Sarcoidosis Mimicking a Malignant Metastatic Disease

Abstract

Sarcoidosis can have pulmonary and extrapulmonary clinical manifestations depending on the organ of involvement. Because multiple organs are involved by the disease, sarcoid can mimic metastatic diseases. Whenever clinical and radiological clues of metastasis are present, differentials other than cancer should not be missed. Herein, we present a case of a middle aged gentleman who presented to the oncology clinic for 1-month history of low back pain associated with a dry cough along with radiological findings of metastatic disease involving the lungs, liver, lymph nodes, axial spine, and adrenal gland. A biopsy of the liver lesion showed non-caseating granuloma. Elevated blood levels of angiotensin-converting enzyme confirmed the diagnosis of sarcoidosis.

Introduction

Sarcoidosis is a multi-organ granulomatous disease that can affect, in addition to the lungs, several organs or systems leading sometimes to unusual presentations. ¹ More than 90% of sarcoidosis cases have a respiratory involvement and thereby have pulmonary manifestations, such as cough and dyspnea. ² In a certain percentage of cases, sarcoidosis can remain silent for years, only to be discovered incidentally peri-operative. ³ In other rare cases, sarcoidosis can have an initial lung involvement, complicated later during the disease course by extrapulmonary manifestations. ⁴ Unusually, the initial manifestation of sarcoidosis can be extrapulmonary clinically mimicking a metastatic disease.^5,6 Nevertheless, the radiological presentation can also mimic a metastatic malignancy. ⁷ Therefore, the diagnosis of sarcoidosis can be sometimes challenging due to the possible diagnostic similarity to malignant metastatic diseases. We present a case of a 54-year-old gentleman who presented for sudden onset of severe lower back pain found by imaging to have diffuse metastatic bone, liver, lung, adrenal, and lymph node disease. A liver biopsy was positive for non-caseating granulomas in the setting of elevated blood angiotensin-converting enzyme (ACE) level.

Case Presentation

A 54-year-old previously healthy gentleman presented with 1-month history of persistent low back pain. The pain started suddenly, was dull in nature, non-radiating, and worse during the night. No alleviating or exacerbating factors. While he denied symptoms of urinary incontinence, saddle anesthesia, or peripheral numbness, he reported an occasional cough that was present since 1 year prior to presentation.

Blood investigations were significant for ACE level of 102.2 U/L (reference: 12-68 U/L). Erythrocyte sedimentation rate (ESR) was elevated at 79 mm/h and C-reactive protein (CRP) was elevated at 52 mg/L. Complete blood count, electrolytes, calcium, hemoglobin A1c, fasting blood sugar, and lipid profile were within normal limits.

A magnetic resonance imaging (MRI) of the lumbar spine showed diffuse metastatic osteolytic bone disease in the lumbar and dorsal spine with L5-S1 degenerative disk disease impinging on the S1 nerve root.

A positron emission tomography (PET) scan showed radiotrace avid liver lesions with multiple bilateral fluorodeoxyglucose (FDG) avid pulmonary nodules. Enlarged mediastinal, bilateral hilar, bilateral axillary, abdominal, and pelvic lymph nodes were noted (Figure 1A to D). In addition, thickened left adrenal gland showing diffuse increased radiotracer uptake indicating likely disease involvement was noted. Furthermore, multiple lytic bone lesions, involving the axial and appendicular skeleton, the skull, ribs, and pelvic bones were evident. An ultrasound guided liver needle core biopsy was performed without evidence of malignancy. The liver was almost completely replaced by back to back non-caseating granulomas (Figure 2A). These granulomas were small and composed of tightly packed epithelioid histiocytes without associated necrosis, caseation, or acute inflammation (Figure 2B). Rare Langerhans-type multi nucleated giant cells were noted (Figure 2C). There were no Schaumann or Asteroid bodies noted in the giant cells. The granulomas were present in the hepatic parenchyma and also adjacent to bile ducts. Periodic acid–Schiff (PAS) and Grocott’s methenamine silver (GMS) stains were negative for fungal organisms. Acid fast stain was negative for mycobacterium tuberculosis. The biopsy ruled out a malignant condition and was most consistent with sarcoidosis. However, other granulomatous conditions were entertained, such as tuberculosis, atypical mycobacteria, fungal infections, sarcoid-like lesions due to cancer, immunodeficiency or medications, heavy metal, and others.

Figure 1.

(A) Axial fusion image of FDG PET/CT scan showing hypermetabolic adenopathy in the mediastinum, hypermetabolic lung nodules, and hypermetabolic bone lesions seen in both scapula. (B) Coronal fusion images of FDG PET/CT scan showing hypermetabolic liver lesions, hypermetabolic diffuse extensive bone lesions, and hypermetabolic lymphadenopathy and lung lesions in the chest. (C) Maximum intensity projection image of FDG PET/CT scan shows diffuse hypermetabolic disease in chest, liver, and bones. (D) Lung window images during FDG PET/CT scan showing bilateral small pulmonary nodules.

Figure 2.

(A) Liver biopsy showing non-caseating granulomas replace a large portion of hepatic parenchyma (H&E 20X). (B) Liver biopsy showing numerous non-caseating granulomas (white arrow) composed of tightly packed epithelioid histiocytes without associated necrosis, caseation, or acute inflammation (H&E 40X). (C) Liver biopsy showing rare Langerhans-type multi-nucleated giant cells are associated with the granulomas (white arrow) (H&E 40X).

Subsequently, a computed tomography (CT) of the chest without contrast was positive for diffuse lung nodule pattern with dispersed lesions seen with mean 5 mm mostly compatible with sarcoidosis. Sub-axillaries and mediastinum small lymph nodes were noted.

As the patient was not severely symptomatic, he was started on prednisone 20 mg daily for 1 week to be tapered by 5 mg weekly. In a 2-month post-treatment visit, the patient reported a significant improvement in the back pain, but slight improvement of the cough.

Discussion

Despite that the pulmonary and extrapulmonary manifestations of sarcoidosis can co-exist in around 50% of cases, ⁸ the unusual organ involvement and presentation of our patient makes the case a unique one.

Involvement of the adrenal glands has been poorly reported. Whenever there is sarcoid involvement, the adrenal gland is replaced by dense fibrosis, leading to adrenal insufficiency. ⁹ Although adrenal sarcoidosis patients respond well to steroid replacement, adrenal crisis ¹⁰ and death ¹¹ have been reported.

Sarcoidosis can co-exist and/or mimic metastatic malignancy. For example, sarcoidosis can rarely co-exist with thyroid cancer ¹² and oropharyngeal cancer. ¹³ Interestingly, sarcoidosis has been rarely reported to mimic a pattern of metastatic breast cancer, ¹⁴ and head and neck cancer. ¹⁵ Very rarely, sarcoidosis can mimic a widespread metastatic disease. ¹⁶

Whenever extrapulmonary involvement occurs, sarcoidosis can involve multiple organs at once. For example, the liver, bone marrow, eyes, and lymph nodes can be simultaneously involved. ¹⁷ Importantly, multisystem organ involvement predicts the need for chronic treatment and reflects a relatively poor prognosis. ¹⁸ Corticosteroids, followed by a tapering course, remain the cornerstone of treatment in symptomatic patients with abnormal function or imaging studies. ¹⁹

Conclusion

Because of the multi-organ involvement, sarcoidosis can present as a metastatic malignant disease. Certain organs, which are unusually involved, such as the adrenal gland, can be affected by the systemic disease. Oncologists can encounter patients with sarcoidosis, especially when imaging studies show metastasis. A biopsy of an involved organ is essential to differentiate metastatic malignancy from sarcoidosis. A long tapering course of corticosteroids are mainly used for treatment, especially in symptomatic patients.