Localization of alpha-fetoprotein and human chorionic gonadotropin to specific histologic types of nonseminomatous testicular cancer

We used an indirect immunoperoxidase technique to localize alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) to specific histologic types of testicular germ cell cancers. Among 20 nonseminomatous tumors studied, yolk sac tumor reacted for AFP in 13 of 15 cases, teratoma in 3 of 11 cases, and embryonal carcinoma in 3 of 14 cases. Syncytiotrophoblasts alone reacted for HCG in 14 of 15 cases, and syncytiotrophoblasts associated with choriocarcinoma reacted for HCG in 2 of 2 cases. There was a close correlation between the tissue demonstration of AFP and HCG and elevated serum levels of AFP and HCG, respectively. We conclude that in nonseminomatous testicular cancer yolk sac tumor is the primary site of synthesis of AFP, and syncytiotrophoblasts are the only site of synthesis of HCG.     

Congenital teratoma: a clinicopathologic study of 22 fetal and neonatal tumors

Extragonadal teratoma is the most common congenital tumor. The prognostic significance of the grade of immaturity and the presence of small foci of conventional yolk sac tumor (YST) in fetal and neonatal teratomas have not been determined. We report detailed histologic studies of 22 congenital teratomas, including eight tumors resected in utero for developing hydrops, and correlate the histologic features with initial serum alpha-fetoprotein (AFP) levels and clinical outcome. All fetal tumors that required in utero intervention were grade 3 immature teratomas, with admixed conventional YST in 44%. Among tumors resected postnatally, those presenting in utero were more commonly immature (71% vs. 50%). All initial post-surgical serum AFP levels were high, as expected in a neonate. No correlation was found between AFP elevation above the mean for gestational age and the presence of YST, hepatic differentiation, or immature endodermal glands in the tumor. Among 15 survivors with follow-up, 5 patients had malignant mixed germ cell tumors (immature teratoma with foci of conventional YST) and 5 had immature teratomas with foci of hepatic differentiation or immature endodermal glands with subnuclear vacuoles (so-called "well-differentiated YST"). No patient has developed recurrent or metastatic disease after treatment by complete surgical excision alone (mean follow-up, 37.6 months). The clinical behavior of congenital teratomas is determined predominantly by whether or not the tumor can be completely resected and in our study did not correlate with the grade of the teratoma or with the presence or absence of foci of hepatic tissue, immature intestinal glands, or foci of conventional YST.     

The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from endometrioid and clear cell carcinomas

Yolk sac tumors (YSTs) have a variety of morphologic patterns, some of which can resemble either endometrioid adenocarcinoma (EAC) or clear cell carcinoma (CCC). Immunohistochemical staining for alpha-fetoprotein (AFP) is usually only focal and thus is not always helpful in the diagnosis of YST, and pancytokeratin (CK) is expressed by all three tumors. We studied a battery of immunohistochemical markers with specific attention to the utility of cytokeratin 7 (CK7) in differentiating YST from EAC and CCC. A total of 46 ovarian tumors were retrieved for this study: 16 YST, 19 EAC, and 11 CCC. The three groups were analyzed for the expression of CK7, AFP, Leu-M1 (CD15), EMA, and WT1 by immunohistochemistry. In addition, CK and c-kit (CD117) were studied in the YSTs. All of the YSTs tested (100%) were positive for CK. CK7 was considered negative in all 16 YST cases (100%), although a few tumor cells (1%-2%) stained in 4 cases. In contrast, 17 of 19 EACs and all 11 CCCs had diffuse 3+ to 4+ positivity for CK7; the two other EACs showed 2+ positivity for CK7 (40% and 30% of the tumors). AFP was positive in 12 of 15 YSTs (80%), but was generally focal with 1+ staining in 10 cases (67%); only 2 cases were 3+. All of the EACs and CCCs were negative for AFP. Leu-M1 was 1+ in 9 of 15 YSTs (60%), while the remaining 6 were considered negative. Leu-M1 was positive in 10 of 15 EACs tested (67%), but the staining was variable with 1 case 3+, 3 cases 2+, and 6 cases 1+. In the CCCs, 10 cases (91%) were 3+ to 4+, and 1 case was 1+. EMA was essentially negative in 15 of 15 YSTs (100%), with 3 completely negative and 12 showing very focal (<5%) staining. Eight of 12 EACs showed 4+ staining, 3 showed 3+ staining, and 1 showed 2+ staining. All of the 11 CCCs (100%) showed 4+ staining. WT1 was negative in all cases of YST and CCC; 16 of 18 EAC tested (89%) were negative for WT1, but 2 (11%) were 4+ positive. C-kit was negative in all YSTs. In conclusion, it is important for pathologists to be aware that YSTs may mimic EACs and CCCs and that this distinction is important for the clinical management of patients with these tumors. AFP staining is focal in most YST, so an absence of staining does not exclude this diagnosis. CK7 and EMA are essentially negative in YST but are diffusely positive in CCC and EAC, making them useful markers for differentiating YSTs from both CCCs and EACs. Leu-M1 may also be helpful for distinguishing YSTs from CCCs.     

Tumor marker levels in post-chemotherapy cystic masses: clinical implications for patients with germ cell tumors

PURPOSE: Increased tumor markers after induction chemotherapy for patients with germ cell tumor usually represent systemic disease and consequently second line chemotherapy is instituted, while retroperitoneal lymph node dissection (RPLND) is reserved for patients with marker normalization. We report the concentration of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the fluid of post-chemotherapy cystic masses to evaluate this as a potential source for serum marker elevation. MATERIALS AND METHODS: From March 2002 to December 2002, 11 consecutive patients with post-chemotherapy cystic masses underwent RPLND. Following resection, aspirated fluid was analyzed for AFP and HCG. Only 5 post-chemotherapy RPLNDs were performed in patients with increased serum tumor markers, including the 3 patients in our study. Patients with increasing tumor markers and/or multifocal disease with noncystic residual masses after induction chemotherapy underwent salvage chemotherapy despite teratomatous elements in the primary tumor. RESULTS: All 11 patients had teratoma in the orchiectomy specimen and retroperitoneum, including one with malignant transformation. Cystic fluid markers were increased in all patients, 9 of 9 with HCG (range 7.0 to 6,880) and 9 of 11 with AFP (27.5 to 521.2). Two patients with an increased serum AFP before surgery (47.9 and 31.6) had cyst levels of 73.5 and 790.4 respectively. Both serum markers normalized postoperatively. One patient with increased pre-RPLND serum HCG (11.6) had a cyst level of 233. HCG continued to increase postoperatively and the patient died of disease. The remaining 10 patients remain disease free. CONCLUSION: Fluid from cystic teratoma contains variably elevated levels of HCG and AFP in all patients and appears to be independent of serum marker level or pathology. It is possible that a "slow leak" of fluid from cystic teratoma may explain elevated serum markers in selected patients with teratoma and thus may potentially avoid second line chemotherapy.     

Mucinous carcinoid as an unusual manifestation of endodermal differentiation in ovarian yolk sac tumors

We present, for the first time, two yolk sac tumors (YST) in women 37 and 18 years of age, one with a typical parietovisceral pattern and the other with a glandular pattern, which were associated with extensive areas of mucinous carcinoid (MC). The tumor in the first case had numerous nodules of tubulopapillary YST that merged with well-differentiated MC. This patient responded well to chemotherapy. The tumor in the second case consisted of an AFP-positive glandular YST, with a glandulopapillary pattern closely resembling fetal lung type adenocarcinoma, coexisting with an AFP-negative, cytokeratin 20-positive, atypical MC; transitional areas between the two components were also seen. In the material from the recurrences and metastases; however, no YST was present, the atypical MC having become the predominant component including areas that had become carcinomatous. There was a poor response to various chemotherapeutic regimens. AFP levels became negative during the course of disease paralleling the disappearance of the YST component and the overgrowth of an increasingly anaplastic MC. The patient died 1 year after diagnosis. We think that, in these cases, MC represented an unusual form of endodermal differentiation of the YST. It is important to differentiate the yolk sac and carcinoid components due to their different responses to chemotherapy and to evaluate the possibility of mucinous carcinoid developing into a highly aggressive carcinoma.     

Recognizing abnormal marker results that do not reflect disease in patients with germ cell tumors

PURPOSE: The judicious use of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase is key to appropriate management of patients with germ cell tumors. Elevated AFP and/or HCG generally indicate active disease. We describe patients with germ cell tumors who had elevated serum AFP and/or HCG but no active disease, despite careful repeat evaluation. MATERIALS AND METHODS: Histories of 6 cases of germ cell tumors that remained in remission despite abnormal serum AFP and/or HCG were reviewed. RESULTS: Markers were only modestly elevated, remained constant or spontaneously normalized during repeat measurements, and there was no other clinical or radiographic evidence of disease. Patients were treated conservatively with physical examination, radiological tests and repeat marker assays, with no relapse to date. CONCLUSIONS: Stable, low increases in serum AFP and HCG may not represent active disease. Careful repeat evaluation will determine whether the markers increase. If no change is noted after appropriate studies have been reviewed by an experienced practitioner to exclude active disease from diagnosis, then consideration should be given to managing such cases with close surveillance to avoid unnecessary chemotherapy.     

Primary Choriocarcinoma of the Jejunum: Report of a Case

We report a case of primary choriocarcinoma of the jejunum in a 45-year-old man, which was finally diagnosed by immunohistochemical analysis of a surgically resected specimen. Despite combined systemic chemotherapy, the patient died of progressive liver metastases 5 months after surgery. The serum human chorionic gonadotropin (HCG) level increased dramatically as the liver tumor progressed. According to our review of the 13 cases of primary or secondary choriocarcinoma of the small intestine reported in the English-language literature up until 2001, the characteristic symptoms are massive gastrointestinal bleeding and elevation of the serum HCG. Early diagnosis and prompt initiation of chemotherapy provide the only chance of improving the extremely poor prognosis associated with this rare neoplasm.     

An immunohistochemical study of intracranial germ cell tumours

Summary Histologically verified intracranial tumours, mainly germ cell tumours of the pineal and suprasellar regions, were studied immunohistochemically using anti-serum of alpha fetoprotein (AFP), human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), human placental lactogen (HPL), pregnancy specific -1 glycoprotein (SP-1), glial fibrillary acidic protein (GFAP), S-100 and neuron specific enolase (NSE). In germinomas, HCG positive cells were occasionally demonstrated in cells presenting as syncytiotrophoblastic giant cells (STGC), and GFAP and S-100 positive cells were found in the surrounding gliotic lesions. Teratomas were positive for CEA in their epithelial components. Endodermal sinus tumours were positive for AFP, choriocarcinomas for HCG and SP-1, and embryonal carcinomas for AFP, HCG and SP-1. HCG and SP-1 positive cells were demonstrated in STGC. As for the relationship between serum AFP level and tissue localization, many cases presenting a serum AFP level exceeding 220 ng/ml were positive for AFP in tumour tissue.     

Cerebrospinal fluid markers in central nervous system metastases from testicular carcinoma.

Serum values of alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) have been used to monitor disseminated testicular carcinoma. Serial measurements of these markers have been used to monitor the response to therapy, to follow the progress of disease, and to detect subclinical recurrences. With increasingly effective chemotherapy for systemic disease, central nervous system (CNS) metastases in testicular carcinoma are becoming increasingly important as a cause of treatment failure. Cerebrospinal fluid (CSF) values of AFP and HCG seem to be important ancillary acids in the neurosurgical management of CNS metastases from testicular cancer. Our preliminary experience with three cases suggests that these CSF markers (plus computerized tomograhic scanning) should be evaluated in patients with this disease.     

睾丸原发性卵黄囊瘤临床病理分析(附8例报告)

目的:探讨睾丸原发性卵黄囊瘤的临床病理特征、诊断、治疗及预后。方法:运用光镜、免疫组化对8例睾丸原发性卵黄囊瘤进行检测。结果:8例睾丸原发性卵黄囊瘤来自我院1998~2013年诊治的病例(2例为外院会诊病例),占我院同期睾丸生殖细胞肿瘤的10.7%(8/75),患者年龄7~43岁,平均23.9岁,8例患者临床表现均为患侧睾丸无痛性肿大,均发生于单侧睾丸。组织学:全部病例肿瘤组织均见微囊或网状结构和嗜酸性透明滴,而作为本瘤结构的S-D小体有5例。8例中仅1例为单纯性卵黄囊瘤,其余7例均为混合性卵黄囊瘤。免疫表型:AFP为其特征性标记物。结论:原发于睾丸的卵黄囊瘤是罕见的恶性肿瘤,术前AFP检测有助诊断,确诊依赖于病理检查。以手术加放、化疗的综合治疗措施,可以延长生存期。     

Testicular tumour markers in tissue correlated to serum levels and clinical stage

Clinical investigation of 11 patients with testicular tumour included tests for the marker substances AFP (alpha fetoprotein) and HCG (human chorionic gonadotropin) in serum and in tumour tissue, using an indirect immunoperoxidase technique. In one case of pure seminoma, neither AFP nor HCG was detectable in tissue or in serum. In eight of ten patients with non-seminomatous germ cell tumour there was AFP-immunoreactivity in tumour tissue, and seven of them also had elevated serum levels of AFP. Five patients showed HCG-immunoreactivity in tumour tissue and the same number had elevated serum levels of HCG. The findings indicated good correlation between immunoreactivity of tumour tissue, serum level of the tumour markers and clinical stage of the neoplastic disease.     

Optimal treatment of clinical stage I yolk sac tumor of the testis in children

Thirty-four children with malignant germ cell tumors of the testis were seen at the Institut Gustave-Roussy from 1970 through 1980, after orchiectomy alone. The tumor was classified according the WHO classification (immature teratoma, embryonal carcinoma, choriocarcinoma, yolk sac tumor). Twenty-four of the 34 children had a stage I yolk sac tumor (YST) defined as a tumor completely removed by the inguinal approach, without clinical node involvement and/or metastases. No lymphadenectomy was performed. All the patients had an alphafetoprotein (AFP) determination before or after orchiectomy. For those (23/24) with an elevated level of AFP the clinical stage I was assigned if the AFP decreased regularly to normal values by 3 months after orchiectomy. Twelve patients received systemic chemotherapy every 3 months [methotrexate, actinomycin D, cyclophosphamide (Cytoxan)]; 12 did not receive any treatment after orchiectomy. An AFP evaluation was assayed for all of these regularly. The 3-year survival rate was 96% and the 3-year relapse-free survival rate was 84%, with no difference found between the two groups receiving or not receiving systemic chemotherapy. This series confirms the advisability of a conservative approach for clinical stage I YST, employing orchiectomy and evaluation including AFP determinations. Ten percent to 20% of patients will suffer a relapse, which can be demonstrated by an increasing level of AFP, and these children can be treated at this time. With this approach, 80% of patients having clinical stage I YST can be treated by orchiectomy alone and will not suffer any sequelae or complication of either lymphadenectomy or chemotherapy. For the few who do relapse, treatment at the time of relapse is curative for the majority. This approach requires absolute adherence to a strict follow-up program.     

Extra embryonic elements in testicular tumours

Extra embryonic elements in germ cell tumours resemble the trophectoderm or yolk sac endoderm which are the extra embryonic membranes of the developing embryo. True chorionic (trophoblastic) differentiation with syncytiotrophoblast and cytotrophoblast, perhaps with a villous pattern, is rare and is associated with a very poor prognosis and with hCG production. Isolated syncytiotrophoblastic cells also produce hCG but are prognostically less sinister. Yolk sac elements occur in two thirds of non seminomatous germ cell tumours, and affect all age groups. Pure forms of yolk sac tumour (YST) occur but are not common except in infants. They are often associated with AFP production but AFP is not a specific marker for YST. Yolk sac tumours have a similar prognosis to malignant teratoma undifferentiated (MTU: embrvonal carcinoma).     

Current optimum management of anaplastic germ cell tumours of the testis and other sites

Between 1977 and 1985, 149 male patients with anaplastic germ cell tumours (AGCT) completed chemotherapy with POMB/ACE (platinum, vincristine (oncovine), methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). By increasing the number of courses of POMB in 1979, we have been able to compensate for adverse prognostic factors. Since then each patient has received at least three courses of POMB and 118 patients have completed therapy. The overall survival rate since 1979 is 89% and for the 100 patients who had not received prior radiotherapy it is 92%. We established that an initial serum concentration of human chorionic gonadotrophin (HCG greater than 50,000 iu/l) and/or alphafetoprotein (AFP greater than 500 ku/l) indicated a poor prognosis. Between 1977 and 1979 the survival rate in 12 patients in this category was only 45%. After increasing the number of courses of POMB, the survival rate rose to 89% in 31 patients. However, patients who had received prior radiotherapy and who presented with high tumour markers (HCG greater than 50,000 iu/l and/or AFP greater than 500 ku/l) continue to have a poor survival rate (20% in five patients). With this chemotherapy, 14 of 16 patients (88%) presenting with liver metastases and 6 of 7 patients (86%) presenting with brain metastases are in complete remission. Neither the stage at presentation nor the volume of metastatic disease was a major adverse prognostic variable. We believe that POMB/ACE chemotherapy, followed by surgery in selected cases, is currently the best treatment for patients with AGCT.     

Clinicopathological study of AFP producing gastric cancer--significance of AFP in gastric cancer

We experienced fifteen cases (3.9%) out of 387 with gastric cancer showing elevation of alphafetoprotein (AFP) in serum. In these cases AFP producing cells in primary lesion demonstrated positive for anti-AFP by means of immunohistochemical study. In this report, clinicopathological feature and clinical significance as a tumor marker of gastric cancer were discussed. Gross type showed Borrmann II and III which were located in atrophic area in the stomach. Histological type revealed papillary, moderately differentiated and poorly differentiated adenocarcinoma, all of which showed medullary growth in stroma. In clinical field, liver metastasis was observed in 12(80%) of 15 cases. In these cases, elevation of serum AFP was already observed before the detection of liver metastases by CT or Echo. Immunohistochemical study showed no difference between primary tumor and metastases, and no AFP positive cells were seen in 68 early gastric cancers without elevation of serum AFP.     

Human chorionic gonadotropin in gastric carcinoma. A useful marker for bone metastasis

Twenty patients with bone metastases from gastric carcinoma resected during the 13 years from 1974 through 1987 were investigated in relation to the serum and tissue carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). The incidence of bone metastases was 2.1% (20/933). The serum AFP, CEA and hCG positive rates were found to be 14.3, 42.9 and 69.2% for patients with bone metastases and 18.3, 19.4 and 14.1% for those without bone metastases, respectively. In addition, the tissue AFP, CEA and hCG positive rates were 11.1, 100 and 77.8% for such patients with bone metastases, and 8.0, 80.8 and 21.1% for those without bone metastases. Only the serum and tissue hCG positive rate was significantly higher for the patients with bone metastases than those without bone metastases. The bone metastatic lesions were investigated for tissue hCG in four cases, and found to be positive in all the four bone lesions. In four of the patients with metachronous bone metastases, serum hCG levels were elevated before or at the time when bone metastases were diagnosed. Furthermore, serum hCG levels fell in response to chemotherapy or tumor resection. On the contrary, the serum AFP or CEA levels did not correlate with the clinical course in patients with bone metastases. These results indicate that the measurement of the tissue and serum hCG in patients with gastric carcinomas could be of extreme value in the search for bone metastases and the serum hCG level could be a useful marker for the prediction of bone metastases in gastric carcinoma.     

Primary intracranial malignant germ cell tumor associated with abnormal high value of alpha-fetoprotein and human chorionic gonadotropin

A case of primary suprasellar germ cell tumor that produced alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in a 8-year-old boy is reported. Partial removal of tumor and combination chemotherapy using cisplatin, vincristine, and bleomycin (modified PVB therapy) resulted in an almost definite regression of the tumor and improvement from clinical symptoms in this case. After the chemotherapy the concentrations of both serum AFP and serum HCG decreased to normal levels as well. Moreover by the immunoperoxidase method AFP, HCG, and placental alkaline phosphatase were found in this particular tumor tissue. In reviewing previous reports the immunohistochemical demonstration of three tumor markers in a single germ cell tumor is seemed to be extremely rare.     

临床Ⅰ期睾丸非精原细胞瘤的监视治疗16例报告

１６例临床Ⅰ期睾丸非精原细胞瘤（ＮＳＧＣＴＴ）患者在单纯切除睾丸肿瘤后,不按常规行腹膜后淋巴结清扫,放疗,化疗,而采取监视治疗方案,即术后两周开始复查血清ＨＣＧ,ＡＦＰ,两月开始复查胸腹部ＣＴ、每两个月一次,连续２年以上,结果１２例无复发,复发的４例中有２例术后瘤标持续升高,另２例瘤标下降后分别在第４月、第８月再次升高,给予ＰＶＢ化疗后,４例患者瘤标恢复正常,病灶消失,认为监视治疗对临床Ｉ期ＮＳＧ     

Beta human chorionic gonadotrophin in serum and urine. A marker for metastatic urothelial cancer

Beta human chorionic gonadotrophin (beta HCG) was measured in 127 urine and 85 serum samples from 175 untreated patients with urothelial cancer. Serum levels of beta HCG were substantially elevated in 16 of 21 patients (76%) with widespread metastases but in only 2 of 64 patients (3%) with disease confined to the pelvis. Urine beta HCG levels were moderately raised in 11 of 25 patients (44%) with locally advanced disease, but greatly elevated in 5 of 7 patients (71%) with metastases. Measurement of serum and/or urine beta HCG appears to be an efficient diagnostic marker for the presence of distant metastases in bladder carcinoma.     

Selective or routine axillary disease staging for patients with clinically lymph node-negative breast cancer?

BACKGROUND: Although sentinel lymph node biopsy (SLNB) has become the standard for patients with clinically lymph node-negative breast cancer, less than one third of patients who undergo SLNB will have lymph node metastases. Therefore, we hypothesized that a subset of patients in whom SLNB can be avoided can be identified before operation. METHODS: We prospectively studied 220 patients with early stage breast cancer who underwent SLNB. We analyzed primary tumor features, biologic markers, and demographic data. RESULTS: Overall, 31% of the patients had lymph node metastases. Although patients with lymph node metastases had larger neoplasms than patients who were lymph node negative (mean, 2.3 +/- 0.1 cm versus 1.5 +/- 0.1 cm; P < .0001), 10% of patients with T1a tumors, 19% of patients with T1b tumors, and 30% of patients with T1c tumors had lymph node metastases. Palpable tumors were lymph node positive in 41% of patients versus 17% for nonpalpable tumors (P = .0001). Lymph node metastases were seen in 71% of patients with tumor angio or lymphatic invasion versus 17% of patients without (P < .0001). Seventy-five percent of patients with an increased preoperative serum CA 27.29 had lymph node metastases, and the mean levels were greater among patients who were lymph node positive (27 U/ml +/- 2 versus 20 +/- 1; P = .0002). There was no significant association between any other demographic, histologic, or molecular feature that was investigated and lymph node metastases. CONCLUSION: We did not identify histologic, demographic, or molecular variables that can exclude the risk of associated lymphatic metastases reliably. Furthermore, not all predictive factors are known before the operation (eg, whether the tumor is T1a or T1b). Therefore, we recommend that SLNB be performed in all patients with clinically lymph node-negative invasive breast cancer.