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Recent studies have indicated that numerical chromosomal abnormalities including changes in p53 and cyclin D1 may be involved in Hurthle cell tumorigenesis. We analyzed a series of Hurthle cell neoplasms of the thyroid to evaluate the diagnostic and prognostic utility of numerical anomalies by DNA fluorescent probes for cyclin D1 and p53 gene loci and chromosomes 5, 7, 11, 12, 17, and 22. Interphase fluorescence in situ hybridization (FISH) analysis was performed on paraffin-embedded tissue sections from 10 Hurthle cell adenomas, 19 Hurthle cell carcinomas, and 7 normal thyroid tissues used as controls. Directly labeled fluorescent DNA probes for the centromere region of chromosomes 7, 11, 12, and 17 and locus-specific probes for chromosomes 5 and 22, cyclin D1, and p53 were utilized for dual-probe hybridizations. Sixty percent (6 of 10) Hurthle cell adenomas and 63% (12 of 19) Hurthle cell carcinomas showed chromosome gains. Twenty percent (2 of 10) Hurthle cell adenomas and 26% (5 of 19) Hurthle cell carcinomas showed chromosome losses. Normal thyroid tissues used as controls showed no chromosomal abnormalities. Among Hurthle cell tumors with chromosomal abnormalities, adenomas averaged 2.7 gains and 0.3 losses per case, and carcinomas averaged 3.3 gains and 0.6 losses per case. The two adenomas with chromosome losses each showed loss of one chromosome, whereas the five carcinomas with losses averaged 1.8 losses per case. Chromosome 22 was the most common loss identified, occurring in three of the 11 patients who died of disease. These results indicate that chromosomal imbalances as gains are common in both benign and malignant Hurthle cell neoplasms, but Hurthle cell carcinomas tend to have more chromosome losses than adenomas. Among Hurthle cell carcinomas in this study, chromosome losses were identified only from patients who died of disease. The loss of chromosome 22 may have prognostic value in Hurthle cell carcinoma of the thyroid.

The recent cloning of the thyroidal protein that is responsible for iodide transport, the sodium iodide symporter (hNIS), has made possible studies designed to characterize its structure, function and expression in thyroidal tissues. Using a mannose binding protein (MBP)-hNIS fusion protein as antigen, we have developed mouse monoclonal antibodies against hNIS to utilize as tools in such studies. Twenty-four clones were initially recovered which recognized the MBP-hNIS fusion protein, but only two of them were specific for hNIS while the others recognized MBP alone. Both antibodies were found to be immunoglobulin G (IgG) 1kappa (kappa). The specificity of antibodies was tested by Western blotting using membranes prepared from COS-7 cells transiently transfected with the pcDNA3 plasmid containing the full-length hNIS cDNA, or cells transfected with the pcDNA3 vector. A major band with a molecular weight (MW) of approximately 97 kDa, and several minor bands with MW of approximately 160 kDa, approximately 68 kDa, approximately 30 kDa and approximately 15 kDa, were detected specifically in the hNIS-transfected cells. After enzymatic deglycosylation, the major band was present at 68 kDa, as expected based upon the amino acid sequence of hNIS. Immunohistochemistry was performed with several different types of thyroid tissue and non-thyroidal tissues, using the monoclonal antibodies. Strong immunostaining was observed in Graves' tissue, with intermediate staining in papillary and follicular thyroid cancers and an absence of staining in Hurthle cell cancer. The staining was specific for the follicular epithelium and was concentrated in the basolateral portion of the cell membrane. These monoclonal hNIS antibodies should prove useful in the characterization of NIS expression in benign and malignant thyroid tissue and in studies characterizing its structure and function.

We analysed 42 differentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary thyroid cancers (PTC) and 14 follicular thyroid carcinomas (FTC) with 13 microsatellite markers specific for the long arm of human chromosome 7 within 7q31; this region is deleted frequently in several other tumor types. Overall, 20 of the 42 samples analysed (48%) displayed LOH with one or more of the markers tested. LOH was detected most frequently (78%) in FTC, the most malignant of the thyroid tumors. A smallest common deleted region (SCDR) was defined in this tumor type flanked by markers D7S480 and D7S490. This SCDR is distinct from D7S522, the most commonly deleted locus in many other tumors, which was deleted in only one FTC. D7S522 did show LOH in two of six informative PTCs. None of the PTC and only two of the FAs showed LOH in the FTC SCDR. Since FA is considered a premalignant stage of FTC, our results suggest that inactivation of a putative tumor suppressor at 7q31.2 may be acquired during adenoma to carcinoma progression. The absence of LOH at this locus amongst PTC suggests that inactivation of this tumor suppressor is specific for FTC. In conclusion, LOH at 7q31 is a frequent event in differentiated thyroid cancer, and we have defined a 2 cM SCDR specific for FTC.

Treatment for recurrence after surgical removal of parotid benign pleomorphic adenoma (PBPA) has not been well defined and is often followed by further recurrence. Surgery is overwhelmingly the most common approach. The risk of facial nerve injury is greater at reoperation since the nerve is less well defined. The value of radiation therapy (RT) has not been determined and incurs with it the risk of possible late occurrence of malignancy or nerve damage. The charts of patients with recurrent PBPA treated consecutively by a single surgeon from 1965 to 1993 were reviewed. All patients had a histopathologically verified diagnosis of PBPA both at the time of primary and subsequent surgeries. Follow-up was obtained from clinical charts and correspondence communication. Recurrence curves were generated using the Kaplan-Meier method. Thirty-nine patients with recurrent PBPA (36 referred and 3 treated primarily at Mayo) were evaluated. The patients were classified according to the type of surgery: 14 patients had previously undergone some form of parotidectomy or had only resection of the tumor for recurrence, and 25 patients underwent parotidectomy since this had not been performed primarily. The mean age in the two groups was 49 and 50 years respectively. The mean follow-up was 10 years after the recurrence treatment. The mean time between initial resection and recurrence in the two groups was 14 and 15 years. The mean time between the recurrence treatment and a second recurrence was 7.5 years. Nine patients had RT in addition to the local resection. Of this group 3 patients (33%) developed another recurrence. Five patients had local resection only, and of this group 1 patient (20%) developed another recurrence. Of the group that had superficial parotidectomy, 3 patients had additional RT and one of these patients (33%) developed another recurrence. Twenty-two patients had superficial parotidectomy only, and of this group 3 patients (14%) developed another recurrence. Only 2 of the 39 patients had complications. One patient developed Frey's syndrome after superficial parotidectomy and 1 patient developed facial paralysis after RT. As in other series, the number of patients is inadequate to allow for firm conclusions. However, it appears that when previous parotidectomy has been performed, simple excision with a margin of surrounding tissue would seem appropriate. Parotidectomy should be carried out if not performed previously. In simple excision after previous parotidectomy, there is a greater risk to the facial nerve because of difficulty in distinguishing the facial nerve from surrounding scar tissue. Our preference is to use general anesthesia so that branches of the nerve are not paralyzed and stimulation of the nerve aids in safe dissection. The value of RT is still indeterminate.

To assess the influence of fine-needle aspiration (FNA) biopsy on the management of nodular thyroid disease.We retrospectively evaluated the effect of the availability of FNA biopsy on thyroid surgical practice at our institution by comparing the data for two study periods--1975-1976 (before the introduction of FNA) and 1985-1986 (5 years after its introduction).The study inclusion criteria were fulfilled by 1,451 patients. In 1975-1976, 938 patients had thyroid operations at our institution. FNA biopsy was introduced into our practice in 1980. In 1985-1986, 513 patients underwent a thyroid surgical procedure. Before the FNA era, the frequency of carcinoma in patients selected for thyroidectomy was 18%, whereas after FNA became available, it increased to 25% (P0.0001). When patients were selected for surgical treatment because of either "suspicious" or malignant cytologic results, the yield of carcinoma increased to 40%.These data suggest that FNA biopsy has improved selectivity for operation in patients with nodular thyroid disease and has reduced the number of patients who undergo thyroidectomy for benign disease. The result is an increasing yield of malignant lesions found at surgical intervention. FNA biopsy has had a substantial cost-saving effect on thyroid practice.

Nodular thyroid disease is a common problem, particularly in women and the elderly population. Furthermore, 5% of thyroid nodules are likely to be malignant. Therefore, assessment for malignant potential is important, and fine-needle aspiration (FNA) biopsy is the most accurate technique. For each nodule, two to four aspirations should be attempted from different areas of the nodule. Although major complications of FNA biopsy are rare, proper cytologic interpretation necessitates special expertise. Cytologic diagnoses are usually categorized as diagnostic or nondiagnostic, and the diagnostic specimens are classified as benign, "suspicious," or malignant. Rebiopsy is indicated for enlarging nodules, recurrent cysts, and nondiagnostic cytologic findings. Because FNA biopsy is a safe, reliable, and rapid means of evaluating thyroid nodules, we recommend its routine use for diagnosis and treatment of thyroid nodular disease.

The present study was designed to define the factors that predict survival in patients with distant metastases (DM) from papillary thyroid carcinoma. We performed a retrospective review of the records of 100 consecutive patients (45 females and 55 males; age range, 8-91 yr) who developed DM after primary treatment at our institution from, 1940-1989. Median follow-up for the 20 survivors was 21 yr (range, 3-38). Cause-specific survival rates at 5, 10, and 15 yr were 40%, 27%, and 24%, respectively, and were not significantly different between the eras 1940-1954, 1955-1969, and 1970-1989 (P = 0.74). By univariate analysis, age at diagnosis of DM was the most important predictor of survival (P < 0.0001), with improved survival occurring in younger patients. Tumor-related factors associated with improved survival included complete resection of the primary tumor (P < 0.005), histological grade 1 (P = 0.006), diploid nuclear DNA (P = 0.03), and lung as first site of DM (P = 0.018). By univariate analysis, use of radioiodine therapy was associated with improved survival (vs. other forms of therapy, P < 0.001). However, by multivariate analysis only age, site of DM, and degree of extrathyroidal invasion of the primary tumor were identified as significant predictors of survival. None of the four treatment variables (external radiation, surgery, chemotherapy, or radioiodine) was a significant predictor of survival in the Cox model. Our retrospective data indicate that 1) outcome has changed little over 5 decades for patients with DM from papillary thyroid carcinoma; and 2) current forms of therapy do not appear to impact on survival.

The major objectives of this prospective study were to compare pathologic findings from stereotaxic core and excisional biopsies performed on patients with impalpable breast lesions and to compare the initial mammographic impression with the final histologic diagnosis.All patients referred for preoperative localization of impalpable breast lesions between October 29, 1991, and January 15, 1993, were eligible for the study. If the patient and the lesion, on the basis of mammography, were considered suitable for core biopsy, the patient was asked to participate. Four hundred forty-five excisional biopsies were performed. One hundred sixty lesions were evaluated by core biopsy; for 104 of these lesions, five or more core samples were removed. Core biopsies were done with 14-gauge biopsy needles and were followed by a localization procedure. The pathologic features of core and excisional specimens were compared.Biopsy results were compared for 93 (58%) benign and 67 (42%) malignant lesions. Of 104 lesions evaluated with at least five core specimens, 56 (54%) were benign and 48 (46%) were malignant. Results of core biopsy corresponded to those of excisional biopsy for 96% of benign lesions, 83% of malignant lesions, and 90% overall; sensitivity of core biopsy for malignant lesions was 85%. Of 56 lesions for which fewer than five core specimens were obtained, 37 (66%) were benign and 19 (34%) were malignant. Results of core biopsy corresponded to those of excisional biopsy for 81% of benign lesions, 79% of malignant lesions, and 80% overall; sensitivity of core biopsy for malignant lesions was 84%. Specificity of core biopsy for the entire series of benign lesions was 100%.For mammographic lesions that are believed to be not malignant or not very likely malignant, stereotaxic core biopsy decreases the need for excisional biopsy.

Objective. To develop guidelines as to which asymptomatic male patients with genital human papillomavirus (HPV) infection need further evaluation of the urethra, we studied two screening methods: urethroscopy and voided urethral cytology. Methods. In a four-year period, 135 asymptomatic men underwent complete screening for HPV infection. They were evaluated because of HPV-related genital disease in their female sex partners or visible genital lesions, or both. Results. Of the 135 patients, 21 (16%) had no clinical, subdinical, cytologic, or urethroscopic evidence of disease, and 114 (84%) had biopsy-proven HPV infection. Of these 114 patients, only 14 (12.3%) had intraurethral condyloma. All of these 14 patients had current or historical evidence of meatal or perimeatal sentinel lesions. They constituted 29.8 percent of 47 such patients with sentinel lesions. In 5 patients (4%), results of voided urine cytology were positive for condyloma cells, but only 1 of these had visible intraurethral disease. Of the 14 patients with urethral disease, only 1 (7%) had positive results of urine cytology. Conclusions. These observations suggest that any asymptomatic male patient undergoing screening for condyloma acuminatum who has a history of or demonstrable subclinical or grossly visible perimeatal or meatal HPV infection should undergo urethroscopy and that voided urine cytology is not a reliable or cost-effective test for the detection of visible intraurethral disease.

To evaluate the accuracy of a Chlamydia diagnosis in our laboratory, cytologic Chlamydia diagnoses for the years 1990 and 1991 were compared with immunofluorescent studies for Chlamydia for the same period. Only one of 22 cases diagnosed cytologically as suggestive of Chlamydia had a positive immunofluorescent result. On rescreen of 110 cervicovaginal smears taken within I mo of a positive fluorescent antibody test, 11 cases were found to contain criteria suggestive of Chlamydia. These correlations represent a 4.5% specificity and 10% sensitivity rate, suggesting that our current efforts in cytology are not effective in determining the presence of Chlamydia. Diagn Cytopathol 1994; 11:20–22. © 1994 Wiley-Liss, Inc.

A retrospective review of 211 computed tomographic (CT)-guided and 58 ultrasound (US)-guided biopsies of pancreatic lesions performed between 1985 and 1989 was undertaken to evaluate the accuracy of diagnosis and the number of complications. Combined CT and US accuracy in the diagnosis of malignancy was 93%. CT-guided biopsies had an accuracy of 86%, and US-guided biopsies had an accuracy of 95%. Accuracy was higher with larger masses (> 3.0 cm, 92%; < or = 3 cm, 81%) and larger needle sizes (16-19 gauge, 92%; 20-22 gauge, 85%) and when the mass was located in the body or tail of the pancreas (93%) rather than the head (84%). Major complications developed in three cases (1.1%). No biopsy-related deaths occurred. Needle passage through the gastrointestinal tract, including the colon, did not cause complications.

The latest World Health Organization International Classification defines papillary thyroid carcinoma by its “follicular cell differentiation ... as well as characteristic nuclear changes”. However the oxyphilic (Hurthle cell) papillary carcinoma have nuclei which generally resemble the nuclei seen in oxyphilic follicular carcinomas, and such oxyphilic papillary tumors may behave more aggressively than typical papillary cancers. To further characterize these rare tumors, we identified during a 32-year period 22 patients with oxyphilic papillary cancer and compared them with 1,084 patients with typical papillary cancers and 57 patients with oxyphilic follicular cancers treated by the Mayo surgical group during the same time period. Although typical papillary and oxyphilic papillary cancers were comparable with regards to patient age, tumor size and extent, TNM stage, and prognostic score (AGES), there were significant differences. Compared to typical papillary tumors, oxyphilic papillary cancers had fewer neck nodal metastases at primary diagnosis (5% vs 40%,p

Recently described immunological functions for heat shock proteins (HSPs) and our previous demonstration of site-selective HSP-72 expression in cultured fibroblasts derived from extrathyroidal manifestations of Graves' disease (GD) prompted us to determine whether expression of the inducible 72-kilodalton HSP can be detected in human thyroid tissues. Immunohistochemistry was performed on formalin-fixed paraffin-embedded thyroid tissue specimens from patients with GD, Hashimoto's thyroiditis (HD), and multinodular goiter (MNG) as well as on normal thyroid tissue. A mouse monoclonal anti-HSP-72 antibody and an ultrasensitive avidin-biotin-peroxidase complex detection system were used for these studies. Striking differences in HSP-72 immunoreactivity were detected both between tissues from GD and HD compared with MNG and normal thyroid and between GD thyroid glands treated preoperatively with antithyroid medication and untreated GD glands. Strong HSP-72 reactivity in GD and HD tissues was detected in thyroid follicles as well lymphocytic infiltrates. No HSP-72 reactivity was detected in MNG or normal thyroid tissue. HSP-72 immunoreactivity was markedly reduced in GD glands that received preoperative antithyroid drug treatment. In conclusion, high levels of HSP-72 expression in autoimmune thyroid disease may reflect a state of chronic cellular stress, but could also represent an immunomodulatory factor of relevance in the autoimmune process in GD.

The finding of papillary carcinoma in a neck mass usually leads to the presumptive diagnosis of metastatic thyroid carcinoma, with total thyroidectomy revealing the primary tumor. We report five cases of metastatic papillary carcinoma of the neck. The primary tumor in three of the cases was found to be nonthyroidal; two being discovered only after total thyroidectomy failed to reveal a primary cancer. In the two thyroidal neoplasms, pathologic examination of the thyroid demonstrated only minimal tumor in one case and no detectable tumor in the other. These cases illustrate the pitfalls of diagnosis and treatment of these tumors and the utility of antithyroglobulin immunostaining in such cases.

• Between 1954 and 1989, 41 patients with melanoma metastatic to the gastrointestinal tract underwent surgical treatment at the Mayo Clinic, Rochester, Minn. The small bowel was most commonly involved (71%), followed by the stomach (27%), large bowel (22%), and esophagus (5%). Gross total excision of all intra-abdominal metastases was performed in 52% of patients. The postoperative mortality was 5% and the median patient survival was 0.8 years, with 1- and 5-year survival rates of 44% and 9%, respectively. Of the patient, tumor, and treatment variables evaluated, patients with small-intestinal metastases had a significantly worse prognosis. Although patients with melanoma metastatic to the bowel have a limited life expectancy, surgical resection of their metastases provides effective palliation. Operative treatment of selected patients with symptomatic melanoma metastatic to the gastrointestinal tract is a worthwhile undertaking. ( Arch Surg. 1991;126:1353-1358)

Distinguishing cellular follicular adenomas (FA) from minimally invasive follicular carcinomas (FC) continues to plague even experienced thyroid pathologists. DNA ploidy analysis has been promoted as a means of making this differentiation; however, the finding of DNA aneuploidy in FA has caused concern that they may demonstrate potential for malignant behavior or should even be reclassified as low-grade noninvasive cancers. In histologically-proven FC, nuclear DNA content has been claimed to have predictive power equivalent to that of all other prognostic factors combined. The aims of the present study, therefore, were to define the DNA ploidy characteristics of FA and FC, to assess the diagnostic potential of cell-cycle parameters, and, in FC, to investigate the prognostic role of such measurements. We measured DNA content of 124 tumors (60 FA, 64 FC). DNA pattern was normal (diploid) in 75% of FA and 45% of FC, tetraploid/polyploid (T/P) in 13% of FA and 25% of FC, and aneuploid in 12% of FA and 30% of FC. FC was histologically verified in 39% of DNA normal, 67% of T/P, and 73% of aneuploid tumors. DNA index, S-phase, G2M, and S-phase plus G2M were analyzed and were not helpful in differentiating between FA and FC. No patient with FA developed tumor recurrence. In FC (excluding the Hurthle cell variant), no significant differences were found among the 3 DNA ploidy groups with respect to either cancer death or tumor recurrence; however, combining the Hurthle cell variant of follicular carcinomas with pure follicular carcinomas, the presence of distant metastases, DNA aneuploidy, and patient age were the only independently significant prognostic variables. Based on these data, while not valuable for determining the presence of malignancy, DNA ploidy determination is of major prognostic value in follicular carcinomas (including the Hurthle cell variant).

Objectives: To determine whether (1) frozen-section (FS) evaluation of follicular and Hurthle cell thyroid neoplasms (FHCNs) is accurate, (2) FS aids in intraoperative decision-making, and (3) FS is cost-effective. Design: Retrospective review of patient histories and FS and paraffin-embedded slides. Permanent histologic sections were considered the standard criterion. Follow-up was achieved in 92% of patients with a mean follow-up of 5.7 years. Setting: Tertiary care referral center. Patients: All patients undergoing thyroidectomy for a suspected FHCN between January 1, 1985, and December 31, 1994. Patients included were those whose condition was diagnosed as FHCN, either on FS, permanent histologic sections, or both. Main Outcome Measures: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FS analysis were determined. Total adjusted hospital charges were compared for those undergoing 1 vs 2 cancer operations. Multivariate analyses were carried out to determine the optimal predictive model for follicular cancer. Results: The study group included 1023 patients (737 women and 286 men), of whom 83 (8.1%) were diagnosed as having a malignant FHCN on permanent section. The diagnosis of malignant neoplasm was correctly established in 65 (78%) of the 83 patients on FS, thereby permitting definitive surgical management at the first operation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for FS diagnosis of malignant FHCN were 78%, 99%, 90%, 98%, and 98%, respectively. In a multivariate analysis, FS was the most significant variable predictive of malignant neoplasm. Approximately $400 000 was saved in hospital charges by the use of FS as a result of the elimination of many 2-stage operations. Conclusion: Frozen-section evaluation of FHCN can be performed with a high degree of accuracy, permitting considerable cost savings. Arch Surg. 1997;132:674-679

Background: Disorders of the thyroid are common in pregnancy. In particular, a thyroid nodule is frequently discovered before or during pregnancy. Objective: To develop guidelines for the management of thyroid nodules during pregnancy. Methods: We reviewed the cases of 40 pregnant patients with thyroid nodules evaluated during a 10-year period. Cytological findings were compared with available histological findings, and concordance rates were determined. The rank sum test was used for statistical analysis. Results: Fine-needle aspirations of thyroid nodules in 62% of patients were benign cytologically (25 patients). Of 8 patients with negative cytological results who had thyroidectomy, all had benign disease histologically (100% concordance rate). Cytological findings of papillary cancer (3 patients) strongly correlated with final histological diagnosis (100% concordance rate), whereas papillary cancer was confirmed histologically in only 2 of 4 patients with cytological findings suspicious for this disease (50% concordance rate). All 3 nodules with cytological findings suspicious for follicular neoplasm were benign adenomas histologically. Of 2 nodules suspicious for Hurthle cell neoplasm, 1 was Hurthle cell adenoma and the other was Hurthle cell carcinoma (100% concordance rate). Thyroidectomy during the second trimester of pregnancy or the early postpartum period was successful. Conclusions: The approach to thyroid nodules in pregnancy should be similar to that for nonpregnant patients. Thyroidectomy should be performed (1) during the second trimester for malignant lesions and cytological findings suspicious for papillary cancer and (2) in the postpartum period for cytological findings suspicious for follicular neoplasm. Arch Intern Med. 1996;156:2317-2320

• Information on gastric leiomyosarcoma, such as important prognostic factors, patterns of disease recurrence, and optimal methods of treatment, are derived from limited patient experience. We address these questions, with specific focus on whether an advantage could be demonstrated for radical resection compared with wide local excision, by retrospectively investigating 53 patients who underwent surgical treatment at Mayo Clinic, Rochester, Minn. Abdominal pain and/or gastrointestinal bleeding associated with an intramural or exogastric mass were typical features of this disease. Only tumor size and histologic grade were statistically significant prognostic factors. With analysis of survival curves and patterns of recurrence, neither the addition of lymphadenectomy nor the wider tumor-free margins of a radical gastrectomy seemed superior to the more conservative local excision. Therefore, wide local excision remains the preferred treatment when technically feasible. ( Arch Surg. 1991;126:985-990)

In contrast to opinions expressed even less than 10 years ago, present sentiment and publications endorse the general technique of fine-needle aspiration (FNA) for the diagnosis of thyroid nodules. 1,2 Following verification that both aspirationist and cytopathologist have achieved a high degree of accuracy and reliability, the results of FNA usually form the principal basis on which thyroid nodules are managed. Recent publications have focused on identifying and further refining the inadequacies of FNA. 3,4 De los Santos et al5 have correctly pointed out a potential problem with the technique, that of establishing a firm diagnosis on thyroid nodules that are at least partially cystic. In contradistinction to nonbloody simple breast cysts that are virtually always benign, the possibility of a partially cystic thyroid malignancy is clearly a real concern. See also p 1422. This retrospective study of 221 surgically resected thyroid nodules demonstrated that nearly one third were cystic

A prominent ultrastmctural finding in eight desmoid tumors was myofibroblastic mesenchymal cells with abundant intercellular collagen. In addition, seven of the tumors had intracytoplasmic collagen fibers. These findings are discussed in relation to other tumors and to nontumorous conditions.

The cytologic features of five cases of hyalinizing trabecular adenoma of the thyroid are reviewed. All of these cases had been initially interpreted as either suspicious or positive for malignancy. On retrospective review, many of the cytologic features did mimic those of other lesions, particularly papillary carcinoma. The smears tended to hypercellularity, and nuclei were often slightly enlarged with pale chromatin, intranuclear holes, and longitudinal grooving of the nuclear membrane. On the other hand, some cytologic features were more suggestive of medullary carcinoma--poor cohesion of cells with elongated and spindle cell forms and hyaline acellular areas. Awareness of the histologic and cytologic features of hyalinizing trabecular adenoma may enable the cytopathologist to avoid a false positive diagnosis of papillary carcinoma or medullary carcinoma, although it is unrealistic to expect a definitive diagnosis of hyalinizing trabecular adenoma.

We studied the impact of fine-needle aspiration biopsy on the management of patients with solitary thyroid nodules. Sixty-four patients were examined before the introduction of fine-needle aspiration biopsy, and 147 patients were examined after its introduction. The percentage of patients who underwent thyroid operation decreased from 67 percent to 43 percent, while the yield of carcinoma increased from 14 percent to 29 percent. Cost of medical care per patient declined by 25 percent. The results suggest that fine-needle aspiration biopsy provides valuable information to assist in the selection for surgery of patients with solitary nodules. Fine-needle aspiration appears to be safe, reliable, and cost-effective. The merits of the technique commend it for routine use in the evaluation of thyroid nodules.

A cytologic examination of pleural fluid was performed on a pleural lavage specimen collected at the completion of operation after pulmonary resection in 135 of 599 patients undergoing curative pulmonary resection for a non-small cell carcinoma of the lung between 1977 and 1982. The cytologic results of lavage was positive for malignant cells in 12 of the 135 patients (8.9%). The incidence of positive results was correlated with lymph node status (N2 > N1 > N0), cell type (adenocarcinoma > other non-small cell lung cancers), stage (III > II > I), and visceral pleural status (invaded > not invaded). No positive cytologic results were noted in 39 patients having a diagnostic excisional pulmonary biopsy prior to more definitive resection. The disease has recurred in nine of the 12 patients with positive cytologic results (only two in the ipsilateral pleural space), and eight have died. The prognostic role of pleural lavage cytology needs more study.

In this article, the current noninvasive and invasive methods used in the evaluation and management of nodular thyroid disease are discussed.

The concentration of carcinoembryonic antigen (CEA) in cerebrospinal fluid (CSF) was determined by using an enzyme immunoassay for 204 patients with various nonneoplastic neurologic disorders, 8 patients with systemic infectious diseases, 19 patients with systemic neoplastic diseases without involvement of the nervous system, and 35 patients with neoplastic neurologic disorders. The highest CEA level in CSF among patients without neoplastic neurologic disorders was 0.6 ng/ml. Of 35 patients with neoplastic neurologic disorders, 10 had CEA levels in CSF that exceeded 0.6 ng/ml, the highest level being 70.5 ng/ml. All 10 patients had carcinomas. Among 14 patients with neoplastic meningitis, 5 of 8 patients with meningeal carcinomatosis had elevated CEA concentrations. Although the efficacy of the assay for CEA in CSF must be compared with that of other laboratory tests such as cytologic examination and the assay for beta-glucuronidase--and any potentially false-positive results should be ruled out by determination of the serum CEA level--the CEA concentration in CSF can be used as an adjunctive diagnostic procedure for detection of meningeal carcinomatosis.

To document the presentation, findings, therapy, and postoperative course of lethal papillary thyroid carcinoma (PTC), 56 fatal cases were studied in a retrospective case-matched control fashion. These patients and their controls were taken from a larger series receiving their primary treatment at one institution (Mayo Clinic; 1946-1970). Mean follow-up for the lethal cohort was 8.5 years and 16.6 years for controls. Age, sex, tumor size, histologic grade, extent of disease at presentation, European Organization for Research on Treatment of Cancer (EORTC) and AGES scores (patient's age, tumor grade, tumor extent, and tumor size), and DNA ploidy pattern were found to be significant prognostic factors. The immediate causes of death were most frequently either local airway obstruction or respiratory insufficiency from pulmonary metastases. The results suggest that it is possible, at the time of initial treatment, to assess an individual patient's risk of dying from PTC. Aggressive postoperative adjunctive therapy should be restricted to that minority of patients who are at highest risk of death from PTC.

The pathologic and clinical findings in cases of desmoplastic melanoma of the head and neck seen at the Mayo Clinic in Rochester, Minnesota, during the past 20 years were analyzed. The nine cases acceptable for study included six usual and three neurotropic variants as defined by light microscopic criteria. Immunopathologic studies of all cases using S-100 protein and desmin, and electron microscopy in four cases, were unsuccessful in distinguishing between the two subtypes. Clinical behavior was aggressive regardless of histologic subtype. Extensive surgical treatment when the diagnosis is made is advocated. The combination of the rarity and the subtle histologic features of desmoplastic melanoma continues to make the correct diagnosis of this entity a challenge for the clinician and pathologist.

Debate surrounds the natural history and appropriate management of Hürthle cell neoplasms of the thyroid. Some of the uncertainty stems from difficulty in the differentiation of benign from malignant lesions. We report the presentation, management, and outcome of patients with invasive Hürthle cell carcinoma who were examined at this institution between 1946 and 1971. We believe that our review allows us to make reasonable recommendations concerning the management of patients with this type of carcinoma.

Ultrastructural study of five typical lesions of dermatofibrosarcoma protuberans revealed that the basic cell is fusiform and has a somewhat indented nucleus and an even distribution of cytoplasmic organelles. Fragments of basal lamina, intercellular junctions, abundant intercellular fibers, and a tendency to form cellular sheaths also were found. The tumor cells had a strong resemblance to pericytes and perineural cells, as well as marked ultrastructural similarities to neurofibroma. The authors conclude that dermatofibrosarcoma protuberans arises from a primitive fibroblastic cell with a "sheath forming cell" differentiation that has a closer relationship to the perineural cell than to the pericyte.

The ultrastructure of two atypical" fibroxanthomas of the skin was studied. The first lesion was a spindle cell tumor on light microscopy, which electron microscopy revealed was composed of undifferentiated mesenchymal cells. The second lesion had a highly pheomorphic appearance on both light and electron microscopy. It was formed by atypical histiocytic cells and abundant "typical" Langerhans cells. The second lesion was considered to be a proliferation either of atypical Langerhans cells or of histiocytes related to Langerhans cells. Thus, atypical fibroxanthoma of skin may not be a homogeneous entity but could be a group of mesenchymal proliferative lesion in a similar clinical setting.

Extraocular sebaceous carcinomas are uncommonly seen neoplasms, and have been confused in the past with basal cell carcinomas showing sebaceous differentiation. In contrast to the latter tumors, however, sebaceous carcinomas have a distinct risk of aggressive behavior. This study presents clinicopathologic data on five cases of sebaceous carcinoma arising in cutaneous locations outside of the ocular adnexae. Four of five patients were men, and the average age at diagnosis was 63 years. Three tumors occurred on the face, one arose in the skin of the neck, and another occurred on the penis, an anatomic site that is extremely rare for sebaceous carcinoma. Three tumors metastasized, and two patients died of tumor or with residual tumor growth. In light of this behavior, the premise that extraocular sebaceous carcinomas rarely spread to distant sites may need reexamination.

Twelve cases of gastrointestinal leiomyoblastoma were studied by electron microscopy, and the findings were compared with those in 12 cases of leiomyoma and nine cases of leiomyosarcoma of the gastrointestinal tract. All of the "classic" ultrastructural features of smooth-muscle tumors, including subplasmalemmal dense patches, pinocytotic vesicles, cytoplasmic microfilaments and dense bodies, and focal basement membrane formation, were present in the leiomyoblastomas ; however, extensive sampling was commonly necessary to demonstrate such findings. In contrast, these features were more prominent in leiomyomas and leiomyosarcomas.

The hyalinizing trabecular adenoma, a distinctive lesion, is important because it may mimic medullary and papillary carcinoma microscopically. We describe 11 such tumors obtained from women ages 27-72 years (mean, 46 years). The initial pathologic diagnoses were carcinoma (five cases), adenoma (two cases), paraganglioma (one case), and "indeterminate" (three cases). None of the tumors recurred or metastasized (mean follow-up, 10 years). Grossly, the neoplasms measured 0.3-4 cm in diameter, and were yellow-tan and circumscribed. Microscopically, they were encapsulated or circumscribed and solid, or vaguely lobulated. The polygonal, oval, and elongated tumor cells were arranged in trabeculae, clusters, or both, and were often inserted vertically into capillaries. The sharply outlined cells had finely granular cytoplasm that was either acidophilic, amphophilic, or clear. Typical features included oval and elongated nuclei, perinucleolar vacuoles, acidophilic nuclear inclusions, fine nuclear grooving, and infrequent mitotic figures. Perivascular hyaline fibrosis and cell degeneration mimicked amyloid, but these tumors were Congo red-negative. Occasional trabeculae featured round or irregularly shaped follicles, sometimes with papillary infoldings, that were either empty or contained colloid-like material and psammoma bodies. Immunostaining of tumor cells was positive for thyroglobulin and negative for calcitonin. Among six tumors analyzed by flow cytometry, five displayed a diploid pattern and one showed an aneuploid peak.

The diagnostic identification of sweat gland carcinomas is hampered by their rarity and their histologic resemblance to various visceral tumors, leading to confusion with metastatic lesions. In this series, 14 cases of eccrine carcinoma in five male and nine female patients, ranging in age from 13 to 84 years, are described. Ten tumors strongly resembled infiltrating ductal adenocarcinomas of the breast, and were thus classified as ductal. Three had a prominent mucinous matrix, similarly explaining their categorization as mucinous carcinomas. Finally, one neoplasm was a classic eccrine porocarcinoma. Four patients with ductal eccrine carcinomas suffered metastasis, and a 50% mortality rate was observed among this group of ten cases. In contrast, only one of three mucinous carcinomas metastasized, although all of these lesions recurred locally, as did the single porocarcinoma. None of the latter four neoplasms proved fatal. The results of conventional special stains in these 14 cases are discussed, and histologic features that they shared, and which may be utilized in distinguishing eccrine carcinomas from benign sweat gland tumors, are presented.

Anaplastic carcinoma of the thyroid accounts for about 10% to 15% of all thyroid carcinomas in the United States. Its lethality is evidenced by a 5-year survival rate of 3.6% and a median survival of 4 months. Rapid growth of a thyroid mass, frequently in a preexisting goiter, is the most common manifestation; the diagnosis should be considered and expeditiously pursued in all patients who present with this finding. Relatively favorable prognostic features seem to be unilateral tumors, a tumor diameter of less than 5 cm, no invasion of adjacent tissue, and absence of nodal involvement. For resectable lesions, thyroid lobectomy with wide margins of adjacent soft tissue on the side of the tumor seems to constitute a safe, appropriately aggressive surgical approach. Total thyroidectomy and radical neck dissection results in an increased complication rate and has no advantage over a more conservative approach. Radiotherapy, chemotherapy, immunotherapy, and combination radiotherapy and chemotherapy need further evaluation.

We studied 15 cases of amelanotic melanoma by using light microscopy (in conjunction with Fontana staining and S-100 immunostaining) and electron microscopy. In 14 of the 15 cases, metastatic melanomas were present; 11 were associated with a history of pigmented primary melanoma. The Fontana stain was positive in 4 cases and negative in 11. The S-100 stain was positive in 13 cases and negative in 2. Of the 11 cases with negative Fontana stains, 9 were positive with the S-100 immunostain and 2 were negative. Electron microscopy showed melanosomes in 13 cases. Melanosomes were seen in the two cases with negative Fontana and S-100 staining. Although all stages of melanosomes were identified, generally the majority were immature melanosomes. This study demonstrates the difficulties associated with the histologic diagnosis of amelanotic melanoma. The Fontana stain may be helpful, and the S-100 stain is generally positive. Electron microscopy provided the only evidence for melanoma in two cases and is considered the most definitive method of diagnosis of amelanotic melanomas. These tumors generally produce some pigment and thus are called amelanotic by convention, not because pigmentation is totally absent.

Nine biopsy specimens taken from the scalps of five children and four adults with subcutaneous necrobiotic granulomas were reviewed. This histopathologic features were similar in both groups. Four of the five children presented clinically with multiple, firm, bound-down subcutaneous nodules limited to the scalp but no associated systemic disease. In addition to the scalp nodules, one child had typical cutaneous lesions of granuloma annulare over the acral areas. Two of the adult patients, however, had severe rheumatoid arthritis with multiple rheumatoid nodules on the arms in addition to the scalp nodules; one of them had rheumatoid vasculitis. Another adult patient had allergic granulomatosis,and one had granuloma annulare lesions involving the scalp, face, and left ankle. Excision biopsy specimens should be taken in all patients--both children and adults--with multiple, deep, bound-down nodules of the scalp. If the specimen shows subcutaneous necrobiotic granuloma, probably no treatment is indicated in children because, in our experience, there is no associated systemic disease. However, in the adult patient with similar scalp lesions, the possibility of systemic disease should be explored.

Three girls had Hashimoto thyroiditis and thyroid cancer. Cervical exploration revealed a follicular carcinoma in one, an oxyphilic cell carcinoma in another, and a papillary carcinoma in the third. These cases add clinical and pathologic data to the previously debated concept that Hashimoto thyroiditis coexists with thyroid carcinoma.

Four cases of malignant giant cell tumor of soft parts (MGCT) were studied ultrastructurally. Most of the cells in three cases were identified as undifferentiated mesenchymal cells and mononuclear monohistiocytic cells. The osteoclastlike cells seemed to arise from fusion of monohistiocytic cells. Immature fibroblastic cells, occasionally containing filaments with densities, were also present. They were scarce in three cases and predominant in the fourth. It was concluded that MGCT is a mesenchymal sarcoma with a bimorphic—monohistiocytic and fibroblastic—differentiation. MGCT is therefore considered a special variant of malignant fibrous histiocytoma. Cancer 40:244–253, 1977.

One of the numerous controversial issues related to the clinical management of breast cancer is the role of fine-needle aspiration (FNA). Despite its enthusiastic use in the diagnosis of thyroid nodules, its application to breast abnormalities has been accepted reluctantly. Breast FNA necessitates technical and interpretative skill and continual practice and is not 100% accurate. It also entails an additional, although moderate, expense. To assess the accuracy and determine the possible role of FNA at our institution, we performed both FNA and excisional biopsy in 100 unselected women with palpable breast nodules and correlated the cytologic and histologic findings. Our results were similar to those in previously published studies. FNA had a false-negative rate of 6%, no false-positive results, and an accuracy of 94%. After reviewing the potential assets and liabilities of this technique, we believe that breast FNA may add a measure of confidence in the diagnosis of benign breast lesions, provides a safeguard for preventing misdiagnosis of malignant lesions, and might expedite and reduce the cost of managing both primary and recurrent breast cancer.

In a series of 25 patients with pseudosarcoma and associated squamous cell carcinoma of the larynx, there was a predominance of elderly (average age 63 years) men (23 to two, male-to-female ratio). Most of the lesions originated from the vocal cord and most were polypoid or pedunculated. The pseudosarcomatous stroma generally predominated, with a relatively diminutive carcinomatous component. Electron microscopic features and enzyme histochemistry of the most recent case suggest that the pseudosarcomatous stroma is a reactive proliferation of histiocytes and fibroblasts, apparently in response to the squamous carcinoma. Follow-up studies indicated that four patients died with contiguous tumor (squamous carcinoma), another 15 died of unrelated causes, and six were alive and free of tumor.

Bowenoid papulosis of the penis is a recently described entity that clinically resembles benign verruca-like papular lesions but, histologically, it is identical to carcinoma in situ, Bowen’s disease or erythroplasia of Queyrat. Although a few cases of spontaneous regression of bowenoid papulosis in men have been reported, conservative therapy, consisting of topical 5-fluorouracil, electrodissection or excision, is recommended. With these treatment modalities recurrences are not uncommon. We report 2 cases of extensive bowenoid papulosis of the penis treated successfully without scarring with the neodymium-yttrium-aluminum-garnet laser.