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Abstrak :
Latar Belakang: Karsinoma papiler tiroid KPT adalah karsinoma tersering 70 dari seluruh keganasan kelenjar tiroid. KPT varian folikular adalah varian terbanyak dari KPT yang menunjukkan diferensiasi sel folikular dengan perubahan inti. Well differentiated tumor of uncertain malignant potential WDT-UMP merupakan tumor berkapsul dengan pola pertumbuhan folikular difus dengan ciri inti karsinoma papiler yang tidak komplit, dan diperkirakan memiliki sifat borderline. KPTVF dan WDT-UMP sulit dibedakan terutama jika perubahan inti tidak secara difus ditemukan sehingga diperlukan metode diagnosis yang sederhana dan akurat dalam membedakan lesi borderline dan ganas, sehingga terapi yang berlebih dapat dihindari pada lesi borderline dengan prognosis baik. Bahan dan Metode: Penelitian ini menggunakan metode potong lintang. Sampel WDT-UMP dan KPTVF, masing-masing 20 kasus, diperoleh dari arsip Departemen Patologi Anatomik FKUI-RSCM pada tahun 2011-2015. Pewarnaan imunohistokimia dengan antibodi primer CK19, dan dinilai secara semikuantitatif dengan skor 1 95 , positif kuat. Hasil: Didapatkan 15 kasus terekspresi 2 dan 5 kasus 3 pada WDT-UMP, sementarra 9 kasus terekspresi 3 dan 11 kasus terekspresi 4 pada KPTVF. Hasil analisis dengan uji Chi square, menunjukkan terdapat perbedaan yang bermakna antara ekspresi imunohistokimia CK19 dengan diagnosis WDT-UMP dan KPTVF, dengan nilai p.

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Background Papillary thyroid carcinoma PTC is the most common carcinoma 70 in all thyroid malignancy. The follicular variant of PTC FVPTC is the most frequent variant of PTC, which shows follicular cell differentiation with nuclear changes. Well differentiated tumor of uncertain malignant potential WDT UMP is an encapsulated tumor with incomplete nuclear features of PTC, estimated to be borderline in nature. It is hard to differentiate FVPTC and WDT UMP especially if the nuclear changes are not diffusely present, so a method which is simple and reliable, is needed to make an accurate diagnosis of borderline and malignant lesion, so overtherapy can be avoided, in borderline lesion with a good prognosis. Method This research use cross sectional methods. Twenty cases of WDT UMP and twenty cases of FVPTC, are obtainted from Anatomical Pathology Departement from 2011 2015. Immunochemistry staining with CK19 primary antibody, and scored semiquantitatively as follows 1 95 , strongly positive. Result In WDT UMP group, 15 cases expression score are 2 and 5 cases score 3. In FVPTC group, all of the cases are strongly positive, 9 cases score 3 and 11 cases score 4. Statistical analysis with Chi square test shows statistical significance difference between CK19 expression in WDT UMP and FVPTC p

Abstrak :
Latar Belakang: Karsinoma tiroid merupakan neoplasma organ endokrin yang paling sering terjadi dan sebagian di antaranya memiliki tipe histologik agresif yang masih sulit ditangani hingga kini. Karsinoma pada kelompok ini cenderung menunjukkan resistensi dengan radioablasi I-131 dan terapi dengan pembedahan juga tidak dapat memberikan hasil yang maksimal. Keberadaan imunoterapi dengan menggunakan inhibitor PD-L1 dapat menjadi peluang terapi baru untuk pasien dengan karsinoma tersebut. Namun, penelitian-penelitian tentang PD-L1 pada karsinoma tiroid hingga saat ini masih menunjukkan hasil yang bervariasi dan belum jelas diketahui apakah karsinoma tiroid tipe histologik agresif memiliki imunoekspresi PD-L1 yang lebih tinggi dibandingkan dengan tipe histologik kurang agresif. Tujuan: Penelitian ini bertujuan untuk mengetahui imunoekspresi PD-L1 pada karsinoma tiroid dan hubungannya dengan tipe histologik agresif dibandingkan dengan tipe histologik kurang agresif. Metode: Penelitian ini menggunakan desain retrospektif dan potong lintang. Populasi terjangkau penelitian adalah kasus karsinoma tiroid di Departemen Patologi Anatomik FKUI/RSCM periode Januari 2015 hingga Desember 2019. Sampel penelitian dibagi menjadi 2 kelompok, yaitu kelompok karsinoma tiroid dengan tipe histopatologik agresif dan kelompok karsinoma tiroid tipe histologik kurang agresif. Pemeriksaan imunohistokimia dilakukan pada blok parafin kedua kelompok sampel dengan menggunakan antibodi primer monoclonal mouse anti-PD-L1, clone 22C3 (Dako) untuk menilai imunoekspresi PD-L1 yang dinyatakan dalam tumor proportion score (TPS). Nilai TPS dihitung berdasarkan persentase jumlah sel tumor yang terwarnai secara total atau parsial pada membran sitoplasma sel tumor dibagi dengan jumlah seluruh sel tumor dalam satu slaid. Data imunoekspresi PD-L1 kemudian dianalisis untuk mengetahui perbedaan nilai TPS di antara kedua tipe histologik karsinoma tiroid tersebut. Hasil: Terdapat total 52 kasus karsinoma tiroid yang terdiri atas 26 kasus tipe histologik agresif dan 26 kasus tipe histologik kurang agresif pada penelitan ini. Imunoekpsresi PD-L1 yang dinilai dalam ukuran TPS (tumor proportion score) ditemukan dengan nilai median 0,60% (0%-95,00%) pada kelompok tipe hitologik agresif, dan 0.07% (0%- 19,53%) pada kelompok tipe histologik kurang agresif (P:0,01; IK:95%). Pada analisis tambahan ditemukan juga perbedaan nilai TPS yang signifikan pada variabel perluasan tumor keluar tiroid (P:0,02; IK:95%). Kesimpulan: Terdapat perbedaan imunoekspresi PD-L1 yang signifikan antara karsinoma tiroid tipe histologik agresif dan kurang agresif. Nilai TPS ditemukan lebih tinggi pada karsinoma tiroid tipe histologik agresif dibandingkan dengan tipe histologik kurang agresif. Temuan ini dapat membuka peluang imunoterapi pada pasien karsinoma tiroid dengan tipe histologik agresif di masa depan. ......Background: Thyroid carcinoma (TC) is the most common endocrine organ neoplasm. Some of TCs may show aggressive histological types that are still difficult to treat nowadays. Carcinomas in this group tend to show resistance to I-131 radioablation and surgical therapy also does not provide optimal results. The existence of immunotherapy using PD-L1 inhibitors can be a new therapeutic opportunity for patients with these carcinomas. However, studies on PD-L1 in TC still show varying results and it is not clear whether the aggressive histological type of TC has a higher immunoexpression of PD-L1 than the less aggressive histological type. Objectives: To investigate the significance of PD-L1 expression in aggressive histological type of TC comprae to the less aggressive type. Material and methods: The population covered by this retrospective cross-sectional study were TC cases at the Department of Anatomic Pathology, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia, period 2015 - 2019. The cases were categorized into two groups, a group of aggressive histological types and a group of the less aggressive histological types of TC. The immunohistochemical examinations were carried out on paraffin blocks of both sample groups using the mouse monoclonal primary antibody anti-PD-L1, clone 22C3 (Dako) to evaluate the tumor proportion score (TPS) value of PD-L1 expression. The TPS value was calculated based on the number of tumor cells that were fully or partially stained in the cytoplasmic membrane of tumor cells divided by the total number of tumor cells in one slide. Data analysis was performed to determine the significance of PD-L1 expression in the aggressive histological types of TC. Results: A total of 52 cases of TC consisting of 26 cases of aggressive histological types and 26 cases of less aggressive histological types has been studied. PD-L1 expression was evaluated by calculating the TPS in both groups. We found a significance difference of the median TPS value of 0.60% (0 - 95.00%) in the aggressive histological type group, and 0.07% (0 - 19.53%) in the less aggressive histological type group (P: 0.01; CI: 95%). A significant difference in TPS value was also found for the extrathyroidal extension in an additional analysis (P: 0.02; CI:95%). Conclusions: The present study found a significant association between PD-L1 expression and the aggressive histological type of TC. The TPS values were found to be higher in the group of aggressive histological types of TC compared to the less aggressive histological types. A significant association between PD-L1 expression and the presence of extrathyroidal extension of TC has also been suggested. These findings may open opportunities for future immunotherapy in patients with thyroid carcinoma with aggressive histologic types.

Abstrak :
[ABSTRAK
Latar Belakang: Karsinoma papiler tiroid (KPT) merupakan keganasan tersering organ endokrin dengan prognosis yang sangat baik, namun pada beberapa kasus dapat terjadi rekurensi dan mortalitas. Beberapa faktor prognostik dan mutasi Btype rapidly accelerated fibrosarcoma V600E (BRAF V600E) dikatakan berhubungan dengan prognosis yang lebih buruk. Pemeriksaan imunohistokimia protein BRAF V600E dipercaya dapat mendeteksi adanya mutasi dengan spesifisitas 100% dan sensitivitas 89%. Tujuan penelitian ini untuk mengetahui imunoekspresi BRAF V600E dan hubungannya dengan faktor-faktor prognostik. Bahan dan Cara: Penelitian dilakukan secara retrospektif, desain deskriptif analitik studi potong lintang. Sampel penelitian berasal dari RSCM berjumlah 50 kasus KPT yang dinilai ulang untuk menentukan faktor-faktor prognostik secara mikroskopik. Pemeriksaaan mutasi BRAF V600E menggunakan tehnik imunohistokimia dan penilaian menggunakan H score. Hasil: Nilai H score ³ 326,5 ditentukan sebagai mutasi BRAF V600E positif dan < 326,5 sebagai mutasi BRAF V600E negatif. Terdapat 17 (34%) kasus positif mengalami mutasi BRAF V600E. Rerata usia pada kasus dengan mutasi BRAF V600E positif adalah 44,71 tahun. Ukuran tumor pada kasus dengan mutasi BRAF V600E positif berkisar antara 0,1-4cm. Tujuh belas kasus yang mengalami mutasi, 6 dlaki-laki dan 11 perempuan. Tujuh kasus dengan perluasan keluar tiroid, 11 kasus dengan metastasis kelenjar getah bening (KGB), dan 8 kasus dengan varian histopatologik tall cell. Kesimpulan: Terdapat hubungan bermakna antara mutasi BRAF V600E dengan perluasan keluar tiroid, metastasis kelenjar getah bening (KGB), dan varian histopatologik tall cell. Tidak terdapat hubungan bermakna antara mutasi BRAF V600E dengan usia, jenis kelamin, dan ukuran tumor.

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ABSTRACT
Backgroud: Papillary Thyroid Carcinoma (PTC) is the most common malignant neoplasm of the endocrine organ with an excellent prognosis, but in some cases present with recurrency and mortality. There are prognostic factors and BRAF V600E mutation that related to worse prognosis. Immunohistochemical investigetion of BRAF V600E protein believe can detect mutation wth 100% specificity and 89% sensitivity. Recent study suggest PTC with BRAF V600E mutation do thyroidectomy with prophylactic lymph node dissection. BRAF V600E specific inhibitor effective to the patient with advance stadium, patient with metastases, and resistant to iodium radioactive. Aim of this study is to obtain BRAF V600E and the relation with prognostic factors. Material and Methods: This is a retrospective descriptive-analytic crosssectional study. Fifty patient with PTC comes from Ciptomangunkusumo Hospital and reviewed to determine prognostic factors microscopicaly. BRAF V600E mutation detected by immunohistochemical staining and assesed with H score. Result: H score ³ 326,5 determined as positive BRAF V600E mutation and < 326,5 as negative BRAF V600E mutation. BRAF V600E mutation was detected in 17 (34%) cases by immunohistochemistry. The mean age of the cases with positive BRAF V600E mutation was 44.71 years, while the negative 41.58. The size of the tumor in cases with BRAF V600E mutation positive range between 0,1-4cm, while negative 0,1-9cm. Seventeen cases have mutations, 6 of them sex male and 11 female. Seven cases with extrathyroidal extension (ETE), 11 cases with lymph node metastasis (KGB), and 8 cases with tall cell variant. Conclusion: There are significant correlation between BRAF V600E mutation with extrathyroidal extension, lymph node metastases, and tall cell variant. There are no significant correlation between BRAF V600E mutation with age, gender, and size of the tumor, Backgroud: Papillary Thyroid Carcinoma (PTC) is the most common malignant neoplasm of the endocrine organ with an excellent prognosis, but in some cases present with recurrency and mortality. There are prognostic factors and BRAF V600E mutation that related to worse prognosis. Immunohistochemical investigetion of BRAF V600E protein believe can detect mutation wth 100% specificity and 89% sensitivity. Recent study suggest PTC with BRAF V600E mutation do thyroidectomy with prophylactic lymph node dissection. BRAF V600E specific inhibitor effective to the patient with advance stadium, patient with metastases, and resistant to iodium radioactive. Aim of this study is to obtain BRAF V600E and the relation with prognostic factors. Material and Methods: This is a retrospective descriptive-analytic crosssectional study. Fifty patient with PTC comes from Ciptomangunkusumo Hospital and reviewed to determine prognostic factors microscopicaly. BRAF V600E mutation detected by immunohistochemical staining and assesed with H score. Result: H score ³ 326,5 determined as positive BRAF V600E mutation and < 326,5 as negative BRAF V600E mutation. BRAF V600E mutation was detected in 17 (34%) cases by immunohistochemistry. The mean age of the cases with positive BRAF V600E mutation was 44.71 years, while the negative 41.58. The size of the tumor in cases with BRAF V600E mutation positive range between 0,1-4cm, while negative 0,1-9cm. Seventeen cases have mutations, 6 of them sex male and 11 female. Seven cases with extrathyroidal extension (ETE), 11 cases with lymph node metastasis (KGB), and 8 cases with tall cell variant. Conclusion: There are significant correlation between BRAF V600E mutation with extrathyroidal extension, lymph node metastases, and tall cell variant. There are no significant correlation between BRAF V600E mutation with age, gender, and size of the tumor]