Transmission electron microscopy of succinate dehydrogenase deficient neoplasms: Cytoplasmic vacuolization seen by light microscopy is compatible with intracellular lipid

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Background: Succinate Dehydrogenase Deficient Neoplasms (SDHN) are a recognized subtype of tumors associated with very characteristic histopathologic features, including flocculent cytoplasmic inclusions that are identifiable by light microscopy. The true nature of the finding has yet to be confirmed (limited data suggesting abnormal mitochondria exists). Succinate dehydrogenase has the chief role of oxidizing succinate to fumarate in step 6 of the citric acid cycle. A lack of succinate dehydrogenase leads to increased levels of intracellular succinate, a known inhibitor of lipid peroxidation. Our study seeks to use transmission electron microscopy (TEM) to provide more insight on the nature of these structures. Design: TEM (retrieval from the paraffin embedded block) was performed on 4 SDHN (3 RCC and one adrenal lesion) from four patients. The diagnosis of SDH deficient carcinoma was confirmed on all lesions by molecular sequencing studies and by demonstration of the loss of SDHB staining with immunohistochemistry (IHC). Light microscopy revealed the presence of abundant intracytoplasmic inclusions. Digital images of each tumor were obtained and analyzed. See Figure 1. Results: Although retrieval of tissue from a formalin fixed, paraffin embedded block can lead to processing artifact, digital images on all cases revealed the presence of multiple, well circumscribed electron lucent vacuoles that were morphologically compatible with intracellular lipid droplets. Normal appearing mitochondria were clearly visible in kidney cases 2 and 3 (arrows). Conclusions: Unfortunately, many of the techniques utilized to identify cellular lipid (i. e. Oil red - O, Sudan Black B) require fresh tissue preparations and the pathologic diagnosis of SDHN is commonly made after formalin fixation has already taken place. Our findings suggest that the size, morphology and biochemical background of the inclusions identified by ultrastructural examination on all cases is compatible with intracellular lipid, thus offering an alternative approach for lipid identification in situations where the only tissue available has been formalin fixed and embedded in paraffin. Further study (potentially in concert with the above described techniques) is required for confirmation.



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