Pembrolizumab-Induced Sarcoid-Like Reaction in a Patient With Lung Cancer

Yousuf, Hira; Mekki, Rasheid; Khan, Khizer; Hussain, Ali

doi:10.7759/cureus.12395

Cited by 6 publications

(7 citation statements)

References 14 publications

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“…However, the patient here didn’t benefit from immunotherapy, with a stable disease evaluated by radiology and 50% residual tumor cells by histology after treatment, and had a recurrence 8 months after surgery. According to the previous case reports of 8 SLR patients with NSCLC ( 21 – 28 ), 4 achieved partial response, 2 had progressive disease, and 2 had stable disease after immunotherapy. The association between SLRs and immunotherapy outcomes in lung cancer seems not clear.…”

Section: Discussionmentioning

confidence: 95%

Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma

et al. 2022

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Immune checkpoint inhibitor-induced sarcoid-like reactions and tertiary lymphoid structures (TLSs) are increasingly recognized but rarely reported in the same patient. We report a patient with lung adenocarcinoma who displayed sarcoid-like reactions in intrathoracic lymph nodes and tertiary lymphoid structures in surgical tumor after neoadjuvant therapy with nivolumab plus ipilimumab. Pathological examination revealed 50% residual tumor cells after treatment, and the CT evaluation of the primary tumor showed a stable disease. The patient experienced a recurrence eight months after surgery. To identify immune correlates of the limited response to immunotherapy, we conducted genomic and transcriptional assays, multiplex immunoassay, and multiplex immunohistochemistry on the pre- and post-immunotherapy tumor, lymph node, and plasma samples. TP53 R181C, KRAS G12C and SMAD4 R361H were identified as driver mutations of the tumor. In addition to abundant infiltrated lymphocytes, immunotherapy induced high levels of inhibitory components in post-treatment tissue samples, especially the FOXP3+ regulatory T cells in tumor and PD-L1 expression in the lymph node. Despite abundant TLSs in the post-treatment tumor, most TLSs were immature. Moreover, increasing levels of circulating checkpoint proteins BTLA, TIM-3, LAG-3, PD-1, PD-L1, and CTLA4 were observed during immunotherapy. Collectively, our observations revealed that high levels of immunosuppressive molecules in tumor, lymph nodes and/or in peripheral blood might indicate poor outcomes after immunotherapy, even in the setting of a patient with concurrent sarcoid-like reactions and tertiary lymphoid structures.

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Section: Discussionmentioning

confidence: 95%

Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma

et al. 2022

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“…Several reports have documented the association between sarcoid reactions and various types of malignant tumors. The factors that cause malignancies to elicit sarcoid reactions are not clearly understood; however, many cases involve therapeutic agents, including immunosuppressive drugs [ 7 – 9 , 23 , 24 ]. Therefore, we summarized the reports of sarcoid reactions with a history of surgery over the past decade, including information regarding adjuvant drug use (Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…We excluded possible cases of sarcoidosis. For cases of drug-induced sarcoid reactions, rapid improvement has been reported after drug discontinuation [ 7 , 24 , 34 , 35 ]. However, in some cases, the sarcoid reactions persist for more than 1 year after the drug is discontinued [ 34 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Splenic sarcoid reaction mimicking metastases in patients after uterine cancer surgery: a report of two cases

Kitamura,

Ogura,

Miyamoto

et al. 2023

surg case rep

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Background Tumor-associated sarcoid reactions have been observed with various tumors; however, they have not been reported with uterine cancer. We present two cases of splenic sarcoid reactions that mimicked metastases a few years after uterine cancer surgery. Case presentation Case 1 involved a 67-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent open total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Three years after the initial surgery, computed tomography (CT) and positron emission tomography CT showed multiple splenic masses with increasing numbers and sizes. Splenic metastases were diagnosed, and laparoscopic splenectomy was performed. The histopathological analysis revealed sarcoid reactions in the spleen. Case 2 involved a 47-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Two years after the initial surgery, multiple splenic masses were observed. We performed laparoscopic splenectomy for the splenic metastases. Granuloma formations were identified in the splenic specimen and perisplenic lymph nodes that were removed simultaneously, resulting in a final diagnosis of sarcoid reaction. A review of the lymph nodes at the time of the previous uterine surgery revealed granuloma formation. Other than the presence of splenic masses, no findings suggestive of recurrence were observed in these cases. Uterine cancer and sarcoid reactions progressed without recurrence after splenectomy. Conclusions To the best of our knowledge, this is the first report of the late development of splenic sarcoid reactions after uterine cancer surgery. Sarcoid reactions and metastases are difficult to diagnose based on preoperative imaging results. However, reviewing the specimen at the time of the initial resection, the number of lesions, and the clinical findings (other than imaging findings) may aid in the determination of the correct diagnosis.

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“…In mouse models of IBD and IBD patients, PD-1 is upregulated on T cells, macrophages, dendritic cells, B cells and in colon tissues that are inflamed. Some examples of drugs that target PD-1 include Pembrolizumab (Keytruda) and Nivolumab [ 127 ]. In addition, ipilimumab (Yervoy) is a monoclonal antibody that inhibits CTLA-4 activity, providing a similar effect.…”

Section: Checkpoint Markersmentioning

confidence: 99%

Cancer Immunotherapy: The Checkpoint between Chronic Colitis and Colorectal Cancer

Ephraim

Feehan

Fraser

et al. 2022

Cancers

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Inflammatory Bowel Disease (IBD) is a group of diseases that cause intestinal inflammation and lesions because of an abnormal immune response to host gut microflora. Corticosteroids, anti-inflammatories, and antibiotics are often used to reduce non-specific inflammation and relapse rates; however, such treatments are ineffective over time. Patients with chronic colitis are more susceptible to developing colorectal cancer, especially those with a longer duration of colitis. There is often a limit in using chemotherapy due to side effects, leading to reduced efficacy, leaving an urgent need to improve treatments and identify new therapeutic targets. Cancer immunotherapy has made significant advances in recent years and is mainly categorized as cancer vaccines, adoptive cellular immunotherapy, or immune checkpoint blockade therapies. Checkpoint markers are expressed on cancer cells to evade the immune system, and as a result checkpoint inhibitors have transformed cancer treatment in the last 5–10 years. Immune checkpoint inhibitors have produced long-lasting clinical responses in both single and combination therapies. Winnie mice are a viable model of spontaneous chronic colitis with immune responses like human IBD. Determining the expression levels of checkpoint markers in tissues from these mice will provide insights into disease initiation, progression, and cancer. Such information will lead to identification of novel checkpoint markers and the development of treatments with or without immune checkpoint inhibitors or vaccines to slow or stop disease progression.

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Pembrolizumab-Induced Sarcoid-Like Reaction in a Patient With Lung Cancer

Cited by 6 publications

References 14 publications

Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma

Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma

Splenic sarcoid reaction mimicking metastases in patients after uterine cancer surgery: a report of two cases

Cancer Immunotherapy: The Checkpoint between Chronic Colitis and Colorectal Cancer

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