{"paper_id":"52b35f37-04e5-4a16-b3f4-1622a29b3893","body_text":"C A S E R E P O R T Open Access\nPrimary extranodal NK/T cell lymphoma, nasal-type\nof uterus with adenomyosis: a case report\nJian-chen Fang *, Jue Zhou, Zheng Li and Zhao-xia Xia\nAbstract\nNatural killer (NK)/T cell lymphoma of the female genital tract is extremely rare. We here report a case of ‘nasal type ’\nNK/T cell lymphoma arising in the uterus with adenomyosis in a 41-year-old woman with fever and hypogastralgia.\nThe histologic analysis demonstrated a highly aggressive tumor with characteristic angiocentric/angiodestructive\ngrowth pattern and focal necrosis. The lymphoma cells displayed a CD3 ε/CD56/TIA-1/granzyme-B/Perforin-positive\nand CD20/CD79a/CD4/CD8-negative immunophenotype and positive for Epstein-Barr virus by EBER in situ\nhybridization. Clinically, the disease was limited to the uterus at the initial diagnosis, but progressed rapidly. The\npatient died on day 54 after hysterectomy, irrespective of intensive chemotherapy.\nVirtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.\neu/vs/1323474831125945\nKeywords: Uterus, NK/T cell lymphoma, Extranasal type\nBackground\nPrimary lymphoma of the female genital tract is uncom-\nmon with a frequency of only 0.002% in all patients with\nextranodal lymphomas [1]. The majority of these cases\nrepresent aggressive B-cell lymphomas. Involvement of\nthe gynecological tract by NK/T cell lymphomas is con-\nsidered to be extremely rare and only 5 cases with pri-\nmary NK/T cell lymphoma involving the endometrium\nof the uterus has been reported in the English literature\n[2-5]. There was no report of such case in uterus associ-\nated with adenomyosis. Here, we report the first case of\nprimary NK/T cell lymphoma arising in the uterus with\nadenomyosis.\nCase presentation\nClinical history\nA 41 year-old woman, without relevant previous anam-\nnesis, presented with fever and hypogastralgia for 2 months.\nComputer tomography and ultrasonography revealed en-\nlargement of the uterus and multinodular intrauterine\nmass. A hysterectomy was performed. She was diag-\nnosed as extranodal NK/T cell lymphoma, nasal-type.\nAfter surgical resection, the patient was treated with\nCHOP chemotherapy (cyclophosphamide, vincristine,\ndaunorubicin and dexamethasone). Despite extensive\nchemotherapy, the disease progressed rapidly; shortly\nfollow-up radiological imaging showed the retroperi-\ntoneal involvement. The p atient died on day 54 after\nsurgical resection of the tumor.\nPathological findings\nMacroscopic examination displayed a yellow, soft, poorly\ncircumscribed mass that invaded about 4 cm in uterine\nwall (Figure 1). Histopathological evaluation revealed lym-\nphomatous infiltrate the endometrial gland (Figure 2A)\nand myometrium with well demarcated large areas of\ncoagulative necrosis containing apoptotic nuclear deb-\nris (Figure 2B). The tumor cells demonstrated a prom-\ninent angioinfiltrative gr owth pattern with concentric\narrangement around small arteries (Figure 2C). The\nlymphoma cells were densely packed, with an abundant\ncytoplasm and enlarged nuclei with open chromatin and\nseveral large nucleoli. Mitotic figures were frequently seen.\nThere was adenomyosis in myometrium without tumour\ninvolvement (Figure 2D).\nThe tumor cells were positive for cytoplasmic CD3\nand membranous CD56 (Figiures 3A and Figure 3B) but\nnegative for CD4, CD5, CD8, CD20, CD79 α, CD30. Cyto-\ntoxic proteins TIA-1 (Figure 3C), granzyme-B and Perforin\ndisplayed strong cytoplasmic granular staining pattern.\n* Correspondence: jianchenfang@sina.com\nNingbo Diagnostic Pathology Center, Ningbo 315031, China\n© 2014 Fang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative\nCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and\nreproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain\nDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,\nunless otherwise stated.\nFang et al. Diagnostic Pathology 2014, 9:95\nhttp://www.diagnosticpathology.org/content/9/1/95\n\nEBER in situ hybridization demonstrated strong posi-\ntivities for all tumor cells (Figure 3D). Based on the\noverall morphological, i mmunophenotypical and EBV\ncharacteristics, the diagnos is of extranodal (uterine)\nNK-cell lymphoma, nasal-type was made.\nDiscussion\nExtranodal NK/T-cell lymphomas characteristically in-\nvolve the upper aerodigestive tract, with the nasal cavity\nbeing the prototypic site [6]. Rarely, the tumour occurs\nin prostate, adrenal glands and lung [7-9]. Thus far, only\na few cases of T- or NK/T-cell neoplasms involved\nuterus have been reported [2-5]. Like most of NK/T cell\nlymphoma in other anatomic sites, these lymphomas in\nthe uterus usually are highly aggressive, and conven-\ntional prognostic factors usually fail to predict their outcome\n[10]. While clinical presentation of NK/T cell lymphoma in-\nvolving the uterus may include vaginal bleeding, and abdom-\ninal or pelvic pain [11], our patient presented with fever and\nhypogastralgia with no evidence of vaginal bleeding. As the\ncommon pathological features of NK/T cell lymphoma\ndefined by WHO classification, the current case dem-\nonstrated a highly aggressive tumor with characteristic\nangiocentric/angiodestruct ive growth pattern and asso-\nciated focal necrosis.\nInterestingly, there is uterus adenomyosis present nearby\nthe lymphoma in the current case; perhaps it might be an\nimportant factor contributing to the onset and process of\nthe tumor. Occurrence of T cells and CD56+ NK cells\nwithin the normal endometrium has been described [12].\nIt seems to be established that uterine NK cells form a\ndynamic lymphoid pool in each menstruation cycle.\nOne could expect that these cells may frequently undergo\ngenetic and regulatory errors leading to malignant trans-\nformation [2]. For this reason it is difficult to understand,\nwhy uterine NK-cells transform to malignant lymphoma\nwith such a low frequency. As one possible explanation,\nthe relatively short duration of a menstrual cycle and the\nregular shed of the endometrium may prevent the expan-\nsion and malignant transformation of NK cells [2]. In the\npresented case, the presence of adenomyosis may prevent\nthe normal NK cell duration and cycling in the uterus,\nperhaps provide the evidence that NK cells frequently\nFigure 1 Macroscopic view. Macroscopic examination displayed a\nyellow, soft, poorly circumscribed mass.\nFigure 2 Histological features of this case. A , Dense lymphomatous cells infiltrate endometrium,partially covered by intact columnar epithelium\n(HE, ×40 magnification).B, The lymphomatous proliferation was interrupted by coagulative necrotic areas (HE, ×200 magnification).C, Angiocentric and\nangiodestructive growth pattern is frequently present (HE, ×100 magnification).D, Adenomyosis in myometrium without lymphomatous infiltrate (HE, ×40\nmagnification).\nFang et al. Diagnostic Pathology 2014, 9:95 Page 2 of 4\nhttp://www.diagnosticpathology.org/content/9/1/95\n\nremained in uterine corps undergo genetic and regulatory\nerrors leading to malignant transformation. The associ-\nation of adenomyosis with NK/T-cell lymphoma was\nlargely not mentioned previously, because that the major-\nity of cases reported with NK/T cell lymphoma in uterus\noften diagnosed by curettage, the way impossible to find\nadenomyosis.\nAccording the WHO criterion, the neoplastic lymphoid\ncells usually coexpress NK cell markers such as CD56 and T\ncell-associated antigens like CD3, CD2 with expression of\ncytotoxic markers such as TIA-1, Perforin and Granzyme-B\n[6]. The current case demonstrated the immuno charac-\nteristics of tumor cells are typical nasal-type NK/T cell\nlymphoma: CD3+, CD56+, TIA1+, Perforin+, Granzyme\nB+. As a hallmark of nasal type NK/T cell lymphoma,\nEBV in situ hybridization clearly supported EBV infec-\ntion of the lymphoma cells. TIA-1 and EBER were the\ntwo most sensitive markers of the disease. However\nPCR-based TCR gene rearrangement analysis might not\nbe a useful technique for making diagnosis of NK/T cell\nlymphoma [13]. Latent membrane protein (LMP) 1 and\nLMP2A encoded by Epstein-Barr virus were associated\nwith the development of malignancies. High expression\nof the two proteins could independently predict poor\noverall survival [14].\nNK/T cell lymphomas were reported to have a median\nsurvival of only 0.28 years [15]. One case of NK/T cell\nlymphomas involved prostate was reported recently, the\npatient died within 4 months after diagnosis [7]. In an-\nother case of the lymphomas occurred in bilateral ad-\nrenal glands, the patient died only 33 days after initial\npresentation [8]. In the present case, the patient died\n54 days (0.15 year) after hysterectomy. Unfortunately,\ntreatment experience is mostly limited to the upper\naerodigestive tract disease. Extranodal NK/T cell lymph-\nomas of other sites are extremely rare and very limited data\nfor optimal treatment strategies are currently available.\nConclusion\nThis case demonstrated a rare NK/T cell lymphoma pri-\nmarily in the uterus, providing a diagnostic pitfall: pa-\nthologists and gynecologists should be aware of its\nexistence and need to consider NK/T cell lymphomas\nwithin the spectrum of differential diagnosis of neoplas-\ntic tumor in the uterus. Because of the clinical aggres-\nsiveness and dismal prognosis of the tumor, more\neffective therapeutic regimens should be actively looked.\nConsent\nWritten informed consent was obtained from the fam-\nily of the patient for publication of this case report and\nany accompanying images. A copy of the written con-\nsent is available for review by the Editor-in-Chief of\nthis journal.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthors’ contributions\nJC F analyzed the data and wrote the manuscript as a major contributor.\nZX X, Z L helped to perform the immunochemical staining. J Z helped to\nrevise the discussion section of this m anuscript. All authors have read and\napproved the final manuscript.\nFigure 3 Phenotypic characteristics of tumor cells. A , The lymphoma cells showed cytoplasmic CD3 ε B and C, Membranous CD56 and\ncytoplasmic granular TIA-1 positivity by immunohistochemistry (×200 magnification). D, In situ hybridization for EBER sequences clearly supported\nEBV infection of the lymphoma cells (×200 magnification).\nFang et al. Diagnostic Pathology 2014, 9:95 Page 3 of 4\nhttp://www.diagnosticpathology.org/content/9/1/95\n\nAcknowledgment\nWe thank Professor Qin Huang for checking and editing the manuscript for\nEnglish.\nReceived: 3 April 2014 Accepted: 11 May 2014\nPublished: 23 May 2014\nReferences\n1. Latteri MA, Cipolla C, Gebbia V, Lampasona G, Amato C, Gebbia N: Primary\nextranodal nonhodgkin lymphomas of the uterus and the breast: Report\nof three cases. Eur J Surg Oncol 1995, 21:432–434.\n2. Méhes G, Hegyi K, Csonka T, Fazakas F, Kocsis Z, Radványi G, Vadnay I, Bagdi E,\nKrenács L: Primary Uterine NK-Cell Lym phoma, Nasal-Type: A Unique\nMalignancy of a Prominent Cell Type of the Endometrium. Pathol\nOncol Res 2012, 18:519–522.\n3. Briese J, Noack F, Harland A, Horny HP: Primary Extranodal NK/T Cell\nLymphoma (‘Nasal Type ’) of the Endometrium: Report of an Unusual\nCase Diagnosed at Autopsy. Gynecol Obstet Invest 2006, 61:164–166.\n4. 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Blood 2009,\n113(17):3931–3937.\ndoi:10.1186/1746-1596-9-95\nCite this article as: Fang et al. : Primary extranodal NK/T cell lymphoma,\nnasal-type of uterus with adenomyosis: a case report.Diagnostic Pathology\n2014 9:95.\nSubmit your next manuscript to BioMed Central\nand take full advantage of: \n• Convenient online submission\n• Thorough peer review\n• No space constraints or color figure charges\n• Immediate publication on acceptance\n• Inclusion in PubMed, CAS, Scopus and Google Scholar\n• Research which is freely available for redistribution\nSubmit your manuscript at \nwww.biomedcentral.com/submit\nFang et al. Diagnostic Pathology 2014, 9:95 Page 4 of 4\nhttp://www.diagnosticpathology.org/content/9/1/95","source_license":"CC0","license_restricted":false}