Elevated Serum Tumor Marker Levels Research Articles

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Systemic Sarcoidosis Induced by Chemotherapy, Mimicking Metastatic Testicular Carcinoma with 18F-FDG PET/CT

A 34-year-old male patient who had left orchiectomy and received three cycles of chemotherapy for testicular mix germ cell carcinoma was referred for 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for complaints of weight loss and fever. PET/CT showed multiple and progressive 18F-FDG uptakes in supra and infra diaphragmatic lymphatic regions, and multiple abnormal 18F-FDG uptakes were noted in the lytic formed skeletal lesions. Clinicians remain in doubt regarding the multiple metastatic lesions without elevated serum tumor marker levels (alpha-fetoprotein, beta-human chorionic gonadotrophin, CA19-9, and carcinoembryonic antigen).Biopsy of the lytic lesion in the iliac bone revealed granulomatous inflammation suggestive of sarcoidosis. Systemic prednisone at 20-40 mg/daily was started. 18F-FDG PET/CT images showed complete metabolic response to prednisone 8 months following the start of treatment.

Serum tumor marker levels at the development of intracranial metastasis in patients with lung or breast cancer

Intracranial metastasis (IM) is observed in various cancers, including in lung and breast cancer, and its timely diagnosis is required for successful patient treatment. Various tumor serum markers, such as carcinoembryonic antigen (CEA), pro-gastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), and cancer antigen 15-3 (CA15-3), serve not only as prognostic indicators in lung and breast cancer but also as risk factors for IM development. This study is the first to assess a subgroup of cancer patients with IM that did not show elevated serum tumor marker levels. This retrospective study included 53 patients with lung or breast cancer in which IM was detected by enhanced brain magnetic resonance imaging between January 2013 and December 2018. IM was classified into three types [parenchymal metastasis (PM), leptomeningeal metastasis and dural metastasis]. Serum CEA level was measured using an electrochemiluminescence immunoassay (ECLIA) or chemiluminescent immunoassay. Plasma ProGRP level was measured using a chemiluminescent enzyme immunoassay (CLEIA), and the serum NSE level was measured using ECLIA. The serum CA15-3 level was measured using CLEIA. Univariate and multivariate analyses were performed using Pearson's χ2 test and logistic regression analysis, respectively. Among the total 53 patients, 15 patients (28.3%) did not show elevated serum tumor marker levels. Univariate analysis showed that the patients with PM only significantly correlated with no increasing tumor marker level compared with other IM types (P=0.030), as well as female patients and patients without symptoms (P=0.010 and 0.046, respectively). Multivariate showed that the patients with PM only and female patients significantly correlated with no increasing tumor marker level (P=0.038 and 0.014, respectively). Our findings describe a subgroup of lung and breast cancer patients with IM that do not show elevated tumor marker levels, indicating the need for the identification of novel indicators for IM or increased monitoring of these patients.

MA 16.10 Treatment Outcomes of Primary Malignant Germ Cell Tumors of the Mediastinum

Primary mediastinal malignant germ cell tumors (GCT) are rare neoplasms with various histopathological findings and contain complicated clinical characteristics. Chemotherapy plays an important role in the treatment and there are some cases where a good prognosis is expected with multimodal treatment including surgical resection, pre- and postoperative chemoradiotherapy. The medical records of 27 patients who were treated in our institution between 1988 and 2014 were retrospectively reviewed. We investigated the clinical characteristics and the outcomes of treatment. All patients were male with a mean age of 30.7 years (range, 16-53 years), including 17 cases of seminoma (SGCT group) and 10 cases of non-seminoma (NSGCT group). Twenty-three patients underwent surgery and the remaining four patients received chemotherapy and/or radiotherapy without surgery. Of the 23 patients who underwent surgery, 17 cases received preoperative chemotherapy and 15 cases were treated with postoperative chemo/radiotherapy. In six patients, surgery was performed without preoperative chemotherapy due to the suspicious of thymoma, and was followed by postoperative chemo/radiotherapy. Among 24 patients whose serum tumor marker levels were measured before the treatment, 15 patients showed elevated serum tumor marker levels [five (35.7%) in SGCT group and 10 (100.0%) in NSGCT group]. Furthermore, among 20 patients whose serum tumor marker levels were measured before surgery, four patients showed elevated serum tumor marker levels [one (9.1%) in SGCT group and three (33.3%) in NSGCT group]. The median follow-up period after the treatment was 68 months (range, 4-316 months). The 5-year and 10-year survival rate was 88% and 88% in SGCT group, respectively, and 60% and 45% in NSGCT group, respectively (p=0.031). Although there was no relationship between the serum tumor marker levels before the treatment and the prognosis, the patients without elevated tumor marker levels revealed better prognosis than those with elevated one (p=0.014). The treatment for mediastinal malignant GCT in our institution was feasible with favorable outcomes. Although malignant GCT has poor prognosis especially in NSGCT group, chemotherapy which normalizes serum tumor marker levels can improve its prognosis.

Causes of Avascular Hypoechoic Testicular Lesions Detected at Scrotal Ultrasound: Can They Be Considered Benign?

The purposes of this study were to determine the cause of avascular hypoechoic lesions detected at scrotal ultrasound and to assess usefulness of sonographic and clinical features in differentiating benign from malignant etiologic factors. This retrospective study included 58 patients with avascular hypoechoic lesions detected at testicular ultrasound. The sonographic features recorded were lesion size and margins and presence of peripheral vascularity and focal calcifications. Also recorded were patient age, symptoms, risk factors, lesion palpability, and levels of serum tumor markers. The reference standard was pathologic results or at least 2-year stability documented with serial follow-up ultrasound studies. Features associated with malignant, including burnt-out, lesions and benign lesions were examined by Fisher exact test, Wilcox-on rank sum test, and the generalized estimating equations method for multivariable models. Sixty-three lesions were identified in 58 patients; 40 of the 63 (63.5%) were benign. Patients with malignant lesions had elevated serum tumor marker levels more often than patients who had benign lesions (26.1% versus 5.7%, p = 0.043). The clinical palpability of lesions and history of testicular cancer were not statistically significantly different between patients with malignant and those with benign lesions. Poorly defined margins of a lesion and focal calcification within the lesion were more often found in malignant lesions. Maximal size of a lesion and peripheral vascularity were not associated with either the benign or the malignant nature of a lesion. Although most avascular hypoechoic testicular lesions are benign, a substantial proportion are malignant. The ultrasound characteristics of a lesion, the patient's clinical presentation, and serum tumor marker status may be useful in differentiating malignant from benign lesions.

Review of ovarian tumors in children and adolescents: radiologic-pathologic correlation.

The incidence, histologic distribution, and clinical manifestations of ovarian tumors in the pediatric population are distinct from those in adults. Although ovarian neoplasms in childhood and adolescence are rare, the diagnosis should be considered in young girls with abdominal pain and a palpable mass. Differential diagnosis in children and adolescents with ovarian tumors should be conducted on the basis of unique clinical manifestations, elevated serum tumor marker levels, and distinctive imaging findings. Although the clinical manifestations are nonspecific and may overlap, they may assist in diagnosis of some types of ovarian tumors. Children who present with a palpable mass or symptoms of precocious puberty have a high likelihood of malignancy. Many ovarian tumors are associated with abnormal hormonal activity and/or abnormal sexual development. Elevated levels of serum tumor markers, including α-fetoprotein, the beta subunit of human chorionic gonadotropin, and CA-125, raise concern for ovarian malignancies. However, negative tumor markers do not exclude the possibility of malignancy. Identification of imaging features at ultrasonography, computed tomography, and magnetic resonance imaging can help differentiate benign from malignant ovarian tumors and, in turn, plays a crucial role in determining treatment options. At imaging, malignant ovarian tumors usually appear predominantly solid or heterogeneous and are larger than benign tumors. Because surgery is the primary treatment for ovarian tumors, ovarian salvage with fertility preservation and use of a minimally invasive surgical technique are important in children and adolescents.

Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features.

Ovarian malignant germ cell tumors (OMGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad. OMGCTs are rare, accounting for about 2.6% of all ovarian malignancies, and typically manifest in adolescence, usually with abdominal pain, a palpable mass, and elevated serum tumor marker levels, which may serve as an adjunct in the initial diagnosis, monitoring during therapy, and posttreatment surveillance. Dysgerminoma, the most common malignant germ cell tumor, usually manifests as a solid mass. Immature teratomas manifest as a solid mass with scattered foci of fat and calcifications. Yolk sac tumors usually manifest as a mixed solid and cystic mass. Capsular rupture or the bright dot sign, a result of increased vascularity and the formation of small vascular aneurysms, may be present. Embryonal carcinomas and polyembryomas rarely manifest in a pure form and are more commonly part of a mixed germ cell tumor. Some OMGCTs have characteristic features that allow a diagnosis to be confidently made, whereas others have nonspecific features, which make them difficult to diagnose. However, imaging features, the patient's age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Malignant ovarian germ cell tumors spread in the same manner as epithelial ovarian neoplasms but are more likely to involve regional lymph nodes. Preoperative imaging may depict local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Because OMGCTs are almost always unilateral and are chemosensitive, fertility-sparing surgery is the standard of care.

Elevated tumor markers in patients with pulmonary alveolar proteinosis

The role of tumor markers in pulmonary alveolar proteinosis (PAP) remains unclear. This study investigated the tumor markers in serum and bronchoalveolar lavage fluid (BALF) in PAP patients and explored the relationship between tumor markers and the severity of PAP. We retrospectively reviewed 38 patients with PAP. Mean serum carcinoembryonic antigen (CEA) and CYFRA21-1 levels were higher than the cut-off values (12.7 ± 17.5 ng/mL and 10 ± 10.66 ng/mL, respectively). Significant correlations were found between levels of CEA and neuron-specific enolase (NSE) in serum and serum lactate dehydrogenase (LDH) values (r=0.60, p<0.001 and r=0.56, p<0.001, respectively). A significant correlation was also observed between levels of squamous cell carcinoma (SCC) in serum and PaO2 and PA-aO2 (r=-0.49 p=0.01 and r=-0.51, p=0.01, respectively). The changes of CEA, SCC and NSE levels were consistent with the changes of LDH and PaO2. The serum levels of CEA, NSE and SCC were significantly lower after whole lung lavage compared with those before (8.7 ± 10.6 vs. 15.7 ± 22, 7.9 ± 5.2 vs. 16.6 ± 11.8, 0.4 ± 0.24 vs. 0.59 ± 0.42; p<0.05, respectively). Elevated serum tumor marker levels were found in PAP patients. The serum levels of CEA, NSE and SCC may reflect the severity of the disease and predict the therapeutic effect of whole lung lavage.

Duodenal metastasis from recurrent invasive lobular carcinoma of breast: a case report and literature review

We present a rare case of duodenal metastasis from invasive breast lobular carcinoma, which first presented clinically as elevated serum tumor marker levels, followed by jaundice but with no other clinical evidence of recurrence and metastasis. A 53-year-old woman underwent modified radical mastectomy of the left breast (pT2 N3 M0 stage III c) followed by postoperative chemo-radiotherapy and hormonal therapy. After about 3 years, the patient presented with elevated serum tumor marker levels and mild jaundice. She was subsequently admitted to the hospital for nausea and severe vomiting. A duodenoscopy revealed the thickening of duodenal papilla on the lateral wall and stenosis. A duodenal tissue biopsy revealed poorly differentiated adenocarcinoma, and immunohistochemical staining suggested that the carcinoma was of breast origin. The patient received further radiation and chemotherapy. Although duodenal metastases of breast cancer are rare, physicans should be alert and vigilant when a patient with a history of breast cancer presents with new gastrointestinal symptoms.

Multiple necrotic nodules of the liver simulating liver metastasis

A 70-year-old man was referred to our hospital due to anemia and elevated serum tumor marker levels. He had advanced colon cancer, and hepatic lesions were found incidentally. On ultrasonography (US) and computed tomography (CT), the hepatic lesions had a maximum diameter of 20 mm and were located in Couinaud's segments V, VI, VII, and VIII, which suggested liver metastasis. On early- and late-phase CT during hepatic arteriography (CTHA), all of the lesions had rim enhancement. On early-phase CT during arterioportography (CTAP), all of the lesions were seen as nodules with an irregular perfusion defect, and on late-phase CTAP, all the lesions gradually became iso-dense, and their shape and size changed. Based on the CTAP findings, these lesions were thought to be fibrotic tumors. Partial resection of the liver (including the lesions in Couinaud's segments V and VIII) was done. Histological examination revealed that the lesions were necrotic nodules. Thus, CT angiography (CTHA and CTAP) was useful for identifying necrotic nodules, because their appearance on this modality is different from that of liver metastases.

Management of primary malignant germ cell tumor of the mediastinum.

Primary mediastinal malignant germ cell tumors (GCTs) are rare and have a worse prognosis than their gonadal counterparts. Although multimodality treatment is a standard therapeutic strategy in mediastinal GCTs, the clinical implications of surgical intervention remain unclear. Forty-eight patients with primary mediastinal malignant GCT who were treated at the National Cancer Center Hospital, Tokyo, from 1962 to 2002 were studied retrospectively with regard to their histology and clinical profile. Mediastinal GCT occurred predominantly in young males, with a mean age of 28.8 years at the time of diagnosis. There were 46 males (96%) and two females (4%). Histologically, seven patients (15%) were diagnosed as having pure seminoma and 41 (85%) had non-seminomatous GCT. Treatment consisted of surgery alone in nine patients, surgery followed by chemotherapy in two, and chemotherapy followed by surgery in 20. The other 17 patients received chemotherapy and/or radiotherapy without surgery. Of these latter 17 patients, 14 developed progressive disease and three were followed up with a sustained partial response. Among the 31 patients who underwent surgery, complete resection was performed in 27 (87%) and incomplete resection was performed in four (13%). Twelve (41%) patients had elevated serum tumor marker levels preoperatively. Among the 20 patients who received preoperative chemotherapy, viable cells were found in the resected specimen in six (30%). With regard to tumor recurrence in patients with surgical intervention, the preoperative serum tumor marker levels and the presence of viable cells in the resected specimen were significantly associated with recurrence. There was no significant association between surgical curability and recurrence. The 5-year overall survival rate in all 48 patients was 45.5%. Surgical intervention for mediastinal GCT may be needed to remove a chemotherapy-refractory tumor or to assess the pathological response to chemotherapy to determine the indications for further chemotherapy.

Elevated serum tumor markers in niacin induced cholestatic jaundice

Niacin is a commonly used vitamin that can cause potentially serious liver abnormalities. We present the case of a 70 year-old man who had cholestatic jaundice secondary to Niacin, that was associated with raised levels of serum tumor markers CA 19–9, and CEA. Though there have been previous case reports of Niacin induced cholestatic jaundice, to our knowledge, this is the first case where elevated serum tumor marker levels were also found. This case also illustrates the importance of obtaining a detailed history, and interpreting diagnostic tests appropriately in patients with deranged liver function tests. A 70 year-old white man presented with significant weight loss, malaise, and fatigue for three months. A questionnaire filled by the patient listed aspirin and vitamins as his medications. Physical exam was unremarkable except for marked scleral icterus. Laboratory data showed Conjugated Hyperbilirubinemia. CA 19–9 was 241u/ml, and CEA was 22.8 ng/ml. A abdominal CT scan and ERCP were normal. On a subsequent office visit the patient was advised to bring all his medicines with him, and it was found that the patient was taking Niacin-2 grams per day in divided doses, which had been listed as vitamins. He was advised to stop the Niacin, and his liver function tests, and CA 19–9 and CEA levels returned to normal levels. Niacin, used to treat hypercholestrolemia, may cause a wide range of liver problems. These side effects are seen more often with the Sustained Release form rather than the Immediate Release form. Many patients report this as a vitamin, and if a more detailed history is not obtained this very important cause of liver abnormality may be missed. CA 19–9 and CEA are used as serum tumor markers especially for GI and Hepato-biliary malignancies. Levels are usually higher in malignancies compared to benign conditions, but because of the poor sensitivity and specificity, these markers are not recommended for screening for malignancies, and are usually used for confirming diagnoses and monitoring response to therapy. In patients with deranged liver function tests a detailed history should be obtained to exclude potentially hepatotoxic over-the-counter medications. Patients should be encouraged to bring their pill bottles to the office at the time of initial consultation. Serum tumor markers should be ordered selectively, and should be interpreted appropriately to avoid expensive, and potentially harmful invasive procedures.

Is there a role for second-look laparotomy in the management of malignant germ cell tumors of the ovary? Experience at Institut Gustave Roussy.

The last two decades have seen great improvements in the management of patients with germ-cell tumors of the ovary. The initial treatment approach includes conservative surgery and cisplatin-based chemotherapy in most cases. At completion of chemotherapy, the role of second-look surgery remains questionable. We retrospectively analyzed the long-term outcome (median follow-up, 8 years) of 40 patients who received various chemotherapy regimens after primary surgery and focused on the role of second-look surgery. A second-look laparotomy was performed at completion of chemotherapy in 22 patients. Histological findings were no tumor in 13; mature teratoma in 5; immature teratoma in 1; active disease in 3. Six of the latter nine patients had persistent radiologic abnormalities after chemotherapy. All three patients with active disease had elevated serum tumor markers. Five out of the six patients with residual teratoma lesions had a teratoma component in the primary tumor. According to histological findings at second-look surgery, the number of patients without long-term evidence of disease is 12, 5, 1 and 0, respectively. Eighteen patients were not subjected to second-look surgery. One of them had clearly progressive disease and the other 17 experienced a clinical complete response at completion of chemotherapy. All patients but one are alive without evidence of disease. We conclude that second-look surgery is not necessary in patients with elevated serum tumor marker levels and in those patients with neither radiologic abnormality nor teratoma element in the primary tumor. However, we recommend a second-look procedure for the small subset of patients with a teratoma component in the primary tumor and persistent radiologic abnormalities along with normal serum tumor markers at the end of chemotherapy.

Chemotherapy in stage II nonseminomatous germ cell tumors of the testis: The institut Gustave roussy experience

To assess the role of chemotherapy in the treatment of stage II nonseminomatous germ-cell tumors of the testis, the outcomes of 154 patients who were included in prospective trials and standard treatment programs at Institut Gustave Roussy between 1984 and 1993 were reviewed. The median follow-up is 5.5 years. Cisplatin-based primary chemotherapy was the treatment regimen for 108 patients. Elevated serum tumor marker levels were found in 27 patients only while 81 had radiologic evidence of retroperitoneal disease. Primary chemotherapy was followed by retroperitoneal lymph node dissection (RPLND) in 41 % of cases. Long-term nonevolutive disease (NED) was diagnosed in 101 (93%) patients. Primary RPLND and adjuvant chemotherapy was the treatment regimen for 46 patients, 100% of whom are long-term NED. Patients with normal serum tumor marker levels following orchiectomy and radiologic evidence of low volume retroperitoneal disease should undergo primary RPLND. Patients with persistently elevated serum tumor marker levels without retroperitoneal involvement should be treated by primary chemotherapy, as should patients with large volume retroperitoneal disease. In patients with elevated serum tumor marker levels and low volume retroperitoneal disease who may benefit equally from up-front chemotherapy or primary RPLND, assessment of risk-benefit, cost-benefit, and quality of life is warranted in future trials.

The Management of Patients with Nonseminomatous Germ Cell Tumors of the Testis with Serologic Disease Only After Orchiectomy

Management of patients with nonseminomatous germ cell tumors of the testis who have persistently elevated serum tumor marker levels (α-fetoprotein and/or human chorionic gonadotropin) following orchiectomy and no clinical evidence of disease is controversial. We reviewed our experience with 15 such patients at our cancer center between March 1977 and November 1991. Group 1 (11 patients) underwent initial retroperitoneal lymph node dissection and group 2 (4 patients) received primary chemotherapy. All group 1 patients required subsequent chemotherapy for retroperitoneal disease or persistent marker elevation, whereas only 1 of the 4 who received primary chemotherapy required later surgery. We conclude that tumor marker elevation in this setting is usually indicative of systemic tumor, which is best treated primarily by initial chemotherapy.