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Ekspresi Topoisomerase II Î± pada Diffuse Large B Cell Lympho-ma dan Hubungannya dengan Respon Terapi Indri Windarti; Endang SR Hardjolukito; Maria Francisca Ham; Tubagus Djumhana Atmakusuma; Wulyo Rajabto
Majalah Patologi Indonesia Vol 22 No 3 (2013): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Indonesia (IAPI)

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ABSTRAK Latar belakang Kemoterapi pilihan untuk Diffuse Large B Cell Lymphoma (DLBCL) adalah regimen yang mengandung doksorubisin. Doksorubisin merupakan obat kemoterapi golongan antrasiklin yang bekerja sebagai anti Topoisomerase II (Top2). Penelitian sebelumnya terhadap galur sel tumor menunjukkan bahwa ekspresi Topoisomerase II Î± (Top2A) yang tinggi berhubungan dengan sensitifitas terhadap antrasiklin yang tinggi pula. Tujuan penelitian ini adalah untuk mengetahui ekspresi protein Top2A pada DLBCL dan hubungannya dengan respon terapi. Metode Studi potong lintang dilakukan terhadap 38 kasus DLBCL dengan pulasan CD20 positif, yang telah mendapat kemoterapi minimal 4 siklus. Imunohistokimia dilakukan pulasan terhadap protein Top2A dengan menggunakan H-score. Hasil Ekspresi Top2A ditemukan pada 37 dari 38 kasus (97%) dengan kisaran H-score 101,5-215,0 dan median 124,1. H-score nilai Top2A dikatakan tinggi jika H-score lebih dari 124,1. Analisis statistik menunjukkan bahwa ekspresi Top2A pada DLBCL tidak berhubungan bermakna dengan respon terapi (p=0,670). Kesimpulan Ekspresi Top2A dan respon terapi tidak memiliki hubungan bermakna. Ekpresi Top2A pada DLBCL tidak dapat dijadikan prediktor respon terapi. Kata kunci: DLBCL, Doksorubisin, ekspresi Top2A, respon terapi. ABSTRACT Background Standard of chemotherapy for Diffuse Large B Cell Lymphoma (DLBCL) is a regimen containing doxorubicin. Doxorubicin is a component of anthracycline based chemotherapy that work as anti Topoisomerase II (Top2). Previous study on tumor cell lines showed that high expression of Topoisomerase II Î± (Top2A) was related to higher sensitivity to anthracycline as well. The aim of this study is to know the expression of Top2A and its relation to treatment response. Methods A cross-sectional study on 38 which DLBCL cases CD20 positive that have been treated with at least 4 cycles of chemotherapy. The immunohistochemical staining was performed on Top2A protein assesed using H-score. Results Expression of Top2A protein were found in 37 of 38 (97%) cases (H-score range: 101.5-215.0 and median 124.1). Value Top2A was defined as high if H-score more was higher than 124.1. Statistical analysis showed that Top2A expression in DLBCL was not significantly related to treatment response (p=0.670). Conclusion There was no significant relation between Top2A expression and treatment response. Top2A expression in DLBCL cannot be used as a predictor of treatment response. Key words: DLBCL, Doxorubicin, Top2A expression, treatment response.

Hubungan Subtipe Imunofenotipik Berdasarkan Ekspresi CD56 dan CD16 dengan Ekspresi CD30 dan Ki-67 pada Limfoma Sel NK/T Ekstranodal Tipe Nasal Stephanie Maris; Kusmardi Kusmardi; Endang SR Hardjolukito; Maria Francisca Ham; Agnes Stephanie Harahap
Majalah Patologi Indonesia Vol 26 No 2 (2017): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Indonesia (IAPI)

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Latar belakangLimfoma sel NK/T ekstranodal tipe nasal (NKTCL; extranodal NK/T-cell lymphoma, nasal type) dapat dikategorikan menjadi beberapa subtipe berdasarkan ekspresi CD56 dan CD16 sesuai dengan pola perkembangan fenotip sel natural killer (NK) normal. Ekspresi CD56 banyak ditemukan pada tahap diferensiasi sel NK yang lebih awal, sedangkan ekspresi CD16 terdapat pada sel NK dengan diferensiasi yang lebih mature. Selain fenotip normal, adanya infeksi virus Epstein-Barr (EBV) sebagai etiologi NKTCL berkaitan dengan fenotip teraktivasi yang ditandai dengan ekspresi CD30, kemudian mengaktifkan jalur sinyal nuclear factor kappa beta (Nf-KB) sehingga dapat menyebabkan pertumbuhan dan proliferasi sel tumor. Pada penelitian ini diteliti hubungan antara subtipe NKTCL berdasarkan ekspresi CD56 dan CD16 dengan ekspresi CD30 serta indeks proliferasi Ki-67.MetodaPenelitian ini menggunakan metoda potong lintang. Sampel terdiri atas 32 kasus NKTCL di Departemen Patologi Anatomik Fakultas Kedokteran Universitas Indonesia/Rumah Sakit Cipto Mangunkusumo (FKUI/RSCM) periode Januari 2010 sampai April 2016. Dilakukan pulasan imunohistokimia CD16, CD30 dan Ki-67, sedangkan pewarnaan CD56 diambil dari arsip. Selanjutnya dihitung persentasis positivitas pada setiap pulasan tersebut.HasilPositivitas CD56 ditemukan pada semua kasus (100%). Positivitas CD16 sebanyak 16 (50%) kasus, positivitas CD30 sebanyak 17 (53,13%) kasus, dan indeks proliferasi Ki-67 tinggi sebanyak 16 (50%) kasus. Tidak terdapat perbedaan bermakna antara subtipe NKTCL (CD56+CD16- dan CD56+CD16+) dengan ekspresi CD30 (p=0,723). Tidak terdapat perbedaan bermakna antara subtipe NKTCL (CD56+CD16- dan CD56+CD16+) dengan indeks proliferasi Ki-67 (p=0,480). Tidak terdapat perbedaan bermakna antara ekspresi CD30 dengan indeks proliferasi Ki-67 (p=0,723).KesimpulanSubtipe imunofenotipik NKTCL (CD56+CD16- dan CD56+CD16+) tidak berhubungan dengan fenotip teraktivasi (CD30) maupun proliferasi (Ki-67).

Hubungan Ekspresi p53 dan Ki-67 dengan Parameter Histopato-logik yang Memprediksi Metastasis pada Karsinoma Sel Skuamo-sa Penis Romi Beginta; Budiana Tanurahardja; Maria Francisca Ham
Majalah Patologi Indonesia Vol 26 No 3 (2017): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Indonesia (IAPI)

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Latar belakangPenelitian untuk mencari faktor risiko metastasis kelenjar getah bening dan prognosis pasien karsinoma sel skuamosa (KSS) penis belum sebanyak KSS pada organ lain. Penggunaan parameter patologik, ekpresi p53, dan Ki-67 yang dipakai pada penelitian ini dapat digunakan sebagai variabel penentu prognosis maupun terapi KSS penis, namun masih diperlukan data yang lebih banyak. Penelitian ini bertujuan untuk menjelaskan hubungan antara ekspresi p53 dan Ki-67 terhadap parameter histopatologik yang mempengaruhi risiko metastasis.MetodeDesain penelitian merupakan studi potong-lintang dengan melakukan pulasan imunohistokimia p53 (Novocastra DO-7) dan Ki-67 (Biocare CRM 325) pada total 25 sampel KSS penis yang dikumpulkan dari arsip Departemen Patologi Anatomik FKUI-RSCM periode 2006-2013.HasilEkspresi p53 positif ditemukan pada 48% KSS penis dan ekspresi Ki-67 tinggi ditemukan pada 52% kasus. Tidak temukan hubungan yang bermakna antara ekspresi p53 dan parameter-parameter histopatologik. Didapatkan hubungan bermakna antara ekspresi Ki-67 terhadap derajat diferensiasi tumor dan adanya invasi ke uretra.KesimpulanEkspresi p53 tidak dapat digunakan sebagai faktor prediktif risiko metastasis KSS penis. Ekspresi Ki-67 secara sebagian berhubungan dengan faktor risiko metastasis KSS penis.

Perbedaan Imunoekspresi Caspase-3 antara Diffuse Large B-Cell Lymphoma Subtipe Germinal Center B-Cell-Like dan Non-Germinal Center B-Cell-Like Rosita Alfi Syahrin; Maria Francisca Ham; Agnes Stephanie Harahap; Benyamin Makes; Endang SR Hardjolukito
Majalah Patologi Indonesia Vol 27 No 1 (2018): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Indonesia (IAPI)

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Latar belakangTipe terbanyak dari limfoma non-Hodgkin (LNH) sel B adalah diffuse large B-cell lymphoma (DLBCL) yang merupakan entitas heterogen. Hans membagi DLBCL menjadi subtipe germinal center B-cell-like (GCB) dan non-germinal center B-cell-like (non-GCB) dengan tehnik pemeriksaan imunohistokimia menggunakan CD10, BCL6 dan MUM1. GCB mempunyai prognosis baik dan non-GCB berprognosis buruk. Caspase-3 adalah protein yang berperan utama dalam mekanisme apoptosis dan dapat mengalami mutasi somatik pada LNH. Tujuan penelitian ini untuk mengetahui perbedaan imunoekspresi Caspase-3 pada DLBCL subtipe GCB dan non-GCB yang mungkin berkaitan dengan perbedaan prognosis kedua subtipe tersebut.MetodePemeriksaaan imunoekspresi Caspase-3 pada kasus pasien DLBCL yang terdiri atas subtipe GCB dan non-GCB dilakukan dengan tehnik imunohistokimia. Subjek penelitian berasal dari blok parafin di Departemen Patologi Anatomik FKUI/RSCM dan enam rumah sakit lainnya di Jakarta. Metode penelitian observasional deskriptif analitik dengan pendekatan cross sectional. Prosedur pulasan imunohistokimia dengan cara Trekavidin biotin dan penilaian dilakukan oleh dua orang peneliti tanpa diketahui jenis subtipe GCB atau non-GCB.HasilDitemukan 41 kasus DLBCL yaitu 18 kasus subtipe GCB dan 23 kasus subtipe non-GCB. Subtipe GCB memberikan hasil positif dengan pulasan Caspase-3 berjumlah 13 kasus (72%) dan negatif berjumlah 5 kasus (28%). Hasil yang didapatkan dari subtipe non-GCB yaitu positif berjumlah 5 kasus (22%) dan negatif berjumlah 18 kasus (78%). Terdapat perbedaan bermakna imunoekspresi Caspase-3 antara DLBCL subtipe GCB dengan subtipe non-GCB (p=0,002). Imunoekspresi Caspase-3 menunjukkan positivitas yang lebih tinggi pada DLBCL subtipe GCB dibandingkan dengan subtipe non-GCB.KesimpulanPenelitian ini menunjukkan bahwa imunoekspresi Caspase-3 pada kedua subtipe DLBCL berbeda secara bermakna, di mana lebih tinggi pada subtipe GCB dibandingkan pada subtipe non-GCB. Hal ini mungkin dapat menjelaskan latar belakang perbedaan prognosis di antara kedua subtipe tersebut.

Perbedaan Ekspresi BCL-2 pada Limfoma Sel B Jenis Sel Besar Difus sebagai Salah Satu Petanda Subtipe Germinal Center B-Cell Like dan Non-Germinal Center B-Cell Like Dayanto Indro Utomo; Maria Francisca Ham; Kusmardi Kusmardi; Endang SR Hardjolukito
Majalah Patologi Indonesia Vol 27 No 1 (2018): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Indonesia (IAPI)

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Latar belakangLimfoma non-Hodgkin sel B jenis sel besar difus (DLBCL; Diffuse Large B-Cell Lymphoma) adalah jenis limfoma non-Hodgkin yang paling banyak ditemukan dan merupakan suatu entitas yang sangat heterogen secara klinik maupun morfologik. Para ahli mengelompokkan DLBCL ke dalam dua subtipe yaitu subtipe Germinal Center B Cell-Like (GCB) dan non-Germinal Center B-Cell Like (non-GCB), di mana GCB memiliki prognosis yang lebih baik. Penjelasan tentang perbedaan dari kedua subtipe belum sepenuhnya diketahui. Penelitian ini dilakukan dengan tujuan untuk mengetahui perbedaan ekspresi Bcl-2 pada kedua subtipe DLBCL yang mungkin dapat menjelaskan perbedaan prognosisnya.MetodeStudi potong lintang dilakukan pada 41 kasus DLBCL, terdiri atas 18 kasus subtipe GCB dan 23 kasus subtipe non-GCB. Dilakukan review diagnosis histopatologik dari sediaan H&E serta review imunofenotip dari sediaan imunohistokimia. Dilakukan pemeriksaan ekspresi Bcl-2 secara imunohistokimia dan penilaian positivitas dengan nilai cut off 31%. Selanjutnya dilakukan analisis statistik menggunakan uji Mann-Whitney.HasilSeluruh kasus DLBCL, sejumlah 18 kasus subtipe GCB, 15 kasus ekspresi Bcl-2 dikategorikan tinggi. Sejumlah 23 kasus subtipe non-GCB ditemukan 22 kasus ekspresi Bcl-2 termasuk kategori tinggi. Ekspresi Bcl-2 pada DLBCL subtipe non-GCB (nilai rerata 78,70%) lebih tinggi secara bermakna dibandingkan ekspresi Bcl-2 subtipe GCB (nilai rerata 66,61%) (p<0,05).KesimpulanEkspresi Bcl-2 pada DLBCL subtipe non-GCB lebih tinggi dibandingkan ekspresi Bcl-2 subtipe GCB. Hal ini mungkin dapat menjadi salah satu penjelasan perbedaan prognosis diantara keduanya.

Scrofuloderma in a 1-year-old girl with severe malnutrition: a case report Jasin, Madeleine Ramdhani; Neldy, Fahreza Aditya; Setyanto, Darmawan Budi; Nugroho, Gufron; Sunhaji, Valerie; Ham, Maria Francisca
Paediatrica Indonesiana Vol. 63 No. 6 (2023): November 2023
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi63.6.2023.511-6

Tuberculosis (TB) remains a global burden and a leading cause of mortality due to infectious diseases worldwide. In 2020, 845,000 new TB cases (312 per 100,000 population) were diagnosed, with 96,000 deaths, including 4,700 deaths of TB with HIV. Tuberculosis typically affects the lungs, but it can also affect other organs, a condition termed extrapulmonary TB. In 2020, 16% of all TB cases had extrapulmonary manifestations.1 The first case of TB affecting the skin was reported in 1826.2,3 There are many types of cutaneous TB; one of the most common is scrofuloderma, more often found in children and young adults.4 Scrofuloderma starts with a lesion in a lymph node, bone, muscle, or tendon that spreads to the skin.5 The lesion progresses very slowly and is usually not painful. Therefore, many patients wait to seek treatment until an advanced stage, leading to poor prognosis.3 In this report, we present a case of a severely malnourished one-year-old girl with scrofuloderma.

Klinikopatologik dan Profil Imunohistokimia Primary Mediastinal Large B-cell Lymphoma dan Limfoma Hodgkin Nodular Sclerosis di Regio Mediastinum Dameria, Flora; Francisca Ham, Maria; Stephanie Harahap, Agnes
Majalah Patologi Indonesia Vol. 32 No. 1, Januari 2023
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v32i1.565

Background Primary mediastinal large B-cell lymphoma (PMBCL) and Hodgkin nodular sclerosis (LHNS) lymphoma was the most common lymphomas involved the mediastinum. These two lymphomas had similar histopathological features. The purpose of this study was to analyzed clinical data, histopathological characteristics, and immunohistochemistry (IHC) profiles on PMBCL and LHNS. Methods This is a retrospective study. Data was collected from archive of Anatomical Pathology Department, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital in 2014-2020. The data collected included clinical data, hematoxylin-eosin (HE) and IHC slides and were reassessed by the researcher and supervisor. The histopathological characteristics data was analyzed statistically using statistical package for the social sciences version 25.0 with Chi-Square test. Results PMBCL and LHNS have similar histopathological features, included the characteristics of tumor cells and infiltration of many fibrosis and inflammatory cells, but difference in architecture, tumor cell types, clear cytoplasmic tumor cells, inflammatory cell and fibrosis types, with p value <0.001. The characterized differences of PMBCL showed diffuse architecture, some cells with RS-like cell structure, clear/pale cytoplasm, lymphocyte cell infiltration, and compartmental fibrosis. Whilst, LHNS showed nodular architecture, Reed Sternberg cells, mixed inflammatory cell infiltration, and band-like fibrosis. PMBCL showed CD20, PAX5, MUM1 strongly positive, CD30 weakly positive, and CD15 negative, while LHNS showed negative CD20, CD30 and MUM1 strongly positive, PAX5 weakly positive, and CD15 positive.

The Role of Bone Marrow Biopsy Morphology and Clinical Characteristics in Facing the Challenges of Diagnosing Primary Myelofibrosis, Polycythemia Vera, and Essential Thrombocythemia at Cipto Mangunkusumo Hospital Rifani, Liyona; Stephanie, Agnes; Sukrisman, Lugyanti; Mira Lubis, Anna; Francisca Ham, Maria
Majalah Patologi Indonesia Vol. 32 No. 1, Januari 2023
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v32i1.567

BackgroundMyeloproliferative neoplasm (MPN) is a neoplasm characterized by the proliferation of one or more myeloid cells and their derivatives. The limitations of molecular examination in Indonesia make the diagnosis of MPN based on clinical and histopathological examination very crucial. The aim evaluate the clinicopathological profile of primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET) and identify the typical morphological characteristics of bone marrow biopsy.MethodsA retrospective study of cases diagnosed with MPN was conducted at the Department of Anatomic Pathology FMUI/RSCM in 2015-2019. Clinical data and evaluation of bone marrow morphology consisting of cellularity, erythroid myeloid ratio, cluster and megakaryocyte morphology, blast cells, fibrosis, osteosclerosis, and sinus dilatation were analyzed.ResultsA total of 172 cases were diagnosed as MPN BCR-ABL1-negative (PMF: 74; ET: 56; PV: 42). On routine blood examination, there was an increase in hemoglobin (Hb) and hematocrit (Ht) in PV, a decrease in Hb in PMF and an increase in platelets in ET (p<0.001). Splenomegaly is mostly found in PMF. Myeloid erythroid ratio was decreased in PV, normal in ET and increased in PMF (p<0.001). Megakaryocytes were arranged in loose clusters in 88.1% of PV cases and 96.4% of ET, dense clusters were found in 91.9% of PMF cases. Staghorn-like megakaryocytes were found in all ET cases and bulbous/cloud-like megakaryocytes were found in 97.3% of PMF cases. Most cases of PV (90.5%) and all cases of ET showed pre-fibrotic bone marrow (grade 0-1), while 77% of PMF cases showed fibrosis grade 2-3.ConclusionIn diagnosing PV, ET, and PMF, correlation between clinical data, laboratory, and bone marrow histomorphological evaluations, especially cellularity, myeloid:erythroid ratio, cluster and megakaryocyte morphology, degree of fibrosis, osteosclerosis, and sinus dilatation is required.

Limfadenitis KronikGranulomatosa Profil Klinikopatologik Limfadenitis Kronik Granulomatosa Tuberkulosis dan non-Tuberkulosis di Departemen Patologi Anatomik FKUI-RSCM Periode Tahun 2018-2022 Nurlia Erdian, Defi; Harahap, Agnes Stephanie; Ham, Maria Francisca
Majalah Patologi Indonesia Vol. 34 No. 1, Januari 2025
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v34i1.609

Background Chronic granulomatous lymphadenitis (CGL) is an inflammatory condition associated with lymphoproliferative lesions, infections, and autoimmune diseases. One of the etiologies of CGL is Mycobacterium tuberculosis (MTB). According to WHO data in 2020, Indonesia still ranks third globally for TB cases. To ensure appropriate patients’ treatment, there is a need to accurately diagnose TB lymphadenitis through clinicopathological. Therefore, this research aimed to determine the clinicopathological features that differentiate TB lymphadenitis from other types. Method This research was a retrospective analytical review and data were collected from the Department of Anatomic Pathology archives, Faculty of Medicine, University of Indonesia/Dr. Cipto Mangunkusumo Hospital for 5 years, from 2018 to 2022. Clinical data were obtained from electronic medical records. The histopathological assessment involved evaluating the presence of polymorphonuclear cells (PMN), datia cells, and central necrosis in CGL. Result A total of 156 CGL cases were identified, with 63.8% of TB lymphadenitis patients being female and the highest age group was <45 years. No significant association was found between age, a history of autoimmune diseases, malignancy, and TB lymphadenitis. The most commonly involved lymph node location was in the colic area, with a proportion of 62.2%. There was a significant association between lymph node location and the occurrence of TB lymphadenitis (p<0.003). Other variables assessed included the presence of PNM cells (81.7%), datia cells (94%), and central necrosis (88.8%), with p-values <0.000 for each variable. The results showed a significant association between PMN cells, datia cells, and central necrosis with TB lymphadenitis. Conclusion The characteristics of the female gender, lymph node location, presence of PMN cells, central necrosis, and datia cells could be considered as features to assess for diagnosing CGL caused by MTB.

Hubungan Kepadatan Limfosit Intratumoral dan Tipe Histopatologik Karsinoma Tiroid di Departemen Patologi Anatomik FKUI/RSCM Kamarudy Lay, Fanny; Stephanie Harahap, Agnes; Francisca Ham, Maria
Majalah Patologi Indonesia Vol. 32 No. 2, Mei 2023
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v32i2.618

Background The presence of tumor-infiltrating lymphocytes (TILs) has been widely explored as one of the factors that can affect the success of immunotherapy in various cancers. This study aims to investigate the TILs in various types of thyroid carcinoma (TC) and its association with the aggressive histopathological type compared to the less aggressive histopathological type of TC. Methods The population covered by this retrospective study was TCs diagnosed at the Department of Anatomic Pathology, Faculty of Medicine, University of Indonesia/Dr. Cipto Mangunkusumo National Central General Hospital, period 2015-2019. The research sample was divided into group of TCs with aggressive histopathological type and less aggressive histopathological type with a total of 25 samples for each group. TILs was calculated in 10 high power fields (HPF) with 400 kali magnification. The analyses were conducted using Mann-Whitney and Kruskal Wallis test. Results TILs count was found with a median value of 43 (3-660) in the aggressive histopathological group and 36 (9-387) in the less aggressive histopathological group (p:0.96, CI:95%). The highest TILs was found in anaplastic thyroid carcinoma (ATC) and papillary thyroid carcinoma (PTC) with anaplastic components. TILs count was also found with a median value of 17.5 (3-75) in male and 48 (9-660) in female (p:0.02, CI:95%). Conclusion There was no significant association between TILs and histopathological types of TC (aggressive and less aggressive). However, there is a tendency for high TILs in ATC and PTC with anaplastic components. There is also a significant difference in TILs between male and female gender.

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