Fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) is a high-grade renal cell carcinoma characterised by mutations in the FH gene. FH-dRCC is highly aggressive and has a poor prognosis, underscoring the importance of accurate diagnosis. Although the histopathological features of this neoplasm have been reported in previous studies, descriptions of its cytopathological features are limited. Here, we report the cytopathological morphologies of two cases of metastatic FH-dRCC in male patients aged 48 and 35 years. Case 1 presented with a cystic solid mass in the right retroperitoneal lumbar rib triangle region after the excision of a cystic tumour in the right kidney. Cytopathological examination of the fine-needle aspiration sample revealed papillary and tubular tumour cells. Case 2 developed abdominal ascites after bilateral nephrectomy, and cytopathological examination of ascitic fluid-characterised tumour cells with a high nuclear grade arranged in papillary and glandular patterns. In both cases, large tumour cells were observed with abundant eosinophilic cytoplasm, coarse chromatin and irregular nuclear shapes. Some cells exhibited characteristic eosinophilic macronucleoli and perinucleolar halos. Tumour cell clusters with a high nuclear grade, papillary structures, prominent eosinophilic macronucleoli and perinucleolar halos are the major cytopathological traits of FH-dRCC. CK7-negative/CA9-negative and PAX8-positive immunophenotypes may serve as important diagnostic markers. Moreover, the AKR1B10-positive/2SC-positive/FH-deficient immunophenotype contributes to the diagnosis of this tumour. Consequently, if the tumour cells have these characteristics, the diagnosis of FH-dRCC should be considered in cytology.

Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by the foamy CD68+CD1a- histiocytes infiltrating multiple organs and tissues. ECD might be asymptomatic or present with variable manifestations. The diagnosis of ECD requires characteristic radiological findings and pathological features. Herein, we described a 52-year-old female patient who was admitted to our hospital for recurrent pericardial effusion for two months. She has a medical history of papillary thyroid carcinoma (PTC) and underwent a total thyroidectomy two years before admission. The radiological findings suggested a potential diagnosis of ECD. Cytological analysis of the effusion cytology specimen revealed CD68+CD1a− histiocytes, confirming the ECD diagnosis. The BRAF V600E mutation was identified in the histiocytes, prompting the administration of vemurafenib, a BRAF inhibitor. After two months of standard-dose vemurafenib treatment, the disease was well controlled with pericardial effusion regression.

Rhabdomyosarcoma (RMS) is a common soft tissue malignant tumor, especially in young patients. Alveolar rhabdomyosarcoma (ARMS) is a subtype of RMS that is prevalent in adolescents. This malignant tumor usually develops in the extremities and can also involve the trunk, perineum, and pelvis. Now, we report a rare case of pelvic lymph node metastatic alveolar RMS in a young patient, which was determined by fine needle aspiration cytology (FNAC). To the best of our knowledge, this is the first case in which the definite diagnosis of ARMS was initially made by FNAC.

Cerebrospinal fluid (CSF) cytology of primary central nervous system lymphoma arising in the immune deficiency/dysregulation setting (IDD-PCNSL) has not been described. This study presented a case of IDD-PCNSL-DLBCL, a GCB phenotype who was successfully diagnosed by CSF cytology in conjunction with ICC, ISH, FCM and clinical information.

OBJECTIVES:To explore the approach to the diagnosis of malignant serous effusion (SE) caused by angioimmunoblastic T-cell lymphoma (AITL).METHODS:The clinical, cytomorphologic, immunophenotypic, and molecular features of 6 patients were summarized.RESULTS:Clinically, SE caused by AITL was predominant in middle-aged and older male patients with multiple SEs and lymphadenopathy. Cytomorphology showed small to medium-sized, irregular lymphocytes with clear cytoplasm and mixed with various inflammatory cells and apoptosis. Hodgkin/Reed-Sternberg-like cells were detected in 2 of 6 cases. Furthermore, 2 patterns of cytomorphology were described for the first time. Flow cytometry revealed abnormal T-cell populations with loss of surface CD3 (3/4 cases) and CD7 (3/4 cases). In addition, B-cell populations lacking surface immunoglobulin (Ig) were identified in 2 of 4 cases. Immunocytochemical staining revealed expression of at least 2 T follicular helper markers. Epstein-Barr virus-encoded RNA (EBER)-positive cells were demonstrated in 4 of 5 cases. Clonal T-cell receptor γ chain rearrangement was detected in 6 cases, and 3 of them had concomitant clonal immunoglobulin gene rearrangement. Moreover, 2 cases revealed discrepant findings regarding IgH/Igκ rearrangements in cytohistologic correlation.CONCLUSIONS:This study broadens the morphologic spectrum of malignant SE caused by AITL and provides diagnostic criteria in routine practice.

Cystic cervical lymph node metastasis from papillary thyroid carcinoma (CLMPTC) initially presents as cervical cystic lesions, which are often underdiagnosed as other cystic cervical lesions. There is no comprehensive diagnostic strategy of fine needle aspiration (FNA) cytology for CLMPTC.The clinical and FNA cytomorphology data of 87 patients with CLMPTC were analyzed. Thyroglobulin (TG) immunostaining was performed in 40 cases; BRAF V600E mutation was evaluated in 42 cases; the thyroglobulin (Tg) levels of aspiration fluids were assessed in 46 cases. Correspondingly, the data of 42 cases with solid cervical lymph node metastasis from papillary thyroid carcinoma (SLMPTC) and 32 cases with other cystic cervical lesions were collected as controls.Compared with SLMPTC, CLMPTC has less classical PTC cytomorphology characteristics-for example, nuclear crowding/overlapping, nuclear irregular contours, etc. (p < .05). Additionally, micropapillary architecture and histiocyte-like tumor cells were more often observed in CLMPTC than in SLMPTC (p < .01). The positive rate of TG immunocytochemistry in CLMPTC was 100% (40/40). The positive rate of BRAF V600E mutation in CLMPTC was 81.0% (34/42), which was higher than that in SLMPTC (64.3%; 27/42) (p = .087). The Tg levels in aspiration fluids were significantly higher in CLMPTC (all>500 μg/L) than in other cervical cystic lesions (range: 2.9 μg/L to 40.1 μg/L) (p < .01).To reduce underdiagnoses of CLMPTC, a reasonable diagnostic strategy, as summarized in this study is needed: according to the number of tumor cells, choosing immunocytochemistry (TG) and/or thyroglobulin in fine needle aspirates testing as auxiliary diagnostic measures.

目的 评估免疫标记半乳糖凝集素-3(Gal-3)、细胞角蛋白-19(CK-19)、间皮细胞角蛋白-1(HBME-1)和BRAF V600E突变联合检测对术前甲状腺细胞学诊断不确定结节的良恶甄别作用.方法 选取四川大学华西医院2014年12月至2019年3月术前细胞学诊断不确定的甲状腺结节患者992例为研究对象,其中行3项免疫标记和/或BRAF V600E突变辅助检测的314例患者为观察组,未行上述辅助检测的678例为对照组,以术后病理学诊断评估上述检测单独或联合应用辅助技术的诊断价值.结果 观察组术后恶性率高于对照组(P<0.001).观察组中,195例患者行Gal-3、CK-19和HBME-1的免疫标记检测,301例患者行BRAF V600E突变检测,其中仅182例患者行3项免疫标记和BRAF V600E突变联合分析.对于单个检测,BRAF V600E突变和CK-19的特异性和敏感性最高,分别为100.0％和90.6％,当联合使用时诊断效能明显提高.BRAF V600E突变检测、Gal-3和CK-19组合的诊断效果最好,准确率最高达92.9％,该组合术前正确分类了168个恶性结节中的161个(95.8％)和14个良性病变中的8个(57.1％),其中159例甲状腺乳头状癌中有158例被本组合正确分类.结论 免疫标记Gal-3、CK-19和BRAF V600E突变检测对细胞学诊断不确定的甲状腺结节有较高的良恶性甄别价值.

目的 探讨术前甲状腺细针穿刺细胞学(FNAC)检查的开展对甲状腺术后疾病谱构成的影响.方法 收集四川大学华西医院2007年1月～2016年12月甲状腺外科手术病例共11574例,逐年统计甲状腺手术总病例数、术前行细针穿刺细胞学病例数、术中冷冻病例数;根据患者术后病理结果统计各年份良恶性病变的占比、恶性肿瘤的具体类型(包括微小乳头状癌)及构成,并对其与术前细针穿刺细胞学检查开展的相关性进行分析.结果 术前细针穿刺率由2.24％增长到了 72.30％、术中冷冻率由85.39％降低到了 47.50％、术后恶性肿瘤占比由25.93％增长到了 83.86％;恶性肿瘤中乳头状癌由86.21％增长到97.53％(其中微小乳头状癌由21.33％增长到了 47.64％),髓样癌由2.87％降低到1.21％,滤泡癌由7.47％降低到0.57％,未/低分化癌十年诊断共计28例.结论 甲状腺细针穿刺细胞学的开展能显著提高甲状腺手术恶性肿瘤的占比,极大的改变了恶性肿瘤的构成,减轻了术中冷冻的压力,可在临床大力推广.

患者女性,39岁,3年前发现颈部包块,最大径3 cm,质软,无红肿、压痛、畏寒、高热及其他不适,在当地医院行颈部包块细针穿刺(fine needle aspiration,FNA)检查,诊断为淋巴结慢性肉芽肿性炎.

目的 探讨人乳头状瘤病毒(human papillomavirus,HPV)与人类疱疹病毒(epstein-barr vi-rus,EBV)重叠感染在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及宫颈癌发病中的意义.方法 收集留存归档的组织标本的CIN 92例及宫颈鳞癌49例,免疫组化法检测组织HPV、EBV表达,并取同期因子宫良性疾病切除子宫但光镜下宫颈上皮无异常病变的30例患者的宫颈组织标本作为对照,统计各组HPV、EBV及两者重叠感染率,分析HPV、EBV重叠感染在宫颈癌发病中的意义.结果 整体比较:随宫颈上皮病变的进展,HPV、EBV阳性率上升(P<0.05).组内比较:正常宫颈组织HPV、EBV阳性率低于CINⅡ～Ⅲ级、宫颈癌组织(P<0.05),CINⅠ级HPV、EBV阳性率低于CINⅡ-Ⅲ级、宫颈癌组织(P<0.05),CINⅡ～Ⅲ级HPV、EBV阳性率又低于宫颈癌组织(P<0.05);正常宫颈组织HPV+EBV阳性率低于CINⅡ～Ⅲ级、宫颈癌组织(P<0.05),CINⅠ级HPV+EBV阳性率低于CINⅡ～Ⅲ级、宫颈癌组织(P<0.05),CINⅡ～Ⅲ级HPV+EBV阳性率低于宫颈癌组织(P<0.05);析因分析显示:HPV、EBV重叠感染对宫颈癌发病存在协同影响(F=5.687,P<0.05).结论 HPV感染参与CIN及宫颈癌发病过程;EBV感染与高级别CIN、宫颈癌发病有关;两者重叠感染与宫颈癌发生有关,或可能存在协同作用,共同参与宫颈癌变进展.

Mucinous breast cancer is a slow-growing neoplasm, which has fewer lymph node metastases and favorable prognosis compared with invasive breast cancer no special type. The hematogenous spread of breast mucinous carcinoma is very rare. Though breast cancer involving thyroid has been reported before, there is still no report about thyroid metastatic breast mucinous carcinoma in the literature. Recently by performing thyroid fine-needle aspiration, a 58-year-old woman who had breast cancer 13 years ago was diagnosed as thyroid metastatic mucinous breast carcinoma, cellular variant with neuroendocrine differentiation. For this patient, the thyroid was the only involved site without widespread metastatic diseases, so thyroidectomy and the right cervical lymph nodes dissection were performed to make better survival. As a result, the patient had not shown any signs of recurrence 9 months after the thyroid surgery.

Background: The aim of this study was to establish the liability of cytological diagnostic and, along with ancillary techniques, to sub-classify hematopoietic malignancies in serous effusions. Methods: We retrospectively reviewed the serous effusions of hematopoietic malignancies over an 11-year period, along with ancillary studies, clinical and histological data. We compared cytological along with histological diagnosis to evaluate the value of cytology itself. Furthermore, the discrepant cases were reviewed. Results: In this study, a total of 242 cases were identified as hematopoietic malignancies. Ancillary technologies were performed: in 24 cases FCM, 242 cases ICC, 35 cases ISH, 81 cases PCR and 10 cases FISH. Cyto-histological correlation was available for 122 cases. The subtyping of hematopoietic malignancies was achieved using cytological material in 65/122 cases (53.3%). Of the 65 cases, T-Acute lymphoblastic leukemia/lymphoma (22.1%) was the leading subtype, followed by Burkitt lymphoma (5.7%), plasmacytoma (5.7%). Cyto-histological correlation showed a 100% concordant rate of diagnosis for hematopoietic malignancies and a high degree of agreement on sub-classification (51.6%). In this regard, T-acute lymphoblastic leukemia/lymphoma, plasmacytoma, extranodal NK/T-cell lymphoma, nasal type, anaplastic large cell lymphoma, myeloid sarcoma, and follicular lymphoma showed the highest degree of agreement (100%). The sub-classification on cytology was achieved in 53 out of the remaining 120 cases without histological diagnosis (44.2%). T-acute lymphoblastic leukemia/lymphoma (20.8%) was again the most frequently encountered subtype, followed by plasmacytoma (5.8%) and Burkitt lymphoma (4.2%). Conclusions: This large series study provided evidence that combining cytology and ancillary studies enabled the accurate serous effusions cytological diagnoses and subsequent sub-classification for the described malignancies.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been widely adopted since its introduction. In this study, we aimed to report our experience using this reporting system at a College of American Pathologists (CAP)‐accredited hospital laboratory in a large series of Chinese patients.

引文格式: Liu N, Li QY, Chang YY,et al. Experience of Surepath liquid-based preparation for non-gynecologic cytology[J]. J Cancer Con-trol Treat, 2019, 32(4):350-354. [刘念,李启源,常樱瑜,等. Surepath非妇科液基制片的经验分享[J].肿瘤预防与治疗,2019,32 (4):350-354. ]

目的:探讨子宫颈细胞人乳头瘤病毒(HPV) L1壳蛋白的表达对宫颈细胞恶性转化及细胞免疫的影响,解析针对宫颈癌进行HPV L1壳蛋白检测的临床应用价值.方法:收集鹰潭市人民医院2012年7月～2014年12月期间在妇科门诊就诊妇女280例,对所有入组人员进行液基细胞学检查(LCT),同时,应用赛泰(R)细胞/组织HPV检测试剂盒对L1壳蛋白进行免疫细胞化学染色以检测脱落细胞中HPV L1壳蛋白的表达,采用CervistaHPV检测系统进行HPV检测,将宫颈活检病理学结果作为基线进行比较,按照病变不同程度分为上皮内病变阴性(NILM)、非典型性鳞状上皮细胞(ASC)、低度鳞状上皮内病变(LSIL)、高度鳞状上皮内病变(HSIL)和鳞状上皮癌(SCC)5组,对比分析HPV L1壳蛋白表达在不同程度病变中的阳性表达率情况.采用ELISA检测细胞中白细胞介素2(IL-2)及肿瘤坏死因子α(TNF-α)的水平,利用流式细胞术检测血清细胞中免疫细胞亚群的情况.结果:HPV L1壳蛋白阳性率随着宫颈活检确定的宫颈病变级别的加重而呈现下降趋势,在SCC中的表达为0.各组间HPV L1壳蛋白阳性表达率的差异具有统计学意义(P＜0.05);IL-2水平随着HPV L1壳蛋白表达阳性率升高而减少,TNF-α水平随着HPV L1壳蛋白表达阳性率升高而增加(P＜0.05);HPV L1壳蛋白阳性表达伴随着免疫激活性细胞亚群的减少,免疫抑制性免疫细胞群体的增加(P＜0.05),且具有强相关性.结论:子宫颈细胞HPV L1壳蛋白表达的检测对于判断宫颈细胞恶性转化以及机体细胞免疫状态具有良好的应用价值,值得临床上加以应用.

Rationale: Indolent T-cell lymphoproliferative disease (T-LPD) of gastrointestinal tract is a rare recently described disease that seldom progresses. We report a case of T-LPD with synchronous diffuse large B-cell lymphoma (DLBCL) that cause aggravation of disease. Patient concerns: A 46-year-old Chinese male presented with intermittent paraumbilical colic pain, bloating, and occasional diarrhea for 10 years. His condition aggravated with partial bowel obstruction recently. The patient was diagnosed as T-LPD initially based on histological result and T-cell receptor-gamma clonal gene rearrangement test. The patient was followed without chemotherapy. His condition stabilized for 1 year and then deteriorated with small intestine perforation. Diagnosis: The patient was diagnosed as indolent T-LPD and DLBCL finally. Interventions: The patient had surgery for intestine perforation and received chemotherapy for DLBCL and T-LPD afterward. Outcomes: At 6 months follow-up, the patient continued to have resolution of his symptoms. Lessons: Early detection of high-grade transformation of T-LPD or the coexistence of aggressive lymphoma is essential for the patient. DLBCL may coexist in the indolent course of T-LPD. The diagnosis of T-LPD should be made cautiously in case with progressing symptoms such as intestinal obstruction.

OBJECTIVE:The objective of this study is to evaluate the effectiveness of diagnosing Burkitt lymphoma (BL) in serous effusion (SE) specimen and summarise the characteristics of BL in SE. We also assess the utility of a germinal centre-associated marker, LMO2, in the differential diagnosis of BL in SE specimens.METHODS:Eleven cases of malignant SE caused by BL were reviewed. SE cytology and histological biopsy diagnoses were compared to determine the concordance rates.RESULTS:A uniform population of non-cohesive medium-sized lymphoid cells with frequent apoptosis was found on SE smears or cell block sections. Cytoplasmic and nuclear vacuoles presented in seven cases. Immunophenotyping demonstrated positivity for CD79a (three of three cases), CD10 (seven of 11 cases), BCL6 (nine of 11 cases), MUM-1 (one of nine cases), CD20 and MYC (11 cases). LOM2 was negative in nine of nine cases. Both IGH/MYC rearrangement and MYC rearrangement were identified in four of six cases, and two of six cases carried isolated MYC rearrangement or isolated IGH/MYC rearrangement, respectively. The diagnoses of eight BLs and three B-cell non-Hodgkin lymphomas were established according to cytomorphology and ancillary studies. SE cytology provided initial pathological diagnoses for eight cases (six BLs and two non-Hodgkin lymphomas). Histodiagnoses were available for eight cases. The concordance rate of cytological-histological diagnosis was 62.5% (five of eight cases).CONCLUSIONS:Combining cytomorphology and ancillary studies enables the accurate diagnosis of BL in SE specimens. Furthermore, LMO2 may be a useful marker in the differential diagnosis of BL.

Primary mediastinal thymoma combined with germ cell tumor (GCT) is extremely rare, and is likely to be misdiagnosed. Here we report a case of mediastinal type B3 thymoma combined with seminoma in which the seminoma component was missed by histologic examination and initially diagnosed by using a pleural effusion sample. The patient was a 46 year old male with chest distress, cough, and supraclavicular lymph node enlargement. A large anterior mediastinal mass was revealed by diagnostic imaging. The tumor was completely removed by thoracotomy. Grossly, a solid mass about 10 cm × 8 cm × 5 cm with cystic degeneration was found. Histologic examination revealed Type B3 thymoma accompanying with multiple lymph node metastases. One year later, CT scan found an irregular mass on the right side of anterior-superior mediastinum with a large amount of effusion in the right side pleural cavity. Cytologic examination and immunostains of the pleural effusion sample revealed metastatic seminoma. Then the original surgical sample was reviewed and the seminoma component also was found besides the thymoma. To the best of our knowledge, this is the first description of type B3 thymoma combined with seminoma, diagnosed by histology and pleural effusion together. We also present a literature review.

AIMS Molecular profiling is important for cancer diagnosis and treatment. For many advanced stage lung cancer patients, cytology specimens may be the only materials available for molecular testing. The aim of this study is to evaluate the utility of Next-Generation Sequencing (NGS) of cytology specimens for the molecular profiling of lung adenocarcinoma. METHODS NGS was performed on cell blocks of pleural effusions and fine-needle aspiration (FNA) samples of lung adenocarcinoma to determine the mutation status of EGFR, KRAS, PIK3CA, BRAF, ALK, PDGFRA, and DDR2. Then, quantitative Real-Time PCR (qPCR) was performed and the results were compared to those of NGS. Next, NGS was performed on available histological specimens from the same patients. Last, DNA Quality Index analysis was performed to further explore the applicability of using cytology samples as the source for NGS. RESULTS NGS detected mutations in EGFR, PIK3CA, and KRAS. NGS and qPCR results showed high concordance. NGS exhibited advantages over qPCR in detecting non-hotspot mutations and providing accurate information for allele sequence and mutation frequency. NGS of cytological and histological samples from the same patients showed high concordance. DNA Quality Index analysis showed that DNA extracted from cell blocks of pleural fluid was of similar quality compared to FFPE tissue blocks. CONCLUSIONS NGS can be successfully performed on both FNA and pleural fluid samples from lung adenocarcinomas. The high quality DNA of FFPE cell block of pleural effusion makes it the first choice for molecular profiling, especially when cytology specimens are the only available samples for molecular profiling.

Background: To gain sufficient tumor tissue for EGFR mutations analysis is of prime clinical importance. Therefore, the objective of present study was to assess whether sputum is suitable for EGFR testing and to assess the consistency between sputum and tissue specimens. Methods: This analysis included 37 paired sputum and tissue specimens obtained from late-stage lung cancer patients followed by EGFR analysis using the ARSM-PCR method, and 11 sputum specimens of COPD were added as negative control. Results: 35 out of 37 (94.6%) patients with lung cancer were found to have tumor cells in the sputum specimen using the LOT method and extracted adequate DNA for EGFR testing. In contrast, only five out of 11 cases of COPD (45.5%) were isolated with sufficient DNA (P<0.001). Among sputum testing, higher EGFR mutation was significantly associated with NCSLC and ADC (40%, 10/25), stage IV (45.5%), and non-smoking status (43.8%). Compared with corresponding tissue specimens, the accuracy, specificity, and sensitivity of EGFR mutation analysis in sputum specimens were demonstrated as 97.1%, 96%, and 90.9%, respectively. Interestingly, a significantly high frequency of L858R in exon 21 was found (P<0.001) in all types of EGFR mutants both on sputum and tissue specimens. Conclusions: The findings of the current study suggest a high concordance between sputum and tissue specimens, reflecting the important potential of sputum specimens for EGFR mutant detection in patients with late-stage lung cancer using the ARSM-PCR method.