1 www.jonoxley.com Slide Seminars for London Uropathology Conference June 18th to 20th 2014 Thursday, 19th June 18:45 - 19:35 : Multiheader Session: Difficult renal tumours – Dr Jon Oxley Thursday, 20th June 08:00 - 08:50 : Multiheader Session: Classifying renal neoplasms on core biopsies: pitfalls in interpretation and diagnosis - Dr Jon Oxley Acknowledgements and Links • Uropathology EQA at www.histopathologyeqa.org • Diagnostic Pathology: Genitourinary: Published by Amirsys (Diagnostic Pathology Series) by Mahul Amin, ISBN-10: 1931884285 • The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia John R. Srigley, Am J Surg Pathol Volume 37, Number 10, October 2013 • Recent advances of immunohistochemistry for diagnosis of renal tumors Naoto Kuroda. Pathology International Volume 63, Issue 8, pages 381– 390, August 2013 • Renal Neoplasms: An update on immunohistochemical and histochemical features. S Bonsib, A Bhalodia, Connection 2010 p178-186 via: • http://www.dako.com/index/knowledgecenter/kc_publications/kc_publications _connection/kc_publications_connection14.htm/28829_2010_conn14_renal_n eoplasms_bonsib_and_bhalodia.pdf • Thanks to Prof Fleming, Dr C Sen, Dr Nick Mayer and Southmead Laboratory for Cases, Catherine Neal for typing immuno table • Other lectures/cut up protocols: www.jonoxley.com Dr Jon Oxley [email protected]Webpage: www.jonoxley.com
Transcript
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Slide Seminars for London Uropathology Conference
June 18th to 20th 2014
Thursday, 19th June
18:45 - 19:35 : Multiheader Session: Difficult renal tumours – Dr Jon Oxley
Solid pap RCC, collecting duct,chromoph, ?ALK1, ACKD RCC
Slide seminar 2: Classifying renal
neoplasms on core biopsies: pitfalls in
interpretation and diagnosis
Section 1: Discussion about role of core biopsies and diagnostic accuracy
Section 2: Examples of biopsies in setting of metastatic disease
RCC (with different grades and immunoexpression), Sarc RCC, soft tissue Bx, tcc,
Section 3: Examples of biopsies in setting of pre-cryo/RFA
AML, onco/chromo/BHD/uncertain, RCC (grading)
Section 4: Examples of biopsies in multiple tumours/diagnostic
Necrotic, Pap/TCC, TCC, lymphoma, Oncocytosis
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References
Difficult renal tumours
Renal angiomyolipoma: report of three cases with regional lymph node involvement and/or with renal cell carcinoma.
Csanaky G1, Szereday Z, Magyarlaki T, Méhes G, Herbert T, Buzogány I. Tumori. 1995 Nov-
Dec;81(6):469-74.
AIMS AND BACKGROUND: Angiomyolipomas (AMLs) are benign hamartoid tumors which frequently occur in tuberous sclerosis (TS). They may be manifest at different organ sites such as kidneys, lymph nodes, liver and lung and may be associated with renal cell carcinoma (RCC). The nature of multiple organ involvement in AML (metastasis versus multicentric synchronous tumors), the malignant transformation and the relation of AML to RCC have not been sufficiently clarified.
STUDY DESIGN: Three cases of renal AMLs in patients with tuberous sclerosis associated with lymphangioleiomyomatosis of the paraaortic lymph nodes and/or with RCC are reported. The concise clinical history of the patients as well as the findings of histology, immunohistochemistry and quantitative DNA analysis are presented.
RESULTS: The multicentric form of AML and coincidence of renal AML and RCC were observed in 2 patients. AML and RCC were found within the same focus in one of the cases. RCCs were either aneuploid or "near diploid", whereas one of the multicentric AMLs showed a discordant DNA ploidy pattern, namely aneuploidy in the kidney and diploidy in the lymph nodes.
CONCLUSIONS:The presented cases (all of them underwent periaortic lymphadenectomy) suggest that lymph node involvement in renal AML may be more frequent than expected (1-2% of all AMLs) on the basis of the few reported cases. The discordant DNA ploidy (renal versus lymph node lesions) observed in one of the cases with multicentric AML implies synchronous tumor growth at different sites rather than metastatic disease. The intimate coexistance of RCC and AML (RCC revealed by immunohistochemistry within a larger mass of renal AML) may indicate that malignant transformation of an AML should only be accepted, if such a coincidence is unequivocally excluded.
Renal Schwannoma 1. Mod Pathol. 2000 Aug;13(8):851-6. Intrarenal schwannoma: a report of four cases including three cellular variants.Alvarado-Cabrero I(1), Folpe AL, Srigley JR, Gaudin P, Philip AT, Reuter VE, Amin MB. Renal schwannomas are extraordinarily rare neoplasms; only six have been reported, the majority of which occurred in the renal pelvis. We report the clinical and pathologic features of four additional cases. The resected kidney in all patients contained a well-demarcated, yellow-tan, smooth, and bulging intraparenchymal tumor (mean size, 9.7 cm; range, 4 to 16 cm). Microscopically, three cases were classified as cellular schwannomas, and one was a usual-type schwannoma, with degenerative nuclear atypia. By immunohistochemistry, all tumors were strongly S-100 protein positive and negative for pan-cytokeratin, CD57, smooth muscle actin, desmin, and CD34. Epithelial elements were not noted in the tumors, and there was no history of any clinical syndromes in these patients. Analysis of the four cases showed the mean age at presentation to be 47 years (range, 18 to 84 years), with no sex predisposition (two men, two women). Most patients were asymptomatic, and all received a diagnosis of renal cell carcinoma and treated as having such. Recognition and awareness of these rare, benign tumors will assist in the differential diagnosis of spindle cell tumors of the kidney and prevent their misdiagnosis as sarcomatoid carcinomas of the kidney or renal sarcomas. Our study, the
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largest series to date of renal schwannomas, demonstrates a predilection for the cellular variant in the kidney, documents that these tumors may present in the nonhilar region of the kidney, and provides clinical evidence of their benign biologic behavior. 2 Another reference with full text at PubMed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531643/ Hybrid tumours Renal hybrid oncocytic/chromophobe tumors - a review.
Hes O, Petersson F, Kuroda N, Hora M, Michal M.
Histol Histopathol. 2013 Oct;28(10):1257-64. Epub 2013 Jun 6. Review Hybrid oncocytic/chromophobe tumors (HOCT) occur in three clinico-pathologic situations; (1) sporadically, (2) in association with renaloncocytomatosis and (3) in patients with Birt-Hogg-Dubé syndrome (BHD). There are no specific clinical symptoms in patients with sporadic or HOCT associated with oncocytosis/oncocytomatosis. HOCT in patients with BHD are usually encountered on characteristic BHD clinicopathologic background. Sporadic HOCT are composed of neoplastic cells with eosinophilic oncocytic cytoplasm. Tumors are usually arranged in a solid-alveolar pattern. Some neoplastic cells may have a perinuclear halo, no raisinoid nuclei are present. HOCT occurring in patients with oncocytomatosis are morphologically identical to sporadic HOCT. HOCT in BHD frequently display 3 morphologic patterns, either in isolation or in combination; (1) An admixture of areas typical of RO and CHRCC, respectively, (2) Scattered chromophobe cells in the background of a typical RO, (3) Large eosinophilic cells with intracytoplasmic vacuoles. The immunohistochemical profiles of HOCT in all clinicopathologic and morphologic groups differ slightly. The majority of tumors express parvalbumin, antimitochondrial antigen and CK 7. CD117 is invariably positive. HOCT show significant molecular genetic heterogeneity. The highest degree of variability in numerical chromosomal changes is present in sporadic HOCT. HOCT in the setting of oncocytomatosis have revealed a lesser degree of variability in the chromosomal numerical aberrations. HOCT in patients with BHD display FLCN gene mutations, which are absent in the other groups. HOCT (all three clinicopathologic groups) seem to behave indolently, as no evidence of aggressive behavior has been documented. However, no report with follow up longer than 10 years has been published.
The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell
carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases.
Pan CC1, Chen PC, Ho DM.
Histopathology. 2004 Nov;45(5):452-9
AIMS:
To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and
CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive
immunohistochemical analysis.
METHODS AND RESULTS:
Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27
papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas
using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12,
Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory
value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10
labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31,
while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs
were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%).
Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were
negative for MOC31 and CD10.
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CONCLUSIONS:
MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC
Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary
RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in
distinguishing renal oncocytoma from RCC. When properly selected, antibodies have
immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.
Renal Biopsies
DIAGNOSTIC YIELD
Image-guided biopsy in the evaluation of renal mass lesions in contemporary urological practice: indications, adequacy, clinical impact, and limitations of the pathological diagnosis.
Shah RB1, Bakshi N, Hafez KS, Wood DP Jr, Kunju LP. Hum Pathol. 2005 Dec;36(12):1309-15. Epub
2005 Oct 28
Abstract With increasing sophistication of imaging modalities, many small indeterminate renal masses are detected, posing therapeutic dilemmas. Minimally invasive techniques such as radio frequency ablation (RFA) and cryotherapy are increasingly used in such settings, making it essential to classify renal mass in biopsies. We evaluated indications, adequacy, spectrum, and limitations of pathological diagnoses in 52 (79%) of 66 adequate biopsies that impacted management by having conservative therapy (less than total nephrectomy). Indication for biopsies in this group was exclusively for indeterminate mass. Biopsies were categorized as 52% clear cell renal cell carcinoma (RCC); 11% papillary RCC; 23% oncocytic neoplasms, subdivided as oncocytoma (10), chromophobe RCC (1), and cannot rule out RCC (1); 8% spindle cell neoplasms; 2% round blue cell tumors; and 4% inflammatory. After biopsy, 29% underwent nephron-sparing surgery, 36% underwent RFA, and 35% were followed up with observation only. One (2%) unresolved oncocytic neoplasm proved to be a chromophobe RCC in the total nephrectomy. Of the 19 patients, 15 who underwent RFA after diagnostic biopsy subsequently underwent post-RFA biopsy to assess therapy response. Complete ablation at first attempt was achieved in 12 of 15 patients. In contemporary urological practice, biopsies are increasingly performed for incidentally detected renal mass to influence the clinical management. Most biopsies can be classified into clinically relevant categories; however, caution is advised while interpreting oncocytic neoplasms because sampling and tumor heterogeneity may adversely affect interpretation
Diagnostic yield of renal biopsy immediately prior to laparoscopic radiofrequency ablation: a multicenter study.
10.1089/end.2008.9717. INTRODUCTION: Ablative therapy is increasing for the management of small renal masses. Laparoscopic as well as percutaneous cryotherapy and radiofrequency ablation (RFA) have been utilized. Herein we review our experience with renal biopsy immediately prior to laparoscopic RFA. METHODS AND MATERIALS: A prospectively collected database containing all patients who underwent laparoscopic RFA by three different surgeons at two different institutions was reviewed. Renal biopsies were performed in each patient during transperitoneal laparoscopy after mobilization of the kidney and prior to RFA. The biopsy needle was passed percutaneously via a sheath through the abdominal wall. Multiple core biopsies (3-5) were taken under visual and ultrasonic guidance. All were submitted for permanent pathologic sectioning. RESULTS:138 patients underwent renal biopsy prior to RFA. Mean tumor size was 3.0 cm (range 1.0-6.9). The mean age was 72 years (range 39-90). There were 42 females and 96 males. Mean blood loss was 28 ml (0-400 ml). Only 5 patients lost more than 50 ml, and in each case the bleeding was associated with complicated renal mobilization and dissection prior to biopsy. Final pathology revealed renal cell carcinoma in 95, oncocytic neoplasm in 26, and angiomyolipoma in 9.8 patients
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were considered to have nondiagnostic biopsies. In this group, final pathology revealed benign cysts in 3, inconclusive specimens in 3, fibrosis in 1, and normal tissue in 1. Hence, a clear diagnosis was possible in 130 of 138 patients, which is 94.2%. RCC was diagnosed in 68.8% of the patients, and in 73.1% of the conclusive biopsies. Eight patients had perioperative complications, including low-grade fevers (2) perirenal/retroperitonal hematoma (2), pleural tear/pneumothorax (2), CHF exacerbation, and wound infection.
CONCLUSIONS: In our multicenter experience, renal biopsy of 138 renal lesions at the time of laparoscopic RFA had a diagnostic yield of 94.2%. RCC was diagnosed in 68.8% of the patients, and in 73.1% of the conclusive biopsies.
Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy.
Leveridge MJ1, Finelli A, Kachura JR, Evans A, Chung H, Shiff DA, Fernandes K, Jewett MA.
Eur Urol. 2011 Sep;60(3):578-84. doi: 10.1016/j.eururo.2011.06.021. Epub 2011 Jun 24. BACKGROUND: Percutaneous needle core biopsy has become established in the management of small renal masses ≤ 4 cm (SRMs). Recent series have reported success rates of ≥ 80%. Nondiagnostic results continue to be problematic. OBJECTIVE: To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy. DESIGN, SETTING, AND PARTICIPANTS: Patients undergoing renal tumor biopsy (RTB) for suspected renal cell carcinoma (RCC) were included in a prospectively maintained database.MEASUREMENTS: The database was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy. Outcomes of patients with nondiagnostic biopsy were determined. Patients undergoing repeat biopsy were identified and their outcomes analyzed. RESULTS AND LIMITATIONS: Three hundred forty-five biopsies were performed (mean diameter: 2.5 cm). Biopsy was diagnostic in 278 cases (80.6%) and nondiagnostic in 67 cases (19.4%). Among diagnostic biopsies, 221 (79.4%) were malignant, 94.1% of which were RCC. Histologic subtyping and grading of RCC was possible in 88.0% and 63.5% of cases, respectively. Repeat biopsy was performed in 12 of the 67 nondiagnostic cases, and a diagnosis was possible in 10 (83.3%). Eight lesions were malignant and two were oncocytic neoplasms. Pathology was available for 15 masses after initial nondiagnostic biopsy; 11 (73%) were malignant. Larger tumor size and a solid nature on imaging predicted a successful biopsy on multivariate analysis. Grade 1 complications were experienced in 10.1% of cases, with no major bleeding and no seeding of the biopsy tract. There was one grade 3a complication (0.3%). This is a retrospective study and some data are unavailable on factors that may affect biopsy success rates. Repeat biopsy was not standard practice prior to this analysis.
CONCLUSIONS: RTB can be performed safely and accurately in the investigation of renal masses ≤ 4 cm. A nondiagnostic biopsy should not be considered a surrogate for the absence of malignancy. Repeat biopsy can be performed with similar accuracy, providing a diagnosis for most patients.
Bernstein M, Tickoo SK, Coleman JA, Russo P.J Urol. 2011 Mar;185(3):795-801. doi: 10.1016/j.juro.2010.10.068. Epub 2011 Jan 15.
Renal oncocytosis is a rare pathological condition in which renal parenchyma is diffusely involved by numerous oncocytic nodules in addition to showing a spectrum of other oncocytic changes. We describe our experience with renal oncocytosis, focusing on management and outcomes. MATERIALS AND METHODS: A total of 20 patients with a final pathological diagnosis of renal oncocytosis from July 1995 through June 2009 were included in the analysis. Patient demographics, intraoperative variables and postoperative outcomes are reported. RESULTS:Median age at nephrectomy was 71 years (IQR 59-75). Of the patients 15 (75%) had bilateral disease. There were 23 operations (9 right side, 14 left side) performed on 20 patients, and of these procedures 13 (57%) were partial nephrectomies and 10 (43%) were radical nephrectomies. Median dominant tumor mass
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diameter was 4.1 cm (IQR 3-6.4, range 1 to 14.6). The most common dominant tumor histology was hybrid tumor between oncocytoma and chromophobe renal cell carcinoma in 13 of 23 specimens (57%), followed by chromophobe renal cell carcinoma in 6 (26%), oncocytoma in 3 (13%) and conventional renal cell carcinoma in 1 (4%). Ten patients (50%) had preexisting chronic kidney disease before nephrectomy and chronic kidney disease developed in 5 more after surgery. After a median followup of 35 months no patients had metastatic disease. CONCLUSIONS: Patients with renal oncocytosis usually present with multiple and bilateral renal nodules. Half of the patients had chronic kidney disease at diagnosis and 25% had new onset of chronic kidney disease. No patient had distant metastatic disease during followup. Our management approach is to perform partial nephrectomy when possible and then use careful surveillance of the remaining renal masses Immunohistochemistry Role of Immunohistochemistry in the Evaluation of Needle Core Biopsies in Adult Renal Cortical Tumors: An Ex Vivo StudyAl-Ahmadie, Hikmat A. MD*; Am J Surg Path 35(7) July 2011. p949
Multiple therapeutic options for renal tumors that are now available have put pathologists under increasing pressure to render diagnosis on limited material. Results on biopsies by hematoxylin and eosin (H&E) have historically not been encouraging. Currently, multiple immunohistochemical markers with differential expression in these renal tumors are available. We studied the utility of such markers on needle biopsies that were obtained ex vivo. After nephrectomy, two 18-guage cores were obtained and processed routinely. Expressions of carbonic anhydrase (CA) IX, CD117, α-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), and CD10 were evaluated. Results, with or without immunostaining, were compared with the final nephrectomy diagnosis. We studied 145 tumors, including 119 renal cell carcinomas (83 clear cell, 18 papillary, 14 chromophobe, and 4 type unclassified), 11 oncocytomas, and 15 miscellaneous tumors. Adequate evaluable material was present in 123 (85%) cases. In such biopsies, 81% of cases were correctly classified by H&E alone, with correct diagnosis in 90% of cases in the most common tumor subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma). By adding immunostains, the accuracy was 90% overall and 99% among the 4 most common subtypes. The following extent and patterns of immuneexpression were highly useful in the diagnoses: diffuse, membranous CAIX expression in clear cell renal cell carcinoma, diffuse positivity for AMACR in papillary renal cell carcinoma, distinct peripheral cytoplasmic accentuation for CD117 in chromophobe renal cell carcinoma, widespread and intense positivity for CK7 in chromophobe and papillary renal cell carcinoma, and diffuse membranous reactivity in clear cell and patchy/luminal in papillary renal cell carcinoma for CD10. In conclusion, utilizing immunostains improves classification of renal tumors on needle biopsy, which may be of particular help for pathologists with limited experience. Both extent and patterns must be considered for a definitive diagnosis.
• 123 cases where adequate material obtained
• 83% just H&E, increasing to 90% for commonest 4 tumours.
• Adding immuno improved to 99% for commonest 4 tumours
• Panel: CAIX, AMACR, CD117, CK7, CD10
Renal Neoplasms: An update on immunohistochemical and histochemical
features. S Bonsib, A Bhalodia, Connection 2010 p178-186 via:
