Elsevier

Clinics in Dermatology

Volume 25, Issue 3, May–June 2007, Pages 326-333
Clinics in Dermatology

Sarcoidosis and malignancy

https://doi.org/10.1016/j.clindermatol.2007.03.010Get rights and content

Abstract

Malignancy in patients with sarcoidosis occurs in 3 settings. The first setting relates to patients with hematologic malignancies. It includes the sarcoidosis-lymphoma syndrome, which refers to the development of lymphoma at least 1 to 2 years after the diagnosis of sarcoidosis. It also includes patients with sarcoidosis who develop other hematologic malignancies. In addition, this subset of individuals includes patients with cancer and hematologic malignancies who subsequently develop sarcoidosis. The second setting consists of patients with sarcoidosis who develop solid tumors and oncologic patients in whom sarcoidosis subsequently appears; in addition to melanoma and nonmelanoma skin cancer, the neoplasms most commonly associated involve the cervix, liver, lung, testicles, and uterus. The third setting of malignancy-related sarcoidosis occurs when sarcoidosis presents as a paraneoplastic syndrome for the associated cancer, specifically when the discovery of cancer is concurrent with or within 1 year of the diagnosis of sarcoidosis or vis-a-vis. Antineoplastic treatment of either the hematologic malignancy or the solid tumor has also been observed to either induce the initial onset or flare the activity of sarcoidosis. Malignancy can also be associated with the occurrence of sarcoid reactions that typically are restricted to the regional lymph nodes or the visceral organ of tumor origin; rarely, the sarcoid reaction can also be observed in the skin or is only limited to the skin.

Introduction

Sarcoidosis is a multisystem granulomatous disease of unknown origin with pulmonary and extrapulmonary manifestations. Pulmonary manifestations can be visualized on chest roentgenogram: asymptomatic bilateral hilar lymph node enlargement and/or pulmonary infiltrates corresponding to symptoms such as cough and shortness of breath. Extrapulmonary sarcoidosis can affect the lymph nodes, parotid gland, liver and spleen, muscles and joints, central nervous system, eyes, electrolytes, and skin. Systemic symptoms and manifestations of extrapulmonary sarcoidosis include fever, peripheral lymphadenopathy, parotid gland swelling, hepatosplenomegaly, arthralgias and arthritis, cranial nerve palsies, subacute meningitis, diabetes insipidus, chorioretinitis, hypercalcemia, and mucocutaneous lesions.1, 2, 3

Patients with sarcoidosis can either present with or subsequently develop mucocutaneous manifestations. Cutaneous manifestations of sarcoidosis include nonspecific lesions and specific lesions. Erythema nodosum is an example of a nonspecific sarcoidosis-related skin lesion that is associated with acute disease; there is no granulomatous inflammation in the dermis. In contrast, specific skin lesions associated with sarcoidosis occur in patients with chronic disease, are pleomorphic in appearance (ranging in presentation from papules and plaques to subcutaneous nodules to ichthyosiform plaques), and are characterized by noncaseating granulomas in the dermis.1, 2, 3, 4, 5, 6, 7

Malignancy can affect the hematopoietic and lymphoreticular systems or the visceral organs. The mucocutaneous lesions of either primary dermatologic conditions or systemic diseases with mucosal and/or cutaneous manifestations can appear in oncologic patients. The sequential or concurrent occurrence of these skin or mucosal lesions in patients with malignancy may be coincidental or associated with the underlying cancer.8, 9, 10, 11

Cancer can eventually occur in patients who have an established diagnosis of sarcoidosis.12 Also, sarcoidosis can subsequently develop in an oncologic patient; in some individuals, a temporal association between the administration of antineoplastic therapy and the appearance of sarcoidosis is evident. Occasionally, a paraneoplastic relationship exists between the onset of sarcoidosis and the discovery of the underlying malignancy. Finally, sarcoid reactions have been observed in patients with cancer. This article summarizes and discusses the literature regarding sarcoidosis, sarcoid reactions, and malignancy.

Section snippets

Sarcoid reactions and malignancy

Sarcoid reactions refer to the development of noncaseating epithelioid cell granulomas in patients who do not fulfill the criteria for systemic sarcoidosis. In oncologic patients, sarcoid reactions (which are also referred to as sarcoidlike reactions) have been most commonly observed in the lymph nodes draining the cancer. In addition, they may occur in the stroma, the organ of tumor origin, or distant tissue sites such as the spleen, bone marrow, and skin.13, 14, 15, 16

Sarcoid reactions were

Sarcoidosis and malignancy

Although a review of the relevant literature suggests that the relationship between sarcoidosis and malignancy is a controversial subject, it has been repeatedly observed and reported that hematologic malignancies and solid tumors develop in patients with sarcoidosis and that the new onset of sarcoidosis occurs in oncologic patients.51, 52, 53, 54, 55, 56, 57 The first attempt to objectively quantify the incidence of cancer in patients with sarcoidosis was derived from a 10-year study (from

Sarcoidosis-lymphoma syndrome

Prompted by his earlier observations23, 56 and his continued clinical work, Brincker67 postulated that the coexistence of sarcoidosis and malignant lymphoproliferative disease evolved through an immunologic mechanism. His analysis of the 17cases he collected, supplemented with 29 similar cases that had previously been reported in the literature, suggested thatthis association was not fortuitous; indeed, lymphoma was noted to be 5.5 times more common in middle-aged patients withchronic active

Sarcoidosis and solid tumors

There is an increased frequency of solid tumors in patients with sarcoidosis. In addition, the new onset of sarcoidosis has subsequently been noted in several oncologic patients with visceral neoplasms.56, 91, 96, 121 A causal relationship between sarcoidosis and the occurrence of several of the neoplasms appears to exist; specifically, these include tumors that affect the cervix, liver, lung, skin(melanoma and nonmelanoma skin cancer), testicles, and uterus.

An increased incidence of lung

Paraneoplastic sarcoidosis

In this article, paraneoplastic sarcoidosis is defined as the onset of sarcoidosis that is coincidental with or within 1 year of the discovery of the patient's unsuspected cancer, and vis-a-vis. The detection of a hematologic malignancy and the diagnosis of sarcoidosis occured concurrently or within 12months of each other in several patients. The associated malignancies include Hodgkin disease,53, 55, 56, 67, 75, 77 non-Hodgkin lymphoma,51, 53, 54, 55, 67, 75, 79, 83, 85, 88 myeloma,55 leukemia,

Antineoplastic treatment–associated sarcoidosis

The new onset of previously undiagnosed sarcoidosis in a patient with cancer or the flare of previously diagnosed—either quiescent or active—sarcoidosis in an oncologic patient has been observed after antineoplastic treatment. This scenario occurs more commonly in patients with hematologic malignancies, such as Hodgkin disease, non-Hodgkin lymphoma, chronic myelogenous leukemia, multiple myeloma, and essential thrombocytosis. Cancer therapy–induced sarcoidosis, however, has also been reported

Conclusions

There is a postulated association between sarcoidosis and malignancy: (1) patients with sarcoidosis develop malignancies, and (2) sarcoidosis and sarcoid reactions occur in oncologic patients. Sarcoid reactions, referring to the development of noncaseating epithelioid cell granulomas in patients who do not fulfill the criteria for systemic sarcoidosis, predominantly occur in patients with Hodgkin disease and, to a lesser extent, in individuals with other hematologic malignancies (such as

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