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      A sarcoidosis–lymphoma syndrome revealed by hypopituitarism

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 1 , 1 , 1
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd
      Adolescent/young adult, Female, White, Belgium, Pituitary, Pituitary, PTH, FSH, ACTH, Cortisol, IGF1, LH, Thyroxine (T4), TSH, Hypopituitarism, Hypercalcaemia, Lymphadenopathy, Headache, Fatigue, Hypercalcaemia, Hypopituitarism, Lymphadenitis, Sarcoidosis, CT scan, MRI, PET scan, PTH, C-reactive protein, 25-hydroxyvitamin-D3, X-ray, Cortisol (9am), ACTH, FT4, FSH, LH, IGF1, TSH, Histopathology, Haematoxylin and eosin staining, Immunohistochemistry, Chemotherapy, Hydrocortisone, Glucocorticoids, Levothyroxine, Dacarbazine, Methylprednisolone, General practice, New disease or syndrome: presentations/diagnosis/management, September, 2019

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          Summary

          A 26-year-old woman presented with persistent headache and tiredness. Biological investigations disclosed a moderate inflammatory syndrome, low PTH-hypercalcemia and complete anterior hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis, and a diagnosis of pituitary sarcoidosis was suspected. As the localization of lymphadenopathies on the fused whole-body FDG-PET/computerized tomography (CT) was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkin’s 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 diagnosis of a sarcoidosis–lymphoma syndrome. The co-existence of these diseases constitutes a diagnostic challenge and we emphasize the necessity of exact staging of disease in order to prescribe adequate treatment.

          Learning points:
          • The possibility of a sarcoidosis–lymphoma syndrome, although rare, should be kept in mind during evaluation for lymphadenopathies.

          • In the case of such association, lymphoma usually occurs after sarcoidosis. However, sarcoidosis and lymphoma can be detected simultaneously and development of sarcoidosis in a patient with previous lymphoma has also been reported.

          • An accurate diagnosis of the disease and the respective organ involvements, including biopsy, is necessary in order to prescribe adequate treatment.

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          Most cited references13

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          Sarcoidosis and malignancy.

          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.
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            The sarcoidosis-lymphoma syndrome.

            H Brincker (1986)
            Analysis of 17 cases of coexistent sarcoidosis and malignant lymphoproliferative disease, supplemented with 29 similar cases reported in the literature indicates that this association is not fortuitous. In addition, significantly more malignancies other than lymphoma were found in this group of patients. A sarcoidosis-lymphoma syndrome appears to exist in which malignant lympho-proliferative disease develops at least 5.5 times more often than expected in middle-aged patients with chronic active sarcoidosis, possibly as a consequence of the immunologic abnormalities observed in the latter disease.
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              Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia.

              Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18,573 matched control subjects, and more than 86,000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions.
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                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                03 September 2019
                2019
                : 2019
                : 19-0091
                Affiliations
                [1 ]Departments of Endocrinology and Nutrition , Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
                [2 ]Internal Medicine , Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
                [3 ]Pathology , Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
                [4 ]Hematology , Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
                [5 ]Nuclear Medicine , Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
                [6 ]Ophthalmology , Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
                Author notes
                Correspondence should be addressed to C Delcourt; Email: charlotte.delcourt@ 123456uclouvain.be
                Article
                EDM190091
                10.1530/EDM-19-0091
                6765315
                c25e1704-3758-4609-9800-d4f8605aff1c
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 30 July 2019
                : 03 September 2019
                Categories
                Adolescent/Young Adult
                Female
                White
                Belgium
                Pituitary
                Pituitary
                PTH
                FSH
                ACTH
                Cortisol
                IGF1
                LH
                Thyroxine (T4)
                TSH
                Hypopituitarism
                Hypercalcaemia
                Lymphadenopathy
                Headache
                Fatigue
                Hypercalcaemia
                Hypopituitarism
                Lymphadenitis
                Sarcoidosis
                CT scan
                MRI
                PET scan
                PTH
                C-reactive protein
                25-hydroxyvitamin-D3
                X-ray
                Cortisol (9am)
                ACTH
                FT4
                FSH
                LH
                IGF1
                TSH
                Histopathology
                Haematoxylin and eosin staining
                Immunohistochemistry
                Chemotherapy
                Hydrocortisone
                Glucocorticoids
                Levothyroxine
                Dacarbazine
                Methylprednisolone
                General Practice
                New Disease or Syndrome: Presentations/Diagnosis/Management
                New Disease or Syndrome: Presentations/Diagnosis/Management

                adolescent/young adult,female,white,belgium,pituitary,pth,fsh,acth,cortisol,igf1,lh,thyroxine (t4),tsh,hypopituitarism,hypercalcaemia,lymphadenopathy,headache,fatigue,lymphadenitis,sarcoidosis,ct scan,mri,pet scan,c-reactive protein,25-hydroxyvitamin-d3,x-ray,cortisol (9am),ft4,histopathology,haematoxylin and eosin staining,immunohistochemistry,chemotherapy,hydrocortisone,glucocorticoids,levothyroxine,dacarbazine,methylprednisolone,general practice,new disease or syndrome: presentations/diagnosis/management,september,2019

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