Is Paraneoplastic Granuloma Annulare Linked to Solid Organ Malignancies?

Granuloma annulare (GA) is rarely associated with solid organ malignancies and may be a paraneoplastic phenomenon, according to the results of a case-control study conducted in the United States and published in the Journal of the American Academy of Dermatology.

The investigators sought to compare the clinical and histopathologic features of paraneoplastic GA with those of classic GA. A total of 7 patients with paraneoplastic GA in association with solid organ malignancies were evaluated. In this study, paraneoplastic GA was defined as “GA occurring within 6 months of the diagnosis of solid organ malignancy and/or persistent GA that resolved with the treatment of the solid organ malignancy.” All medications were reviewed to rule out any possibility of a GA-like drug reaction. For each patient with paraneoplastic GA, 2 patient controls were selected based on age at diagnosis, gender, no cancer diagnosis within 6 month of GA diagnosis, and a minimum of 5 years’ follow-up after GA diagnosis without malignancy development.

Overall, 7 people with paraneoplastic GA and 13 controls were evaluated. All individuals with paraneoplastic GA and GA controls were white, with a similar age at disease onset (68.4 years vs 67.5 years, respectively). Similar rates of diabetes, hypercholesterolemia, and hypertriglyceridemia were reported in both groups. Among those with paraneoplastic GA, 4 were men and 3 were women. Overall, 5 of the 7 cases of paraneoplastic GA were associated with a primary tumor and 2 were associated with tumor recurrence. Most of the cases of paraneoplastic GA (6 of 7) were generalized disease, compared with 6 cases of generalized disease among the 13 classic GA controls. Patients with paraneoplastic GA more typically had involvement of the trunk and extremities, whereas classic GA more commonly involved the extremities.

No statistically significant differences in histopathologic features were observed between the cases and the controls. Most cases and controls were interstitial (5 of 7 and 6 of 13, respectively) and palisaded (3 of 7 and 8 of 13, respectively). Further, no significant differences in the pattern or type of cell infiltrate were reported between the cases and the controls. Of the 7 patients with paraneoplastic GA, 4 underwent treatment for their GA, with 2 receiving systemic therapy and 2 receiving skin-directed therapy. None of the 7 patients exhibited a clinically meaningful response, with 5 of 7 patients undergoing definitive treatment of cancer, with complete response in all patients.

In the current study, paraneoplastic GA was most often observed among patients with lung cancer (4 of 7). Patients with paraneoplastic GA typically have a later onset of disease, a slight male predominance, and a predilection for generalized disease compared with those with classic GA.

Limitations of the current study include its small sample size and retrospective design at a single, multisite institution. Additionally, 3 of the 7 people with paraneoplastic GA did not receive any treatment for their GA, rendering if difficult to determine treatment response.

The investigators recommend additional screening in asymptomatic patients with paraneoplastic GA and no history of cancer, no risk factors, and no concerning signs or symptoms of an underlying malignancy. Treatment of these individuals should focus on the underlying cancer, with the majority of cases resolving following cancer treatment. Recurrence of GA following cancer treatment should signal the possibility of cancer recurrence.

Reference

Mangold AR, Cumsky HJL, Costello CM, et al. Clinical and histopathological features of paraneoplastic granuloma annulare in association with solid organ malignancies: case control study [published June 16, 2016]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.06.022