=Acta NeuFochirurgica
Acta Neurochir (Wien) (1991) 109:78-83
9 Springer-Verlag 1991 Printed in Austria
Bone Metastasis Associated with Shunt-Related Peritoneal Deposits From a Pineal Germinoma Case Report and Review of the Literature R. Pallini, V. Bozzini, M. Seerrati, C. Zuppi 1, B. Zappacosta 1, and G. F. Rossi Institutes of Neurosurgery and 1Human Physiology, Catholic University School of Medicine, Rome, Italy
Summary The case of a 15-year-old boy with a pineal germinoma is reported, The patient first underwent a ventriculoperitoneaI (VP) shunt followed by a stereotactic biopsy, then, because of the rapidly deteriorating neurological status, an emergency craniotomy with subtotal removal of the tumour was performed. Two months after surgery, a left femoral metastasis and extensive peritoneal lesions became evident; they were regarded as due to haematogenous and VP shunt spread of the germinoma. At that time, extremely high serum levels of placental alkaline phosphatase were detected. The patient died 6 months after the inital diagnosis. The occurrence of extraneural metastases as well as of shunt related peritoneal deposits from primary intracranial germinoma is discussed. As far as we know this is the first reported case of a combination of haematogenous as well as VP shunt spread of a pineal germinoma.
Keywords: Pineal germinoma; extracranial metastasis; haematogenous spread; shunt related spread.
Introduction E x t r a n e u r a l metastases from p r i m a r y b r a i n t u m o u r s are rare 24'28' 32. Several p o t e n t i a l routes of metastatic t u m o u r spread outside the central n e r v o u s system have been suggested: diffusion a l o n g the n a t u r a l cerebrospina ! fluid (CSF) p a t h w a y s 3' 8, vascular e m b o l i z a t i o n (arterial and venous)5,13, 22, and lymphatic seedingS, 8,17,23. Pineal g e r m i n o m a s have also been described to metastatize extracranially via the b l o o d stream owing to their p r o p e n s i t y to i n v a d e the cerebral veins2,5, 23. Finally, there are several reports of secondary localization of b r a i n t u m o u r s to the peritoneal cavity as a c o m p l i c a t i o n of C S F diversion procedures in m e d u l l o b l a s t o m a 10, g l i o b l a s t o m a 31, a n d above all in pineal region t u m o u r s 1'9' 13,16,18-19,25,29-30, 34-35. T o prevent this serious complication, the use of Millipore filters 1~ a n d the r e m o v a l of the s h u n t once the C S F
p a t h w a y p a t e n c y has been restored following surgical d e c o m p r e s s i o n or r a d i a t i o n therapy 16 have been proposed. Some factors seem to f a v o u r the metastatic diss e m i n a t i o n of b r a i n t u m o u r s : 1) direct surgical attack, 2) the lenght of the survival period, a n d 3) i m m u n o suppresive therapies, such as r a d i o t h e r a p y a n d prolonged corticosteroid treatments. We report a case of pineal g e r m i n o m a who developed metastatic b o n e a n d peritoneal lesions.
Case Report Antimo D, M., a boy aged 15, was admitted to our Department
in September 1988. One month previously, the patient had been hospitalized at another neurosurgical institution because of headache, lethargy, limitation or upward gaze, and diabetes insipidus. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a large pineal region tumour causing obstructive hydrocephalus (Figs. 1A and B). A ventriculo-peritoneal shunt was inserted. On admission at our Department, neurological examination revealed bilaterally reduced visual acuity, bilateral papilloedema,spontaneous horizontal nystagmus, Parinaud's syndrome, left hypo-acusia, spastic tetraparesis, bilateral cerebellar syndrome, and neck stiffness. A post-shunting CT scan showed normally sized ventricles and confirmed the contrast enhancing mass lesion in the pineal region. A stereotactic biopsy was performed on September 27, 1988. The histological diagnosis was germinoma (Fig. 2). Five days later, the patient became progressivelydrowsy. On the CT scan, intracranial complications related to the biopsy procedure as well as shunt malfunctioning were excluded, however, a marked increase of the tumour size was apparent (Fig. 3). In the following few days, the clinical condition deteriorated; the patient became comatose presenting disturbances of cardiac and respiratory rythms~ hyperthermia, and arterial hypertension. Due to the dramatic and progressive worsening, operative decompression was performed on October 6, 1988. The tumour was exposed through a right paramedian suboccipital supra-transtentorial approach. It appeared as a pinkish soft-
R. Pallini etal.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
79
Uig. 1, Preoperative contrast enhanced CT scan (A) and T2 weigthed MRI (B) showing the mass lesion in the pineal region with obstructive hydrocephalus
Fig. 2. Microphotograph of the biopsy specimen showing the characteristic two-cell pattern of the germinoma with large clear cells and small lymphoid elements (HE, 125 x )
elastic mass in the pineal region involving the eisternal spaces along the tentorial edge and extending ventrally into the third ventricle. Under microsurgical control, the tumour was subtotally removed. The diagnosis of germinoma was confirmed on the surgical specimens. The post-operative course was satisfactory with partial recovery of the neurological deficits, however, the patient required continued intensive management due to persistent diabetes insipidus with electrolyte imbalance and impaired temperature regulation. Twenty days after surgery, whole brain (4200 Gy) irradiation was started. Radiation therapy was completed on December 15, 1988. From the beginning of January, elevated serum levels of alkaline phosphatase were noted on routine examinations (Fig. 4). The alkaline phosphatase isoenzymes were repeatedly assessed by using an affinity electrophoretic method (lectin containing agarose gel) 4, z~-ls The placental alkaline phosphatase (PLAP) isoenzyme, which was confirmed by the heat test and inhibition by phenylalanine7-2s, ranged
from 40 to 65% of the total activity (Figs. 5). At that time, the cranial CT scan did not disclose local recurrence of the pineal turnout (Fig. 6). The skeletal scintigraphy with Tc 99 m revealed an hyperdense area in the distal methaphysis of the left femoral bone (Fig. 7). This area appeared as an osteolytic lesion on plain radiograms. A few days later, the patient complained of tenderness at the left hip, abdominal pain, and constipation. His general condition deteriorated very rapidly. A solid mass became palpable in the left inferior abdominal quadrant. Echography and CT scan demonstrated a diffuse nodular involvement of the peritoneum and a large pelvic inter-vescico-rectal solid mass (Fig., 8). The testes were normal to the physical examination and to the echo scan. No other evidence of neoplastic localization could be detected by clinical and instrumental examinations (CT and echo scans). The opportunity to start chemotherapy was not taken owing to the severely affected general condition. Finally, the skin in the left inferior abdominal region was
80
R. Pallini et al.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
reviewed below. So far the Weiss's criteria to confirm the existance of extra-axial metastases from primary brain tumour 33 are not completely satisfied. Nevertheless, we believe that in our case the secondary origin from the intracranial germinoma of both the bone and the abdominal lesions is strongly favoured by some of our findings, a) PLAP, which is normally present on the plasma membrane of syncytiotrophoblasts 14, has been identified as a specific tumour marker for intracranial germinoma26 and for testicular seminoma 12. Its serum level has been shown to reflect variations of tumour size in three germinoma cases 27. In our patient, testicular tumoural lesions were carefully looked for, with negative results. Furthermore, the behaviour of the PLAP serum level closely matched the clinical and instrumental signs of development of the bone and peritoneal tumoural invasion, b) No clinical and instrumental evidence (CT and echo scans, scintigraphy) of primitive tumours in other parts of the body, to be regarded as the possible origin of spread to the bone and to the peritoneum, were found. The haematogenous spread from pineal germinomas is exceedingly rare. Borden e t a l . 2 reviewed only two published cases of pulmonary metastases after open biopsy of a pineal germinoma. Their additonal case occurred in a young boy who presented a metastasis in the right femur 1 year and 6 months after radiation therapy of a presumed pineal region tumour. More recently, Galassi e t a l . 5 described a 10-year-old
Fig. 3. Post shunting CT scan performed following the stereotactic biopsy at the time of the clinical worsening. Note the marked increase of the tumour size compared to the previous CT scan (see Fig. 1 A)
infiltrated by the tumour and ulcerated. The patient died in cachectic state on March 2, 1989. Autopsy was not performed.
Discussion
We are well aware that our case does not provide the actual proof that the neoplastic lesions in the femur and in the abdomen were secondaries from the pineal region germinoma. Neither can we prove that the bone and the abdominal lesions had the same oncological nature. The crucial evidence could have been obtained by biopsy or post-mortem examination, which were not performed. On the other hand, uncertainties are found also in previous reports on this subject, to be
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Fig. 4. Graph showing the time course of alkaline phosphatase (AP) serum levels in our patient. Note the sudden elevation of serum AP which occurred following January 4, 1989
R. Pallini etal.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
81
Fig. 5. Electrophoresis of the alkaline phosphatase iso-enzymes performed on January 16, 1989. The arrows point out the deposition area of the serum sample. A) Comparison of the alkaline phosphatase zymograms on agarosc gel (a) and on lectinc-treatcd agarose gel (b). The anodic and the cathodic (osseous origin) components are separated in b. B) Zymograms of the alkaline phosphatase iso-enzymes on agarose gel after the inhibition tests. The elelctrophoretic band of the placental alkaline phosphatase is not altered by the heat inhibition test (65 ~ for 10') (a); it is markedly reduced by the Lphenylalanine inhibition test (b)
Fig. 6. Contrast enhanced CT scan performed following the completion of the radiation therapy showing absence of the local recurrence of the pineal tumour. At this time, elevated alkaline phosphatase serum levels were detected on routine controls
Fig. 7. Skeletal scintigraphy with Tc 99 M showing an hyperdense area in the distal metaphysis of the left femoral bone (arrow)
Fig. 8. Computed tomography scans of the abdomen-pelvis showing a diffuse metastatises of the peritoneum (A) around the tip of the VP shunt catheter (arrow), and a large inter-vescico-rectal mass (B)
82
R. Pallini etal.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
Table 1. Summary of Reported Cases of Peritoneal Metastases from Pineal Germinomas Case no.
Age (years), sex
Operations direct
other VP shunt VP shunt VP shunt VP shunt VP shunt VP shunt VP shunt stereo biopsy
l
13, F
0
2
16, M
0
3
0
4
15, M
0
5
27, M
0
6
16, M
1
7
15, M
1
boy who developed multiple lung and bone metastases from a presumed primary pineal germinoma 1 year and 3 months after the initial diagnosis. Thus far, including our patient, the metastases to the bone from a pineal germinoma have occurred in three reported cases only2, 5. It is worth noting that in all of these patients the femur was involved. Metastatic bone involvement has also been reported in a case of suprasellar germin o m a occurring 2.5 years after surgical resection and radiation therapy 6. Other authors 2'21'3~ have detailed the features of repetitive bone lesions as direct extension of spinal metastases from pineal germinomas. In none of all the above mentioned cases, was the systemic metastasis associated with tumoural spread into the peritoneum along the the CSF shunt catheter. Including our personal case, we reviewed 7 cases of abdominal diffusion along the CSF shunt catheter from pineal germinomas (Table 1). Based on available data, the patients' mean age at the onset of the metastatic tumour was 17 years, and the peak incidence was in the second decade of life. The incidence was higher in males than in females (male:female ratio 5:1). The latency period between the initial diagnosis and the appearance of the peritoneal metastases ranged between 5 months and 3 years. Five patients had been treated with chemotherapy. In one case 9, a single peritoneal metastasis was successfully treated by radiotherapy alone. Abdominal metastases via the VP shunt have also been reported in cases of multiple midline germ-cell tumour 2~ and basal ganglia germinoma 11.
Radiotherapy chemotherapy
Latent period
Year, re~ no.
+ + + + + + + + +
I0 months
1979, 35
30 months
1979, 16
1 year
1979, 25
18 months
1980, 30
3 years
1981, 9
10 months
1985, 18
5 months
1990
+ + +
An interesting aspect of the problem of the extraaxial localization of pineal germinoma is that of their time of occurrence. In fact, the time interval between the initial clinical signs of the primary germinoma and the detection of its secondary localization is quite variable. As far as the haematogenous metastases to the bone are concerned, it ranges from the 5 months of our case to the 1.5 years of the case of Borden etal.2; as for the spread along the CSF shunting device, it ranges from 5 months to 3 years (see Table 1). Such a remarkable variability is likely to be related to several factors. Part of the explanation might be found in the biological characters of the primitive germinoma, others in the applied surgical (biopsy, removal, CSF shunt) and radiotherapeutic procedures, and others in the immunological defences of the patient. In conclusion, and in spite of the above mentioned limitations, our case seems worth to be signaled because: 1) it brings further support to the possiblity that extracranial secondary localizations from germinoma tumours can occur both through the blood stream and the CSF shunt device; 2) it shows for the first time that the two modalities of secondary localization from pineal germinoma can occur in the same patient and at the same time or nearly so; 3) it provides further evidence of the value of PLAP as a serum marker of germinoma tumours and of its practical diagnostic reliability.
R. Pallini et al.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
Acknowledgement This work was partially supported by the Ministry of Public Education.
References 1. Bamberg M, Metz K, Alberti W, Heckemann R, Schulz U (1984) Endodermal sinus tumor of the pineal region. Metastases through a ventriculoperitoneal shunt. Cancer 54:903-906 2. Borden S, Weber AL, Tock R, Wang CC (1973) Pineal germinoma. Long-term survival despite hematogenous metastases. Am J Dis Child 126:214-216 3. Choux M, Lena G (1982) Societe de Neurochirurgie de Langue Francaise. XXXII Congres Annuel. Strasbourg 1982. Le medulloblastome. Neurochirurgie [Suppl] 28 4. Fishman WH, Inglis NI, Stolbach LL, Krant MJ (1968) A serum alkaline phosphatase isoenzyme of human neoplastic cell origin. Cancer Res 28:150-154 5. Galassi E, Tognetti F, Frank F, Gaist G (1984) Extraneural metastases from primary pineal tumours. Surg Neurol 21: 497-504 6. Gay JC, Janco RL, Lukens J (1985) Systemic metastases in primary intracranial germinoma. Case report and literature review. Cancer 55:2688-2690 7. Gerhardt W, Lykkegaard Nielsen M, Vagn Niclsen O, Olsen J, Sfafland BE (1974) Routine measurements of liver and bone alkaline phosphatase in human serum. Different inhibition by L-phcnylalanine and carbamide (urea) on the LKB 8600 reaction rate analyzers. Clin Chim Acta 53:281-290 8. Glasauer FE, Yuan RHP (1963) Intracranial tumors with extracranial metastases. Case report and review of the literature. J Neurosurg 20:474-493 9. Haimovic IC, Sharer L, Hyman RA, Bereford HR (1981) Metastasis of intracranial germinoma through a ventriculoperitoheal shunt. Cancer 48:1033-1036 10. Hoffman HJ, Hendrick EB, Humphreys RP (1976) Metastasis via ventriculoperitoneal shunt in patients with medulloblastoma. J Neurosurg 44:562-566 11. Kun E, Tang I, Sty R, Camitta M (I981) Primary cerebral germinoma and ventriculoperitoneal shunt metastasis. Cancer 48:213-216 12. Lange PH, Millan JL, Stigbrand T, Vessella RL, Ruoslahti E, Fishman WH (1982) Placental alkaline phosphatase as a tumor marker for seminoma. Cancer Res 42:3244-3247 13. Lesoin F, Cama A, Dhellemme P, Nuyts JP, Andreussi L, Jomin M, Vallee L (1987) Extraneural metastasis of a pineal tumor. Report of 3 cases and review of the literature. Eur Neurol 27: 55-61 14. Moss WD (1982) Alkaline phosphatase isoenzymes. Clin Chem 28:2007-2016 15. Nathanson L, Fishman WH (1971) New observations on the Regan isoenzyme of alkaline phosphatase in cancer patients. Cancer 27:1388-1397 16. Neuwelt EA, Glasberg M, Frenkel E, Clark K (1979) Malignant pineal region tumors. A clinico-pathological study. J Neurosurg 51:597-607 17. Pasquier B, Pasquier D, N'Goler A, Panh MH, Coudere P (1980) Extraneural metastases of astrocytoma and glioblastoma. Cancer 45:112-125
83
18. Pelissou I, Rayon R, Moreau JJ, Mokhtari F, Vire O (1985) Metastases multiple au cours de l'evolution d'un germinome pineal. Neurochirurgie 31:537-540 19. Pfletschinger J, Olive D, Czorny A, Marchal AL, Hoeffel JC, Schmitt M, Brasse F (1986) Metastases peritoneales d'un pinealblastome chez une patiente porteuse d'une derivation ventriculo-peritoneale. Pediatrie 41, 3:231-236 20. Rich TA, Cassady JR, Strand RD, Winston RK (1985) Radiation therapy for pineal and suprasellar germ cell tumors. Cancer 55:932-940 21. Rubery E, Wheeler T (1980) Metastases outside the central nervous system from a presumed pineal germinoma. J Neurosurg 53:562-565 22. Rubinstein LJ (1967) Development of cxtracranial metastases from a malignant astrocytoma in the absence of a previous craniotomy. Case report. J Neurosurg 26:542-547 23. Russel DS, Rubinstein LJ (1977) Pathology of tumors of the nervous system, ed. 4. Edward Arnold, London, pp 283 298 24. Sakata K, Yamada H, Sakai N, Hosono Y, Kawasako T, Sasaoka I (1975) Extraneural metastasis of pineal tumor. Surg Neurol 3:49-54 25. Salazar OM, Castro-Vita H, Bakos RS, Feldstein ML, Keller B, Rubin P (1979) Radiation therapy for tumors of the pineal region. Int J Radiat Oncol Biol Phys 5:491-499 26. Shinoda J, Miwa Y, Sakai N, Yamada H, Shima H, Kato K, Tokahashi M, Shimokawa K (1985) Immunohistochemical study of placental alkaline phosphatase in primary intracranial germ-cell tumors. J Neurosurg 63:733-739 27. Shinoda J, Yamada H, Sakai N, Ando T, Hirata T, Miwa Y (1988) Placental alkaline phosphatase as a tumor marker for primary intracranial germinoma. J Neurosurg 68:710-720 28. Takeda F, Handa I, Aiba T, Kawafuchi J, Fukai K (1971) Malignant glioma with extraneural metastases. Report of an autopsy case. Adv Neurol Sci (Tokyo) 15:720-730 29. Takei Y, Mirra SS, Miles ML (1977) Primary intracranial yolk sac tumor: report of three cases and an ultrastructural study. J Neuropathol Exp Neurol 36:633 (Abstract) 30. Triolo PJ, Schulz EE (1980) Metastatic germinoma (pinealoma) via a ventriculoperitoneal shunt. AJR 135:854-855 31. Wakamatsu T, Matsuo T, Kawano S, Teramoto S, Matsumura H (1971) Glioblastoma with extracranial metastasis through ventriculopleural shunt. Case report. J Neurosurg 34:697-701 32. Wakamatsu T, Matsuo T, Kawano S, Teramoto S, Matsumura H (1972) Extracranial metastasis of intracranial tumor. Review of literatures and report of a case. Acta Path Jap 22:155-169 33. Weiss L (1955) A metastasizing ependymoma of the cauda equina. Cancer 8:161-171 34. Wilson ER, Takei Y, Bikoff WT, O'Brien MS, Tindall GT, Boehm WM (1979) Abdominal metastases of primary intracranial yolk sac tumors through ventriculoperitoneal shunt: report of three cases. Neurosurgery 5:356-364 35, Wood BP, Haller JO, Berdow WE, Lin SR (1979) Shunt metastases of pineal tumors presenting as pelvic mass. Pediatr Radiol 8:108 109
Correspondence and Reprints: Pallini Roberto, M.D., and Prof. Massimo Scerrati (Reprints), Istituto di Neurochirurgia, Universitfi Cattolica del Sacro Cuore, Largo A. Gemelli 8, 1-00168 Roma, Italy.
Acta Neurochir (Wien) (1991) 109:78-83
9 Springer-Verlag 1991 Printed in Austria
Bone Metastasis Associated with Shunt-Related Peritoneal Deposits From a Pineal Germinoma Case Report and Review of the Literature R. Pallini, V. Bozzini, M. Seerrati, C. Zuppi 1, B. Zappacosta 1, and G. F. Rossi Institutes of Neurosurgery and 1Human Physiology, Catholic University School of Medicine, Rome, Italy
Summary The case of a 15-year-old boy with a pineal germinoma is reported, The patient first underwent a ventriculoperitoneaI (VP) shunt followed by a stereotactic biopsy, then, because of the rapidly deteriorating neurological status, an emergency craniotomy with subtotal removal of the tumour was performed. Two months after surgery, a left femoral metastasis and extensive peritoneal lesions became evident; they were regarded as due to haematogenous and VP shunt spread of the germinoma. At that time, extremely high serum levels of placental alkaline phosphatase were detected. The patient died 6 months after the inital diagnosis. The occurrence of extraneural metastases as well as of shunt related peritoneal deposits from primary intracranial germinoma is discussed. As far as we know this is the first reported case of a combination of haematogenous as well as VP shunt spread of a pineal germinoma.
Keywords: Pineal germinoma; extracranial metastasis; haematogenous spread; shunt related spread.
Introduction E x t r a n e u r a l metastases from p r i m a r y b r a i n t u m o u r s are rare 24'28' 32. Several p o t e n t i a l routes of metastatic t u m o u r spread outside the central n e r v o u s system have been suggested: diffusion a l o n g the n a t u r a l cerebrospina ! fluid (CSF) p a t h w a y s 3' 8, vascular e m b o l i z a t i o n (arterial and venous)5,13, 22, and lymphatic seedingS, 8,17,23. Pineal g e r m i n o m a s have also been described to metastatize extracranially via the b l o o d stream owing to their p r o p e n s i t y to i n v a d e the cerebral veins2,5, 23. Finally, there are several reports of secondary localization of b r a i n t u m o u r s to the peritoneal cavity as a c o m p l i c a t i o n of C S F diversion procedures in m e d u l l o b l a s t o m a 10, g l i o b l a s t o m a 31, a n d above all in pineal region t u m o u r s 1'9' 13,16,18-19,25,29-30, 34-35. T o prevent this serious complication, the use of Millipore filters 1~ a n d the r e m o v a l of the s h u n t once the C S F
p a t h w a y p a t e n c y has been restored following surgical d e c o m p r e s s i o n or r a d i a t i o n therapy 16 have been proposed. Some factors seem to f a v o u r the metastatic diss e m i n a t i o n of b r a i n t u m o u r s : 1) direct surgical attack, 2) the lenght of the survival period, a n d 3) i m m u n o suppresive therapies, such as r a d i o t h e r a p y a n d prolonged corticosteroid treatments. We report a case of pineal g e r m i n o m a who developed metastatic b o n e a n d peritoneal lesions.
Case Report Antimo D, M., a boy aged 15, was admitted to our Department
in September 1988. One month previously, the patient had been hospitalized at another neurosurgical institution because of headache, lethargy, limitation or upward gaze, and diabetes insipidus. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a large pineal region tumour causing obstructive hydrocephalus (Figs. 1A and B). A ventriculo-peritoneal shunt was inserted. On admission at our Department, neurological examination revealed bilaterally reduced visual acuity, bilateral papilloedema,spontaneous horizontal nystagmus, Parinaud's syndrome, left hypo-acusia, spastic tetraparesis, bilateral cerebellar syndrome, and neck stiffness. A post-shunting CT scan showed normally sized ventricles and confirmed the contrast enhancing mass lesion in the pineal region. A stereotactic biopsy was performed on September 27, 1988. The histological diagnosis was germinoma (Fig. 2). Five days later, the patient became progressivelydrowsy. On the CT scan, intracranial complications related to the biopsy procedure as well as shunt malfunctioning were excluded, however, a marked increase of the tumour size was apparent (Fig. 3). In the following few days, the clinical condition deteriorated; the patient became comatose presenting disturbances of cardiac and respiratory rythms~ hyperthermia, and arterial hypertension. Due to the dramatic and progressive worsening, operative decompression was performed on October 6, 1988. The tumour was exposed through a right paramedian suboccipital supra-transtentorial approach. It appeared as a pinkish soft-
R. Pallini etal.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
79
Uig. 1, Preoperative contrast enhanced CT scan (A) and T2 weigthed MRI (B) showing the mass lesion in the pineal region with obstructive hydrocephalus
Fig. 2. Microphotograph of the biopsy specimen showing the characteristic two-cell pattern of the germinoma with large clear cells and small lymphoid elements (HE, 125 x )
elastic mass in the pineal region involving the eisternal spaces along the tentorial edge and extending ventrally into the third ventricle. Under microsurgical control, the tumour was subtotally removed. The diagnosis of germinoma was confirmed on the surgical specimens. The post-operative course was satisfactory with partial recovery of the neurological deficits, however, the patient required continued intensive management due to persistent diabetes insipidus with electrolyte imbalance and impaired temperature regulation. Twenty days after surgery, whole brain (4200 Gy) irradiation was started. Radiation therapy was completed on December 15, 1988. From the beginning of January, elevated serum levels of alkaline phosphatase were noted on routine examinations (Fig. 4). The alkaline phosphatase isoenzymes were repeatedly assessed by using an affinity electrophoretic method (lectin containing agarose gel) 4, z~-ls The placental alkaline phosphatase (PLAP) isoenzyme, which was confirmed by the heat test and inhibition by phenylalanine7-2s, ranged
from 40 to 65% of the total activity (Figs. 5). At that time, the cranial CT scan did not disclose local recurrence of the pineal turnout (Fig. 6). The skeletal scintigraphy with Tc 99 m revealed an hyperdense area in the distal methaphysis of the left femoral bone (Fig. 7). This area appeared as an osteolytic lesion on plain radiograms. A few days later, the patient complained of tenderness at the left hip, abdominal pain, and constipation. His general condition deteriorated very rapidly. A solid mass became palpable in the left inferior abdominal quadrant. Echography and CT scan demonstrated a diffuse nodular involvement of the peritoneum and a large pelvic inter-vescico-rectal solid mass (Fig., 8). The testes were normal to the physical examination and to the echo scan. No other evidence of neoplastic localization could be detected by clinical and instrumental examinations (CT and echo scans). The opportunity to start chemotherapy was not taken owing to the severely affected general condition. Finally, the skin in the left inferior abdominal region was
80
R. Pallini et al.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
reviewed below. So far the Weiss's criteria to confirm the existance of extra-axial metastases from primary brain tumour 33 are not completely satisfied. Nevertheless, we believe that in our case the secondary origin from the intracranial germinoma of both the bone and the abdominal lesions is strongly favoured by some of our findings, a) PLAP, which is normally present on the plasma membrane of syncytiotrophoblasts 14, has been identified as a specific tumour marker for intracranial germinoma26 and for testicular seminoma 12. Its serum level has been shown to reflect variations of tumour size in three germinoma cases 27. In our patient, testicular tumoural lesions were carefully looked for, with negative results. Furthermore, the behaviour of the PLAP serum level closely matched the clinical and instrumental signs of development of the bone and peritoneal tumoural invasion, b) No clinical and instrumental evidence (CT and echo scans, scintigraphy) of primitive tumours in other parts of the body, to be regarded as the possible origin of spread to the bone and to the peritoneum, were found. The haematogenous spread from pineal germinomas is exceedingly rare. Borden e t a l . 2 reviewed only two published cases of pulmonary metastases after open biopsy of a pineal germinoma. Their additonal case occurred in a young boy who presented a metastasis in the right femur 1 year and 6 months after radiation therapy of a presumed pineal region tumour. More recently, Galassi e t a l . 5 described a 10-year-old
Fig. 3. Post shunting CT scan performed following the stereotactic biopsy at the time of the clinical worsening. Note the marked increase of the tumour size compared to the previous CT scan (see Fig. 1 A)
infiltrated by the tumour and ulcerated. The patient died in cachectic state on March 2, 1989. Autopsy was not performed.
Discussion
We are well aware that our case does not provide the actual proof that the neoplastic lesions in the femur and in the abdomen were secondaries from the pineal region germinoma. Neither can we prove that the bone and the abdominal lesions had the same oncological nature. The crucial evidence could have been obtained by biopsy or post-mortem examination, which were not performed. On the other hand, uncertainties are found also in previous reports on this subject, to be
Ul& 3000
2000
1000
0
I
-L~I
I
101519 I
I
5 18'30 I
OCTOBER
I
I
I
1
3
5
I
I
I
I
I
8 11202831
I NOV1E~4BER
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4. 1 0 1 3 1 6 2 8
I DECEMBER
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6 1114..172328
I JANUARY
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Fig. 4. Graph showing the time course of alkaline phosphatase (AP) serum levels in our patient. Note the sudden elevation of serum AP which occurred following January 4, 1989
R. Pallini etal.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
81
Fig. 5. Electrophoresis of the alkaline phosphatase iso-enzymes performed on January 16, 1989. The arrows point out the deposition area of the serum sample. A) Comparison of the alkaline phosphatase zymograms on agarosc gel (a) and on lectinc-treatcd agarose gel (b). The anodic and the cathodic (osseous origin) components are separated in b. B) Zymograms of the alkaline phosphatase iso-enzymes on agarose gel after the inhibition tests. The elelctrophoretic band of the placental alkaline phosphatase is not altered by the heat inhibition test (65 ~ for 10') (a); it is markedly reduced by the Lphenylalanine inhibition test (b)
Fig. 6. Contrast enhanced CT scan performed following the completion of the radiation therapy showing absence of the local recurrence of the pineal tumour. At this time, elevated alkaline phosphatase serum levels were detected on routine controls
Fig. 7. Skeletal scintigraphy with Tc 99 M showing an hyperdense area in the distal metaphysis of the left femoral bone (arrow)
Fig. 8. Computed tomography scans of the abdomen-pelvis showing a diffuse metastatises of the peritoneum (A) around the tip of the VP shunt catheter (arrow), and a large inter-vescico-rectal mass (B)
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R. Pallini etal.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
Table 1. Summary of Reported Cases of Peritoneal Metastases from Pineal Germinomas Case no.
Age (years), sex
Operations direct
other VP shunt VP shunt VP shunt VP shunt VP shunt VP shunt VP shunt stereo biopsy
l
13, F
0
2
16, M
0
3
0
4
15, M
0
5
27, M
0
6
16, M
1
7
15, M
1
boy who developed multiple lung and bone metastases from a presumed primary pineal germinoma 1 year and 3 months after the initial diagnosis. Thus far, including our patient, the metastases to the bone from a pineal germinoma have occurred in three reported cases only2, 5. It is worth noting that in all of these patients the femur was involved. Metastatic bone involvement has also been reported in a case of suprasellar germin o m a occurring 2.5 years after surgical resection and radiation therapy 6. Other authors 2'21'3~ have detailed the features of repetitive bone lesions as direct extension of spinal metastases from pineal germinomas. In none of all the above mentioned cases, was the systemic metastasis associated with tumoural spread into the peritoneum along the the CSF shunt catheter. Including our personal case, we reviewed 7 cases of abdominal diffusion along the CSF shunt catheter from pineal germinomas (Table 1). Based on available data, the patients' mean age at the onset of the metastatic tumour was 17 years, and the peak incidence was in the second decade of life. The incidence was higher in males than in females (male:female ratio 5:1). The latency period between the initial diagnosis and the appearance of the peritoneal metastases ranged between 5 months and 3 years. Five patients had been treated with chemotherapy. In one case 9, a single peritoneal metastasis was successfully treated by radiotherapy alone. Abdominal metastases via the VP shunt have also been reported in cases of multiple midline germ-cell tumour 2~ and basal ganglia germinoma 11.
Radiotherapy chemotherapy
Latent period
Year, re~ no.
+ + + + + + + + +
I0 months
1979, 35
30 months
1979, 16
1 year
1979, 25
18 months
1980, 30
3 years
1981, 9
10 months
1985, 18
5 months
1990
+ + +
An interesting aspect of the problem of the extraaxial localization of pineal germinoma is that of their time of occurrence. In fact, the time interval between the initial clinical signs of the primary germinoma and the detection of its secondary localization is quite variable. As far as the haematogenous metastases to the bone are concerned, it ranges from the 5 months of our case to the 1.5 years of the case of Borden etal.2; as for the spread along the CSF shunting device, it ranges from 5 months to 3 years (see Table 1). Such a remarkable variability is likely to be related to several factors. Part of the explanation might be found in the biological characters of the primitive germinoma, others in the applied surgical (biopsy, removal, CSF shunt) and radiotherapeutic procedures, and others in the immunological defences of the patient. In conclusion, and in spite of the above mentioned limitations, our case seems worth to be signaled because: 1) it brings further support to the possiblity that extracranial secondary localizations from germinoma tumours can occur both through the blood stream and the CSF shunt device; 2) it shows for the first time that the two modalities of secondary localization from pineal germinoma can occur in the same patient and at the same time or nearly so; 3) it provides further evidence of the value of PLAP as a serum marker of germinoma tumours and of its practical diagnostic reliability.
R. Pallini et al.: Bone Metastasis Associated with Shunt-Related Peritoneal Deposits
Acknowledgement This work was partially supported by the Ministry of Public Education.
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Correspondence and Reprints: Pallini Roberto, M.D., and Prof. Massimo Scerrati (Reprints), Istituto di Neurochirurgia, Universitfi Cattolica del Sacro Cuore, Largo A. Gemelli 8, 1-00168 Roma, Italy.
