Surgical Pathology Criteria–

Peripheral T Cell Lymphoma Unspecified

Differential Diagnosis

Angioimmunoblastic T Cell Lymphoma Peripheral T Cell Lymphoma Unspecified
Characteristic morphology with vascular proliferation, follicular dendritic cell proliferation, and polymorphic infiltrate including immunoblasts Morphology varies widely but does onot show all of the features of AITL
Germinal center T cell phenotype (CD10+, CXCL13+) ini 60-90% Usually not germinal center phenotype (only in 10-30% of cases)
Infrequent T cell antigen loss Frequent T cell antigen loss (CD5, CD7)
Characteristic clinical presentation with pruritic rash, immune dysregulation Rash and immune dysregulation uncommon
Both are clinically aggressive nodal T cell lymphomas arising in similar patient populations

 

Peripheral T Cell Lymphoma Unspecified Primary Systemic Anaplastic Large Cell Lymphoma
T cell immunophenotype T cell or null cell immunophenotype
Often CD30+ Always CD30+
ALK1 negative >60% of cases ALK1 positive*
Variety of large pleomorphic cells including hallmark-type cells may be present Hallmark cells present
Both may show large pleomorphic T cells with abundant cytoplasm and be CD30+.  *Cases currently classified as anaplastic large cell lymphoma which are ALK negative are clinically indistinguishable from peripheral T cell lymphoma, unspecified and will likely be merged with this category in the future.

 

Peripheral T Cell Lymphoma Unspecified Extranodal NK/T Cell Lymphoma, Nasal Type
Predominantly nodal, but commonly involves extranodal sites Predominantly extranodal, but may secondarily involve lymph nodes
T-cell receptor rearrangement usually present T-cell receptor usually in germline configuration
Admixed B immunoblasts EBV+ in 1/3 NK/T cell population EBV+
Rare cases CD56+ (~10%) Most cases CD56+
Both are aggressive CD3+ lymphomas which may be CD56+ and show EBV reactivity.

 

Peripheral T Cell Lymphoma Unspecified T Cell / Histiocyte Rich Diffuse Large B Cell Lymphoma
May show monomorphous or polymorphous B cell proliferation, scattered or in sheets <10% scattered large B lymphocytes; morphology varies, but is generally uniform within a case
Monoclonal immunoglobulin gene rearrangement sometimes present (~1/3) Monoclonal immunoglobulin gene rearrangement usually present
T cells usually monoclonal T cells polyclonal
T cell population usually overtly cytologically malignant Background of small T lymphocytes, sometimes with numerous epithelioid histiocytes
Aberrant loss of T cell markers common No aberrant loss of T cell markers
Both show large B cell population in a background of T cells and are clinically aggressive

 

Peripheral T Cell Lymphoma Unspecified Nodular Lymphocyte Predominance Hodgkin Lymphoma
Spectrum of B cells usually present including immunoblasts and Reed-Sternberg-like cells. Scattered L&H cells with “popcorn” nuclei, smaller B cells.
Lymph node usually diffusely effaced; T-zone variant preserves germinal centers Large nodules and sometimes diffuse areas efface the lymph node.
T cell population cytologically malignant T cell population cytologically bland
Aberrant loss of T cell markers common No aberrant loss of T cell markers
T cells usually monoclonal or oligoclonal T cells polyclonal
Monoclonal immunoglobulin gene rearrangement sometimes present (~1/3) Monoclonal immunoglobulin gene rearrangement may be detectable
Aggressive clinical course Generally indolent with localized lymphadenopathy; but may coexist with or recur as diffuse large B cell lymphoma.
Both show scattered large atypical B cells in a T cell rich background

 

Peripheral T Cell Lymphoma Unspecified Classical Hodgkin Lymphoma
Spectrum of B cells usually present including immunoblasts and Reed-Sternberg-like cells. B cells are predominantly large mononuclear and multinucleated Reed-Sternberg variants
Lymph node usually diffusely effaced; T-zone variant preserves germinal centers Broad bands of fibrosis present in the most common (nodular sclerosis) variant
T cell population cytologically malignant T cell population cytologically bland
Aberrant loss of T cell markers common No aberrant loss of T cell markers
T cells usually monoclonal or oligoclonal T cells polyclonal
Monoclonal immunoglobulin gene rearrangement sometimes present (~1/3) Monoclonal immunoglobulin gene rearrangement rarely detectable
Both may show CD30+, CD15+, EBV+, CD20+ large cells with Reed-Sternberg morphology and polymorphic background infiltrate including plasma cells, histiocytes, and eosinophils; generalized lymphadenopathy with constitutional symptoms.

 

Peripheral T Cell Lymphoma Unspecified Reactive T Zone Hyperplasia: Viral (e.g. Infectious Mononucleosis)
Necrosis generally absent Necrosis may be present
EBV often positive in B cells EBV positive in T cells in infectious mononucleosis
Immunoblasts/Reed-Sternberg-like cells B lineage Immunoblasts/Reed-Sternberg-like cells T lineage
T cells usually monoclonal or oligoclonal T cells polyclonal
Aberrant loss of T cell markers common No aberrant loss of T cell markers
1/3 also show B cell clonality EBV-associated monoclonal B-cell proliferations rarely develop (especially with immunodeficiency/immunosuppression).
Aggressive clinical course with generalized lymphadenopathy or mass lesions. Localized lymphadenopathy, viral syndrome, viral serologies.
Both may show paracortical expansion with numerous immunoblasts and sometimes Reed-Sternberg-like cells, residual germinal centers, increased vascularity

 

Peripheral T Cell Lymphoma Unspecified Reactive T Zone Hyperplasia: Anticonvulsant-associated
Necrosis generally absent Necrosis may be present
EBV often positive in B cells EBV negative
Immunoblasts/Reed-Sternberg-like cells B lineage Immunoblasts/Reed-Sternberg-like cells T lineage
Aberrant loss of T cell antigens common No aberrant loss of T cell antigens
T cells usually monoclonal or oligoclonal T cells polyclonal
1/3 also show B cell clonality B cells polyclonal
Aggressive clinical course despite chemotherapy. History of anticonvulsant exposure; symptoms resolve with drug withdrawal.
Both may show paracortical expansion with numerous immunoblasts, sometimes Reed-Sternberg-like cells, residual germinal centers, increased vascularity.

 

Peripheral T Cell Lymphoma Unspecified Reactive T Zone Hyperplasia: Dermatopathic Lymphadenopathy
No increase in interdigitating reticulum cells/Langerhans histiocytes Pale-staining S100+/CD1a+ interdigitating reticulum cells, Langerhans histiocytes
Histiocytes increased but not pigment-laden Hemosiderin and pigment-laden histiocytes
Cytologically malignant T cell population Cytologically bland*
Aberrant loss of T cell antigens common No loss of T cell antigens*
T cells usually monoclonal; 1/3 also show B cell clonality T cells polyclonal*
Follicular dendritic cell proliferation outside germinal centers No follicular dendritic cell proliferation outside germinal centers
Aggressive clinical course. Clinically indolent*.
Both may show paracortical expansion with admixed histiocytes, plasma cells, and eosinophils, increased vascularity, reactive or atretic follicles.
*Except in cases with concomitant lymph node involvement by cutaneous T cell lymphoma.

 

Peripheral T Cell Lymphoma Unspecified Reactive T Zone Hyperplasia: Toxoplasma Lymphadenitis
Pale-staining cells, if present, are T cells Pale-staining cells are monocytoid B cells.
Cytologically malignant T cell infiltrate with sparing of germinal centers Characteristic triad of reactive germinal centers, perifollicular clusters of epithelioid histiocytes, and islands of monocytoid cells
Aberrant loss of T cell antigens common No loss of T cell antigens
T cells usually monoclonal; 1/3 also show B cell clonality B and T cells polyclonal
Aggressive clinical course with generalized lymphadenopathy or mass lesions. Localized lymphadenopathy, positive Toxoplasma serology.
Both may show paracortical expansion with patches of pale-staining cells, admixed histiocytes.

 

Peripheral T Cell Lymphoma Unspecified Granulomatous Disease
Cytologically atypical lymphoid population Cytologically bland lymphoid population
Effacement of lymph node architecture Preservation of lymph node architecture
Cytologically malignant T cell infiltrate Cytologically bland
Aberrant loss of T cell antigens common No loss of T cell antigens
T cells usually monoclonal; 1/3 also show B cell clonality B and T cells polyclonal
Aggressive clinical course with generalized lymphadenopathy or mass lesions. Clinical/serologic findings of granulomatous infection, sarcoidosis, etc.
Both may show clusters of epithelioid histiocytes in a lymphocyte-rich background.

 

Peripheral T Cell Lymphoma Unspecified Autoimmune Lymphoproliferative Syndrome
Lymph node usually effaced; follicle centers may be spared Paracortical expansion with florid reactive follicular hyperplasia
Aberrant loss of T cell antigens common Characteristic T cell immunophenotype: CD4/CD8 double negative, CD45RO–
Cytologically malignant T cell population Medium-large T cells with abundant cytoplasm, T immunoblasts
T cells usually monoclonal
1/3 show B cell clonality		 T cells polyclonal
B cells usually polyclonal*
Aggressive clinical course with generalized lymphadenopathy or mass lesions, rare in children. Generalized lymphadenopathy, splenomegaly, autoimmune phenomena, usually presents in childhood.  FAS mutation present.
Both may show paracortical expansion by atypical T cell population, generalized lymphadenopathy.
*Lymphoma may develop in this setting, most commonly B cell non-Hodgkin type.

 

Peripheral T Cell Lymphoma Unspecified Kikuchi-Fujimoto Disease, Proliferative Phase
Cytologically malignant T cell population Sheets of T immunoblasts
Necrosis rare Prominent non-suppurative necrosis
Histiocytes lack crescentic nuclei, MPO Crescentic histiocytes (MPO+)
Aberrant loss of T cell antigens common No loss of T cell antigens
T cells usually monoclonal
1/3 show B cell clonality		 T cells polyclonal
B cells usually polyclonal
Aggressive clinical course with generalized lymphadenopathy or mass lesions. Cervical lymphadenopathy, flu-like symptoms, spontaneous resolution.
Both may show diffuse effacement by atypical T cell population.

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