A rare case of lung adenocarcinoma: Unusual presentation with miliary mottling.

INTRODUCTION

Miliary mottling on chest X-ray is a well-known entity, usually associated with infectious etiologies such as tuberculosis, histoplasmosis, mycoplasma, nocardia, and blastomycosis. There may also be immune and inflammatory disorders such as sarcoidosis, tropical pulmonary eosinophilia, and hypersensitivity pneumonitis. Noninfectious causes include pneumoconioses such as silicosis and pulmonary hemosiderosis.[12] Rarely, there may be a malignant cause of miliary mottling like hematogenous metastases from carcinoma of the thyroid and kidney or lymphangitic carcinomatosis and may even be primary lung cancer.[3] However, the suspicion of malignancy for patients with miliary mottling remains low, especially in a developing country like India, where tuberculosis is the most common cause. Here is a similar case of a young woman with miliary lung nodules diagnosed as adenocarcinoma of the lung.

CASE REPORT

A 37-year-old female previously healthy, nonsmoker, presented to a primary physician with a history of cough and chest pain of month duration. She was evaluated and started on oral antibiotics with no response to therapy over 2 weeks. On further evaluation, chest X-ray was suggestive of miliary mottling, and sputum was negative for acid-fast bacilli. The patient was subsequently put on empirical antituberculosis therapy. The patient over the next 2 weeks had persistent symptoms and was further evaluated where computed tomography (CT) scan of the chest revealed a left lung lesion with bony and lymph node involvements with bilateral miliary lung nodules and left pleural and pericardial effusion [Figure 1]. However, a CT-guided biopsy revealed a pathological diagnosis of non-small cell lung carcinoma, morphologically favoring adenocarcinoma (solid, micropapillary, and acinar pattern) [Figure 2]. Subsequently, on further workup, immunohistochemistry showed positivity for thyroid transcription factor 1. Mutational analysis revealed no epidermal growth factor receptor mutation, or rearrangement anaplastic lymphoma kinase, ROS, and MET were wild type. The patient was started on pemetrexed (500 mg/m2) plus carboplatin (area under the curve: 5) (every 3 weeks)-based palliative chemotherapy. The patient had a progressive disease after three cycles of chemotherapy and was subsequently started on second-line docetaxel (75 mg/m2) and nintedanib (200 mg twice a day) (every 3 weeks)-based palliative chemotherapy. After 6 cycles, the patient had a clinical response as well as partial response as per the PERCIST criteria on re-evaluation with positron emission tomography–CT scan. However, after 1 month, the patient presented with altered behavior, and imaging revealed rapidly progressive disease in the lung and the mediastinum compared to previous imaging. Brain magnetic resonance imaging (MRI) revealed miliary dissemination in the brain [Figure 3]. The patient refused further treatment and opted for best supportive care. She succumbed to the disease, about after 11 months of initiating treatment.

Figure 1

Computed tomography chest: Suggestive of bilateral miliary lung nodules and left pleural and pericardial effusion

Figure 2

Slide of Lung core shows tumor tissue arranged predominantly in acinar, micropapillary pattern and solid sheets.

Figure 3

Brain magnetic resonance imaging: Revealed miliary dissemination in the brain parenchyma

DISCUSSION

Lung cancer was traditionally a disease of old smoker men; however, recently, the trend is shifting to young nonsmoker women, particularly in Asia.[3] The common radiological presentation includes a lung mass with associated metastasis. However, presentation as a miliary mottling on chest X-ray and miliary brain metastases (also known as carcinomatous encephalitis) is atypical and rarely reported.[45] Miliary brain metastases are an extremely rare form of brain metastasis characterized by the presence of tumor spreading into the perivascular Virchow–Robin spaces, parenchyma, and meninges. Generally seen as an advanced stage of the primary disease, this form of dissemination arises most often from lung adenocarcinoma[567] typically detected by MRI examinations.

In the present case, a female nonsmoker patient with tested driver mutation-negative lung adenocarcinoma developed miliary brain metastases involving gray matter, while on therapy. Lung adenocarcinomas with miliary metastases are usually unresponsive to the platinum-based therapy. We initially treated the patient with pemetrexed-based therapy to which she failed to respond and progressed. To best of our knowledge, this is the first case of lung adenocarcinomas with miliary metastases treated with docetaxel and nintedanib. It appears that our patients benefited from nintedanib therapy, as she showed a partial response with a 5-month progression-free survival following its introduction.

The clinical, radiological, and pathological features of miliary metastatic tumors have not been defined yet.[5] Clinical manifestations of patients with miliary brain metastases are usually silent and differ from patient to patient[7] and may show an atypical clinical course and atypical symptoms. The authors reported convulsion, hemiparesis, memory disturbance, psychiatric symptoms and disorientation as primary symptoms of miliary brain metastasis.[6] The practice of starting empirical ATT for patients with miliary mottling on imaging delays the actual cancer treatment.

Few cases of miliary primary lung carcinoma with miliary brain metastasis are reported in the literature.[3458] Owing to its rarity, clinicians should be vigilant about the possibility of miliary mottling on chest X-ray to be malignant.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.