上海交通大学学报（医学版）

上海交通大学学报(医学版), 2025, 45(5): 653-660 doi: 10.3969/j.issn.1674-8115.2025.05.015

短篇论著

原发口腔外周T细胞淋巴瘤非特指型的特点分析

黄润语1, 张春叶2, 张颖1, 赵峥岩1, 杨扬3, 吴岚,1

1.上海交通大学医学院附属第九人民医院口腔黏膜病科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200011

2.上海交通大学医学院附属第九人民医院口腔病理科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200011

3.徐州医科大学附属口腔医院牙周黏膜病科，徐州 221002

Features of oral peripheral T-cell lymphoma, not otherwise specified

HUANG Runyu1, ZHANG Chunye2, ZHANG Ying1, ZHAO Zhengyan1, YANG Yang3, WU Lan,1

1.Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China

2.Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China

3.Department of Periodontal and Mucosal Diseases, Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou 221002, China.

通讯作者: 吴　岚，主任医师，博士；电子信箱：teana_wu@sina.com。

编委: 张慧俊

收稿日期: 2024-11-07   接受日期: 2025-02-24   网络出版日期: 2025-05-28

基金资助: 上海市科学技术委员会基金.  21S21902000
上海市卫生健康委员会项目［（ZY（2021-2023）-0207-01-04,2022CX009）］
上海交通大学医学院附属第九人民医院交叉基金.  JYJC202111

Corresponding authors: WU Lan, E-mail:teana_wu@sina.com.

Received: 2024-11-07   Accepted: 2025-02-24   Online: 2025-05-28

作者简介 About authors

黄润语（1999—），女，住院医师，硕士生；电子信箱：shdiver@outlook.com。 。

摘要

目的·探讨原发于口腔的外周T细胞淋巴瘤-非特指型（peripheral T-cell lymphoma， not otherwise specified，PTCL-NOS）的临床表现和免疫表型特征。方法·回顾性分析2020年8月至2024年8月就诊于上海交通大学医学院附属第九人民医院口腔黏膜病科、口腔为首发部位、确诊为PTCL-NOS的患者的病史和病理资料，并检索PubMed、Web of Science、Embase、Scopus和中国知网共5个数据库，结合2014年1月至2024年9月国际上相关病例报道，对临床特点、病理学特点进行分析归纳。结果·共20例口腔PTCL-NOS病例纳入研究。其中男性11例（55.0%），女性9例（45.0%）；患者首诊年龄25~77岁，平均（52.53±12.94）岁；好发部位为舌部（25.0%）、腭部（25.0%）及颊部（20.0%）；19例（95.0%）不伴B症状。纳入病例免疫表型阳性表达情况为CD3（19/19）、CD4（11/13）、CD8（7/12）、CD2（5/6）、CD7（5/5）、TIA-1（6/7）、GB（9/13）、perforin（4/6），EBER均阴性表达（8/8）。85%的病例Ki-67增殖指数≥60%。结论·口腔PTCL-NOS极为罕见，临床进展极具侵袭性，口腔表现为深而大的黏膜溃疡，基底高低不平，可扪及结节。病理特征具有异质性，免疫表型检测有助于早期诊断和分型。口腔科医师需加深对该疾病的认识，以避免错过此类恶性疾病的早期诊断与治疗。

关键词： 口腔特征 ; 外周T细胞淋巴瘤 ; 非特指型 ; 临床病理

Abstract

Objective ·To investigate the clinical manifestations and immunophenotypic features of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), involving the oral cavity. Methods ·The medical histories and pathology records of patients diagnosed with oral PTCL-NOS in the Department of Oral Mucosal Diseases of Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, between August 2020 and August 2024 were retrospectively analyzed. In addition, 5 databases, including PubMed, Web of Science, Embase, Scopus, and CNKI, were searched, and relevant cases reported internationally from January 2014 to September 2024 were reviewed. Results ·A total of 20 oral PTCL-NOS cases were included, comprising 11 males (55.0%) and 9 females (45.0%). The patients′ ages at initial diagnosis ranged from 25 to 77 years, with a mean age of (52.53±12.94) years. The most common sites were the tongue (25.0%), palate (25.0%), and buccal mucosa (20.0%). Nineteen cases (95.0%) had no B symptoms. The cases were positive for CD3 (19/19), CD4 (11/13), CD8 (7/12), CD2 (5/6), CD7 (5/5), TIA-1 (6/7), GB (9/13), perforin (4/6). EBER expression was negative (8/8). The Ki-67 proliferation index was ≥60% in 85% of cases. Conclusions ·Oral PTCL-NOS is extremely rare and has an aggressive clinical behavior. The oral manifestation presents as deep and large mucosal ulcers with uneven bases, and nodules can be palpable. The pathological features are heterogeneous. Immunophenotype detection is useful for early diagnosis and classification. It is essential for stomatologists to enhance their awareness of this malignancy to avoid delayed diagnosis and treatment.

Keywords： oral feature ; peripheral T-cell lymphoma (PTCL) ; not otherwise specified (NOS) ; clinical pathology

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本文引用格式

黄润语, 张春叶, 张颖, 赵峥岩, 杨扬, 吴岚. 原发口腔外周T细胞淋巴瘤非特指型的特点分析. 上海交通大学学报(医学版)[J], 2025, 45(5): 653-660 doi:10.3969/j.issn.1674-8115.2025.05.015

HUANG Runyu, ZHANG Chunye, ZHANG Ying, ZHAO Zhengyan, YANG Yang, WU Lan. Features of oral peripheral T-cell lymphoma, not otherwise specified. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2025, 45(5): 653-660 doi:10.3969/j.issn.1674-8115.2025.05.015

外周T细胞淋巴瘤-非特指型（peripheral T-cell lymphoma， not otherwise specified，PTCL-NOS）是具有侵袭性、快速发展的T细胞淋巴瘤［1］。PTCL-NOS发病以淋巴结病变为主，口腔PTCL-NOS非常罕见。目前，国际仅有少数病例报道。本研究旨在探讨发生于口腔的PTCL-NOS的临床表现和免疫表型特征。

1 对象与方法

1.1 研究对象

回顾性分析2020年8月—2024年8月就诊于上海交通大学医学院附属第九人民医院口腔黏膜病科和2014年1月—2024年9月报道于PubMed、Web of Science、Embase、Scopus和中国知网数据库中，依据世界卫生组织淋巴瘤分型标准（2017）［1］确诊为PTCL-NOS且口腔为首发部位的病例。

1.2 研究方法

从上海交通大学医学院附属第九人民医院电子病历信息系统获取患者的一般临床资料，包括性别、首诊年龄、口腔临床表现，完成辅助检查资料收集。同时，检索PubMed、Web of Science、Embase、Scopus和中国知网数据库，以主题词和自由词结合对文章的标题及摘要进行检索，检索时限为2014年1月至2024年9月，文献类型为研究论文和病例报道。其中，在Scopus数据库，检索词格式如下：“（TITLE-ABS-KEY（oral OR intraoral OR mouth OR tongue OR buccal OR lip OR gingival OR palate）AND TITLE-ABS-KEY（lymphoma， T cell， peripheral OR peripheral T-cell lymphoma OR lymphoma， peripheral T-cell OR lymphomas， peripheral T-cell OR peripheral T cell lymphoma OR peripheral T-cell lymphomas OR T-cell lymphomas， peripheral OR T-cell lymphoma， peripheral OR T cell lymphoma， peripheral））”。

1.3 统计学分析

应用SPSS 25.0软件进行数据处理及统计分析。使用Shapiro-Wilk检验方法对定量资料进行正态性检验，符合正态分布的定量资料以x±s表示，不符合正态分布的定量资料以M（IQR）表示；定性资料以频数（百分率）表示。

2 结果

2.1 口腔PTCL-NOS患者的临床特征

检索到相关文献8篇，包含18个病例，加上上述我科2例病例，共20例口腔PTCL-NOS病例纳入研究。男性11例（55.0%），女性9例（45.0%）；患者首诊年龄25~77岁，平均（52.53±12.94）岁；好发部位为舌部（25.0%）、腭部（25.0%）及颊部（20.0%）；19例（95.0%）不伴B症状（表1）。

表1   口腔PTCL-NOS患者的临床特征

Tab 1  Clinical features of oral PTCL-NOS

Year

Patient/

reference

Gender/

age

LocationB symptomRadiographic feature

Ann Arbor

staging

Treatment
2023Case 1F/55TongueNoneMRI showed a vaguely-bordered soft tissue thickening at the anterior tongue. In addition, MRI showed an intermediate T1 signal and slightly high T2 signal lesion at the right side of the tongue, which was about 3.6 cm×1.3 cm. The lesion demonstrated heterogeneous contrast enhancementⅠ EA/
2024Case 2M/44Hard palateNoneMRI illustrated a vaguely-bordered soft tissue thickening, which measured approximately 3.4 cm×2.7 cm×1.2 cm and showed a slightly low T1 signal and slightly high T2 signal. The lesion demonstrated heterogeneous contrast enhancement. There were several enlarged lymph nodes in the level Ⅱ‒level Ⅳ cervicalⅣ AGemOx-D
20141/[2]M/59The right side of the tongue baseNoneCT scan presented an ill-defined, heterogeneous enhancing soft tissue mass lesion in the right tongue base and enlarged lymph nodes in the right level ⅡⅡ ACHOP+RT+VMAT
20162/[3]F/50The left side of the anterior tongueNoneMRI T2WI showed a bordered lesion at the anterior tongueⅠNone
20173/[4]F/42Near the median sulcus of the tongueNoneEnhanced MRI showed a bordered, bar-shaped, irregular lesion with intermediate T1 signal and slightly high T2 signal in the right portion of the tongue, and its size was about 8.5 mm×24.5 mm/Surgery, CHOP
20184/[5]F/25Upper lip, palate, and maxillary sinusFever, weight lossCT scan with contrast showed an expansive and infiltrative formation with irregular contours and ulceration, extending from the upper lip to the nasolabial sulcus, with infiltration into the epidermis and nasal mucosa. The formation affected the right tear duct without bone involvement. In addition, CT showed a bilateral increase in the number and size of the cervical lymph nodes, mainly the submandibular chainⅣ BCHOEP
20205/[6]

M/

75‒80

The right side of the tongue baseNoneCT scan showed a well-bordered cystic mass (2 cm in diameter) at the right base of the tongue extending into the pharynxⅣ AGDP+CHOP
20216/[7]F/63Submandibular region////
20217/[7]M/67Buccal mucosa////
20218/[7]M/57Hard palate////
20219/[7]M/38Soft palate////
202110/[7]M/59Buccal mucosa////
202111/[7]F/56Tonsil////
202112/[7]F/66Tonsil////
202313/[8]M/34Right buccal mucosaNoneCT scan imaging showed destructive and expansive mass with central necrosis, extending to maxillary and ethmoid sinusesⅡ EACHOEP+RT
202414/[9]F/37Maxillary gingivaNone//Anthracycline-based regimens
202415/[9]M/44Buccal mucosaNone///
202416/[9]F/62Palate and gingivaNone//Anthracycline-based regimens
202417/[9]M/55Palate and maxillary sinusNoneCT scan illustrated the neoplasm invading the maxillary sinus and the orbital cavity, and extending toward the base of the skull/Anthracycline-based regimens
202418/[9]M/61Soft palate and tonsilNone///

Note: /—information not described; M—male; F—female; GemOx-D—gemcitabine, oxaliplatin and dexamethasone; CHOP—cyclophosphamide,doxorubicin,vincristine and prednisone; RT—radiation therapy; VMAT—volumetric modulated arc therapy; GDP—gemcitabine, dexamethasone and cisplatin; CHOEP—CHOP +etoposide.

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口腔黏膜溃疡特征为舌部深而大的溃疡，可扪及结节。本院病例1可见舌前部表面见多处溃疡面，基底稍有高低不平，右侧舌体内扪及结节状肿物，大小约3.0 cm×1.5 cm，表面糜烂、黄白色假膜覆盖（图1A），质韧，有触痛。影像学检查：MRI示双侧舌前部见软组织增厚，右侧明显，边界欠清，范围约3.6 cm×1.3 cm，T1WI呈等信号，T2WI压脂高信号，信号欠均，增强明显不均匀强化，口底部累及不明显（图2A）。颅底结构未见明显异常。双侧颈部未见明显肿大淋巴结。双侧唇颊部黏膜增厚强化。病例2见腭部中份溃疡（图1B），大小约3.5 cm×3.0 cm，基底高低不平，质中，表面覆盖黄色厚假膜，周缘红肿隆起，扪诊疼痛。双侧颈部可触及包块，质地偏硬，无压痛，与周围组织无粘连。影像学检查：颌面部MR增强示腭部偏右侧可见弥漫团片状软组织增厚影，边界欠清，范围约3.4 cm×2.7 cm×1.2 cm，T1WI为稍偏低信号，T2WI压脂稍高信号影，增强呈不均匀强化，内见片状坏死无强化影（图2B）。双颈Ⅱ~Ⅳ区可见多发肿大淋巴结影。全身PET-CT结果示两侧副鼻窦未见明显异常密度影。硬腭区软组织增厚，累及范围约3.0 cm×2.5 cm×1.8 cm，伴局部骨质吸收，向上累及右侧鼻腔底部黏膜增厚，糖代谢异常增高，SUVmax=9.30；双侧颈部Ⅱ、Ⅲ、Ⅳ区及左侧颈部Ⅴ区可见多发肿大淋巴结影，较大者大小约2.5 cm×1.5 cm，糖代谢异常增高，SUVmax=21.07。余鼻咽、口咽各壁未见局灶性增厚，咽隐窝及咽旁间隙清晰，糖代谢均匀对称。值得注意的是，回顾接触史，病例2患者近1年频繁接触家装材料，四肢及躯干出现大面积散在红色丘疹，4个月前皮疹消退，腭部出现绿豆大小溃疡，未予重视，面积渐增大，疼痛不明显，颌下淋巴结肿大，否认低热，近期易疲劳。此外，治疗方面，病例2患者1周后于血液内科确诊，收治入院，予GemOx-D方案化学治疗（吉西他滨2 g，第1日；奥沙利铂260 mg，第1日；地塞米松40 mg，第1~4日）。1月后复诊，腭部溃疡缩小为2.0 cm×1.2 cm，表面不平，双侧颈部触及包块，质硬，无压痛，收治入院行第2疗程西达苯胺（30 mg，每周2次）+GemOx-D化学治疗。治疗后溃疡缩小，2周后复发出现腭部穿孔。

图1

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图1   PTCL-NOS的临床表现

Fig 1   Clinical presentation of PTCL-NOS

Note: A. A 55-year-old woman presenting a swollen tongue on her right side with several ulcers and an ulcerated nodular lesion. B. A 44-year-old man showing a destructive palatal ulcer with necrotic grey tissue surrounded by erythematous areas.


图2

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图2   MRI影像学检查

Fig 2   MR imaging findings

Note: A. An axial MRI scan presented local destruction of the tongue tip mucosa with unclear boundaries and high T2 signals at the periphery. B. In a coronal MRI, diffuse soft tissue thickening was shown with an unclear boundary on the right side of the palate, and the T1 signal was slightly low.


最后，这些病例都表现为深而大、迁延不愈的口腔黏膜溃疡。从临床经验而言，PTCL-NOS需与口腔鳞状细胞癌、重型复发性阿弗他溃疡、创伤性溃疡和结核性溃疡等鉴别（表2）。

表2   口腔黏膜溃疡性疾病的鉴别诊断

Tab 2  Differential diagnosis of oral mucosal ulcerative diseases

ItemOral squamous cell carcinomaMajor recurrent aphthous ulcerTraumatic ulcerationTuberculous ulcerPTCL-NOSENKTL-NT
PopulationMiddle-aged and elderly peopleAdultTeenagers and elderly people/Middle-aged peopleMiddle-aged people
Oral clinical manifestationsPersistent ulceration with raised margins and necrotic base; indurated on palpationOval or round ulcers with a white or yellow pseudomembrane and a surrounding erythematous halo; 1 cm or more in diameterFrank ulceration is surrounded by a white hyperkeratotic lesion. The location and the shape of the ulcer correspond to the stimulating factorDeep ulcer with undermined edges and red granular base covered by septic secretionUlceration, mass, or necrosisNecrotic ulceration
Location of lesionsThe margin of the tongue, and the belly of the tongueThe non-keratinized and keratinized oral mucosaIn a trauma-prone siteLabial mucosa, vestibule, and tongueTongue, palate, and buccal mucosaMedian mucosa of the palate
Systemic signsLymph node swelling, pain, or weight loss//Cough, anorexia, fatigue, low-grade fever and weight lossLymph node swelling, extra-nodal involvement of the gastrointestinal tract and skin, anemia, eosinophilia, or hypergammaglobulinaemiaNasal mucosal symptoms or B symptoms
Clinical coursePersistentSelf-limiting, recurrent, and periodicSelf-limitingInfectionAggressiveAggressive

Complementary

examinations

Biopsy//Chest X-ray, tuberculin skin test, bacterial culturingBiopsy, blood test, bone marrow biopsyBiopsy, blood test, bone marrow biopsy, EBER-ISH

Note: /—information not described; PTCL-NOS—peripheral T-cell lymphoma, not otherwise specified; ENKTL-NT—extranodal NK-/T-cell lymphoma, nasal type; EBER-ISH—Epstein-Barr Virus encoding RNA in situ hybridization.

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2.2 口腔PTCL-NOS患者的免疫组织化学特征

所有病例T细胞抗原表达不一。抗原阳性表达情况为CD3（19/19）、CD4（11/13）、CD8（7/12）、CD2（5/6）、CD7（5/5）、TIA-1（6/7）、GB（9/13）、perforin（4/6）。85%的病例Ki-67增殖指数≥60%。EBER阴性表达（8/8）。CD20阴性表达（14/14）。7例检测CD30表达情况，其中5例CD30阴性表达。结果见表3。

表3   口腔PTCL-NOS患者的免疫组织化学特征

Tab 3  Immunohistochemical findings of oral PTCL-NOS

Year

Patient/

reference

EBERCD3CD4CD8CD2CD7CD20Ki-67Others
2023Case 1‒+++++‒60%‒70%

TIA-1 (partial+), GB (partial+),

perforin (few cells+)

2024Case 2/+//++‒>90%TIA-1(+), GB(+), perforin(+)
20141/[2]‒+++//‒80%TIA-1(+), GB(+)
20162/[3]/+++Few cells+Few cells+‒30%‒40%/
20173/[4]‒+‒+//‒30%TIA-1(+)
20184/[5]‒++‒+/‒60%/
20205/[6]‒++‒//‒60%TIA-1(‒), GB(‒)
20206/[7]‒++‒//‒60%‒95%LCA(+)
20207/[7]‒+////‒20%LCA(+), GB(‒), CD30(‒)
20208/[7]‒++///‒60%‒95%
20209/[7]/+////‒60%‒95%GB(+)
202010/[7]///////60%‒95%CD30(+)
202011/[7]/+++‒/‒60%‒95%TIA-1(+), GB(+), perforin(+)
202012/[7]/+++++‒60%‒95%

TIA-1(+), GB(+), perforin(+),

CD30(‒), PD-1(+)

202313/[8]/+///+‒70%‒80%CD30(‒)
202414/[9]/+/////70%Perforin(‒), GB(‒)
202415/[9]/+/////80%GB(‒)
202416/[9]/+‒+///95%Perforin(‒), GB(+), CD30(‒)
202417/[9]/++‒///95%GB(+), CD30(‒)
202418/[9]/++‒///90%GB(+), CD30(+)

Note: /—information not described; PTCL—peripheral T-cell lymphoma; GB—granzyme B.

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本院病例1的活体组织病理学检查：苏木精-伊红（hematoxylin-eosin，H-E）染色结果显示右舌黏膜溃疡，伴淋巴细胞弥漫增生（图3A、B）。免疫组织化学（immunohistochemistry，IHC）检查：AE1/AE3（上皮+），CD20（－），CD3（+）（图3C），CD10（－），CD5（－），CD56（个别+），CD4（少量+），CD8（+），CD2（+），CD7（+），TIA-1（部分+），GB（部分+），perforin（少量+），Ki-67增殖指数（60%~70%+）（图3D）。分子探针结果示EBER显色原位杂交阴性。病理诊断为外周T细胞淋巴瘤，非特指，细胞毒型。

图3

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图3   组织病理学检查

Fig 3   Histopathological examination

Note: A. Ulceration of the right tongue mucosa with diffuse infiltration of lymphoid cells (H-E staining, ×40). B. Atypical lymphoid cells exhibit hyperchromatic nuclei and a high nuclear-to-cytoplasmic ratio (H-E staining, ×200). C. CD3 positive (+) staining (×200). D. Ki-67 positivity in 60%‒70% of cells (×200).


3 讨论

外周T细胞淋巴瘤是一组起源于成熟T淋巴细胞的恶性增殖性疾病，占非霍奇金淋巴瘤的10%~12%［1，10］。一项单中心回顾性研究［7］发现，口腔颌面部成熟NK/T细胞淋巴瘤发病以结外NK/T淋巴瘤-鼻型（extranodal NK-/T-cell lymphoma， nasal type，ENKTL-NT）和PTCL-NOS为主。PTCL-NOS是最常见的T细胞淋巴瘤，以淋巴结病变为主，病情进展迅速，侵袭性强。基因表达谱分析发现与其他PTCL实体相比，PTCL-NOS具有明确的特征，包含2个不同预后的重要亚组：TBX21蛋白过表达者生存期较长，GATA3蛋白过表达则与不良预后显著相关［11］。研究［12］发现外周T细胞淋巴瘤的危险因素有乳糜泻、克罗恩病、先天性免疫功能缺陷、银屑病、吸烟和血液系统恶性肿瘤家族史，也有研究认为与EB病毒（Epstein-Barr virus，EBV）感染相关。本研究病例1有自身免疫性疾病天疱疮病史，病例2有长期家装材料接触史，包含甲醛、三氯乙烯、苯系物等。有证据表明三氯乙烯、苯与非霍奇金淋巴瘤发生相关［13-14］。

临床表现上，PTCL-NOS以淋巴结起病为主，也可出现淋巴结症状和结外症状兼有或仅有结外症状，淋巴结外受累常见于胃肠道及皮肤。约1/3的患者可出现发热、盗汗和体质量减轻等B症状。化验结果可出现贫血、嗜酸性粒细胞增多、高丙种球蛋白血症、乳酸脱氢酶水平明显增加等［10］。口腔PTCL-NOS非常罕见，国内外的病例报道较少，多表现为舌部肿块，可无明显界限。其中，1例患者出现舌偏移受限及构音障碍，检查发现中颅窝内侧硬脑膜不对称增厚，因此，患者构音障碍的临床表现被认为是继发于脑膜增厚导致舌下神经受压［15］。本研究发现，口腔PTCL-NOS好发于舌部、腭部、颊部，也可发生于牙龈、扁桃体。大多患者不伴有B症状。本研究病例1以舌部肿块及溃疡为首发表现，无明显的全身症状，并且患者同时有相似的天疱疮的临床表现，给诊断带来很大的困难。本研究病例2的口腔表现为硬腭中份溃疡，并累及双侧颈部淋巴结，有家装材料接触史和皮肤斑丘疹史，然而，以往病例报道未提及相似的接触史及皮损史。

在组织病理学方面，外周T细胞淋巴瘤具有显著的形态学异质性，需结合免疫表型特征和临床表现才能做出较为正确的诊断。在病理形态学上，多形性或单一的细胞形态均可出现，常见的是中至大细胞的混合背景，细胞核不规则，核仁明显，有丝分裂象多见，有时可见炎症成分诸如嗜酸性粒细胞、中性粒细胞、组织细胞和浆细胞［1，10］。PTCL-NOS没有特征性的免疫表型，表达泛T细胞抗原，表达CD4多于表达CD8的情况，伴1个或多个抗原表达下调或缺失（例如CD5、CD7）［16］，一般不表达B细胞抗原［17］。本文2例病例非典型细胞表达T细胞标志物CD3，不表达CD20，均表达CD2及CD7，Ki-67增殖指数分别为60%~70%及>90%，与预后相关。临床常用国际预后指数（international prognostic index，IPI），主要考虑年龄、临床分期、结外侵犯病灶数量、体能评分和乳酸脱氢酶水平等因素，评估淋巴瘤患者的预后和生存风险［18］。

从病理学角度而言，诊断PTCL-NOS前必须排除外周T细胞淋巴瘤的其他亚型，包括系统性间变性大T淋巴瘤、TFH表型的T细胞淋巴瘤、Lennert淋巴瘤等。从临床表现及预后考虑，病例1的鉴别诊断还包括：口腔鳞状细胞癌、重型复发性阿弗他溃疡、创伤性溃疡、结核性溃疡（表2）。病例2与ENKTL-NT的临床表现相似。但两者免疫表型上不同，预后也不同。ENKTL-NT的非典型细胞表达CD2、CD7、CD56，不表达CD3，常发现肿瘤细胞被EBV感染，EBER原位杂交检测阳性［7］。与外周T细胞淋巴瘤相比，结外NK/T细胞淋巴瘤的完全缓解率和3年总生存率明显较低［18］。

目前，PTCL-NOS化学治疗通常采用CHOP或CHOP样方案，其中CHOP样方案中的CHOEP方案被建议作为青年患者（<60岁）的一线治疗［19］。5例口腔PTCL报道中，4例接受化学治疗，方案均包含CHOP。本研究病例2应用GemOx-D方案化学治疗，国内队列研究［20］报道应用GemOx-D的难治性或复发性外周T细胞淋巴瘤（R/R PTCL）患者总缓解率为50.0%，完全缓解率为29.2%，2年无进展生存率和2年总生存率分别为28%和49%。吉西他滨单药及GDP方案（吉西他滨、地塞米松、顺铂）对复发性或难治性外周T细胞淋巴瘤有较好的疗效［21-22］。

综上所述，在口腔黏膜溃疡类疾病的诊治过程中，对于瓦德耶氏环（Waldeyer′s ring）、扁桃体、软腭、舌、磨牙后区的溃疡或肿物，应观察溃疡发病特点、颌面及头颈部淋巴结情况及全身非特异性症状，采集完整病史，对局部药物治疗无效的溃疡应及时活检，完善相关临床检查，尽可能利于早期诊断与治疗。本研究探讨PTCL-NOS的口腔临床表现、病理组织学特征，旨在为口腔科医师和口腔病理学医师熟悉和认识这种疾病提供参考，以避免错过此类恶性病变的早期诊断。

作者贡献声明

黄润语负责文章撰写、数据分析；张春叶负责病理切片及免疫组织化学观察；张颖、赵峥岩、杨扬负责病例资料收集；吴岚负责病例收集、研究设计、文章审阅及修改。所有作者均阅读并同意最终稿件的提交。

AUTHOR's CONTRIBUTIONS

The original draft writing and analysis were completed by HUANG Runyu. Biopsy observation and immunohistochemistry observations were completed by ZHANG Chunye. Clinical data collection and editing were done by ZHANG Ying, ZHAO Zhengyan, and YANG Yang. The conceptualization, review, and editing were done by WU Lan. All authors have read the last version of paper and consented to submission.

利益冲突声明

所有作者声明不存在利益冲突。

COMPETING INTERESTS

All authors disclose no relevant conflict of interests.

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