|Year : 2020 | Volume
| Issue : 1 | Page : 97-99
Large cell neuroendocrine tumor of the lung: A diagnostic challenge
Jayasri Helen Gali, Harsha Vardhana Varma
Department of Pulmonology, Apollo Institute of Medical Sciences and Research, Hyderabad, Telangana, India
|Date of Submission||28-Feb-2019|
|Date of Decision||14-May-2019|
|Date of Acceptance||20-May-2019|
|Date of Web Publication||08-Jan-2020|
Dr. Harsha Vardhana Varma
Department of Pulmonology, Apollo Institute of Medical Sciences and Research, Jubilee Hills, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
Lung neuroendocrine carcinoma (NEC) is a rare heterogeneous carcinoma with NE cells in the pulmonary and bronchial epithelium as the site of origin. We describe a case of large cell NEC (LCNEC) in a 55-year-old male, smoker with 25 pack-years, who presented with cough, dyspnea, hemoptysis, and loss of appetite for 6 months. There was no diabetes, hypertension, asthma, chronic obstructive pulmonary disease, tuberculosis, or contact with tuberculosis or malignancy. The presence of a large homogenous mass lesion in the right chest on chest X-ray, further clearly defined on chest computed tomography scan (130/94/123 mm) was suggestive of huge mass. There was no mediastinal or pleural involvement. Possibility of LCNEC was suspected as the ultrasound-guided biopsy was indicating the presence of poorly differentiated carcinoma. Immunohistochemistry was negative for thyroid transcription factor, cytokeratin 7 but was positive for synaptophysin and P40, suggestive of high-grade LCNECs. It was in T4N0M0, stage 3A and treatment with combination chemotherapy was initiated.
Keywords: Immunohistochemistry, large cell neuroendocrine tumor, lung neuroendocrine tumor
|How to cite this article:|
Gali JH, Varma HV. Large cell neuroendocrine tumor of the lung: A diagnostic challenge. Indian J Respir Care 2020;9:97-9
| Introduction|| |
Lung neuroendocrine carcinoma (NEC) is a rare heterogeneous carcinoma with NE cells in the pulmonary and bronchial epithelium as the site of origin, accounting for 20% of all lung cancers. It is estimated that ≈3% of NECs are large cell NECs (LCNECs). Awareness regarding lung NECs is low among medical fraternity. We present a case of LCNEC of the lung that was initially unsuspected and undiagnosed.
| Case Report|| |
A 55-year-old gentleman, driver, presented with cough, dyspnea, hemoptysis, and loss of appetite for 6 months. Cough was productive with white mucoid scanty sputum and occasional streaky hemoptysis. Dyspnea was gradual in onset, progressive, Grade 2 on modified Medical Research Council dyspnea scale, not associated with wheeze and aggravated on lying on the left lateral position. He had loss of appetite (2 months) and weight loss (3–4 kg in the last 1 month); there was no chest pain. There was no past/present history of contact with tuberculosis. He was a smoker with 25 pack-years and consumed alcohol occasionally. He had no history of chronic systemic diseases (diabetes, hypertension) or other respiratory illness (asthma, chronic obstructive pulmonary disease, and malignancy). There was no family history of tuberculosis or malignancy. He was evaluated as an inpatient for about 20 days in a private hospital; a large homogenous mass in the right chest [Figure 1] was noted on chest X-ray (CXR), which was further clearly defined on chest computed tomography scan (CT scan). It measured about 130/94/123 mm without any mediastinal or pleural involvement [Figure 2] and [Figure 3]. Fiberoptic bronchoscopy was normal, and the bronchoalveolar lavage was negative for malignant cells; Gram stain, and culture and sensitivity, smear for acid-fast bacilli and Cartridge-Based Nucleic Acid Amplification Test were negative. As there was no evidence of tuberculosis or malignancy, he received symptomatic treatment. He consulted us for the second opinion as the symptoms persisted.
|Figure 1: Chest X-ray – posterior-anterior view – large homogenous mass lesion in the right chest|
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|Figure 2: Computed tomography scan chest – mediastinal cut – large homogenous mass lesion 130/94/123 mm, no mediastinal invasion|
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|Figure 3: Computed tomography scan – chest–lung window – large homogenous mass lesion right chest, no pleural effusion|
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He was moderately built and nourished, without any clubbing or lymphadenopathy on general examination. Vitals were stable, the trachea was centrally placed, reduced chest movements of the right side and total chest expansion, decreased tactile vocal fremitus, dull percussion note on the right chest with reduced breath sounds were noted. As the CXR and CT scan chest showed a large mass touching the right chest wall, ultrasound-guided biopsy of the lung mass was done, and the histopathology revealed features of poorly differentiated carcinoma with possibility of large cell carcinoma [Figure 4].
|Figure 4: Large neoplastic cells with hyperchromatic nuclei and scant cytoplasm (H and E)|
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Immunohistochemistry (IHC) was negative for thyroid transcription factor (TTF), cytokeratin 7 and positive for synaptophysin [Figure 5] and P40, suggesting high-grade LCNEC. He was referred to the oncology department for chemotherapy. As it was a large tumor and was of T4N0M0, stage 3A, he was started on combination chemotherapy (platinum and etoposide regimen). He responded to the treatment initially, with clinical improvement, but was lost to follow-up after 3 months.
|Figure 5: Neoplastic cells with focal synaptophysin positive (IHC, low and high power)|
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| Discussion|| |
In the 1970s, lung cancers were classified based on histological features. Travis et al. defined LCNEC with characteristic, diagnostic histological features. Till date, very few reports of lung LCNEC are available from India.,
The LCNEC tumors of lung occur commonly in the elderly (median age, 65 years), males, and heavy smokers. They are localized peripherally with a high recurrence rate, poorly symptomatic at diagnosis. Cough, hemoptysis, or postobstructive pneumonia is uncommon. They commonly present with an asymptomatic nodule or chest pain, nonspecific flu-like symptoms, dyspnea, night sweats, and rarely as carcinoid or paraneoplastic syndromes. Being a highly metastatic tumor, survival of the patient depends on the rate of its spread; Involvement of the lymph node which is seen in 60%–80% of patients and distant metastasis (40%) are associated with poor survival rates.
Lung LCNEC shares several clinicopathological features with small cell lung cancer (SCLC) and postulated to represent its variant form. It is also essential to distinguish LCNEC from poorly differentiated non-SCLC (NSCLC) and typical and atypical carcinoids. LCNEC has a poor prognosis compared to other NSCLC at stage 1 disease, which is almost comparable with that of patients with SCLC.
LCNEC generally presents as an expanding mass having irregular margins, which is peripherally located, without any specific finding on CXR or CT. The characteristic histological features were not demonstrated in our case. As LCNEC closely mimics SCLC, atypical carcinoid, or NSCLC in biopsy/cytology specimen, differentiating these is a difficult task; while the small samples only suggest a diagnosis of lung LCNECs, IHC is often required for confirmation. Established NE markers include chromogranin A, synaptophysin, and CD56.
In 1991 Travis et al. reported that the prognosis of LCNEC is between that of atypical carcinoids and SCLC. LCNEC was described as having a cell size at least three times that of SCLC, an organoid growth pattern, cellular-palisading or rosette-like areas, a high mitotic rate, and variable granular chromatic pattern.
Typical NE markers, such as chromogranin, neuron-specific enolase, synaptophysin, and somatostatin, are secreted by LCNECs. Biomarkers, i.e., high-molecular-weight cytokeratins, typically expressed by SCLC and other NE tumors, make the diagnosis easier while the conspicuous absence of characteristic markers for LCNECs often poses a difficulty in diagnosis of the latter. Our patient was positive for synaptophysin, TTF, and chromogranin and negative for cytokeratin 7, cytokeratin, and napsin. Takei et al. reported positive IHC staining with chromogranins (82%), using synaptophysin (91%), and neural cell adhesion molecule with no marker expressed in LCNEC cases (91%) and LCNECS expressing all three markers (68%). Positive NE marker (synaptophysin, chromogranin A, or CD56) is sufficient to confirm the diagnosis, but CD56 expression alone requires cautious interpretation.
The National Cancer Control Network recommends treatment for LCNEC according to the NSCLC guidelines; often, the drugs used are the same for both LCNEC and SCLC; reports also suggest that LCNEC is less chemoresponsive to platinum/etoposide regimen unlike SCLC with approximately 50%–80% response rates.
Although highly precise techniques resulted in diagnostic accuracy, delayed/missed diagnosis still remains a challenge in lung LCNEC as many are diagnosed in autopsy specimen. All stage 5-year survival rates for LCNEC range from 13% to 57%, making it worthwhile to invest in increasing the public awareness of LCNEC to improve the treatment-seeking behavior.
| Conclusion|| |
Lung LCNEC requires clinical and pathological expertise for diagnosis and must be considered as a possibility in all poorly differentiated lung cancers. Rarity, aggressive nature, and extremely poor prognosis, comparable with SCLC, demand thorough clinicopathological evaluation and combined modalities of treatment.
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.
We thank Dr. M. S. Latha for editing and proofreading.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]