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Malignancy in primary immunodeficiency

Asghar Aghamohammadi, MD, PhD
Payam Mohammadinejad, MD
Section Editor
Luigi D Notarangelo, MD
Deputy Editor
Anna M Feldweg, MD


Patients with primary immunodeficiency (PID) are at an increased risk of malignancy compared with the normal population [1-4]. After infections, malignancy is the second most common cause of death in these patients [1].

The epidemiology and etiology of common PID-associated cancers, the most common types of cancer seen in patients with different forms of PID, monitoring of patients with PID for malignancies, and issues surrounding cancer treatment, will be reviewed here. An overview of the medical management of immunodeficiency and a discussion of the pulmonary complications of PID are found elsewhere. (See "Primary immunodeficiency: Overview of management" and "Pulmonary complications of primary immunodeficiencies".)


The overall risk for developing cancer in patients with primary immunodeficiency (PID) is estimated to range from 4 to 25 percent [5]. Advances in the therapeutic management of PID, most notably immunoglobulin replacement therapy, have resulted in a longer life expectancy and duration of disease [2]. As patients with PID live longer, malignancies are diagnosed more commonly. However, the cancer risk associated with PID is not well characterized in most studies due to various limitations, including small sample size (because of the rarity of PID), limited follow-up, lack of matched comparison groups, and the scarcity of population-based studies.

The Australasian Society of Clinical Immunology and Allergy (ASCIA) study was the first large study to calculate the standardized incidence ratio (SIR) of malignancy in PID patients, and it remains one of the largest studies performed to date [6]. SIRs were significantly elevated for all cancers (combined SIR 1.60), cancer of the thymus gland (SIR 67.3), non-Hodgkin lymphoma (NHL) (SIR 8.82), stomach cancer (SIR 6.10), and leukemia (SIR 5.36). "All cancer" and site-specific SIRs were not different for men and women, with the exception of thymoma, which was only identified in men [6]. In a study of 745 patients with PID reported in the Netherlands between 2009 and 2012, almost 10 percent of the patients suffered from a malignancy. Compared with the general Dutch population, the relative risk of developing any malignancy was two- to threefold higher, with a >10-fold increase for some solid (eg, thyroid, thymus) and hematologic tumors (eg, leukemia, lymphoma) [7].

Most common types of cancer — According to the Immunodeficiency Cancer Registry (ICR) database on immunodeficiency-associated cancer at the University of Minnesota, the most common types of malignancies among PID patients are NHL and Hodgkin lymphoma, which account for 48.6 and 10 percent of cancers seen in PID patients, respectively [8]. NHL represented 28 percent of all identified cancers in the ASCIA study [6]. The most common type of NHL in PID patients is diffuse large B cell lymphoma [9]. A table summarizing the cancers most commonly seen in patients with different types of PID is provided (table 1).

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Literature review current through: Dec 2017. | This topic last updated: Mar 15, 2016.
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