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Objective To assess the relationship between the ISUP 2014 grading system, biochemical relapse (BCR) and clinical relapse (CLR) following radical prostatectomy, to determine whether the 2014 ISUP grading system is a better predictor of survival compared to the previous Gleason scoring systems, and to investigate whether incorporation of the tertiary pattern/grade into the ISUP scoring system significantly improves its efficacy. Patients and methods 635 radical prostatectomy cases (1991-1999) were identified from a database at a single institution. A histopathology review was performed to re-grade the cases as per the ISUP 2014 grading system. All relevant clinicopathological data and clinical follow up (median 15.25 years, 0.3-26 years) were obtained. Log rank, Kaplan Meier, Cox regression and Harrell's concordance c-indices analyses were performed. Results At a median follow up of 15 years, 276 (44%) of patients had BCR and 41 (7%) had clinical relapse. Grade Groups 1, 2, 3, 4 and 5 were seen in 112 (18%), 307 (48%), 129 (20%), 33 (5%) and 54 (9%) patients respectively: 337 (53%) were upgraded, while 70 (11%) were downgraded compared to the 1992 Gleason system. Grade Group (HR: 4.9, p

Marginal zone lymphoma (MZL), comprised of nodal, extranodal, and splenic subtypes, accounts for 5%-10% of non-Hodgkin lymphoma cases. A detailed evaluation of the independent effects of risk factors for MZL and its subtypes has not been conducted.Data were pooled from 1052 MZL cases (extranodal [EMZL] = 633, nodal [NMZL] = 157, splenic [SMZL] = 140) and 13766 controls from 12 case-control studies. Adjusted unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs).Novel findings for MZL subtypes include increased risk for B-cell activating autoimmune conditions (EMZL OR = 6.40, 95% CI = 4.24 to 9.68; NMZL OR = 7.80, 95% CI = 3.32 to 18.33; SMZL OR = 4.25, 95% CI = 1.49 to 12.14), hepatitis C virus seropositivity (EMZL OR = 5.29, 95% CI = 2.48 to 11.28), self-reported peptic ulcers (EMZL OR = 1.83, 95% CI = 1.35 to 2.49), asthma without other atopy (SMZL OR = 2.28, 95% CI = 1.23 to 4.23), family history of hematologic cancer (EMZL OR = 1.90, 95% CI = 1.37 to 2.62) and of non-Hodgkin lymphoma (NMZL OR = 2.82, 95% CI = 1.33 to 5.98), permanent hairdye use (SMZL OR = 6.59, 95% CI = 1.54 to 28.17), and occupation as a metalworker (NMZL OR = 3.56, 95% CI = 1.67 to 7.58). Reduced risks were observed with consumption of any alcohol (EMZL fourth quartile OR = 0.48, 95% CI = 0.28 to 0.82) and lower consumption of wine (NMZL first to third quartile ORs0.45) compared with nondrinkers, and occupation as a teacher (EMZL OR = 0.58, 95% CI = 0.37 to 0.88).Our results provide new data suggesting etiologic heterogeneity across MZL subtypes although a common risk of MZL associated with B-cell activating autoimmune conditions was found.

The etiology of mantle cell lymphoma (MCL), a distinctive subtype accounting for 2%-10% of all non-Hodgkin lymphoma, is not known.We investigated associations with self-reported medical history, lifestyle, family history, and occupational risk factors in a pooled analysis of 557 patients with MCL and 13766 controls from 13 case-control studies in Europe, North America, and Australia. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each exposure were examined using multivariate logistic regression models.The median age of the MCL patients was 62 years and 76% were men. Risk of MCL was inversely associated with history of hay fever (OR = 0.63, 95% CI = 0.48 to 0.82), and the association was independent of other atopic diseases and allergies. A hematological malignancy among first-degree relatives was associated with a twofold increased risk of MCL (OR = 1.99, 95% CI = 1.39 to 2.84), which was stronger in men (OR = 2.21, 95% CI = 1.44 to 3.38) than women (OR = 1.61, 95% CI = 0.82 to 3.19). A modestly increased risk of MCL was also observed in association with ever having lived on a farm (OR = 1.40, 95% CI = 1.03 to 1.90). Unlike some other non-Hodgkin lymphoma subtypes, MCL risk was not statistically significantly associated with autoimmune disorders, tobacco smoking, alcohol intake, body mass index, or ultraviolet radiation.The novel observations of a possible role for atopy and allergy and farm life in risk of MCL, together with confirmatory evidence of a familial link, suggest a multifactorial etiology of immune-related environmental exposures and genetic susceptibility. These findings provide guidance for future research in MCL etiology.

After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and “in situ” lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications.

Pituitary apoplexy has been recognised much more frequently since the introduction of CT and MRI scanning. Lymphocytic hypophysitis has been increasingly diagnosed in recent years. A case of pituitary apoplexy occurring in a patient with lymphocytic hypophysitis as part of a polyglandular syndrome is reported. This combination does not appear to have been previously reported. The pituitary haemorrhage was confirmed on MRI and at surgery. Lymphocytic hypophysitis was confirmed histologically. The apoplexy was accompanied by severe headache, elevation of the optic chiasm, developing field loss and onset of ptosis. The apoplexy was precipitated by neck extension.

To examine the association between histopathological factors of extraprostatic prostate cancer and outcome.Patients with extraprostatic extension (EPE) without positive margins, seminal vesicle or lymph node involvement were analysed from a consecutive radical prostatectomy cohort of 1136 (2002-2006) for: (i) distance of EPE from the margin; (ii) Gleason score of the EPE; and (iii) extent of EPE. Log-rank, Kaplan-Meier, and Cox regression analyses were performed.The study included 194 pT3a, pN0, R0 patients with a median follow-up of 5.4 years, with 37 (19%) patients experiencing biochemical relapse (BCR). On univariable analysis, patients with a Gleason score of ≥8 in the extraprostatic portion showed increased incidence of BCR compared with those with Gleason scores of ≤7 (P = 0.03). The proximity of the EPE to the margin (0.01-7.5 mm) did not correlate with BCR. On multivariable analysis, the extent of EPE, the Gleason score of the dominant nodule or of the EPE portion did not correlate with BCR.Data from this study using current International Society of Urological Pathology Gleason scoring and EPE criteria indicate that close proximity of EPE to the margin is not associated with recurrence. Gleason score ≥8 within EPE is associated with an increased BCR risk on univariable analysis, but larger studies are required to confirm whether extensive Gleason pattern 4 in an EPE indicates increased risk in an otherwise overall Gleason score 7 cancer.

There are limited data characterizing the subtype-specific incidence of lymphoid neoplasms in the World Health Organization (WHO) Classification era. Data were obtained on all incident lymphoid neoplasms registered in Australia during 1982-2006. Subtypes were grouped using the InterLymph nested hierarchical classification, based on the 2008 WHO Classification. Temporal trends were examined using Joinpoint regression; average annual percentage change in incidence was computed. Multiple Poisson regression was used to compare incidence by sex and age. The incidence of all non-Hodgkin lymphoma (NHL) increased by 2.5%/year during 1982-1996 and was stable thereafter. During 1997-2006, several mature B- and natural killer (NK)-/T-cell NHL subtypes increased in incidence, including diffuse large B-cell (1.3%/year), follicular (2.5%/year), Burkitt (6.8%/year), marginal zone (13.2%/year), mantle cell (4.2%/year), peripheral T-cell lymphoma (4.7%/year) and plasmacytoma (7.1%/year). While chronic lymphocytic leukemia incidence was stable, small lymphocytic lymphoma incidence declined (8.1%/year). Hodgkin lymphoma (HL) incidence increased during 1997-2006 (2.2%/year), both classical (4.3%/year) and nodular lymphocyte predominant (12.1%/year) HL. Diagnostic artifact, evidenced by a sustained decline in the incidence of NHL not otherwise specified (NOS; 5.8%/year) and lymphoid neoplasms NOS (5.6%/year), limits the interpretation of temporal trends for some subtypes. A marked male predominance was observed for almost all subtypes. Incidence of mature B- and NK-/T-cell NHL subtypes increased sharply with age, except for Burkitt lymphoma/leukemia. For HL subtypes, a bimodal age distribution was only evident for nodular sclerosis HL. Variation in incidence patterns over time and by sex and age supports etiological differences between lymphoid neoplasm subtypes.

Given the uncertainty surrounding solar ultraviolet radiation (UVR) exposure and risk of lymphoid neoplasms, we performed an ecological analysis of national Australian data for incident cases diagnosed between 2002 and 2006. Subtype-specific incidence was examined by latitude band (29°S, 29-36°S, ≥37°S), a proxy for ambient UVR exposure, using multiple Poisson regression, adjusted for sex, age-group and calendar year. Incidence increased with distance from the equator for several mature B-cell non-Hodgkin lymphomas, including diffuse large B-cell [incidence rate ratio (IRR) = 1.37; 95% confidence interval (CI): 1.16-1.61 for latitude ≥37°S relative to29°S], lymphoplasmacytic (IRR = 1.34; 95% CI: 1.12-1.61), mucosa-associated lymphoid tissue (IRR = 1.32; 95% CI: 0.97-1.80) and mantle cell lymphoma (IRR = 1.29; 95% CI: 1.05-1.58), as well as plasmacytoma (IRR = 1.52; 95% CI: 1.09-2.11) and plasma cell myeloma (IRR = 1.15; 95% CI: 1.03-1.27). A similar pattern was observed for several mature cutaneous T-cell neoplasms, including primary cutaneous anaplastic large cell lymphoma (IRR = 4.26; 95% CI: 1.85-9.84), mycosis fungoides/Sézary syndrome (IRR = 1.72; 95% CI: 1.20-2.46), and peripheral T-cell lymphoma not otherwise specified (NOS) (IRR = 1.53; 95% CI: 1.17-2.00). Incidence of mixed cellularity/lymphocyte-depleted (IRR = 1.60; 95% CI: 1.16-2.20) and nodular sclerosis Hodgkin lymphoma (IRR = 1.57; 95% CI: 1.33-1.85) also increased with distance from the equator. Many of these subtypes have a known association with infection or immune dysregulation. Our findings support a possible protective effect of UVR exposure on the risk of several lymphoid neoplasms, possibly through vitamin D-related immune modulation critical in lymphomagenesis.

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30-35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin-positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy.• To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin.• Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected. • Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin.• At a median follow-up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%. • On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82-4.32, P0.001) compared with the presence of Gleason grade 3. • Linear extent of margin involvement was also associated with recurrence (P= 0.009). • Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence. • On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29-4.03, P= 0.003).• The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.

Predicting outcome for men with clinically localized prostate carcinoma treated with curative intent remains imprecise and further evaluation of accepted and potential predictive factors is needed.The authors studied 696 men with localized prostate carcinoma diagnosed on transrectal biopsy and treated with radical prostatectomy at one institution between 1986 and 1999 to determine the relation between putative pretreatment prognostic factors and disease-free survival. Clinical stage, Gleason score, perineural invasion, number of biopsies containing tumor, and serum prostate specific antigen (PSA) were evaluated as predictors of extracapsular extension, seminal vesicle involvement, lymph node metastases, and surgical margin involvement as well as outcome after surgery. Kaplan-Meier method and Cox regression analyses were used to evaluate the contribution of different factors to adverse pathologic features and relapse.At mean follow-up of 56.9 months (range, 1.0-177.9 months; median, 54.9 months), 26.1% (182 of 696 patients) of patients had developed a disease recurrence. Pretreatment serum PSA concentration, biopsy Gleason score, and clinical stage as well as number of biopsies involved with tumor as a percentage of the total number obtained were found to be independent predictors of outcome. In patients with PSA10 ng/mL, biopsy perineural invasion and percentage of biopsies containing tumor were found to independently predicted disease recurrent. Increased number of biopsies involved with tumor independently predicted extracapsular extension, margin involvement, seminal vesicle, and lymph node involvement.This study demonstrated that the proportion of prostate biopsy cores containing tumor is an independent predictor of outcome after subsequent radical prostatectomy and suggested that perineural invasion has a predictive role in patients with a preoperative PSA10 ng/ml.

People with congenital or acquired immune deficiency have rates of non-Hodgkin lymphoma (NHL) that are raised 50 fold or more above population rates, but it is unknown whether risk of NHL is associated with other forms of immune dysregulation. We performed a population based case-control study of risk factors for NHL in adults aged 20–74 years in New South Wales and the Australian Capital Territory, Australia. We investigated the association of NHL risk with atopy, which is associated with a Th2 dominant immune response. In addition, we investigated the association of NHL with birth order and childhood crowding, which are known to predict atopy. Cases with NHL were selected from a cancer register (n=704), and controls (n=694) were randomly selected from state electoral rolls and frequency-matched to cases by age, sex and area. Cases with clinically apparent immune deficiency were excluded. Birth order, childhood crowding and history of atopic conditions (hayfever, asthma, eczema, and specific allergies) were assessed by questionnaire and by interview. Logistic regression models of NHL risk included the three matching variables as covariates. Being an only child or first born child of a larger family was strongly inversely associated with risk of NHL. Compared to a fourth or later born child, the odds ratios (OR) for development of NHL were 0.52 (95% CI 0.32–0.84) for an only child, 0.55 (95% CI 0.40–0.75) for a first-born child, and 0.70 (95% CI 0.51–0.96) and 0.81 (95 % CI 0.57–1.14) respectively for second and third born children (p trend < 0.0001). Indicators of crowding in later childhood, such as ever sharing a bed or bedroom, and number of years of sharing, were not associated with NHL risk. Diagnosis of atopic conditions was also inversely associated with NHL risk. Self-reported histories of hayfever, asthma, eczema and food allergies were each associated with reduced NHL risk; this reduction was significant for hayfever (OR 0.65, 95% CI 0.52–0.82) and food allergies (OR 0.29, 95% CI 0.20–0.42), but not significant for asthma (OR 0.88, 95% CI 0.67–1.17) and eczema (OR 0.79, 95% CI 0.57–1.10). In summary, being an only or other first born child and reporting a history of atopic conditions were associated with reduced NHL risk. Taken together, these data suggest a hypothesis that late exposure to infections in early life and atopic conditions, both of which are associated with a predominant Th2 response, are associated with a reduced risk of NHL.

A case of eccrine porocarcinoma in a 63-yr-old man is reported. There was a 10 yr history of an abdominal skin lesion which recurred after cautery and metastasized to skin and abdominal lymph nodes. Histologically, the primary tumour was composed of small squamoid cells with ductal lumina. There was intraepidermal nesting spread and an invasive dermal component. Formation of intracytoplasmic lumina in cells with squamoid features, best seen on electron microscopy, pointed towards poral differentiation and was a useful diagnostic feature which persisted in the less well differentiated metastases. The role of hidroacanthoma simplex as a possible preinvasive precursor lesion is discussed. The differential diagnosis from other skin tumours is described. The literature is reviewed. Despite their sometimes innocuous histological appearance, eccrine porocarcinomas are aggressive lesions which require wide local excision of the primary site and consideration of regional lymph node dissection.