suprasellar germinoma: unresolved problems in diagnosis, pathogenesis, and management

Suprasellar Germinoma

Unresolved Problems in Diagnosis, Pathogenesis, and Management

CANDACE S. KASPER, M.D., Ph.D.

NANCY R. SCHNEIDER, Ph.D., M.D.

JOHN H. CHILDERS, M.D.

JEAN D. WILSON, M.D.

Dallas, Texas

From the Departments of Pathology and Internal Medicine, University of Texas Health Science Center at Dallas, Dallas, Texas. Requests for re- prints should be addressed to Dr. Jean D. Wilson, Department of Internal Medicine, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235. Manuscript accepted January 26, 1983.

A suprasellar germinoma, initially thought to be granulomatous diencephalitis of uncertain cause, responded following chloramphenicol and methicillin treatment both by clinical and radiographic criteria and was not diagnosed until a third biopsy was performed. Analysis of this case and review of the literature lead to the con- clusion that adequate dlagnostlc workup of such lesions requires that biopsy be extensive enough to include the central core as well as the granulomatous reaction that surrounds such tumors. Fur- thermore, since the degree of inflammation may fluctuate, regression does not mean that the lesion is not neoplastic in origin. In the present instance, the correct diagnosis could have been made earlier if the &chain of human chorionic gonadotropin had been measured in spinal fluid.

Germ cell tumors can arise in the presacral area, mediastinum, retroperitoneum, and cranial vault as well as in the gonads themselves [i-3]. Germinomas of the brain (also called atypical teratomas or ectopic pinealomas) are rare tumors that may lead to several distinct syndromes, including diabetes insipidus, Parinaud’s ophthalmoplegia, panhypopituitarism, and signs and symptoms of increased intracranial pressure [4]. We describe a man with a suprasellar germinoma and mature cystic teratoma of the pineal whose condition illustrates some of the unresolved issues in the diagnosis and management of extragonadal germinomas.

CASE REPORT

A 22-year-old black man presented to Parkland Memorial Hospital in March 1978 with polydipsia, polyuria, anorexia, a 15pound weight loss, and symptoms of elevated intracranial pressure, including left frontal headaches, irritability, and vomiting. He had had a generalized seizure disorder, controlled with unknown medications, beginning at age 9, approximately three months after a motor vehicle accident, and persisting until age 15, at which time the medications were discontinued. In the intervening seven years he had remained seizure-free.

He was afebrile, and physical examination demonstrated normal findings except for sinus bradycardll. Lymphocytosis (white blood cell count 50/mrr+, 94 percent lymphocytes) was present in the cerebrospinal fluid. Results of blood and cerebrospinal fluid cuftures were negative. An extensive endocrine evaluation documented both anterior and posterior hypopituitarism, and treatment with vasopressin, hydrocortisone, and L-thyroxine was instituted. Computed axial tomographic scan of the head showed an area of contrast enhancement and edema in the anterior wall of the third ventricle with extension of ths lesion into the right lateral ventricle (Figure IA). These findings were thought to be compatible with a brain tumor (ependymoma or germinoma), granuloma, or abscess.

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SUPRASELLAR GERMINOMA-KASPER ET AL

A neoplasm was considered to be the most likely diagnosis, but because of the possibility of brain abscess, he was treated empirically with chloramphenicol and methicillin for six weeks. A presumptive diagnosis of an infectious origin for the mass was made when repeat computed tomographic scan revealed a dramatic reduction in tumor size during the course of the antibiotic therapy (Figure 1B). Results of cerebrospinal fluid cultures remained negative, and the cerebrospinal fluid lymphocytosis resolved.

The patient remained asymptomatic for four months and then frontal headaches and vomiting again developed. Repeat computed tomographic scan revealed an increase in the size of the mass that impinged on the third ventricle. A brain biopsy specimen obtained during craniotomy consisted of small fragments in which normal tissue was replaced almost completely by noncaseating granuloma. Some large cells with hyperchromatic pleomorphic nuclei were interspersed among the inflammatory elements. These large cells, originally interpreted as reactive in nature, were identified some years later as neoplastic germ cells of the seminoma type (Figure 2A). All special stains and cultures of the biopsy sample for bacteria, viruses, and fungi gave negative results. The working diagnosis was diencephalitis of uncertain cause, presumably infectious in origin.

As a routine part of postcraniotomy care, he was treated

initially with high-dose glucocorticosteroids; the steroids were then tapered, and treatment with methicillin and chloramphenicol was again begun for two weeks. Computed tomographic scan again demonstrated a reduction in the size of the mass, but two weeks after discontinuing antibiotics, signs of increased intracranial pressure developed. Following placement of a ventriculo-peritoneaI,shunt, a left seventh nerve palsy and left hemiparesis developed. When he was discharged, he was receiving vasopressin, glucocorticoids, L-thyroxine, and an empiric trial of oral amoxicillin.

He was admitted four times during the subsequent 16 months for poor control of diabetes insipidus. Serial computed tomographic scans revealed enlargement of the suprasellar mass with extension into the region of the splenium of the corpus callosum. Because of the increasing size of the mass, a second brain biopsy was performed in January 1980. Again, the biopsy specimen showed a noncaseating granulomatous inflammatory process, and special stains and cultures for infectious origins gave negative results. Even in retrospect, none of the large cells with hyperchromatic nuclei seen in the 1978 biopsy specimen was identified in this specimen. The diagnosis of central nervous system sarcoidosis was entertained, but the result of an extensive workup for systemic sarcoklosis, including biopsy of the bone marrow, liver, and conjunctival tissue, was negative.

Figure 1. Representative computed tomographic scans of the brain. A, initial computed tomographic scan showing enhancement and edema in the anterior wall of the third ventricle with extension of the lesion into the right lateral ventricle. B, computed tomographic scan obtained several months after administration of chkuamphenicol and methiciilin, showing reduction in size of the mass. C, computed tomographic scan obtained two years after initial presentation; significant enlargement of the mass has taken place. D, computed tomographic scan demon- strating decrease in size of the brain mass after a cumulative dose of 360 mg cis- platinum, 40 mg vincristine, and 180 mg bleomycin.

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As documented by multiple computed tomographic scans, the brain mass enlarged slowly and relentlessly over the next year, and the patient’s clinical status progressively deterio- rated despite a variety of antibiotic and steroid regimens (Figure 1C). In January 1982, almost four years after the initial presentation, symptoms of brain stem herniation developed. An emergency decompressive craniotomy was performed, and several fragments of firm, grey tissue were removed piecemeal from the mass in the wall of the right lateral ventricle. The biopsy specimen again showed an extensive noncaseating granulomatous inflammatory process char- acterized by clusters of multinucleated giant cells and epithelioid histiocytes intermingled with an infiltrate consisting of lymphocytes, plasma cells, and gemistocytic astrocytes. In areas of confluent granulomas there was widespread de- struction of the cerebral parenchyma. Additionally, neoplastic cells of the germinoma type were identified. They were present either as individual cells, as clusters of cells, or as small aggregates intermixed with lymphocytes (Figure 28).

Figure 2. Representative histologic sections of brain biopsy specimens. A, inittai biopsy specimen showing massive replacement of brain parenchyma by noncaseating granuloma. Several neoplastic cells with hyperchronwtic pleomorphic nuclei are present but were originally interpreted as benign reactive cells (hematoxylin and eosin; original magnification X 1,000). B, third biopsy specimen of the granuloma, showing many neoplastic cells intermixed among an aggregate of lymphocytes. Several neoplastic cells are also present in the granuioma surrounding the lymphocytic infiltrate (hematoxylin and eosin; original magnification X 400). C, periodic acid- Schiff stain of the third biopsy specimen, delineating the glywgen-rich germino~ cells intermingled in the granuloma (original magnification X 400). B, higher magnificatkm of Figure 2B, &?wnstmting the germinoma cells. The nuclei are hyperchromatic, and several mitotic figures are present (hematoxylin and eosin; original magnification X 1,000). Entire figure reduced by 35 percent.

In most areas examined, the neoplastic cells were almost completely obscured by granuloma. These characteristic germinoma cells contained pale, eosinophilic, periodic acid-Schiff-positive cytoplasm and measured approximately 25 pm in diameter (Figure 2C). The cells had hyperchromatic pleomorphic nuclei with prominent nucleoli, and two to four mitotic figures per IO high-power fields (Figure 2D). No teratomatous elements were seen. The diagnosis of intracranial germinoma was made. In retrospect, the samples from the 1978 and 1980 biopsies consisted predominantly of reactive tissue obtained from the edge of the slowly growing primary germinoma and were not representative of the underlying lesion. Results of all special stains and cultures for bacteria, viruses, and fungi were again negative. Cerebrospinal fluid P-human chorionic gonadotropin level was 14 mlU/ml at a time when the serum &human chorionic gonadotropin level was less than 3 mlU/ml (normal). Similar measurements were then made on frozen serum and cerebrospinal fluid that had been obtained at the time of the 1980 biopsy: cerebrospinal



fluid P-human chorionic gonadotropin level was 53 mlU/ml, whereas serum P-human chorionic gonadotropin level was less than 3 mlU/ml.

In February 1982, after a workup of baseline auditory, renal, and pulmonary functions, a triple drug regimen of cis-platinum, vincristine, and bleomycin was instituted. The patient’s condition improved initially, and repeat computed tomographic scan indicated that the brain mass had de- creased in size (Figure 1D). However, in April 1982 (after cumulative doses of 180 units bleomycin, 360 mg cis-platinum, and 40 mg vinblastine) he was admitted because of dyspnea and a dry, nonproductive cough. Chest x-rays showed a bilateral reticulonodular infiltrate, and pulmonary function tests revealed a diffusion capacity that was 28 percent of the predicted value. The result of an extensive workup for an infectious origin of his lung disease was negative. His respiratory function continued to deteriorate, and he died of respiratory failure three weeks after the onset of dyspnea. Postmortem Examination. Four features of the postmortem examination were noteworthy. A 1.5 by 1.0 by 1.0 cm pedunculated, fluid-filled, multilobulated, histologically mature cystic teratoma was attached to the dura in the midline. It occupied an area corresponding to the usual location of the pineal gland and resulted in elevation of the splenium of the corpus callosum and compression of the surrounding brain tissue. The teratoma contained tissue derived from all three germ layers. The endodermal component was represented by alimentary and respiratory epithelium. Elements of smooth muscle, blood vessels, connective tissue, and bone consti- tuted the mesodermal component, and ectoderm was represented by stratified squamous epithelium and glial tissue. The bony elements of the teratoma were almost certainly responsible in large part for the calcification demonstrable radiographically in the area of the pineal. No pineal parenchyma was identified in 10 stepped sections examined.

Second, there was erosion and replacement of the body of the corpus callosum, the posteroinferior portion of the rostrum of the corpus callosum, the septum pellucidum, and the anterosuperior portion of the hypothalamus by an irreg- ular, firm, grey-white granular mass of necrotic and gliotic tissue that protruded into the third ventricle. Despite extensive histologic examination, including special stains, no residual germinoma was identified in this mass.

Third, the thyroid, adrenals, and testes were atrophic, and the pituitary was small and compressed.

Fourth, the lungs were firm and airless with diffuse, dense interstitial fibrosis, hyperplasia of the alveolar cells, and squamous metaplasia of the alveolar ducts, consistent with bleomycin toxicity.

COMMENTS

This case illustrates some of the unresolved issues in the diagnosis and management of germinomas of the brain. Most such tumors, because they arise in or near the pineal, were originally thought to be tumors of pineal derivatives and were termed pinealomas [5,6]. Sub- sequently, three distinct types of pineal tumors were

delineated, two of which (pinealocytoma and pinealo- blastoma) are true tumors of the pineal parenchyma and a third tumor derived from germ cells. The latter tumor resembles gonadal germinomas (and germinomas in other extragonadal sites such as the mediastinum) and, like other germinomas, may contain elements of teratoma, choriocarcinoma, or embryonal cell carcinoma as well as characteristic seminoma cells [7].

Two theories have been proposed to explain how germ cell tumors arise in the brain. In the early embryo, the primordial germ cells are initially located in the wall of the yolk sac near the allantois; from the yolk sac they migrate by ameboid movement along the dorsal mes- entery of the hindgut toward the genital ridges. During the sixth week of human development, the primordial germ cells reach the genital ridges where they patiici- pate in the development of ovary or testis [8]. This migration process is occasionally imperfect, and “lost” germ cells have been identified in normal mouse and chick embryos in a variety of atypical sites, including the central nervous system [9-l l]. Since germ cells can occur in extragonadal sites, it is reasonable to as- sume that such ectopic cells could give rise to tumors [ 121. An alternative view has been proposed by Friedman and Van de Velde [ 131, who have suggested that the thymus and the pineal as well as the germ cells are derived from a common precursor stem cell that originates in the yolk sac and that extragonadal germ cell tumors are derived from these primitive yolk sac elements. The latter theory would provide an explana- tion for the fact that extragonadal germinomas arise almost exclusively in the mediastinum and brain, despite the known migration of the germ cells to other tissues as well. It is of interest in this regard that germ cells have not been demonstrated rostra1 to the genital ridges in normal human embryos as contrasted to the obser- vations in mouse and chick embryos, a finding that implies that misdirected migration of germ cells may be less common in human embtyos [ 141. The presence of more primitive components such as yolk sac elements and teratomas in many central nervous system germinomas is compatible with either theory of pathogenesis. Careful examination of pineal germinomas (as well as gonadal seminomas) often reveals small foci of associated teratomatous tissue.

An unresolved question in the present patient is whether the two neoplasms (germinoma and teratoma) arose independently as histologically and anatomically distinct entities or whether the suprasellar germinoma represented a malignant component of the teratoma that was subsequently eradicated by chemotherapy. The fact that, at autopsy of the present patient, the only calcification demonstrable in the brain was in the teratoma and the fact that this calcification was demonstrable as a midline cystic structure on the earliest


computed tomographic scans and prior to the administration of chemotherapy would seem to indicate that some of the teratomatous regions had been present at least from the time of initial presentation. It is of interest in this regard that it is common to find residual teratomas consisting only of mature elements and associated fibrosis after successful chemotherapy for disseminated testicular cancer [ 15- 171. Presumably, the chemotherapy eradicates the malignant components of these gonadal (testicular) carcinomas and leaves only the benign (teratoid) elements and associated fibrosis.

The clinical manifestations of central nervous system germinomas depend on the location of tumor within the brain [ 181. The present patient had tumor involving the pineal and suprasellar regions. The tumor was manifested clinically by a typical constellation of findings for germinomas in these locations-namely diabetes insipidus, panhypopituitarism, increased intracranial pressure, and cerebrospinal fluid pleocytosis [4,18]. In contrast, germinomas confined to the pineal itself most commonly cause only increased intracranial pressure and diabetes insipidus without impairment of anterior pituitary function; germinomas of the basal ganglia and thalamus typically cause hemiparesis and/or precocious puberty [ 181. Indeed, the correct diagnosis was considered during the initial workup along with other infectious, malignant, and granulomatous causes of parasellar masses [4,19-241.

Despite the characteristic clinical and radiographic features, the documentation of a mass lesion in the appropriate location, and the consideration of the diagnosis at the time of initial presentation, the correct diagnosis was not established until a third brain biopsy was performed some four years after the initial presentation. The delay in establishing the diagnosis was due primarily to three factors.

The first was that the biopsy specimens consisted predominantly of granulomatous infiltrates. The granulomatous inflammatory process that surrounds germinomas is a recognized feature of both gonadal and extragonadal tumors and is thought to be a reflection of the host immune response to the neoplasm [6,25-301. The granulomatous reaction typically con- tains epithelioid histiocytes, multinucleated giant cells, and (usually) lymphocytes. Indeed, the granuloma may extend to the leptomeninges and be so extensive that it masks the underlying tumor itself [6,25-27,29-311. Thus, in the absence of an established infectious origin, the finding of granulomatous inflammation in central nervous system mass lesions should place germinoma high in the differential diagnosis. The hazard in failing to recognize this feature of the tumor has previously been reported [26,29,31] and was a major cause of the delay in diagnosis in the patient we have described in this report.


A second reason for the delay in establishing the diagnosis was the apparent response of the tumor to antibiotic therapy. Such a response occurred on two occasions and was manifested both by clinical im- provement and by decrease in the size of the mass lesion as documented by computed tomographic scan. This response suggested that the granuloma was the result of some infectious agent and caused us to pursue a lengthy, fruitless search for such an infectious origin, including culturing of the biopsy material and perfor- mance of extensive immunologic screening assays. Even in retrospect, the reason for this false lead is not clear. The apparent response might have been coin- cidental to the chloramphenicol therapy, representing some waxing and waning of the inflammatory process that is an unrecognized feature of the natural history of this slowly progressive disease. Alternatively, the phenomenon could have been a direct consequence of chloramphenicol treatment. The antibiotic is known to be an inhibitor of mitochondrial protein synthesis in mammalian cells [32], and it is possible that it may act as a mild antimetabolite under these conditions; this effect could have caused a partial reduction of the granulomatous elements that formed the bulk of the lesion.

The third and most important reason for the error in diagnosis was the failure to measure gonadotropin levels in the spinal fluid. Human chorionic gonadotropin is synthesized by normal testes, but in such small amounts that only trace quantities reach the circulation [33]. However, the level of plasma human chorionic gonadotropin (or the beta subunit of human chorionic gonadotropin) is a useful marker for certain germinomas and is elevated in about a third of patients with germ cell tumors of the nonseminoma type (30 percent of tera- tocarcinomas, 30 percent of yolk sac tumors, and all choriocarcinomas) [34-361. Indeed, an elevated level of plasma human chorionic gonadotropin (or ,@ subunit of human chorionic gonadotropin) in a patient with a testicular tumor that has been classified as a pure seminoma usually indicates that the tumor is of mixed cell origin [37-391. Elevation of the level of human chorionic gonadotropin in cerebrospinal fluid in the absence of elevation of the plasma human chorionic gonadotropin level has been reported in patients with intracranial germinoma [40]. It is not established how frequently this is the case and whether the presence of human chorionic gonadotropin in cerebrospinal fluid is also indicative of a mixed cell origin of such brain tumors. However, the fact that the cerebrospinal human chorionic gonadotropin level was elevated in this patient a year and a half before the diagnosis was eventually made indicates that the diagnosis could have been established earlier if the appropriate measurement had been made. Whether other plasma tumor markers of

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SUPRASELLAR GERMINOMA-KASPER ET A!_

germinoma such as cr-fetoprotein might be equally useful as markers in cerebrospinal fluid is not known [41,42]. In any case, serious neurologic deficits that persisted throughout the remainder of the patient’s life developed during the interim between initial presentation and the establishment of the correct diagnosis.

This case also illustrates unresolved problems as to the appropriate management of central nervous system germinomas. Treatment of germinomas of gonadal origin constitutes one of the real successes of cancer therapy. Indeed, following surgical resection and postsurgical radiation and/or chemotherapy (most commonly involving combinations of cis-platinum, vinblastine, and bleomycin), tumor-free survivals of 97 percent for early disease and 70 percent for disseminated disease have been reported; the overall strategy

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for the management of gonadal seminomas, including debulking, resection of involved lymph nodes, and use of adjuvant radiation and chemotherapy, is relatively straightforward [43-491. The cumulative experience with the use of cancer chemotherapy drugs for the treatment of extragonadal germ cell tumors is small, but some dramatic responses to such therapy have been reported [40,50,51]. Likewise, radiation therapy has been effective in individual instances of central nervous system germinomas [52]. In the present patient, combination chemotherapy obliterated all evidence of the germinoma so that at autopsy only a residual mature teratoma in the region of the pineal was identified. Nevertheless, the patient died of a known side effect of bleomycin therapy, namely pulmonary fibrosis

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REFERENCES

Meares EM, Briggs EM: Occult seminoma of the testis mas- querading as primary extragonadal germinal neoplasms. Cancer 1972; 30: 300-306.

Das S, Bochetto JR, Alpert LI: Primary retroperitoneal seminoma. Cancer 1975; 36: 595-598.

Bush SE, Martinez A, Bagshaw MA: Primary mediastinal seminoma. Cancer 1962; 48: 1877-1882.

Post KD, Kasdon DL: Sellar and parasellar lesions mimicking adenoma. In: Post KD, Jackson IMD, Reichlin S, eds. The pituitary adenoma. New York: Plenum Medical, 1980; 159-215.

Russell DS: The pinealoma: its relationship to teratoma. J Pathol 1944; 56: 145-150.

Friedman NB: Germinoma of the pineal. Its identity with germinoma (“seminoma”) of the testis. Cancer Res 1947; 7: 363-368.

DeGirolami U: Pathology of tumors of the pineal region. In: Schmidek HH, ed. Pineal tumors. New York: Marson USA, 1977; l-19.

Witschi E: Migration of the germ cells of human embryos from the yolk sac to the primitive gonadal folds. Carnegie Insti- tution of Washington. Contributions to Embryology 1948; 32: 69-96.

Mintz B, Russell ES: Gene-induced embryological modifica- tions of primordial germ cells in the mouse. J Exp Zool 1957; 134: 207-229.

Mintz 8: Formation and early development of germ cells. In: Symposium of Germ Cells and Development. Milan, Italy: Fondazione A. Baselli, lnstituto Lombardo, 1961; l-24.

Meyer DB: The migration of primordial germ cells in the chick embryo. Dev Biol 1964; 10: 154-190.

Friedman NB: The comparative morphogenesis of extragenital and gonadal teratoid tumors. Cancer 1951; 4: 265-275.

Friedman NB, Van de Velde RL: Germ cell tumors in man, pleiotropic mice, and continuity of germplasm and soma- toplasm. Hum Pathol 1981; 12: 772-776.

Chiquoine AD: The identification, origin, and migration of the primordial germ cells in the mouse embryo. Anat Ret 1954; 118: 135-146.

Corn&row RH, Grab&Id H: Reexploration for retroperitoneal lymph node metastases from testis tumors. J Urol 1976; 115: 569-571.

Einhorn LH, Donohue JP: Improved chemotherapy in disseminated testicular cancer. J Urol 1977; 117: 65-69.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

Garnick MB. Canellos GP, Richie JP, Stark JJ: Sequential combination chemotherapy and surgery for disseminated testicular cancer: cis-dichlorodiammineplatinum (1 I), vinbtastine, and cyclophosphamkfe and ackiiycin. Cancer Treat Rep 1979; 63: 1681-1686.

Chang CG, Kageyama N, Kobayashi T. Yoshida J, Negoro M: Pineal tumors: clinical diagnosis, with special emphasis on the significance of pineal calcification. Neurosurgery 1981; 8: 656-668.

Udani PM, Parekh C, Dastur DK: Neurological and related syndromes in CNS tuberculosis. Clinical features and pathogenesis. J Neurol Sci 1974; 14: 341-357.

Douglas AC, Maloney AFJ: Sarcoidosis of the central nervous system. J Neurol Neurosurg Psychiatry 1973; 36: 1024- 1033.

Beard W, Foster DB, Kepes JJ, Guillan RA: Xanthomatosis of the central nervous system. Clinical and pathological ob- servations of a case with a posterior fossa syndrome. Neurology 1970; 20: 305-314.

Tibbs PA, Challa V, Mortara RH: Isolated histiocytosis X of the hypothalamus. J Neurosurg 1978; 49: 929-934.

Tekeuchi J, Mori K, Moritake K, Tani F, Waga S, Handa H: Teratomas in the suprasellar region: report of five cases. Surg Neurol 1975; 3: 247-255.

Perlin E. Engeler JE Jr, Edson M, Karp D, Mclntire KR, Wald- mann TA: The value of serial measurement of both human chorionic gonadotropin and alpha-fetoprotein for monitoring germinal cell tumors. Cancer 1976; 37: 215-219.

Marshall AHE, Dayan AD: An immune reaction in man against seminomas, dysgerminomas, pinealomas, and the mediastinal tumours of similar histological appearance. Lancet 1964; II: 1102-1104.

Simson LR, Lampe I, Abell MR: Suprasellar germinomas. Cancer 1968; 22: 533-544.

Jellinger K: Primary intracranial germ cell tumours. Acta Neuropathol (Berl) 1973; 25: 291-306.

Heyderman E, Neville AM: Syncytiotrophoblasts in malignant testicular tumors. Lancet 1976; II: 103.

Koide 0, Watanabe Y, Sato K: A pathological survey of intracranial germinoma and pinealoma in Japan. Cancer 1980; 45: 2119-2130.

Coulson W Surgical pathology. Philadelphia: JB Lippincott, 1978.

Dariano JAF, Furlanetto TW, Costa SS, Prenna FJ, Santos AJ,



32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

Sharer LR: Suprasellar germinoma: an unusual clinical presentation. Surg Neurol 198 1; 15: 294-297.

Sande M, Mandell G: Antimicrobial agents. In: Gilman A, Goodman L, eds. The pharmacological basis of therapeu- tics. 6th ed. New York: Macmillan, 1980; 1191-l 196.

Braunstein GD, Rasor J, Wade ME: Presence in normal human testes of a chorionic-gonadotropin-like substance distinct from human luteinizing hormone. N Engl J Med 1975; 293: 1339-1343.

Cochran JS: Testicular tumor in Dallas: results of surgical management 1960-1977. Dallas Med J 1978; 64: 122- 127.

Cochran JS, Walsh PC, Porter JC, Nicholson TC, Madden JD, Peters PC: The endocrinology of human chorionic gonadotropin-secreting testicular tumors: new methods in diagnosis. J Urol 1975; 114: 549-555.

Keogh 6, Hreshchyshyn MM, Moore RH, Merrin CE. Murphy GP: Urinary gonadotropins in management and prognosis of testicular tumor. Urology 1975; 5: 496-498.

Lange PH, Mclntire KR, Waklmann TA, Hakala TR, Fraley EE: Serum alpha fetoprotein and human chorionic gonadotropin in the diagnosis and management of nonseminomatous germ-cell testicular cancer. N Engl J Med 1976; 295: 1237-1240.

Willemse PHB, Sleijfer DTh, Koops HS, et al: Tumor markers in patients with non-seminomatous germ cell tumors of the testis. Oncodev Biol Med 1981; 2: 117-128.

Willemse PHB, Sleijfer DTh, Koops HS, et al: The value of AFP and HCG half lives in predicting the efficacy of combination chemotherapy in patients with non-seminomatous germ cell tumors of the testis. Oncodev Biol Med 1981; 2: 129-134.

Neuwelt EA, Frenkel EP, Smith FIG: Suprasellar germinomas (ectopic pinealomas): aspects of immunological charac- terization and successful chemotherapeutic responses in recurrent disease. Neurosurgery 1980; 7: 352-358.

Javadpour N: The role of biologic tumor markers in testicular

42.

43. 44.

45.

46.

47.

48.

49.

50.

51.

52.

cancer. Cancer 1980; 45: 1755-1761. Szymendera JJ, Zborzil J, Sikorowa L, Kaminska JA, Gadek

A: Value of five tumor markers (AFP, CEA, hCG, hPL and SP,) in diagnosis and staging of testicular germ cell tumors, Oncology 1981; 38: 222-229.

Donohue JP: Testicular cancer. J Ural 1981; 126: 59. Einhorn LH, Donohue JP: Cisdiamminedichloroplatinum,

vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 1977; 87: 293-298.

Skinner DG, Scardino PT, Daniels JR: Testicular cancer. Annu Rev Med 1981; 32: 543-557.

Kaplan JH, Kudish HG, Sacks SA: Testicular tumors of germ cell origin: 1. Epidemiology, pathogenesis, clinical presentation, and diagnosis. Postgrad Med 1981; 70: 114- 121.

Kaplan JH, Kudish HG, Sacks SA: Testicular tumors of germ cell origin: 2. Classification, staging, treatment, and prognosis. Postgrad Med 1981; 70: 125-131.

Fraley EE, Lange PH, Kennedy BJ: Medical progress. Germ-cell testicular cancer in adults. N Engl J Med 1979; 301: 1370-1377.

Anderson T, Javadpour N, Schilsky R, Barlock A, Young RC: Chemotherapy for testicular cancer: current status of the National Cancer Institute Combined Modality Trial. Cancer Treat Rep 1979; 63: 1687-1692.

Kirshner JJ, Ginsberg SJ, Fitzpatrick AV, Comis RL: Treat- ment of a primary intracranial germ cell tumor with systemic chemotherapy. Med Pediatr Oncol 1981; 9: 361- 365.

Neuwelt EA, Glasberg M, Frenkel E, Clark WK: Malignant pineal region tumors. A clinico-pathological study. J Neu- rosurg 1979; 51: 597-607.

Griffin BR, Griffin TW, Tong DYK, et al: Pineal region tumors: results of radiation therapy and indications for elective spinal irradiation. Int J Radiat Oncol Biol Phys 1981; 7: 605-608.


suprasellar germinoma: unresolved problems in diagnosis, pathogenesis, and management

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