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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).
Am J Surg Pathol. 2016 07; 40(7):982-8.AJ

Abstract

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.

Authors+Show Affiliations

Departments of *Pathology ‡Dermatopathology, University of California, San Francisco, San Francisco, CA †Department of Pharmacology, Physiology & Neuroscience, School of Medicine, University of South Carolina, Columbia, SC.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26945337

Citation

Buelow, Benjamin, et al. "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)." The American Journal of Surgical Pathology, vol. 40, no. 7, 2016, pp. 982-8.
Buelow B, Cohen J, Nagymanyoki Z, et al. 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). Am J Surg Pathol. 2016;40(7):982-8.
Buelow, B., Cohen, J., Nagymanyoki, Z., Frizzell, N., Joseph, N. M., McCalmont, T., & Garg, K. (2016). 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). The American Journal of Surgical Pathology, 40(7), 982-8. https://doi.org/10.1097/PAS.0000000000000626
Buelow B, et al. 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). Am J Surg Pathol. 2016;40(7):982-8. PubMed PMID: 26945337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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). AU - Buelow,Benjamin, AU - Cohen,Jarish, AU - Nagymanyoki,Zoltan, AU - Frizzell,Norma, AU - Joseph,Nancy M, AU - McCalmont,Timothy, AU - Garg,Karuna, PY - 2016/3/6/entrez PY - 2016/3/6/pubmed PY - 2017/7/20/medline SP - 982 EP - 8 JF - The American journal of surgical pathology JO - Am. J. Surg. Pathol. VL - 40 IS - 7 N2 - 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. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/26945337/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__ L2 - http://dx.doi.org/10.1097/PAS.0000000000000626 DB - PRIME DP - Unbound Medicine ER -