W. Böcker

Immunohistochemical analysis of thyroglobulin synthesis in thyroid carcinomas

This immuno-histochemical description of thyroglobulin synthesis in human thyroid carcinomas is based on the analysis of 72 malignant thyroid neoplasms and about 100 cases of thyroid adenomas and other diseases of the thyroid gland. In our experience immuno-histochemistry has been an invaluable diagnostic adjunct to light microscopy for three reasons: 1) as an approach to a functional classification of thyroid carcinomas, 2) as an aid in the differential diagnosis of thyroid carcinomas of follicle cell type from tumors of other origins, 3) as an aid in the functional classification of non-cancerous thyroid tissue. In the field of metastasizing thyroid carcinoma this immuno-histochemical approach combined with a morphometrical method may enable accurate identification of patients for whom radioiodine therapy is appropriate.

Clear‐cell carcinomas of thyroid gland: a clinicopathological study of 13 cases

Thirteen primary thyroid clear‐cell carcinomas and eight thyroid metastases of renal carcinomas are described. A broad variety of features is shown to be responsible for this follicle cell phenotype, some of which also occur in renal carcinomas. In biopsy specimens these two conditions can only be distinguished by immunohistochemistry. Clinical follow‐up disclosed that in the papillary and follicular categories of thyroid cancer the biological behaviour of clear‐cell tumours exhibits no significant difference to their non clear‐cell counterparts. In the case of eight follicle cell carcinomas, various samples were available for study. These revealed some striking variations in histology at different stages, and even during the same stage, of disease. Both reversal of clear cell change and transitions towards other kinds of metaplasia occurred. Morever, maintenance of follicle cell function was documented in several of these lesions by estimations of serum thyroglobulin levels and radioiodine scans. On the basis of these findings the concept of regarding the clear‐cell variant as a distinct subtype of thyroid cancer is refuted. Previous statements on the causal mechanism of clear‐cell change are discussed and it is suggested that metaplastic transformation accounts for this phenomenon in at least some instances of this heterogeneous condition.

Adenolipoma (thyrolipoma) of the thyroid gland report of two cases and review of literature

Rare fat cell-containing adenomas (adenolipomas) found in the thyroid gland of two patients are presented. Previously documented cases are reviewed. An origin from embryonic rests for these tumours as for diffuse lipomatosis of the thyroid is discussed.

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.

Histopathologic types and clinical behaviour of occult papillary carcinoma of the thyroid

On studying 182 papillary neoplasms of the thyroid, 32 nonencapsulated lesions were found to be occult papillary carcinomas (maximum diameter 1.5 cm); out of these 32 patients 18 cases of cervical lymph node metastases were observed. Histologically, 4 circumscribed microcarcinomas, 3 partially encapsulated carcinomas, and 25 occult sclerosing carcinomas were distinguished. The mean diameter of the 4 circumscribed tumours as compared to that of the remaining 28 lesions proved to be statistically significantly smaller, but no significant differences could be observed regarding the rate of lymph node metastasis. One occult sclerosing carcinoma showed a morphologic pattern different from the remaining cases--namely that it had an exclusively solid appearance in the primary lesion and also in its lymph nodes metastases. The follicle cell origin of this lesion was established immunohistochemically by patchy thyroglobulin synthesis. The excellent prognosis of the occult category of papillary thyroid carcinoma was confirmed by a follow-up (mean 7.7 years, range 1.1 to 16.3 years), in which only 2 instances of eradicable recurrent lymph node metastases within the group of occult sclerosing carcinomas were recorded.

Immunhistochemical and electron microscope analysis of adenomas of the thyroid gland

Histological, immunhistochemical and electronmicroscopic studies of 12 human, scintigraphically “cold”, thyroid adenomas with specific cytological differentiation identified four different cell types: oxiphil cell, clear cell, ergastoplasm-rich cell and mitochondrion-rich cell. The oxiphil tumor cell can be recognized light-microscopically by its large size and its eosinophilic granular cytoplasm. Most of these cells do not produce thyroglobulin. The ultrastructural characteristics of oxyphil cells are principally mitochondria in great numbers and many large lysosomes. Clear cell adenomas show a trabecular growth pattern. The tumor cells have an abundance of cytoplasm which contains small acidophilic granules. Immunhistochemically we were able to demonstrate thyroglobulin in small amounts within cytoplasmic granules and more extensively within the follicle lumina. Electronmicroscopically we observed a large number of smooth surfaced vacuoles of varying size, extraordinary large lysosomes and occasional cisternae of rough endoplasmic reticulum, the latter probably corresponding to the immune-histochemically identified thyroglobulin granules. The ergastoplasm-rich-cell adenomas, which to the best of our knowledge have not been previously described, show a predominantly micro-to normofollicular architecture histologically without intrafollicular colloid. The cytoplasm of the ergastoplasm-rich cells reveales a strong positive thyroglobulin-staining reaction. The fine structure of these cells is characterized by the abundance of cisternae of the rough endoplasmic reticulum. The mitochondrion-rich-cell adenomas exhibited a microfollicular structure with an intensive acidophilic granular staining at the basal part of the tumor cells. Immunhistochemically and electronmicroscopically we found some morphologic and functional features which differentiate these cells from the oxyphil cell. Thyroglobulin was located predominantly in the apical portion of the cytoplasm in the mitochondrion-rich cells without sharp demarcation from the luminar thyroglobulin. Electron microscopically fewer basal and laterally located mitochondria were seen in mitochondrion-rich cells compared with oxyphil cells. As we could not find any sign of functional activity in the oxyphilic, clear cell and ergastoplasm-rich cell adenomas we analysed those aspects of the lysosomal system not concerned with the enzymatic digestion of thyroglobulin.

Lipid-rich cell adenoma of the thyroid gland

A thyroid adenoma consisting of lipid-rich follicle cells is presented which has not previously been described in this organ. The discussion focuses on the possibility of its metaplastic origin and on its histological analogy to lipid-rich carcinoma of the breast.

Factors influencing the agreement on histopathological assessments of breast biopsies among pathologists.

Stang A, Trocchi P, Ruschke K, Schmidt‐Pokrzywniak A, Holzhausen H‐J, Löning T, Buchmann J, Thomssen C, Lantzsch T, Hauptmann S, Böcker W & Kluttig A 
(2011) Histopathology 59, 939–949 
Factors influencing the agreement on histopathological assessments of breast biopsies among pathologists

Minimal Thyroid Neoplasia

Every malignant tumor has its prestages; their earliest possible detection is of vital importance for the patient’s prognosis (Grundmann 1979). Consequently, it is necessary to define these early lesions by exact morphologic criteria and to develop appropriate methods for clinical detection and treatment. In the thyroid, carcinoma pathology has many facets such as the different histologic types, stages of evolution, and correlation of morphology and prognosis. In contrast to the minimal cancers of other organs, it is important that some of the very early thyroid tumors are recognized clinically by the evidence of cervical lymph node metastases, and that this type of spread does not affect the generally favorable prognosis.

Mammographic density and inter-observer variability of pathologic evaluation of core biopsies among women with mammographic abnormalities

BackgroundAs high percentage of mammographic densities complicates the assessment of imaging findings, mammographic density may influence the histopathological evaluation of core-biopsies of the breast. We measured the influence of mammographic density on the inter-observer variability of histopathological findings of breast biopsies.MethodsHistological slides of 695 women who underwent core biopsies of the breast at University of Halle between 2006 and 2008 were evaluated in a blinded fashion by two pathologists using the five levels of the B-categorization scheme (B1-B5). To quantify mammographic density, we used a computer-based threshold method (Madena). We calculated observed and chance-corrected agreements (weighted kappa) and 95% confidence intervals (95% CI) according to four categories of mammographic density (<10%, 10<25%, 25<50%, ≥50%).ResultsThe weighted kappa decreased monotonically from 89.6% (95% CI: 85.8%, 93.3%) among women with less than 10% of mammographic density to 80.4% (95% CI: 69.9%, 90.9%) for women with more than 50% of mammographic density, respectively. Results of a kappa regression analysis showed that agreement of pathologists on clinically relevant categories (B1-B2 versus B3-B5) decreased with mammographic density.ConclusionsMammographic density is a relevant modifier of the agreement between pathologists who assess breast biopsies using the B-categorization scheme. The influence of mammographic density on the inter-observer variability can be explained to some extent by varying prevalences of histological entities across B categories that have typically different inter-observer agreement. Women with high mammographic density are at higher risk of inter-observer variability compared to women with low mammographic density and should possibly undergo a second pathology review.