We report a rare case of undifferentiated (embryonal) sarcoma of the liver in a six-year-old girl who at presentation, had fever, right hypochondrium pain and hepatomegaly. The diagnosis was clinched by fine needle aspiration cytology and was subsequently reconfirmed by histopathological examination of the resected tumour. Pre-operative chemotherapy was given because primary resection was deemed not possible. The patient underwent a successful extensive hepatectomy followed by continuation chemotherapy
The tumour suppressor gene p53 and the proto-oncogene Bcl-2 encode respectively, for a nuclear phosphoprotein and for a mitochondrial membrane protein involved in multiple cellular functions. Both proteins are linked to programmed cell death pathways and provide prognostic information on breast carcinoma. Our aim is to study the expression of p53 and Bcl-2 oncoproteins in breast carcinoma and correlate with patients’ age, tumour size, disease stage and histological grade. Fifty nine cases of breast carcinomas from Universiti Kebangsaan Malaysia Medical Centre (UKMMC) were studied with the immunohistochemical method. Our results showed 45.8% (27 of 59) and 40.7% (24 of 59) of the breast carcinomas were immunopositive for p53 and Bcl-2 respectively. There was significant correlation between Bcl-2 expression with early tumour stage (p=0.01). No significant relationship was seen with other variables. Results also showed an inverse relationship between p53 and Bcl-2 expression (p=0.001). These findings indicate a down regulation of Bcl-2 by p53 in breast carcinogenesis.
Primary thyroid lymphoma is a rare disorder accounting for about 2% of all malignant lymphomas and less than 5% of thyroid malignancies. It is an aggressive disease with poor outcome. The majority of thyroid lymphomas are non-Hodgkin lymphomas of Bcell origin. Majority of cases occur in women in the sixth decade. We report two cases of primary thyroid lymphoma and highlight the clinical issues and challenges posed by this rare disease. Both cases presented with respiratory obstructive symptoms that required surgical intervention. The optimal management for a primary thyroid lymphoma be it chemotherapy, radiotherapy, surgery or monoclonal antibodies is still debatable. The role for surgery has evolved through the years but its importance in emergency situations should not be overlooked. Both our patients had to undergo surgery but only one patient received additional chemotherapy and radiotherapy. These two case reports illustrated the difficulties in managing this rare disorder.
Aneusomy is an early genetic event and a characteristic feature of many solid tumors. It is often associated with poor prognosis in cancer patients. The involvement of PAX8-PPARγ rearrangement in tumorigenesis of follicular thyroid lesions has been widely assessed. However, there were few reports on aneusomy of the PPARγ gene at the 3p25 locus in follicular thyroid lesions. It remains undetermined whether these abnormalities can be translated into improved diagnosis, classification, or outcome prediction. Herein, we report three cases of follicular thyroid neoplasms [two follicular thyroid carcinomas (FTCs) and one Hurthle cell adenoma (HCA)] with 3p25 aneusomy detected by fluorescence in situ hybridization (FISH). 3p25 trisomy was observed in one FTC and one HCA while 3p25 tetrasomy was observed in one FTC. Furthermore, all three lesions did not show overexpression of PPARγ protein. Hurthle cell neoplasms (HCN) are distinct clinically and histologically from other follicular thyroid neoplasms (FTN). However, the presence of the aneusomy in HCA and FTC indicates that there could be a biological continuum between the two and chromosomal gains might play an important role in the pathogenesis of these two types of neoplasms. Despite their differences, HCN and FTN may share the same early genetic event in tumour development.
Thyroid nodules are common but thyroid malignancies are not. Fine needle aspiration (FNA) cytology is a diagnostic tool used to screen patients with thyroid nodules who require surgery. We study the diagnostic accuracy of FNA as the initial diagnostic modality in the clinical assessment of thyroid nodules. Between January 1995 until December 2000, 2131 FNA of thyroid nodules were performed. Four hundred and forty-one (20.7%) of these were unsatisfactory and 1690 (79.3%) cases were satisfactory for cytological evaluation. Histopathological diagnosis were available for 361 cases. Cyto-histopathological correlation was carried out for these cases. Our results showed a diagnostic accuracy of 96.2% with sensitivity and specificity rates of 87.7% and 98.4% res- pectively. Our positive predictive value is 93.4% and our negative predictive value is 96.8%. From this study, we conclude that fine needle aspiration is an important initial screening diagnostic tool for the investigation of thyroid nodules.
Pleomorphic adenoma (PA) typically presents as a benign slow growing, painless neoplasm of the parotid gland. PA arising from the submandibular gland in the paediatric age group is rare. Surgical excision is the treatment of choice. A case of PA in an 8-year-old Malay girl is presented. Clinically she presented with a painless right submandibular mass measuring 2x2cm. A diagnosis of Pleomorphic adenoma was made on Fine Needle Aspiration Cytology (FNAC). She underwent submandibulectomy uneventfully. Postoperatively after two years follow up, she is asymptomatic.
One of the most important cervical cancer risk factors is human papillomavirus (HPV) infection. The p53 gene is one of the most important targets of the HPV E6 gene. E6 protein has the ability to stimulate p53 degradation, inhibits several functions of wild-type p53 and it competes with its function including suppression of malignant growth. The aim of this study is to determine the differences in p53 expressions in pre-malignant and malignant cervical neoplasms. This is a retrospective study on 100 cases of cervical neoplasms. There were 21 cases of CIN 1, 8 cases of CIN 2, 25 cases of CIN 3, 36 cases of squamous cell carcinoma, 7 cases of adenocarcinoma and 3 cases of adenosquamouscarcinoma. All cases were evaluated by immunohistochemistry using p53 monoclonalantibody. Thirty six of the 54 pre-malignant cases (66.7%) were positive for p53 protein, n contrast to the malignant cases in which, 40 of the 46 cases (87.0%) were positive. he majority of CIN showed absent to focal staining (29/54, 53.7%). In contrast, 84.8% (39/46( of the invasive carcinoma showed regional to diffuse staining. The expression of p53 is greater in the malignant cervical neoplasms than the pre-malignant cervical lesions, suggesting that p53 overexpression is not an early phenomenon in the pathogenesis of cervical cancer. It is also shown to be slightly higher in percentage in CIN 2 and 3 when compared with CIN 1. However, a number of cases were p53 negative, suggesting that other factors may be involved and further HPV studies are indicated.
Anaplastic large cell lymphoma (ALCL) is a rare tumour, accounting for approximately 3% of adult non-Hodgkin lymphomas.1 Primary systemic ALCL frequently involves both lymph nodes and extranodal sites. A 44-year-old woman presented with a firm, mobile mass in the left iliac fossa region. Ultrasound findings showed a well defined inhomogenous soft tissue mass, measuring 4x4x2.6cm in the deep subcutaneous region. Histopathological examination revealed that the mass was infiltrated by large lymphoid cells with marked nuclear atypia including kidney-shaped nuclei. These neoplastic cells expressed anaplastic lymphoma kinase (ALK) (both nuclear & cytoplasmic staining), CD30 and EMA but not for T-cell (CD45RO and CD3), and B-cell (CD20 & CD79α) markers. Fluorescence in situ hybridization (FISH) analysis showed a t(2;5)(p23;q35) chromosomal translocation. Subsequently the patient developed shortness of the breath and a thoracic computed tomography (CT) scan showed a mass encasing the right upper lobe bronchus. She also had bilateral axillary lymph nodes, measuring 1 cm in diameter (biopsy was not done). The mediastinum and endobronchial region did not show any abnormalities. She received 6 cycles of CHOP chemotherapy and remained disease free 2 years after diagnosis. ALCL, rarely present as a soft tissue tumour and this disease should be included as a differential diagnosis of any soft tissue mass.
We report two cases of biphenotypic acute leukaemia diagnosed in Hospital Universiti Kebangsaan Malaysia (HUKM), their clinical, haematological characteristics and response to chemotherapy. Both patients are middle-aged ladies who presented with hepatosplenomegaly and high white cell count, mainly composed of blast cells. Their bone marrow aspirations were hypercellular comprising of more than 90% heterogenous blast cells. Cytochemical analyses show more than 3% positivity towards peroxidase, with smaller blasts showing block positivity towards PAS. Immunophenotypically, the blasts showed dual expression of CD 33 and CD 19, CD 19 and CD34, intra CD22, intra TdT and intraMPO. One of the patients showed presence of the Philadelphia chromosome on cytogenetic analysis which was confirmed by Fluorecsence In Situ Hybridisation (FISH). Molecular analysis also showed presence of the BCR-ABL fusion protein. Both patients were given combination chemotherapy consisting of daunorubicin and cytosine arabinoside.However, the patient with positive Philadelphia chromosome BCR-ABL did not achieve morphological remission after induction chemotherapy. In view of the poor prognosis of this disease, both the patients were planned for upfront peripheral blood stem cell transplantation.
A cross sectional study was done to determine the prevalence and distribution of human papillomavirus (HPV) genotypes in pre-invasive (cervical intraepithelial neoplasia, grade 3 or CIN 3) and invasive cervical cancer (ICC), in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). A total of 80 paraffin-embedded tumour tissue blocks (20 CIN 3, 60 invasive cancers) between 1999 to 2007 were retrieved from the archives of the Department of Pathology. Patient’s medical records were obtained from the Medical Records Office. Among invasive cancers (n=60), squamous cell carcinoma (SCC) account for 75% and adenocarcinoma 25%. The mean age of cases studied was 52.0 ± 12.2 years and Chinese was the predominant ethnicity (66.3%). Twelve HPV genotypes were identified, namely, HPV 16, 33, 18, 39,52, 45, 58, 59, 31, 35, 6 and 11. The prevalence of HPV was 92.5% with types 16 being the most common (73.8%), followed by types 33 (30%) and 18 (22.5%). A total of 31 cases (38.8%) showed single HPV genotype, while 43 (53.8%) had multiple HPV (two genotypes or more) genotypes. In ICC, HPV 16, followed by types 33, 18, 52 and 39 were the top five common HPV genotypes detected. High prevalence of HPV and multiple HPV infections were major findings among patients with pre-invasive and invasive cervical cancer.
The tetraspanin gene, CD151 is involved in various tumour cell progression and metastasis. Its expression is increased in high grade, estrogen receptor negative and c-erbB-2 positive breast cancer. However, the biological function and expression phenotype among different tumour status, estrogen receptor (ER) status, progesterone receptor (PR) status and c-erbB-2 expression in multi-ethnic Malaysian breast cancer patients has not been well investigated. We used quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to measure the CD151 gene expression in 45 breast cancers. Our preliminary results revealed that CD151 expression is significantly higher in ER positive and PR positive breast cancers at 95% and 99% confidence intervals, respectively. In contrast, there is no significant correlation between CD151 expression and tumour grades or c-erbB-2 status at 95% confidence interval level. Our preliminary findings suggested that CD151 may be involved in the estrogen responsive pathways. CD151 could be a potential prognostic marker and therapeutic target in the treatment of estrogen dependent breast cancer patients.
Cancers of the breast and cervix made up 30.4% and 12% of all cancer cases in Malaysia. Thus screening for reproductive organ cancers as women approached menopause becomes exceedingly important. The study reports the baseline assessment tests of 495 disease free urban Malaysian women aged 45 years and above who volunteered in a healthy lifestyle intervention study. The sample comprised of 58.0% premenopaused and 42.0% postmenopaused women with an average age of 51.27±5.35 years old. Over two thirds were Chinese followed by Malays and Indians. Overall, abnormal Pap smears were seen in 7.6% comprising of 1.3% cervical intraepithelial neoplasia (CIN), 6.1% human papilloma virus (HPV) infection and 0.2% atypical squmous cells of undetermined significances (ASCUS). Yeast and other infections were found in 6.9% and 1.9% respectively. Comparatively, postmenopausal women had a 2.8 fold higher cancerous changes whereas premenopausal women had a higher infection rate, 11.8% vs. 4.7% respectively (p=0.024) with comparable HPV infection rates in both. This study found 1.3% had breast cancer (BC) with 3.6% requiring a biopsy while 3.4% needed regular follow up. Postmenopaused women had more abnormal mammograms (p