Systemic Sarcoidosis

Quick Answer

Sarcoidosis is a multisystem granulomatous disease (noncaseating granulomas), most often involving the lungs and hilar/mediastinal nodes. FDG-PET/CT images disease activity, maps occult extrapulmonary sites, targets biopsy to the most active accessible lesion, and (with dedicated suppression prep) detects cardiac involvement. The legacy Ga-67 signs — panda (lacrimal/parotid) and lambda (hilar/mediastinal) — are classic but largely superseded by FDG.

Definition

Sarcoidosis is a systemic disorder characterized by noncaseating epithelioid granulomas in affected organs, most commonly the lungs and thoracic lymph nodes, but potentially any organ (skin, eyes, heart, nervous system, liver, spleen, bone).

Synonyms

Sarcoid; systemic sarcoidosis; Boeck sarcoid (historical). Syndromic forms: Löfgren syndrome (erythema nodosum + bilateral hilar adenopathy + arthralgia) and Heerfordt syndrome (uveoparotid fever).

Epidemiology

Sarcoidosis typically presents in young-to-middle-aged adults, with higher incidence and often more severe disease in people of African ancestry and in Northern Europeans. Thoracic involvement dominates; cardiac and neurologic disease are less common but disproportionately morbid.

Etiology & Risk Factors

The cause is unknown — a genetically susceptible host mounting an exaggerated Th1 granulomatous response to an unidentified antigen. HLA associations (e.g. HLA-DRB1) and BTNL2 confer risk; occupational/environmental exposures are implicated.

Pathophysiology

CD4⁺ Th1 lymphocytes and macrophages form noncaseating granulomas. Activated macrophages express 1-α-hydroxylase, converting vitamin D and causing hypercalcemia/hypercalciuria, and produce ACE (a nonspecific activity marker). Granulomas are metabolically active — the basis for FDG uptake — and can resolve or progress to fibrosis.

Genetics & Molecular Biology

HLA-DRB1 alleles (some protective, some risk — e.g. certain alleles link to the good-prognosis Löfgren phenotype) and BTNL2 are the best-established genetic associations; sarcoidosis is polygenic with environmental interaction.

Histopathology

Noncaseating epithelioid-cell granulomas with multinucleated giant cells (Schaumann/asteroid bodies may be seen). Diagnosis requires compatible clinicoradiologic features, granulomas on biopsy, and exclusion of infection (TB/fungal) and other granulomatous causes.

Clinical Presentation

• Pulmonary: cough, dyspnea, bilateral hilar adenopathy (often asymptomatic, incidentally found).
• Löfgren syndrome: acute, good-prognosis triad.
• Cardiac: conduction disease, arrhythmia, heart failure (see cardiac sarcoidosis page).
• Neurosarcoidosis, ocular (uveitis), cutaneous (lupus pernio, erythema nodosum), hepatosplenic, and bone involvement.

Laboratory Findings

Elevated ACE (nonspecific), hypercalcemia/hypercalciuria, lymphopenia, and elevated inflammatory markers. Diagnosis is clinicoradiologic + histologic with infection excluded.

Imaging Findings by Modality

• Chest radiograph (Scadding stages 0–IV) and CT: hilar/mediastinal adenopathy and parenchymal patterns.
• FDG-PET/CT: activity, whole-body extent, occult sites, and biopsy targeting; distinguishes active (FDG-avid) inflammation from fibrosis (photopenic).
• Cardiac FDG-PET (dietary suppression prep) + rest perfusion for cardiac sarcoid.
• Ga-67 scintigraphy (legacy): panda (lacrimal/parotid) and lambda (hilar/mediastinal) patterns.

Radiopharmaceutical Uptake Mechanisms

FDG accumulates in the activated macrophages and lymphocytes of metabolically active granulomas (avidity tracks activity; fibrosis is not avid). Ga-67 binds transferrin/lactoferrin at sites of inflammation. The activity-dependence of FDG is what makes it useful for treatment monitoring.

Typical PET Tracers

Typical SPECT Tracers

• Ga-67 citrate (legacy) — panda/lambda signs; largely replaced by FDG.

Therapy Indications

• Observation for asymptomatic/mild disease (many resolve — especially Löfgren).
• Corticosteroids for symptomatic/organ-threatening disease; steroid-sparing agents (methotrexate, azathioprine) and anti-TNF (infliximab) for refractory disease.
• Organ-specific management (cardiac device/therapy, neurosarcoid immunosuppression).

Theranostics

No radioligand therapy — nuclear medicine's role is diagnostic and activity-monitoring (extent, occult sites, biopsy targeting, cardiac detection, and response assessment).

Differential Diagnosis

• Lymphoma (FDG-avid nodal disease — a key mimic), tuberculosis/fungal granulomatous infection, metastatic disease, and IgG4-related disease.
• Sarcoid-like reactions (e.g. checkpoint-immunotherapy irAE, near malignancy) mimic sarcoidosis.

Reporting Checklist

• Report activity (avid vs fibrotic), whole-body extent, and the most active biopsy target.
• For cardiac assessment, confirm dietary suppression adequacy and pair with perfusion.
• Frame FDG activity for treatment monitoring (baseline vs follow-up, matched technique).
• Note lymphoma/infection mimics when relevant.

Prognosis

Many patients (especially Löfgren) remit spontaneously. Cardiac, neurologic, and progressive fibrotic disease carry worse prognosis. FDG activity helps identify who may benefit from (or is responding to) immunosuppression.

Board Pearls

FDG-PET/CT images sarcoidosis activity (avid granulomas vs photopenic fibrosis), maps occult extrapulmonary sites, and targets biopsy to the most active accessible lesion — and, with dietary suppression prep, detects cardiac involvement. Classic Ga-67 signs are panda (lacrimal/parotid) and lambda (hilar/mediastinal).

Cardiac sarcoid FDG imaging requires myocardial glucose suppression (high-fat/very-low-carb + fast ± heparin) so only inflammation lights up — the mirror image of viability prep (see cardiac sarcoidosis page).

FDG activity-dependence makes it valuable for treatment monitoring (falling uptake = response). Beware the key mimics — lymphoma (FDG-avid nodes), TB/fungal granulomatous infection, and checkpoint-immunotherapy sarcoid-like reactions — and remember diagnosis still requires histology with infection excluded.

Related Pages

• Related: Cardiac sarcoidosis (suppression-prep FDG), infection & inflammation, tracer gallium-67 (panda/lambda).
• Pitfalls: Pearls, pitfalls & normal variants.

Figure / Diagram Suggestions

• A whole-body FDG activity map (active granuloma vs fibrosis).
• The panda/lambda Ga-67 sign plate.
• A biopsy-targeting schematic (most active accessible lesion).

Common Pitfalls

• For cardiac imaging, inadequate dietary suppression leaves residual physiologic myocardial FDG (often lateral wall) that mimics or masks active inflammation — verify suppression before interpreting.
• FDG cannot distinguish active sarcoid granulomas from lymphoma, TB/fungal infection, or metastatic nodes — avid disease still requires histology with infection excluded.
• Sarcoid-like reactions (checkpoint-immunotherapy irAE, reaction adjacent to malignancy) can be mistaken for lymphoma progression or metastatic spread — biopsy before calling progression.
• A negative or low-uptake FDG study does not exclude structural disease — burnt-out fibrotic sarcoid is photopenic despite significant organ damage.
• Physiologic uptake (brown fat, muscle, bowel, thymus) can be over-read as active extrapulmonary disease — correlate with CT and pattern.

Self-Check (Board-Style)