RESUMO
OBJECTIVES: Kabuki syndrome (KS) is a rare congenital malformation syndrome associated with germline KMT2D mutations. Recurrent somatic mutations in KMT2D have frequently been observed in B-cell lymphoma, but limited studies are available that evaluate the genetic landscape of B-cell lymphomas in the setting of KS. METHODS: We describe a unique case of B-cell lymphoma that illustrates histologic features of pediatric-type follicular lymphoma (FL) in a young patient with KS and autoimmune disease who showed a systemic presentation of widespread lymphadenopathy and clonal lymphocytosis. RESULTS: We present the first reported case of a young patient with KS harboring a germline KMT2D variant and presenting with a systemic CD10-positive, BCL2-negative B-cell lymphoma of follicle center origin illustrating histologic features of pediatric-type FL. Targeted next-generation sequencing of the B-cell lymphoma showed somatic TET2 and subclonal CXCR4 variants. These findings suggest that abnormal epigenetic regulation caused by alterations in KMT2D and TET2 may have played critical roles in promoting lymphomagenesis in this patient. CONCLUSIONS: This unique case presentation highlights the importance of close clinical monitoring and the value of clinical context in the diagnosis of pediatric FL-like lesions in patients with KS.
Assuntos
Dioxigenases , Doenças Hematológicas , Linfoma de Células B , Doenças Vestibulares , Criança , Humanos , Epigênese Genética , Doenças Vestibulares/genética , Doenças Vestibulares/complicações , Doenças Vestibulares/diagnóstico , Doenças Hematológicas/complicações , Doenças Hematológicas/genética , Doenças Hematológicas/diagnóstico , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Células Germinativas/patologia , Mutação , Proteínas de Ligação a DNA/genética , Dioxigenases/genéticaRESUMO
OBJECTIVE: To establish diagnostic accuracy and reproducibility of a diagnosis of cervical intraepithelial neoplasia 3 (CIN 3) in menopausal women on routinely stained hematoxylin and eosin (H&E) slides and compare it to slides processed for p16 and Ki-67. MATERIALS AND METHODS: Confirmed cases of CIN 3 and benign atrophic changes were reviewed independently by 4 pathologists. The samples were studied on separate occasions using H&E staining, p16, and Ki-67. Differences in sensitivity and specificity between reviewers or methods were tested for significance using the McNemar test, whereas differences in positive and negative predictive values were tested for significance using a marginal probability generalized linear model for agreement. RESULTS: Sensitivity was high for H&E (93.3%-100%) and Ki-67 (93.3%-100%) and lower for p16 (70.0%-90.0%). Intraobserver variability was also lower for p16 (76.7% vs 90.0%, although this difference was not statistically significant, p = .219). p16 agreement, however, for CIN 3 is significantly lower than that for atrophy (76.7% vs 97.4%, p = .018). CONCLUSIONS: Routine histopathologic diagnosis of CIN 3 in menopausal women is highly accurate and reproducible. Both H&E and Ki-67 are useful immunohistochemical stains in helping differentiate atrophy from high-grade cervical intraepithelial lesions in postmenopausal cervical biopsies. There may be more disagreement among readers using p16.