Tubulocystic renal cell carcinoma

Kidney tumor
Adult renal cell carcinoma
Tubulocystic renal cell carcinoma

Authors: Daniel Anderson, M.D., M.B.A., Maria Tretiakova, M.D., Ph.D.

Deputy Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 1 May 2018

Minor changes: 10 March 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: Tubulocystic carcinoma kidney

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Table of Contents

Cite this page: Anderson D, Tretiakova M. Tubulocystic renal cell carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignanttubulocystic.html. Accessed May 24th, 2020.

Definition / general

Renal epithelial neoplasm composed predominately of tubules and cysts lined by a single layer of cells with prominent nucleoli (ISUP grade 3) and abundant eosinophilic cytoplasm (Eur Urol 2016;70:93)
Relatively indolent with < 10% cases showing disease progression, local recurrence or metastasis to bone, liver and lymph nodes (Eur Urol 2016;70:93)
Recognized by the 2016 WHO classification

Essential features

Well circumscribed tumor with spongy bubble wrap appearance
Strong male predominance
Pure cystic and tubular architecture; no solid areas
Single layer of flat, cuboidal or hobnailed eosinophilic cells along fibrotic septa

Terminology

Originally named Bellinien epithelioma or collecting duct carcinoma by Pierre Masson in the 1950s (Am J Surg Pathol 2016;40:1457)
Low grade collecting duct carcinoma (McLennan) (Urology 1997;50:679)
Termed tubulocystic renal cell carcinoma and considered a distinct entity since 2009 (Am J Surg Pathol 2008;32:177)

ICD coding

ICD-10: C64 - malignant neoplasm of kidney, except renal pelvis

Epidemiology

Rare (< 100 cases)
Mean age 54 years
7:1 male:female predominance (Am J Surg Pathol 2009;33:384)

Pathophysiology

Histogenesis remains unclear; cells have some features of proximal nephron differentiation and others relate to distal nephron (Can Urol Assoc J 2015;9:E654)

Clinical features

Often an incidental finding with ~90% low stage
Less commonly presents with abdominal pain, distention, hematuria, weight loss
Prognosis is typically excellent with rare recurrences, distant metastases or death from disease

Case reports

22 year old woman with bone metastasis (J Korean Soc Radiol 2011;65:285)
34 year old man with a 1.4 cm mass (Case of the Month #484)
43 year old man with multiple focal clear cell characteristics (J Carcinog Mutagen 2015;6:213)
45 year old man initially misdiagnosed with a Bosniak type II renal cyst (Rev Urol. 2016;18:118)
47 year old man and 66 year old man with poorly differentiated foci (Int J Clin Exp Pathol 2015;8:11124)
62 year old man with bilateral tumors in diabetic end stage renal disease (Rare Tumors 2013;5:e57)
65 year old man with a large cystic tumor (Can Urol Assoc J 2015;9:E654)

Treatment

Radical or partial nephrectomy depending on tumor size and location in the kidney
No established targeted therapy in metastases but a few case reports suggest a partial response to sunitinib (a tyrosine kinase inhibitor) and everolimus (a mammalian target of rapamycin [mTOR] inhibitor) (Rev Urol 2016;18:118)

Gross description

Well circumscribed but not encapsulated
Cut surface that is grey white with multilocular cystic spaces resembling a sponge, Swiss cheese or bubble wrap appearance
Mean size 4 cm (range 0.2 - 17 cm)
No hemorrhage or necrosis

Gross images

Contributed by Debra Zynger, M.D.

Creamy, soft mass

Contributed by Daniel Anderson, M.D.

Partial nephrectomy with tubulocytic RCC

Images hosted on other servers:

Brown, fleshy tumour with numerous cysts

Tubulocystic renal cell carcinoma

Microscopic (histologic) description

Mixture of closely packed tubules and variably sized cysts with overall low grade morphology (Urology 1997;50:679)
Cysts are separated by fibrous septa; no desmoplasia or cellular stroma
Tubules and cysts are lined by a single layer of flattened, cuboidal or columnar cells; hobnailing may be present with modest to abundant amounts of eosinophilic cytoplasm resembling oncocytoma cells
Uniform round nuclei with distinct nucleoli (ISUP grade 3)
Association with papillary cell neoplasms is not uncommon
Minimal mitotic activity and atypia, very rare necrosis

Microscopic (histologic) images

Contributed by Maria Tretiakova, M.D., Ph.D.

Tubules and variably sized cysts lined by cuboidal epithelium

Hobnailing and distinct nucleoli

Contributed by Sabrina Sopha, M.D.

H&E stained sections showing cysts and tubules lined by cuboidal epithelium with scattered hobnailing

IHC images show cytoplasmic CD10, CK7 and EMA positivity

Contributed by Debra Zynger, M.D.

Numerous cysts

Hobnailed lining

Rigid cysts

Nucleoli

Small tubules

Fumarate hydratase

Positive stains

CK7, AMACR (racemase), vimentin, EMA, PAX8, fumarate hydratase, mucin, keratins (AE1 / AE3, Cam 5.2, [CK8 / 18], CK19, Am J Surg Pathol 2005;29:747)
Variable 34 beta E12, CD10

Negative stains

2 succino cysteine, CAIX and c-kit

Electron microscopy description

Short microvilli with brush border organization
Ultrastuctural features resembling both cells of the proximal tubules and collecting ducts

Electron microscopy images

Images hosted on other servers:

Type I and type II cells

Molecular / cytogenetics description

Distinct molecular signature from other carcinomas (J Mol Diagn 2018;20:34)
Frequent gain of chromosome 7 and 17, loss of Y, similar to papillary renal cell carcinoma Am J Surg Pathol 2009;33:1840, Am J Surg Pathol 2008;32:177)
Targeted next generation sequencing identified mutations in 14 different genes, most frequently (60% of tubulocystic carcinoma cases) in ABL1 and PDFGRA genes (J Mol Diagn 2018;20:34)

Differential diagnosis

Adult cystic nephroma (mixed epithelial and stroma tumor) and pediatric cystic nephroma: in adults, predominance in women; biphasic tumors with epithelial and stromal components; multilocular cysts are lined by attenuated cells with inconspicuous nucleoli; nonepithelial component could be very prominent with hyalinization, fibrosis and ovarian type cellular stroma; overlapping expression profile
Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) syndrome associated renal cancer with tubulocystic carcinoma-like areas: high grade tumors with solid, papillary and glandular architecture; characteristic large cytomegalovirus-like nucleoli with perinuclear halos; FH gene mutations; fumarate hydratase negative and 2 succino cysteine positive (Am J Surg Pathol 2016;40:1457)
Multilocular cystic clear cell renal neoplasm of low malignant potential: cysts lined by clear cells with low grade nuclei (ISUP grade 1 - 2); CAIX positive
Mucinous tubular and spindle cell neoplasm: predominantly women, typically long tubular profiles or cordlike growth pattern of uniform, low cuboidal cells with eosinophilic, focally vacuolated cytoplasm and spindling; stroma is myxoid and bubbly with abundant extracellular mucin

Board review style question #1

The neoplasm shown in the picture is a recently recognized distinct entity of the kidney that has all the following features, except:

Few neoplasms progress and metastasize
It consists of a mixture of tubules and micro/macro cysts lined by hobnailed cells
Male predominance
Neoplasm contains stromal hypercellularity (including ovarian type stroma)
Sponge-like or bubble wrap gross appearance

Board review answer #1

D. Stromal hypercellularity and ovarian type stroma is a feature of adult cystic nephroma / mixed epithelial and stromal tumor.

Reference: Kidney tumor - Tubulocystic renal cell carcinoma

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Board review style question #2

What is the most accurate way to grossly describe tubulocystic carcinoma?

A. Large hemorrhagic tumor of renal medulla
B. Encapsulated multiloculated cystic and solid mass
C. Honeycomb-like yellow tumor
D. Well circumscribed mass with spongy or bubblewrap appearance

Board review answer #2

D. Tubulocystic carcinoma has a very peculiar gross morphology, often compared to bubble wrap, sponge and Swiss cheese.

Reference: Kidney tumor - Tubulocystic renal cell carcinoma

Comment here