Article

Adenomatoid tumour of the adrenal gland in a patient with germline SDHD mutation: a case report and review of the literature.

*Pathology and Laboratory Medicine Institute, Department of Pathology, Cleveland Clinic †Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
Pathology (Impact Factor: 2.66). 08/2011; 43(5):495-8. DOI: 10.1097/PAT.0b013e3283486bb9
Source: PubMed
0 Bookmarks
 · 
96 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The genes for the succinate dehydrogenase (SDH) subunits SDHA, SDHB, SDHC and SDHD are encoded in the autosome. The proteins are assembled in the mitochondria to form the mitochondrial complex 2, a key respiratory enzyme which links the Krebs cycle and the electron transport chain. Thirty percent of phaeochromocytoma and paraganglioma (PHEO/PGL) are hereditary and perhaps as many as half of these familial cases are caused by germline mutations of the SDH subunits. Negative immunohistochemical staining for the SDHB subunit identifies PHEO/PGL associated with germline mutation of any of the mitochondrial complex 2 components and can be used to triage formal genetic testing of all PHEO/PGL for SDH mutations. PHEO/PGL associated with SDHA mutation also show negative staining for SDHA as well as SDHB.A unique subgroup of gastrointestinal stromal tumours (GISTs) are driven by mitochondrial complex 2 dysfunction. These SDH deficient GISTs can also be definitively identified by negative staining for SDHB and show distinct clinical and morphological features including frequent onset in childhood and young adulthood, gastric location, a tendency to multifocality, absence of KIT and PDGFRA mutations, a prognosis not predicted by size and mitotic rate and a tendency to indolent behaviour of metastases. Some of these SDH deficient GISTs are driven by classical SDH mutations, but the precise mechanisms of tumourigenesis in many (including those associated with the Carney triad) remain unknown. Germline SDHB mutation is associated with a newly recognised type of renal carcinoma which commonly but not always demonstrates distinctive morphology and can also be recognised by negative staining for SDHB.Immunohistochemistry for SDHB therefore has emerged as a useful tool to recognise these distinct neoplasias driven by mitochondrial complex 2 dysfunction and to triage formal genetic testing for the associated syndromes.
    Pathology 04/2012; 44(4):285-92. · 2.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adenomatoid tumors (AT) are uncommon, benign tumors of mesothelial origination most frequently encountered in the genital tracts of both sexes. Their occurrences in the extragenital sites are much rarer and could elicit a variety of differential diagnosis both clinically and morphologically. With regard to the adrenal gland, to the best knowledge of us, only 31 cases of AT have been reported in the English literature. Several histologic growth patterns have been documented in AT, among which cystic type is the least common one. We herein present a further case of AT arising in the adrenal of a 62-year-old Chinese man with a medical history for systemic hypertensive disease. The tumor was incidentally identified during routine medical examination. An abdomen computed tomography scan revealed a solitary mass in the right adrenal. Grossly, the poorly-circumscribed mass measured 3.0 x 3.0 x 2.0 cm with a cut surface showing a gelatinous texture with numerous tiny cystic structures. Microscopic examination showed an infiltrated lesion with honeycomb appearance mimicking a lymphangioma, which composed predominantly of variably sized and shaped anastomosing small cystic spaces lined by flattened endothelial-like cells, without any epithelioid or signet-ring like components present. Foci of extraadrenal tumor extension, lymphoid aggregates with occasional germinal centre formation, intralesional fat tissue, stromal myoid proliferation and ossification were also observed. Immunohistochemical analyses confirmed the mesothelial differentiation of this tumor and indicated a diagnosis of cystic lymphangiomatoid AT of the adrenal.
    International journal of clinical and experimental pathology 01/2013; 6(5):943-50. · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma (PCC)/ paraganglioma (PGL) tumors in SDH-x mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinico-pathological phenotype and even causal relatedness to SDH-x mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated.Three unrelated SDHD patients, two with pituitary adenoma (PA) and one with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal cell carcinomas (RCCs) were identified from four European centres. SDHA/SDHB immunohistochemistry (IHC), SDH-x mutation analysis and loss of heterozygosity analysis of the involved SDH-x gene were performed on all tumors. A cohort of 348 tumors of unknown SDH-x mutational status, including renal tumors, PTCs, PAs, neuroblastic tumors, seminomas and adenomatoid tumors, was investigated by SDHB IHC.Of the six index patients, all RCCs and one PA displayed SDHB immunonegativity in contrast to the other PA and PTC. All immunonegative tumors demonstrated loss of the wild-type allele, indicating bi-allelic inactivation of the germline mutated gene. Out of 348 tumors, one clear cell RCC exhibited partial loss of SDHB expression.These findings strengthen the aetiological association of SDH-x genes with pituitary neoplasia, while provide evidence against a link between PTC and SDH-x mutations. Somatic deletions seem to constitute the second hit in SDHB-related renal neoplasia, while SDH-x alterations do not appear to be primary drivers in sporadic tumorigenesis from tissues affected by SDH deficiency.
    European Journal of Endocrinology 10/2013; · 3.14 Impact Factor

Full-text

Download
15 Downloads
Available from
May 26, 2014