+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Immunohistochemistry for 2-Succinocysteine (2SC) and Fumarate Hydratase (FH) in Cutaneous Leiomyomas May Aid in Identification of Patients With HLRCC (Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome)



Immunohistochemistry for 2-Succinocysteine (2SC) and Fumarate Hydratase (FH) in Cutaneous Leiomyomas May Aid in Identification of Patients With HLRCC (Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome)



American Journal of Surgical Pathology 40(7): 982-988



Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is caused by germline mutations in the fumarate hydratase (FH) gene and predisposes to cutaneous and uterine leiomyomas and renal cell carcinoma (RCC). HLRCC-associated renal tumors are clinically aggressive, and patients would benefit from surveillance and early detection. Cutaneous leiomyomas that occur in association with HLRCC typically present early and are multiple. Thus far, the presence of certain morphologic features (large eosinophilic macronucleoli surrounded by halos and eosinophilic cytoplasmic inclusions) in RCC and uterine leiomyomas has been shown to correlate with FH mutations. Immunohistochemistry (IHC) for 2-succinocysteine (2SC) and FH has also been shown to correlate well with FH gene mutation status in RCC and uterine leiomyomas. The aim of this study was to assess the effectiveness of morphologic features and IHC at predicting FH gene mutations in cutaneous leiomyomas. We identified 22 patients with multiple cutaneous leiomyomas (40 total MCLs) and 25 patients with single leiomyomas (25 SCLs). Mutations in the FH gene were detected in 11 of 13 (85%) sequenced MCLs and 1 of 11 (9%) SCLs. A strong association was observed between 2SC positivity by IHC and presence of FH gene mutation (P=0.0028 for 2SC) but not with FH loss by IHC (P=0.4 for FH). All 11 MCLs with an FH mutation showed positive staining for 2SC, whereas 6 of 11 showed complete loss of FH staining. Our study suggests that the presence of MCLs should raise the possibility of HLRCC. IHC for FH and 2SC is helpful in detection of FH gene mutations and should be considered in all newly diagnosed cutaneous leiomyomas.

(PDF emailed within 0-6 h: $19.90)

Accession: 058052627

Download citation: RISBibTeXText

PMID: 26945337

DOI: 10.1097/PAS.0000000000000626


Related references

Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Journal of Cutaneous Pathology 41(11): 859-865, 2015

The syndrome of hereditary leiomyomatosis and renal cell cancer (HLRCC): The clinical features of an individual with a fumarate hydratase gene mutation. Australasian Journal of Dermatology 47(4): 274-276, 2006

Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome. American Journal of Surgical Pathology 40(7): 865-875, 2017

Loss of Fumarate Hydratase and Aberrant Protein Succination Detected With S-(2-Succino)-Cysteine Staining to Identify Patients With Multiple Cutaneous and Uterine Leiomyomatosis and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. American Journal of Dermatopathology 38(12): 887-891, 2016

Novel Fumarate Hydratase Mutation in Siblings With Early Onset Uterine Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. International Journal of Gynecological Pathology 37(3): 256-261, 2017

Evidence for a founder effect of the germline fumarate hydratase gene mutation R58P causing hereditary leiomyomatosis and renal cell cancer (HLRCC). Annals of Human Genetics 72(Pt 1): 35-40, 2007

Novel fumarate hydratase mutation in a family with atypical uterine leiomyomas and hereditary leiomyomatosis and renal cell cancer. Fertility and Sterility 105(1): 144-148, 2016

Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome (HLRCC): A Contemporary Review and Practical Discussion of the Differential Diagnosis for HLRCC-Associated Renal Cell Carcinoma. Archives of Pathology and Laboratory Medicine 142(10): 1202-1215, 2018

Identification of mutations in the fumarate hydratase gene in the multiple cutaneous and uterine leiomyomatosis and renal carcinoma syndrome. Clinical Science (London) 104(Supplement 49): 1P, 2003

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. Human Molecular Genetics 12(11): 1241-1252, 2003

Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. American Journal of Surgical Pathology 37(1): 74-80, 2013

Is Immunohistochemical Screening of Cutaneous Leiomyomas for the Early Detection of Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome Justified?. American Journal of Dermatopathology 40(12): 939-940, 2017

Mutations in fumarate hydratase cause hereditary leiomyomatosis and renal cell carcinoma in North American families. Proceedings of the American Association for Cancer Research Annual Meeting 44: 715, 2003

Multiple cutaneous leiomyomas leading to discovery of novel splice mutation in the fumarate hydratase gene associated with HLRCC. Australasian Journal of Dermatology 58(4): E246-E248, 2017

The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. American Journal of Surgical Pathology 31(10): 1578-1585, 2007