Hereditary leiomyomatosis and renal cell carcinoma syndrome
Hereditary leiomyomatosis and renal cell carcinoma (abbreviated HLRCC), also hereditary leiomyomatosis and renal cell cancer, is an uncommon syndrome caused by fumarate hydratase (FH) gene mutations.[1][2]
HLRCC is classically described as:[3]
- Papillary renal cell carcinoma type 2.
- Benign leiomyomas skin/uterus.
- Uterine leiomyosarcoma.
General
- Autosomal dominant inheritance[4] with variable penetration.[5]
- In one series of 21 families: 62% renal cancer, 76% had cutaneous leiomyomas and 100% had uterine leiomyomas.[6]
Clinical:
- Leiomyomas seen in many patients.
- The associated renal cell carcinoma is often aggressive and significant cause of mortality.[8]
Microscopic
Features - renal cell carcinoma:[8]
- Large eosinophilic nucleolus with perinucleolar clearing - proposed hallmark - important.
- May be focal.
- Variable architecture:
- Papillary - classic description.
- Hyaline material within the fibrovascular cores.
- Tubulopapillary.
- Tubular.
- Solid.
- Sieve-like pattern/cribriform.
- Papillary - classic description.
Notes:
- Not common: psammoma bodies, foamy macrophages.[9]
DDx:
- Papillary renal cell carcinoma (type 2).
- Tubulocystic carcinoma of the kidney.
- Collecting duct carcinoma.[6]
- Renal medullary carcinoma - cells also have a prominent nucleolus.
Images
www:
IHC
- Fumarate hydratase (FH) -ve.
- 2SC +ve -- cytoplasmic,[5] cytoplasmic and nuclear.[8]
- 2SC = S-(2-succino)-cysteine.
Others:
- CK7 -ve (0 +ve/38 cases[4]).
- CD10 -ve.
- May be positive in clear cell RCC-like areas.
- CK20 -ve (0 +ve/38 cases[4]).
- UEA-1 -ve.[4]
- TFE3 -ve (0 +ve/38 cases[4]).
- CK34betaE12 -ve (0 +ve/38 cases[4]).
See also
References
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 136850
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 150800
- ↑ 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.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 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.
- ↑ 5.0 5.1 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 6.2 Pithukpakorn, M.; Wei, MH.; Toure, O.; Steinbach, PJ.; Glenn, GM.; Zbar, B.; Linehan, WM.; Toro, JR. (Sep 2006). "Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.". J Med Genet 43 (9): 755-62. doi:10.1136/jmg.2006.041087. PMID 16597677.
- ↑ 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.
- ↑ 8.0 8.1 8.2 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.
- ↑ 9.0 9.1 Launonen, V.; Vierimaa, O.; Kiuru, M.; Isola, J.; Roth, S.; Pukkala, E.; Sistonen, P.; Herva, R. et al. (Mar 2001). "Inherited susceptibility to uterine leiomyomas and renal cell cancer.". Proc Natl Acad Sci U S A 98 (6): 3387-92. doi:10.1073/pnas.051633798. PMID 11248088.