Malignant hemangioendothelioma of the thyroid. Its immunohistochemical discrimination from undifferentiated thyroid carcinoma.

Eighteen cases of malignant hemangioendothelioma (MHE) of the thyroid and 16 cases of undifferentiated thyroid carcinoma were investigated immunohistochemically with antibodies against endothelial cell specific markers (factor VIII-related antigen, BMA 120, blood group isoantigens, Ulex europaeus agglutinin I), thyroglobulin, and the intermediate filament proteins vimentin and cytokeratin. All MHE were positive for factor VIII-related antigen and vimentin, in 14 of 18 cases for BMA 120, and in 9 of 18 cases for U. europaeus. All other markers were negative in MHE. Endothelial cell specific markers were commonly negative in undifferentiated carcinomas with one exception (one case was moderately positive for U. europaeus). Twelve of 16 undifferentiated carcinomas showed vimentin positivity, and 8 of 16 showed cytokeratin positivity. Four cases showed a vimentin/cytokeratin coexpression. It is concluded that the endothelial origin of MHE can be shown by certain endothelial cell markers in almost all cases.

Small cell carcinoma of the thyroid. A reclassification of cases originally diagnosed as small cell carcinomas of the thyroid.

99 cases of undifferentiated carcinomas of the thyroid and nine cases of primary malignant Non-Hodgkin lymphomas of the thyroid were examined from 1967 to 1983 in our institute. Among the undifferentiated carcinomas nine cases were classified as small cell subtype. Over the years, the histopathological handling in regard to small cell subtype of undifferentiated carcinoma and primary malignant Non-Hodgkin lymphoma has changed. The frequency of primary malignant Non-Hodgkin lymphoma has increased conspicuously in the last few years, whereas the number of small cell carcinomas decreased. A reclassification, based on immunohistochemical investigation for tumor markers of the nine cases originally diagnosed as small cell carcinomas from 1967 to 1983 revealed that five cases were poorly differentiated carcinomas or undifferentiated carcinomas of the spindle cell type. In three cases the primary diagnosis had to be revised into malignant Non-Hodgkin lymphoma of the diffuse "histiocytic" type. The postmortem examination of the patient with the remaining small cell carcinoma "of the thyroid" revealed a clinically undetected small cell carcinoma of the lung with metastases to the cervical lymph nodes and the thyroid gland. These findings are in agreement with the results of several recently published papers indicating that true small cell carcinoma of the thyroid must be a very rare tumor.

A fourteen year practice with the fine needle aspiration biopsy of the thyroid in an endemic area.

In our institute from 1970 to 1983 12,829 fine needle aspiration biopsies (FNB) of the thyroid were cytologically examined. Cytologically unsatisfactory specimens were found in 17.7%. 2,709 patients with representative cytological findings were operated and histological examinations were performed. The cytological and histological findings were correlated. There was a false-negative rate of 2.0% and a false-positive rate of 18.4%. Furthermore we divided the results into two time periods (1970-1977 and 1978-1983) because of a change in the indication for surgery in the last years. Although the indication has changed, cytological findings of both time periods investigated were almost similar.

Papillary carcinoma of the thyroid gland. Analysis of 94 cases with preoperative fine needle aspiration cytologic examination.

From 1979 to 1983, 94 papillary carcinomas of the thyroid gland were examined histologically in our institute after a preoperative cytologic examination. Material for cytologic examination was obtained using fine needle aspiration (FNA) biopsy. Eighty-five (90.4%) of the 94 examined cytologic smears were representative. Among these 85 cases suspicion for malignancy or malignancy itself was found in 64 cases (75.3%). The remaining 21 smears, classified as cytologically not as suspect for malignancy, were reclassified and the previous diagnosis had to be revised in one case. In the other 20 cases no clue for malignancy could be demonstrated even after reexamination. In the 85 cases with representative cytologic findings, tumor size was determined on surgical material, in order to establish how many carcinomas with a diameter less than 3 cm could not be reached by FNA biopsy. Except for one case, all carcinomas with negative preoperative cytologic findings had a diameter less than or equal to 3 cm. The question arising is the possibility of improving the accuracy of FNA biopsy in tumor detection within cold nodules of the thyroid by combined use of scintigraphy and ultrasound-guided FNA biopsy.

Metastatic tumors in fine needle aspiration biopsy of the thyroid.

A series of almost 25,000 thyroids examined by fine needle aspiration (FNA) biopsy was reviewed to ascertain the incidence and presentation of metastatic cancers in thyroid FNA samples. Metastatic cancers in FNA samples from the thyroid were identified in 25 cases (0.1%); the primary tumors were carcinomas of the kidney (8 cases), lung (7 cases), breast (5 cases), cervix uteri (1 case) and colon (1 case) and 1 case each of malignant melanoma, malignant pleural mesothelioma and rhabdomyosarcoma. FNA cytology was positive in all 25 cases. In 11 cases, the primary tumor was clinically known at the time of FNA biopsy; of the other 14 cases, cytology suggested that the malignancy was metastatic in only 5. Metastases of renal and mammary adenocarcinomas were almost indistinguishable from follicular and papillary thyroid carcinomas on cytologic grounds. The results demonstrate the rarity of this finding and the difficulty of diagnosing a metastatic tumor in the thyroid by FNA biopsy, in the absence of a clinical history of a prior primary neoplasm.

Clinicopathologic management of tumors of the thyroid gland in an endemic goiter area. Combined use of preoperative fine needle aspiration biopsy and intraoperative frozen section.

In total, 15,325 fine needle aspiration (FNA) biopsies of the thyroid were examined in the Department of Pathology of the University of Innsbruck, Austria, between 1976 and 1985, with the cytologic results histologically verified in 3,112 cases. Since (1) it is frequently impossible to distinguish benign from malignant encapsulated follicular thyroid tumors by cytologic criteria and (2) there is a high level of follicular thyroid carcinoma in our endemic goiter area, we have adopted a diagnostic strategy that accepts a high percentage of false-positive cytologic results in order not to miss highly differentiated follicular carcinoma. To avoid unnecessarily extensive surgical treatment, 1,079 intraoperative frozen section examinations of the thyroid were performed in the same time period in (1) patients with preoperative suspicious or positive FNA cytologic findings, (2) cases with suspicious clinical and anamnestic data and (3) tumors with a suspicious macroscopic appearance without preoperative FNA or with negative or unsatisfactory cytologic findings. In 48 cases (4.5%), the frozen section diagnosis had to be revised after examination of paraffin-embedded tissue. An intraoperative false-positive diagnosis was obtained in 3 cases (0.3%) while a false-negative diagnosis was made in 45 cases (4.2%). The main effort in examining frozen sections should be concentrated on avoiding false-positive errors, which can lead to unnecessary thyroidectomies.

[Early diagnosis of thyroid cancer in endemic goitre area reflections and management based on the epidemiological situation in Tyrol (author's transl)]. / Die Früherfassung des Schilddrüsenkarzinoms im Strumaendemiegebeit. Uberlegungen und Vorgehen auf der Basis der epidemiologischen Verhältnisse in Tirol.

Until recently the prognosis of thyroid cancer has been poor in this endemic goitre area due to the predominance of aggressive tumour types and belated diagnosis of the carcinoma. Iodine prophylaxis has changed this epidemiological profile: the mortality of goitre has generally decreased and there has been a relative increase in differentiated carcinomas. Preoperative diagnosis and operability have been favourably influenced by this new situation. Thus, whereas from 1960 to 1967 radical operation was impossible in 78.6% of thyroid cancers, between 1978 and 1981 only 12.4% of all cases had invasive tumours of distant metastases at the time of operation and 79.3% of all patients were staged as To-2N0Mo. An improvement in survival rate can be expected with early diagnosis of thyroid cancer. Nevertheless, individual prognostic statements can be made only after evaluation of these findings according to "prognostic systems", for in thyroid cancer--as in no other kind of carcinoma--prognosis is determined by a combination of the patient's age and sex, cell type and histological tumour pattern and TNM status.

[The significance of radioimmunological HPL determination in obstetrics (author's transl)]. / Die Bedeutung der radioimmunologischen HPL-Bestimmung in der Geburtsmedizin

The serum HPL level was studied in normal and high-risk pregnancies. 30 patients with premature labour showed significantly decreased levels. In 24 patients with monosymptomatic toxaemia, HPL patterns showed a statistically significant deviation from the normal standard curve; a highly significant decrease was observed in 23 cases of polysymptomatic gestoses. As opposed to the results of other authors, no significant difference from the normal distribution of HPL was found in cases of Rh sensitisation (13 patients) and diabetes mellitus (16 patients). A noteworthy results was seen in 19 cases of cervix insufficiency: after purse-string suturing of the cervix (original method of Shirodkar), the previously low plasma HPL level rapidly rose to normal levels. Because of the small number of cases without an adequate control group this phenomenon cannot be attributed with certainly, as yet, to the cerclage procedure.

[Malignant hemangioendothelioma of the thyroid gland. Pathology, clinical aspects and prognosis]. / Das maligne Hämangioendotheliom der Schilddrüse. Pathologie, Klinik und Prognose.

Malignant hemangioendothelioma (MHE) of the thyroid still constitutes a relatively important part of our surgical material, with 23 MHE (2.0%) among 1153 primary thyroid tumors diagnosed between 1952 and 1987 (biopsy material of the Innsbruck Pathology Institute). 18 of these cases were investigated immunohistochemically; in 14 cases the data on clinical findings and follow-up were complete. Immunohistochemical results confirm the endothelial origin of this tumor and allow MHE to be definitively distinguished from anaplastic carcinomas. Follow-up and prognosis are determined by the aggressive nature of local tumor spread. 13 patients died after a median survival period of 2.4 months (R: 1.2-9.4). Only one patient has remained alive since over 4 1/2 years now. An improvement of the hitherto dismal prognosis is thought to depend on early tumor diagnosis and an ameliorated combined modality treatment.

[The thyroid gland scintigram. A decision aid for the surgical approach in thyroid gland diseases?]. / Das Schilddrüsenszintigramm. Eine Entscheidungshilfe für die Operationstaktik bei Schilddrüsenerkrankungen?

For the operative proceeding thyroid scintiscan seems widely dispensable in many routine cases as it leads neither to a different operative strategy nor to an improvement of surgical results. In a few selected cases, however, operative proceeding is determined by scintigraphic results. Thus the question of the importance of scintigraphic methods for thyroid diagnostics and therapy as well as for the selection of patients for surgery cannot be answered and must be subject of a separate examination.

[Complications in thyroid surgery (author's transl)]. / Komplikationen in der Schilddrüsenchirurgie. Eine Studie an Hand von 443 Ersteingriffen bei benignen Strumen.

From 1975 to 1979 443 primary operations were performed in benign goiters. The total complication (intra- and immediately postoperatively) rate was 9.2%. Remarkable was the mortality rate of 0% and the rate of postoperative recurrent nerve palsy of 5.4%. The alterations of the surgical material by iodine prophylaxis and by extended thyroid diagnostics are shortly discussed. The topography of the recurrent nerve and its special items in endemic goiter area are described and the problems of intra-operative nerve preparation are commented.

[Prognosis of follicular thyroid cancer in the Tyrolean endemic goiter area]. / Zur Prognose des folliculären Schilddrüsencarcinoms im Tiroler Strumaendemiegebiet.

89 follicular thyroid cancers (from 1952 to 1975) with detailed histology, complete clinical data and follow-up were analysed by several variables of which some prognostic importance could be expected. The observed survival times range from 0.08 to 27.75 years. Observed cumulative and expected survival rates were calculated and evaluated statistically. Evaluation of individual prognosis naturally demands a combination of histological, macropathological and clinical data: extent of primary tumor, capsular penetration and vascular infiltration, lymphnode involvement and distant metastases proved to be important parameters. The classification in intra-and extrathyroid carcinoma is to be preferred to the T-classification of the UICC, because it is simple and of great prognostic value.

[Follicular thyroid cancer. A multivariate analysis]. / Das follikuläre Schilddrüsenkarzinom. Eine multivariate Analyse.

The prognosis of malignant tumors is determined by a number of factors and their interaction. These factors may be assessed statistically by means of regression models for the hazard rates, which are assumed to be proportional. 89 follicular thyroid cancers from 1952 to 1975 were analysed according to clinical, macropathological and special histological criteria. Those variables which significantly influence the survival function were defined precisely and quantified by multivariate analysis. The age of the patients at the time of diagnosis (primary operation), sex, and local tumor extent (and therefore radical surgery) proved to be prognostically significant. Thus, the TNM system alone is sufficient neither for individual prognostic pronouncements nor for forming risk groups.

Surgical aspects of diseases of the thyroid gland in childhood.

The treatment of juvenile struma is the domain of the pediatrician, and operations are rarely necessary, even in struma-endemic regions. An absolute indication for surgery is diagnosed or suspected struma maligna: relative indications are hyperthyroidism and euthyroid goiter. The operative procedure in benign thyroid diseases is based on the pathogenesis: a tissue-saving technique is mandatory to prevent postoperative hypothyroidism. Therapeutic strategy in malignant diseases, i.e., the radicality of surgical and postoperative management, depends, as in adults, on the prognostic relevance of variable parameters.

[Papillary thyroid cancer--prognosis and prognostic factors]. / Das papilläre Schilddrüsencarcinoma--Prognose und prognostische Faktoren.

90 papillary thyroid carcinomas (operated on between 1952 and 1977) were retrospectively analysed. The median follow-up is 5.29 years (range 0.08-29.42 years). After the primary operation only 68.9% of all patients may be classified as "tumor free". The lethality rate from thyroid cancer is 28.9%, the cumulative survival rates at 10 and 20 years are 50.92% and 32.06%, respectively. Thus survival is not significantly different from the one of our follicular carcinomas. The whole material was characterized thoroughly by clinical and morphological parameters. The simultaneous examination of the variables as to their prognostic relevance was performed by means of a log-logistic regression model for survival data. Age, extension of primary tumor, vascular invasion and presence of colloid determined prognosis. For the histopathological practice a differentiation between vascular and lymphatic invasion is demanded.

[Atypical adenoma of the thyroid gland [author's transl)]. / Atypisches Schilddrüsenadenom.

A total of 2204 nonmalignant goiters surgically removed during the years 1958, 1959, 1960 and 1966 were reexamined. Among them 181 adenomas were found, which were classified as 'atypical' by cytological respectively histological means. Those patients who had been primarily operated on at our hospital were questioned about the clinical course after the operation. Our results show a benign development of atypical thyroid adenomas, which means no recurrence of this type of adenoma nor metastasing in either of the cases during the observation period. The criteria of the WHO (Hedinger u. Sobin, 1974) for malignancy typing (with special emphasis on vascular invasion and caposular penetration and less attention to the histological structure and nuclear polymorphism) are thus verified. With exact histological exclusion of malignity, we believe, that in case of atypical adenoma, thyroidectomy is not necessary. Nevertheless a careful postoperative control of the patient is strictly indicated.

[Endemic goitre before and after goitre prophylaxis (author's transl)]. / Die endemische Struma vor und nach der Kropfprophylaxe.

Between 1952 and 1977 there has been a considerable change in the type of goitre operated on in the endemic area of the Austrian Tyrol. Iodine prophylaxis had proved significantly more effective in men: the consequences appear earlier and extend into the middle age groups. As a result, the type of surgical specimen is much more like that seen in non-endemic areas. The incidence of diffuse colloid goitre decreased, as that of adenomatous goitre increased. Among the adenomas, the number of the colloid-rich form has increased. Instead of diffuse or multinodular goitre one now frequently encounters the symptom-free, often uninodular, goitre. The total number of goitre operations has also decreased.

[The intramural duodenal diverticulum, a topical variation of the intraluminal duodenal diverticulum (author's transl)]. / Das intramurale Duodenaldivertikel, eine topographische Varietät des intraluminalen Duodenaldivertikels.

The intramural duodenal diverticulum is a topical variation of the intraluminal duodenal diverticulum. It is manifested not before adult age by noncharacteristic upper abdominal symptoms. Diagnosis is made by radiologic examinations, the therapy is excision of the diverticulum. Structure and topography of the diverticulum are explained by its embryological development.