Sections

Presentation

History and Physical Examination

Lymphadenopathy is the most common manifestation of lymphoma. Lymphadenopathy may wax and wane. Spontaneous remissions have been documented, most commonly in patients with low-grade lymphomas.

Systemic symptoms (B symptoms) known to be associated with adverse prognosis include the following:

Unexplained fevers
Night sweats
Weight loss

Organ-specific symptoms that may lead to identification of specific sites of involvement include the following:

Shortness of breath, chest pain, cough
Abdominal pain and distention
Bone pain
Central nervous system (CNS) symptoms

Typical physical examination findings include the following:

Pallor (suggesting anemia)
Purpura, petechiae, or ecchymoses (suggesting thrombocytopenia)

Findings in patients with an advanced high-grade lymphoma may include the following:

High fever
Tachycardia
Respiratory distress

Examples of findings that might direct further investigations and subsequent therapy include the following:

Pharyngeal involvement
Thyroid mass
Evidence of pleural effusion
Abdominal mass
Testicular mass
Cutaneous lesions

Differential Diagnoses

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Media Gallery

Neoplastic follicles comprising cleaved cells (centrocytes) and larger cells with vesicular nuclei and prominent 2-3 nucleoli (centroblasts).
Mantle cell lymphoma. Small lymphoid cells with oval to slightly irregular nuclei and clumped chromatin and rare admixed pink histiocytes.
Diffuse large B-cell non-Hodgkin lymphoma. Large cells with abundant cytoplasm and large round-ovoid nuclei with thick nuclear membrane and multiple prominent nucleoli.
Burkitt lymphoma. Normal architecture is entirely replaced by lymphoma cells and evenly dispersed macrophages, starry sky (250×).
Burkitt lymphoma cells with round noncleaved nuclei and strongly basophilic cytoplasm (1000×).
Compartmentalizing fibrosis and infiltrate of medium-sized to large lymphoid cells.
Lymphoma cells show strong membranous positivity with CD20 indicative of B-cell origin.

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Table 1. Chromosomal Abnormalities in B-Cell Non-Hodgkin Lymphoma

Cytogenetic Abnormality	Histology	Antigen Rearrangement	Oncogene Expression
t(14;18)(q32;q21)	Follicular, diffuse large cell	IgH*	bcl- 2
t(11;14)(q13;q32)	Mantle cell	IgH	cyclin-D1/bcl-1
t(1;14)(p22;q32)	MALT lymphoma	IgH	bcl- 10
t(11;18)(q21;q21)	MALT lymphoma	IgH	Unknown
t(9;14)(p13;q32)	Lymphoplasmacytic lymphoma	IgH	PAX-5
8q24 translocations t(8;14)(q24;q32) t(2;8)(p11-12;q24) t(8;22)(q24;q11)	Burkitt lymphoma	IgH Ig-8 Ig-6	c-myc
Trisomy 12, deletion 11q22-23, 17p13, and 6q21	CLL	…	…
*Immunoglobulin H (IgH) MALT = Mucosa-associated lymphoid tissue.

Table 2. Characteristic Immunophenotypes of Major Subtypes of Lymphoma

Lymphoma	Immunophenotype
Follicular	CD20⁺, CD3^-, CD10⁺, CD5^-, BCL2⁺, CD23^-/+, CD43^-, cyclinD-1^-, BCL6⁺
Small lymphocytic	CD 20⁺, CD3^-, CD10^-, CD5⁺, CD23⁺,
MALT	CD20⁺, CD3^-, CD 10^-, CD5^-, CD23^-/+, BCL2⁺
Marginal zone	CD20⁺, CD3^-, CD 10^-, CD5^-, CD23^-/+, CD43^-/+, cyclinD-1^-, BCL2
Mantle cell	CD20⁺, CD23^-/+, CD10^-/+, CD5⁺, CD43^-/+, cyclinD-1+
Mediastinal large B-cell	CD20⁺, CD30+, MUM-1⁺
Burkitt	slg⁺,CD20⁺, Tdt^-, CD10⁺, BCL2-^-, BCL6⁺, Ki-67⁺ (≥95%)
B-lymphoblastic	slg-, CD19+, CD10^-/+, CD20^-/+, TdT⁺
MALT = mucosa-associated lymphoid tissue.

Table 3. Lugano Modification of the Ann Arbor Staging System.

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 “bulky disease”.		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
*Stage II bulky disease considered limited or advanced as determined by histology and a number of prognostic factors. Suffixes A and B are not required X for bulky disease replaced with documenting of largest tumor diameter Definition of “Bulky” disease varies depending on lymphoma histology.

Table 4. Non-Hodgkin lymphoma 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 “bulky disease”		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

Table 3. International Society for Cutaneous Lymphoma/European Organization for Research and Treatment of Cancer tumor-node-metastasis classification for cutaneous B-cell lymphoma

Tumor	Involvement	Node	Involvement	Metastatic Spread	Involvement
T1	Solitary skin involvement T1a: ≤5 cm diameter T1b: >5 cm diameter	N0	No lymph node involvement	M0	No evidence of extracutaneous non-lymph node disease
T2	Multiple lesions limited to one body region or two contiguous body regions T2a: all-disease in a < 15-cm diameter T2b: all-disease in a >15- and < 30-cm diameter T2c: all-disease in a >30-cm diameter	N1	Involvement of one peripheral lymph node region	M1	Evidence of extracutaneous non-lymph node disease
T3	Generalized skin involvement T3a: multiple lesions involving two noncontiguous body regions T3b: multiple lesions involving three body regions	N2	Involvement of two or more peripheral lymph node regions or involvement of any lymph node region that does not drain an area of current or prior skin involvement
		N3	Central lymph nodes involvement

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Author

Mohammad Muhsin Chisti, MD, FACP Associate Professor of Medicine (Hematology and Oncology), Oakland University William Beaumont School of Medicine; Medical Director of Research, Karmanos Cancer Institute

Mohammad Muhsin Chisti, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Coauthor(s)

Haresh Kumar, MBBS Resident Physician, Department of Internal Medicine, St Joseph Mercy Oakland Hospital

Disclosure: Nothing to disclose.

Sumeet K Yadav, MD, MBBS Resident Physician, Department of Internal Medicine, St Joseph Mercy Oakland Hospital

Sumeet K Yadav, MD, MBBS is a member of the following medical societies: American College of Physicians, Asian Medical Students' Association International, Bangladesh Medical and Dental Council, European Society for Medical Oncology, Nepal Medical Association, We Care, Jahurul Islam Medical College and Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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.

Additional Contributors

Ajeet Gajra, MD Associate Professor of Medicine, Director of Hematology/Oncology Fellowship Program, State University of New York Upstate Medical University; Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Veterans Affairs Medical Center

Ajeet Gajra, MD is a member of the following medical societies: American Association for Cancer Research, American Medical Association, American Society of Hematology

Disclosure: Nothing to disclose.

Neerja Vajpayee, MD Associate Professor, Department of Pathology, State University of New York Upstate Medical University

Neerja Vajpayee, MD is a member of the following medical societies: American Society of Hematology, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Sara J Grethlein, MD, and Uzma Athar, MD, to the development and writing of the source article.

B-Cell Lymphoma Clinical Presentation

History and Physical Examination

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