Renal Cell Carcinoma Presenting as Carcinoma of Unknown Primary Site: Recognition of a Treatable Patient Subset

Greco, F. Anthony; Hainsworth, John D.

doi:10.1016/j.clgc.2018.03.001

Cited by 20 publications

(27 citation statements)

References 10 publications

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“…Nonclear cell histologies with a large proportion of unclassified RCCs seem predominant in CUP [15]. After initiating the CUPISCO trial, two publications suggested that approximately 4%–5% of CUPs show morphology and IHC consistent with mRCC in the absence of a kidney lesion [14, 15] The authors claim that patients with CUP‐mRCC should be considered for RCC‐specific therapy. Contrast‐enhanced CT/MRI is the imaging modality of choice in the diagnosis of RCC and has a median sensitivity of 88% [25].…”

Section: Discussionmentioning

confidence: 99%

A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience

et al. 2021

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Background. CUPISCO is an ongoing randomized phase II trial (NCT03498521) comparing molecularly-guided therapy versus platinum-based chemotherapy in patients newly diagnosed with 'unfavorable' cancer of unknown primary (CUP). Patients and Methods. Patients with an unfavorable CUP diagnosis, as defined by the European Society of Medical Oncology (ESMO), and available cancer tissue for molecular sequencing are generally eligible. Potential CUP patients entering screening undergo a review involving reference histopathology and clinical work-up by a central Eligibility Review team (ERT). Patients with "favorable" CUP, a strongly suspected primary site of origin, lack of tissue, or unmet inclusion criteria are excluded. Results. As of April 30, 2020, 628 patients had entered screening and 346 (55.1%) were screen failed. Screen fails were due to technical reasons (N=89), failure to meet inclusion/exclusion criteria not directly related to CUP diagnosis (N=89) and other reasons (N=33). 124 (35.8%) patients were excluded because unfavorable adeno-or poorly differentiated CUP could not be confirmed by the ERT. These cases were classified into 3 groups ineligible due to (i) histologic subtype, such as squamous and neuroendocrine, or favorable CUP; (ii) evidence of a possible primary tumor or (iii) non-carcinoma histology. Conclusions. Experience with CUPISCO has highlighted challenges with standardized screening in an international clinical trial and the difficulties in diagnosing unfavorable CUP. Re-confirmation of unfavorable CUP by an ERT in a clinical trial can result in many reasons for screen failures. By sharing this experience, we aim to foster understanding of diagnostic challenges and improve diagnostic pathology and clinical CUP algorithms. Implications for Practice:: A high unmet need exists for improved treatment of cancer of unknown primary (CUP); however, study in a trial setting is faced with the significant challenge of definitively distinguishing CUP from other cancer types. Here we report on our experience of this challenge so far in the ongoing CUPISCO trial, which compares treatments guided by patients' unique genetic signatures versus standard chemotherapy. The data presented will aid future decision-making regarding diagnosing true CUP cases; this will have far-reaching implications in the design, execution and interpretation of

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Section: Discussionmentioning

confidence: 99%

A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience

et al. 2021

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“…A recent retrospective study of 24 CUP patients with mRCC characteristics treated with TT showed a median OS of 12 months. 20 The disease of these patients was all identified by molecular analyses, in contrast Pax8, CK8/18, CD10, CK20 CK7, CaIX, CDX2, TTF1, inhibin, chromogranin A 2 Vimentin, CD10, CaIX, CK7 CK20, estrogen, WT1, GATA 3, MGA, S100, CK 45, CD68 3 Vimentin, P504S, Pax8, CK 8/18, CaIX, Ae1/Ae3, EP4 C5, CK7, CK19, calretinin, WT1, D240, TTF1, thyroglobulin, OCT 3/4, gammaglobulin, CCDp, HER2, estrogen 4 Vimentin, CD10, Pax8, CK8/18, CaIX, Ck7, CD 669 CK20, CDx2, Cadherin17, Glypican3, arginase, synaptophysin, chromogranin A, PSA, CD45, P5dS, hepatocyte antigen, P504S, TTF1, CK5, P40 5…”

Section: Discussionmentioning

confidence: 99%

“…In line with our findings, the study observed a larger number of papillary and unclassified RCC subtypes, and a subset of patients who experienced long-term benefit from TT. 20 Noneclear-cell histologies, with a high fraction of unclassified RCC, seem predominant in CUP-mRCC. A total of 52 cases of CUP-mRCC have now been described in the literature, and CUP-mRCC is surely a true clinical entity, although more research is warranted.…”

Section: Anders Overby Et Almentioning

confidence: 98%

“…This entity has only rarely been described in the literature. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Renal-cell carcinoma (RCC) is a group of cancers arising from the nephron, where 70% of RCC are clear-cell RCC. Because of mutation in the Von Hippel-Lindau gene, a high amount of vascular endothelial growth factor (VEGF) is produced, resulting in increased angiogenesis, cell growth, metabolism, and immunesuppression.…”

Section: Introductionmentioning

confidence: 99%

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Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature

Øverby

Duval

Ladekarl

et al. 2019

Clinical Genitourinary Cancer

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Diagnostic assessment occasionally presents carcinoma of unknown primary site (CUP) with metastatic renalcell carcinoma (mRCC) histologic and immunohistochemical characteristics (CUP-mRCC). We reviewed our single-institution experience and searched the PubMed database, and identified 10 patients treated at our institution; 60% were poor risk patients. Objective response rate was 40%, progression-free survival was 2.5 months, and overall survival was 5.7 months; and the literature search identified 42 CUP-mRCC cases, for a total of 52 cases of CUP-mRCC. Vascular endothelial growth factoretargeted therapy is valid, feasible, and safe in CUP-mRCC, and these patients should thus be identified among CUP patients for specific renal-cell carcinoma therapy. Background: Carcinoma of unknown primary site (CUP) is a heterogenous group of metastatic cancer with no detectable primary tumor site. Diagnostic assessment occasionally presents CUP with metastatic renal-cell carcinoma (mRCC) histologic and immunohistochemical characteristics (CUP-mRCC). Efficacy and toxicity data for vascular endothelial growth factor inhibitor therapies in CUP-mRCC patients are few. Patients and Methods: We retrospectively reviewed consecutive patients with CUP-mRCC at a single institution between 2007 and 2018. Treatment outcomes were assessed from initiation of renal-cell carcinomaespecific therapy, including response rate, progression-free survival, and overall survival. Results: Ten patients with CUP-mRCC were identified. Median age was 64 years. Histologies were clear-cell (30%), papillary type II (20%), and unclassified renal-cell (50%) carcinoma. International Metastatic Renal Cell Carcinoma Database Consortium risk group were favorable, intermediate, and poor in 0, 40%, and 60%, respectively. One patient received empiric first-line chemotherapy. Targeted treatments were pazopanib (n ¼ 7), sunitinib (n ¼ 2), and sorafenib (n ¼ 1). Objective response rate was 40%, progression-free survival was 2.5 months (95% confidence interval, 1.2-3.8), and overall survival was 5.7 months (95% confidence interval, 0-24.0). Stratified for International Metastatic Renal Cell Carcinoma Database Consortium risk, overall survival in intermediate versus poor risk group were 18.6 months and 2.3 months, respectively. Second-line therapy did not result in disease control. No new or unexpected toxicities were observed. Conclusion: CUP-mRCC treated with vascular endothelial growth factoretargeted therapy is valid, feasible, and safe even though these patients had several negative prognostic factors. CUP-mRCC patients should be identified among CUP patients for specific renal-cell carcinoma therapy.

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“…According to Bianchi et al, 3 in a study of a series of 11.157 RCCs, the bones are site of metastasis in 29.5% of the metastatic RCCs (mRCC) and poly‐metastatic patients are quite frequent (39%). The recognition of mRCC patients is of particular clinical interest, since effective treatment for advanced RCC has no overlap with the empiric chemotherapy used traditionally for carcinoma of unknown primary origin (CUP) 4 . Thus, in the clinical settings of polymetastatic sites, a possible diagnostic approach to metastasis consists in obtaining samples from those sites in order to identify the primary neoplasms through morphological, immunophenotypical and molecular characterization.…”

Section: Introductionmentioning

confidence: 99%

Cytological diagnosis of Xp11 translocation renal cell carcinoma: An unusual suspect in bone metastases from unknown primary malignancies

Montella

Franco

Aquino

et al. 2020

Diagnostic Cytopathology

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Background Renal cell carcinoma (RCC) constitutes 3% of all cancers, with a higher incidence in patients with age between 60 and 70 years. RCC frequently present as a metastatic tumor at diagnosis, and bones represent one of the most frequent sites. Many cases, mainly in young patients, includes the Xp11 translocation RCC. The cytological diagnosis of Xp11 translocation RCC in adult population it is rarely performed, likely for the morphological overlap with other adult renal cell carcinoma subtypes. Methods We retrospectively analyze a series of 92 adult patients with metastatic bone tumors, diagnosed on fine‐needle aspiration cytology (FNAC) samples, focusing mainly on the cytological, immunophenotypic and molecular features of Xp11 translocation RCC. Results In our series 6 of 92 (6.5%) cases were metastatic RCC (mRCC), among them 2 cases were metastasis from Xp11translocation RCC. Those cases showed a bloody background, with several groups of atypical cells arranged in syncytial groups or in papillary groups composed by atypical cells with abundant cytoplasm, with scattered clear cells. TFE3 was positive on immunocytochemical analysis and specific translocation t(Xp11.23) was detected by FISH analysis. Conclusions In adult patients with mRCC, it is necessary to consider also Xp11 translocation RCC among the diagnostic hypotheses. FNAC represents a valid tool to investigate bone lesions but cytological features of Xp11 translocation RCC are still poorly described and must necessarily be better defined.

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Renal Cell Carcinoma Presenting as Carcinoma of Unknown Primary Site: Recognition of a Treatable Patient Subset

Cited by 20 publications

References 10 publications

A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience

A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience

Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature

Cytological diagnosis of Xp11 translocation renal cell carcinoma: An unusual suspect in bone metastases from unknown primary malignancies

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