P31. CORRELATION OF MOLECULAR PROFILING WITH HISTOLOGY GROWTH PATTERN IN BIOPSY OF LUNG ADENOCARCINOMA.
Nor Salmah Bakar¹, Mardiana Abdul Aziz¹, Noriah Othman², Ruzi Hamimi Razali³
¹Anatomic Pathology Unit, Department of Pathology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor. ²Histopathology Unit, Department of Pathology, Hospital Serdang, Selangor. ³Medical Genetic Unit, Department of Pathology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sg Buloh, Selangor
The current classification of lung carcinoma further defines adenocarcinomas into five subtypes based on histological growth patterns. The five growth patterns are characterised by their typical architecture, but also by variable tumor biological behaviour. This study was conducted to examine the correlation between histological growth patterns of lung adenocarcinoma to the molecular test results.
Materials and Methods:
This is a retrospective study. All lung carcinomas that were sent for EGFR molecular testing in 2016 and 2017 (UiTM) and 2018 (Serdang) were included. This study excludes lung carcinoma diagnosed from pleural, lymph node, mediastinal biopsy or resection specimens, Non Small Cell Lung Carcinoma (NSCLC)-favour squamous cell carcinoma and cases that no slides could be retrieved for review. The slides then reviewed by two pathologists. A consensus conclusion of the predominant histology growth pattern was obtained; acinar, solid, lepidic, papillary or micropapillary. The histology growth pattern against EGFR results were analysed.
Results and Discussion:
Ninety cases were included with 36%(32/90) showing positive EGFR molecular testing. The frequency of positivity according to histology growth pattern are acinar 59%(16/27), solid 32%(17/53), papillary 25%(1/4) and lepedic 0%(0/6). Predominant histological growth pattern–EGFR result correlation as follows: ACINAR pattern (n=27) showing exon 19 deletion (n=5), exon 21 (L858R) mutation (n=6), double mutation at exon 20 (S768I) and exon 18 (G719X) (n=2), double mutation at exon 20 (S768I) and exon 21 (L858R) (n=1), mutation exon 18 (G719X)(n=1), deletion exon 19 and exon 21(L858R) mutation (n=1); SOLID pattern (n=53) showing exon 19 deletion (n=12), exon 21 (L858R) mutation (n=3), exon 19 insertion (n=1), exon 20 insertion (n=1); PAPILLARY pattern (n=4) showing exon 21 (L858R) mutation (n=1); LEPEDIC pattern (n=6) none showing positive molecular EGFR testing.
Solid growth pattern is the most frequent pattern observed in lung biopsy specimen however tumour with predominant acinar pattern show the most frequent positive EGFR molecular testing.
P32. EXPRESSION OF KI-67 IN INVASIVE BREAST CARCINOMA AND ITS CORRELATION WITH TUMOUR GRADE, STAGE GROUP AND MOLECULAR SUBTYPING
Noor Afidah Abdullah¹, Najah Momin², Haliza Zakaria¹, Muhammad Fakhri¹, Azmawati Mohammed Nawi³, Suria Hayati Md Pauzi¹
¹Departments of Pathology, Hospital Canselor Tuanku Mukhriz, Universiti Kebangsaan Malaysia, ²Departments of Pathology, Hospital Melaka, ³Department of Community Health, Hospital Canselor Tuanku Mukhriz, Universiti Kebangsaan Malaysia.
Ki-67 is a proliferative labelling index which may signify the clinical behaviour and serve as prognostic marker in breast cancer. We aimed to evaluate Ki-67 expression in breast cancer and to correlate with tumour grade, stage group and molecular subtyping.
Material and methods:
A total of 280 invasive breast carcinoma cases from January 2014 to December 2017 were selected. Ki-67 proliferative index was immunohistochemically analyzed and compared with clinicopathological variants.
Results and discussion:
High Ki-67 shows significant association with high tumour grade, stage group and non-luminal molecular subtyping. High Ki-67 shows significant predictor for high tumour grade (Grade 2: aOR 4.183, 95% CI 1.751-9.996 and Grade 3: aOR 26.966, 95%CI 10.044-72.400) and non-luminal molecular subtyping (aOR 4.590, 95%CI 2.328-9.048). There were no significant association found between Ki-67 and lymph node status and lymphovascular invasion.
Evaluation of Ki-67 expression in breast cancer serves as prognostic indicator that helps to guide in the management of patients.
P33. EXPRESSION OF TUMOUR CARCINOEMBRYONIC ANTIGEN AND ITS CORRELATION WITH CLINICOPATHOLOGIC PARAMETERS IN COLORECTAL CARCINOMA PATIENTS IN HOSPITAL SERDANG
Sue Anida Azman¹, Norhafizah Mohtarrudin², Norhayati Omar¹
¹Histopathology Unit, Department of Pathology, Hospital Serdang, Jalan Puchong, 43000 Kajang, Selangor Darul Ehsan
²Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan.
Carcinoembryonic antigen (CEA) is a set of glycoproteins responsible for intercellular adhesion, apoptosis and metastatic potential. It is a tumour-associated antigen for colorectal carcinoma (CRC). While its serum concentration is a well-known prognostic marker for CRC, the prognostic value of tumour CEA expression is controversial.
Materials and methods:
86 patients who underwent curative resection for CRC in Hospital Serdang from January 2010 to December 2015 were enrolled in this study. Immunohistochemical study was conducted using anti-human CEA monoclonal mouse antibody. CEA expressions by tumour tissues were classified based on the staining intensity (weak or strong) and pattern (apical or cytoplasmic). Correlations between CEA expressions with grade, stage, overall survival (OS) and disease free survival (DFS) of the patients were studied using Spearmann’s correlation and Kaplan-Meier survival analysis.
Results and Discussions:
The mean age group of the patients was 63.66 years (SD1.366) with the highest proportion of cases were among males (51 cases, 59.3%) and Chinese (41 cases, 47.7%). Most of the cases (75 cases, 87.2%) were moderately differentiated. 56 cases (65.1%) showed strong CEA expression compared to weak CEA expression in 30 cases (34.9%). 50 (58.1%) and 36 (41.9%) of CRC cases had apical and cytoplasmic CEA expression respectively. Tumour CEA expression pattern had weak correlation with grade of CRC at the 0.01 level (rho value -0.325). However, there was no correlation with stage. Tumours with strong staining intensity and apical tumour CEA expression showed longer mean OS and DFS compared to their counterparts, though it was not statistically significant.
Our results show the prognostic role of tumour CEA expression in CRC remains unclear as there was no definitive correlation between CEA expressions. Further understanding of pathophysiology and regulation of CEA are anticipated. In the era of targeted therapy, predictive role of CEA in CRC should be explored.
P34. OVARIAN SMALL CELL CARCINOMA OF HYPERCALCEMIC TYPE
Shanny Goh, Faizah Ahmad
Department of Pathology, Hospital Melaka
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an extremely rare and highly aggressive tumour which typically affects young women. The prognosis is poor with more than 65% of patients succumb to their disease within 1 to 2 years of diagnosis.
We report a case of a 41-year-old nulliparous lady who presented with one-month history of abdominal distension. Physical examination revealed gross ascites with no other significant finding. The tumour markers were within normal range. Contrast enhanced computerised tomography (CT) examination demonstrated a huge solid enhancing mass arising from left ovary with local infiltration. There are multiple intraabdominal lymphadenopathy with multiple lung nodules suspicious of malignancy with nodal and lung metastasis. Subsequently laparotomy revealed left ovarian tumour with extensive tumour seeding at the peritoneal surface, right ovary and omentum. Histopathological examination showed the tumour was composed of predominantly small cells with large cells component. The malignant cells showed diffuse immunoreactivity to WT-1 and focal positivity to EMA, Pan CK, calretinin, inhibin, CD10 and p53. They were negative for CA125, CK7, CK20, ER, PR, CD30, PLAP, CD45, CD56 and BHCG. The histological and immunohistochemical finding led to the diagnosis of SCCOHT. Subsequently, patient deteriorated rapidly post operatively which required intensive care. She developed metabolic acidosis and multiorgan failure and eventually succumbed.
SCCOHT is a rare tumour with approximately 300 cases reported in the literature. There is no specific clinical manifestation. Role of biopsy and cytological sample are limited. Therefore, the definitive preoperative diagnosis of SCCOHT is difficult and pathological examination remains the gold standard. Recent studies show that SCCOHT is characterized by SMARCA4 (also known as BRG1) mutation which results in loss of BRG1 protein expression in immunohistochemistry. This has been shown to be a useful diagnostic marker in SCCOHT.
P35. PREVALENCE OF CERVICAL SQUAMOUS INTRAEPITHELIAL LESIONS (SIL) ON PAPANICOLAOU STAINED SMEAR CYTOLOGY
Than Than Htwe¹, Siti Aishah binti Anuar¹, Azizah Haziqah binti Ariffin¹, Alia Afiqah binti Zainudin¹, Nur Adlin Syafika binti Shamzul Hisham¹, Nurul Syazwani Zakiah binti Marhassan¹, Muhammad Haziq Khan bin Hajimolkan¹, Sabaridah binti Ismail¹ and Norain Karim²
¹Universiti Kuala Lumpur – Royal College of Medicine Perak (UniKL RCMP), No. 3 Jalan Greentown, 30450, Ipoh, Perak, Malaysia.
²Hospital Raja Permaisuri Bainun (HRPB), Jalan Raja Ashman Shah, 30450, Ipoh, Perak, Malaysia
Cervical cancer is the second most common cancer in Malaysia. The most frequent type of it is squamous-cell carcinoma (70-80%) developed from the precursor lesions squamous intraepithelial lesion (SIL). SIL is classified into low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). Other than human papilloma virus (HPV), other risk factors for cervical cancer include race and age. Early detection through regular Pap smear screening to identify pre-cancerous lesions can greatly reduce at risk population. This study was conducted to observe the prevalence of LSIL and HSIL in the collected samples from HRPB from year 2016 to 2018. Also, to identify the outcomes of LSIL and HSIL by age and race.
This is a retrospective hospital-based descriptive study performed on all Papanicolaou stained smear cytology slide collections from the Pathology Department, HRPB, from 1st June 2016 to 31st May 2018. A total of 3646 data was collected. Slides were reviewed for the degree of LSIL and HSIL. Analysis was done in SPSSv.23.
Results and Discussion:
From 3646 reports, there were 14 (0.4%) cases of HSIL, 53 (1.5%) cases of LSIL and 3579 for others. By ethnicity, Chinese have the highest prevalence (50.0%) of HSIL while Indians have the lowest (0%). However, Indians have the highest (37.7%) prevalence of LSIL while other bumiputera have the lowest (1.9%). By age group, age 51-60 and above have the highest (36%) prevalence of HSIL. Age ≤ 30 years have the lowest (0%) prevalence of HSIL. As for LSIL, age between 31-40 and 41-50 years old have the same (24.5%) highest prevalence of LSIL while age ≤ 30 years old have the lowest (7.5%) prevalence of LSIL.
The overall prevalence of HSIL and LSIL in studied women is low. The Chinese ethnic group have the highest prevalence of HSIL and the Indian ethnic group have highest prevalence of LSIL.
P36. ROLE OF IMMUNOHISTOCHEMICAL STAININGS (PLA2R, THSD7A AND IGG4) IN DIFFERENTIATING PRIMARY AND SECONDARY MEMBRANOUS GLOMERULONEPHRITIS IN HOSPITAL SERDANG RENAL BIOPSIES FROM 2012 TO 2018.
Zulaikha Che Embi¹, Fauzah Abd Ghani², Elmina Mohamad Mokhtar¹, Norhafizah Mohtarrudin²
¹Department of Pathology, Hospital Serdang, ²Department of Pathology, Universiti Putra Malaysia.
Membranous glomerulonephritis (MGN) is a disease characterised by immune complex deposition within the subepithelial region of the basement membrane. It can be classified based on aetiology as primary (idiopathic) or secondary (secondary to underlying causes). Differentiating the two on the renal biopsy can be challenging in light of the fact that the management and prognosis is dependent on the correct identification of aetiopathological profile. This study was conducted to determine the use of PLA2R, THSD7A and IgG4 immunohistochemical stainings in differentiating between the two aetiopathological patterns.
Materials and Methods:
48 confirmed cases of MGN were selected in this retrospective cross sectional study. Immunohistochemical stainings of parafin embedded glass mounted sections with PLA2R (Abcam antibody, 1:1200 dilution at pH 9), THSD7A (Abcam antibody, 1:100 dilution at pH 6) and IgG4 (Abcam antibody, 1:500 dilution at pH 6) were performed. Demographic and clinicopathological data were analysed by frequency analysis. The correlational between MGN and immunohistochemical stains were analysed via Spearman correlation test using SPSS version 24.0.
Results and Discussion:
Primary MGN was diagnosed in 27.1% of all confirmed cases of membranous glomerulonephritis cases. Among the cases of secondary MGN (72.9%), only one (1) had underlying hepatitis B infection. The remaining cases were due to Systemic Lupus Erythematosus (SLE). The mean age for patient with primary MGN was 50 years old while patients with secondary MGN had a mean age of 33 years old. Females were more commonly diagnosed with secondary MGN (56.2%) cases. Most of the patients presented with nephrotic syndrome (68.8%) as an indication for renal biopsy. There is strong correlations between MGN types with PLA2R and IgG4 expression (rho=0.701, p<0.001 and rho=0.721, p<0.001 respectively), while a correlation albeit weak one is present between MGN types and THSD7A (rho=0.299, p =0.05). In addition, there are also moderate correlations between IgG4 with PLA2R and THSD7A stains (rho=0.626, p<0.001 and rho=0.479, p=0.03 respectively).
Our findings are in keeping with similar such studies which have reported correlations between PLA2R, IgG4 and THSD7A positivity in differentiating primary with secondary MGN. Thus, these stains can be used as tandem ancillary tests in daily practice to help pathologists in differentiating primary and secondary MGN.
P37. STROMAL MAST CELLS IMMUNOHISTOCHEMICAL STUDY IN INVASIVE BREAST CARCINOMA AND ITS RELATIONSHIP WITH PROGNOSTIC PARAMETERS IN HOSPITAL TUANKU JA’AFAR FROM 2015 TO 2017
Huzlinda Bt Hussin¹, Razana Bt Mohd Ali¹, Roslina Bt Suboh², Norashikin Bt Haji Awang Ahmad¹
¹Department of Pathology, Universiti Putra Malaysia, ²Department of Pathology, Hospital Tuanku Ja’afar
Mast cells have a role in innate and adaptive immune responses in tumour microenvironment which influence anti-tumour host defence, tumour development, neo-angiogenesis and metastatic propensity, affecting patient’s outcome. Several studies have shown that mast cells accumulate in various malignant tumors. Some studies reported that high number of mast cells was associated with good prognosis while some suggested that it was associated with poor prognosis. This is a study of invasive breast carcinoma where the correlation between mast cell density with prognostic parameters such as tumour size, lymph node metastasis, lymphovascular invasion, histologic type and grade, estrogen and progesterone receptor and HER2 expression was examined.
Materials and Methods:
A total of 160 cases of formalin-fixed paraffin-embedded invasive breast carcinoma tissues were selected and immunostained with CD117 antibody to highlight the mast cells. The stained mast cells were counted at 400x magnification in 10 fields and mast cell density was expressed by mean value.
Results and Discussion:
Most patients were >40 years old (92.5%) and Malay was the highest (66.3 %). For histological type and grade, the highest was no special type (80.6%) and grade 3 (41.3%) respectively. For tumour size, T2 tumour was the highest (63.1%). The majority of cases (51.3%) were negative for lymph node metastasis but 59.4% showed lymphovascular invasion. For estrogen receptor, progesterone receptor and HER2 expression, the expression pattern was in descending order; 64.4%, 53.1% and 25% respectively. There was no significant correlation between mast cell density with prognostic parameters.
Insignificant correlation in prognostic parameters suggest that mast cells density may not be suitable prognostic marker for tumor progression because the density is relatively high in a significant subset of parameters. However, majority of cases demonstrate favorable outcome as most of cases are stage T2 without lymph node involvement and would respond to hormonal therapy.
P38. THE Location And Size Are Helpful Features In Diagnosing Sessile Serrated Adenoma/Polyp.
Shahril Fikri Zul Hasnan Najib¹, Huzlinda Hussin¹, Noor Afidah Bt Mohamed Shabery², Fauzah Bt Abdul Ghani¹
¹Department of Pathology, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
²Department of Pathology, Hospital Selayang, Lebuhraya Selayang-Kepong, 68100, Batu Caves, Selangor.
Sessile serrated adenoma/polyp (SSA/P) is now accepted as a precursor of colorectal carcinoma (CRC) through the serrated neoplastic pathway. Among the serrated colonic polyps (SCP), hyperplastic polyps (HP) show closer morphological features to SSA/P than the rest. It is important to differentiate between HP and SSA/P as SSA/P is a premalignant condition but not HP. In this study, the proportion of SSA/P among SCP and underdiagnosed cases of SSA/P were analysed. The association between SSA/P and non-SSA/P with demographic parameters and colonoscopic findings were also examined.
Material and Methods:
The slides of 198 cases of SCP comprising of HP, SSA/P and traditional serrated adenoma (TSA) were reviewed and reclassified accordingly.
Results and Discussion:
Out of 198 cases of SCP, 164, 29 and 5 cases were reclassified as HP, SSA/P and TSA respectively. Sixteen cases of SSA/P were underdiagnosed as HP. From a total of 29 cases of SSA/P, 58.6% were ≥ 65 years old, 72.4 % were male and the majority (58.6%) were Chinese. For the location and size of SSA/P, 55.2 % were located in the right colon and 31% were ≥ 10mm in size. There were significant associations between SSA/P and non-SSA/P with location (p=0.004) and size (p=0.013) of the polyps.
There were underdiagnosed cases of SSA/P among HP possibly due to their close histological features. The location and size of any SCP may alert the pathologists of the possibility of SSA/P.
P39. SINONASAL EXTRAMEDULLARY PLASMACYTOMA IN MALAYSIA: A SYSTEMATIC REVIEW.
Frhana Rahmat, Nur Aishah Che Roos.
National Defence University of Malaysia
Plasmacytoma is a localized plasma cell neoplasm. It may arise from the bone or other tissues which is also known as extramedullary plasmacytoma (EP). Sinonasal tract is the most common site for EP. According to the literature, two-third of patients are male with the median age of diagnosis is at 55 years. The common clinical presentations include epistaxis, rhinorrhoea and nasal obstruction. Approximately 17-30% of patients with EP may develop multiple myeloma (MM). This study aimed to aggregate and describe the manifestations of sinonasal plasmacytoma reported through a systematic literature review.
Material and Methods:
An extensive search was conducted using SCOPUS, PubMed, and PubMed Central for case report published between inception to the fourth week of June 2019. Keywords used, included extramedullary or extraosseous or sinonasal or solitary and plasmacytoma. The eligible articles reported adult human with sinonasal plasmacytoma within Malaysia.
Results and Discussion:
Altogether, only five articles reporting one patient each were included in this review. All of the cases involved patients aged above 50 years in which three were female and two were male. Two patients presented with epistaxis, two with proptosis and one with rhinorrhoea. The radiological findings of patients with orbital manifestation showed extension of the tumour to the orbital wall. Further investigation for two of the cases shown MM, however, the reporting of diagnostic measure taken were inconsistent. Furthermore, successful response to treatment was dependent on the local extension of the tumour.
Although the number of articles are not extensive, this review highlights gaps in the areas of MM detection associated with EP. Moreover, reporting of additional cases is warranted to reflect the actual trend of disease presentation, response to therapy and disease prevalence in our country.
P40. ANGIOIMMUNOBLASTIC T CELL LYMPHOMA WITH SKIN MANIFESTATION: A DIAGNOSTIC CONUNDRUM
Aliza A¹, Norakmar T¹, Ahmad TS²
¹Department of Pathology, Hospital Tuanku Ja’afar Seremban, Negeri Sembilan
²Department of Pathology, Hospital Queen Elizabeth, Sabah
Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon mature T cell malignancy, currently residing under the umbrella of nodal T-cell lymphoma with follicular T helper phenotype. It represents 1-2% of all cases of Non-Hodgkin lymphoma. It shares common symptom like other lymphomas, variable histological pattern and it must be differentiated from other malignant lympho-proliferative diseases, drug reactions and viral infections. Skin involvement occurs in up to 50% of patients. AITL typically display an aggressive behaviour with poor prognosis.
We are illustrating a case report of a 50-years-old male diagnosed with AITL who presented with prominent skin lesion without any B symptom. Examination showed generalized lymphadenopathy with multiple skin nodule seen. He was treated as infected sebaceous cyst at initial presentation. Skin biopsy show diffuse infiltrates of lymphoma cells in the absence of epidermotropism and histological features of AITL. The cells are positive for CD2, CD3, CD4, CD5, PD1. Immunoblast are CD30+ /ALK-. Occasional EBER+ immunoblast seen. CD8, TIA, perforin are negative. Subsequently peripheral blood showed pancytopenia with presence of atypical lymphoid cells, suggestive of marrow infiltration.
We recommend a lymph node biopsy in diagnosing AITL as it is the gold standard. Skin biopsy poses a diagnostic dilemma because of the limited number of reported cases and subsequent lack of established diagnostic criteria as seen in this case. This is even more difficult in a center with limited resources like ours. Cutaneous and histological findings may be nonspecific. Therefore, clinical history and symptoms combined with current strides in immunohistochemical stains and molecular study helps secure the confidence of the diagnosis likely leading to earlier treatment.