Plexiform fibromyxoma of the gallbladder.

We report the unusual case of a plexiform fibromyxoma, occasionally assessed in a lithiasic gallbladder. The full thickness assessment of the gallbladder wall revealed an intra-mural, well demarked multi-nodular tumor (1 cm), consisting of a plexiform growth of spindle cells, included within a fibromyxoid stroma with a rich micro-vascular network. The tumor cells featured no nuclear atypia, nor mitotic activity. At the immunohistochemical profiling, the spindle shaped cells unequivocally featured vimentin, SMA, HHF35, collagen IV, and CD34; no cells expressed CD117, PDGFRA, CD10, desmin, GFAP, EMA, and S-100. Faint STAT6 nuclear expression was observed in isolated tumor cells. The molecular profiling did not revealed any CKIT and PDGFRA genes mutations. The uncommon site of the tumor presentation and its aberrant CD34 expression both confer to the reported case a unique place among the myxoid tumors of the gastrointestinal tract.

Expression pattern of squamous cell carcinoma antigen in oesophageal dysplasia and squamous cell carcinoma.

The aim of the present study was to evaluate the tissue expression of squamous cell carcinoma antigen (SCCA) in oesophageal dysplasia and squamous cell carcinoma (SCC) with reference to its clinico-pathologic and prognostic significance. Immunohistochemistry using SCCA polyclonal antibody was performed on SCCs from 61 surgical oesophagectomies. Fifteen cases of low-grade dysplasia (LGD) and 37 non-coexistent high-grade dysplasia (HGD) were also sampled from these materials, together with sixteen chronic cases of oesophagitis. SCCA immunoreactivity was present in the maturative compartments of all normal epithelia and oesophagitis. LGDs showed no SCCA immunoreactivity in the dysplastic proliferative component but only in the superficial normal layers. In 94.6% of HGDs, no SCCA immunoreactivity was detected throughout the thickness of the epithelium. In SCCs, SCCA expression higher than 25% was found in 54% of cases. SCCA positivity showed an inverse correlation with histological grade, whereas no statistically significant correlation was found with TNM classifications, stage, or survival. SCCA is not expressed in early oesophageal carcinogenesis but, in SCC, it represents an indicator of histologic differentiation. In differentiated SCC, SCCA may represent a negative factor for cancer invasiveness, through inhibition of proteases.

Nuclear maspin detection in renal cell tumours: possible diagnostic role and correlation with p53 status.

AIMS: To investigate the presence of maspin in renal tumours in an attempt to improve our understanding of the underlying mechanism of renal carcinogenesis and for diagnostic purposes. METHODS AND RESULTS: We examined 122 renal neoplasms of varying histological types and immunohistochemically investigated maspin and p53 expression. All clear cell carcinomas (CC) were negative for maspin, whereas oncocytomas (OC), papillary renal cell carcinomas (PC), chromophobe carcinomas (CPC) and, at least focally, collecting duct carcinomas (CDC) stained positively. We found that p53 positivity had a statistically significant correlation with metastasis (P=0.009) in CC and maspin showed a significant inverse correlation with the presence of metastasis in PC and CDC (P=0.02). CONCLUSIONS: The detection of maspin may be useful for differential diagnostic purposes and suggests a different underlying mechanism in the development of the various histological types of renal carcinomas.

A short course of dissection for second-year medical students at the School of Medicine of Padova.

A "Short course of dissection" was introduced in 1999 for the second-year medical students at the University of Padova. The course aims to offer a direct experience of practical anatomy despite a shortage of time for anatomy courses and lack of availability of cadavers. The course is optional and is planned for 40 students, subdivided into eight working groups. It consists of five sessions on the following topics: the viscera of the male pelvis; the viscera of the female pelvis; the kidney, the testis and spermatic cord; the thorax and abdomen; the brain. Each session lasts 3 hours and is organized as follow: (A) Theory: Teacher: concise review of the systematic and topographic anatomy of the selected topic (20 min); Students: analysis of a dissection guide (20 min). (B) Practice: Students: identification of the viscera and vascular and nervous structures, through inspection and palpation (15 min); step-by-step dissection following the worksheet (80 min); presentation of the visceral blocks as prosections under a closed-circuit telecamera (anatomical variability) (30 min); Teachers and students: three-dimensional conceptualization tests (15 min). At the end of the 2000 and 2001 courses, a questionnaire was administered to the students and the results confirm the usefulness of dissection for developing a three-dimensional knowledge of anatomy. In our opinion the main guidelines in planning a short course of dissection are: (1) selection of the topics, aimed at allowing experience of the gross anatomy of single viscera, fascia and serosa as well as the evaluation of the topographical relationships between parts of different systems including the local vessels and nerves; (2) preparation of a worksheet, presenting in 10-15 points concise instructions for the step-by-step progression from inspection to palpation and dissection of the anatomical structures of the visceral block; (3) direct dissection, brief and selective, by students; (4) clinical correlation; (5) motivational teachers, who stimulate the active involvement of students in "learning by doing" and also "learning how to do".

Follicular dendritic cell tumor of the mediastinum.

Follicular dendritic cell tumor (FDT) is a rare neoplasm usually occurring in the laterocervical lymph nodes, but presentations elsewhere are also well documented. We report a case of FDT in a 48-year-old man with myasthenia gravis, in whom a slow-growing mediastinal mass that had been surgically excised manifested after 3 years with a local recurrence in the same site. The lesion was aspirated and cytology showed a tumor composed of groups of oval or elongated cells intermingled with several mature small lymphocytes. On histology, the tumor was highly cellular with abundant perivascular lymphocytic infiltration; large cells with pale, eosinophilic cytoplasm and round nuclei, arranged in fascicles often showed a storiform pattern. Occasional binucleated cells were also present. A panel of antibodies showed positivity only for CD21 and CD35, and a weak response to S-100. Electron microscopy showed that the layer cells had convoluted nuclei and elongated interdigitating processes with desmosome-like junctions. The definitive diagnosis of FDT can be concluded only with positive immunostaining for CD21 and CD35. However, in the presence of a mixed population of lymphocytes and larger eosinophilic cells the hypothesis of FDT should always be considered.

Childhood leiomyosarcoma: a report from the soft tissue sarcoma Italian Cooperative Group.

BACKGROUND: Only a few reports on the clinical features and management of childhood leiomyosarcoma are available. To contribute additional information on the management of this rare tumor, we report on a series of 16 pediatric patients treated from 1982 to 1998 by the Soft Tissue Sarcoma Italian Cooperative Group. PATIENTS AND METHODS: Primary surgery was conservative in all but two patients, and consisted of biopsy--three cases, non-radical excision--four, and radical resection--nine (involving a primary re-excision in 4 of 9). In two cases secondary radical surgery was performed after primary chemotherapy. Chemotherapy was administered to 9 of 16 patients, radiotherapy to three. RESULTS: After a median follow-up of seven years (range 3-18), the five-year event-free survival (EFS) and overall survival were 56.3% and 72.9%, respectively; 12 of 16 patients were alive (nine of them in continuos complete remission). Univariate analysis was performed to compare EFS according to different subgroups: size represented the most significant prognostic factor. CONCLUSIONS: Complete surgical resection is the mainstay of treatment for leiomyosarcoma. The role of both adjuvant chemotherapy and radiotherapy has yet to be established, and awaits cooperative multicentric studies.

Telomerase activity, Ki-67, cyclin D1 and A expression, and apoptosis in solitary fibrous tumors: additional features of a predictable course?

Solitary fibrous tumors (SFTs) are infrequent soft tissue neoplasms which are usually benign and surgically curable. However, their behavior is not always predictable, although several clinical and pathological criteria of malignancy have been established. In many cancers, including some soft tissue tumors, telomerase activity (TA) has been shown to be a new reliable pathological marker of malignancy. Overexpression of some cyclins is associated with higher degrees of malignancy and predictive of the clinical course. In this study, we evaluated TA, mitotic and apoptotic indices (MI, AI), and the expression of Ki-67, cyclins D1 and A in five typical and two clinicopathologically atypical SFTs, the latter two of which had also recurred. High TA was demonstrated in the two atypical cases, which also showed a higher labeling index to Ki-67, as well as higher cyclin D1 and A expression, and either none or very few apoptoses. We suggest that TA, Ki-67, cyclin expression, and AI be evaluated in SFTs as possible adjunctive pathological criteria of behavior.

MAGE, BAGE and GAGE gene expression in human rhabdomyosarcomas.

MAGE, BAGE and GAGE genes encode tumor-associated antigens that are presented by HLA class I molecules and recognized by CD8(+) cytolytic T lymphocytes. These antigens are currently regarded as promising targets for active, specific tumor immunotherapy because MAGE, BAGE and GAGE genes are expressed in many human cancers of different histotype and are silent in normal tissues, with the exception of spermatogonia and placental cells. MAGE, BAGE and GAGE gene expression has been extensively studied in different tumors of adults but is largely unknown in many forms of pediatric solid cancer. Using RT-PCR, we analyzed MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-6, BAGE, GAGE-1,-2 or -8 and GAGE-3,-4,-5,-6 or -7b gene expression in 31 samples of pediatric rhabdomyosarcoma, the most frequent form of malignant soft tissue tumor in children. MAGE genes were expressed in a substantial proportion of patients (MAGE-1, 38%; MAGE-2, 51%; MAGE-3, 35%; MAGE-4, 22%; MAGE-6, 35%), while expression of BAGE (6%); GAGE-1, GAGE-2 and GAGE-8 (9%); and GAGE-3, GAGE-4, GAGE-5, GAGE-6 and GAGE-7B (16%) was less frequent. Overall, 58% of tumors expressed at least 1 gene, and 35% expressed 3 or more genes simultaneously. Our data suggest that a subset of rhabdomyosarcoma patients could be eligible for active, specific immunotherapy directed against MAGE, BAGE and GAGE antigens.

Leiomyosarcoma of the Oropharynx and Neurogenic Tumors in a Young Patient With Turner's Syndrome.

PATIENT: A case of Turner's syndrome developing a leiomyosarcoma of the oropharynx and metachronous neurogenic tumors (mediastinal 'ganglioneuroblastoma intermixed', subcutaneous neurilemoma) is described. DISCUSSION: To our knowledge, this case is the second reported leiomyosarcoma in a patient with Turner's syndrome. Also the site of involvement (palate and oropharynx) is particularly unusual for the already rare leiomyosarcomas in the young age.

Pleuropulmonary blastoma: management and prognosis of 11 cases.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive malignant tumor that affects children and adults. This neoplasm is histologically characterized by primitive blastema and a malignant mesenchymal stroma that often demonstrates multidirectional differentiation. Despite the introduction of multimodal therapy, the prognosis of patients with PPB remains poor. METHODS: In the current study the authors reported on PPB cases from a national retrospective search performed in 18 Italian Associations for Pediatric Hematology and Oncology centers. Clinical data, surgical notes, pathologic findings, and summaries of chemotherapy and radiotherapy were obtained from reports and correlated with outcome by standard statistical methods. RESULTS: The series included 11 patients (7 boys and 4 girls) with a median age of 32 months. Respiratory distress was the most common clinical symptom. In three patients the PPB developed from other primary dysplastic diseases: cystic adenomatoid malformation in one case and congenital lung cysts in the other two cases. Five patients experienced disease recurrences (local recurrence in three patients and distant metastasis in two patients, within the central nervous system and an intraocular location, respectively). Patients with a type 2 histologic pattern and/or pleural involvement were found to have a worse outcome compared with patients without such features. Event free survival at 2 years from the time of diagnosis was 45% for all patients. Overall survival at 2 years was 72% for all patients. CONCLUSIONS: PPB is an aggressive neoplasm of early childhood and to the authors' knowledge no adequate therapy has been defined to date for patients with PPB. After making the diagnosis, the main goal of therapy should be radical surgery, even in patients with microscopic residual disease. Because the response to chemotherapy is poor, the authors' experience suggests that chemotherapy should be given with local radiotherapy in the majority of patients.

Unusual second malignancies following radiation therapy: subcutaneous pleomorphic rhabdomyosarcoma and cutaneous melanoma. Two case reports.

BACKGROUND: Among nonepithelial second neoplasms which are known to be induced by irradiation, rhabdomyosarcomas are extremely rare, and melanomas are infrequent. We report a high-grade sarcoma with rhabdomyoblastic differentiation, which appeared 30 years after megavoltage irradiation for an endometrial adenocarcinoma, and a malignant melanoma which arose after 6 years in the irradiation field of a fibrosarcoma. METHODS: Histology and immunohistochemistry were performed in both cases. In the first case, electron microscopy was also performed. In the second, the previous tumor was re-evaluated. RESULTS: The first case showed histological, immunohistochemical and ultrastructural features of a rhabdomyosarcoma. In the second case, a lentigoid malignant melanoma was histologically and immunohistochemically demonstrated, whereas the previously resected tumor was a fibrosarcoma negative to melanoma markers. CONCLUSIONS: Rare cases of rhabdomyosarcomas and melanomas are induced by irradiation, although in some cases other factors (i.e., genetic risk, chemotherapy) may have a prominent etiopathogenetic role in their development. A close follow-up and a careful examination of the irradiated area should facilitate an early diagnosis of these aggressive postradiation second neoplasms.

Desmoplastic small round cell tumour in children and adolescents.

BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare highly aggressive neoplasm, and clinical studies are scarce. PROCEDURE: We report six cases of children and adolescents (median age 14 years, range 6.9-17.5) with DSRCT (5 abdominal, 1 paratesticular) registered by the Italian Cooperative Group (ICG) for soft tissue sarcoma over a 9-year period. Patients received a multidisciplinary treatment, including aggressive initial or delayed surgery and radiotherapy. Chemotherapy regimen was based on the use of ifosfamide, vincristine, dactinomycin, and a few doses of antharacyclines (doxorubicin or epirubicin). RESULTS: Complete surgical resection was possible only for the paratesticular tumour. Among the patients with abdominal lesions, macroscopically radical excision was possible in only one case. All patients received multidrug chemotherapy, and tumour reduction was obtained in the 4 evaluable patients. No relapses were evident in the irradiated fields in the 4 patients who received radiotherapy. Two patients remained progression-free 22 and 63 months after diagnosis, one is in third complete remission, whereas three died 10-25 months after diagnosis. CONCLUSIONS: DSRCT is a chemosensitive tumour, but survival rates remain disappointing despite aggressive multimodality therapy. Our results support surgical tumour removal and radiotherapy to achieve local control. Our experience and a review of the literature suggest that patients with localised abdominal tumours or a paratesticular primary may have a better prognosis.

All-trans retinoic acid and interferon-alpha in the treatment of a patient with resistant metastatic osteosarcoma.

BACKGROUND: A boy age 14 years who was in complete remission from Stage IIB small cell osteosarcoma, which was misdiagnosed as Ewing sarcoma and consequently was treated, developed inoperable lung metastases when he was off therapy. He received second-line treatment for recurrent Ewing sarcoma, including chemotherapy and radiotherapy, and obtained only a temporary response. A compassionate treatment with all-trans retinoic acid (ATRA) and interferon-alpha (IFNalpha) was then undertaken. METHODS: The patient initially was treated according to the national SE91 protocol for nonmetastatic Ewing sarcoma. After a bilateral pulmonary recurrence, he received second-line chemotherapy and irradiation of the largest metastasis, with a temporary partial response. The patient was then treated with a combination of oral ATRA (90 mg/m(2) for 3 days per week) and subcutaneous IFNalpha (3 x 10(6) U/m(2) 5 days per week) for 4 months. The same therapy also was administered for the control of residual disease after surgery for a total duration of 1 year of ATRA/IFN treatment. During the first 3 weeks of therapy, ATRA pharmacokinetics were studied. RESULTS: After progression of the patient's disease, despite the administration of first-line and second-line chemotherapy, combined treatment with ATRA/IFNalpha yielded a partial remission, which allowed surgical resection of the largest metastasis. The same therapy was effective in preventing tumor recurrence after incomplete removal of the remaining metastases. Treatment was well tolerated, and the patient is in stable complete remission 14 months after the end of therapy. The pharmacokinetics results confirmed the indication of an intermittent schedule for oral ATRA therapy. CONCLUSIONS: ATRA/IFNalpha treatment may be considered as an alternative approach in the treatment of patients with metastatic osteosarcoma who have disease that is resistant to conventional chemotherapy and in the treatment of patients with minimal tumor residue.

Tumors of the soft tissues composed of large eosinophilic cells.

Soft tissue neoplasms composed of large eosinophilic cells include benign and malignant tumors with different degrees of biological aggressiveness. The main histotypes discussed in this review are the heterogeneous group of benign and malignant granular cell tumors with neural and non-neural differentiation, alveolar soft part sarcomas, rhabdomyomas, and rhabdomyosarcomas. The salient anatomic, clinical, morphological, and immunophenotypic features in differential diagnosis with metastatic melanomas, carcinomas, and paragangliomas are discussed separately for each histotype.

Nuclear p53 protein expression in resected hepatic metastases from colorectal cancer: an independent prognostic factor of survival.

An association has been reported between nuclear p53 protein expression in tumour cells and a poor outcome in patients with colorectal cancer (CRC). In this study we investigated the prognostic significance of nuclear p53 protein expression in CRC liver metastases after curative hepatic resection. The study population consisted of 69 consecutive patients who underwent curative hepatic resection for metastases from CRC at our Institution between February 1987 and October 1993. Immunohistochemical expression of p53 protein was evaluated in formalin-fixed paraffin-embedded sections of CRC liver metastases using the monoclonal antibodies (MAbs) D01 and Pab 1801. The Cox proportional hazards model was used in forward stepwise regression to assess the relative influence of different prognostic factors. Forty-four (63.8%) CRC liver metastases were p53-positive. Kaplan-Meier survival curves demonstrated that patients with p53-positive metastases had a median survival of 27 months versus 93 months for patients with p53-negative metastases (P < 0.01). The 3 and 5 years survival rates were 31.5 and 21.0% in patients with p53-positive metastases and 71.8 and 53.1% in patients with p53-negative metastases. At multivariate analysis p53 protein status was the single best predictor of survival (P = 0.0079); the odds ratio of death among patients with p53-positive tumours was 2.53. Nuclear p53 protein expression in hepatic metastases from CRC is an independent prognostic factor of survival following liver resection. These findings may be of clinical importance in the selection of patients more likely to benefit from liver resection and could be used as criteria for stratification in trials on adjuvant therapy.

Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.