|Ahead of print publication
Spontaneous regression in a primary adenocarcinoma of lung with epidermal growth factor receptor mutation
Farhan Ahmad1, Shalini Singh1, Niraj Kumari2
1 Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||22-Jun-2020|
|Date of Decision||14-Aug-2020|
|Date of Acceptance||30-Sep-2020|
|Date of Web Publication||03-Nov-2021|
Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Spontaneous regression (SR) has been reported sporadically in few tumor types. Its occurrence in non-small-cell lung cancer is relatively rare, more so with adenocarcinoma histology. Various mechanisms of SR have been postulated in literature that may play a role in triggering immune response. However, the exact underlying mechanism has yet to be ascertained. We report a rare case of true SR in a primary adenocarcinoma of lung with tumor-infiltrating lymphocytes and epidermal growth factor receptor mutation.
Keywords: Adenocarcinoma lung, spontaneous regression, tumor-infiltrating lymphocytes
| > Introduction|| |
Spontaneous regression (SR) has been reported sporadically in few tumor types with an incidence of about 1 in 60,000–100,000. It has been generally defined as complete or partial disappearance of a malignant tumor with inadequate or no treatment. Its occurrence in non-small-cell lung cancer (NSCLC) that has a high global incidence, is relatively rare, more so with adenocarcinoma histology., We report the case of a 59-year-old male, who was diagnosed with advanced NSCLC, adenocarcinoma, and epidermal growth factor receptor (EGFR) mutation, who had SR of disease following biopsy, without any treatment.
| > Case Report|| |
A 59-year-old male was referred to our center, after being diagnosed as lung carcinoma. He initially presented to a community physician with complaints of multiple episodes of scanty hemoptysis on a single day, about 1.5 months ago. A chest X-ray posteroanterior view showed a radiopaque shadow in the left upper lobe. There was no history of chest pain, shortness of breath, cough with expectoration, or prolonged fever of recent onset as well as in the past. He was an ex-chronic smoker, 30 pack-years of smoking, and had quit smoking 5 years ago. A contrast-enhanced computed tomography (CECT) scan of the thorax revealed a heterogeneously enhancing mass lesion of size 6.6 cm × 3.2 cm in the anterior segment of the upper lobe of the left lung along with mediastinal lymphadenopathy [Figure 1]a, which was clinically staged as cT3N2M0 (AJCC 8th ed.ition). A video-bronchoscopy showed no endobronchial growth. Histopathological examination of CT-guided biopsy from the lung lesion revealed adenocarcinoma with dense tumor-infiltrating lymphocytes (TILs) around the tumor [Figure 2]a, [Figure 2]b, [Figure 2]c, and EGFR mutation analysis by real-time polymerase chain reaction revealed deletion of exon 19. A GeneXpert® assay for tuberculosis and fungal cultures were found to be negative. He underwent disease staging workup with whole-body positron emission tomography-CT (PET-CT) scan about 2 months postbiopsy, which showed an ill-defined fibro-reticular residual lesion in the anterior segment of the upper lobe of the left lung with surrounding area of ground-glass changes with faint fluorodeoxyglucose-avid and mediastinal lymphadenopathy (maximum standardized uptake value – 4.12). A comparison with the previous CECT scan showed a significant decrease in the size of the primary lung lesion at the time of PET-CT scan. In view of the locoregional disease, he was planned for radical radiotherapy with sequential chemotherapy as per the existing department protocol. A radiotherapy planning CECT scan showed complete resolution of the primary disease except the mediastinal lymph node. He was planned for bronchoscopy-guided fine-needle aspiration cytology from the mediastinal lymph node. However, a repeat CECT scan done at 4 months post biopsy showed a complete resolution of primary and mediastinal nodal disease [Figure 1]b. On a multidisciplinary meeting, it was decided to keep the patient on close follow-up. He has been doing well without any signs and symptoms of disease with a progression-free period of 12 months at present.
|Figure 1: (a) Contrast-enhanced computed tomography scan at diagnosis showing a heterogeneously enhancing mass in the left upper lobe of the lung. (b) Contrast-enhanced computed tomography scan post biopsy showing resolution of the lung mass|
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|Figure 2: (a) Lung tissue core showing infiltrative tumor present in the glands (H and E, ×10). (b) Black arrows – tumor cells arranged in glands, yellow solid arrows – tumor-infiltrating lymphocytes around the glands (H and E, ×40). (c) TTF-1 staining of tumor cells showing nuclear expression, suggesting lung primary (immunohistochemistry, ×20)|
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| > Discussion|| |
SR is a unique and rare entity which was first reported in 1956 by Cole and Everson, who coined the term and laid the criteria. It is most commonly reported in malignant melanoma, neuroblastoma, lymphomas, and renal cell cancers, but its occurrence in primary thoracic malignancies is very less. In a literature review by Challis et al., on 741 SR cases reported with different cancers between 1950 and 2004, lung cancers accounted only for 2.6% of cases. Later, Kumar et al. identified 76 cases of true SR of all thoracic malignancies from 1951 to 2008, of which majority were metastasis and only five cases were of primary lung cancer that included two mesotheliomas. Majority of SR in NSCLC cases are reported in squamous cell cancer.
Various mechanisms of SR have been postulated in literature, mainly infection, fever, injury (trauma and surgery), radiation, pregnancy, and medication that may play a role in triggering immune response.,, However, the exact underlying mechanism has yet to be ascertained. The present case did not have any history of autoimmune disorder, infection, fever, or use of any medication/herbs.
The present case to the best of our knowledge is the only case of advanced EGFR-mutated adenocarcinoma of lung with SR of the tumor and mediastinal lymph nodes without any treatment. Two hypotheses of SR can be proposed in the present case. First, stimulation of change in the intra-tumoral immunological mechanism between the host and the tumor after a direct invasive approach such as biopsy of the lesion as suggested by Ogawa et al. Second, induction of antitumor immune response as there was a dense infiltration of lymphocytes around the tumor on histology. Such a mechanism of SR has also been noticed by Furudate et al., on skin tumors. However, some other authors have suggested that mere presence of TILs might not lead to effective antitumor response. Blood samples were not obtained for immunological evaluation in the present case, as there was no expectation of tumor regression at that time and thus the data elucidating the precise immunological association and the exact mechanism of SR remain unknown in such a scenario. Further studies are needed to utilize genetic and molecular assays to characterize these patients and their tumor and microenvironment and shed light on this rare phenomenon. The rarity of this scenario with lung cancer is also reflected in lack of evidence in literature regarding management options, to balance tumor control and treatment-related sequelae.
| > Conclusions|| |
We described a rare case of true SR in a primary adenocarcinoma of lung with TILs and EGFR mutation that has not been reported so far.
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.
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Conflicts of interest
There are no conflicts of interest.
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