KRAS Mutation: Characterization and Its Impact on Survival Outcome of Patients with Metastatic Colorectal Cancer.

INTRODUCTION: Colorectal cancer (CRC) is one of the most common cancer types, with rising incidence due to imbalanced lifestyle and dietary habit. Association between CRC cases and KRAS mutation has been established recently. Brunei Darussalam, located within the Borneo island, is of diverse ethnicity which could represent the genome of Southeast Asia population. Our study, for the first time, determined the survival outcome of metastatic colorectal cancer (mCRC) and established the link with KRAS mutation by modelling the population in Brunei Darussalam. METHODS: We collected data of 76 metastatic CRC (mCRC) patients undergoing treatment at The Brunei Cancer Centre, the national centre for cancer treatment in Brunei. These patients were diagnosed with Stage 4 CRC between 1 January 2013 and 31 December 2017. Age, gender, ethnicity, date of diagnosis, site of primary tumour, metastatic sites and molecular analysis of KRAS mutation status (either KRAS mutated or KRAS wild-type) of tumour were recorded. The survival outcomes of these mCRC patients were analysed. RESULTS: The end of this study period recorded 73.1% deceased mutant KRAS mCRC patients and 46.0% deceased wild-type KRAS mCRC patients, contributing to death rates of 45.2% and 54.8%, correspondingly. Chi-squared analysis showed a significant difference between the survival outcomes of wild-type KRAS and mutant KRAS mCRC patients (p-value = 0.024). CONCLUSIONS: There is a significant difference between the survival outcomes of wild-type KRAS and mutant KRAS mCRC patients in the Brunei population. In addition, we found that mutations in codon 12 of KRAS gene on mutant KRAS mCRC patients have shorter survival median periods than those with mutations within codon 13 of KRAS gene. This is the first study in Brunei Darussalam to analyse both the survival outcomes of mCRC patients and those of mutant KRAS mCRC patients.

Fine-Needle Aspiration Cytology in the Diagnosis of Breast Paraffinoma.

INTRODUCTION: Paraffin injections for breast augmentation once a popular form of mammoplasty are now considered obsolete. It had been abandoned by clinicians because of its associated serious complications. The practice is however still available and is being practiced by nonmedically qualified people. Paraffin injection results in the formation of multiple foreign-body granulomas known as breast paraffinoma. The clinical features of breast paraffinoma can mimic and be mistaken for breast carcinoma or inflammatory breast carcinoma. The use of fine-needle aspiration cytology (FNAC) in the evaluation of patients with breast paraffinoma has not been fully evaluated. METHODS: Retrospective review was performed on 30 patients who presented with breast paraffinoma between June 1, 2010, and June 30, 2020, who also had FNAC as part of their breast lump evaluation. RESULTS: FNAC of 73.3% patients showed multinucleated giant cells and macrophages or histiocytes containing engulfed clear, empty intracytoplasmic vacuoles of varying sizes. In 13.3% of the patients, macrophages or histiocytes with engulfed clear intracytoplasmic vacuoles of varying sizes were seen. In 6.7% of patients, multinucleated giant cells containing engulfed vacuoles of varying sizes were seen, and in 6.7% of patients, hypocellular smears with large amount of clear spaces were seen. Oily droplets were seen in the background of all the smears, and there were no malignant cells seen. These features were compatible with breast paraffinoma. CONCLUSION: Most patients with breast paraffinoma can be managed conservatively and they do not require further treatment; FNAC with its characteristic features can provide the reliable diagnosis of breast paraffinoma and therefore sparing these patients from more invasive diagnostic procedures.

Isolated Renal Involvement by IG4-Related Disorder Mimicking Multiple Myeloma, a Diagnosis Not to Miss.

IG4-related disorder (IgG4-RD) with isolated kidney involvement is rare. IG4-RD is a fibroinflammatory disorder leading to polyclonal activation of plasma cell and can affect kidney, orbital tissues, salivary glands, pancreas, bile duct, lymph nodes, and can cause inflammatory mass in any organ. Isolated kidney involvement is rare in this order. We share a case of isolated kidney involvement by this order presenting as enlarged kidneys with renal impairment. Kidney biopsy showed CD138 plasma cell interstitial nephritis. The biopsy also showed kappa light chain along IgG on immunofluorescence and was reported as light chain deposition disease initially. In view of hyperproteinemia and initial renal biopsy finding, workup was done for myeloma. Bone marrow biopsy showed around 20% of plasma cell infiltration. Skeletal survey did not show any lytic lesions and immunofixation did not reveal any paraprotein. Flowcytometry of the bone marrow showed nonclonal plasma cell. In view of negative workup for myeloma and nonclonal cells, re-evaluation of the kidney biopsy was done. Biopsy was reanalyzed for both IgG and IgG4. It showed 30 IgG4 cells per high-power field with a ratio of IgG4 / IgG of 40%. The staining for IgM, IgA C3, and C1q was negative. The patient was labeled as having plasma cell interstitial nephritis due toIgG4-RD. The patient responded well to oral prednisolone. It is important not to miss this potentially treatable and reversible condition by staining the biopsy sample for both IgG and IgG4 in clinically suspected cases.

Overexpression of EGFR protein in Bruneian lung cancer patients.

BACKGROUND: Lung cancer is the leading cause of cancer death in Brunei Darussalam, accounting for almost 20% of the total. The epidermal growth factor receptor (EGFR) is a member of the erbB family of tyrosine kinase receptor proteins, which includes c-erbb2(HER2/neu), erb-B3, and erb-B4. EGFR overexpression is found in a third of all epithelial cancers, often associated with a poor prognosis. MATERIALS AND METHODS: Protein expression of EGFR in 27 cases of lung cancer tissue samples and 9 cases of normal lung tissue samples was evaluated using an immunohistochemical approach. RESULTS: The results demonstrated significant increase and overexpression of EGFR in Bruneian lung cancer tissue samples in comparison to normal lung tissue. However, there was no significant relationship between clinicopathologic variables (age and sex) of patients and EGFR protein expression. CONCLUSIONS: EGFR is overexpressed in Bruneian lung cancer patient tissue samples in comparison to normal lung tissue samples. This may indicate that EGFR protein over expression plays an important role in the genesis of this type of cancer in Brunei Darussalam.

Primary biliary cirrhosis in Brunei Darussalam.

BACKGROUND: Primary biliary cirrhosis (PBC) is an uncommon autoimmune cholestatic disease that predominantly affects women. Certain human leukocyte antigens (HLAs) have been reported to be associated with susceptibility for PBC. We describe the profiles of PBC in Brunei Darussalam. METHODS: All patients with PBC (n = 10) were identified from our prospective databases. The HLA profiles (n = 9, PBC) were compared to controls (n = 65) and patients with autoimmune hepatitis (n = 13, AIH). RESULTS: All patients were women with a median age of 51 years (27-83) at diagnosis. The prevalence rate of the disease was 25.6/million-population and the estimated incidence rate varied from 0 to 10.3/million-population per year. Chinese (41.15/million) and the indigenous (42.74/million) groups had higher prevalence rates compared to Malays (22.62/million). The prevalence among female population was 54.6/million-population. All patients were referred for abnormal liver profiles. Five patients had symptoms at presentations: jaundice (20%), fatigue (20%), arthralgia (30%) and pruritus (20%). Serum anti-mitochondrial antibody was positive in 80% of the patients. Overlap with AIH was seen in 30%. Liver biopsies (n = 8) showed stage I (n = 2), II (n = 4) and III (n = 2) fibrosis. There were no significant differences in the HLA profiles between PBC and AIH. Compared to the controls, PBC patients had significantly more HLA class I alleles specifically B7 (P = 0.003), Cw7 (P = 0.002) and Cw12 (P = 0.007) but not the class II alleles. At a median follow-up of 23.5 months (2 to 108), all patients were alive without evidence of disease progression. CONCLUSIONS: PBC is also a predominant female disorder in our local setting and most had mild disease. The HLA profiles of our patients were different to what have been reported.

Chronic inflammatory demyelinating polyneuropathy associated with intestinal tuberculosis.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an increasingly common but under-recognized neurological disorder. It is immune mediated, and usually has a relapsing and remitting course. However, the initial presentation may be rapid. It can be associated with significant morbidity and mortality, particularly if there is a delay in diagnosis and treatment. It has been associated with both infective and non-infective etiologies. We present a case of CIDP associated with ileocecal tuberculosis (TB), presenting with progressive motor weakness and significant weight loss. The patient's symptoms improved to some extent with intravenous immunoglobulin and steroid, but improved significantly after being started on anti-TB therapy. However, his symptoms relapsed when he stopped his anti-TB treatment prematurely whilst continuing the immunosuppressive therapy. Upon resuming the anti-TB therapy, he made a good recovery. CIDP associated with TB has only been reported once. Our case highlights the need to consider TB in patients with neurological disorders.