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Glomerulopathies Index

Indice glomerulopatías

HRLM-TEM index

MOAR-MET Indice

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Processing For HRLM-TEM.
Procesando Para MOAR-MET

It is obvious that for the pathologist to recognize accurately a morphologic pattern must have access to the best preserved tissues and histologic sections to optimize the resolving power of the light microscope (0.2 um). This is not possible with the paraffin sections. In our Laboratories we have replaced paraffin embedding with epoxy embedding. This method (High Resolution Light Microscopy or HRLM) permits full utilization of the resolving power of the light microscope and needs no routine special stains. For the complete, comprehensive examination of the renal biopsies we need only two samples: one for HRLM-TEM studies and one sample for IH studies. "THE SAMPLES MUST NOT BE MINCED." The tissue for HRLM-TEM is fixed in aldehydes and post-fixed in osmium tetra oxide. Embedding is accomplished with Spurr epoxy, stat (3h) or overnight schedules. The blocks with the intact samples, are sectioned in an ultramicrotome with glass knives, stained with toluidine blue and basic fuchsine (TB-BF). Serial sections are studied under the light microscope obtaining resolution of the smallest lesions possible in the light microscope (02.um, about the size of a mitochondria) without the need of special stains. Probably more than 90% of the diagnostic features are visible in these sections for HRLM ( ).

STEP BY STEP DIRECTIONS: The specimen is submitted in fixative of choice, our laboratory strongly recommends and, upon request, provide Paraformaldehyde-G Fixative for High Resolution Light Microscopy (HRLM) - Transmission Electron Microscopy (TEM). The documentation of what fixative (upon doing the gross description and on the PROCESSING SCHEDULE) the specimen is submitted is very important as the final HRLM-TEM stain will be affected.If processing using the EM automatic processor, program # 1 would be used. When manually processing, the tissues ARE NOT removed from the original vial they are submitted in.When any of the reagents used to process are introduced to the specimen the vial is capped and AGITATION is extremely critical, especially with this STAT technique.
Working with a vent-a-hood, the fixative is collected and then discarded in Hazardous Waste Container DO NOT POUR DOWN THE DRAIN, CHECK WITH YOUR SAFETY HAZARDOUS WASTE MANAGEMENT IN YOUR INSTITUTION and if Paraformaldehyde-G Fixative was not the fixative of choice, a 15 minute change in Paraformaldehyde-G is recommended before processing is begun.

1.POST-FIXATION begins with Working Osmium Tetroxide. Working Osmium Tetroxide is added to the specimen (the volume has to be 1 to 10) in the vial. The vial(s) are placed inside an Explosive Proof Refrigerator for 30 minutes.

2.Remove the specimen vials from the Explosive Proof Refrigerator and working with a vent -a -hood collect and discard the working osmium tetroxide in Hazardous Waste Container DO NOT POUR DOWN THE DRAIN, CHECK WITH YOUR SAFETY HAZARDOUS WASTE MANAGEMENT IN YOUR INSTITUTION. And now dehydration begins with 25% Ethanol.

Dehydration is done at room temperature, utilizing a vent-a -hood. REMEMBER, AGITATE

3.DEHYDRATION begins with three changes of 25% Ethanol to total 1-2 minutes.

4.Discard the 25% Ethanol and add 50% Ethanol, agitate for 1 minute.

5.Discard 50% Ethanol and add 75% Ethanol, agitate for 1 minute.

6.Discard 75% Ethanol and add 90% Ethanol, agitate for 1 minute.

7.Discard 90% Ethanol and add Absolute Ethanol for three changes to total 3 minutes-agitate.

8.Discard the last change of Absolute Ethanol and add EM Grade Acetone for two changes to total 3 minutes-agitate.

9.Discard the last change of Acetone and begin infiltration with a 1:1 mixture of EM Grade Acetone and prepared Firm Epoxy Media.

INFILTRATION IS ENHANCED IN A 40oC incubator

10.INFILTRATION begins with a one to one mixture of EM Grade Acetone and prepared Firm Epoxy Media for two changes to total 20 minutes, remember to cap, agitate and place in 40o incubator.

11.Discard the last 1:1 mixture and add prepared firm epoxy media for six changes of 10 minutes each to total 1 hr, remember to cap, agitate and place in 40o incubator.

12.After the last change of prepared Firm Epoxy Media, the tissues are now ready to be embedded. For STAT cases, the specimen is embedded in the BOJAK mold using Hard Epoxy Media and microwaved at Control 50 for 5 minutes at clock position 9, 12, and 3. This will total 15 minutes. For next day cases, the specimen is embedded in the BEEM capsules using Hard Epoxy Media and polymerized in a 70oC incubator.

13.EMBED the tissues in BEEM capsule only after appropriately labeling the inside of the BEEM capsule with the Referred Surgical number that has either been written in india ink or typed on bonded paper. Fill the BEEM capsule with prepared epoxy media of choice.

14.Place the tissue that corresponds to the referred surgical number inside the BEEM capsule and let gravity pull the tissue towards the bottom . Ori '¨ê $Ä ( ðnecessary wh '© rying to align needle biopsies next to each other.

15.POLYMERIZE by placing BEEM capsules in a 90oC incubator for 1hour and 45minutes.

16.Remove the BEEM capsule holder from the 90oC incubator and place BEEM HOLDER and epoxy blocks, inside the lower part of a 15oC refrigerator for 10 minutes. Remove the BEEM capules from the refrigerator and thenplace them on the BEEM remover and pop out the epoxy blocks. Trim the excess epoxy, without touching the tissue using an oil free straight edge razor. DO NOT USE THE INFRARED LAMP TO SOFTEN EPOXY BLOCKS, THEY WILL SHATTER! Blocks are now ready for sectioning and staining as per routine.

Beem capsules that have been polymerized overnight are removed from the 70oC oven and the polymerized epoxy blocks are removed from the BEEM capsule using the BEEM remover. The blocks polymerized in the 70oC incubator are trimmed of the excess epoxy, without touching the tissue, with an oil free, straight edge razor.

REFERENCES / REFERENCIAS

Bancroft, J.D. and Stevens, A.: Theory and Practice of Histological Techniques, Churchill Livingstone. third Ed., 1990.

Flores TR, Hoffmann EO and Coover J: Improved High Resolution Light Microscopy and Transmission Electron Microscopy Techniques in Diagnostic Pathology. J Histotec:20 (#1): 45-52, March 1997. (Click left for complete article).

Flores TR, Hoffmann EO and Velasquez M: Stat high resolution light microscopy (HRLM) - Transmission Electron Microscopy (TEM) Techniques for transplant renal biopsies. J. Histortec 21 (#3): 213-217, 1998. (Click left for complete article).

Glauert, A.M.: Fixation, Dehydration and Embedding of Biological Specimens. North Holland Publishing Co., New York, 1975.

Hoffmann E.O., Coover J, Flores TR, et al: Improvements for routine renal pathology. Lab Med 16: 237, 1985.

Holliday MA, Barratt TM, Avner ED (1994): Pediatric Nephrology, 3rd edn. Williams and Wilkins, Baltimore.

McDowell, E.M., and Trump, B.F.: Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Path Lab Med 100:405, 1976.

Results of the stain

Resultados de las coloraciones

Alcohol hyaline: Pink with purple core

Amyloid: Light blue, pink

Bacteria: Blue or red

Basophil granules: Dark blue

Bile granules: Light blue

Bowman's capsule: Light blue- pink

Cells, necrotic: Dark blue

Collagen, cartilage (Type III): Red

Collagen, interstitial (Type I, II): Red (Extra-cellular)

Collagen, basement membrane (Type IV): Light blue to pink

Cytoplasmic sap: Pink

Desmosomes: Dark blue

Effaced podocytes: Blue line

Elastic tissue: Purple

Eosinophil granules: Dark blue

Erithrocytes: Blue

Fibrin: Dark blue

Fungi: Blue, red

Glycogen: Pink, red (intracellular)

Hyaline material:(Hyalinosis) Blue-gray

Immuno-protein deposits: Dark blue

Laminated bodies (Myelinosomes): Dark blue

Lipid droplets: Green to blue

Lipofushsin: Dark blue and green

Lysosomes: Blue, red or gray

Melanin granules: Dark brown, blue

Microbodies: Blue

Mucus: Blue, pink or red

Myelin: Dark blue

Neutrophil granules: Light blue

Nuclear envelope: Dark blue

Nucleolus: Dark blue

Nucleus: Light blue to pink

Phagolysosomes: Blue to pink

Proteinaceous deposits: Dark Blue

Red cells: Dark Blue

Secretory granules: Blue or pink

 Tonofilaments: Dark blue

Viral inclusions: Blue or pink

Amiloide: Azul claro, rosado.

Bacterias: Azul o rojo

Cápsula de Bowman: Azul claro-rosado

Células necróticas: Azul denso

Citoplasma: Azul claro-rosado

Colageno intersticial: Rojo (Extracelular)

Complejos inmunes: Azul denso

Desmosomas: Azul obscuro

Eritrocitos: Azul

Fagolisosomas: Multicolor

Fibras elasticas: Rojo-purpura

Fibrina: Azul obscuro

Granulos de melanina: Cafe obscuro-azul

Granulos de mucina: Rojo-azul

Glicogeno: Rojo (Intracelular)

Gotas de lipidos: Azul-verde

Gránulos de los basofilos: Azul

Gránulos de los eosinofilos: Azul

Gránulos de los neutrofilos: Azul

Gránulos mucina: rosado

Globulos rojos: Azul

Hialino alcoholico: Rosado-purpura

Hialinosis: Azul-gris

Hongos: Azul, rojo

Inclusiones virales: Azul-rosado

Inmunoproteins: Azul obscuro

Lipofucsina: Azul-verde

Lipidos: Azul-verde

Lisosomas: Azul, rojo, gris

Material hialino (Hialinosis): Azul claro-rosado

Membranas basales: Azul claro-rosado

Mielinosomas: Azul obscuro

Mitocondrias: Azul-rosado

Microcuerpos: Azul

Nucleo: Azul claro o rosado

Nucleolo: Azul obscuro

Proteinas: Azul

Polisacáridos: rojo

Parasitos: Azul-rosado

Podocitos, borramiento: Linea azul

Sobre (membrana) nuclear: Azul

Tonofilamentos: Azul

Virus (Inclusiones): Azul o rosado