Prostatic transitional cell carcinoma: pathologic features and clinical management

Prostatic involvement by transitional cell carcinoma (pTCC) in patients with bladder cancer is a frequent finding, particularly in patients with high-grade invasive tumor and urothelial carcinoma in situ. Various patterns and levels of prostatic involvement have been described, and their impact in patients’ management and their prognosis recognized. The role of prostatic urethral biopsy and intraoperative frozen section in the management of bladder cancer, tailoring to the bladder tumor stage is still not well defined and universally accepted. This review discusses the current understanding of the biology and histological patterns of pTCC and their clinical significance and management options. A rational approach for management of pTCC in patients with bladder cancer will be proposed on the basis of our experience and our review of literature.     

Prostatic transitional cell carcinoma: pathologic features and clinical management

Prostatic involvement by transitional cell carcinoma (pTCC) in patients with bladder cancer is a frequent finding, particularly in patients with high-grade invasive tumor and urothelial carcinoma in situ. Various patterns and levels of prostatic involvement have been described, and their impact in patients' management and their prognosis recognized. The role of prostatic urethral biopsy and intraoperative frozen section in the management of bladder cancer, tailoring to the bladder tumor stage is still not well defined and universally accepted. This review discusses the current understanding of the biology and histological patterns of pTCC and their clinical significance and management options. A rational approach for management of pTCC in patients with bladder cancer will be proposed on the basis of our experience and our review of literature.     

Case report. Fatal Aspergillus flavus pericarditis in a patient with acute myeloblastic leukaemia

We report a case of Aspergillus flavus pericarditis treated with fluconazole for oral candidosis. The patient with acute myeloblastic leukaemia developed tachypnoea after antileukaemic chemotherapy. Pericardial effusion was seen in the echocardiogram. Aspergillus flavus was isolated from the pericardial fluid. The patient died from aspergillosis, before the antimycotic treatment could be changed to amphotericin B.     

Metastatic prostate carcinoma to bone: clinical and pathologic features associated with cancer-specific survival

BACKGROUND: The objective of this study was to examine the clinical and pathologic features of metastatic prostate carcinoma to bone in a large cohort of men, and the associations of these features with outcome. METHODS: Sixty-eight men who underwent surgery for metastatic prostate carcinoma to bone for stabilization of a pathologic fracture or impending fracture were studied. Clinical characteristics included the type of treatment for the primary and metastatic prostate carcinoma, age and serum prostate specific antigen (PSA) at the diagnosis of the metastatic prostate carcinoma, radiographic findings of the metastasis (osteoblastic, osteolytic, or mixed), and the number of metastatic sites at the time of the surgery for the metastasis. Pathologic features examined included Gleason score of the metastatic prostate carcinoma. Immunohistochemical stains for MIB-1, cytokeratin, PSA, synaptophysin, chromogranin A, serotonin, estrogen receptor, progesterone receptor, and androgen receptor were performed for all cases. The Kaplan-Meier method was used to estimate cancer-specific survival. The duration of follow-up was defined as the interval from the date of surgery for the metastasis to the date of death or last follow-up. Univariate and multivariate Cox proportional hazards models were fit to assess the features that were associated with death from prostate carcinoma. RESULTS: The average (standard deviation) time from the surgery for the metastasis to death from prostate carcinoma was 1.5 (1.9) years, ranging from 0 days to 10 years, with a median of 1 year. The estimated cancer-specific survival rates at 1 year, 2 years, and 3 years were 54.3%, 28.8%, and 22.9%, respectively. Median cancer-specific survival occurred at 1.1 years. After 4 years of follow-up, there were only seven patients left at risk for death from prostate carcinoma. Features that were found to be significantly associated with death from prostate carcinoma univariately included the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), androgen deprivation therapy before surgery for the metastasis (P = 0.002), presentation with metastasis (P = 0.003), the number of metastatic sites (P = 0.034), Gleason score of the metastasis (P = 0.002), and tumor positivity for chromogranin A (P = 0.041). On multivariate analysis, the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), Gleason score of the metastasis (P < 0.001), and tumor positivity for chromogranin A (P = 0.009) were associated significantly with death from prostate carcinoma. CONCLUSIONS: Although cancer-specific survival for patients after surgery for prostate carcinoma metastatic to bone is poor, assessments of tumor differentiation of the metastasis and chromogranin A positivity provide prognostic information.     

Non-Hodgkin's lymphoma of the gastrointestinal tract: an analysis of clinical and pathologic features affecting outcome

Clinical and histopathologic data from 87 patients with primary non-Hodgkin's lymphoma of the gastrointestinal (GI) tract diagnosed between 1974 and 1984 were reviewed. B-cell lymphomas of intermediate- or high-grade histology constituted 78% of lesions. Stage of disease varied with histologic grade, with a preponderance of advanced disease (stages IIIE and IV) in patients with low-grade lymphoma (15 of 21) (71%), compared with higher grade lesions (38%, P = .01). Among patients with nonlocalized (stages IIE through IV) lymphoma of intermediate- or high-grade histology, surgical resection of the primary focus afforded a higher rate of complete remission (CR) (70% v 50%) and sustained CR (61% v 21%, P = .04) after cytotoxic therapy compared with the nonresected cohort. The median survival in the resected group was 51 months + compared with 13 months in the nonresected patients (P = .012). Differences in outcome were attributable to a high risk of treatment-related complications (perforation and/or hemorrhage) (43% v 0%, P = .001) and local relapse (29% v 4%, P = .05) in nonresected individuals. Life-threatening local complications were not observed in patients with low-grade lymphoma managed solely with medical therapy. Histologic findings from surgically staged patients identified presence of extravisceral disease and intermediate- or high-grade tumor histology as features predictive of transmural invasion, enabling potential identification of patients who might be optimally managed by resection of the primary GI focus before initiation of cytotoxic therapy.     

Differences in the pathologic features of ductal carcinoma in situ of the breast based on patient age

BACKGROUND: Young patient age at diagnosis has been reported as a risk factor for recurrence in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast-conserving therapy (BCT). The authors examined pathologic features of DCIS in three different age groups of patients to identify differences that might explain why young patient age at the time of diagnosis is a risk factor for recurrence. METHODS: Excised specimens from 177 breasts of 172 patients with DCIS treated with BCT were studied. All slides from all specimens were reviewed. Patients were divided into 3 age groups: those age < 45 years, those ages 45-59 years, and those age >/= 60 years. The histologic features that were quantified included most common and highest nuclear grades, DCIS architectural pattern, amount of central necrosis (quartiles), calcifications, amount of DCIS, and number of terminal duct lobular units (TDLUs) with cancerization of lobules (COL) within 0.42 cm of the margin, margin status, and size and volume of excision specimens. RESULTS: Patients age < 45 years at the time of diagnosis more frequently had higher nuclear grade DCIS (highest nuclear Grade 3: 69%, 60%, and 39%; P = 0.003), respectively and central necrosis (72%, 62%, and 44%; P = 0. 01), respectively. Although not statistically significant, younger patients tended to have comedo subtype DCIS more often (31%, 23%, and 19%; P = 0.35), respectively. Younger patients also more often had smaller initial biopsy specimen maximum dimensions (4.3 cm, 5.2 cm, and 5.7 cm; P = 0.004), respectively, with close or positive margins (89%, 61%, and 64%; P = 0.03), and more TDLUs with COL in the 0.42-cm rim of tissue adjacent to the margin (5.2, 3.6, and 1.9; P = 0.23), respectively. No other features including the amount of DCIS when classified as > 50% or > 75% of ducts, calcifications within DCIS ducts, pattern of DCIS involvement, number of slides examined, number of slides with DCIS, and mean number of DCIS ducts near the margin were found to occur more frequently in younger patients. CONCLUSIONS: Younger patients with DCIS may have an increased risk of local recurrence when treated with BCT due to smaller initial excision volumes, a greater proportion of high nuclear grade DCIS, and central necrosis.     

Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical risk factors and pathologic features

Introduction

Recent, international declines in breast cancer incidence are unprecedented, and the causes remain controversial. Few data sources can address breast cancer incidence trends according to pertinent characteristics like hormone therapy use history.

Methods

We used the prospective California Teachers Study to evaluate changes in self-reported use of menopausal hormone therapy (HT) between 1995 to 1996 and 2005 to 2006 and age-adjusted breast cancer incidence among 74,647 participants aged 50 years or older. Breast cancer occurrence was determined by linkage with the California Cancer Registry.

Results

During 517,286 woman years of follow up, 565 in situ and 2,668 invasive breast cancers were diagnosed. In situ breast cancer incidence rates in this population did not change significantly from 2000 to 2002 to 2003 to 2005, whereas rates of invasive breast cancer declined significantly by 26.0% from 528.0 (95% confidence intervals (CI) = 491.1, 564.9) per 100,000 women in 2000 to 2002 to 390.6 (95% CI = 355.6, 425.7) in 2003 to 2005. The decline in invasive breast cancer incidence rates was restricted to estrogen receptor-positive tumors. In 1996 to 1999 and 2000 to 2002 invasive breast cancer incidence was higher for women who reported current HT use especially estrogen-progestin (EP) use at baseline than for never or past users; but by 2003 to 2005 rates were comparable between these groups. For women who were taking EP in 2001 to 2002,75% of whom had stopped use by 2005 to 2006, incidence had declined 30.6% by 2003 to 2005 (P = 0.001); whereas incidence did not change significantly for those who never took HT (P = 0.33).

Conclusions

Few data resources can examine prospectively individual HT use and breast cancer diagnosis. Stable in situ breast cancer rates imply consistent levels of screening and suggest recent declines in invasive breast cancer to be explained predominantly by changes in HT use.     

Acute leukemias of childhood: pathologic features

Major advances have been made in the diagnosis and therapy of childhood leukemia over the last two decades (Zuelzer and Flatz, 1960; Miller, 1980; Steinhorn and Myers, 1981; Kobrinsky et al., 1980). Sophisticated phenotypic analysis of these leukemias has partially revealed their complexity; there are at least three to five distinct clinical pathological entities in the childhood leukemia groups. Improved therapy has resulted in marked increases in survival and cures. Less attention has been given to the pathology of childhood leukemia, although the frequency and complexity of tissue examinations have greatly increased. In particular, the pathologic manifestation of relapses, detection of focal leukemia after treatment and the pathology of complications have not been systematically reviewed. Our goal was to look at all of the pathologic manifestations of leukemia and to relate these manifestations to homogeneous patient populations grouped by their type of leukemia. Therefore all of the cytologic, hematologic, histopathologic, ultrastructural and immunologic materials on a consecutive group of leukemic children seen at Vanderbilt from 1970 to 1981 were reviewed; pathologic manifestations of leukemia were then analysed in relationship to diagnostic categories.     

Herpes simplex virus infection in the immunocompromised cancer patient

The development of infection remains a significant source of morbidity and mortality in the oncology patient. This patient population is at increased risk for infection because of alterations in cell-mediated immunity generated by the underlying neoplastic process and/or immunosuppressive therapy. Viral infection, particularly that attributable to herpes simplex virus (HSV), is being seen with increased frequency in the oncology patient. Because effective therapy is available with the early use of antiviral agents, it is important to be aware of the potential for viral infection and to recognize the signs and symptoms that are evident early in its course. An overview of HSV infection is provided here, including discussion of the virus itself, its pathogenesis, its clinical spectrum, and current prophylactic and therapeutic approaches.     

涎腺硬化性多囊性腺病的临床病理及影像学分析

目的:探讨涎腺硬化性多囊性腺病（SPA）的影像学、临床病理特征及预后。方法:对1例SPA进行影像学、组织学形态及免疫组化染色观察,随访26个月并结合文献复习,探讨该病的临床病理特征及预后。结果:SPA临床上主要表现为涎腺缓慢生长的无痛性肿块。组织学特征与乳腺纤维囊肿性病变相似,表现为不规则的导管及腺泡分布于丰富的硬化性胶原间质中,形成模糊的小叶状结构。腺上皮细胞形态多样,有的呈大汗腺样化生,有的胞质内含丰富的嗜伊红酶原颗粒,导管上皮可以增生并伴有非典型性。免疫组化染色显示腺上皮EMA弥漫强阳性,导管及腺泡周围肌上皮SMA及Calponin阳性。Ki-67指数＜1%。影像学表现:彩超结果表现为边界相对清楚或不清楚的低回声团,可以探及稀疏的血流信号。CT:表现为软组织密度肿块影,边缘较光滑,与正常腮腺分界清楚,也可边界不清。结论:硬化性多囊性腺病是一种罕见的涎腺疾病。主要发生于腮腺,预后较好。影像学缺乏特征表现,界限不清时易误诊为恶性肿瘤。需与黏液表皮样癌、多形性低度恶性腺癌、慢性涎腺炎等鉴别。     

Malignant lymphoma of peripheral T-lymphocyte origin: immunologic, pathologic, and clinical features in six patients.

In a continuing study of patients with lymphoproliferative diseases, six adult patients were encountered with a distinctive malignant lymphoma of peripheral T-lymphocyte origin. Cell suspensions from lymph nodes of these patients contained a pleomorphic, cytologically atypical population of lymphocytes, of which an average 58% marked as T cells in the E-rosette test. The average percent of surface immunoglobulin-bearing B cells in these suspensions was 6%; they were of polyclonal distribution. Lymph node biopsies revealed a malignant lymphoma with certain characteristic features of the organization of the infiltrate, the morphology of the lymphoid cells, and the nature of non-lymphoid cellular elements. The average age of the patients was 67 years; they presented with generalized lymphadenopathy, anorexia, and significant loss of weight. Four patients hd lung and/or pleural involvement by lymphoma at presentation. The immunologic, pathologic, and clinical features of these patients serve to characterize this recently recognized malignant lymphoma further.     

Prognostic implication of clinical,radiologic, and pathologic features in patients with anaplastic gliomas

BACKGROUND: The clinical evolution of anaplastic glioma (anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma) is variable. Previous studies merged patients with anaplastic glioma and the much more common glioblastoma multiforme. Therefore, the conclusions on prognostic factors reflected in part the consequences of an analysis in a heterogeneous population. METHODS: To identify clinical, neuroradiologic, pathologic, and molecular factors with prognostic significance, we analyzed 95 treated patients with a histologic diagnosis of anaplastic glioma. Variables included age, gender, clinical manifestations at diagnosis (seizures, focal neurologic deficit, and cognitive changes), computed tomographic (CT) scan characteristics (diffuse, ring, and no enhancement), tumor location, extent of resection, histopathology, postoperative Karnofsky performance status (KPS) score, adjuvant chemotherapy, tumor response, proliferation index (Ki-67 expression), and p53, p16, pRb, and epidermal growth factor receptor immunohistochemical expression. RESULTS: Ninety-five patients with a histologic diagnosis of anaplastic astrocytoma (73%), anaplastic oligoastrocytoma (16.6%), or anaplastic oligodendroglioma (10.4%) constituted the basis of this study. Median overall survival was 29 months. Multivariate analysis revealed that an age of 49 years or younger (P < 0.03), postoperative KPS score of 80 or higher (P < 0.007), absence of ring enhancement (P = 0.03), and a proliferation index of 5.1% or lower (P = 0.044) were independently associated with longer survival. The presence of an oligodendroglial component was associated with better prognosis in the univariate analysis (P = 0.009), although this lost power in the multivariate analysis. CONCLUSIONS: In addition to previously recognized prognostic variables such as age and KPS score, CT ring enhancement and tumor proliferation index were identified as independent predictors of survival in a homogeneous series of patients with anaplastic gliomas.     

Candida jejunitis: A rare cause of intestinal pneumatosis in the immunocompromised patient

A case of fatal necrotizing jejunitis caused by Candida albicans is described in a patient with acute myeloid leukaemia undergoing chemotherapy. The diagnosis was made at autopsy. Computed tomography findings were of small bowel dilatation with pneumatosis.     

Molecular, pathologic, and clinical features of early-onset endometrial cancer: identifying presumptive Lynch syndrome patients

PURPOSE: A woman with early-onset endometrial cancer (EC) may represent the "sentinel" cancer event in a Lynch syndrome kindred. The aim of this study was to determine the incidence of Lynch syndrome in a series of young-onset EC, and to identify molecular, clinical, and pathologic features that may alert clinicians to the presence of this disorder. EXPERIMENTAL DESIGN: Patients with EC, ages < or =50 years, were identified from the Queensland Centre for Gynaecological Cancer. Tumor sections underwent histopathology review and were immunostained for mismatch repair proteins. Tumor DNA was tested for microsatellite instability and methylation of MLH1. Patients were conservatively classified as presumptive Lynch syndrome if their tumors showed loss of at least one mismatch repair protein and were negative for methylation of MLH1. Personal and family history of cancer was reviewed where available. RESULTS: Presumptive Lynch syndrome was seen in 26 of 146 (18%) tumors. These tumors were more likely to be poorly differentiated, International Federation of Gynecology and Obstetrics stage II and above, have tumor-infiltrating lymphocytes, have higher mitotic rate, and have deeper myometrial invasion (P < 0.05). Lynch syndrome cases were more likely to be associated with a positive family history when analyzed for Amsterdam criteria II, diagnosis of a Lynch syndrome spectrum cancer in at least one first-degree relative, and family history of any cancer (P < 0.05). CONCLUSION: Presumptive Lynch syndrome was identified in 18% of early-onset EC. A risk of this magnitude would argue for routine immunohistochemical testing of tumors in patients diagnosed with EC at or before the age of 50 years.     

BRAF V600E mutation in metastatic colorectal cancer: Methods of detection and correlation with clinical and pathologic features

The screening for BRAF V600E mutation is employed in clinical practice for its prognostic and potentially predictive role in patients with metastatic colorectal carcinoma (mCRC). Little information is available on the sensitivity and specificity of the testing methods to detect this mutation in CRC. By using serial dilution of BRAF mutant DNA with wild type DNA, we found that the sensitivity of allelic discrimination-Real Time PCR was higher than PCR-Sequencing (10% vs 20%). In agreement, the Real Time PCR assay displayed increased analytical sensitivity in detecting the BRAF V600E mutation as compared with PCR-Sequencing in a cohort of 510 consecutive CRCs (21 vs 16 cases). Targeted resequencing demonstrated that all cases negative by PCR-Sequencing had an allelic frequency of the BRAF mutation <20%, thus suggesting tumor heterogeneity. The association of BRAF mutations with clinical and pathological features was assessed next in a cohort of 840 KRAS exon 2 wild type CRC patients screened with the Real Time PCR assay. The BRAF V600E mutation frequency in this cohort was 7.8% that increased to 33.4% in females over 70 y of age with right-sided tumor location. BRAF mutations were also detected in 4.4% of male patients with left-sided tumors and aged <70 y. Fourteen of 61 (22.9%) BRAF V600E mutation bearing patients exhibited microsatellite instability (MSI) as assessed by T17 mononucleotide sequence within intron 8 of HSP110. Our study indicates that Real Time PCR-based assays are more sensitive than PCR-Sequencing to detect the BRAF V600E mutation in CRC and that BRAF mutations screening should not be restricted to selected patients on the basis of the clinical-pathological characteristics.     

Survival analysis of clinical, pathologic, and genetic features in neuroblastoma presenting as locoregional disease

BACKGROUND: Locoregional neuroblastoma is a clinical subgroup characterized by the absence of distant metastasis (International Neuroblastoma Staging System Stages 1, 2, and 3). Although these patients generally have an excellent survival with minimal therapy, some do experience recurrence with lethal consequences. METHODS: To identify risk factors for disease progression, the authors performed a retrospective analysis of clinical (age and stage) and tumor biologic markers (histology, MYCN, DNA index, and allelic analysis of chromosomes 1p, 11q12-qter, and 14q12-q32) in 44 patients (10 Stage 1, 18 Stage 2, and 16 Stage 3). Allelic analysis was performed using polymorphic polymerase chain reaction markers in a semiautomated, fluorescent detection system. RESULTS: Sixteen patients (38%) were younger than 365 days at diagnosis. Seventeen of 39 tumors (43%) had unfavorable histology, 6 (13%) were MYCN amplified, 14 (31%) were diploid, 17 (38%) had 1p36 loss of heterozygosity (LOH), 11 (25%) had 1p22 LOH, 10 (22%) had 11q LOH, and 13 (29%) had 14q LOH. Seventeen patients (38%) progressed, including 6 who progressed to Stage 4 disease (13%). Sixteen patients with progressive disease received cytotoxic therapy. Thirty-seven patients are alive (84%) with a median follow-up of 51 months. By permutation log rank test, both MYCN amplification and diploidy were associated with overall survival (OS), but only diploidy was associated with progression free survival (PFS) and progression to Stage 4 disease. LOH of 1p36, 1p22, 11q, or 14q did not show correlation with either OS or PFS. CONCLUSIONS: Locoregional neuroblastoma tumors with diploid DNA index, regardless of other biologic features, have increased risk of local recurrence and Stage 4 progression.     

In situ follicular lymphoma: pathologic characteristics and diagnostic features

The diagnosis of in situ follicular lymphoma (FL) is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. We usually use a selected diagnostic panel of antibodies (CD10, CD20, CD23, BCL2, BCL6, and Ki67) in lymph nodes with follicular hyperplasia only when we analyze an unexplained lymphadenopathy. Molecular studies, for example, fluorescence in situ hybridization analysis for t(14;18), are restricted to doubtful cases in which immunohistochemistry data are ambiguous. Immunohistochemically, the involved follicles show strongly positive staining for BCL2 and CD10. The BCL2+ cells are confined only to germinal centers and are not seen in the interfollicular region or elsewhere in the lymph node. The BCL2 staining in the abnormal follicles is notable for its high-level and uniform intensity. In situ FL may be associated with overt FL or with lymphomas other than FL or with other malignancies. The crucial point relies on distinguishing in situ FL arising in asymptomatic patients from cases with presence of lymphoma at the same or other sites. Other open questions remain on the frequency with which in situ FLs occur and the frequency of concomitant systemic disease.     

Anaplastic Wilms' tumor: clinical and pathologic studies

A review of almost 1,200 children participating in the first and second National Wilms' Tumor Study (NWTS-1 and -2) has demonstrated a number of significant differences in the clinical presentation and response to therapy of anaplastic and nonanaplastic Wilms' tumor. Compared to their counterparts, children with anaplastic Wilms' tumor were generally one to two years older at diagnosis, more were non-white, and more had lymph node metastases at diagnosis. Consistent with previous studies, children with anaplastic Wilms' tumor survived for a significantly shorter time than those with non-anaplastic Wilms' tumor. A hopeful outlook, however, was suggested by the NWTS-2 experience since the more aggressive chemotherapies used in this study appear to have substantially improved the survival of patients with diffusely anaplastic tumors. Also, the survival of NWTS-2 patients with anaplastic Wilms' tumor was determined in part by clinicopathologic stage. It may be possible therefore to refine therapy according to stage so as to provide children with localized disease a chance for cure with fewer untoward treatment-related sequelae.