Bladder - Nested variant

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Bladder

Urothelial carcinoma

Nested variant

Reviewer: Rugvedita Parakh, Cedars-Sinai Medical Center, Los Angeles, California

Revised: 6 June 2010, last major update June 2010

Definition

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● Rare tumor of irregular and confluent small nests and abortive tubules composed of urothelial cells infiltrating the lamina propria or muscularis propria, usually without surface involvement

● First described in 1989 (Am J Surg Pathol 1989;13:374)

Clinical features

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● Either rare or underreported; estimated incidence is less than 0.3% of invasive bladder tumors

● Aggressive behavior despite bland cytologic features (Mod Pathol 2003;16:1289)

● Similar clinical outcome if pure or mixed with usual urothelial carcinoma (Hum Pathol 2010;41:163)

● Often advanced stage at presentation

● Tumor often at ureteral orifices

Epidemiology

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● Usually men > 60 years, similar to classic urothelial carcinoma

Case reports

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● 71 year old man with recurrent tumor (Actas Urol Esp 2009;33:90)

● 2 cases with aggressive behavior (Pathol Oncol Res 2006;12:105)

Treatment

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● Radical surgical resection

Gross description (Macroscopy)

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● Often no clearly defined tumor

Micro description (Histopathology)

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● Irregular and confluent small nests and abortive tubules composed of urothelial cells infiltrating the lamina propria or muscularis propria, usually without surface involvement

● Tumor cells have only mild atypia (mild pleomorphism, slightly increased N/C ratios, occasional prominent nucleoli, rare mitotic figures) and resemble cystitis glandularis et cystica

● Deep tumor-stroma interface is jagged and infiltrative

● Often more atypia and focal anaplasia with increasing depth of invasion

● Typical urothelial carcinoma is often present (Mod Pathol 1996;9:989)

● Retraction artifact may be seen

● By definition, these tumors cannot be high grade or have overlying surface carcinoma in situ

Micro images

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Nests of bland urothelial cells in lamina propria

AFIP 2-30: The tumor usually presents as multiple, deceptively benign appearing nests in the lamina propria. In contrast to cystitis glandularis, the nests lack cellular organization around lumina, and appear to infiltrate rather than cluster. At high power, the cellular disorganization and atypia are prominent. AFIP images courtesy of Dr. Daniel M. Lundblad, Parkersburg, West Virginia

Fig 1: Lamina propria infiltrated by neoplastic proliferation of fairly homogeneous nests

Fig. 2: Tumor cells are small/medium and uniform, with a low N/C ratio and a low mitotic index; nuclei are slightly irregular with occasional prominent nucleoli

Fig. 3: Tumor cells infiltrate muscularis propria

Various images

Cytology description

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● Subtle features are not diagnostic by themselves; include medium sized round/polygonal cells with abundant, dense, slightly granular basophilic cytoplasm and well defined cell borders; irregular nuclear contours, increased N/C ratio, coarse chromatin, occasional prominent nucleoli (Cancer 2003;99:23)

Cytology images

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A: Single cells in a voided urine specimen

B/C: Clusters in cystoscopic urine specimens

Tumor cells are medium sized, round/polygonal with abundant cytoplasm, well defined cell borders, increased N/C ratio, irregular nuclear contour, coarse chromatin

Positive stains

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● CK7, CK20, p63, Ki-67, CK903 (Arch Pathol Lab Med 2003;127:e333)

● Variable p53

Negative stains

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● bcl2, EGFR, PSA

Differential Diagnosis

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● Adenocarcinoma: colonic differentiation; more prominent atypia

● Cystitis cystica / glandularis: no atypia, no invasion

● Nephrogenic metaplasia / adenoma: usually has papillary component, prominent tubular or cystic structures lined by single layer of cuboidal cells, no atypia, no invasion

● Inverted papilloma: no deep invasion

● Prostatic adenocarcinoma: centered in prostate, PSA+, PSAP+

● Urothelial carcinoma with small tubules: invasive carcinoma with small gland-like spaces lined by urothelial cells without intracellular mucin or columnar lining; some consider this part of nested variant (Hum Pathol 2004;35:769)

● von Brunn’s nests: no invasion, no prominent atypia; no focal anaplasia (Am J Surg Pathol 2003;27:1243)

Additional references

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● Mod Pathol 1992;5:240, Am J Surg Pathol 1996;20:1448, Arch Pathol Lab Med 2007;131:1725

End of Bladder > Urothelial carcinoma > Nested variant

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