ELOC-mutated renal cell carcinoma

ELOC-mutated renal cell carcinoma
	Diagnosis in short
	; RCC with clear cells and fibromuscular band - morphology compatible with TCEB1 mutation. H&E stain. (WC)
Synonyms	TCEB1-mutated renal cell carcinoma (old name)
LM	clear cells with abundant cytoplasm and basal nuclei (may have luminal nuclei), usually ISUP nucleolar grade 2, fibromuscular bands
LM DDx	clear cell renal cell carcinoma, clear cell papillary renal cell tumour (clear cell papillary RCC), renal cell carcinoma with fibromyomatous stroma
IHC	CK7 +ve, CD10 +ve, CK34betaE12 -ve
Molecular	TCEB1 mutation
Site	kidney - see kidney tumours
Syndromes	possibly tuberous sclerosis - see tuberous sclerosis-associated renal cell carcinoma
Prevalence	very rare - evolving entity
Prognosis	good - based on limited data

ELOC-mutated renal cell carcinoma is a type of renal cell carcinoma that is morphologically similar to clear cell renal cell carcinoma and clear cell papillary renal cell tumour (previously clear cell papillary renal cell carcinoma).^[1] It was formally recognized in the WHO 2022 classification of renal neoplasia.^{[citation needed]}

It was previously known as TCEB1-mutated renal cell carcinoma and renal cell carcinoma with TCEB1 mutation. It should not be confused with TFEB renal cell carcinoma, also known as renal tumour with t(6;11) translocation.

It is unrelated to the previously described renal angiomyoadenomatous tumour^[1]^[2] that was lumped with clear cell papillary renal cell carcinoma in the Vancouver modification of the WHO classification.

General

Entity part of WHO Blue Book (5th Edition).
TCEB1 (transcription elongation factor B, polypeptide 1) is part of a complex that binds with the product of the VHL gene;^[3] thus, it acts as a tumour suppressor.
Good prognosis - based on limited data.^[1]

Gross

Cystic changes.

Microscopic

Features:

Clear cells with abundant cytoplasm and basal nuclei.
- Luminal nuclei (like in clear cell tubulopapillary RCC) may be seen.
Usually ISUP nucleolar grade 2.
Fibromuscular bands - key feature.

DDx:

Clear cell renal cell carcinoma.
Clear cell papillary renal cell tumour (previously clear cell papillary renal cell carcinoma) - have luminal nuclei.
Tuberous sclerosis-associated renal cell carcinoma.
Renal cell carcinoma with fibromyomatous stroma has TSC/mTOR pathway mutation.

Images

Morphology compatible

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

IHC

Features:^[1]

CK7 +ve.
CD10 +ve.
- Typically negative in clear cell papillary renal cell tumour.
CK34betaE12 -ve.
- Usually positive in clear cell papillary renal cell tumour.

Others:

GPNMB -ve.
- TSC1/TSC2/MTOR mutated RCC is GPNMB +ve.^[4]

Comparison between some renal tumours with clear cells

Tumour	CK7	CD10	CK34betaE12 (K903)	GPNMB
Clear cell renal cell carcinoma	-ve (may be focal)	+ve	-ve	usu. -ve
Clear cell papillary renal cell tumour	+ve (diffuse)	-ve	+ve	-ve^[4]
ELOC-mutated renal cell carcinoma	+ve	+ve	-ve	-ve
Renal cell carcinoma with fibromyomatous stroma and TSC/mTOR-mutation	+ve	+ve	-ve	+ve

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Molecular lacking

Right Kidney, Radical Nephrectomy: 
     - RENAL CELL CARCINOMA with clear cells, cysts and leiomyomatous stroma, see comment.
     -- Margin clear.
     -- Please see synoptic report for details.

Comment:
The tumour stains as follows:
POSITIVE: CD10 (moderate), EMA (patchy), CAM5.2, CK7 (focal), PAX8 (diffuse).
NEGATIVE: CK34betaE12, CK20.

The differential diagnosis includes: (1) clear cell renal cell carcinoma, (2) RCC with a mTOR pathway mutation, and (3) ELOC-mutated RCC.

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Hakimi, AA.; Tickoo, SK.; Jacobsen, A.; Sarungbam, J.; Sfakianos, JP.; Sato, Y.; Morikawa, T.; Kume, H. et al. (Jun 2015). "TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype.". Mod Pathol 28 (6): 845-53. doi:10.1038/modpathol.2015.6. PMID 25676555.
↑ Michal, M.; Hes, O.; Kuroda, N.; Kazakov, DV.; Hora, M. (Jun 2009). "Difference between RAT and clear cell papillary renal cell carcinoma/clear renal cell carcinoma.". Virchows Arch 454 (6): 719. doi:10.1007/s00428-009-0788-9. PMID 19471960.
↑ URL: http://www.omim.org/entry/600788. Accessed on: 12 June 2015.
↑ ^4.0 ^4.1 Li H, Argani P, Halper-Stromberg E, Lotan TL, Merino MJ, Reuter VE, Matoso A (November 2023). "Positive GPNMB Immunostaining Differentiates Renal Cell Carcinoma With Fibromyomatous Stroma Associated With TSC1/2/MTOR Alterations From Others". Am J Surg Pathol 47 (11): 1267–1273. doi:10.1097/PAS.0000000000002117. PMID 37661807.

[pmid25676555-1] 1.0 ^1.1 ^1.2 ^1.3 Hakimi, AA.; Tickoo, SK.; Jacobsen, A.; Sarungbam, J.; Sfakianos, JP.; Sato, Y.; Morikawa, T.; Kume, H. et al. (Jun 2015). "TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype.". Mod Pathol 28 (6): 845-53. doi:10.1038/modpathol.2015.6. PMID 25676555.

[pmid19471960-2] Michal, M.; Hes, O.; Kuroda, N.; Kazakov, DV.; Hora, M. (Jun 2009). "Difference between RAT and clear cell papillary renal cell carcinoma/clear renal cell carcinoma.". Virchows Arch 454 (6): 719. doi:10.1007/s00428-009-0788-9. PMID 19471960.

[3] URL: http://www.omim.org/entry/600788. Accessed on: 12 June 2015.

[pmid37661807-4] 4.0 ^4.1 Li H, Argani P, Halper-Stromberg E, Lotan TL, Merino MJ, Reuter VE, Matoso A (November 2023). "Positive GPNMB Immunostaining Differentiates Renal Cell Carcinoma With Fibromyomatous Stroma Associated With TSC1/2/MTOR Alterations From Others". Am J Surg Pathol 47 (11): 1267–1273. doi:10.1097/PAS.0000000000002117. PMID 37661807.

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