Journal of Clinical Neuroscience xxx (2016) xxx-xxx
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Journal of Clinical Neuroscience
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Journal of Clinical neuroscience
Case Report
Metastatic adrenal cortical carcinoma to T12 vertebrae
Daniel Lee a,c, Vijay Yanamadala b,c,*, Ganesh M. Shankar b,c, John H. Shin b,c
a Harvard-MIT Sciences and Technology, Harvard Medical School, Boston, MA, USA
b Department of Neurosurgery, Massachusetts General Hospital, 15 Parkman Street, WACC 021, Boston, MA 02115, USA
” Harvard Medical School, Boston, MA, USA
ARTICLE INFO
Article history: Received 7 November 2015 Accepted 13 November 2015 Available online xxxx
Keywords: Adrenal cortical carcinoma Metastasis Spinal metastasis
ABSTRACT
We report spinal metastasis of adrenal cortical carcinoma (ACC) to the T12 vertebrae with epidural exten- sion. ACC is a rare malignancy with poor prognosis and high rates of metastasis. However, spinal lesions of ACC are rare, and few have been reported in the literature. We discuss our management of this lesion and review the current understanding and treatment of ACC and spinal metastasis.
@ 2015 Elsevier Ltd. All rights reserved.
1. Introduction
Spinal metastasis of adrenal cortical carcinoma (ACC) is rare, with only a few cases having been reported previously [1-4]. In general, ACC has poor prognosis and high recurrence rates, even with aggressive resection and medical/chemotherapeutic therapy [5,6]. Here, we report a patient with spinal metastasis to the T12 vertebrae with epidural extension. Given the recurrent nature of ACC and limited adjuvant therapeutic options, aggressive surgical treatment is ideal for oligometastatic disease to the spine.
2. Patient report
A 55-year-old man with a history of ACC and papillary thyroid carcinoma presented with lower-back pain radiating to the chest and groin area. A total thyroidectomy and left-adrenal mass resec- tion had been performed 2 and 5 months prior, respectively.
Positron emission tomography (PET) and CT imaging showed avid soft tissue nodules and uptake at the right pedicle of T12. MRI confirmed PET/CT scan findings (Fig. 1). On examination, the patient stood at neutral sagittal alignment. Palpable spinal or para- spinal tenderness was absent. Lower extremity strength, gait and reflexes were normal. Neurological examination was normal.
In response to findings, stereotactic body radiation therapy was administered to the T12 lesion using one fraction at 18 Gy. Symp- toms were relieved temporarily for 2-3 months.
On 1 year follow-up, CT scan and MRI demonstrated new growth of the soft-tissue mass with cortical breakthrough and
encroachment on the epidural space at T12-L1 (Fig. 2). CT scan- guided biopsy was conducted to differentiate between radiation necrosis and tumor progression. Results were positive for malig- nant cells.
Given the biopsy findings and the worsening pain, T12 verte- brectomy with complete tumor resection was undertaken, fol- lowed by cage reconstruction and posterior segmental instrumentation T10-L2 (Fig. 3). On histopathological examina- tion, there was evidence of both radiation necrosis and tumor within the pedicle and epidural space. Pathological examination confirmed the epidural mass to be ACC. Extensive radiation- induced changes were also observed at the anterior longitudinal ligament, pleura and paraspinal tissues.
Post-operatively, the patient recovered well (Fig. 4). Adjuvant stereotactic radiosurgery at a dose of 12 Gy was administered 6 weeks post-operatively. Back, chest and groin pain were resolved on 1.5 month follow-up. Neurological examination and motor function were normal. Gait was normal and ambulation was at a pre-operative status.
3. Incidence and background of ACC and spinal metastasis
ACC is a rare malignancy with a poor prognosis. Incidence is 0.7-2.0 cases/million habitants/year and is bimodally distributed at 0-10 years and 40-50 years of age [7,8]. Five year survival rates of stages I, II, III and IV are 84%, 63%, 51% and 15%, respectively, with an overall rate of <35%, as per the German ACC registry (n = 215) [5,9].
The 5 year recurrence rate of ACC is greater than 50%, with some estimates being as high as 85% [10,11]. Recurrent lesions can be locoregional or systemic, with the latter being marginally more
* Corresponding author. Tel .: +1 617 726 3303; fax: +1 617 726 2424. E-mail address: vyanamadala@mgh.harvard.edu (V. Yanamadala).
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common [12-14]. Locoregional recurrences tend to involve sur- rounding structures (including pancreas, spleen, liver, diaphragm and retroperitoneum), while systemic recurrences occur most fre- quently in the lungs and liver (39-65%), lymph nodes (25%) and bone (15%) [12,13,15].
ACC lesions are usually secretory (40-60%) and present typi- cally as steroid hormone excess, alongside other non-specific signs such as lymphadenopathy, hepatomegaly and edema [16,4]. Rapidly progressive Cushing’s syndrome is the most frequent pre- sentation, though androgen, estrogen, aldosterone and dehy- droepiandrosterone surface (DHEA-S) excess are also regularly reported [7]. Non-secreting tumors (30%) are common as well, and can manifest as abdominal mass effect (for example nausea, abdominal fullness and/or back pain). Incidental diagnosis
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additionally accounts for a significant number of ACC cases (15-20%) [16,17].
CT scan and MRI are the primary means of diagnosing ACC. Tumor size is particularly predictive of malignancy [7]. Adrenal tumors of radius >6 cm are diagnostic of ACC with a sensitivity of 91% and specificity of 80%, and are recommended for excision by the USA National Institutes of Health [18,16]. PET imaging is also insightful, as ACC exhibits high 18F-fuorodeoxyglucose (FDG) uptake [17,18].
Imaging should be followed by pathological confirmation, par- ticularly in cases of small tumors (radius <3 cm), for which benign adrenal neoplasia should be excluded [18,19]. Steroidogenic factor 1 has been attributed as the definitive marker of ACC [3]. A Weiss score (0-9) should also be attained, with a score ≥3 being indica- tive of ACC [7,20].
Presentation of spinal metastases is typically local or radicular pain and/or neurological symptoms, including sensory loss, lack of sphincter control and muscle weakness [21]. MRI is the standard imaging modality to characterize site, number and extent of lesions [21]. As with our patient, metastases are generally
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extradural (95%) and located most frequently at thoracic (60-80%) and lumbar sites (15%) [21,3,22].
4. Previous cases of spinal metastasis
Metastasis of ACC to the spine is rare, despite the frequency of spinal metastasis across malignancies [21,4]. In a study of 32 patients with ACC, 10 patients had bone metastasis, of whom four had spinal lesions [4]. Other bony metastasis in the same study included to the pelvis (n = 4), extremities (n = 4), ribs (n = 3), skull (n = 2), clavicle (n = 2) and bone marrow (n = 2) [4]. To our knowl- edge further literature describing spinal metastasis of ACC is lar- gely limited to three case reports. Two of these reports detailed metastasis in adults at lumbar (L1) and sacral sites, as confirmed by imaging and pathology [3,2]. The third report described spinal metastasis in an 8-month-old baby at T8-T10 [1].
5. Management of ACC and extradural spinal metastasis
Standard of care for localized ACC (stages I-III) is complete (RO) resection [7,5,17]. Resection is the only means by which to attain long-term disease-free survival in ACC. Unfortunately, post- operative recurrence is high. Rates at 5 years are greater than 50%, with overall values being reported up to 85% [10,11].
Standard of care for advanced ACC (stage IV) is medical therapy in the form of mitotane (also known as o,p’-DDD) [23]. Mitotane is the only adrenal-specific therapeutic currently available for ACC. Given its high recurrence rate, ACC is treated adjuvantly with mito- tane either alone or in combination with cytotoxic drugs (etopo- side, doxorubicin, cisplatin) from initial diagnosis [7,24,23]. However, the efficacy of medical treatment, as for resection, is lim- ited. Mitotane has a response rate of 24% [23]. Pairing mitotane with certain chemotherapeutics marginally improves this outcome for some patients [7,24]. Research into newer therapies, including tyrosine kinase inhibitors (insulin-like growth factor 1 receptor) and rapamycin signaling components (mechanistic target of rapa- mycin) show some promise, but are years from clinical implemen- tation [7,17,25].
Surgical intervention in the case of advanced ACC has met with some success. R0 resection of local regional recurrences is associ- ated with improved survival rates, according to several retrospec- tive studies [17,26,27]. Debulking surgeries are also noted to be of benefit in cases of hormonal excess for which medical treatment has failed [9]. However, surgical indications should be carefully considered for patients with advanced ACC. Incomplete resection of recurrent or metastatic disease is associated with worsened prognosis, averaging a post-operative survival time of less than 12 months [17,27-29].
Radiotherapy has also shown promise as a treatment for advanced ACC. Response rates to irradiation have been reported up to 42% [17,10]. In fact, the German ACC consortium recom- mends that adjuvant radiotherapy be pursued for lesions of stage III or of indeterminate resection margins following resection [12]. Nonetheless, there are conflicting clinical findings regarding the use of radiotherapy in advanced ACC. While some studies have reported encouraging response rates to radiotherapy, others have shown no difference in outcome with its use [30,31]. One report in particular found reduced recurrence rates (4.7:1), but no differ- ence in overall survival between radiotherapy plus surgery and surgery-only cohorts [33]. Thus, while ACC appears to be radiosen- sitive, a clear consensus on radiotherapy has yet to be reached [17].
6. Treatment of spinal metastasis
Surgical intervention is the treatment of choice for symptomatic spinal metastasis, provided the patient is suitable for operation
[21,32]. Total or partial vertebrectomy with stabilization is the pre- ferred intervention for lesions involving a single vertebra or two adjacent vertebrae, as it is locally curative and provides good long-term outcomes [32]. Less invasive techniques are recom- mended for patients with multiple lesions due to the associated co-morbidities of multi-site disease and the immunocompromise of chemotherapy [32,33]. Adjunct vertebroplasty can be useful for pain relief in the case of symptomatic pathological compression fractures where a more aggressive resection cannot be performed, providing relief in up to 85% of patients, with a limited symp- tomatic complication rate of 10% [34,35].
External beam radiation (EBT) and stereotactic radiosurgery (SRS) are also important in the treatment of spinal metastasis. EBT, including intensity modulated radiation therapy, is the accepted standard worldwide. Intensity modulated radiation ther- apy and SRS are newer techniques than traditional EBT, allowing for greater spatial specificity and thereby higher dosage or re- irradiation [21]. Treatment with these two therapies has been said to relieve pain in 85% of patients [21,36]. In the case of SRS, a single dose of 8 Gy has been shown to improve pain in 60-73% of patients [21,37,38].
In spinal metastatic disease, Patchell et al. reported in 2005 that pairing surgical intervention and radiation improves outcomes fur- ther. A study of 101 patients comparing surgical intervention plus radiotherapy to radiotherapy alone found that 84% of patients who were provided with both interventions were ambulatory, as opposed to 57% of patients who were provided only radiotherapy; pain relief was also greater with the combined treatment [39]. A meta-analysis of cohort studies discovered similar findings, report- ing higher ambulatory function (1.3:1), pain relief (90% versus 70%) and urinary control (66% versus 26%) when surgery and radiother- apy were both used [40]. While these studies do not examine ACC in particular, this is the best data currently available, to our knowledge.
In this patient, for whom radiotherapy had failed once, complete tumor excision through vertebrectomy followed by low-dose radiation seemed to be the best option for achieving long lasting local control. In contrast, a previously reported patient with ACC metastasis to the L1 vertebrae was treated with laminectomy alone [3]. The patient, who had suffered from Cushing syndrome pre-operatively, became normotensive and attained normal cortisol levels following intervention [3]. However, malignancy recurred a year later in the soft tissue immediately anterior to the sacrum [3]. This outcome in light of the aggressively recurrent nature of ACC argues against simply decompressing spinal metas- tasis of ACC and in favor of a more aggressive vertebrectomy approach.
Other reported cases of spinal metastasis of ACC were not trea- ted surgically due to the severe extent of disease [1,2]. Treatment was instead palliative [1] or chemotherapeutic [2].
It should be noted that for intracranial metastasis of ACC, surgi- cal resection has been recommended, as it provides a median sur- vival time comparable with the that for other intracranial metastases (4-5 months) [41].
7. Conclusion
The treatment of spinal metastasis of ACC requires careful con- sideration of its aggressive nature. Just as R0 resection is the pre- ferred treatment of the primary disease in stages I-III, complete resection, paired with radiotherapy, would be the logical approach to spinal metastasis of ACC, provided the patient is amenable to intervention. The established efficacy of radiotherapy in the treat- ment of spinal metastasis justifies its use in this case, despite its
debated utility in ACC. Mitotane, while shown to limit recurrence, remains lacking in evidence for survival and response rates.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other con- flicts of interest in relation to this research and its publication.
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