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Primary cutaneous marginal zone B-cell lymphoma

European Journal of Dermatology. Volume 15, Number 6, 480-3, November-December 2005, Clinical report

Summary

Author(s) : Kazuhide Tsuji, Daisuke Suzuki, Youko Naito, Yumiko Sato, Tadashi Yoshino, Keiji Iwatsuki , Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan, Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Summary : We report a Japanese case of primary cutaneous marginal zone B-cell lymphoma (PCMZL). This 46-year-old woman presented with a subcutaneous nodule on her right forearm. With the combined morphology,the immunophenotype, and molecular analysis, we diagnosed this lesion as PCMZL. Furthermore, we reviewed the 16 cases of PCMZL in the Japanese literature. The ages of the patients ranged from 26 to 75 years (mean 55.7 years) with a slight female predilection. Clinically, most of the skin lesions were erythematous nodular lesions. The involved regions were the face and neck in eight cases, the trunk in six and the arms in five. None had Borrelia burgdorferi infection or a history of thyroiditis. Two patients had suffered from Sjögren’s syndrome. Histopathologically, lymphoepithelial lesions were found in nine cases. The chromosomal aberrations in MALT lymphoma such as t(11\;18)(q21\;q21), t(14\;18)(q32\;q21) and t(3\;14)(p14.1\;q32) were not reported in any of the Japanese cases. Although two patients developed metastasis on the skin after radiation therapy, none died of lymphoma.

Keywords : cutaneous B-cell lymphoma, cutaneous marginal zone B-cell lymphoma, MALT lymphoma

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ARTICLE

Auteur(s) : Kazuhide Tsuji¹, Daisuke Suzuki¹, Youko Naito¹, Yumiko Sato², Tadashi Yoshino², Keiji Iwatsuki¹

¹Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan
²Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

accepté le 17 Août 2005

Marginal zone B-cell lymphoma (MZBL) was first recognized as a low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) by Isaacson and Wright [1]. Extranodal MZBL was defined as a new entity of lymphoma in the Revised European-American classification of lymphoid neoplasms (REAL classification) [2] and the World Health Organization (WHO) classification [3]. Although extranodal MZBLs have been mainly described by the name “mucosa-associated lymphoid tissue lymphoma”, they arise not only from the stomach [4], but also from various nongastrointestinal sites [5]. Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is also considered part of the broad group of extranodal marginal zone B-cell lymphomas [6]. Because PCMZL has only recently been recognized and few Asian cases have been described, we reported our case and reviewed the cases of PCMZL in the Japanese literature.

Case report

A 46-year-old woman was referred to our hospital in March 2001 because of a subcutaneous nodule on her right forearm. The nodule had been present for a year and gradually enlarged without ulceration despite treatment with topical steroids. There was no history of either acute inflammation or insect bite on the lesion. Examination revealed a solitary, firm, subcutaneous nodule, 1- 2 cm in diameter, on the right forearm ( (figure 1) ). The nodule was not attached to the underlying tissue. There was neither lymphadenopathy nor hepatosplenomegaly. The results of routine laboratory examinations were normal except for slightly increased total cholesterol (T.Cho 227 mg/dl). Anti-Ro (SS-A) and anti-La (SS-B) antibodies, anti-human T-cell lymphotrophic virus type 1 antibody, anti-H. pylori antibodies, and anti-and anti-Borrelia burgdorferi antibodies of serum were negative. Although she had a slight stomachache and a history of gastritis, both upper and lower gastrointestinal endoscopies showed no evidence of malignancy. A bone marrow biopsy, computed tomography, magnetic resonance imaging, and various scintigrams did not reveal any evidence of primary or metastatic lesions.

Hematoxylin-eosin-stained specimens revealed variously sized, irregularly shaped nests in the dermis ( (figure 2A) ). The overlying epidermis was not involved. The infiltrates were composed of small lymphocytes, centrocyte-like cells, lymphoplasmacytoid cells, plasma cells, and many reactive cells ( (figures 2B and 2C) ). Lympho-epithelial complexes were not presented. On paraffin immunoperoxidase stains, the atypical lymphocytes within the nodules were positive for CD20 ( (figure 3A) ) and alkaline phosphatase, and negative for CD5, CD10. The detection rate for κ-light chain was much higher than λ-light chain by in situ hybridization ( (figures 3B and 3C) ). Although clonal immunoglobulin heavy chain gene rearrangement using JH probe by Southern blot analysis was negative in the tumor tissue, molecular analysis by VDJ-PCR on paraffin embedded tissue showed evidence of monoclonal B-cell population ( (figure 4) )[7]. In this case, t(11;18)(q21;q21) involving API2 and MALT1 genes was not detected by fluorescence in situ hybridization (FISH) analysis on fresh tissue. With the combined morphology, immunophenotype, and molecular analysis, we diagnosed a PCMZL of mucosa associated lymphoid tissue (MALT) of the skin. Electron beam irradiation (total 40 Gy) was applied after extirpation. Neither local recurrence nor metastasis has appeared during 24 months of follow-up.

Discussion

Table 1( Table 1 ) summarizes clinicopathological findings of the 16 cases of PCMZL described in the Japanese literature during last ten years. The age of the patients at the time of diagnosis ranged from 26 to 75 years (mean 55.7 years old) with a slight female predilection (male/female ratio 7:9). The regions involved were the face and neck in eight cases, the trunk in six and the arms in five. Clinically, most of the skin lesions were erythematous nodular lesions. Three cases were recognized as plaques, 1 as papules and 12 as nodules. The lesions were solitary in nine cases and multiple in seven. In three of seven multiple cases, more than one anatomic site was involved. None of the 16 patients had B.burgdorferi and H. pylori infection. In the Japanese, involvement of B. burgdorferi and H. pylori seems extremely rare and plays a limited role in the development or pathogenesis of PCMZL, as described in Taiwanese cases [9]. Two patients had a history of Sjögren’s syndrome (cases 2, 13). No patients had suffered from thyroiditis. Histopathologically, the dermis was the major site of tumor infiltration, and the upper subcutis was frequently involved (seven cases). In contrast, the epidermis was never involved. Lymphoepithelial lesions were found in nine cases in which neoplastic cells invaded the skin adnexa with lymphoepithelial complex formation. As Servitje et al. [10] reported that adnexal involvement was seen in about 90% of cases (20/22), lymphoepithelial lesions might be common in PCMZL.

Recently, a number of recurring chromosomal translocations have been described in MALT lymphoma. Although neither t(11;18)(q21;q21) nor t(1;14)(q22;q32) has been identified in PCMZL, including Japanese cases, t(14;18)(q32;q21) involving IGH and MALT1 and t(3;14)(p14.1;q32) involving IGH and FOXP1 have been detected in some PCMZL cases [11, 12]. The clinicopathological significances of these two novel gene alterations are important translocations in a site-dependent subset of MALT lymphomas [13].

Of the Japanese cases investigated for cytoplasmic or surface light chain expression, monotypic expression of light chains was observed in 12 cases (seven κ; five λ). With the light chain immunoglobulin expression, Southern blot analysis of the immunoglobulin gene is the established method for molecular genetic demonstration of monoclonality but it is complex and requires fresh frozen tissue samples. PCR-based clonality analysis is sufficiently sensitive and reliable for use as a routine diagnostic adjunct [14]. The combination with immunohistochemical and PCR-based clonality analysis can be useful in differentiating PCMZL from a reactive process, especially for small specimens.

Local treatment results in remission in most cases. 11 cases were treated by surgery and 12 by radiation. Two patients developed skin-limited recurrences affecting the initially treated site or distant skin sites after radiation therapy (cases 2, 8), however, none of the 16 cases died of PCMZL (the median follow-up period was 18.3 months after treatment (range: 4-36 months)). There is a significant risk of relapse, however, only a small minority of these patients will die of their disease.
Table 1 Clinical characteristics of 16 patients with primary cutaneous marginal zone B-cell lymphoma

Case No.	Age	Sex	Primary site	Gross appearance	Solitary or multiple	Sjogren’s syndrome	subcutis involvement	Lympho- epithelial lesion	Method of detecting Ig rearrangement^a	Light chains	Therapy^b	Course^c	Ref.
1	36	M	lt. shoulder	Nodule	Solitary	n/r	Yes	n/r^d	SB	λ	EB 40Gy	CR(34)^e	[8]
2^f	57	F	abdomen	Plaque	Solitary	Yes	Yes	Yes	SB	κ	Ext+EB40-Gy CHOP	rec(4)
3^g	49	M	lt. eye lid	Papule	Solitary	No	No	Yes	PCR	λ	Ext + EB 30Gy	CR(15)
4^h	70	M	lt. arm	Plaque Nodules	Multiple	No	Yes	No	PCR	κ	Ext	CR(12)
5ⁱ	52	F	lt. cheek	Nodule	Solitary	n/r	Yes	Yes	SB	κ	Ext + EB 40Gy	CR(24)
6^j	26	M	rt. shoulder and neck	Nodules	Multiple	No	No	Yes	SB	κ	EB 30Gy	CR(24)
7^k	34	F	rt. upper arm	Nodule	Solitary	No	No	Yes	n/r	λ	Ext	n/r
8^l	75	F	rt. cheek and eyelids	Grouped Nodules	Multiple	n/r	No	Yes	SB	n/r	Ext + EB 40Gy + 30Gy	rec
9^m	73	F	lt. upper arm	Plaque	Solitary	No	No	No	SB	n/r	Ext	CR(12)
10ⁿ	51	F	lt. cheek	Nodule	Solitary	No	Yes	n/r	n/r	κ	Ext + EB 34Gy	CR(12)
11^o	75	M	back	Plaques	Multiple	n/r	Yes	Yes	n/r	λ	Ext + RT	n/r
12^p	59	M	lt. lower eyelid	Nodule	Solitary	No	Yes	No	PCR	n/r	Ext + EB 30Gy	CR(36)
13^q	61	F	back, shoulder, arms	Nodules	Multiple	Yes	n/r	Yes	SB	κ	EB	CR(12)
14^r	68	F	retroauricular forehead	Nodules	Multiple	n/r	Yes	Yes	SB	n/r	PSL 15mg	SD(5)
15^s	59	M	forehead, cheek, chest	Nodules	Multiple	No	No	n/r	SB	λ	RT+CHOP	CR(24)
16	46	F	rt. arm	Nodule	Solitary	No	Yes	No	PCR	κ	Ext + EB 40Gy	CR(24)	Our case

^{^a}SB, Southern blot analysis; PCR, PCR-based clonality analysis.

^{^b}RT, radiotherapy; EB, electron-beam; Ext, extirpation.

^{^c}CR, complete response; rec, recurrence; SD, stable disease.

^{^d}n/r, not referred.

^{^e}Months of follow-up.

^{^f}Furutani K et al. Jpn J Dermatol 2001; 111: 843.

^{^g}Hayashi M et al. Rinsho Derma 2004; 46: 1381.

^{^h}Takatsuka S et al. Rinsho Hifuka 2001; 55: 175.

^ⁱFuruta M et al. Rinsho Hifuka 2003; 57: 1210.

^{^j}Namba Y et al. Hifu no lymphoma 1997; 16: 98.

^{^k}Harada M et al. Nihon Hifubyorisoshiki Gakkaishi 1999; 15: 10.

^{^l}Saito M et al. Rinsho Derma 2003; 57: 193.

^{^m}Kimura T et al. Jpn J Dermatol 2000; 110: 1602.

^ⁿKakeda N et al. Jpn J Dermatol 2003; 113: 315-6.

^{^o}Kodanagi M et al. Jpn J Dermatol 2004; 114: 592.

^{^p}Iyoda E et al. Jpn J Dermatol 2003; 113: 1026.

^{^q}Onoda N et al. Nippon Byori Gakkai Kaishi Transactiones Societatis Pathologicae Japonicae 1995; 84: 206.

^{^r}Koiso H et al. Rinsho Ketsueki 1999; 40: 910.

^{^s}Watanabe I et al. Hifu no kagaku 2002; 1: 149.

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