Guang-Qian Xiao

Nephrogenic Adenoma: Immunohistochemical Evaluation for Its Etiology and Differentiation From Prostatic Adenocarcinoma

CONTEXT Nephrogenic adenoma is a rare benign lesion of the urinary tract. Owing to its strong association with a history of urinary tract irritation, nephrogenic adenoma was initially thought to originate from urothelial metaplasia; however, no solid proof of this association has been found. More recent investigation has pointed to a renal tubular cause. In addition to its uncertain origin, there can be diagnostic difficulty in distinguishing nephrogenic adenoma from prostatic carcinoma, particularly when dealing with lesions from the prostatic urethra. OBJECTIVE To elucidate a possible histogenic relationship between nephrogenic adenoma and renal tubules, and also to evaluate the role of immunohistochemistry in the diagnostic distinction between nephrogenic adenoma and prostate carcinoma. DESIGN Immunohistochemical studies were performed for P504S, prostate-specific antigen, CD10, p63, and epithelial membrane antigen on 9 cases of nephrogenic adenoma, 10 cases of normal renal parenchyma, and 10 cases of prostatic tissue, both benign and malignant. RESULTS Nephrogenic adenoma shares the same immunohistochemical profile as distal renal tubules: both are positive for P504S and epithelial membrane antigen and negative for p63, CD10, and prostate-specific antigen. Prostatic adenocarcinoma tissue was positive for P504S and prostate-specific antigen, and normal prostatic gland tissue was positive for prostate-specific antigen and negative for P504S; p63-stained basal cells in normal prostatic gland tissue but did not react with prostatic adenocarcinoma tissue. The CD10 inconsistently stained normal and neoplastic prostatic gland tissue. Epithelial membrane antigen stain was negative in prostatic carcinoma, with rare occasional reactivity in normal prostatic glands. CONCLUSION These findings provide supporting evidence that nephrogenic adenoma is derived from distal renal tubules. Our results also demonstrated that the combination of P504S and prostate-specific antigen with epithelial membrane antigen is a valuable tool in distinguishing prostatic carcinoma from nephrogenic adenoma.

Loss of PLZF Expression in Prostate Cancer by Immunohistochemistry Correlates with Tumor Aggressiveness and Metastasis

PLZF is a transcription repressor, which plays a critical role in development, spermatogenesis and oncogenesis. Down-regulation of PLZF has been found in various tumor cell lines. There has been virtually no tissue study on the expression of PLZF in prostate cancer (PCa). PCa is a heterogeneous disease, most of which are indolent and non-lethal. Currently there are no biomarkers that distinguish indolent from aggressive PCa; therefore there is an urgent need for such markers to provide clinical decision support. This study aimed to investigate the expression of PLZF by immunohistochemistry in different grade as well as metastatic PCa and to correlate the alteration of PLZF expression with PCa aggressiveness. We studied a total of 83 primary PCa from biopsies, 43 metastatic PCa and 8 paired primary and metastatic PCa from radical prostatectomies with lymph node dissection. Our results demonstrated that PLZF was strongly expressed in almost all (~100%) benign luminal cells (n=77) and low grade (Gleason pattern 3) PCa (n=70) and weak or absent (100%) in basal cells (n=70). Decreased or lost expression of PLZF was evidenced in 26% of high-grade (Gleason 4 and 5) primary PCa (n=70) and 84% metastatic PCa (n=43). The primary high grade PCa in the prostatectomies shared similar PLZF loss/decrease and histomorphology to that of paired parallel lymph node metastases. These data demonstrated that down-regulation of PLZF is an important molecular process for tumor progression and loss of PLZF expression detected by routine immunohistochemistry is a promising and valuable biomarker for PCa aggressiveness and metastasis in the personalized care of PCa.

Metastatic Tumors to the Urinary Bladder Clinicopathologic Study of 11 Cases

Secondary neoplasms of the urinary bladder are uncommon, with metastatic tumors being an even rarer event. The authors studied the clinicopathology of 11 cases of metastatic tumors to bladder, which were collected from their archives between 1995 and 2010. The most common metastases in this series were breast. Some unusual metastases, including several not being previously reported, were also presented, namely, ileal carcinoid tumor, ileal gastrointestinal stromal tumor, ovarian squamous carcinoma, pancreatic gastrinoma, and renal collecting duct carcinoma. Vast majority of these patients (10/11, 91%) were female. Ninety percent of the patients presented with hematuria and/or obstructive urinary symptom as well as bladder lesions in the area of trigone, posterior wall, and/or bladder neck. Seven of the 11 patients had a known history of other metastases besides the bladder. Most of the patients (4/7, 57%) died within 1 year after diagnosis of bladder metastasis. Metastasis must be distinguished from a primary bladder neoplasm. Morphology and clinical correlation supplemented with immunohistochemical study is critical for the correct diagnosis.

Bilateral Sertoli cell tumors of the testis—a likely new extracolonic manifestation of familial adenomatous polyposis

Testicular Sertoli cell tumors are rare and usually sporadic and unifocal. The large cell calcifying Sertoli cell tumor variant is known to be associated with Carney and Peutz–Jeghers syndromes and can be bilateral in these patient populations. There has been no documented association of Sertoli cell tumor with familial adenomatous polyposis (FAP) in the literature. The case presented is a bilateral Sertoli cell tumor occurring in a 34-year-old patient with FAP. The tumor had a conventional Sertoli cell tumor morphology, but with different morphology in the left and right sites. Beta-catenin immunostain showed strong nuclear reactivity in the tumor cells but not the nonneoplastic Sertoli cells. The presence of bilaterality as well as overexpression of beta-catenin by this tumor supports an association of the development of Sertoli cell tumor with the patient’s FAP syndrome and adenomatous polyposis coli inactivation.

Undifferentiated carcinoma of the renal pelvis with osteoclast-like giant cells: a report of two cases

McCash SI, Unger P, Dillon R, Xiao G‐Q. Undifferentiated carcinoma of the renal pelvis with osteoclast‐like giant cells: a report of two cases. APMIS 2010; 118: 407–12.

‘Mohs surgery of the prostate’: the utility of in situ frozen section analysis during robotic prostatectomy: MOHS SURGERY OF THE PROSTATE

Study Type – Therapy (case series) Level of Evidence 4

Telangiectatic oncocytoma: a previously undescribed variant of renal oncocytoma.

OBJECTIVES To identify, describe, and investigate the clinical, radiologic, and pathologic features of 8 cases of telangiectatic oncocytoma. METHODS Fifty-three consecutive renal oncocytomas were reviewed for the telangiectatic pathologic features that were subsequently correlated with the demographic, clinical, and radiographic findings. RESULTS Telangiectatic oncocytoma accounted for 15% of the 53 renal oncocytomas collected in the past 7 years in our institution. On radiology, almost all presented as an enhancing mass and were suspicious for or consistent with a renal malignant tumor. Grossly, the tumors ranged from 2.4 to 6.0 cm (mean, 3.5 cm) and macroscopically were hemorrhagic spongy or multicystic masses without a central stellate scar. Microscopically, they were characterized by variably sized blood-distended spaces (<0.1-mm to 2- to 3-mm blood lakes) lined by typical oncocytoma cells and without evidence of degenerative changes. CONCLUSIONS With its unique radiologic and pathologic presentations in comparison with classic renal oncocytoma, it is important to recognize this new variant of renal oncocytoma.

Cytologic Findings of Rhabdoid Meningioma in Cerebrospinal Fluid

Rhabdoid meningioma is a recently described highgrade meningioma with rhabdoid cytomorphology.1 So far, only 1 case of rhabdoid meningioma with exfoliated neoplastic cells in cerebrospinal fluid (CSF) has been reported, which has been shown to be useful in diagnosis.2 We present here an additional such case. A 50-year-old man presented with headache, dizziness, increasing confusion and difficulty speaking. Computed tomography scan revealed a 3.5-cm, left anterior temporal lobe, intracerebral hemorrhagic lesion. Magnetic resonance imaging showed an enhanced left temporal, dura-based nodular component. Physical examination revealed no other remarkable neurologic symptoms. A CSF specimen was collected. Left temporal craniotomy was performed, and the left temporal lobe lesion was resected. Papanicolaou stain on a cytospin-prepared CSF specimen showed an increased cellular number of neoplastic cells, predominantly dispersed, with occasional loose clusters. The tumor cells displayed rhabdoid morphology; the nuclei were pleomorphic and eccentrically located, with irregular nuclear contour. The chromatin was coarsely granular, and nucleoli were inconspicuous. The cytoplasm was dense and well defined. No intranuclear inclusions were seen. Occasional mitoses were noted. Examination of the histologic section revealed loosely cohesive sheets of neoplastic cells with similar cytomorphology and typical rhabdoid features. The nuclei were pleomorphic and were oval to elongated, indented or irregular in shape, with coarsely granular chromatin and inconspicuous nucleoli. Cytoplasm was abundant, eosinophilic and dense. Mitoses were frequent (4 mitotic figures per 10 high-power fields). Illdefined whorls and intranuclear cytoplasmic pseudoinclusions were occasionally seen. Small foci of necrosis were present. Immunohistochemical stain on

ZBTB16: a novel sensitive and specific biomarker for yolk sac tumor

Although the function of zinc finger and BTB domain containing 16 (ZBTB16) in spermatogenesis is well documented, expression of ZBTB16 in germ cell tumors has not yet been studied. The aim of this study was to investigate the immunohistochemical expression and diagnostic utility of ZBTB16 in germ cell tumors. A total of 67 adult germ cell tumors were studied (62 testicular germ cell tumors, 2 ovarian yolk sac tumors, 1 mediastinal yolk sac tumor, and 2 retroperitoneal metastatic yolk sac tumors). The 62 testicular primary germ cell tumors are as follows: 34 pure germ cell tumors (20 seminomas, 8 embryonal carcinomas, 2 teratomas, 1 choriocarcinoma, 1 carcinoid, and 2 spermatocytic tumors) and 28 mixed germ cell tumors (composed of 13 embryonal carcinomas, 15 yolk sac tumors, 15 teratomas, 7 seminomas, and 3 choriocarcinomas in various combinations). Thirty-five cases contained germ cell neoplasia in situ. Yolk sac tumor was consistently reactive for ZBTB16. Among the 15 testicular yolk sac tumors in mixed germ cell tumors, all displayed moderate to diffuse ZBTB16 staining. ZBTB16 reactivity was present regardless of the histologic patterns of yolk sac tumor and ZBTB16 was able to pick up small foci of yolk sac tumor intermixed/embedded in other germ cell tumor subtype elements. Diffuse ZBTB16 immunoreactivity was also observed in 2/2 metastatic yolk sac tumors, 1/1 mediastinal yolk sac tumor, 2/2 ovarian yolk sac tumors, 2/2 spermatocytic tumors, 1/1 carcinoid, and the spermatogonial cells. All the other non-yolk sac germ cell tumors were nonreactive, including seminoma (n=27), embryonal carcinoma (n=21), teratoma (n=17), choriocarcinoma (n=4), and germ cell neoplasia in situ (n=35). The sensitivity and specificity of ZBTB16 in detecting yolk sac tumor among the germ cell tumors was 100% (20/20) and 96% (66/69), respectively. In conclusion, ZBTB16 is a highly sensitive and specific marker for yolk sac tumor.

Renal pelvic urothelial carcinoma with divergent morphology

Compared with that of urinary bladder, urothelial carcinoma of renal pelvis is infrequent and its morphologic features and presentations have seldom been described. Fifty-nine renal pelvic urothelial carcinomas were evaluated in this study. Seventy-eight percent of these were high-grade tumors, of which 39% contained variable amount of divergent morphology. Forty-four percent of the high-grade urothelial carcinomas presented with an advanced tumor stage. Seventy-eight percent of urothelial carcinomas with divergent morphology displayed a tumor stage of pT2 and above, compared with 21% of classical urothelial carcinomas, which presented at stage pT2 and above. In summary, high-grade and unusual morphology as well as advanced tumor stage were the frequent findings in pelvicalyceal urothelial carcinomas. In addition, divergent morphology was correlated with advanced tumor stage. The clinicopathologic features of pelvicalyceal urothelial carcinomas with unusual divergent morphology were particularly emphasized in this study.