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John R Srigley

Publications and source records attributed to John R Srigley.

18 recordsLinked to original sources
PubMed2006

Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer.

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.

Adenocarcinoma↗
PubMed2006

Immunohistochemical analysis of mucinous tubular and spindle cell carcinoma and papillary renal cell carcinoma of the kidney: significant immunophenotypic overlap warrants diagnostic caution.

Mucinous tubular and spindle cell carcinoma, a rare, recently described distinctive subtype of renal cell carcinoma, may have some morphologic similarities to the more common papillary renal cell carcinoma, particularly the basophilic (type 1) tumors with prominent solid growth pattern. Tumor circumscription, compact tubular architecture, focal papillations, mucin production and foam cells (features seen in both papillary renal cell carcinoma and mucinous tubular and spindle cell carcinoma), as well as spindle cell morphology, have resulted in some cases sent to us in consultation with a question of possible sarcomatoid papillary renal cell carcinoma. In this study, tissue microarrays with triplicate samples each from 27 mucinous tubular and spindle cell carcinomas and 20 papillary renal cell carcinomas were created to simulate experience in renal biopsy specimens. From immunohistochemistry (IHC) data, published in the contemporary literature, a panel consisting of alpha-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), epithelial membrane antigen (EMA), renal cell carcinoma marker (RCC Ma), CD10, high molecular weight cytokeratin (HMWK), and c-kit was designed to test its utility in differential diagnosis. The immunoreactivity in mucinous tubular and spindle cell carcinoma was AMACR 93%, CK7 81%, EMA 95%, RCC Ma 7%, CD10 15%, HMWK 15%, and c-kit 5% and in papillary renal cell carcinoma was AMACR 95%, CK7 65%, EMA 88%, RCC Ma 25%, CD10 80%, HWMK 15%, and c-kit 18%. This largest study to date on IHC of mucinous tubular and spindle cell carcinoma dispels the specificity of AMACR for papillary renal cell carcinoma among the RCC subtypes. The histogenesis of mucinous tubular and spindle cell carcinoma from the distal nephron continues to be debatable, as our study showed the expression of the proximal convoluted tubule-related marker AMACR among these tumors. Thus, in tumors with predominant compact tubular growth and focal papillary architectures, careful attention to the presence of a low-grade spindle cell population may be helpful in the distinction of mucinous tubular and spindle cell carcinoma, as the key immunohistochemical stains for papillary renal cell carcinoma are also expressed in this subtype of renal cell carcinoma.

Adenocarcinoma, Mucinous↗
PubMed2006

Key issues in handling and reporting radical prostatectomy specimens.

CONTEXT: Patients with prostatic adenocarcinoma commonly undergo radical prostatectomy, and it is often difficult and time consuming to handle the resulting specimens and to report the findings. Pathologic information derived from the radical prostatectomy specimen is used for selecting adjuvant therapy, such as radiotherapy and hormone therapy, and for determining a patient's prognosis. The prostate specimen must be handled in a systematic fashion to derive the appropriate prognostic parameters. OBJECTIVE: To review the prognostic factors of relevance in classifying radical prostatectomy specimens, using the College of American Pathologists categorization system, including a detailed survey of the morphologic-based factors but excluding other factors such as DNA ploidy and novel phenotypic and genotypic markers. CONCLUSIONS: Gleason score, pathologic stage, and margin status are considered category 1 prognostic factors, which are of proven prognostic significance and are useful in patient management. Factors such as tumor volume (intraglandular extent) and tumor subtype are considered category 2 prognostic factors, which show significant promise but require validation in multivariate analysis. Lymphovascular space invasion is a promising category 3 prognostic factor that needs additional study. Perineural invasion is an almost ubiquitous finding in radical prostatectomy specimens and is considered a category 3 prognostic factor. After prognostic factors have been analyzed at the histologic level, it is critical to report the findings in a clear and unambiguous fashion. The synoptic style of reporting is ideal for describing complex cancer resection specimens. A synoptic report based on an evidence-based checklist, such as the one developed by the College of American Pathologists, effectively communicates complex cancer-related data, such as radical prostatectomy specimen findings. This information is used not only for individual case management with respect to treatment and prognostication but also for purposes such as education, research, quality monitoring, and system planning.

Adenocarcinoma↗
PubMed2005

Mucin-producing urothelial-type adenocarcinoma of prostate: report of two cases of a rare and diagnostically challenging entity.

The differential diagnosis of mucin-producing adenocarcinoma of the prostate includes conventional prostatic adenocarcinoma with mucin production, secondary adenocarcinoma usually of colorectal origin and, very rarely, urothelial-type adenocarcinoma arising from either the prostatic urethra or proximal ducts. Conventional prostatic adenocarcinoma with mucin production is readily identified by routine microscopy and immunohistochemistry. The distinction between secondary adenocarcinoma and urothelial-type adenocarcinoma, however, can present a significant diagnostic challenge. In addition, documented examples of the latter in the prostate are exceptionally rare. A transurethral resection of prostate specimen and prostatic needle biopsies from two patients showing urothelial-type adenocarcinoma of the prostate were identified in our consultation files. One of the patients subsequently underwent a radical prostatectomy. Both patients had negative gastrointestinal endoscopic workups. Transurethral resection of prostate material from two patients with clinically confirmed secondary adenocarcinoma of colonic origin involving the prostate and a prostatectomy specimen with mucinous conventional prostatic adenocarcinoma were also identified for comparison purposes. Formalin-fixed, paraffin-embedded sections were stained for prostate-specific antigen (PSA), prostatic acid phosphatase, carcinoembryonic antigen, cytokeratin 7, cytokeratin 20 and high molecular weight cytokeratin 34betaE12. The urothelial-type adenocarcinoma cases were diffusely positive for cytokeratin 7 and focally positive for 34betaE12 and cytokeratin 20, consistent with an origin from the urothelium of the prostatic urethra or proximal prostatic ducts. In contrast, the secondary adenocarcinoma of colonic origin cases were diffusely cytokeratin 20 positive and either negative or focally positive for cytokeratin 7 and negative for 34betaE12. The mucinous conventional prostatic adenocarcinoma was positive for PSA and prostatic acid phosphatase and negative for cytokeratin 7, cytokeratin 20 and 34betaE12. All tumors were positive for carcinoembryonic antigen.

Acid Phosphatase↗
PubMed2005

Prognostic and predictive factors in prostate cancer: historical perspectives and recent international consensus initiatives.

An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer. More recently, serum prostate-specific antigen measurement has assumed a significant prognostic role. Over the last two decades there has been an explosion of research into biomarkers, many of which have been purported to have prognostic significance. In this paper we present an overview of the various consensus initiatives that have transpired over the last dozen years. Criteria for evaluating prognostic factors and classifications of predictive factors have emerged that have proven useful and advanced our understanding of the biology of prostate cancer. The results of these consensus initiatives form a foundation on which the current international consultation on prognosis (prediction) in prostate cancer is built. Advances in our understanding of the new and promising prognostic factors will require a more rigorous evidence-based approach to the analysis of published studies. Furthermore, appropriate mathematical models for the analysis of the multiple factors that influence a prognostic system will have to be employed.

Adenocarcinoma↗
PubMed2005

Prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens.

The information provided in the surgical pathology report of a prostate needle biopsy of carcinoma has become critical in the subsequent management and prognostication of the cancer. The surgical pathology report should thus be comprehensive and yet succinct in providing relevant information consistently to urologists, radiation oncologists and oncologists and, thereby, to the patient. This paper reflects the current recommendations of the 2004 World Health Organization-sponsored International Consultation, which was co-sponsored by the College of American Pathologists. It builds on the existing work of several organizations, including the College of American Pathologists, the Association of Directors of Anatomic and Surgical Pathologists, the Royal Society of Pathologists, the European Society of Urologic Pathology and the European Randomized Study of Screening for Prostate Cancer.

Biomarkers, Tumor↗
PubMed2005

Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens.

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry.

Biomarkers, Tumor↗
PubMed2004

Benign mimickers of prostatic adenocarcinoma.

The diagnosis of prostatic adenocarcinoma, especially when present in small amounts, is often challenging. Before making a diagnosis of carcinoma, it is prudent for the pathologist to consider the various benign patterns and processes that can simulate prostatic adenocarcinoma. A useful method of classifying benign mimickers is in relationship to the major growth patterns depicted in the classical Gleason diagram. The four major patterns are small gland, large gland, fused gland and solid. Most mimickers fit within the small gland category and the most common ones giving rise to false-positive cancer diagnosis are atrophy, post-atrophic hyperplasia, atypical adenomatous hyperplasia and seminal vesicle-type tissue. A number of other histoanatomic structures such as Cowper's gland, verumontanum mucosal glands, mesonephric glands and paraganglionic tissue may be confused with adenocarcinoma. Additionally, metaplastic and hyperplastic processes within the prostate may be confused with adenocarcinoma. Furthermore, inflammatory processes including granulomatous prostatitis, xanthogranulomatous prostatitis and malakoplakia may simulate high-grade adenocarcinoma. Atypical adenomatous hyperplasia (adenosis), a putative precursor of transition zone adenocarcinoma, has overlapping features with low-grade adenocarcinoma and may cause problems in differential diagnosis, especially in the needle biopsy setting. The pathologist's awareness of the vast array of benign mimickers is important in the systematic approach to the diagnosis of prostatic adenocarcinoma. Knowledge of these patterns on routine microscopy coupled with the prudent use of immunohistochemistry will lead to a correct diagnosis and avert a false-positive cancer interpretation.

Adenocarcinoma↗
PubMed2004

Basal cell proliferations of the prostate other than usual basal cell hyperplasia: a clinicopathologic study of 23 cases, including four carcinomas, with a proposed classification.

Basaloid proliferations of the prostate with morphologic patterns other than usual basal cell hyperplasia are rare, and the distinction between benign and malignant lesions has been difficult. We describe 23 such lesions and classify them into two groups: adenoid cystic-like hyperplasia and adenoid cystic or basaloid carcinoma. Adenoid cystic-like hyperplasia (n = 19) was characterized by an older age at presentation (mean, 71.8 years), transition zone location with background of nodular hyperplasia, multifocality, lobulation, circumscription, and small acini with occasional hyalinization. A cribriform pattern limited to small- and medium-sized glands, squamous metaplasia, and hypercellular myxoid stroma were occasionally seen. Adenoid cystic carcinoma (n = 3) was characterized by a younger age at presentation (mean, 46.0 years), peripheral zone involvement, and large acini that were often dilated and exhibited extensive interanastomoses, prominent intraglandular hyalinization, perineural invasion, and extraprostatic extension. Basaloid carcinoma (n = 1) showed infiltration between normal glands, perineural invasion, and extraprostatic extension but lacked a cribriform architecture. The degree of cytologic atypia and mitotic rate overlapped between the hyperplasia and carcinoma cases. Both hyperplastic lesions and adenoid cystic carcinomas showed a basal cell phenotype with strong immunoreactivity to cytokeratins 14 and 34betaE12, but the basaloid carcinoma was negative for these markers. In all cases, the proliferating basal cells were nonreactive for myoepithelial and prostatic secretory cell markers. The 8 patients with adenoid cystic-like hyperplasia with available follow-up information had no progression of disease (mean follow-up period, 8.6 years). One patient with adenoid cystic carcinoma died with widespread metastases, but the 3 other patients with carcinomas had no disease progression (mean follow-up period, 7.0 years). In conclusion, most florid basaloid proliferations of the prostate fall into one of two categories. In the first, there is a clear association with nodular hyperplasia (adenoid cystic-like hyperplasia) and, although cytologic atypia and mitoses may be seen, they are present within a lesion that retains an orderly, vaguely nodular (noninfiltrative) pattern. The second group of cases (adenoid cystic and basaloid carcinoma) shows a widespread, haphazard infiltrative growth pattern. This study suggests that adenoid cystic carcinomas are biologically indolent following prostatectomy but have a low risk of distant metastasis.

Adult↗
PubMed2003

Inflammatory myofibroblastic tumors of the kidney: a clinicopathologic and immunohistochemical study of 12 cases.

Inflammatory myofibroblastic tumor is a rare entity composed of spindle cells admixed with variable amounts of extracellular collagen, lymphocytes, and plasma cells. In the genitourinary tract, inflammatory myofibroblastic tumor most commonly occurs in the bladder. Isolated case studies of inflammatory myofibroblastic tumor of the kidney, renal pelvis, and ureter have been previously reported. Our series includes 12 cases of inflammatory myofibroblastic tumor occurring in the renal pelvis (six cases), renal parenchyma (four cases), and immediate perirenal soft tissue (two cases). Clinical presentation included flank pain (two patients), painless gross hematuria (one patient), and ureteropelvic junction stenosis with hydronephrosis (one patient). The remaining eight patients were asymptomatic. All patients underwent nephrectomy. The tumors were characterized by firm white tissue or had a myxoid "gelatinous" appearance. Three histologic patterns were identified in the tumors, including a myxoid vascular pattern, a compact spindle cell pattern, and a hypocellular fibrous pattern. Immunohistochemical and electron microscopic studies supported a myofibroblastic proliferation. All cases were negative for anaplastic lymphoma kinase. Follow-up was available in eight cases and ranged from 1 to 17 years with no evidence of recurrence. Based on this series, renal inflammatory myofibroblastic tumor is a proliferative lesion of myofibroblasts of uncertain pathogenesis with no identified potential for recurrence or metastases.

Actins↗
PubMed2002

Pathologic effects of neoadjuvant cyproterone acetate on nonneoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma: a detailed analysis of radical prostatectomy specimens from a randomized trial.

Neoadjuvant hormonal therapy (NHT; androgen ablation) is used prior to radical prostatectomy (RP) in an attempt to pathologically "downstage" prostatic adenocarcinoma and ultimately to improve disease-free survival. This study describes the pathologic effects of NHT with the antiandrogen cyproterone acetate, 300 mg/day for 12 weeks, on the RP specimens from men with clinically localized (stage T1 or T2) prostatic adenocarcinoma. There were 101 men in the pretreatment group (CPA) and 91 men in a control group who were treated with surgery alone. The prevalence and extent of morphologic effects were recorded for the nonneoplastic prostate, high-grade prostatic intraepithelial neoplasia, and invasive adenocarcinoma. The commonest effects on the nonneoplastic prostate were atrophy and basal cell hyperplasia and prominence. High-grade prostatic intraepithelial neoplasia was more commonly identified in the surgery alone group than the CPA group (p <0.01). In the CPA group, flat and low tufted patterns of high-grade prostatic intraepithelial neoplasia predominated. Following NHT, the adenocarcinoma showed characteristic morphologic alterations, including reduction in cytoplasmic quantity, cytoplasmic vacuolation, nuclear pyknosis, reduced gland diameter, and mucinous breakdown. In many cases there was prominence of collagenous stroma, obscuring malignant glands. Compared with the surgery alone group, the CPA group RP specimens had a significantly lower mean specimen weight (40.3 g vs 46.5 g, p = 0.025) and less tumor extent by several measures. Organ-confined tumor (stage pT2, margin negative) was found in 41.6% of the CPA group compared with 19.8% of the surgery alone group (p = 0.0017). The overall rate of margin positivity was lower in the CPA group (27.7% vs 64.8%, p = 0.001). We consider that the difference in margin positivity is the result of tumor shrinkage with a decreased likelihood of sampling in routine sections. There was no significant difference in the rate of extraprostatic extension between the two groups. There was elevation of the Gleason score in the RP specimens versus baseline biopsy in 60% of the CPA group compared with 33% of the surgery alone group (p = 0.02). The higher rate of elevation in the CPA group largely resulted from an increase in primary or secondary Gleason score 5 tumor, a morphologic artifact introduced by NHT. Because of this, we recommend not giving a Gleason grade to RP specimens following NHT. Monotherapy with CPA has similar pathologic effects on benign and malignant prostate tissue as does dual agent androgen blockade. Prolonged follow-up of these patients is required to determine if NHT with CPA leads to improved disease-free survival.

Adenocarcinoma↗
PubMed2002

Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells.

We report 19 Leydig cell tumors (LCTs) of the testis with adipose differentiation (n = 12) and/or spindle cell growth (n = 8) in patients 28-70 years of age; three tumors with adipose differentiation showed psammomatous calcifications, two of which also had foci of ossification. In eight tumors fat-like cells apparently derived from lipid accumulation within neoplastic Leydig cells and appeared as focal to prominent clusters in a background of vacuolated, neoplastic Leydig cells. The fat-like cells were usually immunoreactive for Leydig cell markers (inhibin-alpha, calretinin, and melan-A) but were typically strongly positive for the adipose tissue marker, S-100 protein, supporting a hybrid cell phenotype. Four tumors had fat of stromal derivation. In two of these there were intermixed mature adipocytes, but in two others only lipoblastic cells were present. These four tumors lacked vacuolated, neoplastic Leydig cells, and the fat cells in the single case studied were negative for inhibin-alpha and melan-A but positive for S-100. Three of the 12 LCTs with adipose differentiation were clinically malignant, and each had several of the established malignant features. Eight tumors with spindle cells occurred in men 34-70 years of age. Two tumors had ill-defined fascicles of spindle cells, and three showed prominent edematous to myxoid areas with spindle-shaped tumor cells. Two additional tumors had a fibroma-like spindled component that blended with islands of more plump, polygonal to spindle-shaped Leydig cells. Finally, one tumor had foci resembling an unclassified sarcoma that merged with conventional LCT; the spindle cell component in this case did not react for Leydig cell markers in contrast to the spindle cells in five of the six other cases in which immunostains were performed. Spindle cell differentiation, by itself, did not appear to have prognostic significance. Of the six patients with available follow-up, two developed metastases, but their tumors had malignant features apart from spindle cells; the remaining four patients were disease free at a mean of 3.6 years. Awareness of these unusual patterns in LCTs may prevent misinterpretation of fat admixed with neoplastic Leydig cells as evidence of extratesticular growth (a criterion for malignant LCT) may help avoid misdiagnosis of a LCT as a testicular "tumor" of the adrenogenital syndrome (which may contain fat) and may prevent misdiagnosis of a LCT with spindle cells as a sarcoma or unclassified sex cord-stromal tumor.

Adipose Tissue↗
PubMed2002

Solutions must include the community hospitals.

The authors of this commentary acknowledge that Academic Health Sciences Centres(AHSCs) will need to change, but they assert that the need for change and urgency are even more dramatic than presented by Lozon and Fox. While the AHSCs are likely to survive, their form and fabric are likely to change dramatically in the new order. Any solutions to the problems of the AHSCs have to include the community hospital stakeholders, especially the evolving regional teaching hospitals. This applies not only to patient care but also to the potential teaching and research (clinical trials) contributions of the community/regional players. There must also be more involvement by non-medical faculties in defining the vision, mission and values of the AHSC. Federal funding should be available not only to enhance the research activity of the AHSCs and the regional partners but also to provide the informatic linkages between players. Alternative funding programs for academic physicians along with enhanced productivity measures in areas of patient care, education and research are important in order to level the playing field not only with respect to remuneration but also with respect to other incentives such as recognition and promotion.

Academic Medical Centers↗
PubMedDate not supplied

Common and uncommon histologic subtypes of renal cell carcinoma: imaging spectrum with pathologic correlation.

Renal cell carcinoma (RCC) is a cause of significant morbidity and mortality, with an estimated 35,000 new cases and 12,480 deaths in the United States in 2003. Recent advances in imaging technology, pathology, urology, and oncology permit early diagnosis of RCC and facilitate optimal management. The 2004 World Health Organization classification for renal neoplasms recognizes several distinct histologic subtypes of RCC. These subtypes include clear cell RCC, papillary RCC, chromophobe RCC, hereditary cancer syndromes, multilocular cystic RCC, collecting duct carcinoma, medullary carcinoma, mucinous tubular and spindle cell carcinoma, neuroblastoma-associated RCC, Xp11.2 translocation-TFE3 carcinoma, and unclassified lesions. Different histologic subtypes of RCC have characteristic histomorphologic and biologic profiles. Clear cell RCC is the most common subtype and has a less favorable prognosis (stage for stage) than do papillary RCC and chromophobe RCC. Collecting duct carcinoma and renal medullary carcinoma are associated with aggressive clinical behavior and a poor prognosis.

Carcinoma, Renal Cell↗