Multifocal adenocarcinoma of the lung - EGFR-mutated
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At the time the case was submitted for publication Bruno Di Muzio had no recorded disclosures.View Bruno Di Muzio's current disclosures
50 year old female Asian presents with hemoptysis. Non-smoker.
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Multiple bilateral focal ground glass and solid lesions, a few of them with cavitation. Left upper lobe collapse. Left-sided pleural effusion. No lymphadenopathy by size criteria. Thyroid nodules. Aortic arch anomaly.
Macroscopy: Bronchoalveolar lavage - 5ml of blood-stained fluid. Cellblock prepared.
Microscopy: The prepared smears are cellular and contain low numbers of a predominantly dispersed population of atypical cells which possess enlarged hyperchromatic nuclei with irregular nuclear contours and variably prominent nucleoli. Binucleate forms are frequently observed. The cells possess a moderate amount of cytoplasm which is occasionally granular with fine vacuolisation. Occasional atypical cohesive clusters are seen, but there is no gland formation identified. There is no keratin identified. Unequivocal pigment is not identified. Pulmonary macrophages and the bronchial epithelium are seen in the background and no fungi identified. There is no acute inflammation or granulomatous inflammation identified. Small numbers of benign squamous cells are also present.
Very small numbers of atypical cells are present in the cell block demonstrating a similar morphology and may be insufficient for adequate assessment by immunohistochemistry which is being attempted. A separate report will be issued if contributory.
Conclusion: Bronchoalveolar lavage: Suspicious for malignancy; see comment below.
Comment: Small numbers of atypical cells are identified which are suspicious for malignancy. Limited material is present in the cell block which may be insufficient for further assessment. Immunohistochemistry is being attempted and a supplementary report will be issued if contributory.
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There is intense FDG activity corresponding to an irregular soft tissue density in the left upper lobe that extends from the left hilum to the level of the manubrium. The mass measures 60 x 20 x35mm. FDG uptake in the mass is heterogeneous, particularly anteriorly, suggesting a central tumor with post obstructive atelectasis. A number of smaller FDG avid satellite lesions are present, the largest in the inferior lingula.
The left hilum is markedly FDG avid consistent with hilar nodal involvement. There is FDG avid interstitial thickening extending away from the hilum concerning for lymphangitis carcinomatosis. Enlarged AP window nodes are not FDG avid. No axillary or supraclavicular nodes identified.
At least 7 right-sided nodules and one right upper lobe mass, measuring 30mm, show variable FDG uptake depending on size. They are consistent with contralateral metastases.
There is a large left pleural effusion that demonstrates faint peripheral FDG avidity suspicious for malignant effusion. This has increased in size since external CT-chest.
There are several intensely FDG avid bony lesions consistent with metastases. A C5 vertebral body lesion that extends anteriorly into soft tissues demonstrates cortical thinning and erosion and is at risk of pathological fracture. Further bony metastases demonstrated in the left lateral 11th rib and right L4 pedicle. Mildly increased FDG activity associated with linear sclerotic change in the left 9th and 10th ribs may also reflect metastases in this clinical picture however may also reflect old fractures.
No metabolically active solid organ metastases are demonstrated.
A right 11mm hypodense thyroid lesion that is mildly FDG avid is suspicious for thyroid malignancy/adenoma.
Asymmetric FDG activity associated with vocal cords (right > left) is probably physiologic.
Conclusion: 1. Over-all the findings are best explained by a primary right-left upper lobe lung primary with metastases to contralateral lung and bone. The primary lesion should be amenable to percutaneous biopsy targeting most FDG avid component.
2. C5 metastases may warrant more urgent direct therapy as is at risk for pathological fracture.
2. Progressive increase in the left pleural effusion since prior imaging with partial left lower lobe collapse.
3. Thyroid nodule, mildly FDG avid, suspicious for thyroid malignancy/adenoma. Ultrasound +/- histopathological could be considered.
4. Asymmetric FDG Activity in vocal cords (right > left) of uncertain etiology, likely related to left recurrent laryngeal nerve infiltration and left palsy.
CT-guided lung biopsy performed:
Macroscopy: Labeled with patient details only. Two core biopsies 6mm & 18mm.
Microscopy: Both cores show a malignant tumor, with a small amount of alveolated lung tissue. The tumor is in the form of fused glandular arrangements surrounded by a fibroblastic stromal response. Tumor cells have moderately to markedly pleomorphic nuclei with prominent nucleoli and a moderate amount of cytoplasm. The features are of pulmonary adenocarcinoma, acinar pattern.
Conclusion: Lung core biopsy: Adenocarcinoma.
The L858R mutation results in an amino acid substitution at position 858 in EGFR, from a leucine (L) to an arginine (R). This mutation occurs within exon 21, which encodes part of the kinase domain, and occurs with a frequency of approximately 43% in EGFR-mutated lung tumors (Mitsudomi and Yatabe 2010).
Multiple EGFR tyrosine kinase inhibitors (TKIs) have been developed or are in development conferring increased sensitivity.
There is currently no role for EGFR mutation in predicting response in NSCLC
Conclusion: Mutation detected - EGFR c.2573T>G p.Leu858Arg (L858R)
This case illustrates multifocal adenocarcinoma with widespread metastases and EGFR mutation. As in this patient, this presentation is commonly seen in the East Asian population and non-smokers.
Stage 4 disease - managed with osimertinib and radiotherapy for the spinal lesion.
- 1. O'Neill AC, Jagannathan JP, Ramaiya NH. Evolving Cancer Classification in the Era of Personalized Medicine: A Primer for Radiologists. (2017) Korean journal of radiology. 18 (1): 6-17. doi:10.3348/kjr.2017.18.1.6 - Pubmed