Mucosal CD30-positive T-cell lymphoproliferations of the head and neck show a clinicopathologic spectrum similar to cutaneous CD30-positive T-cell lymphoproliferative disorders.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
CD30-positive T-cell lymphoproliferative disorders are classified as cutaneous (primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis) or systemic. As extent of disease dictates prognosis and treatment, patients with skin involvement need clinical staging to determine whether systemic lymphoma also is present. Similar processes may involve mucosal sites of the head and neck, constituting a spectrum that includes both neoplasms and reactive conditions (eg, traumatic ulcerative granuloma with stromal eosinophilia). However, no standard classification exists for mucosal CD30-positive T-cell lymphoproliferations. To improve our understanding of these processes, we identified 15 such patients and examined clinical presentation, treatment and outcome, morphology, phenotype using immunohistochemistry, and genetics using gene rearrangement studies and fluorescence in situ hybridization. The 15 patients (11 M, 4 F; mean age, 57 years) had disease involving the oral cavity/lip/tongue (9), orbit/conjunctiva (3) or nasal cavity/sinuses (3). Of 14 patients with staging data, 7 had mucosal disease only; 2 had mucocutaneous disease; and 5 had systemic anaplastic large cell lymphoma. Patients with mucosal or mucocutaneous disease only had a favorable prognosis and none developed systemic spread (follow-up, 4-93 months). Three of five patients with systemic disease died of lymphoma after 1-48 months. Morphologic and phenotypic features were similar regardless of extent of disease. One anaplastic lymphoma kinase-positive case was associated with systemic disease. Two cases had rearrangements of the DUSP22-IRF4 locus on chromosome 6p25.3, seen most frequently in primary cutaneous anaplastic large cell lymphoma. Our findings suggest mucosal CD30-positive T-cell lymphoproliferations share features with cutaneous CD30-positive T-cell lymphoproliferative disorders, and require clinical staging for stratification into primary and secondary types. Primary cases have clinicopathologic features closer to primary cutaneous disease than to systemic anaplastic large cell lymphoma, including indolent clinical behavior. Understanding the spectrum of mucosal CD30-positive T-cell lymphoproliferations is important to avoid possible overtreatment resulting from a diagnosis of overt T-cell lymphoma.
10.1038/modpathol.2012.38
Intravascular NK/T-cell lymphoma: clinicopathological and integrated molecular analysis of two cases provides a clue to disease pathogenesis.
Fujikura Kohei,Yamashita Daisuke,Sakamoto Ryo,Ishikawa Takayuki,Chuang Shih-Sung,Itoh Tomoo,Imai Yukihiro
Journal of clinical pathology
AIMS:To elucidate the clinicopathological and molecular features of intravascular NK/T-cell lymphoma (IVNKTCL). METHODS:Two cases of IVNKTCL were retrieved from a single-centre cohort composed of 25 intravascular lymphomas. Whole-exome and RNA sequencing and immunohistochemistry were performed. RESULTS:We identified somatic mutations in the following epigenetic regulators: four histone genes (, , and histone deacetylase (), two helicases ( and ), two methylation-related enzymes ( and ) and the SNI/SWF pathway (). Copy number analysis identified driver gene alterations comprising the loss of , and , and the gain of and histone clusters. RNA sequencing analysis did not indicate the presence of any fusion gene. Both cases were positive for Epstein-Barr virus (EBV) and showed strong expression of programmed death-ligand 1 (PD-L1). CONCLUSIONS:This study raises the possibility that, at least for some patients, IVNKTCL may be considered an epigenetic disease with EBV infection-associated aetiopathogenesis.
10.1136/jclinpath-2019-205727
Transcriptome complexity in intravascular NK/T-cell lymphoma.
Fujikura Kohei,Yoshida Makoto,Uesaka Kazuma
Journal of clinical pathology
AIMS:Intravascular NK/T-cell lymphoma (IVNKTCL) is a rare disease, which is characterised by exclusive growth of large cells within the lumen of small vessels, Epstein-Barr virus infection and somatic mutations in epigenetic regulator genes. Here, we elucidate the transcriptomic complexity of IVNKTCL. METHODS:IVNKTCL cases were retrieved from a single-centre cohort of 25 intravascular lymphomas. RNA-seq and whole exome sequencing (WES) were performed to analyse transcriptomic abnormalities and mutations in splicing factors. RESULTS:Approximately 88% of the total reads from the RNA-seq were considered exonic, while the remaining reads (12%) were mapped to intronic or intergenic regions. We detected 28,941 alternative splicing events, some of which would produce abnormal proteins rarely found in normal cells. The detected events also included tumour-specific splicing alterations in oncogenes and tumour suppressors (e.g., , and ). WES identified premature termination mutations or copy number losses in a total of 15 splicing regulator genes, including , and . CONCLUSIONS:This study raises the possibility that IVNKTCL may be driven by multiple complex regulatory loops, including non-exonic expression and aberrant splicing, in addition to defects in epigenetic regulation.
10.1136/jclinpath-2020-206461