The Regional Classification of Parathyroid Tissue as used for Tissue Selection prior to Autotransplantation.

Helmut Hörandner and Ulrich Neyer

Electron Microscopy Laboratory Mauer, Vienna
Department of Nephrology and Dialysis,
VIVIT, Vorarlberg Institute for Vascular Investigation and Treatment, LKH Feldkirch, Austria

(Appendix to the Contribution : Parathyroidectomy in Renal Hyperparathyroidism)

elmilabor@nusurf.at

Introduction: this review summarizes the results of citations 71, 72 and 73 of the Lecture Parathyroidectomy in renal hyperparathyroidism, which are in german. Some updates and correlations to new published data were added.

Classification: we use a parathyroid tissue classification based on macroscopic criteria. This means, that tissue can be identified by the surgeon at the site, which is the crucial point for avoiding relapse.

A and B regions represent diffuse tissue, C and D regions nodular tissue.

A regions represent normal or hypertrophic polyclonal tissue, B, C and D regions monoclonal expanding tissue.

In diffuse glands (1) A and B regions can be found, in nodular glands (2) A,B,C and D regions.

Methods

Experimental: in an initial period all resected parathyroid glands were documented by macrophotography. The tissue was investigated by morphological (semithin, ultrathin sections) and functional methods (determination of PTH secretion after incubation at different calcium levels) as follows:

1mm³ tissue pieces were incubated at different Ca⁺⁺ levels and PTH measured in the culture media (c-terminal,midmolecular,intact). Typical results are depicted: A,B,C,D are the different regions which were dissected according to macroscopic criteria. Cm means nodular regions with reduced Ca⁺⁺ receptor density, which was attributed later according to literature (fig2 in Akerstrøm et al:World J.Surgery 15:672, 1991).

Morphological and functional data were correlated to macrophotography. This led to the above classification.

In the following period morphological documentation was maintained and refined, biochemical testing (c-terminal, midmolecular, intact PTH determination) was done only in 40 consecutive patients.

Surgical: the initial period (until 1987) comprised 25 patients in Vienna and 8 in Feldkirch. Total parathyroidectomy + autotransplantation was performed in all cases.Tissue selection for autotransplantation was performed according to standard recommendations still in use (smallest gland, diffuse or homogeneous tissue).

In the following period (until recent, 165 patients in Vienna, 75 in Feldkirch) only A regions were used for AT. Tissue was selected in situ following the above classification. Refinements (increase of magnification, optimization of optics and illumination) were added.

Results

Functional - morphologic classification of glandular regions:

A-Regions represent normal or minimally changed parathyroid tissue. Having presumably a normal setpoint, this tissue is under continuous suppression in vivo.

This leads to morphologic alterations, which can be demonstrated on a microscopic and macroscopic level: prolonged inactivity leads to intracellular accumulation of glycogen and lipid droplets, which can be detected in the electron microscope and in semithin sections (fig 1,4,6).

Figure 3

Figure 4

Figure 5

Macroscopically this leads to a yellowish colour of the tissue. Furthermore stromal fat cells represent a variable, but considerable part of the tissue volume and represent the most prominent macroscopic feature (fig 2). Cells are small (10 - 12000/mm²) and do not proliferate (1 mitosis <150000 cells, MIB - 1 or PCNA activity below 12 cells/ mm² [green in fig 5 and 8]).

Minimally changed A - regions may show slight hypertrophy (8 - 10000 cells/mm²), and proliferation (one mitosis <40000 cells, MIB - 1 or PCNA activity up to 40 cells/ mm²[yellow in fig 5 and 8]). Intracellular lipid vacuoles are reduced, glycogen still present and mitochondria augmented (fig 4). This may reflect hyperactivity.

B-Regions represent highly hypertrophic/hyperplastic tissue without a visible capsule. Stromal fat cells and intracellular lipid are absent, causing sometimes a whitish colour macroscopically (fig 2). Cells are enlarged (6 - 8000/mm²) and usually arranged in follicles (fig6,10). Mitochondria are abundant , golgi enlarged and branched, endoplasmic reticulum usually arranged in parallel stacks. Highest proliferation rates could be found (up to one mitosis in 300 cells, MIB - 1 or PCNA activity up to 600 cells/ mm²[orange and red in fig 5 and 8]) in confined regions up to 3mm in diameter (fig 3,5). Monomorphic ultrastructure suggests monoclonal origin (fig 6,10). Sinusoidal capillaries can be detected already macroscopically.

Hypertrophy of the cells leads to dramatic reduction in connective tissue content (fig7). B-Regions are almost unsuppressible and cause highest PTH levels in vivo.

Nodular C-Regions show identical cytologic details as B-Regions and are surrounded by a capsule (fig9). This enables identification with the naked eye. Proliferation is high, usually lower than in B - regions. Cells are usually arranged in follicles, which are sealed by tight junctions (fig10). Their uniform ultrastructure suggests monoclonality, which has been established for large nodules.

PTH-values vivo are lower than in comparable B-glands: the drawings on the left represent the largest cross sections of the parathyroid glands in patients with pure diffuse or nodular gland population (which is rare). The difference may be up to 50times expressed as pg PTH/ mg tissue mass. We found frequently atypical Ca/PTH response curves indicating diminished Ca++ -receptor density (see Cm above).

Nodular D-Regions consist almost exclusively of oxyphil cells, many of them with hypertrophic mitochondria and pycnotic nuclei (fig 13). Macroscopically they are detected by white colour, caused by the hypertrophic mitochondria (fig 11, 12). Ultrastructure is suggestive for apoptosis, although biochemical characterization failed up to now (fig 13). Proliferation is similar or slightly lower than in C-Regions.

Clinical outcome

In the initial period 3 (out of 25 patients) relapses occurred in Vienna, and 3 (out of 8 patients) in Feldkirch.

In the following period only one relapse occurred in Vienna (1987) and in Feldkirch (1992).

No other true relapses occurred. Further reoperations had been necessitated by supernumerary glands, in 2 patients by parathyromatosis in the neck.

A detailed statistically relevant investigation on the long term outcome of total PTx+AT has been presented. (in lit (77) of: parathyroidectomy in renal hyperparathyroidism) .

REFERENCES

71.- Hörandner H, Neyer U, Gruber U, et al: Pathomorphologie von autotransplantiertem Nebenschilddrüsengewebe. Nieren- und Hochdruckkrankheiten, 1997; 26: 319-327

72.- Niederle B, Hörandner H, Roka R, et al: Parathyreoidektomie und Autotransplantation beim renalen Hyperparathyreoidismus. I. Morphologische Untersuchungen zur Gewebeauswahl. Langenbecks Arch Chir 1988; 373: 325-336

73.- Niederle B, Hörandner H, Roka R, et al: Parathyreoidektomie und Autotransplantation beim renalen Hyperparathyroidismus. II. Funktionelle Untersuchungen zur Gewebeauswahl. Langenbecks Arch Chir 1988; 373: 337-344