Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Pathophysiology | Clinical features | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Anderson D, Tretiakova M. Tubulocystic. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignanttubulocystic.html. Accessed April 10th, 2021.
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
- M:F = 7:1 (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
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
Positive stains
Electron microscopy description
- Short microvilli with brush border organization
- Ultrastuctural features resembling both cells of the proximal tubules and collecting ducts
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 style 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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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
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 style 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
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Reference: Kidney tumor - Tubulocystic renal cell carcinoma
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