| Abstract|| |
Context: Thymectomy is an effective therapy for patients with myasthenia gravis, and the lesions usually identified are lymphoid hyperplasia and thymomas. Nodular epithelial proliferations, termed as microscopic thymoma, are rare. Aims: Our aim was to assess the incidence and clinicopathological features of microscopic thymomas. Setting and Design: Retrospective analyses. Materials and Methods: Thymectomies performed in 105 patients with myasthenia gravis were reviewed, and patients with microscopic thymomas were studied with respect to their clinicopathological features. These were compared with those in other reports in literature. Results: Four thymuses showed features of microscopic thymomas, an incidence of 3.8%. There were 2 males and 2 females, all myasthenic; the mean age was 31 years. The resected thymic tissues were seen as soft, capsulated adipose tissue. They showed variable degrees of involution or were atrophic. All had multifocal proliferation of ovoid-to-polygonal cells with tongue-like insinuations into the fat. After thymectomy, there was improvement in the symptoms. Eight patients reported in literature had similar clinicopathological features. Conclusions: Thorough examination of the thymectomies is required to increase the detection of these lesions for assessment of their incidence, causes, pathogenesis and functional significance.
Keywords: Microscopic thymoma, myasthenia gravis, surgical pathology, thymus
|How to cite this article:|
Vaideeswar P. Microscopic thymoma: A report of four cases with review of literature. Indian J Pathol Microbiol 2011;54:539-41
| Introduction|| |
Myasthenia gravis (MG) is a well-characterized neuromuscular autoimmune disorder, mediated by at least three autoantibodies directed to acetylcholine receptors (AChR), titin and voltage-gated potassium channel 1.4.  In over 80% of patients, muscle weakness is produced by anti-AChR antibodies.  Thymectomy is an effective therapy in such patients, and the abnormalities identified commonly are lymphoid hyperplasia and thymomas.  Occasionally, myasthenic thymectomies reveal multifocal epithelial proliferation designated as microscopic thymoma.  In this paper, we describe 4 cases of this unusual thymic pathology.
| Materials and Methods|| |
Over a span of 10 years (2000 to 2009), 107 patients had undergone thymectomy in a large tertiary care center. Two of them had Cushing's syndrome and were excluded from the study. The remaining cases with MG were further reviewed with reference to their clinicopathological features. All the thymectomies were fixed in 10% buffered formalin. The weight, dimensions and gross appearances of all these were recorded. Four to 7 samples were taken from the fibrofatty tissue and submitted for histology. Sections were embedded in paraffin, sectioned at 5 μm and stained with routine hematoxylin and eosin stain.
| Results|| |
Among the 105 thymectomies performed for MG [Table 1], 4 thymuses showed features of microscopic thymomas, an incidence of 3.8%. The clinical features have been summarized in [Table 2]. The pathological features were similar in all cases. The resected thymic tissues were sent as a single piece or multiple pieces of soft, capsulated focally hemorrhagic adipose tissue, weighing 20 to 45 g; gray-white specks were seen in 2 cases [Figure 1]a and b. There was no tumor. The thymuses showed variable degrees of involution or were atrophic. Lymphoid hyperplasia was present in 1 of them. All had multifocal un-encapsulated proliferations of ovoid-to-polygonal cells, devoid of lymphocytic infiltrate [Figure 2]a and b. At places, there were tongue-like insinuations into the fat. Mitoses, nuclear atypia or squamous differentiation was not found. After thymectomy, there was clinical improvement; one patient was lost to follow-up.
|Figure 1: (a) Thymectomy composed of capsulated fibrofatty tissue. One area (arrows) was fi rm in consistency; (b) Serial slices revealed firm white tissue, which represented atrophic thymus with multifocal hyperplasia|
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|Figure 2: (a) Islands of epithelial cells leaving the confi nes of atrophic thymus and extending into the surrounding fat (hematoxylin and eosin, x250); (b and c) The cells are ovoid with round-to-ovoid nuclei and appear benign (hematoxylin and eosin, x400)|
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| Discussion|| |
Herein, we have described microscopic thymoma, or multifocal epithelial hyperplasia, in 4 "myasthenic" thymuses, which on gross examination showed only capsulated fibrofatty tissue. A review of English literature using key term microscopic thymoma revealed only 4 published studies [Table 2]. ,,, There were 8 patients with MG, 3 males and 5 females, with a mean age of 40.4 years. The lesions were multifocal in 2 thymuses. Multifocality was seen in all our 4 cases, and this report is, to the best of our knowledge, the first of its kind in Indian literature. This rare lesion constituted 3.8% of the 105 thymectomies and was not encountered in our previous study, since it has been hypothesized that the proliferation may be a forerunner of thymoma., It is interesting to note that the term microscopic thymoma was first introduced by Rosai  in 1976. However, the description "The smallest tumor we have seen measured 1 mm; it represented an incidental microscopic finding in a thymus removed during cardiac surgery" and the illustration provided by them (their Figure 31, designated as microscopic thymoma) are also appropriate for what is currently refferred to as microthymoma, which is just a conventional thymoma measuring less than 1 cm.  Hence some authors (including us) advocate the use of the term thymic nodular epithelial hyperplasia., This hyperplasia is also encountered in atrophic thymuses, devoid of autoimmune disorders  and also as a reaction to non-thymomatous disease. 
We propose a classification wherein the nodular hyperplasia can be categorized into primary and secondary (reactive) lesions. The primary hyperplasia can be seen in asymptomatic or symptomatic patients, with or without other thymic lesions. Since the lesion can be missed by limited sectioning, thorough examination of the thymectomies is required to increase the detection of these hyperplasias for assessment of their incidence, causes, pathogenesis and functional significance.
| References|| |
|1.||Suzuki S, Utsugisawa K, Nagane Y, Satoh T, Terayama Y, Suzuki N, et al. Classification of myasthenia gravis based on autoantibody status. Arch Neurol 2007;64:1121-4. |
|2.||Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duare DD. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976;26:1054-9. |
|3.||Drachmann DB. Myasthenia gravis. N Engl J Med 1994;330:1797-810. |
|4.||Rosai J, Sobin LH. Histological typing of tumors of the thymus. World Health Organization international histological classification of tumors 2 nd ed. New York: Springer-Verlag; 1999. |
|5.||Pescarmona E, Rosati S, Pisacane A, Rendina EA, Venuta F, Baroni CD. Microscopic thymoma: Histological evidence of multifocal cortical and medullary origin. Histopathology 1992;20:263-6. |
|6.||Puglisi F, Finato N, Mariuzzi L, Marchini C, Floretti G, Betrami CA. Microscopic thymoma and myasthenia gravis. J Clin Pathol 1995;48:682-3. |
|7.||Chalabreysse L, Orsini A, Vial C, Tronc F. Microscopic thymoma. Interact Cardiovasc Thorac Surg 2007;6:133-5. |
|8.||Cornea R, Lazae E, Dema A, Herman D. A nodular hyperplasia of the thymic epithelium (so-called microscopic thymoma) Rom J Morphol Embryol 2009;50:729-31. |
|9.||Vaideeswar P, Padmanabhan A, Deshpande JR, Pandit SP. Thymoma: A pathological study of 50 cases. J Postgrad Med 2004;50:94-7. |
|10.||Rosai J, Levine GD. Tumors of the thymus. In: Atlas of tumor pathology. 2 nd series, Fascicle 13, Washington DC: Armed Forces Institute of Pathology; 1976. |
|11.||Cheuk W, Tsang WY, Chan JK. Microthymoma: Definition of the entity and distinction from nodular hyperplasia of the thymic epithelium (so-called microscopic thymoma). Am J Surg Pathol 2005;29:415-9. |
|12.||Ito W, Kojima K, Fujiwara K, Nanba Y, Yoshino T, Shinagawa K, et al. Thymic epithelial hyperplasia with nodular sclerosis Hodgkin's disease. Leuk Lymphoma 2002;43:2229-31. |
Department of Pathology (Cardiovascular and Thoracic Division), Seth G. S. Medical College and KEM Hospital, Parel, Mumbai - 400 012
[Figure 1], [Figure 2]
[Table 1], [Table 2]