May 16, 2011 — Even small incidentally detected, nonfunctioning pancreatic endocrine tumors (PETs) are potentially lethal and should be removed, clinicians from Massachusetts General Hospital in Boston advise.
These patients also need careful postoperative surveillance, even if surgical pathologic findings suggest benign disease, Alex B. Haynes, MD, MPH, and colleagues say.
"Management of incidentally identified lesions poses a quandary to health care professionals, especially when they represent rare conditions, such as PETs," the authors note in an article published in the May issue of the Archives of Surgery.
In their article, the researchers report the short- and long-term outcomes for 139 patients who underwent resection of an incidentally identified nonfunctioning PET between May 1, 1977, and July 31, 2009. More than three quarters of the resections (78.4%) were performed after 2000.
"The past decade marks the advent of the incidentaloma era in pancreatic surgery," Charles M. Vollmer Jr, MD, from Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, notes in an invited critique published with the study. "This series adds substantial knowledge to the topic."
Some Findings "Disconcerting"
Dr. Haynes and colleagues report that the median age of subjects in their cohort was 56 years, and that men and women were equally represented. The median tumor size was 3.0 cm (range, 0.4 - 17.0 cm). Most of these tumors (71.9%) were larger than 2 cm.
Based on the World Health Organization (WHO) classification system for PETs, 26 tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. The researchers were not able to "confidently" classify 2 of the tumors, they say, because of the lack of information on the mitotic rate in the pathology report.
Dr. Vollmer says the fact that more than half of the tumors were graded as uncertain is "disconcerting" and exposes doubt about the WHO pathologic classification system. He also points out that 14.9% of tumors classified as benign or uncertain ultimately showed disease progression, indicating that they were actually malignant at the time of resection.
"The most important take home points are that malignancy does occur in small tumors and also can be evident (ultimately) in presumably benign lesions," Dr. Vollmer writes.
There were no perioperative deaths. One or more perioperative complications occurred in 61 patients (43.9%). "We were surprised to find that 28 patients (20.1%) had lymph nodes that tested positive and 15 (10.8%) had distant metastases at the time of surgery," the study authors note.
Dr. Haynes and colleagues had complete follow-up data for 112 patients (80.6%), with a median follow-up of 34.2 months. There was no significant survival difference between tumors of benign and uncertain designations.
Table 1. 5- and 10-Year Actuarial Survival by WHO Classification
Tumor-related 5-year and 10-year mortality rates were 7.1% and 7.1% for the benign group, 6.1% and 14.0% for the uncertain group, and 35.9% and 78.6% for the malignant group.
Late metastasis, tumor recurrence, or disease progression occurred in 1 patient (3.8%) with a tumor initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant.
Small tumor size did not guarantee a good outcome, the researchers say, noting that 3 (7.7%) of 39 patients with tumors 2 cm in size or smaller eventually had late metastases or recurrence and died of their disease.
Overall, the researchers say outcomes of the patients with incidentally detected nonfunctioning PETs were "almost identical" to those of 30 patients (17.8% of the total sample) who underwent resection during the same period for symptomatic, nonfunctioning PETs.
To the researchers' knowledge, this is the largest single-institution series of incidentally discovered, nonfunctioning PETs. "We found that these represent 82.2% of all resected nonfunctioning PETs," they note.
On the basis of their experience, Dr. Haynes and colleagues say resection should be offered to "surgically fit" patients with incidentally identified PETs. "No size cutoff exists beyond which malignancy can be safely excluded."
In addition, the authors say all resected patients should be followed long-term, including those with tumors classified as benign. In his commentary, however, Dr. Vollmer wonders whether busy surgeons will be able to do accomplish this. "My policy," he says, "is to have every patient with a resected PET evaluated by a medical oncologist."
Dr. Haynes and colleagues and Dr. Vollmer have disclosed no relevant financial relationships.
Arch Surg. 2011;146;534-539. Abstract
These patients also need careful postoperative surveillance, even if surgical pathologic findings suggest benign disease, Alex B. Haynes, MD, MPH, and colleagues say.
"Management of incidentally identified lesions poses a quandary to health care professionals, especially when they represent rare conditions, such as PETs," the authors note in an article published in the May issue of the Archives of Surgery.
In their article, the researchers report the short- and long-term outcomes for 139 patients who underwent resection of an incidentally identified nonfunctioning PET between May 1, 1977, and July 31, 2009. More than three quarters of the resections (78.4%) were performed after 2000.
"The past decade marks the advent of the incidentaloma era in pancreatic surgery," Charles M. Vollmer Jr, MD, from Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, notes in an invited critique published with the study. "This series adds substantial knowledge to the topic."
Some Findings "Disconcerting"
Dr. Haynes and colleagues report that the median age of subjects in their cohort was 56 years, and that men and women were equally represented. The median tumor size was 3.0 cm (range, 0.4 - 17.0 cm). Most of these tumors (71.9%) were larger than 2 cm.
Based on the World Health Organization (WHO) classification system for PETs, 26 tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. The researchers were not able to "confidently" classify 2 of the tumors, they say, because of the lack of information on the mitotic rate in the pathology report.
Dr. Vollmer says the fact that more than half of the tumors were graded as uncertain is "disconcerting" and exposes doubt about the WHO pathologic classification system. He also points out that 14.9% of tumors classified as benign or uncertain ultimately showed disease progression, indicating that they were actually malignant at the time of resection.
"The most important take home points are that malignancy does occur in small tumors and also can be evident (ultimately) in presumably benign lesions," Dr. Vollmer writes.
There were no perioperative deaths. One or more perioperative complications occurred in 61 patients (43.9%). "We were surprised to find that 28 patients (20.1%) had lymph nodes that tested positive and 15 (10.8%) had distant metastases at the time of surgery," the study authors note.
Dr. Haynes and colleagues had complete follow-up data for 112 patients (80.6%), with a median follow-up of 34.2 months. There was no significant survival difference between tumors of benign and uncertain designations.
Table 1. 5- and 10-Year Actuarial Survival by WHO Classification
| PET Designation | 5-Year Survival | 10-Year Survival |
| Benign | 88.8% | 67.7% |
| Uncertain | 92.5% | 77.8% |
| Malignant | 49.8% | 16.6% |
Late metastasis, tumor recurrence, or disease progression occurred in 1 patient (3.8%) with a tumor initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant.
Small tumor size did not guarantee a good outcome, the researchers say, noting that 3 (7.7%) of 39 patients with tumors 2 cm in size or smaller eventually had late metastases or recurrence and died of their disease.
Overall, the researchers say outcomes of the patients with incidentally detected nonfunctioning PETs were "almost identical" to those of 30 patients (17.8% of the total sample) who underwent resection during the same period for symptomatic, nonfunctioning PETs.
To the researchers' knowledge, this is the largest single-institution series of incidentally discovered, nonfunctioning PETs. "We found that these represent 82.2% of all resected nonfunctioning PETs," they note.
On the basis of their experience, Dr. Haynes and colleagues say resection should be offered to "surgically fit" patients with incidentally identified PETs. "No size cutoff exists beyond which malignancy can be safely excluded."
In addition, the authors say all resected patients should be followed long-term, including those with tumors classified as benign. In his commentary, however, Dr. Vollmer wonders whether busy surgeons will be able to do accomplish this. "My policy," he says, "is to have every patient with a resected PET evaluated by a medical oncologist."
Dr. Haynes and colleagues and Dr. Vollmer have disclosed no relevant financial relationships.
Arch Surg. 2011;146;534-539. Abstract
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