Pheochromocytoma penetrance varies by RET mutation in MEN 2A.

BACKGROUND: The occurrence of pheochromocytoma in multiple endocrine neoplasia type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC expression for specific MEN 2A RET mutations. METHODS: Charts of MEN 2A patients enrolled in our multiple endocrine neoplasia program from 1990 to 2001 were reviewed retrospectively. Statistical analysis was performed using SAS software (SAS Institute, Inc, Cary, NC). RESULTS: RET mutation data and pheochromocytoma data were compiled for 323 patients. Overall, penetrance of pheochromocytoma occurred in 102 of 323 patients (32%). Bilateral pheochromocytomas were observed in 67 patients (66%). The following codon-specific expression of pheochromocytoma was observed: 1 of 24 patients expressed codon 609 (4%), 0 of 5 patients expressed codon 611 (0%), 23 of 105 patients expressed codon 618 (22%), 4 of 45 patients expressed codon 620 (9%), and 74 of 149 patients expressed codon 634 (50%) (P < .001). An association between pheochromocytoma expression and amino acid substitutions at codon 618 was observed as follows: 0 of 7 patients with C618F, 5 of 21 patients with C618G (24%), 11 of 27 patients with C618R (41%), 7 of 41 patients with C618S (17%), and 0 of 9 patients with C618Y (P = .04.) In our cohort, no deaths were attributable to PC with a median follow-up of 9 years. CONCLUSIONS: The penetrance of PC varies between MEN 2A RET codon mutations. Furthermore, we observed variable expression with different amino acid substitutions at the same codon. These results may help guide screening and therapy for MEN 2A patients.

Ultrasound facilitates minimally invasive parathyroidectomy in patients lacking definitive localization from preoperative sestamibi scan.

BACKGROUND: Sestamibi scanning is commonly used for preoperative localization in patients with hyperparathyroidism. However, 12% to 15% of these studies are equivocal or negative. Ultrasound may also be used to identify patients suitable for a minimally invasive parathyroidectomy. METHODS: Data from patients treated for hyperparathyroidism between January 2000 and April 2006 were reviewed retrospectively. Sestamibi and ultrasound results were scored as definitive, suggestive, or negative. Patients with suggestive or negative sestamibi scans were included in the analysis. RESULTS: A total of 261 patients underwent operation without a definitively localizing sestamibi scan. Preoperative neck ultrasound was performed in 80 of these patients. Overall, ultrasound was either conclusive or suggestive in 45 of 80 patients (56%) without a definitively localizing sestamibi scan and correctly correlated with the surgical findings in 38 of 45 (84%) of these patients. CONCLUSION: In patients with nonlocalizing sestamibi scans, neck ultrasound increases the number of patients suitable for minimally invasive parathyroidectomy.

Needle biopsy of incidentally discovered adrenal masses is rarely informative and potentially hazardous.

INTRODUCTION: The role of fine needle aspiration (FNA) biopsy in patients with incidentally discovered adrenal masses is limited. However, image-guided biopsy continues to be performed in this setting, in some cases before biochemical workup. The purpose of this study was to review the value of FNA biopsy of adrenal masses in patients referred to a large university endocrine surgical practice. METHODS: Patients referred to the endocrine surgery service at our institutions from 1997 through 2006 for evaluation of an adrenal mass were identified and those who underwent needle biopsy were selected for analysis. RESULTS: Of the 347 patients evaluated for adrenal masses, 22 (6.3%) had undergone needle biopsy before referral. Clinical presentations were incidentaloma (n = 15), suspected metastasis (n = 4), and symptomatic large mass (n = 3). In 10 cases, a radiology report had either suggested a biopsy or stated that the mass was "amenable" to biopsy. In the 15 patients with incidentaloma, 12 (80%) had nondiagnostic biopsy results and 2 showed pheochromocytoma. Biopsies were diagnostic in 2 of 4 patients with suspected metastasis and in 1 of 3 patients with a large symptomatic mass. There were 3 biopsy-related complications: 1 liver hematoma, 1 hemothorax, and 1 duodenal hematoma. No biochemical testing for pheochromocytoma was performed before biopsy in 10 patients, 5 of whom were ultimately diagnosed with pheochromocytoma. Biopsy results did not alter clinical management in any of the 22 patients in this study. CONCLUSIONS: FNA biopsy is not useful in the diagnostic workup of patients with incidentally discovered adrenal masses and rarely alters management in patients with resectable adrenal metastases and primary adrenal malignancies. Furthermore, biopsy in this setting can also be potentially hazardous. Language that suggests biopsy of adrenal masses should be avoided in radiology reports.

Colorectal lymphoma.

Lymphoma involving the colon and rectum is rare and can occur either as primary colorectal lymphoma or as a manifestation of systemic disease. Most patients with primary colorectal lymphoma present with abdominal pain, and obstruction is unusual. Although lesions may be evident on radiographic studies, the findings are generally nonspecific. Historically, aggressive B-cell lymphomas have been the most common gastrointestinal lymphomas reported in the literature. However, recent reports suggest increased rates of mucosa-associated lymphoid tissue (MALT) lymphoma and mantle cell lymphoma (MCL) with increased surveillance.1 Most patients with colorectal lymphoma undergo surgery, but multiagent chemotherapy remains the mainstay of treatment. B-cell lymphomas tend to be most aggressive, with a median survival of about 2 years.

Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes.

Medullary thyroid carcinoma (MTC) is a rare malignancy with several distinctive features that distinguish its management from other thyroid cancers. First, MTC may be sporadic (75% of cases), or may occur as a manifestation of the hereditary syndrome Multiple Endocrine Neoplasia type 2 (MEN 2) (25% of cases). Additionally, while MTC is more difficult to cure than differentiated thyroid cancer and has higher rates of recurrence and mortality, it is usually a slow growing tumor compared with other malignancies. Finally, unlike differentiated thyroid cancer, there is no known effective systemic therapy for MTC. MTC cells do not concentrate radioactive iodine, and MTC does not respond well to external beam radiation or conventional cytotoxic chemotherapy. These distinguishing features should be considered in planning surgical management of MTC.

Hereditary medullary thyroid carcinoma in patients greater than 50 years old.

BACKGROUND: Despite near complete penetrance and frequent early evaluation of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia 2 (MEN 2) variants, a significant minority of patients are evaluated later in life. METHODS: With the aim of characterizing the expression of hereditary MTC in an older cohort, MEN 2 patients from our institutional database who were evaluated after age 50 years were identified, and clinical data were reviewed. RESULTS: Thirty-nine patients (36 MEN 2A, 3 FMTC, and no MEN 2B) who were evaluated after age 50 years were identified; they represented 9% of all MEN 2 patients who were enrolled in our program. Most of the patients (79%) had abnormal screening examinations, and the AJCC staging was significantly higher in this cohort compared with younger patients. Overall, 43% of the patients had normal calcitonin levels after operation. There were 3 observed MTC-related deaths, all from distant metastases; the overall survival rate was 86% at 5 years and 74% at 10 years. The distribution of RET mutations in this cohort was similar to younger patients. CONCLUSIONS: These results suggest the presence of modifiers of MTC expression. Despite the tendency of older patients with hereditary MTC to have advanced stage disease at evaluation, they have high rates of biochemical cure, and the overall survival is excellent.