Kidney tumor
Adult renal cell carcinoma - rare
Medullary carcinoma

Topic Completed: 1 September 2017

Minor changes: 27 October 2020

Copyright: 2002-2019,, Inc.

PubMed Search: Medullary carcinoma [title] kidney

Daniel Anderson, M.D., M.B.A.
Maria Tretiakova, M.D., Ph.D.
Page views in 2020: 6,502
Page views in 2021 to date: 230
Cite this page: Anderson D, Tretiakova M. Medullary carcinoma. website. Accessed January 18th, 2021.
Definition / general
  • Rare, highly aggressive medulla centered carcinoma
  • Associated with sickle cell trait or other 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 may be pathognomonic
  • Majority show loss of SMARCB1 / INI1
  • Poor prognosis
ICD coding
  • Renal neoplasms start at C64; there are 3 codes below C64 that describe this diagnosis in greater detail (ICD10Data: 2017 ICD-10-CM Diagnosis Code C64)
    • 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
  • Arises in the renal medulla (Mod Pathol 2007;20:914) from the distal segment of the collecting ducts (Koo: The Kidney, 2016)
  • Believed to arise from the renal papillae or calyceal epithelium and may be triggered by chronic medullary hypoxia as a result of sickled red cells (Urology 2002;60:1083)
  • Called the seventh sickle cell nephropathy (others: unilateral hematuria, papillary necrosis, renal infarct, nephrotic syndrome, pyelonephritis, inability to concentrate urine)
Clinical features
  • Gross hematuria, flank pain and weight loss in virtually all patients (J Oncol Pract 2017;13:414)
  • Fever, nausea, vomiting and a palpable abdominal mass may also be present
  • Aggressive; usually advanced disease at presentation with metastases to lymph nodes, adrenal gland, peritoneum, perinodal retroperitoneum, liver, lungs or inferior vena cava
  • Poor prognosis with a median overall survival of 6 - 13 months (J Oncol Pract 2017;13:422)
Radiology description
Case reports
Gross description
  • Poorly circumscribed, lobulated, firm, rubbery, gray tumor in renal medulla
  • Size range from 4 to 12 cm, mean 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.

Various images

Images hosted on other servers:

2: Well circumscribed yellowish white tumor

Focally infiltrative

Medullary based infiltrative tumor with abundant necrosis

Lobulated tumor

Microscopic (histologic) description
  • Variety of morphologic patterns: distinctive patterns include reticular, microcystic and adenoid cystic-like; tubular, glandular, tubulopapillary and solid overlaps with collecting duct carcinoma patterns
  • Tumor cells are pleomorphic with hyperchromatic enlarged nuclei, prominent nucleoli, eosinophilic cytoplasm and may have rhabdoid features
  • Hemorrhagic and geographic necrosis, frequent mitotic figures
  • Angiolymphatic invasion, desmoplastic stroma and infiltrative borders
  • Abundant intratumoral neutrophils and lymphocytes at tumor rim
  • Abundant sickled erythrocytes (drepanocytes) may be pathognomonic
Microscopic (histologic) images

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





Images hosted on other servers:

High magnification

Low magnification

Variety of architectural patterns

Cribriform areas resembling adenoid cystic carcinoma

Areas of tumor necrosis

Tubular and glandular structures

Extensive myxoid stroma and sieve-like areas

Perineural invasion

Solid nests of tumor cells

Solid nests of tumor cells in desmoplastic stroma

Vascular invasion

Reticular growth pattern

Microcystic pattern

Solid pattern

Adenoid cystic pattern

Collections of neutrophils

Sickled RBCs

Case reports:

15 year old black girl with sickle cell trait - fig. 1: CT shows upper pole mass; fig. 2: FNA shows cohesive three dimensional tumor cell balls with prominent nucleoli; fig. 3: cell block shows cells with eosinophilic cytoplasm, macronucleoli, brisk mitotic activity; fig. 4: lymph node biopsy shows solid pattern of large anaplastic cells

20 year old pregnant black woman with sickle cell trait - fig. 1: tumor extends into hilus and renal vein; fig. 2: sheets of intermediate to large cells with ill defined borders, moderate cytoplasm, vesicular nuclei, prominent nucleoli; also extensive necrosis, inflammation, mitotic figures; fig. 3: adjacent stroma shows spindle cells with vesicular nuclei, desmoplastic stroma, inflammation

21 year old black man with sickle cell disease

40 year old black man with HbSC

Cytology description
  • Cohesive groups of cells with vacuolated cytoplasm that often displace or indent the nuclei; nuclei often have irregular membranes, coarse or vesicular chromatin and prominent nucleoli (Cancer 2005;105:28)
Cytology images

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33 year old black man with sickle cell trait:
Fig. 1: touch imprints show clusters of large malignant cells with well defined borders, hyperchromatic nuclei, irregular nuclear borders and prominent nucleoli
Fig. 2: biopsy shows sheets and cords of large epithelioid cells, with abundant eosinophilic cytoplasm, enlarged hyperchromatic nuclei and prominent nucleoli
Fig. 3: EM shows large tumor cells with streaming bundles of cytokeratin, varying rough endoplasmic reticulum, mitochondria and lysosomes and irregular nuclei

Various images

Positive stains
Molecular / cytogenetics description
Differential diagnosis
Board review style question #1
Renal medullary carcinoma (RMC) has all of the following characteristics, EXCEPT:

  1. Strongly positive for vascular endothelial growth factor and hypoxia inducible factor
  2. Majority of RMCs are located in the right kidney
  3. Majority show mutations in SMARCB1 / INI1 leading to loss of INI1 expression by immunohistochemistry
  4. Minority of RMCs show TFE3 (on Xp11) translocation with ASPL (17q25), which is a good prognostic indicator
Board review style answer #1
D. All are true except D (minority of RMCs show TFE3 (on Xp11) translocation with ASPL (17q25) and is a good prognostic indicator). The described translocation in part D is associated with MiT family translocation renal cell carcinoma. TFE3 (on Xp11) has been reported with multiple gene partners including ASPL (17q25), PRCC (1q21), NONO (Xq12), PSF / SFPQ (1p34), CLTC (17q23). This neoplasm is also associated with a balanced translocation in TFEB with MALAT1 t(6;11)(p21;q12). Translocation associated carcinomas usually have an aggressive clinical course but t(6;11)(p21;q12) appears to have lower malignant potential in contrast to other translocation carcinomas (MiT family translocation renal cell carcinomas).

RMCs are strongly positive for vascular endothelial growth factor and hypoxia inducible factor stemming from the hypothesized mechanism of arising from the renal papillae or calycleal epithelium, which is triggered by hypoxia caused by sickled red blood cells (A). The majority of RMCs (75 - 89%) occur in the right kidney and are located in the renal medulla (B). The majority of RMCs show SMARCB1 / INI1 leading to loss of INI1 protein expression (C). Loss of INI1 can be found in other neoplasms (MiT family translocation renal cell carcinomas).

Reference: Kidney tumor - Medullary carcinoma

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