Category Archives: Carcinoids

Typical and Atypical Pulmonary Carcinoids: Discussion

Typical and Atypical Pulmonary CarcinoidsPulmonary carcinoid tumors comprise 1 to 2% of all lung malignancies. 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. 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 cell carcinoma.
In general’ patients with typical carcinoids have good prognoses’ with > 87% of patients surviving for 10 years. In contrast’ approximately 25 to 69% of patients with atypical carcinoid tumors survive 5 years’ and many develop widespread disease. Multivariate analyses from four studies suggest that pathologic stage and atypical histology are the most important factors affecting survival; however’ not all studies have confirmed this. In a study of 93 patients with typical carcinoid tumors, the presence of lymph node metastases in 9 patients (all with N1 disease) did not have any prognostic significance. Eight patients survived a mean of 8 years, while one patient died of unrelated causes. In another report of 120 patients, there was insufficient information to allow any conclusions about the significance of either atypical features or lymph node metastases (only 7 patients had lymph node metastases). No prior studies specifically analyzed the subset of patients with typical or atypical pulmonary carcinoid tumors who presented with lymph nodal metastases at the time of surgical resection. As shown in Table 3, we compare the survival data for patients with typical or atypical pulmonary carcinoid tumors presenting with lymph node metastases with a historical series of patients with pulmonary carcinoid tumors.
In the present study, patients with typical pulmonary carcinoid tumors with thoracic lymph node metastases did well after surgical resection alone. The overall survival rate was excellent, with only two patients (8.7%) developing systemic disease at a median time of 66 months after diagnosis and two patients dying. This is in contrast to patients with atypical pulmonary carcinoid tumors with thoracic lymph node metastases. When treated with surgical resection alone, most of these patients (63.6%) developed SM at a median time of 17 months after diagnosis. The majority of patients with SM (54.5%) died shortly thereafter (median time, 25.5 months after initial diagnosis).

Typical and Atypical Pulmonary Carcinoids: 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 were reclassified as having atypical carcinoid tumors. In addition, three patients originally receiving diagnoses of atypical carcinoid tumor were reclassified as having typical carcinoid tumors, and two patients originally receiving diagnoses of atypical carcinoid tumors were reclassified as having large cell neuroendocrine carcinoma. Therefore, using the current WHO criteria, there were 23 patients with typical carcinoid tumors (10 men and 13 women; mean age, 52 years; age range, 17 to 74 years), 11 patients with atypical carcinoid tumors (4 men and 7 women; mean age, 63 years; age range, 34 to 77 years), and 2 patients with large cell neuroendocrine carcinoma (1 man, age, 68 years; 1 woman, age, 64 years; Table 3).
Typical carcinoid tumors had a mean mitotic rate of 0.19/2 mm2 (10 high-power fields) and, by definition, did not have necrosis. Three tumors, however, had foci of discohesive cells with somewhat pyknotic nuclei and condensed, shrunken-appearing cytoplasms in comparison to adjacent cells (Fig 1); but, because of a lack of karyorrhexis, associated eosinophilic debris, or apoptosis, such foci were not accepted as necrosis. All three patients are currently alive and without metastatic disease at a median time of 88 months.
Atypical carcinoid tumors had a mean mitotic rate of 1.78/2 mm2; 10 of 11 atypical carcinoid tumors also had foci of necrosis (Fig 2). Six tumors were classified as atypical carcinoid only on the basis of necrosis with a mitotic rate of < 2/2 mm2. Three patients from this subgroup are alive without evidence of metastases, one developed metastases 12 months after diagnosis but is still alive at 89 months, and two patients developed metastases and died. The two patients with large cell neuroendocrine carcinoma had foci of necrosis and mitotic rates of 19/2 mm2 and 32/2 mm2 (Fig 3).
Among the 23 patients with typical pulmonary carcinoid tumors, 8 had stage IIA disease (T1N1M0), 6 had stage IIB disease (T2N1M0), and 9 had stage
IIIA disease (T1N2M0 or T2N2M0). Nineteen patients (82.6%) had no evidence of disease (NED) at follow-up (median, 84 months after diagnosis; range, 12 to 242 months after diagnosis). Only two patients (8.7%) developed systemic metastases (SM) at 54 and 78 months after diagnosis. Both patients are currently alive. Two patients died (one at 29 months of unknown causes, and the other at 223 months of “natural causes” at age 93 years; Table 3).

Typical and Atypical Pulmonary Carcinoids

Typical and Atypical Pulmonary CarcinoidsPulmonary carcinoid tumors are malignant neoplasms that show neuroendocrine differentiation. Although the distinction between typical and atypical carcinoid tumors was first described by Engelbreth-Holm in 1944, it was not until 1972 that histologic criteria for separating these tumors were proposed by Arrigoni et al. In the intervening 25 years, numerous studies have continued to confirm that there is a spectrum of neuroendocrine-appear-ing tumors from the carcinoid tumorlet to small cell undifferentiated carcinoma. However, the distinction between typical carcinoids and more aggressive neuroendocrine neoplasms has been problematic, and several classification schemes have been proposed but none have been widely accepted or ap-plied. The 1981 World Health Organization (WHO) classification of neuroendocrine neoplasms stated only that atypical carcinoid tumors had “increased mitotic activity, cellularity and could have necrosis.” While this statement is true in general, strict criteria were not suggested. The most recent WHO classification has proposed more strict criteria for separating these two tumors, based on work by Travis et al. The new WHO classification (Table 1) also lays out criteria for large cell neuroendocrine carcinoma, a tumor that undoubtedly has, in the past, been included in at least some series of atypical carcinoid tumors.
Typical pulmonary carcinoid tumors rarely metastasize and, in general, patients with these tumors have a good prognosis, with 5-year survival rates ranging from 87 to 100%. This is in contrast to patients with atypical carcinoid tumors, who have a greater tendency to have metastases and a 25 to 69% 5-year survival rate (Table 2). Although previous studies have reported the outcome of patients with typical and atypical carcinoid tumors, none have specifically investigated the subset of patients who have thoracic lymph node metastases at the time of surgical staging. It is uncertain whether the survivalrate is significantly worse in this subset of patients and whether consideration of more aggressive management and follow-up is indicated for them. In this study, we retrospectively analyzed the clinical characteristics and survival rates of surgically treated patients with typical and atypical pulmonary carcinoid tumors who had thoracic lymph node metastases.
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 group was selected because we were specifically interested in the outcomes of patients with completely resected carcinoid tumors having regional lymph node metastases. Carcinoid tumor patients presenting with distant metastases or concurrent cancers were excluded from the study.
The histologic diagnosis of pulmonary carcinoid tumor was confirmed by review of all histologic sections by a single pathologist with special expertise in neuroendocrine tumors who was blinded to the initial diagnosis (ie, typical or atypical carcinoid tumor). Histologic sections were available for all 36 patients. Because the histologic criteria for the diagnosis of pulmonary carcinoid tumors changed significantly during the dates of this study, all tumors were classified on the basis of the newly proposed WHO classification scheme and were compared to the original diagnoses. The pathologic stage of disease using the TNM classification for non-small cell lung cancer also was confirmed. Two sets of survival curves were generated using the Kaplan-Meier method, one based on the original pathologic diagnosis and the second based on tumor classification according to the new WHO criteria.