Objective: To investigate the clinicopathological features, immunophenotypic characteristics, molecular genetic profiles for an accurate diagnosis of renal tumors associated with Birt-Hogg-Dubé (BHD) syndrome. Methods: Clinicopathological data from 10 patients with BHD syndrome-associated renal tumors were collected from Ningbo Clinical Pathology Diagnosis Center (4 cases) and Ruijin Hospital, Shanghai Jiaotong University School of Medicine (5 in-house cases and 1 consultation case) from January 2015 to December 2025. Their clinical characteristics and histological features were studied and analyzed. Immunohistochemical staining and next-generation sequencing (NGS) were performed. Follow-up data were obtained and relevant literature was reviewed. Results: All 10 patients were adults, including 6 males and 4 females, with an age 57 (54, 67) years old. Seven patients had pulmonary bullae/pneumothorax and one patient had a right anterior chest wall fibroma. For the patients with renal tumor, 6 cases presented with a unilateral single tumor, 1 case with unilateral multiple tumors and 3 cases with bilateral multiple tumors (totaling 16 renal tumors). Four cases of the renal tumor were associated with multiple renal cysts. Histologically, among the 16 tumors, 10 were hybrid oncocytic/chromophobe tumors (HOCT) with the typical "mosaic" pattern, 4 with chromophobe renal cell carcinoma-like morphology, 1 with predominantly sarcomatoid morphology and focal areas of low-grade oncocytic renal tumor, and 1 renal angiomyolipoma. The immunophenotype of BHD-associated renal tumors was not specific. Immunohistochemistry revealed diffuse positive for GPNMB in all epithelial-derived renal tumors (15/15). CK7 and CD117 were focally expressed in 7/15 cases each, CD10 was focally expressed in 6/15 cases, and carbonic anhydrase Ⅸ (CAⅨ) was negative in all tumors (0/15). ALK, TFE3 and TFEB were negative. No loss of SDHB or FH expression was identified. DNA next-generation sequencing identified FLCN mutations in all cases, including 7 cases with germline FLCN mutations and 3 cases with somatic FLCN mutations. During a 9-120 months follow-up, the patient with sarcomatoid differentiation passed away 6 months after renal tumor identified, and another patient experienced relapse in the left kidney 6 years after bilateral nephron-sparing surgery. No relapse or metastasis was identified in the remaining 8 patients. Conclusions: Morphologically, BHD syndrome-associated renal tumors can mimic various low-grade oncocytic renal tumors. In addition to the classic HOCT morphology, they may also present with high-grade sarcomatoid differentiation. GPNMB is a highly sensitive marker for BHD-associated renal tumors. Molecular genetic analysis to detect FLCN mutation is the gold standard for definitive diagnosis. BHD syndrome-associated renal tumors typically show indolent biological behavior, with sarcomatoid differentiation as a morphological feature of poor prognosis.
目的:探讨原发中枢神经系统（CNS）ALK阳性组织细胞增生症（APH）的临床病理学特征。方法:对中山大学肿瘤防治中心病理科于2022—2024年间确诊的4例原发CNS APH病例（均以CNS为唯一受累部位）进行回顾性分析，包括其组织学形态、免疫表型、遗传学特征及预后，并复习相关文献。结果:例1~4患者年龄分别为2、6、14、14岁，例1和例4为男性，例2和例3为女性。组织学形态显示，在炎性细胞背景中见中等至大的肿瘤细胞，胞质丰富、淡嗜酸性，细胞核呈卵圆形或不规则折叠，染色质细腻，核仁不明显。免疫表型方面，4例肿瘤细胞均强阳性表达CD68、CD163及ALK（D5F3）。例1、3、4通过二代测序检出KIF5B：：ALK基因融合；例2、3经荧光原位杂交（FISH）检测出ALK基因断裂。4例患者术后接受了ALK抑制剂治疗，随访截至2025年9月，均恢复良好。结论:原发CNS APH少见，其多样的组织学形态易与其他原发CNS肿瘤/病变混淆。KIF5B：：ALK融合是最常见的分子事件。目前，以ALK抑制剂为核心的靶向治疗可获得显著疗效。病理医师需充分认识其组织学形态、免疫表型以及分子改变，对于实现精准诊断、指导临床治疗及改善患者预后至关重要。
Objective: To investigate the clinicopathological characteristics, molecular genetics, treatments and prognosis of aggressive B-cell lymphomas (ABCL) with MYC gene cluster amplification. Methods: Eight cases of ABCL with MYC gene cluster amplification were collected, including 6 cases from the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China and 2 consultation cases from outside hospitals. The histomorphology, immunohistochemical profiles, and molecular genetic characteristics were analyzed. Clinical follow-up and literature review were also conducted. Results: Among the eight patients, six were male and two were female, with an age 71.5 (61.7, 74.2) years. All six in-house patients presented with abdominal pain at onset, without B symptoms. Most cases were classified as Ann Arbor stage Ⅲ-Ⅳ. Extranodal involvement occurred in 5 of the 6 in-house cases, primarily affecting the gastrointestinal tract (4/5). All initial bone marrow biopsies showed no evidence of lymphoma. One patient had a history of immunosuppression following renal transplantation. Two cases exhibited diffuse large B-cell lymphoma (DLBCL) morphology. The other six showed high-grade features, while three of them showed Burkitt lymphoma-like morphology. Except for one case of blastoid variant mantle cell lymphoma, the remaining six cases (6/7) displayed a germinal center B-cell phenotype. None of the in-house cases harbored bcl-2 or bcl-6 rearrangements as shown by fluorescence in situ hybridization. 11q alterations were identified in all but one consultation case, including gain/loss type in five cases and 11q gain in two. 11q telomere loss of heterozygosity by chromosomal microarray analysis was not detected in one of the two cases with 11q gain that was subject to the test. The duration of follow-up ranged from 5.9 to 55.5 months, with 5 patients alive at the end of the study. Conclusions: ABCL with MYC gene cluster amplification often presents high-grade morphology and gastrointestinal involvement, which strongly suggests the alteration of 11q. It seems to have a favorable prognosis.
乳腺鳞状细胞癌（BSCC）是乳腺化生性癌中的罕见亚型。BSCC在临床上常表现为生长迅速、体积较大的肿块，多为三阴性表型，总体预后较差。目前研究提示其组织起源并非单一路径，可能源自良性囊性或增生性病变中鳞状化生区域发生恶变、非特殊型浸润性癌的克隆演化以及乳房植入物相关鳞状细胞癌。病理形态以典型鳞状分化为诊断要点，肿瘤内常伴成分与受体表达的空间异质性，故需充分取材并结合免疫表型综合评估。分子层面以TP53、PIK3CA等高频体细胞突变及PI3K/AKT相关通路异常为主要特征，部分病例可见PTEN失活、HRAS-PIK3R1共突变及TERT启动子突变等事件。鉴于BSCC需与转移性鳞状细胞癌、腺鳞癌、非特殊型浸润性癌伴鳞状分化及其他化生性肿瘤严格区分，本文在综述其临床病理与分子特征基础上，提出“排除转移、确认鳞状分化、界定化生性亚型”的三步法诊断路径，以期提高诊断一致性，并为分层治疗探索提供参考。
目的:探讨儿童睾丸大细胞钙化型支持细胞瘤（LCCSCT）的临床病理学特征。方法:回顾性分析2012年1月至2025年6月徐州市儿童医院（2例）和首都医科大学附属北京儿童医院（2例）共4例儿童睾丸LCCSCT的临床资料，观察其病理组织学形态、免疫表型及分子遗传学特征，并复习相关文献。结果:例1~4均为男性患儿，无隐睾或假两性畸形，发病年龄分别为3岁3个月、6岁9个月、6岁6个月和6岁5个月。例1双侧睾丸相继受累，例2、例3和例4左侧单侧发病，均为单发病灶，肿瘤最大径分别为2.1 cm（左）/1.6 cm（右）、1.2 cm、1.8 cm、1.5 cm。临床表现为无痛性睾丸肿块，影像学检查示睾丸内混合回声伴钙化。大体观察见肿瘤切面灰黄实性、质地中等至硬、伴沙砾感。镜下观察见肿瘤细胞呈条索状、巢状或小管状排列，细胞呈卵圆形，胞质丰富且嗜酸性，核大空泡状，核仁清晰，伴钙化，局灶见黏液样间质及中性粒细胞浸润。免疫组织化学结果示4例均弥漫阳性表达α抑制素、钙视网膜蛋白及S-100蛋白，蛋白激酶A调节亚基1A（PRKAR1A）均为阴性。二代测序结果：1例检出PRKAR1A基因移码突变（p.Ser14fs）及无义突变（p.R42*），1例检出17q24.2区域杂合缺失性胚系突变（此例合并Carney综合征）。随访31~98个月，4例患儿均无病生存。结论:LCCSCT是儿童睾丸原发肿瘤中的罕见类型，多为散发，部分合并Carney综合征。组织学上存在钙化和PRKAR1A蛋白缺失表达有助于与其他类型支持细胞瘤鉴别，手术完整切除后患儿预后良好。
