Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ DEFINITION ++ T-cell large granular lymphocytic leukemia (T-LGLL) results from an indolent clonal expansion of large granular lymphocytes (LGLs) with a T-cell (CD3+) phenotype and a clonal T-cell receptor gene rearrangement(s), usually α and β chains. Diagnosis of T-LGLL requires an arbitrary level in the blood of CD3+CD8+CD57+ cells that is greater than 0.5 × 109/L maintained for at least 6 months. CD5 is dimly expressed. Chronic lymphoproliferative disorders of natural killer cells (CLPD-NK) is a clonal expansion of LGL with a NK cell (CD3–) phenotype. It lacks convenient markers to determine clonality, such as antigen receptor rearrangements. (See Chap. 67.) Diagnosis of CLPD-NK requires an arbitrary level in the blood of CD3–CD8+CD16+ and/or CD16+CD56+ cells that is greater than 0.75 × 109/L maintained for at least 6 months. +++ LARGE GRANULAR LYMPHOCYTIC LEUKEMIAS +++ Etiology and Pathogenesis ++ In T-LGLL, it is postulated, based on complementarity determining region 3 (CDR3) patterns and Vβ family usage, that this malignancy arises secondary to chronic antigen stimulation. Most patients are not infected with either HTLV-I or HTLV-II. Cytomegalovirus is possibly implicated in rare cases of CD4+ T-LGLL. Chronic immune dysregulation and aberrant cytokine production may contribute to the LGLL proliferation and survival. Platelet-derived growth factor (PDGF) and interleukin (IL)-15 appear to be the key cytokines regulating LGLL proliferation and survival. Constitutive overexpression of Fas (CD95) and the Fas ligand (CD178), which also is found at high levels in patients’ sera, may also contribute to the LGL proliferation. Chronic activation of the JAK/STAT3 pathway is a hallmark of LGLLs. Gain-of-function STAT3 mutations have been demonstrated in 28% to 75% of cases of T-LGLL and 30% to 48% of cases of CLPD-NK. STAT5B mutations are also found but less frequently. +++ Clinical Features ++ About half the patients with T-LGLL are asymptomatic at diagnosis, and diagnosis is based on examination of blood (Table 58–1). About half of patients have palpable splenomegaly. About one-third of patients have recurrent bacterial infections. “B symptoms” (eg, low-grade fevers, night sweats, and/or weight loss) (aggressive variant) are very infrequent. About one-fourth of patients have rheumatoid arthritis, often with features of Felty syndrome. Less than one-tenth of patients have lymphadenopathy. ++Table Graphic Jump LocationTABLE 58–1CLINICAL FEATURES OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIAView Table||Download (.pdf) TABLE 58–1 CLINICAL FEATURES OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA Pandolfi (1990) Loughran (1993) Dhodapkar (1994) Semenzato (1997) Neben (2003) Bareau (2010) Number of patients 151 129 68 162 44 201 Median age 55 57 61 59 63 59 Male/female 1.3 0.8 1 0.8 1.0 0.8 Symptomatic 72% – 69% – 73% 82% Splenomegaly 50% 50% 19% 50% 35% 24% Hepatomegaly 34% 23% 1% 32% – 10% Adenopathy 13% 1% 3% 13% 5% 6% B symptoms – – 12% – – 7% Infections 38% 39% 15% 56%... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Download the Access App: iOS | Android Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.