Cutaneous granulomatous inflammation has been reported in association with underlying lymphoproliferative disorders in primarily two patterns: granulomas within or surrounding the cutaneous lymphoma itself, and a nonspecific reactive pattern to an underlying systemic or cutaneous lymphoproliferative disease.¹ Similar inflammatory patterns of granulomas have also been described in Hodgkin lymphoma within other organ systems, including lymph nodes, spleen, liver, and bone marrow, and in forms of granulomatous mycosis fungoides.^2,3 The granulomatous response to a cutaneous lymphoma can be prominent, even potentially obscuring the underlying lymphoma.¹ This is hypothesized to be the host defense response to the tumor, but the exact mechanism is unknown. The nonspecific granulomatous inflammation in association with underlying systemic and cutaneous lymphomas could result from a similar immune response.

Granuloma annulare (GA) is a benign, idiopathic, often self-limited granulomatous dermatitis characterized by red, brown, or violaceous papules or plaques that can be annular or polycyclic or more solitary in appearance (Fig. 63-1). GA is most commonly located on the dorsal hands and feet. The eruption may consist of solitary or locally grouped lesions, or it may be a more generalized eruption with lesions on the trunk as well as the extremities. Histopathologic features can comprise a palisaded granulomatous reaction composed of mononuclear histiocytes and multinucleated giant cells surrounding altered collagen, which often has mucinous change; or a diffuse interstitial histiocytic eruption with prominent mucin deposition (Fig. 63-2). The exact, underlying etiology is unknown, but is thought to be a potentially reactive process to underlying, often unidentified triggers, including diabetes, infections, and malignancies. Although evidence for causation is lacking, GA and other granulomatous disorders have been reported in association with neoplasms, including solid organ and visceral cancers.^4,5,6 GA has also been reported in association with hematolymphoproliferative malignancies, which will be the focus of the remainder of this chapter.

Although GA is a relatively common disease, affecting up to 0.4% of patients who present to dermatology,⁷ only a small number of these patients have been reported to develop an underlying hematologic malignancy, and the exact incidence is difficult to calculate secondary to the rarity. GA-like eruptions have been in association with several types of underlying lymphoproliferative disorders, both at the primary site of the malignancy and with the GA occurring at sites distant from the malignancy itself. The largest report by Barksdale et al.⁸ reported 13 cases of GA with lymphoma. In this report, GA-like lesions occurred in association with Hodgkin disease in three cases. Other than Hodgkin disease, there were three cases of follicular lymphoma, three cases of small lymphocytic lymphoma/chronic lymphocytic lymphoma, three cases of diffuse lymphoma, and one case of Sézary syndrome.⁸ The GA eruptions were reported over a wide range of time in association with the malignancy, ranging from 5 years before the diagnosis to 27 years after the diagnosis. The histopathologic features of GA were typical in nature and indistinguishable from other lesions of GA; however, painful lesions and lesions in unusual locations such as the palms, soles, and face were frequently reported in this series.⁸ A variety of GA lesions have been reported in association with Hodgkin disease with different morphologies including widespread near-erythrodermic disease, subcutaneous GA, and GA occurring within scars from prior herpes zoster infection, which can occur in nonmalignancy-associated GA as well.^{3,9,10,11,12,13,14,15}