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About Lymphoma > Diagnosis & Pathology 

Last update: 11/05/2014

Diagnosis & Biopsy Information | Resources | Classifications | Pathology Background |
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Getting a Second Pathology Evaluation

 Diagnosis & Pathology

TOPIC SEARCH microenvironment AND prognosis WEB | PubMed

Related Topics
 Getting a Second Pathology Evaluation

Prognostic indicators

Performance Standards

Diagnostic Tests

Disease Direction Indicators
"About 85% of non- Hodgkin's lymphomas arise in B-cells; 

the rest occur in T-cells.

Activation of a gene called BCL-2 is believed to be partly responsible for many B-cell lymphomas.

This defect prevents apoptosis in the lymphoma cells (a natural process whereby cells self- destruct)."
"Storing all frozen specimens in the vapor phase of liquid nitrogen freezers will ensure that physical and chemical reactions within tissue are slowed so that the specimens remain stable for use over many years, and biomarkers of interest to researchers preserved. If cryopreservation for viable cells is required, biospecimens should undergo controlled rate freezing to prevent damage by ice crystallization." 

NBN blueprint. PDF
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Lymphoma often first appears as an enlarged lymph nodes, a condition called lymphadenopathy. Importantly, most cases of enlarged lymph nodes are NOT cancers, as the  following resource describes:

Lymphadenopathy: Differential Diagnosis and Evaluation, 
Robert Ferrer, M.D., M.P.H.  American Family Physician

 "Although the finding of lymphadenopathy sometimes raises fears about serious illness, it is, in patients seen in primary care settings, usually a result of benign infectious causes.

Most patients can be diagnosed on the basis of a careful history and physical examination. Localized adenopathy should prompt a search for an adjacent (nearby) precipitating lesion and an examination of other nodal areas to rule out generalized lymphadenopathy."
Pathology of Hodgkin's and Non-Hodgkin's Lymphomas pdf

To make an accurate diagnosis of lymphoma, a lymph node biopsy must be performed by the surgical removal (resection) of a lymph node.  A fine needle aspiration (FNA) may be performed if a lymph node is not accessible, but this is not considered a definitive way to determine the diagnosis*

* FNA, being a small way to get a sample, can miss malignant cells (leading to a false negative finding) and can lack the information needed to determine the type of lymphoma and the grade when positive (requiring a full biopsy anyway).

A series of tests will then be performed to determine the characteristics of the cells.  If a malignancy is determine, these characteristics will allow your doctors to determine the appropriate treatments to use when needed.  

Waiting for the results of a biopsy may be the most stressful time for the patient and his or her loved ones.  It can take many weeks to accurately determine the pathology of the sample.

NOTE: Snap-freezing part of this tissue is advised at this time as custom vaccines and potentially other advanced therapies can be developed from this tissue if it's stored correctly.  You may have to request this in order to make it happen, as fast freezing is not yet a mainstream procedure in all hospitals.  

This simple request is likely to result in improved diagnosis and more rational selection of treatments in the near future. 

A bone marrow biopsy may also be ordered to determine the extent of involvement in the bone marrow.  This sounds ominous, but the presence of malignant cells in the bone marrow is not unusual because the bone marrow is part of the immune system. It is where b-cells form.  Treatment can also clear the marrow of malignant cells.

The science of making a diagnosis is evolving rapidly.  Uncovering genetic and molecular characteristics of lymphomas will also lead to new treatment targets. You need to first identify the characteristics of the enemy before you can exploit its weaknesses. 

CT scans and other tests may be ordered to determine where the disease is forming tumors.  This will serve as a baseline to allow your doctor to monitor how fast or slow your lymphoma is progressing and/or evaluate response to treatment.

When monitoring disease, you may wish to consult with your doctor about alternatives to CT scans, such as sonograms, especially when accurate measurements are not required.  See How Many CTs?

Lung nodules -- is it lymphoma or a cancer?

* NEJM, 2013:
Probability of Cancer in Pulmonary Nodules Detected on First Screening CT

the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation (needle-like structure).


Hematopathology Approaches to Diagnosis and Prognosis of Indolent B-Cell Lymphomas 2005 

(The advent of new technologies has contributed to improvements in the diagnosis and classification of the non-Hodgkin lymphomas (NHL)
Overview of Diffuse and Follicular patterns
Immunohistochemistry in the Evaluation of Follicular or Nodular Lymphoid Lesions - pdf 

October 2003 by Rodney T. Miller, M.D., Director of Immunohistochemistry 
Recommendations for the Reporting of Lymphoid Neoplasms - Medscape

(free  login req.)
A checklist for pathologists and surgeons on how to evaluate and store lymphoid tissue at biopsy. 
Technical Resource on diagnosis of lymphoma
New Approaches to Lymphoma Diagnosis  ASHedbooksonline

Research News

Randomized comparison of power Doppler ultrasound-directed excisional biopsy with standard excisional biopsy for the characterization of lymphadenopathies in patients with suspected lymphoma.
J Clin Oncol. 2004 Sep 15;22(18):3733-40. PMID: 15365070 | Related articles


Also see for more information
on lymphoma



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There are many classifications of Non-Hodgkin's and other b-cell lymphomas, which are determined by appearance of the cells under microscopic examination (morphologic), and the stage of development of the cell (immunophenotypic). Increasingly, assessment of genetic characteristics -- the expression of genes in the malignant cells -- will be used to refine our understanding of types and subtypes of lymphomas.  See REAL and WHO systems for classifying lymphomas. 

Clinical classifications describe how fast the lymphoma is likely to grow (histology), and how wide spread it is at diagnosis (stage). Most often, patients are diagnosed with stage 4 disease, but this does not mean treatment is required or that the disease cannot be successfully treated.

Ann Arbor Stages of Non-Hodgkin's Lymphoma  Grade
BCL2 Negative?
Comparing classifications of Lymphoma, WHO to Rappaport

When older terminology is used to diagnose, this table becomes very useful.  
Salient cytogenetic entities  Antonio Cuneo
WHO Classification of B-cell Lymphoid Neoplasms 
World Health Organization Classification of Neoplastic Diseases
Who's WHO in Lymphoma 


Also see Pathology
- Getting a Second Evaluation
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Unfortunately, there is no lab test to screen for lymphoma. Symptoms can resemble many other conditions, such as infection. 

Therefore, the diagnosis of lymphoma generally requires a biopsy -- the surgical resection of a lymph node. The tissue is then analyzed with numerous tests to determine if the cells are normal or have malignant characteristics. 

It's important to receive an accurate diagnosis, so that the treatments selected will be appropriate.  For this reason, some pathologists recommend getting a second evaluation of the tissue.  See Getting a Second Evaluation

If a lymphoma is diagnosed, additional tests may be performed, such as imaging (CT or MRI) and a bone marrow biopsy, to determine the stage of the disease.  

Also see Classifications, above, and Pathology below.

A biopsy and subsequent evaluation by a trained pathologist is the only way to definitively diagnose lymphoma. It may take weeks to get the results, which is a major source of anxiety for patient and family.  

When surgical resection (removal) of a lymph node is not possible, a Fine Needle Aspiration or Large Needle/Core Biopsy may be performed, but each of these procedures have important diagnostic limitations. 


About diagnosis  Oncology Channel

Pathology Background

Also see Pathology - Getting a Second Evaluation
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Pathology is the science of defining characteristics of malignant cells compared to normal cells from which the cancer cells originate.  

You are likely to receive a pathology report of a lymph node tissue and possibly a report of a sample taken from your bone marrow. 

You may find the meaning of terms in your pathology report in the links provide here.  

We recommend that you ask for a copy of this report, as it is needed when consulting experts about your treatment options.

Technical Resources

Atlas of Hematology - Nagoya University Hematology Gallery
Blood Cells, Molecules, & Diseases -
Blood cells maturation chart (U Minn)
Hematopathology Links (The Karolinska Institute)
Flow panels, diagnosis, and general info - Univ of Washington Hematopathology Laboratory)
Disclaimer:  The information on is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns, you should always consult your doctor. 
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