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Case 22 - Discussion

Hematopathology Case

 

CD20 CD3
CD3 CD4
CD5 CD7
CD8 TIA-1
  • Additional immunostains show that the tumor cells are negative for CD5, CD30 and Granzyme B.

  • The patient in this case had no history of Celiac disease, and the tumor cells are monotonous and small to intermediate in size. They express CD8 but not CD103. Overall, it is consistent with entropathy-associated T-cell lymphoma (EATL), type II.

  • The major differential diagnosis includes classic type EATL and extranodal NK/T cell lymphoma. Classic EATL is often associated with Celiac disease and typically shows large polymorphic tumor cells with expression of CD103 and no expression of CD8. Extranodal NK/T-cell lymphoma typically shows prominent vascular proliferation and strong association with EBV infection. Both types of EATL are positive for clonal TRG@ gene rearrangement, whereas TRG@ is germline in extranodal NK/T-cell lymphoma.

Flow cytometry:

An abnormal population of T-cells is detected, expressing bright CD45, CD2, cytoplasmic CD3, CD7, CD8, and CD11c. They are negative for surface CD3, CD5, CD25, CD26 and CD103.

                                            

     Total events       Bright CD45+         

     analyzed = 24701   events = 8981 (85% of   

                        total nucleated cells)    

        CD45+/CD14-           93%             

        CD19+/CD3-            <2%

        CD3+/CD19-             8%

        CD19+/CD20+           <2%

        CD19+/CD38+           <2%

        CD19+/CD10+           <2%

        CD5+/CD19+            <2%

        CD5+/CD19-             6%

        CD19+/CD23+           <2%

        CD19+/FMC+            <2%

        CD11c+                72%

        CD25+                  3%

        CD103+                11%

        CD26+                  2%

        CD2+/CD7+             91%

        CD3+/CD5+              5%

        CD4+                   7%

        CD8+                  90%

        CD16+                  9%

        CD3-/CD56+            <2%

        cCD3+                 86%

        CD7+/nTDT+            <2%

 

Enteropathy-Associated T Cell Lymphoma (EATL), Classic Type

  • Typically in sixth and seventh decades of life, M=F

  • Most commonly in northern Europe, rarely in Far East

  • Most cases have HLADQA1*0501, DQB*0201 genotype

  • Associated with celiac disease

  • Presentations: mostly malabsorption, abdominal pain, ichthyotic rash and finger clubbing; or acute abdominal emergency due to small intestinal perforation or hemorrhage

  • Mostly tumor involves multiple segments of small intestine with dissemination to mesenteric lymph nodes, liver, spleen, bone marrow, lung, and skin

  • Gross: most cases arise in the jejunum, and may involve any part of small intestine and occasionally colon and stomach; usually multifocal and forms ulcerating nodules, plaques, strictures, or large masses; mesentery and mesenteric lymph nodes often infiltrated

  • Histopathology

    • Variable histologic features

    • Tumor cells: mostly highly pleomorphic, bizarre, multinucleated

    • Some cases: more monomorphic cells, prominent central nucleoli

    • Some cases: extensive necrosis, abundant inflammatory cells, particularly eosinophils

    • Usually prominent intraepithelial tumor cells

    • Granulomas may be present

    • Non-neoplastic intestinal mucosa: villous atrophy, crypt hyperplasia, plasmacytosis in lamina propria, ↑intraepithelial lymphocytes

    • Mesenteric lymph node with predominant intrasinusoidal and/or paracortical infiltrate and often necrosis

  • Immunophenotype

    • Positive: CD3, CD7, CD103, granzyme B, TCR-αβ

    • CD30+ in cases with anaplastic cells

    • Negative: CD4, CD8, CD56, TCRγδ

  • Clonal rearrangement of TCRαβ; HLADQA1*0501, DQB*0201 genotype in almost all cases; +9q31.3 or -16q12.1 > 80% cases, also gains at 1q32.2-q41 and 5q34-q35.2

  • Very unfavorable clinical course

Enteropathy-Associated T Cell Lymphoma (EATL),  Type II

  • Usually not associated with Celiac disease

  • Morphology:

    • Tumor cells: slightly larger than normal small lymphocytes, with a rim of pale cytoplasm, no overt atypia

    • Often monomorphic sheet-like infiltrates in the submucosa and muscularis propria

    • Intraepithelial lymphocytosis maybe so extreme as to virtually obscure the epithelial cells

  • Immunophenotype

    • Positive: CD3, CD8, CD56, and granzyme B

  • HLADQA1*0501, DQB*0201 genotype in 30-40% cases; + 9q31.3 or -16q12.1 in most cases, but no gains at 1q32.2-q41 or 5q34-q35.2; gain of 8q24 (MYC) in > 70% of cases

 

Classic EATL

Type II EATL

Frequency

80%-90%

10%-20%

Morphology

Variable

Monomorphic small cell

Immunophenotype

 

 

   CD8

Negative (20%+)

Positive

   CD56

Negative

Positive

   HLA-DQ2/-DQ8

90% positive

30%-40% positive

   Granzyme B

Positive

Positive

Genetics

 

 

   +9q31.3 or −16q12.1

86%

83%

   +1q32.2-q41

73%

27%

   +5q34-q35.2

80%

20%

   +8q24 (MYC)

27%

73%