# CD7-Positive Diffuse Large B-Cell Lymphoma Presenting as an Intranasal Tumor

Authors: Kazuaki Teshima; Masaaki Kume; Yasushi Kawaharada; Takashi Saito; Ko Abe; Sho Ikeda; Hideaki Ohyagi; Megumi Zuguchi; Masashi Zuguchi; Yosuke Kubota; Yoshitaka Enomoto; Masahito Miura; Satsuki Takahashi; Masahiro Saito; Ken Saito; Naoto Takahashi
Journal: Case Reports in Hematology
 (2020)

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## Abstract

We report a case of a 74-year-old man with a cluster of differentiation (CD) 7-positive diffuse large B-cell lymphoma (DLBCL) in the right nasal cavity. Flow cytometry analyses showed CD7 and CD20 positivity in tumor cells. The patient received 6 cycles of R-CHOP plus local radiation therapy because positron emission tomography-computed tomography after R-CHOP revealed an intranasal lesion. The patient achieved complete remission (CR) after radiation therapy. The frequency of CD7-positive DLBCL is rare, and only 11 cases with follow-up of clinical course have been reported thus far. CR or partial response was noted in 8 of 11 cases after receiving rituximab combined with chemotherapy. In total, 9 of 12 cases involved the development of extranodal lesions, which occurred as an intranasal tumor in 3 cases. It is important to examine the clinical features by accumulation of further cases.


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## Body

## 1. Introduction

Aberrant expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) is occasionally observed in diffuse large B-cell lymphoma (DLBCL) [1]. In particular, expression of CD5 is noted in approximately 10% DLBCL cases, and it is related to a poor prognosis [2]. However, the clinical significance of the expression of other T-cell markers, including CD7, is unclear. Here, we report a rare case of CD7-positive DLBCL presenting as an intranasal tumor.


## 2. Case Presentation

A 74-year-old male patient with a history of left lung inferior lobe resection due to localized lung cancer who complained of rhinostenosis was diagnosed with a tumor in the right nasal cavity (Figure1(a)). Positron emission tomography-computed tomography (PET-CT) showed intense focal uptake of SUVmax 18.3 in the right nasal cavity (Figure 1(b)). The tumor biopsy showed diffuse proliferation of large, atypical lymphoid cells. Flow cytometry (FCM) analyses showed clear CD7 and CD19 positivity in the tumor cells, while CD20 was expressed at weak intensity (Figure 1(d)). These data were analyzed by FACSCanto II (BD Biosciences) using the antibody of CD7 (3A1-RD1; Beckman Coulter). These data were obtained from the SRL Laboratory (Hachioji city, Tokyo, Japan). Immunohistochemistry (IHC) results were positive for L26 (CD20), bcl-2, bcl-6, and MUM1 and negative for CD3, CD4, CD8, CD7 (LP15; Novocastra), CD10, and EBER (Figure 1(c)). Fluorescent in situ hybridization (FISH) did not reveal IgH/c-MYC rearrangement. Southern blotting revealed immunoglobulin heavy-chain gene rearrangement, however not T-cell receptor (TCR) gene rearrangement. Bone marrow biopsy was negative for the involvement of atypical large cells. The patient was diagnosed with stage IA DLBCL. The patient received 6 cycles of R-CHOP therapy; however, residual disease was found on the PET-CT. Therefore, the patient received local radiation therapy for the residual disease. He achieved complete remission after radiation therapy. At 18 months after chemoradiation therapy, there was no evidence of recurrence.Figure 1
Imaging findings: (a) brain computed tomography scan at diagnosis; (b) positron emission tomography-computed tomography findings at diagnosis; (c) pathological findings at diagnosis (hematoxylin and eosin staining) and immunostaining with anti-CD3, anti-CD4, anti-CD8, anti-CD7, and anti-CD20; (d) flow cytometry analysis at diagnosis.
(a)
(b)
(c)
(d)


## 3. Discussion

CD7 is expressed on the surface of most thymocytes and T-cells preceding TCR-β-chain gene rearrangement and is the earliest differentiation antigen found during T-cell development [3]. Aberrant T-cell marker expression is occasionally observed in B-cell lymphoma [4]. Inaba et al. reported that CD7 was expressed in 5 (5%) of 101 DLBCL patients [5]. Table 1 describes the clinical characteristics of 12 cases, including the present case, of CD7-positive DLBCL reported thus far. Two cases were detected by FCM, 1 case was detected by IHC, and 9 cases were detected with both. In the present case, FCM showed CD7 positivity and IHC showed CD7 negativity. There are several possible causes for CD7-negative immunostaining results. One reason is that the antigenicity of CD7 may decline in the process of formalin fixation. Another reason is that epitope of lymphoma may be different from that of normal cells. FCM shows CD7 expressions despite no expression of CD3. Clonal immunoglobulin heavy-chain rearrangement was observed using Southern blotting, which detected no clonal TCR gene rearrangement. This means that clonally restricted B-cells in our DLBCL case express CD7. Suzuki et al. reported that aberrant T-cell marker expression detected by FCM could be confirmed in some, but not in all, cases detected by IHC [6]. They reported that among 6 CD7-positive cases by FCM, only 3 were confirmed to be positive for CD7 by IHC. They considered that it was important to employ FCM because the ability of IHC to detect aberrant T-cell marker expression is restrictive.Table 1
Clinical characteristics of CD7-positive B-cell lymphoma.
Case No.
Age
Sex
Histology
Cell of origin
Main site(s) of involvement
Stage
Extranodal involvement
Treatment
Response
Status
Follow-up (months)
Detection method
References
Case 1
54
F
DLBCL
Non-GC
Inguinal LN
IIA
−
R-CHOP
CR
Alive, CR
NA
FCM, IHC
Sangle et al.
Case 2
66
M
DLBCL
NA
Thoracic cavity
IA
+
CHOP + RT
PR
Died of disease
NA
FCM, IHC
Tomita et al.
Case 3
47
M
Non-Hodgkin lymphoma
NA
Intra-abdominal mass
IVA
+
High dose CHOP
PD
Died of disease
5
FCM
Takahashi et al.
Case 4
64
M
DLBCL
GC
Cecum
IIA
+
Surgery + R-CHOP
CR
Alive, CR
68
IHC
Tsuyama et al.
Case 5
66
F
DLBCL
Non-GC
Axillary LN
IVB
+
R-CHOP + RT
PD
Died of disease, refractory
24
FCM, IHC
Tsuyama et al.
Case 6
62
F
DLBCL
GC
Nasal cavity
IIA
+
R-CHOP
PR
Alive with disease, relapse
34
FCM, IHC
Tsuyama et al.
Case 7
82
M
DLBCL
Non-GC
Nasal cavity
IA
+
R-CHOP
CR
Alive, CR
45
FCM, IHC
Tsuyama et al.
Case 8
64
M
DLBCL
Non-GC
Orbit
IB
+
R-CHOP
PD
Died of disease
2
FCM, IHC
Tsuyama et al.
Case 9
81
M
DLBCL
Non-GC
Soft tissue of leg
IVA
+
R-CHOP
CR
Died of disease, relapse
40
FCM, IHC
Tsuyama et al.
Case 10
55
M
DLBCL
Non-GC
Cervical LN
IVA
+
R-CHOP
CR
Died of disease, relapse
12
FCM, IHC
Tsuyama et al.
Case 11
65
M
DLBCL
Non-GC
Prostate
IVA
+
R-CHOP
CR
Alive, CR
49
FCM, IHC
Tsuyama et al.
Case 12
74
M
DLBCL
Non-GC
Nasal cavity
IA
+
R-CHOP + RT
CR
Alive, CR
18
FCM
Our case
M, male; F, female; DLBCL, diffuse large B-cell lymphoma; GC, germinal centre; LN, lymph node; CR, complete response; PR, partial response; PD, progressive disease; NA, not available; FCM, flow cytometry; IHC, immunohistochemistry.Inaba et al. reported that extranodal involvement and a higher international prognostic index are significantly more frequent in B-cell lymphomas positive for T-cell markers than in B-cell lymphomas negative for T-cell markers [5]. Tsuyama et al. reported the clinical examination of 223 DLBCL patients for T-cell marker antigen [7]. According to their report, the CD5-positive DLBCL group had a significantly poorer prognosis than the T-cell marker-negative group. In contrast, there was no significant difference in prognosis between T-cell marker-positive DLBCL other than CD5 and T-cell marker-negative DLBCL. Furthermore, Suzuki et al. reported 150 cases of DLBCL; however, the clinicopathological significance and prognosis of CD7 in DLBCL are still unknown [6].As shown in Table1, of the 11 previously reported cases of CD7-positive B-cell lymphoma, 9 cases involved the development of extranodal lesions, including 2 cases of intranasal tumor; 8 patients achieved complete response or partial response after receiving rituximab combined with chemotherapy. Similarly, the patient in the present case presented with an intranasal tumor and achieved complete remission with radiotherapy following R-CHOP therapy. Currently, there is no evidence of recurrence in the patient. According to the literature, CD2 or CD7 expression is associated with extranodal involvement in B-non-Hodgkin’s lymphoma at diagnosis [5]. It is important to examine the clinical features by the accumulation of further cases.



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