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LETTER TO EDITOR
Ahead of print publication  

Postmalignancy sarcoid-like reaction


1 Department of Rheumatology and Immunology, Apollo BGS Hospitals, Mysore, Karnataka, India
2 Department of Gastrosurgery, Apollo BGS Hospitals, Mysore, Karnataka, India

Correspondence Address:
Shiva Prasad,
Apollo BGS Hospital, Mysore, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_104_19



How to cite this URL:
Prasad S, Shivathirthan N, Patel KY. Postmalignancy sarcoid-like reaction. Indian J Rheumatol [Epub ahead of print] [cited 2019 Nov 20]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=269119



Dear Editor,

A 50-year-old female presented with complaints of multiple swellings in axillae, groin and neck region for last 4 weeks. There was no history of fever, loss of appetite, loss of weight, chest pain, breathlessness, cough, arthritis, or skin lesions. She had history of Whipple's pancreaticoduodenectomy done 5 years back for periampullary carcinoma. Histopathology of the resected segment had revealed moderately differentiated adenocarcinoma-Grade II. The patient was on regular follow-up postsurgery, regular imaging had revealed no relapse of carcinoma, and she was asymptomatic. On examination, she had multiple lymphadenopathy, involving bilateral axillary, supraclavicular, and inguinal lymph nodes, which were firm in consistency, nonmatted, and nontender. Her systemic examination was normal. Routine laboratory tests including hemoglobin, leukocyte count, platelet count, renal function tests, liver function tests, pancreatic enzymes, and coagulation profile were in normal range. Chest X-ray was normal. Positron emission tomography (PET) scan revealed 1.2 cm × 0.8 cm soft tissue density metabolically active lesion at periportal region likely representing lymph node. It also detected multiple metabolically active bilateral supraclavicular, bilateral axillary, mediastinal, hilar, interlobar, bilateral iliac, and inguinal lymphadenopathy. No obvious hepatic metastases were noted in the study. With FDG uptake not being significantly high to suggest metastasis, differential diagnosis of lymphoma or tuberculosis (TB) was made, and to make a histological diagnosis, excision biopsy of the left axillary lymph node was done. Microscopic examination of the resected lymph node revealed numerous dense noncaseating granulomas of variable size and shape [Figure 1] and [Figure 2]. Ziehl–Neelsen stain for acid fast bacilli was negative and TB polymerase chain reaction of the tissue was also negative. It was also negative for metastases. Fine-needle aspiration cytology (FNAC) of the iliac lymph node also revealed noncaseating granuloma [Figure 3]. Further investigations revealed serum calcium 8.7 mg/dL (8.6–10.2), angiotensin converting enzyme 38.7 U/L (8–52 U/L), erythrocyte sedimentation rate 20 (<20 mm/1st h), and C-reactive protein 5.1 (<5.0 mg/L). Mantoux test was negative. A diagnosis of sarcoid-like reaction was made. She was treated with nonsteroidal anti-inflammatory drugs (NSAIDs, tablet Naprosyn 500 mg BID). She was treated for 6 weeks and was followed up for the next 6 months. She had no relapse of the lymphadenopathy. She is on regular follow-up with recovery of all lymph node swellings.
Figure 1: Biopsy of the axillary lymph node revealing noncaseating granuloma

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Figure 2: Biopsy of the axillary lymph node revealing multinucleated giant cells

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Figure 3: Fine-needle aspiration cytology of the iliac lymph node revealing noncaseating granuloma

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Lymph node enlargement in a case of previous malignancy usually denotes the relapse of malignancy. It is imperative to evaluate the patient and look for the cause of lymphadenopathy. There may be causes other than metastasis, as this case denotes. In India, TB has to be ruled out.

The presence of nonnecrotising granulomas in a previously treated malignancy patient without any systemic symptoms or signs of sarcoidosis is referred to as sarcoid-like reaction. Sarcoid-like reaction related to a tumor was first reported in the early nineteenth century.[1] Sarcoid-like reaction can be found in the stroma of the primary tumor itself, in lymph nodes draining the area of the primary tumor, and even in organs such as the liver, spleen, stomach, and lungs.[2],[3],[4] Pathologically, sarcoid-like reaction includes noncaseating epithelioid cell granuloma that is comprised of focal accumulation of epithelioid cells and multinucleated giant cells, and patients with sarcoid-like reaction show no clinical symptoms of systemic sarcoidosis. The noncaseating epithelioid granuloma is a result of antigen-specific cell-mediated immunity caused by macrophages and T-lymphocytes.[5] Although the pathogenesis of sarcoid-like reaction has been reported, no consensus has been reached on a complete definition. Sarcoid-like reaction is hypothesized to represent an antineoplastic immune phenomenon caused by antigenic factors derived from the tumor, with the high reactivity of the host immune system against such antigenic factors, leading to the development of noncaseating epithelioid granuloma.[1],[3],[4],[5]

There have been cases of therapy-induced sarcoid-like reactions, associated with a wide variety of cytotoxic chemotherapeutics (cisplatin, bleomycin, and paclitaxel), immunomodulating agents (alpha-interferon and interleukin-2), and radiotherapy.[6],[7] The reason why antineoplastic treatment appears to evoke such reactions or amplify existing ones is probably due to increased tissue breakdown or direct modulation of the immune system. Brincker[1] reported that sarcoid-like reactions may occur in 4.4% of cancer patients, 13.8% of patients with Hodgkin's disease, and 7.3% of patients with non-Hodgkin's lymphoma. Fong et al.[8] summarized 15 cases of hepatopancreatobiliary tumor with sarcoid-like reaction in 2012.

Identifying sarcoid-like reactions as metastasis results in disease upstaging. This in turn could lead to overtreatment risking treatment-related toxicities and death[9] or to undertreatment due to the referral of the patient to conservative/palliative therapy, when a more aggressive course of treatment should be pursued. Interestingly, sarcoid-like reactions were four times more likely to occur in metastasis-free lymph nodes than in lymph nodes with metastatic disease. On the contrary, it is possible for a sarcoid-like reaction to encompass micro-metastatic disease that can be missed and treatment be withheld. Therefore, adequate material from multiple biopsy sites, a comprehensive pathologic examination, and immunohistological analysis are all necessary to avoid potential pitfalls.[10]

In this case, it has to be noted that there is generalized lymphadenopathy. In majority of the cases, sarcoid-like reactions are seen in the lymph nodes around the primary malignancy lesion. We had taken FNAC and biopsy from two different sites, and both of them revealed the same histology and there was no evidence of metastasis. PET computed tomography was also not suggestive of malignancy. Treatment with NSAIDs resolved the lymph nodes. this was also supportive of the diagnosis of sarcoid like reaction. As the patient did not have any systemic symptoms or any organ-threatening involvement, we chose Naprosyn as the initial treatment and she responded to it. In sarcoidosis also, if there is only lymph node involvement, Naprosyn is the drug of choice, so we used Naprosyn for the treatment.

Metastasis is the most common cause of lymphadenopathy in a previously diagnosed and treated case of malignancy. However, care has to be taken to rule out other causes such as infection and sarcoid-like reaction. They can also present in the same way and lead to over- or underdiagnosis of malignancy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Brincker H. Sarcoid reactions in malignant tumours. Cancer Treat Rev 1986;13:147-56.  Back to cited text no. 1
    
2.
Craun JB, Banks KP, Clemenshaw MN, Moren RW. Sarcoidlike reaction of neoplasia causing hypermetabolic thoracic adenopathy in setting of extrathoracic malignancy: Report of two cases and a review of the differential diagnostic considerations. J Nucl Med Technol 2012;40:231-5.  Back to cited text no. 2
    
3.
Chowdhury FU, Sheerin F, Bradley KM, Gleeson FV. Sarcoid-like reaction to malignancy on whole-body integrated (18) F-FDG PET/CT: Prevalence and disease pattern. Clin Radiol 2009;64:675-81.  Back to cited text no. 3
    
4.
Murata Y, Tachibana T. Sarcoid reactions in malignant tumor. Kekkaku 1979;54:510-1.  Back to cited text no. 4
    
5.
Sugiyama Y, Oshikawa K. Mechanism of sarcoid granuloma formation participation of cytokines and chemokines. Nihon Rinsho 2002;60:1728-33.  Back to cited text no. 5
    
6.
Trump DL, Ettinger DS, Feldman MJ, Dragon LH. 'Sarcoidosis' and sarcoid-like lesions. Their occurrence after cytotoxic and radiation therapy of testis cancer. Arch Intern Med 1981;141:37-8.  Back to cited text no. 6
    
7.
Butt S, Alzebdeh R, Kable TD, Soubani AO. Non-caseating granulomas in patients after the diagnosis of cancer: Clinical characteristics and outcome. Sarcoidosis Vasc Diffuse Lung Dis 2011;28:44-9.  Back to cited text no. 7
    
8.
Fong ZV, Wong J, Maley WR, Sandorfi N, Winter JM, Koniaris LG, et al. Sarcoid-reaction mimicking metastatic malignant hepatopancreatobiliary tumors: Report of two cases and review of the literature. J Gastrointest Surg 2012;16:1245-50.  Back to cited text no. 8
    
9.
Kok TC, Haasjes JG, Splinter TA, ten Kate FJ. Sarcoid-like lymphadenopathy mimicking metastatic testicular cancer. Cancer 1991;68:1845-7.  Back to cited text no. 9
    
10.
Tjan-Heijnen VC, Vlasveld LT, Pernet FP, Pauwels P, De Mulder PH. Coincidence of seminoma and sarcoidosis: A myth or fact? Ann Oncol 1998;9:321-5.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

 
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