Thoracic Pathology: A Volume in the High Yield Pathology Series 1st Edition

Mediastinal T-Lymphoblastic Lymphoma (T-LBL)

Definition

• T-LBL is a neoplasm of lymphoblasts committed to T-cell lineage. When peripheral blood and bone marrow involvement is extensive, the term acute lymphoblastic leukemia (T-ALL) is used

Pathogenesis

• T-cell progenitor or thymic lymphocytes are considered the normal counterparts for T-ALL and T-LBL, respectively

Clinical features

Epidemiology

• T-LBL comprises approximately 85% to 90% of all lymphoblastic lymphomas; most frequent in adolescent males but may be seen in any age group

• Primarily involves the thymus and lymph nodes in the mediastinum; also extranodal involvement

Presentation

• T-LBL is frequently seen as a mass in the anterior mediastinum, often exhibiting rapid growth. Patients sometimes present with respiratory emergency; pleural effusions can also occur

• Patients with T-ALL present with large mediastinal or other tissue masses with a high leukocyte count

Prognosis and treatment

• Prognosis of T-LBL depends on the age of the patient, stage, and lactate dehydrogenase levels

• T-ALL in childhood has a worse outcome than B-ALL. Patients have a higher risk of induction failure, early relapse, and isolated central nervous system relapse. In adults, T-ALL has a better prognosis than B-ALL because of the lower incidence of adverse cytogenetic abnormalities

Pathology

Histology

• In smears, medium size neoplastic cells with high nuclear/cytoplasmic ratio; round to irregular to convoluted nuclear outlines. Condensed nuclear chromatin with no evident nucleoli or larger blasts with finely dispersed chromatin and relatively prominent nucleoli with numerous mitotic figures may be seen. Cytoplasmic vacuoles may also be present

• In the thymus, complete replacement of thymic parenchyma with a permeative pattern of infiltration is noted. Lymph nodes generally show complete effacement of architecture. Occasionally, partial involvement in a paracortical location with sparing of the germinal centers may be seen

• T lymphoblasts usually positive for and variably express CD1a, CD2, CD3, CD4, CD5, CD7 and CD8; CD7 and CD3 are most often positive. Tumor cells express TdT, CD99, CD34, and CD1a consistent with their precursor nature

• Other markers that may be expressed: CD79a (10% of cases), CD13, and CD33 (19%-32%), nuclear TAL-1 (29%-48%)

• T-ALL/T-LBL can be further stratified into different stages of intrathymic differentiation according to the expression profile of various antigens: pro-T, pre-T, cortical T, and medullary T. Studies have shown correlation between stages of T-cell differentiation and survival

• The most common recurrent cytogenetic abnormality involves the alpha and delta TCR loci

Main differential diagnoses

• Burkitt lymphoma: composed of intermediate size B cells with prominent nucleoli negative for TdT and CD34

• B-ALL: positive for B-cell markers

• Mature T-cell lymphoproliferative process: negative for CD34 and TdT

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Fig 1 Mediastinal T-lymphoblastic lymphoma. Mediastinal lymph node biopsy from a 17-year-old with anterior mediastinal mass and lymphadenopathy, showing effacement of architecture in this low power.

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Fig 2 Mediastinal T-lymphoblastic lymphoma. Medium-power view of case in Fig 1. Residual scattered normal lymphocytes, which are smaller and darker, are present.

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Fig 3 Mediastinal T-lymphoblastic lymphoma. High-power view of case in Fig 1 showing neoplastic cells with rounded nuclear contours, high nuclear–cytoplasmic ratio, and fine dispersed chromatin with distinct nucleoli.

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Fig 4 Mediastinal T-lymphoblastic lymphoma. Low-power image of CD4 stain showing strong, membrane/surface immunoreactivity.

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Fig 5 Mediastinal T-lymphoblastic lymphoma. High-power image for CD8 immunostain shows diffuse membranous pattern. Strong immunoreactivity for CD4 and CD8 supports the T-cell lineage of this lesion.

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Fig 6 Mediastinal T-lymphoblastic lymphoma. TdT stain showing nuclear positivity in tumor cells.

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Fig 7 Mediastinal T-lymphoblastic lymphoma. Frozen section of same case as in Fig 1. Small blue cells are seen replacing the lymph node architecture.

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Fig 8 Mediastinal T-lymphoblastic lymphoma. Frozen section of same case as in Fig 1. High power shows both crushed cells and well-preserved cells, which can be identified as lymphoid.