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All Journal Journal of the Medical Sciences (Berkala Ilmu Kedokteran) The Indonesian Biomedical Journal Paediatrica Indonesiana

Dwianingsih, Ery Kus

Departement Of Anatomical Pathology, Faculty Of Medicine, Public Health And Nursing, Universitas GadjahMada, Yogyakarta, Indonesia

Author-ID : 951019

Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Public Health

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Articles

Sinonasal or nasopharyngeal undifferentiated Carcinoma?: diagnostic pitfall and the role of Epstein-Barrvirus (EBV) and human papillomavirus(HPV) examination Wahyu Tri Widayati; Ery Kus Dwianingsih; Bustanul Ardianto; Didik Setyo Heriyanto; Sagung Rai Indrasari; Camelia Herdini; . Irianiwati
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 52, No 2 (2020)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Undifferentiated carcinoma of the head and neck is frequently observed in nasopharynx, however it may also occur in oropharynx, salivary gland and sinonasal. Overlapping lesions in those regionscreate difficulty in determining the origin of the tumor. Thus, it causes diagnostic pitfall not only for pathologists, but also for clinicians. A 40 yearold man, presented with nasal obstruction, epistaxis, diplopia, and headache for a yearand showed nasal cavitysinistra and nasopharynx masses on CT-scan. Lymph node enlargement was not detected. First biopsywas performed and histopathologically diagnosed as nasopharyngeal undifferentiated carcinoma(NPC), extended into nasal cavity. Chemo-radiation protocol for NPC was conducted, and showing uncomplete response. Second biopsy was done, and reviewed with the first biopsy result. Thetumourwas arranged insolid, syncytial and trabecular pattern, with vesicular nuclei, prominent nucleoli, and lack of lymphoplasmacytic infiltrat. Immunohistochemistry (IHC) analysis of p16, EBNA1 and LMP1 were negative. PCR analysis of HPV-18 was positive, while EBV detection showed negative result. General association of EBV with NPC suggests that the presence of latent EBV infection can serve as a positive marker for NPC. Therefore, in this case, the EBV negativity and strong HPV association led to diagnosis of SNUC. The distinction of sinonasal undifferentiated carcinoma (SNUC) or from NPC was important for appropriate management and therapy.

The accuracy of fine needle aspiration biopsy to diagnose breast neoplasm Hifdza Faza Felisha; Hanggoro Tri Rinonce; Sumadi Lukman Anwar; Ery Kus Dwianingsih
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 51, No 3 (2019)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Breast lump is a very common complaint among women, especially during the reproductive year. Fine needle aspiration biopsy (FNAB) is a less invasive procedure. It is usually performed as an initial diagnosis prior to the operative procedure. The accuracy of the FNAB in Indonesia needs to be elaborated. The study aimed to evaluate the sensitivity and specificity of FNAB in diagnosing breast neoplasm. This is a retrospective study with cross sectional design, involving 145 patients with breast lump who underwent FNAB and histopathology examination in Dr. Sardjito General Hospital, Yogyakarta, from 2012 to 2014. Data analysis showed that female to male ratio was 23. 2:1 commonly occurred at 41-50 years old. Forty-one cases (28.28%) diagnosed as a benign lesion with fibrocystic changes as the most frequentcase (11.19%). The malignant case was 104 cases (71.72%) with ductal carcinoma as the highest case (51.49%). FNAB achieved a sensitivity of 85.58%, a specificity of 100% and a total accuracy of 89.66% in determining the benign or malignant breast lump. The accuracy, sensitivity and specificity of FNAB in diagnosing ductal carcinoma were 83.58%, 85.51% and 81.54%, respectively. The accuracy, sensitivity and specificity of FNAB to diagnose fibrocystic changes lesion were 85.82%, 26.67% and 93.28%, respectively. FNAB can be used as an alternative diagnostic tool to diagnose breast neoplasm. It provides rapid, cheaper, effective, valuable, and less invasive procedure in diagnosis of breast lump.

Accuracy of fine needle aspiration biopsy to diagnose lymphadenopathy in Dr.Sardjito General Hospital, Yogyakarta, Indonesia Ery Kus Dwianingsih; Claudia Priska Adelin; Andre Stefanus Panggabean; Linda Pratiwi; Naomi Yoshuantari; Mardiah Suci Hardianti; I Indrawati
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 52, No 1 (2020)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Lymphadenopathy is a non-specific enlargement of lymph nodes which may be caused by infection, cancer, or autoimmune disease. To date, only a few studies reported the diagnostic value of fine-needle aspiration biopsy (FNAB) in lymphadenopathy. This study was performed to evaluate diagnostic reliability of FNAB for benign and malignant lymphadenopathy. This was a retrospective cross-sectional study. The obtained data were statistically analyzed for its sensitivity, specificity, and accuracy. Out of 126 collected FNAB cases with histopathological confirmed results in Dr. Sardjito General Hospital, Yogyakarta, 85 (67.4%) were malignant lymphadenopathy, consisting of 42 metastatic tumor cases, 38 non-Hodgkin lymphoma (NHL) cases, and 4 Hodgkin lymphoma (HL) cases.The overall diagnostic sensitivity, specificity, and accuracy of FNAB in lymphadenopathy was 85.88, 70.73, and 80.95%, respectively. In diagnosing metastatic tumors, FNAB had sensitivity of 83.33%; specificity of 89.28%; and accuracy of 87.3%. The sensitivity, specificity, and accuracy of FNAB in diagnosing NHL was 60.52, 94.31, and 84.12%, respectively. FNAB had a sensitivity of 25%, specificity of 95,90%, and accuracy of 93.65% to diagnose HL. Meanwhile, the accuracy of FNAB in diagnosing malignancies in generalized lymphadenopathy, head-neck lymphadenopathy, and inguinal lymphadenopathy was 90.90; 81.39 and 44.44%, respectively. In conclusion,FNAB has moderate diagnostic value in diagnosing overall malignant lymphadenopathy, including metastatic tumors. FNAB also has some limitations in diagnosing NHL and HL, with sensitivity less than 70% for both diseases. However, it has high accuracy to diagnose generalized lymphadenopathy.

Correlation between vascular endothelial growth factor (VEGF) expression with histopathological findings in osteosarcoma Fikar Arsyad Hakim; Yuni Artha Prabowo Putro; Yudha Mathan Sakti; Rahadyan Magetsari; Irianiwati Widodo; Ery Kus Dwianingsih
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 53, No 2 (2021)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Vascular endothelial growth factor (VEGF) expression is associated with malignancy progression, metastasis, and poor prognosis in many malignancies, including osteosarcoma. However, studies concerning correlations between VEGF expression and histopathological prognostic factors ofosteosarcoma are limited. This study aimed to evaluate the correlations between VEGF expression and histopathological findings in osteosarcoma’spatients.This was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) samples of 32 osteosarcoma’s patients from Dr. Sardjito General Hospital, Yogyakarta. Histopathological findings of specimens were re-evaluated by two independent observers, recorded for the subtypes, invasiveness, grading, mitotic counts, and tumor infiltrating lymphocytes (TIL). Expression of VEGF was determined based on immunostaining and evaluated using immunoreactivity score (IRS).Chi-square and Spearman correlation test were used to analyze the association between variables. Range of VEGF expression score was 0 to 11, with mean 5.09. Significant negative correlation between the VEGF expression and TIL was observed (p=0.046). However, there was no significant correlations between the VEGF expression and osteosarcomas subtypes, invasion, grading or mitotic counts (p> 0.05). In conclusion, the VEGF expression is associated with TIL. Further study is needed to evaluate the roles of VEGF and lymphocytes in osteosarcoma development dan progression in order to better understand of the role of VEGF in immunotherapy of osteosarcoma.

Malignant bilateral ovarian steroid cell tumor without androgenic manifestation: an unusual finding Emilia Theresia; Bob Irsan; Ery Kus Dwianingsih; Moh Nailul Fahmi; Heru Pradjatmo; . Irianiwati
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 54, No 1 (2022)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.19106/JMedSci005401202208

Steroid cell tumor is a rarest ovarian neoplasm, classified as a pure stromal tumor and mostly is unilateral. Even though this tumor can exhibit malignant behavior but the morphology of cells showed benign characteristics which can become a diagnosis pitfall especially in the frozen section. Moreover patient without any hormonal imbalance or virilizing signs could make the diagnosis process more difficult. Here we reported a case bilateral steroid cell tumor of the ovary in a 42 y.o. unmarried woman without any virilization or hirsutism symptoms. Abdominal ultrasonography and computed tomography (CT) scan revealed a right ovarian solid tumor accompanied by ascites and right pleural effusion. There was significantly increased of Ca 125 level (1138 U/mL) and normal level of testosterone (0.10 ng/mL). Frozen section was done from the right ovarium mass and ascites fluid, the result was benign. From the total abdominal hysterectomy and bilateral salpingo-oophorectomy tissues, histological picture showed diffuse and nests tumor separated by thin fibrous connective tissue with small round centered nuclei, mild atypia, and abundant pale cytoplasm. Large area of necrosis was found especially in the right ovarian tumor, tumor implant to the right fallopian tube and in the uterine serous layer. Periodic acid-Schiff (PAS) stain was negative in more than half tumor cells population. Immunostaining for Melan-A and Calretinin were focally positive, with Ki-67 labeling index ± 5%, and negative for cytokeratin 7 (CK7), cytokeratin 20 (CK20) and smooth muscle actin (SMA). Based on the tumor size, necrosis area, tumor implantation, and immunohistochemistry profiles, we conclude that were malignant steroid cell tumor. Currently, the patient is undergoing postoperative recovery and planned for platinum-based chemotherapy. A careful correlation between clinical and radiological findings, as well as histopathological results, is always essential, as is amply demonstrated by this particular case.

WIF1 Qualitative-Methylation from Peripheral Blood Could Not Be Used as Biomarker for The Risk of Nasopharyngeal Carcinoma or Smoking Behavior in Yogyakarta Panel Aditya Kurniawan; Erika Diana Risanti; Saihas Suhda; Hanggoro Tri Rinonce; Ery Kus Dwianingsih; Jajah Fachiroh
The Indonesian Biomedical Journal Vol 11, No 3 (2019)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v11i3.810

BACKGROUND: Tobacco smoking plays an important role in nasopharyngeal carcinoma (NPC) risk. The Wingless-related integration site (WNT) Inhibitory Factor 1 (WIF1) as one of the tumor suppressor gene (TSG), functions to control cell proliferation through suppression of WNT signaling pathway. WIF1 methylation is one of epigenetic mechanisms which causes overactivated of WNT pathway in NPC development. WIF1 methylation from buffy coat related to smoking status and NPC risk is not known yet.METHODS: This was a nested case-control study involving 39 newly diagnosed NPC patients and 40 healthy controls. All subjects were enrolled at Dr. Sardjito Hospital, Yogyakarta. Subjects were male, with known smoking status, duration, and quantity of cigarette consumed. Parallel DNA isolated from buffy coat was used for WIF1 DNA methylation analysis, by using methylation-specific PCR (MSP) method. Chi-square analysis was used to determine distribution of differences among groups. Two tailed p-value≤0.05 was considered as statistically significant.RESULTS: No significant difference between WIF1 methylation of cases and controls (p=0.30), nor smoking habit among smokers (p=0.51) and non-smokers (p=0.43).CONCLUSION: WIF1 methylation from buffy coat could not be used as an NPC marker nor as a smoking behavior marker.KEYWORDS: buffy coat, cigarette smoking, methylation, nasopharyngeal carcinoma, WIF1

Association of Peripheral Blood RASSF1A and CDKN2A Methylation Status with Smoking Behaviour in Nasopharyngeal Carcinoma Erika Diana Risanti; Aditya Kurniawan; Laila Wahyuningsih; Ery Kus Dwianingsih; Hanggoro Tri Rinonce; Jajah Fachiroh
The Indonesian Biomedical Journal Vol 10, No 2 (2018)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v10i2.381

BACKGROUND: Hypermethylation of RASSF1A and CDKN2A is one of epigenetic factor underlies nasopharyngeal carcinoma (NPC) development. Smoking behavior as an NPC’s risk factor causes aberrant DNA methylation. RASSF1A and CDKN2A promoter hypermethylation from peripheral blood cells correlates with smoking behavior. The use of body fluids including peripheral blood as a specimen for DNA methylation analyzes are widely developed, as less invasive method compared to the use of tissue biopsy. This study aims to observe the association between RASSF1A and CDKN2A methylation in peripheral blood and smoking behavioramong NPC patients.METHODS: Newly diagnosed NPC subjects were recruited from ear-nose-throat (ENT) outpatient clinic of Dr. Sardjito Hospital, Yogyakarta. DNA from buffycoat of 19 smokers and 20 non-smokers NPC’s patients were isolated. Bisulphite modification was applied to 500 ng of the isolated DNA. The methylation status was detected by MSP (methylation-specific polymerase chain reaction (PCR)). The association between smoking status and promoter hypermethylation was analysis using Chi-Square test.RESULTS: MSP analysis of RASSF1A showed that 68.42% smoker and 75% non-smoker NPC’s patients were methylated. MSP analysis of CDKN2A showed that 21.05% smoker and 25% non-smoker NPC’s patients were methylated. There was no association between smoking behavior with RASSF1A and CDKN2A methylation (p>0.05).CONCLUSION: Statistical analysis showed that smoking behavior is not associated with methylation of RASSF1A and CDKN2A among NPC’s patients.KEYWORDS: DNA methylation, CDKN2A, RASSF1A, Nasopharyngeal carcinoma, Smoking

Clinicopathological Characteristic and Prognostic Significance of Indonesian Triple Negative Breast Cancer Irianiwati Widodo; Ery Kus Dwianingsih; Teguh Aryandono; Soeripto Soeripto
The Indonesian Biomedical Journal Vol 11, No 3 (2019)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v11i3.831

BACKGROUND: Triple negative breast cancer (TNBC) is a breast cancer subtype with negative expressions of estrogen receptors (ER), progesterone receptors (PR) and Her-2 protein receptors. This subtype exhibits aggressive behavior and poor prognosis since it is unresponsive to hormonal and Her-2 targeted therapy. The identification of clinicopathological characteristics and their prognostic values will provide guidance in developing effective treatment. This study was performed to analyze the clinicopathological characteristics and prognostic significance in Indonesian TNBC.METHODS: Forty paraffin-embedded tissues of TNBC, stage I to IIIA, dating from 2008 to 2010 in Dr. Sardjito Hospital, were enrolled. Survival follow-up was done from January 2008 to June 2013. The samples were immunostained with ER, PR and Her-2 monoclonal antibodies to determine the TNBC subtypes. The clinicopathological characteristics were statistically analyzed. The survival was analyzed using the Kaplan Meier method. The Cox proportional hazards model was used for multivariate analysis.RESULTS: Mean age of TNBC patients was 51.42±11.72 years old, whereas the mean of tumor size was 5.4±2.92 cm. Lymph node metastasis was found in 70% of cases. Number of locally advanced samples (IIIA) was 37.5%, while moderate to high grade samples were 95%. Number of still alive patients at the end of the study was 55%. Number of patients that still alive up to the end of the study was 45.50%. Lymph node was an independent prognostic factor for survival of TNBC patients as positive status of lymph node increases the death risk to 6 times higher (p=0.02, RR=6.6). However, after being adjusted with age and stage, lymph node status was suggested as a modifier effect for the survival of TNBCs patients (RR=0.19).CONCLUSION: Indonesian TNBC patients were mostly found already with large tumor size, lymph node metastasis, high pathological grade and relatively young age. Lymph node status serves as a modifier effect for the survival of Indonesian TNBC.KEYWORDS: NBC, clinicopathological characteristics, prognostic significance

Clinicopathologic and molecular profiles of Duchenne and Becker muscular dystrophy Ery Kus Dwianingsih; Meydita Fuzia Putri Insani; Linda Pratiwi; Irianiwati Widodo; Rusdy Ghazali Malueka
Paediatrica Indonesiana Vol 59 No 5 (2019): September 2019
Publisher : Indonesian Pediatric Society

Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked recessive diseases caused by mutations in the dystrophin (DMD) gene. To our knowledge, molecular analysis to differentiate between DMD and BMD has never been performed in Indonesia. Objective To elaborate the clinicopathologic and molecular profiles of DMD/BMD patients in Yogyakarta, Indonesia. Methods Eighteen muscle biopsy specimens of patients clinically suspected to have DMD/BMD were collected. Possible associations of clinical manifestations, histopathological grading, and immunohistochemistry (IHC) results were analyzed. Polymerase chain reaction (PCR) was performed to identify mutations in exon 52. Results. Positive Gowerâ€™s sign and high serum creatine kinase (CK) were observed in most patients. The IHC of dystrophin in two female patients suggested that they were manifesting carriers. Of the 16 male patients, 12 showed negative IHC staining, indicating DMD, while 4 patients demonstrated weak expression of dystrophin, indicating BMD. There was a significant association between high CK level and IHC results (P=0.005), indicating higher CK level in DMD patients. Histopathological grading of muscle biopsy was significantly associated with diagnosis of DMD/BMD using IHC (P=0.01), showing more severe tissue damage in DMD patients. None of the subjects had the single exon 52 deletion. Conclusion This is the first report of a clinicopathologic and molecular profile of DMD/BMD in an Indonesian population. Serum CK level and histopathological grading of muscle biopsy are useful in distinguishing DMD from BMD in settings where an IHC assay is not available.

Co-Authors . Irianiwati Aditya Kurniawan Aditya Kurniawan Andre Stefanus Panggabean Anwar, Sumadi Lukman Bob Irsan Bustanul Ardianto Camelia Herdini Claudia Priska Adelin Didik Setyo Heriyanto Emilia Theresia Erika Diana Risanti Fikar Arsyad Hakim Hanggoro Tri Rinonce Hanggoro Tri Rinonce Hanggoro Tri Rinonce Heru Pradjatmo Hifdza Faza Felisha I Indrawati Irianiwati Widodo Jajah Fachiroh, Jajah Laila Wahyuningsih Linda Pratiwi Linda Pratiwi Malueka, Rusdy Ghazali Mardiah Suci Hardianti Meydita Fuzia Putri Insani Moh Nailul Fahmi Naomi Yoshuantari Rahadyan Magetsari Sagung Rai Indrasari Saihas Suhda Soeripto Soeripto Teguh Aryandono Wahyu Tri Widayati Yudha Mathan Sakti Yuni Artha Prabowo Putro

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