Lung colloid adenocarcinoma: A multidisciplinary diagnostic challenge

Abstract

Colloid adenocarcinoma of the lung is a rare subtype, often difficult to diagnose due to its indolent behavior and atypical imaging. We report a 76-year-old man and former smoker with an incidentally detected right lower lobe mass. Computed tomography (CT) showed a well-defined, lobulated lesion with poor contrast enhancement and internal calcifications and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) demonstrated low uptake. Multiple percutaneous and surgical biopsies were nondiagnostic. Progressive growth and new onset of mediastinal lymphadenopathy ultimately led to right lower lobectomy, confirming stage IIIA colloid adenocarcinoma. This case highlights imaging limitations, the value of sequential biopsies, and the role of surgical biopsy when less invasive methods repeatedly fail, especially with high clinical suspicion.

Introduction

Primary pulmonary colloid adenocarcinoma is a rare entity, with limited cases reported in the literature. It is a subtype of lung adenocarcinoma characterized by abundant extracellular mucin pools and scant malignant epithelium [1]. Although it generally demonstrates an indolent clinical course, metastatic spread may occur [2]. The tumor frequently presents with nonspecific clinical and radiological findings, making preoperative diagnosis challenging and often requiring histopathological and immunohistochemical evaluation for accurate characterization [1,2].

This report aims to describe a case of primary pulmonary colloid adenocarcinoma with a challenging preoperative diagnosis and to highlight the importance of radiological-pathological correlation and multidisciplinary evaluation in establishing the diagnosis.

Case presentation

A 76-year-old asymptomatic man, former ceramic industry worker with a history of heavy smoking, was referred to the Pulmonology outpatient clinic for further evaluation of a right lower lung mass identified on chest radiography performed due to his risk for lung cancer. He had a 100 pack-year smoking history and quit smoking 15 years ago. His medical history also included type 2 diabetes mellitus, and coronary artery disease. Pulmonary function testing demonstrated preserved spirometry, without significant obstructive or restrictive ventilatory defect, with mildly reduced diffusing capacity for carbon monoxide (67% of predicted value).

A thoracic contrast-enhanced computed tomography (CT) scan revealed a well-defined mass measuring approximately 6 × 4 cm, with smooth margins and lobulated contours, located in the right lower lobe. On noncontrast images, the lesion demonstrated fluid attenuation (approximately 20 Hounsfield units), with small internal calcifications and no enhancement after contrast administration. Associated perilesional pleural thickening and fibrosis were noted, without mediastinal or hilar lymphadenopathy or pleural effusion.

For further characterization of the mass, an ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) scan was performed, revealing mild uptake within the lesion, with a maximum standardized uptake value (SUV_max) of 1.4. Figs. 1 and 2 illustrate the imaging characteristics of the lesion on CT and ¹⁸F-FDG PET/CT, respectively.

Fig. 1.

Initial CT imaging of colloid adenocarcinoma. Coronal (A) and axial (B) thoracic CT in the lung window, axial noncontrast CT (C), and axial contrast-enhanced CT (D). (A, B) A peripheral, well-defined lobulated mass (*) is seen in the posterior segment of the right lower lobe, abutting the pleura (orange arrows), with adjacent fibrotic strands (blue arrows). (C) On noncontrast CT, the lesion demonstrates fluid attenuation, with a mean attenuation value (M) of 21 Hounsfield units (HU) and (D) Following contrast administration, attenuation remains essentially unchanged, with a mean attenuation value (M) of 23 HU, indicating minimal contrast enhancement.

Fig. 2.

Axial contrast CT (A) and axial ¹⁸F-FDG PET/CT fusion image (B) of the right lower lobe lesion (asterisk). On CT, the lesion demonstrates small peripheral punctate calcifications (orange arrows). On ¹⁸F-FDG PET/CT, no significant radiotracer uptake is identified within the lesion.

Percutaneous biopsy under CT guidance failed to yield representative tissue of the lesion. Subsequently, surgical biopsy via video-assisted thoracoscopic surgery (VATS) demonstrated pulmonary ossification with associated inflammatory changes, including lymphoplasmacytic infiltrates and focal areas of organizing pneumonia, but without a definitive diagnosis of malignancy. Given the discrepancy between the VATS biopsy findings and the radiological features, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was also performed, obtaining 4 tissue fragments that showed sinus ectasia and sinus histiocytosis, without evidence of metastatic disease.

According to pathological findings from VATS biopsy and EBUS-TBNA, a multidisciplinary team decision was made to proceed with clinical and radiologic surveillance, with chest CT and ¹⁸F-FDG PET/CT scans performed every 6 months.

After 1 year of follow-up, CT demonstrated progressive enlargement of the lesion, measuring 8 × 6 cm, along with new onset of mediastinal and hilar lymphadenopathy (Fig. 3). On ¹⁸F-FDG PET/CT, the lesion showed increased peripheral radiotracer uptake, reaching a SUV_max of 8.8, with central photopenia, as illustrated in Fig. 4. The lymph nodes identified on CT also demonstrated abnormal radiotracer uptake, with SUV_max values ranging from 2.2 to 3.9, consistent with nodal tumor involvement. The patient underwent right lower lobectomy with mediastinal lymphadenectomy. Gross examination revealed a cavitated mass measuring 9.5 × 6 × 4.5 cm, filled with translucent gelatinous material. Microscopically, extensive pools of extracellular mucin lined by columnar epithelial cells with mild atypia were observed. Immunohistochemistry showed positivity for CK7 and CDX2 and negativity for CK20 and TTF-1. Although CDX2 expression may raise suspicion for a gastrointestinal primary tumor, the immunophenotypic profile, together with the exclusion of a gastrointestinal malignancy by upper gastrointestinal endoscopy and colonoscopy, supported the diagnosis of primary pulmonary colloid adenocarcinoma. One of 3 hilar lymph nodes showed metastatic involvement, while mediastinal nodes were negative. Resection margins were clear, although adjacent adipose tissue was invaded. Staging ¹⁸F-FDG-PET/CT showed no abnormal uptake suggestive of distant metastatic disease, and the final pathological staging was pT4 N1 M0 (stage IIIA).

Fig. 3.

Axial noncontrast CT (A) and axial contrast-enhanced CT (B) of the right lower lobe lesion. Following contrast administration, the lesion demonstrates mild peripheral enhancement (orange arrows), with central cystic areas separated by thin internal septa (*).

Fig. 4.

Follow-up imaging after 1 year. (A) Axial contrast-enhanced CT demonstrates an enlarged subcarinal mediastinal lymph node (orange circle), measuring 12 mm in short-axis diameter. (B) ¹⁸F-FDG PET/CT demonstrates metabolic activity within the subcarinal lymph node (orange circle), consistent with nodal involvement. (C) Additional hilar lymph nodes also demonstrate increased ¹⁸F-FDG uptake (orange arrows) and (D) The right lower lobe lesion demonstrates peripheral hypermetabolic uptake, visualized in red, with relative absence of central uptake, corresponding to the peripheral enhancement pattern observed in figure 3.

Following multidisciplinary discussion, adjuvant chemotherapy with carboplatin and vinorelbine was initiated but discontinued after 1 cycle due to grade 2 anemia requiring transfusion and intravenous ferric carboxymaltose. At that time, the patient had an ECOG performance status of 3 and was referred to palliative care, dying 9 months later.

Discussion

Colloid adenocarcinoma of the lung is a rare subtype of adenocarcinoma recognized in the 2021 World Health Organization classification of lung tumors, accounting for approximately 0.24% of all lung cancers [2,3].

According to the literature, colloid adenocarcinoma may present in asymptomatic patients and is often detected incidentally [4]. In the present case, the patient was asymptomatic, and the lesion was identified as an incidental finding within the context of lung cancer screening on chest radiography, given his smoking history [4]. The mean age at presentation is 66 years, with a range of 54-74 years [4].

On imaging, colloid adenocarcinoma of the lung may appear as a solitary nodule or mass with lobulated contours and well-defined margins, usually located in the peripheral lung [1,4]. On CT scans, previous reports have described low attenuation values and poor enhancement after contrast administration [4]. The tumor is often associated with surrounding areas of mosaic low attenuation and linear bands, corresponding histologically to emphysema, bronchiolization, or fibrosis [4]. These lesions typically present as large masses, with reported diameters ranging from 10 to 80 mm [3,4]. Interestingly, stippled tumor calcifications have been reported in some cases, as observed in ours [4].

Additionally, previous PET/CT findings suggest that FDG uptake in colloid adenocarcinoma is typically low [4]. Reported mean SUV_max values are approximately 3.8, ranging from 1.2 to 8.6, while other series have described scant intratumoral FDG uptake and metabolic activity, with SUV_max values ranging from 1.5 to 4.5 [3,4]. In our patient, ¹⁸F-FDG PET/CT demonstrated low radiotracer uptake, consistent with findings reported in other clinical cases.

Histologically, colloid adenocarcinoma is characterized by the presence of scant neoplastic epithelium and abundant extracellular mucin within the alveolar spaces, leading to alveolar distension and destruction of the alveolar walls [1,4].

Immunohistochemically, colloid adenocarcinoma frequently shows tumor cell positivity for CK7, CK20, and CDX2, with negative expression of TTF-1 [5]. Differentiation of colloid adenocarcinoma from extrapulmonary mucinous metastases relies on characteristic histological features, including extensive mucin pools with alveolar wall destruction involving at least 50% of the tumor. Clinical history and imaging are often required due to overlapping immunohistochemical profiles [1,5]. In the present case, exclusion of a gastrointestinal primary by endoscopic examination and the presence of abundant extracellular mucin pools disrupting alveolar architecture, in association with diffuse CK7 positivity, were consistent with primary pulmonary colloid adenocarcinoma.

Surgical resection represents the preferred treatment strategy for primary pulmonary colloid adenocarcinoma, as it enables a definitive histological diagnosis and offers therapeutic benefits [1,3]. Although uncommon, this tumor has been associated with a reported 5-year survival rate of 51% following surgical management [3].

In the literature, Kim et al. [3] described a case in which preoperative biopsy, including transbronchial lung biopsy, was nondiagnostic. Similarly, in our case, no definitive diagnosis was obtained from the preoperative biopsies. The low ¹⁸FDG uptake, along with CT follow-up, reflects the tumor’s low metabolic activity and indolent behavior [3]. However, lymph node metastasis can still occur, as reported by Kim et al. [3], leading to advanced staging and the need for systemic therapies with higher morbidity, as in our patient.

This case highlights the importance of multidisciplinary team discussion in rare pulmonary malignancies with challenging preoperative diagnosis, particularly when radiological and histopathological findings are discordant. Integration of radiological, pathological, and clinical data through a multidisciplinary approach may be particularly valuable in determining alternative diagnostic strategies and supporting appropriate clinical management [6]. Although causality cannot be inferred from a single case, this report raises the possibility that earlier intervention might limit nodal spread and improve survival outcomes; however, further investigation and analysis of additional cases are required.

Conclusion

This case highlights the limitations of minimally invasive biopsy techniques in diagnosing primary pulmonary colloid adenocarcinoma, underscores the need for further research to improve diagnostic strategies, and emphasizes that surgical resection may be necessary for definitive diagnosis and management when clinical suspicion remains high.

Author contributions

M. Antónia Góis Serrano: conceptualization, writing – original draft. Marta Maia: data curation, resources. Cristina Ferreira: supervision, writing - review, and editing. Idílio Gomes: supervision, writing - review, and editing.

Declaration of generative AI and AI-assisted technologies in the manuscript preparation process

During the preparation of this work the author(s) used ChatGPT (OpenAI) in order to improve language quality and assist with grammar, wording, and manuscript editing. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the published article.

Patient consent

Written informed consent was obtained from the patient for publication of this case report and the accompanying images.