Sticking to basics pays even today: Diagnosis of adenocarcinoma lung on sputum examination in patient reluctant to undergo biopsy – Providing opportunity for targeted therapy for palliation if not early detection

Abstract

Sir, The value of sputum examination in early detection of lung cancer has been established by several workers. In clinical setting, studies have shown the sensitivity of sputum cytology for malignancy to be ∼60%, which also depends on the adequacy of sample, processing methodology and the number of sputum samples examined.[1] Sputum examination in malignancy patients not only helps in histopathological diagnosis but is being utilized for molecular testing also.[2] Bronchorrhea is defined as production of more than 100 mL of thin, mucoid sputum per day.[3] Most common causes include bronchiectasis and lung abscess and rarely mucinous adenocarcinoma. Formerly called as bronchoalveolar carcinoma, incidence of bronchorrhea in adenocarcinoma is estimated to be 6%.[4] We present a case of a 76-year-old gentleman, former smoker (5 pack years), with no prior comorbidities who presented in the outpatient department with complaints of cough with daily expectoration of more than 300 ml of dark-brown-colored sputum for the past 5 years and increased over the past 1 year. He also had significant weight loss (20 kg) in the past 1 year. The patient had to carry a bag with himself for such amount of expectoration which was also causing him social discomfort [Figure 1a]. Chest X-ray showed homogeneous opacity in the right lower zone. Computed tomography (CT) chest done 2 years ago showed mass in the right lower lobe (11 cm × 10.4 cm) with multiple nodules in the right upper and middle lobes, and subsequent scan after 8 months had similar findings with enlarged mediastinal and subcarinal lymph nodes [Figure 1b and c]. Fiber-optic bronchoscopy done after the first CT scan was nondiagnostic. Figure 1 (a) The amount of sputum production per day that the patient has collected in the bag. (b and c) Computed tomography picture showing multiple nodules’ mass with variegated appearance in the right middle and lower lobes, (d) sputum microscopic picture showing papillaroid and acinar arrangement of neoplastic cells with finely granular chromatin suggestive of adenocarcinoma The patient was advised CT-guided lung biopsy or endobronchial ultrasound (EBUS)-guided lymph node aspiration for definitive diagnosis and treatment, but the patient and his family deferred any invasive procedure despite consulting many chest physicians. The patient had a family history of lung cancer in his father and brother, who had a poor experience with the biopsy procedure and knew about dismal outcome of disease. The patient was seeking palliative care for his bronchorrhea and cough. As the patient was unwilling for lung biopsy, his sputum collected over a day (approximately 300 ml) was sent for malignant cell analysis. Sputum examination showed papillaroid and acinar arrangement of neoplastic cells with finely granular chromatin suggestive of adenocarcinoma [Figure 1d]. Sputum cell block was also made and was utilized for immunohistochemistry and mutation analysis. The epidermal growth factor receptor (EGFR) exon 19 mutation was detected positive in the analysis, and the patient was started on tyrosine kinase inhibitor (erlotinib). On treatment after 1 month, his sputum production reduced to <100 ml/day with overall improvement in quality of life. Sputum examination for malignant cells has been considered for early diagnosis in patients with suspected lung cancer in various studies.[5] It has been shown to detect premalignant changes in high-risk groups several years before a clinical diagnosis of lung cancer.[2] Studies showed that tumor cells can be detected by sputum cytology with a sensitivity of around 66%[6] and a wide variety of mutation analysis can be performed by various methods with variable success.[2] However, in today's era of newer diagnostic modalities, e.g., bronchoscopy, EBUS- or CT-guided biopsies, it is generally omitted from the workup of cases with lung cancer. In developed countries, the procurement of tumor biopsies/tumor cytology has replaced the use of sputum cytology as standard for lung cancer diagnosis.[6] This case demonstrated the utility of this basic noninvasive procedure as a diagnostic tool which is often forgotten and not practiced while investigating lung cancer. In our patient unwilling to undergo any invasive procedure, it emphasizes the role of a simple affordable noninvasive sputum test in providing valid sample for diagnosis, immunohistochemistry as well as mutation analysis. This forgotten basic tenet ultimately provided much-sought palliative care to this patient. Hence, it is best not to forget that basic sputum examination for malignant cells is not only for early detection of lung cancer in trials but should also be extended as means of investigations in suspected lung cancer, especially in resource-poor settings like ours.[7] Molecular tests on sputum performed in this case also highlight that targeted therapy can be offered even in such advanced cases. It has been shown in the study that targeted therapy is effective in improving bronchorrhea in adenocarcinoma patient.[8] In the eternal debate of “Tissue is an Issue,” simple sputum sample showed that basics must not be forgotten. Sputum specimen for analysis can either be collected spontaneously or induced. Usual practice is to give three consecutive day sample for evaluation to increase sensitivity.[9] However, our patient had bronchorrhea and 1-day sample (300 ml) was adequate enough for analysis. To the best of our knowledge, this is the first Indian case report utilizing sputum for diagnosis and mutation analysis in lung cancer for palliation therapy of the patient. With the use of sputum cytology and diagnosis of EGFR adenocarcinoma, the patient was started on erlotinib with significant improvement of bronchorrhea. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.