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Fulltext Hurthle cells in fine needle aspiration cytology of the thyroid: a potential diagnostic dilemma?

Wong YP, Md Isa N, Md Zin RR, Noor Akmal S

Malays J Pathol, 2015 Apr;37(1):49-52.
PMID: 25890614 MyJurnal

Hurthle cells are not uncommonly encountered in thyroid fine needle aspiration cytology (FNAC) smears. They are easily recognized by their distinct cytomorphology in cytological preparations, i.e. large, polygonal cells displaying uniform, rounded nuclei, often prominent nucleoli and abundant granular cytoplasm. Hurthle cells can be seen in both non-neoplastic and neoplastic thyroid lesions which can pose diagnostic dilemma to cytopathologists, especially when the lesions are focally sampled. We describe a case of solitary thyroid nodule in a 46-year-old male, whose aspirates comprised predominantly of Hurthle cells exhibiting nuclear features suspicious of papillary carcinoma, which turned out to be Hurthle cell carcinoma on subsequent histological sections. The potential diagnostic pitfalls of Hurthle cell lesions and associated conditions in thyroid FNA are discussed. The presence of Hurthle cell change in a wide variety of thyroid lesions can be diagnostically challenging. However, accurate diagnosis can still be made with careful observation of the predominant cell population, nuclear features and whether there is abundant colloid or lymphocytes in the background.
Ewing Sarcoma presenting as a gluteal mass in adult woman: Diagnostic approach and its challenges

Tuan Sharif SE, Alzallal O, Wan Ismail WF, Md Zin RR

Malays J Pathol, 2020 Apr;42(1):121-125.
PMID: 32342941

INTRODUCTION: Sarcomas of the Ewing family of tumours are aggressive neoplasms occurring in bone and soft tissue of mostly children and young adults. It usually affects male more than female with peak incidence 10 to 15 years of age, and rarely encountered in adults especially in more than 40 years old. It is an aggressive, rare tumour with a tendency toward recurrence after resection and early metastasis.
CASE REPORT: We reported a rare case of Ewing Sarcoma in a 62-year-old woman who had an unusual clinical presentation. She had right painless buttock swelling only for a month. Magnetic resonance imaging (MRI) revealed soft tissue sarcoma originated from right gluteal muscle. The diagnosis of Ewing sarcoma (ES) was made in a limited diagnostic material in an initial tru-cut biopsy, followed by an excision supported by immunohistochemistry (IHC) and Fluorescent In-Situ Hybridization (FISH).
DISCUSSION: The purpose of this study is to document ES in an adult woman and its diagnostic challenges in histopathologic perspective.
Extranodal NK/T-cell lymphoma mimicking Crohn's colitis

Wan Ahmad Kammal WS, Mohd Rose I, Md Zin RR, Raja Ali RA, Masir N

Malays J Pathol, 2019 Aug;41(2):195-199.
PMID: 31427556

INTRODUCTION: Extranodal NK/T cell lymphoma is a rare tumour, typically involving the upper aerodigestive tract. Even rarer is primary extranasal disease involving the skin, testis, soft tissue and gastrointestinal tract.
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.
Ezrin is Significantly Overexpressed in Luminal A, Luminal B, and HER2 Subtype Breast Cancer

Jais MH, Md Zin RR, Muhd Hanapi NA, Md Ali SA

Appl Immunohistochem Mol Morphol, 2017 01;25(1):44-48.
PMID: 26469327

Ezrin, a membrane-linking protein, has been shown to play an important role in the carcinogenesis of infiltrating breast ductal carcinoma and its strong expression has been used to predict poor prognosis in patients with breast carcinoma. In this study, we compared ezrin protein distribution pattern in benign breast disease and breast cancer molecular subtypes and evaluated their association with clinicopathologic variables. A total of 376 breast cases (142 benign and 234 malignant cases) were studied. Immunohistochemical analysis for ezrin was performed and its expression was observed in terms of its distribution, intensity, and proportion of cells reactive for ezrin. Ezrin was expressed in all benign cases and 91.7% of malignant cases. Apical staining was positively associated with benign breast disease, whereas membranous and cytoplasmic staining were more frequently observed in malignant cases, specifically of hormone receptor-positive subtypes (luminal A and luminal B). Ezrin was significantly overexpressed in luminal A, luminal B, and HER2 subtypes. Reduced ezrin expression was significantly associated with triple-negative breast cancer molecular subtype. No significant association was demonstrated between ezrin expression and Her2 gene amplification, tumor grading, or staging.
Fulltext Multicentric Castleman Disease of the Supraglottis: A Surgeons' Dilemma

Jumaat AF, Mohamad Yunus MR, Yong DJ, Md Zin RR, Mat Baki M

Iran J Otorhinolaryngol, 2023 Mar;35(127):101-108.
PMID: 37223400 DOI: 10.22038/IJORL.2023.57806.2995

INTRODUCTION: An abnormal mass in the head and neck involving the supraglottic and cervical region offers a wide range of differential diagnoses. The pathology is either benign or malignant in nature. Castleman disease (CD) is an uncommon lymphoproliferative disorder characterised by hypervascular lymphoid hyperplasia and is classified into unicentric or multicentric disease. Histopathologically it is divided into hyaline vascular (HV), plasma cell (PC), and mixed cellularity variants. The multicentric disease is linked with PC and has the propensity to progress to lymphoma or Kaposi Sarcoma.
CASE REPORT: We report a case of a 45-year-old gentleman who presented with a painless anterior neck swelling and left supraglottic mass for six months. Computed tomography (CT) contrast imaging demonstrated a homogenous enhancing lesion at the left supraglottic and the midline of the anterior neck with erosive changes of the thyroid cartilage. A surgical resection of the anterior neck mass was performed. The diagnosis of Castleman disease plasma cell variant was made by histopathologic evaluation. The patient remained well post-resection.
CONCLUSION: Supraglottic multicentric Castleman disease is the least expected diagnosis in this case. Unicentric disease is treated with surgery. However, limited studies are available in determining the effectiveness of surgery in multicentric diseases. The plasma cell variant requires a multidisciplinary and multimodal approach due to an inclination towards malignancy. Research is needed to determine the role of surgery in multicentric disease and to develop optimum guidelines for managing cases. To date, there is unsubstantial literature describing supraglottic multicentric disease.
The potential roles of lncRNA TINCR in triple negative breast cancer

Azman AA, Siok-Fong C, Rajab NF, Md Zin RR, Ahmad Daud NN, Mohamad Hanif EA

Mol Biol Rep, 2023 Sep;50(9):7909-7917.
PMID: 37442895 DOI: 10.1007/s11033-023-08661-5

Triple negative breast cancer (TNBC) is the most aggressive intrinsic breast cancer subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and low levels of human epidermal growth factor receptor 2 (HER2). The complex nature of TNBC has resulted in little therapeutic progress for the past several decades. The standard of care remains the FEC cocktail (5-fluorouracil (5-FU), epirubicin and cyclophosphamide). However, early relapse and metastasis in TNBC patients persists in causing dismal clinical outcomes. Due to complex heterogeneity features of TNBC, identifying the biomarker associated to the chemoresistance remains a challenge. The emergence of the long non-coding RNA (lncRNA) as a potential signature may have proven to be a new deterrent to diagnostic and treatment options. Previous studies unveiled the associations of lncRNA in the development of TNBCs whereby the aggressiveness and response to therapies may be associated by the abrogation of the molecular mechanism lncRNA. Terminal differentiation induced ncRNA (TINCR) is a lncRNA which have been linked with many cancers including TNBC. The expression and behavior of TINCR may exert unfavorable outcome in TNBCs. Nevertheless, the underlying molecular mechanism of TINCR in driving chemoresistance in TNBC is not well understood. This review will highlight the potential molecular mechanisms of TINCR in TNBC chemoresistance and how it can serve as a future potential prognostic and therapeutic target for a better treatment intervention.
The Effect of Surgical Intervention of Endometriosis to CA-125 and Pain

Abdul Karim AK, Abd Aziz NH, Md Zin RR, Mohd Mokhtar N, Shafiee MN

Malays J Med Sci, 2020 Dec;27(6):7-14.
PMID: 33447130 DOI: 10.21315/mjms2020.27.6.2

Endometriosis is an inflammatory condition characterised by the presence of endometrial growth beyond the uterine cavity. It is a debilitating disease requiring multiple modalities of treatment. In considering surgery as the option of treatment, the benefits should outweigh the risk. Besides direct surgical risk, intervention may lead to a reduction of ovarian reserve, in addition to premature menopause and low fecundity. To date, there is an inconclusive evidence to support any specific parameters in monitoring disease progression following surgical intervention. Serum cancer antigen (CA)-125 is expressed by coelomic epithelium and has been extensively studied as a biomarker for endometriosis. Elevated expression of CA-125 has been shown in endometrial tissues and the marker increased indirectly from peritoneal irritation that accompanies an extensive form of endometriosis. Additionally, the visual analogue scale (VAS) scores have been used as an objective measurement for measuring pain, especially in a complex disease such as endometriosis. This review aims to consolidate a series of clinical trials that utilised CA-125 level and VAS score as tools for monitoring patients undergoing surgery for endometriosis.
Reviewing the role of progesterone therapy in endometriosis

Abdul Karim AK, Shafiee MN, Abd Aziz NH, Omar MH, Abdul Ghani NA, Lim PS, et al.

Gynecol Endocrinol, 2019 Jan;35(1):10-16.
PMID: 30044157 DOI: 10.1080/09513590.2018.1490404

Endometriosis is a benign, chronic inflammatory condition characterized by the presence and growth of endometrial implants outside the uterine cavity. The cause of endometriosis is multifactorial. It is due to the diversity of hypothesis and plausibility of hormonal alterations which could play a major role. Evidence has shown that progesterone resistance is a key factor for endometriosis sufferers. Medical therapy can avoid surgical intervention, which may lead to a reduced in ovarian reserve, and its effects of earlier menopause and reduced fecundity. Progesterone receptor isoform has provided new insight as the potential treatment. Progestin, anti-progestin and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating. Numerous types of these medications have been used on and off labeled to treat endometriosis with varying success. This review aims to consolidate series of clinical trials using progestins in endometriosis.
Fulltext PD-L1 Expression in Endometrial Cancer and Its Association with Clinicopathological Features: A Systematic Review and Meta-Analysis

Mamat Yusof MN, Chew KT, Kampan N, Abd Aziz NH, Md Zin RR, Tan GC, et al.

Cancers (Basel), 2022 Aug 13;14(16).
PMID: 36010904 DOI: 10.3390/cancers14163911

Endometrial cancer (EC) is one of the most common malignancies of the female genital tract and its current treatment mainly relies on surgical removal of the tumour bulk, followed by adjuvant radiotherapy with or without chemotherapy/hormonal therapy. However, the outcomes of these approaches are often unsatisfactory and are associated with severe toxicity and a higher recurrence rate of the disease. Thus, more clinical research exploring novel medical intervention is needed. Involvement of the immune pathway in cancer has become important and the finding of a high positive expression of programmed cell death-ligand 1 (PD-L1) in EC may offer a better targeted therapeutic approach. Numerous studies on the PD-L1 role in EC have been conducted, but the results remained inconclusive. Hence, this systematic review was conducted to provide an update and robust analysis in order to determine the pooled prevalence of PD-L1 expression in EC and evaluate its association with clinicopathological features in different focuses of tumour cells (TC) and immune cells (IC). A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases. Twelve articles between 2016 and 2021 with 3023 EC cases met the inclusion criteria. The effect of PD-L1 expression on the outcome parameters was estimated by the odds ratios (ORs) with 95% confidence intervals (CIs) for each study. The pooled prevalence of PD-L1 was 34.26% and 51.39% in the tumour cell and immune cell, respectively, among women with EC. The PD-L1 expression was significantly associated with Stage III/IV disease (in both TC and IC) and correlated to the presence of lympho-vascular invasion in IC. However, the PD-L1 expression in TC was not associated with the age groups, histology types, myometrial invasion, and lympho-vascular invasion. In IC, PD-L1 expression was not associated with age group, histology type, and myometrial invasion. The meta-analysis survival outcomes of PD-L1 high expression had a significant association with worse OS in IC but not in TC.
Fulltext Early Surgery Is Feasible for a Very Large Congenital Infantile Fibrosarcoma Associated With Life Threatening Coagulopathy: A Case Report and Literature Review

Alias H, Abdul Rashid AH, Lau SCD, Loh CK, Sapuan J, Ibrahim S, et al.

Front Pediatr, 2019;7:529.
PMID: 31956645 DOI: 10.3389/fped.2019.00529

Background: Congenital infantile fibrosarcoma (CIF) is a rare malignant soft tissue tumor that predominantly occurs in children under 1 year of age. CIF is frequently misdiagnosed with other conditions like hemangioma of infancy, infantile fibromatosis, or kaposiform hemangioendothelioma. Disseminated intravascular coagulopathy (DIVC) is rarely reported to be associated with CIF. Case presentation: We describe an infant who presented with a large mass over the right arm. She was initially treated conservatively as hemangioma but was later confirmed by tissue histopathological examination to have CIF as the mass rapidly increased in size. She developed massive intra-tumoral bleed with DIVC whilst receiving neoadjuvant chemotherapy requiring multiple blood products transfusion. An urgent near-total resection of the tumor was performed in view of life threatening bleeding despite multiple blood transfusions. Post-operatively, she received further adjuvant chemotherapy. Subsequently, she remained in complete remission 32 months off-treatment and has full function of the affected limb. Conclusions: CIF is an important condition to be considered in infant who has large mass over the extremity. DIVC could be associated with large CIF and when it occurs can be life-threatening. Whenever feasible early surgery should be performed in very young patients with large CIF to prevent mortality from bleeding.
Fulltext Prognostic Value of TNFR2 and STAT3 among High-Grade Serous Ovarian Cancer Survivors According to Platinum Sensitivity

Silva Raju J, Abd Aziz NH, Atallah GA, Teik CK, Shafiee MN, Mohd Saleh MF, et al.

Diagnostics (Basel), 2021 Mar 16;11(3).
PMID: 33809542 DOI: 10.3390/diagnostics11030526

This study's goal was to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in high-grade serous ovarian cancer (HGSC) tissues in relation to the platinum-based chemotherapy response and the prognosis outcome. A total of 25 HGSC patients underwent primary surgical debulking followed by first-line adjuvant platinum-based chemotherapy. Tissue microarray (TMA) slides were constructed utilising archived formalin fixed paraffin embedded (FFPE). The protein expression of TNFR2 and STAT3 were analysed using immunohistochemistry (IHC) staining and subsequently were correlated to the clinicopathological characteristics, platinum sensitivity as well as the duration of progression-free survival. About 14 out of 25 patients (56.0%) were platinum-sensitive. The progression free survival was significantly longer in the platinum-sensitive (PS) group when compared to those with the platinum-resistant group (PR), p = 0.0001. Among patients with TNFR2 strong expression on ovarian tissue, there was a significantly longer progression-free survival interval of 540 days in the PS group compared to PR, p = 0.0001. Patients with STAT3 expression also showed significantly better progression-free survival of 660 days in the PS group when compared to the PR group, p = 0.0001. In conclusion, patients with strong TNFR2 and STAT3 expression in the ovarian tissue had significantly longer progression-free survival interval in the PS group. Nevertheless, further research with a larger number of tissues may be required to demonstrate further significant differences.
Fulltext The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

El Bairi K, Haynes HR, Blackley E, Fineberg S, Shear J, Turner S, et al.

NPJ Breast Cancer, 2021 Dec 01;7(1):150.
PMID: 34853355 DOI: 10.1038/s41523-021-00346-1

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

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