Large solitary fibrous tumour of the retroperitoneum: a case report and review of the literature.

INTRODUCTION: This report describes an unusual case of a large solitary fibrous tumour (SFT) arising in the retroperitoneum. CASE PRESENTATION: A 53-year-old woman presented at the Emergency Department with urinary retention and lumbar pain. The urological examination was negative, whereas a presacral retroperitoneal mass was disclosed on ultrasound. The laboratory studies, including tumour markers, were negative. On laparotomy, it was not possible to remove the mass completely due to the difficulty of dissecting it free of the sacrum. Grossly, the fragment had a yellowish-white surface, with areas of necrosis and haemorrhage. On immunohistochemistry, tumour cells were positive for CD34, CD99 and Bcl-2 and negative for CD45, synaptophysin, chromogranin, S100, neuron-specific enolase, CK AE1-AE3, CK7, Wilms' tumour 1, smooth muscle actin, factor VIII, myogenin, epithelial membrane antigen, thyroid transcription factor-1 and CD117, leading to a diagnosis of SFT. Molecular investigation ruled out synovial sarcoma. CONCLUSION: Although SFT usually has a favourable prognosis, close follow-up is recommended due to the limited information on its long-term behaviour.

Locally advanced breast implant-associated anaplastic large-cell lymphoma: a combined medical-surgical approach.

OBJECTIVE: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin's T-cell lymphoma that develops around breast implants. CASE PRESENTATION: This report illustrates the case of a patient affected by a locally advanced BIA-ALCL which infiltrated the thoracic wall (stage T4N0M0) following implant-based reconstruction after left mastectomy. Given the initial inoperability due to the patient's poor general condition, the treatment plan provided for a primary cycle of systemic neoadjuvant immunotherapy/chemotherapy, surgical removal of the mass, and subsequent systemic chemotherapy/immunotherapy. This resulted in complete remission - the patient remained disease-free even over a year later - without the need for adjuvant radiotherapy. CONCLUSIONS: Our real-life case shows how the existing guidelines can be successfully adapted as part of an individualized approach to advanced and/or difficult cases.

OCT4 controls mitotic stability and inactivates the RB tumor suppressor pathway to enhance ovarian cancer aggressiveness.

OCT4 (Octamer-binding transcription factor 4) is essential for embryonic stem cell self-renewal. Here we show that OCT4 increases the aggressiveness of high-grade serous ovarian cancer (HG-SOC) by inactivating the Retinoblastoma tumor suppressor pathway and enhancing mitotic stability in cancer cells. OCT4 drives the expression of Nuclear Inhibitor of Protein Phosphatase type 1 (NIPP1) and Cyclin F (CCNF) that together inhibit Protein Phosphatase 1 (PP1). This results in pRB hyper-phosphorylation, accelerated cell proliferation and increased in vitro tumorigenicity of ovarian cancer cells. In parallel, OCT4 and NIPP1/CCNF drive the expression of the central Chromosomal Passenger Complex (CPC) components, Borealin, Survivin and the mitotic kinase Aurora B, promoting the clustering of supernumerary centrosomes to increase mitotic stability. Loss of OCT4 or NIPP1/CCNF results in severe mitotic defects, multipolar spindles and supernumerary centrosomes, finally leading to the induction of apoptosis. These phenotypes were recapitulated in different cancer models indicating general relevance for human cancer. Importantly, activation of these parallel pathways leads to dramatically reduced overall survival of HG-SOC patients. Altogether, our data highlights an unprecedented role for OCT4 as central regulator of mitotic fidelity and RB tumor suppressor pathway activity. Disrupting this pathway represents a promising strategy to target an aggressive subpopulation of HG-SOC cells.

B cell lymphoma of the thymus and salivary gland.

A case of primary low grade B cell lymphoma of the salivary gland associated with a low grade B cell lymphoma of the thymus and involvement of the skin is reported. The lesions in the salivary gland and in the thymus showed the typical features of a lymphoma arising from the mucosa associated lymphoid tissue (MALT) and comprised lymphatic follicles, centrocyte-like (CCL) cells and lymphoepithelial lesions. Immunohistochemistry and Southern blot analysis supported the hypothesis that these lesions can originate from the same cellular clone. These findings confirm the occurrence of low grade B cell MALT lymphoma in the thymus and the possibility of spread of MALT lymphoma to other mucosal sites.

Microscopic thymoma and myasthenia gravis.

A rare case of microscopically sized thymoma is described in a 56 year old man suffering from myasthenia gravis. Histological examination of the surgically removed thymus showed the presence of several epithelial thymoma-like islands. As controls, 100 thymuses obtained from consecutive necropsies were sampled: 4% of these cases showed epithelial islands. This case is further proof that "microscopic thymoma" is a true pathological entity and suggests that every thymus removed from myasthenic patients in which there is no macroscopic evidence of thymoma should be examined microscopically on serial sections.

BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy-adenosine.

Bcl-2 overexpression has been shown to be associated with several malignancies, including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL), mainly low-grade and follicular in type. It has as yet not been described in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were consecutively selected for treatment with purine analogues (Fludarabine in CLL and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression in leukemic cells on marrow sections that were taken before treatment and stained immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive, with a staining intensity that was moderate to strong in CLL and weak to moderate in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues. These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL and that bcl-2 overexpression does not predict a poor response to purine analogues, which are believed to induce apoptosis.

Evolutionary somatic cell changes in cervical tumour progression quantitatively evaluated with morphological, histochemical and kinetic parameters.

The somatic cell changes which characterise malignancy evolution in human cervical preneoplastic and neoplastic lesions have been assessed on histological sections by means of a computerised image analyser. Many features have been simultaneously measured on each cell of the lesions studied, and the following results have been obtained: Some features, mainly kinetic, show continuously increasing values which express changes correlated to the increasing malignancy; other features, especially related to nuclear atypia, cellular heterogeneity and the degree of aneuploidy, have values dropping at the level of early stromal infiltration, which can be morphometrically characterised as composed of relatively homogeneous phenotypes; these features seem to express the degree of genetic instability and relate to the evolutionary somatic cell changes; tumour progression evolves through sequential discontinuous steps, each of them characterised by specific phenotypical features of the neoplastic cell population; the neoplastic cells in the foci of early stromal infiltration and vascular invasion, phenotypically more homogeneous than the parent cell populations of carcinoma in situ and infiltrating carcinoma, seem to possess a greater genetic stability.

Quantitative study of ductal breast cancer progression. Morphometric evaluation of phenotypical changes occurring in benign and preinvasive epithelial lesions.

Fifty-nine cases of Breast Epithelial Proliferative Lesions (BEPL) and Ductal Carcinoma in Situ (DCIS), were studied by image analysis, to evaluate the nuclear changes occurring in the conventional diagnostic categories of ductal hyperplasia, atypical ductal hyperplasia and DCIS with quantitative methods. Diagnosis reproducibility is the main practical problem of these breast lesions. In fact, with subjective methods, the reproducibility appears to be very low and precarious especially for clinical demands. The objective, quantitative evaluation of cell phenotypical changes should be the method for both practical diagnostic problems and study of ductal cancer progression. The distribution pattern of the data in the feature, obtained with quantitative analysis, strongly suggests a continuum of changes, indicating an evolutionary process of Breast Ductal Carcinoma (BDC) progression in its preinvasive stage. Each observed case may be characterised by its own cellular, objective alterations and a progressive trend toward BDC can be stated. Since the actual changes of the proliferative phenotypes can be measured, and the values are reproducible, karyometric measurement may allow an objective grading of individual cases.

Quantitative study of ductal breast cancer--patient targeted prognosis: an exploration of case base reasoning.

Current analytic methodologies allow the extraction, even from small tumor masses, of extensive information on the biologic characteristics of malignant lesions, such as tumor aggressivity, metastatic potential, drug resistance, and host interactions. Clinical practice now offers a wide range of therapeutic strategies. Information technological advances offer the opportunity to refer to very large data bases of patient anamnestic data, response to treatment and clinical outcome. There is a need to formulate therapy and prognosis for each individual case. Case based reasoning is a knowledge based methodology where the outcome for complex situations can be predicted by referring to a large data base of cases of known outcomes. The preliminary data obtained from this study suggest that case based reasoning may offer a promising approach to individual targeted prognosis.

Quantitative study of ductal breast cancer progression. A progression index (P.I.) for premalignant lesions and in situ carcinoma.

The diagnostic subjective assessment of ductal premalignant proliferative lesions and in situ carcinoma of the breast produces unsatisfactory results. Since the phenotypical cell changes in tumour progression toward infiltrating cancer constitute a continuum, a grading on a continuous scale of values produces a more reliable and reproducible characterization. The diagnostic assessment for any individual patient may be expressed by a progression index (P.I.): its numerical values are based on the cellular changes measured in the individual cases. In this study, the progression index is based on two morphometric features, nuclear size and nucleolar area. In addition, the method presented may produce a ratio, stating the relative likelihood that each case represents one of the conventional diagnostic categories. Such a likelihood ratio may be obtained from the bivariate distribution of nuclear size and nucleolar area for the conventional diagnostic categories.

Laryngeal leiomyosarcoma.

We report one case of leiomyosarcoma (LMS) of the larynx occurring in a patient with a history of immunosuppressive therapy, and offer a critical review of the literature. Epstein-Barr virus (EBV) genome was not identified in the neoplastic cells. The patient was treated with endoscopic resection and post-operative radiotherapy. Lung metastasis and thyroid infiltration became evident 14 months following treatment despite the absence of laryngeal recurrence. Progressive decline occurred and the patient died 15 months after diagnosis.

[An aneurysm of the extracranial carotid. A report of an interesting clinical case]. / Aneurisma della carotide extracranica. Descrizione di un caso clinico interessante.

One case of extracranial carotid artery aneurysm observed is reported. This uncommon and interesting vascular disorder is still under discussion even if the present tendency is to treat it actively by reconstructive surgical procedures that make it possible to avoid the natural aneurysm complications with a low risk of postoperative neurological lesions.

[A case of malignant pancreatic apudoma producer of serotonin and pancreatic polypeptide]. / Su un caso di apudoma maligno pancreatico a produzione di serotonina e polipeptide pancreatico.

Taking as their starting point the observation of a pancreatic malignant endocrine neoplasm with mixed production of serotonin and pancreatic polypeptide, the authors go on to review the literature on the diagnosis and treatment of pancreatic apudomas. The possibility of performing an extempore intraoperative histological examination makes it possible to obtain a correct diagnosis of endocrine neoplasm and thus to proceed with surgery which could not be contemplated in adenocarcinomatous forms at an equivalent stage. Chemotherapy may then provide additional therapeutic possibilities, using specific markers for malignancies of the APUD system in order to detect possible recurrences.

[Biology and differentiation of lymphocytes in the classification of lymphomas]. / Biologia e differenziazione dei linfociti per la classificazione dei linfomi.

The classifications of non-Hodgkin's lymphomas are briefly discussed and the processes of proliferation and differentiation of B and T lymphocytes are analyzed. The B and T lymphocytes engaged in the immune response arise from precursor cells through a two-cycle process of proliferation and differentiation: the first cycle produces cells with antigen receptors of varying specificity (resting circulating B and T lymphocytes); the second cycle produces B and T type effector cells and "memory" cells. Each phase of B and T differentiation can give rise to a type of lymphoma; in fact, malignant lymphomas can be divided into categories of precursor B and T cell lymphomas, resting B and T cell lymphomas and activated B and T cell lymphomas. Hodgkin's lymphoma could be considered a lymphoma arising from activated cells with atypical phenotype, i.e. Hodgkin and Reed-Sternberg cells. These cells secrete cytokines which recruit lymphocytes, histiocytes, eosinophils and plasma cells which form the cellular background typical of this tumor.

Early stromal invasion in cervical cancer: immunocytochemical changes occurring in infiltrating neoplastic cells.

Early Stromal Invasion (ESI) in cervical cancer progression should be considered as a separate histological diagnostic category for its morphological characters very different from those of both carcinoma in situ (CIS) and microcarcinoma (MIC). To have some more microscopical details on these differences we performed immunocytochemical investigation addressed to evaluate, in cervical cancer malignancy progression, the evolutionary changes in the expression of some proteins involved in cell differentiation and cell cycle regulation. The results provide data improving the knowledge about ESI and supporting, with objective proofs, the nosological autonomy of ESI, with respect to CIS and MIC.

Reproducibility of DNA measurements in imprints of thyroid adenoma. Variation sources.

DNA measurement represents a type of quantitative analysis which allows us to gain prognostic information on malignant tumors and to study the natural history of the epithelial neoplasia. However, there are sources of variation in evaluating the DNA content. These include variation due to field selection, variation between observers (interobserver variation), and variation between laboratories (interlaboratory variation). The influence of various variation sources was studied in 4 experiments. When DNA measurements were made from the same microscopic fields, the results did not differ remarkably. However, observer training proved to be important. Intra- and interobserver variation was lower among experienced morphometrists than among inexpert observers. Different laboratories and image analyzers may give different results when the same case is measured. To overcome at least part of the potential variation sources, undergraduates and postgraduates at the Departments of Pathology of Ancona and Kuopio Universities are specially trained in the use and application of morphometry. Special sampling rules should be applied and observers encouraged to follow the rules as uniformly as possible.

Cytometric evidence that cervical intraepithelial neoplasia I and II are dysplasias rather than true neoplasias. An image analysis study of factors involved in the progression of cervical lesions.

Image analysis was performed on 40 Feulgen-stained histologic samples and 48 Feulgen-stained cytologic preparations representing normal squamous epithelium and all grades of cervical lesions (from mild dysplasia to invasive carcinoma) in order to characterize the evolutionary progressive changes in cervical epithelial proliferative disease toward malignancy. Quantitative studies included the analysis of proliferative features, differentiation features, nuclear morphology and DNA content. The data obtained on the histologic sections showed that the various features, to a different extent, detected a gradual increase in phenotypic cellular disarrangements related to the progression of the cervical lesions toward malignancy--that is, the modifications to nuclear area, perimeter, DNA content, percentage of nuclei with nucleoli, nuclear/cytoplasmic ratio and percentage of cells with no membrane positivity for soybean agglutinin lectin were progressively greater, moving from normal epithelium and mild dysplasia toward infiltrating carcinoma. In particular, all the morphologic and histochemical features appeared to parallel a diploid reduction and the appearance of aneuploidy. The simultaneous evaluation of proliferation- and differentiation-related features, together with those of nuclear DNA content, showed two main successive preneoplastic lesions: one characterized by an increase in cell turnover without alterations in its organization and another by a true neoplastic disorder. The data obtained on sequential cytologic examinations showed that individual cell changes are detectable and seem basically to be characterized by the appearance of clusters of cells with somatic characteristics not observed in previous cytologic checks. From the results of our study, the cervical intraepithelial neoplasia (CIN) concept appears to be inaccurate. In fact, only CIN III (severe dysplasia/carcinoma in situ) lesions have the morphologic and proliferative alterations of true neoplasia. In contrast, CIN I and some cases of CIN II lesions lack these characteristics and seem to be properly classified as dysplasia, thus avoiding the term neoplasia, implicit in CIN. Moreover, the multivariate study of data sets of features related to the progressive somatic changes, both in histologically and cytologically studied cases, allows us to detect the steps of progression; they are marked by the appearance of cell clusters with qualitatively different phenotypic characters when compared to the cell populations from which they presumably arise. These results seem to provide a further argument against the CIN theory, which stresses the concept that progression is related only to a gradual numerical increase in an initially established phenotype with the characteristics of malignancy.

Combined yolk sac tumor and adenocarcinoma in a gastric stump: molecular evidence of clonality.

BACKGROUND: Extragonadal yolk sac tumors of the gastrointestinal tract are extremely rare neoplasms. Their greater rarity compared with other extragonadal yolk sac tumors suggests that different pathogenetic mechanisms could be involved according to the site of origin. This report describes a case of a combined yolk sac tumor and adenocarcinoma that arose in a gastric stump in a man age 61 years 43 years after he underwent distal gastric resection and gastrojejunostomy (Billroth II operation) for a benign duodenal ulcer. The coexistence of an adenocarcinomatous component with the yolk sac component suggests that the two histologic patterns may represent distinct phenotypes arising from a common mucosal epithelial cell. METHODS: Immunohistochemical and molecular techniques were used to define the mutation pattern of p53 in both components of the tumor. RESULTS: Single-strand conformation polymorphism and sequencing analyses demonstrated the same pattern of p53 mutation in the adenocarcinomatous and yolk sac tumor components. CONCLUSIONS: This finding suggests that the two tumors could have been derived from the same cellular clone and supports the hypothesis that the two components represented a heterogeneous differentiation of the same tumor.