涎腺黏膜相关淋巴瘤的临床病理特点和染色体异常的研究

Clinicopathologic characteristics and chromosomal abnormalities in salivary mucosa associated lymphoid tissue lymphomas

目的探讨涎腺黏膜相关边缘区B细胞（mucosa associated lymphoid tissue，MALT）淋巴瘤的组织形态特点及其与染色体异常的关系。方法收集复旦大学附属肿瘤医院病理科2005—2008年间28例涎腺MALT淋巴瘤临床和随访资料，所有患者均行肿块切除或部分涎腺腺叶切除手术，术后根据HE切片总结其组织学特点；用荧光原位杂交分别检测AP12-MALT1、bcl-10、MALT1和IgH基因的异常。结果28例患者中女16例，男12例；中位年龄52岁。其中18例发生在腮腺，6例发生在颌下腺，4例发生在舌下腺。10例表现为涎腺内一个孤立性肿块，18例表现为淋巴组织在涎腺内弥漫浸润。仅8例（28．6％）有口干或鼻干、眼干等干燥综合征表现。病理检查全部表现为涎腺组织萎缩和减少，淋巴组织显著增生，其中22例（78．6％）出现成片分布的单核样B细胞增生，并常围绕在上皮岛周围，形成一圈空亮的晕。18例次（64．3％）有浆细胞增生，Russel小体和Dutcher小体易见；10例次（35．7％）可见神经或血管壁的侵犯。荧光原位杂交显示3例（10．7％）为t（11；18），2例（7．1％）为18号染色体3体，但所有病例均无IgH和bcl一10基因异常。22例患者术后有随访，1例患者在术后15个月死亡，其他患者存活，除手术外未系统性放化疗处理，8例患者在术后（8～15个月）开始出现原手术部位结节或颈淋巴结肿大，未再手术切除或活检，患者随访时间为23—54个月。结论涎腺MALT淋巴瘤多见于腮腺，多数患者不具有干燥综合征或其他自身免疫性疾病的病史。临床确诊需依靠病理检查，淋巴上皮岛周围或之间出现成片分布的单核样B细胞、成片的浆细胞增生、血管或神经侵犯等特征具有一定的提示意义。t（11；18）和18号染色体3体是主要的染色体异常，但发生率较低。

Objective To study the morphological and genetic characteristics in salivary gland marginal zone B cell lymphoma of mucosa associated lymphoid tissue （MALT） lymphomas. Methods Twenty-eight cases of MALT lymphomas of salivary gland were collected from Department of Pathology, Cancer Hospital of Fudan University. Morphological review based on HE sections, and specific chromosomal abnormalities were detected by two-color interphase fluorescent in situ hybridization （FISH）. Four different probes were available to detect for API2-MALT1 fusion gene, bcl-10, IgH and MALT1 gene, respectively.Results There were 16 females and 12 males, median age was 52. In those cases, 18 originated from parotid gland, 6 from submandibular and 4 from sublingual gland. Ten were localized mass and 18 were masses diffusely involved the glands. According to the clinical information, only 8 cases showed symptoms of dry mouth, dry nose or dry eye. Pathological findings showed that all cases had a dense lymphoid infiltration and obliteration and atrophy of acini and ducts. Twenty-two （78.6%） showed prominent monocytoid B cells and more often formed broad halos around epithelial islands. Eighteen （64. 3% ） showed clusters of lymphoplasic cells or plasma ceils, Russel＇ and Dutcher＇ body were easily seen. Ten （35.7%） showed nerve or blood vessel infiltration. Interphase FISH showed that 3 cases harbored t （11;18） and 2 cases harbored trisomy 18, but none of all found IgH and bcl-10 transloeations. After operation, 22 patients＇ follow-up information was available. One case died on 15 months later after operation, the rest of 21 cases were alive. Except surgical resection, patients did not get systematic radio-or chemotherapy. Eight to fifteen months after operation, 8 cases found recurred nodules on the original resected sites or cervical lymph nodes,but did not get repeated biopsy. All follow-up time was from 23 to 54 months. Conclusions Most salivary MALT lymphomas are arising from parotid glands. Most patients do not have the symptoms of the Sjogren＇s syndrome. The final diagnosis depends on the pathological findings, the number and distribution of monocytoid B cells and clusters of plasmacytoid cells are hints for diagnosis of salivary MALT lymphomas, invasion of blood vessels or nerve also help for malignant diagnosis, t（11;18） and trisomy 18 may be the main chromosomal abnormalities in salivary gland MALT lymphomas, but with low morbidity. This genetic characteristic may connect with the low malignancy and slow progression in biological behavior.