this tumor has not been established. Our case may be useful in defining treatment for MRT.     

An adult multifocal medulloblastoma with diffuse acute postoperative cerebellar swelling: immunohistochemical and molecular genetics analysis

Medulloblastoma (MB), the most common malignant tumor typically affecting children, occurs only exceptionally in adults. Multifocal presentation of this malignancy in adulthood is even much rarer—only four cases with favorable postoperative course have been reported, so far. The study illustrates a very rare rapid postoperative clinical deterioration due to diffuse cerebellar swelling (DCS) in an adult multifocal MB (MMB). To the best of their knowledge, authors for the first time performed genetic analysis of MMB and demonstrated expression patterns of selected markers that put the patient within the sonic hedgehog (SHH) molecular subgroup and at least partially explain her unsatisfactory clinical course. Herein, authors summarized the relevant literature concerning this issue with the aim to determine features that would facilitate diagnosis and therapy of such a scarce clinical entity.     

Isolated imperforate anus in monozygotic twins: case report and implications

The authors report a case of isolated imperforate anus with perineal fistula in monozygotic twins. Only 4 other well-documented cases of monozygotic twins concordant for isolated anorectal malformation have been reported in the literature. In all these cases the defect occurred below the levator ani muscle. This case confirms previous reports on the incidence of low anorectal anomalies in monozygotic twins where the defect was isolated. A review of the literature relating to this condition in twins and siblings points toward low anomalies and more severe malformations having different genetic backgrounds.     

Malignant rhabdoid tumor of the vulva: is distinction from epithelioid sarcoma possible? A pathologic and immunohistochemical study

Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) have heretofore been regarded as two separate clinicopathologic entities. However, they have some histologic similarities, and both represent histogenetic and phenotypic enigmas. This study reports the pathologic and immunohistochemical findings of four vulvar neoplasms occurring in young women that represented diagnostic dilemmas because of their similarity to both ES and MRT. Only one case had the classic histologic features of ES, whereas, in our opinion, the other three cases fulfilled the histologic criteria of MRT, despite the fact that two of the three cases were reported earlier as examples of ES. Neither electron microscopy nor immunohistochemistry has been found to be helpful in separating ES from MRT, mainly because they share several ultrastructural and immunophenotypic features. The behavior of these vulvar tumors--ours and the few published examples of ES--is generally aggressive, more in keeping with MRT than classic ES. We believe that some, if not most, putative ES of the vulva are in fact MRT, a neoplasm with an unfavorable prognosis.     

Heritability of bone density: Regional and gender differences in monozygotic twins

Bone mineral density (BMD) is a measure of a person's skeletal mineral content, and assessing BMD by dual x‐ray absorptiometry (DEXA) can help to diagnose diseases of low bone density. In this study, we determine the heritability of BMD in male and female monozygotic twin subjects using DEXA in 13 specific anatomical regions. In an attempt to quantify the genetic contribution of gender and skeletal region to BMD heritability, we scanned 14 pairs of identical twins using DEXA and calculated the broad‐sense heritability coefficient (H²) in each of the 13 different body regions. The region of the body that was most heritable for both genders was the head (H² ≥ 95%). When males were compared to females, H² values for male hip (H² = 87%) and lower extremities (H² = 90%) were higher than those in females (H² = 49% and 56%, respectively). Conversely, H² value for the female pelvis (H² = 68%) was higher than that for males (H² = 26%). These data show that different regions of the skeleton exhibit different degrees of heritability, and that the variation depends on gender. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:150–154, 2009     

Disc degeneration and bone density in monozygotic twins discordant for insulin-dependent diabetes mellitus.

The effects of insulin-dependent diabetes mellitus on bone density and connective tissue degeneration have theoretical interest and practical relevance. Several experimental studies in animals have demonstrated the harmful effects of insulin deficiency on connective tissues. However, clinical studies in humans have produced somewhat contradictory results, most likely due to difficulties controlling for general degeneration and factors associated with diabetes. In nine pairs of monozygotic twins discordant for insulin-dependent diabetes mellitus, we compared femoral and lumbar bone mineral density (assessed by dual-energy x-ray absorptiometry) and spinal degeneration (assessed by magnetic resonance imaging). The bone densities were, on average, 0.1-0.3% lower (p = 0.87-0.96) in diabetic patients. However, after controlling for smoking, we found that the bone density in the femoral neck was 2.5% (0.025 g/cm2) lower in diabetic individuals than in their twins (p = 0.09). The five magnetic resonance imaging parameters used to evaluate disc degeneration did not differ between diabetic patients and their twins. In conclusion, our results provide no evidence that insulin-dependent diabetes mellitus has any major effect on bone density or disc degeneration.     

Analysis of chromosome 22q as an aid to the diagnosis of rhabdoid tumor: a case report.

Malignant rhabdoid tumor is a highly aggressive tumor of childhood that may present as a soft-tissue primary tumor. We report a soft-tissue neoplasm that was polyphenotypic by immunohistochemical expression of epithelial, mesenchymal, and neural markers and did not meet the criteria for any of the usual pediatric small round-cell tumors. The findings raised the diagnosis of rhabdoid tumor, leading to testing for WT1 mRNA and protein expression, which were positive, as has been reported for renal rhabdoid tumor. This tumor had the typical clinical behavior of rhabdoid tumor with therapy resistance and early tumor-related death. Multicolor spectral karyotyping of this neoplasm showed a balanced translocation between chromosomes 1 and 22 with breakpoints at 1p36 and 22q11-12. The latter region is commonly involved in rhabdoid tumor. This change was also identified by fluorescence in situ hybridization. This case suggests that studies of chromosome 22 may be required to distinguish rhabdoid tumor from other soft-tissue tumors.     

Concordance for neuroblastoma in monozygotic twins: case report and review of the literature

The patients were infant male twins born by cesarean delivery following a healthy pregnancy at 36 weeks' gestation to unrelated parents. At 4 months of age, twin 2 presented with hepatomegaly and a right suprarenal mass. Resection of an adrenal tumor and a liver tumor biopsy were performed. Twin 1 had no symptoms at 4 months of age. Screening by abdominal ultrasonography showed multiple masses in the liver but no adrenal mass. Metaiodobenzylguanidine scintigraphy showed positive findings in multiple liver masses. A laparoscopic biopsy for a liver tumor was performed. All primary tumor and liver tumor specimens from twin 2 and the liver tumor of twin 1 had the same histologic classification of neuroblastoma and nearly identical genetic aberrations, including a chromosome gain or loss using array-comparative genomic hybridization. From these clinical and pathologic findings and genetic analyses, we strongly demonstrate the transplacental metastatic spread from twin 2 to twin 1. In the literature, 9 pairs of concordant twin neuroblastomas, including the current twin, have been presented; and the clinical findings of 5 twin pairs may represent placental metastases from one twin with congenital neuroblastoma to the other twin. This study is the first report presenting the possibility of twin-to-twin metastasis in monozygotic twins with neuroblastoma based on an analysis of the clinical features and genetic aberrations.     

Testicular germ cell tumors in monozygotic twins: case report and review of the literature

We report the eleventh instance of testicular germ cell tumors in monozygotic twins. The tumors were concomitant but of different histology. The comparable lymphography and computerized tomography scan findings, tumor response to chemotherapy and side effects are discussed. We conclude that there is no definite evidence for an increased risk in relatives of patients with this disease.     

Congenital scoliosis in non-identical twins: case reports and literature review

Congenital scoliosis due to vertebral anomalies may occur in less than 0.1% of the population. Several different theories have been put forth in the literature to account for the etiology of congenital scoliosis and the vertebral anomalies which contribute to its development. The study of scoliosis in twins has contributed to the understanding of causative factors including genetics, environment and in utero events during embryologic development. Case reports of fraternal (non-identical) juvenile male twins with congenital scoliosis associated with differing congenital vertebral anomalies are presented. Both children were asymptomatic at the time of the initial consultation and showed no signs of neurologic compromise. Rapidly progressive, severe genetic scoliosis requires prudent observation and referral to a pediatric orthopedic surgeon to determine appropriate options for care and to screen for potentially life threatening disorders. Chiropractors may be seen as gatekeepers for scoliosis and a thorough understanding of appropriate standards of care is required.     

胰腺恶性内分泌肿瘤的诊断和治疗经验

目的 总结胰腺恶性内分泌肿瘤的诊治经验.方法 回顾性分析1969年1月至2008年12月南京医科大学第一附属医院收治的38例胰腺恶性内分泌肿瘤患者的临床资料.其中胰岛素瘤6例,胰多肽瘤23例,胰高血糖素瘤4例和胰腺类癌5例.结果除1例胰岛素瘤外,所有患者经术前影像学检查发现胰腺占位;手术切除率87%(33/38),病理学检查提示肝转移7例,淋巴结转移5例,血管、淋巴管发现瘤栓1例,局部浸润28例.术后随访24例,1例胰岛素瘤局部复发再次手术切除,1例胰腺类癌肝转移再次射频治疗,其余无转移、复发表现.结论 影像学检查是胰腺内分泌肿瘤的主要诊断依据.其恶性程度应根据术前影像学表现、术中探查、术后病理检查并结合随访综合判定.恶性胰腺内分泌肿瘤恶性程度低,手术切除率高,预后良好.     

Successful treatment of malignant rhabdoid tumor of the vulva in an older patient: a case report and review of the literature

PURPOSE: Malignant rhabdoid tumor (MRT) of the vulva is a rare and very aggressive neoplasm. Only 7 cases have been reported thus far in the English literature. This case reports the oldest patient to date with MRT. This 63 year old was successfully treated with surgery and radiation therapy. The current literature is reviewed, and different treatment modalities are considered and evaluated.