pT1 bladder carcinoma

pT1 carcinoma is defined by invasion into lamina propria, but not into muscularis propria.

Recognition of lamina propria invasion is challenging. Pathologists should be aware of various diagnostic pitfalls, including tangential section, poor specimen orientation, obscuring inflammation, thermal injury, deceptively bland cytology in some variants of urothelial carcinoma and pseudoinvasive nests of benign proliferative urothelial cells.

pT1 carcinomas often invade the underlying stroma as single cells or irregularly shaped nests of tumor cells.

Sometimes tentacular or finger-like extensions arise from the base of the papillary tumor.

Retraction artifact provides an important clue for the diagnosis of early invasion.

The invading nests appear cytologically different from cells at the base of the noninvasive component.

Invasive tumor cells often have more abundant cytoplasm and less nuclear pleomorphism than in situ carcinoma.

In some cases, particularly in microinvasive carcinoma, the invasive tumor cells acquire abundant eosinophilic cytoplasm.

At low to medium power magnification, these microinvasive cancer cells appear to be more differentiated than the overlying noninvasive tumor cells, a feature known as paradoxical differentiation.

Pittfalls

 Tumor cells involving von Brunn’s nests, either by pagetoid spread or by direct extension from adjacent tumor, can be confused with lamina propria invasion. This is especially problematic when von Brunn’s nests are prominent, or when they have been distorted by inflammation or cautery artifact. When urothelial carcinoma involves von Brunn’s nests, the basement membrane preserves a regular contour. If this smooth delineation is absent, there may be true lamina propria invasion. A parallel array of thin-walled vessels often line the basement membrane of noninvasive nests; whereas these vessels are usually absent next to invasive nests.

 Thermal injury or cautery artefact can produce severely distorted morphology, rendering accurate diagnosis of invasion difficult. Immunohistochemistry with pan-cytokeratin may be helpful in these cases by highlighting invasive tumor cells.

 Papillary urothelial carcinoma may be tangentially sectioned in multiple planes, resulting in isolated nests of noninvasive tumor cells surrounded by connective tissue. Smooth, round, and regular contours favor tangential sectioning, whereas irregular, jagged nests containing haphazardly arranged cells favor stromal invasion.

 stromal growth patterns

• Assessment of different stromal growth patterns may provide important diagnostic clues to minimally invasive carcinoma.
• A stromal response to invading carcinoma, however, is not uniformly present with urothelial carcinoma. Thus, the diagnosis of invasion may rely predominantly on characteristics of the invading epithelium.
• When present, the stromal reaction of lamina propria to invasive tumor may be myxoid, fibrous, pseudosarcomatous, desmoplastic or inflammatory.
• Urothelial carcinoma may show brisk inflammation at the epithelial–stromal interface. This cellularity and distortion obscure isolated cells or small nests of invasive tumor. Immmunostaining with anti-cytokeratin antibodies can facilitate the diagnosis of invasion in cases with prominent inflammation obscuring the interface between epithelium and stroma.
• Microinvasive carcinoma may have only subtle signs of stromal response. In some cases, retraction artifact around superficially invasive individual tumor cells may mimic vascular invasion. This finding is often focal and may itself be an early sign of lamina propria invasion. Retraction artifact may be distinguished from true vascular invasion using CD31 and CD34 immunohistochemistry.
• Identification of vascular invasion has recently been considered an important prognostic feature.

Link

 http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol20091a.html