Diagnosis Of Germ Cell Tumors Research Articles

The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors

Apart from a recognized association between extragonadal mediastinal germ cell tumors (GCT) and the occurrence of hematologic malignancies, the risk of developing second nongerminal solid tumors after the diagnosis or treatment of extragonadal GCT is unknown. Six hundred thirty-five consecutive patients with extragonadal GCT treated at 11 centers in the U.S. and Europe during the era of cisplatin-based chemotherapy (1975-1996) were included into a large database. These patients were evaluated for the occurrence of second malignancies. No treatment-related leukemia was observed in 611 patients treated with chemotherapy. In 7 patients, second solid tumors were observed, resulting in a frequency of 1.86% (95% confidence interval [95% CI], 1.79-1.93%) after a median follow-up of 55 months (95% CI, 50-60 months) (annual incidence, 0.30% [95% CI, 0.14-0.59]). Four solid tumors (57%) developed in patients with primary mediastinal and 3 tumors (43%) developed in patients with retroperitoneal GCT. Three patients (43%) had a nonseminomatous and 4 patients (57%) had a seminomatous histology. Six patients had been treated with chemotherapy and one patient with radiotherapy. Six of 7 solid tumors (86%) had developed within 5 years and 7 of 7 solid tumors within 10 years of diagnosis. The median time period to the occurrence of neoplasia was 47 months (range, 9-145 months). Four cutaneous tumors were observed (melanoma, two patients; basal cell carcinoma, one patient; and squamous cell carcinoma, one patient); the other three tumors were angiosarcoma, nonsmall cell lung carcinoma, and colorectal carcinoma. The overall risk for developing a second tumor was not increased compared with an age-matched general population with a standard incidence ratio (SIR) of 1.49 (95% CI, 0.60-3.06). An elevated risk for skin tumors was observed in all extragonadal GCT patients (SIR, 4.00 [95% CI, 1. 09-10.24]), as well as in the subgroup of patients treated with chemotherapy (SIR, 5.33 [95% CI, 1.45-13.65]). This analysis excludes an increased biologic risk of developing second solid malignancies in patients with extragonadal GCT except for the previously reported association between primary mediastinal nonseminoma and hematologic disorders. The overall risk of developing second malignancies in extragonadal GCT patients appears to be comparable to that in patients with primary testicular carcinoma. The incremental occurrence of skin malignancies in patients treated with chemotherapy should be investigated further.

Establishing germ cell origin of undifferentiated tumors by identifying gain of 12p material using comparative genomic hybridization analysis of paraffin-embedded samples.

An estimated 10% of adult cancer patients present with undifferentiated carcinoma. The diagnosis of germ cell tumor (GCT) in such patients can be difficult but has important implications for patient management. Male testicular GCT is characterized by an isochromosome 12p, i(12p), or additional 12p material, in some cases restricted to the 12p11.2-p12.1 region. A gain of 12p material can indicate that a tumor, which may not be present in the testis, is of germ cell origin. Formalin-fixed, paraffin-embedded samples are the most widely available material for diagnostic analysis and retrospective studies. We have compared the identification of 12p gain in snap-frozen samples with corresponding paraffin-embedded material from three clearly defined testicular GCTs using comparative genomic hybridization analysis. In this preliminary study, paraffin-embedded tumor samples of uncertain histogenesis from seven patients were then analyzed. Tumor samples from three of these patients showed a gain of 12p material, and in one patient, gain was restricted to the 12p11.2-p12 region. The clinical picture and response to therapy were generally consistent with the 12p status, though lack of 12p gain may not exclude a diagnosis of GCT.

Nephroblastoma-like tumors in patients with testicular germ cell tumors.

Nephroblastoma-like tumors (NLTs) developed in metastatic sites in nine men with testicular germ cell tumors (GCTs). These tumors had a characteristic "triphasic" admixture of primitive tubular structures, sometimes with a glomeruloid pattern, blastema and stroma. Skeletal muscle differentiation was apparent in two cases. Specific neuroendocrine markers (synaptophysin and chromogranin A) were negative. All patients were treated by surgical excision. Six patients were alive with no evidence of disease from 4 to 12 years after diagnosis of GCT and NLT. One patient was alive with disease 6 years after diagnosis of GCT and 3 years after diagnosis of NLT. One man who also had metastatic primitive neuroectodermal tumor (PNET) had short survival, and one patient died of postoperative infection. We conclude that patients with testicular GCTs in whom NLTs develop in metastatic sites often experience prolonged survival. Surgical excision appears to be adequate treatment for NLT arising in metastatic testicular GCT in most patients. It is important to distinguish NLTs from PNETs in metastatic GCTs because of the more aggressive course and the frequently fatal outcome of the latter.

Cytology of germ cell tumors

BACKGROUND Germ cell tumors (GCTs) and their metastases may be found in numerous sites that are accessible to cytologic sampling, and many are responsive to chemotherapy. METHODS The authors reviewed 20 examples of GCT cytology from 16 males and 3 females ranging in age from 1.5 to 61 years (median, 34 years). With two exceptions, one benign cystic ovarian teratoma in which intraoperative cytology was used to diagnose an associated adult-type carcinoma and one undescended testis in which seminoma presented as an abdominal mass, the material reviewed included no examples of primary gonadal GCT. RESULTS The authors studied 7 primary and 13 metastatic GCTs; these studies were based on 13 in vivo aspirations, 4 intraoperative preparations, and 3 samples of body cavity fluids. All samples were correctly interpreted as malignant, and only one was incorrectly classified as a non-GCT malignancy. CONCLUSIONS Clinical and cytologic findings are useful in the diagnosis of GCTs and their metastases. Incorrect interpretation of these neoplasms as poorly differentiated malignancies of other types may deprive the patient of effective chemotherapy. Air-dried, Romanowsky-stained smear material and cell block sections may contribute to the resolution of diagnostic dilemmas. Cancer (Cancer Cytopathol) 1997; 81:220-7. © 1997 American Cancer Society.

Cytology of germ cell tumors

Germ cell tumors (GCTs) and their metastases may be found in numerous sites that are accessible to cytologic sampling, and many are responsive to chemotherapy. The authors reviewed 20 examples of GCT cytology from 16 males and 3 females ranging in age from 1.5 to 61 years (median, 34 years). With two exceptions, one benign cystic ovarian teratoma in which intraoperative cytology was used to diagnose an associated adult-type carcinoma and one undescended testis in which seminoma presented as an abdominal mass, the material reviewed included no examples of primary gonadal GCT. The authors studied 7 primary and 13 metastatic GCTs; these studies were based on 13 in vivo aspirations, 4 intraoperative preparations, and 3 samples of body cavity fluids. All samples were correctly interpreted as malignant, and only one was incorrectly classified as a non-GCT malignancy. Clinical and cytologic findings are useful in the diagnosis of GCTs and their metastases. Incorrect interpretation of these neoplasms as poorly differentiated malignancies of other types may deprive the patient of effective chemotherapy. Air-dried, Romanowsky-stained smear material and cell block sections may contribute to the resolution of diagnostic dilemmas.

Fine-Needle Aspiration Biopsy (FNAB) Diagnosis of Germ Cell Tumors: Histologic and Cytologic Correlations

Fine-Needle Aspiration Biopsy (FNAB) Diagnosis of Germ Cell Tumors: Histologic and Cytologic Correlations

Is it feasible to diagnose germ-cell tumors by fine-needle aspiration biopsy?

Fine needle aspiration biopsy is an extremely useful procedure for the diagnosis of germ cell tumors. Most of the subtypes can be easily recognized and differentiated from other subtypes. For difficult cases clinical pathologic correlation may be extremely helpful in establishing a precise diagnosis. Mixed germ cell tumors may cause some difficulty if one of the components is predominant. Immunohistochemistry may also play an important role in arriving at a definitive diagnosis.

Improved Management of Abdominal Undescended Testicular Tumors with Bulky Confluent Retroperitoneal Nodal Metastases

Purpose Germ cell tumors of the abdominal undescended testis associated with confluent bulky retroperitoneal metastases are challenging problems. We report the results of neoadjuvant cisplatin based chemotherapy after diagnosis of germ cell tumors by fine needle aspiration cytology of the abdominal testicular mass. After chemotherapy all patients underwent abdominal orchiectomy with retroperitoneal lymph node dissection for residual nonseminomatous germ cell tumors or radiotherapy for pure seminomas. Materials and Methods Between 1980 and 1991, 57 of 425 patients (13.4 percent) with germ cell tumors of the testicle had malignancy in an undescended testis, while 39 (68.4 percent) had tumor in an abdominal testis with confluent bulky metastasis. Metastatic evaluation included tumor marker studies, chest x-ray and computerized tomography of the abdomen. Among the tumors 29 (74.4 percent) were large volume seminomas (stages IIc, III and IV) and 10 (25.6 percent) were large volume nonseminomas. All 39 patients received 3 cycles of induction chemotherapy, and orchiectomy was deferred until its completion (14 received vinblastine, actinomycin D and bleomycin-6, and 25 received bleomycin, etoposide and cisplatin). After evaluation of response, the testis was excised. Overall followup was 2 to 12 years (median 4.6). Results Of 29 seminomas 14 (48.3 percent) showed a complete and 11 (37.9 percent) showed a partial response. The latter tumors were treated subsequently with radiotherapy. Four patients with progressive disease died, for an actuarial survival rate of 86 percent. Of the 10 patients with nonseminomatous germ cell tumor 2 (20 percent) had a complete response and 4 had a partial response. All patients with a partial response underwent retroperitoneal lymph node dissection. Overall, 4 patients with progression and 2 with a partial response died, for an actuarial survival rate of 39 percent. Of 39 post-chemotherapy orchiectomy specimens 24 (61.5 percent) showed viable tumor cells. Furthermore, 16 of 39 patients (41 percent) had additional ilioinguinal metastases requiring adjuvant radiotherapy or surgery. Conclusions Surgical removal of the primary tumor in an undescended testis with bulky metastasis is difficult. We believe that initial chemotherapy followed by 1-stage surgical removal of the primary and residual metastasis is a favorable option to improve compliance and decrease the incidence of loss to followup. Atypically altered ilioinguinal metastases may necessitate a change in radiotherapy ports and/or retroperitoneal lymph node dissection boundaries. The significantly poorer survival with nonseminomatous germ cell tumor could be due to the fact that 50 percent of the lesions were stage IV at presentation. However, multivariate analysis showed only tumor histology to be the significant parameter and not initial stage at presentation.

Pediatric germ cell tumor. An experience with BEP.

This study is an analysis of our experience with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, in pediatric germ cell tumors (GCTs). The study included all children (age < 16 years) who were registered between May 1988 and May 1993 with a histologically confirmed diagnosis of GCT and received BEP chemotherapy. In addition to the clinicopathological features, the response rate, survival rate, and toxicity were analyzed. There was a total of 56 patients, of whom 22 had an ovarian tumor and 17 each had a testicular or an extragonadal tumor. Histologically, endodermal sinus tumor was the most common type (62%). Tumor markers were increased in 89% (50 of 56). Complete responses were observed in 89.1% (49 of 55) and partial responses in 10.9% (6 of 55) of the evaluable patients. Five-year actuarial survival was 83% and progression free survival was 93%. Median follow-up was 18 months. Median survival is not yet reached. The chemotherapy was well tolerated. From the present report, it is apparent that BEP chemotherapy is very effective and well tolerated in children with GCT. The data probably suggests that conservative surgery, when combined with effective chemotherapy, can result in cure of the majority of children with GCTs.

Malignant germ cell tumors in men infected with the human immunodeficiency virus: natural history and results of therapy.

To determine how men infected with the human immunodeficiency virus (HIV) tolerate and respond to treatment for malignant germ cell tumors (GCTs), and how GCT histology and stage compare among HIV-infected versus non-HIV-infected men. Two hundred ninety-four cases of GCT diagnosed or treated from 1980 to 1993 were reviewed. Nine new cases among HIV-infected men were identified; these were analyzed together with six cases previously reported from our institution. Low-stage tumors (stages I and IIA) comprised 67% of HIV-infected and 63% of non-HIV-infected cases. Sixty-seven percent of HIV-infected cases were seminomas versus 51% of non-HIV-infected cases. Ten patients had AIDS at the time of GCT diagnosis. Five patients underwent radiation therapy and one patient underwent retroperitoneal lymphadenectomy without complications. Seven patients received chemotherapy with four cycles of cisplatin, etoposide, and bleomycin (PEB) or cisplatin, vinblastine, and bleomycin (PVB) without excess cytopenias or new opportunistic infections. Of seven patients treated for advanced disease, there were five complete and two partial responses. Six patients have died of AIDS at a median of 20 months after diagnosis of GCT. The median follow-up time for surviving patients has been 42 months (range, 8 to 87) and all but one remain without evidence of active disease. In no case was a patient's HIV disease classification altered by antitumor therapy. The natural history of GCTs is comparable in HIV-infected and non-HIV-infected men and standard therapy including orchiectomy, retroperitoneal lymph node dissection, radiation therapy, and chemotherapy is well tolerated.

Muscular necrosis after retroperitoneal lymphadenectomy

A 36-year-old man was admitted to the hospital because of advanced germ cell tumor. The diagnosis of germ cell tumor was proven histologically after radical orchiectomy. Abdominal CT disclosed multiple masses adjacent to the aorta and vena cava. Four courses of chemotherapy consisting of 800 mg carboplatin per day were given. After chemotherapy, contrast-enhanced abdominal CT disclosed multiple masses with a total diameter of 15 x 7.5 x 16 cm adjacent to the aorta and vena cava. The masses extended from the iliac arteries to both renal hilars. The back muscles were unremarkable (Fig. la). Four weeks after the last course of chemotherapy, the patient underwent radical retroperitoneal lymph node dissection with removal of the residual masses. In order to remove these masses extending from both iliac vessels to both renal hilars, the lumbar arteries were ligated on both sides. The pathologic studies showed necrotic tumor and fibrotic changes without evidence of viable tumor.

Primary mediastinal germ cell tumour and acute monocytic leukaemia occurring concurrently in a 15-year-old boy

This report describes the case of a 15-year-old boy who presented with a primary mediastinal germ cell tumour and while receiving chemotherapy developed an acute monocytic leukaemia. The occurrence of these conditions simultaneously is extremely rare, and the possible shared aetiology is discussed. Also, the role of the chromosome marker i(12p) in the diagnosis of germ cell tumours is examined.

Monoclonal antibody 43-9F: an immunohistochemical marker of embryonal carcinoma of the testis.

Discrimination between different types of germ cell tumours may be difficult in routine histological preparations. Additionally, none of the established immunohistochemical markers is completely reliable in diagnosis of embryonal carcinoma. A pilot study indicated that monoclonal antibody 43-9F--a marker of carcinoma-in-situ germ cells--may also react with embryonal carcinoma of the testis. In order to elucidate the applicability of 43-9F in diagnosis of embryonal carcinoma, 42 consecutive testicular germ cell tumours were tested immunohistochemically. Among the 42 tumours, 23 were seminomas and 19 were non-seminomas with seminomatous components in seven of them. Embryonal carcinomas were found in 15 tumours, two being of pure type and the remaining 13 a part of mixed tumours. Additionally, the material included 11 teratomas, nine yolk sac tumours and one choriocarcinoma. Immunohistochemical stainings were performed with 43-9F and additionally with antibodies against placental-like alkaline phosphatase, cytokeratins, alpha-foetoprotein and human chorionic gonadotropin. Using 43-9F a strong colour reaction was found in 13 of the embryonal carcinomas, whereas the reaction was moderate in the remaining two cases. A weak positive reaction was found in six seminomas and the remaining 24 did not react at all. 43-9F exhibited a positive reaction in four of 11 teratomas. The reactivity was generally weak with some focal areas with strong staining. In five cases the yolk sac tumour elements did not stain with this monoclonal antibody. The reaction was weak in three cases and in only one case was the staining intensity scored as moderate. Finally, no reaction was found in the choriocarcinoma element. Compared to the other antibodies tested, including the antibody against cytokeratins, in embryonal carcinoma immunohistochemical staining with 43-9F was more specific, stronger and more constantly expressed. The monoclonal antibody 43-9F may be of value in histological diagnosis of germ cell tumours. Additionally, the study confirmed the pathogenetical link between pre-invasive carcinoma in situ and embryonal carcinoma.

Genetic Analysis as an Aid in Diagnosis for Patients With Midline Carcinomas of Uncertain Histologies

The tumors of nine patients with carcinomas of uncertain histogenesis (eight with poorly differentiated carcinomas involving primarily midline structures and one with a diagnosis of seminoma and atypical clinical features) were studied by cytogenetic and Southern blot analyses. Four of the eight patients with poorly differentiated carcinomas had abnormalities of chromosome 12 consistent with a diagnosis of germ cell tumor. These abnormalities comprised an i(12p) in two patients and a del(12q) in a third patient detected by cytogenetic analysis and multiple copies of 12p detected by Southern blot analysis in a fourth patient. Three of these four patients with a diagnosis of germ cell tumor established by genetic analysis achieved a complete response to cisplatin-based chemotherapy. The tumor biopsy of one patient showed a t(11;22) (q24;q12), and this patient had chemotherapy directed to neuroepithelioma. Cytogenetic analysis was unsuccessful for the tumors of three patients; these tumors did not have multiple copies of 12p detected by Southern blot analysis. These patients did not respond to cisplatin-based chemotherapy. One patient with a diagnosis of extragonadal seminoma failed to respond to cisplatin-based chemotherapy and had a second tumor biopsy performed that demonstrated a t(8;14) (q24;q32). This patient's diagnosis was changed to a non-Hodgkin's lymphoma. Thus, genetic analysis provided a diagnosis in six of nine patients. Cytogenetic and molecular analyses are useful clinical tools for the determination of histogenesis in some patients with poorly differentiated carcinomas of uncertain histology.

Metastatic testicular cancer and extragonadal germ cell tumor presenting with neurological symptoms

We present two patients with testicular cancer and extragonadal germ cell tumor respectively in whom neurological symptoms due to metastases preceded the correct diagnosis. Testicular cancer and extragonadal germ cell tumor are today curable malignancies even when distant metastases are present at diagnosis. The diagnosis of germ cell tumor should be considered whenever a young man presents with metastases of uncertain origin, and all histological specimens should be revised with the diagnosis of germ cell tumor in mind.

Germ Cell Tumors originating in the Basal Ganglia and Thalamus

Two patients with germ cell tumors of the basal ganglia and the thalamus are described. A 10year-old boy developed left hemiparesis and precocious puberty. Computed tomography (CT) of the brain revealed a small lesion in the right basal ganglia, which appeared to be rapidly growing. Elevation of human chorionic gonadotropin (HCG) in both serum and cerebrospinal fluid was compatible with germ cell tumor. A craniotomy was performed and the tumor was partially removed. Histological examination verified a mixed-type germ cell tumor composed of embryonal carcinoma, choriocarcinoma, and germinoma. An 11-year-old boy complained of right hemiparesis, and a CT scan showed a well-enhanced, cystic tumor in the left thalamic region. The tumor was partially resected and was diagnosed histologically as germinoma. A high level of HCG was found in the contents of the cyst. HCG and alpha-fetoprotein, which are so-called tumor markers, decreased over the course of treatment in both cases, and seemed to be indicators of the effectiveness of treatment. However, the authors feel that the differential diagnosis of germ cell tumors cannot be based solely on the level of these tumor markers. The characteristic features of germ cell tumors of the basal ganglia and thalamus are discussed.