Open Access

Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic dilemma (Review)

  • Authors:
    • Christoph Spiekermann
    • Meike Kuhlencord
    • Sebastian Huss
    • Claudia Rudack
    • Daniel Weiss
  • View Affiliations

  • Published online on: October 20, 2017     https://doi.org/10.3892/ol.2017.7247
  • Pages:7643-7652
  • Copyright: © Spiekermann et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Sarcoidosis, a chronic, inflammatory disease that affects various different organs, is characterized by noncaseating epitheloid granulomas. This systemic inflammatory process is associated with an increased risk of cancer. Several cases of sarcoidosis that mimic metastatic tumor progression in radiological findings have been reported so far. However, there are also cases that have presented a coexistence of sarcoidosis and metastasis, which have caused a diagnostic and therapeutic dilemma. Due to inadequate current therapies, a reliable differentiation between benign and malignant lesions is crucial. This review focuses on the residual risk of the coexistence of metastases within radiological suspicious lesions in patients with a history of solid tumors and sarcoidosis, as well as immunological findings, in order to explain the potential associations. Sarcoidosis has the potential to promote metastasis as it includes tumor‑promoting and immune‑regulating cell subsets. Notably, myeloid derived suppressor cells may serve a pivotal role in metastatic progression in patients with sarcoidosis. In addition, the present review also evaluates the potential novel diagnostic approaches, which may be able to differentiate between metastatic lesions and sarcoidosis. The risk of coexistent metastasis in sarcoidosis lesions must be considered by clinical practitioners, and a multidisciplinary approach may be required to avoid misdiagnosis and the subsequent unnecessary surgery or insufficient treatments.

Introduction

Sarcoidosis is a chronic, inflammatory, systemic disease affecting primarily the lungs, the mediastinum and the lymphatic system but also salivary glands, heart, nervous system, joints and various other organs (1). Diagnosis depends on the existence of typical clinicoradiological findings in association with noncaseating epitheloid cell granulomas in biopsy and the absence of known, alternative or local causes provoking granulomas (1). Granulomas are nonspecific inflammatory lesions and can occur during mycobacterial, fungal or parasitic infections as well as other diseases like Wegener's granulomatosis (2). Due to the differentiation of granulomas the pathologists play a pivotal role in finding the correct diagnosis (2). In sarcoidosis, granuloma formation is characterized by infiltrating Th1 helper cells and macrophages. The latter show a transformation process into epitheloid cells and can fuse into multinucleate giant cells. Although small amounts of necrosis can be observed, the sarcoid granuloma is referred to the group of nonnecrotizing or noncaseating granulomas (2). Caseating granulomas are typically found in infectious diseases like syphilis or tularemia or infection with tuberculous and nontuberculous mycobacterium (2). In some, especially oncologic patients treated with immunotherapy, noncaseating granulomas can be found although they do not fulfill the criteria for systemic sarcoidosis and are thus referred to as sarcoid-like reactions (3). Due to the toxicity profile of immunotherapies immune-related adverse events can provoke those sarcoid-like reactions which may occur in the organ of tumor origin or in the tumor-draining lymph nodes (3). Sarcoidosis is associated with an increased risk for cancer development in several organs like lung, liver, stomach or for melanoma and lymphoma. Sarcoid-like reactions can be found in 13.8% of patients with Hodgkin-disease, 7.3% with non Hodgkin lymphoma and 4.4% of cases with carcinomas (4,5). Furthermore, simultaneous occurrence of sarcoidosis and cancer is associated with a diminished survival rate (6). Although no increased risk for malignancy in the head and neck has been described so far, there are a few cases that report the simultaneous occurrence of sarcoidosis and malignoma of the head and neck (79). Notably, in follow-up computed tomography (CT) scans or those done for the detection of primary tumors or metastatic lesions (e.g., 18-Fluorodeoxyglucose positron emission tomography-(PET)-CT, 18FDG-PET-CT) sarcoidosis can mimic cancer recurrence or metastatic progress (10,11). However, it is possible that metastatic lesions coexist next to lymph nodes with sarcoid-like lesions and it is unclear whether sarcoidosis has an influence on metastasis of malignoma. Therefore, a review of the current literature was performed to analyze the residual risk of metastasis within radiological suspicious lesions in patients with a history of solid tumors and sarcoidosis.

Methods

In this review we analyzed reported cases of patients with solid tumors whose staging or follow-up analysis revealed an unclear lymphadenopathy owing to metastasis or sarcoidosis. A systematic literature search was done in Pub Med data base (from inception to April 2017) without any limitation using the terms: Sarcoidosis [title] AND metastasis. All cases with a solid tumor and sarcoidosis were included and the provided information concerning age, gender, tumor region, tumor entity, tumor classification, therapy, as well as information about diagnosis of sarcoidosis were collected. Analyzing the data, the risk of simultaneous occurrence of metastasis and sarcoidosis in concordance to positive radiological and histological findings was elucidated.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors. For this retrospective study and review of anonymized clinical records an ethical permission was not required.

Results

Review of the literature

Review of the literature revealed 115 cases in Pub Med Data Base based on the search criteria mentioned above. Cases without malignancy were excluded and 59 cases with cancer and sarcoidosis were identified and are listed in Table I. The median age at cancer diagnosis was 49.5 +/- 13.4 years and cases of 31 female and 23 male patients were reported. In 5 cases, the sex of the patient was not documented. Systemic sarcoidosis treatment consisted of oral steroids (n=12) or chloroquine (n=1). Local steroids were applied in one case with uveitis. No therapy was initiated in 15 cases and 30 cases did not provide any information about the sarcoidosis therapy approach. However, independent from the treatment strategy the patients' outcome was described to be good with a stable status or complete remission. The most frequent cancer origin was breast (n=12) followed by malignoma of the thyroid gland (n=8). Sarcoidosis occurred in 20 cases after an average of 34.4 months and in 7 cases 10.25 years before diagnosis of malignoma. In most reported cases (n=24) sarcoidosis was revealed simultaneously with diagnosis of malignoma. In 25 cases, surgery was performed to remove the tumor. 24 patients had a combination of surgery and radio-, chemo- or radiochemotherapy. Two cases were only treated by radiochemotherapy and in seven cases, no information about therapeutic aspects concerning the tumor was provided. Occurrence of sarcoidosis after surgery was reported in 3/25 cases and in 17/24 cases after surgery and radio-/chemotherapy. In 17% of the cases, simultaneous detection of sarcoidosis or sarcoid-like lesions and metastasis was reported (n=10). These reports are now described in more detail.

Table I.

Characteristics of patients from literature review.

Table I.

Characteristics of patients from literature review.

Tumor characteristicsPatientSarcoidosis



Author, yearTumor regionTumor entityTNM classificationTherapyAgeSexDiagnoses toolBiopsySarcoidosis manifestationsTime between Diagnostic (months)(Refs.)
Altinkaya et al, 2015BreastDuctal invasive carcinomaT1N0M0OP70FPETEBUSLN mediastinal0(31)
Conte et al, 2015BreastDuctal invasive carcinomapT3pN1OP50FPETOP+BiopsyLN pelvic, supradiaphragmatic0(12)
Zivin et al, 2014BreastDuctal invasive carcinomankOP32FPETBiopsy+EBUSLN hilar + mediastinalnk(32)
El Hammoumi et al, 2015BreastLobular carcinomaT1N2MxOP + aRCTx (Tamoxifen)48FCTBiopsyLN mediastinal36(11)
Kim et al, 2014BreastDuctal invasive carcinomaT1N2M0OP + aRCTx44FPET MediastinoscopyLN paraesophageal, hilar24(33)
Akhtari et al, 2014BreastDuctal invasive carcinomaT2N0MxOP + aCTx + aRT47FPETFNALN supraclav., mediastinal, periportal0(34)
Braza and Nelson, 2014BreastDuctal invasive carcinomaT1N0M0nk68FMRIBone biopsyLesions lumbosacral spinenk(35)
DeFilippis et al,2013BreastLobular carcinomankOP + aRTx63FMRIBiopsyLN axillary0(36)
Bush et al, 2011BreastDuctal invasive carcinomaN0OP42FPETBiopsyLN cervical, abdominal, bone, spleen0(37)
Viswanath et al, 2009BreastDuctal invasive carcinomaT4aN1M0OP + aRCTx50FCIBiopsyDermal lesions24(38)
Whittington et al, 1986BreastCarcinomaN0nknkFnk MediastinoscopyLN mediastinal0(39)
Whittington et al, 1986BreastCarcinomaN0nknkFnkEBUSLN hilar0(39)
El Hammoumi et al, 2015CervixEpidermoid CarcinomanknaCTx + OP47FPET MediastinoscopyLN mediastinal36(11)
Tamauchi et al, 2015EndometriumAdenocarcinomaT1bN0MxOP + aCTx67FCTOPLN hilar, paraaortic, pelvine0(40)
Powell et al, 2005EndometriumAdenocarcinomaN0OP67FCTFNALN mediastinal, liver lesions48(41)
Takanami et al, 2008EsophagealSquamous cell carcinomaN0OP72MPETBiopsyLN mediastinal + hilar−168(42)
Takanami et al, 2008EsophagealSquamous cell carcinomapT1bOP59MPETBiopsyLN mediastinal + hilar0(42)
Arana et al, 2013Ethmoid sinusAdenocarcinomaT3N0M0OP + aRCTx42FPET MediastinoscopyLN mediastinal + hilar0(7)
Kachalia et al, 2014LungAdenocarcinomaTxNxM2OP80FX-ray MediastinoscopyLN0(13)
Kim et al, 2011LungAdenocarcinomaT2N0M0OP65FPETBiopsyLN mediastinal0(43)
Mimura et al, 2011LungSquamous cell carcinomapT1N0M0OP69MCTBiopsyLN mediastinal−120(44)
Urushiyama et al, 2015LungSquamous cell carcinomaN0OP60MCTBiopsyLN mediastinal + hilar−24(45)
Bouaziz et al, 2006LungSquamous cell carcinomanknk49MMRIEBUSLN mediastinal, hepatic nodules0(46)
Shields et al, 2005LungPapillary carcinomaM1OP57FPETRadiologySalivary and lacrimal glands, LN hilar0(14)
Sato et al, 2003LungAdenocarcinomaN1nknknknkThoracoscopyLN mediastinal, interlobar0(15)
Muramatsu et al, 2000LungSquamous cell carcinomaN0 M0OP64MCTBiopsyLN mediastinal0(47)
Abdel-Galiil et al, 2008MaxillaSquamous cell carcinomankOP51MPET MediastinoscopyLN mediastinal+hilar + peribronchial24(8)
Yao et al, 2005OropharynxSquamous cell carcinomaT3N2cM0RCTx49MPET MediastinoscopyLN mediastinal, pretracheal, subcarinal2(9)
Yonenaga et al, 2006OvarMucinous CystadenocarcinomankOP + aCTx21FPETnkSpleen, Liver36(48)
Kim et al, 2013OvarPapillary cystadenocarcinomankOP + aCTx52FPETEBUSLN paratracheal, supraclavicular, diaphragmal12(49)
Pollock and Catalano, 1979Parotid glandDuctal carcinomaN2OP + aRCTx38MCIBiopsyLN hilar−60(50)
Montini and Tulchinsky, 2012RectumCancernknk45MPETBiopsy skeletalLN mediastinal,0(51)
Abdi et al, 1987RenalRenal cell carcinomaN2OP + aRTx (IFNα)57FCTEBUSLN mediastinal24(52)
Fukutani et al, 1987RenalRenal cell carcinomaNOOP75FnkBiopsyLN pelvic0(53)
Khan and Khan, 1974RenalHypernephromaM1OP52MX-rayBiopsyLN hilar0(19)
Gharavi et al, 2013SacrumChordomankOP48MPETBiopsyLN iliacal + femoral12(54)
Wilgenhof et al, 2012SkinMelanomaM1cOP + aCTx (Dacarbazine, Cisplatin)48FPETEBUSLN hilar84(55)
Vogel et al, 2012SkinMelanomaN1OP + aCTx (αCTLA-4)49MPETEBUSLN mediastinal, hilar168(56)
Heinzerling et al, 2010SkinMelanomapT4N0M0OP + aCTx (INFα)50MnkBiopsyLN mediastinal7(57)
Chiagne et al, 2011SkinMelanomankOP35MPETBiopsyLN inguinal0(18)
Heinzerling et al, 2010SkinMelanomapT3bpN1acM0OP + aCTx (INFα)47MPETBiopsyLN mediastinal+ hilar + peribronchialnk(57)
Heinzerling et al, 2010SkinMelanomaN1OP + aCTx (INFα)47MPET MediastinoscopyLN mediastinal+ hilar + peribronchial2(57)
Suarez-Garcia et al, 2009SkinMelanomaN1OP + aCTx (INFα)42MCIBiopsyDermal lesions3(58)
Massaguer et al, 2004SkinMelanomankCTx (IFNα)nkFCT MediastinoscopyLN mediastinalnk(59)
Matsubara et al, 2015StomachAdenocarcinomaN0OP64FnkEndoscopyGastric sarcoidosis−120(60)
El Hammoumi et al, 2015StomachAdenocarcinomankOP + aCTx59FCT MediastinoscopyLN paratracheal36(11)
Tissot et al, 1985StomachAdenocarcinomanknk63FOPBiopsyCombined gastric lesions−336(61)
Claus et al, 2012TestisSeminomaT2N0M1OP + aCTx (Carboplatin)34MCTEBUSLN mediastinal24(62)
Claus et al, 2012TestisSeminomaT1N0M0OP + aCTx (Carboplatin)36MCTBiopsyLN abdominal0(62)
Teo et al, 2013TestisSeminomaT1N2M1aOP + aCTx (Cisplatin, Etoposid)20MCTEBUSLN mediastinal60(63)
Tjan-Heijnen et al, 1998TestisSeminomaN2OP + aRTx41MCT MediastinoscopyLN mediastinal24(64)
Salih et al, 2015ThyroidPapillary thyroid carcinomaT2N1MxOP48FX-rayNeck dissectionLN cervical and hilar0(10)
Lebo et al, 2015ThyroidPapillary thyroid carcinomaT1bN1aMxOP41FPET MediastinoscopyCervical + mediastinal0(16)
Myint et al, 2015ThyroidPapillary thyroid carcinomankOP + I-13168FPETBone biopsyLN hilar + mediast. Bonenk(65)
Ergin and Nasr, 2014ThyroidPapillary thyroid carcinomaN0OPnknknkOPCervicalpre(17)
Ergin and Nasr, 2014ThyroidPapillary thyroid carcinomaN0OPnknknkFNACervicalpost(17)
Ergin and Nasr, 2014ThyroidPapillary thyroid carcinomaN1OPnknkPETOPCervical0(17)
Ergin and Nasr, 2014ThyroidPapillary thyroid carcinomaN0OPnknknkOPCervical0(17)
Zimmermann-Belsing et al, 2000ThyroidPapillary adenocarcinomaN2OP27MScintigraphyBiospyLN hilar−36(66)

[i] nk, not known; OP, operation; aCTx, adjuvant chemotherapy; aRTx, adjuvant radiotherapy; aRCTx, adjuvant combined radiochemotherapy; naCTx, neoadjuvant chemotherapy; INFα, Interferon alpha; PET, positron emission tomography; CT, computed tomography; F, female; M, male; MRI, magnetic resonance imaging; CI, clinical investigation; EBUS, endobronchial ultrasound based biopsy; FNA, fine needle aspiration; LN, lymph node.

The first case describes a 50-year-old female patient suffering from ductal invasive breast carcinoma with local lymph node metastasis (pT3pN1). Chest X-ray and 18FDG-PET-CT were performed for staging of the tumor and showed a bilateral mediastinal lymphadenopathy and an increased FDG-uptake in supra-diaphragmatic and pelvic lymph nodes. Biopsy of an example lesion obtained sarcoidosis (12). Secondly, an 80-year-old female's CT scan revealed a tumor suspicious mass in the upper lobe of the right lung, multiple smaller nodules and hilar lymphadenopathy. Subsequent biopsy of the mass and a mediastinal lymph node showed just noncaseating granulomas but no malignant cells and led to insufficient treatment. Six months later, symptoms like cough and chest pain were exacerbated and a thoracocentesis revealed adenocarcinoma cells. Further staging examination showed pleural, pericardial and diaphragmatic metastasis. Due to tumor progress, palliative care was initiated (13). The third case describes a 57-year-old female patient who was found to have a choroidal mass in the left eye. Total body gallium 67 scan showed an increased uptake in salivary and lacrimal glands and was misinterpreted as typical for sarcoidosis. Progress of symptoms resulted in enucleation and revealed a choroideal metastasis of a papillary lung carcinoma (14). Sato et al (15) report on a patient with concomitant sarcoidosis and lung adenocarcinoma. Thoracoscopic biopsy of altered lymph nodes did not detect metastasis but sarcoidosis. Surgery was performed and a permanent pathological slide showed that several nodes contained both sarcoidosis and lung cancer metastasis (15). Three other reports describe patients suffering from papillary thyroid carcinoma that underwent thyreoidectomy and modified neck dissection. Pathology revealed concurrent existence of sarcoidosis and regional lymph node metastasis (10,16,17). One patient (27-year-old, male) shows a papillary thyroid carcinoma upon a previously diagnosed sarcoidosis. Local lymph nodes contained sarcoidosis mixed with metastasis. A 35-year-old male with a previous history of melanoma developing metastatic involvement and sarcoidosis in regional lymph nodes was described by Chaigne et al (18). Khan and Khan (19) described a 52-year-old patient with cough and chest pain. Radiologic examination showed bilateral hilar lymphadenopathy. Furthermore, within a biopsy of an enlarged lymph node, a metastasis of a left kidney hypernephroma was detected (19).

Taken together, these ten patients had a median age of 49 years ranging from 27 to 80 years at the time point of simultaneous detection of metastasis and sarcoidosis. The gender ratio was 0.6:1 (male to female) although no information concerning the sex was provided in two cases. In 8 cases (80%), the metastases were localized in regional lymph nodes whereas just 2 cases showed distant metastases. Furthermore, the region and entity of the associated tumor differed greatly (breast: n=1, lung: n=3, thyroid: n=4, skin: n=1, kidney: n=1).

Discussion

Sarcoidosis and metastasis

Although there are several published cases concerning coexistence of malignoma and sarcoidosis, the causal relationship between these entities is still unclear. On the one hand, it is possible that patients with sarcoidosis develop malignancies and, on the other hand, there are oncologic patients developing sarcoidosis and sarcoid-like reactions, especially after chemotherapy (3). Several cases describe a mimicking of metastatic disease by sarcoidosis but just a few cases actually report a simultaneous occurrence of sarcoidosis and metastases.

Active sarcoidosis is characterized by an enhanced local expression of T helper 1 (Th1) and T helper 17 (Th17) chemokines and cytokines like IFN-γ, TNF-α, IL-17A and IL-22. In various chronic, autoimmune, inflammatory diseases, such as sarcoidosis, the percentage of IL-17A+/IFN-γ+ double-producing Th-cells is increased in peripheral blood and is related to high disease activity. Furthermore, in these pathological conditions, a dysfunctional response of regulatory T-cells (Tregs) has been described that is characterized by an insufficient immunosuppressive function (20). Interestingly, cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression is decreased while PD-1 (programmed death-1) expression is increased in Th17-cells in the mediastinal lymph nodes during sarcoidosis (20). CTLA-4 is present on Th-cells and mediates an inhibitory effect on further T cells responses. Hence, a diminished CTLA-4 level maintains inflammatory reactions. Similarly, PD-1 is expressed on the surface of T-cells upon activation and is involved in limiting inflammatory reactions (21). Its ligand, PD-1L, can be found on tumor cells and provokes upregulation of PD-1 in T cells. Consequently, activation of tumor antigen-specific T-cells in pancreatic adenocarcinoma is inhibited (22). Hence, the bivalent adaptive immune response in patients with sarcoidosis and metastasis promotes both pathological conditions by maintaining sarcoidosis-related inflammation due to the decreased anti-inflammatory CTLA-4 expression while limiting tumor-specific T cell activation, marked by an increased PD-1 expression, that enables tumor escape from the immune system and metastasis. Increased PD-1 expression on T-cells in sarcoidosis lymph nodes could thus be a possible predictor of metastasis on the basis of sarcoidosis. Furthermore, myeloid-derived suppressor cells (MDSC) might play a pivotal role in the pathogenic association between sarcoidosis and metastasis. MDSC pursue immunoregulatory and T-cell suppressive functions (23). Although it has not been described yet, an influence of MDSC on sarcoidosis is assumable because of their important role in other inflammatory diseases (24). Th-17 cells are the main source of IFN-γ production in sarcoidosis and IFN-γ induces MDSC differentiation and promotes their immunosuppressive function (20,25). In cancer models, MDSC accumulation was promoted by several cytokines and growth factors, such as IL-6, IL-1ß and S100A8/A9, resulting in an anti-inflammatory tumor microenvironment (23). MDSC themselves express cytokines and chemokines like IL-6, TNF, IL-1β, IL-23 and S100A9 and have the potential to attract both further myeloid cells and tumor cells (26). Furthermore, in a melanoma and lung carcinoma mouse model, S100A9 expressing MDSC were identified as important players in enabling tumor metastasis (27). Consequently, they are generally recognized as dominant tumor-promoting forces (28). Patients suffering from sarcoidosis have increased serum levels of S100A8/A9 and an enhanced cytoplasmatic S100A8/A9 expression in monocytes and multinuclear giant cells in granulomas (29). Because of the sarcoidosis-related inflammation, marked by the expression of IFN-γ, IL-6, IL-23 and S100A8/A9, we can suspect a similar microenvironment to tumors that are characterized by an increased accumulation and immunosuppressive function of MDSC. Accordingly, we can assume that sarcoidosis has the potential to promote metastasis by inducing tumor-promoting and immune-regulating cell subsets. Further analysis is necessary to verify the influence of MDSC on sarcoidosis as well as the cellular immune response concerning the association between sarcoidosis and metastasis.

Differentiation between benign and malignant lesions

PET-CT scan is a very useful diagnostic tool to identify malignant lesions with a sensitivity between 47 and 100% and a specificity of 86–100% (30). Unfortunately, elevated FDG uptake can also be detected in inflammatory diseases such as sarcoidosis causing a diagnostic dilemma. The case of a 61-year-old carpenter with a history of adenocarcinoma of the paranasal sinus and simultaneous occurrence of multiple cervical metastases and sarcoidosis detected during follow-up investigation impressively demonstrates the risk to overlook metastatic lesions within sarcoidosis (Fig. 1). Especially PET scans for staging or restaging of oncologic diseases supply important information about tumor progression. Decisions on curative or palliative therapy are based on this information, emphasizing the importance to avoid misdiagnosis. Inclusion of an additional tracer would be helpful to differentiate between inflammation and tumor. F18-labeled 3′deoxy-3′fluorothymidine (FLT) is such a promising tracer to minimize diagnostic and subsequent therapeutic mistakes. By measuring DNA synthesis instead of metabolic activity that seems to be more specific to detect tumor diseases, FLT might be a useful candidate to discriminate between tumor and sarcoidosis lesions (7).

An additional helpful tool to discriminate inflammatory bone marrow involvement, like skeletal sarcoidosis, from metastatic disease might be the diffusion whole-body magnetic resonance imaging (b-values 50–900s/mm2). In contrast to malignant lesions (cut-off value of 774 µm2/s), sarcoidosis or other inflammatory skeletal reactions show high signal intensity on diffusion-weighted images and a lower apparent diffuse coefficient (ADC) (12).

Bioptical evaluation of radiologically altered lymph nodes is necessary for selection of appropriate oncological treatment strategy. However, examination of each PET-CT positive lesion is not feasible and the chance to detect metastatic lesions next to sarcoidosis is rather rare (Fig. 2). Thus, even if pathological findings were suspicious of sarcoidosis, concomitant metastasis cannot be certainly excluded. Hence, correlation between the radiological and histological findings with the probability of distant or local metastasis corresponding to the tumor entity is important for the careful assessment of the residual metastasis risk.

Conclusion

Correlation between PET-Scan, histological findings and knowledge about typical tumor behavior is necessary to avoid misdiagnosis. Nevertheless, a residual risk of overlooking metastases in systemic inflammatory diseases still remains existent. Therefore, it is important for clinical practice to be aware of the simultaneous occurrence of sarcoidosis and metastatic malignancy. Further cell subset analysis in these pathologies might additionally reveal immunological distinct cell populations as useful markers to distinguish between sarcoidosis, cancer and the coexistence of these two and help in overcoming the current diagnostic dilemma.

Acknowledgements

This study was supported by a fellowship from the medical faculty of the University of Münster, Germany to C. Spiekermann.

References

1 

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. 160:736–755. 1999.PubMed/NCBI

2 

Rosen Y: Pathology of sarcoidosis. Semin Respir Crit Care Med. 28:36–52. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Cohen PR and Kurzrock R: Sarcoidosis and malignancy. Clin Dermatol. 25:326–333. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Brincker H: Sarcoid reactions in malignant tumours. Cancer Treat Rev. 13:147–156. 1986. View Article : Google Scholar : PubMed/NCBI

5 

Askling J, Grunewald J, Eklund A, Hillerdal G and Ekbom A: Increased risk for cancer following sarcoidosis. Am J Respir Crit Care Med. 160:1668–1672. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Boffetta P, Rabkin CS and Gridley G: A cohort study of cancer among sarcoidosis patients. Int J Cancer. 124:2697–2700. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Yi Arana C, McCue P, Rosen M, Machtay M, Axelrod R and Morris GJ: Sarcoidosis mimicking metastatic bone disease in head and neck cancer. Semin Oncol. 40:529–534. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Abdel-Galiil K, Anand R, Sharma S, Brennan PA, Ramchandani PL and Ilankovan V: Incidence of sarcoidosis in head and neck cancer. Br J Oral Maxillofac Surg. 46:59–60. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Yao M, Funk GF, Goldstein DP, DeYoung BR and Graham MM: Benign lesions in cancer patients: Case 1. Sarcoidosis after chemoradiation for head and neck cancer. J Clin Oncol. 23:640–641. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Salih AM, Fatih SM and Kakamad FH: Sarcoidosis mimicking metastatic papillary thyroid cancer. Int J Surg Case Rep. 16:71–72. 2015. View Article : Google Scholar : PubMed/NCBI

11 

El Hammoumi M, El Marjany M, Moussaoui D, Doudouh A, Mansouri H and Kabiri el H: Mediastinal sarcoidosis mimicking lymph malignancy recurrence after anti-neoplastic therapy. Arch Bronconeumol. 51:e33–e35. 2015.(In English, Spanish). View Article : Google Scholar : PubMed/NCBI

12 

Conte G, Zugni F, Colleoni M, Renne G, Bellomi M and Petralia G: Sarcoidosis with bone involvement mimicking metastatic disease at (18)F-FDG PET/CT: Problem solving by diffusion whole-body MRI. Ecancermedicalscience. 9:5372015. View Article : Google Scholar : PubMed/NCBI

13 

Kachalia AG, Ochieng P, Kachalia K and Rahman H: Rare coexistence of sarcoidosis and lung adenocarcinoma. Respir Med Case Rep. 12:4–6. 2014.PubMed/NCBI

14 

Shields JA, Shields CL and Eagle RC Jr: Choroidal metastasis from lung cancer masquerading as sarcoidosis. Retina. 25:367–370. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Sato Y, Sasano S, Oyama K, Sakuraba M, Onuki T and Nitta S: Lung cancer associated with sarcoidosis. Jpn J Thorac Cardiovasc Surg. 51:21–24. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Lebo NL, Raymond F and Odell MJ: Selectively false-positive radionuclide scan in a patient with sarcoidosis and papillary thyroid cancer: A case report and review of the literature. J Otolaryngol Head Neck Surg. 44:182015. View Article : Google Scholar : PubMed/NCBI

17 

Ergin AB and Nasr CE: Thyroid cancer & sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 31:239–243. 2014.PubMed/NCBI

18 

Chaigne B, Perrinaud A, Penaud A, Machet MC, Venel Y, Marchand-Adam S and Machet L: Melanoma lymph node metastasis occurring simultaneously with multifocal sarcoidosis affecting lymph nodes and the lung: A diagnostic pitfall. Eur J Dermatol. 21:798–799. 2011.PubMed/NCBI

19 

Khan A and Khan FA: Hypernephroma: A rare cause of bilateral adenopathy, and an example of the importance of tissue diagnosis in suspected cases of sarcoidosis. Chest. 66:722–723. 1974. View Article : Google Scholar : PubMed/NCBI

20 

Broos CE, Hendriks RW and Kool M: T-cell immunology in sarcoidosis: Disruption of a delicate balance between helper and regulatory T-cells. Curr Opin Pulm Med. 22:476–483. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Hashemi-Sadraei N, Sikora AG and Brizel DM: Immunotherapy and checkpoint inhibitors in recurrent and metastatic head and neck cancer. Am Soc Clin Oncol Educ Book. 35:e277–e282. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Seo YD and Pillarisetty VG: T-cell programming in pancreatic adenocarcinoma: A review. Cancer Gene Ther. 24:106–113. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Crook KR and Liu P: Role of myeloid-derived suppressor cells in autoimmune disease. World J Immunol. 4:26–33. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Nagaraj S, Collazo M, Corzo CA, Youn JI, Ortiz M, Quiceno D and Gabrilovich DI: Regulatory myeloid suppressor cells in health and disease. Cancer Res. 69:7503–7506. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Zhao Y, Wu T, Shao S, Shi B and Zhao Y: Phenotype, development, and biological function of myeloid-derived suppressor cells. Oncoimmunology. 5:e10049832015. View Article : Google Scholar : PubMed/NCBI

26 

Liu Y, Kosaka A, Ikeura M, Kohanbash G, Fellows-Mayle W, Snyder LA and Okada H: Premetastatic soil and prevention of breast cancer brain metastasis. Neuro Oncol. 15:891–903. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Yang Q, Li X, Chen H, Cao Y, Xiao Q, He Y, Wei J and Zhou J: IRF7 regulates the development of granulocytic myeloid-derived suppressor cells through S100A9 transrepression in cancer. Oncogene. 36:2969–2980. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Zamarron BF and Chen W: Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci. 7:651–658. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Terasaki F, Fujita M, Shimomura H, Tsukada B, Otsuka K, Otsuka K, Katashima T, Ikemoto M and Kitaura Y: Enhanced expression of myeloid-related protein complex (MRP8/14) in macrophages and multinucleated giant cells in granulomas of patients with active cardiac sarcoidosis. Circ J. 71:1545–1550. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Zanation AM, Sutton DK, Couch ME, Weissler MC, Shockley WW and Shores CG: Use, accuracy, and implications for patient management of [18F]-2-fluorodeoxyglucose-positron emission/computerized tomography for head and neck tumors. Laryngoscope. 115:1186–1190. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Altinkaya M, Altinkaya N and Hazar B: Sarcoidosis mimicking metastatic breast cancer in a patient with early-stage breast cancer. Ulus Cerrahi Derg. 32:71–74. 2015.PubMed/NCBI

32 

Zivin S, David O and Lu Y: Sarcoidosis mimicking metastatic breast cancer on FDG PET/CT. Intern Med. 53:2555–2556. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Kim HS, Lee SY, Oh SC, Choi CW, Kim JS and Seo JH: Case report of pulmonary sarcoidosis suspected to be pulmonary metastasis in a patient with breast cancer. Cancer Res Treat. 46:317–321. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Akhtari M, Quesada JR, Schwartz MR, Chiang SB and Teh BS: Sarcoidosis presenting as metastatic lymphadenopathy in breast cancer. Clin Breast Cancer. 14:e107–e110. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Braza DW and Nelson PA: Vertebral sarcoidosis masquerading as breast metastasis. Am J Phys Med Rehabil. 93:2742014. View Article : Google Scholar : PubMed/NCBI

36 

DeFilippis EM and Arleo EK: New diagnosis of sarcoidosis during treatment for breast cancer, with radiologic-pathologic correlation. Clin Imaging. 37:762–766. 2013. View Article : Google Scholar : PubMed/NCBI

37 

Bush E, Lamonica D and O'Connor T: Sarcoidosis mimicking metastatic breast cancer. Breast J. 17:533–535. 2011. View Article : Google Scholar : PubMed/NCBI

38 

Viswanath L, Pallade S, Krishnamurthy B, Naveen T, Preethi BL, Pramod KP, Reddy O and Padma G: Darier-roussy sarcoidosis mimicking metastatic breast cancer. Case Rep Oncol. 2:251–254. 2009. View Article : Google Scholar : PubMed/NCBI

39 

Whittington R, Lazarus A, Nerenstone S and Martin A: Sarcoidosis developing during therapy for breast cancer. Chest. 89:762–763. 1986. View Article : Google Scholar : PubMed/NCBI

40 

Tamauchi S, Shimomura Y and Hayakawa H: Endometrial cancer with sarcoidosis in regional lymph nodes: A case report. Case Rep Oncol. 8:409–415. 2015. View Article : Google Scholar : PubMed/NCBI

41 

Powell JL, Cunill ES, Gajewski WH and Novotny DB: Sarcoidosis mimicking recurrent endometrial cancer. Gynecol Oncol. 99:770–773. 2005. View Article : Google Scholar : PubMed/NCBI

42 

Takanami K, Kaneta T, Yamada T, Kinomura S, Yamada S, Fukuda H and Takahashi S: FDG PET for esophageal cancer complicated by sarcoidosis mimicking mediastinal and hilar lymph node metastases: Two case reports. Clin Nucl Med. 33:258–261. 2008. View Article : Google Scholar : PubMed/NCBI

43 

Kim JJ, Park JK, Wang YP, Choi SH and Jo KH: Lung cancer associated with sarcoidosis - A case report. Korean J Thorac Cardiovasc Surg. 44:301–303. 2011. View Article : Google Scholar : PubMed/NCBI

44 

Mimura K, Mochizuki Y, Nakahara Y, Kawamura T, Sasaki S and Katsuda R: A case of primary lung cancer with swollen mediastinal lymph nodes due to pre-existing sarcoidosis. Nihon Kokyuki Gakkai Zasshi. 49:208–213. 2011.(In Japanese). PubMed/NCBI

45 

Urushiyama H, Yamauchi Y, Suzuki S, Sunohara M, Kouyama T, Ohishi N, Fukami T, Nakajima J, Ushiku T, Oota S, et al: Case of sarcoidosis with squamous cell carcinoma which originated from solitary bronchial papilloma. Nihon Kokyuki Gakkai Zasshi. 48:815–820. 2010.(In Japanese). PubMed/NCBI

46 

Bouaziz H, Kaffel N, Charfi N, Fourati M, Abid H and Abid M: Panhypopituitarism revealing metastasis of small-cell lung carcinoma associated with sarcoidosis. Ann Endocrinol (Paris). 67:259–264. 2006.(In French). View Article : Google Scholar : PubMed/NCBI

47 

Muramatsu M, Kuriyama M, Takahashi K, Miyamoto H, Uekusa T, Danbara T and Fukuchi Y: A case of resected squamous cell carcinoma of the lung complicated with sarcoidosis. Nihon Kokyuki Gakkai Zasshi. 38:720–725. 2000.(In Japanese). PubMed/NCBI

48 

Yonenaga Y, Kushihata F, Inoue H, Watanabe J, Tohyama T, Sugita A and Takada Y: Sarcoidosis manifesting as hepatic and splenic nodules mimicking ovarian cancer metastases: A case report. Oncol Lett. 10:2166–2170. 2015.PubMed/NCBI

49 

Kim MH, Lee K, Kim KU, Park HK, Lee MK and Suh DS: Sarcoidosis mimicking cancer metastasis following chemotherapy for ovarian cancer. Cancer Res Treat. 45:354–358. 2013. View Article : Google Scholar : PubMed/NCBI

50 

Pollock JL and Catalano E: Metastatic ductal carcinoma of the parotid gland in a patient with sarcoidosis. Arch Dermatol. 115:1098–1099. 1979. View Article : Google Scholar : PubMed/NCBI

51 

Montini KM and Tulchinsky M: False-positive bone metastases on PET/CT secondary to sarcoidosis in a patient with rectal cancer. Clin Nucl Med. 37:307–310. 2012. View Article : Google Scholar : PubMed/NCBI

52 

Abdi EA, Nguyen GK, Ludwig RN and Dickout WJ: Pulmonary sarcoidosis following interferon therapy for advanced renal cell carcinoma. Cancer. 59:896–900. 1987. View Article : Google Scholar : PubMed/NCBI

53 

Fukutani K, Kawabe K, Moriyama N, Kitamura T and Murakami T: Carcinoma of the renal pelvis and bladder associated with sarcoidosis: A case report. Urol Int. 42:224–226. 1987. View Article : Google Scholar : PubMed/NCBI

54 

Gharavi MH, Wu HH and Toms SA: High fluorodeoxyglucose ((18)F)PET-uptake lymph nodes in a patient with chordoma: Tumor metastasis or sarcoidosis? Am J Case Rep. 14:373–375. 2013. View Article : Google Scholar : PubMed/NCBI

55 

Wilgenhof S, Morlion V, Seghers AC, Four Du S, Vanderlinden E, Hanon S, Vandenbroucke F, Everaert H and Neyns B: Sarcoidosis in a patient with metastatic melanoma sequentially treated with anti-CTLA-4 monoclonal antibody and selective BRAF inhibitor. Anticancer Res. 32:1355–1359. 2012.PubMed/NCBI

56 

Vogel WV, Guislain A, Kvistborg P, Schumacher TN, Haanen JB and Blank CU: Ipilimumab-induced sarcoidosis in a patient with metastatic melanoma undergoing complete remission. J Clin Oncol. 30:e7–e10. 2012. View Article : Google Scholar : PubMed/NCBI

57 

Heinzerling LM, Anliker MD, Muller J, Schlaeppi M and von Moos R: Sarcoidosis induced by interferon-α in melanoma patients: Incidence, clinical manifestations, and management strategies. J Immunother. 33:834–839. 2010. View Article : Google Scholar : PubMed/NCBI

58 

Suarez-Garcia C, Pérez-Gil A, Pereira-Gallardo S, Codes-Villena M, García-Escudero A and Camacho Miguel F: Interferon-induced cutaneous sarcoidosis in melanoma. Melanoma Res. 19:391–394. 2009. View Article : Google Scholar : PubMed/NCBI

59 

Massaguer S, Sánchez M and Castel T: Mediastinal sarcoidosis induced by high-dose alpha-2-interferon therapy in a patient with malignant melanoma. Eur Radiol. 14:1716–1717. 2004. View Article : Google Scholar : PubMed/NCBI

60 

Matsubara T, Hirahara N, Hyakudomi R, Fujii Y, Kaji S, Taniura T and Tajima Y: Early gastric cancer associated with gastric sarcoidosis. Int Surg. 100:949–953. 2015. View Article : Google Scholar : PubMed/NCBI

61 

Tissot E, Bringeon G, Berger F and Kalb JC: Cancer and gastric sarcoidosis. J Chir (Paris). 122:479–481. 1985.(In French). PubMed/NCBI

62 

Claus F, De Wever L and Moerman P: Coincidence of seminoma and sarcoidosis in two patients presenting with peritoneal surface disease. Int J Urol. 19:11262012. View Article : Google Scholar : PubMed/NCBI

63 

Teo M, McCarthy JE, Brady AP, Curran DR and Power DG: A case of sarcoidosis in a patient with testicular cancer post stem cell transplant. Acta Oncol. 52:869–871. 2013. View Article : Google Scholar : PubMed/NCBI

64 

Tjan-Heijnen VC, Vlasveld LT, Pernet FP, Pauwels P and De Mulder PH: Coincidence of seminoma and sarcoidosis: A myth or fact? Ann Oncol. 9:321–325. 1998. View Article : Google Scholar : PubMed/NCBI

65 

Myint ZW and Chow RD: Sarcoidosis mimicking metastatic thyroid cancer following radioactive iodine therapy. J Community Hosp Intern Med Perspect. 5:263602015. View Article : Google Scholar : PubMed/NCBI

66 

Zimmermann-Belsing T, Christensen L, Hansen HS, Kirkegaard J, Blichert-Toft M and Feldt-Rasmussen U: A case of sarcoidosis and sarcoid granuloma, papillary carcinoma, and Graves' disease in the thyroid gland. Thyroid. 10:275–278. 2000. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Spiekermann, C., Kuhlencord, M., Huss, S., Rudack, C., & Weiss, D. (2017). Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic dilemma (Review). Oncology Letters, 14, 7643-7652. https://doi.org/10.3892/ol.2017.7247
MLA
Spiekermann, C., Kuhlencord, M., Huss, S., Rudack, C., Weiss, D."Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic dilemma (Review)". Oncology Letters 14.6 (2017): 7643-7652.
Chicago
Spiekermann, C., Kuhlencord, M., Huss, S., Rudack, C., Weiss, D."Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic dilemma (Review)". Oncology Letters 14, no. 6 (2017): 7643-7652. https://doi.org/10.3892/ol.2017.7247