A case report and assessment of the literature on spontaneous remission of advanced, progressing, remission means in cancer, and poorly differentiated non-small cell lung cancer.
Background: Remission means in cancer is a relatively rare occurrence whose mechanism is unknown. There are limited cases of ER from non-small cell lung cancer in particular (NSCLC).
The example of a 74-year-old lady with advanced, poorly differentiated NSCLC (high expression of programmed death-ligand 1 [PD-L1]) who progressed despite multiple courses of treatment and then spontaneously remitted is presented.
Presentation of the case: By bronchoscopy biopsy, the patient had hemoptysis and was diagnosed as poorly differentiated stage IIIA NSCLC. Her medical history was devoid of significant features, and her functional level was moderate. After neoadjuvant chemotherapy, the first treatment plan included surgery.
Despite conventional chemotherapy, the patient’s tumor progressed gradually on follow-up computed tomography (CT), and the patient elected not to continue treatment after fifth-line chemotherapy.
One year after stopping treatment, a follow-up chest CT scan revealed that the tumor mass had shrunk significantly. A percutaneous biopsy sample of the reduced lung mass revealed no live tumor cells, and positron emission tomography images taken during follow-up revealed diminished metabolic activity in the tumor mass.
The patient’s diagnosis of ER from NSCLC was confirmed, and the tumor had not progressed at the nine-month follow-up. remission in cancer, Later, immunostaining for PD-L1 in the initial tumor cells revealed significant positivity (> 99 percent).
Conclusion: Our case demonstrates a link between immunity and tumor regression in advanced NSCLC that is poorly differentiated and unresponsive to many lines of treatment.
The partial or total elimination of a malignant tumor without any standard treatment for cancer control or with inadequate treatment is known as spontaneous remission (SR). In 1956, Cole and Everson published the first report on 47 cases of ER cancer, which were verified by biopsy remission means in cancer, and suggested the nomenclature and criteria for ER.
Although ER is common in neuroblastoma, bladder cancer, and lymphoma , ER from non-small cell lung cancer (NSCLC) is uncommon, with only a few cases recorded worldwide. After many lines of chemotherapy failed, a 74-year-old woman was diagnosed with poorly differentiated advanced NSCLC, which she spontaneously remitted.
Report on a case
According to a chest X-ray obtained at another hospital to investigate recurrent hemoptysis, a 74-year-old woman was admitted to our institution with a history of a lung mass. The patient didn’t have any relevant medical history and wasn’t on any medications.
She was a stay-at-home mom who had never smoked. Except for hemoptysis, she experienced no respiratory symptoms. There had been no previous exposure to the environment or at work. The physical examination revealed reduced lung sounds in the lower left lung region upon admission.
Except for a modest increase in C-reactive protein (0.44 mg/dL, reference: 0-0.3 mg/dL), laboratory tests were normal. A 5.1 2.9 cm lung mass in the left upper lobe was discovered on first chest radiography and computed tomography (CT), with a ground-glass attenuation halo surrounding it (Fig. 1a and b).
Malignancy could not be ruled out because of small pulmonary nodules in the right upper and lower lobes, as well as an enlarged left hilar lymph node (11 L). Images from positron emission tomography/computed tomography (PET/CT) revealed a mass in the left lung, as well as elevated metabolic activity.
Figure 1: Thoracic radiographs and successive CT images of a 74-year-old lady with non-small cell lung cancer in spontaneous remission. (a): A tumor in the left lung is visible on an X-ray dated January 2015. (white arrow).
(b): On computed tomography (CT) pictures taken at the time of the initial chest radiograph, a 5.1 2.9 cm lung mass can be detected in the left upper lobe (black arrow) (a). (a), (b), (c), (d), (e), (f), (g), (h Follow-up radiography (c) and CT imaging (d) in April 2017 revealed an increase in the size of the lung mass after fifth-line chemotherapy.
(e) and (f): A follow-up radiograph (e) and CT images (f) taken in July 2018 showed a significant reduction one year after stopping the chemotherapy. remission in cancer.
Figure 2: Before and after spontaneous remission of the mass in the left lung, 18F-fluorodeoxyglucose positron emission tomography / computed tomography images were compared. (a) and (b) are two different ways of expressing the same thing.
A mass with intense metabolic activity (arrowhead) in the left lung
(a) corresponding to the density of soft tissue in an image Combination of PET and CT fusion (arrow) was discovered in a coronary positron emission tomography image in January 2015.
(B). In October 2018, a reduction in the size and activity of the mass in the left lung was seen on a coronal PET picture
(c) and a combined PET and CT fusion image (arrow)
(d) following spontaneous remission.
A polypoid mass with luminal blockage of the lower segmental bronchus of the left lingual was discovered during diagnostic bronchoscopy (Fig. 3a). Without problems, a bronchoscopy biopsy of the lung tumor was conducted.
The initial bronchoscopy biopsy revealed a poorly differentiated carcinoma with numerous tumor-infiltrating lymphocytes on histological evaluation (Fig. 4a). Antibodies to cytokeratin (CK) -7, CK-20, thyroid transcription factor 1, napkin A, p63, p40, and CD56 were negative in immunohistochemistry.
Non-small cell carcinoma was the first pathology diagnosis, with no further details provided. remission in cancer. In terms of the epidermal growth factor receptor, the tumor was wild-type. Because the ALK inhibitor was not available, the anaplastic large cell lymphoma kinase (ALK) rearrangement was not determined.
Long before the ALK inhibitor was licensed for lung cancer treatment, the patient was diagnosed with lung cancer in January 2015. Retrospective PD-L1 (PD-L1) immunostaining (Window PD-L1 SP263 Assay, Roche Diagnostics, Switzerland) revealed strong PD-L1 expression, with a tumor ratio score of 99 percent (Fig. 4b).
Figure 3: Bronchoscopy findings before and after lung cancer diagnosis and spontaneous remission.
(a): On initial bronchoscopy, an endobronchial polypoid mass nearly completely obstructed the lingual segment’s bronchial opening.
(b): The opening to the bronchus was replaced by a scar lesion when the tumor went into spontaneous remission.
Figure 4: shows the histopathological results of the original and later bronchoscopy biopsies.
(a): A bronchoscopy biopsy revealed a poorly differentiated carcinoma with many tumor-infiltrating lymphocytes. (b): Almost all tumor cells expressed PD-L1 when stained immunohistochemically.
(c): A second bronchoscopy biopsy revealed persistent inflammation and foamy histiocytic infiltration, remission in cancer. indicating tumor regression.
(d): A percutaneous needle lung biopsy revealed significant fibro elastosis in the absence of tumor cells, which is another histological sign of tumor regression.
A tentative diagnosis of lung cancer was proposed with T3N1M0 after an MRI scan of the lung for cancer staging revealed a non-metastatic lesion (stage IIIA according to the TNM system, 7th edition). Initially, the patient intended to have surgery following two cycles of paclitaxel with carboplatin neoadjuvant therapy, which resulted in a reduction in lung mass size from 5.1 2.9 cm to 4.1 1.5 cm.
However, remission means in cancer due to a self-prescribed herbal drug, the patient developed toxic hepatitis, with aspartate aminotransferase (AST) / alanine aminotransferase (ALT) titers of 110/182 IU / L, and surgery was postponed for two weeks. The number of AST/ALT titles has dropped.
During this time, the tumor mass expanded slightly (4.1 2.6 cm), and the patient questioned whether surgery was necessary.
As a result, she had two additional cycles of paclitaxel plus carboplatin, remission means in cancer for a total of four cycles of paclitaxel plus carboplatin. The tumor, however, continued to grow, and chemotherapy was given in stages, up to the fifth line, according to the following schedule:
Second line: four gemcitabine plus carboplatin cycles; third line: two pemetrexed cycles; fourth line: four docetaxel cycles weekly; fifth line: one vinorelbine cycle weekly Due to general weakness, the patient refused additional chemotherapy after vinorelbine monotherapy.
On a follow-up chest radiograph (Fig. 1c) and CT (Fig. 1d) four months after stopping chemotherapy, the tumor had grown significantly (6.8 6.0 cm), immediately infiltrating the left major pulmonary artery, the left atrium, and the lower lobe remission means in cancer.
As a result, the patient received irinotecan + carboplatin as sixth-line chemotherapy. Despite the fact that the tumor size had shrunk after four cycles of chemotherapy, the patient elected to discontinue treatment due to her general bad health and drug side effects, and a regular follow-up session for tumor surveillance was scheduled.
A chest radiograph was taken a year after therapy ended revealed that the tumor mass had shrunk in size (Fig. 1e). In prior months, the patient had received herbal treatment (RootsTech’s jap onus extracts).
The size of the tumor in the left lingual segment was reduced to 3.6 2.5 cm on CT scans collected after hospitalization for review of disease status (Fig. 1f). The size and metabolic activity of the lung mass (Fig. 2c and d) and the hilar lymph node were also reduced by PET/CT.
We did a bronchoscopy and attempted to replicate the tumor biopsy in order to arrange the upcoming treatment.
Instead of an endobronchial tumor, we discovered a fibrotic scar blocking the lingual segment (Fig. 3b). The second bronchoscopy sample demonstrated persistent inflammation with foamy histiocytic infiltrate on histological analysis (Fig. 4c). Remission means in cancer tumor in the left lung was next subjected to a fluoroscopic lung biopsy.
The left lung lesion included a large deposit of collagen and elastic fibers, but no tumor cells, according to a percutaneous needle biopsy (Fig. 4d). The second bronchoscopy biopsy and percutaneous needle biopsy revealed histopathological evidence of tumor regression.
A diagnosis of ER from NSCLC was made, and the patient was determined to be cancer-free nine months after ER was discovered in a follow-up outpatient session.
Conclusion and discussion:
Our patient had an ER of advanced NSCLC that was poorly differentiated, PD-L1 positive, and resistant to standard treatment. Cancer-related ER is a rare occurrence, and there are few studies on it. According to the kind of neoplasia, ER occurs in 1 in 60,000 to 100,000 cancer patients [2,20].
According to Challis and Stem’s review of the literature, nine types of cancer (kidney, neuroblastoma, melanoma, choriocarcinoma, bladder, retinoblastoma, lymphoma, leukemia, and breast cancer) accounted for 69 percent of all ER cases between 1900 and 1987, while ER from lung cancer occurred in only 2.6 percent of all ER patients . Remission means in cancer a few cases of ER from biopsy-confirmed NSCLC have been recorded due to the extremely rare prevalence of ER in lung cancer (Table 1).
Review of the literature on histologically proven spontaneous remission means in cancer of non-small cell lung cancer
RE’s mechanism is still unknown. Interestingly, poorly differentiated cancer is prevalent in NSCLC patients with ER. Light microscopy alone may not be enough to detect poorly differentiated cancer with a poor prognosis [21,22]. The pathologist’s interpretation and sufficient sample size are crucial in the diagnosis of poorly differentiated cancer.
Despite evidence from recently established novel immunochemical markers, many ER cases involve tumors with weakly differentiated features, suggesting that malignancies of this origin may have been misclassified. In addition, when compared to well-differentiated NSCLC, poorly differentiated NSCLC has a high fluoride on glucose (FDG) incorporation and a high Ki-67 proliferation index on positron emission tomography . In addition, some cases of poorly differentiated lung cancer with a leukemic reaction have been reported [24,25,26].
Acute inflammation is physiologically self-limiting; activated neutrophils produce specialized pro-resolving mediators (SPM), such as lipoxins, resolving, proteins, and mares’ ins, which are produced from essential fatty acids. In vitro research suggests that PMS regulates both innate and adaptive immunity.
Decreasing inflammatory cytokine production (e.g., tumor necrosis factor-alpha and interferon-gamma) and antibody production by B cells [29.30]. Given the link between cancer progression and inflammation, an increase in cell proliferation in a poorly differentiated carcinoma could, paradoxically, cause tumor growth to be suppressed by PMS, resulting in cancer ER.
Our patient was a non-smoker, in contrast to prior ER cases that involved smokers. Several studies have lately indicated that immunotherapy is more effective in smokers than in non-smokers, but they have not explained why .
Similarly, an intense positive for PD-L1 and a high presence of tumor-infiltrating lymphocytes (tumor-infiltrating lymphocytes, TIL) were found in this patient, both of which are immunotherapy biomarkers . Our findings, together with those of earlier studies, point to a link between immunity and cancer prevention.
After stopping chemotherapy, our patient used herbal medicine (O. jap amicus extracts). Glad wish et al. described a patient with stable IIB NSCLC ER who received an herbal drug (Essie tea) , which has an antiproliferative impact in vitro on tumor cells at high concentrations . Chung et al.
recently described a case of an NSCLC ER patient who received herbal therapy during and after chemotherapy . O. jap meniscus is a flowering plant that contains organic solvent extractable compounds such as ethyl acetate, which has anti-cancer properties in human stomach cancer cells .
O may potentially play a role, according to a study using an in vivo model. By enhancing the dispersion of immune cells and the generation of immunological-related cytokines, jap onus increases immunity .
The tumor in our case showed a lot of TILs and a lot of PD-L1, indicating that the patient had an anticancer immune response and would have been a good candidate for an immune checkpoint inhibitor remission means in cancer. Although there is no evidence that O. jap onus is effective in people, the ER in our instance could have been altered by O. jap onus consumption.
There is a potential of a pseudo-progression or a delayed response to chemotherapy in our patient because she had received numerous cycles of chemotherapy prior to the onset of ER. The chemotherapy regimen, on the other hand, had changed multiple times, and tumor regression was found one year after the previous treatment, indicating a high likelihood of ER.
Furthermore, because all of the chemotherapeutic medications given to our patients are conventional medicines rather than immune checkpoint inhibitors, they are unlikely to produce pseudo progression.
Finally, we present a case of RE in a patient with NSCLC who had failed to respond to conventional treatment. Although the exact mechanism of ER, in this case, is unknown, it is possible that decreased immunity is to blame. Although a single case cannot be used to draw firm conclusions, ours demonstrates the relevance of immunity in lung cancer.
Reference: Kari A. Kubalanza, MD, Gynecologic Oncology, Fellow, American Society of Clinical Oncology.