J Pathol Transl Med.  2021 Mar;55(2):94-101. 10.4132/jptm.2020.10.19.

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution’s 20-year experience

• Yoo Y
• Lee J
• Park HS
• Cho MS
• Sung SH
• Park S
• Choi E

• KMID: 2513894
• DOI: http://doi.org/10.4132/jptm.2020.10.19

Abstract

Background
Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology.
Methods
We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding.
Results
Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis.
Conclusions
Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Keyword

Bladder neoplasms; Distant metastasis; Urothelial carcinoma; Histologic variant; Tumor budding

Figure

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  Fig. 1 Representative morphology of tumor budding at the invasive front. (A, B) Hematoxylin and eosin staining shows single or small clusters of tumor cells with up to 5 cells per cluster (arrows) detached from the main tumor mass.

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  Fig. 2 Histologic features of three histologic variants that are concurrently displayed in both primary and metastatic lesions. (A) In case 1, the primary bladder tumor focally shows a micropapillary carcinoma component characterized by small tight nests or balls with reverse polarity within lacunae. (B) A subsequent pulmonary metastatic lesion is entirely comprised of a micropapillary carcinoma component. (C) The primary bladder tumor in case 4 shows marked squamous differentiation. (D) Squamous differentiation seen in the primary tumor of case 4 is preserved in the subsequent colonic metastatic lesion. (E) In the primary bladder tumor of case 6, the tumor cells are entirely composed of highly atypical discohesive plasmacytoid cells arranged in a solid sheet-like arhitecture. These histologic findings are compatible with plasmacytoid urothelial carcinoma. (F) Plasmacytoid morphology was maintained in the metastatic tumor cells in the axillary lymph node.

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  Fig. 3 Histologic and immunohistochemical findings of case 3. (A) In the primary tumor, polygonal tumor cells are arranged in large nests and have highly pleomorphic nuclei and abundant clear to eosinophilic cytoplasm. (B) On immunohistochemistry, most tumor cells show strong positivity for α-fetoprotein (AFP), implicating tumor-derived AFP production. (C) Representative histologic features of hepatic metastatic lesion.

Reference

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