Ann Thorac Surg 2008;86:657-660. doi:10.1016/j.athoracsur.2008.02.007
© 2008 The Society of Thoracic Surgeons
Case Reports
Intrathoracic Psammomatous Melanotic Schwannoma Associated With the Carney Complex
Soeren Torge Mees, MDa,*,
Tilmann Spieker, MDb,
Elke Eltze, MDb,
Jens Brockmann, PhDa,
Norbert Senninger, PhDa,
Matthias Bruewer, PhDa
a Department of General Surgery, University Hospital of Muenster, Muenster, Germany
b Gerhard-Domagk-Institute for Pathology, University Hospital of Muenster, Muenster, Germany
Accepted for publication February 5, 2008.
* Address correspondence to Dr Mees, Department of General Surgery, University Hospital of Muenster, Waldeyerstr. 1, Muenster, 48149, Germany (Email: soerentorge.mees{at}ukmuenster.de).
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Abstract
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The Carney complex is a multiple neoplasia syndrome characterized by myxomas, schwannomas, mucocutaneous spotty pigmentations, and endocrine overactivity with or without endocrine tumors. Herein, we report the rare case of a 49-year-old man with a paravertebral intrathoracic tumor, a history of bilateral adrenalectomy, and resection of an atrial myxoma. A thoracoscopic en-bloc tumor extirpation with minimal safety margins was performed. Histopathologic examination revealed the diagnosis of a malignant psammomatous melanotic schwannoma that is associated with the Carney complex in 50% of these patients. Prognosis of all melanotic schwannomas is usually poor due to local recurrences or metastases. Although treatment guidelines for this rare tumor do not exist, radiotherapy was performed in our patient to prevent possible recurrence or regrowth of this malignant tumor. Twenty-four months after operation the patient showed no signs of tumor recurrence or metastases.
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Introduction
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In 1985, Carney and Stratakis [1] described a multiple neoplasia syndrome characterized by myxomas (heart, skin, and breast), schwannomas, mucocutaneous spotty pigmentations (lentigines and blue nevi), and endocrine overactivity (due to thyroid dysfunction or hypophyseal adenoma or Cushing's syndrome secondary to adrenocortical pigmented primary nodular hyperplasia) with or without endocrine tumors (adrenal, testicular, and pituitary). Recently, molecular genetic studies showed that mutations in the PRKAR1A gene (encoding the R1
regulatory subunit of cyclic adenosine monophosphate-dependent protein kinase A) are the underlying cause for this autosomal dominant disorder in approximately half of the patients [2].
One component of the Carney complex (CNC) is schwannoma. Melanotic schwannomas are rare neoplasms, classifiable as a peripheral nerve sheath tumor, which are differentiated from typical schwannomas by heavy pigmentation. Interestingly approximately 50% of these schwannomas are associated with CNC and are called psammomatous melanotic schwannomas (PMS) [3]. Most frequently, these involve the spinal cord or sympathic ganglia and rarely arise in the gastrointestinal tract, heart, liver, bronchus, soft tissue, or bone [4, 5].
We report the rare case of a 49-year-old man with known CNC who subsequently had an intrathoracic PMS resected that we believe has not been described in the literature to date. The recent literature is reviewed and therapy options are discussed.
A symptom-free 49-year-old man with a history of a bilateral adrenalectomy, because of Cushing's syndrome and the resection of a left-sided atrial myxoma, was referred to our hospital showing a tumor of the right thorax in a follow-up plain roentgenogram. An 18-fluoro-deoxyglucose (FDG-PET) positron emission tomographic–computed tomographic imaging revealed a 3.5 x 2.5 cm sized intrathoracic tumor on the right side next to the vertebral column with an increased metabolic activity (standardized uptake value of 6.4 [normal range, < 1.5]) (Figs 1 and 2).
The familial history regarding malignancies was uneventful. The physical examination revealed normal results without any hypertensive blood pressure values. The routine laboratory data were within normal limits, whereas 24-hour urinary catecholamines were repeatedly increased up to fivefold above the normal range (normetanephrine, 403 to 798 µg [normal range, 105 to 354]; noradrenaline, 123 to 139 µg [normal range, 23 to 105]). We assumed the intrathoracic tumor to be a pheochromocytoma; therefore, the patient received antihypertensive medication preoperatively (phenoxybenzamine 20 mg 3 x 1 per os for 2 weeks).
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Fig 1. Computed tomography of the thorax. Illustration of a 3.5 x 2.5 cm sized intrathoracic tumor on the right side next to the vertebral column. No further tumors or abnormalities detectable.
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Fig 2. Positron-emission tomographic–computed tomographic (PET-CT) scan of the thorax. (A) Fusion of conventional CT scan (to pinpoint the exact location, size, and shape of the tumor) and PET scan (to determine the metabolism of the tumor). (B) PET scan: increased metabolic activity with a standardized uptake value of 6.4 (normal range: <1.5).
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A complete tumor extirpation (R0) could be performed by thoracoscopy. However, safety margins as recommended for potential malignant tumors could not be obtained due to the nearby vertebral body. The postoperative course was uneventful. The patient was discharged from our ward after 7 days.
The 4 x 4 x 2 cm excised tumor was mostly solid, revealed a soft consistence, and showed a dark red to black color with osseous components.
Histologically, the tumor showed a moderate cellular proliferation of spindle-shaped or oval to polygonal cells. The polymorph nuclei were greatly enlarged with hyperchromatic nucleoli. Mitoses were infrequently observed (in total 6 mitoses in 10 high-power fields) and occasionally psammomatous calcifications were seen.
The tumor cells were strongly immunopositive for S-100 protein, HMB-45, and Melan A, whereas all tumor cells were negative for cytokeratin, chromogranins, and synaptophysin. Expression of MIB1 was found in 15% of the nuclei.
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Comment
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Melanotic schwannoma is an uncommon neural tumor that was first described in 1932 by Millar [6] as a malignant melanotic tumor of ganglion cells. Melanotic schwannoma affects male and female subjects equally and generally occurs in young adults at a mean age of 38 years [3]. Melanotic schwannoma shows a predilection for spinal nerve involvement (46%), particularly at the cervical and thoracic levels [7, 8]. Furthermore, soft tissue and visceral organs, such as the gastrointestinal tract, heart, liver, and bronchus can also be affected [1–3]. Recently, case reports with CNC-associated tumors of brain, temporozygomatic region, or fibula have been published [9–11]. We believe that an intrathoracic paravertebral PMS associated with CNC has not been described yet; therefore, this diagnosis was not considered before surgery. We rather considered extra-adrenal pheochromocytoma due to the strongly elevated urinary catecholamines to be the most likely diagnosis. Other potential diagnoses for intrathoracal tumors are metastatic malignant melanoma, solitary neurofibromas, and neurofibromas associated with neurofibromatosis type 1 (Von Recklinghausen's disease). Neurofibromatosis type 1 and CNC show many similarities including schwannomas. However, neurofibromatosis type 1 shows mutations on neurofibromatosis type 1-gen on the long arm of chromosome 17 (17q11), whereas genetic analyses for CNC show the presence of an altered locus at chromosome 17q24 (PRKAR1A gene). Furthermore, CNC lack characteristic neurofibromas and café au lait spots.
Regarding the melanotic features of the tumor, a relation to excessive melanocyte stimulating hormone (MSH) production after bilateral adrenalectomy was considered. Although MSH was not measured in our patient, adrenocorticotropic hormone was only slightly increased (87 pg/mL) above the normal value (10 to 60 pg/mL). As adrenocorticotropic hormone regulates MSH production, it is unlikely that the melanotic feature of the tumor is related to excessive MSH production. A conclusive explanation for the melanotic feature of this tumor is unknown.
In retrospect, we consider this patient to be diagnosed as CNC for the following reasons: Cushing's syndrome secondary to adrenocortical pigmented primary nodular hyperplasia, heart myxoma, and PMS, whereas cutaneous signs of neurofibromatosis were lacking. However, for definitive diagnosis, a genetic analysis of inactivating mutations of the PRKAR1A gene is required. However, in our patient, without family history for CNC or children, expensive genetic testing would not be of any further benefit and was therefore not performed.
Approximately 100 cases of melanotic schwannoma in different locations have been reported and approximately 10% are malignant. Moreover, some studies indicate that the long-term prognosis of melanotic schwannoma is critical because these tumors can be aggressive with local recurrences occurring even several years after surgery [3, 8]. For that reason, a radical tumor extirpation should be performed to prevent recurrence of the tumor or possible malignant transformation of tumor remnants. For dumbbell tumors, that have both an intraspinal and a paraspinal component and are connected through a frequently enlarged and eroded intervertebral foramen, a radical tumor resection means (hemi)laminectomy to achieve adequate safety margins [12, 13].
Despite the questionable efficiency of adjuvant therapies, we decided to perform adjuvant radiotherapy with 60 Gray rather than a reoperation with laminectomy to minimize the risk of possible recurrence or regrowth of this malignant tumor. Twenty-four months after surgery and radiotherapy, our patient is alive and well without tumor recurrence or metastases.
In summary, we have described a very rare case of intrathoracic PMS associated with CNC. Due to potential malignancy of PMS, a complete surgical extirpation of the tumor is crucial, whereas the efficiency of adjuvant radiotherapy and chemotherapy has not been proven yet. A long-term follow-up for a period of more than 5 years is recommended for all psammomatous melanotic schwannomas.
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References
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- Carney JA, Stratakis CA. Epithelioid blue nevus and psammomatous melanotic schwannoma: the unusual pigmented skin tumors of the Carney complex Semin Diagn Pathol 1998;15216–4.
- Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase A type 1- regulatory subunit in patients with Carney complex Nat Genet 2000;26:89-92.[Medline]
- Carney JA. Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol 1990;14:206-222.[Medline]
- Gelfand ET, Taylor RF, Hendin D, Akabutu J, Callaghan JC. Melanotic malignant schwannoma of the right atrium J Thorac Cardiovasc Surg 1977;74:808-812.[Abstract]
- Kim MJ, Choi J, Khang SK, Kim JS, Lee JS, Cho KJ. Primary intraosseous melanotic schwannoma of the fibula associated with the Carney complex Pathology International 2006;56:538-542.[Medline]
- Millar WG. A malignant melanotic tumor of ganglion cells arising from the thoracic sympathetic ganglion J Pathol Bacteriol 1932;35:351-357.
- Çulhaci N, Dikicioglu E, Meteoglu I, Boylu S. Multiple melanotic Schwannoma Ann Diagn Pathol 2003;7:254-258.[Medline]
- Carney JA, Ferreiro J. The epithelioid blue nevus: a multicentric familial tumor with important associations, including cardiac myxoma and psammomatous melanotic schwannoma Am J Surg Pathol 1996;20:259-272.[Medline]
- Carrasco CA, Rojas-Salazar D, Chiorino R, Venega JC, Wohllk N. Melanotic nonpsammomatous trigeminal schwannoma as the first manifestation of Carney complex: case report Neurosurgery 2006;59:1334-1335.
- Kim MJ, Choi J, Khang SK, Kim JS, Lee JS, Cho KJ. Primary intraosseous melanotic schwannoma of the fibula associated with the Carney complex Pathol Int 2006;56:538-542.[Medline]
- Dhouib M, Briki S, Ben Mahfoudh K, et al. Melanotic schwannoma of the temporozygomatic region Rev Stomatol Chir Maxillofac 2007;108:139-142.[Medline]
- Marton E, Feletti A, Orvieto E, Longatti P. Dumbbell-shaped C-2 psammomatous melanotic malignant schwannoma. Case report and review of the literature. Neurosurg Spine 2007;6:591-599.[Medline]
- De Cerchio L, Contratti F, Fraioli MF. Dorsal dumb-bell melanotic schwannoma operated on by posterior and anterior approach: case report and a review of the literature Eur Spine J 2006;15:664-669.[Medline]
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Abstract
Introduction
