Case Reports in Medicine

Case Reports in Medicine / 2020 / Article

Case Report | Open Access

Volume 2020 |Article ID 5730704 |

A. I. Parejo-Morón, M. L. Tornero-Divieso, M. R. Férnandez-Díaz, L. Muñoz-Medina, O. Preda, N. Ortego-Centeno, "Necrotizing Sarcoid Granulomatosis: A Disease Not to be Forgotten", Case Reports in Medicine, vol. 2020, Article ID 5730704, 4 pages, 2020.

Necrotizing Sarcoid Granulomatosis: A Disease Not to be Forgotten

Academic Editor: Rolando Cimaz
Received29 Aug 2019
Revised14 Dec 2019
Accepted08 Jan 2020
Published28 Jan 2020


Sarcoidosis is a systemic granulomatous disease of unknown aetiology characterised by the appearance of noncaseifying epithelioid granulomas in the affected organs, most commonly the lungs, skin, and eyes (Iannuzzi et al. 2007). Necrotizing Sarcoid Granulomatosis (NGS) is a rare and little-known form of disease, which also presents nodular lung lesions, and it shares pathologic and clinical findings with sarcoidosis, where the presence of necrosis may lead to misdiagnosis of tuberculosis (TB), leading to a consequent delay in treatment of the underlying entity (Chong et al. 2015). This is exactly what happened with the two cases that we present here.

1. Case Presentation

Case 1 was a 24-year-old woman who was 37 weeks pregnant, referred to our Internal Medicine unit because of a deep supraclavicular lymphadenopathy on the left side whose fine needle aspiration biopsy (FNAB) revealed granulomas with necrosis. Case 2 was a 31-year-old male with neurological symptoms (bradypsychia, peripheral vertigo, weakness in right lower limb, instability, and sphincter incontinence), whose cerebral nuclear magnetic resonance (NMR) revealed the presence of meningeal uptake; chest tomography scan (CT) showed mediastinal nodules and bilateral bronchoalveolar infiltrates; and the open lung biopsy showed sarcoid-like granulomas with extensive necrosis. Both patients received initially standard antituberculous treatment, but due to lack of response, the possibility of a necrotizing sarcoid granulomatosis raised up. After the start of treatment with glucocorticoids, the evolution was favourable in both cases. Table 1 provides more details of these cases.

Case 1Case 2

Sex and age24-year-old female. 37 weeks pregnant31-year-old male
Family historyFather diagnosed with discoid lupusBrother diagnosed with sarcoidosis (pulmonary and cutaneous involvement)

PresentationLeft supraclavicular lymphadenopathyPeripheral vertigo, weakness in right lower limb, instability, and sphincter incontinence

Physical examinationApprox. 4 × 4 cm supraclavicular tumour attached to deep planesBradipsychia. Right horizontal nystagmus. Paresis 4+/5 left upper limb and lower limbs. Left extensor cutaneous plantar reflex. Unstable romberg

LaboratoryNo lymphopoenia. T CD4/CD8 lymphocyte ratio: 1.43. Normal SACE. Calcium/phosphorus metabolism: normal. 24 h urine calciuria slightly higher than normal (264 mg/dL).
Positive Mantoux.
Discrete lymphopoenia. T CD4/CD8 lymphocyte ratio: 0.97. High SACE. Calcium/phosphorus metabolism: normal. Calciuria in urine at 24 h: normal.
Positive Mantoux.
Lumbar puncture: High ACE and ADA.
Cultures (including fungi) and indian ink: negative.
Sputum culture and mycobacterial PCR: negative.
BAL and sputum samples: negative for AFB

Imaging testsCervical CT scan, lymphadenitis that does not suggest pyogenic origin.
Chest x-ray: normal.
EEG: delta activity, more frequent on the right side.
Brain NMR: meningeal uptake that extends to the cervical area.
Chest CT scan: mediastinal nodules and bronchoalveolar infiltrates in both bases

Anatomical pathologyFNAB supraclavicular adenopathy: necrosis and granulomas. PCR mycobacterium tuberculosis: negative.
Ganglion exeresis: chronic lymphadenitis with sarcoid granulomas (Figure 1)
Open lung biopsy: necrotizing granulomatous infiltrates. PCR mycobacterium tuberculosis: negative

2. Discussion

Necrotizing sarcoid granulomatosis was first described in 1973 by Liebow, who noted the histological presence of confluent epithelioid granulomas with small central necrosis foci or more extensive necrosis, as well as vasculitis [1]. Liebow diferentiated this granulomatous disease from other forms of noninfectious pulmonary angiitis and granulomatosis: Wegener’s granulomatosis, Churg–Strauss syndrome, bronchocentric granulomatosis, and lymphomatoid granulomatosis. Actually most authors consider the entity as a form of sarcoidosis more than a distinct entity, differing in the fact that there is more intense necrosis and vasculitis [2].

Clinically, very few differences have been described between the two variants: classical and necrotizing, with pulmonary involvement predominating in both. Table 2 provides more detail on differences between them. In case 1, the clinical manifestation was a supraclavicular lymphadenopathy; peripheral lymphadenopathy appears in 40% of sarcoidosis patients. It should be noted that the presence of intrathoracic lymphadenopathies is more frequent in the classic form (85%) than in the necrotizing form (33%). In case 2, the predominant manifestation was central nervous system (CNS) involvement, which appears in 5.78% of NGS patients [3] and in the same proportion in patients with the classic form [4].

Nodular sarcoidosisNecrotizing variant

EpidemiologyPrevalence: 10 to 20 per 100,000 population
Males 44%
Females 56%
Median age: 35
<300 cases have been reported
Males 37%
Females 63%
Median age: 42
HistologyNonnecrotizing epithelioid granulomasGranulomas
Necrosis (coagulative or caseous) and vasculitis
Foci of infarction
Clinical presentation88%
Pulmonary and/or systemic symptoms (fever, weight loss, night sweats, malaise, and so on)
Pulmonary and/or systemic symptons (fever, weight loss, night sweats, malaise, and so on)
Involved organs
>>SACE elevation17%4%
>>Eye involvement14%12%
>>Skin involvement10%2%
>>Liver involvement9%1%
>>Erithema nodosum3%1%
>>Sjögren or sicca syndrome1%3%
>>CNS involvement2%7%
>>Splenic involvement2%1%
>>Lacrimal gland involvement1%2%
DiagnosisTransbronchial lung biopsy (35%)
Tissue obtained by surgical procedures (33%)
Needle biopsy (9%)
Bronchial biopsy (2%)
Intrathoracic lymph node biopsy (8%)
Extrathoracic lymph node biopsy (3%)
Tissue obtained by surgical procedures (98%)

SACE: serum angiotensin converting enzyme; CNS: central nervous system.

In respect of tuberculosis, the most frequent clinical presentation is also pulmonary involvement. The most frequent extrapulmonary form is lymph node tuberculosis, which is responsible for 43% of peripheral lymphadenopathies in the developed world [6]; CNS involvement is rarer (5.5%); due to this, it requires haematogenous dissemination either from a distal focus or during disseminated TB [7].

Correct diagnosis is vital because of the different treatments for the pathologies. Necrotizing sarcoidosis has a good response to corticoids, becoming benign [2, 5], and exceptionally severe neural involvement leading to death has been reported [3]. In contrast, tuberculosis disease requires TB treatment over a period of time that depends on the area affected [7].

Given the low effectiveness of cultures from most extrapulmonary locations for studying extrapulmonary tuberculosis, biopsy may be required for diagnosis. Visualising granulomas with caseification necrosis in biopsy samples, together with a compatible medical history, is practically diagnostic. Even so, samples should always be processed for microbiological study (staining, PCR, and culturing). A lack of microbiological isolation in the samples should therefore lead us to suspect a different granulomatous disease, such as necrotizing sarcoid granulomatosis [8].

Similarly, in patients suspected of having an active tuberculosis infection (based on clinical radiological findings), it is recommended to initiate the antituberculous regimen prior to microbiological isolation and evaluate the response after 2-3 weeks, while the microbiological results are being prepared. If there are no clinical or radiological changes and the microbiological study is negative, steroid therapy can be started [8].

In the two cases presented here, TB treatment was initiated. Given the absence of a favourable response, it was performed a biopsy that led to the diagnosis, allowing corticoid treatment to be initiated. In both patients, good disease control was achieved with low doses of corticoids, combined with methotrexate in case 2, permitting rapid reduction in prednisone doses.

3. Conclusion

Necrotizing sarcoid granulomatosis should be considered within the differential diagnosis of granulomatous diseases (Table 3), and knowledge of this variant is essential in order not to rule out sarcoidosis due to the presence of necrosis. The extended duration of the disease, its glucocorticoid response, negative cultures, and lack of response to TB treatment make it less likely for the aetiology to be infectious [8].


EpydemiologyMean age at diagnosis: 40–60 years
No gender predominance
Mean age at diagnosis: 40 years
No gender predominance
100 per 100,000 or higher: Sub-Saharan Africa, India, and the islands of Southeast Asia and Micronesia
26 to 100 cases per 100,000: China, central and South America, Eastern Europe, and northern Africa
Less than 25 cases per 100,000: United States, Western Europe, Canada, Japan, and Australia
Environmental contaminants in soil and water, having been isolated from the domestic water distribution network, hot tubs, swimming pools, and workplaces
HistologyGranulomatous inflammation, vasculitis, and necrosisEosinophilic infiltration
Areas of necrosis
Interstitial and perivascular necrotizing granulomas
An eosinophilic, giant cell vasculitis, especially of the small arteries and veins
Granulomas caseating which contain epithelioid macrophages, Langhans giant cells, and lymphocytesGranulomatous inflammation
Clinical presentationConstitutional symptoms (fever, malaise, anorexia, and weight loss)
Ear, nose, and throat manifestations (nasal crusting, sinusitis, otitis media, earache, otorrhea, persistent rhinorrhea, purulent/bloody nasal discharge, oral and/or nasal ulcers, and polychondritis)
Tracheal and pulmonary disease (nodules cavitary, and pulmonary opacities)
Renal manifestations (FSGS)
Poorly controlled asthma and lung disease (migratory infiltrates, pleural effusion, nodules rarely cavitary, and alveolar hemorrhage)
Upper airway and ear disease
Skin involvement
Peripheral neuropathy (mononeuritis multiplex)
Constitutional symptoms (fever, malaise, and weight loss)
Primary disease: pleuritic chest pain, fatigue, cough, arthralgia, and pharyngitis
Persistent fever, night sweats, weight loss, fatigue, malaise, and anorexia
Pulmonary disease
Superficial lymphadenitis
Skin and soft tissue infection
Laboratory testsANCA positive
Urinary sediment disorder
Peripheral blood eosinophilia
ANCA positive
BAL: high percentage of eosinophils in the lavage fluid
CRP elevated. Leukocytosis Hyponatremia, may be associated with the SIADHElevated acute phase reactants
DiagnosisBiopsy of a site of suspected active diseaseSurgical lung biopsyRadiographic imaging (radiography and TC) and microbiologic testing (sputum AFB smear, mycobacterial culture, and molecular tests)Recurrent isolation of mycobacteria from sputum or isolated from at least one bronchial wash in a symptomatic patient
Culture of blood for mycobacteria

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.


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Copyright © 2020 A. I. Parejo-Morón et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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