766363 research-article20182018
PSH0010.1177/2010105818766363Proceedings of Singapore HealthcareTan et al.
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Sarcoid-like reaction associated with lung adenocarcinoma: A case report
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Qiao Li Tan1, Leong Chai Leow1, Salahudeen Mohamed Haja Mohideen2 and Duu Wen Sewa1
Abstract A 71-year-old woman with a history of left lower lobe lobectomy 4 years ago for adenocarcinoma of the lung presented with new mediastinal and bilateral hilar lymphadenopathy on surveillance imaging, suspicious for disease recurrence. She underwent an endobronchial ultrasound-guided transbronchial needle aspiration of the lymph nodes and histology yielded non-necrotizing epithelioid granulomas with no evidence of malignancy. A diagnosis of sarcoid-like reaction associated with lung adenocarcinoma was made. The significance of this rare condition is discussed. Keywords Sarcoid-like reaction, lung adenocarcinoma, lymph node, epithelioid granuloma
Introduction Sarcoid-like reaction is a rare condition that has been described in patients with cancer, either upon diagnosis of the malignancy during staging or subsequently during follow up after anti-neoplastic treatment. This reaction can be found in regional lymph nodes with the presence of non-necrotizing epithelioid granulomas, and has also been described within the primary tumor, or distally, in the bone marrow, liver and spleen. It is an important differential of lymph node and distal metastasis as management is significantly different and impacts on patients’ outcomes. We discuss a case of sarcoid-like reaction of the regional lymph nodes associated with previously resected stage 1b lung adenocarcinoma.
Case report A 71-year-old Chinese woman presented with hemoptysis and a left lower lobe mass. Histological sampling by trans-thoracic needle aspiration and staging positron emission tomographycomputed tomography (PET-CT) scan showed a cT2aN0M0 (stage 1b) carcinoma of lung origin with no evidence of nodal or distal hypermetabolic disease. She underwent a left lower video-assisted thoracic surgery lobectomy and pathological stage was confirmed to be pT2aN0M0. No adjuvant therapy was given. She was then followed up with annual surveillance CT imaging. She remained well with no cough, hemoptysis or dyspnea. She also did not report any fever, weight loss or anorexia. Systems review was unremarkable. Routine postoperative surveillance CT scan of the thorax 4 years later revealed new mediastinal and bilateral
hilar lymphadenopathy which raised concerns of cancer recurrence with nodal metastasis (Figure 1(a) and (b)). The lung parenchyma did not reveal interstitial fibrotic changes or nodularity in perilymphatic distribution and there was no local recurrence at the resected site of previous left lower lobectomy nor any suspicious pulmonary nodules. Full blood count, liver function tests and electrolytes panel including alkaline phosphatase and serum calcium were normal. She underwent histological sampling by endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) of the right upper paratracheal and precarinal lymph nodes. Histology revealed non-necrotizing epithelioid granulomas with no evidence of malignancy. Gomori methenamine silver and Periodic acid–Schiff (PAS) stains were negative for fungal organisms. Acid fast bacilli smear and Mycobacterium culture of the lymph node samples were negative. Hence, she was diagnosed with sarcoid-like reaction of regional lymph nodes
1Department
of Pulmonary and Critical Care Medicine, Singapore General Hospital, Singapore 2Department of Diagnostic Radiology, Singapore General Hospital, Singapore Corresponding author: Qiao Li Tan, Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Academia, 20 College Road, Level 3, 169856, Singapore. Email:
[email protected]
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Figure 1. Axial and coronal contrast-enhanced CT soft-tissue images of the thorax; (a) at level of carina, involving the right precarinal (measuring 3.0 cm × 2.4 cm), prevascular and aortopulmonary window nodes; (b) coronal section demonstrating the subcarinal, right and left hilar nodes. CT: computed tomography.
Figure 2. Axial contrast-enhanced CT soft-tissue image of the thorax 3 years later showed interval decrease in size of the right upper and lower paratracheal, prevascular and bilateral hilar nodes. CT: computed tomography.
on a background of previously resected stage 1b lung adenocarcinoma. The patient remained asymptomatic and was not started on any medication. Subsequent repeat CT scans over the next 3 years showed interval decrease in size of the lymphadenopathy and no evidence of local recurrence (Figure 2). She is still on annual surveillance.
Discussion Sarcoid-like reactions associated with cancer were first described by Wolbach et al. in 1911 as ‘groups of epithelioid cells and giant cells’ of which ‘extensive necrosis or caseation does not occur’. 1 He presented a series of five autopsy cases of which two were patients with carcinoma of the colon and jaw, where sarcoid-like reactions were found in the interlobular septa of the lung and bronchial lymph nodes respectively. Since then, the development of sarcoid-like reactions has been observed in other patients with malignancies, either
concurrently or on follow up after treatment. In 1986, Brincker et al. described an overall occurrence in 4.4% of carcinomas.2 Case series of patients with non-small cell lung carcinoma (NSCLC) staged with mediastinoscopy and surgical resection found sarcoid-like reactions in 4.3 to 14.9% of the patients.3–5 Other associated malignancies include hematologic malignancies such as lymphoma and solid organ tumors of the stomach, colon, breast and kidney.6 These granulomatous reactions can be found within the regional lymph nodes or in the vicinity of the tumor. They can also be seen within the stroma of the primary tumor itself, or more distantly, in non-regional lymph nodes, spleen, liver and bone marrow.7 The exact mechanism of malignancy-related sarcoid-like reactions is unknown and an immunological process has been postulated. Soluble tumor related antigens expressed by the malignant tumor drain into regional lymphatic system where activation of host’s immunity occurs, leading to a T-cell mediated granulomatous response within these lymph nodes. Other mechanisms include a local tissue reaction to tumor
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Tan et al. embolism within the lymphatic and capillary system, or reaction to a foreign body from previous procedures.2,6–8 Sarcoid-like reactions can be differentiated from systemic sarcoidosis by the lack of clinical and radiographic evidence of multisystemic involvement, such as of the skin, heart, lungs and eyes.6 Although a standard diagnostic criterion for sarcoid-like reactions is lacking, the diagnosis is supported by histological evidence of non-necrotizing epithelioid cell granulomas, after exclusion of other disorders known to cause a similar granulomatous process. These include infections by Mycobacterium tuberculosis, syphilis and fungal infections; and other non-infectious causes such as inflammatory bowel disease, vasculitis and drug reactions.9 Frequently, sarcoid-like reactions are noted on staging or surveillance CT or PET scans, where they give rise to concerns of neoplastic disease with nodal metastasis or of recurrence and dissemination if the patient has had previous curative therapy, although the duration from initiation of therapy to onset of the sarcoid-like reaction is unclear. Manifestations of sarcoidlike reaction on CT often demonstrate abnormalities in the thorax, with symmetrically enlarged hilar and mediastinal lymph nodes, pulmonary nodules and ground glass opacities.10,11 Benign lymph nodes from sarcoid-like reactions also demonstrate non-specific 18F-fluorodeoxyglucose (FDG) uptake and may mimic malignant lymphadenopathy on FDG-PET-CT. Increased FDG uptake has also been described in the pulmonary parenchyma and extra-thoracic involvement of lymph nodes outside the mediastinum, the spleen and liver.11,12 Koo et al.11 performed a study on mediastinal lymph nodes using CT and FDG-PET-CT in which a comparison of radiologic findings of sarcoidosis, sarcoid reaction and malignant lymph nodes was done. In contrast with malignant lymph nodes, lymph nodes from sarcoid reaction tend to be bilateral and larger in size with significantly more lymph nodes measuring >1 cm although the total volume of lymph nodes was less than that of the malignant lymph nodes. The sarcoid reaction was also observed more in younger female patients. The diverse metabolic uptake on FDG-PET-CT was not adequate to differentiate lymphadenopathy from metastasis with that from sarcoid reaction and sarcoidosis, and hence the authors maintained that a histological diagnosis for confirmation is needed for subsequent appropriate management. Another study by Kaira et al. evaluated the use of FDGPET-CT with addition of L-[3-18F]-α–methyltyrosine (18FFMT) PET in 24 patients with sarcoidosis and suspected malignancy and found that while FDG uptake was noted in both nodal and extra-nodal sarcoid disease, 18F-FMT uptake was absent. Similarly, when performed on a control group of lung cancer patients, both FDG and 18F-FMT uptake were demonstrated.13 While there is suggestion that when used in combination both FDG and 18F-FMT-PET scans may aid in differentiating sarcoid tissue from malignant lesions, further investigations are needed to determine if imaging modalities can replace the need for a histological diagnosis. The overall prognostic significance of malignancy associated sarcoid-like reaction in patients is uncertain. Studies describe positive prognostic significance in patients with Hodgkin disease with longer disease-free survival.6 Similarly in patients with NSCLC, sarcoid-like reactions which were predominantly found in stage I disease appear to predict a lower rate of recurrence after curative surgical resection.3,4 Currently, there is a paucity of data for long term follow up of
patients with sarcoid-like reactions and their outcomes, although patients may show spontaneous remission with reduced metabolic activity on PET-CT.
Conclusion In summary, this case illustrates a well described but rare occurrence of sarcoid-like reaction within the regional lymph nodes of a patient with lung adenocarcinoma four years postsurgical resection. The CT findings of bilateral mediastinal and hilar lymphadenopathy and histological confirmation with minimally invasive EBUS-TBNA demonstrating presence of non-necrotizing granulomas helped to clinch the diagnosis and rule out cancer recurrence. Declaration of conflicting interest The authors declare that there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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