Background Histopathology & Immunohistochemistry Reference

BACKGROUND AND CLINICAL INFORMATION: Head

Summary: First described by Brooke and Neville in 1972. This is a rare congenital myopathy. The baby may develop normally at the beginning but reducing myopathy often takes a rapid downhill road leading to death at an early age. Congenital onset can also occur. Occasionaly milder cases and rare adult onset cases have been described. Histochemically, the muscle fibers containsmall inclusion on light microscopy that are capable of reducing tetrazolium salts. These bodies also have a distinctive ultrastructural appearance.

Clinical: Three clinical types are recognized.

· Infantile or early childhood onset type: this type usually follows a rapidly progressive clinical course with a fatal outcome in a few years.

· Late childhood onset type: This type has painless weakness that is often asymmetrical. The course is relatively benign.

· Late onset type: Relatively benign.

Etiology: The etiology is unknown. Coxsackievirus B antibody titers have been elevated in some patients. The ultrastructure of the filamentous deposits and the large amount of RNA in the reducing bodies may be suggestive of viral inclusion. These two features suggest a viral etiology. They react with Coomassie blue, indicating that they contain protein.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head

Histology: The reducing bodies are strikingly eosinophilic on HE. When they are numerous, they may distend the fibers. Rimmed vacuoles resulted from nuclear breakdown has been reported.

Histochemistry: The reducing bodies have the following characteristics

· Trichrome: The reducing bodies are green with the modified trichrome.

· Tetrazolium salt reduction: The reducing bodies in skeletal muscle fibers stain strongly with the menadione-nitro-blue tetrazolium stain. They can still give the staining without the substrate a-glycerophosphate. Other than some lysommal deposits in infantile acid maltase deficiency (glycogen storage disease type I or Pompe’s disease) have been reported to have this staining property (one reported case), almost nothing else does.

· Pyroninophilic: These bodies are strongly pyroninophilic and might possibly be made of ribonucleoprotein. RNAse A, however, can only removes part of the pyroninophilia.

· Routine enzymes: They do not stain with NADH, ATPase, succinate dehydrogenase, cytochrome c oxidase.

· Fiber type: The affected fibers may be type I perdominant.

· PAS: Usually negative but can be strongly positive.

· Congo red: They may be stained by Congo red but do not display dichroism.

Semi-thin sections: The reducing bodies appear as dense osmiophilic bodies.

Electon microscopy: The reducing bodies appear as very dense osmophilic aggregates on low magnification. These aggregates tend to be found on the outer surface of the nuclear membrane and occasionally they can rim the whole nucleus. They are also found in subsarcolemmal and interfibrillary locations but they have never been reported inside nuclei. On higher magnification, the reducing bodies are made of round granules or short filaments.

REFERENCES: Head

Figarella-Branger D, Putzu GA, Bouvier-Labit C, Pouget J, Chateau D, Fardeau M, Pellissier JF. Adult onset reducing body myopathy. Neuromuscul Disord 1999 Dec;9(8):580-6

Kiyomoto BH, Murakami N, Kobayashi Y, Nihei K, Tanaka T, Takeshita K, Nonaka I. Fatal reducing body myopathy. Ultrastructural and immunohistochemical observations. J Neurol Sci 1995 Jan;128(1):58-65

Tome FM, Fardeau M. Congenital myopathy with "reducing bodies" in muscle fibres. Acta Neuropathol (Berl) 1975;31(3):207-17

Brooke MH, Neville HE. Reducing body myopathy. Neurology 1972 Aug;22(8):829-40