HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome.

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.

Biologic basis for the treatment of microscopic, occult well-differentiated thyroid cancer.

BACKGROUND: Management of thyroid microcancer or occult well-differentiated thyroid cancer (OWDTC) is controversial. Our present study compared some clinical features of OWDTC and gross well-differentiated 10-mm thyroid carcinoma (GWDTC), which may offer a basis for treatment policy. METHODS: From 1964 to 2000, 1000 patients underwent thyroidectomy for thyroid cancer. We randomly selected 428 cases for study in which node sampling was carried out in 88% of GWDTC and 60% of OWDTC and who were demographically comparable. All data were obtained by chart review and analyzed by chi-square test. RESULTS: With the maximum limit of 10 mm for defining OWDTC, we found 113 such cases with a mean size of 6.1 mm and 315 GWDTC cases with a mean size of 27.6 mm. The incidence of metastatic nodal disease was 16.8% in OWDTC cases and 25.7% in GWDTC cases (P = .057). Distant metastases occurred in 1 of 113 (0.9%) cases of OWDTC and 11 of 315 (3.5%) cases of GWDTC (P = .149). After a mean follow-up time of 55.8 months, neck metastatic recurrent disease occurred in 3 of 113 (2.7%) cases of OWDTC and 7 of 315 (2.2%) cases of GWDTC (P = .770). OWDTC was found in 11.1% of the GWDTC group undergoing an operation. Multicentricity occurred in 31.9% of OWDTC cases and 35.9% of GWDTC cases (P = .447). No cause-specific death occurred. CONCLUSIONS: One cannot be dogmatic in treatment of microcancer, but one is justified in extending similar treatment principles for OWDTC as in GWDTC, which in our center usually indicates near-total thyroidectomy and consideration for radioactive iodine ablation.

Immunohistochemical diagnosis of papillary thyroid carcinoma.

In thyroid, the diagnosis of papillary carcinoma (PC) is based on nuclear features; however, identification of these features is inconsistent and controversial. Proposed markers of PC include HBME-1, specific cytokeratins (CK) such as CK19, and ret, the latter reflecting a ret/PTC rearrangement. We applied immunohistochemical stains to determine the diagnostic accuracy of these three markers. Formalin-fixed, paraffin-embedded tissue from 232 surgically resected thyroid nodules included 40 hyperplastic nodules (NH), 35 follicular adenomas (FA), 138 papillary carcinomas (PC; 54 classical papillary tumors and 84 follicular variant papillary carcinomas [FVPC]), 4 follicular carcinomas (FC), 6 insular carcinomas (IC), 7 Hürthle cell carcinomas (HCC), and 2 anaplastic carcinomas (AC). HBME-1 and ret were negative in all NH and FA; some of these exhibited focal CK19 reactivity in areas of degeneration. Half of the FC and AC exhibited HBME-1 staining but no positivity for CK19 or ret. In PC, 20% of cases stained for all three markers. Classical PC had the highest positivity with staining for HBME-1 in 70%, CK19 in 80%, and ret in 78%. FVPC were positive for HBME-1 in 45%, for CK19 in 57%, and for ret in 63%; only 7 FVPC were negative for all three markers. The six IC exhibited 67% staining for HBME-1 and 50% positivity for CK19 and ret. The seven HCC had 29% positivity for HBME-1 and CK19, and 57% positivity for ret. This panel of three immunohistochemical markers provides a useful means of diagnosing PC. Focal CK19 staining may be found in benign lesions, but diffuse positivity is characteristic of PC. HBME-1 positivity indicates malignancy but not papillary differentiation. Only rarely are all three markers negative in PC; this panel therefore provides an objective and reproducible tool for the analysis of difficult thyroid nodules.

Future of thyroid surgery and training surgeons to meet the expectations of 2000 and beyond.

What is the future of thyroid surgery in the new millennium? How can surgeons keep abreast of advances in thyroid endocrinology, genetics, surgical therapy, and other aspects of thyroid disease management? How should surgeons be trained to become highly competent in thyroid disease and to perform safe, effective thyroid operative procedures? Nine internationally recognized endocrine surgeons were asked to express their views on these and related subjects. They noted that advances in molecular biology, pathology, and genetics of thyroid disease should allow more tailored surgical approaches during the twenty-first century. Current training of general surgical residents in thyroid and other types of endocrine surgery is highly variable, which may contribute to increased complication rates and number of second operations. The leadership for addressing these deficiencies and promoting a more organized approach to thyroid disease management should come from national endocrine surgery associations and their leaders. It is incumbent upon endocrine surgeons to maintain their central role in the management of many aspects of thyroid disease. Organizing teams of specialists into thyroid centers (centers of excellence) can (1) increase efficiency; (2) increase quality of care; (3) decrease costs; (4) encourage a more individualized approach to surgery; (5) lower complication rates; and (6) foster innovation in technology and disease management. Two years of additional fellowship training in thyroid and endocrine surgery is now being advocated by increasing numbers of national endocrine surgical associations as the best way to prepare surgeons for society's needs for highly skilled, competent thyroid surgeons of the future.

Hyperparathyroidism-jaw tumor syndrome: the HRPT2 locus is within a 0.7-cM region on chromosome 1q.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease characterized by the development of multiple parathyroid adenomas and multiple fibro-osseous tumors of the maxilla and mandible. Some families have had affected members with involvement of the kidneys, variously reported as Wilms tumors, nephroblastomas, and hamartomas. The HPT-JT gene (HRPT2) maps to chromosome 1q25-q31. We describe further investigation of two HPT-JT families (K3304 and K3349) identified through the literature. These two expanded families and two previously reported families were investigated jointly for linkage with 21 new, closely linked markers. Multipoint linkage analysis resulted in a maximum LOD score of 7.83 (at recombination fraction 0) for markers D1S2848-D1S191. Recombination events in these families reduced the HRPT2 region to approximately 14.7 cM. In addition, two of these four study families (i.e., K3304 and K11687) share a 2.2-cM length of their (expanded) affected haplotype, indicating a possible common origin. Combining the linkage data and shared-haplotype data, we propose a 0.7-cM candidate region for HRPT2.

Oncogene profile of papillary thyroid carcinoma.

BACKGROUND: Our purpose was to study the expression of multiple oncogenes in papillary thyroid cancer for possible interactions and prognostic significance. METHODS: Twenty papillary thyroid carcinomas were studied for expression/mutation of 3 oncogenes: ras, ret/PTC, and erbB-2/neu. H, N, and K ras codons were examined by polymerase chain reaction (PCR), single-stranded conformation polymorphism, and sequencing. The thyroid oncogene ret/PTC was identified by reverse transcription (RT)-PCR. Gene amplification of erbB-2/neu was analyzed by differential PCR. The transmembrane domain of erbB-2/neu was sequenced for activating mutations. Quantitation of erbB-2/neu mRNA was evaluated by competitive RT-PCR, and protein expression was determined by immunohistochemistry. RESULTS: Among 20 tumors, 3 had insular/anaplastic dedifferentiation, 13 were intrathyroidal, and 7 were metastatic to cervical lymph nodes (6) or lung (1). An H-ras 13 mutation was found in 1 metastatic tumor and an N-ras 61 mutation in 1 intrathyroidal tumor. ret/PTC was identified in 3 intrathyroidal and 5 metastatic tumors. No erbB-2/neu DNA amplification or mutations were identified, although 4 tumors had elevated erbB-2/neu mRNA levels. Three of 20 patients had abnormalities detected in multiple oncogenes; 2 had elevated erbB-2/neu mRNA and ret/PTC rearrangements, and 1 of these had pulmonary metastasis. An intrathyroidal papillary cancer had an N61 ras mutation and a ret/PTC gene rearrangement. CONCLUSIONS: ret/PTC rearrangements are present in 40% of papillary thyroid carcinomas and may play a role in metastatic behavior. In contrast, ras mutations are rare (10%). erbB-2/neu gene amplification and activating mutations are not detected, although elevated mRNA levels were found in 20% of papillary carcinomas. The lack of correlation among the 3 oncogenes in 17 of 20 (85%) papillary thyroid carcinomas suggests that they were not cumulative factors in the pathogenesis of these tumors.

Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia.

Rearrangements involving the RET protooncogene have been implicated in the development of papillary thyroid carcinoma (PC). Transgenic mice, expressing thyroid-targeted RET/PTC-1, develop PC; but the clinical significance of this oncogene remains uncertain. We examined the expression of RET/PTC-1, -2, and -3 in human thyroid microcarcinomas and clinically evident PC to determine its role in early stage vs. developed PC and to examine the diversity of RET/PTC in multifocal disease. RNA was extracted from paraffin-embedded microcarcinomas and clinically evident PCs; the results obtained from paraffin-embedded tissue were confirmed on RNA from corresponding snap-frozen tissue of clinically evident PCs. RT and PCR was performed using primers for RET/PTC-1, -2, and -3; PGK-1 (the housekeeping gene) analysis was used to ensure integrity of the RNA and efficiency of the RT reaction. PCR products were resolved by gel electrophoresis, and Southern hybridization was performed with RET/PTC-1, -2, and -3 probes. A polyclonal antibody to the carboxyterminus of RET was used for immunohistochemistry on paraffin sections. Thirty-nine occult papillary thyroid microcarcinomas from 21 patients were analyzed. Of the 30 tumors (77%) positive for RET/PTC rearrangements, 12 were positive for RET/PTC-1, 3 for RET/ PTC-2, 6 for RET/PTC-3, and 9 for multiple RET/PTC oncogenes. In clinically evident tumors, 47% had RET/PTC rearrangements. Immunohistochemistry demonstrated close correlation with RT-PCR-derived findings. RET/PTC expression is highly prevalent in microcarcinoma and occurs more frequently than in clinically evident PC (P < 0.005). Multifocal disease, identified in 17 of the 21 patients, exhibited identical RET/PTC rearrangements within multiple tumors in only 2 patients; the other 15 patients had diverse rearrangements in individual tumors. Our results indicate that RET/PTC oncogene rearrangements may play a role in early-stage papillary thyroid carcinogenesis, but they seem to be less important in determining progression to clinically-evident disease. In multifocal disease, the diversity of RET/PTC profiles, in the majority of cases, suggests that individual tumors arise independently in a background of genetic or environmental susceptibility.

Cytoplasmic staining of erbB-2 but not mRNA levels correlates with differentiation in human thyroid neoplasia.

OBJECTIVE: Amplification and overexpression of the erbB-2 proto-oncogene in human carcinomas may have prognostic significance. Its role in thyroid carcinoma is controversial. We investigated human thyroid tumours for erbB-2 gene amplification, activating mutations in the transmembrane domain, quantitative mRNA expression and protein expression. MATERIALS AND METHODS: DNA and mRNA were extracted from 47 morphologically characterized, frozen thyroid tumours including 10 nodular hyperplasias, 3 follicular carcinomas and 34 papillary carcinomas (4 with tall-cell features, 2 with insular and 2 with anaplastic de-differentiation). DNA amplification was analysed by differential PCR. The transmembrane domain of erbB-2 was sequenced in all tumours for activating mutations in position 659. Levels of mRNA expression were determined by competitive mRNA RT-PCR. Immunohistochemistry (IHC) for erbB-2 protein expression in corresponding paraffin-embedded samples was evaluated. RESULTS: Our results showed no DNA amplification of erbB-2. Sequencing of the transmembrane domain of erbB-2 revealed no activating mutations. The level of mRNA expression was variable, 11 papillary carcinomas showing statistically significant elevated mRNA levels compared with corresponding normal thyroid tissue; however, this did not correlate with other indicators of poor prognosis. In contrast to elevated mRNA levels in tumours, the level of protein staining correlated with degree of differentiation, normal and hyperplastic tissue being strongly positive and poorly differentiated tumours negative. CONCLUSION: There are no mutations or amplifications of the erbB-2 gene in human thyroid tumours. Elevated erbB-2 mRNA expression in some thyroid tumours is not associated with clinical features of poor prognosis; however, the significance of the elevated mRNA levels is unclear, as it did not result in protein overexpression. Instead, cytoplasmic erbB-2 protein detection by IHC correlates with differentiation of human thyroid tumours and may be a feature of good prognosis.

Prognostic features in tall cell papillary carcinoma and insular thyroid carcinoma.

Tall cell papillary carcinoma (TCPC) and insular carcinoma (IC) are variants of thyroid carcinoma that are considered to be more aggressive than well differentiated papillary or follicular carcinoma. To determine the clinical significance of these diagnoses, we evaluated 65 patients with these tumors. There were 30 TCPCs, 27 ICs, and 8 ICs or TCPCs with focal anaplastic carcinoma (FAC). Forty-two patients (27 TCPCs, 14 ICs, and 1 FAC) are alive and free of disease. Nine patients with IC are alive with distant metastases. Ten patients (2 TCPCs, 2 ICs, and 7 FACs) died of disease. Univariate analysis of disease-free interval determined that, as for all thyroid carcinomas, patient age, tumor size, extrathyroidal extension, and lymph node metastases were significant for prognosis. ICs did significantly worse than TCPCs. Focal anaplastic dedifferentiation predicted a worse prognosis. Multivariate analysis for disease-free interval showed age, number of lymph node metastases, and tumor type to be significant. Analysis of the same factors for prediction of mortality showed that TCPC and IC were not significantly different. These data suggest that TCPC is less aggressive than IC, which often results in disseminated disease. Focal AC predicts poor survival.

Evaluation of single isotope technetium 99M-sestamibi in localization efficiency for hyperparathyroidism.

BACKGROUND: Regardless of surgical effectiveness, ongoing activity in parathyroid localization in hyperparathyroidism (HPT) is an established enterprise. Sestamibi (MIBI), the most recent new modality, is being assessed in this regard. METHODS: Twenty mCI of 99 TC Sestamibi was administered intravenously in patients with prospective HPT. Images were assessed by pinhole and full-field gamma camera at 20 minutes and 2 hours. Dual-phase one isotope only was utilized. Patients were then studied for pathology and MIBI correlation. RESULTS: Sixty-three cases underwent MIBI scanning, 50, or 79%, of which were due to a single adenoma. Sensitivity showed in 41 of 50 adenomas and was 82% correct. Quadrant localization was 97%. Eleven patients showed hyperplasia with MIBI sensitivity of 82% on a case basis but only 31% for multiglandular disease. Overall MIBI sensitivity is 80%. One false-positive and one true-negative case were observed. All patients achieved eucalcemia. No operative morbidity of significance occurred. CONCLUSION: Scanning with 99M Sestamibi dual-phase technique is the preferred mode of parathyroid localization in current practice. It is of assistance in primary HPT, essential in recurrent HPT, and of use in ectopic gland detection. It can support surgical intervention in the marginal HPT patient. Scanning still requires bilateral exploration for complete assessment.

ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential?

The ret/PTC oncogene is unique to papillary thyroid cancer. Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene, result in constitutive kinase activation. Correlation with clinical outcome is controversial; ret/PTC-1 has been suggested to predict aggressive behavior. There is no morphological description of ret/PTC-positive tumors. We analyzed 60 thyroid carcinomas for ret/PTC expression to determine correlation with clinical history, disease stage, or tumor morphology. Ribonucleic acid extracted from frozen tissue was reverse transcribed; PCR was performed to amplify ret/PTC-1, 2, and -3. The TPC-1 cell line was the positive control for ret/PTC-1. All tumors were characterized morphologically. Clinical data were collected. The 57 papillary and 3 follicular carcinomas were resected from 44 female patients and 15 males. The average age at diagnosis was 46.2 yr (range. 24-83 yr). Three patients had a history of neck irradiation. At diagnosis, 11 patients had extrathyroidal tumor extension, 20 had lymph node metastases, and 1 had lung metastasis. Thirteen patients had tall cell papillary carcinomas; 3 tumors had focal insular or anaplastic dedifferentiation. The average follow-up was 13.4 months, during which 4 patients had recurrent disease. No deaths occurred. One papillary carcinoma (1.7%) was positive for ret/PTC-1, none was positive for ret/PTC-2, and 2(3.4%) were positive for ret/PTC-3. Although all 3 patients who had tumors containing ret/PTC rearrangements were under the age of 45 yr (range, 26-44 yr) and had small tumors (< 1.2 cm), 2 of these 3 patients presented with lymph node metastases, and the third had lymphatic invasion. ret/PTC oncogene expression did not correlate with radiation history. In summary, ret/PTC oncogene rearrangements were found in 3 of 60 (5%) thyroid carcinomas and were not present in tumors with aggressive morphological features. However, we found ret/PTC rearrangements in young patients (< 45 yr of age) with small thyroid carcinomas showing a predisposition for lymphatic involvement, suggesting a possible role in the development of this subgroup of tumors.

Occult micropapillary carcinoma associated with benign follicular thyroid disease and unrelated thyroid neoplasms.

Surgically resected thyroids from 425 patients with thyroid disease other than carcinoma of follicular cell derivation were thoroughly examined for occult micropapillary carcinoma (MPC). There were 317 cases of nodular hyperplasia, 36 of thyroiditis, 44 follicular adenomas, and 28 others. Glands were sectioned at 2- to 3-mm intervals and fixed in formalin. Every section was examined histologically. There were 71 cases (16.7%) of MPC containing 118 tumors. Among 343 women, 51 (14.9%) had MPC; among 82 men, 20 (24.4%) had MPC. The average age of all of the patients was 46.9 years and of those with MPC, 50.5 years. The occurrence of MPC peaked between 40 and 70 years and declined in older patients. MPC was found in 8.9% of patients who underwent lobectomies, 10.8% who had hemithyroidectomies, and 24.1% of those who had total thyroidectomies. Logistic regression analysis revealed significant associations between the presence of MPC and the patient sex, age, and extent of surgery; in contrast, there was no association between the occurrence of MPC and the underlying thyroid disease. These data indicate that MPC is present in up to 24.1% of thyroids removed for unrelated thyroid disease. The predominance of this lesion in men is in striking contrast to the occurrence of clinically significant thyroid cancer. This suggests that the initiation of carcinogenesis is not sexually dimorphic, whereas promoters of tumor growth are. A rational management of this common disease awaits the results of careful controlled trials.

Dr. Norman Bethune as a surgeon.

Dr. Norman Bethune's recognition as a Canadian of renown resulted from his devoted work in China during the late 1930s. He had received a general surgical training, but his personal illness with tuberculosis led him to specialize in thoracic surgery. A surgical program at McGill University under Dr. Edward Archibald, a pioneer thoracic surgeon, was initially successful, but by the mid-1930s Bethune was rejected by McGill and Dr. Archibald. He became chief of thoracic surgery at the Hôpital du Sacré-Coeur outside Montreal. H developed thoracic surgical instruments and wrote numerous scientific papers. The outbreak of civil war in Spain in 1937 attracted Bethune to oppose what he viewed as fascist aggression. He went to Spain, where he established the value of mobile blood banking. On his return to Canada in 1937 he became aware of the escalating war between China and Japan. He joined the Chinese communist forces in northern China and spent 18 months doing Herculean mobile war surgery, while improving the state of medical services in primitive, depressing conditions. He died in 1939 at the age of 49 years of septicemia as a result of accidental laceration of his finger during surgery. The Chinese have venerated Norman Bethune and stimulated his memorialization in Canada. His surgical record can be viewed as mixed in quality, but overall his performance remains impressive for its achievement.

Management of the hot thyroid nodule.

BACKGROUND: Solitary hyperfunctioning nodules of the thyroid gland are usually viewed as benign. They may present with autonomous euthyroidism but are of concern for potential progression to hyperthyroidism. Various methods of treatment are worthy of consideration. PATIENTS AND METHODS: Forty-five patients with solitary hot thyroid nodules verified by radioisotope scintiscanning were selected for treatment. Thirty-one underwent surgery, usually partial thyroidectomy. Eight euthyroid patients received no treatment, 5 underwent therapy with radioactive iodine (RAI), and 1 received thyroid suppression treatment. The cases were assessed retrospectively. RESULTS: Thyroidectomy patients had no morbidity, were well, and showed 1 Hürthle cell tumor and 5 coincidental small malignancies associated with benign hot nodules, including a contralateral cancer. Untreated patients showed continuance of good health, but nodules persisted and 1 Graves' orbititis occurred. The RAI-treated patients had persistent nodularity, improved function, and 1 case of hyperparathyroidism. Thyroid feeding only caused iatrogenic toxicity and was discontinued. CONCLUSIONS: There are various techniques for managing the hot nodule. Nonsurgical methods may be effective, but can result in persistent nodularity and iatrogenic sequelae. Excision had no morbidity in this series and was effective in providing immediate relief of problems present and potential.

Management considerations in Hürthle cell carcinoma.

BACKGROUND: Hürthle cell tumors still pose issues concerning diagnosis and management. METHODS: From 1984 to 1993 forty-seven patients underwent thyroidectomy, and they were diagnosed after operation to have presumptive Hürthle cell tumors. The surgical pathologic findings were reviewed. In the neoplastic group the chart was reviewed for clinical features and outcome. RESULTS: Thirty-one patients had nonneoplastic Hürthle cell nodules. Eleven (69%) of the 16 tumors were malignant affecting 11 women and five men ranging in age from 22 to 86 years. Two patients died of cancer for a 18% rate; one patient is alive with disease. Operations were uncomplicated. Factors for adverse outcome include tumor size greater than 4 cm, woman older than 60 years of age, and complete capsular invasion on surgical pathologic findings. CONCLUSIONS: Fine-needle aspiration biopsy demonstration of Hürthle cell lesion is an indication for operation, providing Hashimoto's thyroiditis is excluded. Our surgical practice (I.B.R.) is to perform total thyroidectomy for all Hürthle cell neoplasms, as well as jugular node sampling and adjuvant radioiodine for cancer. Stringent histologic interpretation is possible and necessary for true appreciation of Hürthle cell tumor incidence and behavior. Cancer mortality of 18% is greater than the rate (2%) of our well-differentiated thyroid cancer group.

Adverse aspects of small thyroid cancer and need for treatment.

BACKGROUND: Small, well-differentiated thyroid cancer (tumor < 1.5 cm) is frequently dismissed as biologically inconsequential, although varied reports have offered differing experiences. METHODS: A total of 382 thyroid cancer patients were reviewed. Of these, 99 patients had tumors that were < or = 1.5 cm. Thirty-five patients in this group with positive nodes, extrathyroidal invasion, or metastatic disease were studied. RESULTS: Thirty-five patients (one-third of the < 1.5 cm group) showed other sites of involvement: nodes, 28; lung, 1; muscle, 7; nerve, 5; and bone, 2. Six patients had residual cancer following surgery. Surgery included thyroidectomy and neck dissection as well as orthopedic procedures for metastatic bone disease. Radioiodine ablation was used in 33 patients, external radiation in 5. Thirty-one patients are well without disease, 3 are alive with disease, 1 died of disease. CONCLUSIONS: Small, well-differentiated thyroid cancer is infrequently aggressive, but it may be a source for metastatic morbidity and recurrence and can be viewed as potentially lethal. Need for treatment should not be ignored based solely on the size of the tumor.

Congenital thyroid hemiagenesis.

Failure of embryologic development of a lobe of the thyroid gland is a rare anomaly. In order to characterize this unusual entity, we report our experience in seven patients with thyroid hemiagenesis involving the left lobe in five and the right lobe in two patients. The diagnosis was made as a result of evaluation and treatment of a thyroid nodule (4), diffuse thyroid enlargement with thyrotoxicosis (2), and a simple goiter in a patient with a prior history of radiation treatment for facial acne. In five patients thyroid scintigraphy demonstrated unilateral absence of function, four of whom had an ultrasound exam of the neck that revealed a corresponding absence of thyroid tissue. In one patient the diagnosis was made incidentally on a screening ultrasound exam of the neck. Thyroid hemiagenesis was unsuspected preoperatively in one patient with Graves' disease because of marked hyperplasia of a single thyroid lobe and isthmus. Thyroid hemiagenesis was confirmed in four patients who underwent thyroidectomy. The presence of a thyroid isthmus was established in six patients. Postoperatively, all patients were treated with thyroid hormone. Associated thyroid pathology included adenoma (1), follicular carcinoma (1), colloid nodule (2), Graves' disease (2), and a simple goiter (1). In conclusion, the diagnosis of thyroid hemiagenesis should be considered in any patient with unilateral absence of function on thyroid scintigraphy and confirmed by ultrasonography. Recognition of this rare congenital anomaly is important to avoid unnecessary contralateral neck exploration with its potential morbidity and to insure that all patients receive careful follow-up and appropriate thyroid hormone therapy when necessary.

Secondary malignancy of the thyroid gland and its management.

BACKGROUND: Secondary cancer of the thyroid gland is widely acknowledged as infrequent but is a persistent problem requiring ongoing awareness, particularly with respect to clinical recognition and treatment. METHODS: From 1978 to 1993, a 15-year period, patients demonstrating secondary involvement of the thyroid gland as a surgical problem were collected and analyzed with regard to pathology, demography, behavior of primary and secondary disease, treatment, and patient outcome. RESULTS: In the 15-year span, 11 patients with secondary involvement of the thyroid gland were recognized, consisting of 3 men and 8 women with primary lesions occurring in oral cavity, esophagus, stomach, colon, pancreas, breast, skin, unknown, kidney, and lung. Needle biopsy produced a 90% malignancy rate but in only half of such cases was the diagnosis specific for secondary malignancy. Eight of 11 underwent palliative surgery, usually total thyroidectomy. No patient survived > 2 years. There was no undue surgical morbidity. One patient died of pulmonary embolus postoperatively. CONCLUSIONS: Secondary cancer of the thyroid is rare and can be detected by fine-needle aspiration biopsy in the face of clinical findings. Where indicated, palliative thyroidectomy can be effective, because other methods of treatment appear ineffective.