Objective: This study aims to determine inter-laboratory variation in HER2 IHC testing through a slide-exchange program between five main reference laboratories.
Method: A total of 20 breast carcinoma cases with different known HER2 expression and gene status were selected by the central laboratory in five testing rounds. Three unstained tissue sections from each case were sent to participating laboratories, which immunostained and interpreted the HER2 immunohistochemistry result. One of the stained slides was sent to one designated participating laboratory for evaluation. Results were analyzed by the central laboratory.
Results: A complete concordance was achieved in six IHC-positive and six IHC-negative cases, its gene status of which was confirmed by in-situ-hybridization (ISH) study. The discordant results were observed in six equivocal cases, one negative case and one positive case with a concordance rate of 50-88.3%. Interestingly, the negative discordant case actually displays tumor heterogeneity. Good inter-observer agreement was achieved for all participating laboratories (k = 0.713-1.0).
Conclusion: Standardization of HER2 testing method is important to achieve optimum inter-laboratory concordance. Discordant results were seen mainly in equivocal cases. Intra-tumoral heterogeneity may impact the final HER2 IHC scoring. The continuous quality evaluation is therefore paramount to achieve reliable HER2 results.
MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.
RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.
CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.
METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).
RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).
CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.
CASE REPORT: We report a case of a 46-year-old Chinese male who presented with six months history of abdominal pain, weight loss and rectal bleeding. Diagnostic colonoscopy revealed multiple aphthous ulcers within the ileo-caecal region and distal transverse colon, separated by normal mucosa, mimicking skip lesions of Crohn's colitis. Computer topography (CT) scan of the abdomen showed multiple circumferential thickenings involving predominantly the right colon. A clinical diagnosis of colonic Crohn's disease with possible perforation was made. An extended right hemicolectomy was performed due to uncontrolled rectal bleeding. Histopathology examination of the colon showed infiltration by malignant lymphoid cells associated with necrosis, angiocentricity and angiodestruction. Immunohistochemical studies confirmed T-cell monoclonality, presence of cytotoxic granules and Epstein-Barr virus (EBV) infection. A diagnosis of extranodal NK/T cell lymphoma of the colon was made.
DISCUSSION: These findings highlight that colonic NK/T cell lymphoma may clinically mimic other benign inflammatory lesions and should be one of the differential diagnoses in patients presenting with gastrointestinal lesions. The final diagnosis is only possible with appropriate histological and immunohistochemical studies.
MATERIALS & METHODS: In total 141 local series of DLBCL cases from UKM Medical Centre were retrospectively studied.
RESULTS: Of these cases, we classified our patients into two subtypes: 32.7% (37/113) GCB and non-GCB 67.3% (76/113) by Hans algorithm and the results showed strong agreement with the results by Choi algorithm (κ = 0.828, P<0.001). Survival analysis indicated significant difference in between GCB and non-GCB subtypes (P=0.01), elevated serum LDH (P=0.016), age more than 60-year-old (P=0.021) and the presence of B symptoms (P=0.04). We observed 12% DLBCL cases were CD5 positive and 81.8% of them died of the disease (P=0.076). Analysis on the dual expression of MYC/BCL2 revealed that there is no significant difference in DE and non-DE groups (P=0.916). FISH study reported there were 9.22% (13/141) rearranged cases observed in our population at which highest frequency of BCL6 gene rearrangement (76.9%), followed by MYC (15.4%) and BCL2 (7.7%); no BCL10 and MALT-1 gene rearrangement found regardless of using TMAs or whole tissue samples. More cases of MYC protein overexpression observed compared to MYC translocation.
CONCLUSION: Relatively lower frequency of GCB tumours and low gene rearrangement rates were observed in Malaysian population. A national study is therefore warranted to know better the immunogenotypic characteristics of DLBCL in Malaysia and their implications on the survival.
Case Report: We report a rare case of nasal angiomyolipoma in a young male. To the best of our knowledge, this is the first documented case of angiomyolipoma originating from the posterior end of the inferior turbinate, clinically mimicking juvenile nasopharyngeal angiofibroma (JNA). The tumor was removed completely via coblator-assisted endoscopic sinus surgery. The patient was asymptomatic at a 2-year follow-up.
Conclusion: Nasal AML located in the posterior nasal cavity in a male patient can mimic the presentation of JNA. A computed tomography scan of the paranasal sinuses played an important role in differentiating nasal AML from JNA. The coblator-assisted endoscopic technique is useful in controlling intraoperative hemostasis in the removal of a suspicious vascular tumor.
CASE REPORT: We report a 54-year-old Caucasian man who presented with chronic diarrhoea and weight loss. He was diagnosed with coeliac disease based on positive serology results and duodenal, jejunal, and ileal biopsies that showed villous atrophy. Despite adherence to a gluten-free diet, there was no clinical remission and enteropathy-associated T cell lymphoma was suspected. Repeated endoscopic biopsy showed persistent mucosal disease but no evidence of lymphoma. Several weeks later he presented with a perforated jejunum. Histology of the resected jejunum showed diffuse infiltration of submucosa and muscularis propria by malignant lymphoid cells sparing the mucosa. The cells expressed CD20, CD79α, CD10 and BCL6 and ki67 of 80%, consistent with diffuse large B-cell lymphoma.
DISCUSSION: It is suspected that the undetected lymphoma may have contributed to the persistent malabsorption syndrome rendering the patient unresponsive to treatment. Despite thorough clinical and endoscopic evaluation and multiple biopsies, histologic diagnosis of DLBCL was only confirmed following resection of the perforated jejunum.
CASE REPORT: We report a case of a 75-year-old man who presented with symptoms of obstructive jaundice. Ultrasonography and computed tomography (CT) showed an ill-defined lobulated soft tissue lesion at the head/uncinate process of the pancreas measuring 4.5 x 4.9 x 5.8 cm. The patient underwent pancreaticoduodenectomy for suspected pancreatic head/uncinate process carcinoma. Histopathology and immunohistochemical assessment of the pancreatic lesion established the diagnosis of a low-grade follicular lymphoma.
DISCUSSION: Clinical and imaging features of primary pancreatic lymphoma may often overlap with pancreatic carcinoma. There is a value of obtaining preoperative tissue diagnosis such as tissue biopsy and fine needle aspiration (FNA) cytology with or without flow cytometry to make an accurate diagnosis of non-Hodgkin lymphoma and alleviate the need of more radical surgery in pancreatic lymphoma.
MATERIALS AND METHODS: We retrospectively analysed the histopathological material and data from 82 breast cancer patients diagnosed over a period of four years who underwent intraoperative frozen section evaluation of sentinel lymph nodes.
RESULTS: Frozen section analysis detected metastasis in 13 out of 82 cases and definitive pathological examination on the paraffin section confirmed these positive findings. There was no false positive case (specificity of 100%). The true positive cases comprised seven macrometastases, five micrometastases and one isolated tumour cells. Sampling error was noted in two cases in which the malignant cells were only present in the deeper final paraffin sections (false negative rate of 13.3%). The test sensitivity was 86.7% and the accuracy rate was 97.5%. These findings are comparable to other published data.
CONCLUSION: Intraoperative frozen section analysis is a safe and reliable method for assessment of sentinel lymph node. Knowledge on limitation of frozen section analysis with diligent evaluation of frozen section specimen will be beneficial in reducing interpretation error.
Materials and Methods: We analyzed 101 cases of prostate adenocarcinoma diagnosed from January 2011 to June 2015 in 100 patients. Immunohistochemical staining of ER-beta and Ki67 was analyzed according to Gleason score categorized into prognostic groups of 1 to 5. Double-immunofluorescent staining of ER-beta and Ki67 was performed in a total of 20 cases to study the co-expression and the relationship between these markers within the same tumor.
Results: A total of 53 of 101 cases (52.5%) were positive for ER-beta expression. There was a positive correlation whereby a high percentage of ER-beta expression was seen in the higher prognostic groups (groups 4 and 5; p=0.007). High Ki67 expression was observed in the higher prognostic group, whereas low Ki67 or negative expression was found in the lower prognostic group (p<0.001). The majority of cases evaluated with double-immunofluorescent staining (14/20) showed co-expression of ER-beta and Ki67 at the individual cell level.
Conclusions: ER-beta and Ki67 are independent tumor markers in high prognostic groups. Hence, co-expression of ER-beta and Ki67 indicates a more aggressive tumor with a poorer prognosis.
METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).
RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).
CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.