- Email: [email protected]
Myasthenia gravis associated with ectopic cervical thymoma
Available online at www.sciencedirect.com
Journal of Clinical Neuroscience 15 (2008) 1393–1395 www.elsevier.com/locate/jocn
Case Reports
Myasthenia gravis associated with ectopic cervical thymoma Hojin Choi a, Seong-Ho Koh a, Moon Hyang Park b, Seung H. Kim a,* a
Department of Neurology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, 133–792, Seoul, Korea b Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea Received 26 May 2006; accepted 21 June 2007
Abstract It is well known that thymoma is often associated with myasthenia gravis. Although ectopic thymoma can be found anywhere from the pharynx to the anterior mediastinum, it is usually benign and has not been reported in association with myasthenic symptoms. Moreover, ectopic thymoma located in the neck region is apt to be misdiagnosed as a thyroid mass or other infiltrative lesion. We report the case of a patient with myasthenia gravis associated with ectopic cervival thymoma, whose myasthenic symptoms were well controlled after removal of the ectopic thymomas. Ó 2008 Elsevier Ltd. All rights reserved. Keywords: Cervical thymoma; Myasthenia gravis; Thymectomy
1. Introduction Thymoma or thymic hyperplasia are often associated with myasthenia gravis (MG),1,2 and detection and removal of the thymoma are essential diagnostic and therapeutic procedures. However, using routine diagnostic approaches, it is not easy to detect ectopic thymoma. Developmental abnormalities of the thymus gland may induce an ectopic thymus gland anywhere from the pharynx to the anterior mediastinum.3 Although rare, a few cases of MG with cervical thymoma have been reported, but there has been no link established between the thymoma and the myasthenic symptoms.2–5 We present the case of a patient with uncontrolled MG associated with ectopic cervical thymoma, which was initially misdiagnosed as a thyroid tumor. In this patient, symptoms improved after removal of the ectopic thymic mass. 2. Case report A 53-year-old woman with a 3-year history of fluctuating general weakness, particularly in both upper extremities (Medical Research Council grade 2–4), and right ptosis, was admitted to the Department of Neurology at Hanyang *
Corresponding author. Tel.: +82 2 2290 8371; fax: +82 2 2296 8370. E-mail address: [email protected] (S.H. Kim).
University Hospital, Seoul, Korea. She had been diagnosed with MG in another hospital 2 years prior to presentation at our hospital, but had not responded to the pyridostigmine (240 mg/day) and steroidal medication (30 mg/day prednisolone) prescribed at that time. On physical examination, a well-defined, firm mass was found in the left side of her neck. Upon neurological examination, right ptosis and severe weakness in both distal upper extremities were observed. General weakness and ptosis improved after injection of edrophonium. Repetitive nerve stimulation tests revealed significant abnormal decremental responses in the trapezius and obicularis oculi with low rate stimulation (2, 3 and 5 Hz). The titer of acetylcholine receptor antibody in serum was >8.00 nmol/L (normal range: <0.25 nmol/L). There were no abnormal findings in routine laboratory tests, thyroid function tests, or other laboratory tests to suggest other autoimmune diseases, including rheumatoid arthritis, Sjogren’s syndrome, lupus, pernicious anemia, and autoimmune thyroiditis. CT of the thorax showed no masses in the anterior mediastinum. The mass in the neck was initially thought to be thyroid tissue. Radiological investigations showed a well-defined and margined mass in the left portion of the patient’s thyroid gland (Fig. 1A). Fine needle aspiration biopsy showed only lymphocyte infiltration without thyroid cells (Fig. 1B), and excision was performed under the impression that the lesion was a lymphoma, a metastatic tumor in the
1394
Case Reports / Journal of Clinical Neuroscience 15 (2008) 1393–1395
Fig. 1. (A) Neck CT scan and (B) fine needle aspiration biopsy specimen from the neck mass. The CT scan shows a well-defined and margined mass (4 5 cm) in the left portion of the thyroid gland (A, arrow). The photomicrograph shows that the biopsy specimen contains many lymphocytes but no thyroid cells (B, arrow, hematoxylin and eosin staining, 400).
Fig. 2. Findings after excisional biopsy of the neck mass. The gross specimen was a well-encapsulated lobulated mass (5 5 3.5 cm) (A). Epithelial and lymphocytic cells were seen in sections of the mass (hematoxylin and eosin staining, 400) (B).
neck region, or possibly ectopic thymoma. The excised specimen was well encapsulated and lobulated (Fig. 2A). Lymphocytes and epithelioid cells were identified by hematoxylin and eosin staining (Fig. 2B), cytokeratin immuno staining was used to identify epithelioid cells, and CD5 immuno staining revealed thymic cells (not shown). The neck mass mimicking a thyroid mass was confirmed as ectopic cervical thymoma, classified into the World Health Organization B1 group. After the successful complete excision of this mass, the patient’s clinical course slowly improved. One year later, her symptoms were well controlled by 120 mg/day pyridostigmine (60 mg twice daily). 3. Discussion Toward the end of the sixth embryonic week, the human thymic primordium becomes visible. It develops from the ventral portions of the third and, in a minority of cases, the fourth pharyngeal pouches, and descends to its usual location in the anterior mediastinum by the end of the second month of gestation.3–5 Ectopic thy-
moma may be found anywhere from the pharynx to its normal location in the anterior mediastinum.6 When situated in the vicinity of the thyroid gland, it can mimic a thyroid nodule.3,4,6 The diagnosis of primary thymoma in the neck is very difficult to make.3–8 Most cases present as a thyroid nodule in imaging studies, and further clinical examination and multiple pathological considerations are needed.5 Some cases of ectopic cervical thymoma can display misleading pathologic features because of the mixture of epithelial and lymphoid elements.5 If one cellular element is more prominent, it could be misdiagnosed as nasopharyngeal carcinoma or lymphoma. In this case, our initial clinical impression was that the lesion was a thyroid mass that was not related to the myasthenia gravis. With only a frozen section examination of the needle biopsy without any special staining, a finding of lymphocytic predominance and no thyroid cells meant that we were unable to differentiate between lymphoma or other metastatic tumor. However, thymic tissue was found after complete excision of the thyroid mass.
Case Reports / Journal of Clinical Neuroscience 15 (2008) 1395–1398
The association between thymoma and MG is known to be related to the intratumorous generation of mature T-cells. These cells play an immunological stimulator role in MG in that they can synthesize anti-ACh receptor antibodies.2 Thus, thymectomy is considered to be the most effective treatment for achieving sustained improvement, as well as remission in patients with MG. Most neurologists favor the use of this procedure.8 The presence of ectopic thymic tissue could have prognostic value in determining the outcome of the operation.9 However, the majority of reported ectopic cervical thymomas have a benign clinical course with no recurrence of the tumor, metastasis or myasthenic symptoms.3,5 In cases of multiple remnant thymoma, intractable myasthenic symptoms and poor prognosis have been reported.9 In contrast to previous cases, our patient had only cervical thymoma, but myasthenic symptoms were not well controlled until the mass was excised. This case is the first report of MG associated with ectopic cervical thymoma, and suggests that inspection and removal of ectopic cervical thymoma is very important for the treatment of MG.
1395
References 1. Richman DP, Agius MA. Acquired myasthenia gravis: immunopathology. Neurol Clin 1994;12:273–84. 2. Tuncer Elmaci N, Ratip S, Ince-Gunal D, et al. Myasthenia gravis with thymoma and autoimmune haemolytic anaemia: A case report. Neurol Sci 2003;24:34–6. 3. Lanka KP, Sarin B, Prasad V, et al. Benign cervical thymoma masquerading as a malignant thyroid nodule. Clin Nuclear Med 2002;27:862–4. 4. Cohen JB, Troxell M, Kong CS, et al. Ectopic intrathyroidal thymoma: A case report and review. Thyroid 2003;13:305–8. 5. Oh YL, Ko YH, Ree HJ. Aspiration cytology of ectopic cervical thymoma mimicking a thyroid mass. A case report. Acta Cytol 1998;42:1167–71. 6. Miller WT Jr, Gefter WB, Miller WT. Thymoma mimicking a thyroid mass. Radiology 1992;184:75–6. 7. Jaurbe C, Conley JJ, Gillooley JF, et al. Metastatic cervical thymoma. Otolaryngol Head Neck Surg 1989;100:232–6. 8. Tellez-Zenteno F, Cardenas G, Estanol B, et al. Associated conditions in myasthenia gravis: response to thymectomy. Eur J Neurol 2004;11:767–73. 9. Ashour M. Prevalence of ectopic thymic tissue in myasthenia gravis and its clinical significance. Thorac Cardiovasc Surg 1995;109:632–5
doi:10.1016/j.jocn.2007.06.018
Synchronous moyamoya syndrome and ruptured cerebral aneurysm in Alagille syndrome Ron C. Gaba a,*, Rajesh P. Shah a, Andrew A. Muskovitz b, Grace Guzman c, Edward A. Michals a a
Department of Radiology, University of Illinois Medical Center at Chicago, 1740 West Taylor Street, MC 931, Chicago, IL 60612, USA b Department of Internal Medicine, University of Illinois Medical Center at Chicago, Chicago, IL, USA c Department of Pathology, University of Illinois Medical Center at Chicago, Chicago, IL, USA Received 21 March 2007; accepted 22 May 2007
Abstract Moyamoya syndrome and cerebral aneurysm formation are rare cerebrovascular manifestations of Alagille syndrome. Although previously reported in isolation, occurrence of these complications in a single patient has not been described. We report clinical and imaging features of synchronous moyamoya syndrome and ruptured cerebral aneurysm in a patient with Alagille syndrome. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Alagille syndrome; Moyamoya syndrome; Cerebral aneurysm
1. Introduction Alagille syndrome, or arteriohepatic dysplasia, is an uncommon autosomal dominant congenital multisystem *
Corresponding author. Tel.: +1 312 996 3971; fax: +1 312 996 0511. E-mail address: [email protected] (R.C. Gaba).
disorder consisting of bile duct hypoplasia associated with a variety of cardiovascular, skeletal, ophthalmologic, and neurologic abnormalities.1 Rare cerebrovascular manifestations of this condition include moyamoya syndrome, an idiopathic vascular occlusive disease, and aneurysm formation, both of which have previously been reported in isolation.2–6 To the best of our knowledge, concurrent
Journal of Clinical Neuroscience 15 (2008) 1393–1395 www.elsevier.com/locate/jocn
Case Reports
Myasthenia gravis associated with ectopic cervical thymoma Hojin Choi a, Seong-Ho Koh a, Moon Hyang Park b, Seung H. Kim a,* a
Department of Neurology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, 133–792, Seoul, Korea b Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea Received 26 May 2006; accepted 21 June 2007
Abstract It is well known that thymoma is often associated with myasthenia gravis. Although ectopic thymoma can be found anywhere from the pharynx to the anterior mediastinum, it is usually benign and has not been reported in association with myasthenic symptoms. Moreover, ectopic thymoma located in the neck region is apt to be misdiagnosed as a thyroid mass or other infiltrative lesion. We report the case of a patient with myasthenia gravis associated with ectopic cervival thymoma, whose myasthenic symptoms were well controlled after removal of the ectopic thymomas. Ó 2008 Elsevier Ltd. All rights reserved. Keywords: Cervical thymoma; Myasthenia gravis; Thymectomy
1. Introduction Thymoma or thymic hyperplasia are often associated with myasthenia gravis (MG),1,2 and detection and removal of the thymoma are essential diagnostic and therapeutic procedures. However, using routine diagnostic approaches, it is not easy to detect ectopic thymoma. Developmental abnormalities of the thymus gland may induce an ectopic thymus gland anywhere from the pharynx to the anterior mediastinum.3 Although rare, a few cases of MG with cervical thymoma have been reported, but there has been no link established between the thymoma and the myasthenic symptoms.2–5 We present the case of a patient with uncontrolled MG associated with ectopic cervical thymoma, which was initially misdiagnosed as a thyroid tumor. In this patient, symptoms improved after removal of the ectopic thymic mass. 2. Case report A 53-year-old woman with a 3-year history of fluctuating general weakness, particularly in both upper extremities (Medical Research Council grade 2–4), and right ptosis, was admitted to the Department of Neurology at Hanyang *
Corresponding author. Tel.: +82 2 2290 8371; fax: +82 2 2296 8370. E-mail address: [email protected] (S.H. Kim).
University Hospital, Seoul, Korea. She had been diagnosed with MG in another hospital 2 years prior to presentation at our hospital, but had not responded to the pyridostigmine (240 mg/day) and steroidal medication (30 mg/day prednisolone) prescribed at that time. On physical examination, a well-defined, firm mass was found in the left side of her neck. Upon neurological examination, right ptosis and severe weakness in both distal upper extremities were observed. General weakness and ptosis improved after injection of edrophonium. Repetitive nerve stimulation tests revealed significant abnormal decremental responses in the trapezius and obicularis oculi with low rate stimulation (2, 3 and 5 Hz). The titer of acetylcholine receptor antibody in serum was >8.00 nmol/L (normal range: <0.25 nmol/L). There were no abnormal findings in routine laboratory tests, thyroid function tests, or other laboratory tests to suggest other autoimmune diseases, including rheumatoid arthritis, Sjogren’s syndrome, lupus, pernicious anemia, and autoimmune thyroiditis. CT of the thorax showed no masses in the anterior mediastinum. The mass in the neck was initially thought to be thyroid tissue. Radiological investigations showed a well-defined and margined mass in the left portion of the patient’s thyroid gland (Fig. 1A). Fine needle aspiration biopsy showed only lymphocyte infiltration without thyroid cells (Fig. 1B), and excision was performed under the impression that the lesion was a lymphoma, a metastatic tumor in the
1394
Case Reports / Journal of Clinical Neuroscience 15 (2008) 1393–1395
Fig. 1. (A) Neck CT scan and (B) fine needle aspiration biopsy specimen from the neck mass. The CT scan shows a well-defined and margined mass (4 5 cm) in the left portion of the thyroid gland (A, arrow). The photomicrograph shows that the biopsy specimen contains many lymphocytes but no thyroid cells (B, arrow, hematoxylin and eosin staining, 400).
Fig. 2. Findings after excisional biopsy of the neck mass. The gross specimen was a well-encapsulated lobulated mass (5 5 3.5 cm) (A). Epithelial and lymphocytic cells were seen in sections of the mass (hematoxylin and eosin staining, 400) (B).
neck region, or possibly ectopic thymoma. The excised specimen was well encapsulated and lobulated (Fig. 2A). Lymphocytes and epithelioid cells were identified by hematoxylin and eosin staining (Fig. 2B), cytokeratin immuno staining was used to identify epithelioid cells, and CD5 immuno staining revealed thymic cells (not shown). The neck mass mimicking a thyroid mass was confirmed as ectopic cervical thymoma, classified into the World Health Organization B1 group. After the successful complete excision of this mass, the patient’s clinical course slowly improved. One year later, her symptoms were well controlled by 120 mg/day pyridostigmine (60 mg twice daily). 3. Discussion Toward the end of the sixth embryonic week, the human thymic primordium becomes visible. It develops from the ventral portions of the third and, in a minority of cases, the fourth pharyngeal pouches, and descends to its usual location in the anterior mediastinum by the end of the second month of gestation.3–5 Ectopic thy-
moma may be found anywhere from the pharynx to its normal location in the anterior mediastinum.6 When situated in the vicinity of the thyroid gland, it can mimic a thyroid nodule.3,4,6 The diagnosis of primary thymoma in the neck is very difficult to make.3–8 Most cases present as a thyroid nodule in imaging studies, and further clinical examination and multiple pathological considerations are needed.5 Some cases of ectopic cervical thymoma can display misleading pathologic features because of the mixture of epithelial and lymphoid elements.5 If one cellular element is more prominent, it could be misdiagnosed as nasopharyngeal carcinoma or lymphoma. In this case, our initial clinical impression was that the lesion was a thyroid mass that was not related to the myasthenia gravis. With only a frozen section examination of the needle biopsy without any special staining, a finding of lymphocytic predominance and no thyroid cells meant that we were unable to differentiate between lymphoma or other metastatic tumor. However, thymic tissue was found after complete excision of the thyroid mass.
Case Reports / Journal of Clinical Neuroscience 15 (2008) 1395–1398
The association between thymoma and MG is known to be related to the intratumorous generation of mature T-cells. These cells play an immunological stimulator role in MG in that they can synthesize anti-ACh receptor antibodies.2 Thus, thymectomy is considered to be the most effective treatment for achieving sustained improvement, as well as remission in patients with MG. Most neurologists favor the use of this procedure.8 The presence of ectopic thymic tissue could have prognostic value in determining the outcome of the operation.9 However, the majority of reported ectopic cervical thymomas have a benign clinical course with no recurrence of the tumor, metastasis or myasthenic symptoms.3,5 In cases of multiple remnant thymoma, intractable myasthenic symptoms and poor prognosis have been reported.9 In contrast to previous cases, our patient had only cervical thymoma, but myasthenic symptoms were not well controlled until the mass was excised. This case is the first report of MG associated with ectopic cervical thymoma, and suggests that inspection and removal of ectopic cervical thymoma is very important for the treatment of MG.
1395
References 1. Richman DP, Agius MA. Acquired myasthenia gravis: immunopathology. Neurol Clin 1994;12:273–84. 2. Tuncer Elmaci N, Ratip S, Ince-Gunal D, et al. Myasthenia gravis with thymoma and autoimmune haemolytic anaemia: A case report. Neurol Sci 2003;24:34–6. 3. Lanka KP, Sarin B, Prasad V, et al. Benign cervical thymoma masquerading as a malignant thyroid nodule. Clin Nuclear Med 2002;27:862–4. 4. Cohen JB, Troxell M, Kong CS, et al. Ectopic intrathyroidal thymoma: A case report and review. Thyroid 2003;13:305–8. 5. Oh YL, Ko YH, Ree HJ. Aspiration cytology of ectopic cervical thymoma mimicking a thyroid mass. A case report. Acta Cytol 1998;42:1167–71. 6. Miller WT Jr, Gefter WB, Miller WT. Thymoma mimicking a thyroid mass. Radiology 1992;184:75–6. 7. Jaurbe C, Conley JJ, Gillooley JF, et al. Metastatic cervical thymoma. Otolaryngol Head Neck Surg 1989;100:232–6. 8. Tellez-Zenteno F, Cardenas G, Estanol B, et al. Associated conditions in myasthenia gravis: response to thymectomy. Eur J Neurol 2004;11:767–73. 9. Ashour M. Prevalence of ectopic thymic tissue in myasthenia gravis and its clinical significance. Thorac Cardiovasc Surg 1995;109:632–5
doi:10.1016/j.jocn.2007.06.018
Synchronous moyamoya syndrome and ruptured cerebral aneurysm in Alagille syndrome Ron C. Gaba a,*, Rajesh P. Shah a, Andrew A. Muskovitz b, Grace Guzman c, Edward A. Michals a a
Department of Radiology, University of Illinois Medical Center at Chicago, 1740 West Taylor Street, MC 931, Chicago, IL 60612, USA b Department of Internal Medicine, University of Illinois Medical Center at Chicago, Chicago, IL, USA c Department of Pathology, University of Illinois Medical Center at Chicago, Chicago, IL, USA Received 21 March 2007; accepted 22 May 2007
Abstract Moyamoya syndrome and cerebral aneurysm formation are rare cerebrovascular manifestations of Alagille syndrome. Although previously reported in isolation, occurrence of these complications in a single patient has not been described. We report clinical and imaging features of synchronous moyamoya syndrome and ruptured cerebral aneurysm in a patient with Alagille syndrome. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Alagille syndrome; Moyamoya syndrome; Cerebral aneurysm
1. Introduction Alagille syndrome, or arteriohepatic dysplasia, is an uncommon autosomal dominant congenital multisystem *
Corresponding author. Tel.: +1 312 996 3971; fax: +1 312 996 0511. E-mail address: [email protected] (R.C. Gaba).
disorder consisting of bile duct hypoplasia associated with a variety of cardiovascular, skeletal, ophthalmologic, and neurologic abnormalities.1 Rare cerebrovascular manifestations of this condition include moyamoya syndrome, an idiopathic vascular occlusive disease, and aneurysm formation, both of which have previously been reported in isolation.2–6 To the best of our knowledge, concurrent