Extramammary Paget's Disease: 20 Years of Experience in Chinese Population

Background. To examine the results of treatment of Extramammary Paget's disease (EMPD) in ethnic Chinese. Method. Between 1990 and 2010, patients treated for EMPD were reviewed. Data were analyzed retrospectively. Results. Forty-eight patients were treated by surgical resection. Local recurrence rate was 14.6%. The postresection defects were repaired by primary closure (8.3%), partial thickness skin graft (72.9%), or local/regional flaps (18.8%). Dermal invasion was found in 9 patients (18.8%). Seven patients (14.6%) developed regional lymph node metastasis (concurrent with surgery, n = 1; subsequent to surgery, n = 6), and 3 patients (6.3%) had systemic metastasis after surgery. The presence of dermal invasion was associated with significantly higher incidence of regional lymph nodes and systemic metastasis. The incidence of associated internal malignancy was 8.3%. Conclusion. The mainstay of treatment for EMPD is surgery. Pathological dermal invasion increases the chance of regional lymph node as well as systemic metastasis. The association with internal malignancy warrants preoperative endoscopic examination in all patients

Extracranial head and neck schwannomas: a study of the nerve of origin

Schwannoma is a type of benign nerve sheath tumour arising from the Schwann cell. Because of the close relationship between the tumour and the nerve of origin (NOO), the operation of extracranial head and neck schwannoma may lead to palsy of major nerve. For this reason, an accurate diagnosis of schwannoma with the identification of the NOO is crucial to the management. The aim of this review was to find out the distribution of the NOO and the usefulness of the investigations in the diagnosis of schwannoma. Medical records of the patients who underwent operation of the extracranial head and neck schwannoma in our division were reviewed. Between January 2000 and December 2009, 30 cases of extracranial head and neck schwannoma were operated. Sympathetic trunk (10, 33%) and vagus nerve (6, 20%) were the two most common NOOs. In five (17%) cases, the NOO was not found to be arising from any major nerve. For these 30 patients, 20 received fine needle aspiration cytology (FNAC) and 26 underwent imaging studies (computed tomography or magnetic resonance imaging) before operation. The specificity of FNAC and imaging studies in making the diagnosis of schwannoma was 20 and 38%, respectively. For the patients who had nerve palsies on presentation, their deficits remained after operation. The rate of nerve palsy after tumour excision with division of NOO and intracapsular enucleation was 100 and 67%, respectively. The diagnosis of schwannoma is suggested by clinical features and supported by investigations. Most of the time, the diagnosis can only be confirmed on the histological study of the surgical specimen. Sympathetic trunk and vagus nerve are the two common NOOs. MRI is the investigation of choice in the diagnosis of schwannoma and the identification of NOO

Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies

miR-124-1 is a tumour suppressor microRNA (miR). Epigenetic deregulation of miRs is implicated in carcinogenesis. Promoter DNA methylation and histone modification of miR-124-1 was studied in 5 normal marrow controls, 4 lymphoma, 8 multiple myeloma (MM) cell lines, 230 diagnostic primary samples of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), MM, and non-Hodgkin's lymphoma (NHL), and 53 MM samples at stable disease or relapse. Promoter of miR-124-1 was unmethylated in normal controls but homozygously methylated in 4 of 4 lymphoma and 4 of 8 myeloma cell lines. Treatment of 5-Aza-2′-deoxycytidine led to miR-124-1 demethylation and re-expression of mature miR-124, which also associated with emergence of euchromatic trimethyl H3K4 and consequent downregulation of CDK6 in myeloma cells harboring homozygous miR-124-1 methylation. In primary samples at diagnosis, miR-124-1 methylation was absent in CML but detected in 2% each of MM at diagnosis and relapse/progression, 5% ALL, 15% AML, 14% CLL and 58.1% of NHL (p<0.001). Amongst lymphoid malignancies, miR-124-1 was preferentially methylated in NHL than MM, CLL or ALL. In primary lymphoma samples, miR-124-1 was preferentially hypermethylated in B- or NK/T-cell lymphomas and associated with reduced miR-124 expression. In conclusion, miR-124-1 was hypermethylated in a tumour-specific manner, with a heterochromatic histone configuration. Hypomethylation led to partial restoration of euchromatic histone code and miR re-expression. Infrequent miR-124-1 methylation detected in diagnostic and relapse MM samples showed an unimportant role in MM pathogenesis, despite frequent methylation found in cell lines. Amongst haematological cancers, miR-124-1 was more frequently hypermethylated in NHL, and hence warrants further study

Prognostic factors of survival in treatment of scalp angiosarcoma in Chinese population

AbstractBackgroundScalp angiosarcoma is a rare soft tissue sarcoma with a very poor prognosis and high mortality. Due to its low incidence, prognostic factors and treatment strategies are not well defined.ObjectiveThis study aims to report our long-term results in terms of survival and prognostic factors affecting survival through retrospective analysis of 38 consecutive patients with scalp angiosarcoma who underwent treatment at two different plastic centers in Hong Kong.ResultThe overall survival rate for 1, 3, and 5 years of maximally treated patients was 56%, 24%, and 12%, respectively. Univariate analysis with Cox regression model showed that age >70 years (risk ratio, RR 5.0; p = 0.02), satellite lesion on presentation (RR 8.4, p = 0.02), and tumor of size >5 cm (RR 2.79, p = 0.05) were factors affecting the overall survival. Multivariate analysis showed that only the involved deep resection margin was a significant risk factor (RR 8.6, p = 0.02) However, univariate analysis showed that the involved deep resection margin (RR 10.2, p = 0.01) and satellite lesion on presentation (RR 0.73, p = 0.01) were factors affecting disease-free survival. Besides, satellite lesion on presentation predicted local recurrence on univariate analysis (RR 2, p = 0.01).ConclusionsThe prognosis in terms of overall survival and local disease control was poor with a 5-year survival rate of 12% in maximally treated patients

Effect of 5-Aza-2′-deoxycytidine (5-AzadC) treatment on lymphoma and myeloma cells.

<p>(A) M-/U-MSP analysis of <i>miR-124-1</i> promoter methylation status and stem-loop qRT-PCR analysis of the mature <i>miR-124</i> expression. 5-AzadC treatment resulted in progressive demethylation of <i>miR-124-1</i> promoter, and re-expression of the mature <i>miR-124</i> in cell lines harbouring homozygous <i>miR-124-1</i> methylation. (B) ChIP analysis for trimethyl H3K4, trimethyl H3K9, acetyl H3K9, trimethyl H3K27 in <i>miR-124-1</i> promoter. 5-AzadC treatment led to augmentation of euchromatin code of trimethyl H3K4. (C) Western blot analysis of CDK6 in response to 5-AzadC treatment. Bottom row showed densitometric quantization of the Western blot, indicating relative CDK6 expression under actin normalization.</p

Promoter methylation of <i>miR-124-1</i> and expression of <i>miR-124</i> in primary samples.

<p>(A) Methylation of <i>miR-124-1</i> in primary samples. (B) M-/U-MSP analysis of <i>miR-124-1</i> promoter methylation status and (C) Stem-loop qRT-PCR analysis of the mature <i>miR-124</i> expression in 25 primary NHL samples with matched DNA and RNA. ΔC_t, C_t<i>miR-124</i> -C_t<i>RNU48</i>.</p

Methylation of <i>miR-124-1</i>.

<p>(A) Schematic diagram showing the distribution of CpG dinucleotides (solid vertical lines) over the precursor (solid black box) and mature <i>miR-124-1</i>. Sequence analysis of the M-MSP product from bisulfite-treated positive control DNA showed that the cytosine [C] residues of CpG dinucleotides were methylated and remained unchanged, whereas all the other C residues were unmethylated and were converted to thymidine [T], indicating complete bisulfite conversion and specificity of MSP. Grey bars indicated the amplification regions of the MSP, ChIP, and BGS primers. (B) U-MSP showed that the methylated positive control [P] was totally methylated, and all five normal controls (N1–N5) were unmethylated. In the M-MSP, the methylated control was positive (methylated) but all normal controls were negative (unmethylated). For the cell lines, SUP-T1, SUP-M2 (ALK+), SU-DHL-1 (ALK+), KARPAS-299 (ALK+), KMS-12-PE, LP-1, OPM-2, and WL-2 were completely methylated of <i>miR-124-1</i>. (C) Bisulfite genomic sequencing for the bisulfite-treated promoter region of <i>miR-124-1</i> of normal controls (N1–N5), lymphoma and myeloma cell lines of different methylation statuses (MM, UM, or UU), and the methylated positive control were depicted. Unmethylated (empty circle) and methylated (filled circle) CpG dinucleotides were shown by eight independent clones for each sample.</p