Wolfgang Rehpenning

Prognostic indices for tumor relapse and tumor mortality in follicular thyroid carcinoma

To establish an objective basis for therapeutic decisions and follow‐up programs in patients with follicular thyroid cancer, the authors developed a prognostic scoring system. The prognostic impact of nine clinical, histologic, and therapeutic parameters was quantified retrospectively based on a multivariate analysis covering 149 patients. The relative relapse risk in follicular thyroid cancer (RR) was 6.8‐fold increased in the presence of a moderate when compared with a high degree of histologic tumor differentiation. The RR rose with increasing age of the patient at time of tumor diagnosis by a factor of 1.8 per 20 years. The RR was reduced by a factor of 4.3 after the performance of a neck dissection and by a factor of 2.3 after percutaneous radiation therapy of the neck. The relative mortality risk in follicular thyroid cancer (RM) rose in the absence of a tumor capsule by a factor of 10, in the presence of a moderate compared with a high degree of histologic tumor differentiation by a factor of 5.9, in the presence of distant metastases by a factor of 3.2, and with increasing age of the patient at the time of tumor diagnosis by a factor of 2.2 per 20 years. From these data prognostic indices denoting the individual risk for tumor relapse (IRR index) and tumor mortality (IMR index) were calculated. The indices categorize patients into low‐risk, medium‐risk, or high‐risk groups with regard to tumor relapse and tumor‐related death. Consequently, the IRR and IMR indices contribute to select patients with follicular thyroid cancer who need an aggressive form of treatment and an intensive follow‐up program. The indices may also be used for risk stratification in prospective therapy trials.

Prognostic significance of Leu-M1 immunostaining in papillary carcinomas of the thyroid gland.

Leu-M1 antigen is a monocyte/granulocyte-related marker known to be consistently expressed in the Reed-Sternberg cells of patients with Hodgkins disease. Recently, however, the presence of Leu-M1 has also been noted in tumour cells of a variety of non-haematopoietic neoplasms, most of them adenocarcinomas. The biological significance of this aberrant reaction has not been clarified. We have been able to demonstrate marked epithelial Leu-M1 immunoreactivity (>15% tumour cells positively stained) in 24 out of 76 (32%) papillary carcinomas of the thyroid gland (PC). This phenomenon was more frequently observed among PCs at an advanced stage of disease (pT4 vs. pT1–3 and M1 vs. M0 p<0.05). The degree of epithelial Leu-M1 positivity was also shown to be significantly correlated to the clinical course of PC. Irrespective of other morphological and clinical features, death resulting from cancer occurred 17 times more frequently among PCs with marked Leu-M1 positivity (8/24) when compared with tumours with only slight or absent immunoreactivity (1/52) (p<0.00005). These findings suggest that Leu-M1 immunostaining provides significant prognostic information for patients with papillary carcinoma of the thyroid gland.

DNA cytophotometry and prognosis in ovarian tumors of borderline malignancy. A clinicomorphologic study of 80 cases

Surgical specimens of 80 ovarian tumors of borderline malignancy (OTBM) were investigated by scanning DNA cytophotometry. Diploid or euploid DNA histograms were found for 21 tumors, whereas 59 OTBM showed noneuploid or aneuploid DNA patterns. All patients were followed‐up after surgery for at least 3 years (mean observation period, 6.7 years). Follow‐up showed 11 cases of recurrent disease and 6 deaths. DNA findings and several other morphologic and clinical details (including patient age, histologic type and stage of disease, and extent of therapy) were correlated to the postoperative course. Statistical analyses disclosed that, of these parameters, only DNA content significantly affected prognosis. Recurrences and deaths resulting from tumor exclusively were observed among patients with noneuploid or aneuploid OTBM, whereas none of the diploid or euploid tumors recurred (P < 0.05). DNA cytophotometry thus might be regarded as an effective complementary means to assess the prognosis of individual OTBM cases.

Radioprotection of minipig salivary glands by orciprenaline-carbachol : an ultrastructural and semiquantitative light microscopic study

Parotid and submandibular glands of miniature pigs were exposed to 36 Gy X-irradiation given as 6×6 Gy in 3 weeks. Half of the animals received orciprenaline and carbachol before each dose. The effects were analysed 6 months later by light and electron microscopy. Ultrastructural examination showed less change in the pretreated glands. Semi-quantitative light microscopic data confirmed the significance of the differences. Acinar cells of both glands were significantly more numerous (P<0.01) and the cells were better preserved (P<0.01) in the pretreated group. The effect was more pronounced in the parotid gland, which appeared almost normal. Intercalated ducts of the parotid glands (P<0.01) and striated ducts of the submandibular glands (P<0.05) showed less change in pretreated animals. The findings confirm the radioprotective effect of pharmacologically induced degranulation of acinar cells. The biological effects of the radiation schedule (cumulative radiation effect value 18.76) as well as the dosage of orciprenaline and carbachol are within the normal range of medical treatment. Similar results may be expected from future studies in man.

Leu-M1 immunoreactivity and prognosis in medullary carcinomas of the thyroid gland.

SummaryLeu-M1 antigen is a monocyte/granulocyte-related marker known to be consistently expressed in the Reed-Sternberg cells of patients with Hodgkins disease and to be present in tumour cells of a variety of non-haematopoietic neoplasms, most of them adenocarcinomas. The biological significance of this aberrant reaction has not yet been clarified. Recently, however, we have demonstrated that marked epithelial Leu-M1 immunoreactivity significantly correlated with an unfavourable clinical course in papillary carcinomas of the thyroid gland. The findings of the present study obtained from surgical speciments of 39 tumours suggest that Leu-M1 immunostaining also provides significant prognostic information in patients with medullary carcinoma (MC) of this organ. Irrespective of other morphological and clinical features, local recurrences occurred 2.9 times (P<0.005) and death resulting from tumour occurred 4.3 times (P<0.03) more frequently among MCs with marked Leu-M1 positivity (>15% tumour cells positively stained) in comparison to tumours with only slight or absent immunoreactivity. A significantly higher recurrence rate of intense Leu-M1-positive MCs was even evident when comparing only tumours of stage pT1-3N0M0 (P<0.005). Our findings infer that Leu-M1 immunostaining might be of clinical relevance to the selection of different aggressive adjuvant therapeutic procedures to be used in MCs with high or low malignant potential.

Prognosekriterien des papillären Schilddrüsencarcinoms

A retrospective study of 202 papillary thyroid carcinomas was conducted to determine the prognostic value of different morphological and clinical features. The biological behaviour was primarily influenced by tumor type: Among encapsulated (n = 28) and occult lesions (n = 34), each time recurrence-free survival was seen, whereas 22% of patients with widely invasive tumours (n = 140) died from carcinoma (mean observation period: 9.6 years). In the latter group, dismal prognosis was demonstrated for older patients (greater than 52 years) and oxyphilic or poorly differentiated tumours; the same effect was shown for presence of distant haematogenous spread and tumour invasion of cervical soft tissue. Since lethal outcome was seen even in cases lacking the aforenamed unfavourable criteria, total thyroidectomy should be performed for all widely invasive neoplasms regardless of cellular or histological differentiation, stage of disease and age at diagnosis. The same applies for the two prognostically excellent subtypes in the case of regional metastases. As opposed to this, hemithyroidectomy and life-long TSH-suppressive oral hormone replacement therapy is regarded to be sufficient in encapsulated and occult papillary tumours not accompanied by regional or distant metastases.SummaryA retrospective study of 202 papillary thyroid carcinomas was conducted to determine the prognostic value of different morphological and clinical features. The biological behaviour was primarily influenced by tumor type: Among encapsulated (n = 28) and occult lesions (n = 34), each time recurrence-free survival was seen, whereas 22% of patients with widely invasive tumours (n = 140) died from carcinoma (mean observation period: 9.6 years). In the latter group, dismal prognosis was demonstrated for older patients (> 52 years) and oxyphilic or poorly differentiated tumours; the same effect was shown for presence of distant haematogenous spread and tumour invasion of cervical soft tissue. Since lethal outcome was seen even in cases lacking the aforenamed unfavourable criteria, total thyroidectomy should be performed for all widely invasive neoplasms regardless of cellular or histological differentiation, stage of disease and age at diagnosis. The same applies for the two prognostically excellent subtypes in the case of regional metastases. As opposed to this, hemithyroidectomy and life-long TSH-suppressive oral hormone replacement therapy is regarded to be sufficient in encapsulated and occult papillary tumours not accompanied by regional or distant metastases.ZusammenfassungIn einer retrospektiven Studie an 202 papillären Schilddrüsencarcinomen wurden verschiedene Parameter auf ihre prognostische Bedeutung geprüft. Ihr Verhalten wurde vorrangig durch den Wachstumstyp bestimmt: Alle Patienten mit gekapselten (n = 28) oder occulten Carcinomen (n = 34) zeigten anhaltend rezidivfreies Überleben, während 22% der Patienten mit grob invasivem Carcinom (n = 140) am Tumor verstarben (mittlere Beobachtungszeit: 9,6 Jahre). In dieser Gruppe fand sich eine signifikant schlechtere Prognose bei älteren Patienten (> 52 Jahre), bei Nachweis niedriger Differenzierung oder eines oxyphilen Zelltyps, weiterhin bei Vorliegen von Fernmetastasen oder einer Halsweichteilinfiltration. Da auch bei grob invasiven Carcinomen ohne vorgenannte Kriterien letale Verläufe auftraten, sollte bei diesen Tumoren unabhängig von cellulärer oder histologischer Differenzierung, Stadium und Patientenalter obligat eine totale Thyreoidektomie durchgeführt werden. Dasselbe gilt für die zwei prognostisch exzellenten Subtypen dann, wenn initial Metastasen manifest sind. Dagegen wird bei gekapselten und occulten Carcinomen ohne Lymphknoten- bzw. Fernmetastasen die Hemithyreoidektomie mit lebenslanger TSH-suppressiver Schilddrüsenhormongabe als ausreichend angesehen.

Morphometric lightmicroscopic and immunohistochemical analyses of differentiated thyroid carcinomas

Twenty-four differentiated human thyroid carcinomas were investigated light microscopically and immunohistochemically by morphometric methods. The study revealed that thyroglobulin synthesis in follicular and papillary carcinomas is independent of tumor type and histostructural differentiation. The immunohistochemical results suggest that a defect in thyroglobulin synthesis and thyroglobulin secretion in addition to iodine accumulation and organification defects impairs the effectiveness of postoperative radioiodine treatment of differentiated thyroid carcinomas.