Laboratory markers and germ cell tumors

The International Germ Cell Consensus Classification (IGCCC) of testicular germ cell tumors (TGCT) in 1997 included three serum tumor markers, serum lactate dehydrogenase catalytic concentration (S-LD), serum alpha fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG). The recommendation should be implemented for all patients with TGCT and is also useful for patients with ovarian and extragonadal germ cell tumors. A fourth serum tumor marker for TGCT, S-LD isoenzyme 1 (S-LD-1), is also relevant for TGCT. Patients with seminoma have a raised S-LD-1 more often than a raised S-AFP and S-hCG, whereas patients with nonseminoma have a raised S-AFP more often than a raised S-LD-1 and S-hCG. A new model combining IGCCC and S-LD-1 predicts survival better than previous staging systems. LD-1 is related to a characteristic chromosomal abnormality in all types of TGCT, a high copy number of chromosome 12p. In contrast, AFP and hCG are found mainly in nonseminomatous germ cell tumors and they related to the histologic differentiation of the tumors. The different biologic background for the serum tumor markers may contribute to the difference in their clinical behavior.     

睾丸混合性生殖细胞瘤的超声表现

目的 观察睾丸混合性生殖细胞瘤（TMGCT）的超声表现。方法 回顾性分析我院经手术病理证实的48例TMGCT的超声表现。结果 48例中,22例肿瘤位于左侧睾丸,26例位于右侧睾丸。17例伴腹膜后淋巴结转移,9例伴肺转移,5例伴腹股沟区淋巴结转移,2例伴肝转移,2例伴纵隔转移,1例伴颈部淋巴结转移。28例超声可见睾丸内囊实混合回声病灶,18例低回声病灶,2例稍强回声病灶。38例肿瘤边界不清晰,10例边界清楚;29例肿瘤形态规则,19例形态不规则。CDFI示46例肿瘤内可见彩色血流信号。结论 TMGCT的超声表现有一定的特征性,可为诊断提供影像学依据。     

睾丸生殖细胞肿瘤及睾丸原位癌中鞘糖脂GB3的表达及意义

目的检测鞘糖脂神经酰胺三己糖苷(GB3)在睾丸生殖细胞肿瘤及睾丸原位癌组织中的表达,并探讨其临床意义。方法应用免疫组化方法检测62例睾丸生殖细胞肿瘤及14例睾丸原位癌组织标本中GB3的表达。结果 62例生殖细胞肿瘤中,54例GB3(+)(87%);14例睾丸原位癌中,11例GB3(+)(78.6%),其中8例强(+),其曲细精管内支持细胞及残留生精细胞均呈GB3(-)。结论睾丸原位癌是睾丸生殖细胞肿瘤早期阶段,睾丸生殖细胞肿瘤及睾丸原位癌细胞中鞘糖脂成分GB3改变,提示GB3在睾丸生殖细胞肿瘤发生发展过程中起着作用。GB3可作为睾丸生殖细胞肿瘤标记物,特别在睾丸原位癌早期诊断中有实用价值。     

Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors.

The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum alpha-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification. In an evaluation series of 44 patients from Odense University Hospital, Denmark, a raised S-LD-1 (>1.0 x upper limit of reference values) had a predictive value for death from tumor in 5-years observation of 46%. The predictive value was 46% for S-LD, 25% for S-AFP, and 40% for S-hCG. A normal SLD-1 had a predictive value for survival over 5-years observation of 100%. It was 81% for S-LD, 75% for SAFP, and 77% for S-hCG. The fraction of the patients who died of tumor and had a raised tumor marker value was 100% for S-LD-1, 46% for S-LD, 9% for S-AFP, and 18% for S-hCG. The fraction of patients with a normal serum tumor marker value among those who survived was 61% for S-LD-1, 81% for S-LD, 94% for SAFP, and 94% for S-hCG. A validation series of 37 patients treated at the University of Texas MD Anderson Cancer Center showed similar findings. Combining the patients in the two series, a raised value of SLD-1 classified more patients into a subgroup with an impaired survival (53%) than S-LD (35%), S-AFP (6%), or S-hCG (11%), and the high risk subgroups based on the international classification (40%). The findings have implications for the staging and treatment of patients with metastatic testicular germ cell tumors.     

Serum tumor markers

Monoclonal antibodies are used to detect serum antigens associated with specific malignancies. These tumor markers are most useful for monitoring response to therapy and detecting early relapse. With the exception of prostate-specific antigen (PSA), tumor markers do not have sufficient sensitivity or specificity for use in screening. Cancer antigen (CA) 27.29 most frequently is used to follow response to therapy in patients with metastatic breast cancer. Carcinoembryonic antigen is used to detect relapse of colorectal cancer, and CA 19-9 may be helpful in establishing the nature of pancreatic masses. CA 125 is useful for evaluating pelvic masses in postmenopausal women, monitoring response to therapy in women with ovarian cancer, and detecting recurrence of this malignancy. Alpha-fetoprotein (AFP), a marker for hepatocellular carcinoma, sometimes is used to screen highly selected populations and to assess hepatic masses in patients at particular risk for developing hepatic malignancy. Testing for the beta subunit of human chorionic gonadotropin (beta-hCG) is an integral part of the diagnosis and management of gestational trophoblastic disease. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG also may be useful in evaluating potential origins of poorly differentiated metastatic cancer. PSA is used to screen for prostate cancer, detect recurrence of the malignancy, and evaluate specific syndromes of adenocarcinoma of unknown primary.     

Genetics of rectal cancer and novel therapies: primer for radiologists

Rectal cancer accounts for one-third of newly diagnosed colorectal cancer cases. Given its anatomical location and risk for local recurrence, a multidisciplinary treatment program including surgery, radiation therapy, and chemotherapy has demonstrated improved outcomes in localized disease. Genetic analysis has become part of the standard approach for management of advanced disease and new trials are considering tailored therapies for locally advanced disease. This review describes molecular subsets of colorectal cancer; implications for clinical management, including patterns of metastatic spread and response to therapies; and emerging matched therapies. During the last decade, significant biological differences have been noted based on colorectal cancer primary location and here we focus on rectal cancers and relevant markers for this disease. As more treatment for localized rectal cancer is shifted to the neoadjuvant setting and more targeted regimens are developed for metastatic disease, radiologists will increasingly see patients defined by molecular subsets and their awareness of the genetics of rectal cancer will help further refine our understanding of this disease.

     

DWI结合ADC值鉴别诊断睾丸生殖细胞瘤

目的 探讨DWI结合ADC值鉴别诊断睾丸精原细胞瘤和非精原细胞瘤的价值。方法 回顾性分析经手术及病理证实的22例睾丸生殖细胞瘤患者,其中精原细胞瘤10例,非精原细胞瘤12例。均行MRI平扫、DWI扫描,并测量不同肿瘤实质部分的ADC值,采用独立样本t检验比较精原细胞瘤和非精原细胞瘤ADC值的差异。结果 10例精原细胞瘤的DWI多呈均匀性高信号,平均ADC值为（0.63±0.12）×10^-3 mm²/s,12例非精原细胞瘤的DWI多呈不均匀高信号,平均ADC值为（0.98±0.22）×10^-3 mm²/s,二者的ADC值差异有统计学意义（t=4.61,P<0.01）。结论 DWI结合ADC值有助于鉴别精原细胞瘤与非精原细胞瘤。     

Overview of systemic treatment in recurrent and advanced cervical cancer: a primer for radiologists

Imaging has a central role in surveillance of cervical cancer, guiding decision on when to initiate treatment for recurrent disease and to guide management in advanced cervical cancer. Due to the increased availability of pelvic radiation therapy, the rate of atypical presentation of recurrent disease has increased. Simultaneously, the array of systemic therapies now available for advanced cervical cancer has considerably expanded in the last few years, with therapies now available in mid and low-income countries. While pelvic recurrences are amenable of loco-regional treatment, recurrent disease may present with metastases to the thoracoabdominal organs, lymph nodes, bones, skin and brain, for which systemic treatment represent the standard of care. Besides combined chemotherapy regimens, alternative chemotherapies, biosimilars and immune checkpoint inhibitors are now available, each associated with a definite pattern of response and toxicity. In this review, after describing the typical and atypical presentations of recurrent and advanced cervical carcinoma on cross-sectional imaging, we will discuss systemic treatment for recurrent or advanced disease and their associated radiographic sequelae, in light of the newly available therapies.

     

Serum tumor markers for primary lung carcinoma

A number of serum tumor markers are clinically relevant for primary lung carcinomas. None of them, however, is applied to screening of lung cancers because of their unsatisfactory sensitivity and specificity. Among them, measurements of CEA, CYFRA 21-1, NSE, and pro GRP frequently give subsidiary information as to differential diagnosis, monitoring of treatment, and early detection of recurrence. Current trend of the tumor markers for lung cancer includes development of new markers such as p53 tumor suppressor gene product and I-CTP for detecting bone metastasis. Attempts to detect micrometastases by means of RT-PCR of these marker genes are also discussed.     

Acute tumor lysis syndrome in poor-risk germ cell tumors: does it exist?

Acute tumor lysis syndrome (ATLS) is a well-known adverse event described after effective chemotherapy for extensive, highly proliferative, and chemosensitive tumors. While its occurrence with hematological malignancies is frequently described, there have been scattered case reports documenting ATLS in solid tumors. However, such events have not been reported in poor-risk germ cell tumors. We reviewed retrospectively 46 cases of such tumors treated in our department between 1988 and 1993 by aggressive cisplatin-based chemotherapy. All patients received systematically 61/24 h hydration according to the cisplatin-protocol administration. Blood chemistry data for potassium, phosphorus, calcium, alkaline reserve, uric acid, creatinine and lactate dehydrogenase were obtained before treatment and during the 7 days of the induction chemotherapy. No metabolic abnormalities suggestive of ATLS were observed. Nevertheless, 2 patients with bulky disease of the chest experienced early death from respiratory distress complicated by multiorgan failure. ATLS seems to be an unlikely event in poor-risk germ cell tumors and therefore special prophylactic therapy may be unnecessary.     

Testicular tumors of germ cell origin

Testicular tumors may be classified as seminoma, embryonal carcinoma, teratocarcinoma, teratoma, and choriocarcinoma. Staging is valuable to determine the extent and natural progression of disease, to select an appropriate treatment regimen, and to provide prognostic guidelines. Megavoltage irradiation to the retroperitoneal and ipsilateral pelvic node-bearing locations is the basis of treatment for patients with pure seminoma diagnosed by radical orchiectomy. Survival rates range from up to 100% for stage I to as low as 20% for stage III. Regional therapy is appropriate for management of nonseminomatous germinal malignancies. Prognosis depends somewhat on treatment, which consists of inguinal orchiectomy combined with either retroperitoneal lymphadenectomy or retroperitoneal radiation therapy alone, or with retroperitoneal lymphadenectomy plus either radiation therapy or chemotherapy.     

性腺外恶性生殖细胞肿瘤37例临床病理分析

目的 探讨性腺外恶性生殖细胞肿瘤的病理类型和临床特点。方法 根据WHO肿瘤国际组织学分类(第2版)对37例性腺外恶性生殖细胞肿瘤重新评价，部分病例做相应免疫组化染色，并将肿瘤的组织类型和临床特点与性腺恶性生殖细胞肿瘤进行比较分析。结果 患者年龄1．5～58岁，中位年龄24岁。男性28人，女性9人，男女之比为3．1：1。发生于纵隔28例，腹膜后5例，前列腺、骶尾部、鞍区、阴道各1例。列前三位的肿瘤分别是卵黄囊瘤、畸胎瘤(未成熟畸胎瘤、PNET和畸胎瘤恶变)和精原细胞瘤，另有5例为混合型生殖细胞瘤。结论 性腺外恶性生殖细胞肿瘤相对少见，预后差，发病率与年龄、性别关系密切，好发部位为纵隔和腹膜后，卵黄囊瘤最为多见。     

Gastric adenocarcinoma with germ cell tumor components: a rare case report

Germ cell tumors (GCTs) often occur in male testes and female ovaries. Extragonadal GCTs account for approximately 2% to 5% of all GCTs and mainly occur in the mediastinum, retroperitoneum, and pineal gland. In this study, we reported a rare case of gastric adenocarcinoma with GCT components. The patient’s serum α-fetoprotein (AFP) level was higher than normal. Abdominal computed tomography (CT) showed a 10-cm × 10-cm tumor between the spleen and the bottom of the stomach. Gastric endoscopy indicated an ulcerative lesion extending from the bottom of the stomach to the antrum. Tissue biopsy identified the tumor as an adenocarcinoma. The patient underwent abdominal tumor resection, subtotal gastrectomy, D2 lymphadenectomy, and splenectomy. Postoperative histopathology showed that the tumor was a moderately to poorly differentiated adenocarcinoma. Immunohistochemistry analysis revealed positive staining for AFP, glypican-3, and placental alkaline phosphatase. Gastric adenocarcinoma with GCT components is particularly uncommon and rarely reported. Elevated serum AFP and/or β-human chorionic gonadotropin levels, abdominal CT, histopathology, and immunohistochemistry may help diagnose GCTs. Radical surgery resection is the primary treatment method for GCTs. Adjuvant chemotherapy and radiotherapy are effective for advanced GCTs.     

Liquid biopsy in germ cell tumors: biology and clinical management

ABSTRACT

Introduction: Liquid biopsy is an increasingly studied approach for optimal and minimally invasive diagnostics of malignant tumors. The aim of this review is to provide evidence and discuss the utility of liquid biopsy in the management of germ cell tumors (GCTs).

Areas covered: Herein, we summarize the evidence on liquid biopsy in GCTs including serum tumor markers, circulating tumor cells, microRNA and cell-free DNA. The search of literature was conducted from Pubmed/Medline, ASCO-meeting library searching for terms ‘liquid biopsy’, ‘germ cell tumors’, ‘circulating tumor cells’, ‘microRNA’, ‘cell-free DNA’. Obtained original studies were included. Reference lists of review articles and key original articles were searched for additional original studies. We included articles published between1990 and 2019.

Expert opinion: Liquid biopsy is a minimally invasive tool using body fluids for diagnostic purposes in cancer. The established value of serum tumor markers may be already considered a liquid biopsy technique in diagnosis of GCTs. Possible near-future refinements in diagnosis of GCTs are emerging. Further information on diagnosis, prognosis and resistance is added with recently described microRNAs, circulating tumor cells and cell-free DNA. While great promise is shown, further large-scale validation is needed to incorporate these novel liquid biopsies into clinical practice.