复发难治性多发性骨髓瘤伴多病灶髓外浸润合并肺腺癌1例报道

doi:10.3969/j.issn.1674-8115.2025.01.015

摘要/Abstract

摘要：

当前多发性骨髓瘤仍然不可治愈，多数患者经历多线复发，最终难治。髓外浸润是复发的一种常见形式，同时期的多病灶髓外浸润与继发的第二肿瘤难以鉴别。该文报告了1例复发难治性多发性骨髓瘤多处髓外浸润的患者，经多学科会诊，明确其为骨髓瘤髓外浸润与肺腺癌共存的病例。多病灶髓外浸润与肺腺癌的共存在临床上较为罕见，给患者的诊治决策带来了重大挑战。该文通过病例报道和文献复习，探讨骨髓瘤多病灶髓外浸润与共存的继发肿瘤的诊治，强调多学科会诊在实现精确诊断和优化患者预后方面的关键作用。

关键词: 复发难治性多发性骨髓瘤, 髓外浸润, 肺腺癌, 同期共存, 诊疗

Abstract:

Multiple myeloma (MM) remains an incurable disease, with most patients experiencing multiple relapses before ultimately progressing to refractory stage. Extramedullary infiltration is a common manifestation of relapse. However, distinguishing synchronous multifocal extramedullary infiltration from secondary malignancies poses significant diagnostic challenges. This study presents a case of relapsed refractory MM with multifocal extramedullary infiltration, diagnosed as coexistence of multiple myeloma extramedullary infiltration and pulmonary adenocarcinoma through multidisciplinary team (MDT) collaboration. Such coexistence is exceedingly rare in clinical practice and introduces substantial complexity in diagnosis and treatment planning. Through a comprehensive case report and literature review, this paper explores the diagnostic and therapeutic approaches to managing multifocal extramedullary infiltration coexisting with secondary malignancies in MM, highlighting the pivotal role of MDT in achieving precise diagnosis and optimizing patient outcomes.

Key words: relapsed and refractory multiple myeloma, extramedullary infiltration, pulmonary adenocarcinoma, synchronous coexistence, diagnosis and treatment

中图分类号:

R733.3

杜芳, 周凌云, 陈姣, 刘丹波, 向泓先, 陈海飞. 复发难治性多发性骨髓瘤伴多病灶髓外浸润合并肺腺癌1例报道[J]. 上海交通大学学报（医学版）, 2025, 45(1): 122-128.

DU Fang, ZHOU Lingyun, CHEN Jiao, LIU Danbo, XIANG Hongxian, CHEN Haifei. A case report of relapsed and refractory multiple myeloma with multifocal extramedullary infiltration and pulmonary adenocarcinoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(1): 122-128.

图/表 5

表1 患者治疗方案

Tab 1 Patient treatment plan

Chemotherapy protocol	Therapeutic efficacy
Bortezomib+cyclophosphamide+dexamethasone (BCD, 7 courses)	VGPR
Bortezomib+dexamethasone+thalidomide (BDT, 3 courses)	CR
Bortezomib (maintenance)	—
Bortezomib+thalidomide (BT, maintenance)	CR
Thalidomide (maintenance)	CR
Bortezomib+(R, S)-lenalidomide+dexamethasone (BRD, 3 courses)	PD
Bortezomib+cyclophosphamide+dexamethasone+thalidomide (BCDT)	PR
Ixazomib+dexamethasone (ID)	PD
Ixazomib+pomalidomide+dexamethasone (IPD)	SD
Daratumumab+pomalidomide+dexamethasone (DPD, 9 courses)	PR
Resection of thoracoscopic left lower lobe and chest wall mass (lung adenocarcinoma and multiple myeloma chest wall invasion)	PD
Daratumumab+carfilzomib+dexamethasone (DKD, 2 courses)	PD
Carfilzomib+cyclophosphamide+dexamethasone (KCD, 5 courses)	PR
Carfilzomib+bendamustine+dexamethasone (KBD, 2 courses)	PD
Daratumumab+carfilzomib+pomalidomide+dexamethasone (DKPD)	PR

图1 骨髓形态的细胞学观察（×1 000）Note： A. Plasma cells of varying sizes with round nuclei (arrow). B. Plasma cells showing double nuclei, nuclear displacement, and a clear perinuclear halo (arrow).

Fig 1 Cytological observation of bone marrow morphology (×1 000)

图2 胸部增强CT显像Note： A/B. Two different layers of contrast-enhanced chest CT scans. Multiple elongated strip shadows are visible around the same site, and mild sustained enhancement is visible on contrast-enhanced scans (arrow). C. Contrast-enhanced chest CT showing a chest wall mass (arrow) at the mediastinal window level. D. Contrast-enhanced chest CT showing a chest wall mass (arrow) at the lung window level.

Fig 2 Contrast-enhanced chest CT scans

图3 肺结节病理诊断Note： A/B. H-E staining. C. Immunohistochemistry of CK7. D. Immunohistochemistry of Napsin A. E. Immunohistochemistry of TTF-1.

Fig 3 Pathological diagnosis of pulmonary nodules

图4 胸壁肿瘤病理检查结果Note： A‒C. H-E staining. D. Immunohistochemistry of CD38. E. Immunohistochemistry of CD138. F. Immunohistochemistry of κ.

Fig 4 Pathological examination results of chest wall tumor

参考文献 21

1	中国医师协会血液科医师分会, 中华医学会血液学分会. 中国多发性骨髓瘤诊治指南(2022年修订) [J]. 中华内科杂志, 2022, 61(5): 480-487.
	Chinese Hematology Association, Chinese Society of Hematology. Guidelines for the diagnosis and management of multiple myeloma in China (2022 revision) [J]. Chinese Journal of Internal Medicine, 2022,61(5): 480-487.
2	CASTANEDA O, BAZ R. Multiple myeloma genomics: a concise review[J]. Acta Med Acad, 2019, 48(1): 57-67.
3	MOREAU P, GARFALL A L, VAN DE DONK N W C J, et al. Teclistamab in relapsed or refractory multiple myeloma[J]. N Engl J Med, 2022, 387(6): 495-505.
4	MOREAU P, KUMAR S K, SAN MIGUEL J, et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group[J]. Lancet Oncol, 2021, 22(3): e105-e118.
5	USMANI S Z, QUACH H, MATEOS M V, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study[J]. Lancet Oncol, 2022, 23(1): 65-76.
6	de WEERS M, TAI Y T, van der VEER M S, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors[J]. J Immunol, 2011, 186(3): 1840-1848.
7	AGARWAL R, GUPTA R, BHASKAR A, et al. Synchronous presentation of multiple myeloma and lung cancer[J]. J Clin Oncol, 2008, 26(35): 5814-5816.
8	KAISER M F, CROFT J, SHAH P, et al. Durable response of multiple myeloma and non-small cell lung cancer with simultaneous, biologically targeted treatment[J]. Br J Haematol, 2020, 189(1): e1-e3.
9	WANG Z, DENG H, ZHANG L, et al. Daratumumab for refractory IgD multiple myeloma with lung cancer and persistent thrombocytopenia: a case report [J]. Clin Lab, 2021, 67(11):2589.
10	DONG H H, LI J, KANG L, et al. Simultaneous multiple myeloma and non-small cell lung carcinoma: a case report and review of the literature[J]. Oncol Lett, 2022, 23(6): 195.
11	ZUO W, ZHU X, YANG J, et al. Bortezomib combined with lenalidomide as the first-line treatment for the rare synchronous occurrence of multiple myeloma and pulmonary adenocarcinoma: a case report[J]. Medicine (Baltimore), 2017, 96(1): e5787.
12	LIN J, ZHU H, LU X, et al. Autologous cytokine-induced killer cells in the treatment of multiple myeloma concomitant with lung cancer and paraneoplastic dermatoses[J]. Intern Med, 2010, 49(21): 2341-2346.
13	GIBSON S J, COOPER J D, PHAM K, et al. Prognostic impact of second primary malignancies in multiple myeloma: an ASCO CancerLinQ discovery analysis of the modern era[J]. Am J Hematol, 2023, 98(11): E325-E327.
14	KLEBER M, IHORST G, TERHORST M, et al. Comorbidity as a prognostic variable in multiple myeloma: comparative evaluation of common comorbidity scores and use of a novel MM-comorbidity score[J]. Blood Cancer J, 2011, 1(9): e35.
15	ENGELHARDT M, IHORST G, LANDGREN O, et al. Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years[J]. Haematologica, 2015, 100(10): 1340-1349.
16	MACLACHLAN K, DIAMOND B, MAURA F, et al. Second malignancies in multiple myeloma; emerging patterns and future directions[J]. Best Pract Res Clin Haematol, 2020, 33(1): 101144.
17	JONES J R, CAIRNS D A, GREGORY W M, et al. Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial[J]. Blood Cancer J, 2016, 6(12): e506.
18	ORMEROD A, FAUSEL C A, ABONOUR R, et al. Observations of second primary malignancy in patients with multiple myeloma[J]. Clin Lymphoma Myeloma Leuk, 2012, 12(2): 113-117.
19	SCHRANK Z, CHHABRA G, LIN L, et al. Current molecular-targeted therapies in NSCLC and their mechanism of resistance[J]. Cancers (Basel), 2018, 10(7): E224.
20	EGUREN-SANTAMARIA I, SANMAMED M F, GOLDBERG S B, et al. PD-1/PD-L1 blockers in NSCLC brain metastases: challenging paradigms and clinical practice[J]. Clin Cancer Res, 2020, 26(16): 4186-4197.
21	PALUMBO A, AVET-LOISEAU H, OLIVA S, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group[J]. J Clin Oncol, 2015, 33(26): 2863-2869.

[1]	吴雷, 杜凤麟, 赵明娜, 任逸喆, 张先洲, 娄加陶. N型蛋白酪氨酸磷酸酶受体在肺腺癌中的表达及其促进肿瘤转移的机制[J]. 上海交通大学学报（医学版）, 2025, 45(7): 846-857.
[2]	许万星, 王琳, 郭巧梅, 王薛庆, 娄加陶. 多模态肺结节诊断模型的临床验证及应用价值探索[J]. 上海交通大学学报（医学版）, 2024, 44(8): 1030-1036.
[3]	朱鸣阳, 许元元, 任江浩, 黄嘉正, 李若楠, 谭强. 以磨玻璃结节为表现的肺腺癌亚肺叶切除研究综述[J]. 上海交通大学学报（医学版）, 2024, 44(7): 922-927.
[4]	王梦菲, 杨守志, 乔永霞, 黄琳. 基于临床检验指标建立肺腺癌患者浸润程度判别模型[J]. 上海交通大学学报（医学版）, 2024, 44(1): 98-107.
[5]	赵雪, 董春燕. WD40重复蛋白43在肺腺癌中的表达及其对细胞紫杉醇耐药的影响[J]. 上海交通大学学报（医学版）, 2022, 42(12): 1656-1665.
[6]	熊雷, 易茜, 许明芳, 陈健. MRPL12在肺腺癌中的表达和预后分析[J]. 上海交通大学学报(医学版), 2021, 41(8): 1033-1040.
[7]	陈亮，王喆歆，姚烽. Ⅰ A期肺腺癌气道播散临床病理因素分析[J]. 上海交通大学学报(医学版), 2020, 40(7): 957-961.
[8]	冉淑君，梁景平. 口腔诊疗中新型冠状病毒气溶胶传播的防控[J]. 上海交通大学学报（医学版）, 2020, 40(3): 282-.
[9]	钱洁蕾，束蓉. 牙周诊疗中针对新型冠状病毒感染的防控[J]. 上海交通大学学报（医学版）, 2020, 40(2): 145-.
[10]	张伟然1, 2，林雪峰3，李鑫2，张浩2，王猛2，孙伟2，韩兴鹏2，孙大强1, 4. 转录组分析鉴定肺腺癌潜在的生物标志物[J]. 上海交通大学学报(医学版), 2020, 40(12): 1598-1606.
[11]	蒋蓓蓓，张亚平，张琳，刘桂雪，解学乾. 深度卷积神经网络对≤ 3 cm的亚实性肺腺癌 CT图像病理学分型预测的可视化研究[J]. 上海交通大学学报（医学版）, 2019, 39(9): 1045-.
[12]	董晓晶 1，张男 1，甘露 1，吴怡颖 1，陈允允 1，方琼 2. 个案管理模式下老年乳腺癌患者辅助治疗依从性分析[J]. 上海交通大学学报（医学版）, 2019, 39(2): 170-.
[13]	丁语,王新,王兵,赵海光 . 环激光联合硬化剂注射治疗下肢静脉功能不全的中短期疗效分析#br#[J]. 上海交通大学学报（医学版）, 2017, 37(8): 1138-.
[14]	孟爽，汪洋*，雷绘敏，唐亚斌，朱亮 . 基于液相色谱-高分辨质谱技术的厄洛替尼获得性耐药肺腺癌细胞代谢轮廓分析[J]. 上海交通大学学报（医学版）, 2017, 37(5): 571-.
[15]	马静，沈鸣，段友容，杜联芳 . 载紫杉醇纳米诊疗体的制备及初步应用[J]. 上海交通大学学报（医学版）, 2017, 37(2): 166-.