Aerogenous Metastases: A Potential Game Changer in the Diagnosis and Management of Primary Lung Adenocarcinoma

Gaikwad, Anand; Souza, Carolina A.; Inácio, J.; Gupta, Ashish; Sekhon, Harmanjatinder S.; Seely, Jean M.; Dennie, Carole; Gomes, Marcio M.

doi:10.2214/ajr.13.12088

Cited by 54 publications

(53 citation statements)

References 84 publications

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“…The preoperative clinical features of the present case included prominent bronchorrhea and multicentric and centrilobular GGOs with a pneumonic presentation on chest CT, very similar to the typical features of IMAs, 1-4 but unexpectedly, the resected specimen showed histopathological characteristics of non-mucinous LPAs with significant aerogenous spread that was considered to be a quite unusual finding. In general, typical IMAs frequently present with aerogenous spread, recognized as multicentric and centrilobular GGOs on CT, 1-4 while typical non-mucinous LPAs barely show aerogenous spread, especially to the extensive degree seen in the present case.…”

Section: Discussionsupporting

confidence: 63%

“…In general, typical IMAs frequently present with aerogenous spread, recognized as multicentric and centrilobular GGOs on CT, 1-4 while typical non-mucinous LPAs barely show aerogenous spread, especially to the extensive degree seen in the present case. 3 In the current case, innumerable disrupted lepidic or papillary growth lesions consisting of Clara type tumor cells with identical morphology to that of the main tumor were confirmed to be aerogenous spread reflecting the multicentric GGOs on CT.…”

Section: Discussionmentioning

confidence: 40%

“…1-4 IMAs also present with ground glass opacities (GGOs) with ill-defined margins and infiltrative shadows within (so-called pneumonic presentation) , which originate from mucin filling the alveoli. 3,4 …”

Section: Introductionmentioning

confidence: 99%

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Non-Mucinous Lepidic Predominant Adenocarcinoma Presenting with Extensive Aerogenous Spread

et al. 2016

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An extremely rare case of non-mucinous lepidic-predominant invasive adenocarcinoma (LPA) showing extensive aerogenous spread with a pneumonic presentation is reported. A 73-year-old woman was referred to our hospital because of an infiltrative shadow on chest xray. Chest computed tomography revealed extensive ground glass opacities in the right lower lobe, which was accompanied by infiltrative shadow with a pneumonic presentation. Invasive mucinous adenocarcinoma was presumed, and a partial resection of the right lower lobe was done. Histopathological examination revealed lepidic growth-predominant invasive adenocarcinoma with Clara type tumor cells, and there were innumerable aerogenous metastases also consisting of Clara cells. Because Alcian Blue and periodic acid-Schiff staining disclosed no mucus, the tumor was diagnosed as a non-mucinous LPA. The patient showed a poor response to 5 courses of pemetrexed, and she died one year after the diagnosis due to cancer progression. Nonmucinous LPA showed a rare presentation characterized by extensive aerogenous spread followed by a poor prognosis.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 40%

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Non-Mucinous Lepidic Predominant Adenocarcinoma Presenting with Extensive Aerogenous Spread

et al. 2016

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“…However, in case of patients with short DFI/or lung comorbidities, when concomitant signs of potential NSCLC aggressiveness are present, such as the spreading of tumor cells through the bronchial tree, both indication and surgical resection extension might be questionable. Indeed, aerogenous tumor spread is an acknowledged negative prognostic factor gaining increasing attention in recent years . Under these circumstances, we believe that indication for surgery should be carefully discussed by a multidisciplinary team and tailored to the individual patient.…”

Section: Commentmentioning

confidence: 99%

Lymphadenectomy during pulmonary metastasectomy: Impact on survival and recurrence

Londero

Morelli

Parise

et al. 2019

Journal of Surgical Oncology

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Background and Objectives: Lymphadenectomy during pulmonary metastasectomy (PM) is widely carried out. We assessed the potential benefit on patient survival and tumor recurrence of this practice. Methods: One hundred eighty‐one patients undergoing a first PM were studied. Eighty‐six patients (47.5%) underwent lymphadenectomy (L+ group) whereas 95 (52.5%) did not undergo nodal harvesting (L−group). Main outcomes were overall survival (OS) and disease‐free survival (DFS). Median follow‐up was 25 months (interquartile range [IQR], 13‐49). Results: At follow‐up 84 patients (46.4%) died, whereas 97 (53.6%) were still alive with recurrence in 78 patients (43%). There was no difference in 5‐year survival (L+ 30.0% vs L− 43.2%; P = .87) or in the 5‐year cumulative incidence of recurrence (L + 63.2% vs L−80%; P = .07) between the two groups. Multivariable analysis indicated that disease‐free interval (DFI) less than 29 months (P < .001) and lung comorbidities (P = .003) were significant predictors of death. Metastases from non‐small–cell lung cancer increased the risk of lung comorbidities by a factor of 19.8, whereas the risk of DFI less than 29 months was increased nearly 11‐fold. Competing risk regression identified multiple metastases (P = .004), head/neck primary tumor (P = .009), and age less than 67 years (P = .024) as independent risk factors for recurrence. Conclusion: Associated lymphadenectomy showed not to give any additional advantage in terms of survival and recurrence after PM.

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“…Despite exhibiting different histological subtypes, L4 and L6 had 28 non-silent mutations in common. Given the absence of metastatic disease in local lymph nodes, it is possible that progenitor tumor cells underwent aerogenous metastasis, which is a discontinuous spread of cancer cells from the primary tumor through the airways to adjacent or distant lung parenchyma [15]. Furthermore, although L1-L3 were in different lobes of the patient's right lung, they shared three nonsynonymous mutations, including KRAS G12C.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive genomic profiling aids in understanding the lesion origins of a patient with six synchronous invasive lung adenocarcinomas: a case study

Song

Jia

et al. 2020

BMC Pulm Med

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Background: Synchronous multiple primary lung cancers (sMPLC) are rare forms of lung cancer, and their diagnosis remains as a significant challenge. Distinguishing sMPLC from advanced disease is important as their prognoses and therapeutic management vary dramatically. Case presentation: The patient was a 56-year-old Chinese male who exhibited six synchronous invasive adenocarcinomas at diagnosis [T2(6)N0M0], and who achieved durable clinical benefit under adjuvant chemotherapy for 41 months following wedge resection and lobectomy. Whole-exome sequencing revealed that two lesions (L4 and L6) in the left upper lobe of the patient's lung shared 28 nonsynonymous mutations; thus, suggesting that the lesions may have arisen from a common ancestor at the early stages of tumorigenesis, and spread into distinct histologic subtypes. Moreover, while L5 was in the same lobe as L4 and L6, it represented a distinct lineage as it did not share any mutations with other lesions. Notably, the BRAF V600E oncogenic mutation was exclusive to L5. In addition, the KRAS G12C mutation was identified in three lesions (L1-L3) located in the right lung, which may have resulted from convergent evolution. Conclusion: We report a patient with six synchronous invasive adenocarcinomas who demonstrated durable clinical benefits under adjuvant chemotherapy following surgical treatment. While cancer staging is one of the many challenges associated with sMPLC, the data generated through next-generation sequencing can provide information on lesion origins, and thus, advance the era of precision medicine.

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Aerogenous Metastases: A Potential Game Changer in the Diagnosis and Management of Primary Lung Adenocarcinoma

Cited by 54 publications

References 84 publications

Non-Mucinous Lepidic Predominant Adenocarcinoma Presenting with Extensive Aerogenous Spread

Non-Mucinous Lepidic Predominant Adenocarcinoma Presenting with Extensive Aerogenous Spread

Lymphadenectomy during pulmonary metastasectomy: Impact on survival and recurrence

Comprehensive genomic profiling aids in understanding the lesion origins of a patient with six synchronous invasive lung adenocarcinomas: a case study

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