This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ascani, S. Articles by Pileri, S. A. Search for Related Content PubMed PubMed Citation Articles by Ascani, S. Articles by Pileri, S. A. Social Bookmarking                            What's this?

Difficult Diagnostic and Therapeutic Cases

CASE 1. True Thymic Hyperplasia in a Patient Treated for T-Cell Lymphoma

Unit of Hematopathology, Institute of Hematology and Clinical Oncology L. & A. Seràgnoli, Bologna University, St Orsola Hospital, Bologna; Institute of Hematology, Perugia University, Perugia, Italy; and Institute of Pathology, Basel University, Basel, Switzerland

A 24-year-old woman presented with rapidly enlarging supraclavicular lymphadenopathy. Biopsy showed complete effacement of the lymph node by a neoplastic population morphologically consistent with lymphoma/leukemia of precursor T-lymphocytes (so-called T-cell lymphoblastic lymphoma/leukemia). The phenotypic profile was as follows: CD34⁺, TdT⁺, CD3⁺, CD1a^-, CD4^-, CD8^-, and Ki-67/MIB-1 95%. No involvement of the bone marrow and peripheral blood was found. She underwent chemotherapy according to the L2 protocol, followed by autologous bone marrow transplantation, which produced complete remission. Six months later, a follow-up computed tomography scan displayed a newly developed mass in the anterior-superior mediastinum that was regarded as suspicious for disease relapse (Fig 1). Given that no other signs and symptoms of malignant lymphoma were present, the mediastinal tumor was surgically removed. On gross examination, it was an encapsulated bilobate mass that measured 11 x 8 x 3.5 cm and weighed 180 g. At light microscopy, the mass consisted of normal thymic tissue with typical lobular architecture, Hassall's corpuscles, and well-defined cortical and medullary compartments (Fig 2, low power with cortex on left and medulla with Hassall's corpuscles on right; Fig 3, high power, with cortical thymocytes and admixed macrophages and epithelial cells). Immunohistochemistry on paraffin sections were carried out by the alkaline phosphatase-antialkaline phosphatase complexes technique [1] with application of specific antibodies against cytokeratins, CD1a, CD2, CD3, CD4, CD8, CD20, CD30, Bcl-2 oncogene product, Bcl-6 protein, TdT, Oct-1, Oct-2, BOB.1, and Ki-67, which showed the expected positivities both in the cortex and medulla [2,3] for true thymic hyperplasia (TTH). Most, if not all, cortical thymocytes did express the proliferation-associated nuclear antigen Ki-67. Interestingly, no lymphoid follicles were observed, in contrast to the thymic lymphoid hyperplasia occurring in patients with myasthenia gravis and other autoimmune disorders [4]. Twenty-eight months after the onset of disease, the patient died of acute respiratory failure as a result of Cytomegalovirus pneumonitis. Unfortunately, the permission for autopsy was denied.

View larger version (55K): [in this window] [in a new window]   Fig 1.

View larger version (163K): [in this window] [in a new window]   Fig 2.

View larger version (153K): [in this window] [in a new window]   Fig 3.

Based on the present case, one should be aware that in patients with a previous history of T-cell lymphoblastic lymphoma/leukemia or other malignancy, a newly developing mediastinal mass does not always herald a disease relapse with TTH belonging to the spectrum of possible underlying conditions. Notably, under these circumstances, the positron emission tomography scan is of no diagnostic value, since both TTH and T-cell lymphoblastic lymphoma/leukemia consist of highly proliferating cells that avidly uptake 2-deoxy-2 fluoro-D-glucose. In order to achieve the correct diagnosis and to avoid the risk of inappropriate therapeutic decisions (including chemotherapy and total thymectomy), a biopsy is warranted, which should be as large as to allow the identification of the normal thymic structure in case of TTH versus organ infiltration with destruction of the epithelial network in T-cell lymphoblastic lymphoma/leukemia.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Cordell JL, Falini B, Erber WN, et al: Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229, 1984[Abstract]

2. Hyjek E, Chadburn A, Liu YF, et al: BCL-6 protein is expressed in precursor T-cell lymphoblastic lymphoma and in prenatal and postnatal thymus. Blood 97:270–276, 2001[Abstract/Free Full Text]

3. Marafioti T, Ascani S, Pulford K, et al: Expression of B-lymphocyte-associated transcription factors in human T-cell neoplasms. Am J Pathol 162:861–871, 2003[Abstract/Free Full Text]

4. Pirronti T, Rinaldi P, Batocchi AP, et al: Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings. Acta Radiol 43:380–384, 2002[CrossRef][Medline]

5. Rizk G, Cueto L, Amplatz K: Rebound enlargement of the thymus after successful corrective surgery for transposition of the great vessels. Am J Roentgenol Radium Ther Nucl Med 116:528–530, 1972[Medline]

6. Lee Y, Moallem S, Clauss RH: Massive hyperplastic thymus in a 22 month old infant. Ann Thorac Surg 27:356–358, 1979[Abstract]

7. Mishra SK, Melinkeri SR, Dabadghoo S: Benign thymic hyperplasia after chemotherapy for acute myeloid leukemia. Eur J Haematol 67:252–254, 2001[CrossRef][Medline]

8. Budavari AI, Whitaker MD, Helmers RA: Thymic hyperplasia presenting as anterior mass in 2 patients with Graves disease. Mayo Clin Proc 77:495–499, 2002[Abstract/Free Full Text]

9. Inoue K, Sugio K, Inoue T, et al: Hyperplasia of the thymic gland in a patient with Graves' disease. Ann Thorac Cardiovasc Surg 6:397–400, 2000[Medline]

10. Woywodt A, Verhaart S, Kiss A: Massive true thymic hyperplasia. Eur J Pediatr Surg 9:331–333, 1999[Medline]

11. Suster S, Rosai J: Thymus, in Sternberg SS (ed): Histology for pathologists. New York, Raven Press, 1992, pp 261–277

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. B. C C. Neto, M. C. Machado, F. Mesquita, N. R. de Castro Musolino, A. C. Toscanini, G. Ochman, V. A. S Cescato, R. Marino Jr, and M. J. Teixeira Thymus hyperplasia after resolution of hypercortisolism in ACTH-dependent Cushing's syndrome: the importance of thymic vein catheterization. Eur. J. Endocrinol., June 1, 2006; 154(6): 807 - 811. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ascani, S. Articles by Pileri, S. A. Search for Related Content PubMed PubMed Citation Articles by Ascani, S. Articles by Pileri, S. A. Social Bookmarking                            What's this?