Hepatosplenic T cell Lymphoma

Question 1

What is the definition of

Hepatosplenic T cell lymphoma ?

Answer 1

• aggressive T cell lymphoma with medium sized cells
• presents with the hepatic and splenic sinusoids
• cytotoxic T cell type - usually gamma delta T cells

Question 2

What is the epidemiology of

hepatosplenic T cell lymphoma ?

Answer 2

• rare, only 1-2% of all peripheral T cell lymphomas
• peak incidence:
  
  • adolescents and young adults
  • median age: 35
• male predominance

Question 3

What is the etiology of

hepatosplenic T cell lymphoma?

Answer 3

• 20% HSTLs arise in the setting of chronic immune suppression due to solid organ transplantation or chronic immune stimulation (may be a late onset, host origin PTLD)
• cases reported in kids being treated for Crohns disease
  
  • Azathioprine
  • Infliximab
• Rare cases associated with psoriasis and RA
  
  • TNF inhibitors
  • immunmodulators

Question 4

What is the localization of

HSTL ?

Answer 4

• marked splenomegaly and hepatomegaly
• no lymphadenopathy
• bone marrow is almost always involved

Question 5

What is the clinical presentation of

HSTL ?

Answer 5

• hepatosplenomegaly with systemic symptoms
  
  • thrombocytopenia, anemia, and leukopenia
• PB involvement is uncommon until late in the disease
• easy to differentiate clinically from other gamma delta, extranodal T cell lymphomas
  
  • difficult to differentiate clinically from T-LGL leukemia with gamma-delta immunophenotype

Question 6

What are the key microscopic features

of HSTL ?

Answer 6

• monotonous, medium in size with rim of pale cytoplasm
• loosely condensed chromatin with inconspicuous nucleoli
• occasional pleomorphism can be seen
• spleen
  
  • infiltrate the red pulp with white pulp atrophy
• liver and bone marrow
  
  • predominantly intrasinusoidal distribution
• IMP
  
  • disease progression can have large cell or blastic changes

Question 7

What is the immunophenotype of

HSTL ?

Answer 7

• CD3+
• CD8+
• gamma delta T cell receptor +
• CD56 +/-
• TIA-1 and Granzyme M +
• CD4 and CD5 -
• Granzyme B and Perforin -
• KIR receptor CD94 dim to absent

** this phenotype means they are mature, non-activated cytotoxic T cells with aberrancy

Note: a minority of cases appear to be alpha/Beta type which is considered a variant of the more common gamma delta type

Question 8

What would the phenotype of T-LGL

leukemia with gamma delta phenotype be

and the pattern of bone marrow involvement ?

Answer 8

• CD8 and CD57+
• granzyme B +
• diffuse, may be subtle interstitial infiltrate rather than sinusoidal

Question 9

What is the postulated normal

counterpart of HSTL ?

Answer 9

• peripheral gamma/delta cytotoxic T cells
• innate immune system
• memory immunophenotype

Question 10

What is the genetic profile of

HSTL?

Answer 10

• rearranged TCR Gamma and beta genes
• IMP
  
  • isochromosome 7q present in most cases
  • disease progression includes additional FISH patterns of 2-5 copes of (i)7q10 or numerical or structural abberations to the second chromosome 7
  • ring chromosomes of 7 have also been identified
• Trisomy 8 may be present
• EBV ISH is negative

Question 11

What gene mutations have been

identified in about 40% of cases ?

Answer 11

• missense mutations of STAT5B and STAT3 (40%)
  
  • consistent with genes of JAK2/STAT pathway
• chromatin remodelling genes have also been implicated in 60% of cases
  
  • SETD2
  • INO80
  • ARID1B

Question 12

What are the prognostic and predictive

factors for HSTL ?

Answer 12

• clinical course is aggressive
• initially respond to chemotherapy but relapses are seen in a majority of patients in < 2 years