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. 2023 Oct 16;32(4):821–824. doi: 10.1177/10668969231195071

Clear Cell Renal Cell Carcinoma with Prominent Micropapillary Pattern: A Case Report of a Previously Undescribed Morphology

Ibrahim Fahoum 1,✉, Dov Hershkovitz 1,2, Ariel Erental 1, Pedram Argani 3,4
PMCID: PMC11089822  PMID: 37844624

Abstract

The classic morphology of clear cell renal cell carcinoma consists of nests of cells with clear cytoplasm. Nevertheless, other histologic patterns may be seen including cells with eosinophilic cytoplasm, bizarre multinucleated giant tumor cells and pseudopapillary structures. In this article, we present the first case of clear cell renal cell carcinoma with a prominent micropapillary pattern.

Keywords: clear cell renal cell carcinoma, micropapillary

Introduction

Clear cell renal cell carcinoma (RCC) is the most common type of renal cancer, accounting for 60%–75% of adult renal tumors. 1 The classic histologic features of clear cell RCC are nests of cells with optically clear cytoplasm, surrounded by intricate branching fibrovascular network. Occasionally, clear cell RCC can have different morphologic patterns, some of which can be deceptive and diagnostically challenging. Areas with eosinophilic cytoplasm may be seen and are usually associated with high nucleolar grade. Some tumors may mimic papillary architecture, often related to tumor cell dropout and pseudopapillary architecture. High-grade tumors may contain bizarre syncytial-type multinucleated giant tumor cells. 2 With thorough sampling, classic clear cell areas are usually evident, confirming the diagnosis. In this article, we report a sarcomatoid clear cell renal cell carcinoma with a prominent unusual micropapillary pattern.

Case Report

A 69-year-old man with a history of hypertension and hyperlipidemia, underwent ultrasonography scan due to right flank pain, which revealed a mass in the right kidney. Computed tomography scan showed a 12 × 11 × 9.5 cm mass that involved mid-kidney to upper pole, without involvement of the renal vein. In addition, there were several enlarged lymph nodes in the renal hilum area and the inter-aortocaval space, measuring up to 4 cm. The patient underwent open radical nephrectomy with retroperitoneal lymph node dissection. Macroscopically, there was a white-yellow large renal mass with areas of necrosis and hemorrhage that invaded the renal sinus fat. Microscopic examination revealed areas with different morphologic patterns. The tumor had a prominent component that consisted of eosinophilic cells with large nuclei and prominent nucleoli (high nucleolar grade) arranged in micropapillary clusters of tumor cells surrounded by retraction spaces with surrounding desmoplastic reaction. Multiple clusters of tumor cells were present within the retraction spaces. This micropapillary morphology constituted 70% of the tumor. Other areas demonstrated the classic solid nested morphology of clear cell RCC. Importantly these two areas gradually merged with each other both within the primary tumor and lymph node metastases (Figure 1). In addition, there was a minor component of atypical spindle cells, consistent with sarcomatoid features (WHO/ISUP grade 4). Tumor necrosis was seen in 20% of the mass. The tumor invaded the renal sinus fat and showed extensive lymphovascular invasion that included lymphatics in the renal parenchyma, the renal sinus, the soft tissue around renal vein margin and even in the ureter wall. Immunohistochemical stains showed that the micropapillary component was focally positive for PAX8 and CD10, and diffusely positive for CA9, PanKRT, and vimentin. Stains for KRT7, keratin 34BE12, GATA3, p63, TTF1, CDX2, P504S, KIT, HMB45, MelanA, TFE3, and ALK were all negative. Examination of the retroperitoneal lymph node dissection revealed 15 lymph nodes, all of which were involved by metastatic carcinoma with prominent micropapillary component. The classic clear cell areas that merged with the prominent micropapillary component, along with the immunophenotype of the tumor were consistent with the diagnosis of clear cell RCC with prominent micropapillary features and focal sarcomatoid change. Molecular analysis was performed using the Oncomine Comprehensive Assay (OCA), a targeted next generation sequencing assay that simultaneously detects mutations and fusions of above 500 genes associated with cancer from formalin-fixed paraffin-embedded tissues. A missense mutation in VHL gene c.239G > A was identified, further supporting the diagnosis of clear cell renal cell carcinoma. Additional molecular alterations found include mutations in RPA1 and PARP4 genes.

Figure 1.

Figure 1.

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The renal neoplasm contains a solid nested area (right) and a micropapillary area associated with lymphoid tissue (left) (A). The micropapillary patterned-tumor permeates the renal parenchyma between native renal tubules (B). The solid area demonstrates the typical morphology of clear cell renal cell carcinoma (C) and demonstrates strong membranous labeling for CA9 (D). The micropapillary foci extensively involves renal sinus lymphatics (E) and similarly demonstrates membranous labeling for CA9 (F). In many areas of the neoplasm and including lymph node metastases, the solid areas merge gradually with the slightly higher-grade micropapillary areas (G, H).

Discussion

In this article, we present a clear cell renal cell carcinoma with a prominent micropapillary component. The morphologic spectrum of clear cell RCC includes the classic nests of cells with clear cytoplasm surrounded by fibrovascular septations, in addition to other features described such as cells with granular eosinophilic cytoplasm, regressive and cystic changes. 3 These features are not uncommon in clear cell RCC. However, to our knowledge, this is the first reported case of micropapillary architecture seen in clear cell renal cell carcinoma. Micropapillary carcinoma is a well-known pattern of carcinoma in several organs, including breast, lung, urinary bladder, and colon.4–7 It is characterized by small nests and papillary structures lacking fibrovascular cores with surrounding retraction spaces. This histologic subtype is associated with high -stage at presentation mainly due to lymphatic spread and lymph node metastasis and thus aggressive clinical behavior and poor prognosis.8–13 Since micropapillary pattern has not been reported in renal cell carcinomas, metastatic carcinoma to the kidney needed to be excluded from this tumor, and immunohistochemical stains were performed to rule this out. Stains for breast (GATA3), urinary bladder (GATA3, KRT7, p63, keratin 34BE12), lung (TTF1, napsin) and colon (CDX2, KRT20) performed and were all negative. The positivity for PAX8 and PanKRT supported primary renal cell origin. Urothelial carcinoma of the pelvicalyceal system may present as a renal mass and may show micropapillary morphology.14,15 It may also label for PAX8, causing confusion with renal cell carcinoma. However, negative immunohistochemical stains for urothelial markers, as well as the nested clear cell areas, ruled it out. Micropapillary architecture has also been described in papillary renal cell carcinoma.16,17The morphologic patterns of the tumor included eosinophilic cells arranged in micropapillary structures and surrounded by desmoplastic stroma, in addition to areas with nests of clear cells and a small component with sarcomatoid features. The morphology and immunohistochemical stains of the tumor were not compatible with papillary renal cell carcinoma. The papillary structures had no fibrovascular cores, and no foamy macrophages were present. Immunohistochemical stains for KRT7 and P504S were negative. Additional stains were performed to rule out rare subtypes of renal cell carcinoma. TFE3, Melan A and HMB45 were negative, arguing against TFE3 rearranged renal cell carcinoma. 18 The ALK immunohistochemical stain was negative which helped to rule out ALK rearranged renal cell carcinoma, an extremely rare subtype of renal cell carcinoma that may show infiltrative growth with multiple architectures, including tubulopapillary structures, embedded in a desmoplastic stroma.19–21

In summary, we present the first reported case of clear cell RCC with prominent micropapillary morphology. The areas with classic clear cell RCC morphology along with the diffuse staining for CA9 and vimentin support the diagnosis of a primary clear cell RCC. The clinical behavior of the tumor presented in this article is aggressive with extensive lymph node involvement, a finding frequently found in micropapillary carcinoma of other organs. Investigation of additional tumors with similar morphology is needed to assess the prognostic value of this peculiar pattern in clear cell renal cell carcinoma.

Acknowledgements

We would like to thank Dr. Jonathan Epstein for his contribution to this article.

Footnotes

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval: Anonymized case reports in the hospital are exempted from approval.

Trial Registration: Not applicable, because this article does not contain any clinical trials.

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