Carolyn Choy

Aberrant promoter CpG methylation as a molecular marker for disease monitoring in natural killer cell lymphomas

Summary. Natural killer (NK) cell lymphomas lack suitable clonal markers for tumour cell detection, making the monitoring of minimal residual lymphoma difficult. Aberrant promoter CpG methylation occurs frequently in NK cell lymphomas. The objective of this study was to assess the potential of aberrant methylation as a surrogate tumour marker. Twenty‐five primary tumours and 105 serial biopsies taken at various time points after treatment were examined using a methylation‐specific polymerase chain reaction (MSP) for a panel of genes, comprising p73, p16, hMLH1, RARβ and p15, previously shown to be methylated in NK cell lymphomas. All samples underwent independent morphological examination, supplemented by immunostaining for CD56 and in‐situ hybridization for Epstein–Barr‐virus‐encoded RNA. Primary tumours showed the frequent methylation of the genes p73 (92%), p16 (71%), hMLH1 (61%), RARβ (56%) and p15 (48%). MSP results in serial post‐treatment biopsies were correlated with clinicopathological findings. Results were concordant in 89 follow‐up samples (18 samples, histology positive/MSP positive; 71 samples, histology negative/MSP negative) and discordant in 16. Fifteen samples were histology negative/MSP positive, and tumour involvement was subsequently confirmed (positive re‐biopsies or relapses at the same sites), indicating that MSP was more sensitive for minimal lymphoma detection. One sample was histology positive/MSP negative; a subsequent histological review and continuous clinical remission of the patient did not support tumour involvement. Our findings suggest that MSP for aberrantly methylated genes is a potentially valuable molecular marker for detecting either residual or relapsed disease in NK cell lymphoma patients.

Cytologic findings of angioimmunoblastic T-cell lymphoma: Analysis of 16 fine-needle aspirates over a 9-year period

Peripheral T‐cell lymphoma often represents an important diagnostic pitfall in fine‐needle aspiration biopsy due to the heterogeneous cell population present. A classic example of this group is angioimmunoblastic T‐cell lymphoma (AILD‐T). The fine‐needle aspiration cytology of this relatively well‐defined histologic subtype of T‐cell lymphoma is rarely described in the literature.

Isolated Uterine Relapse of Nasal T/Nk Cell Lymphoma

A case of isolated uterine relapse of nasal T/NK cell lymphoma is reported. A 47-year old lady developed menstrual symptoms a year after attaining complete remission from her nasal T/NK cell lymphoma. Endometrial tissue showed characteristic zonal necrosis, angiocentricity and infiltration by lymphoma cells that were positive for both the characteristic immunopheotypic profile of T/NK cell (CD2+, surface CD3-, cytoplasmic CD3 [CD3epsilon]+ and CD56+) and EBER.

Cytologic and immunocytochemical findings of anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) has raised much controversy in the field of hematolymphoid pathology. Its nature is becoming better characterized with recent advances in molecular genetics. However, to the authors knowledge, a detailed description of the fine‐needle aspiration (FNA) cytology of ALCL is lacking and the application of immunocytochemical study, including immunostaining for anaplastic lymphoma kinase (ALK) protein, to cytology samples has not been studied to date.

Chronic T-cell lymphoproliferative disease expressing natural killer cell receptors: clinicopathological and molecular features.

The frequency and clinicopathological significance of the expression of natural killer cell receptors (NKRs) in T-cell malignancies remain undefined. A 71-year-old man presented with leukocytosis, generalized lymphoadenopathy, and hepatosplenomegaly. Bone marrow and lymph node biopsies showed a T-cell lymphoproliferative disease expressing NKRs (CD2(+), CD3(+), CD4(+), CD5(+), CD7(+), CD8(-), CD56(-), CD94(+), CD158a(+), CD158b(+), CD161(-), p70(-), TCRalphabeta(1), TCRgammadelta(2), TIA-1(-)). An abnormal clone, 46,Y,add(X)(p14),der(1)t(1;6)(p33;p21),t(7;12)(p10;q10), was found on conventional karyotyping. Comparative genomic hybridization confirmed these findings, and showed a deletion of 12p that was not apparent on karyotyping. Clinically, the disease remained indolent and responded transiently to purine analogs but not to intensive chemotherapy. Peripheral T-cell lymphoproliferative disease of CD4(+)alphabeta(1)NKR(+) phenotype is hitherto undescribed. The issues of whether this case was derived from transformation of a rare T-cell subtype or represented aberrant T-cell expression of NK-cell antigens, and the clinicopathologic significance of these T-cell neoplasms warrant further studies.