Andreas O. Myking

Prognostic importance of various clinicopathological features in papillary thyroid carcinoma

The influence of various pathological features on tumour recurrences and cancer deaths has been studied in 173 consecutive cases of surgically treated papillary thyroid carcinoma recorded in 1971-1985. During the follow-up (median 7.3 years), 18.6% of the 161 radically treated patients had recurrent disease, and 8.7% died of thyroid cancer. In the univariate life-table analysis, recurrence-free survival was significantly related to age, pTNM category, tumour size, presence of certain growth patterns, tumour necrosis, tumour infiltration in surrounding thyroid tissue and thyroid gland capsule, lymph node metastases, presence of extra-nodal tumour growth and number of positive lymph nodes, whereas only tumour diameter, thyroid gland capsular infiltration and presence of extra-nodal tumour growth remained as significant prognostic factors in the multivariate analysis. Regarding thyroid cancer deaths, sex, age, pTNM category, radicality of surgical treatment, tumour diameter, macroscopic appearance, cellular atypia, tumour necrosis, thyroid gland capsular infiltration, vascular invasion, extra-thyroidal extension and lymph node metastases were all significant variables in the univariate analysis. However, only sex, age, radicality of surgical treatment and vascular invasion were found to be significant predictors of thyroid cancer deaths in the final multivariate Cox model, whereas cellular atypia and necrosis showed a borderline significance. Our study thus documents the independent importance of certain histological features for morbidity and mortality in surgically treated cases of papillary thyroid cancer.

Multi-element analysis of trace element levels in human autopsy tissues by using inductively coupled atomic emission spectrometry technique (ICP-AES)

Autopsy tissue samples from the brain front lobe, cerebellum, heart, kidney (cortex and medulla), liver, pancreas, spleen and ovary were analysed for AL, B, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, Sr and Zn in 30 (17 women and 13 men) subjects ranging in age from 17 to 96 years at Haukeland University Hospital in Norway. The tissues were selected from macroscopically normal organs and samples were handled according to guidelines recommended to avoid contamination in the pre-analytical phase. Concentration of the trace elements were determined by the inductively coupled plasma atomic emission spectrometry technique (ICP-AES). In most tissues the concentrations of the essential trace elements followed the order Fe> Zn> Cu> Mn> Se> Cr> Co except in the ovary where Se was higher than Mn. The liver was the major site of deposition for Co, Cu and Mn as well as the spleen for Co, brain front lobe for Cu and pancreas for Mn. Ba, Sr and Ni built up in the ovary foLLowed by the kidney. Older subjects accumulated Ba and Sr in most tissues, whereas Al accumulated in the kidney cortex and Cd in the brain cerebellum. Generally males had higher concentrations of trace elements in the different tissue sampLes than females with the exception of Mn in the brain front lobe and heart and Sr in the liver. ICP-AES is a useful method to assess the concentration and the profiLe of trace elements in human autopsy tissues.

Chronic cold agglutinin disease of the “idiopathic” type is a premalignant or low-grade malignant lymphoproliferative disease

We investigated the clinical, pathological, and immunological features of “idiopathic” cold agglutinin disease (CAD) in a population‐based study. Fourteen patients were studied, giving a prevalence of about 14 per million with a mean age of 75 years. Haemolysis was present in all cases, but only eight patients had clinical symptoms of peripheral haemagglutination. Serum electrophoresis, immunofixation, morphological bone marrow evaluation, and flow cytometric immunophenotyping were used to detect any monoclonal lymphoproliferative disorder. Flow cytometry seemed to be a sensitive way to demonstrate a clonal B‐cell proliferation. Some evidence of clonality was found in 13 patients, and a clonal lymphoproliferative disease was documented by flow cytometry or biopsy in 10 out of 11 patients. We conclude that CAD is a symptom‐producing monoclonal lymphoproliferative disorder in nearly all patients.

Titin and ryanodine receptor epitopes are expressed in cortical thymoma along with costimulatory molecules.

Cortical-type thymomas are associated with myasthenia gravis (MG) in 50% of the cases. MG is caused by antibodies against the acetylcholine receptors (AChR), but additional non-AChR muscle autoantibodies such as those against titin and ryanodine receptor (RyR) are found in up to 95% of MG patients with thymoma. To elucidate the induction of non-AChR autoantibodies in thymoma-associated MG, we studied cortical-type thymomas from seven thymoma MG patients, and sera from six of them. All six had titin antibodies, and four had RyR antibodies. Titin and RyR epitopes were co-expressed along with LFA3 and B7 (BB1) costimulatory molecules on thymoma antigen-presenting cells (APC) in all thymomas. In normal thymus, the staining by anti-titin, anti-RyR, anti-LFA3, and anti-BB1 antibodies was weak and occurred exclusively in the medulla and perivascularly. Our results indicate a primary autosensitization against titin and RyR antigens inside the thymoma. In MG-associated thymoma, the mechanisms involved in the initial autosensitization against titin and RyR are probably similar to those implicated in the autosensitization against AChR. In all cases, there is an overexpression of muscle-like epitopes and costimulatory molecules indicating that the T-cell autoimmunization is actively promoted by the pathogenic microenvironment inside the thymoma.

The Porto-Systemic Collateral Pattern in the Rat

The porto-systemic collaterals were studied in rats 14 weeks after making a 1.2-mm stenosis of the portal vein. A prominent shunt from the coronary-lienal vein to the left suprarenal and renal veins w

Disease severity and outcome in thymoma myasthenia gravis: a long-term observation study.

Thymomas occurring in myasthenia gravis (MG) are usually of the cortical subtype and are usually treated by thymectomy. However, the factors that influence MG outcome in thymoma MG patients are not known. In a long‐term study, MG severity and treatment was observed in 24 thymoma and 24 non‐thymoma MG patients for up to 30 years, and the occurrence of muscle autoantibodies was assayed. The rate of complete stable remission was low and did not differ between the two groups. There was no significant difference in MG severity between thymoma and non‐thymoma MG patients at any time during the study. Titin and ryanodine receptor (RyR) antibody occurrence was significantly higher in thymoma MG patients. Four thymoma (all titin and RyR antibody positive) and two non‐thymoma (both titin and one RyR antibody positive) MG patients died from MG‐related respiratory insufficiency. Seventy percent of thymoma and 75% of non‐thymoma MG patients were treated with immunosuppressive drugs. The number of patients who received plasmapheresis did not differ in those who were treated because of acute MG deterioration, irrespective of planned surgery.This study shows equal MG severity and outcome in thymoma and non‐thymoma MG, but the presence of RyR antibodies in thymoma MG and titin/RyR in non‐thymoma MG indicates a less favorable prognosis.

Prehepatic portal hypertension in the rat. Immediate and long-term effects on portal vein and aortic pressure of a graded portal vein stenosis, followed by occlusion of the portal vein and spleno-renal collaterals.

The creation of a portal vein stenosis with a diameter of 1.2 mm in Wistar rats resulted in a sustained elevation of the portal vein pressure to approximately twice the control value lasting for at least 8 weeks. The alterations in portal vein pressure following occlusion of the stenosed portal vein and splenorenal collaterals, either separately or in combination, indicate that a considerable quantity of portal blood is diverted into the inferior caval vein through the splenorenal collaterals, and that the development of these collaterals occurs during the first 3-4 weeks after the establishment of the stenosis. The concomitant reduction in aortic pressure and increase in heart rate following total occlusion of the portal vein were most pronounced during the first weeks after stenosis, and were probably due to diminished venous return to the heart.

Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis

Thymectomy is still widely carried out in myasthenia gravis (MG) patients, but its role, especially in late‐onset MG patients, is not established. These patients are immunologically heterogeneous, some with thymoma‐like and others with early onset‐like features. We evaluated whether any therapeutic effects of thymectomy correlate with the presence of non‐acetylcholine receptor (AChR) muscle antibodies. The severity of MG, and titin and ryanodine receptor (RyR) antibodies, were assessed yearly starting from MG onset in 21 thymectomized and 22 non‐thymectomized AChR antibody positive late‐onset MG patients, who were followed for 2, 3 and 5 years. Clinical or pharmacological remission were seen in six of 11 titin antibody negative but none of the 10 titin antibody positive thymectomized patients, however, the non‐thymectomized cases showed an opposite trend. The three MG‐related deaths were all in patients with titin antibodies. There was no significant difference in MG severity between thymectomized and non‐thymectomized patients; 2 years after MG onset, both groups were significantly improved. This study showed no dramatic benefit from thymectomy in late‐onset MG in general. Any limited improvement appeared less likely in cases with titin and/or RyR antibodies.

Large intramuscular spindle-cell lipoma

A case of a large spindle‐cell lipoma in an intramuscular (subfascial) localization is reported. The tumour occurred in a 58‐year‐old male patient and was localized subfascially in his left deltoid muscle. The tumour measured 20 × 8 × 8 cm; its weight was 780 grams. After initial biopsy, the tumour was extirpated. Microscopically, the tumour tissue consisted of mature fat cells and spindle‐cell areas in varying amounts, constituting a typical appearance of a spindle‐cell lipoma. There were no histological signs of malignancy. Especially, no areas of liposarcoma differentiation were detected. The patient is well, with no signs of recurrence, one and a half years after the operation. We have reviewed the literature on spindle‐cell lipoma, and we believe this is the first example of this neoplasm to be reported in an intramuscular (subfascial) localization.

The histomorphology of the thymus in late onset, non-thymoma myasthenia gravis

Twenty‐two late‐onset, non‐thymoma myasthenia gravis (MG) patients were selected for study based on the combined presence of MG and involution of the thymus. Thymectomy specimens from all the patients were examined histologically and immunohistologically and compared with an age‐matched control group in which tissue was removed from the thymic gland during operations for various cardiac conditions. We were not able to find any morphological differences between thymi from MG patients and patients in the control group. Germinal centres were present in 7/22 in the patient group and 6/20 in the control group. Seven of our 22 MG patients had auto‐antibodies to titin. Germinal centres in the thymus were found in only one. In contrast germinal centres were present in the thymus of 6/15 MG patients with no detectable antibody response to titin (p= 0.01). Our study suggests that late‐onset MG is pathogenetically heterogeneic with different modes of auto‐sensitisation.