Introduction: Sarcoidosis is a systemic disease of unknown aetiology, characterized by non-caseified granulomatous reaction that can involve multiple organs. The disease typically presents with pulmonary infiltrates, bilateral hilar and mediastinal lymphadenopathy and uveitis, but may also less frequently affect other organs, including the hypothalamic-pituitary axis. Malignancy rates in sarcoidosis patients have been reported as 1 to 2%1,2, chronic inflammation being a risk factor. The risk of hematologic malignancy is especially higher among these patients, so that the existence of a specific sarcoidosis-lymphoma syndrome has been suggested. We report here for the first time the co-occurrence of Hodgkins lymphoma (HL) and proven pituitary sarcoidosis.
Case report: A 26-year-old woman presented with recent headache and fatigue. Biological investigations disclosed an inflammatory syndrome (CRP 57.3 mg/l; normal range (NR) <5.0 mg/l), mild hypercalcemia (2.60 mmol/l; NR: 2.152.50) with low PTH (19 pg/ml; NR 1580) and complete anterior hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was therefore performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis. A puncture of the anterior chamber was also performed for measurements of IL-10 concentration which was low (1.01 pg/ml) and IL-6 concentration which was high (200 pg/ml). This low IL-10/IL-6 ratio was more consistent with uveitis of non-neoplastic etiology. A diagnosis of pituitary sarcoidosis was suspected.
A 18-FDG-PET fused with total body CT scan was performed and showed large hypermetabolic left unilateral hilar and mediastinal lymphadenopathies, left supraclavicular and axillar adenopathies, and an enhanced signal in the pituitary gland. As the localization of lymphadenopathies was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkins lymphoma (HL). A diagnostic transsphenoidal biopsy of the pituitary gland was proposed for accurate staging of the HL and surprisingly revealed typical granulomatous inflammation secondary to sarcoidosis, leading to the final diagnosis of a sarcoidosis-lymphoma syndrome.
Discussion: A diagnosis of systemic sarcoidosis was first considered in our patient, based of low PTH-hypercalcemia, bilateral uveitis of non-neoplastic origin, a pituitary inflammatory mass at MRI with complete anterior hypopituitarism (which was the initial manifestation) and hilar lymphadenopathies detected on FDG PET/CT. However, the localization and asymmetry of lymphadenopathies was not fully typical of sarcoidosis. Excisional biopsy of a left supraclavicular adenopathy was therefore performed to exclude another diagnosis and indeed showed typical pathological features of nodular sclerosis HL.
As involvement of the CNS is very uncommon in HL, any lesion in the brain of a patient known for HL should be investigated by biopsy for adequate staging and to rule out a second disease process3. In our patient, the pituitary biopsy indeed revealed a second diagnosis of sarcoidosis. Such association of sarcoidosis and lymphoproliferative disease has previously been reported as the sarcoidosis-lymphoma syndrome. Both diseases may be detected simultaneously, but usually lymphoma occurs after sarcoidosis with a median interval of 24 months4. However, the development of sarcoidosis in patients with lymphoma has been also reported5. The pathogenesis of this association may be explained by the inflammatory response in sarcoidosis increasing mitotic activity in lymphocytes and the greater risk of lymphocytes undergoing mutations, or by some common immunological abnormalities seen in both disorders In any case, the co-existence of sarcoidosis and lymphoma at first evaluation constituted a real diagnostic challenge.
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3. Himiz K, Foyle A, Wilke D, Burrell S, Brownstone R, Ago C, Pahil R & Couban S. Intracranial presentation of systemic Hodgkins disease. Leukemia and Lymphoma 2004; 45: 16671671.
4. Maayan H, Ashkenazy Y, Nagler A, Izbocki G. Sarcoidosis and lymphoma: case series and literature review. Sarcoidosis Vasculitis and Diffuse Lung Diseases 2011; 28: 146152.
5. London J, Grados A, Fermé C, Charmillon A, Maurier F, Deau B, Crickx E, Brice P, Chapelon-Abric C, Haioun C et al. Sarcoidosis occurring after lymphoma report of 14 patients and review of the literature. Medicine 2014; 93: 121.
21 Oct 2019
Belgian Endocrine Society