INFLUENCE OF IMMUNE STATUS OF THE IMMUNE DEFICIENT MICE ON THE METASTATIC PHENOTYPES OF THE HETEROGENEOUS CLONAL SUBLINES OF HUMAN LUNG GIANT CELL CARCINOMA

By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.

Quantitative analysis of butyric acid-induced nuclear ultrastructural alterations in cells of human lung giant cell carcinoma in vitro

The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of the tu-mor cells incubated with 2mmol of BA was approximately equal to that of thecontrol whereas the nuclear area was increased by 1.4times,which implies thatthe nuclear profile tends to become more regular after BA treatment.In addition,the optical density of the nuclei of the experimental group decreased significantlyas compared with that of the control,which indicates that the chromatin in thenuclei was decreased by BA.It was concluded on the basis of the findings thatBA may have a biological effect of reverse-transformation on the malignant cells.

DIFFERENTIAL EXPRESSION AND RESPONSE OF GROWTH FACTORS IN DIFFERENT METASTATIC VARIANTS OF HUMANPULMONARY GIANT CELL CARCINOMA

The cell lines PGbE1 and PGLH7, which have high and low metastatic potential respectively, were two different variants isolated from human pulmonary giant cell carcinoma cell line PG. This study compared the expression and response of several growth factors TGFa, TGFb, bFGF, IL 6, IL 8 and ANG in the two cell lines. By using RT PCR analysis and thymidine incor poration assay, it was found that IL 6, TGFa and their receptors IL 6R and EGFR were expressed at higher level in PGbE1 cells than in PGLH7 cells, while no significant differences were found in the expression of ANG, bFGF, IL 8, IL 8R and TGFβ. Recombinant IL 6 and TGFα stimulated the proliferation of both cells, while TGFβ had dual effects. These results suggest that ANG, bFGF IL 6, IL 8 and TGFα, β may be involved in the proliferation of pulmonary giant cell carcinoma via autocrine mechanism, and IL 6 and TGFa may play an important role in the metastasis of tumor cells.

Huge undifferentiated carcinoma of the pancreas with osteoclast-like giant cells

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells(OGCs)is very rare,less than1%of all pancreatic malignancies,and shows worse prognosis than that of invasive ductal adenocarcinoma of the pancreas.We present a case of en bloc resection for a huge undifferentiated carcinoma with OGCs that invaded the stomach and transverse mesocolon.A 67-year female was admitted for left upper quadrant pain and computed tomography demonstrated a mass occupying the lesser sac and abutting the stomach and pancreas.There were no distant metastases and the patient underwent subtotal pancreatectomy with splenectomy,total gastrectomy,and segmental resection of the transverse colon.Histopathological examination confirmed an 11 cm-sized undifferentiated carcinoma of the pancreas with OGCs.Immunohistochemical staining revealed reactivity with pan-cytokeratin in adenocarcinoma component,with vimentin in neoplastic multinucleated cells,with CD45/CD68 in OGCs,and with p53 in tumor cells,respectively.The patient had suffered from multiple bone metastases and survived9 mo after surgery.This case supports the ductal epithelial origin of undifferentiated carcinoma with OGCs and early diagnosis could result in favorable surgical outcomes.Investigations on the surgical role and prog-nostic factors need to be warranted in this tumor.

Giant cutaneous squamous cell carcinoma of the popliteal fossa skin:A case report

BACKGROUND Cutaneous squamous cell carcinoma(cSCC)is a common malignant hyperplasia of the skin epithelium.However,cSCC progressing to giant squamous cell carcinoma of the popliteal fossa skin has not been reported.We used full-thickness skin graft from the lower left quadrant of the abdomen to reconstruct the popliteal fossa skin defect in our patient.CASE SUMMARY A 64-year-old woman presented with a 3-year history of a progressively enlarged integumentary tumor located on her left popliteal fossa,which was surgically treated.The resultant defect(15 cm×25 cm)was repaired using full-thickness skin graft from the lower left quadrant of the abdomen.CONCLUSION Full-thickness skin graft is a good choice to repair popliteal fossa defect.

Lung carcinoma with spindle and/or giant cell： a clinicopathological analysis of 17 cases

Objective： Lung carcinoma with spindle and （or） giant cell （LCSG） is a rare epithelial malignant tumor. The aim of our study is to investigate the clinicopathological and prognostic characteristics of 17 cases of LCSGs. Methods： Among 421 patients underwent resection of lung carcinomas, 17 cases of LCSG were studied for clinical, gross and histological parameters. Follow-up information was obtained and analyzed to clarify prognostically significant parameters. Results： The LCSG patients consisted of 15 males and 2 females, with the age ranging from 45 to 78 years （median, 58 years）; 5 cases of stage Ⅰ, 3 of stage Ⅱ, 9 of stage Ⅲ by pathological TNM staging; 2 cases of exclusively spindle cell carcinoma, 5 cases of lung carcinoma with spindle cell, 10 cases of lung carcinoma with giant-cell carcinoma. Cough, chest distress, or chest pain were the most common presenting symptoms, occurring in 15 patients （88.2%）. Of 5 patients in stage Ⅰ, 4 were alive and free of relapse for more than 5 years. The difference in survival was statistically significant between LCSG and squamous cell carcinoma patients （median survival, 36 vs. 61 months; P = 0.027）. Lymph node metastasis and carcinoma with giant cell were the hazardous factors impacting postoperative prognosis of LCSG patients. Conclusion： LCSG patients in early stage may have an optimistic outcome. Lung carcinomas with giant cell displayed multiple cell components in histopathology, and poor outcome due to more lymph node involved.

Pleomorphic hepatocellular carcinoma following consumption of hypericum perforatum in alcoholic cirrhosis

Hepatocellular carcinoma (HCC) often develops in patients with underlying liver disease, yet HCC with syncytial giant cells (SGCs) is extremely rare. Herein, we report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during his regular checkup presented with marked elevation of alpha-fetoprotein. Clinical examination and imaging analyses revealed a tumor-like lesion in segment 4 of the liver, which was removed by limited wedge resection. Histological analysis by hematoxylin and eosin staining indicated pleomorphic and atypical nodules, with some SGCs, embedded within the boundaries of the neoplastic lesion. The adjacent liver parenchyma showed microvesicular steatosis, pericellular fibrosis, and moderate hemosiderin accumulation (grade 2, as determined by Prussian blue iron stain) in hepatocytes and Kupffer cells but no copper accumulation (as determined by orcein stain). Immunohistochemical analysis showed hepatocyte antigen-positive staining for the neoplastic cells and SGCs. The diagnosis was made for cirrhosis-related HCC with SGCs. The previous reports of pleomorphic HCC have featured osteoclast-like (i.e., mesenchymal type) giant cells, making this case of epithelial type giant cells very rare. The patient’s 6-month history of hypericum perforatum/St John’s wort self-medication may have prompted the cirrhosis or HCC progression or the unusual SGC manifestation.

Hugl-1 induces apoptosis in esophageal carcinoma cells both in vitro and in vivo

AIM: To determine whether the human giant larvae homolog 1 gene (Hugl-1/Llg1/Lgl1) exerts tumor suppressor effects in esophageal cancer. METHODS: We constructed a Hugl-1 expression plasmid, pEZ-M29-Hugl1, for gene transfection. We transfected the pEZ-M29-Hugl1 plasmid into Eca109 esophageal cancer cell lines with Lipofectamine 2000 to overexpress Hugl-1. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the effects of the plasmid on Hugl-1 expression. In vitro cell proliferation and apoptosis were examined separately by cell counting Kit-8 (CCK-8) assay, flow cytometry, and Western blotting before and after the transfection of the plasmid into Eca109 cells. Cell cycle distribution was assessed with flow cytometry. The effect of Hugl-1 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice. Expression of Hugl-1 in xenograft tumor was analyzed by immunohistochemistry.The transferase-mediated dUTP nick end-labeling (TUNEL) technique was performed to detect and quantitate apoptotic cell. RESULTS: The transfection efficiency was confirmed with real-time RT-PCR and Western blotting. Our results show that compared with control groups the mRNA levels and protein levels of Hugl-1 in pEZ-M29-Hugl1-treated group were remarkably increased (P < 0.05). The CCK-8 assay demonstrated that the growth of cells overexpressing Hugl-1 was significantly lower than control cells. Cell cycle distribution showed there was a G 0 /G 1 cell cycle arrest in cells overexpressing Hugl-1 (64.09% ± 3.14% vs 50.32% ± 4.60%, 64.09% ± 3.14% vs 49.13% ± 2.24%). Annexin V-fluorescein isothiocyanate revealed that apoptosis was significantly increased in cells overexpressing Hugl-1 compared with control group (17.33% ± 4.76% vs 6.90% ± 1.61%, 17.33% ± 4.76% vs 6.27% ± 0.38%). Moreover, we found that Hugl-1 changes the level of the anti-apoptotic protein Bcl-2 and the proapoptotic protein Bax and the activation of both caspase-3 and caspase-9. With a TUNEL assay, we found that Hugl-1 markedly increased the apoptosis rate of Eca109 cells in vivo (60.50% ± 9.11% vs 25.00% ± 12.25%). It was shown that Hugl-1 represents a significantly more effective tumor suppressor gene alone in a xenograft tumor mouse model. This data suggest that Hugl-1 inhibited tumor growth and induced cell apoptosis in vivo . CONCLUSION: These results suggest that Hugl-1 induces growth suppression and apoptosis in a human esophageal squamous cell carcinoma cell line both in vitro and in vivo .

Anal carcinoma in giant anal condyloma, multidisciplinary approach necessary for optimal outcome:Two case reports and review of literature

BACKGROUND Anal cancers are caused by human papilloma virus(HPV). Buschke-Lowenstein tumor also known as giant anal condyloma(GCA) is a variant of giant neglected anal tumors arising from warts caused by HPV infection. HPV are a family of double-stranded DNA viruses and primarily cause sexually transmitted disease of the genitalia and oropharyngeal mucosa. These tumors are slow growing;locally destructive large verrucous masses.CASE SUMMARY We present a series of two cases with large anal tumors harboring invasive cancers and highlight their presentation and management. Tumors with high risk HPV subtypes(HPV 16, 18, 31, 33) may progress into invasive squamous cell carcinoma(SCC). Untreated GCA can attain enormous size and extend into the pelvic organs and bony structures. Some tumors show malignant degeneration into SCC and are often difficult to diagnose given the large size of the tumors.Complete surgical excision with negative margins is the treatment of choice and necessary to prevent recurrence. This is often not feasible and leaves large surgical wounds with tissue defects with delay in healing and increases postoperative morbidity. Pelvic reconstructive techniques including muscle flaps and grafts are often necessary to close the defects. Human immunodeficiency virus and immunocompromised patients generally do poorly with standard treatments.CONCLUSION A multidisciplinary team of colorectal and plastic surgeons, medical and radiation oncologists along with combination treatment modalities are necessary when malignant transformation occurs in GCA, for optimal outcomes.

Clinicopathological features and surgical outcomes of four rare subtypes of primary liver carcinoma

Objective：This study aimed to analyze clinicopathological and prognostic features of four rare pathological subtypes of primary liver malignancies to make better understanding of their clinical features.Methods：The clinicopathological data of 114 patients who were diagnosed with histologically proven four subtypes：clear cell carcinoma（CCC）,giant cell carcinoma（GCC）,sarcomatoid carcinoma（SC）,and combined hepatocellular-cholangiocarcinoma（CHC）between October 1998 and August 2015 were reviewed.Their survival data were compared with those of 908 patients with histologically proven common hepatocellular carcinoma（HCC）（early-and advanced-stage HCC）during the same period.Results：The outcome of the CCC group was better than that of the other three subgroups,and was similar to that of the early-stage HCC group.Also,the smallest tumor size and the highest incidence of pseudocapsule formation were observed in the CCC group.The SC group had the worst outcome among these four subgroups;the prognosis was much poorer than that of any other subgroups,even poorer than that of the advanced-stage common HCC group.No statistical difference was observed between the GCC,CHC and advanced-stage HCC groups on survival analysis.The incidences of tumor vascular emboli,TNM staging and non-radical resection were three risk factors of the prognosis.Conclusions：CCC is a low-degree malignancy and relatively favorably prognostic subtype of HCC.However,GCC,SC,and CHC are three rare high-degree malignancy subtypes of HCC with poor prognosis.

A case report of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct

We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor.Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas,accompanied with severe dilatation of the main pancreatic duct,which was diagnosed as an intraductal papillary-mucinous neoplasm.We performed distal pancreatectomy and splenectomy.The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma(giant cell type)and adenocarcinoma in the pancreas.There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct.The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery.In this case,we could observe a remarkable intraductal tumor growth into the main pancreatic duct.We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas diagnosed by endoscopic ultrasonography-guided fine-needle aspiration

Undifferentiated carcinoma with osteoclast-like giant cells, also formerly known as osteoclast-like giant cell tumor, is a rare neoplasm of the pancreas and usually diagnosed after pancreatectomy. The presence of non-neoplastic osteoclast-like giant cells is the histological hallmark of this tumor and the diagnosis is usually not difficult on tissue sections. However there have been relatively few reports regarding the cytological features of this type of tumor in literatures. Here we present a case of undifferentiated pancreatic carcinoma with osteoclast-like giant cells coexisting with ductal adenocarcinoma diagnosed by endoscopic ultrasonography （EUS）-guided fine-needle aspiration （FNA） and liquid-based cytology test. To our knowledge,

3D打印技术辅助治疗甲状腺乳头状癌合并脊柱骨巨细胞瘤一例报告

目的报告一例罕见的甲状腺乳头状癌(PTC)合并脊柱骨巨细胞瘤(GCTB)的病例,增加对两种疾病的医学了解,并探讨3D打印技术在手术中的应用、治疗方法及其成效。方法32岁女性患者,在接受全甲状腺切除术及淋巴结清扫后,因胸背部疼痛就医,最终被诊断为脊柱GCTB。治疗过程中,采用3D打印技术辅助进行GCTB的手术切除,并使用3D打印人工椎体进行脊柱重建。结果手术成功切除GCTB并通过3D打印技术重建脊柱,术后患者获得良好的支撑和稳定性的恢复。分子病理学检查显示H3F3A基因G34W错义突变,符合骨巨细胞瘤的诊断。结论该病例报告增加了对甲状腺乳头状癌与脊柱骨巨细胞瘤的了解,并强调了跨学科合作和分子生物学在诊断和治疗中的重要性。此外,本病例还展示了3D打印技术在脊柱手术中的应用,为未来的手术治疗提供了新的视角和方法。

肺大细胞癌外科治疗体会

本文报告了１６例肺大细胞癌外科治疗体会。认为大细胞癌的临床表现与其他类型肺癌无明显区别。Ｘ线检查表现为周围型巨大肿块无空洞为其特点；血行转移为主。其组织来源复杂，术前获确切病理诊断较困难。可分为巨细胞癌和透明细胞癌两个亚型。前者侵袭力强，常侵及临近肺叶及相邻器官，早期出现全身转移，预后极差，平均生存期６．５个月。后者外任不明显，根治切除预后良好并可获长期生存。二者之间的联系与区别有待进一步揭示。

伴有梭形和/或巨细胞肺癌的病理学观察

目的研究伴有梭形和/或巨细胞肺癌的病理学特征。方法采用光镜及免疫组织化学方法,研究20例伴有梭形和/或巨细胞肺癌患者的病理学资料。结果20例患者中,15例为多形性癌,其中10例伴腺癌成分,3例伴大细胞癌成分,1例伴鳞癌成分,1例伴巨细胞癌成分;4例为梭形细胞癌;1例为巨细胞癌。免疫组织化学结果显示,19例患者梭形细胞和/或巨细胞成分AE1/AE3阳性,20例患者Vimentin均为阳性,10例患者P53阳性,20例患者甲状腺转录因子1(TTF-1)均为阴性。结论伴有梭形和/或巨细胞的肺癌是一组分化差、含有梭形细胞、巨细胞和/或两种细胞混合成分的非小细胞癌,病理组织学及免疫组织化学AE1/AE3、Vimentin有助于确定其诊断。

肺巨细胞癌6例临床病理分析

目的 探讨肺巨细胞癌 (GCC)的临床及病理特点。方法 利用HE染色及免疫组化方法对 6例GCC的组织形态进行观察 ,对其临床特点及随访材料进行分析。结果 患者均为男性 ,平均年龄 6 3 8岁。临床表现为胸痛、咳嗽、血痰。右肺 4例 ,左肺 2例。 3例肿瘤位于周边 ,3例近肺门。肿瘤直径 3～ 9cm ,平均 6 8cm。GCC的主要组织学特征是大量肿瘤性巨细胞的存在。巨细胞体积较大 ,形态各异 ,胞质丰富 ,单核或多核伴明显异型。排列疏松 ,部分区域似多形性肉瘤 ,可见巨细胞形成的腺管样结构。 2例有明显的中性粒细胞浸润。巨细胞对上皮性标记呈阳性表达。尤其是CK18,同时也高比例地表达Vim。随访 3例 ,均死亡 ,平均存活 13 3个月。结论 肺巨细胞癌具有临床及组织形态特点 ,与腺癌密切相关 。

伴神经内分泌分化的小肠转移性肺巨细胞癌临床病理观察

目的探讨伴神经内分泌分化的小肠转移性肺巨细胞癌的临床病理特点。方法采用光镜、电镜及免疫组化等方法，观察1例伴神经内分泌分化的小肠转移性肺巨细胞癌患者的临床与病理学资料，并复习相关文献。结果患者空肠肠壁有3处瘤结节，瘤细胞呈肉瘤样疏松排列，弥漫浸润肠壁全层，局部累及肠黏膜上皮。瘤细胞体积巨大，形态不规则，多见巨核与多核瘤巨细胞，间质多量中性粒细胞浸润。免疫组化标记显示瘤细胞CK-L、CK7、Vimenfin、NSE、CgA和TIF-1（＋），而CK20和villin（-）。电镜观察瘤细胞具有上皮特征和神经内分泌颗粒。依据光镜电镜的形态观察与免疫组化检测，再结合以往病史，确诊为伴神经内分泌分化的小肠转移性肺巨细胞癌。结论肺癌肠转移很少见，但当肺癌患者术后出现消化道症状或腹部占位病变时，要首先考虑到肺癌肠转移的可能，尤其肺巨细胞癌更易发生消化道转移。伴有神经内分泌分化的肺巨细胞癌发生小肠转移者预后不良。

白细胞介素18在肺癌细胞的表达及其在肿瘤转移中功能的初步探讨

目的 检测白细胞介素18(IL-18)在肺巨细胞癌高、低转移株的差异表达,探讨IL-18在肺巨细胞癌转移中介导的作用。方法 采用半定量RT-PCR或Western blot技术,检测IL-18在肺巨细胞癌高、低转移株的差异表达;构建IL-18 cDNA的重组质粒,测序分析其序列同源性;同时把IL-18基因导入肺巨细胞癌低转移株,观察IL-18对肿瘤细胞体外转移能力和转移表型的影响。结果 同肺巨细胞癌低转移株相比,IL-18 mRNA和蛋白均只能在肺巨细胞癌高转移株检测到;从肺巨细胞癌高转移株扩增出的IL-18 cDNA序列与文献报道完全一致;此外,将IL-18基因导入肺巨细胞癌低转移株后,稳定转染株细胞可正确表达IL-18融合蛋白,且转染细胞的体外迁移能力显著上调,为空对照组的3倍左右,而上皮细胞间黏附分子E-cadherin蛋白表达显著下调,为空对照组的50％左右。结论 肺巨细胞癌高转移株可组成性表达IL-18,且IL-18可能通过下调E-cadherin表达促进肺巨细胞癌细胞的转移。

95D细胞转移相关基因在原发灶、循环肿瘤细胞和转移灶中的差异表达

目的利用人巨细胞肺癌高转移株(95D)裸鼠自发转移模型,分析CD9、RHOA、MYL12A、B2M、PTOV1、HSPA1B肿瘤转移相关基因在原发灶、循环血肿瘤细胞(circulating tumor cells,CTCs)和转移灶中的差异表达。方法根据前期实验结果并利用GoSufer软件进行GO(gene ontology)分析,筛选出可能与肿瘤转移相关的基因CD9、RHOA、MYL12A、B2M、PTOV1、HSPA1B。利用稳定表达绿色荧光蛋白(GFP)的人巨细胞肺癌细胞株95D/GFP,建立肺癌裸鼠自发转移模型,用流式细胞分选术(fluorescence-activated cell sorting,FACS)分别纯化原发灶、外周血和转移灶中的肿瘤细胞,利用Real-time PCR技术检测上述基因在上述肿瘤细胞中的相对表达量。结果 CD9、RHOA、MYL12A基因在CTCs中表达较少,其次是肝转移灶,在皮下原发灶中表达较多;B2M基因在皮下原发灶、CTCs和肝转移灶中依次降低;PTOV1基因在CTCs中高表达,其次是皮下原发灶,肝转移灶中表达最少;HSPA1B基因只在原发灶中表达。结论 CD9、RHOA、MYL12A、B2M、HSPA1B基因可能是潜在的肺癌转移抑制基因,而PTOV1可能促进肺癌微转移。

含破骨巨细胞样细胞的胰腺多形性癌1例及文献复习

目的 探讨含破骨巨细胞样细胞的胰腺多形性癌的临床病理特征。方法 对 1例含破骨巨细胞样细胞的胰腺多形性癌进行临床、病理组织学和免疫组织化学观察。结果 患者为 5 8岁女性 ,因中上腹部持续性隐痛 2个月余就诊 ,B超、CT检查发现胰腺占位。切除标本示实性结节状肿块 ,灰白、灰黄色 ,有灶性坏死。镜下见肿瘤由低分化腺癌伴梭形肉瘤样细胞构成 ,两种细胞均示CK、Vim、α AT阳性。可见多灶性巨细胞瘤样结构 ,由单核瘤细胞和形态上良性的破骨巨细胞样细胞构成 ;前者见CK散在阳性 ,Vim和α AT阳性 ;后者仅见CD6 8和Vim阳性。结论 含破骨巨细胞样细胞的胰腺多形性癌是多形性胰腺癌的一种亚型 ,破骨巨细胞为反应性细胞 ,非肿瘤成分。