Diagnostic accuracy of percutaneous renal tumor biopsy May 10 th 2018

Diagnostic accuracy of percutaneous renal tumor biopsy May 10 th 2018 Dr. Tzahi Neuman Dep.Of Pathology Hadassah Medical Center Jerusalem, Israel, (tneuman@hadassah.org.il) Disclosure: 1 no conflicts of interests

Historical perspective Until recently, RTB was rarely performed Low diagnostic yield Risk of bleeding Potential for needle tract seeding With SRM 20-30% benign and 50-55% indolent low grade tumors Even tumors <1 cm in diameter have malignant potential Frank I. et al. Solid renal tumors: an analysis of pathological features related to tumor size. J Urol 2003; 170 (6 Pt 1): 2217-2220

Clinical perspective Active surveillance Serial imaging - delayed intervention Minimally invasive alternatives (ablative therapies) Partial V.S radical nephrectomy Treatment options depend heavily on the histopathological characteristics of the tumor as determind by RTB

Issues related to sampling Inherent assumption that the tissue sampled accurately reflects the entire lesion In the setting of renal masses of any size, this assumption may rest on a weak foundation Even SRMs can show heterogeneity with respect to cytological features, architecture, grade and molecular/genomic characteristics Omaszewski J.J., Uzzo R.G., and Smaldone M.C.: Heterogeneity and renal mass biopsy: a review of its role and reliability. Cancer Biol Med 2014; 11: pp. 162-172

Sampling issues need to be considered when reading and reporting RTBs Non-diagnostic biopsy Heterogeneity of grade Mixed clear cell and papillary features Sub-classifying papillary renal cell carcinoma

Sampling issues need to be considered when reading and reporting RTBs Tumor cells with oncocytic/eosinophilic cytoplasm Cystic masses Tumors that infiltrate the renal parenchyma

Sampling issues need to be considered when reading and reporting RTBs Non-diagnostic biopsy Heterogeneity of grade Mixed clear cell and papillary features Sub-classifying papillary renal cell carcinoma

Non-diagnostic biopsy The most frequent finding- renal parenchyma (~70%) A predominance of fat- consider the possibility of AML or WDLS review/report imaging and IHC Tiny amount of lesional tissue (most often found on the end of a core) levels, IHC prioritization What is an adequate biopsy? Richard PO, Bhatt JR, Evans AJ, Finelli A, et al. The outcome of renal tumor biopsies are small renal masses: A single-center 13- year experience. Eur Urol. 2015 Dec;68(6):1007-13

Sampling issues need to be considered when reading and reporting RTBs Non-diagnostic biopsy Heterogeneity of grade Mixed clear cell and papillary features Sub-classifying papillary renal cell carcinoma

Heterogeneity of grade Lack of reliability owing to tumor heterogeneity Most series report exact concordance for grade in approximately 60% of cases (higher with high grade). The reporting of tumor grade on biopsy is not mandatory (due to the CAP) Ball M.W., Bezerra S.M., Gorin M.A., et al: Grade heterogeneity in small renal masses: potential implications for renal mass biopsy. J Urol. 2015 Jan;193(1):36-40

Heterogeneity of grade The ISUP formally adopted a modification of the original Fuhrman grading scheme at its 2011 Consensus Conference on Renal Neoplasia in Vancouver. The ISUP system is based only on nucleolar prominence (as opposed to nuclear size and shape and nucleolar prominence in the Fuhrman system) Delahunt B., Cheville J.C., Martignoni G., et al: The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 2013; 37: pp. 1490-1504

Heterogeneity of grade When more than one ISUP grade is present in a RTB, the highest grade should be reported ChrRCC should not receive an ISUP grade

Sampling issues need to be considered when reading and reporting RTBs Non-diagnostic biopsy Heterogeneity of grade Mixed clear cell and papillary features Sub-classifying papillary renal cell carcinoma

Tumours showing mixed clear cell and papillary features CCRCC Clear cell (tubulo) papillary RCC PRCC MiTF family translocation RCC (including Xp11.2 and t(6;11) translocation RCC)

Tumours showing mixed clear cell and papillary features The use of IHC panel should allow the correct classification to be established in the majority of cases (up to 95%) Otherwise: RCC with mixed clear cell and papillary features, not otherwise specified Ross H., Martignoni G., and Argani P.: Renal cell carcinoma with clear cell and papillary features. Arch Pathol Lab Med 2012; 136: pp. 391-399

CK7

CA-IX

CD-10

AMACR

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Sampling issues need to be considered when reading and reporting RTBs Non-diagnostic biopsy Heterogeneity of grade Mixed clear cell and papillary features Sub-classifying papillary renal cell carcinoma

Sub-classifying papillary renal cell carcinoma PRCC is currently divided into Type 1 and Type 2 subtypes based on H&E morphology, IHC and clinical behavior

Sub-classifying papillary renal cell carcinoma Papillary type 1 tumors Most common Non-stratified cells Pale cytoplasm Uniform nuclei Foamy macrophages CK7 + and AMACR + Indolent clinical course Slow growth rate

Sub-classifying papillary renal cell carcinoma Papillary type 2 tumors Stratified cells Eosinophilic cytoplasm High-grade pleomorphic nuclei with prominent nucleoli CK7 (weak to absent) AMACR + Locally advanced, more aggressive and show more rapid growth rates than Type 1 tumors.

Sub-classifying papillary renal cell carcinoma The tumours will be reported as PRCC, not otherwise specified in situations where doubt exists concerning the presence of aggressive features

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Sampling issues need to be considered when reading and reporting RTBs Tumor cells with oncocytic/eosinophilic cytoplasm Cystic masses Tumors that infiltrate the renal parenchyma

Tumours with oncocytic/eosinophilic cytoplasm Oncocytoma CrRCC, eosinophilc variant Hybrid oncocytic-chromophobe tumours CCRCC with eosinophilic cytoplasm (usually high grade) PRCC with oncocytic features

Tumours with oncocytic/eosinophilic cytoplasm Tubulocystic renal cell carcinoma Follicular thyroid-like carcinoma Acquired cystic kidney disease associated renal cell carcinoma Renal tumors associated with SDH-B mutations Epithelioid angiomyolipoma MiTF family translocation renal cell carcinoma Renal cell carcinoma of any histologic type with rhabdoid features

Tumours with oncocytic/eosinophilic cytoplasm The issue of whether an unequivocal diagnosis of oncocytoma can be made on biopsy is unresolved

Tumours with oncocytic/eosinophilic cytoplasm It is controversial whether a definitive diagnosis of oncocytoma can be rendered on needle biopsy. Although some experts make a definitive diagnosis on biopsy, for needle core biopsy specimens that have morphologic and immunophenotypic findings of oncocytoma, we interpret them as oncocytic renal cell neoplasm. We add the following comment: If this biopsy is representative of the entire lesion, it would be consistent with an oncocytoma. However, renal cell carcinoma (RCC) and hybrid tumor may uncommonly show focal areas with oncocytic features. Kryvenko ON1, Jorda M, Argani P, Epstein JI. Diagnostic approach to eosinophilic renal neoplasms. Arch Pathol Lab Med. 2014 Nov;138(11):1531-41

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Sampling issues need to be considered when reading and reporting RTBs Tumor cells with oncocytic/eosinophilic cytoplasm Cystic masses Tumors that infiltrate the renal parenchyma

Cystic renal masses There is a tendency for RTBs of incidentallyfound cystic renal masses of any size to be nondiagnostic Whether RTB should even be performed on such lesions? Sahni V.A., and Silverman S.G.: Biopsy of renal masses: when and why. Cancer Imaging 2009; 9: pp. 44-55

Sampling issues need to be considered when reading and reporting RTBs Tumor cells with oncocytic/eosinophilic cytoplasm Cystic masses Tumors that infiltrate the renal parenchyma

Tumours showing infiltration of the renal parenchyma Metastatic tumors (most frequently lung, breast, GYN and H&N origin, also adrenocortical carcinoma and melanoma) Collecting duct carcinoma Medullary RCC Invasive urothelial carcinoma (GATA-3)

Take home massages Mars and Venus can join forces for adequate interpretations and good clinical practice: Good clinical and radiological information Sharing in real time clinical dilemmas (bilateral) Dealing better with scanty material Consulting molecular options Sharing clinical results

Thank you