Primary Uterine NK-Cell Lymphoma, Nasal-Type: A Unique Malignancy of a Prominent Cell Type of the Endometrium

Abstract

Natural killer (NK) cells host in the human endometrium with dedicated role in reproductive physiology. Interestingly, malignant transformation of these specialized cells has not been presented thus far. Here we report a primary endometrial NK-cell lymphoma of a 48 year-old patient presenting with irregular bleeding. The endometrial curetting showed a dense lymphomatous infiltrate demonstrating highly infiltrative aggressive features with characteristic angiocentric, partially angiodestructive growth pattern and accompanying focal necroses. The lymphoma cells displayed a CD3ε/CD56/TIA-1/granzyme-B-positive and CD5/CD4/CD8/TCRγδ-negative immunophenotype, proved to be positive for Epstein-Barr virus by EBER in situ hybridization, and revealed no clonal T-cell receptor gene rearrangement. The diagnosis of uterine extranodal NK-cell lymphoma, nasal-type was made. Clinically, the disease was limited to the uterus at diagnosis, but progressed rapidly, and the patient died within 5 months due disseminated lymphoma, irrespective of intensive chemotherapy. Genuine NK-cell lymphomas occurring in the uterus as primary site seem to be rare making the therapeutic decisions extremely complicated.

Primary extranodal NK/T cell lymphoma, nasal-type of uterus with adenomyosis: a case report

“…For this reason it is difficult to understand, why uterine NK-cells transform to malignant lymphoma with such a low frequency. As one possible explanation, the relatively short duration of a menstrual cycle and the regular shed of the endometrium may prevent the expansion and malignant transformation of NK cells [2]. In the presented case, the presence of adenomyosis may prevent the normal NK cell duration and cycling in the uterus, perhaps provide the evidence that NK cells frequently remained in uterine corps undergo genetic and regulatory errors leading to malignant transformation.…”

“…Rarely, the tumour occurs in prostate, adrenal glands and lung [7-9]. Thus far, only a few cases of T- or NK/T-cell neoplasms involved uterus have been reported [2-5]. Like most of NK/T cell lymphoma in other anatomic sites, these lymphomas in the uterus usually are highly aggressive, and conventional prognostic factors usually fail to predict their outcome [10].…”

“…It seems to be established that uterine NK cells form a dynamic lymphoid pool in each menstruation cycle. One could expect that these cells may frequently undergo genetic and regulatory errors leading to malignant transformation [2]. For this reason it is difficult to understand, why uterine NK-cells transform to malignant lymphoma with such a low frequency.…”

“…The majority of these cases represent aggressive B-cell lymphomas. Involvement of the gynecological tract by NK/T cell lymphomas is considered to be extremely rare and only 5 cases with primary NK/T cell lymphoma involving the endometrium of the uterus has been reported in the English literature [2-5]. There was no report of such case in uterus associated with adenomyosis.…”

Two Cases of Non-Hodgkin’s Lymphoma Involving the Uterus

“…Until present, there have been a considerable number of case reports describing uterine involved NHL. A Medline search resulted in nine case reports describing total of 10 cases of primary uterine lymphoma within the past 5 years [5][6][7][8][9][10][11][12][13]. A summary is shown in Table 1.…”