Erdheim-chesters disease (ECD) is a non-Langerhans cell histiocytic disorder characterized by infiltration of foamy histiocytes in multiple organs. Herein, we describe an unusual presentation of ECD with concomitant diagnosis of papillary thyroid carcinoma. The majority of the cases of ECD are BRAF V600E mutation positive. Whether there is an increased risk of BRAF mutant papillary thyroid carcinoma in patients with ECD needs to be further investigated. ECD is undoubtedly a rare disease, however it is an overlooked diagnosis and raising awareness of ECD in the medical community is highly warranted.
 

Delivanis DA, Fatourechi V, Dean DS (2016) An Unusual Case of Bilateral Orbital Infiltrative Disease and Papillary Thyroid Cancer. JSM Thyroid Disord Manag1(1): 1004.

A 38-year-old woman presented with swelling of bilateral eye lids and yellowish discoloration of the overlying skin (Figure 1).

Figure 1 Cutaneous involvement of the skin (xanthelasma)

On evaluation, magnetic resonance imaging (MRI) of the head revealed symmetrical orbital infiltrative processes of unknown origin (Figure 2).

Figure 2 18FDG PET/CT scan. High FDG uptake of bilateral orbital muscles.

Work up for Graves’ disease with thyroidstimulating immunoglobulin testing was negative. Given prior history of follicular hyperplasia of a right inguinal lymph node, a PET/CT scan was performed to rule out lymphoproliferative disorder. Marked FDG uptake (SUV max 7.8) of the extra ocular musculature was noted (Figure 3)

Figure 3 MRI of the head-bilateral symmetrical infiltration of the orbital musculature.

together with an intensely FDG avid (SUV max 10.9) nodule within the posterior left thyroid lobe (Figure 4).

Figure 4 18FDG PET/CT scan. Focal FDG uptake of the left thyroid gland

No bony involvement was identified.

Patient underwent biopsy of the left orbital mass and a xanthogranulomatous inflammation was noted on pathology. Immunoperoxidase studies revealed IgG4 positive and CD1a negativecells, supporting the diagnosis of Erdheim-chesters disease (ECD). BRAF V600E mutation was negative. Subsequently, fine needle aspiration of the 1.6 cm thyroid nodule was consistent with papillary thyroid carcinoma (PTC).

ECD is a rare non-Langerhans histiocytic disorder, characterized by infiltration of tissues by foamy lipid-laden macrophages [1]. Clinical presentation is highly variable with most patients presenting with osseous involvement and orbital disease is seen in only 22% of the cases [2]. The pathogenesis is poorly understood, however an activating point mutation of the proto-oncogene BRAF V600E is identified in 38-100% [3,4] of cases of ECD and an NRAS mutation in some BRAF V600Enegative ECD patients. Two case reports of concomitant ECD and papillary thyroid carcinoma have been reported in the literature [5,6]; whether there is a true association between ECD and BRAF mediated tumors, such as papillary thyroid cancer remains unknown. ECD is undoubtedly a rare disease; however it is an overlooked diagnosis and raising awareness of ECD and its potential association with PTC in the medical community, is warranted.

1. Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood. 2014; 124: 483-492.

2. Arnaud L, Gorochov G, Charlotte F, Lvovschi V, Parizot C, Larsen M, et al. Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients. Blood. 2011; 117: 2783-2790.

3. Cangi MG, Biavasco R, Cavalli G, Grassini G, Dal-Cin E, Campochiaro C, et al. BRAFV600E-mutation is invariably present and associated to oncogene-induced senescence in Erdheim-Chester disease. Ann Rheum Dis. 2015; 74: 1596-1602.

4. Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013; 121: 1495-1500.

5. David Aparício NM, Carlos Leichsenring, Alice Rodrigues, Ana João, António Soares, Marta Fragoso, et al. Erdheim-Chester disease and papillary thyroid carcinoma: case report of a common association in a rare disease. Endocrine Abstracts. 2016.

6. Johnson WT PP, Hernandez A, Grandinetti LM, Huen AC, Marks S, Ho J, et al. Langerhans cell histiocytosis and Erdheim-Chester disease, both with cutaneous presentations, and papillary thyroid carcinoma all harboring the BRAF(V600E) mutation. J Cutan Pathol. 2016; 43: 270-275.