Elsevier

Heart & Lung

Volume 42, Issue 1, January–February 2013, Pages 67-71
Heart & Lung

Issues in Infectious Disease
Fever of unknown origin (FUO) due to large B-cell lymphoma: The diagnostic significance of highly elevated alkaline phosphatase and serum ferritin levels

https://doi.org/10.1016/j.hrtlng.2012.05.004Get rights and content

Abstract

Background

Determining the cause of fever of unknown origin (FUO) is often a vexing and difficult diagnostic process. In most cases, the signs and symptoms in adult FUOs suggest a malignant, infectious, or rheumatic/inflammatory etiology. The diagnosis of FUO may be narrowed if specific findings are present (eg, hepatosplenomegaly) that limit the diagnostic possibilities. Infectious causes of FUO with hepatosplenomegaly include miliary tuberculosis, typhoid fever, and visceral leishmanosis (kala-azar). However, FUOs with hepatosplenomegaly are most often attributable to malignant neoplasms, ie, Hodgkin lymphoma, non-Hodgkin lymphoma, hepatoma, hypernephroma (renal-cell carcinoma), or preleukemia.

Methods and Results

We present a middle-aged woman with FUO and hepatosplenomegaly. Inpatient nonspecific laboratory findings included a highly elevated erythrocyte sedimentation rate, and elevated levels of vitamin B12, lactate dehydrogenase, angiotensin-converting enzyme, ferritin, and alkaline phosphatase. These individual findings are nonspecific, but together point to a lymphoma. An important test in differentiating malignant from infectious FUOs is the Naprosyn test, and her Naprosyn test was positive, indicating malignancy. A gallium scan suggested a uterine lymphoma. A computed tomography scan revealed hepatosplenomegaly, but the gallium uptake was not increased in her liver and spleen. Uterine and bone marrow biopsies were negative for lymphoma.

Conclusion

We present a case of FUO with hepatosplenomegaly attributable to large B-cell lymphoma as diagnosed via liver biopsy.

Section snippets

Case

A 63-year-old woman, born in El Salvador, was admitted after 6 weeks of high fevers. Vital signs during admission included a temperature of 102.3°F and a pulse of 98/minute (relative bradycardia). Her physical examination was otherwise unremarkable. During hospitalization for her FUO workup, she continued to manifest fevers >102°F, chills, and night sweats.

Laboratory tests included a WBC count of 4.2 K/mm3 (lymphocytes, 14%; monocytes, 17%). Her hemoglobin level was 10.9 g/dL, her hematocrit

Discussion

This case of FUO was interesting in several respects. Firstly, although typhoid fever, visceral leishmaniasis, and miliary TB were initial diagnostic considerations, nonspecific laboratory findings suggested malignancy.3, 4, 5, 6 The problem involved localizing the malignancy to an organ to limit the differential diagnostic possibilities and to provide a tissue diagnosis.12, 20 Her imaging studies revealed conflicting results, ie, her gallium scan indicated increased uptake in the uterus, but

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