Glen Kristiansen

Glen_KTumours of the prostate and testis – update on WHO classification, IHC and molecular morphology

The 2016 WHO classification of genitourinary tumours has implemented major changes for prostate and testicular tumors.
In the prostate, the concept of intraductal carcinoma (IDC-P, M8500/2) has been introduced and defined in a practicable manner. As IDC-P has independent prognostic value, pathologists and urologists ought to be aware of this lesion. Also, the latest update on Gleason Grading provided by the International Society of Urological Pathology (ISUP) has been adopted, which includes, in addition to modifications and refinements of Gleason patterns, a description of prostate cancer variants (atrophic, pseudohyperplastic, microcystic, foamy gland, mucinous, pleomorphic giant cell, signet ring-like cell and sarcomatoid variant) and a novel approach to categorize Gleason scores into five “Grade Groups” of clinical utility. Immunohistochemistry (IHC) in prostate diagnostics still only requires a small spectrum of markers but necessitates a broader knowledge of morphology to put it into context successfully. Basal cell markers, complemented by AMACR remain the mainstay for the initial diagnosis of malignancy, whereas a broader spectrum of prostate specific markers (PSA, Prostein, NKX3.1) may be useful in late stage disease. Prognostic IHC is not recommended and molecular means of prognostication are an interesting development but will require further validation.

The concept of the classification of testicular tumors has also undergone major changes. The intratubular precursor lesion of germ cell neoplasms (formerly named IGCNU, TIN or CIS) has now been termed Germ Cell Neoplasia In Situ (GCNIS, M9064/2).  Accordingly, testicular tumors are now classified upon their relationship to GCIS, as either derived from (e.g.  seminoma, embryonal carcinoma, postpubertal-type yolk sac tumour or teratoma) or unrelated (prepubertal dermoid/epidermoid cyst, yolk sac tumour or teratoma, spermatocytic tumour) to GCNIS. Importantly, the formerly known “spermatocytic seminoma” (sometimes called the seminoma of the elderly) has been re-classified as “Spermatocytic Tumour” (M9063/3), as it is molecularly unrelated to seminoma (e.g. OCT4 negative) and clinically rarely metastasizes. Also, the spectrum of trophoblastic tumors has been broadened by the recognition of Epitheloid Trophoblastic Tumor (ETT, M9105/3), a very rare tumor with a squamoid morphology. The panel of immunohistochemical markers in testicular tumors has markedly grown. For the confirmation of seminoma CD117, PLAP, OCT3/4, SALL4 and SOX17 are recommended. Embryonal carcinoma can be discriminated by CD30, AP-2γ and SOX2. Yolk sac tumours are positive for AFP, Glypican-3 and CDX2. Choriocarcinomas express β-HCG and GATA3 and commonly also Glypican-3. For routine purposes testicular tumors presently do not require further molecular diagnostics.

Selected references

Delahunt B, Grignon DJ, Samaratunga H, Srigley JR, Leite KR, Kristiansen G, Evans AJ, Kench JG, Egevad L. Prostate Cancer Grading: A Decade After the 2005 Modified Gleason Grading System. Arch Pathol Lab Med. 2017 Feb;141(2):182-183. doi: 10.5858/arpa.2016-0300-LE. PubMed PMID: 28134585.

Varma M, Egevad L, Delahunt B, Kristiansen G. Reply: ‘A plea for greater standardization in intraductal carcinoma of the prostate -greater standardization requires greater evidence’: let’s use the available evidence. Histopathology. 2017 May;70(6):1013-1014. doi: 10.1111/his.13152. Epub 2017 Feb 9. PubMed PMID: 27992960.

Berney DM, Algaba F, Camparo P, Compérat E, Griffiths D, Kristiansen G, Lopez-Beltran A, Montironi R, Varma M, Egevad L. The reasons behind variation in Gleason grading of prostatic biopsies: areas of agreement and misconception among 266 European pathologists. Histopathology. 2014 Feb;64(3):405-11. doi:10.1111/his.12284. Epub 2013 Nov 6. PubMed PMID: 24102975.

Sailer V, Stephan C, Wernert N, Perner S, Jung K, Dietel M, Kristiansen G. Comparison of p40 (ΔNp63) and p63 expression in prostate tissues–which one is the superior diagnostic marker for basal cells? Histopathology. 2013 Jul;63(1):50-6. doi: 10.1111/his.12116. Epub 2013 May 13. PubMed PMID: 23668398.

Kristiansen G. [Immunohistochemical algorithms in prostate diagnostics: what’s new?]. Pathologe. 2009 Dec;30 Suppl 2:146-53. doi: 10.1007/s00292-009-1230-4. Review. German. PubMed PMID: 19795124.


CV

Highlights: Entitled the degree Medical Doctor at the Humboldt University, Berlin, 2000 (Research on cell cycle- and cell adhesion associated proteins in non-small cell lung cancer).
Entitled the degree Private Docent at the Charité University Medicine Berlin 2004 (Identification of Differentially expressed Genes in Solid Tumors exemplified in Prostate Cancer and the use of selected Genes (CD24, CD166) as Molecular Prognostic Markers).
Full Professor (W3) and Chairman, May 2011-, Institute of Pathology, University Hospital Bonn, Germany.
Full CV, Click on CV_Kristiansen_1