Difference between revisions of "Hereditary leiomyomatosis and renal cell carcinoma syndrome"
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Characteristics: | Characteristics: | ||
* [[ | * [[Fumarate hydratase-deficient renal cell carcinoma]]. | ||
* Benign [[leiomyoma]]s skin/[[uterine leiomyoma|uterus]]. | * Benign [[leiomyoma]]s skin/[[uterine leiomyoma|uterus]]. | ||
* Uterine [[leiomyosarcoma]]. | * Uterine [[leiomyosarcoma]]. | ||
==Formal criteria== | |||
The diagnosis of the HLRCC syndrome requires both #1 and #2:<ref>{{Cite journal | last1 = Adam | first1 = MP. | last2 = Ardinger | first2 = HH. | last3 = Pagon | first3 = RA. | last4 = Wallace | first4 = SE. | last5 = Bean | first5 = LJH. | last6 = Mefford | first6 = HC. | last7 = Stephens | first7 = K. | last8 = Amemiya | first8 = A. | last9 = Ledbetter | first9 = N. | title = Hereditary Leiomyomatosis and Renal Cell Cancer | journal = | volume = | issue = | pages = | month = | year = | doi = | PMID = 20301430 }}</ref> | |||
#A pathogenic FH mutation is present by molecular testing. | |||
#One of the following (pathologic) findings: | |||
#*Multiple cutaneous leiomyoma where one was proven histologically. | |||
#*One cutaneous leiomyoma in the context of a family history of HLRCC. | |||
#*RCC with a morphology suggestive of HRLCC syndrome-associated RCC. | |||
==General== | ==General== | ||
*Autosomal dominant inheritance<ref name=pmid17895761>{{Cite journal | last1 = Merino | first1 = MJ. | last2 = Torres-Cabala | first2 = C. | last3 = Pinto | first3 = P. | last4 = Linehan | first4 = WM. | title = The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. | journal = Am J Surg Pathol | volume = 31 | issue = 10 | pages = 1578-85 | month = Oct | year = 2007 | doi = 10.1097/PAS.0b013e31804375b8 | PMID = 17895761 }}</ref> with variable penetration.<ref name=pmid24309325>{{Cite journal | last1 = Reyes | first1 = C. | last2 = Karamurzin | first2 = Y. | last3 = Frizzell | first3 = N. | last4 = Garg | first4 = K. | last5 = Nonaka | first5 = D. | last6 = Chen | first6 = YB. | last7 = Soslow | first7 = RA. | title = Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry. | journal = Mod Pathol | volume = 27 | issue = 7 | pages = 1020-7 | month = Jul | year = 2014 | doi = 10.1038/modpathol.2013.215 | PMID = 24309325 }}</ref> | *Autosomal dominant inheritance<ref name=pmid17895761>{{Cite journal | last1 = Merino | first1 = MJ. | last2 = Torres-Cabala | first2 = C. | last3 = Pinto | first3 = P. | last4 = Linehan | first4 = WM. | title = The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. | journal = Am J Surg Pathol | volume = 31 | issue = 10 | pages = 1578-85 | month = Oct | year = 2007 | doi = 10.1097/PAS.0b013e31804375b8 | PMID = 17895761 }}</ref> with variable penetration.<ref name=pmid24309325>{{Cite journal | last1 = Reyes | first1 = C. | last2 = Karamurzin | first2 = Y. | last3 = Frizzell | first3 = N. | last4 = Garg | first4 = K. | last5 = Nonaka | first5 = D. | last6 = Chen | first6 = YB. | last7 = Soslow | first7 = RA. | title = Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry. | journal = Mod Pathol | volume = 27 | issue = 7 | pages = 1020-7 | month = Jul | year = 2014 | doi = 10.1038/modpathol.2013.215 | PMID = 24309325 }}</ref> | ||
**In one series of 21 families: 62% had renal cancer, 76% had cutaneous leiomyomas and 100% had [[uterine leiomyoma]]s.<ref name= | **In one series of 21 families: 62% had renal cancer, 76% had cutaneous leiomyomas and 100% had [[uterine leiomyoma]]s.<ref name=pmid15937070>{{Cite journal | last1 = Wei | first1 = MH. | last2 = Toure | first2 = O. | last3 = Glenn | first3 = GM. | last4 = Pithukpakorn | first4 = M. | last5 = Neckers | first5 = L. | last6 = Stolle | first6 = C. | last7 = Choyke | first7 = P. | last8 = Grubb | first8 = R. | last9 = Middelton | first9 = L. | title = Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. | journal = J Med Genet | volume = 43 | issue = 1 | pages = 18-27 | month = Jan | year = 2006 | doi = 10.1136/jmg.2005.033506 | PMID = 15937070 }}</ref> | ||
Features - clinical: | Features - clinical: | ||
*[[Leiomyoma]]s - high penetrance. | *[[Leiomyoma]]s - high penetrance. | ||
**Manifestation: skin rash.<ref name=pmid24999901>{{Cite journal | last1 = Toon | first1 = CW. | last2 = Hasovits | first2 = C. | last3 = Paik | first3 = J. | last4 = Field | first4 = M. | last5 = Chou | first5 = A. | last6 = Hugh | first6 = TJ. | last7 = Pavlakis | first7 = N. | last8 = Gill | first8 = AJ. | title = Skin rash, a kidney mass and a family mystery dating back to World War II. | journal = Med J Aust | volume = 201 | issue = 1 | pages = 58-60 | month = Jul | year = 2014 | doi = | PMID = 24999901 }}</ref> | **Manifestation: skin rash.<ref name=pmid24999901>{{Cite journal | last1 = Toon | first1 = CW. | last2 = Hasovits | first2 = C. | last3 = Paik | first3 = J. | last4 = Field | first4 = M. | last5 = Chou | first5 = A. | last6 = Hugh | first6 = TJ. | last7 = Pavlakis | first7 = N. | last8 = Gill | first8 = AJ. | title = Skin rash, a kidney mass and a family mystery dating back to World War II. | journal = Med J Aust | volume = 201 | issue = 1 | pages = 58-60 | month = Jul | year = 2014 | doi = | PMID = 24999901 }}</ref> | ||
**Involvement may be minimal or extensive.<ref name= | **Involvement may be minimal or extensive.<ref name=pmid15937070/> | ||
*[[Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma]]. | *[[Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma]]. | ||
**Often aggressive and significant cause of mortality.<ref name=pmid24441663>{{Cite journal | last1 = Chen | first1 = YB. | last2 = Brannon | first2 = AR. | last3 = Toubaji | first3 = A. | last4 = Dudas | first4 = ME. | last5 = Won | first5 = HH. | last6 = Al-Ahmadie | first6 = HA. | last7 = Fine | first7 = SW. | last8 = Gopalan | first8 = A. | last9 = Frizzell | first9 = N. | title = Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. | journal = Am J Surg Pathol | volume = 38 | issue = 5 | pages = 627-37 | month = May | year = 2014 | doi = 10.1097/PAS.0000000000000163 | PMID = 24441663 }}</ref> | **Often aggressive and significant cause of mortality.<ref name=pmid24441663>{{Cite journal | last1 = Chen | first1 = YB. | last2 = Brannon | first2 = AR. | last3 = Toubaji | first3 = A. | last4 = Dudas | first4 = ME. | last5 = Won | first5 = HH. | last6 = Al-Ahmadie | first6 = HA. | last7 = Fine | first7 = SW. | last8 = Gopalan | first8 = A. | last9 = Frizzell | first9 = N. | title = Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. | journal = Am J Surg Pathol | volume = 38 | issue = 5 | pages = 627-37 | month = May | year = 2014 | doi = 10.1097/PAS.0000000000000163 | PMID = 24441663 }}</ref> | ||
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Note: | Note: | ||
*The RCC in the past was typically diagnosed as ''[[papillary renal cell carcinoma]]''.<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref> | *The RCC in the past was typically diagnosed as ''[[papillary renal cell carcinoma]]''.<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref> | ||
*Case reports describing an association with [[adrenal cortical carcinoma]].<ref>{{cite journal |authors=Silverman E, Addasi N, Azzawi M, Duarte EM, Huang D, Swanson B, Ganti AK, Reiser G, Fingeret AL, Kotwal A |title=Recurrent Cushing Syndrome From Metastatic Adrenocortical Carcinoma With Fumarate Hydratase Allelic Variant |journal=AACE Clin Case Rep |volume=8 |issue=6 |pages=259–263 |date=2022 |pmid=36447829 |pmc=9701913 |doi=10.1016/j.aace.2022.09.003 |url=}}</ref> | |||
==See also== | ==See also== | ||
Latest revision as of 18:58, 24 March 2024
Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma showing the classically described prominent nucleoli with perinucleolar clearing. H&E stain. (WC/Nephron)
Hereditary leiomyomatosis and renal cell carcinoma syndrome (abbreviated HLRCC), also hereditary leiomyomatosis and renal cell cancer, is an uncommon syndrome caused by fumarate hydratase (FH) gene mutations.[1][2]
Characteristics:
- Fumarate hydratase-deficient renal cell carcinoma.
- Benign leiomyomas skin/uterus.
- Uterine leiomyosarcoma.
Formal criteria
The diagnosis of the HLRCC syndrome requires both #1 and #2:[3]
- A pathogenic FH mutation is present by molecular testing.
- One of the following (pathologic) findings:
- Multiple cutaneous leiomyoma where one was proven histologically.
- One cutaneous leiomyoma in the context of a family history of HLRCC.
- RCC with a morphology suggestive of HRLCC syndrome-associated RCC.
General
- Autosomal dominant inheritance[4] with variable penetration.[5]
- In one series of 21 families: 62% had renal cancer, 76% had cutaneous leiomyomas and 100% had uterine leiomyomas.[6]
Features - clinical:
- Leiomyomas - high penetrance.
- Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma.
- Often aggressive and significant cause of mortality.[8]
Note:
- The RCC in the past was typically diagnosed as papillary renal cell carcinoma.[9]
- Case reports describing an association with adrenal cortical carcinoma.[10]
See also
References
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 136850
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 150800
- ↑ Adam, MP.; Ardinger, HH.; Pagon, RA.; Wallace, SE.; Bean, LJH.; Mefford, HC.; Stephens, K.; Amemiya, A. et al. Hereditary Leiomyomatosis and Renal Cell Cancer. PMID 20301430.
- ↑ Merino, MJ.; Torres-Cabala, C.; Pinto, P.; Linehan, WM. (Oct 2007). "The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.". Am J Surg Pathol 31 (10): 1578-85. doi:10.1097/PAS.0b013e31804375b8. PMID 17895761.
- ↑ Reyes, C.; Karamurzin, Y.; Frizzell, N.; Garg, K.; Nonaka, D.; Chen, YB.; Soslow, RA. (Jul 2014). "Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry.". Mod Pathol 27 (7): 1020-7. doi:10.1038/modpathol.2013.215. PMID 24309325.
- ↑ 6.0 6.1 Wei, MH.; Toure, O.; Glenn, GM.; Pithukpakorn, M.; Neckers, L.; Stolle, C.; Choyke, P.; Grubb, R. et al. (Jan 2006). "Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.". J Med Genet 43 (1): 18-27. doi:10.1136/jmg.2005.033506. PMID 15937070.
- ↑ Toon, CW.; Hasovits, C.; Paik, J.; Field, M.; Chou, A.; Hugh, TJ.; Pavlakis, N.; Gill, AJ. (Jul 2014). "Skin rash, a kidney mass and a family mystery dating back to World War II.". Med J Aust 201 (1): 58-60. PMID 24999901.
- ↑ Chen, YB.; Brannon, AR.; Toubaji, A.; Dudas, ME.; Won, HH.; Al-Ahmadie, HA.; Fine, SW.; Gopalan, A. et al. (May 2014). "Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry.". Am J Surg Pathol 38 (5): 627-37. doi:10.1097/PAS.0000000000000163. PMID 24441663.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 290. ISBN 978-0781765275.
- ↑ Silverman E, Addasi N, Azzawi M, Duarte EM, Huang D, Swanson B, Ganti AK, Reiser G, Fingeret AL, Kotwal A (2022). "Recurrent Cushing Syndrome From Metastatic Adrenocortical Carcinoma With Fumarate Hydratase Allelic Variant". AACE Clin Case Rep 8 (6): 259–263. doi:10.1016/j.aace.2022.09.003. PMC 9701913. PMID 36447829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701913/.