Kidney tumor - adult malignancies
Adult renal cell carcinoma
Medullary carcinoma

Author: Daniel Anderson, M.D., MBA (see Authors page)
Editor: Maria Tretiakova, M.D., Ph.D.

Revised: 2 October 2017, last major update September 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Medullary carcinoma [title] kidney

Cite this page: Anderson, D. Medullary carcinoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/kidneytumormalignantmedullarycar.html. Accessed November 23rd, 2017.
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-10 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
Epidemiology
Pathophysiology
  • 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
Treatment
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

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Images contributed by Daniel Anderson, M.D., MBA



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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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Images contributed by Daniel Anderson, M.D., MBA

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Infiltrative carcinoma in cribriform pattern

Infiltrative carcinoma with high grade nuclei

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

Tubular pattern with prominent desmoplasia

Microcystic pattern

Solid pattern


Adenoid cystic pattern

Collections of neutrophils

Sickled RBCs

Rhabdoid versus medullary tumor: H&E and INI1



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
Molecular:
Cytogenetics:
Differential diagnosis
Board review 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 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).