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[18F]FDG- PET/CT in Staging and Restaging of Fetal Type Adenocarcinoma of the Lung: A Case Report and a Review of the Literature
Address for correspondence: Dr. Pietro Bellini, Department of Nuclear Medicine, Spedali Civili di Brescia, P.le Spedali Civili, 1, Brescia 25123, Italy. E-mail: bellini.pietro@outlook.it
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Received: ,
Accepted: ,
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Fetal type adenocarcinoma (FTA) is a rare malignant tumor of the lung that histologically resembles an embryonic lung. Due to its rarity, no studies had investigated the possible role of the 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in the initial assessment and/or in the restaging of the disease yet. We present a case of a male patient with tongue carcinoma and incidental findings of well-differentiated FTA at [18F]FDG PET/CT. The patient was treated by specific therapy and also performed a subsequent [18F]FDG PET/CT scan that showed a significant reduction of the uptake on lung lesion. This case highlights the potential role and usefulness of PET imaging for staging and posttherapeutic restaging of well-differentiated FTA. The review of the available literature underlined the rarity of the disease since only seven reports were present. Anyway, a possible role of the [18F]FDG PET/CT in the staging of FTA is conceivable.
Keywords
18F-fluorodeoxyglucose positron emission tomography/computed tomography
fetal adenocarcinoma
review
Introduction
Fetal-type adenocarcinoma (FTA) is a rare malignant tumor of the lung that shares histological similarities with the embryonic lung.[1] Particularly, it exhibits a regression of the tissue observed in the pseudoglandular stage of development in embryos between 8 and 16 weeks old.
This disease typically presents in the fourth decade of life, and a high percentage of patients affected by this condition are smokers.[2] FTA can be divided into a well differentiated form (WDFTA), which presents aberrant cytoplasmic expression of β catenin, and a poorly differentiated form (PDFTA), with other types of genetical alteration, such as p53 overexpression. The prognosis is generally favorable in cases of well-differentiated disease, particularly when surgical resection is complete. The 5-year survival rate in such cases is approximately 80%.[3,4] Conversely, poorly differentiated diseases or neoplasms that are associated with specific mutations have a poor prognosis.[5,6] The use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in the management of other forms of lung tumors,[7] such as adenocarcinoma[8910] and squamous cell carcinoma,[11,12] is well established and documented in the literature.
This case study presents a patient with incidental findings of FTA at [18F]FDG PET/CT, which suggests the potential utility of hybrid imaging for staging and restaging of disease.
Case Report
A 55-years-old male with a diagnosis of squamous-cell carcinoma of the tongue performed a [18F]FDG PET/CT total-body scan acquired 60 min after 3.5 MBq/kg injection of 18F-FDG on a Discovery 690 tomograph (GE; Milwaukee, Wis; 64-slice CT, 100 mA, 120 kV; 2.5 min/bed; 256 matrix, 60-cm field of view), for the staging of disease.
[18F]FDG PET/CT images revealed an intense uptake of the tongue lesion with multiple nodal metastases. Furthermore, an incidental focal uptake on a 9 mm nodule localized in the apicoposterior segment of the upper lobe of the left lung was reported [Figure 1].
Subsequent cytological examination of the pulmonary lesion revealed the presence of synchronous WDFTA of the lung.
Otorhinolaryngoiatric surgery and radiotherapy on the tongue and the WDFTA lung lesions were subsequently performed.
A posttreatment [18F]FDG PET/CT scan was performed 1 year later on the same tomograph, with the same parameter, in the same patient for re-staging of diseases. The images exhibited the complete disappearance of the cervical uptakes and also demonstrated a reduction in size and a near-total eclipse of the uptake, with a residual minimal FDG activity, of a WDFTA lesion [Figure 2]. Two years after treatment the patient is still alive and disease-free.
Methods for Literature Review
A PubMed/Medline and Scopus databases research was performed. The algorithms used for the research of the paper were (“fetal”) AND (“type”) AND (“adenocarcinoma”) AND (“PET”), (“fetal”) AND (“type”) AND (“carcinoma”) AND (“PET”), (“fetal”) AND (“adenocarcinoma”) AND (“PET”), (“fetal”) AND (“carcinoma”) AND (“PET”), (“lung”) AND (“fetal”) AND (“adenocarcinoma”) AND (“PET”), and (“lung”) AND (“fetal”) AND (“carcinoma”) AND (“PET”).
Case reports, case series, original articles, and reviews published online up to July 22, 2024, were selected and reviewed. The reference list was defined based on the relevance of each paper to the scope of this review.
Results of the Literature Research
A total of 50 articles were extracted by the literature research. After the selection of the article, seven case reports were included in the review focusing in particular on staging and metabolic characterization of FTA[1,131415161718] [Figure 3]. Three of the articles[151617] were only available in the Japanese language, and only the abstracts were in English. However, due to the limited number of papers and the fact that the abstracts provided the essential information for the review, the cases were ultimately included. No case series, original articles, reviews, and/or other types of articles in the field of interest were found. No other papers were also found screening the references of all of the seven case reports selected.
In all of the papers included in the narrative review, an [18F]FDG PET/CT was performed for the staging of lung disease and characterization of a lung nodule.
The main information of the seven selected case reports was reported in the following Table 1. In addition, the case reports were divided based on the histological classification of the FTA into well-differentiated, moderately differentiated, and poorly differentiated.
| Firts author | Reference number | Year of publication | Country | Patient age | Patient sex | FTA type | PET result | SUVmax | Outcome - FU length |
|---|---|---|---|---|---|---|---|---|---|
| Hakiri | [1] | 2020 | Japan | 20 | Female | Well-differentiated | Positive | 7.1–8.4* | Disease-free – 1 year of FU |
| Paone | [13] | 2014 | Italy | 71 | Male | Moderate differentiated | Positive | 10.2 | Disease-free – 3 months of FU |
| Pasricha | [14] | 2015 | India | 58 | Female | Well-differentiated | Positive | ND | ND |
| Kanda | [15] | 2008 | Japan | 69 | Male | Poorly differentiated | Positive | 12.2 | Patient died 81 days after surgery |
| Kita | [16] | 2020 | Japan | 61 | Male | Poorly differentiated | Positive | 2.47 | Disease-free – 6 months of FU |
| Ito | [17] | 2018 | Japan | 53 | Male | Poorly differentiated | Positive | 5.68 | Disease-free – 9 months of FU |
| Paull | [18] | 2006 | USA | 47 | Female | Well-differentiated | Positive | ND | ND |
*7.1 in early PET acquisition, 8.4 in late acquisition. PET: Positron emission tomography, FU: Follow-up, FTA: Fetal type adenocarcinoma, SUVmax: Maximum standardized uptake value, NA: Not avaiable
Well-differentiated fetal adenocarcinoma
Hakiri et al., Pasricha et al., and Paull et al.[1,14,18] describe a high uptake of [18F]FDG in all cases of WDFTA. In particular, Hakiri et al. reported the case of a 20-year-old female patient with an incidental lung finding that had a final diagnosis of FTA and with a maximum standardized uptake value (SUVmax), respectively, of 7.1 in early and 8.4 in late imaging acquisitions. The patient did not wish to receive adjuvant therapy and no disease recrudescence was detected during the 1st year of follow-up. Unfortunately, Pasricha et al. and Paul et al. did not report the value of SUVmax in their cases, despite a high FDG uptake described in both cases, consistent with the diagnosis of lung malignancy.
It is worth to underline that none of the three cases of well-differentiated FTA presented underwent a [18F]FDG PET/CT after treatment.
Moderate differentiated fetal adenocarcinoma
The only report focusing on this histological subtype was developed by Paone et al.,[13] that described a case of moderate differentiated FTA with a synchronous mucinous adenocarcinoma that occurred in a 71-year-old man. The FTA presented a high [18F]FDG PET uptake with an SUVmax of 10.2. The patient underwent upper left lobectomy and was disease-free 3 months after surgical treatment. No further PET examinations were conducted following the lobectomy.
Poorly differentiated fetal adenocarcinoma
In their respective papers, Kanda et al., Ito et al., and Kita et al. described cases of PDFTA. First, in a case report by Kanda et al.,[15] a 69-year-old male patient presented with dyspnea and was diagnosed with carcinosarcoma with the epithelial component of a high-grade adenocarcinoma of fetal lung type. The disease exhibited a high [18F]FDG PET uptake, with an SUVmax of 12.2. The patient succumbed to the disease a few months after diagnosis and surgical treatment.
Ito et al.[17] presented a case of a 53-year-old male patient with a 28 mm PDFTA, exhibiting an SUVmax of 5.68 at [18F]FDG PET. The patient was treated with surgical resection and subsequent chemotherapy. The patient also did not experience disease relapse within the 9 months following the conclusion of therapy.
In contrast, Kita et al.[16] present a case of an 11 mm PDFTA that occurred in a 61-year-old male with only moderate glucose metabolism, as indicated by an SUVmax of 2.47. The patient was treated with surgical resection of the tumor and exhibited no recurrence 6 months after surgery.
Discussion
Traditional imaging plays an important role in the staging and assessment of response to therapy of lung cancer and also in the FTA of the lung. However, the limited evidence on the radiological features associated with this disease, due to its rarity and potential heterogeneity in presentation, has so far precluded a more in-depth investigation of this topic.[19202122] Particularly, as reported in a recent review,[21] FTA is usually detected and described incidentally on chest radiographs, in most cases followed by a subsequent computed tomography, but the diagnosis remains histological and is made after surgical resection and/or biopsy. The imaging examinations are usually performed in asymptomatic patients and/or with symptoms of bronchial irritation, such as chest pain, cough, and dyspnea.
In this setting, hybrid imaging with [18F]FDG PET/CT showed in some single cases reported its possible role for the initial assessment of the disease[1,131415161718] with a high FDG uptake in six cases, although in two of them the SUVmax was not reported, and a moderate but consistent uptake in one case. At least one other case of PDFTA with a concomitant papillary and lepidic adenocarcinoma in a 75-years-old male patient associated with high SUVmax on [18F]FDG PET/CT has recently been reported in the literature.[23] This case is not included in this review because it was not selected by the algorithms. Apparently, considering the limitation of the very small sample, the significant [18F]FDG uptake at PET examination is confirmed in WDFTA as in the PDFTA, despite the histological difference. No statistical analysis on SUVmax difference could be performed due to the only 5 data available.
The values of SUVmax reported suggest the presence of a high glucose metabolism by the FTA lesion. This finding could be explained by at least two distinct mechanisms. The first hypothesis regarding the cellular characteristics of FTA: fetal lung tissue expresses high levels of glucose transporter (GLUT) isoform 1[24] and this is thought to be the reason for its intense [18F]FDG uptake, similar to embryonic lung tissue. A similar mechanism due to the over-expression of specific GLUT isoform is described also in malignant lung cancer.[25] The second explanation regarding other cases represented by patients with PDFTA, who apparently often have other primary lung neoplasms associated with the disease: in this setting, a high SUVmax on [18F]FDG PET/CT could be partially justified by the presence of the concomitant tumor with high glucose metabolism.[11,21] In both cases, [18F]FDG PET/CT appears to be useful in staging FTA with a reasonable explanation of the mechanism of uptake.
For the same reason, the disappearance of intense glucose metabolism at [18F]FDG PET/CT in a known lesion histologically characterized after specific therapy could be considered as an expression of cellular death and consequently as a good response to therapy, such as in the case reported: in this setting none of the other cases reported in the literature described the performance of [18F]FDG PET/CT for the evaluation of the response to therapy, adding value to our finding.
The FTA represents only about 0.1%–0.5% of all lung tumors and the consequently small number of patients which developed the disease, as it is well shown by the only few cases found in the literature review, is obviously a limitation in the research: The case presented could be the only one reported in literature with a pre-and posttreatment assessment by [18F]FDG PET/CT and for that reason it represents an interesting cue for further studies underlining the possible role and usefulness of [18F]FDG PET/CT imaging for staging and restaging after therapy of WDFTA.
Conclusion
This case underlines the possible usefulness of [18F]FDG PET/CT imaging for the initial assessment of WDFTA as previously underlines by other case reports focusing in general on FTA. In addition, our case suggests that this technique could also be useful in evaluating the efficacy of therapeutic interventions.
Conflicts of interest
There are no conflicts of interest.
Nil.
References
- Well-differentiated fetal adenocarcinoma of the lung: Positron emission tomography features and diagnostic difficulties in frozen section analysis-a case report. Surg Case Rep. 2020;6:152.
- [Google Scholar]
- Fine needle aspiration cytology of pulmonary, well-differentiated fetal adenocarcinoma prepared by the ThinPrep method. Cytopathology. 2003;14:87-90.
- [Google Scholar]
- Clinical-pathologic conference in general thoracic surgery: Pulmonary blastoma. J Thorac Cardiovasc Surg. 2003;126:1247-50.
- [Google Scholar]
- Well differentiated fetal-type pulmonary adenocarcinoma: A tumour with a good prognosis. Rev Mal Respir. 2003;20:429-32.
- [Google Scholar]
- Novel genetic characteristics in low-grade fetal adenocarcinoma of the lung. Thorac Cancer. 2021;12:2789-95.
- [Google Scholar]
- Distinct properties of pure- and mixed-type high-grade fetal lung adenocarcinomas by genetic profiling and transcription factor expression. Virchows Arch. 2022;480:609-19.
- [Google Scholar]
- (18)F-fluorodeoxyglucose positron emission tomography-computed tomography interpretation criteria for the assessment of therapeutic response in patients with advanced stage of lung cancer: Inter-reader reliability, accuracy, and survival outcomes. Indian J Nucl Med. 2022;37:304-9.
- [Google Scholar]
- Prognostic role of baseline (18)F-FDG pet/CT in stage I and stage ii non-small cell lung cancer. Clin Imaging. 2023;94:71-8.
- [Google Scholar]
- Role of radiomics features and machine learning for the histological classification of stage I and stage II NSCLC at [(18)F]FDG PET/CT: A comparison between two PET/CT scanners. J Clin Med. 2022;12:255.
- [Google Scholar]
- Role of PET/CT in management of early lung adenocarcinoma. AJR Am J Roentgenol. 2020;214:437-45.
- [Google Scholar]
- Positron emission tomography/magnetic resonance imaging radiomics in predicting lung adenocarcinoma and squamous cell carcinoma. Front Oncol. 2022;12:803824.
- [Google Scholar]
- Diagnostic value of FDG PET-CT in differentiating lung adenocarcinoma from squamous cell carcinoma. EJNMMI Rep. 2024;8:1.
- [Google Scholar]
- A rare case of synchronous fetal type adenocarcinoma and mucinous adenocarcinoma of the lung evaluated by 18F-FDG PET/CT. Clin Nucl Med. 2014;39:e384-6.
- [Google Scholar]
- “Low-grade adenocarcinoma of fetal lung type: In an elderly non-smoker female” with aberrant β-catenin expression. Indian J Cancer. 2015;52:555-6.
- [Google Scholar]
- A case of giant pulmonary carcinosarcoma with the epithelial component of high-grade adenocarcinoma of fetal lung type (H-FLAC) Haigan. 2008;48:709-14.
- Experience with high-grade fetal lung adenocarcinoma;report of a case. Kyobu Geka. 2020;73:1125-7.
- [Google Scholar]
- Positron emission tomography in well differentiated fetal adenocarcinoma of the lung. Clin Nucl Med. 2006;31:213-4.
- [Google Scholar]
- Well-differentiated fetal adenocarcinoma of the lung: Early-phase sequential high-resolution computed tomographic findings. J Comput Assist Tomogr. 2008;32:806-9.
- [Google Scholar]
- Well differentiated fetal adenocarcinoma of the lung in a 38-year-old woman: Dynamic computed tomography findings. Jpn J Radiol. 2013;31:143-7.
- [Google Scholar]
- Comprehensive review of fetal adenocarcinoma of the lung. Lung Cancer (Auckl). 2018;9:57-63.
- [Google Scholar]
- Pure high-grade fetal adenocarcinoma of the lung: A case report. Surg Case Rep. 2018;4:70.
- [Google Scholar]
- A component of high-grade fetal lung adenocarcinoma diagnosed as the cause of lymph node metastasis. Thorac Cancer. 2024;15:1112-6.
- [Google Scholar]
- Glucose transporter expression in developing fetal lungs and lung neoplasms. Histol Histopathol. 1999;14:895-904.
- [Google Scholar]
- Correlation of GLUT-1 glucose transporter expression with [(18)F]FDG uptake in non-small cell lung cancer. Eur J Nucl Med. 2000;27:1778-85.
- [Google Scholar]