Clinical and radiological features of extra-pulmonary sarcoidosis: a pictorial essay

Abstract

The aim of this manuscript is to describe radiological findings of extra-pulmonary sarcoidosis. Sarcoidosis is an immune-mediated systemic disease of unknown origin, characterized by non-caseating epitheliod granulomas. Ninety percent of patients show granulomas located in the lungs or in the related lymph nodes. However, lesions can affect any organ. Typical imaging features of liver and spleen sarcoidosis include visceromegaly, with multiple nodules hypodense on CT images and hypointense on T2-weighted MRI acquisitions. Main clinical and radiological manifestations of renal sarcoidosis are nephrolithiasis, nephrocalcinosis, and acute interstitial nephritis. Brain sarcoidosis shows multiple or solitary parenchymal nodules on MRI that enhance with a ring-like appearance after gadolinium. In spinal cord localization, MRI demonstrates enlargement and hyperintensity of spinal cord, with hypointense lesions on T2-weighted images. Skeletal involvement is mostly located in small bone, showing many lytic lesions; less frequently, bone lesions have a sclerotic appearance. Ocular involvement includes uveitis, conjunctivitis, optical nerve disease, chorioretinis. Erythema nodosum and lupus pernio represent the most common cutaneous manifestations encountered. Sarcoidosis in various organs can be very insidious for radiologists, showing different imaging features, often non-specific. Awareness of these imaging features helps radiologists to obtain the correct diagnosis.

Teaching points: • Systemic sarcoidosis can exhibit abdominal, neural, skeletal, ocular, and cutaneous manifestations. • T2 signal intensity of hepatosplenic nodules may reflect the disease activity. • Heerfordt's syndrome includes facial nerve palsy, fever, parotid swelling, and uveitis. • In the vertebrae, osteolytic and/or diffuse sclerotic lesions can be found. • Erythema nodosum and lupus pernio represent the most common cutaneous manifestations.

Keywords: Granulomatous disease, chronic; Magnetic resonance imaging; Multidetector computed tomography; Positron-emission tomography; Sarcoidosis.

Fig. 1

A 61-year-old female patient affected by pulmonary sarcoidosis, proved by biopsy. Routine abdominal ultrasound exam (on Fig. 1a and b) shows multiple, small, randomly distributed, hypoechoic nodules in the liver parenchyma. Nodules were histologically related to sarcoidosis

Fig. 2

Hepatosplenic sarcoidosis. Liver MRI demonstrates multiple, scattered, small, hyperintense nodules (white arrows) on T2-weighted images (Fig. 2a and b) and on diffusion weighted imaging (DWI) (Fig. 2c and d); after gadolinium administration, nodules appear hypointense (Fig. 2e and f). In hepato-splenic sarcoidosis, T2 signal intensity reflects the degree of activity of disease: nodules can appear hyperintense in case of inflammation due to oedema and high vascular permeability; they have hypointense signal, when fibrosis is prevalent (see curved arrows for nodular lesions of the spleen)

Fig. 3

A 40-year-old female patient affected by pulmonary and splenic sarcoidosis. Figure 3a shows splenic sarcoidosis in a nodular pattern; the nodules (black arrowheads) are revealed as small hypodense nodules on contrast-enhanced CT images. Ill-defined pulmonary opacities, with small nodules around, are also depicted on Fig. 3b, resembling the typical sarcoid galaxy sign (white arrow)

Fig. 4

Splenic sarcoidosis in a 58-year-old female. Splenic parenchyma, on Fig. 4a, appears slightly inhomogeneous. After contrast administration (Fig. 4b and c), large nodules (exceeding 1 cm) with hypodense appearance are clearly depicted

Fig. 5

MRI appearance of a splenic sarcoidosis (same patient as Fig. 2). The visualization of the nodules reaches an optimal level on T2-weighted acquisition with fat suppression (Fig. 5a) and in the early gadolinium-enhanced T1 images (Fig. 5b)

Fig. 6

FDG uptake on PET-CT in a 57-year-old woman affected by pulmonary and splenic sarcoidosis. Increased metabolic activity is appreciable in the left pulmonary hilum, due to pathological lymph nodes (white arrowheads on Fig. 6a–b). Similarly, splenic foci of increased metabolic activity are clearly seen on axial CT-PET acquisitions (empty white arrowheads respectively on Fig. 6c–d), and on coronal and sagittal reformatted images (white arrows in Fig. 6e–h)

Fig. 7

Parotid gland sarcoidosis (histologically proven). On enhanced-CT images, parotid glands show inhomogeneous pattern (white arrowheads), with multiple and punctuate small hypodense lesions. Figure 7c show typical pattern of thoracic disease on CT acquisitions

Fig. 8

Parotid sarcoidosis (histologically proven), with enlargement of glands (white arrows). Nodular lesion is clearly depicted in the parenchyma of left parotid (white arrowheads in Fig. 8a and b)

Fig. 9

A 66-year-old female patient affected by sarcoidosis, which involves mediastinal and abdominal lymph nodes (histologically proven). Unenhanced abdominal CT image (Fig. 9a) demonstrate enlarged lymph nodes (white arrows), located in perihepatic region and close to the liver hilus; inside these lymph nodes, very small calcifications are recognizable (black arrowheads). Chest CT-scan shows mediastinal lymphadenopathy, with some punctate calcifications (white arrowhead on Fig. 9b). After contrast administration, both CT and MRI acquisitions show inhomogeneous enhancement of enlarged lymph nodes (white arrowheads on Fig. 9c and d)

Fig. 10

Incidental sarcoidosis diagnosis in a 59-year-old woman complaining of acute abdominal pain. Unenhanced CT scan shows a gallbladder calculus (white arrow on Fig. 10a) and some peri-pancreatic lymph nodes (white arrowheads on Fig. 10b); then CT scan extended through the chest (Fig. 10c) showed multiple, small subpleurical nodules. Histological exam confirmed diagnosis of sarcoidosis for the mentioned peri-pancreatic lymph nodes

Fig. 11

CT scan of a 55-year-old woman with multiple histologically proven sarcoidosis lymphadenopathy. Contrast-enhanced axial CT images (Fig. 11a–c) show multiple enlarged and confluent lymph nodes, located in the mediastinum (Fig. 11a), in the celiac region (Fig. 11b), and in the mesentery (Fig. 11c). Coronal MPR image (Fig. 11d) clearly depicts lymphadenopathy in the right side of the mediastinum, in the aorto-pulmonary recess (white arrow), at the right paratracheal level (empty  white arrowheads), and in the left perirenal space (white asterisk). Spleen enlargement can also be detected (white curved arrow)

Fig. 12

Multiorgan sarcoidosis, with multiple hypodense lesions in the renal parenchyma (white arrows in Fig. 12a–c). In the left kidney, in the lower part of the parenchyma, lesions have nodular appearance. Splenomegaly can also be observed (white arrowheads). In the Fig. 12d, a sarcoidosis pattern is observed on HRCT images (white arrows). Sarcoid lesions in the renal parenchyma were confirmed by biopsy

Fig. 13

“Heerfordt’s syndrome” in a 60-year-old woman. Clinically, the patient complained of sudden appearance of blurred vision, headache, and mouth deviation to the left after fever. MRI shows bilateral enhancement of facial nerve (white arrows on Fig. 13a), recognizable on T1-weighted image obtained after gadolinium administration. She showed a complete facial palsy and a bilateral enlargement of the cheeks. Physical examination revealed an unpainful enlargement of the left parotid gland, left facial nerve and left abducent nerve palsy. Nodular lesions were found in the parotid glands (same patient in Fig. 8), with evident contrast enhancement on T1-weighted acquisitions after contrast enhancement (Fig. 13b, empty white arrowhead) and on DWI sequences (Fig. 13c, white arrowheads). Chest CT scan and fibrobronchoscopy with bronchoalveolar lavage were suggestive of sarcoidosis. The biopsy of the left parotid gland depicted dense, non-caseating granulomatous infiltrate (Fig. 13d). Lymphocytes and epithelioid histiocytes with abundant eosinophilic cytoplasm and oval vesicular nuclei are observed (H&E 250X). The clinical, radiological and histopathological patterns were consistent with the diagnosis of Heerfordt’s syndrome

Fig. 14

Leptomeningeal localizations of sarcoidosis. Lesions are more visible on enhanced T1-weighted acquisitions, with increased enhancement along the surface of the brainstem (white arrows in Fig. 14a–b). Sarcoid nodules are also visible in the superior cerebellar cistern (white arrows in Fig. 14c–d)

Fig. 15

MRI images show spinal cord involvement in a 54-year-old man. T2-weighted image (Fig. 15a) demonstrates an extensive area of high signal intensity in the spinal cord (white arrow). On enhanced T1-weighted acquisitions, a peripheral enhancement (white arrows) can be depicted (Fig. 15b and c), suggesting meningeal involvement

Fig. 16

53 year-old man with hand involvement. A lacy pattern with small osteolytic areas is recognizable in the digits (white arrows in Fig. 16a and b)

Fig. 17

Multiple bone lesions in a 51 year-old man. Sagittal multiplanar CT image (Fig. 17a) and axial CT image (Fig. 17b) show a lytic area involving a dorsal vertebra (white arrows), with increased uptake on PET-CT scan (Fig. 17c). Histological examination revealed the presence of sarcoid disease of dorsal vertebra. Sarcoid lesion is also recognizable in the right ischial tuberosity (white arrows of Fig. 17d and e)

Fig. 18

49 year-old woman with axial skeleton involvement. Axial CT images show osteosclerotic lesions (arrowheads) of dorsal vertebrae (Fig. 18a), sacrum (Fig. 18b), and bilateral iliac crest (Fig. 18b). A lymphadenopathy can be also observed on Fig. 18b (white asterisk). Coronal reconstruction clearly depicts small osteosclerotic foci in dorsal vertebrae. Sagittal reconstruction (Fig. 18d) demonstrates lesions in contiguous or non-contiguous vertebrae in the dorsal and lumbar spine

Fig. 19

Skeletal sarcoidosis in a 71-year-old woman. Bilateral thoracic hilar lymphadenopathy is shown on PET-CT (Fig. 19a, white arrowheads). Increased sites of metabolic activity are also recognizable in the right scapula (Fig. 19b), in the sacrum and in the iliac crest (Fig. 19d). In presence of thoracic features of sarcoidosis, bone sites of increased uptake can be interpreted as “skeletal sarcoidosis”

Fig. 20

A 62-year-old woman with retinal involvement. Patient complained a left superior palpebral neoformation, which was subsequently biopsied: histological examination revealed the presence of a sarcoid nodule. She also referred to light flashes and blurred vision. Digital retinal angiography scan shows “punched-out” choroidoretinal lesions (white arrows on Fig. 20a–d). Chest CT (Fig. 20e and f) demonstrates mediastinal nodal enlargement, suggesting sarcoidosis in stage I

Fig. 21

Pattern of skin involvement in different patients with sarcoidosis. Erythema nodosum occurs with subcutaneous erythematous nodules, as well recognizable on Fig. 21a; it represents the most common non-specific lesions of cutaneous disease. Papules, clearly appreciable on Fig. 21b, represent the most common “specific” cutaneous manifestation of sarcoidosis: they may occur anywhere. Multiple large annular plaques can be a cutaneous appearance of sarcoidosis (Fig. 21c). Finally, Fig. 21d shows a lupus pernio, which represents a typical clinical manifestation of cutaneous sarcoidosis

Fig. 22

Cardiac MRI involvement in a patient with systemic sarcoidosis. Triple inversion recovery (Fig. 22a) and double-inversion recovery sequences (Fig. 22b), both obtained on short axis views, clearly show hypointense calcified myocardial and pericardial nodules (white arrows). After gadolinium administration, foci of delayed enhancement (white arrows), involving also the pericardium, are recognizable (Fig. 22c)