Peripheral T-cell and NK-cell lymphoma

Question 1

What is the epidemiology and classification of Peripheral T-cell and NK-cell lymphomas?

Answer 1

• Peripheral T-cell and natural killer (NK)-cell lymphomas are a heterogeneous group of lymphomas comprising <15% of all non-Hodgkin lymphomas
• They occur more common in Asia and generally have an aggressive clinical course
• The pathogenesis of these lymphomas remains poorly understood
• The World Health Organization (WHO) classification
  
  • ​based on morphologic and immunophenotypic features
  • in conjunction with clinical and genetic findings
  • delineate a prognostically and therapeutically meaningful subclassification
• The most common type of peripheral T-cell lymphomas is peripheral T-cell lymphoma, not otherwise specified (NOS)
  
  • Several specific subtypes have been defined by the WHO classification

Question 2

What are the major subcategories of peripheral T-cell and NK-cell lymphomas?

Answer 2

• Anaplastic large cell lymphoma
• Angioimmunoblastic T-cell lymphoma
• Hepatosplenic T-cell lymphoma
• Adult T-cell leukemia/lymphoma
• Extranodal NK/T-cell lymphoma, nasal type
• Mycosis fungoides and syndrome
• Others (rare entities)

Question 3

What are peripheral T-cell lymphoma, not otherwise specified (NOS)?

Answer 3

• This is the most common subtype of T-cell lymphoma comprising 25-30% of all peripheral T-cell lymphomas
  
  • This subtype includes all T-cell lymphomas that do not meet the criteria for any specific subtypes of peripheral T-cell lymphomas defined by WHO
• Clinical features:
  
  • Most patients present with generalized lymphadenopathy and B symptoms (fever, night sweats, unintentional weight loss)
  • These tumors are aggressive and respond poorly to therapy
• Morphology: The neoplastic cells may range from small lymphocytes indistinguishable from the normal lymphocytes to large and highly pleomorphic lymphocytes
• Immunophenotype:
  
  • The neoplastic T cells may show aberrant T-cell antigen expression, most commonly diminished or absent expression of one or more of the pan T-cell antigens, such as CD5 and CD7
    
    • Pan T-cell antigens: CD3, CD2, CD5, CD7
• Molecular and cytogenetic features: These lymphomas often show clonal rearrangement of T-cell receptor (TCR) genes and complex chromosomal abnormalities

Question 4

What is Anaplastic large cell lymphoma?

Answer 4

• Most ALCLs express anaplastic lymphoma kinase (ALK)
  
  • ALK-positive ALCL accounts for 10-20% of childhood lymphomas and 3% of adult non-Hodgkin lymphoma
• Most patients present with advanced stage disease with involvement of lymph nodes and extranodal sites
  
  • ALK-positive ALCL has a good prognosis
• Morphologically, the lymphoma cells are often large, and some have horseshoe- or kidney-shaped nuclei (so-called “Hallmark” cells). (Figure 1).
• Although ALCL is a T-cell lymphoma, majority of cases are negative for CD3
  
  • However, all cases of ALCL express CD30, and majority cases are ALK+
  • Both antigens can be detected by immunohistochemical stain in formalin-fixed, paraffin-embedded tissue (Figure 1).
• The genetic hallmark of ALCL is the alteration of ALK gene on chromosome 2
  
  • The most frequent abnormality is t(2;5)(p23;q35) (ALK /NPM)

Question 5

What is Angioimmunoblastic T-cell lymphoma (AITL)?

Answer 5

• AITL is the second most common peripheral T-cell lymphoma comprising 15-20% of all peripheral T-cell lymphoma
  
  • AITL is derived from a unique T-cell subset in the germinal center of lymphoid follicles, the CD4+ follicular helper T cells
• Patients often present with:
  
  • generalized lymphadenopathy
  • hepatosplenomegaly
  • pruritic skin rash and systemic symptoms
• Clinical features associated with dysregulated immune responses are frequently present such as autoimmune antibodies
  
  • The clinical course is aggressive
• Morphologically, the involved lymph nodes often show prominent vascular proliferation and a diffuse polymorphic infiltrates composed of small to medium-sized lymphocytes with reactive B cells, plasma cells and eosinophils
• Similar to normal follicular helper T cells, AITLs are positive for CD4, CD10 and BCL-6 (CD10 and BCL-6 are germinal center cell markers)
  
  • Many cases are positive for EBV, which can be detected by in-situ hybridization in formalin-fixed, paraffin-embedded tissue sections
• Clonal TCR gene rearrangement is present in most cases; no specific chromosomal abnormalities have been identified

Question 6

What is Hepatosplenic T-cell lymphoma (HSTCL)?

Answer 6

• HSTCLs are rare and predominantly affect young males
• Patients often present with marked splenomegaly
  
  • The clinical course is highly aggressive, and patients often die within a year
• HSTCL is derived from CD4-/CD8- and TCRgamma/delta+, T cells
• Isochromosome 7q is present in most cases

Question 7

What is Adult T-cell leukemia/lymphoma (ATLL)?

Answer 7

• ATLL is associated with T-cell leukemia virus type 1 (HTLV-1) infection (know this!)
• It is most commonly seen in Japan and the Caribbean
• The disease affects adults and often present with widespread lymph node, peripheral blood and bone marrow involvement
• The neoplastic cells in the peripheral blood are described as “flower cells” because of the multiple nuclear convolutions

Question 8

What is Extranodal NK/T-cell lymphoma, nasal type?

Answer 8

• This type of lymphoma is more prevalent in Asia and strongly associated with EBV infection
  
  • The nasal cavity is the most common site of involvement
• Most cases are derived from NK cells (surface CD3-, CD56+)
  
  • Rare cases arise from cytotoxic T cells
  • The tumor often shows necrosis and high mitotic activity
• No specific genetic abnormalities have been identified

Question 9

What is Mycosis fungoides (MF) and Sézary syndrome?

Answer 9

• MF is a peripheral T-cell lymphoma involving skin
  
  • It generally has an indolent clinical course, but the disease may progress to syndrome where the patient has erythroderma, generalized lymphadenopathy, and peripheral blood involvement by neoplastic cells with cerebriform (convoluted) nuclei ( cells).
• Skin biopsies of MF show cerebriform lymphocytes in the upper dermis and in the epidermis
  
  • Small epidermal collections of neoplastic cells are called “Pautrier microabscesses”
• The neoplastic T cells are CD3+ and CD4+, and often show lost expression of pan T-cell antigen CD7 (CD3+, CD4+, CD7-)
• Complex karyotypes are present in many cases

Question 10

What is the epidimiology and classifications of Hodgkin’s Lymphoma?

Answer 10

• HL is derived from B cells, but classified as a separate entity from other B-cell lymphomas due to its unique clinicopathological features
• HL accounts for approximately 30% of all lymphomas. It is classified into two major categories: nodular lymphocyte predominant HL (5%) and classical HL (95%)
• Classical HLs are further subclassified into four types:
  
  • nodular sclerosis
  • mixed cellularity
  • lymphocyte-rich
  • lymphocyte-depleted

Question 11

What is the common clinical presentation of Hodgkin Lymphoma?

Answer 11

• Nodular lymphocyte predominant HLs preferentially affect young males and usually present as localized peripheral lymphadenopathy
• This type of HL has very good prognosis, but multiple relapses and transformation to diffuse large B-cell lymphoma (DLBCL) may occur
• Classical HL has a bimodal age distribution and often involves cervical lymph nodes and the mediastinum

Question 12

What is the morphology and immunophenotype of Hodgkin Lymphoma?

Answer 12

• Nodular lymphocyte predominant HL
  
  • This subtype is characterized by a nodular or nodular/diffuse proliferation of lymphocytes with scattered large neoplastic cells known as “popcorn cells” or lymphocyte predominant cells (LP cells)
  • The large neoplastic cells are typically CD45+, CD20+, CD30- and CD15-
• Classical HL
  
  • The four subtypes of classical HL differ in the clinical features, composition of cellular background and growth pattern
  • In general, all types of classical HL show a proliferation of large neoplastic cells composed of mononucleated Hodgkin cells or bi- or multinucleated Reed-Sternberg cells in a reactive inflammatory background
  • The large neoplastic cells in all four subtypes of classical HL are typically CD45-, CD20-, CD30+ and CD15+ EBV is present in a subset of classical HL
• Molecular and cytogenetics:
  
  • No specific molecular or cytogenetic abnormalities have been identified in HL

Question 13

What are the unique histological features of Anaplastic large cell lymphoma (ALCL)?

Answer 13

• The lymph node biopsy shows a diffuse proliferation of large cells
  
  • Some cells (arrows) have horseshoe-like nuclei (“hallmark” cells)
• The large cells are positive for CD30 by immunohistochemical stain (brown color)
• The neoplastic cells are positive for ALK (brown color)

Question 14

What are the unique histological features of Adult T-cell leukemia/lymphoma (ATLL)?

Answer 14

the peripheral blood smear shows abnormal lymphocytes with flower-like nuclei

Question 15

What are the unique histological features of Classical Hodgkin lymphoma, nodular sclerosis type?

Answer 15

• The fibrous bands divide the lymph node tissue into multiple nodules
• A typical binucleated Reed-Sternberg cell (arrow) in a background of reactive inflammatory cells including eosinophils
• The large neoplastic cells are positive for CD30 by immunohistochemical stain (brown color)
• The large neoplastic cells are also positive for CD15 (brown color)