Diagnostic Considerations

Other conditions to consider in the differential diagnosis of Hodgkin lymphoma include the following:

Any disease presenting with lymphadenopathy and constitutional symptoms
Infection with human immunodeficiency virus (HIV)
Hypersensitivity reaction
Other solid tumors
Non-Hodgkin lymphoma, particularly diffuse large B cell lymphoma and anaplastic large cell lymphoma, both of which may have CD30 expression^[33]

Because Hodgkin lymphoma is considered a curable malignancy and the differential diagnosis is broad, medicolegal problems may arise from failure to diagnose the disease in a timely manner, possibly due to the following factors:

The misinterpretation of B symptoms
A lack of follow-up for abnormal chest radiographs or physical examination findings
A missed pathologic diagnosis because a needle biopsy was obtained rather than an excisional lymph node biopsy

Occasionally, Hodgkin lymphoma can present as hemophagocytic syndrome (hemophagocytic lymphohistiocytosis).^[34]The hemophagocytic syndrome may be more prevalent in patients with Epstein-Barr virus (EBV) antigen expression and has the following characteristics:

Pancytopenia
Fever
Hepatosplenomegaly with liver function test abnormalities
Elevated serum levels of ferritin and triglycerides
Phagocytosis of hematopoietic lineage cells by benign macrophages

Differential Diagnoses

Workup

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Media Gallery

Micrograph of Hodgkin lymphoma in a fine-needle aspiration lymph node specimen (field stain). Eosinophils, Reed-Sternberg cells, plasma cells, and histocytes can be seen.
Nodular sclerosing Hodgkin lymphoma of the mediastinum. The diagnosis is strongly suggested by the presence of distinct nodules on the cut surface of this lymph node.
A Reed-Sternberg cell in Hodgkin lymphoma. Reed-Sternberg cells are large, abnormal lymphocytes that may contain more than one nucleus. Image courtesy of National Cancer Institute.
Mixed cellularity Hodgkin lymphoma showing both mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells (hematoxylin and eosin, original magnification x200).
Very high magnification micrograph of nodular lymphoctye predominant Hodgkin lymphoma (NLPHL), with a popcorn-shaped Reed-Sternberg cell (hematoxylin and eosin).
A positron emission tomography (PET) scan obtained with fluorodeoxyglucose (FDG) that shows increased FDG uptake in a mediastinal lymph node.
A computed tomography (CT) scan showing bulk disease in a patient with Hodgkin lymphoma.
This computed tomography scan is from a 46-year patient with Hodgkin lymphoma at the level of the neck. Enlarged lymph nodes are visible on the left side of the neck (red-shaded region).
This image depicts a computed tomography (CT) scan, positron-emission tomography (PET) scan, and maximum intensity projection (MIP) PET scan from a patient with histologically proven Hodgkin lymphoma.

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Table 1. Stage Distribution and 5-Year Relative Survival by Stage at Diagnosis for All Races and Both Sexes: 2011-2015

Stage at Diagnosis	Stage Distribution, %	5-year Relative Survival, %
Stage I (only in originating layer of cells)	15	92.3
Stage II (confined to primary site)	40	93.4
Stage III (spread to regional lymph nodes)	21	83.0
Stage IV (cancer has metastasized)	20	72.9
Unstaged	4	82.7
Source: National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at: http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: September 12, 2018

Table 1. Cotswold Modification of Ann Arbor Staging System

Stage	Area of Involvement
I	Single lymph node group
II	Multiple lymph node groups on same side of diaphragm
III	Multiple lymph node groups on both sides of diaphragm

Table 2. International Conference on Malignant Lymphomas Modification of Ann Arbor Staging

Stage		Area of Involvement	Extranodal (E) Status
I	Single node or adjacent group of nodes		Single extranodal lesions without nodal involvement
II	Multiple lymph node groups on same side of diaphragm		Stage I or II by nodal extent with limited contiguous extranodal involvement
II bulky*	Multiple lymph node groups on same side of diaphragm with bulk >10 cm		N/A
III	Multiple lymph node groups on both sides of diaphragm; nodes above the diaphragm with spleen involvement		N/A
IV	Multiple noncontiguous extranodal sites		N/A
A/B	B symptoms: weight loss >10%, fever, drenching night sweats		N/A
*Stage II bulky disease is defined as limited or advanced on the basis of histology and a number of prognostic factors.

Table 3. Unfavorable Risk Factors for Stages I and II Hodgkin Lymphoma

Risk Factor	GSHG	EORTC/LSA
Age	–	≥50 y
Histology	–	MC or LD
ESR or B symptoms	>50 mm/hr if A or >30 if B	>50 mm/hr if A or > 30 if B
Mediastinal mass*	MMR >0.33	MMR >0.35
Number of nodal sites	>2	>3
Extranodal lesions	Any	–
* Mediastinal mass is measured on chest x-ray by the mediastinal mass ratio (MMR), which is the maximum width of the mass/maximum intrathoracic diameter.ESR = erythrocyte sedimentation rate; LD = lymphocyte depletion; MC = mixed cellularity.

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Author

Bradley W Lash, MD Attending Physician, Lehigh Valley Cancer Institute

Bradley W Lash, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Zachary Wolfe, MD Fellow in Hematology/Oncology, Lehigh Valley Health Network

Zachary Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Athanassios Argiris, MD Professor, Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine

Athanassios Argiris, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Scott K Dessain, MD, PhD Associate Professor, Lankenau Institute for Medical Research

Disclosure: Genentech Speaker's bureau.

Virginia Kaklamani, MD, Fellow, Department of Internal Medicine, Division of Hematology-Oncology, Northwestern University Medical School

Disclosure: Nothing to disclose.

Koyamangalath Krishnan, MD, FRCP, FACP Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

James L Spears, MD Consulting Staff, Bux-Mont Hematology Oncology Medical Associates

James L Spears, MD is a member of the following medical societies: American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Christine Wasilewski, MD, MPH, Fellow, Department of Medicine, Division of Hematology-Oncology, Thomas Jefferson University Hospital

Disclosure: Nothing to disclose.