Hodgkin Lymphoma

Anwar Rjoop, MD FCAP

Lymphoma

Hodgkin Lymphoma

Non Hodgkin Lymphoma

Low Grade

Intermediate Grade

(aggressive)

High Grade

(very aggressive)

Hodgkin lymphoma

• 30% of all lymphomas

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• Classified
• Clinical features/behavior
• Morphological and immunophenotypic findings
• Differences of Reed-Sternberg cells and variants
• Composition of cellular response

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Classification

• Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)

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• Classical Hodgkin lymphoma (CHL)
• Nodular sclerosis (65-70%).
• Mixed cellularity (20-25%).
• Lymphocyte-rich (<1%).
• Lymphocyte-depleted

Hodgkin Lymphoma�

• Most common malignancy of young adults
• Bimodal age distribution:
• First peak between 20 and 30 years of age.
• Second peak > 50 years of age.

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• Cervical and supraclavicular nodes are the most commonly affected.
• Spread is usually to contiguous nodes (stepwise fashion) following an anatomic course followed by spleen, liver and bone marrow.

• Historical background
• Thomas Hodgkin described, in 1832, clinical and autopsy findings of 7 patients with massive lymphadenopathy and splenomegaly.
• Later similar cases were described and given the name Hodgkin disease by Wilks.
• The abnormal cells were described by Reed and Sternberg. Both thought the process is infectious.

Hodgkin Disease�Clinical Presentations

• Painless peripheral lymphadenopathy. Mostly cervical and supraclavicular
• B-symptoms (cytokines release):
• Fever
• Night sweats
• Weight loss (10% of body weight)
• Splenomegaly in 16% of the cases
• Anemia due to bone marrow involvement in 5% of the cases

Epidemiology of Hodgkin Disease

• Bimodal age distribution in developed countries
• Early childhood peak in developing countries
• Case clustering
• High economic standards association with the young adult peak

Hodgkin Lymphoma

Histopathology:

• Neoplastic cells (Reed-Sternberg cells).
• Immunologic reaction to tumor

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The quality and the quantity of each component determines the subtype of Hodgkin disease.

Morphologic Features of Classic Reed-Sternberg Cells

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1. Large in size (15-45 m in diameter).

2. Polylobated nucleus.

3. Huge round inclusion-like nucleoli.

Variants of Reed-Sternberg cells

• Hodgkin cells (Mononuclear variant): Insufficient for diagnosis but can be used for diagnosing extra-nodal sites in known cases.

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• Mummified cells: dark smudge degenerating cells with pyknotic nuclei and eosinophilic cytoplasm.

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• Lacunar cells: Large polylobated nuclei surrounded by pale cytoplasm and contain inconspicuous nucleoli.

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• (LP) L&H cells: cells with hyperlobated nuclei, finely granular chromatin and inconspicuous small nucleoli.

Neoplastic Cells in Hodgkin Disease

R-S Cell

Lacunar cell

L&H cell

Multilobated

R-S cell

Mummified cell

Hodgkin cells

Classification of Hodgkin Disease

WHO Classification

• Classic HL
• Nodular sclerosis (65-70%).

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• Mixed cellularity (20-25%).

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• Lymphocyte depletion (<1%).

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• Lymphocyte Rich (adults)
• Nodular lymphocyte predominant (NLPHL).

�1. Classical HL (RS cells: CD45-, CD20-, CD15+, CD30+, PAX5+ (weak), MUM1+)��2. NLPHL (L&H cells: CD45+, CD20+, CD30-, CD15-) �

HL immunophenotype

Hodgkin Disease

Non-neoplastic reactive cells:

• Lymphocytes: composed mostly of small lymphocytes with the CD4 immunophenotype.
• Histiocytes.
• Eosinophils
• Plasma cells.
• Neutrophils.
• Fibroblasts and fibrous tissue.

Immunophenotypic Characteristics of Reed-Sternberg cells

Positive for:

• CD30 (Ki-1)
• CD15
• CD25 (IL-2 receptor)
• HLA-DR
• CD71 (transferrin receptor)

Negative for:

• CD45 (LCA)
• CD20*
• CD3*

*Variable expression of T and B- cell markers

Non-Classical Hodgkin Lymphoma� Nodular Lymphocyte predominant �(NLPHL)

• 5% of all cases of HL.
• Affects predominantly young males (<35 years).
• Cervical and/or axillary nodes are the most frequently involved.
• Intra-abdominal involvement is rare.
• Good prognosis.

Hodgkin Lymphoma� Nodular Lymphocyte predominant �(NLPHL)

Histopathology:

• Diffuse or nodular pattern.
• Background of small lymphocytes. Neutrophils, eosinophils and plasma cells, fibroblasts and necrosis are absent
• L&H cells (popcorn cells): resemble transformed lymphocytes with hyperlobated nuclei, finely granular chromatin and inconspicuous small nucleoli. Mummified cells and aberrant mitosis are common.
• Classical Reed-Sternberg cells are rare.

Nodules of various sizes

www.webpathology.com

Immunophenotype

CD20

CD20

CD3

CD30

Classical Hodgkin Lymphoma �(1) Mixed Cellularity

• 25% of cases of HL.
• Superficial adenopathy.
• HIV infection
• Granuloma-like clusters of histiocytes or granulomas may be seen. (immune-compromised patients)
• Abdominal involvement is seen in half of the patients.
• Numerous easily identified Reed-Sternberg cells in the appropriate setting.
• Background cells: lymphocytes, eosinophils, macrophages, plasma cells, neutrophils.

Classical Hodgkin Lymphoma�(2) Lymphocyte depleted

• Affects mostly patients over 50 years of age.
• Males are affected more than females.
• B-symptoms are common.
• Usually involves intra-abdominal sites/retroperitoneal nodes.
• Stages III&IV are usual.
• Pancytopenia.
• Prognosis is unfavorable.

Classical Hodgkin Lymphoma�(3) Nodular Sclerosis

• 70% of cases of HD.
• High incidence in females.
• Patients present at an early stage (I&II).
• Mediastinum is the most commonly involved site.
• Excellent prognosis.

Histopathology:

Triad of

• Sclerosis: Orderly bands of birefringent interconnecting collagenous tissue that circumscribe nodules of abnormal lymphoid tissue.
• Lacunar cells.
• Reed-Sternberg cells (rare).

Classical Hodgkin Lymphoma�(4) lymphocyte Rich

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*Absence of PMNs and eosinophils�*Peripheral LN are typically involved�*Stage I or II disease�*HIV uncommon�*Bulky disease uncommon

Hodgkin Lymphoma

Etiology:

• ? Viral:
• Case clustering
• Occurrence of multiple cases in a single household
• EBV has been found by serologic and epidemiologic studies.
• 20-80% of the cases have the EBV genome.
• ? Genetic

Hodgkin Lymphoma�Poor Prognostic Factors

• Stage IV, and B symptoms
• Age ≥ 45yr
• Male gender
• Histology (particularly the lymphocyte-depleted)
• ESR (>50)
• Albumin level (<4g/dl),
• Low Hb. (<10.5gldl)

Clinical Differences Between HL and NHL

Feature

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Sites of involvement

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Spread

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Waldeyer ring &

mesenteric node

involvement

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Extranodal involvement

HD

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Often single axial

lymph node region

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Contiguous

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Rare

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Uncommon

NHL

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Often multiple

peripheral nodes

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Noncontiguous

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Common

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Common

Thank you