Pathology International 2012; 62: 60–64 doi:10.1111/j.1440-1827.2011.02747.

Case Report
Peripheral T-cell lymphoma arising from an intraglandular lymph
node in the parotid gland: A case report and literature review pin_2747 60..64

Naoki Yanagawa,1 Mitsumasa Osakabe,1 Hidekazu Furuse,2 Kunihiko Maeda3 and Gen Tamura1
Departments of 1Pathology and Laboratory Medicine and 2Otorhinolaryngology, Yamagata Prefectural Central
Hospital and 3Department of Nursing, Yamagata Prefectural University of Health Sciences, Yamagata, Japan

T/NK-cell lymphoma of the salivary gland is rare. A 58- T/NK-cell lymphomas are extremely rare.4,5 Herein, we
year-old man complained of a tumor mass in the left parotid describe the case of peripheral T-cell lymphoma, not other-
gland region and he was diagnosed to have a left parotid wise specified (PTCL-NOS) arising from an intraglandular
tumor. The tumor was subsequently resected, revealing a
lymph node in the parotid gland.
diffuse growth pattern of medium to large sized atypical
cells. The tumor was surrounded by fibrous connective
tissue in the form of a capsule, and those were positive for
CD3, CD4, CD5 and CD30, but negative for Bcl2, CD8, CD10,
CLINICAL SUMMARY
CD15, CD20, CD25, CD56, CD79a, CD246, EMA, granzyme B,
TdT and TIA-1. There was no molecular evidence of Epstein-
Barr virus (EBV) infection. It was diagnosed as peripheral A 58-year-old man presented at the Yamagata Prefectural
T-cell lymphoma (PTCL) arising from an intraglandular Central Hospital, Yamagata, Japan, after finding a tumor
lymph node in the parotid gland. In conclusion, Only 17 mass in the left parotid gland region. He had no past history
cases of primary T/NK-cell lymphoma of the salivary glands or family history of malignancy. Upon physical examination,
have been recorded until now, and the characteristics of the tumor mass was found to be 2.5 ¥ 2.5 cm in size. Swelling
these are not clear yet. Additional study is needed. of cervical lymph nodes was not detected. Laboratory data
revealed no significant abnormal findings. Serological analy-
Key words: intraglandular lymph node, salivary gland, T-cell sis of human T-cell leukemia virus type 1 antibodies was
lymphoma
negative. Computed tomography revealed a tumor 2.6 ¥
2.4 cm in size, located in the lower region of the left parotid
Malignant lymphomas arising from the salivary gland are
gland and slightly enhanced by contrast examination. Mag-
uncommon, accounting for approximately 5% of extranodal
netic resonance imaging revealed a tumor 2.7 ¥ 3.0 ¥ 2.5 cm
lymphomas, 2% of salivary gland neoplasms and 10% of
in size, with a smooth surface and no invasion of the sur-
malignant diseases of the salivary glands.1–3 The majority of
rounding tissue. T1-weighted sequences (Fig. 1a) indicated a
salivary gland lymphomas are of B-cell lineage such as low
relatively low-intensity tumor but T2-weighted sequences
grade B-cell lymphomas of mucosa-associated lymphoid
showed a high-intensity tumor (Fig. 1b) that was slightly
tissue, diffuse large B-cell lymphomas and follicular lympho-
enhanced by contrast examination (Fig. 1c). He was diag-
mas. A large proportion of such primary B-cell neoplasms
nosed to have a left parotid tumor and tumor resection was
have been shown to occur against a background of sia-
performed.
ladenitis associated with autoimmune disorders such as
Sjoegren’s syndrome. In contrast, primary salivary gland

Correspondence: Naoki Yanagawa, MD, Department of Pathology PATHOLOGICAL FINDINGS

and Laboratory Medicine, Yamagata Prefectural Central Hospital
1800 Aoyagi, Yamagata 990-2292, Japan. Email: nyanagaw@ Macroscopic findings
ypch.gr.jp
Received 26 July 2011. Accepted for publication 1 September
A specimen including the tumor was obtained at surgery. The
2011.
© 2011 The Authors cut surface of the tumor was whitish-gray, glossy and rela-
Pathology International © 2011 Japanese Society of Pathology and tively well-defined. However, parts of the tumor were ill-
Blackwell Publishing Asia Pty Ltd defined (Fig. 2).

Figure 1 Magnetic resonance imaging
revealed (a) a relatively low-intensity tumor
on T1-weighted sequences; however, (b)
T2-weighted sequences showed a high-
intensity, and (c) slightly contrast-enhanced
tumor.
Histopathological and immunohistochemical analyses
Histopathological features of the tumor were assessed on the
hematoxylin and eosin-stained sections of the formalin-fixed,
paraffin-embedded tissue specimens. Immunohistochemical
studies were performed on paraffin-embedded tissues using
the avidin-biotin peroxidase complex method. The primary
antibodies used were Bcl2 (124), CD3 (PS1), CD4 (1F6),
CD5 (4C7), CD8 (C8/144B), CD10 (56C6), CD30 (1G12),
CD56 (1B6), CD79a (JCB117), D2-40 (D2-40), EMA (E29)
and TdT (SEN28) from Nichirei (Tokyo, Japan); CD15 (C3D-
1), CD246 (ALK1) and granzyme B (GrB-7) from Dako Japan
Inc. (Tokyo, Japan); CD25 (4C9) from Novocastra (New-
castle, UK); and TIA-1 (TIA-1) from Abcam (Cambridge, UK).
The Epstein-Barr Virus (EBV) was detected by in situ hybrid-
ization (ISH).
Histopathological findings
Histopathologically, medium to large sized atypical cells with
round to irregular nuclei were diffusely proliferated with small
lymphocytes without atypia (Fig. 3a). Frequent mitotic activity
and apoptotic bodies were evident. The tumor was sur-
rounded by fibrous connective tissue in the form of a capsule,
© 2011 The Authors
Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd
T-cell lymphoma of an intraparotid 61
but in some parts, the tumor extended over the capsule and
invaded the acinic cells and ducts of the parotid gland
(Fig. 3b,c). Lymphatic vessels were seen in subcapsular
sinus.
Immunohistochemical findings
The medium to large sized atypical cells were positive for
CD3, CD4, CD5 and CD30, but negative for Bcl2, CD8,
CD10, CD15, CD20, CD25, CD56, CD79a, CD246, EMA,
granzyme B, TdT and TIA-1 upon immunohistochemical
staining (Fig. 4). EBV-RNA was not detected by ISH. From
these findings, we diagnosed this tumor as PTCL-NOS.
DISCUSSION
Salivary gland T/NK-cell lymphomas are extremely rare. To
the best of our knowledge, only 17 such cases have been
reported (Table 1).6–12 The age range of patients is from 24 to
79 years old (mean, 58.9 years old), most cases are from
East Asia and male. The parotid gland is the most common
site of such lesions and the submandibular gland the second
most common site. Histological subtypes are variable and
62 N. Yanagawa et al.
Figure 2 The cut surface of the tumor was whitish-gray, glossy and
relatively well-defined. However, parts of the tumor were ill-defined.
Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd
include PTCL, anaplastic large cell lymphoma (ALCL), T/NK-
cell lymphoma and adult T-cell lymphoma/leukemia. At first,
we considered this case to be ALCL because the tumor was
positive for CD30. However, it proved negative for CD246,
EMA, granzyme B and TIA-1. In addition, medium-sized
atypical lymphocytes were predominant rather than the larger
sized atypical lymphocytes. Therefore, we finally diagnosed
the tumor as a PTCL-NOS. EBV was detected in seven of the
12 cases where data have been recorded and it is consid-
ered to have an association with the development of salivary
gland T/NK-cell non-Hodgkin’s lymphoma. However, no
infection was detected in our case. As to prognosis, only a
few studies have been reported for salivary T/NK-cell lym-
phoma, these outcome are variable with survival after diag-
nosis ranging from six weeks to over four years. The three
patients with long survival were EBV negative.
The definition of a true primary salivary gland lymphoma is
an issue. Schmid et al.13 reported that if a lesion has no
Figure 3 Histopathology of the tumor and surrounding
tissue. (a) Medium to large sized atypical cells with round
to irregular nuclei were diffusely proliferated with small
lymphocytes without atypia. (b,c) The tumor was sur-
rounded by fibrous connective tissue in the form of a
capsule; but, in some parts, the tumor extended over the
capsule and invaded the acinic cells and ducts of the
parotid gland. Remnant acinic cells and ducts were
observed in the tumor tissue.
Figure 4 Immunohistochemical staining of the tumor
showing that the tumor cells were positive for (a) CD3 (b)
CD4 (c) CD5 and (d) CD30.
© 2011 The Authors
 T-cell lymphoma of an intraparotid 63

capsule-like structure reminiscent of an expanded lymph

ALCL, anaplastic large cell lymphoma; EBV, Epstein-Barr virus; N/A, data not available/mentioned in the original literature; NHL, non-Hodgkin’s lymphoma; NK, natural killer; PTCL-NOS, peripheral T-cell
>18 months, alive

>48 months, alive

>30 months, alive

65 months, alive

>3 months, alive

36 months, died
6 months, died

5 months, died

8 months, died
6 weeks, died
node capsule and no lymph nodes, it can be defined as a true
Survival

primary salivary gland lymphoma. Based on their report, the

lymphoma in our case is not a true primary lymphoma of
N/A
N/A
N/A

N/A

N/A
N/A
N/A
parotid gland origin but rather a lymphoma originating from
an intraparotid lymph node because of the existence of a
capsule-like structure and remaining lymphatic vessels in
Chemoradiation

Chemoradiation

Chemoradiation

Chemoradiation
Chemoradiation
Chemotherapy

Chemotherapy

Chemotherapy
subcapsular sinus. However, as far as we examined with
Treatment

regard to parotid gland T/NK-cell lymphomas, most articles

Resection

Resection

Resection

Resection

Resection
have not distinguished lymphoma of parotid gland origin from
N/A
N/A

N/A

N/A

N/A
N/A
N/A
lymphoma originating from the intraparotid lymph nodes, and
both have been reported as primary parotid gland lympho-
mas. In order to explore the development of lymphoma, it is
Negative
Negative

Negative

Negative

Negative
important to differentiate the former from the latter. Also the
Positive

Positive
Positive
Positive

Positive
Positive
Positive
EBV

same thing might be applicable to other PTCL developed in

N/A
N/A

N/A

N/A
N/A
Histopathological features of cases of T-cell lymphoma of the salivary glands reported in the literature (including our case)

the other extranodal organs that have intra-organ lymph

nodes, such as thyroid gland, mammary gland and lung.
Besides this thing might be applicable to B-cell and Hodgkin
T-NHL pleomorphic

T-NHL(PTCL-NOS)

T-NHL(PTCL-NOS)
T/NK angiocentric

T/NK angiocentric

lymphomas. Careful examination will be required from now.

Histology

In conclusion, T-cell lymphoma of the salivary gland is rare.

Only 17 cases of primary T-cell lymphoma of the salivary
T-NHL
T-NHL

T-NHL
T-NHL
T-NHL
T-NHL
ALCL
ALCL

ALCL

ATLL
ATLL
T/NK

glands have been recorded until now and the characteristics

are not yet clear. Additional study is needed.
Intra-salivary gland

Intra-salivary gland
Site of origin

ACKNOWLEDGMENTS
lymph node

lymph node

We are grateful to Professor K. Ohshima (Kurume University

School of Medicine) and Dr H. Miyoshi (Kurume University
N/A
N/A

N/A
N/A
N/A
N/A
N/A
N/A

N/A

N/A
N/A
N/A
N/A
N/A
N/A

School of Medicine) for their kind advice.

Submandibular

Submandibular

Submandibular

Submandibular

Submandibular
Disease site

REFERENCES
Sublingual
Sublingual
Parotid
Parotid

Parotid

Parotid

Parotid

Parotid
Parotid
Parotid
Parotid
N/A

1 Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of

extranodal lymphomas. Cancer 1972; 29: 252–60.
2 Mehle ME, Kraus DH, Wood BG, Tubbs R, Tucker HM, Lavertu
P. Lymphoma of the parotid gland. Laryngoscope 1993; 103:
(years)

17–21.
N/A

N/A
N/A
N/A
Age

48
71
79

46
65
24
64
64

62

69
59
57
58

3 Balm AJ, Delaere P, Hilgers FJ, Somers R, Van Heerde P.

Primary lymphoma of mucosa associated lymphoid tissue
(MALT) in the parotid gland. Clin Otolaryngol Allied Sci 1993; 18:
528–32.
N/A

N/A
N/A
N/A
Sex

4 Harris NL. Lymphoid proliferations of the salivary glands. Am J

M
M
M

M
M
M
M
M

M
M

M
F

Clin Pathol 1999; 111: S94–103.

5 Nakamura S, Ichimura K, Sato Y et al. Follicular lymphoma
lymphoma, not otherwise specified.

frequently originates in the salivary gland. Pathol Int 2006; 56:

Racial origin

576–83.
Japanese
Japanese

Japanese
Japanese
Japanese
Chinese
Chinese
Chinese
Chinese
Chinese

Chinese

Chinese
Chinese
Chinese

6 Takahashi H, Tsuda N, Tezuka F, Fujita S, Okabe H. Non-

White

Hodgkin’s lymphoma of the major salivary gland: A morphologic

N/A

N/A

and immunohistochemical study of 15 cases. J Oral Pathol Med

1990; 19: 306–12.
7 James M, Norton AJ, Akosa AB. Primary T-cell lymphoma of
submandibular salivary gland. Histopathology 1993; 22: 83–5.
Takahashi

MacLeod

Our case
Table 1

8 MacLeod CB, Frable WJ. Fine-needle aspiration biopsy of the

Author

James

Miyagi
Chan

salivary gland: Problem cases. Diagn Cytopathol 1993; 9: 216–

Wen

Hew

24; discussion 224–5.

© 2011 The Authors

Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd
64 N. Yanagawa et al.
9 Chan JK, Tsang WY, Hui PK et al. T- and T/natural killer-cell
lymphomas of the salivary gland: A clinicopathologic, immuno-
histochemical and molecular study of six cases. Hum Pathol
1997; 28: 238–45.
10 Wen S, Mizugaki Y, Shinozaki F, Takada K. Epstein-Barr virus
(EBV) infection in salivary gland tumors: Lytic EBV infection in
nonmalignant epithelial cells surrounded by EBV-positive
T-lymphoma cells. Virology 1997; 227: 484–7.
11 Hew WS, Carey FA, Kernohan NM, Heppleston AD, Jackson R,
Jarrett RF. Primary T cell lymphoma of salivary gland: A report
Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd
of a case and review of the literature. J Clin Pathol 2002; 55:
61–3.
12 Miyagi T, Nagasaki A, Taira T et al. Extranodal adult T-cell
leukemia/lymphoma of the head and neck: A clinicopathological
study of nine cases and a review of the literature. Leuk Lym-
phoma 2009; 50: 187–95.
13 Schmid U, Helbron D, Lennert K. Primary malignant lymphomas
localized in salivary glands. Histopathology 1982; 6: 673–87.
© 2011 The Authors