Clinical Brief
Thymoma Associated with Myasthenia Gravis in Infancy J.B. Ghosh, Mahua Roy1 and Tanushree Peters1 Institute of Post Graduate Medicine and Research, Kolkata, 1North Bengal Medical College and Hospital, Darjeeling, India
ABSTRACT Thymomas are associated with various autoimmune disorders in adults, most commonly with myasthenia gravis (MG). In MG antibodies developed against acetylcholine (ACh) receptors, resulting weakness of muscle after repeated use and recovery following a period of rest. However, MG due to thymoma is extremely rare in pediatric age group.1We report an infant with MG due to invasive thymoma. [Indian J Pediatr 2009; 76 (10) : 1057-1058] E-mail: drmahuaroy@ gmail.com
Key words : Myasthenia gravis (MG); Thymoma
Thymoma is exceedingly rare in the first 20 years of life and only a few well-defined cases are documented till date. Thymomas in adults are commonly associated with various autoimmune diseases, the most frequent being myasthenia gravis (MG). 1 However, this association has been reported very rarely in children.2 We report an infant with such rare association. To our knowledge, this is the youngest patient of myasthenia gravies associated with thymoma reported so far.
REPORT OF CASE An 11-mo-old male baby presented with gradual onset of drooping of right eyelid since 6 mo of age, appearing late in the day but disappearing after sleep. The child was a full-term, delivered normally and born out of a non-consanguineous marriage. There was no history suggestive of myasthenia in the mother. Neonatal period was uneventful and the milestones were normal. There was no history of difficulty in swallowing or respiration. Examination revealed an infant with normal physical and mental development. Neurological examination revealed ptosis, moderate in right and mild in left side with normal pupillary reflex in both eyes. The child was responsive to both visual and auditory stimuli. Mild sagging of face was noticed with normal gag reflex. No in-coordination, hypotonia, ataxia, or
Correspondence and Reprint requests : Dr. Mahua Roy. (MD Ped). 931, Jawpur Road, Kolkata- 700074, India. [Received July 17, 2008; Accepted October 15, 2008]
Indian Journal of Pediatrics, Volume 76—October, 2009
areflexia were noted. The child was examined twice after a period of sleep and similar findings were recorded again. No arrhythmia was detected by cardiovascular examination. Other systemic examinations were unremarkable. With a clinical diagnosis of MG in an infant of a non-myasthenic mother, the infant was investigated. Neostigmine tests (0.320 mg) given intramuscularly showed a good response in the form of improvement in ptosis. Repetitive nerve stimulation (RNST) was done on both left & right facial nerve which showd decremental response bilaterally with improvement by neostigmine temporarily. Anti- acetylcholine receptor antibody titer was 1.76 nmol/L (normal less then 0.25nmol/L). Chest X- ray showed mediastenal widening. High-resolution computerized tomography scans (HRTC) of thorax detected anterior mediastinal mass with encasement of mediastinal vascular structure and aortic arch suggestive of thymoma. Thyroid function test, anti nuclear antibody, and CT scan of brain were within normal limit. The child was put on oral pyridostigmine (7mg/kg/day), 6 times a day during waking hours and he showed a moderate response in the form of improvements in ptosis. He was referred to cardio- thoracic department for thymectomy after giving intravenous immunoglobulin. Removal of total tumor mass was not possible due to extensive vascularity and invasion into the great vessels (stage - III). Histopathology of removed mass revealed large, polygonal tumor cells that are arranged in loose networks exhibit abundant eosnophilic cytoplasm and large vesicular nuclei with prominent large nucleoli with islands of epithelial cell and sprinkle of lymphocytes suggestive of cortical thymoma (B2). 3 Immediate postoperative period was uneventful but 1057
J.B. Ghosh et al there was insignificant improvement of MG after thymectomy. Due to incomplete resection and invasive character of thymoma further treatment was planned (chemo/ radiation) but his parents refused to give consent to it. For the next 2 months he was on oral pyridostigmine therapy and doing well, unfortunately after that he was lost to follow up.
DISCUSSION MG is characterized by abnormal fatigability after repeated or sustained muscle activity and subsequent improvement after rest. Peak incidence is seen in young adults but it may also occur in infancy and childhood. One can recognize three separate entities in childhood period: (a) transient neonatal myasthenia in an infant of myasthenic mother, (b) congenital or infantile myasthenia in an infant of non-myasthenic mother and (c) juvenile myasthenia similar to adult myasthenia. 4 Our patient was absolutely all right for first 6 mo of life and there was no history of less intra-uterine movement, difficult delivery, and feeding difficulty. The weakness was gradually progressive and his mother was non-myasthenic, so clinically it was not a case of transient neonatal myasthenia. The therapy consists of repetitive doses of cholinesterase inhibitor. Steroids, immunosuppressants, plasmapheresis or thymectomy are not helpful. Drugs such as curare, gallamine, succinylcholine, quinine, quinidine, neomycine, procaine and morphine should be avoided. 4 Juvenile myasthenia gravis comprises approximately 1% of all cases of myasthenia gravis.5 It is considered to be a variant of adult myasthenia with similar clinical and autoimmune mechanism of production. 6 In juvenile MG seen in pediatric population, anti Ach receptor antibodies should be assayed in plasma, but it is inconsistently demonstrated. About 30% of affected adolescent show elevation, but only occasionally demonstrated in plasma of pre-pubertal children. 5 Unlike our case, high level of anti Ach receptor antibody in an infant’s plasma is extremely rare.
generalized MG, whereas in children it is less than 5%. When thymoma occurs in children, it is likely to be malignant.6 In the present case HRCT of thorax revealed thymoma in anterior mediastinum. Treatment options of juvenile MG are multiple doses of anticholiesterases (neostigmine, pyridostigmine). Long-term steroid therapy is effective due to autoimmune basis of the disease. Thymectomy is most effective in patients with high titer of anti Ach receptor antibodies in the plasma and who are symptomatic for less than 2 yr of age. 7 Temporary remissions may be achieved by plasmapheresis and or intravenous immunoglobulin (IVIG) in those patients with high titer of anti Ach receptor antibodies. Refractory cases may respond to rituximab, a monoclonal antibody to B cell CD antigen.5 Contributions: JBG-Concept and design, MR-Literature Review and TP. Manuscript preparation. Conflict of Interest: None Role of Funding Source: None
REFERENCES 1. Pescarmona E, Giardini R, Brisigotti M et al. Thymoma in childhood: a clinicopathological study of five case. Histopathology 1992; 21: 45-68. 2. Wayne LF, Patrick JB, Alexander AG, Dennis CS, Lawrence TC. Thymoma and myasthenia gravis in a 4-year-old child case report and review of the literature. Cancer 1985; 56: 2703–2706. 3. Okumura M, Ohta M, Tateyama H et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 2002; 94 : 624-632. 4. Dubowitz, V. Myasthesia gravis. In Schaffer AI, Markowitz M eds. “Muscle disorders in childhood,”-”Major Problems in Clinical Practice,”. , Philadelphia and London. W.B. Saunders Company Ltd., 1978; 191-201. 5. Kini PG. Juvenile myasthenia gravis with predominant facial weakness in a 7-year-old boy. Int J Pediatr Otorhinolaryngol 1995; 32: 167-169. 6. Jaison SG, Abraham AP. Childhood myasthenia gravis in a toddler. Ind J Ophthalmol 1995; 43 : 136-138. 7. Sarnat HB. Neuromuscular disorders. In Behrman RE, Kliegman RM, Jenson HB, Stanton BF, eds. Nelson textbook of pediatrics, 18th ed. Philadelphia, WB saunders Co; 2008: 2554-2557.
Thymoma is present in 15% of adults with
1058
Indian Journal of Pediatrics, Volume 76—October, 2009
