Medullary thyroid carcinoma: prognosis of familial versus sporadic disease and the role of radiotherapy.

A retrospective study of 202 patients with medullary thyroid carcinoma (MTC) diagnosed between 1943 and 1987 was done to compare the prognosis of patients with sporadic disease and those with the familial form of multiple endocrine neoplasia type II and to study the effect of radiotherapy. Patients with multiple endocrine neoplasia type II had a significantly higher survival rate than did patients with the sporadic variety (P less than 0.005), but most patients with sporadic tumors were older and had more advanced disease. No differences in survival rates were found when patients from these 2 groups were matched for age and involvement of the thyroid gland only (P greater than 0.3), involvement of the thyroid gland plus cervical nodes (P greater than 0.3), and involvement of the thyroid gland, cervical nodes, and soft tissue (P greater than 0.7). When patients with MTC who received radiotherapy were matched for age, extent of disease, and surgery with patients who had had no radiotherapy, the latter group was found to live significantly longer (P less than 0.05). We conclude that 1) the apparently poor prognosis of patients with the sporadic variety of MTC may be related to the patients' older age at detection rather than to inherent differences in the two forms of disease, and 2) radiotherapy has little effect on MTC.

A comparison of thyroid carcinoma in those who have and have not had head and neck irradiation in childhood.

Among 1324 patients with well differentiated (papillary, follicular, Hurthle cell) thyroid carcinoma treated at the University of Texas M. D. Anderson Hospital and Tumor Institute between January 1950 and July 1984, 125 had a history of external irradiation to the head and neck region during childhood. This study was a comparison of the characteristics and disease course of thyroid carcinoma in these patients with those of patients who had not received such irradiation. Each irradiated patient was matched to 3 nonirradiated patients by age, sex, and extent of disease. The groups had similar distributions of histological type of lesion, surgical procedures, and number of patients who received radioactive iodine as part of their initial treatment. The two groups' recurrence and mortality rates were similar as well, although patients who had head and neck irradiation as children more often presented with thyroid cancer not limited to the thyroid gland and bilateral thyroid lobe involvement (P less than 0.005). The data indicate that patients who received head and neck irradiation have, at the time of diagnosis, more extensive thyroid carcinoma. However, the prognosis of well differentiated thyroid carcinoma in patients who have a history of head and neck irradiation is similar to that in patients without such a history.

The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients.

This study analyzed the impact of prognostic variables of age, sex, histopathological diagnosis, extent of disease at diagnosis, and surgical intervention on well differentiated thyroid carcinoma and how surgical treatment, radioactive iodine, and radiotherapy influence the patients' outcomes. There have been 1599 patients with well differentiated thyroid cancer treated and followed at the University of Texas M.D. Anderson Cancer Center from 1948 to 1989. The median follow-up for all patients was 11.0 yr, with the maximum follow-up being 43 yr and the minimum follow-up being 1 yr. The patients were predominantly female (2.3:1), with papillary (81%) and intrathyroidal carcinomas (42%) at the time of diagnosis. Sixty-six percent of the patients had a total thyroidectomy, 7% received external radiotherapy, and 46% had radioactive iodine as part of the treatment of the original disease; the overall recurrence rate was 23%, and the death rate was 11%. This study showed that treatment with radioactive iodine was the single most powerful prognostic indicator for increased disease-free interval (P less than 0.001) and that its use significantly increased survival as well. No benefit was obtained from treatment with external radiotherapy. Children had the best overall survival, but of the adult patients, females who had intrathyroidal papillary disease treated with total thyroidectomy, who had been given radioactive iodine, and whose disease had been diagnosed between 20-59 yr of age had the best prognosis.

Impact of therapy for differentiated carcinoma of the thyroid: an analysis of 706 cases.

A retrospective analysis of clinical and pathological data was conducted on 706 patients (514 females and 192 males) treated for differentiated thyroid carcinoma at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston from 1951 to 1975 and followed to 1981. The histological diagnoses were mixed papillary/follicular carcinoma (66.7%), papillary carcinoma (14.6%), follicular carcinoma (15.3%), or Hurthle cell carcinoma (3.4%). Patients diagnosed before the age of 40 yr lived significantly longer than those diagnosed over the age of 40 yr, and females lived longer than males. According to survival analyses and disease-free intervals, the order of increasing aggressiveness of the tumors was papillary, mixed, follicular, and Hurthle cell. Total thyroidectomy was associated with longer disease-free intervals and fewer recurrences. The 136 patients who received ablative 131I after surgery had fewer recurrences than a matched group who did not, but the disease-free interval and survival rate showed no significant difference. Further classification showed that patients with follicular and mixed tumors, and those who underwent total thyroidectomy benefited from 131I. There were 78 deaths attributed to thyroid cancer in the whole group. Approximately two thirds occurred in the first 10 yr after diagnosis. In conclusion, total thyroidectomy is recommended, when feasible, for differentiated thyroid cancer, followed by ablative 131I therapy, at least for follicular and mixed varieties.

Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients.

The natural history and prognostic factors of medullary carcinoma of the thyroid (MCT) were studied in 161 patients seen at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1944 and 1983. One hundred twenty-five patients (77.6%) had the sporadic variety of MCT, 31 patients (19.3%) had multiple endocrine neoplasm (MEN) type IIa and 5 patients (3.1%) had MEN-IIb. The disease occurred equally in both sexes (M:F ratio 1:1.05). Thyroid nodules were the most common presenting feature especially in patients with the sporadic disease and MEN-IIb. Fifteen patients with MEN-IIa had occult MCT; the diagnosis was made through screening of family members with calcitonin measurement before and after stimulation with calcium or pentagastrin. Sixteen patients with MEN-II had pheochromocytoma and 7 had hyperparathyroidism. Total thyroidectomy was the most commonly performed operation. The lowest incidence of recurrence occurred in patients who underwent total thyroidectomy and modified neck dissection. Radioactive 131I was used as adjunct to surgery in 19 patients but it did not improve the survival or lower the incidence of recurrence. Patients who received postoperative radiotherapy had significantly lower adjusted survival rates than those treated by surgery alone, but we tended to irradiate patients with more advanced disease. Chemotherapy was administered to 11 patients with disseminated metastases but the response was poor. The 5- and 10-year adjusted survival rates of all the patients with MCT were 78.2% and 61.4%, respectively. Patients with MEN-IIa had much better rates than patients with sporadic disease (p = 0.0005), who were 7.74 times more likely to die of MCT. The stage of the disease at presentation was a major prognostic factor. Patients with stages III or IV disease were 7.31 times more likely to die of MCT than those with stages I or II. There was no significant difference in survival between patients with stages I and II or III and IV. The presence of cervical lymph node metastases did not affect the survival adversely. Direct extension with involvement of tissue was a bad prognostic sign. Patients younger than 40 years old at the time of diagnosis of MCT had a significantly better adjusted survival rate than those who were older. Women had a better prognosis than men, who were 1.89 times more likely to die of MCT. Diarrhea was a bad prognostic sign. However, it occurred more frequently in patients with advanced stages of the disease and larger tumor mass.(ABSTRACT TRUNCATED AT 400 WORDS)

Intrapericardial pheochromocytoma.

A patient with intrapericardial pheochromocytoma is described, and the literature on this subject is reviewed. Iodine 131-labeled metaiodobenzylguanidine scintigraphy was superior to computed tomography in localizing the tumor. This newly introduced method is safe, specific, noninvasive, and may prove to be the method of choice for localizing pheochromocytomas. The patient was prepared for surgery with alpha- and beta-adrenoceptor blocking agents. The tumor was markedly adherent to the posterior wall of the left and right atria. Cardiopulmonary bypass was used to allow excision of the tumor. Hemostasis was attained with difficulty due to marked vascularity of the tumor.

Immunoperoxidase study of uncommon parathyroid tumors. Report of two cases of nonfunctioning parathyroid carcinoma and one intrathyroid parathyroid tumor-producing amyloid.

Nonfunctioning carcinomas of the parathyroid gland are rare and difficult to diagnose. They are often confused with thyroid tumors or with metastasis from other sites. We report two cases of nonfunctioning parathyroid carcinomas; one was originally diagnosed as follicular carcinoma of the thyroid gland. The immunohistochemical demonstration of parathormone in the tumor cells established the parathyroid origin of these neoplasms. An intrathyroid parathyroid tumor, associated with large amounts of interstitial amyloid, mimicking medullary carcinoma of the thyroid, in a patient with primary hyperparathyroidism is also reported. Positive immunoreaction in the tumor cells for parathormone, negative staining for calcitonin, and the return of patients' serum calcium levels to normal after tumor resection, confirmed the parathyroid nature of this neoplasm. Immunohistochemistry studies proved to be extremely helpful in establishing the diagnoses of these unusual parathyroid tumors.

Adrenal medullary disease in multiple endocrine neoplasia type 2. Appropriate management.

This article discusses screening for pheochromocytoma and timing of surgery, unilateral versus bilateral adrenalectomy. Anterior, posterior, and laparoscopic operative techniques are reviewed also.

Comparison of HMB-45 monoclonal antibody and S-100 protein in the immunohistochemical diagnosis of melanoma.

The value of HMB-45 mouse monoclonal antibody in the immunohistochemical diagnosis of melanoma was compared with that of two antibodies to S-100 protein. Tissue from 32 (91.4%) of the 35 melanomas studied reacted with HMB-45, however, none of the 98 nonmelanoma tumors stained with this antibody. In contrast, 31 (88.5%) melanomas and 24 (24.4%) of the nonmelanoma neoplasms expressed S-100 protein. These results indicated that HMB-45 monoclonal antibody has a higher specificity for melanoma cells than did S-100 protein and that, because of its reactivity in routinely processed tissues, it may be helpful in surgical pathology.

Functioning oxyphil cell adenomas of parathyroid gland: immunoperoxidase evidence of hormonal activity in oxyphil cells.

Functional oxyphil adenomas of parathyroid gland are rare. Several studies have suggested that these tumors consist of a mixed cell population and that the transitional oxyphil cells and/or chief cells are the main source of parathormone, while the fully developed oxyphil cells have minimal or no hormonal activity. This report describes light, ultrastructural, and immunocytochemical features of six parathyroid adenomas, and confirms that these neoplasms are composed of a mixed cell population. It also demonstrates that the oxyphil cells have strong hormonal activity and therefore can play a significant role in the pathogenesis of hyperparathyroidism.

Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases.

To study the histogenesis of and determine the most useful markers for diagnosing anaplastic thyroid carcinoma (ATC), 32 cases, including 2 with numerous osteoclast-like cells, were stained with a battery of antibodies to epithelial (keratin, epithelial membrane antigen [EMA], carcinoembryonic antigen [CEA]), mesenchymal (vimentin, desmin, muscle-specific actin [MSA], Factor VIII-related antigen [FVIII:RAg]), endocrine (thyroglobulin, calcitonin, chromogranin [Cg]), lymphocytic (leukocyte common antigen [LCA]), histiocytic (alpha-1-antitrypsin [alpha 1AT], alpha-1-antichymotrypsin [alpha 1AChy], KP1), melanocytic (HMB-45), and Schwann cell (S-100 protein) markers. Five tumors were associated with papillary carcinoma. In one of these cases, a morphologic continuum between the well-differentiated carcinoma and the ATC was visualized by their positive immunostaining for both vimentin and keratin, thus supporting the hypothesis that the latter tumor originated from the former. Twenty-five (78.1%) tumors expressed keratin, 10 (31.3%) reacted for EMA, and 3 (9.4%) expressed CEA, confirming the epithelial nature of this neoplasm. Reactivity for thyroglobulin was seen in a small number of cells in five (15.6%) thyroglobulin was seen in a small number of cells in five (15.6%) ATCs. Because all of the cases that expressed keratin also stained positively for EMA, CEA, or thyroglobulin, it is believed that keratin is the most useful epithelial marker for diagnosis of ATC. A lack of reactivity for calcitonin and Cg indicates that these tumors are not derived from C cells, as has been proposed by some authors. Reactivity for KP1 (CD68), a monoclonal antibody that reacts with a macrophage-associated antigen, occurred in the osteoclast-like cells but not in the anaplastic tumor cells. This finding, together with negative keratin staining of the osteoclast-like cells, indicates that these cells are not epithelial in nature and therefore should be considered reactive rather than neoplastic. Thirty tumors (93.8%) expressed vimentin, 15 (46.9%) marked for alpha 1AChy, 11 (34.4%) exhibited alpha 1AT, and 11 (34.4%) expressed S-100 protein. Because all of these markers can be seen in a wide variety of tumors of different histogeneses, they have no value in the diagnosis of ATC. Although immunostaining for FVIII:RAg, desmin, and MSA was negative in all of these tumors, these markers can help to differentiate between ATCs and some soft tissue sarcomas with which they can be confused.

Indeterminate fine-needle aspiration biopsy of the thyroid: identification of subgroups at high risk for invasive carcinoma.

BACKGROUND: We examined the various cytologic features of indeterminate thyroid fine-needle aspirates along with known clinical and radiologic risk factors to determine whether any parameters were predictive of malignancy. METHODS: Indeterminate fine-needle aspirates were prospectively categorized into four subgroups: (1) suspicious for papillary carcinoma, (2) follicular neoplasm, (3) Hürthle cell neoplasm, and (4) hypercellular follicular aspirates with colloid. Several clinical risk factors were examined, and subgroup comparisons were performed with Fisher's exact test. RESULTS: Of 571 fine-needle aspirate cytologic findings 104 were interpreted as indeterminate for malignancy, and 81 patients underwent thyroidectomy. Invasive cancer was diagnosed in 9 of 10 lesions cytologically suspicious for papillary carcinoma, 8 of 43 follicular neoplasms, 5 of 18 Hürthle cell neoplasms, and 0 of 10 hypercellular aspirates. Cytologic subgroup (p < 0.0001) and age of 50 years or older (p = 0.008) were the only significant predictors of malignancy. When used together, age of 50 years or older and a cytologic diagnosis of follicular or Hürthle cell neoplasm also identified a subgroup of patients at high risk (9 of 20) of invasive malignancy (p = 0.01). CONCLUSIONS: The majority of invasive cancers (18 of 22, 82%) were found in patients whose lesions were suspicious for papillary carcinoma or in patients 50 years or older with follicular or Hürthle cell neoplasms. The risk of carcinoma in these combined subgroups (18 of 30, 60%) warrants early surgical intervention.

Thyroglossal duct carcinoma.

Thyroglossal cysts are common developmental abnormalities of the thyroid gland. The malignant form of these cysts, however, is extremely rare, with fewer than 100 cases reported since 1915. Here we add 10 cases of malignant thyroglossal cysts, nine women and one man, encountered at M.D. Anderson Cancer Center, based on a retrospective review of 51 recorded cases of thyroglossal cysts between 1950 and 1990. All 10 patients underwent a primary Sistrunk procedure. Histologic findings showed nine papillary and one follicular carcinoma. Based on review of the histopathologic material, four patients required no additional therapy. Five patients underwent total thyroidectomy; three of the five also underwent neck dissection. A single microscopic focus of carcinoma in the thyroid gland was found in only two instances. No evidence of nodal metastases was found. One patient with an abnormal thyroid scan is awaiting further treatment. Based on these findings, the Sistrunk procedure is an effective form of therapy for malignant thyrogloassal cysts.

Cortical-sparing adrenalectomy for patients with bilateral pheochromocytoma.

BACKGROUND: Bilateral pheochromocytomas are common in patients with multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau disease (VHL). In an effort to avoid long-term steroid dependence and Addisonian crisis, we have performed cortical-sparing adrenalectomy in this patient population. METHODS: Retrospective chart review was completed for patients with MEN 2- or VHL-related pheochromocytomas who underwent laparotomy at our institution for intended cortical-sparing adrenalectomy between June 1965 and March 1995. RESULTS: Fifteen patients (MEN 2A [10], MEN 2B [2], VHL [3]) underwent laparotomy for cortical-sparing adrenalectomy. None of the tumors were malignant. Cortical-sparing adrenalectomy was possible in 14 (93%). Thirteen of these 14 patients (93%) had normal postoperative plasma cortisol measurements and did not require steroid hormone supplementation. At a median follow-up of 138 months, two patients had died of metastatic medullary thyroid cancer, no patient had suffered Addisonian crisis, and three patients (21%) had recurrent pheochromocytomas (at 118, 176, and 324 months after operation). The remaining nine patients were alive without pheochromocytomas. CONCLUSIONS: Cortical-sparing adrenalectomy can be performed successfully in MEN 2 or VHL patients with bilateral pheochromocytomas, avoiding chronic steroid hormone replacement and the risk of Addisonian crisis in most patients. Long-term follow-up is necessary because recurrence may develop many years after operation.

Parathyroid carcinoma: features and difficulties in diagnosis and management.

The objective of this review was to study the clinical course and the applicable diagnostic criteria in 12 patients with functioning parathyroid carcinoma, two patients with nonfunctioning parathyroid carcinoma, and a fifteenth patient who had an atypical intrathyroid tumor. The biologic patterns fell into four groups. The patients with functioning parathyroid carcinoma had either a prolonged tumor existence punctuated by hypercalcemic episodes ameliorated by operation to remove the tumor or an aggressive course with widespread metastases. The nonfunctioning cancers were aggressive cancers. The fourth group had one patient (others could have been considered) in whom a definitive diagnosis could not be made. The initial recognition of this cancer is sometimes difficult because consistent diagnostic features, either clinically or pathologically, are lacking. Enbloc resection at the first operation remains the best chance for cure. Surgical resection of recurrent disease appears to be the most effective palliative approach. Death results from hypercalcemia rather than from organ replacement by tumor.

Clinicopathologic and flow cytometric DNA study of medullary thyroid carcinoma.

Sixty-one patients with medullary thyroid carcinoma were investigated to establish relationships between the neoplasm's DNA content, other clinicopathologic factors, and patient survival (at least 5 years' follow-up). There were 26 (42.6%) familial and 35 (57.4%) sporadic carcinomas. Forty-two neoplasms (68.8%) were diploid and 19 (31.2%) were aneuploid by flow cytometric assessment. In univariate analysis, age, hereditary background, DNA content, calcitonin immunoreactivity, and type of surgery were strong predictors of clinical outcomes. In multivariate regression analysis, none of these factors was an independent prognosticator. Patients' gender, clinical stage, histologic subtype, and amyloid content of the tumor did not influence survival.

Hypercalcemia in patients with known malignent disease.

In 82 patients, a preoperative diagnosis of primary hyperparathyroidism has been established by means of transfemoral neck vein catheterization and measurement of serum immunoreactive parathyroid hormone (iPTH). Twenty-five of these patients have had cancer in other parts of the body but with no evidence of recurrence or metastasis. One patient had carcinoma of the colon with metastases, and four were members of families with multiple endocrine adenomatosis (MEA, Types I and II). In six other hypercalcemic patients, high levels of iPTH were found also in the effluent blood from cancer sites other than the parathyroid gland, secondary to ectopic hormone production or pseudohyperparathyroidism. In addition, a high serum level of iPTH was found in the superior vena cava of a seventh patient who had carcinoma of the breast but no clinical or radiological signs of recurrence or metastasis with the exception of an enlarged liver. This iPTH finding was interpreted as being, probably, the result of parathyroid adenoma in either the neck or the mediastinum. At the time of operation, a transcervical mediastinal search was made. Four normal cervical parathyroid glands were found; three were removed. Hypercalcemia persisted after operation, and the patient died. At postmortem examination, microscopic study revealed that the disease had metastasized to lungs and hilar lymph nodes. There was massive metastasis in the liver; the liver contained a large amount of iPTH. The results of these investigations suggest that (1) venous catheterization of the neck veins and the effluent blood from extraparathyroid tumors aid in identifying and localizing iPTH production; (2) primary benign hyperparathyroidism is not uncommon in patients with cancer, and its co-existence must be recognized; (3) high serum iPTH level in the superior vena cava may be found in patients with metastatic or primary cancer of the thoracic cavity; and (4) hyperparathyroidism may be the first hint of a familial multiple endocrine syndrome.

Pharmacologic intervention can reestablish baseline hemodynamic parameters during laparoscopy.

BACKGROUND: Several studies in both animal models and human beings have shown that CO2 abdominal insufflation for laparoscopy can cause a variety of alterations in hemodynamic and pulmonary physiology. These physiologic changes could potentially have deleterious effects in patients with underlying cardiopulmonary disease. METHODS: We prospectively evaluated 15 patients with preexisting heart and/or lung disease to determine whether the use of invasive monitoring would allow early identification and treatment of these physiologic alterations and thus enable laparoscopy to be performed safely in this group of patients. RESULTS: CO2 abdominal insufflation caused statistically significant increases in systemic vascular resistance, mean arterial pressure, left ventricular stroke work index, and pulmonary capillary wedge pressure along with a concomitant decrease in cardiac index and oxygen delivery in these patients. The use of intravenous nitroglycerin resulted in a rapid return of the systemic vascular resistance, mean arterial pressure, pulmonary capillary wedge pressure, and cardiac index to baseline levels. No significant intraoperative or postoperative cardiac or pulmonary complications were noted. CONCLUSIONS: These results suggest that laparoscopy with CO2 pneumoperitoneum can be safely performed in high-risk patients if appropriate monitoring and pharmacologic interventions are used.

Unknown primary cancer presenting as an adrenal mass: frequency and implications for diagnostic evaluation of adrenal incidentalomas.

BACKGROUND: Fine-needle aspiration biopsy to identify adrenal metastasis from an occult primary malignancy has been recommended as part of the evaluation of the patient who presents with an incidentally discovered adrenal mass. This recommendation was assessed by examining the frequency of adrenal involvement in patients with suspected unknown primary cancer. METHODS: Data from 1715 patients referred for evaluation of suspected unknown primary cancer were retrospectively reviewed. RESULTS: Of 1639 patients found to have cancer, the adrenal gland was identified as a site of involvement at presentation in 95 (5.8%). Involvement was limited to the adrenal gland in 4 patients (0.2%). All 4 patients had large (> or = 6 cm) adrenal tumors, 3 of 4 had bilateral involvement, and all had symptoms that otherwise mandated evaluation for an occult malignancy; none had a true adrenal incidentaloma. CONCLUSIONS: Although cancer of an unknown primary site occasionally involves the adrenal gland, metastatic cancer presenting as a true adrenal incidentaloma is extremely rare. Therefore, in the absence of a history of prior malignancy or symptoms, physical examination findings, radiographic findings, or laboratory findings suggestive of an occult malignancy, we do not recommend fine-needle aspiration biopsy as part of the diagnostic evaluation of the patient who presents with a unilateral adrenal mass.

Surgical management, DNA content, and patient survival in adrenal cortical carcinoma.

BACKGROUND: Surgical resection is the only potentially curative treatment for adrenal cortical carcinoma, yet the value of extended resection, palliative resection, and tumor DNA analysis remains unclear. METHODS: The records of 23 patients with adrenal cortical carcinoma who underwent primary surgical resection at our institution were retrospectively reviewed. Flow cytometric DNA analysis was performed on primary tumor tissue from 14 patients. RESULTS: Sixteen of 23 patients underwent complete resection. For these 16 patients the median follow-up was 43 months, the actuarial median survival was 46 months, and the actuarial 5-year survival rate was 46%. The seven patients who underwent incomplete resection all died of disease with a median survival of 8.5 months. Isolated local recurrence as the first site of failure occurred in two patients. Only completeness of resection (p = 0.004) and stage at presentation (p = 0.006) were significant prognostic indicators. None of the following predicted a poor prognosis in patients who underwent complete resection: (1) need for extended resection, (2) presence of renal vein or inferior vena cava tumor thrombus, or (3) tumor aneuploidy (14 of 14 tumors were aneuploid). CONCLUSIONS: Long-term survival is possible in patients with adrenal cortical carcinoma if complete, margin-negative tumor resection can be achieved. Isolated local recurrence is uncommon after complete resection. Because adrenal cortical carcinomas are consistently aneuploid, tumor DNA content is not a useful prognostic factor.