AIMS: Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH-deficiency. METHODS AND RESULTS: We have tested 42 smooth muscle neoplasms, 13 lesions of patients with suspicious or confirmed HLRCC, 20 sporadic piloleiomyomas, two angioleiomyomas and 7 leiomyosarcomas. FH staining grades from 1 to 3. Ten of the 13 lesions from the patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented grade 3 FH staining although five cases presented grade 1 FH staining. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. CONCLUSIONS: This staining could indicate a high risk of HLRCC in most of the confirmed cases but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. HLRCC syndrome should be rule out in FH negative piloleiomyomas after complete anamnesis if multiple lesions or positive familiar history is found.
AIMS: Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH-deficiency. METHODS AND RESULTS: We have tested 42 smooth muscle neoplasms, 13 lesions of patients with suspicious or confirmed HLRCC, 20 sporadic piloleiomyomas, two angioleiomyomas and 7 leiomyosarcomas. FH staining grades from 1 to 3. Ten of the 13 lesions from the patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented grade 3 FH staining although five cases presented grade 1 FH staining. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. CONCLUSIONS: This staining could indicate a high risk of HLRCC in most of the confirmed cases but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. HLRCC syndrome should be rule out in FH negative piloleiomyomas after complete anamnesis if multiple lesions or positive familiar history is found.
Authors: Steven C Smith; Kiril Trpkov; Ying-Bei Chen; Rohit Mehra; Deepika Sirohi; Chisato Ohe; Andi K Cani; Daniel H Hovelson; Kei Omata; Jonathan B McHugh; Wolfram Jochum; Maurizio Colecchia; Mitual Amin; Mukul K Divatia; Ondřej Hes; Santosh Menon; Isabela Werneck da Cunha; Sergio Tripodi; Fadi Brimo; Anthony J Gill; Adeboye O Osunkoya; Cristina Magi-Galluzzi; Mathilde Sibony; Sean R Williamson; Gabriella Nesi; Maria M Picken; Fiona Maclean; Abbas Agaimy; Liang Cheng; Jonathan I Epstein; Victor E Reuter; Satish K Tickoo; Scott A Tomlins; Mahul B Amin Journal: Am J Surg Pathol Date: 2016-11 Impact factor: 6.394
Authors: Petr Martínek; Petr Grossmann; Ondřej Hes; Jiří Bouda; Viktor Eret; Norma Frizzell; Anthony J Gill; Ondrej Ondič Journal: Virchows Arch Date: 2015-05-19 Impact factor: 4.064
Authors: Cody S Carter; Stephanie L Skala; Arul M Chinnaiyan; Jonathan B McHugh; Javed Siddiqui; Xuhong Cao; Saravana M Dhanasekaran; Douglas R Fullen; Amir Lagstein; May P Chan; Rohit Mehra Journal: Am J Surg Pathol Date: 2017-06 Impact factor: 6.394