Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, characterized by a range of subtypes that differ in their cytologic features, clinical behavior, and prognosis. Accurate cytologic evaluation of PTC using fine-needle aspiration is essential but can be challenging due to the morphologic diversity among subtypes. This review focuses on the distinct cytologic characteristics of various PTC subtypes, including the classic type, follicular variant, tall cell, columnar cell, hobnail, diffuse sclerosing, Warthin-like, solid/trabecular, and oncocytic PTCs. Each subtype demonstrates unique nuclear features, architectural patterns, and background elements essential for diagnosis and differentiation from other thyroid lesions. Recognizing these distinct cytologic patterns is essential for identifying aggressive subtypes like tall cell, hobnail, and columnar cell PTCs, which have a higher risk of recurrence, metastasis, and poorer clinical outcomes. Additionally, rare subtypes such as diffuse sclerosing and Warthin-like PTCs present unique cytologic profiles that must be carefully interpreted to avoid diagnostic errors. The review also highlights the cytologic indicators of lymph node metastasis and high-grade features, such as differentiated high-grade thyroid carcinoma. The integration of molecular testing can further refine subtype diagnosis by identifying specific genetic mutations. A thorough understanding of these subtype-specific cytologic features and molecular profiles is vital for accurate diagnosis, risk stratification, and personalized management of PTC patients. Future improvements in diagnostic techniques and standardization are needed to enhance cytologic evaluation and clinical decision-making in thyroid cancer.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new subset within the spectrum of thyroid malignancies. This review aims to provide a comprehensive overview of DHGTC, focusing on its historical perspective, diagnosis, clinical characteristics, molecular profiles, management, and prognosis. DHGTC demonstrates an intermediate prognosis that falls between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma. Previously unenumerated, this entity is now recognized for its significant impact. Patients with DHGTC often present at an older age with advanced disease and exhibit aggressive clinical behavior. Molecularly, DHGTC shares similarities with other thyroid malignancies, harboring driver mutations such as BRAFV600E and RAS, along with additional late mutations. The unique behavior and histologic features of DHGTC underscore the necessity of precise classification for prognostication and treatment selection. This highlights the critical importance of accurate diagnosis and recognition by pathologists to enrich future research on this entity further.

Introduction: BRAFV600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAFV600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAFV600E and RAS mutations, and their association with clinicopathologic characteristics. Methods: Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAFV600E, BRAFK601E, exon 2 and 3 of NRAS, HRAS, and KRAS. Analyses were performed to determine the associations of BRAFV600E and RAS mutations with clinicopathologic characteristics. Results: Of 172 PTC patients, BRAFV600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAFK601E mutation. There was a significant association of BRAFV600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048– 10.259), tall-cell variants (p ≤ 0.001, OR: 41.143; 95% CI: 11.979– 141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008– 8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018– 3.592), extrathyroidal extension (p = < 0.001, OR: 3.983; 95% CI: 1.970– 8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224– 4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690– 18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161– 5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052– 7.940) were associated with RAS mutations. Conclusion: A significant association between BRAFV600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS-mutated PTC frequently exhibited tumor multifocality.

Background: Papillary thyroid carcinoma (PTC) is the most prevalent thyroid carcinoma that possesses a wide range of biological behavior. Various clinical and histopathological features, including BRAF V600E profile, are used to stratify the risk of disease recurrence in thyroid carcinoma. Recent studies have taken an interest in the potential of the proliferation index, Ki-67, in predicting the aggressive nature of PTC. Methods: This is a single-center, retrospective study that included 92 PTC cases diagnosed at the Department of Anatomical Pathology, Faculty of Medicine/Dr. Cipto Mangunkusumo Hospital, from January 2019-December 2022. Continuous and categorical analysis of Ki-67 labeling index (LI) was studied and compared with various clinicopathological features and BRAF V6000E status. Results: Ki-67 LI was identified in PTCs (range = 0.1–17.1%, median = 2.45%). Higher Ki-67 LI (median value and Ki-67 LI > 5%) is significantly correlated with older age, advanced stage, lymph node metastasis, distant/organ metastasis, aggressive histological subtypes, unencapsulated tumors, lymphovascular invasion, extrathyroidal extension, and BRAF V600E mutation. Conclusion: The proliferation activity shown by Ki-67 LI correlates with aggressive tumor characteristics and may imply possible prognostic significance in diagnosing PTC.

Background: Treatment response in diffuse large B-cell lymphoma (DLBCL) is heterogenous. The Hans algorithm (using 30% cut-offs for CD10, BCL6, and MUM1 protein expression) has been the most favored method to categorize DLBCL into germinal center B-cell (GCB) and non-GCB subtypes in order to predict prognosis. However, the algorithm’s ability to prognosticate is not always consistent. Methods: This retrospective cohort study was conducted on DLBCL patients receiving R-CHOP therapy at Dr. Cipto Mangunkusumo Hospital, Jakarta from 2014 to 2017. We aimed to compare the prognostic value of Hans algorithm as well as the protein levels of CD10, BCL6, MUM1, and Ki67 at different cut-offs. Ninety-two patients were classified based on Hans algorithm and various proteins at different cut-off values were analyzed with regard to event-free survival at 24 months using survival analysis. The cut-off values were then compared using receiver operating characteristic curves. Results: A significant survival difference was observed with MUM1 expression cut-off of 50% or more (log rank p = 0.035). CD10, BCL6, Ki67, and Hans algorithm showed AUCs below or near 0.5 (0.405, 0.436, 0.498, and 0.413, respectively), whereas MUM1 showed an AUC of 0.835, in predicting events within 24 months. MUM-1 cut-off of 70.5% yielded an optimal trade-off for sensitivity and specificity. Conclusion: MUM1 expression of 50% or more can help predict prognosis in DLBCL patients receiving R-CHOP therapy and can be considered as for use as a single marker to predict prognosis.