Abstract The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO “blue book”), published in 2016, contains significant revisions. These revisions were ...performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions. This review summarizes the most significant differences between the newly published classification and the prior version for renal, penile, and testicular tumours. Newly recognized epithelial renal tumours are hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome–associated RCC, succinate dehydrogenase–deficient RCC, tubulocystic RCC, acquired cystic disease–associated RCC, and clear cell papillary RCC. The WHO/International Society of Urological Pathology renal tumour grading system was recommended, and the definition of renal papillary adenoma was modified. The new WHO classification of penile squamous cell carcinomas is based on the presence of human papillomavirus and defines histologic subtypes accordingly. Germ cell neoplasia in situ (GCNIS) of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours, and testicular germ cell tumours are now separated into two fundamentally different groups: those derived from GCNIS and those unrelated to GCNIS. Spermatocytic seminoma has been designated as a spermatocytic tumour and placed within the group of non–GCNIS-related tumours in the 2016 WHO classification. Patient summary The 2016 World Health Organization (WHO) classification contains new renal tumour entities. The classification of penile squamous cell carcinomas is based on the presence of human papillomavirus. Germ cell neoplasia in situ of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has ...been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of “usual type” urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report. Patient summary Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In 2016 the World Health Organization published a revised classification of testicular neoplasms based upon advances in understanding their pathogenesis and molecular biology. The rationale for this ...revision and additional clinically relevant observations were the topics of a talk given to the Houston Society of Clinical Pathologists in April 2017. This paper summarizes that talk.
To summarize and explain the most important changes to the classification of testicular neoplasms in the World Health Organization 2016 revision.
Peer-reviewed published literature and contributions by individuals with expertise in this area that were also reviewed by genitourinary pathologists.
Most changes occurred in the germ cell tumor classification, including replacement of the terms
and
by
; subdivision of the tumors into 2 main categories, those derived from germ cell neoplasia in situ and those not derived from germ cell neoplasia in situ; distinction of germ cell neoplasia in situ from germ cells with delayed maturation and pre-germ cell neoplasia in situ; expansion of the trophoblastic tumor category to include epithelioid trophoblastic tumor and cystic trophoblastic tumor; and substitution of
for
and its placement in the non-germ cell neoplasia in situ group. Other revisions included eliminating sclerosing Sertoli cell tumor as a distinct entity; the recognition of intratubular hyalinizing Sertoli cell tumor; and acceptance of the role of undifferentiated gonadal tissue in the pathogenesis of gonadoblastoma.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
A recent study demonstrated that NKX3.1-positive staining can uncommonly be seen in testicular Sertoli cell tumors (1 of 4 cases). Also, it was reported that 2 of 3 Leydig cell tumors of the testis ...showed diffuse cytoplasmic staining for P501S, although it was unclear whether it was specific granular staining that defines true positivity. However, Sertoli cell tumors do not typically pose a diagnostic dilemma with metastatic prostate carcinoma to the testis. In contrast, malignant Leydig cell tumors, which are exceedingly rare, can closely resemble Gleason score 5 + 5 = 10 prostatic adenocarcinoma metastatic to the testis.
To evaluate the expression of prostate markers in malignant Leydig cell tumors and steroidogenic factor 1 (SF-1) in high-grade prostate adenocarcinoma, as no data are currently published on these topics.
Fifteen cases of malignant Leydig cell tumor were collected from 2 large genitourinary pathology consult services in the United States from 1991 to 2019.
All 15 cases were negative immunohistochemically for NKX3.1, and all 9 with available additional material were negative for prostate-specific antigen and P501S and positive for SF-1. SF-1 was negative immunohistochemically in a tissue microarray with cases of high-grade prostatic adenocarcinoma.
The diagnosis of malignant Leydig cell tumor and its distinction from metastatic adenocarcinoma to the testis can be made immunohistochemically on the basis of SF-1 positivity and negativity for NKX3.1.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Some recent reports suggested that many Sertoli cell tumors, not otherwise specified (SCTs-NOS) of the testis were analogs of the solid pseudopapillary neoplasm (SPN) of the pancreas. One of the most ...relied on pieces of information for this assertion was the shared occurrence in both neoplasms of exon 3 mutations of the CTNNB1 gene, which was reflected by nuclear β-catenin expression. We, therefore, compared the morphologic and immunohistochemical features of 18 SCTs-NOS with strong, diffuse nuclear β-catenin expression with 16 SPNs that also showed such positivity. Although there were clear similarities in the light microscopic features of these neoplasms, there were also significant differences that included, in SCT-NOS and SPN, respectivelyhollow tubules (53% vs. 0%), sheet-like growth (44% vs. 94%), circumscription (79% vs. 25%), corded or trabecular patterns (81% vs. 31%), formation of papillae or pseudopapillae (24% vs. 69%), growth in nests or clusters (94% vs. 50%), perivascular pseudorosettes (13% vs. 56%), and rhabdoid cytology (6% vs. 50%). Commonly shared morphologic features included signet-ring cells, pale or foamy cytoplasm, myxoid stroma, cyst formation, perivascular hyalinization, and globular or band-like basement membrane deposits. On immunohistochemical study, sex cord markers were frequently positive in SCTs-NOS (steroidogenic factor-1—94%; FOXL2—87%; SOX9—69%; calretinin—60%; Wilms tumor-1—38%; inhibin—29%) whereas all of these markers were negative in the SPNs. We conclude that even though SCT-NOS and SPN share some morphologic features and nuclear immunoreactivity for β-catenin, there remain differences, both morphologically and immunohistochemically, between these neoplasms to the degree that SCT-NOS should not be equated with pancreatic SPN.
Ovarian-type epithelial tumors involving the testis and paratestis are rare, with clear cell carcinomas (CCC) one of the least frequent. We report our experience with 4 müllerian-type (MT) CCCs ...presenting as testicular/scrotal masses and arising in the paratestis (n=2) and seminal vesicle (n=2; well supported in 1 case and likely in the other). In addition, we document 3 cases of papillary CCC exclusively within the rete testis (RTCCC) and seminiferous tubules and differing from the MT tumors. The patients with MTCCC were 24 to 85 years old (median, 42 y), and 2 had metastases at presentation. The 2 originating in the paratestis were associated with other MT tumors, an endometrioid borderline tumor and a papillary serous borderline tumor. The other 2 MTCCCs likely involved the testis via extension from seminal vesicle primaries through the vasa deferentia. All MTCCCs showed typical features, including tubules, simple papillae with hyalinized cores, and solid nests of polygonal clear cells with occasional hobnail features. Both paratesticular primaries showed sarcomatoid foci with tumor-associated neutrophilic infiltrates. The 3 RTCCCs presented in 54-, 57-, and 60-year-old men as testicular masses; they showed intrarete arborizing papillary growth with nonhyalinized fibrous cores and piled-up, solid foci, lacked hobnail cells, and expressed carbonic anhydrase IX (2/2) and CD10 (2/2) but not CA125, unlike the MTCCCs. On follow-up, 2 patients with MTCCC died of metastatic tumor (4 and 13.5 mo), a third developed ileal and retroperitoneal metastases at 13 months; and the fourth died at 13.5 months of unspecified cause. Follow-up of 2 patients with RTCCCs showed 1 disease free at 8 months and another alive with unknown disease status at 13 years. We conclude that CCCs involving the testis may either be of MT with often aggressive courses or show some features of renal tumors, with confinement to the rete testis and indolent behavior.
Embryonic-type neuroectodermal elements are often intimately mixed with primitive endodermal-type glands, like those of yolk sac tumors, in germ cell neoplasia in situ (GCNIS)-derived germ cell ...tumors of the testis. Because the primitive glands mimic tubules or rosettes of embryonic-type neuroectodermal elements, these embryonic-type neuroectodermal/glandular complexes may be misinterpreted as pure lesions of embryonic-type neuroectodermal elements, which, if of sufficient size, may lead to a diagnosis of embryonic-type neuroectodermal tumor, despite that the criteria of the World Health Organization for a "somatic-type malignancy" are not met. A diagnosis of embryonic-type neuroectodermal tumor in the testis may lead to retroperitoneal lymphadenectomy even in clinical stage I patients, and in postchemotherapy resections indicates a poor prognosis. The distinction of the neuroectodermal and glandular elements is not always straightforward based on morphology alone. We, therefore, studied 34 testis-derived germ cell tumors with embryonic-type neuroectodermal/glandular complexes and 2 purely glandular yolk sac tumors to characterize the immunophenotypes and determine an efficient immunohistochemical panel to aid in this differential. We found that GFAP, synaptophysin, and paired-like homeobox 2B (PHOX2B) expression was specific to embryonic-type neuroectodermal elements, although PHOX2B had poor sensitivity. In contrast, positive reactions with antibodies directed against AFP, villin, and CDX2 were specific for the glandular elements, although CDX2 had poor sensitivity. Other markers, including AE1/AE3 cytokeratin, SALL4, glypican 3, SOX2, SOX11, CD56, INSM1, and neurofilament, proved less helpful because of their nonspecificity and/or poor sensitivity. We conclude that the optimal immunohistochemical panel for distinguishing the components of embryonic-type neuroectodermal/glandular complexes includes stains for synaptophysin, GFAP, villin, and AFP.
The pre‐invasive lesion associated with post‐pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow‐up ...studies. Until this year, this scientific story has been confused by resistance to the entity and disagreement on its name. Initially termed ‘carcinoma in situ’ (CIS), it has also been known as ‘intratubular germ cell neoplasia, unclassified’ (IGCNU) and ‘testicular intraepithelial neoplasia’ (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce the reasoning for uniting behind a new name, endorsed unanimously at the World Health Organization (WHO) consensus classification 2016: germ cell neoplasia in situ (GCNIS).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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