Wan Faiziah Wan Abdul Rahman

Solid variant of papillary thyroid carcinoma in a 14-year-old girl

Solid variant of papillary thyroid carcinoma (PTC) is a rare, poorly characterised variant and predominantly reported in children with a history of radiation exposure. This variant has a high propensity for extra-thyroidal extension and cervical lymph node metastases. A 14-year-old Malay girl who had no history of radiation exposure, presented with multiple cervical lymphadenopathy and it was clinically suspicious for tuberculosis or lymphoma. An incisional biopsy revealed a metastatic PTC. The patient underwent total thyroidectomy with bilateral lateral neck dissection and histopathology report was solid variant of PTC. Whole-body I131 scan was performed which revealed an intense tracer uptake in the neck. She was planned for radioactive iodine ablation and now on regular follow-up for monitoring of possible tumour metastasis.

Expression of DNA methylation marker of paired-like homeodomain transcription factor 2 and growth receptors in invasive ductal carcinoma of the breast.

BACKGROUND Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2). METHODS We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH). RESULTS PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001). CONCLUSION PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

Keratinous inclusion cyst of oesophagus: unusual finding

Cysts of the oesophagus are unusual findings and they are classified according to the embryological site of origin. It may represent inclusion cysts, retention cysts and developmental cysts. We present a case of keratinous inclusion cyst of the lower oesophagus in a 71-year-old Malay woman who presented with dyspepsia and severe epigastric pain. An oesophago-gastro-duodenoscopy demonstrated a sliding hiatus hernia with whitish ulcer-like lesion at the lower oesophagus. Biopsy from the lesion revealed a keratinous inclusion cyst. The patient was given pantoprazole and put on regular follow-up for monitoring any other development.

Carcinoma Ex Pleomorphic Adenoma Presented as a Gigantic Tumor: Treatment and Diagnostic Challenges

Parotid gland surgery can be challenging due to intricate relationship between the gland and facial nerve. Besides complete removal of the lesion, the main focus of surgery is centered on the facial nerve. Surgery can be technically demanding especially when the tumor is large or involves the deep lobe. We report a patient with a 30-year history of gigantic parotid mass, which initial fine-needle aspiration cytology reported as pleomorphic adenoma. The tumor, weighing 1.3 kg, was successfully resected with facial nerve preservation. Histopathological examination of the excised mass confirmed as carcinoma ex pleomorphic adenoma (CaExPA) of adenocarcinoma, not otherwise specified type. We describe the specific surgical and reconstruction techniques for successful removal of large parotid tumors with facial nerve preservation. To our knowledge, this is the heaviest CaExPA of the parotid gland in South-East Asian region.

Bilateral orbital paraganglioma: A report of a unique case and updates on its clinicopathological features

S S161 Compared to the control group, the CDK6 protein level was decreased in OCI-LY1/miR-320d group (p<0.05). OCI-LY1/ miR-320d group and OCI-LY1/CDK6 shRNA group cells’ proliferation ability were markedly decreased compared to the control group (p<0.05). Relative luciferase activity value of experimental group is lower than that of the control group (p<0.05). Conclusions: Up-regulation of miR-320d expression can inhibit the ability of malignant proliferation of DLBCL cell. The mechanism is concerned with that miR-320d could inhibit the expression of target gene CDK6 at the post-transcriptional level. 131. IMPROVED IMMUNOHISTOCHEMICAL METHOD FOR DETECTING ANTI-BCL-2 AND C-MYC ANTIBODIES IN MOUSE XENOGRAFT MODELS Xiaoling Xia, Jean Boyer, Liping Zhang, Burton Holmes, Rajalakshmy Ramalingam, Penny Towne Ventana Medical Systems, Roche, USA Background: Antigen detection is known to be affected by preanalytical conditions such as fixative types, fixation time and delay to fixation. We used human breast carcinoma cell lines (BT-474 and ZR-75-1) generated xenograft tumors as model systems to analyze the impact of different pre-analytical conditions on BCL-2 and c-MYC staining. Antigen detection on mouse tissue is complicated by high level background staining due to the binding of secondary anti-mouse antibody to endogenous mouse tissue Igs and other components. We developed methods to use modified OptiView DAB detection system and unique linker methodology to almost completely eliminate non-specific staining and achieve satisfactory staining results. Methods: Human breast carcinoma cell lines (BT-474 and ZR75-1) xenograft tumors were fixed across a range of times in 6 different commonly used fixatives as well as delay to fixation with a range from immediate fixation to a 24 hour delay to fixation in 10% NBF. Two new IHC staining methods were developed to stain either anti-BCL-2 (124), a mouse monoclonal antibody or anti-cMYC (Y69), a rabbit monoclonal antibody, to compare with standard OptiView DAB detection system on a Ventana automatic staining instrument. An Abcam monoclonal rabbit anti-mouse IgG was employed as linker followed by a modified OptiView DAB system to detect BCl-2 expression. We also used a modified OptiView DAB detection system to measure c-MYC expression. Results: Antigen detection with indirect immunohistochemical methods is hampered by high background staining if the primary antibody is from the same species as the examined tissue. This high background was eliminated by using an Abcam monoclonal rabbit anti-mouse IgG as a linker followed by a modified OptiView DAB detection system. New methods ensured us to achieve a more precise understanding of protein expression level. The xenografts tissues fixed with zinc formalin and Z-5 showed equivalent staining to 10% NBF after fixation for at least 6 hours. However, AFA, 95% EtOH, Prefer fixative did not perform equivalently over the range of fixation times when compared to 10% NBF, regardless of fixation time. This study also demonstrated degradation of BCL-2 and c-MYC antigenicity in response to delay in fixation if tissue was left unfixed at room temperature for more than two hours. Conclusion:Our study recommended that the best fixatives were 10% NBF, Zinc fixative and Z-5 between 6 hours and 72 hours for both anti-BCL-2 and anti-c-MYC antibodies. In addition, the tissues should be fixed within 2 hours after tissue collection. New IHC methods yielded minimum reduction of BCL-2 and c-MYC specific signaling. Using this method, the tissue sections were remarkably free of the background staining that is typically seen in mouse tissues with mouse antibodies. Hence, this procedure provides an improved, high sensitive method for detecting protein expression level loss due to inappropriate pre-analytical sample treatment. 132. RARE HISTOLOGICAL PATTERNS OF ANGIOFIBROMA OF SOFT TISSUE Yuichi Yamada, Hidetaka Yamamoto, Kenichi Kohashi, Yoshinao Oda Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan Background:Angiofibroma of soft tissue (AFST) is a rare benign soft tissue neoplasm, which is characterized by fibroblastic cytomorphology, prominent vascular pattern and novel fusion genes NCOA2-AHRR/AHRR-NCOA2 or GTF2I-NCOA2. AFSTs present a wide spectrum of morphology, making a challenge to diagnosis, thus we came to the cogitation to report the special histological features confirmed by genetic analysis. Aims: The study aims to reveal the histological variety of AFST confirmed by genetic data. Methods: We reviewed all the 274 cases diagnosed as solitary fibrous tumor/hemangiopericytoma (232 cases), undeterminated tumors of fibroblastic differentiation (36 cases) and recently diagnosed as AFST (6 cases), and picked up the 12 cases histologically compatible with AFST. All the 12 cases were genetically analyzed by RT-PCR method, and immunohistochemical stains were performed for available cases. Results: Highlighted histological findings were as follows; amianthoid fibers, ossification, lymphoid follicles, lymphoid cuff, hemosiderin deposition, aggregate of foamy histiocytes, cystic change, necrosis, and hemorrhage. Immunohistochemically, the tumor cells were positive for EMA (4/10 cases), desmin (4/10 cases), CD163 (6/6 cases), CD68 (3/6 cases), estrogen receptor (7/7 cases), progesterone receptor (1/6 case), D2-40 (4/7 cases) and STAT6 (1/6 case, weak nuclear stain), but negative for CD34, alpha-smooth muscle actin, musclespecific actin, S-100 protein, pan-cytokeratin, beta-catenin, MDM2 and CDK4. AHRR-NCOA2 fusion gene was detected in 8 cases. Conclusions: We revealed the unreported histological variation and immunohistochemical findings of AFST and confirmed them by genetic methods. It was suggested that AFST should be considered in the diagnosis of fibrous or fibrohistiocytic tumors with unspecified features.

Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening.

BACKGROUND Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry. MATERIALS AND METHODS A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. RESULTS Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively. CONCLUSIONS Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

Lipomatous Caecal Polyp Causing Ileocaecal Intussusception in an Elderly Lady: A Case Report and Literature Review

Intussusception is an uncommon cause of intestinal obstruction especially in adult. Adult intussusception accounts for only 5% of all cases of intussusceptions. We presented a case of a 63-yearold lady who presented with 1 week history of rightsided colicky abdominal pain which gradually became generalized, associated with vomiting out bile stained fluids. After series of investigations and worsening condition, emergency exploratory laparotomy was performed an(d unfortunately ileocolic intussusception was found. The patient underwent right hemicolectomy. Histopathological report confirmed lipomatous polyps arising from ileocaecal junction. Most recommendations of management are going towards resection of the involved segment without attempt of reduction as the causes of the intussusceptions in adults are usually due to pathological conditions within the involved segment.