Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Characteristic ultrasound features of mucosaassociated lymphoid tissue lymphoma of the salivary and thyroid gland Yorihisa Orita, Yasuharu Sato, Nobuhiko Kimura, Hidenori Marunaka, Tomoyasu Tachibana, Yasuhiko Yamashita, Hiroyuki Hanakawa, Tadashi Yoshino & Kazunori Nishizaki To cite this article: Yorihisa Orita, Yasuharu Sato, Nobuhiko Kimura, Hidenori Marunaka, Tomoyasu Tachibana, Yasuhiko Yamashita, Hiroyuki Hanakawa, Tadashi Yoshino & Kazunori Nishizaki (2014) Characteristic ultrasound features of mucosa-associated lymphoid tissue lymphoma of the salivary and thyroid gland, Acta Oto-Laryngologica, 134:1, 93-99, DOI: 10.3109/00016489.2013.831994 To link to this article: https://doi.org/10.3109/00016489.2013.831994
Published online: 21 Nov 2013.
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Citing articles: 4 View citing articles
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Acta Oto-Laryngologica. 2014; 134: 93–99
ORIGINAL ARTICLE
Characteristic ultrasound features of mucosa-associated lymphoid tissue lymphoma of the salivary and thyroid gland
YORIHISA ORITA1, YASUHARU SATO2, NOBUHIKO KIMURA3, HIDENORI MARUNAKA4, TOMOYASU TACHIBANA5, YASUHIKO YAMASHITA6, HIROYUKI HANAKAWA1, TADASHI YOSHINO2 & KAZUNORI NISHIZAKI1 1
Department of Otolaryngology Head and Neck Surgery, 2Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama and Departments of Otolaryngology Head and Neck Surgery, 3Department of Iwakuni Medical Center, Yamaguchi, 4Department of Okayama Medical Center, Okayama, 5Department of Himeji Red Cross Hospital, Hyogo and 6Department of Fukuyama City Hospital, Hiroshima, Japan
Abstract Conclusion: The characteristic ultrasound appearance of mucosa-associated lymphoid tissue (MALT) lymphoma of the head and neck provides diagnostic information regarding masses or swellings in the head and neck region. Objectives: There are only a few reports about ultrasound features of malignant lymphoma (ML) of the head and neck. We have noticed that the ultrasound appearances of cases with MALT lymphoma resembled each other even when the appearances of other images like computed tomography were absolutely different. The objective of this study was to delineate the reliability of this characteristic ultrasound appearance of MALT lymphoma of the head and neck. Methods: The ultrasound examinations of 30 patients with histopathologically proven primary ML of the head and neck (15 cases of MALT) were reviewed. The ultrasound results of each case were independently compared to the results of the histopathological examination. Results: Two ultrasound patterns were observed for MALT lymphoma. The first was characterized by a marked hypoechoic area with interspersed linear echogenic strands (linear echogenic strands pattern), and the second was characterized by multiple, relatively large, hypoechoic segments (segmental pattern). Histopathologically, these patterns could be explained on the basis of the expansion of lymphoma cells demarcated by narrow or wide fibrous bands.
Keywords: MALT lymphoma, head and neck, fibrous bands, thyroid gland, salivary gland
Introduction Ultrasound might be the most useful noninvasive tool to identify patients suspected of having malignant lymphoma (ML) in the head and neck [1]. Although the subtype of ML cannot be determined without adequate tissue sampling, we previously reported [2] that the ultrasound features characteristic of mucosa-associated lymphoid tissue (MALT) lymphoma of the head and neck included welldemarcated, markedly hypoechoic, hypervascular
regions, with interspersed linear echogenic strands. These ultrasound features were very similar to those described in other reports [3–5] and seemed to be characteristic of MALT lymphoma of the head and neck region. However, these previous studies were limited by the fact that they were single case reports or small case series. Here, we report on our study of the ultrasound examinations of 30 patients with histopathologically confirmed ML of the head and neck, including 15 patients with MALT lymphoma.
Correspondence: Yorihisa Orita MD PhD, Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-Ku, 700-8558, Okayama, Japan. Tel: +81 86 235 7307. Fax: +81 86 235 7308. E-mail: [email protected]
(Received 18 June 2013; accepted 30 July 2013) ISSN 0001-6489 print/ISSN 1651-2251 online Ó 2014 Informa Healthcare DOI: 10.3109/00016489.2013.831994
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Table I. Sonographic patterns of 15 MALT lymphoma cases. Case no.
Age (years)
Sex
Diagnosis
Sonogram pattern
Primary
LN
1
23
F
MALT
Linear echogenic strands
PG (bilateral)
–
2
35
F
MALT
Linear echogenic strands
SG
–
3
40
F
MALT
Linear echogenic strands
Accessory PG
–
4
62
F
MALT
Segmental
PG
–
5
69
F
MALT
Linear echogenic strands
Thyroid
–
6
74
F
MALT + DLBCL
Linear echogenic strands*
Thyroid
+
7
75
M
MALT
Linear echogenic strands
Thyroid
+
8
76
M
MALT
Linear echogenic strands
Thyroid
–
9
77
M
MALT
Linear echogenic strands
PG
–
10
78
F
MALT
Linear echogenic strands
Thyroid
–
11
79
F
MALT
Linear echogenic strands
Thyroid
–
12
81
M
MALT
Linear echogenic strands
Thyroid
–
13
81
M
MALT
Segmental
PG (bilateral)
–
14
84
F
MALT
Linear echogenic strands
Thyroid
+
15
84
F
MALT
Mixed pattern†
PG
–
DLBCL, diffuse large B-cell lymphoma; F, female; LN, involvement of cervical lymph nodes; M, male; MALT, mucosa-associated lymphoid tissue lymphoma; PG, parotid gland; Primary, primary lesions; SG, submandibular gland. *The sonogram of case 6 included both the linear echogenic strands pattern and the destructive linear echogenic pattern. †The sonogram of case 15 showed a mixed pattern where relatively large hypoechoic segments contained linear echogenic strands.
Material and methods The subjects comprised 30 patients with untreated primary ML of the head and neck (thyroid and major salivary glands) who underwent ultrasound evaluations between January 2006 and April 2012 at Okayama University Hospital or one of its branch hospitals. The Department of Pathology at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences is a tertiary referral center for ML. The primary disease sites were defined in accordance with the established definition of primary, extranodal, non-Hodgkin lymphomas [6]. The ultrasound characteristics were compared with the histopathologic features of resected or biopsy specimens, as determined by hematopathologists. The investigators were blinded to the diagnoses during the review of the ultrasound features. However, the reports of the images were referred to a certain extent because we believe that the first practical impression by the observers might be important, particularly in the case of ultrasound, when conducting evaluations. Results We reviewed the records of 12 male and 18 female patients; at the time of the first presentation, the median age was 77 years (range 23–91 years). None of the patients had received any treatment before their
ultrasound examinations. MALT lymphoma was diagnosed in 14 patients; diffuse large B-cell lymphoma (DLBCL) in 12; follicular lymphoma (FL) in 2; peripheral T-cell lymphoma (PTCL) in 1; and MALT lymphoma coexisting with DLBCL in 1. All diagnoses were histopathologically confirmed, and the primary sites included the thyroid gland (17 cases), parotid gland (9 cases), submandibular gland (3 cases), and accessory parotid gland (1 case). MALT lymphoma was diagnosed in 5 male and 10 female patients, with a median age of 76 years (range 23–84 years) (Table I): 14 patients had MALT lymphoma and 1 patient had MALT lymphoma coexisting with DLBCL. Of the 14 MALT lymphomas, the cervical lymph nodes were involved in 2 cases (14%). Eight patients had MALT lymphoma in the thyroid gland; five in the parotid gland; one in the submandibular gland; and one in the accessory parotid gland. For the diagnosis of MALT lymphoma, histopathological examination was conducted on paraffin sections of formalin-fixed tissue after staining with hematoxylin and eosin (H&E). Immunohistochemical staining for CD20 + , CD5–, CD10–, low Ki-67 labeling index, and positive pancytokeratin (AE1/AE3), which revealed lymphoepithelial lesions, were required to confirm the diagnosis. We observed two ultrasound patterns that were associated with MALT lymphoma. The first was characterized by a markedly hypoechoic area, with
Ultrasound of MALT lymphoma
a
95
b
Figure 1. (a) Transverse ultrasound of case 5 (MALT lymphoma of the thyroid) showing a relatively rough linear echogenic strands pattern. (b) Hematoxylin and eosin staining (H&E, original magnification 4) shows the fibrous bands (arrows).
mainly of the MALT component (Figure 4a), and apparent destruction of the linear echogenic strands pattern (‘destructive linear echogenic pattern’) in the area that appeared to be mainly DLBCL (Figure 4b). The linear echogenic strands could be histopathologically explained on the basis of the expansion of the lymphoma cells demarcated by fibrous bands (Figure 1), and if the fibrous bands were wider, denser linear echogenic strands were seen (Figure 2). Furthermore, if the fibrous bands were rather wide,
interspersed linear echogenic strands, and was referred to as the ‘linear echogenic strands’ pattern (Figures 1a and 2a, b). The second pattern was characterized by a markedly hypoechoic, lobulated, segmental appearance and was referred to as the ‘segmental’ pattern (Figure 3). One case (case 15) showed a mixed pattern, with relatively large hypoechoic segments containing linear echogenic strands. Interestingly, case 6 showed the linear echogenic strands pattern in an area that appeared to consist
a
c
b
d
Figure 2. (a) Transverse ultrasound of case 7 (MALT lymphoma of the thyroid) showing a relatively dense linear echogenic strands pattern. (b) The involved cervical lymph nodes show the same ultrasound pattern as the primary lesion. (c) The histopathologic features of case 7 seem to be consistent with sonographic findings. H&E, original magnification 1. (d) The high power view of case 7 shows wide fibrous bands that demarcate lymphoma cell nests.
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Figure 3. Transverse ultrasound of case 13 (MALT lymphoma of the parotid glands) showing relatively large hypoechogenic lobulated segments characteristic of the segmental pattern.
the ultrasound appearance of segmental pattern was observed. The patients with histopathologically proven ML, but who did not have MALT lymphoma, included seven male and eight female patients, with a median age of 78 years (range 54–91 years) (Table II). Of these 15 cases, Eight (53%) showed cervical lymph node involvement. Unlike the MALT lymphomas, the nonMALT MLs presented with a variety of ultrasound appearances (Figure 5). Among the patients with nonMALT ML, the ultrasound appearances of two patients (cases 17 and 27, both with DLBCL) were similar to those of patients with MALT lymphoma (Figure 6a). However, the involved cervical lymph nodes in these two DLBCL cases showed a diffuse hypoechoic appearance (Figure 6b). On the other hand, the ultrasound appearance of the involved
a
cervical lymph nodes in two of the MALT lymphoma cases (cases 7 and 14) showed the MALT pattern (Figure 2b). The ultrasound appearance of the involved lymph nodes in the five DLBCL cases, other than cases 17 and 25, also showed a diffuse hypoechoic appearance. Because only a core needle biopsy specimen was available for case 17, the histopathological study for case 27 was conducted with special attention. The evaluation indicated a typical DLBCL appearance, while marked fibrous bands similar to those observed in patients with MALT lymphoma were observed (Figure 6c, d). Similar to case 5, the ultrasound features of case 20 (DLBCL) showed the destructive linear echogenic pattern. Although the histopathological appearance of this case included low-grade components unlike other DLBCL cases, evidence that this DLBCL had originated from MALT lymphoma could not be found. Discussion Two ultrasound patterns characteristic of MALT lymphoma of the head and neck were observed; the linear echogenic strands pattern and the segmental pattern. To the best of our knowledge, the ultrasound patterns of MALT lymphomas of the head and neck region in other case reports or small series of case studies have always belonged to either of these two patterns [3–5,7–9]. In these previous reports, the linear echogenic strands pattern was referred to as ‘multiple small hypoechoic nodules’ [5], ‘tortoiseshell pattern’ [7], ‘internal septation’ [8], or ‘linear echogenic strands’ [3], and the segmental pattern was referred to as ‘multiple hypoechoic signals’ [9] or ‘multiple larger hypoechoic masses’ [8]. When these ultrasound patterns are detected in masses or swollen lesions in the head and neck, the possibility of MALT lymphoma should be considered, especially
b
Figure 4. (a) Longitudinal ultrasound of case 6 (MALT lymphoma of the thyroid) partially showing the linear echogenic strands pattern. This part probably represents the MALT lymphoma component. (b) Transverse ultrasound of the other region of case 6 showing the destructive linear echogenic strands pattern. This region might represent the diffuse large B-cell lymphoma (DLBCL) component.
Ultrasound of MALT lymphoma
97
Table II. Sonographic patterns of 15 malignant lymphoma (ML) cases other than MALT lymphoma. Case no.
Age (years)
Sex
Diagnosis
Sonogram pattern
Primary
LN
16
54
F
DLBCL
Diffuse hypoechoic
PG
–
17
57
M
DLBCL
Linear echogenic strands
Thyroid
+
18
59
M
DLBCL
Diffuse hypoechoic
Thyroid
–
19
65
M
FL
Various levels of hypoechogenicity
SG
–
20
73
M
DLBCL
Destructive linear echogenic strands
PG
+
21
77
M
DLBCL
Various levels of hypoechogenicity
Thyroid
–
22
77
F
DLBCL
Diffuse hypoechoic
Thyroid
+
23
78
F
DLBCL
Diffuse hypoechoic
Thyroid
+
24
80
F
PTCL
Various levels of hypoechogenicity
PG
+
25
82
F
DLBCL
Various levels of hypoechogenicity
PG
+
26
84
M
FL
Diffuse hypoechoic
SG
+
27
85
M
DLBCL
Linear echogenic strands
Thyroid
+
28
85
F
DLBCL
Various levels of hypoechogenicity
Thyroid
–
29
88
F
DLBCL
Various levels of hypoechogenicity
Thyroid
–
30
91
F
DLBCL
Diffuse hypoechoic
Thyroid
–
DLBCL, diffuse large B-cell lymphoma; F, female; FL, follicular lymphoma; LN, involvement of cervical lymph nodes; M, male; PG, parotid gland; Primary, primary lesions; PTCL, peripheral T-cell lymphoma; SG, submandibular gland.
a
c
b
d
Figure 5. Transverse ultrasound images of (a) case 16 (diffuse large B-cell lymphoma (DLBCL) of the parotid gland) and (b) case 18 (DLBCL of the thyroid). In both cases, a homogeneous hypoechoic lesion is observed. (c) Longitudinal ultrasound of case 21 (DLBCL of the thyroid) showing an inhomogeneous, relatively hypoechoic lesion. (d) Transverse ultrasound of case 29 (DLBCL of the thyroid) showing an inhomogeneous, complicated appearance.
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c
a
b Figure 6. (a) Transverse ultrasound of case 27 (diffuse large B-cell lymphoma (DLBCL) of the thyroid) showing the linear echogenic strands pattern. (b) The involved cervical lymph nodes of case 27 show a diffuse hypoechoic lesion. (c, d) Histopathologic examination shows that this case had features typical of DLBCL, although it included fibrous bands (arrow). c: H&E, original magnification 4, d: H&E, original magnification 10.
in patients with Hashimoto’s thyroiditis or Sjögren’s syndrome [10,11]. In some exceptional cases of nonMALT types of ML, most frequently DLBCL, the ultrasound pattern may be similar to that associated with MALT lymphoma. Although the number of cases in the present study is insufficient to draw solid conclusions, non-MALT, high-grade MLs appear to show cervical lymph node involvement (8 of 15 patients in the present study) more frequently than do MALT lymphomas (2 of 14 cases in the present study). It was interesting that ultrasound of the involved cervical lymph nodes in DLBCL patients showed an ultrasound pattern unlike that of MALT lymphomas, even in the cases where the primary lesions exhibited a pattern similar to that of MALT lymphomas. The presence of nodal affection is one of the factors associated with a poor prognosis in nongastric MALT lymphoma [12]. The rarity of lymph node involvement and the characteristic ultrasound features of the involved lymph nodes could form a basis for suspected MALT lymphoma diagnosis, rather than DLBCL diagnosis. In addition, because DLBCL is relatively easy to diagnose, for example, by cutting needle biopsy, compared with low-grade MLs such as MALT lymphoma [1,2,13], discrimination between DLBCL and MALT lymphoma is not normally difficult. The ultrasound appearances of MALT lymphomas seemed to depend on the quantity of the observed fibrous bands. If the fibrous bands in the specimens were relatively thin, the ultrasound pattern would
resemble the linear echogenic strands pattern; if the fibrous bands were dominant in the specimens, the ultrasound pattern would range from a dense linear echogenic strands pattern to a segmental pattern. The progression of ML with fibrous bands is relatively slow [14], and MALT lymphomas usually have an indolent clinical course [15]. However, MALT lymphomas occasionally progress to highgrade lymphomas [16]. A previous report described 6 patients, out of a cohort of 180 patients with nongastric MALT lymphoma, who demonstrated highgrade transformation into DLBCL [17]. Although even in the cases with coexistence of MALT lymphoma and DLBCL, the pathogenesis of the MALT lymphoma and DLBCL components differ from each other, especially in the cases of thyroid involvement [18], the ultrasound appearance of the destructive MALT pattern might suggest the transformation of MALT lymphoma into a high-grade ML. This ultrasound pattern might also indicate cases of high-grade MLs that originated from MALT lymphomas; however, evidence could not be found in the present study to indicate that the described DLBCL cases, with this ultrasound pattern, had originated from MALT lymphomas. Most MALT lymphomas are treated with surgery or field radiotherapy, without chemotherapy [19]. However, if the ultrasound appearance of the MALT lymphoma changes to a different pattern during the follow-up period, rediagnosis and reconsideration of the therapeutic strategy might be indicated.
Ultrasound of MALT lymphoma For correct ultrasound evaluations, we think that the observer’s first impression might be more important than a later review of the images. Moreover, accurate ultrasound diagnoses need experienced observers [20], making it more difficult to establish diagnostic criteria for ultrasound examinations. Nonetheless, the ultrasound patterns for MALT lymphomas described in this study are relatively easy to detect, even by inexperienced observers. Although similar ultrasound patterns may occasionally be seen in advanced or end-stage Sjögren’s syndrome [20], such advanced immune-mediated conditions may cause ML, and require histopathologic information. Thus, familiarity with these ultrasound patterns might be useful in guiding the decision as to whether to take a conservative approach or to proceed to histopathologic examination. In conclusion, the characteristic ultrasound appearance of MALT lymphomas of the head and neck provides information to aid the diagnosis of masses or swelling in the head and neck region. Ultrasound is a sensitive first-line imaging method that facilitates the identification of patients suspected of having MALT lymphoma of the head and neck. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Orita Y, Nose S, Sato Y, Miki K, Domae S, Hirai M . Cervical lymph node extirpation for the diagnosis of malignant lymphoma. Surg. Today 2013;43:67–72. [2] Orita Y, Sato Y, Kondo E, Ishihara H, Hirai H, Hanakawa H . Minimally invasive procedure for accurate diagnosis of mucosa-associated lymphoid tissue lymphoma of the head and neck. Jpn. J. Clin. Oncol. 2012;42:325–30. [3] Bahn YE, Lee SK, Kwon SY, Kim SP. Sonographic appearances of mucosa-associated lymphoid tissue lymphoma of the submandibular gland confirmed with sonographically guided core needle biopsy. J Clin Ultrasound 2011;39: 228–32. [4] Wickramasinghe A, Howarth A, Drage NA. Multiple bilateral parotid sialoliths in a patient with mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the salivary glands. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:496–8. [5] Matsushita T, Takashima S, Takayama F, Momose M, Wang J, Ishiyama T. Sonographic detection of secondary MALT lymphoma of the submandibular gland. J Clin Ultrasound 2001;29:462–5.
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[6] d'Amore F, Christensen BE, Brincker H, Pedersen NT, Thorling K, Hastrup J . Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group. Eur. J. Cancer 1991;27:1201–8. [7] Asai S, Okami K, Nakamura N, Ogawa Y, Ohta Y, Ogase Y . The tortoiseshell pattern in one or both sides of the submandibular glands in mucosa-associated lymphoid tissue lymphoma is related to chromosomal aberrations and the disease extent. J Ultrasound Med 2010;29:111–15. [8] Lewis K, Vandervelde C, Grace R, Ramesar K, Williams M, Howlett DC. Salivary gland mucosa-associated lymphoid tissue lymphoma in 2 patients with Sjögren's syndrome: clinical and sonographic features with pathological correlation. J Clin Ultrasound 2007;35:97–101. [9] Ando M, Matsuzaki M, Murofushi T. Mucosa-associated lymphoid tissue lymphoma presented as diffuse swelling of the parotid gland. Am J Otolaryngol 2005;26:285–8. [10] Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR . Increased risk of lymphoma in sicca syndrome. Ann. Intern. Med. 1978;89:888–92. [11] Saxena A, Alport EC, Moshynska O, Kanthan R, Boctor MA. Clonal B cell populations in a minority of patients with Hashimoto's thyroiditis. J. Clin. Pathol. 2004;57:1258–63. [12] Sretenovic M, Colovic M, Jankovic G, Suvajdzic N, Mihaljevic B, Colovic N . More than a third of non-gastric malt lymphomas are disseminated at diagnosis: a single center survey. Eur. J. Haematol. 2009;82:373–80. [13] Ben-Yehuda D, Polliack A, Okon E, Sherman Y, Fields S, Lebenshart P . Image-guided core-needle biopsy in malignant lymphoma: experience with 100 patients that suggests the technique is reliable. J. Clin. Oncol. 1996;14:2431–4. [14] Bennett MH. Sclerosis in non-Hodgkin’s lymphomata. Br J Cancer 1975;31(Suppl II):44–52. [15] Isaacson PG. Lymphomas of mucosa-associated lymphoid tissue (MALT). Histopathology 1990;16:617–19. [16] Yoshino T, Omonishi K, Kobayashi K, Mannami T, Okada H, Mizuno M . Clinicopathological features of gastric mucosa associated lymphoid tissue (MALT) lymphomas: high grade transformation and comparison with diffuse large B cell lymphomas without MALT lymphoma features. J. Clin. Pathol. 2000;53:187–90. [17] Zucca E, Conconi A, Pedrinis E, Cortelazzo S, Motta T, Gospodarowicz MK . Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood 2003; 101:2489–95. [18] Sato Y, Nakamura N, Nakamura S, Sakugawa S, Ichimura K, Tanaka T, Deviated VH4 immunoglobulin gene usage is found among thyroid mucosa-associated lymphoid tissue lymphomas, similar to the usage at other sites, but is not found in thyroid diffuse large B-cell lymphomas. Modern Pathol 2006;19:1578–84. [19] Tsang RW, Gospodarowicz MK, Pintilie M, Wells W, Hodgson DC, Sun A . Localized mucosa-associated lymphoid tissue lymphoma treated with radiation therapy has excellent clinical outcome. J. Clin. Oncol. 2003;21: 4157–64. [20] Shimizu M, Okamura K, Yoshiura K, Ohyama Y, Nakamura S, Kinukawa N. Sonographic diagnostic criteria for screening Sjögren's syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:85–93.
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Characteristic ultrasound features of mucosaassociated lymphoid tissue lymphoma of the salivary and thyroid gland Yorihisa Orita, Yasuharu Sato, Nobuhiko Kimura, Hidenori Marunaka, Tomoyasu Tachibana, Yasuhiko Yamashita, Hiroyuki Hanakawa, Tadashi Yoshino & Kazunori Nishizaki To cite this article: Yorihisa Orita, Yasuharu Sato, Nobuhiko Kimura, Hidenori Marunaka, Tomoyasu Tachibana, Yasuhiko Yamashita, Hiroyuki Hanakawa, Tadashi Yoshino & Kazunori Nishizaki (2014) Characteristic ultrasound features of mucosa-associated lymphoid tissue lymphoma of the salivary and thyroid gland, Acta Oto-Laryngologica, 134:1, 93-99, DOI: 10.3109/00016489.2013.831994 To link to this article: https://doi.org/10.3109/00016489.2013.831994
Published online: 21 Nov 2013.
Submit your article to this journal
Article views: 171
View related articles
View Crossmark data
Citing articles: 4 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20
Acta Oto-Laryngologica. 2014; 134: 93–99
ORIGINAL ARTICLE
Characteristic ultrasound features of mucosa-associated lymphoid tissue lymphoma of the salivary and thyroid gland
YORIHISA ORITA1, YASUHARU SATO2, NOBUHIKO KIMURA3, HIDENORI MARUNAKA4, TOMOYASU TACHIBANA5, YASUHIKO YAMASHITA6, HIROYUKI HANAKAWA1, TADASHI YOSHINO2 & KAZUNORI NISHIZAKI1 1
Department of Otolaryngology Head and Neck Surgery, 2Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama and Departments of Otolaryngology Head and Neck Surgery, 3Department of Iwakuni Medical Center, Yamaguchi, 4Department of Okayama Medical Center, Okayama, 5Department of Himeji Red Cross Hospital, Hyogo and 6Department of Fukuyama City Hospital, Hiroshima, Japan
Abstract Conclusion: The characteristic ultrasound appearance of mucosa-associated lymphoid tissue (MALT) lymphoma of the head and neck provides diagnostic information regarding masses or swellings in the head and neck region. Objectives: There are only a few reports about ultrasound features of malignant lymphoma (ML) of the head and neck. We have noticed that the ultrasound appearances of cases with MALT lymphoma resembled each other even when the appearances of other images like computed tomography were absolutely different. The objective of this study was to delineate the reliability of this characteristic ultrasound appearance of MALT lymphoma of the head and neck. Methods: The ultrasound examinations of 30 patients with histopathologically proven primary ML of the head and neck (15 cases of MALT) were reviewed. The ultrasound results of each case were independently compared to the results of the histopathological examination. Results: Two ultrasound patterns were observed for MALT lymphoma. The first was characterized by a marked hypoechoic area with interspersed linear echogenic strands (linear echogenic strands pattern), and the second was characterized by multiple, relatively large, hypoechoic segments (segmental pattern). Histopathologically, these patterns could be explained on the basis of the expansion of lymphoma cells demarcated by narrow or wide fibrous bands.
Keywords: MALT lymphoma, head and neck, fibrous bands, thyroid gland, salivary gland
Introduction Ultrasound might be the most useful noninvasive tool to identify patients suspected of having malignant lymphoma (ML) in the head and neck [1]. Although the subtype of ML cannot be determined without adequate tissue sampling, we previously reported [2] that the ultrasound features characteristic of mucosa-associated lymphoid tissue (MALT) lymphoma of the head and neck included welldemarcated, markedly hypoechoic, hypervascular
regions, with interspersed linear echogenic strands. These ultrasound features were very similar to those described in other reports [3–5] and seemed to be characteristic of MALT lymphoma of the head and neck region. However, these previous studies were limited by the fact that they were single case reports or small case series. Here, we report on our study of the ultrasound examinations of 30 patients with histopathologically confirmed ML of the head and neck, including 15 patients with MALT lymphoma.
Correspondence: Yorihisa Orita MD PhD, Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-Ku, 700-8558, Okayama, Japan. Tel: +81 86 235 7307. Fax: +81 86 235 7308. E-mail: [email protected]
(Received 18 June 2013; accepted 30 July 2013) ISSN 0001-6489 print/ISSN 1651-2251 online Ó 2014 Informa Healthcare DOI: 10.3109/00016489.2013.831994
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Table I. Sonographic patterns of 15 MALT lymphoma cases. Case no.
Age (years)
Sex
Diagnosis
Sonogram pattern
Primary
LN
1
23
F
MALT
Linear echogenic strands
PG (bilateral)
–
2
35
F
MALT
Linear echogenic strands
SG
–
3
40
F
MALT
Linear echogenic strands
Accessory PG
–
4
62
F
MALT
Segmental
PG
–
5
69
F
MALT
Linear echogenic strands
Thyroid
–
6
74
F
MALT + DLBCL
Linear echogenic strands*
Thyroid
+
7
75
M
MALT
Linear echogenic strands
Thyroid
+
8
76
M
MALT
Linear echogenic strands
Thyroid
–
9
77
M
MALT
Linear echogenic strands
PG
–
10
78
F
MALT
Linear echogenic strands
Thyroid
–
11
79
F
MALT
Linear echogenic strands
Thyroid
–
12
81
M
MALT
Linear echogenic strands
Thyroid
–
13
81
M
MALT
Segmental
PG (bilateral)
–
14
84
F
MALT
Linear echogenic strands
Thyroid
+
15
84
F
MALT
Mixed pattern†
PG
–
DLBCL, diffuse large B-cell lymphoma; F, female; LN, involvement of cervical lymph nodes; M, male; MALT, mucosa-associated lymphoid tissue lymphoma; PG, parotid gland; Primary, primary lesions; SG, submandibular gland. *The sonogram of case 6 included both the linear echogenic strands pattern and the destructive linear echogenic pattern. †The sonogram of case 15 showed a mixed pattern where relatively large hypoechoic segments contained linear echogenic strands.
Material and methods The subjects comprised 30 patients with untreated primary ML of the head and neck (thyroid and major salivary glands) who underwent ultrasound evaluations between January 2006 and April 2012 at Okayama University Hospital or one of its branch hospitals. The Department of Pathology at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences is a tertiary referral center for ML. The primary disease sites were defined in accordance with the established definition of primary, extranodal, non-Hodgkin lymphomas [6]. The ultrasound characteristics were compared with the histopathologic features of resected or biopsy specimens, as determined by hematopathologists. The investigators were blinded to the diagnoses during the review of the ultrasound features. However, the reports of the images were referred to a certain extent because we believe that the first practical impression by the observers might be important, particularly in the case of ultrasound, when conducting evaluations. Results We reviewed the records of 12 male and 18 female patients; at the time of the first presentation, the median age was 77 years (range 23–91 years). None of the patients had received any treatment before their
ultrasound examinations. MALT lymphoma was diagnosed in 14 patients; diffuse large B-cell lymphoma (DLBCL) in 12; follicular lymphoma (FL) in 2; peripheral T-cell lymphoma (PTCL) in 1; and MALT lymphoma coexisting with DLBCL in 1. All diagnoses were histopathologically confirmed, and the primary sites included the thyroid gland (17 cases), parotid gland (9 cases), submandibular gland (3 cases), and accessory parotid gland (1 case). MALT lymphoma was diagnosed in 5 male and 10 female patients, with a median age of 76 years (range 23–84 years) (Table I): 14 patients had MALT lymphoma and 1 patient had MALT lymphoma coexisting with DLBCL. Of the 14 MALT lymphomas, the cervical lymph nodes were involved in 2 cases (14%). Eight patients had MALT lymphoma in the thyroid gland; five in the parotid gland; one in the submandibular gland; and one in the accessory parotid gland. For the diagnosis of MALT lymphoma, histopathological examination was conducted on paraffin sections of formalin-fixed tissue after staining with hematoxylin and eosin (H&E). Immunohistochemical staining for CD20 + , CD5–, CD10–, low Ki-67 labeling index, and positive pancytokeratin (AE1/AE3), which revealed lymphoepithelial lesions, were required to confirm the diagnosis. We observed two ultrasound patterns that were associated with MALT lymphoma. The first was characterized by a markedly hypoechoic area, with
Ultrasound of MALT lymphoma
a
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b
Figure 1. (a) Transverse ultrasound of case 5 (MALT lymphoma of the thyroid) showing a relatively rough linear echogenic strands pattern. (b) Hematoxylin and eosin staining (H&E, original magnification 4) shows the fibrous bands (arrows).
mainly of the MALT component (Figure 4a), and apparent destruction of the linear echogenic strands pattern (‘destructive linear echogenic pattern’) in the area that appeared to be mainly DLBCL (Figure 4b). The linear echogenic strands could be histopathologically explained on the basis of the expansion of the lymphoma cells demarcated by fibrous bands (Figure 1), and if the fibrous bands were wider, denser linear echogenic strands were seen (Figure 2). Furthermore, if the fibrous bands were rather wide,
interspersed linear echogenic strands, and was referred to as the ‘linear echogenic strands’ pattern (Figures 1a and 2a, b). The second pattern was characterized by a markedly hypoechoic, lobulated, segmental appearance and was referred to as the ‘segmental’ pattern (Figure 3). One case (case 15) showed a mixed pattern, with relatively large hypoechoic segments containing linear echogenic strands. Interestingly, case 6 showed the linear echogenic strands pattern in an area that appeared to consist
a
c
b
d
Figure 2. (a) Transverse ultrasound of case 7 (MALT lymphoma of the thyroid) showing a relatively dense linear echogenic strands pattern. (b) The involved cervical lymph nodes show the same ultrasound pattern as the primary lesion. (c) The histopathologic features of case 7 seem to be consistent with sonographic findings. H&E, original magnification 1. (d) The high power view of case 7 shows wide fibrous bands that demarcate lymphoma cell nests.
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Figure 3. Transverse ultrasound of case 13 (MALT lymphoma of the parotid glands) showing relatively large hypoechogenic lobulated segments characteristic of the segmental pattern.
the ultrasound appearance of segmental pattern was observed. The patients with histopathologically proven ML, but who did not have MALT lymphoma, included seven male and eight female patients, with a median age of 78 years (range 54–91 years) (Table II). Of these 15 cases, Eight (53%) showed cervical lymph node involvement. Unlike the MALT lymphomas, the nonMALT MLs presented with a variety of ultrasound appearances (Figure 5). Among the patients with nonMALT ML, the ultrasound appearances of two patients (cases 17 and 27, both with DLBCL) were similar to those of patients with MALT lymphoma (Figure 6a). However, the involved cervical lymph nodes in these two DLBCL cases showed a diffuse hypoechoic appearance (Figure 6b). On the other hand, the ultrasound appearance of the involved
a
cervical lymph nodes in two of the MALT lymphoma cases (cases 7 and 14) showed the MALT pattern (Figure 2b). The ultrasound appearance of the involved lymph nodes in the five DLBCL cases, other than cases 17 and 25, also showed a diffuse hypoechoic appearance. Because only a core needle biopsy specimen was available for case 17, the histopathological study for case 27 was conducted with special attention. The evaluation indicated a typical DLBCL appearance, while marked fibrous bands similar to those observed in patients with MALT lymphoma were observed (Figure 6c, d). Similar to case 5, the ultrasound features of case 20 (DLBCL) showed the destructive linear echogenic pattern. Although the histopathological appearance of this case included low-grade components unlike other DLBCL cases, evidence that this DLBCL had originated from MALT lymphoma could not be found. Discussion Two ultrasound patterns characteristic of MALT lymphoma of the head and neck were observed; the linear echogenic strands pattern and the segmental pattern. To the best of our knowledge, the ultrasound patterns of MALT lymphomas of the head and neck region in other case reports or small series of case studies have always belonged to either of these two patterns [3–5,7–9]. In these previous reports, the linear echogenic strands pattern was referred to as ‘multiple small hypoechoic nodules’ [5], ‘tortoiseshell pattern’ [7], ‘internal septation’ [8], or ‘linear echogenic strands’ [3], and the segmental pattern was referred to as ‘multiple hypoechoic signals’ [9] or ‘multiple larger hypoechoic masses’ [8]. When these ultrasound patterns are detected in masses or swollen lesions in the head and neck, the possibility of MALT lymphoma should be considered, especially
b
Figure 4. (a) Longitudinal ultrasound of case 6 (MALT lymphoma of the thyroid) partially showing the linear echogenic strands pattern. This part probably represents the MALT lymphoma component. (b) Transverse ultrasound of the other region of case 6 showing the destructive linear echogenic strands pattern. This region might represent the diffuse large B-cell lymphoma (DLBCL) component.
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Table II. Sonographic patterns of 15 malignant lymphoma (ML) cases other than MALT lymphoma. Case no.
Age (years)
Sex
Diagnosis
Sonogram pattern
Primary
LN
16
54
F
DLBCL
Diffuse hypoechoic
PG
–
17
57
M
DLBCL
Linear echogenic strands
Thyroid
+
18
59
M
DLBCL
Diffuse hypoechoic
Thyroid
–
19
65
M
FL
Various levels of hypoechogenicity
SG
–
20
73
M
DLBCL
Destructive linear echogenic strands
PG
+
21
77
M
DLBCL
Various levels of hypoechogenicity
Thyroid
–
22
77
F
DLBCL
Diffuse hypoechoic
Thyroid
+
23
78
F
DLBCL
Diffuse hypoechoic
Thyroid
+
24
80
F
PTCL
Various levels of hypoechogenicity
PG
+
25
82
F
DLBCL
Various levels of hypoechogenicity
PG
+
26
84
M
FL
Diffuse hypoechoic
SG
+
27
85
M
DLBCL
Linear echogenic strands
Thyroid
+
28
85
F
DLBCL
Various levels of hypoechogenicity
Thyroid
–
29
88
F
DLBCL
Various levels of hypoechogenicity
Thyroid
–
30
91
F
DLBCL
Diffuse hypoechoic
Thyroid
–
DLBCL, diffuse large B-cell lymphoma; F, female; FL, follicular lymphoma; LN, involvement of cervical lymph nodes; M, male; PG, parotid gland; Primary, primary lesions; PTCL, peripheral T-cell lymphoma; SG, submandibular gland.
a
c
b
d
Figure 5. Transverse ultrasound images of (a) case 16 (diffuse large B-cell lymphoma (DLBCL) of the parotid gland) and (b) case 18 (DLBCL of the thyroid). In both cases, a homogeneous hypoechoic lesion is observed. (c) Longitudinal ultrasound of case 21 (DLBCL of the thyroid) showing an inhomogeneous, relatively hypoechoic lesion. (d) Transverse ultrasound of case 29 (DLBCL of the thyroid) showing an inhomogeneous, complicated appearance.
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c
a
b Figure 6. (a) Transverse ultrasound of case 27 (diffuse large B-cell lymphoma (DLBCL) of the thyroid) showing the linear echogenic strands pattern. (b) The involved cervical lymph nodes of case 27 show a diffuse hypoechoic lesion. (c, d) Histopathologic examination shows that this case had features typical of DLBCL, although it included fibrous bands (arrow). c: H&E, original magnification 4, d: H&E, original magnification 10.
in patients with Hashimoto’s thyroiditis or Sjögren’s syndrome [10,11]. In some exceptional cases of nonMALT types of ML, most frequently DLBCL, the ultrasound pattern may be similar to that associated with MALT lymphoma. Although the number of cases in the present study is insufficient to draw solid conclusions, non-MALT, high-grade MLs appear to show cervical lymph node involvement (8 of 15 patients in the present study) more frequently than do MALT lymphomas (2 of 14 cases in the present study). It was interesting that ultrasound of the involved cervical lymph nodes in DLBCL patients showed an ultrasound pattern unlike that of MALT lymphomas, even in the cases where the primary lesions exhibited a pattern similar to that of MALT lymphomas. The presence of nodal affection is one of the factors associated with a poor prognosis in nongastric MALT lymphoma [12]. The rarity of lymph node involvement and the characteristic ultrasound features of the involved lymph nodes could form a basis for suspected MALT lymphoma diagnosis, rather than DLBCL diagnosis. In addition, because DLBCL is relatively easy to diagnose, for example, by cutting needle biopsy, compared with low-grade MLs such as MALT lymphoma [1,2,13], discrimination between DLBCL and MALT lymphoma is not normally difficult. The ultrasound appearances of MALT lymphomas seemed to depend on the quantity of the observed fibrous bands. If the fibrous bands in the specimens were relatively thin, the ultrasound pattern would
resemble the linear echogenic strands pattern; if the fibrous bands were dominant in the specimens, the ultrasound pattern would range from a dense linear echogenic strands pattern to a segmental pattern. The progression of ML with fibrous bands is relatively slow [14], and MALT lymphomas usually have an indolent clinical course [15]. However, MALT lymphomas occasionally progress to highgrade lymphomas [16]. A previous report described 6 patients, out of a cohort of 180 patients with nongastric MALT lymphoma, who demonstrated highgrade transformation into DLBCL [17]. Although even in the cases with coexistence of MALT lymphoma and DLBCL, the pathogenesis of the MALT lymphoma and DLBCL components differ from each other, especially in the cases of thyroid involvement [18], the ultrasound appearance of the destructive MALT pattern might suggest the transformation of MALT lymphoma into a high-grade ML. This ultrasound pattern might also indicate cases of high-grade MLs that originated from MALT lymphomas; however, evidence could not be found in the present study to indicate that the described DLBCL cases, with this ultrasound pattern, had originated from MALT lymphomas. Most MALT lymphomas are treated with surgery or field radiotherapy, without chemotherapy [19]. However, if the ultrasound appearance of the MALT lymphoma changes to a different pattern during the follow-up period, rediagnosis and reconsideration of the therapeutic strategy might be indicated.
Ultrasound of MALT lymphoma For correct ultrasound evaluations, we think that the observer’s first impression might be more important than a later review of the images. Moreover, accurate ultrasound diagnoses need experienced observers [20], making it more difficult to establish diagnostic criteria for ultrasound examinations. Nonetheless, the ultrasound patterns for MALT lymphomas described in this study are relatively easy to detect, even by inexperienced observers. Although similar ultrasound patterns may occasionally be seen in advanced or end-stage Sjögren’s syndrome [20], such advanced immune-mediated conditions may cause ML, and require histopathologic information. Thus, familiarity with these ultrasound patterns might be useful in guiding the decision as to whether to take a conservative approach or to proceed to histopathologic examination. In conclusion, the characteristic ultrasound appearance of MALT lymphomas of the head and neck provides information to aid the diagnosis of masses or swelling in the head and neck region. Ultrasound is a sensitive first-line imaging method that facilitates the identification of patients suspected of having MALT lymphoma of the head and neck. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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