Search

Background: The emergence of a primitive neuroectodermal tumor (PNET) within a germ-cell tumor (GCT) is rare. We assess the prognosis and response to treatment., Patients and Methods: Eighty-one patients were identified. Selected patients were treated with cyclophosphamide 1200 mg/m(2), doxorubicin 75 mg/m(2), and vincristine 2 mg i.v. alternating with ifosfamide 1.8 g/m(2) x 5 days plus etoposide 100 mg/m(2) x 5 days (CAV/IE). Ewing's sarcoma (EWS) translocation was assessed using a FISH-based method., Results: Median follow-up was 41 months. Seventy-six patients had PNET in the primary tumor or in initial metastasis. Five harbored PNET only at relapse. Twenty-six of 76 underwent primary retroperitoneal lymph node dissection, 13 of whom had retroperitoneal PNET and four are dead of disease (DOD). Fifty of 76 were initially treated with GCT chemotherapy (n = 49) or CAV/IE (n = 1). Twenty-seven of these 50 underwent complete postchemotherapy resection of residual PNET and 17 are DOD. Ten patients received CAV/IE. Eight achieved an objective response, and five are currently alive. One of the 14 specimens examined carried the EWS translocation., Conclusions: PNET of GCT origin is associated with an adverse outcome. For low-volume disease, surgery is the optimal initial therapy. CAV/IE may have a role in patients with unresectable disease.

It is controversial if the rare dermoid cyst of the testis should be classified as a variant of mature teratoma or separately. The spectrum of findings is also ill defined, as is the relationship of dermoid cyst to intratubular germ cell neoplasia of the unclassified type (IGCNU). This study therefore reports the findings in five testicular dermoid cysts that occurred in five patients, 17-42 years of age, who presented with testicular masses. Four lesions consisted of a keratin-filled cyst with a thickened wall, whereas one had islands of "shadow" squamous epithelial cells with superimposed calcification and ossification (pilomatrixoma-like variant). Hair was identified grossly in two cases. On microscopic examination, four tumors had hair follicles with sebaceous glands showing a typical, cutaneous-type orientation to an epidermal surface, although no hair shafts were present in two. In addition, the fibrous wall contained smooth muscle bundles (all tumors) and eccrine or apocrine sweat glands (4 tumors). In some cases there were also glands lined by ciliated epithelium (4 tumors, including the pilomatrixoma-like variant), intestinal mucosa (1 tumor), and bone (2 tumors). There was no cytologic atypia or apparent mitotic activity, and no case had IGCNU in the seminiferous tubules. All patients were clinical stage I and were treated by orchiectomy without adjuvant therapy. All were well on follow-up from 1.5 to 9.5 years later. This study supports that dermoid cyst may have noncutaneous teratomatous elements and that an important criterion for its diagnosis is the absence of IGCNU. It also supports that it should be categorized separately from mature testicular teratoma because of the malignant nature of the latter in postpubertal patients. These observations suggest that there are at least two pathways for testicular teratomas in postpubertal patients: the more common being through IGCNU by differentiation from an invasive malignant germ cell tumor and the less common one, taken by dermoid cyst, by direct transformation from a nonmalignant germ cell.

Background: Pure testicular teratoma in adults is a relatively rare malignant tumor with the ability to invade and metastasize. Pure teratoma generally is believed to be less aggressive and less likely to progress, to present in lower stages, and to have better survival rates then other forms of germ cell tumor. Consequently, clinical stage A patients with pure testicular teratoma commonly have been considered to be managed best by surveillance., Methods: A computerized database search identified 41 patients presenting to Indian University with pure teratoma in the orchiectomy specimen. These patients were further subdivided into four groups based on clinical stage, as follows: Group I, 18 patients with clinical Stage A disease; Group II, 4 patients with clinical Stages A-B1 disease based on questionable computed tomography findings; Group III, 3 patients with clinical Stage B1 disease; Group IV, 16 patients with advanced stage (B3-C) disease. The experience with these patients was reviewed., Results: The overall risk of lymph node metastasis in retroperitoneal lymph node dissection (RPLND) and the risk of relapse after RPLND for patients with low stage pure testicular teratoma (groups I-III) were 40 and 16%, respectively. In patients with clinical Stage A teratoma, the risk of retroperitoneal metastasis in RPLND was 16.7% and the relapse rate was 11.1%. In addition, nearly 37% of referred patients with pure teratoma presented with advanced disease., Conclusions: These data provide additional confirmation of the metastatic potential of pure testicular teratoma. The proper management of the adult clinical stage A patient with primary pure teratoma of the testis should not necessarily differ from the management of any other histologic type of nonseminomatous testicular tumor. Accordingly, histologic diagnosis of pure teratoma should not mandate surveillance. Instead, patients must be given adequate information regarding management options, as are all other patients presenting with clinical Stage A nonseminoma.

Carcinomas derived from teratomatous epithelium occur rarely in the metastases of patients with testicular cancer. These carcinomas of teratomatous origin (CTO) are easily confused with residual embryonal carcinoma (EC). For that reason, we compared the light and electron microscopic appearances of 6 CTOs with those of 12 ECs. As seen by light microscopy, the CTOs formed glands and more frequently had well-defined cytoplasmic borders, eosinophilic cytoplasm, and nonoverlapping, regular nuclei with small or absent nucleoli and little chromatin clumping and clearing, compared with the ECs. Mucin was present in the cells or glandular lumina of three CTOs but was absent in all the ECs. The demonstration of cytoplasmic glycogen was of no differential aid. The most useful differentiating ultrastructural features were long tight junctions and telolysosomes, which occurred in all of the EC but which were absent in the six cases of CTO. Desmosomes with inserting tonofilaments were present in three cases of CTO but were much less developed in EC. Two cases of CTO had microvilli with anchoring rootlets; such anchoring rootlets were not observed among EC. The distinction of CTO from residual EC is important, because CTO will likely need to be treated in a different manner.

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.

Eleven male patients had germ cell tumors of the testis (7), mediastinum (3), or retroperitoneum (1) in which non-germ cell malignancies developed. Such malignant non-germ cell elements were present in the primary excisions of five patients and were subsequently found in additional resected tissue in 10 of 11 patients. In the patients who had multiple pathology specimens examined, a progression from atypia to predominant non-germ cell malignancy was often found. The authors believe these malignant elements arose within teratomatous foci, since eight of nine cases had teratoma in the primary tumor, and teratoma was found in subsequently resected tissue in one additional case. Cisplatin therapy frequently "unmasked" the non-germ cell malignant elements by destroying the more chemosensitive germ cell cancers. The prognosis was worst for five patients who developed progressive embryonal rhabdomyosarcoma: two of these patients died of local spread of tumor, whereas a third died of metastatic sarcoma. Only one patient, who had total surgical excision of rhabdomyosarcoma, survived. Other forms of sarcoma that developed within germ cell tumors did not appear to adversely affect the prognosis beyond that of teratoma. It is currently recommended, when feasible, that patients with teratoma and sarcoma undergo total surgical excision. Further treatment with cisplatin regimens, after eradication of the germ cell component, has not been helpful. The role of other forms of chemotherapy remains speculative.

A correction to the article "Lessons from human teratomas to guide development of safe stem cell therapies" that was published in the June 4, 2013 issue is presented.