Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients.

AIM: To investigate the protein expression profile of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations. METHODS: Immunohistochemical analysis of tumor samples was performed to determine the protein expression profile of MMR protein. Germline mutation screening was carried out on peripheral blood samples. The entire exon regions of MLH1 and MSH2 genes were amplified by polymerase chain reaction, screened by denaturing high performance liquid chromatography (dHPLC) and analyzed by DNA sequencing to characterize the germline mutations. RESULTS: Three out of 34 tissue samples (8.8%) and four out of 34 tissue samples (11.8%) showed loss of nuclear staining by immunohistochemistry, indicating the absence of MLH1 and MSH2 protein expression in carcinoma cells, respectively. dHPLC analysis followed by DNA sequencing showed these samples to have germline mutations of MSH2 gene. However, no deleterious mutations were identified in any of the 19 exons or coding regions of MLH1 gene, but we were able to identify MLH1 promoter polymorphism, -93G > A (rs1800734), in 21 out of 34 patients (61.8%). We identified one novel mutation, transversion mutation c.2005G > C, which resulted in a missense mutation (Gly669Arg), a transversion mutation in exon 1, c.142G > T, which resulted in a nonsense mutation (Glu48Stop) and splice-site mutation, c.2006-6T > C, which was adjacent to exon 13 of MSH2 gene. CONCLUSION: Germline mutations were identified in four Malaysian Lynch syndrome patients. Immunohistochemical analysis of tumor tissue proved to be a good pre-screening test before proceeding to germline mutation analysis of DNA MMR genes.

Cryptococcocis: a rare fungal infection of the tongue.

Fungal infection in the oral cavity is not uncommon. The site involved is usually species related. Cryptococcus rarely infects the oral cavity. We report an elderly patient who presented with a central lesion on the dorsum of the tongue. Biopsy revealed a fungal infection. Special stains confirmed cryptococcus. Being a rare location for cryptococcal infection, clinical suspicion should be correlated with histopathological examination. Once confirmed, the patient should be treated with an antifungal medication.

Intra-abdominal desmoplastic small round cell tumor: Presentation of four cases and review of the literature.

Desmoplastic small round cell tumor (DSRCT) of the abdomen is a recently identified aggressive neoplasm. Very few cases have been reported in the literature. Thus, the treatment guidelines are yet to be defined. The role of chemotherapy, radiotherapy and surgery is evolving. We treated four cases of DSRCT involving the abdomen using combination chemotherapy and/or tumor cytoreductive surgery. There were two men and two women. The chemotherapy drugs consisted of cisplatin, adriamycin, etoposide, ifosphamide, vincristine and cyclophsophamide. All patients achieved meaningful partial response to chemotherapy, which maintained for 6-9 months. There were very minimal chemotherapy-related complications. At the time of reporting, the median survival time was 15 months. Thus, DSRCT is an aggressive intra-abdominal tumor with excellent chemoresponsiveness, but relapse is frequent.

Lymphatic channel density in colorectal adenocarcinoma.

AIMS: The purpose of this study was to count the number of lymphatic channels present in colorectal adenocarcinoma and correlate it with site, size, and stage of tumor, lymph node metastasis. MATERIAL AND METHODS: A total of 29 cases of colorectal carcinomas were retrieved from the archives of the pathology department, School of Medical Sciences. One paraffin block containing tumor was selected from each case. Sections of three to five micron thickness were cut from this paraffin block and stained using the monoclonal antibody D2-40[DAKO] specifically to stain lymphatic channel endothelium in normal and neoplastic tissue. The highest number of lymphatic channels in an area of 0.196 mm2 [high power field] was counted in each tumor using NIKON microscope. These findings were correlated with the clinical parameters and also with lymph node metastasis. Statistical software used: SPSS version 11. RESULTS: The highest density of lymphatic channels in colorectal carcinoma was counted after identifying the appropriate "hot spot". The lymphatic channel density was in the range of 15 - 50/ 0.196 mm 2 [high power field]. There was poor association of this lymphatic channel density with site, size, and stage of tumor and also with lymph node metastasis. This result is in concordance with results of studies done elsewhere. CONCLUSION: In this study no significant association was seen between lymphatic channel density and site, size, stage and lymph node metastasis in colorectal carcinoma. This indicates that lymphatic channel proliferation does not influence tumor aggressiveness. Further studies are needed to validate our findings.

Choristoma of the base of the tongue.

Choristoma is a benign tumor where new bone formation occurs. It occurs exclusively in the flat bones of the skull and face. These are slow growing lesions that are usually completely asymptomatic and only present when there is a disruption in the function of the organ due to its large size as it grows. These choristomas can rarely occur in soft tissues especially in the head, eye, tongue, or extremities. Choristomas of the soft tissues are very rare. Only 61 cases of choristomas of the tongue have been reported in literature. Here we report a case of choristoma in the base of the tongue in a 25-year-old Malay female.

Prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinoma : a histochemical study.

To determine the prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinomas by histochemial staining and to investigate the most sensitive histochemical staining method to detect this metaplasia, a total of 90 tissue blocks representing 30 non-neoplastic cervix, 30 non-neoplastic endometrium, 30 endocervical and endometrial adenocarcinoma cases were obtained for histochemical staining with Toluidine Blue (TB), Methylene Blue (MB), Mucicarmine (MUC), Periodic Acid Schiff before and after Diastase digestion (PAS, PAS-D), Alcian Blue pH 2.5 (AB), and Periodic Acid Schiff after Alcian Blue pH 2.5 (PAB). The cases were blinded and evaluated by a pathologist [NHO] for the presence of goblet cell metaplasia, the amount of goblet cells present and the histochemical differentiation of the goblet cells compared with its surrounding glandular epithelium. Goblet cell metaplasia was present in 2 out of 30 cases in non-neoplastic cervix, 0 out of 30 cases in non-neoplastic endometrium, 7 out of 15 cases in endocervical adenocarcinoma and in 2 out of 15 cases in endometrial adenocarcinoma. Relatively few goblet cells were seen in endometrial adenocarcinoma, few to moderate amounts were seen in endocervical adenocarcinoma and relatively more goblet cells were seen in non-neoplastic cervix. The differentiation of the goblet cells with its surrounding glandular epithelium was moderate to strong in non-neoplastic cervix and endocervical adenocarcinoma, while the differentiation in endometrial adenocarcinoma was weak to moderate. The various staining methods showed differences in presence, amount and differentiation of the goblet cells. Goblet cell metaplasia of the reproductive organs is not as rare as previously reported. There was no statistical difference in presence, amount and differentiation of goblet cells according to the various cases. The must optimum staining methods for staining goblet cells in non-neoplastic cervix, endocervical adenocarcinoma and endometrial adenocarcinoma were PAS, PASD and AB.

Heterotopic ossification in skeletal muscle metastasis from colonic adenocarcinoma--a case report.

Colonic adenocarcinoma metastasising to the skeletal muscle is rare. A-56-yr-old Malay man was diagnosed to have adenocarcinoma of the right colon [Dukes B] for which a right hemicolectomy was performed, followed by radiotherapy and chemotherapy. Five years later the patient presented with a mass in the rectus abdominis muscle. The serum carcinoembryonic antigen was 71 ng/Ml. The mass was resected. Gross and microscopical examination showed multiple deposits of mucin-secreting adenocarcinoma with prominent heterotopic ossification in the stroma. The exact pathogenesis and significance of heterotopic ossification is not clear, but bone morphogenetic proteins may play an important role.

Abdominal cocoon in association with adenomyosis and leiomyomata of the uterus and endometriotic cyst : unusual presentation.

Abdominal cocoon or sclerosing encapsulating peritonitis is a rare condition. A 46 year old Malay woman with adenomyosis and leiomyomata of the uterus and ovarian endometriotic cyst in association with abdominal cocoon is reported.

Malignant mixed mullerian tumour, heterologous in a 66-year-old malay lady - a case report.

A 66-year-old Malay woman, known hypertensive, presented with post menopausal bleeding associated with clot for three months. She was postmenopausal for last ten years. She also complaints of developing a mass in the abdomen which was growing in size also for last three months. Abdominal examination revealed a twenty week size mass, movable from side to side but unable to get below the mass. Vaginal examination revealed a fleshy fungating mass arising from the uterus coming out through the vagina. Cervix could not be visualized properly. Subsequent histopathology of the removed mass was reported as a Malignant Mixed Mullerian Tumour - Heterologous.