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Vol. 54. Issue 10.
Pages 531-533 (October 2018)
Vol. 54. Issue 10.
Pages 531-533 (October 2018)
Scientific Letter
DOI: 10.1016/j.arbr.2018.01.037
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Extrapulmonary Tumors and Sarcoidosis: An Incidental or Real Association?
Tumores extrapulmonares y sarcoidosis. ¿Relación casual o real?
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Tara Pereiroa,
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tpereirobrea@gmail.com

Corresponding author.
, Antonio Golpea,b, Tamara Louridoa, Luis Valdésa,b
a Servicio de Neumología, Complejo Hospitalario Universitario Santiago de Compostela, Santiago de Compostela, Spain
b Grupo Interdisciplinar de Investigación en Neumología, Instituto de Investigaciones Sanitarias de Santiago (IDIS), Santiago de Compostela, Spain
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Tables (1)
Table 1. Characteristics of the 14 patients.
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To the Editor:

Sarcoidosis is a systemic granulomatous disease of unknown etiology that usually affects young patients, with an estimated incidence in Spain of 1.36/100000 inhabitants.1 The pathogenesis of sarcoidosis is thought to be related with exposure to certain environmental factors in genetically predisposed individuals.2,3 Whether or not patients with sarcoidosis have a greater risk of developing cancer is debatable,4,5 but reports in the literature of the tumor appearing before the diagnosis of sarcoidosis are rare and limited to case series. We report a series of 14 patients who were diagnosed with sarcoidosis during oncological follow-up of extrathoracic cancers.

We performed a retrospective, descriptive, observational follow-up (January 2012–June 2017) of patients with extrathoracic tumors referred to the bronchoscopy unit for the exploration of new mediastinal lymphadenopathies on a chest computed tomography (CT).

A total of 2420 patients were evaluated, of which 437 candidates met the study criteria; 404 were finally included. Reasons for exclusion were contraindication for endobronchial ultrasound for various reasons (12 cases), mediastinal lymphadenopathies already present at the time of cancer diagnosis (15 cases), or patient's refusal to perform more diagnostic tests (6 cases). All patients underwent linear endobronchial ultrasound for lymphadenopathy aspiration (Olympus BF-UC180F; Olympus ViziShot needle NA-201SX-4022, 21G) under sedation with midazolam. Fourteen patients (7 men and 7 women; mean age at diagnosis of the tumor 54.2±13.9 years) were diagnosed with sarcoidosis on the basis of clinical and radiological criteria with histological confirmation6 (mean age at sarcoidosis diagnosis: 56.6±13.7 years). Mean time between both diagnoses was 2.4±2.3 years. The most common tumors were gastrointestinal (three cases), breast, gynecological, and oropharyngeal (two each) (Table 1). Two patients had two tumors (cervical-ovarian and epiglottal-tonsillar; interval between diagnoses 36 and 4 months, respectively). Most tumors were diagnosed in early stages [stages I–II; 12/16 (75%); stage III: 3/16 (18.8%); stage IV: 1/16 (6.2%)]. The stations most often aspirated were the subcarinal (7; 100%) and lower right paratracheal [4R; 9/14 (64.3%)]. Eight patients (57.1%) had sarcoidosis at radiological stage II and six patients presented stage I (42.9%). Eight of the 14 patients (57.1%) were asymptomatic, 4 (28.6%) had arthralgia, 2 (14.3%) had asthenia, 1 (7.1%) had polyneuropathy, and another (7.1%) had skin involvement. In all cases, cultures to identify Mycobacterium tuberculosis in lymphadenopathy samples were negative. In addition to bilateral enlargement of the mediastinal lymph node chains, seven patients (50%) had diffuse bilateral millimetric pulmonary nodules. Increased mediastinal uptake on positron emission tomography was observed in 7 of the 14 patients (SUVmax 16.2±12.9; range 4.2–24.9). Only 10 of the 14 patients received chemotherapy (four cisplatin and two docetaxel) (Table 1). Two patients were treated with corticosteroids (those with polyneuropathy and skin involvement) for 3 and 24 months (maximum doses of 50 and 30mg prednisone, respectively). Response was favorable in both cases. Mean patient follow-up was 57.8±24.1 months after diagnosis of the tumor (with only one tumor relapse and no deaths), and 28.1±15.8 months after the sarcoidosis diagnosis.

Table 1.

Characteristics of the 14 patients.

CaseSexAge at diagnosis of cancer/sarcoidosis (years)  History of cancerHistory of sarcoidosis
Interval between diagnoses (years)Origin of cancer/stageTreatmentCancer relapseaFollow-up (monthsb)Clinical characteristicsCTTreatment/monthsSUVmaxFollow-up (monthsc)LFT
Regimen  Chemotherapy agent 
50.6
59.3
8.7 
Colon
T1N1M0 
Surg+ACT  FOLFOX  No  115  Arthralgia  HMLNCE
Pulmonary nodules (2) 
10.7  No  14  Obstruction 
49.9
53.8
3.9 
Ovarian
T1N0M0 
Surg+ACT  Carbotaxol  No  54  Polyneuropathy  HMLNCE
BPMN 
24.9  CS/3  Normal 
43.4
44.5
1.1 
Rectum
T3bN1bM0 
Surg+ACT+RT  Capecitabine  No  40  Arthralgia
Asthenia 
HMLNCE
BPMN 
Negative  No  27  Normal 
62.3
66.7
4.4 
Stomach
T2N2Mx 
Surg+ACT  5-fluorouracil  No  67  Asymptomatic  HMLNCE  10.1  No  18  Normal 
62.5
63.9
1.4 
Breast
T1N2M0 
Surg+ACT  Docetaxel  No  56  Skin involvement
Arthralgia 
HMLNCE
BPMN
RP lymph nodes 
Negative  CS/24  37  Normal 
53.6
53.9
0.3 
Tonsil
T2NxMx 
Surg+ACT+RT  Docetaxel
Cisplatin
Xeloda 
No  45  Arthralgia  HMLNCE
BPMN 
11.2  No  43  Obstruction 
26.6
28.3
1.7 
Ovarian
Stage IIIc and
Cervix
T1N1M0 
CT+RT
CT+conization 
Cisplatin
Etoposide 
No  62  Asymptomatic  HMLNCE  Negative  No  37  Normal 
73.3
74.4
1.1 
Parotid gland
T4cN2M0 
CT+RT  Cisplatin  No  75  Asymptomatic  HMLNCE  4.2  No  65  Normal 
35.4
37.4
Testicle
T1N3M0 
CT  Bleomycin  No  60  Asymptomatic  HMLNCE  Negative  No  35  Normal 
10  60.6
65.5
4.9 
Bladder
T4N2M0 
CT  Cisplatin
Gemcitabine 
No  79  Asthenia  HMLNCE
Inguinal LNE 
Negative  No  22  Obstruction DLCO 64% 
11  71.7
72.1
0.4 
Melanoma
T1N0M0 
Surg  –  No  10  Asymptomatic  HMLNCE
BPMN 
Negative  No  Normal 
12  41.1
44.4
3.3 
Breast
T1cN0M0 
Surg+RT+tamoxifen  –  Yes  63  Asymptomatic  HMLNCE
BPMN 
6.5  No  23  Normal 
13  68.1
68.6
0.5 
Kidney
T1aN0M0 
Surg  –  No  47  Asymptomatic  HMLNCE  Negative  No  37  Obstruction 
14  59.8
60.8
Tonsil
T1-2N0M0 and
Epiglottis
T1N0M0 
Surg  –  No  36  Asymptomatic  HMLNCE
BPMN 
No  24  Normal 

ACT, adjuvant chemotherapy; BPMN, bilateral pulmonary micronodules; CS, corticosteroids; CT, chemotherapy; F, female; HMLNCE, hilar-mediastinal lymph node change enlargement; LFT, lung function tests; LNE, lymph node enlargement; M, male; RP, retroperitoneal; RT, radiation therapy; Surg, surgery; SUVmax, standardized maximum uptake value on positron emission tomography.

a

Before or after sarcoidosis diagnosis.

b

Follow-up after cancer diagnosis (months).

c

Follow-up after sarcoidosis diagnosis (months).

This study shows that the development of new mediastinal lymphadenopathies in a cancer patient does not necessarily mean tumor extension, even if hyperenhancement is observed, and the possibility of sarcoidosis (or other diseases) must be considered.7 Histological confirmation is always needed.8 Another important finding is that the diagnosis of sarcoidosis was always subsequent to the tumor diagnosis. The inverse order has been described more often, and very few published series report a diagnostic chronology of tumor followed by sarcoidosis.9,10

It is sometimes difficult to differentiate between sarcoidosis, tuberculosis or a sarcoid-like reaction. The diagnosis of tuberculosis, a real possibility in our region which has an incidence of 21.3 cases/100000 inhabitants/year,11 was ruled out in all cases by a negative culture for M. tuberculosis in a sample of mediastinal lymphadenopathy obtained by endobronchial ultrasound. A sarcoid-like reaction (development of non-caseifying epithelioid cell granulomas in patients who do not fully meet the criteria for sarcoidosis) can occur in cancer patients in the first regional lymph node chain to which a particular tumor might metastasize, taking into account the strategic position occupied by each nodal group.12,13 This phenomenon is more common in testicular cancers and lymphomas. As mediastinal lymphadenopathies would be the first chains to which lung and pleural cancers would metastasize, these tumors were excluded from the study. Moreover, the fact that our patients were in remission, yet presented systemic symptoms or mediastinal lymphadenopathies with uptake on PET7 (six and seven of our patients, respectively), was suggestive of a diagnosis of sarcoidosis. However, even with these differentiating factors, it may be difficult to distinguish between these two entities.

Although the association between cancer and sarcoidosis was formerly believed to be incidental, the current thinking is that certain etiopathogenic mechanisms may be involved in genetically predisposed individuals, such as immune hyperresponsiveness of the host to the cancer itself (or antigens produced by the tumor),9 or the treatment of the tumor itself,12 as in the case of nivolumab in metastatic melanoma.13

The main limitation of this study is that we may have generated some bias by limiting inclusion to patients referred to a bronchoscopy unit, as this procedure might not be requested in all patients, metastasis of the underlying tumor perhaps being assumed in many cases.

In conclusion, the appearance of mediastinal lymphadenopathies in patients with extrapulmonary tumors should not be assumed to be tumor recurrence, and other causes, including sarcoidosis, must be considered. Histological diagnosis is the technique of choice in these cases. Although the relationship between cancer and sarcoidosis and the pathogenic mechanisms that might link them have not been clearly established, either the tumor itself or else the anticancer treatment may possibly promote the development of sarcoidosis in genetically predisposed individuals. More studies are needed to clarify this association and its clinical value and prognosis.

References
[1]
A. Xaubet, J. Ancochea, R. Blanquer, C. Montero, F. Morell, E. Rodríguez Becerra, et al.
Diagnosis and treatment of diffuse interstitial lung diseases.
Arch Bronconeumol, 39 (2003), pp. 580-600
[2]
J. Ji, X. Shu, X. Li, K. Sundquist, J. Sundquist, K. Hemminki.
Cancer risk in hospitalized sarcoidosis patients: a follow-up study in Sweden.
Ann Oncol Off J Eur Soc Med Oncol, 20 (2009), pp. 1121-1126
[3]
D.T. Alexandrescu, C.L. Kauffman, T.E. Ichim, N.H. Riordan, F. Kabigting, C.A. Dasanu.
Cutaneous sarcoidosis and malignancy: an association between sarcoidosis with skin manifestations and systemic neoplasia.
Dermatol Online J, 17 (2011), pp. 2
[4]
M. Bonifazi, F. Bravi, S. Gasparini, C. la Vecchia, A. Gabrielli, A.U. Wells, et al.
Sarcoidosis and cancer risk: systematic review and meta-analysis of observational studies.
Chest, 147 (2015), pp. 778-791
[5]
P. Ungprasert, N. Srivali, K. Wijarnpreecha, C. Thongprayoon, W. Cheungpasitporn, E.L. Knight.
Is the incidence of malignancy increased in patients with sarcoidosis? A systematic review and meta-analysis.
Respirology, 19 (2014), pp. 993-998
[6]
Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160:736–55.
[7]
N.M. Long, C.S. Smith.
Causes and imaging features of false positives and false negatives on 18F-PET/CT in oncologic imaging.
Insights Imaging, 2 (2011), pp. 679-698
[8]
A. Kis, N. Eszes, L. Tamasi, G. Losonczy, A. Csekeo, J. Csomor, et al.
Sarcoidosis lymphoma syndrome—the value of PET-CT in the diagnosis.
World J Surg Oncol, 11 (2013), pp. 235
[9]
A. Grados, M. Ebbo, E. Bernit, V. Veit, K. Mazodier, R. Jean, et al.
Sarcoidosis occurring after solid cancer: a nonfortuitous association.
Medicine (Baltimore) [Internet], 94 (2015),
[accessed 30 Jul 2017]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617083/
[10]
J. London, A. Grados, C. Fermé, A. Charmillon, F. Maurier, B. Deau, et al.
Sarcoidosis occurring after lymphoma.
Medicine (Baltimore) [Internet], (2014), pp. 93
[accessed 9 Ago 2017]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616278/
[11]
A tuberculose en Galicia. 1996–2015.pdf [Internet] [citado 28 Oct 2017]. Available at: https://www.sergas.es/Saude-publica/Documents/4154/A%20tuberculose%20en%20Galicia.%201996-2015.pdf
[12]
B.M. Hunt, E. Vallières, G. Buduhan, R. Aye, B. Louie.
Sarcoidosis as a benign cause of lymphadenopathy in cancer patients.
Am J Surg, 197 (2009), pp. 629-632
discusión 632
[13]
F.-X. Danlos, C. Pagès, B. Baroudjian, L. Vercellino, M. Battistella, M. Mimoun, et al.
Nivolumab-induced sarcoid-like granulomatous reaction in a patient with advanced melanoma.
Chest, 149 (2016), pp. e133-e136

Please cite this article as: Pereiro T, Golpe A, Lourido T, Valdés L. Tumores extrapulmonares y sarcoidosis. ¿Relación casual o real? Arch Bronconeumol. 2018;54:531–533.

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