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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).
Among the 11 patients with atypical carcinoid tumors, 3 had stage IIA disease (T1N1M0), 4 had stage IIB disease (T2N1M0), and 4 had stage IIIA disease (T2N2M0 or T3N1M0). Only four patients (36.4%) showed NED at the time of follow-up, while seven patients (63.6%) developed SM at a median time of 17 months after diagnosis (range, 2 to 57 months after diagnosis). Six patients with SM died within a median time of 25.5 months after the initial diagnosis (range, 2 to 123 months after diagnosis). One patient with SM is still alive at 89 months (Table 3).
Both patients with large cell neuroendocrine carcinoma (one man, age 68 years; one woman, age 64 years) had stage IIIA disease (T1N2M0 or T2N2M0) and developed SM at 4 months and 21 months after receiving their diagnoses, respectively. Both patients died shortly thereafter, 15 months and 21 months, respectively, after the initial diagnoses (Table 3).
Survival curves for the patients classified according to the original pathologic diagnosis and the diagnosis based on the new classification scheme are shown in Figure 4. Although the number of patients in this study was too small to permit a meaningful statistical analysis between the two groups (old vs new classification), the new classification scheme does separate tumors that behave worse than the atypical carcinoid tumors, as previously classified.
 Table 3—Demographics of the 36 Patients With Typical Carcinoid Tumors, Atypical Carcinoid Tumors, or Large

Patient/Age’ yr/Sex Stage Reclassification Original Classification Mitoses/10 HPF and Presence of Necrosis’ No. Duration of Follow-Up’ mo Outcome at Last Follow-Up
1/17/M T2N2M0 TC TC 0 110 NED
2/21/F T2N2M0 TC TC 0 242 NED
3/27/M T2N2M0 TC TC 0 15 NED
4/39/M T1N2M0 TC TC 0.33 84 SM (54 mo but alive)
5/41/F T2N1M0 TC TC 0 158 NED
6/41/M T2N2M0 TC TC 0 75 NED
7/47/F T2N2M0 TC AC 0 96 NED
8/48/M T2N2M0 TC TC 0 88 NED
9/50/F T1N1M0 TC TC 1.67 87 SM (78 mo but alive)
10/52/F T2N1M0 TC AC 0 75 NED
11/52/F T1N1M0 TC TC 0 43 NED
12/53/F T1N1M0 TC TC 1 52 NED
13/59/F T2N1M0 TC TC 0 150 NED
1461/F T1N1M0 TC AC 0.3 168 NED
15/62/F T1N2M0 TC TC 0.33 29 Died
16/63/M T1N2M0 TC TC 0 118 NED
17/64/M T2N1M0 TC TC 0 74 NED
18/66/M T2N1M0 TC TC 0.33 85 NED
19/70/F T2N1M0 TC TC 0 36 NED
20/71/M T1N1M0 TC TC 0 70 NED
21/72/F T1N1M0 TC TC 0.33 25 NED
22/73/M T1N1M0 TC TC 0 33 NED
23/74/F T1N1M0 TC TC 0 223 Died
24/34/M T2N2M0 AC TC 0.33/N 123 SM (57 mo/died)
25/44/F T3N1M0 AC AC 4.7/N 21 SM (2 mo/died)
26/48/F T2N1M0 AC TC 0/N 102 NED
27/54/F T2N1M0 AC AC 2.6/N 53 SM (17 mo/died)
28/59/M T1N1M0 AC AC 3.6/N 2 SM (2 mo/died)
29/62/F T1N1M0 AC TC 1/N 74 NED
30/67/M T2N1M0 AC AC 4.3/N 30 SM (24 mo/died)
31/69/F T2N1M0 AC TC 2 65 NED
32/70/M T1N1M0 AC AC 0/N 89 SM (12 mo)
33/73/F T2N2M0 AC AC 1/N 21 SM (21 mo/died)
34/77/F T2N2M0 AC AC 0/N 67 NED
35/64/F T1N2M0 LCNEC AC 19/N 15 SM (4 mo/died)
36/68/M T2N2M0 LCNEC AC 32/N 21 Died

Fig1

Figure 1. Typical carcinoid tumor with central (top, A) and peripheral (bottom, B) foci (arrows) of cell discohesion, nuclear hyperchromatism, pyknosis, and condensed cytoplasm. Such foci were not accepted as tumor necrosis (hematoxylin-eosin, original X 100 [top, A], original X 200 [bottom, B]).

Fig2

Figure 2. Atypical carcinoid tumor with focus of central necrosis (arrows; hematoxylin-eosin, original X 200).

Fig3

Figure 3. Large cell neuroendocrine carcinoma with numerous mitotic figures (arrows; hematoxylin-eosin, original X 100)

Fig4

Figure 4. Kaplan-Meier survival analysis of study patients using the Arrigoni criteria (top, A) or the current WHO classification (bottom, B).