What Is the 5 Year Prognosis for Hodgkin's Lymphoma

Summary

Hodgkin lymphoma (HL) is a malignant lymphoma that is typically of B-cell origin. The incidence of HL has a bimodal age distribution, with peaks in the 3^rd and 6^th–8^th decades of life. The WHO classifies HL into two types: classical HL (CHL) and nodular lymphocyte-predominant HL (NLPHL). CHL is further divided into four subtypes, which are nodular sclerosis (most common), mixed cellularity, lymphocyte-depleted, and lymphocyte-rich CHL. Risk factors for developing HL include a history of infectious mononucleosis caused by the Epstein-Barr virus (EBV) and immunodeficiency (e.g., HIV infection). HL typically presents with painless cervical lymphadenopathy, fever, night sweats, and involuntary weight loss. Pel-Ebstein fevers (cyclical fever with periods of both high and normal temperature) and alcohol-induced pain at affected lymph nodes are less common but specific for HL. Suspicious lymph nodes are excised and definitive diagnosis is made via histological analysis, which characteristically reveals pathognomonic Reed‑Sternberg cells (malignant B-cells). The modified Ann Arbor classification (Cotswold staging system) is used to stage HL based on both the localization of the lymphoma with respect to the diaphragm and on the presence of systemic symptoms. Treatment is typically initiated with curative intent. In early stages, treatment is generally limited to involved-field radiation and chemotherapy. In later stages, when local radiation is often unsuccessful or not feasible due to tumor spread, polychemotherapy is the mainstay of treatment.

Epidemiology

• Incidence
  • 2–3/100 000 per year ^[1]
  • Subtype variance with age (see "Pathology" below)
    • Young adults: nodular sclerosing HL
    • Elderly adults: mixed-cellularity HL
• Age : bimodal distribution ^[2]
  • 1^st peak : 25–30 years
  • 2^nd peak : 50–70 years
• Sex: ♂ > ♀ ^[2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

The exact causes are unknown, but several risk factors have been associated with HL. ^{[3] [4]}

• Strong association with Epstein-Barr virus ( EBV )
• Immunodeficiency : e.g., organ or cell transplantation, immunosuppressants, HIV infection , chemotherapy
• Autoimmune diseases (e.g., rheumatoid arthritis, sarcoidosis)

Clinical features

• Painless lymphadenopathy
  • Cervical lymph nodes (in ∼ 60–70% of patients) > axillary lymph nodes (in ∼ 25–35% of patients) > inguinal lymph nodes (in ∼ 8–15% of patients) ^[5]
  • Involvement of a single group of lymph nodes
  • Contiguous pattern of lymph node spread
  • Mediastinal mass → chest pain, dry cough, and shortness of breath
  • Splenomegaly or hepatomegaly may occur if the spleen or liver are involved.
• B symptoms ^[5]
  • Night sweats , weight loss > 10% in the past 6 months , fever > 38°C ( 100.4°F )
  • Can occur in a variety of diseases (see "Differential diagnosis of B symptoms " below)
  • In the case of confirmed HL, the presence of a single B symptom suffices for a positive diagnosis of B symptoms .
• Pel-Ebstein fever : Intermittent fever with periods of high temperature for 1–2 weeks, followed by afebrile periods for 1–2 weeks . Relatively rare but very specific for HL.
• Alcohol-induced pain : Pain in involved lymph nodes after ingestion of alcohol. Relatively rare but highly specific for HL.
• Pruritus (focal or generalized)

Stages

Staging is based on the number of affected nodes, the presence or absence of B symptoms , and whether or not the disease is present on both sides of the diaphragm.

Diagnostics

Diagnosis of HL is primarily based on medical history and clinical features ( B symptoms , localization of lymph node involvement) and is confirmed with lymph node biopsy.

Blood tests

• Complete blood count
  • Elevated or decreased WBC count
  • Anemia
  • Eosinophilia
• Serum chemistry

Histology

• Obligatory diagnostic step
• Lymph node excision
  • Reed-Sternberg cells (RSCs)
    • Tumor cells that are pathognomonic of HL
    • Originate from B cells
    • Large cells with binuclear/bilobed nuclei with dark centers of chromatin and pale halos , which result s in an owl-eye appearance on histopathologic examination .
    • CD15/CD30-positive
  • Hodgkin cells: mononuclear, malignant B lymphocytes
  • Inflammatory background containing the following cell types in varying numbers: lymphocytes , neutrophils , eosinophils , macrophages / histiocytes , plasma cells , and fibroblasts
  • Granuloma formation

Reed-Sternberg cells are bi( 2 )nucleate with CD15/CD30 positivity. To recall the cell markers, remember that 2 x 15 = 30 .

Imaging

• Chest x-ray or CT-scan : detection and measurement of masses and enlarged lymph nodes in chest, abdomen, and pelvis
• Bone scintigraphy or PET-CT : performed before treatment to assess disease spread

Pathology

Histological classification of Hodgkin lymphoma (WHO)
Classification	Subtype	Characteristics	Prognosis	Pathology
Classical Hodgkin lymphoma (95%)	Nodular sclerosing classical HL (NSHL)	Most common subtype (> 60%) Localization: mostly mediastinal and cervical	Good	Nodules of Reed-Sternberg cells within lacunae, separated by collagenous tissue with sclerosing appearance (hence the name "nodular sclerosing"). Lymphocyte rich .
	Mixed-cellularity classical HL (MCHL)	Commonly found in immunocompromised patients (e.g., HIV-positive individuals) Localization: mostly abdominal and splenic	Good (but slightly worse than NSHL)	Nodules with numerous Reed-Sternberg cells, and increased number of histiocytes, eosinophils, and plasma cells (hence the name "mixed-cellularity").
	Lymphocyte-rich classical HL (LRHL)	Rare Localization: mostly cervical and axillary	Very good	Presence of Reed-Sternberg cells, and reactive lymphocytosis that causes distortion of the lymph node architecture.
	Lymphocyte-depleted classical HL (LDHL)	Very rare (< 1%) Commonly found in immunocompromised patients Localization: mostly below the diaphragm	Poor	Numerous Reed-Sternberg cells, and decreased number of lymphocytes.
Lymphocyte predominant Hodgkin lymphoma (5%)	Nodular lymphocyte predominant HL (NLPHL)	Rare (5%) Localization: mostly neck, axillary, and inguinal [9]	Very good (but slightly worse than LRHL)	Presence of popcorn cells : a variant of a Reed-Sternberg cell characterized by polylobulated nuclei that resemble popcorn. Lymphocyte predominant ( LP ) cells express CD20 , CD79a, and CD45 . [10] Unlike in classical Hodgkin lymphoma , tumor cells are negative for CD15 and CD30. [10]

Differential diagnoses

Differential diagnoses of lymphadenopathy

Examining lymph nodes can yield important diagnostic clues. Generalized lymphadenopathy is usually a sign of systemic illness, such as HIV, mycobacterial infection (e.g., tuberculosis), infectious mononucleosis, systemic lupus erythematodes, or serum sickness. Signs of malignancy include rapid growth, painlessness, hardness/coarseness, and being fixed to underlying or surrounding tissue. Most often, though, there is no discernible cause or pathology.

Feature	Normal	Infection	Malignancy
Size	< 1 cm	> 1 cm	> 1 cm
Consistency	Soft		Hard (various malignancies) Rubbery (typical of lymphoma)
Tender/nontender	Nontender	Tender	Nontender
Fixation	Freely movable	May be fixed or freely movable	Fixed to the underlying tissue

Differential diagnosis of B symptoms

• Non-Hodgkin lymphomas, Hodgkin lymphomas
• Other hematopoietic malignancies (e.g. CML, ALL )
• Solid tumors
• Tuberculosis
• HIV

The differential diagnoses listed here are not exhaustive.

Treatment

Independent of stage, treatment is typically initiated with curative intent.

Prognosis

• Good prognosis
• Prognosis is largely determined by disease stage (i.e., lower stage has a better prognosis)
• ∼ 10–20% of patients will develop secondary malignancies (especially lung cancer; related to radiation therapy and chemotherapy) ^[11]
• Unfavorable factors for Hodgkin lymphoma (relevant when selecting a treatment regimen)
• International Prognostic Score (IPS): evaluation of prognosis in patients with advanced disease (for each factor present, the patient receives one point)
  • IPS factors
    • Albumin < 4 g/dL
    • Hemoglobin < 10.5 g/dL
    • Gender ♂
    • Age ≥ 45 years
    • Stage IV disease
    • Leukocytosis: white cell count (WBC) > 15,000/μL
    • Lymphopenia: lymphocyte count < 8% of WBC count and/or absolute lymphocyte count < 600 cells/μL
  • IPS categories: Based on the calculated IPS, patients can be categorized as follows:
    • Good prognosis (IPS 0–1)
    • Fair prognosis (IPS 2–3)
    • Poor prognosis (IPS 4–7)

References

1. Ansell SM. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016; 91 (4): p.434-442. doi: 10.1002/ajh.24272 . | Open in Read by QxMD
2. Asif S, Raza S. Long-term time trends in incidence, survival and mortality of Hodgkin lymphoma in the United States: A surveillance, epidemiology, and end results (SEER) database study 1975-2015.. Journal of Clinical Oncology. 2019; 37 (15_suppl): p.e19014-e19014. doi: 10.1200/jco.2019.37.15_suppl.e19014 . | Open in Read by QxMD
3. Hodgkin lymphoma risk factors. http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/hodgkin-lymphoma/risk-factors. Updated: February 8, 2017. Accessed: February 8, 2017.
4. Ansell SM. Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol. 2018; 93 (5): p.704-715. doi: 10.1002/ajh.25071 . | Open in Read by QxMD
5. Mauch PM, Kalish LA, Kadin M, Coleman CN, Osteen R, Hellman S. Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis. Cancer. 1993; 71 (6): p.2062-2071. doi: 10.1002/1097-0142(19930315)71:6<2062::aid-cncr2820710622>3.0.co;2-0 . | Open in Read by QxMD
6. Mauch PM, Canellos GP, Arnold S Freedman AS, Rosmarin AG. Staging and Prognosis of Hodgkin Lymphoma. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/staging-and-prognosis-of-hodgkin-lymphoma.Last updated: February 21, 2017. Accessed: August 4, 2017.
7. T A Lister, D Crowther, S B Sutcliffe, E Glatstein, G P Canellos, R C Young, S A Rosenberg, C A Coltman, M Tubiana. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting.. Journal of Clinical Oncology. 1989; 7 (11): p.1630-1636. doi: 10.1200/jco.1989.7.11.1630 . | Open in Read by QxMD
8. Lugano Classification for Hodgkin and Non-Hodgkin Lymphoma. https://www.ncbi.nlm.nih.gov/books/NBK66057/table/CDR0000062707__1075/. Updated: January 20, 2021. Accessed: February 14, 2021.
9. Porwit A, McCullough JJ, Erber WN. Blood and Bone Marrow Pathology. Churchill Livingstone ; 2011
10. Friedman DL. Hodgkin Lymphoma. Elsevier ; 2016 : p. 429-441
11. Paul Lorigan, John Radford, Anthony Howell, Nick Thatcher. Lung cancer after treatment for Hodgkin's lymphoma: a systematic review. Lancet Oncol. 2005; 6 (10): p.773-779. doi: 10.1016/s1470-2045(05)70387-9 . | Open in Read by QxMD
12. Smolewski P, Robak T, Krykowski E, et al. Prognostic factors in Hodgkin's disease: multivariate analysis of 327 patients from a single institution.. Clin Cancer Res. 2000; 6 (3): p.1150-60.
13. Liu R, Cao J, Gao X, et al. Overall survival of cancer patients with serum lactate dehydrogenase greater than 1000 IU/L. Tumor Biology. 2016; 37 (10): p.14083-14088. doi: 10.1007/s13277-016-5228-2 . | Open in Read by QxMD

What Is the 5 Year Prognosis for Hodgkin's Lymphoma

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