Search

Pathologic processes involving the urachus are usually related to inflammatory or sinofistular conditions. Neoplasms rarely arise within this structure, and when they do occur, they are typically epithelial, with mucinous adenocarcinoma being the most common. Mesenchymal lesions, both benign and malignant, have rarely been described in this location. We report the case of a 66-year-old white man who presented with a primary urachal malignant fibrous histiocytoma and died of metastatic disease 20 months after the initial diagnosis. This is an unusual case of malignant fibrous histiocytoma arising in a urachal remnant. [ABSTRACT FROM AUTHOR]

Aberrant prostatic tissue occurs commonly in the adult male urethra and bladder. Ectopic prostatic tissue occurring outside the urinary system is rare. One case with scattered prostate-type glands in epididymis has been reported in the literature. We report a related case, in which the presence of prostate gland-like epithelium was recognized in epididymal glands in routine histology and was confirmed by subsequent immunohistochemical analysis using prostate-specific antigen. We then examined 23 additional orchiectomy specimens for the presence of prostate-like epithelium. The possibility of this being true ectopia versus an unusual metaplastic change is discussed. [ABSTRACT FROM AUTHOR]

The nested variant of urothelial carcinoma is a recently described bladder tumor entity with a rare incidence. Two cases of this disease are presented in this report; the patients in both cases were elderly men, with a predominant involvement of the trigone region. Histologically, the tumor cells were arranged in ill-defined nests and had low-grade nuclear features. Both cases had a diffusely infiltrating growth pattern with widespread local disease at cystectomy. Strong immunohistochemical staining for p63 in the neoplastic cells supports the urothelial cell nature of this neoplasm. High p53 and Ki-67 indices of this tumor correlate with the aggressiveness of this subtype. [ABSTRACT FROM AUTHOR]

Background and Purpose: To determine the factors associated with a positive post-treatment prostate biopsy (PB) and the effects of local failure on biochemical control and cause-specific survival (CSS) in men receiving prostate brachytherapy., Methods and Materials: Of 545 men with post-implant PB, 484 were routine (median 24 months) while 61 (median 55 months) were for cause. 114 had a repeat PB for rising PSA. Initial mean PSA was 10.5 ng/ml (±13.9) while 244 (44.8%), 202 (37.1%) and 99 (18.2%) had low, intermediate or high-risk disease. Treatments were implant only in 287 (52.7%), and implant with androgen deprivation therapy (ADT) ± external beam in 258. Radiation doses were converted to the biologically equivalent dose (BED). Final biopsy results were the last biopsy performed on that patient. Associations for the first and final biopsies with PSA, clinical stage (CS), Gleason grade group, time on hormone therapy (ADT) and BED were determined by ANOVA, chi-square and binary linear regression. Freedom from Phoenix failure (FFPF) and cause-specific survival were estimated by Kaplan Meier method and Cox proportions hazards., Results: After a median of 11.4 years the first and final biopsy were positive in 10.8% and 8.8%, respectively. Significant linear regression associations with first positive PB were ADT (p = 0.005), CS (p = 0.044) and BED (p = 0.030) while only BED (p < 0.001) was significant for the final PB. Positive biopsy occurred in 21/112 (18.8%), 16/230 (7.0%) and 3/182 (1.6%) for BED ≤150, >150-200 and >200 Gy (p < 0.001), and in 29/261 (11.1%) for BED (median) ≤185 Gy vs. 5/263 (1.9%) for > 185 Gy (OR 4.2, p < 0.001). 15-year FFPF was 75.6 vs. 17.5% and cause-specific survival was 94.2 vs. 75.5% for negative vs. positive biopsy., Conclusions: Higher radiation doses are associated with 1.9% late local failure following prostate brachytherapy. A negative post-implant PB is associated with superior FFPF and decreased prostate cancer mortality., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The morphology of Gleason 4 prostate cancer (PCa) can be subdivided into cribriform and non-cribriform patterns. A large body of evidence has shown that pattern 4 cribriform PCa (especially non-glomeruloid type) is associated with adverse pathologic features and clinical outcomes compared with non-cribriform pattern 4 PCa. The underlying mechanisms for the aggressiveness of cribriform PCa are not fully understood. The aim of this study is to compare the immunohistochemical expression of various biomarkers and to determine the potential proteins that may account for their biologic and clinical differences. A total of 14 biomarkers were studied. The number of non-glomeruloid cribriform PCa cases studied for each biomarker ranged from 18 to 74 and the number of non-cribriform pattern 4 PCa studied for each biomarker ranged from 29 to 112. We demonstrated that, compared with non-cribriform Gleason pattern 4 PCa, EGFR was significantly upregulated and standard CD44 (CD44s) was significantly downregulated in cribriform PCa; no significant differences were found in the expression of AR, NKX3.1, ERG, EZH2, p53, Rb, C-Myc, BCL2, p16, CyclinD1, Her2/Neu, and Synaptophysin between these two groups of pattern 4 PCa. The study also showed, compared to non-cribriform PCa, cribriform PCa presented with significantly higher serum PSA and more advanced tumor stage. The significant overexpression of EGFR and downregulation of CD44s in non-glomeruloid cribriform PCa may, at least, partly explain the unfavorable pathology and clinical results for this growth pattern. Given that EGFR targeted inhibitors are now available, the findings may also have significant therapeutic implications., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Muscle invasive bladder cancer, an aggressive disease with heterogeneous molecular profiles, has recently been subclassified into three major molecular subtypes -basal, luminal and "p53-like" urothelial carcinomas (UCas), which bear prognostic and therapeutic implication. Similar to breast cancer, basal and luminal subtype UCas are designated by basal (CK5/14) and luminal (CK20) markers. The "p53-like" subtype presents with wild-type p53 gene with upregulated p53 pathways and is implicated in chemoresistance. Urinary bladder is one of the most common primary sites of extrapulmonary small cell carcinoma (SmCC). Bladder SmCC frequently coexists with UCa; however, the relation of SmCC with specific UCa molecular subtypes has not been studied. The aim of this study is to investigate the clinicopathology and immunophenotypes of the combined SmCC and UCa molecular subtypes. A total of 22 combined SmCC and UCa cases were studied for the clinicopathology and immunohistochemical (IHC) profiles by luminal and basal cell markers as well as Her2/Neu and p53. Our results demonstrated that all the urinary bladder SmCCs were associated with high grade UCas. They were more commonly seen in older male patients with a smoking history and had a poor prognosis. Based on the reported molecular subtyping, the UCas could be immunohistochemically subclassified into luminal, basal, dual and null types, which showed different clinicopathologic and IHC features. Compared to non-SmCC associated UCa, the subtypes of UCa in the combined SmCCs and UCas were characterized by: 1) Although overall luminal type was still relatively more common in men, basal marker-expressing subtypes were significantly increased in incidence and were more common in women. 2) Her2/Neu overexpression was more commonly observed in luminal than basal cell marker-expressing UCas. 3) IHC overexpression of p53 was common in all the subtypes, with UCas and SmCCs sharing the same p53 expression pattern. Although limited by relatively a small number of cases, the results of this study will enhance our understanding of the combined SmCC and UCa entity and potentially lead to a future therapeutic management.

Sertoliform cystadenoma is a rare benign tumor of the rete testis with 8 previously reported cases and an additional 14 cases reported in an abstract form. It usually presents with a unilateral scrotal mass, clinically and radiologically indistinguishable from malignant testicular tumors. We report a 39-year-old man who presented with a right testicular mass. The patient underwent radical inguinal orchiectomy. Grossly, no masses were appreciated. After histologic examination with subsequent immunohistochemical staining, a sertoliform cystadenoma of the rete testis was diagnosed.

Signet ring cell prostatic intraepithelial neoplasia is a rare speculated variant of high-grade prostatic intraepithelial neoplasia (HGPIN). Here, we present a free-standing and isolated signet ring cell HGPIN that was not associated with invasive carcinoma on needle biopsy and demonstrated the existence of this type of HGPIN variant. The differentiation between HGPIN and intraductal carcinoma of prostate is also discussed.

Prostate cancer is one of the most common cancers among men worldwide and in the USA. Most prostate cancer progression either locally invades to seminal vesicles or metastasizes distally to bone. Skin is not a common site of metastasis for the majority of malignancies including prostate cancer. This paper reports two extremely rare cases of prostate carcinoma metastatic to the skin: a 74-year-old man previously treated with radiation for prostate cancer with cutaneous metastases to the shoulder and a 68-year-old man with prostate adenocarcinoma and cutaneous metastases to the groin. Both patients were diagnosed with skin punch biopsy and later confirmed with immunohistochemical staining for PSA and prostate specific acid phosphatase, specific for prostatic carcinoma. Although unusual, development of multiple skin lesions in patients with prostate adenocarcinoma should raise the flags of cutaneous metastases.

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.

There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P < .0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P < .0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P < .05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Histone H1.5 (HH1.5) is a somatic subtype of the histone H1 family of linker proteins that are located in the nucleus and play a role in stabilizing higher-order chromatin structure, gene expression, DNA repair, and cell proliferation. Recently, differential immunohistochemical expression of HH1.5 has been found in various neuroendocrine neoplasms. This study aimed to investigate the immunohistochemical expression of HH1.5 in prostatic adenocarcinomas. Sixty-three prostate needle core biopsies, 9 radical prostatectomy specimens, and 3 metastatic prostate cancer cases were evaluated. HH1.5 immunohistochemistry revealed strong nuclear reactivity in 68 (93%) of 73 cases of prostate adenocarcinomas, compared to only 7 (9%) of 75 cases of benign prostatic glands (P ≤ .0001). In all positive benign prostate epithelium, HH1.5 was limited to focal and weak reactivity. Similarly, all 23 foci of high-grade prostatic intraepithelial neoplasia exhibited focal staining, with the vast majority having only weak nuclear reactivity. Increased HH1.5 reactivity was observed in Gleason patterns 4 and 5 as compared to Gleason pattern 3, 72% and 56%, respectively (P ≤ .02). All 3 metastatic prostate cancer cases showed strong nuclear reactivity. HH1.5 may be a useful diagnostic tool in evaluating prostatic biopsies, particularly with small foci of cancer. Further studies are needed to support these findings and investigate the possible prognostic significance of HH1.5 in prostatic adenocarcinomas., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We present a case of a 61-year-old female presenting with a bladder tumor that occurred 7 years after her previous diagnosis of Clark's level III mid-back melanoma. The bladder tumor was submitted to histopathology without accompanying clinical history, and an initial diagnosis of high-grade urothelial carcinoma was rendered based on epithelioid and sarcomatoid appearing pleomorphic histopathology. We present this case to highlight the diagnostic challenge presented by the rare occurrence of metastatic melanoma to the urinary bladder and the potential pitfall of this lesion being diagnosed as high-grade urothelial carcinoma in the presence of limited clinical history., (© The Author(s) 2013.)

Micropapillary pattern of growth (MPG) of carcinoma is a unique morphologic pattern. It is uncommon but a predictor of poor outcome. MPG has not been described in any germ cell tumor, most notably embryonal carcinoma, which may have papillary configuration. In this study, we reviewed 25 primary testicular germ cell tumors (pure or mixed) containing embryonal carcinoma and 2 lymph node metastases with embryonal carcinoma. Five of the 25 primary cases demonstrated MPG. With available clinical information, 3/3 (100%) cases with MPG and 5/12 (42%) cases without MPG showed evidence of metastases. The 2 lymph node metastases contained predominantly MPG. At metastasis, the median tumor size in primary tumors with MPG was significantly smaller than in those without MPG. Reticulum staining was negative in the regions of MPG and positive for other coexisting non-micropapillary growth patterns in all the 6 embryonal carcinomas. In conclusion, we described MPG in embryonal carcinoma. Although limited by the number of cases, our clinicopathological correlation results raised the possible association of the presence of MPG to the high-rate metastasis of embryonal carcinoma, similar to that seen in other carcinomas with MPG. It is therefore of importance to document this variant growth pattern if present in embryonal carcinoma. We also demonstrated that reticulum is a useful negative marker for identification of MPG.

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.

Inactivation of the transcription factor/tumor suppressor Krüppel-like factor 6 (KLF6) has been described in prostate cancer (PC). This study investigated the prevalence and significance of KLF6 exon 2 mutations and splice variants (SVs) in different stages of human PC progression. By using laser-capture microdissection and recombinant clone isolation of DNA sequences to enhance sensitivity, base changes were found in 20 (24.7%) of 81 PC tissues versus 1 (4%) of 25 normal prostate tissues (P = 0.02). Of 26 base changes, 54% produced nonsynonymous mutations. Only three mutations had driver characteristics (PCs, 4%; NPs, 0%). By using microdissection of fresh-frozen tissues and recombinant isolation of RNA sequences, SVs were found in 39 (75%) of 52 PCs and in 10 (45%) of 22 NPs (P = 0.01). Sixteen different SVs, including 13 unique SVs, were identified that used cryptic splicing sites and encoded nonfunctional KLF6 proteins. PCs that had survived hormone (androgen)-deprivation therapy (n = 21) had a significantly higher (P < 0.05) incidence, number, and expression level of nonfunctional SVs than either NPs (n = 22) or hormone-naïve PCs (n = 25). Forced expression of nonfunctional SVs conferred a survival advantage of androgen-dependent LNCaP cells under castration-simulated culture conditions. Together, these data suggest that decreased availability of functional KLF6 contributes to clinical PC progression. This decrease arises infrequently by somatic mutation and more commonly by the acquisition of SVs that provide a survival advantage under castrate conditions, enabling resistance to hormone therapy., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

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.

Diagnoses of prostatic carcinoma (PC) have increased with widespread screening. While the use of α-methylacyl coA racemase and high molecular weight cytokeratins have aided in distinguishing benign mimics from malignancy, their sensitivity and specificity are limited. We studied 6C4, a monoclonal antibody to glutamate receptor 2, an excitatory amino acid receptor subunit distributed throughout the central nervous system, on benign prostatic epithelium, high-grade prostatic intraepithelial neoplasia, and PC. Ten cases with post-atrophic or adenosis-like prostate glands were also stained with prostatic intraepithelial neoplasia 4, an immunostain cocktail against α-methylacyl coA racemase, p63, and high molecular weight cytokeratin, in parallel with 6C4. Immunoreactivity for 6C4 was graded as negative (0% to 10%), +1 (11%% to 50%), and +2 (>50%). Malignant epithelium was classified by Gleason patterns. Gleason patterns 4 and 5 were subdivided into cribriform or noncribriform type. Its utility in distinguishing postatrophic or adenosis-like glands from prostate cancer, both of which show absence of basal cells on prostatic intraepithelial neoplasia 4 immunostain, was also investigated. Our results revealed a statistically significant difference in staining of benign secretory prostatic epithelium, high-grade prostatic intraepithelial neoplasia, and low Gleason pattern carcinomas. The results also showed 6C4 is a sensitive marker in separating basal cell negative postatrophic or adenosis-like glands from prostate carcinoma. In addition, there was a statistically significant difference between staining of cribriform versus noncribriform Gleason pattern 4 and 5 carcinomas. A limited number of lymph node metastases from cribriform and noncribriform carcinomas were studied, and they stained the same as the primary tumor in the majority of cases. In conclusion, our preliminary data demonstrated potential utility of 6C4 in the pathologic evaluation of PC.

The gC1qR (i.e., gC1q receptor, gC1q binding protein, p32, p33) is a multifunctional cellular protein that interacts with components of the complement, kinin, and coagulation cascades and select microbial pathogens. Enhanced gC1qR expression has been reported in adenocarcinomas arising in a variety of organs. The present study compared gC1qR expression in normal, inflammatory, dysplastic, and malignant tissue of epithelial and mesenchymal origin. gC1qR expression was visualized in tissue sections by immunohistochemistry using the 60.11 monoclonal antibody (i.e., IgG(1) mouse monoclonal antibody directed against gC1qR) and the UltraVision LP Detection System. Sections were counterstained with hematoxylin and examined by light microscopy. Strongest gC1qR expression was noted in epithelial tumors of breast, prostate, liver, lung, and colon, as well as in squamous and basal cell carcinoma of the skin. However, increased gC1qR staining was appreciated also in inflammatory and proliferative lesions of the same cell types, as well as in normal continuously dividing cells. In contrast, tumors of mesenchymal origin generally stained weakly, with the exception of osteoblasts, which stained in both benign and malignant tissues. The data suggest that increased gC1qR expression may be a marker of benign and pathologic cell proliferation, particularly in cells of epithelial origin, with potential diagnostic and therapeutic applications.

Although urothelial metaplasia has been reported in the fallopian tube, urothelium in the seminal vesicle has been rarely reported. We report 2 cases of urothelial epithelium in seminal vesicles from radical prostatectomy specimens. One case involved a 63-year-old patient with pT2c prostatic adenocarcinoma (Gleason pattern 3+4; total score, 7). The other case involved a 60-year-old patient with pT2c prostatic adenocarcinoma (Gleason pattern 4+3; total score, 7; with focal Gleason pattern 5). Representative sections of the left seminal vesicles from both patients demonstrated a portion of urothelial epithelium consisting of 3 to 8 cell layers, which included superficial (umbrella), intermediate, and basal cells. An abrupt transition from the normal single layer of cuboidal cells of seminal vesicle to multilayered urothelium was identified in 1 case, and circumferential urothelium was identified in the other case. No urothelial metaplasia was seen in the prostatic tissue. The histogenesis of urothelial metaplasia in the seminal vesicle is unclear, but it possibly is a reaction to mechanical irritation, inflammation, or infection, as has been proposed for urothelial metaplasia in the fallopian tube and squamous metaplasia of the pelvic peritoneum. Nevertheless, a rare congenital malformation cannot be ruled out as an etiology. Clinical follow-up of patients with urothelial cell metaplasia of the fimbriae suggests that it bears no biologic significance, yielding no instances of carcinoma. However, whether there will be an impact on fertility awaits further study., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Paraganglia are an uncommon but previously reported finding in the genitourinary system. Recognition of this entity in the prostate is important in distinguishing it from prostatic adenocarcinoma. In this series, 1230 radical prostectomy specimens were examined for the presence of paraganglia, and a total of 57 cases (4.5%) were found to contain paraganglia. The majority of paraganglia were extraprostatic and could easily mimic extension of prostatic adenocarcinoma into extraprostatic tissue. It is important to recognize paraganglia, particularly when they are extraprostatic and could confer a falsely higher tumor stage to the patient. The paraganglia demonstrated characteristic histology, and immunohistochemistry was supportive when enough tissue was available. No association between patient age and frequency of paraganglia was found.

Two cases are presented in which microscopic groups of retroperitoneal paraganglionic cells simulated metastatic seminomatous tumor. Both patients had histories of mixed testicular germ cell tumor with abdominal metastases and had been treated with chemotherapy. Persistent retroperitoneal disease was favored on follow-up imaging studies. Subsequent retroperitoneal lymph node dissection disclosed multifocal epithelioid cell groups with clear/vacuolated cytoplasm in the fibroconnective and adipose tissue, ranging from 1.0 to 3.0 mm in size. These cell groups were initially interpreted as recurrent metastatic seminoma, but were later reinterpreted as paraganglionic cells, which were confirmed by immunohistochemical analysis. The pathologic features for distinguishing paraganglionic cells from metastatic seminoma are discussed. Awareness of the presence of paraganglia and their distinction from metastatic disease is of practical importance in avoiding an overdiagnosis of malignancy and assuring proper patient management.

Müllerianosis of the bladder is an infrequently described lesion consisting of multiple Müllerian-type tissues within the urinary bladder. Few previous cases of pure endosalpingiosis have been described. Here we present a 54-year-old post-menopausal female with a history of prior pelvic surgery with traumatic bladder injury, who was found to have a cystic lesion in the posterior wall of the bladder. Routine histology demonstrated cyst epithelium characteristic of endosalpingiosis. Three benign Fallopian tube specimens were obtained and stained with the relevant immunohistochemical markers for comparison. Results showed an identical immunohistochemical profile between the bladder cyst lining and the normal Fallopian tube controls. This case represents a rare instance of pure endosalpingiosis of the urinary bladder, with a likely implantative origin. This form of bladder Müllerianosis should therefore be considered within the differential diagnosis of cystic lesions of the bladder.

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

Changes in morphologic patterns over a time course following radiation and their corresponding PSA levels were investigated. A total of 60 patients with prostatic adenocarcinoma treated with brachytherapy between 1993 and 2003, who had at least one positive post-radiation biopsy, were evaluated for their morphologic patterns as well as the associated PSA levels. A total of 86 positive post-radiation biopsies were performed. There were 17 patients with more than 1 positive post-radiation biopsy and 43 patients with single positive biopsy. Among the 17 with more than 1 positive biopsy, the morphologic patterns of treatment effect were commonly followed by patterns without treatment effect on subsequent biopsies. The morphology without treatment effect followed by treatment effect was infrequent. Furthermore, over a time course, the later the positive post-radiation biopsy, the much more common the morphologic pattern without treatment effect was observed. Compared to the morphologic pattern with treatment effect, the morphology without treatment effect was associated with a significantly higher PSA level (mean 0.69 versus 2.78 ng/ml, p<0.05). An increase in the Gleason's score in recurrent carcinoma was also noted in 14% of the cases. Multiple factors were likely involved in the variability of the changes in post-radiation morphologic patterns. A new neoplastic process was particularly considered in some of our cases, which may merit clinical attention. The significant difference in PSA levels between carcinomas without treatment effect and those with treatment effect also suggested a post-radiation variation of tumor biology and a potential role of these patterns in monitoring and managing the patients treated with brachytherapy.

There are 3 case series reports describing benign epithelial inclusions in nodal sinuses of perinephric lymph nodes of pediatric patients. The majority of these inclusions were observed in perinephric lymph nodes removed during nephrectomies from pediatric patients with Wilms' tumors. We report 2 cases of benign renal tubular epithelial inclusions located in the perinephric hilar lymph nodes. One of our cases is, to our knowledge, the first case of benign renal epithelial inclusions reported in an adult patient.

We report 2 patients with conventional prostatic adenocarcinoma who developed sarcomatoid carcinoma of probable prostatic origin 6 and 2.5 years after radiation treatment (seed implantation and external beam). Our cases had histologic features consistent with those cases previously reported in the literature. The tumors consisted of spindle cells with large hyperchromatic nuclei and a pattern mimicking a sarcoma. Immunohistochemical studies showed the tumors to be weakly positive for EMA, CK7, and vimentin. Ki67 staining showed positivity in more than 50% of tumor cells. The tumors also stained diffusely positive for p53 and p63. PSA and PAP were negative. Clinically, the sarcomatoid carcinomas appeared to be of prostatic origin. The pathogenesis of the tumors is still uncertain but most likely represent a radiation-induced dedifferentiation of prostatic adenocarcinoma.

Urinary bladder adenocarcinomas are rare malignancies accounting for approximately 2.5% of all urothelial neoplasms. Intestinal metaplasia of the urothelium indicates the presence of intestinal-type goblet cells and was generally observed to coexist with or to precede the diagnosis of bladder adenocarcinomas. Controversy continues of whether intestinal metaplasia is an acquired precancerous lesion, secondary to different insults to the urothelium, or a concomitant lesion in glandular carcinogenesis. Patients with neurogenic bladders are particularly at risk for developing bladder cancer, mostly squamous cell carcinoma and rarely adenocarcinoma. In these patients, chronic irritation of the urothelium as well as long-term indwelling urinary catheters were the most significant risk factors. Spina bifida is a congenital developmental abnormality that may result in neurogenic bladder. There is only one previously reported case of urothelial carcinoma with associated squamous metaplasia of the bladder occurring in a spina bifida patient. We report the first case of bladder adenocarcinoma associated with intestinal metaplasia occurring in a spina bifida occulta patient. The patient had a complicated clinical course and suffered recurrent urinary tract infections, renal calculi, and urinary incontinence and was managed with intermittent as well as indwelling catheterization.

The X-linked inhibitor of apoptosis (XIAP) is the most potent of the inhibitors of apoptosis, a group of related caspase inhibitors. X-linked inhibitor of apoptosis expression correlates with radio- and chemoresistance and clinical aggressiveness in certain tumors. XIAP expression was examined in 106 specimens from neoplastic and other thyroid disorders, which underwent citrate-based antigen retrieval and staining with monoclonal anti-XIAP. Normal thyroid was XIAP-negative. Of 35 papillary thyroid carcinomas (PTCs), 29 (83%) stained variably in intensity and/or extent. An insular carcinoma was strongly positive and 1 of 4 anaplastic carcinomas moderately positive. Follicular, medullary, and 3 of 4 anaplastic carcinomas, oncocytic neoplasms, and a hyalinizing trabecular tumor were nonstaining. Hashimoto's thyroiditis and adenomatous goiters were either nonstaining or occasionally stained in oncocytic foci. Because XIAP was highly specific for PTC among the thyroid neoplasms, it may be a useful marker for differential diagnosis when used alone or in combination with other markers. XIAP may also be useful in differentiating insular carcinoma from follicular neoplasm in certain difficult cases. In addition, the selective expression of XIAP in PTC and some high-grade thyroid malignancies also provides clues to the role of the apoptotic pathway in the tumorigenesis of these neoplasms.

p63 is a novel transcription factor-encoding gene with sequence homology to p53. p63 proteins have epithelial stem-cell regulatory functions and play a critical role in tissue development. Study of p63 expression in testicular germ cell tumors has been limited. Thirty-four archival cases of testicular germ cell neoplasia were examined and stained with monoclonal anti-p63 antibody 4A4 using standard methods. Included were 19 seminomas, 1 pure teratoma, 3 pure embryonal carcinomas, 1 pure yolk sac tumor, and 10 mixed germ cell tumors. p63 staining was consistently positive in teratomas in areas of squamous differentiation and in basal reserve-like cells in foci of respiratory/endodermal differentiation. Strong p63 staining was observed within cytotrophoblasts of choriocarcinoma (1/1), whereas focal positivity was detected in embryonal carcinomas (4/10) and yolk sac tumors (2/5). Seminomas and intratubular germ cell neoplasia were p63-negative. These findings may suggest the presence of pluripotent p63-positive stem cell-like nests in yolk sac tumors and embryonal carcinomas or may represent areas of an occult teratoma phenotype undetectable histopathologically on hemotoxylin-eosin sections. p63 positivity in cytotrophoblasts of choriocarcinoma is consistent with gynecologic studies, possibly reflecting the role of p63 in the oncogenesis of neoplastic trophoblasts. The consistent p63 negativity in seminomas may reflect a precommitted embryonic precursor-like phenotype.

Aggressive angiomyxoma (AA), first described by Steeper and Rosai (Am J SurgPathol. 1983;7:463-475), is a rare locally infiltrative tumor that usually arises in the pelvic and perineal soft tissues of young women. Approximately 150 cases have been reported in women. Aggressive angiomyxoma has a high rate of local recurrence because of its infiltrative growth and anatomical location making complete excision with wide margins difficult. To our knowledge, 39 cases of AA occurring in men have been reported in the literature. Sites frequently involved include the scrotum, spermatic cord, inguinal region, and perineum. The gross and microscopic appearances and clinical course are similar to those described in female cases. Immunohistochemistry evaluating estrogen and progesterone receptors (ER and PR, respectively), although frequently positive in the female cases, has rarely been studied in the male cases. We report the clinicopathologic features of 4 additional cases of AA in men with particular emphasis on hormone (ER/PR) receptor status. Hormone reactivity is significant in that AA may arise from specialized hormonally responsive stromal cells of the perineum and may potentially play a therapeutic role in unresectable tumors. From our small series, hormone positivity (1 case of ER+, 3 cases of PR+) does occur in the male cases of AA, and a large number of cases should be examined to determine the frequency at which these tumors express hormone receptors.

Adrenocortical oncocytoma is exceptionally rare. Most of these tumors are benign and nonfunctioning. We report a case of functioning adrenocortical oncocytoma located in the right adrenal gland in a 53-year-old woman who presented with Cushing's syndrome. The tumor was small, with exclusively oncocytic histologic features. A discussion of this case and a review of the literature on this entity is presented.

Testicular carcinoids are rare and the majority are of primary testicular origin. Testicular carcinoids can also be secondary from extra-testicular primary tumors, but the incidence is even less common. The case described here is a patient who initially had an infiltrating cecal carcinoid with hepatic metastasis. Following surgery, he was managed with octreotide and had close monitoring of the levels of serum serotonin and its urinary metabolite. He experienced a fairly indolent clinical course and 5 years after excision of the primary cecal carcinoid, his hepatic lesion has virtually been unchanged. However, he developed a secondary testicular metastasis. He has otherwise remained well, without evidence of metastases elsewhere on imaging studies.

Pathologic processes involving the urachus are usually related to inflammatory or sinofistular conditions. Neoplasms rarely arise within this structure, and when they do occur, they are typically epithelial, with mucinous adenocarcinoma being the most common. Mesenchymal lesions, both benign and malignant, have rarely been described in this location. We report the case of a 66-year-old white man who presented with a primary urachal malignant fibrous histiocytoma and died of metastatic disease 20 months after the initial diagnosis. This is an unusual case of malignant fibrous histiocytoma arising in a urachal remnant.

Prostate androgen regulated (PAR) is a 1038bp novel gene located on chromosome 1 in epidermal differentiation complex. The gene is ubiquitously expressed in normal tissues and is overexpressed in most of their malignant counterparts. PAR cellular function is unknown. Here we report the effect of increased PAR expression induced by transfection of PAR cDNA on NIH3T3 cell phenotype. PAR-NIH3T3 transfectants expressing 3- to 4-fold higher PAR levels compared to controls grew faster in tissue cultures, formed colonies in soft agar, and exhibited a shortening of G1 and S phases of cell cycle and formed tumors in SCID mice. Transfection of NIH3T3 cells with increased ectopic PAR expression with a 22 mer oligonucleotide in antisense orientation with PAR mRNA abrogated their ability to form colonies in soft agar. The data presented here along with our previously reported results on DU145 cells transfected with antisense PAR cDNA suggest that PAR gene behaves like a proto-oncogene.

A cDNA clone of 1.1 kb encoding a 108-aa polypeptide was isolated from a human pituitary cDNA library by expression cloning. This protein was named tumor differentiation factor (TDF). The recombinant TDF protein and a 20-aa peptide, P1, selected from the ORF of the gene, induced morphological and biochemical changes consistent with differentiation of human breast and prostate cancer cells. Fibroblast, kidney, hepatoma, and leukemic lymphocytic cell lines were unaffected. Breast and prostate cancer cells aggregated in spheroid-like structures within 24 h of exposure to TDF. This effect was abrogated by a specific affinity-purified rabbit polyclonal anti-P1 Ab. E-cadherin expression was increased in a dose-dependent manner by TDF. Treatment of MCF7 cells with TDF led to production of a lactalbumin-related protein. Peptide P1 significantly decreased the growth of androgen-independent DU145 prostate cancer in severe combined immunodeficient mice. The presence of TDF protein in human sera was detected by the anti-P1 Ab, suggesting a role of TDF in endocrine metabolism. The fact that all activities of TDF can be mimicked by a peptide derived from the encoding TDF sequence opens the possibility of therapeutic applications.

Atypical fibrous histiocytoma is a rare neoplasm. A scrotal location for this tumor is even more unusual. We report a case of a 90-year-old man with scrotal atypical fibrous histiocytoma. Our case had histologic features consistent with those cases previously reported in the literature. The tumor consists of cells with large hyperchromatic irregular nuclei, bizarre multinucleated cells (monster cells), and xanthomatous cells with large prominent nuclei set in a background of classic fibrous histiocytoma. Rare mitotic figures are identified. Immunohistochemical studies showed the tumor cells to be positive for vimentin, smooth muscle actin, desmin, KP-1, factor XIIIa, and MIB-1 (less than 10%). In addition to the expected immunohistochemical studies, the tumor stained diffusely positive for CD117. To our knowledge, this is the first report of atypical fibrous histiocytoma of the scrotum.

Angiomyolipoma of the bladder is an extremely rare neoplasm. We report a case of a 55-year-old woman with an angiomyolipoma of the bladder visualized on pelvic sonogram as a 5 mm polyp in the floor of the bladder. The lesional tissue consisted of spindle cells, epithelioid cells, and adipocytes, with occasional thick-walled blood vessels. Immunohistochemical studies showed the spindle and epithelioid cells to be focally positive for HMB-45 and diffusely positive for actin and muscle cell antigen (HHF-35), which confirmed the diagnosis of angiomyolipoma. A review of the recent literature on the pathogenesis of angiomyolipoma follows., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Granulosa cell tumor is almost exclusively an ovarian tumor. Rare cases of granulosa cell tumor have been reported involving the testes. We report a testicular gonadal stromal tumor with granulosa cell differentiation in a 54-year-old white man. The tumor was discovered by an ultrasound evaluation for left hydrocele. The patient was clinically asymptomatic. On frozen section, the initial impression was a malignant lymphoma. Final histology on the orchiectomy specimen showed a gonadal stromal tumor with granulosa cell features. Immunohistochemical studies excluded malignant lymphoma and germ cell tumors, consistent with a stromal tumor. This case report illustrates the challenges for the pathologist in making an accurate diagnosis in unusual testicular tumors., (Copyright 2002 by W.B. Saunders Company)

Primary angiosarcomas of the adrenal gland are exceptionally rare vascular tumors. We report a case of a 63-year-old man with an epithelioid angiosarcoma of the left adrenal gland. Visualized on computed tomography as a nonhomogeneous round mass, the tumor measured 3 cm in diameter. Histology showed a vascular tumor composed of epithelioid cells with vesicular nuclei and prominent nucleoli that lined irregular vascular spaces and also formed solid areas and showed pleomorphism and rare mitotic activity. Immunohistochemical stain confirmed the diagnosis of epithelioid angiosarcoma. We report our findings and review previously described literature cases of this rare entity., (Copyright 2001 by W.B. Saunders Company)

We report the case of a 77-year-old white woman who presented with a left breast mass, lethargy, and weight loss. Pelvic computed tomographic scan revealed a 9.5-cm mass in the right kidney. Surgical pathology demonstrated a diffuse large B-cell lymphoma of the subcutaneous tissue of the breast and renal cell carcinoma with concurrent extensive intravascular lymphomatosis. Systemic dissemination of malignant lymphoma to a concurrent visceral primary neoplasm is rare. To the best of our knowledge, this is the first case illustrating a renal cell carcinoma collision with intravascular lymphomatosis.

The presence of immunoreactive prostate-specific antigen (IR-PSA) has been reported in breast cancers and has been suggested to confer a positive prognosis. However, recent large, well-controlled studies have found no significant prognostic value when IR-PSA positivity is examined as an independent variable, even when ultrasensitive immunofluorometric techniques are utilized. The present study, using indirect immunohistochemistry on 75 formalin-fixed, paraffin-embedded breast cancers shows PSA immunoreactivity in only seven of 75 cases (9%), suggesting that PSA positivity in breast carcinoma is not useful as a prognostic or tumor marker with hospital-based methods.

We report a patient who presented initially with a right lower quadrant mass which was attached to the anterior abdominal wall. The final pathological diagnosis was adenocarcinoma of the urachus, an exceedingly rare bladder tumor.

Objective: Localized seminal vesicle amyloidosis is an unusual finding in surgical pathology material. Previous studies have demonstrated that the amyloid is directly produced by the seminal vesicle epithelial cells. We investigated the possible association of seminal vesicle amyloid in patients hormonally treated for prostate carcinoma., Methods: Cases were collected from over 200 prostate needle biopsies, seminal vesicle biopsies, and prostatectomy specimens from the surgical pathology files at The Mount Sinai Hospital, New York, NY. None of the patients with seminal vesicle amyloidosis had a chronic inflammatory disorder, serum or urine protein abnormalities, or other identifiable masses., Results: Six cases of localized seminal vesicle amyloidosis were found in the surgical pathology material examined. Five of the six cases had prostatic carcinoma, and one case was seen in a biopsy for benign prostatic hyperplasia. Four of the five carcinoma cases had prior hormonal treatment (luteinizing hormone-releasing hormone agonist with an antiandrogen agent, and one patient, in addition, had received radiotherapy). The amyloid deposits were limited to the seminal vesicle lamina propria without involvement of vascular walls. The amyloid reacted with Congo red staining that was sensitive to potassium permanganate. Immunohistochemically, all cases were negative for AA amyloid, beta 2-microglobulin, and kappa and lambda light chains., Conclusion: We raise the possibility that in some instances, prior hormonal therapy may act as a seminal vesicle epithelial stimulant for the elaboration of this protein.