H. Dralle

Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma

Lymph node metastases have been proven to be the main prognostic factor in medullary thyroid carcinoma (MTC). This retrospective study was undertaken to evaluate the efficiency of two surgical techniques of regional lymph node dissection with regard to the normalization of pentagastrin-stimulated serum calcitonin level and patient survival: selective lymphadenectomy, i.e., the excision of macroscopically or microscopically involved lymph nodes, versus a systematic lymphadenectomy performed by the new technique of a compartment-oriented microdissection. From 1970 to 1990, 82 patients with sporadic (n=57) and hereditary (n=25) MTC underwent a total of 142 operations including 63 selective lymphadenectomies and, since 1986, 35 systematic lymphadenectomies. The study revealed that in node-positive MTC the rate of interventions with a postoperative normalization of pentagastrin-stimulated serum calcitonin was higher after systematic lymphadenectomy (29.2%) than after selective lymphadenectomy (8.5%) (P<0.01). The rate of patients undergoing repeat surgery due to a recurrence of MTC was 48% after selective lymphadenectomy and 10% after systematic lymphadenectomy. Survival was significantly better for patients after systematic versus selective lymphadenectomy (P<0.005). This study thus emphasizes that systematic lymphadenectomy, using the technique of a compartment-oriented microdissection of cervicomediastinal lymph nodes, represents the preferred surgical treatment as well as the optimum technique in primary as well as secondary node-positive MTC.

Human thyrotropin receptor gene: expression in thyroid tumors and correlation to markers of thyroid differentiation and dedifferentiation.

Human thyrotropin (TSH) receptor steady-state transcript levels were analyzed by Northern blot analysis in thyroids of patients with thyroid carcinoma, with hyperfunctioning adenoma and in normal controls. In control tissue and benign tumors expression levels of TSH receptor mRNA were high whereas in anaplastic carcinomas no normal TSH receptor mRNA was detected. In papillary and follicular tumors it varied from normal to markedly reduced levels. Thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA were strongly expressed in normal tissue and in hyperfunctioning adenomas but were completely lost in all anaplastic tumors. In papillary tumors expression of TPO and Tg mRNA varied from normal to a complete loss of expression of either TPO, Tg or both. Tg and TPO steady-state expression did not correlate to TSH receptor transcript levels. C-myc mRNA was highly expressed in anaplastic carcinomas, very variable in normal controls and in differentiated thyroid tumors and low in hyperfunctioning adenomas. In summary, TSH receptor mRNA is persistently expressed in all differentiated thyroid tissues and tumors but lost in undifferentiated carcinomas. Its persistence far along the transformation pathway further supports the concept that this gene which inserts the thyrocytes in the physiological regulatory network is almost constitutively expressed in this cell.

The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study

Abstract. Clinical data of 139 patients with hereditary medullary thyroid carcinoma (HMTC) from nine european centres surgically treated from 1980 to 1991 were reviewed retrospectively to analyse the value of systematic versus selective lymphadenectomy (LA). Biochemical cure rate was significantly higher in patients who underwent LA compared to patients who did not. In nodal‐positive HMTC, systematic LA compared to selective LA improved biochemical cure in small but not large tumours. In nodal‐negative HMTC, systematic LA compared to selective LA could not improve biochemical cure in either small or large primary tumours. To prevent local recurrences with the risk of increased surgical and tumour‐related morbidity, systematic LA should be performed in all HMTC patients regardless of the primary tumour stage. However, an improvement of biochemical cure by systematic LA seems to be possible only in nodal‐positive small primary tumours without distant metastases.

Surgical management of MEN 2.

The multiple endocrine neoplasia (MEN) syndromes are genetically transmitted endocrinopathies. In both types of MEN syndrome, usually one organ predominantly is affected; however, the individual manifestation of the disease with regard to time and extent of organ involvement varies considerably. Unlike in MEN 1, in MEN 2 surgical treatment represents the therapy of choice for each part of the disease.

Die transsternale zervikomediastinale Primärtumorresektion und Lymphadenektomie beim Schilddrüsenkarzinom

SummaryThyroid carcinoma may invade the mediastinum by direct extension of the primary tumor or metastases to the paratracheal or retroclavicular-parajugular lymph nodes. From 1975 to 1991 in 47 out of 622 thyroid cancer patients (7.6%) [14 papillary (PTC), 5 follicular (FTC), 16 medullary (MTC) and 12 undifferentiated carcinoma (UTC)] transsternal tumor resection has been performed. Four patients (UTC three, MTC one) deceased 7, 8, 35, and 41 days after resection of the primary tumor due to cardiac or tumor disease, and in one patient because of acute arteriotracheal haemorrhage after external irradiation; no patient deceased after transsternal resection as a result of cervicomediastinal lymphadenectomy. At the time of primary operation 80% of patients showed an advanced tumor stage (> pT3). In 34% of patients (PTC 64%, FTC 40%, MTC 13%, UTC 25%) no tumor recurrence was observed neither by imaging nor by biochemical methods. In 18 patients a transsternal microdissection of all four cervico-mediastinal lymph node compartments has been performed. Histological analyses of excised and tumor involved lymph nodes revealed in 9 patients unilateral cervical and mediastinal and in 9 patients bilateral cervical and mediastinal lymph node metastases. In the case of unilateral cervicomediastinal lymph node metastases 2 out of 2 patients with papillary and 2 out of 6 patients with medullary thyroid carcinoma could be cured surgically. In the case of bilateral cervicomediastinal lymph node metastases 3 out of 4 patients with papillary thyroid carcinoma, but no other thyroid cancer patient were free of disease. In conclusion, main indications for transsternal cervicomediastinal resection in thyroid carcinoma are (1) primary tumors extending to the upper mediastinum, but without lymph node metastases, and (2) thyroid carcinomas with unilateral cervicomediastinal lymph node metastases. In the case of bilateral cervicomediastinal lymph node metastases probable only papillary thyroid carcinomas are supposed to be curable by transsternal multicompartmentectomy.ZusammenfassungSchilddrüsenkarzinome können das Mediastinum infiltrieren durch direkte Ausdehnung des Primärtumors oder Metastasierung in die paratrachealen oder retroklavikulär-parajugulären Lymphknoten. Von 1975–1991 wurde bei 47 von 622 Schilddrüsenkarzinom-patienten [7,6%, 14 papillary (PTC), 5 follikuldre (FTC), 16 medulläre (MTC) und 12 undifferenzierte Karzinome (UTC)] eine transsternale Tumorresektion durchgeführt. Vier Patienten mit UTC bzw. MTC verstarben 7, 8, 35 und 41 Tage nach der Primärtumorresektion an den Folgen kardialer Vorerkrankungen bzw. am Tumorleiden und, in einem Fall, an einer akuten arteriotrachealen Blutung nach hyperfraktionierter Radiatio; nach transsternaler zervikomediastinaler Lymphadenektomie traten keine letalen Komplikationen auf. 80% der Patienten hatten zum Zeitpunkt der Primäroperation ein fortgeschrittenes Tumorstadium (> pT3). 34% (PTC 64%, FTC 40%, MTC 13%, UTC 25%) waren postoperativ bildgebend und laborchemisch tumorfrei. Bei 18 Patienten wurde eine transsternale Mikrodissektion aller vier zervikomediastinalen Lymphknotenkompartimente durchgeführt. Die histologische Auswertung der entnommenen und tumorbefallenen Lymphknoten ergab bei je 9 Patienten eine unilateral-zervikale und mediastinale oder eine bilateral-zervikale und mediastinale Lymphknotenmetastasierung. Bei unilateral-zervikomediastinaler Lymphknotenmetastasierung konnte bei 2 von 2 Patienten mit papillärem und bei 2 von 6 Patienten mit medullärem Schilddrüsenkarzinom Tumorfreiheit erreicht werden. Bei bilateral-zervikomediastinaler Lymphknoten-metastasierung waren 3 von 4 Patienten mit papillärem, jedoch kein Patient mit anderen Karzinomtypen im postoperativen Verlauf tumorfrei. Als bevorzugte Indikationen zur transsternalen zervikomediastinalen Tumor-resektion beim Schilddrüsenkarzinom sind somit anzusehen: Primärtumoren mit zervikomediastinaler Ausdehnung ohne Lymphknotenmetastasen und lymphogen metastasierte Schilddrüsenkarzinome mit unilateral-zervikomediastinalem Lymphknotenbefall. Bei bilateral-zervikomediastinalen Lymphknotenmetastasen besteht wahrscheinlich nur beim papilldren Karzinomtyp Aussicht, durch eine transsternale Mehrkompartmentektomie Tumorfreiheit zu erreichen.

Histology and immunocytochemistry of differentiated thyroid carcinomas do not predict radioiodine uptake: A clinicomorphological study of 62 recurrent or metastatic tumours

Sixty-two metastases or recurrences of differentiated thyroid carcinomas were investigated using conventional histology and immunocytochemistry for thyroglobulin (TG), thyroxine (T4) and triiodothyronine (T3). In each patient,131I total body scans had been performed 4–10 weeks before surgery. Twenty-seven of the 62 tumours exhibited a predominance of follicles (A1), while 35 either exclusively or predominantly consisted of papillae or, in the case of follicular carcinomas, were predominantly trabecular or solid in structure (A2). TG and T4 immunoreactivity was observed in 60 cases, only 4 of these also expressing T3. Positive radioiodine uptake (RIU) was noted in 27 of 62 (44%) cases (A1: 18/ 27=67%; A2: 9/35=26%), 25 of which showed intraluminal TG and T4 positivity. Two follicular carcinomas showing RIU lacked follicular lumina, but exhibited strong diffuse cytoplasmic positivity for both TG and T4. In another 95 differentiated thyroid carcinomas, the structure of primary and secondary lesions was assessed. Of these, 27 (28%) showed a discordant pattern (A1/A2 or A2/A1) when comparing the structure of primary and secondary lesions. Our data suggest that differentiated thyroid carcinomas show a dissociation of TG/T4 expression and RIU, defects of iodine uptake and storage being found more frequently than a depression of TG and T4 synthesis. Intact synthesis of TG and T4, but not of T3 may be regarded as a prerequisite for RIU. Positive RIU is based on the presence of mature neoplastic follicles containing TG and T4 immunoreactive colloid and among follicular carcinomas, positive RIU may be encountered in neoplasms lacking follicular lumina but exhibiting strong cytoplasmic TG and T4 staining. Finally, the RIU of recurrent and metastatic PC and FC is not predictable from histological features of the primaries.

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.

Transcytosis of IgG from the Basolateral to the Apical Membrane of Human Thyrocytes in Autoimmune Thyroid Disease

The thyroid is affected by one of the most common organ-specific autoimmune diseases in humans. Three major autoantigens are involved in thyroid autoimmune disease: thyroglobulin (TG), thyroid peroxidase (TPO), and thyroid-stimulating hormone (TSH) receptor. Both hyperthyroidism and the development of goitre in Graves’ disease are caused by stimulating autoantibodies against TSH receptors. Autoantibodies against TG and TPO can be detected in Graves’ disease and Hashimoto’s thyroiditis.

Die transsternale zervikomediastinale Primrtumorresektion und Lymphadenektomie beim Schilddrsenkarzinom@@@Transsternal cervicomediastinal primary tumor resection and lymphadenectomy in thyroid cancer

SummaryThyroid carcinoma may invade the mediastinum by direct extension of the primary tumor or metastases to the paratracheal or retroclavicular-parajugular lymph nodes. From 1975 to 1991 in 47 out of 622 thyroid cancer patients (7.6%) [14 papillary (PTC), 5 follicular (FTC), 16 medullary (MTC) and 12 undifferentiated carcinoma (UTC)] transsternal tumor resection has been performed. Four patients (UTC three, MTC one) deceased 7, 8, 35, and 41 days after resection of the primary tumor due to cardiac or tumor disease, and in one patient because of acute arteriotracheal haemorrhage after external irradiation; no patient deceased after transsternal resection as a result of cervicomediastinal lymphadenectomy. At the time of primary operation 80% of patients showed an advanced tumor stage (> pT3). In 34% of patients (PTC 64%, FTC 40%, MTC 13%, UTC 25%) no tumor recurrence was observed neither by imaging nor by biochemical methods. In 18 patients a transsternal microdissection of all four cervico-mediastinal lymph node compartments has been performed. Histological analyses of excised and tumor involved lymph nodes revealed in 9 patients unilateral cervical and mediastinal and in 9 patients bilateral cervical and mediastinal lymph node metastases. In the case of unilateral cervicomediastinal lymph node metastases 2 out of 2 patients with papillary and 2 out of 6 patients with medullary thyroid carcinoma could be cured surgically. In the case of bilateral cervicomediastinal lymph node metastases 3 out of 4 patients with papillary thyroid carcinoma, but no other thyroid cancer patient were free of disease. In conclusion, main indications for transsternal cervicomediastinal resection in thyroid carcinoma are (1) primary tumors extending to the upper mediastinum, but without lymph node metastases, and (2) thyroid carcinomas with unilateral cervicomediastinal lymph node metastases. In the case of bilateral cervicomediastinal lymph node metastases probable only papillary thyroid carcinomas are supposed to be curable by transsternal multicompartmentectomy.ZusammenfassungSchilddrüsenkarzinome können das Mediastinum infiltrieren durch direkte Ausdehnung des Primärtumors oder Metastasierung in die paratrachealen oder retroklavikulär-parajugulären Lymphknoten. Von 1975–1991 wurde bei 47 von 622 Schilddrüsenkarzinom-patienten [7,6%, 14 papillary (PTC), 5 follikuldre (FTC), 16 medulläre (MTC) und 12 undifferenzierte Karzinome (UTC)] eine transsternale Tumorresektion durchgeführt. Vier Patienten mit UTC bzw. MTC verstarben 7, 8, 35 und 41 Tage nach der Primärtumorresektion an den Folgen kardialer Vorerkrankungen bzw. am Tumorleiden und, in einem Fall, an einer akuten arteriotrachealen Blutung nach hyperfraktionierter Radiatio; nach transsternaler zervikomediastinaler Lymphadenektomie traten keine letalen Komplikationen auf. 80% der Patienten hatten zum Zeitpunkt der Primäroperation ein fortgeschrittenes Tumorstadium (> pT3). 34% (PTC 64%, FTC 40%, MTC 13%, UTC 25%) waren postoperativ bildgebend und laborchemisch tumorfrei. Bei 18 Patienten wurde eine transsternale Mikrodissektion aller vier zervikomediastinalen Lymphknotenkompartimente durchgeführt. Die histologische Auswertung der entnommenen und tumorbefallenen Lymphknoten ergab bei je 9 Patienten eine unilateral-zervikale und mediastinale oder eine bilateral-zervikale und mediastinale Lymphknotenmetastasierung. Bei unilateral-zervikomediastinaler Lymphknotenmetastasierung konnte bei 2 von 2 Patienten mit papillärem und bei 2 von 6 Patienten mit medullärem Schilddrüsenkarzinom Tumorfreiheit erreicht werden. Bei bilateral-zervikomediastinaler Lymphknoten-metastasierung waren 3 von 4 Patienten mit papillärem, jedoch kein Patient mit anderen Karzinomtypen im postoperativen Verlauf tumorfrei. Als bevorzugte Indikationen zur transsternalen zervikomediastinalen Tumor-resektion beim Schilddrüsenkarzinom sind somit anzusehen: Primärtumoren mit zervikomediastinaler Ausdehnung ohne Lymphknotenmetastasen und lymphogen metastasierte Schilddrüsenkarzinome mit unilateral-zervikomediastinalem Lymphknotenbefall. Bei bilateral-zervikomediastinalen Lymphknotenmetastasen besteht wahrscheinlich nur beim papilldren Karzinomtyp Aussicht, durch eine transsternale Mehrkompartmentektomie Tumorfreiheit zu erreichen.

Therapie eines malignen sympathischen Paraganglioms des Zuckerkandl'schen Organs — ein Fallbericht

We present a case report on a 35-year-old patient in whom a malignant sympathetic paraganglioma of the organ of Zuckerkandl was the cause of severe hypertension with excessive perspiration at night. Since curative surgery was not possible medical treatment was initiated. Interferon alfa 2b (Intron A, Essex Pharma) and the somatostatin-analogue SMS 201-995 (Sandostatin, Sandoz) had no effect on catecholamine production and progression of the tumor. Treatment with alpha-methyl-para-tyrosin (MPT, [Metyrosin], Demser, MSD) turned out to be an effective and well tolerable therapy in this patient with peritoneal carcinosis. Clinical and hormonal progression of the paraganglioma resumed only after two years of therapy, which constitutes the longest documented period of time of successful MPT treatment. The superior efficacy of MPT in our patient should encourage postoperative medical treatment with MPT in malignant pheochromocytoma or malignant paraganglioma, particularly when the tumor turns out to be resistent to alpha blocking drugs.SummaryWe present a case report on a 35-year-old patient in whom a malignant sympathetic paraganglioma of the organ of Zuckerkandl was the cause of severe hypertension with excessive perspiration at night. Since curative surgery was not possible medical treatment was initiated. Interferon alfa 2b (Intron A, Essex Pharma) and the somatostatin-analogue SMS 201–995 (Sandostatin, Sandoz) had no effect on catecholamine production and progression of the tumor. Treatment with alpha-methyl-para-tyrosin (MPT, [Metyrosin], Demser, MSD) turned out to be an effective and well tolerable therapy in this patient with peritoneal carcinosis. Clinical and hormonal progression of the paraganglioma resumed only after two years of therapy, which constitutes the longest documented period of time of successful MPT treatment. The superior efficacy of MPT in our patient should encourage postoperative medical treatment with MPT in malignant pheochromocytoma or malignant paraganglioma, particularly when the tumor turns out to be resistent to alpha blocking drugs.