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.

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.

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.

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.

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.

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.

Nonfunctioning islet cell carcinoma of the pancreas.

BACKGROUND: Nonfunctioning islet cell carcinoma of the pancreas has a variable and often indolent natural history, which has resulted in a wide range of treatment recommendations. To more clearly define the natural history and appropriate treatment of this disease, we reviewed our institutional experience over the last 39 years. METHODS: The records of all patients confirmed to have a nonfunctioning islet cell carcinoma of the pancreas were retrospectively reviewed. Kaplan-Meier life tables were constructed and log-rank comparisons were performed. RESULTS: The 73 patients studied had an overall 5-year actuarial survival rate of 50%. Patients with localized disease at presentation (n = 39) had a significantly higher survival rate (p = 0.03) compared with patients with metastatic disease (n = 34). The 19 patients who underwent a potentially curative resection of the primary tumor had a significantly higher survival rate (p = 0.03) compared with the 20 patients with locally advanced, unresectable, nonmetastatic disease. Nine of these 20 patients died of complications of the primary tumor. In contrast, only 2 of 22 cancer-related deaths in the 34 patients with metastatic disease at diagnosis were due to the primary tumor. CONCLUSIONS: (1) Surgical resection should be performed in patients with resectable nonmetastatic disease. (2) Resection of the primary tumor in the presence of metastatic disease is rarely indicated. (3) Innovative treatment strategies are needed for patients with locally advanced, unresectable, nonmetastatic tumors of the pancreatic head.

Case report: diagnosis of thyroid cancer by bone marrow biopsy in a patient with lymphoma and goiter.

Metastatic follicular thyroid carcinoma was diagnosed by bone marrow biopsy performed during the staging evaluation in a patient with large-cell lymphoma and diffuse goiter who showed lung and bone lesions upon radiologic examination. After thyroidectomy, both sites concentrated radioactive iodine, confirming their thyroid origin and allowing for the appropriate treatment.

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.

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.

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.

Parathyroid adenoma in a cancer center patient population.

The association of parathyroid adenoma and antecedent events or relationships was examined retrospectively in 103 patients with parathyroid adenoma drawn from a cancer institute patient population. Patients were divided into two study groups by the referral pattern-intramural or community. The major contrast between the two groups was that the intramural patients had cancer diagnoses. The factors of advanced age, female gender, and prior regional irradiation appeared to be associated with the development of parathyroid adenoma. An interrelationship of incidental cancer and parathyroid adenoma, however, was not supported. Breast and differential thyroid cancers were most frequently associated with parathyroid adenoma, but age, gender, and irradiation were bias influences.

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.

Extended en bloc resection of a primary mediastinal parathyroid carcinoma.

Parathyroid carcinoma is a rare endocrine tumor infrequently seen in the mediastinum. This report describes a patient who underwent en bloc resection of a primary mediastinal parathyroid carcinoma. The tumor originated from the thymus and extended from the aortic arch to the thyroid; local invasion suggested malignancy. En bloc resection of this carcinoma with all surrounding tissue provided local control of the tumor and relief of symptomatic hypercalcemia.

Anaplastic carcinoma of the thyroid. A clinicopathologic study of 121 cases.

One hundred twenty-one cases of anaplastic carcinoma of the thyroid treated at M.D. Anderson Cancer Center, Houston, were reviewed. Anaplastic carcinoma is a rapidly growing neoplasm with a dismal prognosis. The mean survival of our patients was 7.2 +/- 10 months. A significant percentage of our patients (35%) had areas of well-differentiated thyroid carcinoma elsewhere, supporting the hypothesis that anaplastic thyroid carcinoma arises from preexisting well-differentiated thyroid carcinoma. Twenty-four of 30 tumors analyzed (84%) stained for keratin, 28 (93.3%) stained for vimentin, and ten (33%) stained for epithelial membrane antigen. Younger patients lived longer than older patients, and patients whose disease was earlier-stage at presentation responded better than patients with metastases at presentation. Radical surgery alone did not significantly increase survival duration over less radical surgery. The role of multimodality therapy needs further evaluation.

Islet cell carcinoma of the pancreas. A study of 98 patients.

In 98 patients with histologically proved pancreatic islet cell carcinoma who were studied between 1950 and 1987, 55 had functioning tumors and 43 had nonfunctioning tumors. Both patient groups were compared in regard to age at presentation, metastases, and survival. Mean age at diagnosis was 51.1 years for the 55 men and 47 years for the 43 women. At diagnosis, 51 of the patients had regional disease and 47 had distant metastases. When matched for age, sex, and extent of disease, survival did not differ significantly in cases of functioning and nonfunctioning tumors. The patients' ages and the extent of disease at presentation were the most significant factors in prognosis and survival.

C-myc, N-myc, N-ras, and c-erb-B: lack of amplification or rearrangement in human medullary thyroid carcinoma and a derivative cell line.

We investigated the copy number and possible rearrangement of the four protooncogenes, c-myc, N-myc, N-ras, and c-erb-B, in DNA from seven untreated primary cancers or metastases of medullary thyroid carcinoma and an established human medullary thyroid carcinoma cell line, TT, using the Southern blotting technique. The purpose of this study was two-fold: 1) to examine whether protooncogene perturbations in medullary thyroid carcinoma could be considered as a prognostic marker; and 2) to determine whether the protooncogenes could have a possible role in medullary thyroid tumorigenesis. Neither amplification nor rearrangement of the protooncogenes was detectable in the DNA from any tumor samples or in the cell line. Our results suggest that DNA-evident amplification and rearrangement of the c-myc, N-myc, N-ras, and c-erb-B oncogenes may not be mechanisms through which these oncogenes become activated in this malignancy.

Current results of treatment for distant metastatic well-differentiated thyroid carcinoma.

Between 1960 and 1986, 37 patients were treated at M. D. Anderson Hospital and Tumor Institute, Houston, Tex, for metastases beyond the thyrocervical region arising from well-differentiated thyroid carcinomas. Patient, tumor, and treatment factors were analyzed in this group for their influence on survival. No specific factors achieved statistical significance; however, patients having more than one site of metastasis and patients whose metastases arose less than 5 years after treatment of the primary tumor tended to have shorter overall survival times. More than one modality of treatment was used in the majority of patients. Complete surgical resection of metastases offered the best chance for prolonged survival and palliation. With long survival times being the rule, several treatment modalities are often required to provide continuous palliation.