Lymphadenopathy and Splenomegaly (Case 29)

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Lymphadenopathy and Splenomegaly (Case 29)

Bridgette Collins-Burow PhD, MD

Case: A 21-year-old healthy woman presents to her gynecologist in March for her yearly Pap smear. Upon further questioning she reports fatigue, persistent upper respiratory symptoms with a nonproductive cough, as well as persistent low-grade fever for several months. She also reports a weight loss of about 10 pounds over the past several months and attributes this to the fact that she was attempting to lose weight. She denies any travel, sick contacts, or high-risk sexual behaviors. Her physical examination is remarkable for two firm, palpable, rubbery, left anterior cervical nodes that measure 2 cm in diameter. She is reassured by her physician and prescribed a 10-day course of oral penicillin.

Four weeks later, these lymph nodes are still present, and she feels that her left neck is “slightly fuller and tender.” Clearly upset about the swelling in her neck, she returns to her primary-care physician. In addition to her previous pertinent positive findings, on review of systems, she reports early satiety and night sweats. She has looked on the Internet for alternative explanations for her symptoms, and she is nervous now about the possibility that she may have lymphoma. She has lost an additional 7 pounds and is noted to have a palpable spleen on physical examination, in addition to both cervical and axillary lymphadenopathy. Her CBC and peripheral blood smear are normal.

Differential Diagnosis

Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL)

Mononucleosis/EBV infection


Primary HIV infection


Speaking Intelligently

When I encounter a patient with lymphadenopathy, I always take a detailed medical history and perform a complete physical examination. Of greatest concern is the possibility of malignancy. While the prevalence of malignancy in the general population presenting with unexplained lymphadenopathy is low, there are both historical and physical clues that can be suggestive of a diagnosis, including the age of the patient, the duration of lymphadenopathy, whether the lymphadenopathy is localized or generalized, the location of the lymphadenopathy, and associated clinical symptoms. Rubbery lymph nodes often suggest the diagnosis of lymphoma, whereas carcinomatous nodes are usually hard. Splenomegaly, in association with lymphadenopathy, focuses the differential on infectious mononucleosis, primary HIV infection, lymphomas, and sarcoidosis. When malignancy is of concern, excisional biopsy of a node is necessary to establish the diagnosis.


Clinical Thinking

• When evaluating a patient with lymphadenopathy, it is first important to obtain a detailed medical history.

• The age of the patient is very important in the evaluation. A majority of healthy young children have palpable cervical, axillary, and inguinal adenopathy; in fact, total lymph node mass reaches a maximum in early adolescence.

• Exposures related to travel, infection, the environment, and occupation are relevant for the evaluation of unexplained lymphadenopathy.

• Physical examination is equally important and must include a complete lymphatic examination with attention to lymphatic drainage patterns, as well as size and character of the lymph nodes.

• Iatrogenic causes of lymphadenopathy, with medications such as phenytoin, can be ruled out by history.

• The presentation of splenomegaly in association with lymphadenopathy in the above case focuses the differential on infectious mononucleosis, primary HIV infection, lymphomas, and sarcoidosis.

• The malignancies of particular concern in our patient’s presentation with classical “B” symptoms (i.e., fever, night sweats, and unexplained weight loss) include that of Hodgkin lymphoma and non-Hodgkin lymphoma.


• While patients who present with an underlying malignancy may often be asymptomatic, a history of fever, chills, night sweats, and unexplained weight loss should warrant further evaluation and workup.

• A good history should include investigation into infectious etiologies, as well as a detailed exposure history, sexual history, and medication history.

Physical Examination

• A patient who has evidence of an active pharyngitis, otitis media, or other focal infection may require no further evaluation of the lymphadenopathy. Other infectious etiologies of lymphadenopathy, however, may require specific testing, as in the examples of infectious mononucleosis and HIV.

• Important characteristics of lymph nodes on physical examination include the location, whether the lymphadenopathy is localized or generalized, the size and consistency of the node, whether fixed or mobile, and whether the lymph node is tender or nontender.

Tests for Consideration

Heterophile antibody test: This test is sensitive for the diagnosis of EBV infection; however, the test will be negative early after infection and will be negative if the mononucleosis is caused by other infections, such as CMV.
If the test is negative, serologic assays for specific agents should be considered.


HIV RNA testing: Could be considered in the setting of a high-risk patient with symptoms of acute HIV infection with a negative enzyme-linked immunosorbent assay (ELISA) and Western blot, which may represent the “window period” before seroconversion.


Serum angiotensin-converting enzyme (ACE) concentration:
Although some studies report an elevated ACE concentration in approximately 75% of patients with sarcoidosis, it is both an insensitive and a nonspecific test.


Excisional lymph node biopsy: The preservation of the nodal architecture is critical in the evaluation of lymphoma. In patients with Hodgkin lymphoma, the pathologic interpretation based on histology and the putative malignant cell, the Reed-Sternberg cell, is necessary for diagnosis. In patients with non-Hodgkin lymphoma, histologic, cytologic, and immunologic features as well as cytogenetic abnormalities are all instrumental in the classification. Fine-needle aspirates are never adequate to diagnose lymphoma.


Bone marrow biopsy and aspirate: Important in evaluating disease involvement outside of the lymphatic system in patients with lymphoma.


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Hodgkin Lymphoma

Hodgkin lymphoma is characterized by the presence of the Reed-Sternberg cell. The exact mechanism by which these cells derive and their role in the malignant process remain unclear. The majority of these cells are monoclonal B cells believed to be derived from preapoptotic germinal-center cells that have lost the capacity to express a high-affinity B-cell receptor. Reed-Sternberg cells are therefore able to subvert the apoptotic process.