Extranodal NK/T-cell Lymphoma, Nasal Type
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ORIGINAL ARTICLE
Extranodal NK/T-cell Lymphoma, Nasal Type
A Report of 73 Cases at MD Anderson Cancer Center
Shaoying Li, MD,* Xiaoli Feng, MD,* Ting Li, MD,w Shuang Zhang, MD,w Zhuang Zuo, MD, PhD,*
Pei Lin, MD,* Sergej Konoplev, MD, PhD,* Carlos E. Bueso-Ramos, MD, PhD,*
Francisco Vega, MD, PhD,* L. Jeffrey Medeiros, MD,* and C. Cameron Yin, MD, PhD*
Abstract: Extranodal NK/T-cell lymphoma, nasal type
(ENKTL) is uncommon in the United States. We report 73
E xtranodal NK/T-cell lymphoma, nasal type (ENKTL)
is a rare type of lymphoma that is endemic to East
Asia and parts of Central and South America. Most (80%
patients with ENKTL, including 49 men and 24 women (median to 90%) patients present with nasal obstruction, sinusitis,
age, 46 y). Sixty-three patients had nasal/upper aerodigestive ulcer, and epistaxis due to a destructive mass involving
tract disease; 10 had extranasal disease involving skin, small the midline facial tissues. ENKTL most often presents as
intestine, epiglottis, testis, adrenal glands, kidney, and breast. a localized disease, clinical stage I-II; however, wide-
Complete staging data were available for 68 patients: 44 stage spread dissemination can occur in a subset of patients.
I/II and 24 stage IV. Fifteen of 69 (22%) had lymphadenopathy Occasionally, patients with ENKTL present with only
and 10/63 had bone marrow involvement. Histologically, 67/73 extranasal sites of disease, most often skin, lung, and
(92%) showed necrosis, and 48/70 (69%) had an angiocentric/ gastrointestinal tract, but a variety of other extranasal
angiodestructive growth pattern. The neoplastic cells showed a sites have been reported.1–9
wide spectrum: medium sized (n = 34), mixed small and large Accurate diagnosis of ENKTL can be challenging,
(n = 21), large (n = 13), and small (n = 5). In situ hybridization especially in small biopsy specimens or in frozen sections,
for Epstein-Barr virus–encoded small RNA was positive in every as the neoplastic cells are often admixed with in-
case. Immunohistochemical studies showed expression of cyto- flammatory cells and necrosis. An angiocentric and an-
toxic markers (100%), T-bet (96%), CD2 (96%), CD3 (93%), giodestructive growth pattern is common and has been
CD56 (90%), and ETS-1 (64%). Ki-67 was Z60% in 46% emphasized in the literature, but this pattern is not in-
cases. Therapy was known for 64 patients; 14 received only variable.1 Most cases of ENKTL are thought to be of
chemotherapy, 8 radiation alone, and 42 received combined NK-cell lineage or derived from an NK/T-cell precursor
radiation and chemotherapy. Median survival was 4.2 years, cell, but a subset of cases meets the criteria for T-cell
and 5-year overall survival was 46% (median follow-up, 3.8 y). lineage.1 In the 2008 World Health Organization classi-
Extranasal disease, high International Prognostic Index score, fication, presence of Epstein-Barr virus (EBV), usually
and high proliferation rate correlated with poorer prognosis. We shown by assessment for EBV-encoded small RNA
conclude that ENKTL cases in the United States are similar to (EBER), was included in the disease definition, and EBV
those reported in Asia and other countries. Absence of the an- has been implicated in disease pathogenesis.1,10–13
giocentric/angiodestructive pattern and presence of lympha- Although the clinicopathologic features of ENKTL
denopathy, features underemphasized in the literature, occurred are well recognized, most current data are derived from
in appreciable subsets of patients. The International Prognostic patient populations in endemic regions, particularly East
Index score, anatomic site of disease, and proliferation rate had Asia.3,5–7 Data on patients with ENKTL in developed
prognostic value in this patient cohort. countries are limited.9 In this study, we report the clin-
Key Words: extranodal NK/T-cell lymphoma, nasal type, icopathologic and immunophenotypic features of a large
southern United States series of patients with ENKTL at our institution in the
United States.
(Am J Surg Pathol 2013;37:14–23)
MATERIALS AND METHODS
From the *Department of Hematopathology, The University of Texas Case Selection
MD Anderson Cancer Center, Houston, TX; and wDepartment of
Pathology, Peking University First Hospital, Beijing, China. We searched the database of the Department of
Conflicts of Interest and Source of Funding: The authors have disclosed Hematopathology at The University of Texas MD An-
that they have no significant relationships with, or financial interest derson Cancer Center from January 1, 1985 to March 31,
in, any commercial companies pertaining to this article. 2012 for cases of ENKTL. The diagnosis was based on
Correspondence: C. Cameron Yin, MD, PhD, Department of Hema-
topathology, The University of Texas MD Anderson Cancer Center, morphologic and immunophenotypic criteria as specified
Houston, TX 77030 (e-mail: cyin@mdanderson.org). in the World Health Organization classification.1 Clinical
Copyright r 2012 by Lippincott Williams & Wilkins information was obtained by review of medical records.
14 | www.ajsp.com Am J Surg Pathol Volume 37, Number 1, January 2013
Am J Surg Pathol Volume 37, Number 1, January 2013 Nasal ENKTL From the United States
Hematoxylin-eosin-stained slides of tissue biopsy and RESULTS
bone marrow biopsy specimens and Wright-Giemsa-
stained bone marrow aspirate smears and touch imprints Clinical Features
were reviewed. The study group was composed of 73 patients with
ENKTL, including 49 men and 24 women. The median
age at the time of diagnosis was 46 years (range, 18 to
Immunophenotypic Analysis 88 y). There were 43 (59%) whites, 18 (25%) Hispanics, 8
Immunohistochemical studies were performed using (11%) Asians, 2 (3%) African Americans, and 2 patients
formalin-fixed, paraffin-embedded tissue sections as de- of unknown race. Sixteen of 67 (24%) patients with
scribed previously.14 Tissue sections of 4 mm thickness available history had B-type symptoms. Sixty-three (86%)
were deparaffinized, and endogenous peroxidase was patients had tumors in the nasal/upper aerodigestive tract
blocked with hydrogen peroxide. Heat-induced epitope region, and 10 presented with extranasal sites of in-
retrieval was performed using citrate buffer, pH 6.0. The volvement. Patients with nasal disease presented with
monoclonal antibodies used are specific for CD2, CD3, nonspecific sinonasal symptoms, such as nasal ob-
CD4, CD5, CD7, CD8, CD20, CD30, CD56, TIA-1, struction, nasal drainage, or facial swelling. Forty-four
granzyme B, Ki-67 (Dako, Carpinteria, CA), CXCL13 (60%) patients had localized disease, stage I or II, and 24
(R&D Systems, Minneapolis, MN), and PD-1 (Cell patients had stage IV disease; complete staging in-
Marque, Rocklin, CA). Analysis for T-bet (H-210; 1:100; formation was not available for 5 patients. Ten patients
Santa Cruz, Santa Cruz, CA) and ETS-1 (1G11, 1:100; presented with extranasal disease involving the following
Santa Cruz) was performed using N-Histofine detection sites: skin (n = 3), small intestine (n = 2), epiglottis
kit (Nichirei Biosciences Inc., Japan). Nuclear staining for (n = 1), testis (n = 1), bilateral adrenal glands (n = 1),
T-bet and ETS-1 was considered positive as reported kidney (n = 1), and breast (n = 1). Seven of 10 patients
previously.15 In situ hybridization analysis for EBER was with extranasal disease had complete staging information:
performed for all cases as described previously.14 stage IV (n = 4), stage II (n = 1), and stage I (n = 2).
Flow cytometry immunophenotypic analysis was Twenty-four (33%) patients had >1 site involved. Fifteen
performed on cell suspensions of tissue biopsy or bone of 69 (22%) patients with complete clinical data had
marrow aspirate specimens using a FACScan or FACS- lymphadenopathy, and most of these patients had nasal
Calibur instrument (Becton-Dickinson Biosciences, San disease. Ten of 63 (16%) patients assessed had bone
Jose, CA) as described previously.16 The lymphocyte marrow involvement.
population was gated using side scatter and CD45 ex- Laboratory data were available for 66 patients. Ten
pression. The panel of monoclonal antibodies included (15%) patients had a hemoglobin level of
Li et al Am J Surg Pathol Volume 37, Number 1, January 2013
the third case the neoplastic cells were a mixture of small
TABLE 1. Clinical Features of ENKTL
and large cells. Two patients presented with gastro-
Features Presence Total Presence% intestinal disease involving the ileum or jejunum. The
Age >60 y 14 73 19 patients with disease in the ileum underwent segmental
Male 49 73 67 resection of the ileum revealing a 4.5 4.5 4.0 cm mass
White 43 73 59
Extranasal 10 73 14
associated with a perforation (Fig. 2). Microscopic ex-
Nasal 63 73 86 amination of both tumors in the gastrointestinal tract
B-symptoms 16 67 24 revealed that they were composed of small to medium-
Smoking 34 68 50 sized cells associated with necrosis, mucosal ulcer, and an
Hb < 11 g/dL 10 66 15 angiocentric growth pattern (Fig. 2). One patient had a
Platelet 2 17 63 27 periadrenal fat were diffusely replaced by a monomorphic
Ki-67Z60% 18 39 46 population of medium-sized lymphoid cells with brisk
Large cell morphology 13 71 18 mitotic activity (Fig. 3C). The clinical features of this case
BM indicates bone marrow; Hb, hemoglobin. have been reported previously.18 In 1 patient, a core
needle biopsy specimen from the right kidney and peri-
renal adipose tissue were effaced by ENKTL composed of
a diffuse proliferation of large lymphoma cells with ir-
Cytologically, the lymphoma cells exhibited a broad regular nuclei, distinct nucleoli, and dispersed chromatin.
spectrum, ranging from small (n = 5, 7%), to medium One case involved the epiglottis and was composed of
sized (n = 34, 46%), to large (n = 13, 18%), or mixed medium-sized cells with an angiocentric pattern, an-
small and large cells (n = 21, 29%) Fig. 1). In 1 neoplasm gioinvasion, and necrosis. In the patient who had
composed of large cells the neoplastic cells had anaplastic ENKTL involving the breast, the neoplasm was asso-
features. ciated with a breast implant placed for cosmetic reasons.
The 10 extranasal cases are described here in more This neoplasm was a diffuse proliferation composed of
detail. Skin biopsy specimens in 3 patients showed an medium-sized and large neoplastic cells extensively in-
extensive perivascular infiltrate within the dermis and volving breast parenchyma associated with extensive co-
subcutis. In 1 case, the infiltrate was composed of large agulative necrosis, numerous mitotic figures, and
lymphoid cells with irregular nuclei, fine chromatin, and apoptotic cells (Fig. 3D). Angiocentricity with angioin-
inconspicuous nucleoli. In a second case, the infiltrate was vasion was identified, but these areas were not a major
composed predominantly of medium-sized cells, and in component of the tumor.
TABLE 2. Clinical Features of ENKTL: Extranasal Group Versus Nasal Group
Extranasal Nasal
Features Presence Total Presence% Presence Total Presence%
Age >60 y 1 10 10 13 63 21
Male 7 10 70 42 63 67
White 5 10 50 38 63 60
B-symptoms 4 7 57 12 60 20
Smoking 3 7 43 31 61 51
Hb < 11 g/dL 2 7 29 8 59 14
Platelet 2 2 6 33 15 57 26
Ki-67Z60% 3 4 75 15 39 38
Large cell morphology 3 10 30 10 61 16
BM indicates bone marrow; Hb, hemoglobin.
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Am J Surg Pathol Volume 37, Number 1, January 2013 Nasal ENKTL From the United States
FIGURE 1. Microscopic features of ENKTL. The neoplastic cells exhibited a broad spectrum, ranging from small (A), to medium
sized (B), to large cells (C) (hematoxylin and eosin).
Immunophenotypic and Molecular Results CD5, and B-cell antigens. CD56 was positive in all 8 cases
Flow cytometry immunophenotypic analysis was assessed.
performed on 11 cases. In every case the neoplastic cells Immunohistochemical analysis was performed on
were positive for CD2, but negative for surface CD3, most cases. The antibody panel used was variable over
FIGURE 2. Morphologic features of a case of ENKTL in ileum. A, Grossly, the tumor presents as a fungating mass associated with a
perforation. B, Low-power view shows that the tumor is associated with necrosis and mucosal ulcer (hematoxylin and eosin). C,
High-power view shows that the tumor is composed of small to medium-sized cells with an angiocentric growth pattern
(hematoxylin and eosin). D, The lymphoma cells are positive for EBER by in situ hybridization.
r 2012 Lippincott Williams & Wilkins www.ajsp.com | 17Li et al Am J Surg Pathol Volume 37, Number 1, January 2013
FIGURE 3. Microscopic features of 3 cases of ENKTL arising from extranasal sites. A and B, A case of ENKTL arising from testis. The
tumor is composed of large neoplastic cells associated with mitotic figures and necrosis (hematoxylin and eosin). C, A case of
ENKTL arising from the adrenal gland. The adrenal parenchyma and periadrenal fat were replaced by a monomorphic population
of medium-sized cells (hematoxylin and eosin). D, A case of ENKTL involving the breast. The tumor cells are medium-sized to
large and are associated with angioinvasion, necrosis, and mitotic figures (hematoxylin and eosin).
time. For this study, additional immunostaining analyses cases, we assessed for CXCL13 and PD-1 expression. For
were performed on cases with available unstained slides. each antibody 4 cases (40%) were positive, but these
The neoplastic cells expressed CD2 (22/23; 96%), CD3 antigens were not expressed by the same 4 cases. In situ
(68/73; 93%), CD4 (9/31; 29%), CD5 (7/39; 18%), CD7 hybridization analysis for EBER was positive in all 73
(10/25; 40%), CD8 (11/33; 33%), CD30 (17/40; 43%), cases and in virtually all cells of each case (Fig. 4).
and CD56 (62/69; 90%). For the 7 cases negative for T-cell receptor-g gene rearrangement analysis was
CD56 by immunohistochemical analysis, 4 were assessed performed on 20 cases, including 15 nasal and 5 extra-
by flow cytometry, and all were positive for CD56. All nasal tumors. Monoclonal T-cell receptor-g gene
cases assessed expressed cytotoxic granule-associated
proteins, either TIA-1 (n = 30) or granzyme B (n = 19) or
both (n = 17). T-bet and ETS-1 were positive in 24/25 TABLE 3. Expression of T-bet and ETS-1 in Cases of ENKTL
(96%) and 16/25 (64%) of the cases, respectively T-bet (n = 25), [N (%)] ETS-1 (n = 25), [N (%)]
(Table 3). The proliferation index, as demonstrated by the
1 (4) 9 (36)
MIB1 (Ki-67) antibody, was assessed in 39 cases and 1+ 3 (12) 1 (4)
showed a median proliferation rate of 50% (range, 5% to 2+ 6 (24) 7 (28)
95%). Fifteen cases showed a low (< 30%) proliferation 3+ 15 (60) 8 (32)
rate, 6 had medium (30% to 59%) proliferative activity, indicates negative.
and 18 showed high (Z60%) proliferative activity. In 10
18 | www.ajsp.com r 2012 Lippincott Williams & WilkinsAm J Surg Pathol Volume 37, Number 1, January 2013 Nasal ENKTL From the United States
FIGURE 4. Immunohistochemical findings of ENKTL. Immunostains show that the tumor cells are positive for CD3 (A), CD56 (B),
and TIA-1 (C). The lymphoma cells are positive for EBER by in situ hybridization (D).
rearrangements were identified in 8 (40%) cases, including vincristine, and prednisone. Fourteen patients received
4 (27%) nasal and 4 (80%) extranasal cases. The stem cell transplantation. Treatment information was not
frequency of T-cell receptor gene rearrangements in nasal available for 9 patients.
versus extranasal tumors was not statistically significant For the 44 patients with low-stage (stage I/II) dis-
(P = 0.10; Fisher exact test). ease, 7 were treated with radiation alone, 2 chemotherapy
On the basis of combined immunophenotypic data alone, and 30 received combined radiation and chemo-
and molecular results we were able to determine the lin- therapy. For 5 patients, no treatment information is
eage of the neoplasms in 41 cases. Twenty-four of 41 available. OS was significantly better for patients treated
(59%) ENKTL were of NK-cell lineage, and 17 (41%) with combined radiation and chemotherapy rather than
cases were of T-cell lineage. In the subgroup of 11 cases radiation therapy alone (8.33 vs. 1.51 y, P = 0.013). For
assessed by flow cytometry and shown to be negative for the 24 patients with stage IV disease, there was no sig-
surface CD3, 2 cases had monoclonal T-cell receptor-g nificant difference in OS between patients treated with
gene rearrangements and were therefore classified as combined radiation and chemotherapy versus chemo-
T-cell lineage. In 32 cases in this study the data were therapy alone (P = 0.29; Fig. 5).
incomplete, and lineage could not be assigned. With a median follow-up of 3.8 years (range, 0.04 to
19.33 y), 30 (42%) patients died. The median OS was
Treatment and Clinical Outcome 4.2 years (95% confidence interval, 1.27-7.07 y), and
Fourteen patients were treated with various che- the 5-year OS was 46%. The median PFS was 3 years
motherapy regimens, 8 patients were treated only with (95% confidence interval, 2.17-4.29 y). Patients with ex-
radiation therapy, and 42 received combined radiation tranasal disease had a significant shorter OS compared
and chemotherapy. The most commonly used chemo- with patients who had nasal disease (0.55 vs. 5.01 y;
therapy regimen was cyclophosphamide, doxorubicin, P = 0.045).
r 2012 Lippincott Williams & Wilkins www.ajsp.com | 19Li et al Am J Surg Pathol Volume 37, Number 1, January 2013
FIGURE 5. Overall survival of patients with ENKTL by therapy. A, Stage I/II. B, Stage IV.
Prognostic Factors (Fig. 6). After adjusting for therapy, extranasal disease
We performed univariate analysis to evaluate the (P = 0.005, hazard ratio = 69.04) and IPI score >2
association between 17 clinicopathologic features and (P = 0.037, hazard ratio = 29.58) were independent risk
prognosis (Table 4). The results showed that extranasal factors for worse OS (P = 0.005). Among the 17 factors
disease, hemoglobin 2 were associated with poorer OS
(P < 0.05). Except for extranasal disease, ALC < 1000/
mL, elevated serum LDH, and large cell morphology, DISCUSSION
these factors were also associated with a worse PFS ENKTL has a strong ethnic and geographic predi-
(P < 0.05). Presence of B-symptoms and thrombocyto- lection, being most common in Asia and in Native
penia (platelet 60 vs. r60 y) 0.275 1.90 0.64-5.58 0.486 1.43 0.52-3.90
Sex 0.490 1.25 0.57-2.74 0.660 1.19 0.54-2.63
B-symptoms 0.064 2.36 0.95-5.87 0.047 2.54 1.00-6.44
Smoking 0.352 1.45 0.67-3.14 0.171 1.73 0.79-3.77
Hb (< 11 vs. Z11 g/dL) 0.037 3.83 1.09-12.55 0.035 3.94 1.10-13.99
Platelet (low vs. normal) 0.060 2.74 0.92-8.19 0.001 9.87 2.51-38.79
ALC (< 1000 vs. Z1000/mL) 0.023 2.52 1.14-5.59 0.078 2.08 0.96-4.54
LDH (high vs. normal) 0.011 3.10 1.30-7.34 0.063 2.16 0.96-4.91
b2M (high vs. normal) 0.027 3.53 1.15-10.67 0.033 3.37 1.12-10.65
Lymphadenopathy 0.230 0.60 0.26-1.38 0.280 0.63 0.27-1.46
BM involvement 0.311 1.98 0.54-7.97 0.375 1.79 0.49-6.52
Extranodal sites Z2 0.008 3.27 1.37-7.82 0.001 4.63 1.83-11.72
Ki-67 (Z60% vs. 2 vs. r2) 0.000 10.50 3.67-32.47 0.001 6.87 2.38-18.16
BM indicates bone marrow; CI, confidence interval; Hb, hemoglobin; HR, hazard ratio.
20 | www.ajsp.com r 2012 Lippincott Williams & WilkinsAm J Surg Pathol Volume 37, Number 1, January 2013 Nasal ENKTL From the United States
FIGURE 6. Survival of patients with ENKTL by IPI. A, OS. B, PFS.
series from Asian countries,3,5–7 with a recent large study shown). None of these B-cell lymphomas was positive for
from Brazil2 and only rare reports of small series from T-bet or ETS-1. These results suggest that T-bet and ETS-
developed countries.9 In this study, we analyzed the 1 may have biological roles in ENKTL pathogenesis. The
clinicopathologic, immunophenotypic, and prognostic results also indicate that T-bet is a sensitive marker for
characteristics of 73 cases of ENKTL seen at our in- ENKTL, equivalent to pan-T/NK markers such as CD2
stitution in the United States. The clinical features of this or CD3 but more specific for ENKTL. Therefore, we
cohort are similar to those reported in Asian countries,5–7 conclude that T-bet can be a valuable addition to an
with a male predominance, a wide age range with a me- antibody panel for the workup of suspected cases of
dian age at diagnosis of 46 years, a predilection for the ENKTL.
nasal cavity and paranasal sinuses, and an association We also assessed for expression of 2 follicular T-
with nonspecific symptoms related to nasal obstruction helper–associated markers, CXCL13 and PD-1, in a small
or sinusitis. Unlike other studies, however, in this study subset of cases and found that each marker was expressed
extranasal disease was relatively less common. The in 40% of cases, in an apparently mutually exclusive
ratio of extranasal to nasal disease in this study, 1 to 6.3, manner. We initially found these results surprising as
was much lower compared with ratios of approxi- ENKTL is thought to be derived from cytotoxic NK or T
mately 1 to 3 or 4 in other studies in the literature.3,5,9,19 cells. However, Gualco et al2 showed CXCL13 expression
Recently, newer markers have been used in the in a small subset of the ENKTL cases they studied, and
evaluation of ENKTL. We assessed these markers in a more recently Pongpruttipan et al20 suggested that
subset of cases with available blocks or unstained slides. CXCL13 was expressed more frequently in ENKTL of
T-bet is a transcription factor that plays an essential role NK-cell lineage, whereas PD-1 was seen more often in
in the development and differentiation of lymphocytes. ENKTL of T-cell lineage. We could not appreciate this
T-bet is expressed widely in CD8+ T lymphocytes, NK correlation, but the number of cases we assessed was too
cells, a subset of B cells, monocytes, and dendritic cells.15 small to draw any conclusions.
T-bet has also been reported to be overexpressed in The role of proliferation rate in the prognosis of
ENKTL and a subset of unspecified cases of peripheral T- patients with ENKTL has been reported in only a few
cell lymphoma but not in most B-cell lymphomas.15 ETS- studies in the literature. Ki-67Z65% has been reported
1 has been shown to be an important cofactor of T-bet to be associated with worse prognosis in stage I/II
and positively regulates the development and cytotoxic ENKTL,21 and Ki-67 > 50% predicted poor OS in an-
function of NK cells.15 ETS-1 has also been reported to other study.3 Our results showed that Ki-67Z60% pre-
be expressed in ENKTL but not in peripheral T-cell dicted poorer OS and PFS. For the 39 cases with Ki-67
lymphoma or B-cell lymphomas.15 To date, most cases of results available, 18 (46%) had Ki-67Z60%. The OS for
ENKTL assessed for T-bet and ETS-1 have been from patients with ENKTL with Ki-67Z60% was 2.68 years
Asia. In this study, we used immunohistochemical versus 5.83 years for patients with ENKTL with
methods to assess for T-bet and ETS-1, and these markers Ki-67 < 60% (P = 0.01). Similarly, PFS was shorter for
were expressed in 96% and 64% of cases, respectively. patients with ENKTL with high Ki-67: 2.25 years if Ki-
For the sake of comparison, we also assessed 10 B-cell 67Z60% versus 4.17 years if Ki-67 < 60% (P = 0.03).
lymphomas for T-bet or ETS-1 expression, including The median survival and 5-year OS of patients with
diffuse large B-cell lymphoma (n = 5), follicular lym- ENKTL reported in the literature ranges from 13 to 42
phoma (n = 3), mantle cell lymphoma (n = 1), and ex- months and 20% to 65%, respectively.3,5–7,21–26 Our study
tranodal marginal zone lymphoma (n = 1) (data not showed similar results with a median survival of 4.2 years
r 2012 Lippincott Williams & Wilkins www.ajsp.com | 21Li et al Am J Surg Pathol Volume 37, Number 1, January 2013 and a 5-year OS of 46%. Previous studies have shown that whether the presence of an angiocentric/angioinvasive the following features are associated with poorer clinical pattern could simply be related to biopsy specimens, with outcome: age (> 60 y), male sex, presence of B-symptoms, larger specimens more likely to have an angiocentric elevated serum LDH, hemoglobin
Am J Surg Pathol Volume 37, Number 1, January 2013 Nasal ENKTL From the United States
8. Barrionuevo C, Zaharia M, Martinez MT, et al. Extranodal NK/T- 19. Oshimi K, Kawa K, Nakamura S, et al. NK-cell neoplasms
cell lymphoma, nasal type: study of clinicopathologic and prognosis in Japan. Hematology. 2005;10:237–245.
factors in a series of 78 cases from Peru. Appl Immunohistochem Mol 20. Pongpruttipan T, Sukpanichnant S, Assanasen T, et al. Extranodal
Morphol. 2007;15:38–44. NK/T-cell lymphoma, nasal type, includes cases of natural killer cell
9. Panano L, Gallamini A, Trape G, et al. NK/T-cell lymphomas and ab, rd, and ab/gd T-cell origin: a comprehensive clinicopatho-
‘nasal type’: an Italian multicentric retrospective survey. Ann Oncol. logic and phenotypic study. Am J Surg Pathol. 2012;36:481–499.
2006;17:794–800. 21. Kim SJ, Kim BS, Choi CW, et al. Ki-67 expression is predictive of
10. Kanavaros P, Lescs MC, Briere J, et al. Nasal T-cell lymphoma: a prognosis in patients with stage I/II extranodal NK/T-cell lympho-
clinicopathologic entity associated with peculiar phenotype and with ma, nasal type. Ann Oncol. 2007;18:1382–1387.
Epstein-Barr virus. Blood. 1993;81:2688–2695. 22. Lee J, Park YH, Kim WS, et al. Extranodal nasal type NK/T-cell
11. Medeiros LJ, Jaffe ES, Chen YY, et al. Localization of Epstein-Barr lymphoma: elucidating clinical prognostic factors for risk-based
viral genomes in angiocentric immunoproliferative lesions. Am J stratification of therapy. Eur J Cancer. 2005;41:1402–1408.
Surg Pathol. 1992;16:439–447. 23. Harabuchi Y, Takahara M, Kishibe K, et al. Nasal natural killer
12. Harabuchi Y, Imai S, Wakashima J, et al. Nasal T-cell lymphoma (NK)/T-cell lymphoma: clinical, histological, virological, and
causally associated with Epstein-Barr virus: clinicopathologic, genetic features. Int J Clin Oncol. 2009;14:181–190.
phenotypic, and genotypic studies. Cancer. 1996;77:2137–2149. 24. Lim ST, Hee SW, Quek R, et al. Comparative analysis of extra-
13. Harabuchi Y, Yamanaka N, Kataura A, et al. Epstein-Barr virus in nodal NK/T-cell lymphoma and peripheral T-cell lymphoma:
nasal T-cell lymphomas in patients with lethal midline granuloma. significant differences in clinical characteristics and prognosis. Eur
Lancet. 1990;335:128–130. J Haematol. 2008;80:55–60.
14. Kanungo A, Medeiros LJ, Abruzzo LV, et al. Lymphoid neoplasms 25. Ng SB, Lai KW, Murugaya S, et al. Nasal-type extranodal natural
associated with concurrent t(14;18) and 8q24/c-MYC translocation killer/T-cell lymphomas: a clinicopathologic and genotypic study of
generally have a poor prognosis. Mod Pathol. 2006;19:25–33. 42 cases in Singapore. Mod Pathol. 2004;17:1097–1107.
15. Zhang S, Li T, Zhang B, et al. Transcription factors engaged in 26. Bossard C, Belhadj K, Reyes F, et al. Expression of the granzyme B
development of NK cells are commonly expressed in nasal NK/ inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma:
T-cell lymphomas. Hum Pathol. 2011;42:1319–1348. results of a Western series of 48 patients treated with first-line
16. Yin CC, Lin P, Carney DA, et al. Chronic lymphocytic leukemia/ polychemotherapy within the Groupe d’Etude des Lymphomes de
small lymphocytic lymphoma associated with IgM paraprotein. Am l’Adulte (GELA) trials. Blood. 2007;109:2183–2189.
J Clin Pathol. 2005;123:594–602. 27. Huang JJ, Zhu YJ, Xia Y, et al. A novel prognostic model for
17. Vega F, Medeiros LJ, Jones D, et al. A novel four-color PCR assay extranodal natural killer/T-cell lymphoma. Med Oncol. 2011. [Epub
to assess T-cell receptor gamma gene rerarrangements in lympho- ahead of print].
proliferative lesions. Am J Clin Pathol. 2001;116:17–24. 28. Jaffe ES, Chan JKC, Su IJ, et al. Report of the workshop on nasal
18. Thompson MA, Habra MA, Routbort MJ, et al. Primary adrenal and related extranodal angiocentric T/natural killer cell lymphomas:
natural killer/T-cell nasal type lymphoma: first case report in adults. definition, differential diagnosis, and epidemiology. Am J Surg
Am J Hematol. 2007;82:299–303. Pathol. 1996;20:103–111.
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