Typical and Atypical Pulmonary Carcinoids: Outcome in Patients Presenting With Regional Lymph Node Involvement

doi:10.1378/chest.119.4.1143

Chest

Volume 119, Issue 4, April 2001, Pages 1143-1150

https://doi.org/10.1378/chest.119.4.1143 Get rights and content

Study objective

Typical pulmonary carcinoid tumors are well-differentiated neuroendocrine tumors that are associated with good patient survival rates, while atypical carcinoid tumors are more aggressive and have worse patient survival rates. Because these tumors rarely involve the thoracic lymph nodes at presentation, it is currently unknown to what extent the presence of thoracic lymph node metastases at the time of diagnosis influences patient survival.

Methods

A computerized search of the medical records for pulmonary carcinoid tumor at the Mayo Clinic from 1976 to 1997 revealed 517 patients, from which we identified 36 patients with pulmonary carcinoid tumors involving regional thoracic lymph nodes but without distant disease. For each patient, we reviewed the tumor histology, stage, and outcome. In addition, because the histologic criteria for the diagnosis of carcinoid tumors had changed significantly during the time of the study, we reexamined all of the histologic specimens using the current World Health Organization (WHO) criteria for classifying pulmonary neuroendocrine tumors.

Results

After reclassification with the WHO criteria for neuroendocrine tumors, 23 patients had typical carcinoid tumors with thoracic lymph node involvement. At the last follow-up, 19 patients had no evidence of disease (NED), 2 patients had developed systemic metastases (SM) and are still alive, and 2 patients had died. Eleven patients had atypical carcinoid tumors with thoracic lymph node involvement. At the last follow-up, four patients had NED, seven patients had developed SM within a median time of 17 months, and six patients with SM died shortly thereafter (median survival time, 25.5 months), while one is still alive. Two patients had been reclassified with large cell neuroendocrine carcinoma at the time of this review; both of these patients had developed SM (at 4 months and 21 months after diagnosis) and had died (at 15 months and 21 months after diagnosis, respectively).

Conclusions

These data suggest that patients with atypical pulmonary carcinoid tumors with regional lymph node metastases have a high likelihood of developing recurrent disease if treated with surgical resection alone and have significantly worse outcome (p < 0.001) compared to those patients with typical carcinoid tumors with thoracic lymph node involvement.

Section snippets

Materials and Methods

A computerized search of the medical records at the Mayo Clinic from 1976 to 1997 revealed 517 patients with pulmonary carcinoid tumors, from which we identified 36 patients with pulmonary carcinoid tumors involving regional thoracic lymph nodes but without distant disease. The medical records of these 36 patients were reviewed, and the study population included only patients with pulmonary carcinoid tumors presenting with thoracic lymph node metastases at the time of surgical resection. This

Results

Thirty-six patients with pulmonary carcinoid tumors had thoracic lymph node involvement at the time of surgical resection and staging from 1976 to 1997. These included 15 men and 21 women with a mean age of 55.9 years (age range, 17 to 77 years). The original classification was 24 typical carcinoid tumors and 12 atypical carcinoid tumors (Table 3). Using the current criteria for classifying pulmonary neuroendocrine tumors, four patients originally receiving diagnoses of typical carcinoid tumors

Discussion

Pulmonary carcinoid tumors comprise 1 to 2% of all lung malignancies.¹^,¹⁵^,²³ Historically called bronchial adenomas, they were thought to be benign tumors. The recognition of a more aggressive variety of carcinoid tumor, the atypical carcinoid, suggested that they might all be malignant.⁴^,⁵^,¹¹^,¹⁸^,²⁰ Currently, typical and atypical carcinoids are considered to be part of a spectrum of malignant neoplasms with neuroendocrine differentiation along with large cell neuroendocrine carcinoma and small

ACKNOWLEDGMENT

We thank Darrell R. Schroeder from the Mayo Clinic Section of Biostatistics for performing the statistical analysis in this study.

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Video bronchoscopic electrocautery fulguration of endobronchial carcinoids: Case series from an Indian tertiary care center
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Carcinoid tumors are slow-growing tumors noticed in the tracheobronchial tree and pulmonary parenchyma. Generally, these tumors are slow growing with minimum risk of distant metastasis, but the atypical type of carcinoids has greater malignant potential with lower survival rates. The primary and most effective treatment for all pulmonary carcinoid tumors is surgical resection if no contraindications to surgery exist. Compared to surgical resection, bronchoscopic management is minimally invasive and parenchyma sparing. The present case series describes six patients, all young males, diagnosed with typical (n = 4) and atypical (n = 2) carcinoids, and managed with electrocautery fulguration carried out through video bronchoscope. Three cases were suggested pneumonectomy, while the other three cases were suggested for lobectomy by the Hospital Tumour Board. After the electrocautery fulguration procedure, the procedures of lobectomy or pneumonectomy were successfully prevented in all the cases, thereby saving these young males from life-threatening surgeries and permanent disabilities that would have affected their health and career. This is one of its kind case series that shows the importance of bronchoscopic management in carcinoid cases, from developing countries that can help in preserving the lungs.
Neuroendocrine neoplasms of the lung
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The pathologic diagnosis of neuroendocrine tumors of the lung requires integration of histologic and cytologic findings with clinical and radiologic consideration. Despite advances in diagnosis, challenges remain in their accurate classification. A search of relevant literature in PubMed was conducted with terms that included neuroendocrine, lung, and the terms in the chapter subheadings of individual entities combined with lung. In addition, a review of archived cases in the file of Weill Cornell Pathology was conducted.
Neuroendocrine tumors, including preinvasive lesions, were described from the perspective of classification, clinical presentation, pathology, ancillary studies, molecular findings, and treatment impact. New information focused on diagnostic criteria for large cell neuroendocrine carcinoma including overlap with small cell carcinoma and adenocarcinoma, mitotic counting, specificity of CD56, utility of INSM1, and potential diagnostic pitfalls. Molecular advances have led to new insights on the origin and classification of neuroendocrine tumors, especially of neuroendocrine carcinomas. The integration of clinical and radiologic findings to enhance diagnostic certainty was addressed.
Emerging knowledge supports the classification of neuroendocrine tumors into low, intermediate, and high grade categories. Use of Ki-67 to distinguish high from low grade lesions is established but not as a replacement for mitotic counting in well-preserved samples and excisions. Molecular data in large cell neuroendocrine carcinoma show some heterogeneity in this category with potential treatment implications. New data support the observation that most carcinoids and atypical carcinoids do not progress into higher grade lesions; however, this may occur in a small subset of cases. In addition, there appear to be atypical carcinoid tumors with mitotic rates higher than 10 in 2 mm²; their biologic behavior needs to be better defined. The consideration of rare entities in the differential diagnosis of neuroendocrine tumors is prompted by unusual epidemiology, histology, and clinical presentation.
An unusual clinical manifestation of a relapsed typical pulmonary carcinoϊd tumor
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Typical carcinoid tumors of the lungs carry an excellent prognosis after complete surgical excision. However, recurrence of these cancers remains poorly described in the literature and may occur many years after surgery.
We report a case of carcinoid tumor of the lung. Clinical presentation and follow-up were uneventful.
The 55 years old patient had got a surgical removal of a huge typical carcinoid tumor of the left lung. A left pneumonectomy with a mediastinal lymph node resection were performed. Thirteen years later, paraneoplastic acromegaly revealed a pulmonary and extrapulmonary recurrence of the tumor. We prescribed a chemotherapy regimen including Cisplatin and Etoposide.
Endocrine paraneoplastic syndromes are related to mutations in specifically known genes. Several mutations may become a promising therapeutic target in the future. In the case of neuro-endocrine pulmonary tumors, authors described BCOR gene mutation as an oncogenic development inducer and an eventual generator of ectopic tumoral secretions.
The more we get familiar with carcinoid tumor mutations, the closer we get to targeted therapy for non-resectable tumors.
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We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcomes. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2 mm², necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlated with clinical outcomes. Based on our analysis, we consider that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of overgrading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcomes.
Neuroendocrine tumors of the lung: A five-year retrospective experience of Egyptian NCI (2010–2014)
2018, Journal of the Egyptian National Cancer Institute
The spectrum of lung neuroendocrine tumors (NETs) encompasses low grade typical carcinoid (TC), intermediate grade atypical carcionid (AC) and high grade, both large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), with extreme differences in management and survival.
To study clinicopathologic and prognostic factors affecting survival of lung NETs.
This is a retrospective study evaluating 35 patients with primary lung NETs treated at National Cancer Institute of Egypt (NCI-E) between January 2010 and December 2014. Pathological diagnosis depended on definite morphology and positivity to at least one of the neuroendocrine markers by immunohistochemistry.
The mean age of the patients was 53 ± 11.2 years with male predominance. Performance status (PS) I was encountered in 48.6%. SCLC was the prevalent histology in 68.6%, followed by LCNEC & TC in 20 & 11.4%, respectively. Curative surgery was employed in 100 & 57% of TC & LCNEC patients, respectively. Stage IV was anticipated in 87.5 & 43% of SCLC & LCNEC, respectively. For the entire cohort, the median event-free survival (EFS) and overall survival (OS) were 8.0 and 13.7 months, respectively, whereas the 3-year EFS and OS were 17.8 & 20%, respectively. SCLC patients showed significantly the worst OS compared to other NETs (p = 0.001). Patients who presented with stage IV and PS > I demonstrated significantly shorter OS than those with locoregional and PS I (p = 0.00001 & p = 0.002, respectively).
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Chest

Clinical Investigations: TumorsTypical and Atypical Pulmonary Carcinoids: Outcome in Patients Presenting With Regional Lymph Node Involvement

Study objective

Methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

ACKNOWLEDGMENT

Mayo Clin Proc

Thorac Cardiovasc Surg

Thorac Cardiovasc Surg

Thorac Cardiovasc Surg

Ann Thorac Surg

Respir Med

Thorac Cardiovasc Surg

Chest

Hum Pathol

Hum Pathol

Surgery

Chest

Neuroendocrine differentiation in lung tumours

Thorax

Neuroendocrine tumors of the lung: pathology and molecular biology

Chest Surg Clin North Am

Benign bronchial adenomas

Acta Chir Scand

Atypical carcinoid tumor of the lung: a clinicopathologic study of 17 cases

Am J Surg Pathol

Neuroendocrine cells and neuroendocrine neoplasms of the lung

Pathol Annu

Clinical Investigations: Tumors
Typical and Atypical Pulmonary Carcinoids: Outcome in Patients Presenting With Regional Lymph Node Involvement