Synchronous penile metastasis from a high-grade adenocarcinoma of the prostate.

Metastasis to the glans penis is a rare phenomenon and usually occurs in a late stage of disease. A 68-year-old man was referred to our clinic because of two indurated lesions of the glans penis and minor lower urinary tract symptoms. Digital rectal examination revealed a hard nodular prostate, and serum prostate-specific antigen (sPSA) level was 13.3 ng/mL. Biopsies of the penile lesions and transrectal ultrasound-guided prostate biopsies were taken. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue exposed a synchronous penile metastasis from a high-grade adenocarcinoma of the prostate. Except a pathologically enlarged lymph node detected with MRI there was no suspicion on other metastases. Currently this patient is being treated with a Gonadoreline (GnRH) antagonist. Nevertheless, the prognosis will be poor.

The diagnostic and therapeutic approach of a primary bilateral leiomyoma of the ovaries: a case report and a literature review.

INTRODUCTION: A primary fibroid (leiomyoma) arising from both ovaries is rare and can be difficult to diagnose as a result of the low incidence and its indistinctive presentation. A literature review on the diagnostic and therapeutic approach of this rare benign tumour is presented. We describe a case of bilateral primary ovarian fibroid with an unusual presentation to illustrate our recommendations for treatment. CASE PRESENTATION: A 37-year-old woman was admitted with symptoms of acute severe abdominal pain. She had a history of faint abdominal discomfort. Due to the acute deterioration of the abdominal pain a diagnostic laparoscopy was performed. A tumour arising from both ovaries was seen and a biopsy was taken in order to decide on further therapy. Histology showed a fibroid for which excision by a second laparoscopic intervention was planned. Due to excessive adhesions conversion to laparotomy was necessary. CONCLUSION: We recommend that in the case of an abnormal adnexal mass, particularly in women who want to preserve their fertility, frozen section histology be performed laparoscopically. A frozen section diagnostic procedure, instead of a regular biopsy, seems to be a useful tool during an elective diagnostic laparoscopic procedure in order to prevent potential morbidity as a result of possible future laparoscopy or even laparotomy. Previous laparoscopic procedures can cause massive adhesions that could impede a subsequent laparoscopic approach.

[Intracystic carcinoma of the breast: diagnosis and treatment in retrospective investigation and published literature]. / Intracystisch mammacarcinoom: diagnostiek en behandeling in retrospectief onderzoek en literatuurgegevens.

OBJECTIVE: To describe policy and prognosis of patients with a cystic mammary lesion caused by an intracystic mammary carcinoma (ICMC). DESIGN: Retrospective, descriptive. METHOD: The study concerned retrospective analysis of 17 patients presenting with intracystic carcinoma of the breast in an educational clinic in the period 1988-2000, who were selected by searching the national pathology database (PALGA). None of the patients was on hormone replacement therapy. In addition a literature search was carried out in the Medline system. RESULTS: The patients with an intracystic carcinoma of the breast were 10 years older compared to the other breast cancer patients and presented themselves with a palpable mass. Mammography showed a single, well-defined and lobulated mass. Microcalcifications were uncommon. Ultrasound investigation showed a well-defined, inhomogenous and hypoechoic mass. 6 patients had encysted lesions and in 3 a solid, hypoechoic component within the cystic mass was found. Cytology of the cystic fluid is false negative in 36% (5/14). All patients were treated surgically, varying from excisional biopsy to modified radical mastectomy. In 15 patients an intracystic papillary carcinoma (ICPC) was found. 5 patients show a 'pure' ICPC. In the other 10 patients, 5 had an ICPC with a component of DCIS and 5 patients an ICPC with an invasive component. The median follow-up was 84 months (range: 28-165). In 15 patients no evidence of disease was found at follow-up; 2 patients developed local recurrence. The survival was 100%. CONCLUSION: Based on the investigation and on the available literature it is concluded that cysts in breasts of postmenopausal women, who do not use hormone replacement therapy, are malignant until proved otherwise. Ultrasound is invaluable in the diagnostic pathway of intracystic carcinoma of the breast. When ICPC is suspected excisional biopsy with sentinel node biopsy is the treatment of choice. The prognosis is good.

alpha-Catenin expression pattern and DNA image-analysis cytometry have no additional value over primary histology in clinical stage I nonseminomatous testicular cancer.

OBJECTIVE: To determine whether the alpha-catenin expression pattern and DNA content have additional value over primary tumour histology, including information on vascular invasion and tunica albuginea invasion, in detecting occult metastasis in patients with clinical stage I nonseminomatous germ cell tumours of the testis (NSGCT). PATIENTS AND METHODS: Fifty consecutive patients with clinical stage I NSGCT underwent retroperitoneal lymphadenectomy (RPLND) between 1986 and 1992. The orchidectomy specimens were histopathologically reviewed and immunohistochemically stained with mouse monoclonal anti-alpha-catenin antibody. The presence of an aberrant or negative staining in >10% of the malignant cells was defined as abnormal; in all other cases tumours were classified as normal. Furthermore, intact nuclei were isolated from 50 microm thick paraffin sections of the primary tumour, Feulgen stained, and analysed with an image-analysis system. RESULTS: Of the 50 patients, 14 had positive retroperitoneal nodes (stage IIa, 28%), one pathologically staged I patient developed a lung metastasis (stage IV) within 3 months of RPLND. Univariate analysis showed that the presence of embryonal cell carcinoma, vascular invasion and tunica albuginea invasion were predictive for occult metastases. In multivariate logistic regression analysis only vascular and tunica albuginea invasion were significant. All 11 patients with no embryonal cell carcinoma in the primary tumour were classified as having pathological stage I disease. Also, the tumours which were DNA-diploid (three) or DNA-polyploid (two) were pathologically stage I. In screening for occult metastases the DNA content and the alpha-catenin expression pattern had no additional value. CONCLUSION: Vascular and tunica albuginea invasion have prognostic value in identifying patients with clinical stage I NSGCT at high risk for occult retroperitoneal disease. In contrast, the absence of embryonal cell carcinoma could predict all patients at low risk for metastasis. The DNA-ploidy also identified patients at low risk. Other DNA-analyses and the alpha-catenin expression pattern provided no additional information. Further studies are recommended to identify patients who are at low or high risk for metastasis.

A giant cell tumor of the sacrum or a soft tissue giant cell tumor? A case report.

STUDY DESIGN: A case report. OBJECTIVE: Giant cell tumors are rare primary bone tumors. Generally, these tumors are expanding osteolytic lesions, but soft tissue giant cell tumors can occur. This is a case report of an unusual incidence of a giant cell tumor within the spinal sacral canal, in which there was no involvement of the surrounding bone or ligament structures and that was signaled by radicular pain. The pathologic course of the tumor is described. SUMMARY OF BACKGROUND DATA: A 24-year-old woman had monoradicular pain in the right leg in the region of S2. Neuroradiologic examination showed a mass within the sacral spinal canal compromising the right S2 root, with no sign of bone involvement. METHODS: A sacral laminectomy was performed. A tumor was located entirely intraspinally and extradurally and was removed completely. A giant cell tumor was identified in histologic examination. RESULT: The patient recovered completely. No local regrowth or metastasis occurred during a 20-month follow-up. CONCLUSION: The treatment of choice in giant cell tumors is complete surgical resection. Radiotherapy is recommended in cases of subtotal resection. Careful follow-up is warranted, because recurrence and metastasis are not uncommon.

Intratumoral nuclear morphologic heterogeneity in prostate cancer.

OBJECTIVES: Tumor heterogeneity can be measured by quantifying variance of nuclear characteristics by image analysis. Heterogeneity of cell nuclear features correlated with increased local progression in prostate cancer. In the present study, the influence of tumor heterogeneity on prostate-specific antigen (PSA) recurrence after radical retropubic prostatectomy was analyzed and tumor heterogeneity was compared in patients with and without neoadjuvant hormonal therapy. METHODS: Retrospectively, radical prostatectomy material of 44 patients without and 12 patients with neoadjuvant hormonal treatment with a postoperative follow-up of at least 4 years was studied. Each prostatectomy specimen was systematically embedded in paraffin, and each tumor area within the prostate was marked and analyzed by an image analysis system for 32 nuclear features comprising nuclear shape, size, DNA content, and chromatin pattern. Several clinical features were available: preoperative serum PSA, hemoglobin concentration, Karnofsky score, tumor stage, and Gleason score. RESULTS: Increased tumor heterogeneity, as expressed by differences in karyometric values between tumor areas in nuclear shape and chromatin pattern within the tumor, was significantly correlated with earlier PSA recurrence rate. As compared with nonpretreated patients, hormonally pretreated specimens showed smaller and less heterogeneous tumors. In particular, chromatin pattern heterogeneity was decreased in patients who underwent preoperative hormonal treatment compared with patients who were not pretreated. However, decreased heterogeneity was accompanied by a higher percentage of aneuploid areas per tumor in the pretreated patients. Cox regression analysis showed that karyometric determination of nuclear shape heterogeneity in combination with preoperative PSA level could predict time to PSA recurrence after radical prostatectomy in patients without hormonal pretreatment. CONCLUSIONS: Increase in karyometric tumor heterogeneity in nuclear shape and chromatin pattern was correlated with a shorter PSA recurrence-free interval after radical prostatectomy. Preoperative PSA and karyometric tumor heterogeneity were the best predictors of PSA recurrence in a multivariate analysis. Intratumoral heterogeneity was decreased in patients with prostate cancer who underwent neoadjuvant hormonal therapy.

Cytokeratin and vimentin expression in normal epithelium and squamous cell carcinomas of the larynx.

The immunohistochemical expression patterns of cytokeratin polypeptides and vimentin were investigated in normal epithelia and squamous cell carcinomas of the larynx with special emphasis on tumor grading. During malignant transformation of epithelial cells, the cytokeratin expression patterns changed, depending on the differentiation grade of the carcinomas. In low-grade carcinomas, the expression patterns were close to those of the normal epithelium. With increasing tumor grade, there was decreased expression of stratification cytokeratins and increased expression of basal cell, simple cell and hyperproliferation-related cytokeratins. Increasing tumor grade was also associated with the expression of vimentin, a cytoskeletal protein of mesenchymal cells. No relationship was found between vimentin expression and the presence of lymph-node metastases.

Cytokeratin and vimentin expression in normal epithelium and benign lesions of the vocal cords.

The expression of cytokeratins and vimentin was studied immunohistochemically in normal epithelium and 12 benign lesions of the vocal cord with the use of a broad panel of monoclonal antibodies against cytokeratins and vimentin. Histology showed that the various lesions contained hyperkeratotic, hyperplastic and atrophic epithelium, irrespective of their clinical appearance. Especially the Ck profile of the (hyper)keratotic lesions was changed in comparison with the native epithelium. Increased expression of the keratinization marker Ck 10 was associated with decreased expression of the stratification markers Cks 4 and 13. Expression of the basal cell marker Ck 14 and hyperproliferation-associated Cks 16 and 17 was increased in all the benign lesions, except in atrophic epithelium. These expression patterns differ from those observed in malignant epithelial lesions. The latter show a marked expression of simple cell Cks and vimentin and more pronounced expression of hyperproliferation-associated markers than the benign lesions.

Comparison of P53 protein overexpression with P53 mutation in bladder cancer: clinical and biologic aspects.

BACKGROUND: Alterations of the tumor suppressor gene p53 are known to occur in bladder cancer. Although p53 overexpression is associated with mutation of the p53 gene, a substantial discrepancy between molecular genetic alteration in p53 and overexpression of the protein has been found. EXPERIMENTAL DESIGN: Tumor specimens of 39 bladder cancer patients were immunohistochemically analyzed for p53 overexpression, and the results were compared with the presence of a mutation as assessed by single strand conformation polymorphism (SSCP) and direct sequencing. Both clinical and biologic aspects were studied. RESULTS: A significant correlation between p53 overexpression and poor survival in the whole group studied was found (p < 0.01). No association between p53 overexpression and decreased survival was found for invasive tumors in contrast with other studies. Differences in treatment of the patients and different Ab and scoring systems used might explain these differences. In our study, the Kaplar-Meier curves showed the same result for p53 overexpression and p53 mutation when the whole group and the invasive tumors were studied. However, in the group of superficial tumors, which was unfortunately too small for statistical analysis, we found p53 overexpression in three tumors, and no p53 mutations were found. A good concordance between p53 mutation and p53 overexpression was found (p < 0.02). However, two out of eight tumors with an SSCP-proven p53 mutation showed no p53 immunoreactivity, probably as a result of loss of the nuclear localization signal. Twenty three percent (7/31) of the tumors showed p53 overexpression without any sign of a mutation. CONCLUSIONS: Our results indicate that, despite good concordance between p53 mutation and p53 overexpression, there is no direct casual relationship between mutation and protein accumulation. Apparently, other events than mutation can trigger p53 stability.

Numerical aberrations of chromosomes 1 and 7 in renal cell carcinomas as detected by interphase cytogenetics.

Alcohol-fixed single cell suspensions of 37 renal cell carcinomas (RCCs) were assessed by both flow cytometry (FCM) and the fluorescence in situ hybridization (FISH) technique, using chromosome 1- and chromosome 7-specific centromere DNA probes. DNA diploidy or near-diploidy was observed in 30 of the 37 RCCs and only 12 of these (near-)diploid tumours were disomic for both chromosomes 1 and 7. Numerical aberrations of chromosome 1 and/or chromosome 7 were present in 18 of the 30 (near-)diploid RCCs and five of these cases showed monosomy for chromosome 1 in more than 50 per cent of the tumour cells. A double target FISH, with a centromeric and a telomeric specific probe for 1p36, excluded misinterpretation on the basis of clustering of 1q12, and suggested a complete loss of chromosome 1. All these five (near-)diploid RCCs with monosomy for chromosome 1 were eosinophilic chromophilic cell carcinomas, according to the Thoenes classification of RCC. This observation is of special interest, because it was recently concluded from cytogenetic studies that the diagnosis of chromophilic renal cell carcinoma must be considered as obsolete. Monosomy for chromosome 1 seems to be a non-random numerical aberration of (near-)diploid eosinophilic chromophilic cell carcinomas, and a gain of one or more chromosomes 1 appeared to be a common phenomenon in RCCs, especially in the DNA aneuploid tumours. As these chromosomal abnormalities were not found in the earlier classical cytogenetic studies, we conclude that in situ hybridization techniques are required in addition to chromosome banding techniques to obtain a complete characterization of the chromosome imbalances in RCCs.

Pulmonary tumour and inferior vena cava tumour thrombus: rare presentation of renal transitional cell carcinoma. Case report.

A transitional cell carcinoma from the pyelocaliceal system, initially presenting as a pulmonary tumour, extended into the inferior vena cava, the tenth reported case of this type. The literature is reviewed with special reference to vena cava involvement by such tumours and immunohistochemical staining pattern.

Postmortem findings in the Nijmegen breakage syndrome.

Autopsy findings for two patients with the Nijmegen breakage syndrome (NBS) are presented. This syndrome has the same type of immunologic and cytogenetic abnormalities as ataxia telangiectasia (AT). In NBS, however, microcephaly is found and progressive cerebellar ataxia and oculocutaneous telangiectasia are lacking. We demonstrate a clear neuropathologic difference between these two syndromes, as the diffuse cortical cerebellar degeneration characteristic of AT was absent in NBS. In the thymus the histologic picture was suggestive of simple dysplasia. Lymphoid tissues were slightly atrophic but otherwise structurally normal. In one of the two presented cases an extranodal diffuse large cell malignant non-Hodgkin lymphoma of B cell immunoblastic type was found in Waldeyer's ring, in the small and large intestines, and in the brain, whose sequelae had caused death. Six of the 19 patients known with certainty to have this syndrome have developed lymphoid malignancy, which indicates that these patients are prone to develop malignancies.

Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer.

Decreased levels of the cell-cell adhesion molecule E-cadherin are associated with loss of differentiation in a number of human carcinomas. However, the value of E-cadherin as a prognostic marker in these cancers is largely undetermined. A previous study of E-cadherin levels in prostate cancer revealed that almost 50% of tumors examined had reduced or absent levels of this protein (Umbas et al., Cancer Res., 52: 5104-5109, 1992). To determine the potential prognostic significance of this finding, prostate cancer specimens from 89 patients were evaluated immunohistochemically for E-cadherin expression, and the results were related to histopathological grade, tumor stage, presence of metastases, and survival. As previously observed, a significant inverse correlation was found between E-cadherin expression and tumor grade. Importantly, we also found significant correlations between E-cadherin expression and tumor stage and overall survival. Sixty-three percent of the tumors that extended beyond the prostate capsule (T3-4) versus 33% of the tumors confined to the prostate (T1-2) had aberrant expression (chi 2 = 8.1, P < 0.005). Seventy-six percent of the primary tumors from patients that presented with metastases showed aberrant staining compared to 32% from patients without metastases (chi 2 = 14.9; P < 0.001). The life table analysis showed a significantly higher survival rate for patients with normal staining compared to patients with aberrant expression (chi 2 = 20.4, P < 0.001 by log rank test). Moreover, abnormal expression of E-cadherin correlated significantly with progression after radical prostatectomy (P < 0.005). These results suggest that E-cadherin expression can serve as a prognostic indicator for the biological potential of prostate cancer.

The influence of review pathology on study outcome of a randomized multicentre superficial bladder cancer trial. Members of the Dutch South East Cooperative Urological Group.

OBJECTIVE: To determine whether differences between local and review pathology in a multicentre study influence the results of treatment and results from prognostic factor analysis. PATIENTS AND METHODS: A randomized multicentre study in superficial bladder cancer is reported, in which the influence of local and review pathology on the study outcome was investigated. RESULTS: The conformity between local and review pathology of the pT category was 79.3%, of the grade 70.2%, and the combination of both 59.7%. In local pathology, undergrading was more frequent than overgrading and overstaging more frequent than understaging. However, the risks of recurrent disease in the separate stage and grade groups remained the same after correcting the pathology result. A prognostic factor analysis with regard to the risk of recurrent disease was carried out. The Cox hazard ratios of tumour localization, multiplicity, patient age (significant factors), tumour grade, size, history and gender (not significant) remained almost the same after correction for review pathology. Only the prognostic relevance of tumour stage increased after pathology correction. CONCLUSION: We conclude that, although review pathology caused considerable changes in the pathology results, this did not change the results of treatment, and hardly altered the results of a prognostic factor analysis in this randomized study.

The reliability of computer analysis of ultrasonographic prostate images: the influence of inconsistent histopathology.

This article describes a method to investigate the influence of inconsistent histopathology during the development of tissue discrimination algorithms. Review of the pathology is performed on the biopsies used as training set of a computer system for cancer detection in ultrasonographic prostate images. The influence of the discrepancies found between independent pathologists on the discriminating power of the system is investigated. A high diagnostic consistency in histopathology concerning only the categories malignant and nonmalignant is found. Therefore, review of the pathology does not significantly influence the results of tissue discrimination algorithms for cancer detection. However a high interobserver variability is obtained in the differentiation between more histology classes.