Introduction A specific subset of papillary microcarcinoma of thyroid (PMC) can metastasize regionally and to distant organs, and thus, have a significant effect on the overall survival of the patient cohort. Objectives We aim to analyze the prognostic significance of various clinicopathologic parameters including BRAFV600E mutation by immunohistochemistry in PMC, in order to identify the subset of cases with aggressive behavior. Materials and Methods Data regarding the PMC cases was retrieved retrospectively from medical records. The clinicopathologic factors like age, tumor size, focality, capsular invasion, histologic subtype, lymphovascular invasion, perithyroidal fat invasion (PTFI), lymph node (LN) metastasis, and distant metastasis were studied in depth. Tissue microarray was constructed to perform immunohistochemistry with CK19 and BRAFV600E. Information regarding overall survival (OS) and development of metastasis, if any, was noted. Chi-squared test was performed to know the association between various factors. To determine odds ratio, logistic regression was done. Survival analysis was done using Kaplan–Meier and Cox-regression analysis. Results PMC was diagnosed in 48 patients (M:F = 1:2.4), between 22 and 70 years of age (median = 46.5 years). Chi-squared test showed significant association of fibrosis with tumor size more than or equal to 0.5 cm, infiltrative borders, PTFI, and LN metastasis. Tumor size was also associated with infiltrative borders; and LN metastasis with PTFI. BRAFV600E positivity showed significant association with histologic pattern, PTFI and distant metastasis. On logistic regression, tumor size showed significantly increased odds ratio with presence of fibrosis and infiltrative borders. Presence of fibrosis also showed significant association with infiltrative borders and LN metastasis. BRAF V600E had significantly increased odds ratio with histologic pattern, both on univariate and multivariate logistic regression. Kaplan–Meier analysis revealed significantly reduced OS with presence of LN metastases (p-value = 0.050, log-rank test). Cox-regression did not yield a significant hazard ratio for the various factors studied. Conclusion This study shows association of LN metastasis with intratumoral fibrosis, PTFI and reduced OS. Intratumoral fibrosis was also associated with tumor size more than 5mm, infiltrative borders and PTFI. Increasing tumor size and infiltrative borders also showed an association. In addition, BRAFV600E positivity was found to be associated with histologic pattern, PTFI and distant metastasis.
Non-granulomatous necrotizing lymphadenopathy (NGNL) is not a specific entity. It is seen in various conditions like Kikuchi-Fujimoto disease (KFD), Systemic Lupus Erythematosus (SLE), tuberculosis, lymphoma/metastasis and lymph node infarction. These conditions mimic each other histologically but it is necessary to identify the correct pathology as the treatment differs significantly. To highlight the subtle morphological features which lead to the etiological diagnosis in NGNL. The lymphnode biopsies (N=198), reported in our institute as NGNL, over 4½ year study period, were retrieved. Of these, the benign cases were 64 in total, with 40 cases of KFD and 8 cases of SLE. H&E, special stains and immunohistochemistry slides were reviewed by two pathologists. Histomorphological features like amount of necrosis, apoptotic debris, vasculitis, presence of neutrophils, eosinophils, histiocytes, plasma cells, hematoxylin bodies, Azzopardi phenomenon and thrombus formation were studied. Logistic regression analysis was performed to identify the most significant histopathological parameter with each disease. Kendall’s Tau matrix plot analysis was used to measure the correlation between the disease and the histopathologic variables. Features like vasculitis, hematoxylin bodies and Azzopardi phenomenon showed strong correlation with SLE and inverse correlation with KFD. Apoptotic debris, paucity of neutrophils and eosinophils had a strong positive association with KFD. The histological features help in differentiating the various entities associated with NGNL. It is necessary to correlate with clinical details and various laboratory parameters to reach a conclusive diagnosis because these conditions have varied treatment modalities.
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