Prognostic factors of insular versus papillary/follicular thyroid carcinoma

The study aims were to characterize patients with insular thyroid cancer and to provide data on patient outcome after surgical therapy. We compared nine patients with insular thyroid cancer at the Department of Surgical Science of "La Sapienza" University of Rome with 27 patients of similar age and tumor size who had follicular and papillary cancer, for a minimum follow-up period of 24 months (range, 24-72 months). All of the patients examined underwent total thyroidectomy. Vascular invasion was observed in 44.4 per cent of insular carcinomas (P < 0.05 vs papillary carcinomas). No significant differences were observed regarding diagnostic method, multifocality, tumor nodes metastases (TNM), or stage. The death rate of patients with insular carcinoma (33.3%) was found to be higher than that of patients with follicular carcinoma (P < 0.05) and papillary carcinoma (P < 0.01). Relapsing lymph-node pathologies were observed in 4 patients (44.4%) with insular carcinoma (P < 0.05 vs those with follicular and papillary carcinomas). Distant metastases were observed in 66.6 per cent of insular carcinomas (P < 0.005 vs follicular carcinoma and P < 0.001 vs papillary carcinoma). At the end of follow-up, 2 patients (22.2%) with insular carcinoma were disease-free (P < 0.001 vs those with follicular and papillary carcinomas). Our study demonstrates an unfavorable prognostic role of the insular phenotype of thyroid cancer, such that this tumor can be classified as an autonomous clinical and pathological entity.     

Thyroid carcinomas with distant metastases: a review of 111 cases with emphasis on the prognostic significance of an insular component

Distant metastases (DM) are rare in well-differentiated thyroid carcinomas and correlate with a poor survival. Among the histologic subtypes, insular carcinoma has an intermediate prognosis that lies between well and undifferentiated carcinomas. To assess the characteristics that could predict a worse prognosis, we reviewed the initial thyroid cancer slides from patients with DM. We achieved a comparative statistical analysis with a control group without DM. Among 1230 differentiated carcinomas treated from 1960 to 1999, 9% developed DM. In this group the mean age was 53 years, with a 73% rate of death. The histologic slides were available in 80 cases. The primary thyroid tumors were classified as papillary (51 cases), follicular (25), and pure insular carcinomas (4). Extrathyroidal extension was present in 47% of papillary carcinomas. The mean tumor size was above 5 cm for all the histologic subtypes, and at least a vascular invasion was found in 69%. Fifty-four percent of these tumors had an insular component compared with only 6.5% in the control group. The statistical analysis confirmed by univariate and multivariate logistic regression that the risk of DM was highly elevated in the presence of insular carcinoma. Our study indicates that elevated age, large tumor size, vascular invasion, and extrathyroidal extension are important prognostic factors in well-differentiated carcinomas. We also demonstrate that the presence of an insular component in an otherwise differentiated carcinoma is a strong independent poor prognostic factor.     

Histologic variants of papillary and follicular carcinomas associated with anaplastic spindle and giant cell carcinomas of the thyroid: an analysis of rhabdoid and thyroglobulin inclusions

We describe the histologic variants of papillary and follicular carcinomas associated with 109 spindle and giant cell carcinomas (SGCC) of the thyroid and determine the incidence of rhabdoid and thyroglobulin inclusions in these tumors. In addition, we searched for rhabdoid and thyroglobulin inclusions in 120 papillary carcinomas (PC) (all 15 variants included), 23 differentiated follicular carcinomas (DFC), (6 with insular pattern), 6 poorly differentiated follicular carcinomas (PDFC) and 34 follicular adenomas (FA). The following differentiated thyroid carcinomas coexisted with SGCC: 51 (46.8%) PC, (34 conventional type, 14 tall cell variant and 3 follicular variant), 6 (5.5%) DFC, 1 follicular carcinoma with insular pattern (0.9%), and 3 oncocytic carcinomas (2.8%). Eleven SGCC (10%) and 2 (33%) PDFC showed rhabdoid features, but lacked thyroglobulin inclusions. Thyroglobulin inclusions were found in 10 FA (29%), 8 (17%) follicular variants of PC and in 7 (30.4%) DFC. There were no rhabdoid inclusions in any of these differentiated thyroid tumors. Our findings support the hypothesis that most SGCC result from dedifferentiation or anaplastic transformation although the mechanisms that underlie this transformation remain unknown. The finding that only 1 (0.9%) SGCC was associated with follicular carcinoma with insular pattern contradicts the opinion that this tumor occupies an intermediate position between differentiated and anaplastic carcinomas. Rhabdoid features are markers of PDFC and SGCC while thyroglobulin inclusions are markers of FA and differentiated thyroid carcinomas with follicular phenotype.     

Clinicopathologic significance of histologic vascular invasion in papillary and follicular thyroid carcinomas

BACKGROUND: The association of angioinvasion with tumor aggressiveness in follicular and papillary thyroid carcinoma remains unclear. This study addresses this problem focusing on clinicopathologic relevance of angioinvasion in the treatment of papillary thyroid carcinoma and follicular thyroid carcinoma. METHODS: From a university hospital database, 358 patients with papillary thyroid carcinoma or follicular thyroid carcinoma were randomly selected. Their charts were retrospectively analyzed and divided into papillary thyroid carcinoma and follicular thyroid carcinoma groups. Each group was subdivided into angioinvasive and nonangioinvasive tumor subgroups. All data were analyzed using Student's t-test, Mann-Whitney rank sum test, chi-square test, and Fisher's exact test. RESULTS: There were 289 women and 69 men, ages 18 to 89 years. Papillary thyroid carcinoma (86%) was more frequent than follicular thyroid carcinoma. Most patients had nonangioinvasive tumor (90.2%). After a mean followup of 43.6 months, there were no significant differences between papillary thyroid carcinoma subgroups for local recurrence (p = 0.69), persistent elevated serum thyroglobulin (p = 0.568), and distant metastasis rates (p = 0.422). No death related to the cancer was observed in both papillary thyroid carcinoma subgroups (p = 1), except for one death resulting from a concomitant nasopharyngeal cancer. The longterm prognosis was less favorable for angioinvasive papillary thyroid carcinoma based on AJCC (American Joint Committee on Cancer staging), AMES (age, distant metastasis, tumor extent, and size), and MACIS (distant metastasis, age, completeness of primary tumor resection, local invasion, and tumor size), but the angioinvasive papillary thyroid carcinoma were larger than nonangioinvasive papillary thyroid carcinomas. The short-term clinical outcomes in both follicular thyroid carcinoma, after a mean followup of 72.3 months, were comparable in terms of local recurrence (p = 0.34), persistent elevated serum thyroglobulin (p = 1), and distant metastasis (p = 0.597). There was no death related to cancer in both follicular thyroid carcinoma subgroups (p = 1). There were no significant differences between both follicular thyroid carcinoma subgroups for longterm prognosis. CONCLUSIONS: Our results indicate that angioinvasion does not adversely influence short-term outcomes or longterm prognosis in follicular thyroid carcinoma and short-term outcomes in papillary thyroid carcinoma. Angioinvasion is a postoperative pathologic finding that does not justify an ominous prognosis or drastic therapeutic measures.     

Do the prognoses of papillary and follicular thyroid carcinomas differ?

Our 44 patients with follicular thyroid carcinoma had a survival rate similar to patients of the same age and sex with papillary carcinoma. By matching our patients by age and sex, this study appears to show that the biologic behavior of differentiated thyroid carcinomas is better correlated with the age and sex of the patients than with the pathologic classification of papillary carcinoma or follicular carcinoma; therefore, it is unnecessary to distinguish between patients with papillary carcinoma and follicular carcinoma from a prognostic standpoint. A classification considering all well-differentiated thyroid carcinomas as one disease with behavioral variability due to constitutional factors such as age and sex should be adopted.     

Evidence-based protocols for the management of well-differentiated carcinomas of the thyroid

OBJECTIVES: In recent years, well-differentiated carcinomas of the thyroid have been stratified into low-risk and high-risk groups. The pattern of thyroid cancer in India is different from that seen in the West. Moreover, patients present with more advanced stages of the disease. Our aim was to develop protocols for the management of well-differentiated thyroid cancer, based on the analysis of our data and our experience. METHODS: Cases of thyroid carcinoma, which were surgically treated at the Tata Memorial Hospital during 1970-5, were studied. The survival curves were plotted according to the Kaplan-Meier method. Univariate analysis was done using the log rank test. The prognostic factors analyzed were age, sex, tumour size, extra-thyroid extension, distant metastases and lymph node metastases. Multivariate analysis using the Cox regression model was performed. Analyses were separate for follicular and papillary carcinomas. RESULTS: Four hundred and seventeen cases were entered in the study, of which 198 were follicular and 219 were papillary. Based on the evidence derived from this study, we stratified our cases into low- and high-risk groups. The low-risk group consisted of patients below 40 years of age, nodules smaller than 5 cm, absence of extra-thyroidal spread and absence of distant metastases. For follicular carcinoma, the low-risk group had 100% survival at 15 years, compared with 40% for the high-risk group. (p < 0.001). For papillary carcinomas, the survival at 15 years was 95% for the low-risk group and 40% for the high-risk group (p < 0.001). CONCLUSIONS: We recommend lobectomy for the low-risk group, and total thyroidectomy for the high-risk group and for cases with lymph node metastases. In the latter, total thyroidectomy facilitates the use of 131I.     

Results of tracheal or esophageal resections in invasive thyroid carcinomas

STUDY AIM: The aim of this retrospective study was to report results of 21 tracheal or esophageal resections for invasive thyroid carcinomas. PATIENTS AND METHODS: Between January 1988 and August 2000, 21 patients (mean age: 66 years) had a tracheal (n = 10) or esophageal (n = 11) resection for involvement by an invasive thyroid carcinoma. There were eight undifferentiated carcinomas, 11 papillary, one follicular and one epidermoid carcinomas. RESULTS: One patient died from pulmonary embolism during the postoperative period. Complications were: tracheal fistula (n = 2), tracheal stenosis (n = 1), esophageal fistula (n = 2), recurrent nerve palsies (n = 8) and hypoparathyroidism (n = 4). Seven patients presented local recurrence and seven presented distant metastases. Ten patients were alive and ten patients died of their carcinoma. The mean survival in this study was 26 months (21 months for anaplastic carcinomas and 41 months for differentiated carcinomas). CONCLUSION: Differentiated thyroid carcinomas have to benefit from a complete tumoral resection; tracheal or esophageal resection is indicated in case of involvement. Anaplastic carcinomas have a poor prognosis; complete resection is indicated only for selected patients; radiotherapy and chemotherapy are used, because surgery is often impossible.     

Predictors of outcome for patients with differentiated and aggressive thyroid carcinoma.

OBJECTIVE: To identify the risk factors affecting the outcome of operations for differentiated and aggressive thyroid carcinoma which may indicate the need for a more aggressive surgical treatment. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: 143 patients underwent total thyroidectomy with or without central neck lymphadenectomy or modified neck dissection. There were 85 papillary, 34 follicular, 6 widely-invasive follicular, 6 insular, five oxyphilic, five tall cell, and two diffuse sclerosing papillary carcinomas. MAIN OUTCOME MEASURE: Disease-related survival. RESULTS: At 12-years, the survival was 96%, being 98% among patients with differentiated and 83% among those with aggressive carcinoma (p = 0.0006). Insular and oxyphilic carcinomas had the worst prognosis (at 10 years, 67% and 60%, respectively, p < 0.0001). The high-risk age, metastases, and extent score (AMES) group had worse survival than the low-risk group (12 years, 84% compared with 98%, p = 0.001). Among patients with differentiated carcinoma, the low-risk AMES group had also better outcome than those in the high-risk AMES group (at 12 years, 100% compared with 86%, p < 0.0001), but there was no such difference among patients with aggressive disease. Multivariate analysis showed that women (RR 14.28, 95% confidence interval (CI) 1.13 to 180.28), patients with tumours > or = 5 cm in size (RR 9.60, 95%CI 1.01 to 91.43) and AMES high-risk patients (RR 30.17, 95% CI 1.57 to 577.48) had the worst outcome. CONCLUSION: In patients with differentiated thyroid carcinoma, total thyroidectomy and, if the AMES score indicates a high risk, central neck lymphadenectomy with or without modified neck dissection, is associated with a favourable outcome. Poorer outcome is expected if the carcinoma is aggressive, and an aggressive surgical approach is advocated as a routine.     

Is the timing of completion thyroidectomy for differentiated thyroid carcinoma prognostic significant?

The purpose of this study was to evaluate whether the timing of completion thyroidectomy for differentiated thyroid carcinoma had an influence on the risk of the operation and patient's survival.From January 1, 1985 to March 31, 2001, 230 consecutive patients underwent surgery for differentiated thyroid carcinoma (178 papillary and 52 follicular carcinomas). In this article completion thyroidectomy was defined as the removal of the remaining thyroid tissue after any initial surgical procedure less than total thyroidectomy within an interval ranging from 3 days to 4 months after the initial surgical procedure.Of 99.1 % (n = 228) of the 230 patients the postoperative course is known for 1 month to 36 years with a median follow-up of 5 years. Among 81 patients undergoing thyroidectomy as the initial operation, recurrent laryngeal nerve palsy occurred in 13.5 % (n = 11). In 2 of these patients (2.5 %) recurrent laryngeal nerve palsy was permanent. Transient recurrent laryngeal nerve palsy occurred more frequent in patients who underwent completion thyroidectomy within 8 days to 3 months of the initial surgical procedure (20.5 %) than in patients, in whom completion thyroidectomy was performed either within 7 days of the primary operation or after a minimum of 3 months (5.2 % in each group). Disease-free survival as well as long-term survival was not different after thyroidectomy or completion thyroidectomy for all differentiated thyroid carcinomas and in patients with papillary carcinomas.In order to reduce surgical morbidity we suggest that completion thyroidectomy should be performed either within 7 days of the primary operation or after a minimum of 3 months.     

A population-based analysis of survival factors in differentiated and medullary thyroid carcinoma.

OBJECTIVE: The study purpose was to determine survival and prognostic factors for differentiated thyroid carcinoma (DTC). METHODS: Cases of DTC were extracted from the Surveillance, Epidemiology and End Results database from 1988 through 1998. Kaplan-Meier survival analysis was conducted for papillary, follicular, and medullary histologies. Cox proportional hazard analysis was used to examine the influence of age, gender, tumor size, local extension, and cervical node involvement on overall survival. RESULTS: A total of 18,118 cases were identified, including 15,820 (87.3%) papillary carcinomas, 1799 (9.9%) follicular carcinomas, and 499 (2.8%) medullary carcinomas. Mean survival (10-year survival) was 122 (87.7%), 117 (80.2%), and 108 (73.7%) months for papillary, follicular, and medullary tumors, respectively. For each histology, increasing age, male gender, and degree of local extension substantially reduced survival. Cervical metastasis did not influence survival for papillary or follicular carcinomas but approached significance for medullary carcinoma (P = 0.065). CONCLUSIONS: Degree of local extension in thyroid carcinoma should be subclassified to more accurately determine prognosis. Treatment of the neck should be considered for medullary thyroid carcinoma.     

Classification, staging, prognostic factors and risk factors in thyroid carcinoma

Thyroid carcinomas arise from follicular cells (papillary, follicular, Hurthle, anaplastic), parafollicular cells (medullary) and stroma (lymphoma, sarcoma). Gradation and prognostic factors are different for every one of histological type. Most patients with papillary and follicular thyroid cancer have an excellent prognosis. At the other extreme is anaplastic thyroid cancer whose usual mean survival can be measured in months. Exposure to external radiation and living in endemic goiter area increase the frequency of thyroid cancer. Medullary thyroid carcinoma is often familial and may occur in associations with the multiple endocrine neoplasia syndromes.     

Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21

OBJECTIVE: To analyze the clinicopathologic features of a large cohort of patients with insular or anaplastic carcinomas treated at a single institution. SUMMARY BACKGROUND DATA: Insular and anaplastic carcinomas of the thyroid, although uncommon, have more aggressive clinical behavior than well-differentiated carcinomas of the thyroid. In the literature, the incidence and features of these carcinomas have not been fully characterized. METHODS: The authors reclassified 740 primary thyroid carcinomas diagnosed and treated between January 1, 1954, and December 30, 1998, to select those with features that met the histologic criteria of insular or anaplastic carcinoma. The clinicopathologic features of these carcinomas were studied and compared. The expression of p53 and p21 in these tumors was analyzed by immunohistochemistry. RESULTS: Twenty-two patients (5 men, 17 women) with insular carcinoma and 38 patients (7 men, 31 women) with anaplastic carcinoma were found. Patients with insular carcinomas were younger (mean age 45 vs. 70 years) and had smaller tumors than those with anaplastic carcinomas (mean diameter 5 vs. 8 cm). Insular carcinomas were commonly mislabeled as other histologic subtypes, whereas anaplastic carcinomas might be overdiagnosed on pathologic examination. A history of longstanding goiter (>10 years) was noted in 27% of patients with insular carcinoma and 24% of patients with anaplastic carcinomas. Concomitant well-differentiated carcinomas of the thyroid were noted in 59% of patients with insular carcinoma and 39% of patients with anaplastic carcinoma. In anaplastic carcinomas, 13% of patients had concomitant insular carcinoma. Calcification or bone was noted in the stroma of 23% of patients with insular carcinomas and 47% of those with anaplastic carcinomas. The 10-year survival rates for patients with insular carcinoma and anaplastic carcinoma were 42% and 3%, respectively. Distant metastases were seen in 32% of patients with insular carcinoma and in 47% of patients with anaplastic carcinomas. In both types of carcinomas, metastatic tumors were often seen in bone and lung. Distant metastases were noted in a variety of organs in anaplastic carcinomas. In insular carcinoma, neither p53 nor p21 expression was present. In anaplastic carcinoma, p53 and p21 expression was identified in 69% and 3%, respectively. Concomitant expression of p53 and p21 was noted in one tumor. CONCLUSIONS: Insular carcinoma and anaplastic carcinoma had distinctive clinicopathologic features, and recognition of these histologic variants is important for better management of these tumors in the future. p53 overexpression might have a role in dedifferentiation from insular carcinoma to anaplastic carcinoma.     

甲状腺功能亢进合并甲状腺癌的诊断和外科治疗

目的 探讨甲状腺功能亢进合并甲状腺癌的诊断及治疗方法.方法 回顾性分析北京协和医院从1983年1月至2009年7月收治的并经外科手术治疗和病理证实的48例甲状腺功能亢进合并甲状腺癌患者的临床资料.结果 甲状腺功能亢进合并甲状腺癌患者占同期甲状腺功能亢进手术患者的2.02%(48/2378),占同期甲状腺癌手术患者的3.03%(48/1584).手术方式包括双侧甲状腺大部切除术(31例)、患侧全切对侧大部切除和区域性淋巴结清扫术(6例)、双侧全切及淋巴结清扫术(11例).术前超声诊断阳性率为61.3%,甲状腺核素显像的诊断阳性率为62.5%;48例患者中获随访40例,时间1～264个月,中位随访时间130.5个月.随访中无甲状腺功能亢进复发病例,2例患者术后第二年出现肺、骨转移.结论 超声检查和核素显像对于术前诊断有重要意义,甲状腺功能亢进合并甲状腺隐匿癌和微小癌的临床诊断较困难,多于手术后病理诊断.甲状腺功能亢进合并甲状腺乳头状癌的患者手术治疗效果良好,预后较好.     

Insular carcinoma of the thyroid in a 10-year-old child

Thyroid carcinomas are relatively infrequent in the pediatric age group, the majority of which are papillary carcinomas. Poorly differentiated carcinomas are very rare in this age group. Insular carcinoma is a unique subset of poorly differentiated carcinoma of thyroid, which occurs predominantly in adults older than 50 years. In terms of prognosis, insular carcinoma of thyroid occupies a place in between that of well-differentiated papillary/follicular carcinoma and anaplastic carcinoma. The authors describe a case of insular carcinoma of thyroid in a 10-year-old girl who underwent hemithyroidectomy based on a preoperative diagnosis (by fine-needle aspiration cytology) of colloid goiter, and after histopathologic diagnosis of the specimen, a completion thyroidectomy was performed with block dissection of the neck. The authors believe this to be the youngest case of insular carcinoma of thyroid to be reported.     

Necessity and safety of completion thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND. The diagnosis of thyroid carcinoma during the course of lobectomy for a dominant nodule occasionally cannot be rendered on the basis of frozen section. Once the diagnosis of carcinoma is made, the question of completion thyroidectomy arises. The decision to perform completion thyroidectomy and the timing, safety, and efficacy of this procedure are reviewed. METHODS. During the past 25 years (1965 to 1990), we operated on 351 consecutive patients with thyroid carcinoma. One hundred of these patients (84 women and 16 men) were initially treated by unilateral thyroid lobectomy for the previously stated reasons. Histopathologic examination of the permanent sections of the initial thyroid lobectomy specimen demonstrated papillary carcinoma in 70 patients and follicular carcinoma in 30 patients. Within a few months, a completion thyroidectomy was performed. RESULTS. The completion thyroidectomy specimen contained papillary carcinoma in 33 (47%) of the 70 patients with papillary carcinoma and 10 (33%) of the 30 patients with follicular carcinoma. Overall, 43 of these 100 patients harbored thyroid carcinoma in the contralateral lobe. Complications of completion thyroidectomy were transient recurrent nerve paresis in two patients and temporary hypoparathyroidism in three patients, requiring calcium and vitamin D therapy for a few months. CONCLUSIONS. Although the significance and treatment of papillary carcinoma are debated on the basis of size and grade of the primary lesion and age and sex of the patients, once the diagnosis is made in one lobe we believe that a completion thyroidectomy should be considered, not only for papillary carcinomas but also for follicular carcinomas because 47% (papillary) to 33% (follicular) of these patients will harbor the neoplasm in the contralateral lobe.     

A twenty-year experience with thyroid carcinoma in children

During the past 20 years, 23 patients (7 males, 16 females) were operated on for thyroid carcinoma in our institution. The average age was 13.6 years (range, 22 months to 27 years). Our series includes papillary carcinoma in 11, follicular carcinoma in four, and medullary thyroid carcinoma in eight patients. Follow-up ranged from 8 months to 20.3 years, with an average of 7.5 years for well-differentiated carcinomas and 4.3 years for medullary thyroid carcinomas. All patients are presently alive with no evidence of progressive disease. Patients with papillary and follicular carcinomas underwent partial thyroidectomy; those with medullary carcinoma underwent total thyroidectomy. Serious complications included three permanent hypoparathyroidism and two tracheostomies, all after secondary neck explorations. The overall results observed in our series of patients seem to support the current conservative approach to well-differentiated thyroid carcinoma, reserving total thyroidectomy for medullary cancer of the thyroid. A more aggressive search for familial medullary carcinoma through use of pentagastrin stimulation leads to early detection and more effective therapy.     

Differentiated thyroid carcinoma: comparison between papillary and follicular carcinoma in a single institute

PURPOSE: To compare and contrast the clinical presentation and treatment outcome of patients with papillary and follicular thyroid carcinoma and to study the pattern of practice of treatment of differentiated thyroid carcinoma in Hong Kong. METHOD: The clinical presentation and treatment outcomes were reviewed for 1057 patients with differentiated thyroid cancers who were treated at the Queen Elizabeth Hospital, Hong Kong, from 1960 to 1997. Eight hundred forty-two patients had papillary thyroid carcinomas (PTC), and 215 had follicular thyroid carcinomas (FTC). The mean follow-up was 9.2 years. RESULTS: The differences in the clinical factors of PTC to FTC were as follows: PTC had a higher incidence (3.9:1); these patients were younger at presentation (median age, 44 vs 49), showed a higher female-male ratio (4.5 vs 2.9) and smaller primary tumor size (median 2 cm vs 3.5 cm), and a higher incidence of multifocal disease (28.3% vs 18.1%), extrathyroidal extension (39.4% vs 14%), and more lymph node metastases (33.3% vs 12.1%). The incidence of distant metastases was higher for patients with FTC (28.8% vs 8.9%), and cause-specific survival rates were lower (p =.001). The locoregional control rates were not significantly different (p =.2). The 10-year cause-specific survival, freedom from distant metastasis, and locoregional failure figures for PTC compared with FTC were 92.1% vs 81%, 90.8% vs 72.3%, and 78.5% vs 83%. CONCLUSIONS: Although patients with PTC tend to have more advanced locoregional disease compared with those with FTC, the likelihood of locoregional control is similar, and the probability of cure is better.     

Nodal Microinvolvement in Patients with Carcinoma of the Papilla of Vater Receiving No Adjuvant Chemotherapy

Background  To assess the prognostic significance of nodal microinvolvement in patients with carcinoma of the papilla of Vater. Methods  From 1993 to 2003 at the University Clinic Hamburg, 777 patients were operated upon pancreatic and periampullary carcinomas. The vast majority of patients were operated upon pancreatic ductal adenocarcinoma (n = 566, 73%), followed by carcinomas of the papilla of Vater (n = 112, 14%), pancreatic neuroendocrine carcinomas (n = 39, 5%), intraductal papillary mucinous neoplasms (n = 33, 4%), and distal bile duct carcinomas (n = 27, 3%). Fresh-frozen tissue sections from 169 lymph nodes (LNs) classified as tumor free by routine histopathology from 57 patients with R0 resected carcinoma of the papilla of Vater who had been spared from adjuvant chemotherapy were immunohistochemically (IHC) examined, using a sensitive IHC assay with the anti-epithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathology, 39 (63%) of the patients were staged as pT1/pT2, 21 (37%) as pT3/pT4, 30 (53%) as pN0, while 38 (67%) as G1/G2. Results  Of the 169 “tumor-free” LNs, 91 LNs (53.8%) contained Ber-EP4-positive tumor cells. These 91 LNs were from 40 (70%) patients. The mean overall survival in patients without nodal microinvolvement of 35.8 months (median—not yet reached) was significantly longer than that in patients with nodal microinvolvement (mean 16.6; median 13; p = 0.019). Multivariate Cox regression analysis for overall survival revealed that grading was the most significant independent prognostic factor (p = 0.001), followed by nodal microinvolvement (p = 0.013). Conclusions  The influence of occult tumor cell dissemination in LNs of patients with histologically proven carcinoma of the papilla of Vater supports the need for further tumor staging through immunohistochemistry.     

Flow cytometric DNA analysis of thyroid carcinoma

Abnormal DNA content has been considered as an additional criterion for determining the biological behavior of a tumor. Flowcytometric DNA analysis was done on 121 patients with thyroid carcinoma encountered during the period between 1975 and 1987. Tumor tissues were sampled from paraffin-embedded blocks and the histology of thyroid carcinoma found to consist of 91 papillary, 23 follicular, 2 medullary, 1 squamous cell and 4 anaplastic carcinomas. The incidence of aneuploidy in thyroid carcinoma was 7.4 per cent (9 patients) while that of diploidy was 92.6 per cent (112 patients). The aneuploid specimens consisted of 6 papillary, 1 follicular, 1 medullary and 1 anaplastic carcinomas and, of 4 anaplastic carcinoma patients with subsequent death within 6 months, only 1 was aneuploid. As an indicator of proliferative potential, S-phase fraction (SPF) was also determined by flow cytometry, but this could not be used as an independent prognostic factor. The aneuploid patients showed a significantly decreased survival rate (p<0.01). Thus, although DNA measurement proved useful for predicting the survival of aneuploid patients, there is some discrepancy between DNA content and the biological behavior of the tumor.