Hematopathology / ADULT T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA

We analyzed the clinicopathologic and molecular findings in 26 adults (age 16-72 years) with T-cell acute lymphoblastic leukemia (T-ALL) and observed features that correlated with age. Patients older than 60 years (n = 5) had a low frequency of hepatosplenomegaly (0 [0%]), anterior mediastinal mass (1 [20%]), and lymphadenopathy (2 [40%]), and completely responded to chemotherapy (4 of 4). The T-ALL in this group commonly expressed myeloid antigens (4 [80%]), had lineage-inappropriate gene rearrangements (2/3 [67%]) and chromosome 2 deletion (3/4 [75%]), and exclusively used the VIII or VIV families of the T-cell receptor (TCR) gamma gene. In comparison, patients 16 to 60 years old (n = 21) more commonly had an anterior mediastinal mass (8 [38%]), hepatosplenomegaly (10 [48%]), and lymphadenopathy (16 [76%]). The tumors in these patients commonly used the TCR gamma gene VI or VII families (17/25 total rearrangements [68%]). Myeloid antigen expression (5 [24%]) and lineage inappropriate gene rearrangements (4/15 [27%]) were uncommon. Within this group, CD1a expression correlated with age 28 to 60 years. These results illustrate considerable age-related heterogeneity in adult T-ALL, which may reflect differences in tumor cell maturation. Malignant lymphoid neoplasms of precursor T-cell origin have been designated as precursor T-cell lymphoblastic leukemia/lymphoma in the recently published World Health Organization classification for hematologic neoplasms.1 Most of these neoplasms arise in patients in the second and third decades of life, who commonly develop an anterior mediastinal mass, lymphadenopathy, and organomegaly. Although most patients have involvement of the bone marrow or peripheral blood at the time of diagnosis, the true incidence of leukemic involvement is unclear.2 Arbitrary cutoffs that have been used to separate acute lymphoblastic leukemia (ALL) from lymphoblastic lymphoma include the presence of circulating blasts and more than 25% blasts in the bone marrow.3 T-cell ALL (T-ALL) represents approximately 15% to 20% of all cases of ALL in Western countries. Only a small subset of these tumors occur in adults, and this disease is less common with increasing patient age, being truly rare in patients exceeding 60 years of age.4-7 Owing to its relative rarity, T-ALL arising in adults, particularly in elderly people, has not been studied extensively. While older age has been associated with worse prognosis in ALL, most of these studies have focused predominantly on precursor B-cell ALL, which is far more common than T-ALL in the elderly.4-9 Furthermore, although it is well documented that precursor B-cell ALL occurring in elderly people (ie, older than 60 years) has a poor prognosis, possibly related to a relatively high prevalence of the Philadelphia chromosome, the prognosis of T-ALL in this age group is unclear. To address these issues, we collected all cases of T-ALL in adult patients at our institution during a 6-year interval, defined for the purposes of this study as older than 15 years Hematopathology / ORIGINAL ARTICLE Am J Clin Pathol 2002;117:252-258 253 © American Society for Clinical Pathology of age at time of diagnosis. We identified 26 cases and analyzed their clinicopathologic, immunophenotypic, cytogenetic, and molecular features. Our results demonstrate significant heterogeneity among cases of adult T-ALL that correlate with patient age, with T-ALL in elderly patients (older than 60 years) having distinctive clinical and molecular features. Materials and Methods