Difference between revisions of "Hereditary leiomyomatosis and renal cell carcinoma syndrome"

From Libre Pathology
Jump to navigation Jump to search
(tweak)
 
(16 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:Hereditary leiomyomatosis and renal cell carcinoma associated RCC -- high mag.jpg|thumb|250px|right|[[Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma]] showing the characteristic hyalinized papillary cores. [[H&E stain]]. (WC/Nephron)]]  
[[Image:Hereditary leiomyomatosis and renal cell carcinoma associated RCC - TC-like -- very high mag.jpg|thumb|325px|right|[[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.<ref name=omim136850>{{OMIM|136850}}</ref><ref name=omim150800>{{OMIM|150800}}</ref>
'''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.<ref name=omim136850>{{OMIM|136850}}</ref><ref name=omim150800>{{OMIM|150800}}</ref>


HLRCC is classically described as:<ref name=Ref_WMSP290>{{Ref WMSP|290}}</ref>
Characteristics:
* [[Papillary renal cell carcinoma]] type 2.
* [[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/>
*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% renal cancer, 76% had cutaneous leiomyomas and 100% had [[uterine leiomyoma]]s.<ref name=pmid16597677>{{Cite journal  | last1 = Pithukpakorn | first1 = M. | last2 = Wei | first2 = MH. | last3 = Toure | first3 = O. | last4 = Steinbach | first4 = PJ. | last5 = Glenn | first5 = GM. | last6 = Zbar | first6 = B. | last7 = Linehan | first7 = WM. | last8 = Toro | first8 = JR. | title = Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer. | journal = J Med Genet | volume = 43 | issue = 9 | pages = 755-62 | month = Sep | year = 2006 | doi = 10.1136/jmg.2006.041087 | PMID = 16597677 }}</ref>
**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>


Clinical:
Features - clinical:
*[[Leiomyoma]]s seen in many patients.
*[[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=pmid16597677/>
**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/>
**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>
 
Note:
*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:

Formal criteria

The diagnosis of the HLRCC syndrome requires both #1 and #2:[3]

  1. A pathogenic FH mutation is present by molecular testing.
  2. 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:

Note:

See also

References

  1. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 136850
  2. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 150800
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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/.
Retrieved from "https://librepathology.org/w/index.php?title=Hereditary_leiomyomatosis_and_renal_cell_carcinoma_syndrome&oldid=52803"