Kidney tumor

Adult renal cell carcinoma - rare

SMARCB1 deficient renal medullary carcinoma

Last author update: 27 February 2023
Last staff update: 27 February 2023

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PubMed Search: SMARCB1 deficient renal medullary carcinoma

Daniel Anderson, M.D., M.B.A.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Anderson D, Tretiakova M. SMARCB1 deficient renal medullary carcinoma. website. Accessed June 1st, 2023.
Definition / general
  • Rare, highly aggressive, typically medulla centered carcinoma with SMARCB1 (INI1) deficiency
  • Associated with sickle cell trait or other sickle hemoglobinopathies
Essential features
  • Rare carcinoma arising in the renal medulla
  • Occurs predominately in young patients with sickle cell trait
  • Variety of histologic patterns
  • Sickled erythrocytes (drepanocytes) may be pathognomonic
  • Shows loss of SMARCB1 / INI1
  • Poor prognosis
  • SMARCB1 deficient renal medullary carcinoma, renal medullary carcinoma
ICD coding
  • ICD-O: 8510/3 - medullary carcinoma, NOS
  • ICD-10:
    • C64.1 - malignant neoplasm of right kidney, except renal pelvis
    • C64.2 - malignant neoplasm of left kidney, except renal pelvis
    • C64.9 - malignant neoplasm of unspecified kidney, except renal pelvis
  • ICD-11: 2C90.Y & XH2YP5 - other specified malignant neoplasm of kidney, except renal pelvis & medullary carcinoma, NOS
  • Involves the kidney, more often the right kidney, in any location of the renal medulla and with or without cortex
  • Arises in the renal medulla from the distal segment of the collecting ducts (Mod Pathol 2007;20:914, Hansel: The Kidney, 1st Edition, 2016)
  • Believed to arise from the renal papillae or calyceal epithelium and may be triggered by the chronic medullary hypoxia and hypertonic environment resulting from sickled red cells and microvascular occlusion (Urology 2002;60:1083, Clin Cancer Res 2018;24:2044)
    • Environment promotes double strand DNA breaks
    • Chronic hypoxia also leads to repression of the RAD51 and BRCA1 pathways associated with high fidelity homologous recombination and induces a switch to nonhomologous end joining (NHEJ) repair pathways, which are more likely to produce deletions and translocations
    • Translocations and deletions are the most common causes of SMARCB1 inactivation / loss of expression, a chromatin remodeler and tumor suppressor gene
    • Right side predominance may be due to differences in vascular anatomy, particularly the greater length of the right renal artery, which results in less blood flow and therefore relative hypoxia
  • Considered to be the seventh sickle cell nephropathy (others: unilateral hematuria, papillary necrosis, renal infarct, nephrotic syndrome, pyelonephritis, inability to concentrate urine) (Afr Health Sci 2016;16:490, Am J Surg Pathol 1995;19:1)
Diagrams / tables

Images hosted on other servers:

Proposed pathogenesis model

Morphologic patterns

Clinical features
  • Symptoms including hematuria, flank / abdominal pain, dysuria and weight loss in virtually all patients (J Oncol Pract 2017;13:414)
  • Fever, nausea, vomiting and a palpable abdominal mass may be present
  • Aggressive; usually advanced disease at presentation with metastases to lung, liver, lymph nodes, adrenal gland, peritoneum, retroperitoneum, inferior vena cava, etc.
    • 90% of patients present with metastasis at the time of diagnosis
  • Essential: SMARCB1 deficient, high grade, infiltrating adenocarcinoma
  • Desirable: clinical / laboratory evidence of sickle hemoglobinopathy
  • Consideration of other carcinomas with SMARCB1 deficiency (see Differential diagnosis)
Radiology description
Prognostic factors
Case reports
Gross description
  • Poorly circumscribed, lobulated, firm, rubbery, gray-white tumor centered in renal medulla
  • Size ranges from 4 to 12 cm, mean is 5.9 cm (Am J Surg Pathol 2013;37:368)
  • Hemorrhage and necrosis are common
  • Typically extends into the calyces and pelvis
  • Satellite nodules in the cortex, extension into the perinephric and sinus fat can be present
Gross images

Contributed by Daniel Anderson, M.D., M.B.A.

Medulla centered mass

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Well circumscribed yellowish white tumor

Focally infiltrative

Lobulated tumor

Microscopic (histologic) description
  • Variety of morphologic patterns:
    • Distinctive patterns include reticular / yolk sac tumor-like and sieve-like / cribriform / microcystic / adenoid cystic-like
    • Cords, nests, tubular, glandular, tubulopapillary and solid / sheet-like patterns overlaps with collecting duct carcinoma and fumarate hydratase (FH) deficient renal cell carcinoma (Am J Surg Pathol 2018;42:279)
  • Tumor cells are pleomorphic with hyperchromatic enlarged nuclei, vesicular chromatin, prominent nucleoli, nuclear grooves, eosinophilic cytoplasm and may have rhabdoid features
  • Hemorrhage, necrosis (may be ischemic, geographic or central / comedo type)
  • Frequent mitotic figures
  • Angiolymphatic invasion, desmoplastic stroma and infiltrative borders
  • Abundant intratumoral neutrophils (sometimes abscess forming) and lymphocytes at tumor rim
  • Abundant sickled erythrocytes (drepanocytes) may be pathognomonic
Microscopic (histologic) images

Contributed by Daniel Anderson, M.D., M.B.A.

Cribriform, reticular and nested growth

Cribriform nest

Reticular growth

Nuclear details

Cytology description
  • Loosely cohesive groups, sheets or single cells
  • High grade / pleomorphic cells with vacuolated fine pale cytoplasm that often displace nuclei
  • Nuclei often have irregular membranes, coarse or vesicular chromatin, smooth borders, membrane grooves and prominent nucleoli (Cancer 2005;105:28, J Am Soc Cytopathol 2021;10:187)
Cytology images

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Loosely cohesive groups

Positive stains
Negative stains
Electron microscopy description
  • Cells contain tight junctions and large intracytoplasmic lumina, which contain long slender microvilli
  • Condensed fibrillary electron dense filamentous luminal deposits are also seen (Ultrastruct Pathol 2008;32:252)
Molecular / cytogenetics description
  • Molecular:
    • Inactivation of SMARCB1 / INI1 (22q11.2) from chromosomal translocations or deletions is a major driver mutation
    • Hypoxia inducible factor and VHL abnormalities (Hum Pathol 2011;42:1979)
    • DNA topoisomerase II amplification (BJU Int 2010;106:62)
    • Chromosome 8q gain, where c-MYC is located, was noted in 46.7% of renal medullary carcinoma tumors and contains recurrent focal copy number alterations (CNA) in regions of genes related to cell proliferation including a distinct CNA pattern that results in Notch pathway activation (Cancer Cell 2020;37:720)
  • Cytogenetics (Arch Pathol Lab Med 2019;143:1556, Eur Urol 2016;69:1055, Histopathology 2012;61:428, Am J Surg Pathol 2011;35:e47):
    • Rearrangement of chromosome 8 resulting in a loss of 8p and a gain of 8q can be observed
    • Gains of chromosomes 7, 8, 10 and 11 can be seen along with losses of chromosomes 9 and 13
    • Additional unknown material on 10p, a deletion of 7q and a dicentric chromosome composed of 13q and 21q
    • Rare instances of ABL gene amplification or translocation have also been described

Pathology mini tutorial of renal medullary carcinoma

Cytomorphologic study of renal medullary carcinoma involving serous cavity fluids

Sample pathology report
  • Right kidney, radical nephrectomy:
    • SMARCB1 deficient renal medullary carcinoma (X cm), extends into the renal sinus, margins are negative (see comment and synoptic report)
    • Comment: The patient's history of sickle cell trait is noted. Immunohistochemistry for SMARCB1 (INI1) is performed and shows loss of expression within the tumor cells. The clinical, morphologic and immunohistochemical findings support the diagnosis.
Differential diagnosis
Board review style question #1

A 24 year old man with sickle cell trait presents with hematuria and flank pain. Imaging shows a 6 cm medulla centered renal mass. A radical nephrectomy is performed. What will the pathologic workup likely show?

  1. Inactivation of 12q11.2 due to deletion or translocation
  2. Papillary growth with pale to eosinophilic, flocculent cytoplasm
  3. Reticular or cribriform growth pattern with high grade cells
  4. TFE3 (on Xp11) translocation with ASPSCR1 (ASPL)
Board review style answer #1
C. Reticular or cribriform growth pattern with high grade cells. SMARCB1 deficient renal medullary carcinoma, also known as renal medullary carcinoma, often shows a reticular / yolk sac tumor-like and sieve-like / cribriform / microcystic / adenoid cystic-like morphology on a desmoplastic stroma with an associated inflammatory infiltrate. The tumor is found in patients with sickle cell trait and is defined by loss of SMARCB1 / INI1 (found on chromosome 22q11.2). TFE3 rearranged renal cell carcinoma often shows solid to papillary growth with psammoma bodies and can show voluminous clear to eosinophilic cytoplasm. TFE3 rearranged renal cell carcinomas are molecularly defined with TFE3 fusions with one of multiple genes including ASPSCR1 (ASPL), PRCC, NONO (P54NRB), SFPQ (PSF), RBM10, etc.

Comment here

Reference: SMARCB1 deficient renal medullary carcinoma
Board review style question #2
A 1 year old boy with hypercalcemia and without evidence of any hemoglobinopathy presents with a right renal mass. Histologically, the tumor displays a diffuse growth pattern of rhabdoid cells with prominent nucleoli and intracytoplasmic inclusions. What similarities will this tumor show to renal medullary carcinoma?

  1. Both tumors have an indolent prognosis
  2. CD20 positivity
  3. May show positive staining for GFAP, SMA, synaptophysin, CD99
  4. Will show SMARCB1 (INI1) loss / inactivation by immunohistochemistry
Board review style answer #2
D. Will show SMARCB1 (INI) loss / inactivation by immunohistochemistry. The scenario is describing rhabdoid tumor of the kidney. This entity will show biallelic inactivation of the SMARCB1 or SMARCA4 genes, leading to a lack of SMARCB1 / INI1 immunostaining, a feature shared with renal medullary carcinoma. Both tumors share a dismal prognosis. Rhabdoid tumors of the kidney have a reported 5 year overall survival rate ranging from < 15% to 25% and show a diverse range of immunoreactivity including cytokeratins, GFAP, SMA, synaptophysin and CD99 staining. CD20 positivity has not been described in either tumor.

Comment here

Reference: SMARCB1 deficient renal medullary carcinoma
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