Hangbo Zhou

Renal cell carcinoma in children and young adults: clinicopathological, immunohistochemical, and VHL gene analysis of 46 cases with follow-up.

To further study the characteristics of renal cell carcinoma (RCC) in young patients and better define their biological features, 46 RCCs of patients younger than 25 years were morphologically and immunohistochemically characterized with follow-up. Loss of heterozygosity (LOH) analysis of the von Hippel—Lindau (VHL) gene region and screening for VHL gene mutations were performed in all tumors. Applying the 2004 WHO classification for RCC, there were 19 Xp11.2 translocation RCCs, 9 clear cell RCCs, 17 papillary RCCs, and 1 unclassified RCC. All 19 Xp11.2 translocation RCCs showed moderate to strong immunoreactivity for TFE3. None had TFEB immunoreactivity. One Xp11.2 translocation RCC had an unreported morphology with empty or ground glass nuclei, occasional nuclear grooves, inconspicuous nucleoli and abundant mucinous material in stroma.VHL gene analysis revealed deletions at 3p25-26 in 1 clear cell RCC and 1 papillary type 2 RCC. The papillary type 2 RCC was also presented with a family history of VHL disease and found a germline mutation G → C on a splicing site at position 553+5. The present case widens the spectrum of microscopic features to be found in VHL-associated RCC. There were no VHL mutations in the remaining 45 RCCs. Statistical analysis of stage and outcome revealed that TFE+ pediatric RCCs were significantly more frequently associated with a higher pTNM pT3/pT4 stage and a poorer outcome than TFE-RCCs (P < .05). Owing to the already known aggressive behavior of these Xp11.2 translocation RCCs, patients with TFE+ pediatric RCCs should benefit from a stricter follow-up.

EphB1 is underexpressed in poorly differentiated colorectal cancers.

Background: Over- or underexpression of certain Eph receptors has been associated with tumorigenesis of some types of cancer. EphB1 is a member of receptor tyrosine kinases of the EphB subfamily involved in the development, progress and prognosis of colorectal cancers. The expression levels of EphB1 in colon cancer cell lines and human colorectal carcinoma specimens were determined and association of EphB1 expression with clinicopathological parameters was analyzed. Methods: Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry were used. Results: The EphB1 transcript is expressed in all colon cancer cell lines tested. However, there is marked variability in the expression of the EphB1 transcripts and proteins among colorectal carcinoma specimens. Reduced expression of EphB1 in colorectal cancers more often occurred in poorly differentiated and mucinous adenocarcinomas than in well- and moderately differentiated adenocarcinomas. Further, cancer cells with a low level of EphB1 protein showed more invasive power. Conclusion: Our data indicate that EphB1 may have roles in the pathogenesis and development of colorectal cancer.

Primary adenosquamous carcinoma of the colon: Report of five cases

Primary adenosquamous cell carcinomas (Ad-SCCs) of the colon and rectum are rare malignancies with a poor prognosis, in comparison to adenocarcinoma alone. Different roles of human papilloma virus (HPV) in its pathogenesis have been reported and the role of P16 in Ad-SCCs has not been explored. This report presents five cases of Ad-SCC of the colon to explore the clinicopathological features and the roles of P16, HPV 6/11, and 16/18. There was no confirmed evidence to support the relationship between the infection of HPV 6/11, 16/18, and pathogenesis of Ad-SCC of the colon. P16 overexpression was not related to HPV carcinogenesis and there might be another mechanism of P16 upregulation in Ad-SCC of the colon.

NK/T-cell lymphoma in a child with hypersensitivity to mosquito bites.

Hypersensitivity to mosquito bite (HMB) is defined as intense skin reactive lesion after mosquito bite. However, some kind of malignant tumor is closely associated with HMB, especially natural killer (NK)/T-cell lymphoma. We described a nasal-type NK/T-cell lymphoma in a 9-year-old girl after a history of 2 years earlier of HMB. Pathologic evaluation revealed the typical histologic features of NK/T-cell lymphoma, and the dermal and subcutaneous inflammatory reaction of HMB lesions. HMB is rarely reported and should be kept in mind as a clinical sign of subsequent NK/T-cell lymphoma in Asian country where HMB is relatively frequently encountered.

A meta-analysis of highly active anti-retroviral therapy for treatment of plasmablastic lymphoma

BACKGROUND AND OBJECTIVES Plasmablastic lymphoma is a recently described B-cell derived lymphoma. The prognosis of plasmablastic lymphoma patients is usually poor. We performed a systematic review of the literature on the use of highly active anti-retroviral therapy (HAART) and the prognosis of plasmablastic lymphoma. METHODS A comprehensive search of relevant databases, including Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library, and the Science Citation Index yielded ten randomized controlled trials. Trials were divided into two groups according to therapy. The rates of plasmablastic lymphoma were analyzed using a fixed-effects model. Sensitivity analyses (on publication type, statistical model) were performed to further detect and evaluate clinically significant heterogeneity. Tests of survival for plasmablastic lymphoma were also performed by using Kaplan-Meier method. RESULTS Meta-analysis result showed that the prognosis of plasmablastic lymphoma patients was statistically different in the patients receiving HAART in addition to chemotherapy and/or radiotherapy than in the patients receiving the chemotherapy and/or radiotherapy alone (pooled relative risk=3.04; P=.03). Survival analyses also displayed a statistically significant difference (chi-square=6.22, P=.013). CONCLUSION HAART in addition to chemotherapy and/or radiotherapy is effective in improving the prognosis of plasmablastic lymphoma. However, the small sample sizes increase the likelihood of bias in the studies in this meta-analysis, and therefore, the results should be taken cautiously.

Primary kaposiform hemangioendothelioma of a long bone: two cases in unusual locations with long-term follow up.

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm of low malignant potential that mainly affects infants and adolescents. The tumor almost exclusively occurs in somatic soft tissue or the retroperitoneum. We report herein two cases of primary KHE occurring in a long bone without cutaneous changes with long‐term follow up in young patients. The patients were a 9‐year‐old girl and 5‐year‐old boy presenting with lytic lesions of the femur and humerus, respectively, without cutaneous lesions. Histologically, the neoplasms were comprised of nodules of spindle‐ to oval‐shaped cells growing in an infiltrative fashion. The neoplastic cells formed poorly canalized or slit‐like blood vessels alternating with solid spindle areas. Immunohistochemical studies showed that the tumor cells expressed CD31, CD34 and Fli1, but not HHV8, LNA‐1 or GLUT1. D2‐40 stained the neoplastic spindle cells and lymphatic channels adjacent to vascular lobules. The girl remains well with 15 years and 6 months follow up after a second complete excision. The boy has no signs of recurrence or metastasis nearly 5 years after local complete excision. To our best knowledge, this is the first report in the English literature of primary long bone occurrences of KHE without cutaneous changes with long‐term follow up.

Molecularly genetic analysis of von Hippel-Lindau associated central nervous system hemangioblastoma

Von Hippel‐Lindau (VHL) disease is an autosomal dominant inherited cancer predisposition syndrome, characterized by development of a variety of neoplasms in multiple organs. Central nervous system hemangioblastoma (CHB) is the most common manifestation of VHL disease. The germline mutations in the VHL tumor suppressor gene are responsible for the inherited cancer predisposition syndrome. To expand the VHL mutation data and to investigate the tumorigenesis of VHL‐associated CNS hemangioblastoma, 24 CHB tissue samples and blood samples of 14 patients from 10 Chinese VHL families were collected and subjected to molecular genetic analysis. Six distinctive germline mutations were identified, and the 601 G to C (Val130Phe) mutation is reported for the first time. Somatic mutations analysis of the VHL gene in VHL‐associated CHB showed that loss of heterozygosity (LOH) occurred in more than half of the cases. In addition, expression of the ZAC1 tumor suppressor gene protein was studied using immunohistochemistry staining in CHB tissues with a specific polyclonal antibody. The ZAC1 protein was lost in all CHB. Our data exhibited high frequency of LOH of ZAC1 gene in VHL‐associated CHB, indicating that ZAC1 may have a role in tumorigenesis of VHL‐associated CHB.

Expression analysis of Wnt-5a in renal epithelial neoplasms: distinguishing renal oncocytoma from a wide spectrum of renal cell carcinomas

OBJECTIVE To study the expression of a novel marker, Wnt-5a, in renal epithelial neoplasms and determine its clinicopathological significance. METHODS Immunohistochemical analysis of Wnt-5a was carried out in normal human kidney samples as well as in 123 primary renal epithelial neoplasms including 37 clear cell renal cell carcinomas (RCCs), 24 papillary RCCs (15 type 1 and 9 type 2), 25 chromophobe RCCs, 11 Xp11 translocation carcinomas, 6 mucinous tubular and spindle cell carcinomas, and 20 oncocytomas. RESULTS Wnt-5a was expressed in 18.9% (7/37) of clear cell RCCs, 12.5% (3/24) of papillary RCCs, 16% (4/25) of chromophobe RCCs, 18.2% (2/11) of Xp11 translocation carcinomas, 0% (0/6) of mucinous tubular and spindle cell carcinomas, and 100% (20/20) of oncocytomas. There was a significant difference in Wnt-5a immunohistochemistry between renal oncocytoma and the other subtypes of RCC (P < 0.01). CONCLUSIONS Our results indicate that Wnt-5a is a potentially useful immunohistochemical marker for the complex differential diagnosis between oncocytoma and other subtypes of RCC and also suggest that Wnt-5a may be a tumor suppressor gene in RCC.

Cribriform-morular variant of papillary thyroid carcinoma: report of three cases and review of the literature

and clues regarding histogenesis. Neurosurgery 2004; 54: 753–8. 7. Kowalski RJ, Prayson RA, Mayberg MR. Pituicytoma. Ann Diagn Pathol 2004; 8: 290–4. 8. Takei H, Goodman JC, Tanaka S, et al. Pituicytoma incidentally found at autopsy. Pathol Int 2005; 55: 745–9. 9. Shah B, Lipper MH, Laws ER, et al. Posterior pituitary astrocytoma: a rare tumor of the neurohypophysis: a case report. AJNR Am J Neuroradiol 2005; 26: 1858–61. 10. Nakasu Y, Nakasu S, Saito A, et al. Pituicytoma. Two case reports. Neurol Med Chir (Tokyo) 2006; 46: 152–6. 11. Benveniste RJ, Purohit D, Byun H. Pituicytoma presenting with spontaneous hemorrhage. Pituitary 2006; 9: 53–8. 12. Gibbs WN, Monuki ES, Linskey ME et al. Pituicytoma: diagnostic features on selective carotid angiography and MR imaging. AJNR Am J Neuroradiol 2006; 27: 1639–42.

Four cases of distinctive meningiomas with Zellballen growth pattern

Dong Y, Zhou X, Wu B, Wang J, Ma H, Zhou H, Jiang S, Lu G, Hu Q. Four cases of distinctive meningiomas with Zellballen growth pattern. APMIS 2009; 117: 936–40.