Male GU Flashcards
3 features that are diagnostic of prostate carcinoma.
Perineural invasion, glomerulations, mucinous fibroplasia/collagenous micronodules.
Causes of male infertility.
Can be pretesticular (extragonadal endocrine disorders), testicular, or posttesticular (primarily obstruction). Testicular causes include hypospermatogenesis, maturation arrest, Sertoli-cell-only syndrome, and seminiferous tubule hyalinization. In hypospermatogenesis, full maturation occurs, but the total number of germ cells is decreased. The pattern can be uniform across tubules, but more often there is variability between tubules including some with extensive sclerosis or a Sertoli-cell-only pattern. Remember that spermatogenesis does not appear complete in every tubular cross section in a biopsy even in a completely normal testis. Maturation arrest (AKA germ cell arrest AKA spermatogenic arrest) should be applied when there is complete interruption of spermatogenesis uniformly in all tubules. The arrest is most frequently observed at primary spermatocyte level but can occur at earlier or later levels. There should be homogenous spermatocyte maturation arrest in all the tubules obtained in the biopsy. This is relatively rare in biopsied tissue, so some apply a less strict definition and refer to cases with focal spermatid maturation as “incomplete” maturation. These cases, however, are best classified as hypospermatogenesis with a heterogeneous pattern. Sertoli-cell-only syndrome (AKA germ cell aplasia) applies to a testicle in which germ cells at any stage of maturation are absent, but the tubular architecture is not effaced by fibrosis and supporting cells continue to be present. The picture superficially resembles the prepubertal testis. Biopsies with seminiferous tubule hyalinization are also known as the “end-stage testis” or “tubular sclerosis” and characterized by extensive intratubular and peritubular hyalinization with an absence of germ cells. Sertoli cells are commonly absent as well, although Leydig cells may persist in the tubular interstitium.
Causes of Sertoli-cell-only syndrome in the testis.
Idiopathic (most cases), Klinefelter syndrome, exposure to chemicals/toxins, hormonal therapy for prostate cancer, viral orchitis, radiation, congenital (microdeletions of the Y chromosome).
Prostate basal cell-associated markers?
34betaE12 AKA high molecular weight cytokeratin 34betaE12 AKA CK903. Is a cytoplasmic marker that highlights intermediate cytokeratin filaments in glandular basal cells. The monoclonal antibody clone targets CK1, CK5, CK10, and CK14. CK 5/6 is a good substitute for 34betaE12. p63 targets the p63 nuclear protein, which is homologous to the TP53 tumor suppressor gene. Is comparable to HMCK in sensitivity and specificity in needle biopsies (and may actually have better sensitivity than HMCK 34betaE12 in TURP specimens).
Prostate cancer-associated marker AMACR (p504s)?
AMACR=Alpha-methylacyl coA racemace. The difference between p-AMACR (polyclonal) and p504s (monoclonal) antibody is marginal and clinically insignificant. AMACR shows circumferential, strong, cytoplasmic staining with a granular quality. Immunoreactivity may be absent in 5-25% of typical prostate carcinomas and even more often in variants. Reactivity with AMACR can be seen in benign entities, such as in 35-58% of nephrogenic adenoma, 4% of atrophic carcinoma, and 2-36% of typical benign glands. Reactivity with AMACR can also be seen in some secondary tumors involving the prostate, such as urothelial carcinoma and colonic adenocarcinoma.
PSA and PSAP uses?
PSA and PSAP (Prostate-Specific Acid Phosphatase) are useful in ruling out nonprostatic carcinoma mimics, such as seminal vesicle/ejaculatory duct, hyperplastic mesonephric glands, nephrogenic adenoma, Cowper glands, and paraganglionic tissue. Also useful is in the DDx of unusual variants of prostate carcinoma (ie, ductal, mucinous, and signet ring carcinoma), which stain positive for PSA and PSAP, versus secondary tumors involving the prostate (such as bladder or colonic adenocarcinomas), which are typically negative.
The steps of spermatogenesis.
The process begins with the spermatogonium, which resides next to the basal lamina of the seminiferous tubules. It is a relatively small cell (~12 um) with pale-staining nuclear chromatin. At sexual maturity, the spermatogonium divides and either develops into a type A spermatogonia, remaining an undifferentiated stem cell, or differentiates through mitotic cycles into a type B spermatogonia. This latter cell gives rise to the primary spermatocyte, which quickly undergoes its first meiotic division and passes through 4 prophase stages, leptotene, zygotene, pachytene, and diplotene, before undergoing meiotic metaphase. The 4 prophase stages require ~3 weeks; thus, numerous primary spermatocytes are present in the cross sections of tubules in a typical biopsy. The primary spermatocyte is the largest of the germ cells in the tubules, and the various stages are distinguished based on the degree of chromosome coiling. After the meiotic division, a smaller secondary spermatocyte is formed. These cells are occasionally visible but typically far fewer in number due to the short time interval of this stage. They quickly undergo a second meiotic division resulting in spermatids, which are only 7-8 um in size. Spermatids are recognizable not only by their smaller size but also by their dark, condensed chromatin and juxtaluminal position within the tubule. Further differentiation including development of a flagellum, continued loss of cytoplasm, and nuclear elongation result in the formation of a mature spermatozoon, the final end product released into the lumen.
What are the 3 types of atrophy that can be seen in the prostate?
Simple atrophy, partial atrophy (PTAT), and postatrophic hyperplasia (PAH). Simple atrophy appears as a well-circumscribed area of glands of normal caliber that are spaced apart in a configuration similar to that of normal epithelium. PAH consists of small, crowded acini arranged in a lobular configuration, often surrounding a central, dilated duct. In both simple atrophy and PAH, the glands appear basophilic, due to lack of apical and lateral cytoplasm, compared with normal epithelium. PTAT generally retains its lobular architectural pattern of growth but can also show a more disorganized, diffuse growth pattern. The glands in PTAT do not have the typical atrophic, basophilic appearance, but appear as a focus of crowded glands with pale, scant cytoplasm. The attenuated cytoplasm is mostly apical.
What are 6 features seen in partial atrophy in the prostate that mimic prostatic acinar adenocarcinoma?
- Crowded and sometimes disorganized patterns of growth. 2. Relatively high N:C with slightly enlarged nuclei. 3. Straight luminal borders in some glands. 4. The presence of visible but small nucleoli. 5. Negative staining of some glands for basal cell markers. 6. Positive staining of some glands for racemase.
Malignant testicular sex cord-stromal tumors are usually treated with ___, while malignant testicular germ cell tumors are usually treated with ___.
Malignant testicular sex cord-stromal tumors are usually treated with orichiectomy and retroperitoneal lymphadenectomy (they are resistant to radiation and chemotherapy), while malignant testicular germ cell tumors are usually treated with… depends on if it is a seminoma or not. Seminomas are sensitive to both radiation and chemotherapy, while nonseminomatous TGCT respond to chemotherapy only.
Are testicular seminoma and embryonal carcinoma closely related entities?
Yes. Seminoma cells morphologically and immunophenotypically resemble embryonic germ cells (primordial gonocytes/gonocytes), whereas embryonal carcinoma cells resemble pluripotent stem cells from the inner cell mass of the blastocyst. Both express markers of “stemness”, including OCT3/4 (POU5F1) and NANOG. In the current histogenetic model of testicular germ cell tumors, embryonal carcinoma may arise from seminoma through transformation.
What 2 variants of seminoma may closely mimic embryonal carcinoma on routine stains?
One is seminoma having increased nuclear atypia, darker cytoplasm, and increased cell crowding. These features may be diffusely present in some “atypical” seminomas or occur focally within separate nodules of a single tumor. Similar findings are often identified in areas surrounding small, punctate foci of tumor necrosis in typical seminomas, and in that circumstance, these findings are likely reflective of ischemia-induced changes. Helpful light microscopic clues include its retention of the typical tumor architecture and lymphocytic reaction and the absence of any distinct epithelial differentiation. The other mimicker is the tubular variant of seminoma, in which the tumor architecture resembles gland-forming embryonal carcinoma yet retains the cytologic features of seminoma. The tubular structures in these seminomas are formed by pseudoglandular arrangements in solid sheets of tumor cells, with no real glandular lumens, similar to embryonal carcinoma.
How do seminomas and embryonal carcinomas stain with CK AE1/AE3, CD30, CD117, podoplanin (D2-40), SOX2, and SOX17?
AE1/AE3 and CD30 are diffusely positive in embryonal carcinoma and negative (or focally positive) in seminoma. CD117 and podoplanin (D2-40) are diffusely positive in seminoma and negative (or focally positive) in embryonal carcinoma. SOX2 is expressed in the nuclei of embryonal carcinoma but is not expressed in those of seminoma, whereas SOX17 shows nuclear reactivity in seminoma but not in embryonal carcinoma.
Differentiating dermoid cysts and epidermoid cysts from teratomas in the testis.
Dermoid cysts are lined by squamous epithelium and skin adnexal structures. Prominent lipogranulomas may be seen. In addition to the cutaneous-type components, dermoids may have components of other tissues, including glandular elements, adipose tissue, cartilage, and bone, further mimicking postpubertal teratoma. Epidermoid cysts are lined by squamous epithelium with no adnexal structures or other tissue types. Teratomas often contain multiple cysts, lined by glandular or squamous epithelium, neuroectodermal tissue, noncystic glands, and mesenchymal tissues such as adipose tissue and cartilage. A critical feature of dermoid and epidermoid cysts, which distinguishes them from the usual teratoma, is the absence of IGCNU (Intratubular Germ Cell Neoplasia, Unclassified type) in the adjacent testes, whereas IGCNU occurs with a usual teratoma in 90% of cases. Also, usual teratomas have cytologic atypia of its elements and associated testicular atrophy with impaired spermatogenesis. Dermoid cysts lack cytologic atypia, and in most cases, the adjacent testis has a normal appearance with active spermatogenesis, although there may be compressive atrophy in the parenchyma immediately adjacent to the cyst. Also, isochromosome 12p is present in most postpubertal teratomas, but not epidermoid cysts.
What features are seen in regressed testicular germ cell tumors?
A scarred nodule/stellate scar within the testis can be due to injuries or vascular lesions, or due to a regressed TGCT. Two pathognomonic findings of regressed TGCT are: large coarse intratubular calcifications in the scarred focus, and the presence of IGCNU associated with a scar. Other features that can be seen are: background testicular tissue wtih dysgenetic features including impaired spermatogenesis, tubular atrophy, and microliths; Leydig cell hyperplasia; clusters of hemosiderin within macrophages; hyalinized “ghost” tubules; many small vessels; and lymphoplasmacytic infiltrates.
IGCNU (Intratubular Germ Cell Neoplasia, Unclassified type) is present in the seminiferous tubules adjacent to ~___% of TGCTs. Men with IGCNU have a ___% chance of developing a TGCT in 5 years. IGCNU cells resemble ___ cells morphologically.
IGCNU (Intratubular Germ Cell Neoplasia, Unclassified type) is present in the seminiferous tubules adjacent to ~90% of TGCTs. Men with IGCNU have a 50% chance of developing a TGCT in 5 years. IGCNU cells resemble seminoma cells morphologically. They are located at the basilar aspects of seminiferous tubules lacking spermatogenesis, often in a patchy distribution. These cells usually stand out at low magnification b/c they have clear cytoplasm, and their nuclei are ~1.5x larger than the nuclei of the background spermatogonia. At high magnification, IGCNU cells have enlarged, hyperchromatic, polygonal nuclei with clumped chromatin and frequently “squared-off” flat edges; thickened nuclear membranes; 1 or 2 prominent nucleoli; and distinct cell membranes.
Atypical germ cells, some of which may simulate IGCNU, can be seen in the testes of patients with ___ (4).
Atypical germ cells, some of which may simulate IGCNU, can be seen in the testes of patients with cryptorchidism, hypofertility or infertility, sex development disorders, and, sometimes, in the background testis of pediatric TGCTs. They are germ cells with delayed maturation (in the pediatric cases), abnormal germ cells reflective of testicular maldevelopment, mature spermatogonia with reactive changes to an adjacent mass lesion, or atypical germ cells of unknown significance. Their features may include enlarged nuclei, multinucleation, nuclolar prominence, or nuclear hyperchromasia in the absence of nucleolar prominence. They may or may not be present in tubules with impaired spermatogenesis, whereas IGCNU usually occurs in tubules lacking spermatogenesis. Some atypical germ cells, although not neoplastic precursors themselves, may develop secondarily to factors that are also important in the pathogenesis of germ cell tumors.
Sertoli cell nodules in the testis.
Sertoli cell nodules, sometimes termed Pick adenomas, are nonneoplastic, probably self-regressing lesions that are usually incidental findings in either cryptorchid or normally descended testes. Although they usually present as incidental microscopic findings, Sertoli cell nodules may form macroscopic testicular masses up to 1 cm or greater. Macroscopic Sertoli cell nodule is a source of potential confusion with Sertoli cell tumors, which have malignant potential. Sertoli cell nodules are typically small (1 cm), composed of cells that are larger than fetal-type Sertoli cells, often with increased pleomorphism, mostly lack associated spermatogonia, and typically do not have prominent basement membrane deposits. Conspicuous mitotic figures may occur in some Sertoli cell tumors, and ~10% exhibit malignant behavior.
What is IDC-P?
Intraductal carcinoma of the prostate is a distinct clinicopathologic entity, characterized by an expansile proliferation of secretory cells within prostatic ducts and acini that demonstrate marked architectural and cytologic atypia. It is strongly associated with high-grade and high-volume, invasive prostate cancer and a poorer prognosis than cases without IDC-P. The distinction between IDC-P and cribriform HGPIN is important (especially in needle biopsies) b/c a diagnosis of IDC-P in a biopsy mandates an immediate repeat biopsy or even definitive therapy in the absence of documented invasive prostate cancer, while cribriform HGPIN on needle biopsy may not even be associated with a significantly increased cancer risk and whether rebiopsy is necessary is questioned.
What are histologic features that may be seen in intraductal carcinoma of the prostate?
Number of glands involved by IDC-P are many; often >6 per prostate gland. The gland size is larger than normal glands; can be >1 mm. Ductal-lobular structure show native ducts and acini are expanded and may show irregular and branching contours. Intraductal growth pattern can be of 4 types: 1. Loose cribriform with cells forming narrow strands (often 2 cells thick); spanning lumen without stromal support and intersecting randomly to form an orderly lacework of empty spaces. 2. Micropapillary with cells forming papillae with inconspicuous fibrovascular cores. 3. Dense cribriform with cells forming small, round “punched out” lumens that comprise >50% of the luminal space. 4. Solid cell mass. Four cytologic features: 1. Cuboidal or low columnar. 2. Significant nuclear atypia. 3. Nuclei 6 times larger than adjacent nonneoplastic nuclei. 4. Two cell populations with central small and uniform nuclei and peripheral pleomorphic nuclei may be seen in dense cribriform and solid patterns. Also, comedonecrosis may be present, and a basal cell layer is preserved at least focally.
