Classification of Lymphoid Neoplasms Pathology Notes

Lymphoid Neoplasms

Definition of Lymphoid:

• Lymphomas are malignant lymphoid neoplasms due to lymphoid tissue proliferation that arise as discrete tissue masses. Lymphomas are mainly subdivided into Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHLs).
• Leukemias are neoplasms that present with widespread involvement of the bone marrow and (usually, but not always) the peripheral blood.

Many “lymphomas” occasionally have leukemic presentations, and evolution to “leukemia” is not unusual during the progression of incurable “lymphomas.” Conversely, a few “leukemias” may sometimes arise as soft tissue masses without detectable bone marrow disease.

Therefore, the terms leukemia and lymphoma reflect the usual tissue distribution of the disease at presentation.

Classification of Lymphoid Neoplasms:

WHO classification of the lymphoid neoplasms (2008):

Read And Learn More: Pathology for Dental Students Notes

WHO classification of lymphoid neoplasms depends on clinicopathological and immunological profiles and has clinical and therapeutic importance.

Cell type and its antigens detected by monoclonal antibodies:

Non-Hodgkin Lymphoma And Follicular Lymphoma (FL)

Write short notes on follicular lymphoma.

Composed of follicle center (germinal center) B cells of lymphoid follicles (centrocytes and centroblasts).

Morphology of Follicular Lymphoma:

• Gross:
  
  • Involves lymph nodes, spleen, and bone marrow.
  • The architecture of lymph nodes is lost; frequently infiltrate the perinodal tissue

Microscopy of Follicular Lymphoma:

• Follicular (nodular) growth patterns and neoplastic follicles are poorly defined.

Two types of B cells.

1. Centrocytes (small cleaved cells):
   1. Cleaved nuclei
   2. Inconspicuous nucleoli
2. Centroblasts (large non-cleaved cells):
   1. Round or oval nuclei with open nuclear (vesicular) chromatin
   2. Multiple (1 to 3) nucleoli
   3. Usually 3 times the size of a lymphocyte.

• Immunophenotype: Expresses CD19, CD20 (pan-B cell markers), CD10 (CALLA), surface immunoglobulin and BCL2 protein.
• Cytogenetics and molecular genetics: t (14; 18) (q32:q21), with IgH and BCL2 as partner genes and leads to constitutive overexpression of BCL2 protein.

Clinical Features  of Follicular Lymphoma:

• The peak in the sixth and seventh decades.
• Generalized lymphadenopathy.

Diffuse Large B Cell Lymphoma (DLBCL)

• A heterogeneous group of aggressive, neoplasm of the large B cell with diffuse growth patterns.
• Constitutes about 20 to 30% of NHL and 60% to 70% of aggressive lymphoid neoplasms.

Microscopy of Large B cell :

• Loss of lymph node architecture with diffuse growth pattern.
• Neoplastic cells:
  • Large round or oval cells, 4 to 5 times of a small lymphocyte.
  • Moderate pale or basophilic cytoplasm.
  • The nucleus equals or is larger than the nucleus of a macrophage with different appearances.

Immunophenotype of Large B cell:

• Express pan-B cell markers such as CD19, CD20, CD22 and CD79a.
• Also, express germinal center markers like CD10 and BCL6.
• Negative for TdT.

Cytogenetics and Molecular Profile of Large B cell :

• Translocation of BCL2 gene: t (14; 18) translocation
• Mutations of the BCL6 gene.

Clinical Features of Large B Cell:

• More common between 65 and 70 years of age.
• Slight male preponderance.
• Rapidly enlarging mass at single or multiple nodal or extranodal sites.

Burkitt Lymphoma (BL)

Write short notes on Burkitt lymphoma.

• Highly aggressive B cell neoplasm often presents as extranodal lymphoma or as acute leukemia.
• Composed of medium-sized, monomorphic lymphoid cells with basophilic vacuolated cytoplasm.

Clinical Variants of Burkitt Lymphoma:

1. Endemic (African) Burkitt lymphoma (BL):
   • Occurs in Africa, and affects children and adolescents.
   • Associated with Epstein-Barr virus infection and malaria.
   • Usually involves the jaw and presents as a mandibular mass.
2. Sporadic (nonendemic) BL:
   • Occurs in children or young adults.
   • Abdominal mass and involves ileocecum and peritoneum.
3. Immunodeficiency-associated (HIV) BL:
   • Involves lymph nodes and bone marrow.

Microscopy of Burkitt lymphoma:

• Burkitt lymphomas, irrespective of the categories, are histologically similar.
• The lymph node shows a loss of architecture.
• Involved tissues show diffuse infiltrate of monotonous medium-sized lymphoid cells

The appearance of neoplastic lymphoid cells:

• • Medium-sized cells.
  • Round or oval nuclei having clumped coarse chromatin with several (2 to 5) nucleoli.
  • A moderate amount of deeply basophilic cytoplasm, multiple, small, round lipoid (clear) vacuoles which stain positive with oil red O.
  • Numerous mitotic fiures.
• Starry sky pattern: Tumor cells undergo apoptosis and nuclear remnants of these apoptotic cells are phagocytosed and cleared by benign macrophages. The macrophages in the background of lymphoid cells create a “starry sky” appearance

Immunophenotype of Burkitt lymphoma:

• Express surface IgM, monotypic κ or λ light chain.
• Positive for common B cell antigens (CD19, CD20, and CD22).
• Positive for CD10 and BCL6.
• BCL2 negative.

Cytogenetic and Molecular Genetic Features of Burkitt Lymphoma:

• Translocations of c-MYCgene
• MYC (c-MYC) is a proto-oncogene-on chromosome 8.
• Most common translocation is t (8:14) (q24; q32).
• Translocations of the c-MYC gene convert proto-oncogene into MYC oncogene, which leads to overexpression of MYC protein (oncoprotein).
• This causes uncontrolled cell proliferation and stimulation of apoptosis.
• Mutations inactivate p53.
• Poor prognostic factors:
  • Involvement of blood, bone marrow, and central nervous system.
  • The bulk of the disease-unresected tumor of more than 10 cm in diameter.
  • High serum LDH levels.
  • Presence of residual disease after excision.

Lymph Nodes Mature T Cell and NK Cell Neoplasms

Peripheral T Cell Lymphoma (PTCL), NOS: Mainly involves lymph nodes.

Microscopy of T Cell Lymphoma:

• Lymph node with effacement of the normal architecture.
• Paracortical or diffuse infiltration by neoplastic T cells.
• Neoplastic T cells:
  • Small, intermediate to large cells with sparse or abundant; clear, eosinophilic, or basophilic.
  • Vesicular or hyperchromatic nuclei, prominent nucleoli.

Immunophenotype of T Cell Lymphoma:

• Lack of TdT (expressed by immature T cells).
• Express pan-T cell-CD2, C3, CD5, and either α β or γ δ T cell receptors (TCR).

Mycosis fungoides of T Cell Lymphoma:

• Cutaneous T cell lymphoma.
• Lymphoid cells with irregular nuclear outlines.
• Limited to skin.
• Age: Most are adults or elderly.

Microscopy of T Cell Lymphoma:

• The epidermis (epidermotropism) and upper dermis is infiltrated by neoplastic T cells.
• Groups of neoplastic cells in the epidermis—Pautrier’s microabscess.
• Tumor cells have convoluted (cerebriform) nuclear contours.

Sézary Syndrome of T Cell Lymphoma:

Rare disease and is defined by the triad namely:

• Widespread exfoliative erythroderma
• Generalized lymphadenopathy
• Presence of characteristic Sézary cells in the skin, lymph nodes, and peripheral blood.

Prognosis: Aggressive disease and most die of opportunistic infections.

Hodgkin Lymphoma

Hodgkin Lymphoma(HL):

• Malignant lymphoid neoplasms with the following characteristics:
• A minority (1–3%) of specific neoplastic cells (Hodgkin cells and Reed-Sternberg cells).

WHO classification (2008) of Hodgkin lymphoma:

Majority background of reactive non-neoplastic cells:

• Usually involves lymph nodes.
• The majority occurs in young adults.

Classifiation of Hodgkin Lymphoma Or Classify Hodgkin lymphoma:

Hodgkin lymphoma (HL) is broadly divided into two types, which differ in clinical features, behavior, morphology, and immunophenotype.

Cell of Origin and Immunophenotype:

• Classical Hodgkin lymphoma
  • Cell of origin: Germinal center or post-germinal center B cell
  • Immunophenotype: CD15 and CD30 positive
• Nodular lymphocyte predominant Hodgkin lymphoma
  • The cell of origin: Germinal center B cell at the centroblasts stage of differentiation.
  • Immunophenotype: CD15 and CD30 negative.

Morphology of Neoplastic Cells:

Write a short note on the RS cell and its variants.

• Reed-Sternberg (RS) Cells are neoplastic cells. pathognomonic of Hodgkin lymphoma.
• Appearance and description of diagnostic Reed-Sternberg cells and its variants are shown in below.

‘

Various types of cells found in Hodgkin lymphoma are listed in Tabl.e

Types of cells found in Hodgkin Lymphoma:

Classical Hodgkin Lymphoma:

Classical Hodgkin lymphoma (CHL) accounts for 95% of Hodgkin lymphomas and has 4 subtypes.

1. Nodular Sclerosis Classical Hodgkin Lymphoma (NSCHL):

Write a short note on nodular sclerosis HL.

• A subtype of CHL characterized by collagen bands that surround nodules and have lacunar cell variant of Reed-Sternberg cells.
• Most common: 40% to 70% of cases.
• Most are between 20 and 30 years of age with equal frequency in males and females.
• Rarely associated with EBV.
• Involves mediastinal lymph nodes.

Microscopy of NSCHL:

• Loss of lymph node architecture.
• Sclerosis and nodules: Broad collagen bands (sclerosis) divide the lymphoid tissue into nodules of varying sizes and shapes.
• Presence of lacunar cell.
• Background: Small T lymphocytes, eosinophils, plasma cells, and macrophages.

Immunophenotype of NSCHL:

• RS cells are CD15+ and CD30+; CD45- and T cell markers negative.
• EBV negative.

2. Mixed Cellularity Classical Hodgkin Lymphoma (MCCHL):

Write a short note on Mixed cellularity HL.

• Second common subtype: 20% to 25% of cases
• More common in males
• Strongly associated with EBV
• Older age, with systemic symptoms (such as night sweats and weight loss) and advanced tumor stage
• Involves peripheral lymph nodes.

Microscopy of MCCHL:

• Lymph node architecture obliterated
• Plenty of Reed-Sternberg cells and Hodgkin cells
• Background: Small lymphocytes, eosinophils (sometimes numerous), neutrophils, plasma cells, and benign macrophages (histiocytes).

Immunophenotype of MCCHL: RS cells are CD15+, CD30+, and EBV+ (about 70%).

3. Lymphocyte-rich Classical Hodgkin Lymphoma (LRCHL):

• A subtype of classical Hodgkin lymphoma with scattered Hodgkin and RS cells.
• Uncommon—about 5% of classical HL.
• More in elderly patients, associated with EBV in 40% of cases.
• Involves peripheral lymph nodes.

Microscopy of LRCHL:

• Growth patterns: May show two patterns
• Nodular—common
• Diffse—rare
• Only a few Reed-Sternberg cells and Hodgkin cells
• Background: Abundant reactive small lymphocytes.

Immunophenotype of LRCHL: CD45–, CD20–, CD15+ and CD30+.

4. Lymphocyte-depleted Classical Hodgkin Lymphoma (LDCHL):

• Subtype of classical Hodgkin lymphoma rich in Hodgkin and RS cells in a background depleted in non-neoplastic lymphocytes.
• Rarest — Less than 5% of cases
• Predominantly in older, HIV-positive patients, often EBV-associated (over 90%)
• Predominantly retroperitoneal lymph nodes, abdominal organs, and bone marrow.

Microscopy of LDCHL:

• The paucity of lymphocytes.
• Plenty of RS cells or their anaplastic/pleomorphic variants.
• Histological types
  • Reticular: Numerous Hodgkin and RS cells with depletion of lymphocytes.
  • Diffuse sclerosis/fibrosis: Hypocellular infiltrate containing bizarre RS cells with fiefirosis.

Immunophenotype of LDCHL: RS cells are CD15+, and CD30+; the majority are EBV+.

Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL):

• Uncommon — 5% of all Hodgkin lymphomas.
• Not associated with EBV.
• The majority of males are usually 30–50 years of age.
• Involves mainly cervical or axillary lymph nodes.

Microscopy of NLPHL:

• Loss of lymph node architecture.
• Nodular and/or diffuse infiltrate of abundant small lymphocytes with histiocytes and scattered LP cells.
• Lymphocyte predominant cells (LP cells)/”popcorn” cells
  • Specific to NLPHL.
  • Large with relatively abundant, pale cytoplasm.
  • The single large delicate multilobulated nucleus or folded nuclei resembling bubbly outlines of popcorn kernels.
  • One or more inconspicuous nucleoli.
• Hodgkin and RS cells are not found.

Immunophenotypes of NLPH:  LP cells are CD20+, CD 45+, and CD15–, C30–, and EBV–ve. Express BCL6.

Etiology and Pathogenesis of Hodgkin Lymphoma:

• EBV: Previous EBV infection (infectious mononucleosis) ↑ risk of HL.
• Genetic factors: HLA-B18 is higher in HL.
• Immune status: HL is more frequent in immunocompromised patients and autoimmune diseases (for example, Rheumatoid arthritis).

Laboratory Findings:

• Peripheral smear:
  • RBCs: Normocytic normochromic anemia.
  • WBCs: Leukocytosis occurs in 1/3rd of the patients. Eosinophilia is frequent.
  • Platelets: Normal or increased.

Fine Needle Aspiration Cytology (FNAC):

RS cells/its variants against a background of inflammatory cells (depending on the subtype).

Spread of FNAC:

• Mainly by contiguity
• First nodal disease → Then splenic disease, Hepatic disease → And finally marrow involvement and extranodal disease.

Staging of Hodgkin lymphoma:

Clinical staging of Hodgkin lymphomas (Cotswold revision of Ann Arbor staging classification):

Differences between Hodgkin Lymphoma and Non-Hodgkin Lymphoma:

List the differences between HL and NHL.

HL differs from NHL in several respects and their main differences are shown in Table.

Differences between Hodgkin and non-Hodgkin lymphomas:

Metastatic Carcinoma

The most common pathway of spread for carcinomas is spread through lymphatics. Once the tumor cells gain access into the lymphatic vessels, they are carried to the regional draining lymph nodes.

The pattern of lymph node involvement follows the natural routes of lymphatic drainage:

• A sentinel lymph node biopsy is done to know the presence or absence of metastatic lesions.
• Skip metastasis: When local lymph nodes are bypassed and lymphatic metastases develop in lymph nodes distant from the site of the primary tumor; these are called “skip metastasis”. Example: Abdominal cancers may be first detected by an enlarged supraclavicular node.
• Retrograde metastasis: Tumors spreading against the flow of lymphatics may cause metastases at unusual sites. Example: Carcinoma prostate metastasizing to the supraclavicular lymph node.

The microscopic pattern of deposits:

• Initially, tumor cells are deposited in the marginal sinus and later extend throughout the node.
• Micrometastases consist of single tumor cells or very small clusters.
• Significance of lymph node metastases: Prognostic value-for example In breast cancer, involvement of axillary lymph nodes is very important for assessing prognosis and for type of therapy.