OBJECTIVE: Tumour grading is an essential part of the pathologic assessment that promotes patient management. The International Association for the Study of Lung Cancer (IASLC) proposed a grading system for non-mucinous lung adenocarcinoma in 2020. We aimed to validate the prognostic impact of this novel grading system on overall survival (OS) and recurrence-free survival (RFS) based on literature data.
RESULTS: The review protocol was registered in PROSPERO (CRD42023396059). We aimed to identify randomized or non-randomized controlled trials published after 2020 comparing different IASLC grade categories in Medline, Embase, and CENTRAL. Hazard ratios (HRs) with 95% confidence intervals (CIs) of OS and RFS were pooled and the Quality In Prognosis Studies (QUIPS) tool was used to assess the risk of bias in the included studies. Ten articles were eligible for this review. Regarding OS estimates, grade 1 lung adenocarcinomas were better than grade 3 both in univariate and multivariate analyses (HROSuni = 0.19, 95% CI: 0.05-0.66, p = 0.009; HROSmulti = 0.21, 95% CI: 0.12-0.38, p < 0.001). Regarding RFS estimates, grade 3 adenocarcinomas had a worse prognosis than grade 1 in multivariate analysis (HRRFSmulti: 0.22, 95% CI: 0.14-0.35, p < 0.001).
CONCLUSIONS: The literature data and the result of our meta-analysis demonstrate the prognostic relevance of the IASLC grading system. This supports the inclusion of this prognostic parameter in daily routine worldwide.

Tumor lysis syndrome (TLS) is a potentially fatal oncological emergency that typically develops during the treatment of rapidly proliferating malignancies. It is infrequently reported in solid tumors, such as pulmonary adenocarcinoma. A 59-year-old male patient with shortness of breath presented with a 3.3 cm × 3.0 cm mass in the right upper lobe, along with massive right-sided pleural effusion. A percutaneous needle biopsy was performed, and a diagnosis of pulmonary adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation was made. The patient was treated with afatinib because of the malignant pleural effusion and multiple metastases to the intrathoracic lymph nodes, left scapula, and brain. After 4 days of afatinib treatment, he developed oliguric acute kidney injury and progressively worsening dyspnea. Based on the clinical and laboratory findings, the patient was diagnosed with afatinib-induced TLS. To the best of our knowledge, this is the first reported case of afatinib-induced TLS in pulmonary adenocarcinoma.

The occurrence of ureteral metastasis from distant primary tumors is uncommon, and appears to be especially rare when it originates from the lungs. In the case presented here, a patient with lumbago and left hydronephrosis was diagnosed with left ureteral metastasis of pulmonary adenocarcinoma after a CT-guided percutaneous transthoracic needle biopsy of the lung and retroperitoneal laparoscopic left nephroureterectomy. He accepted the targeted therapy because the lung tumor epidermal growth factor receptor mutation (exon19 deletion) was positive, and preoperative staging of lung adenocarcinoma was stage IVA. After an 8-month follow-up, he is still alive and well, with no local recurrence or distant metastases. The therapy outcome assessment is stable disease. Although rare, our case has demonstrated that pulmonary adenocarcinoma has the possibility of metastasizing to the ureter, a risk that should be considered in some lung cancer patients.

We report a case of 46-year-old male operated on for moderately differentiated lung adenocarcinoma. Postoperatively, he underwent six courses of chemotherapy and radiotherapy. He developed progressive severe inferior paraparesis accompanied by excruciating pain between the shoulders two years later. Magnetic resonance imaging revealed metastases in the bodies of T2 and T3 vertebrae with adjacent intradural extramedullary lesion compressing the spinal cord. The patient underwent surgical decompression and vertebral body cement augmentation that lead to pain relief and partial neurological recovery. The histological examination was consistent with metastases from low differentiated pulmonary adenocarcinoma. Surgical resection of intradural extramedullary metastasis improves patient quality of life by reducing pain intensity and neurological deficit.

Intramedullary spinal cord metastasis (IMSCM) is a rare entity which lacks well-defined treatment guidelines, yet sees rising incidence. We report a case of a 67-year-old man who presented with severe neck pain and numbness in his right fourth and fifth digits, and was found to have a C5-7 IMSCM of previously unknown lung adenocarcinoma. He underwent gross total resection of the IMSCM, afatinib, and radiation treatment. He had full reversal of his pain and sensory deficit, and remained ambulatory without any focal neurological deficit. Additionally, we conducted a literature review of original case series of IMSCM published between 1983 and 2016, representing 138 unique cases, and discuss various treatments with a focus on surgical resection and general treatment of stage IV lung adenocarcinoma. 18.75% of cases of IMSCM were an initial presentation of underlying malignancy. Rapidly progressive pain and weakness was the most common presentation, often compromising ambulatory status. Median survival ranged from 3.8 to 11.6 months after treatment in patients who were deceased at time of publication. Treatments included corticosteroids, chemotherapy, various radiotherapies, and surgical resection. Surgical resection was found to greatly improve symptoms and preserve ambulatory status, and was associated with increased survival time up to double that of non-surgical treatments. Most authors recommended surgical resection only in symptomatic patients with reversible deficits, to palliate symptoms and preserve ambulation. IMSCM can herald an underlying malignancy, and surgical resection can preserve ambulatory status and palliate symptoms as well increase survival time in a subset of patients.

A pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies is reported. A 63-year-old woman presented with an invasive ductal carcinoma of the breast and a lung adenocarcinoma. After multidisciplinary discussion, the patient underwent pulmonary left lower lobectomy followed by radio-chemotherapy with cisplatin and vinorelbine and started hormone therapy with letrozole. Ten months later, a left mastectomy with axillary lymph nodes dissection was performed. Histologically, a pathological complete response (pCR) was documented. With a review of the Literature, we discuss the issue of multiple primary malignancies, with its diagnostic and therapeutic implications. In cases of multiple synchronous malignancies it has been highlighted the importance of the choice of the best therapeutic approach for both the malignancies, reducing collateral individual effects.

The anaplastic lymphoma tyrosine kinase (ALK) gene was first described as a driver mutation in anaplastic non-Hodgkin\'s lymphoma. Dysregulated ALK expression is now an identified driver mutation in nearly twenty different human malignancies, including 4-9% of non-small cell lung cancers (NSCLC). The tyrosine kinase inhibitor crizotinib is more effective than standard chemotherapeutic agents in treating ALK positive NSCLC, making molecular diagnostic testing for dysregulated ALK expression a necessary step in identifying optimal treatment modalities. Here we review ALKmediated signal transduction pathways and compare the molecular protocols used to identify dysregulated ALK expression in NSCLC. We also discuss the use of crizotinib and second generation ALK tyrosine kinase inhibitors in the treatment of ALK positive NSCLC, and the known mechanisms of crizotinib resistance in NSCLC.