Kidney tumor

Adult renal cell carcinoma - rare

Collecting duct carcinoma



Last author update: 17 October 2022
Last staff update: 17 October 2022

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PubMed Search: Collecting duct 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. Collecting duct carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantcollectingduct.html. Accessed January 28th, 2023.
Definition / general
  • Rare (< 1% of kidney cancers) aggressive carcinoma of renal medulla arising from the principal cells of the distal collecting ducts of Bellini
  • Morphology: irregular, infiltrating tubules with high grade cells often containing mucin; marked stromal desmoplasia and inflammatory infiltrate
  • Essentially a diagnosis of exclusion (Am J Surg Pathol 2020;44:e47)
Essential features
  • Major diagnostic criteria
    • Medullary involvement
    • Predominantly tubular architecture
    • Marked desmoplasia
    • Cytologically high grade cuboidal or hobnail cells
    • Infiltrative growth pattern
  • Minor diagnostic criteria
    • Central location (large tumors)
    • Tubulopapillary architecture
    • Inflammatory stroma with neutrophils
    • Extensive renal, extrarenal and vascular infiltration
    • Mucin positive
  • Required diagnostic criteria
Terminology
  • Collecting duct carcinoma (preferred)
  • Bellini duct carcinoma or carcinoma of the collecting ducts of Bellini (historic name, discouraged)
ICD coding
  • ICD-10: C64 - malignant neoplasm of kidney, except renal pelvis
Epidemiology
Sites
  • Arising centrally from renal medulla but often involving both the cortex and medulla because of large size
Diagrams / tables

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Morphological patterns

Clinical features
  • Approximately 67% of patients present with pain, gross hematuria, weight loss, fatigue and flank mass
  • Has the poorest prognosis of common renal cell carcinoma subtypes
  • Often limited responses to immunotherapy and chemotherapy (J Urol 2007;177:1698)
Diagnosis
  • Diagnosis is made primarily on H&E with a focus on the major, minor and required criteria; there should be adequate sampling, including of the adjacent renal pelvis
  • Presence of any component of the tumor showing classic appearances of clear cell renal cell carcinoma, papillary renal cell carcinoma or mucinous tubular and spindle cell carcinoma likely supports a diagnosis of the corresponding entity with high grade features / transformation
  • Clinical history, prior cytology or pathology, and radiologic correlation may sometimes be helpful in considering a metastasis or urothelial carcinoma in the differential
  • Panel of immunostains such as PAX8, 34 beta E12, GATA3, SMARCB1, OCT 3/4 and fumarate hydratase may be useful in the diagnosis
Radiology description
  • CT imaging shows good correlation with histopathologic findings
  • Mass in the renal medulla and involving renal sinus; 50% with a cystic component
  • Lymphadenopathy and metastases noted in 56% and 33% of cases, respectively
  • Perinephric stranding and vascular invasion present in 56% and 28% cases, respectively
  • Infiltrative growth (67%) and preservation of the renal contour (61%) more common than expansile growth (33%) and exophytic configuration (39%) (Eur J Radiol 2006;57:453)
  • Features distinguishing cystic renal cell carcinoma from collecting duct carcinoma (Cancer Imaging 2021;21:52)
Radiology images

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MRI, T2 and T1 weighted

Prognostic factors
  • Median survival: 7.6 - 11 months with 67% of patients dying within the first 2 years (Can Urol Assoc J 2015;9:E589, Curr Oncol 2013;20:e223, J Urol 2009;182:2595)
  • Distant metastases in most patients either at presentation or after nephrectomy; metastases are usually to lymph nodes, liver, lungs, bones, adrenal gland or contralateral kidney (J Clin Oncol 2002;20:2376)
    • Approximately 40% present with metastasis (WHO 5th edition)
  • One study showed that absence of lymph node metastasis, distant metastasis, sarcomatoid differentiation; earlier stage could be used to predict a better survival
    • Multivariable analysis showed that sarcomatoid differentiation and absence of renal surgery were predictors of mortality (Urology 2022;164:163)
  • One study associated neutrophil to lymphocyte ratio ≥ 4 (median) with worse cancer specific survival in collecting duct carcinoma (Jpn J Clin Oncol 2018;48:692)
Case reports
Treatment
Gross description
  • Infiltrative, firm gray or white mass
  • Centered in the medulla but often involving both cortex and medulla
  • Tumor size range from 2.5 - 12 cm (mean 5 cm)
  • Hemorrhage, necrosis and cystic changes are common
  • May have satellite nodules and renal vein invasion
  • Often infiltrates perirenal and renal sinus fat
Gross images

Contributed by Daniel Anderson, M.D., M.B.A. and Debra L. Zynger, M.D.

Involving kidney and pelvis

Partially necrotic

Large tumor



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Infiltrative gray white tumor

Infiltrative gray-white tumor

Tumor invades renal capsule and infiltrates adipose tissue

Microscopic (histologic) description
  • Complex, infiltrative, poorly circumscribed, sometimes multinodular tumor
  • Mainly interstitial growth patterns with preserved glomeruli
  • Composed of cords, tubules or tubulopapillary structures with infiltrating glands embedded into inflamed desmoplastic stroma
    • Solid, sheet-like growth, nested, cord-like, papillary, micropapillary growth or individual cells may be present
  • Sieve-like / cribriform, intracystic papillary and reticular / yolk sac tumor-like patterns were identified as minor components
    • Intracystic pattern demonstrated delicate fibrovascular cores and hyalinization present in 33% of cases in one study (Am J Surg Pathol 2018;42:279)
  • Tubulocystic growth was not seen in any case in one study (Am J Surg Pathol 2018;42:279)
  • Irregular channels are lined by high grade cuboidal to hobnail cells, usually with eosinophilic cytoplasm
  • Nuclei are large, pleomorphic with prominent nucleoli and coarse chromatin
  • Numerous mitotic figures; apoptotic cells and necrosis is common
  • Intracytoplasmic and intraluminal mucin may be present
  • May have microcystic changes from dilation of the tubular structures
  • May have sarcomatoid differentiation
  • Adjacent to the tumor, tubular epithelium lining collecting ducts may appear dysplastic
  • Lymphovascular invasion and regional lymph node involvement are common
  • Often prominent inflammatory reaction, including neutrophils, within and around the tumor
  • Reference: Am J Surg Pathol 2018;42:279
Microscopic (histologic) images

Contributed by Daniel Anderson, M.D., M.B.A. and Garrison F. Pease, M.D.

Adjacent renal parenchyma

Architecture

Infiltrative border

Prominent nucleoli

Tumor and nonneoplastic kidney

Tumor and nonneoplastic


Cords, tubules, inflammation

Tumor tubules and cords

Cords, tubules, inflammation

Cellular details

Eosinophilic cytoplasm, large nuclei

Cellular and nuclear details

Tumor and nonneoplastic kidney

Border tumor and nonneoplastic

Tumor and nonneoplastic kidney

Possible dysplastic tubule epithelium

Virtual slides

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Infiltrative cords and tubules

Involving renal sinus fat

Cytology description
  • Aspirate may contain cohesive nests of tumor cells with glandular features or individual cells
  • Eosinophilic, vacuolated cells with intracytoplasmic mucin; nuclei are large irregular hyperchromatic with vesicular chromatin and large nucleoli
  • Ductal / tubular differentiation with benign, dysplastic and malignant features, prominent desmoplastic stroma, neutrophils (Acta Cytol 2004;48:843)
  • Sarcomatoid features may be seen (Diagn Cytopathol 2010;38:603)
  • Cases of collecting duct carcinoma cells in urine cytology have been reported (Diagn Cytopathol 1997;16:446)
Positive stains
Negative stains
Electron microscopy description
  • Features of adenocarcinoma, including intracellular and extracellular lumina
  • Well formed cell junctions, prominent basal lamina and short apical microvilli
Molecular / cytogenetics description
  • A defining set of molecular alterations is not currently recognized
  • Not associated with loss of 3p
  • Not associated with trisomies 7 and 17
  • Complex chromosomal aberrations, especially copy number losses or loss of heterozygosity involving multiple chromosomes, such as 1p, 6, 8, 9, 14 and 22 (WHO 5th edition)
  • HER2 / neu amplifications have been reported in 45% of cases (J Urol 1997;158:245)
  • Genomic alterations in NF2 (29%), SETD2 (24%), SMARCB1 (18%) and CDKN2A (12%) (Eur Urol 2016;70:516)
  • Whole exome sequencing and transcriptome sequencing (RNASeq) showed recurrent somatic single nucleotide variants (SNV) in MLL in 2 samples; somatically mutated SNVs identified in ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53 and ZNF521
  • Single nucleotide polymorphism (SNP) array identified a CDKN2A homozygous deletion and SNV analysis showed a nonsense mutation of the CDKN2A gene with unknown somatic status
  • Dysregulation in solute carrier family genes, including overexpression in SLC7A11 (cystine transporter, xCT), a cisplatin resistance associated gene (Oncotarget 2016;7:29901)
    • Other gene expression study showed downregulation in 4 solute carrier genes: SLC3A1, SLC9A3, SLC26A7 and SLC47A1; also upregulated keratin 17 and downregulation MARC2, cubulin (Cancers (Basel) 2019;12:64)
  • RNA sequencing study found shift towards aerobic glycolysis and overexpression of immune genes (Sci Rep 2016;6:30988, Cancers (Basel) 2021;13:2903)
  • Molecularly heterogeneous tumor with at least 2 subtypes distinguished by cell signaling and metabolic and immune related alterations (Cancers (Basel) 2021;13:2903, Cancers (Basel) 2021;13:3807)
  • Whole genome sequencing study of a Chinese population showed 8 recurrently somatically mutated genes: BM14, MTUS1, GAK, DST, ASPM, CDC27, RNF213 and XIRP2
    • TP53 / RB1 and CDKN2A alterations documented
    • Copy number variant mutation spectrum appeared unique from urothelial carcinoma and other renal cell carcinoma subtypes
    • CDKN2A altered patients displayed a worse overall survival (OS) (BMC Med Genomics 2022;15:1)
Videos

Collecting duct carcinoma

Sample pathology report
  • Kidney, nephrectomy:
    • Collecting duct carcinoma (X cm); tumor invades perirenal fat and renal sinus fat; margins are negative (see synoptic report and comment)
    • Comment: Immunohistochemistry is performed. The carcinoma cells are positive for PAX8, 34 beta E12, fumarate hydratase (retained), SMARCB1 / INI1 (retained) and negative for GATA3 and OCT 3/4.
Differential diagnosis
Board review style question #1
BRQ image BRQ image


A 76 year old man with history of noninvasive low grade papillary urothelial carcinoma undergoes a nephrectomy for a 5 cm centrally located urothelial mass involving the renal pelvis, medulla and cortex. Photomicrographs are shown of the invasive component and results of renal pelvis sampling. Which of the following is true regarding this neoplasm?

  1. Has a multilocular, sponge-like cut surfaces on gross examination
  2. May show aneuploidy in chromosome 3, 7 or 17 or loss of 9p21 locus
  3. Will often demonstrate loss of fumarate hydratase by immunohistochemistry
  4. Will often show positive immunohistochemical expression for PAX8 and negative for p63 and GATA3
Board review style answer #1
B. May show aneuploidy in chromosome 3, 7 or 17 or loss of 9p21 locus. The findings support the diagnosis of invasive urothelial carcinoma with glandular differentiation. The clinical history and demonstration of a noninvasive high grade papillary component in the renal pelvis supports the diagnosis. Urothelial carcinoma often demonstrates aneuploidy in chromosomes 3, 7 or 17 or loss of 9p21 locus, which is the basis for the UroVysion FISH assay. The criteria for positivity on UroVysion is ≥ 4 of 25 morphologically abnormal cells showing a gain of ≥ 2 chromosomes in the same cell or ≥ 12 of the 25 cells having a loss of 9p21. Urothelial carcinomas will be positive for p63, GATA3 and negative for PAX8 (as opposed to renal cell carcinomas). They will demonstrate retained fumarate hydratase (as opposed to fumarate hydratase deficient RCC). A multilocular sponge-like cut surface on gross evaluation is characteristic of tubulocystic renal cell carcinoma.

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Reference: Collecting duct carcinoma
Board review style question #2

A 59 year old man is diagnosed with collecting duct carcinoma. Which of the following is true regarding this entity?

  1. Has no morphologic overlap with fumarate hydratase deficient
  2. Has prominent stromal desmoplasia, infiltrative growth and inflammatory cell reaction
  3. Is correlated with sickle cell trait
  4. Will show papillary growth with foamy macrophages in papillae
Board review style answer #2
B. Has prominent stromal desmoplasia, infiltrative growth and inflammatory cell reaction. Collecting duct carcinoma (CDC) often presents with advanced disease over a wide age range and with male predominance. The carcinoma arises from the principal cells of the distal collecting ducts of Bellini and often shows a multinodular, infiltrative growth pattern of cords, tubules, tubulopapillary, nested, solid or sheet-like growth with high grade nuclei and associated inflammatory reaction. The presence of papillary growth in CDC can raise the differential of papillary renal cell carcinoma; however, the latter will show typical papillary morphology, including foamy macrophages within papillae. CDC has morphologic overlap with fumarate hydratase deficient renal cell carcinoma. In one study, 25% of cases of CDC were reclassified to fumarate hydratase deficient renal cell carcinoma using fumarate hydratase and 2SC IHC stains. CDC is morphologically similar to medullary carcinoma. Renal medullary carcinoma usually presents in younger patients with sickle cell trait or hemoglobin SC disease; few have sickle cell disease. Renal medullary carcinoma usually demonstrates loss of SMARCB1 (also known as INI1, SNF5 or BAF47).

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Reference: Collecting duct carcinoma
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