ischaemia, infections, haematomas and vasculitides. Less common associations include vertebral artery dissection,4 cervical disc her- niation,1 rapid acceleration and deceleration following roller coast- er rides5 and chiropractic manipulation.6
A sympathetic lesion, whether in the brain, spinal cord or sym- pathetic chain of the neck, will produce a Horner’s syndrome con- sisting of ipsilateral miosis (unopposed parasympathetic action on the sphincter pupillae), ptosis (loss of the visceral muscle com- ponent of levator palpebrae) and anhydrosis (only when the lesion is below the superior sympathetic ganglion). Common causes of Horner’s syndrome include carcinoma of the lung apex, neck malig- nancy or trauma, carotid arterial dissection or aneurysm, brainstem lesions (especially the lateral medullary syndrome) and iatrogenic.7 A brief search of the literature revealed only three prior cases of traumatic BSS associated with Horner’s syndrome.8-10
A brief review of power drill injuries revealed five documented cases of power drill trauma, including four suicide attempts11 and one case of an accidental death following a fall from a ladder with a power drill.12
References
1. Rumana CS, Baskin DS. Brown-Sequard syndrome produced by cervical disc herniation: case report and literature review. Surg Neurol:359-61.
2. Roth EJ, Park T, Pang T, et al. Traumatic cervical Brown-Sequard and Brown- Sequard-plus syndromes: the spectrum of presentations and outcomes. Paraplegia 1991;29:582-9.
3. Lipschitz R, Block J. Stab wounds of the spinal cord. Lancet 1962;2:169-72.
4. Muscat P, Lidov M, Nahar T, et al. Vertebral artery dissection in Turner’s syndrome: diagnosis by magnetic resonance imaging. J Neuroimaging 2001;11:50-4.
5. Bateman DE, Pople I. Brown-Sequard at a theme park. Lancet 1998;352:1902.
6. Lipper MH, Goldstein JH, Do HM. Brown-Sequard syndrome of the cervical cord after chiropractic manipulation. AJNR Am J Neuroradiol 1998;19:1349-52.
7. Talley NJ, O’Connor S. Examination Medicine. 4th ed. MacLennan & Petty; 2001. p. 260.
8. Edwards A, Andrews R. A case of Brown-Sequard syndrome with associated Horner’s syndrome after blunt injury to the cervical spine. Emerg Med J 2001;18:512-3.
9. Garcia-Manzanares MD, Belda-Sanchis JI, Giner-Pascual M, et al. Brown- Sequard syndrome with Horner’s syndrome after a penetrating trauma at the cervicomedullary junction. Spinal Cord 2000;38:705-7.
10. Shen CC, Wang YC, Yang DY, et al. Brown-Sequard syndrome associated with Horner’s syndrome in cervical epidural haematoma. Spine 1995;20:244-7.
11. Schmeling A, Lignitz E, Strauch H. Case reports of suicide with an electric drill. Arch Kriminol 2003;211:65-72.
12. Constantinides F. A fatal case of accidental cerebral injury due to power drill. Am J Forensic Med Pathol 1982;3:241-3.
doi:10.1016/j.jocn.2008.10.013
A rare bone-leptomeningeal metastasis from an adrenal cortical carcinoma
Gennaro Capone ª, Giuseppe Maria Della Pepa ª,*, Giovanni Sabatinoª, Elena Bartoccioni b, Alessio Albanese ª, Stefano Manninoª, Giulio Maira ª
a Institute of Neurosurgery, Catholic University, Rome, Italy
b Institute of Plastic and Reconstructive Surgery, Catholic University, Rome, Italy
ARTICLE INFO
Article history: Received 20 August 2008 Accepted 4 October 2008
Keywords: Adrenal cortical carcinoma Metastasis Skull neoplasm
ABSTRACT
We report a rare bone-leptomeningeal metastasis from an adrenal cortical carcinoma (ACC). ACC is a rare malignancy and represents one of the most unusual sources of intracranial metastases (0-0.2%); the localization to the skull bone and meninges is uncommon. A 45-year-old man underwent surgery for a non-functioning ACC; 4 months later he developed a soft left frontal mass. The CT scans and MRI showed a large tumor with bone and leptomeningeal involvement. Despite chemotherapy, the lesion increased in volume, which led to local pain and right hemiparesis. Thus, the patient underwent excision of the mass; histopathological diagnosis confirmed that it was an ACC metastasis. The patient underwent standard radiation therapy after surgery. At post-operative follow-up, the patient was in a good neurological condition with no radiological evidence of a cranial recurrence; however, there was a voluminous abdominal regrowth of the primary tumor. To our knowledge, this is the second case of bone and leptomeningeal metastasis arising from an ACC. This patient report confirms the effectiveness of aggres- sive surgery for management of large intracranial metastases, particularly those that arise from primary tumors that are resistant to radiotherapy and chemotherapy. In our opinion, surgery represents the most appropriate treatment for voluminous intracranial metastasis - even when there are no neurological signs.
@ 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Metastases are the most common intracranial neoplasm in adults and may involve the brain, the dura, the leptomeninges, and the skull.1,2 Metastases represent about 10% of intracranial tu- mors.2 The primary cancers that result in intracranial metastases most frequently are those of the lung, breast, gastrointestinal tract,
genitourinary tract, and malignant melanoma.1 Metastases from breast and lung carcinoma cause intracerebral metastases more fre- quently than skull or cranial vault metastases, which are uncom- mon. The latter are generally lytic, and are associated with the destruction of both the inner and the outer table of the skull. Ther- apeutic approaches to management of brain metastases include sur- gery, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) and chemotherapy. Many patients are treated using a combi- nation of these techniques; treatment decisions must take into account clinical prognostic factors in order to maximize survival and neurologic function while avoiding unnecessary treatments.
* Corresponding author. Present address: c/o Carleo, via Urbino, 51, 00182, Rome, Italy. Tel .: +39 3394559769; fax: +39 6233 241 819.
E-mail address: gdellapepa@hotmail.com (G.M.D. Pepa).
Adrenal cortical carcinoma (ACC) is a rare malignancy in all age groups, and accounts for 0.02% of all cancers reported annually.3 A bimodal incidence rate has been observed, with a first peak in chil- dren younger than 5 years of age, and a second peak in mid-adult life. Given the generally advanced stage at diagnosis, the overall 5 year survival rate remains poor, and varies between 20% and 45%. These malignancies can either be hormonally active and present as an endocrine syndrome, or can be hormonally inactive. Most of those who have ACC are diagnosed when the neoplastic process has spread from the adrenal glands (stage III or IV).
The most common metastatic locations are the lung, liver, ipsi- lateral and contralateral kidney, peritoneum, lymph nodes and bone, while metastases to the pancreas, small intestine and brain are most uncommon.4 Multiorgan metastases are common. How- ever, ACC is one of the most unusual sources of intracranial metas- tases (0-0.2%), and localization to the skull bone and meninges is exceedingly rare.3,4
Few of the available studies focus on the neurological manifes- tations associated with ACC. To our knowledge, there are nine re- ports of intracranial metastases arising from ACC (Table 1).5-13 We report a patient, the second to our knowledge, who had skull and leptomeningeal metastasis from ACC.
2. Case report
A 45-year-old man underwent right adrenalectomy and resection of the VIIth hepatic segment for a non-functioning, poorly differentiated ACC with associated hepatic metastases. After
surgery, the patient was treated with standard polychemotherapy and mitotane.
Four months after the adrenalectomy, the patient noted a left frontal cutaneous lump. A CT scan revealed a solid, hyperdense left frontal lesion with extra- and intracranial growth, destruction of the inner and the outer table of the skull, epidural expansion, mass effect and little vasogenic edema. An MRI study confirmed the voluminous mass (8.3 cm × 5.7 cm × 6.2 cm) with intense but het- erogeneous contrast enhancement, and thickened and enhanced dura with superior sagittal sinus compression and infiltration .
Total body scintigraphy showed radionuclide capitation at the level of the cranial erosion. A further cycle of chemotherapy was administered without clinical benefit; 2 months later, the patient presented with slowly progressive neurological deficit (right hem- iparesis, worse in the lower limb than the upper limb). An MRI study demonstrated enlargement of the mass associated with intradural extension and compression of the underlying brain parenchyma (Fig. 1).
A bifrontal cutaneous flap was performed, which revealed the lesion to be a polylobulated, purple, well-circumscribed mass. The lesion was excised completely in three steps; with the assis- tance of plastic surgeons, the extracranial component was easily separated from the subcutaneous tissue. A wide craniectomy allowed the removal of the eroded and infiltrated bone, and both the leptomeningeal and the intradural components were removed in bulk after surgical closure of the anterior third of the superior sagittal sinus. The histopathological findings were typical for a poorly differentiated ACC (Supplementary Fig. 1).
| Author | Age (years) | Intracranial location | Sites of other metastases | Treatment | Post-treatment survival (months) |
|---|---|---|---|---|---|
| Bartley et al. (2001)9 | 24 | Orbit/brain | Lung and vertebrae | Surgery | 15 |
| Hertel et al. (2003)8 | 14 | Meninges | Lung and femoral | No treatment | 12 |
| Kubota et al. (1997)5 | 47 | Brain | Lung and liver | Surgery/radiation | 3 |
| Lefvre et al. (1984)12 | 4 | Brain | – | Surgery | 3 |
| Piniella and Siatkowski (2000)6 | 9 | Brain | – | Surgery | (>4)* |
| Romaguera et al. (2001)10 | 9 | Brain | Lung | Surgery | 24 |
| Saracco et al. (1988)11 | Congenital | Brain | – | No treatment (spontaneous resolution after resection of the primary tumour) | (>12)* |
| Seabold et al. (1977)13 | 35 | Brain | Liver and lung | No treatment | Not provided |
| Wagner et al. (2005)7 | 10 | Brain | Lung and liver | Surgery | 9 |
- = No other metastases.
* Findings were published prior to patient death, so these data may not be accurate.
A
B
:500
B9/1 15.ikiz
:20:26
5.6khz
the/1.0sp
12:99
V
0mm
0cm
+0.00cm
-0.99cm
ND
5
0
C
₹
I
20 kV 0 mA
3.0 sec
-CAL
The post-operative period was uneventful, with slight but pro- gressive improvement of the right-sided hemiparesis. The patient received adjuvant WBRT (3000 cGy in 10 fractions). The follow- up at 8 months confirmed the improving neurological deficit and imaging did not show any radiological signs of cranial tumor recur- rence (Fig. 2). However, an abdominal MRI revealed a voluminous regrowth of the adrenal mass. The adrenal recurrence was treated again with surgical resection and mitotane. The patient died from hepatic and pulmonary disease recurrence 30 months after the ini- tial diagnosis of the primary tumor (24 months after the neurosur- gical excision of the bone-leptomeningeal lesion).
3. Discussion
Patients who have intracranial metastases have a poor progno- sis. Without any intervention, the prognosis is a median survival time of 1 month.14 No significant advances in the treatment of ACC have been developed. For patients who have favorable prognostic factors and a limited number of brain metastases, local therapies such as surgery and SRS improve control rates and may extend survival compared to WBRT alone. Surgery remains the mainstay for primary and recurrent disease, including selected patients with isolated liver metastases.15 Recent, single metastasis, complete surgical resection, and adjuvant radio/chemotherapy are generally associated with prolonged survival.1
ACC is a rare malignant tumor; the diagnosis is usually made when the tumor has already led to distant metastases and/or in- vaded the adjacent tissues (30-50% of instances). Despite radical surgery and adjuvant radiotherapy or chemotherapy, the prognosis is still poor, with a 5 year survival of 30% to 40%, depending on the disease stage at diagnosis. One-year survival in a patient with a distant metastasis is 9%, with a median survival time of 4 months. 16,17
Intracranial metastasis associated with ACC is rare; only 9 pa- tients who have this combination have been described.5-13 There- fore, little is known regarding the biological behaviour of intracranial metastases from ACC and the best possible clinical ap- proach to management of these lesions.
The results of our literature review suggest that patients who develop brain metastases with ACCs first develop antecedent lung metastases, implying that a secondary metastasis to the brain, or “metastasis from a metastasis”, is responsible for the intracranial lesion. We identified six out of nine patients from the literature who had had prior metastatic recurrence in the lungs. The litera- ture is unclear regarding the typical time frame between the devel- opment of the lung metastasis and the development of the brain metastases from ACC. A 47-year-old patient was reported to pres- ent with both brain and lung metastases 9 months after adrenalec- tomy.5 In contrast, Romaguera et al. reported a brain metastasis in a 9-year-old girl who had no symptoms for 5 years.1º Saracco et al. reported a patient with simultaneous congenital brain and cutane- ous metastases from ACC.11 Wagner et al. reported on a 10-year- old boy in whom the interval between development of lung and brain metastases was just over 2 years.7 These examples suggest, however, that the timeframe for developing brain metastases after lung lesions is unpredictable; hence, clinicians need to be vigilant for this uncommon occurrence.
For our patient, lung metastases were detected shortly after the discovery of the intracranial recurrence. However, considering the literature, a undetected lung recurrence before the onset of intra- cranial disease could be assumed. Surgery was essential in our patient because of the rapidly enlarging tumor volume, the neuro- logical deficits and the risk of skin ulceration. The superficial loca- tion and collaboration with a plastic surgeon allowed a straight forward removal of the lesion without complication, and with post-operative neurological recovery. Standard radiation therapy was also administered, as it improves overall survival when there is a solitary intracranial metastasis.14 One literature review reports improved survival in patients with ACC after resection of the pri- mary lesion, recurrence or distant metastasis.3 In our experience, considering the poor response to chemotherapy, we recommend surgery in combination with standard radiation therapy as the pri- mary treatment for ACC cranial solitary metastasis, particularly when the patient is young and of good general health.
In our opinion, surgery represents the most appropriate treat- ment for voluminous intracranial metastasis. Both our patient and the literature review (Table 1) highlight that surgical excision of the intracranial metastasis of ACC is associated with both satis- factory prognosis and survival comparable to other intracranial metastases after surgical excision (median survival of 4-5 months).2
4. Conclusions
Although ACC is a rare neoplasm, it must be considered in the differential diagnosis of intracranial lesions in patients who have a history of this tumor. We suggest close observation for a pro- longed period, with a regular metastatic work-up that should in- clude brain imaging for those patients who develop neurological symptoms, to exclude metastatic disease.
There is no clear data on the clinical behaviour of these lesions; the literature suggests that the time frame for developing brain metastases is unpredictable. Therefore, we advise vigilance when observing patients with ACC, especially those who have metastases in other sites, such as the lungs. Any alterations in the neurological status should prompt consideration of intracranial metastatic disease.
Considering the poor response to chemotherapy, we recom- mend that surgical excision associated with standard radiation therapy should be the primary treatment for a solitary ACC cranial metastasis. This is particularly recommended when the patient is young and of good general health, including those select patients with isolated liver metastases.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at doi: 10.1016/j.jocn.2008.10.013.
References
1. Hall WA, Djalilian HR, Nusbaum ES, et al. Long-term survival with metastatic cancer to the brain. Med Oncol 2000; 17:279-86.
2. Eichler AF, Plotkin SR. Brain metastases. Curr Treat Options Neurol 2008;10:308-14.
3. Roman S. Adrenocortical carcinoma. Curr Opin Oncol 2006;18:36-42.
4. Boscaro M, Fallo F, Barzon L, et al. Adrenocortical carcinoma: epidemiology and natural history. Minerva Endocrinol 1995;20:89-94.
5. Kubota Y, Iwai T, Nakatani K, et al. Central nervous system metastasis from nonfunctioning adrenocortical carcinoma: report of a case. No Shinkei Geka 1997;25:1039-42.
6. Piniella A, Siatkowski RM. Adrenal cortical carcinoma metastatic to the brain in a child. J Neuroophthalmol 2000;20:35-7.
7. Wagner AS, Fleitz JM, Kleinschmidt-Demasters BK. Pediatric adrenal cortical carcinoma: brain metastases and relationship to NF-1, case reports and review of the literature. J Neurooncol 2005;75:127-33.
8. Hertel NT, Carlsen N, Kerndrup G, et al. Late relapse of adrenocortical carcinoma in Beckwith-Wiedemann syndrome. Clinical, endocrinological and genetic aspects. Acta Paediatr 2003;92:439-43.
9. Bartley GB, Campbell RJ, Salomão DR, et al. Adrenocortical carcinoma metastatic to the orbit. Ophthal Plast Reconstr Surg 2001;17:215-20.
10. Romaguera RL, Minagar A, Bruce JH, et al. Adrenocortical carcinoma with cerebral metastasis in a child: case report and review of the literature. Clin Neurol Neurosurg 2001;103:46-50.
11. Saracco S, Abramowsky C, Taylor S, et al. Spontaneously regressing adrenocortical carcinoma in a newborn. A case report with DNA ploidy analysis. Cancer 1988;62:507-11.
12. Lefevre M, Gerard-Marchant R, Gubler JL, et al. Adrenal cortical carcinoma in children: 42 patients treated from 1958 to 1980 at Villejuif. In: Humphrey GB, Grindly GB, Dehner LP, et al., editors. Adrenal and Endocrine Tumors in Children. Adrenal Cortical Carcinoma and Multiple Endocrine Neoplasia. Boston: Martinus Nijhoff; 1984. p. 265-76.
13. Seabold JE, Haynie TP, DeAsis DN, et al. Detection of metastatic adrenal carcinoma using 1311-6-beta-iodomethyl-19-norcholesterol total body scans. J Clin Endocrinol Metab 1977;45:788-97.
14. Andrews DW. Current neurosurgical management of brain metastases. Semin Oncol 2008;35:100-7.
15. Guillamo JS, Emery E, Busson A, et al. Current management of brain metastases. Rev Neurol (Paris) 2008;164:560-8.
16. Kuruba R, Gallagher SF. Current management of adrenal tumors. Curr Opin Oncol 2008;20:34-46.
17. Jensen JC, Pass HI, Sindelar WF, et al. Recurrent or metastatic disease in select patients with adrenocortical carcinoma: aggressive resection vs chemotherapy. Arch Surg 1991;126:457-61.
doi:10.1016/j.jocn.2008.10.013