Succinate dehydrogenase-deficient renal cell carcinoma

Succinate dehydrogenase-deficient renal cell carcinoma
	Diagnosis in short
	; SDH-deficient renal cell carcinoma (left of image). H&E stain.
LM	eosinophilic cells with clear (flocculent) cytoplasmic inclusions, round nuclei with mildly granular chromatin pattern, intratumoural mast cells, solid architecture
LM DDx	renal oncocytoma, chromophobe renal cell carcinoma, clear cell renal cell carcinoma, other renal tumours with eosinophilic cytoplasm
IHC	SDHB -ve, CK7 -ve, CD117 -ve, PAX8 +ve, CA9 -ve
Gross	mass lesion, commonly cystic
Grossing notes	partial nephrectomy grossing, total nephrectomy for tumour grossing
Site	kidney - see kidney tumours
Syndromes	familial pheochromocytoma and renal cell carcinoma syndrome
Prevalence	extremely rare
Prognosis	usually good prognosis (limited data)
Clin. DDx	other kidney tumours

Succinate dehydrogenase-deficient renal cell carcinoma, also succinate dehydrogenase renal cell carcinoma (abbreviated SDH-RCC), is a very rare type of renal cell carcinoma.

It is in the 2016 World Health Organization classification of renal neoplasia.

General

Extremely rare - estimated to represent up to 0.2% of renal cell carcinomas.^[1]
May be assocated with paraganglioma and familial, as with several SDH mutations.^[2]
Primarily described with a SDHB mutation.^[3]
- SDHA has been described.^[3]
- SDHC has been described.^[4]
Usually good prognosis.

Gross

Mass lesion - commonly cystic.

Microscopic

Features:^[3]

Eosinophilic cells with clear (flocculent) cytoplasmic inclusions. ‡
Round nuclei with mildly granular chromatin pattern.
Intratumoural mast cells - usu. not prominent.
Solid architecture - typical.

Notes:

‡ Occasional cells may look like signet ring cells.
Typically low ISUP nucleolar grade.
- May be sarcomatoid.

DDx:

Renal oncocytoma - granular cytoplasm.
Chromophobe renal cell carcinoma.
Clear cell renal cell carcinoma.
Other renal tumours with eosinophilic cytoplasm.

Images

www:

Case 1

SDH-RCC low mag.
SDH-RCC intermed. mag.
SDH-RCC intermed. mag.
SDH-RCC high mag.
SDH-RCC very high mag.

Case 2

SDH-RCC intermed. mag.
SDH-RCC high mag.
SDH-RCC very high mag.

Case 3

Pictures demonstrates the variability between different regions of the tumour:

SDH-RCC - low mag.
SDH-RCC - intermed. mag.
SDH-RCC - high mag.
SDH-RCC - low mag.
SDH-RCC - intermed. mag.
SDH-RCC - high mag.
SDH-RCC - low mag.
SDH-RCC - intermed. mag.
SDH-RCC - high mag.

IHC

Features:

SDHB -ve (11 of 11 cases^[3]).
- Normal tubules +ve.
- May be (pseudo)negative in clear cells (as few mitochondria).
CD117 -ve - important.
CA9 -ve.

Others:

PAX8 +ve.
EMA +ve (10/10^[3]).
CK7 -ve (1 +ve/35^[1]).
AE1/AE3 -ve/+ve (4 +ve/10^[3]).
CK20 -ve.
CD10 usually focal (most common) or -ve.^[1]

References

↑ ^1.0 ^1.1 ^1.2 Gill, AJ.; Hes, O.; Papathomas, T.; Šedivcová, M.; Tan, PH.; Agaimy, A.; Andresen, PA.; Kedziora, A. et al. (Dec 2014). "Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients.". Am J Surg Pathol 38 (12): 1588-602. doi:10.1097/PAS.0000000000000292. PMID 25025441.
↑ Hernandez, KG.; Ezzat, S.; Morel, CF.; Swallow, C.; Otremba, M.; Dickson, BC.; Asa, SL.; Mete, O. (Mar 2015). "Familial pheochromocytoma and renal cell carcinoma syndrome: TMEM127 as a novel candidate gene for the association.". Virchows Arch. doi:10.1007/s00428-015-1755-2. PMID 25800244.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 Williamson, SR.; Eble, JN.; Amin, MB.; Gupta, NS.; Smith, SC.; Sholl, LM.; Montironi, R.; Hirsch, MS. et al. (Jan 2015). "Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma.". Mod Pathol 28 (1): 80-94. doi:10.1038/modpathol.2014.86. PMID 25034258.
↑ ^4.0 ^4.1 ^4.2 Ricketts, CJ.; Shuch, B.; Vocke, CD.; Metwalli, AR.; Bratslavsky, G.; Middelton, L.; Yang, Y.; Wei, MH. et al. (Dec 2012). "Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer.". J Urol 188 (6): 2063-71. doi:10.1016/j.juro.2012.08.030. PMID 23083876.

External links

Succinate dehydrogenase-deficient renal carcinoma (cancerdxpathology.org.au) - virtual slides from Gill.

[pmid25025441-1] 1.0 ^1.1 ^1.2 Gill, AJ.; Hes, O.; Papathomas, T.; Šedivcová, M.; Tan, PH.; Agaimy, A.; Andresen, PA.; Kedziora, A. et al. (Dec 2014). "Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients.". Am J Surg Pathol 38 (12): 1588-602. doi:10.1097/PAS.0000000000000292. PMID 25025441.

[pmid25800244-2] Hernandez, KG.; Ezzat, S.; Morel, CF.; Swallow, C.; Otremba, M.; Dickson, BC.; Asa, SL.; Mete, O. (Mar 2015). "Familial pheochromocytoma and renal cell carcinoma syndrome: TMEM127 as a novel candidate gene for the association.". Virchows Arch. doi:10.1007/s00428-015-1755-2. PMID 25800244.

[pmid25034258-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 Williamson, SR.; Eble, JN.; Amin, MB.; Gupta, NS.; Smith, SC.; Sholl, LM.; Montironi, R.; Hirsch, MS. et al. (Jan 2015). "Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma.". Mod Pathol 28 (1): 80-94. doi:10.1038/modpathol.2014.86. PMID 25034258.

[pmid23083876-4] 4.0 ^4.1 ^4.2 Ricketts, CJ.; Shuch, B.; Vocke, CD.; Metwalli, AR.; Bratslavsky, G.; Middelton, L.; Yang, Y.; Wei, MH. et al. (Dec 2012). "Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer.". J Urol 188 (6): 2063-71. doi:10.1016/j.juro.2012.08.030. PMID 23083876.

[1]

[2]

[3]

[4]