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p53 and p185 expression in primary breast cancer with microsatellite instability (MSI) is still largely unexplored. To investigate the relationship between these oncoproteins and the pathways of genomic instability, we examined 52 primary invasive breast cancers stratified by the presence and absence of MSI. We determined the status of eight microsatellite loci using radioactive and silver staining methods, and evaluated the immunohistochemical expression of p53 and p185 in a consecutive series of Italian cancer patients characterized by clinical-pathological and biological parameters. Nineteen cases (36.5%) were MSI-positive in at least two loci. p53 was expressed in 15 cases (28.8%) and p185 in eight (15.4%). MSI-positive tumors were inversely correlated with p53 expression (p = 0.0007); in addition, the percent of p53-expressing cells decreased as the number of MSI-positive loci increased. MSI-positive tumors were correlated with a larger tumor size (p = 0.04), lymph-node metastasis (p = 0.001), and advanced clinical stage (p = 0.0006). These data demonstrate the existence of two subsets of primary breast cancers: one characterized by MSI, the other by p53 expression. MSI-positive patients had a more advanced and/or aggressive disease.

Purpose: To evaluate the predictive value of sentinel lymph node biopsy versus axillary node dissection on lymph node status in patients with T1-T2 breast cancer., Material and Methods: Twenty-nine patients with T1 and 12 with T2 breast carcinoma and clinically N0 axillary lymph nodes, underwent lymphoscintigraphy following the administration of 99mTc-human albumin nanocolloids. The tracer was injected subdermally, over the tumor mass, in the 34 patients with palpable lesions and peritumorally (n=3) or intratumorally (n=4), under stereotactic or ultrasound guidance, in the 7 patients with non-palpable lesions. Anterior and lateral planar images were acquired 15 min after the injection of the tracer and repeated every 30 min up to 3 hr until identification of sentinel lymph node. At the end of the scintigraphic study, sentinel node skin projection was marked using a dermographic pen. Eighteen hours after lymphoscintigraphy, sentinel lymph node was identified and removed during surgery by hand-held gamma probe, then, the remaining axillary lymph nodes were dissected. All surgical specimens underwent histologic examination. Sentinel lymph nodes free of metastasis at histology, underwent additional examination with immunohistochemistry using monoclonal antibodies against cytokeratin and EMA to search for micrometastases., Results: Sentinel lymph node was identified in the 34 patients injected subdermally and in the 3 patients injected peritumorally, while it remained undetected in the 4 patients injected intratumorally except for one case in which it was isolated by radioguided surgery but not scintigraphically. Sentinel nodes resulted free of metastases both at histology and immunohistochemistry in 32 cases and metastatic in 6. In the 32 patients with non-metastatic sentinel lymph nodes the other axillary nodes were also free of metastases. Among the 6 metastatic sentinel lymph nodes, in 3 cases they were the only metastatic nodes of the axilla while in the other 3 cases metastases were spread to other axillary nodes., Conclusions: In agreement with previous studies, our results showed that sentinel lymph node radioguided biopsy is a simple and reliable method for predicting axillary lymph nodes status and for avoiding axillary dissection in early breast cancer patients with sentinel node free of metastases.

Testicular tumours represent 2% of all male malignancies, mostly concerning young men (20-40 years old). The polyembryoma is one of the uncommonest lesions and just recently it has been identified as autonomous nosographic entity. The reported case is peculiar because the patient was older than the most ones described in the literature and the tumour arose after polychemotherapy for non Hodgkins' disease. The Authors analyse some aspects concerning etiology, pathology and clinical approach to such rare neoplasm.

Hematopoiesis is controlled by numerous interdependent humoral and endocrine factors. Erythropoietin (EPO), a hydrophobic sialoglycoproteic hormone, plays a crucial role in the regulation of hematopoiesis, and induces proliferation, maturation and differentiation of the erythroid cell line precursors. Thanks to recombinant DNA techniques, different recombinant hormones can now be produced at low cost and in large amounts. This has led to greater understanding of the pathophysiological factors regulating hematopoiesis. This in turn, hasprompted the search for new therapeutic approaches. EPO might also be used to treat patients with different types of anemia: uremics, newborns, patients with anemia from cancer or myeloproliferative disease, thalassemia, bone marrow transplants, chronic infectious diseases. Besides erythroid cells, EPO affects other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. It can also enhance polymorphonuclear cell phagocytosis and reduce macrophage activation, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same origin, and the discovery of eyrthropoietin receptors also on mesangial, myocardial and smooth muscle cells has prompted research into the non-erythropoietic function of the hormone. EPO has an important, direct, hemodynamic and vasoactive effect, which does not depend only on an increase in hematocrit and viscosity. Moreover, EPO and its receptors have been found in the brain, suggesting a role in preventing neuronal death. Finally, the recently discovered interaction between EPO and vascular endothelial growth factor (VEGF), and the ability of EPO to stimulate endothelial cell mitosis and motility may be of importance in neovascularization and wound healing.

We analysed the differential expression pattern of the three distinct TAG-72 carbohydrate epitopes detected by monoclonal antibodies (MAbs) B72.3, CC83 and CC49 in a consecutive series of 114 patients with primary breast cancer and in 39 synchronous lymph node metastases. B72.3, CC83 and CC49 were expressed in respectively 81 (71%), 68 (60%) and 96 (84%) of the 114 cases. Interestingly, MAb B72.3 was significantly expressed in a subgroup of patients characterised by larger tumour size (p=0.013), lymph node metastasis (p=0.0002), high histopathological grade (p=0.006), high cell kinetics (p=0.04) and advanced clinical stage (p=0.0019). In 20 (51%) of the 39 pairs of matched primary breast cancers and synchronous lymph node metastases, TAG-72 was expressed in the tumour but not in the corresponding metastatic lymph node; tumours with TAG-72-negative lymph nodes appeared to be clinicopathologically more aggressive. CC49, the most immunoreactive and widely used MAb, was not detected in 34% of the metastases of expressing primary tumours. All three MAbs were found in a significantly lower per cent of synchronous metastases with respect to primary tumours (p<0.001).

Sarcomatoid carcinoma (SC) is a well defined tumor type that may occur in all organs and anatomic sites but most commonly in the head, neck, respiratory tract, breast, and genitourinary tract. It is a biphasic tumor showing both epithelial- and mesenchymal-like differentiation; however, its carcinomatous nature is widely recognized. SC is rare in the gastrointestinal tract. In the esophagus it accounts for less than 5% of all malignancies and approximately only 35 cases have been described in the stomach. Very few cases have been observed in the small intestine, anorectal junction, liver, and pancreas. To our knowledge only eight cases of SC have been reported in the colon. We report a case of primary colonic SC. Both morphological and immunohistochemical analyses are provided along with an evaluation of the unusual clinical history, therapeutic implications, and controversial differential diagnosis.

A case of Kaposi sarcoma with HIV-negative and sequence of HHV-8 positive and exclusive rectosigmoid and descending colon involvement without immunodeficiency is reported. Histologically, in addition to typical features of Kaposi sarcoma, Cowdry type A inclusions were seen. PCR analysis of the tumor showed positivity for human herpesvirus 8. Two of the six reported cases of Kaposi sarcoma limited to the bowel were from African men before the AIDS epidemic. J. Surg. Oncol. 2001;76:197-200., (Copyright 2001 Wiley-Liss, Inc.)

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are established drugs for the treatment of hypercholesterolemia, but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering. Moreover, in experimental models of progressive renal disease, statins have reduced the extent of glomerulosclerosis. This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy, stable renal function, and no indicators of poor long-term prognosis. The effects of therapy were evaluated on the basis of 24-hour proteinuria (total proteinuria and albuminuria), albuminemia, creatinine clearance, cholesterol, and triglyceride values. Renal function remained stable in all patients. A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations. An increase in serum albumin was observed after 6 months of therapy. This study suggests that there is an antiproteinuric effect of HMG-CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy.

Amyloid deposition in secondary amyloidosis frequently involves thyroid gland, but rarely is responsible of a goiter. Amyloid goiter in secondary amyloidosis is characterized by deposition of amyloid A protein (AA) in the gland, associated to atrophic follicles. We identified cases of amyloid goiter in the files of our department in the period from 1985 to 1998. Five cases of amyloid goiter with ingravescent symptomatology, characterized by dyspnea, dysphagia and hoarseness were selected. In four cases of five we observed predisposing conditions as, for example, tuberculosis, Crohn's disease, or rheumatoid arthritis. In all cases the symptoms relative to thyroid enlargement preceded or, anyway, predominated over other clinical evidence of systemic amyloidosis. In one case a symptomatology of systemic amyloidosis was not evident. We would like to underline that in all cases the immunoreactivity for amyloid A in the amorphous material present in the gland permitted the diagnosis of secondary amyloidosis even in the absence of systemic symptoms.

We measured neovascularization, epidermal growth factor receptor, and c-erbB-2 expression in a consecutive series of 233 surgically resected axillary lymph node-negative breast cancer patients with a long-term follow-up to define the usefulness of these parameters as independent prognostic indicators of overall survival (OAS). Microvessel count (MVC), as a measure of neovascularization, was determined using a monoclonal antibody against human factor VIII-related antigen. The median MVC of 20 (range, 4-76) was used as a cutoff value for discriminating between low and high vascularized tumors. Epidermal growth factor receptor and c-erbB-2 expression were evaluated by immunohistochemistry. Tumors were considered positive if >10% of the cells showed specific membrane staining. OAS curves were estimated by the Kaplan-Meier method. The independent prognostic effect of each variable was determined with the Cox proportional hazards model. High MVC (P = 0.04), high nuclear grade (P = 0.005), and high S-phase (P = 0.02) significantly affected OAS at univariate analysis. In a Cox multivariate analysis, the characteristics with an independent prognostic effect on OAS were: MVC (relative hazard, 2.12; 95% confidence interval, 1.18-3.81; P = 0.01) and nuclear grade (relative hazard, 2.83; 95% confidence interval, 1.12-7.17; P = 0.01). These results demonstrate that quantification of neovascularization adds useful independent prognostic information on survival in node-negative breast cancer patients with long-term follow-up.

Background: Intraabdominal desmoplastic small round cell tumor (DSRCT) is a recently recognized type of primitive sarcoma characterized by a predilection for young males, a usually very aggressive course and generally unsuccessful therapy. A primitive histologic appearance with prominent desmoplasia and striking divergent multilineage differentiation are well-described morphologic features of this tumor, along with a consistent fusion of the EWS and WT1 genes at the molecular level. The cytologic literature contains only scattered references to this type of neoplasm. Detailed information on the clinical and fine needle aspiration (FNA) biopsy and the immunocytochemical and ultrastructural findings in a patient with DSRCT is presented., Case Report: A 23-year-old male had a firm abdominal mass with multiple secondary lesions of the liver. An FNA biopsy was performed under ultrasonographic guidance., Conclusion: FNA of the liver nodules showed cohesive groups of small cells with hyperchromatic nuclei and inconspicuous nucleoli; immunocytochemically vimentin and desmin showed characteristic perinuclear globular positivity. FNA cytology is an effective means of diagnosing deeply located lesions. The cytologic features of DSRCT need to become familiar to pathologists and must be considered in the differential diagnosis of liver metastasis.

We evaluated blood concentrations of bcl-2, a proto-oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl-2 were higher in patients with proteinuria than in those without proteinuria. A 6-month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl-2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl-2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin-converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.

Ten cases of breast hamartomas were reviewed; the patients' age ranged from 31 to 55 (mean 40.4, median 39). All cases presented with a palpable, sometimes tender, lump. The typical mammographic feature was a well defined, round to lens shaped, variable dense mass, occasionally surrounded by a thin radiolucent zone. All hamartomas were unilateral (4 in the right and 6 in the left breast, respectively) and no recurrence occurred after local excision. The tumor size ranged from 5 to 150 mm (mean 54 mm). Histologically all hamartomas were composed of a typical fibrous, adipose and glandular tissue combination. Immunohistochemically there was a strong positivity for cytokeratin and epithelial membrane antigen in the epithelial cells, a positive finding for vimentin and muscle-specific actin in stromal and myoepithelial cells, and for S-100 protein in myoepithelial cells. Vessels endothelial cells were immunoreactive for Factor VIII. Immunohistochemical analysis of hormone receptors completed on formaldehyde-fixed paraffin-embedded specimens, showed estrogen and progesterone receptors positivity in 9 cases and estrogen positive progesterone negative receptors in one case. In all cases the receptorial positivity was limited to the epithelial elements. These data revealed that 1) breast hamartoma is a benign, tumor-like lesion, histologically dissimilar from other lesions such as fibroadenoma and pseudoangiomatous hyperplasia; and 2) hamartoma tissue is influenced by hormones like the surrounding normal breast parenchyma.

The superiority of intensive versus standard chemotherapy for aggressive (I: intermediate; H: high grade) NHL is still debated; increased antitumor activity may be counterbalanced by increased toxicity. We have designed a first-line five-drug regimen (vincristine, idarubicin, cyclophosphamide, etoposide and deflazacort), with the aim of potentiating the CHOP protocol without losing tolerability and ease of administration. Seventy-one patients (33% aged > or = 65) entered the study. CR was obtained in 66.7% of patients (I: 74%; H: 56%), PR in 19.7%: overall response rate was 86.4%. Six patients were resistant, two died during treatment. With a median follow up of two years, relapse has occurred in 14 patients (8 I, 6 H). At 3 years, overall survival was projected to be 62.5% (I 73.5%; H 31.4%), disease free survival 66% (I 71%, H 56.3%). No organ toxicity occurred. Myelosuppression was moderate, with a nadir on the 14th day. Febrile episodes occurred in 16% of courses, dose delay in 19% of courses; dose reduction in 3% of patients. No patient required hospitalization. G-CSF was only occasionally used. This regimen has shown a potent antitumor effect with an excellent tolerance, even in elderly patients.

Benign lesions represent the most frequent lesions of the breast. Such lesions often onset with nodules or palpable masses simulating a breast cancer. In uncertain cases, an excisional biopsy may be at the same time a diagnostic and a therapeutic solution. A high percentage (40%) of the diagnosed lesions belongs to fibrocystic disease. A remaining 50% can be shared among tumor-like lesions, inflammatory lesions or benign tumors like fibroadenomas. Only in the 10% of palpable breast masses, biopsy reveals a breast cancer. The role of the pathologist is strictly related to the surgeon's one. Clinically benign lesions may be excised throughout a biopsy performed under local anesthesia. Clinically uncertain lesion must be evaluated by a fine needle aspiration biopsy (FNAB), nevertheless in some cases the doubt may persist. In such cases an excisional biopsy performed while the patient is under general anesthesia may finally solve the question. In case of breast malignancies the intervention can be enlarged as described for cancer.

The effect of administration of human recombinant erythropoietin on leukocytic cells has been evaluated. In humans the administration of 20,000 U i.v. of rHuEPO caused a rapid and transitory leukopenia that seemed to be caused by a preferential reduction of lymphocytes (2715 +/- 513 mm3 t 0; 1898 +/- 506 t 60', p < 0.002). Pretreatment with imidazole-2-hydroxybenzoate, a drug capable of inhibiting the synthesis of prostaglandins, caused a less marked and later reduction of lymphocytes (2242 +/- 477 t 0; 1560 +/- 318 t 180 minutes, p < 0.001). A less marked and later lymphocytopenia was also shown in subjects affected by chronic renal insufficiency (2907 +/- 726 t 0; 1944 +/- 512 t 180 minutes, p < 0.005).

A new case of breast tumor with features of eccrine spiradenoma is described. This neoplasm is exceedingly rare, because only two cases, arising in breast parenchima, have been previously reported. The patient was a 43-year-old woman and she experienced three local recurrences at 7, 20, and 30 months from the first excision. No distant metastases were observed. Microscopically, the tumor was circumscribed and showed a lobulated pattern. Neoplastic lobules consisted of packed, monotonous, basaloid epithelial cells with round to ovoid nuclei and scant cytoplasm. At the periphery, the lobules were delimitated by smaller cells with dark nuclei. Immunohistochemical reactivity in tumoral cells was found for both cytokeratin and epithelial membrane antigen; vimentin, muscle-specific actin, glial fibrillary acidic protein, S-100 protein, and carcinoembryonal antigen were all negative. Furthermore, the lesion showed a diffuse positivity for estrogen and progesterone receptors and a high growth fraction labelled by MIB-1 (Ki-67) antibody. These findings, in conjunction with the deep location of the tumor, suggest an origin of the neoplasm from the breast epithelium. Because of a potential local aggressive behavior, the excision of a wide rim of uninvolved breast tissue is recommended.

Three cases of endometriosis of the bowel with lymph node involvement were studied. Histologically, endometriotic glands with typical stroma were recognized throughout the intestinal wall, from the subserosal tissue to the mucosa. Foci of endometriosis were found in a number of pericolic lymph nodes occupying the subcapsular area or the cortex. The cytological smears were cellular, composed of large sheets of mucous columnar cells of intestinal origin, mixed with groups of recognizable endometrial cells and smaller spindly cells of endometrial stroma. Immunohistochemically, endometriotic cells showed positivity for cytokeratin and EMA, and they retained immunoreactivity for estrogen and progesteron in the intestinal lesions, as well as in the lymph nodes. Lymph nodal endometriosis was disclosed in two out of three cases only by multistep section examination of the pericolic lymph nodes, previously reported as negative for this feature.

Sex cord-stromal tumors of the pediatric testis present diagnostic and therapeutic challenges. This study examines the clinicopathologic features of 16 testicular sex cord-stromal tumors from children less than 18 years of age. Four juvenile granulosa cell tumors and five tumors of Sertoli or incomplete differentiation in this study had high mitotic rates and/or sarcomatoid areas that suggested malignancy, but none of these children developed recurrence or metastases. Some of these tumors had been initially misdiagnosed as yolk sac tumors or rhabdomyosarcomas because of the presence of areas superficially resembling these neoplasms. These morphologic pitfalls have received little attention in the literature. Even incompletely differentiated sex cord-stromal tumors have at least focal areas characteristic of juvenile granulosa or Sertoli cell differentiation. In addition, immunohistochemical negativity for alpha-fetoprotein, muscle specific actin, and desmin are useful for ruling out yolk sac tumor and rhabdomyosarcoma. Four patients had Leydig cell tumors and three had large cell calcifying Sertoli cell tumors. Children with Leydig cell tumors are not at risk for metastasis, but children with large cell calcifying Sertoli cell tumors are at risk for endocrine syndromes as illustrated by one of our cases. The differential diagnosis of these tumors is also discussed.

The tumor designated by Stout and Murray as "hemangiopericytoma" (HPC) more than 50 years ago continues to represent a source of uncertainty and disagreement among pathologists. In particular, questions exist regarding the synonymity of a hemangiopericytomatous growth pattern--defined by a monomorphic population of compact polygonal or bluntly fusiform cells and a branching stromal vascular pattern with a "staghorn" configuration--and the presence of a reproducible biological entity. It has been shown repeatedly that these same histologic features may be observed at least focally in a diversity of neoplasms, including "true" hemangiopericytomas, synovial sarcomas, mesenchymal chondrosarcomas, infantile fibrosarcomas, malignant fibrous histiocytomas, malignant peripheral nerve sheath tumors, leiomyosarcomas, endometrial stromal sarcomas, solitary fibrous tumors, myofibromas, malignant mesotheliomas, thymomas, sarcomatoid carcinomas, malignant melanomas, and "phosphaturic mesenchymal tumors." Despite their potential sharing of the microscopic attributes in question, such neoplasms have individualistic clinical features and can also be distinguished from one another by specialized pathologic analyses. HPC is "defined" in that context by reactivity for vimentin, with or without CD34 and CD57, but it lacks other immunodeterminants of epithelial, neural, and myogenous differentiation. Paradoxically, this phenotype is indeed associated with the presence of myogenous-type cytoplasmic filaments in ultrastructural evaluations of HPC. Other lesions that may resemble "true" HPC--but which possess dissimilar subcellular and clinical characteristics--include solitary fibrous tumors, hemangiopericytomalike tumors of the sinonasal tract, and "infantile (congenital) hemangiopericytomas." Such observations suggest that the hemangiopericytoma is both a pathologic entity and a morphological pattern, and they emphasize the utility of adjuvant pathologic studies in this diagnostic context.

We analyzed retrospectively the relationships and the prognostic significance of four anatomopathological features (elastosis, fibrosis, necrosis, inflammatory cell reaction) of the primary tumor in a series of 1,457 cases of infiltrating ductal carcinoma observed at our institution from January 1978 to December 1991. Necrosis, elastosis, fibrosis and inflammatory cell reaction were strongly associated among themselves (all p < 0.0001), the only exception being necrosis and elastosis. Necrosis was significantly related to tumor size (odds ratio [OR] = 5.40, p < 0.0001) and tumor grade (OR = 2.22, p < 0.0001). Univariate analysis showed that the presence of necrosis and cell reaction were significantly related to worse survival (p < 0.0001 and p = 0.03, respectively). Multivariate analysis, including the four variables plus nodal status, tumor size, grading, adjuvant therapy, age and first order interactions, revealed that greater tumor size (p < 0.0001), positive nodal status (p < 0.0001), higher histologic grade (p < 0.0001) and presence of inflammatory cell reaction (p = 0.0007) independently worsened survival. On the other hand, adjuvant therapy had a significant independent role in preventing deaths (p = 0.03). The only first-order interaction retained in the model was that between grading and cell reaction (p = 0.002). Cell reaction had a different prognostic behaviour in the groups G1-G2 and G3: in the former group, survival was worse (p = 0.0001) when the inflammatory cell reaction was present. In conclusion, we demonstrate that cell reaction is an independent prognostic factor in the G1-G2 subgroup of patients, and propose a hypothesis as to the role of cell reaction in primary breast cancer.

Four cases of gastric carcinoma are described that are associated with an osteoclast-like giant cell (OGC) stromal component. The patients were all middle-aged men (range 53-63 years). Microscopically, the tumors were characterized by a bland cytologic appearance, and an either solid or cribriform pattern. Osteoclast-like giant cells were found adjacent to, or intimately intermixed with, the neoplastic cells in the primary gastric masses and in the lymph nodal metastases and were often associated with lymphocytes, histiocytes, and desmoplastic stroma. By immunohistochemistry, mononuclear cells and OGCs showed diffuse positivity for alpha-1-antichymotrypsin, alpha-1-antitrypsin, and CD68. Neoplastic cells that were positive for keratin and CEA, also showed reactivity for vimentin and the latent membrane protein of Epstein-Barr virus in one case. At follow-up, three patients had died at 13, 15, and 24 months after diagnosis, and one is still alive, without evidence of disease, after 120 months. This report describes a novel variant of gastric carcinoma with distinctive and histologic features.

We report a case of pilomatrix carcinoma in a 42 year old woman. The patient presented a rapidly growing 4-cm subcutaneous mass in the right preauricular area. She was free of recurrence 24 months after surgery. Immunoreactivity was studied for cytokeratins, epithelial membrane antigen, S-100 protein, blood group antigens, Leu-M1, beta-2-microglobulin, vimentin, neuron-specific-enolase and cellular binding for peanut agglutinin. Squamous cells were reactive for cytokeratin AE1/3, epithelial membrane antigen, blood group antigens B and H, and peanut agglutinin. Basaloid cells were focally reactive for cytokeratin AE1/3 and epithelial membrane antigen. Flow cytometry revealed a euploid DNA content and a high proliferative rate of the pilomatrix carcinoma and in benign pilomatrixoma studied for comparison. The pathological diagnosis must be based on histomorphological criteria.

Two cases of fibromatosis of the breast, characterized by a proliferation of spindle cells containing intracytoplasmic, spherical, eosinophilic inclusion bodies, are reported. The light and electron microscopic features, as well as the immunohistochemical features, are indistinguishable from those found in infantile digital fibromatosis. The proliferating spindle cells are characterized as myofibroblasts, whereas the inclusion bodies show an immunohistochemically nonreactive, hollow-like pattern with peripheral reactivity for actin filaments. This lesion, observed for the first time in the breast, expands the number of extradigital inclusion body fibromatoses.

Twenty cases of papillary cystic tumor of the pancreas were studied (19 female patients, one male patient; median age, 19.5 years). Most tumors developed in the head or body of the pancreas as well-circumscribed, large masses. Gross examination showed that they were solid, cystic, and hemorrhagic. Preoperative fine-needle aspiration biopsy anticipated the diagnosis in four cases. Histologic examination showed that uniform cells formed solid sheets, and loss of cohesion produced pseudopapillae. Hemorrhage, foam cells, cholesterol granulomas, and entrapped nests of pancreatic parenchyma were often found. Fifteen cases studied immunohistochemically were reactive for vimentin and alpha-1-antitrypsin, 13 expressed neuron-specific enolase, 2 expressed cytokeratin, and 1 expressed S-100 protein. None were reactive for pancreatic hormones, opioid peptides, hormonal receptors, or neuroendocrine markers. Electron microscopic examination in five cases showed oval nuclei, moderate amounts of rough endoplasmic reticulum, and many mitochondria; it also showed that annulate lamellae were common. No diagnostic secretory granules were found. DNA study in nine cases revealed a diploid GO/1 peak in eight and hyperdiploid (diploid index = 1.1) DNA content in one case. Fourteen patients with follow-up were free of disease (mean, 2.6 years). Papillary cystic tumor of the pancreas possibly originates from primordial pancreatic cells and lacks definite evidence of endocrine or exocrine differentiation.

The adenoid variant of squamous cell carcinoma has been well-documented in several anatomic sites, including the skin. This tumor is characterized by acantholytic arrays of neoplastic keratinocytes that form pseudoglandular profiles. Although it is typically confused with adenocarcinomas, adenoid squamous cell carcinoma also may be mistaken for malignant vascular proliferations. This report concerns six acantholytic cutaneous squamous cell carcinomas that closely simulated angiosarcomas on conventional histologic examination. They arose in sun-exposed skin areas in middle-aged or elderly patients (mean age, 60 years), five of whom were men. In contrast to the typical clinical appearance of angiosarcoma, pseudovascular adenoid squamous cell carcinoma presented itself as a discrete cutaneous ulcer or crusted tanpink nodule. Microscopically, this lesion was characterized by interanastomosing cordlike arrays of polygonal or flattened tumor cells, with internal pseudolumina that contained detached tumor cells. A connection between the dermal neoplasm and the epidermis was apparent in three cases, but it was focal. Erythrocytes were seen in pseudovascular spaces in five tumors. Immunohistochemically, all examples of pseudovascular adenoid squamous carcinoma were reactive with antibodies to cytokeratin and epithelial membrane antigen (EMA). In addition, three expressed vimentin, two exhibited blood group antigen-positivity, and two bound Ulex europaeus I agglutinin. None of them was immunoreactive for Factor VIII-related antigen, and two of three studied for CD34-reactivity were likewise negative. A control group of six cutaneous angiosarcomas was uniformly nonreactive for cytokeratin and EMA, but they showed positivity for vimentin, Ulex binding, and CD34 positivity in all instances. Pseudovascular adenoid squamous cell carcinoma may be distinguished effectively from angiosarcoma of the skin by attention to its clinical features and by appropriate immunohistochemical studies. These two tumors differ in biologic behavior; three patients with pseudovascular adenoid squamous cell carcinoma died of their tumors, whereas all angiosarcomas in this series proved fatal.

To examine the reliability of the diagnoses reached on multiple small fragments of cerebral glial tumors obtained via stereotactic biopsy, samples obtained from 100 consecutive glial tumors (during real or simulated biopsy) were studied by cytology and histology. In comparison to the definitive diagnosis made on the whole tumor, a correct positive diagnosis on the biopsy sample was made by histology in 96% of cases and by cytology in 93% of the cases (with 96% correct results when combining both methods). A correct identification of the tumor type and grade was achieved by histology in 82% of cases and by cytology in 80% of the cases (with 85% correct results when combining both methods). The limits of stereotactic biopsy are related to the difficulty of identifying all of the typical tumor features on tiny tissue fragments of a pleomorphic neoplasm, such as a glioma. This study demonstrates that better results may be obtained by using both cytology and histology to study multiple stereotactic biopsy samples from glial tumors.

Two cases of primary fibromatosis of the breast are described. The lesions were suspected to be carcinomas both clinically and mammographically. Fine needle aspiration (FNA) yielded bland-appearing isolated spindle cells associated with small groups of benign ductal cells and lymphocytes. Immunoperoxidase staining performed on the original FNA smears showed positivity for vimentin and muscle-specific actin only in the spindle cells and for cytokeratin only in the epithelial cells. Electron microscopy study of one case demonstrated the ultrastructural characteristics of well-differentiated fibroblasts and myofibroblasts.

The fine needle aspiration (FNA) cytologic, immunocytochemical and ultrastructural findings of a primary multilobated T-cell lymphoma arising in the breast of a 61-year-old woman are described. Large pleomorphic multilobated malignant cells were primarily identified as lymphomatous in origin and phenotypically as T-cells by a selected panel of monoclonal antibodies applied to the original smears obtained by FNA biopsy. This appears to be the second report of a multilobated lymphoma arising in the breast and the first with a T-cell phenotype in this anatomic site.

From 1970 to 1987, 32 male and female patients with the prune belly syndrome were evaluated. Of these patients 11 died as neonates or infants, and autopsy in 9 revealed 6 cases of diffuse and severe renal dysplasia. In the 10 surviving patients renal insufficiency developed and a total of 13 nephrectomies and renal biopsies were performed. Renal dysplasia was noted in 9 specimens, but unlike the infant kidneys, the dysplastic changes involved less than 25% of the parenchyma in most cases. Renal failure in these 10 patients was caused by pyelonephritis and obstruction. In our estimation perinatal renal failure in patients with the prune belly syndrome results from renal dysplasia caused by an in utero insult, while in older patients pyelonephritis and obstruction are the causes. Careful treatment of reflux, obstruction and urinary tract infections may decrease the incidence of renal failure in patients with the prune belly syndrome who survive infancy.

The above study was intended to assess the effect of a bicarbonate sulfate alkaline water of medium mineral contents in long-distance runners during training. Several parameters relating to water-electrolyte and lactate-pyruvate metabolism, and to the patterns of serum enzymes of variable cellular localization were determined. Altogether twelve indices were taken into account. No significant changes were observed fron the start to the end of mineral water treatment. This goes to show that training was well balanced and did not impair the athletes' biochemical homeostasis. At the end of the treatment period, non negligible fluctuations of CCK and LDH were observed. This finding is not devoid of interest and deserves further study.

We describe seven female patients with deficient abdominal wall musculature and urinary tract and genital anomalies that represent the female equivalent of the prune belly syndrome. Urethral atresia, uterine duplication, and anorectal anomalies occurred frequently. The perinatal mortality rate was high; of the four surviving patients, renal failure developed in two and renal transplantation was required. The analysis of these cases suggests that urethral obstruction is an important factor contributing to the development of the prune belly syndrome in females.

Six cases of intestinal ganglioneuromatosis (GN) included in this study reveal the occurrence of two morphologic patterns. Transmural GN was characterized by neural hyperplasia in all layers of the bowel wall with predominant involvement of the myenteric plexus. It was found in three patients affected by multiple endocrine neoplasia IIb. Mucosal GN, having predominant involvement of the mucosa without concomitant hyperplasia of the myenteric plexus, was associated with von Recklinghausen's disease, adenocarcinoma of the colon, and multiple adenomas with megacolon in one case each. Clinicopathologic correlations and review of the literature suggest that mucosal GN might represent a distinct entity with a lower morbidity rate than the transmural variant. Immunohistochemical stains reveal considerable heterogeneity. S-100 protein, neuron-specific enolase, and synapto-physin immunostaining followed the distribution of the nervous hyperplasia in the different intestinal layers as identified morphologically and allowed precise determination of the proliferating cells. Increased reactivity for vasoactive intestinal polypeptide, opioid peptides leu-enkephalin and met-enkephalin, and substance P was present in all cases with transmural involvement; mucosal GN showed normal reactivity for opioid peptides and focal increased staining for substance P (one case) and vasoactive intestinal polypeptide (two cases) in the lamina propria. Mild increased immunoreactivity for tyrosine hydroxylase was present in the myenteric plexus of four out of four cases. Histochemical determination of acetylcholinesterase, performed in one case of transmural type, demonstrated hyperplasia of parasympathetic fibers and neurons. Electron microscopic study of another case suggested the presence of several neurotransmitters. These results indicate that the physiopathology of GN is related to a complex hyperplasia of several peptidergic, cholinergic, and probably adrenergic nerve fibers instead of a selective overgrowth of one type of nerve fiber.

Ten cases of melanotic neuroectodermal tumor of infancy (MNTI) were studied. There were nine males and one female ranging in age from 2 weeks to 10 months; one patient was 8 years old. Sites of origin were the maxilla (five), epididymis (two), mandible (one), skull (one), and soft tissues of the cheek (one). Six tumors recurred from 1 to 18 months after diagnosis. One patient had widespread dissemination. Electron microscopic study of four cases showed cells with melanosomes at various stages of maturation, and cells with neuroblastic features, including neurosecretory granules and cytoplasmic processes. Nine cases of MNTI were studied immunohistochemically. Small neuroblastic cells and large cells in all cases were reactive for neuron-specific enolase (NSE), synaptophysin, HMB45, and dopamine-beta-hydroxylase, large cells in all cases and few small cells were reactive for cytokeratin (CK) and vimentin (VIM). Epithelial membrane antigen was observed in large cells in three cases, four cases expressed Leu 7 antigen, three were focally positive for glial fibrillary acidic protein, one for desmin, and one for chromogranin. All cases were nonreactive for retinol-binding protein, neurofilaments, alpha-fetoprotein, S-100 protein, and carcinoembryonic antigen. Five normal adult retinas were studied similarly; the pigmented epithelium of the retina was reactive for CK, VIM, HMB45, NSE, and S-100. DNA study, performed in eight tumors, revealed aneuploidy in two (DNA index = 1.7 and 1.8); these cases recurred within 1 month. No differences were observed according to site or behavior. MNTI is a primitive neuroectodermal tumor with polyphenotypic expression of neural and epithelial markers, melanin production, occasional glial, and rhabdomyoblastic differentiation, and no photoreceptor differentiation. It probably represents a dysembryogenetic neoplasm that recapitulates the retina at 5 weeks of gestation.

Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more often labeled than malignant lesions (28% reactive) by this antibody; overall, 53 (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast. Furthermore, the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck, and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves.

We describe a malignant pelvic tumor with rhabdoid-like features that arose in the sacroiliac region of a 15-year-old girl. Fine-needle aspiration (FNA) cytology showed large cells with glassy cytoplasm, globular hyaline cytoplasmic inclusions, and prominent nucleoli. Immunocytochemical methods applied to FNA material revealed immunoreactivity for cytokeratin, epithelial membrane antigen, and vimentin; the cells failed to react with antibodies to desmin. This distinct appearance and phenotype was most consistent with a diagnosis of extrarenal malignant rhabdoid tumor. Electron microscopy confirmed this interpretation, showing whorled filamentous aggregates in the cytoplasm of the tumor cells.

A fine needle aspiration (FNA) biopsy of an enlarged lymph node in a three-year-old boy who had asymptomatic cervical and submandibular lymphadenopathy showed large histiocytes with abundant pale, eosinophilic cytoplasm containing well-preserved lymphocytes and occasional plasma cells and granulocytes. These features were consistent with a diagnosis of sinus histiocytosis with massive lymphadenopathy (SHML). Immunophenotypic study of the histiocytes, performed on the FNA smears and on paraffin-embedded sections, showed reactivity for S-100 protein and alpha-1-antichymotrypsin and negativity for lysozyme. These features, which are characteristic of SHML, demonstrate the reliability of FNA cytology in making the diagnosis of this disorder.

The findings of fine needle aspiration biopsy cytology, histology, immunohistochemistry and electron microscopy in an extraskeletal myxoid chondrosarcoma of the soft tissue of the thigh detected in a 65-year-old man are described. In addition to the more usual cytologic findings of chondroblasts and pleomorphic mesenchymal cells, this tumor displayed distinctive intranuclear cytoplasmic inclusions and microtubular aggregates in the rough endoplasmic reticulum. Cytologic study made the diagnosis of malignancy, suggesting a myxoid sarcoma; the precise diagnosis was made by the subsequent studies on the resected tumor and resin-embedded samples of the aspirate. The suitability of aspirated material in the differential diagnosis of myxoid soft tissue tumors is discussed.

Twenty cases of inflammatory myofibroblastic tumor (IMT) were studied; 19 involved the lung and 1 the esophagus only. The patients' ages ranged from 3 to 72 years. There were 9 males and 11 females. Involvement of a bronchus was seen in one case and of mediastinal structures in four. Chest pain and dyspnea were common symptoms; eight patients were asymptomatic. Seven patients underwent lobectomy, 12 local excision, and 1 biopsy alone. The lesions were nonencapsulated and ranged from 1.2 to 15 cm. Various proportions of plasma cells, histiocytes, and spindle cells were observed; the latter corresponded ultrastructurally to fibroblasts and myofibroblasts, were immunoreactive for vimentin and actin and focally for desmin, and were negative for epithelial markers. Plasma cells were polyclonal for light chains. One patient had two recurrences, and in one case a large pleural IMT was found eight years after the excision of a similar lesion in the lung. All patients with follow-up (ten) were well as long as ten years after the diagnosis (average, 3.7 years).

Twenty examples of angiomatoid malignant fibrous histiocytoma (AMFH) were studied. Patients ranged in age from 3 mo to 42 yr, with a mean of 13.4 yr (median 10.5 yr). There were 12 males and eight females. Tumors occurred in the upper extremities in eight cases, lower extremities in 10 cases, and one case each in the buttock and neck. Five patients had local recurrence from 5 to 18 mo after initial surgery, and one patient developed regional lymph node metastases and eventually died of disease. Eight of nine patients with follow-up information were alive from 11 to 31 mo after the diagnosis. Preoperative fine needle aspiration cytology performed in two patients showed features that suggested the correct diagnosis. Ultrastructural and immunohistochemical studies demonstrated findings consistent with a fibroblastic-histiocytic nature of the neoplasm and failed to detect endothelial differentiation of the tumor cells. Flow cytometric analysis performed in six cases, including three recurrent tumors, revealed a DNA diploid pattern in all instances. AMFH appears to be a distinctive low grade sarcoma in the spectrum of malignant fibrous histiocytoma.

A 53-year-old man presented porokeratosis palmaris, plantaris et disseminata with some features (exacerbation of lesions, in the sun light, zosteriform fashion of them on the trunk and extremities) distinctive of other variants of porokeratosis. Lately, four squamous cell carcinomas had arisen on the areas involved by disease. Histologic study of porokeratosis lesions showed epidermal changes typical of the disease ("cornoid lamella"), but also a mild disorder of malpighian stratification. Neoplasms were removed surgically and the patient was given etretinate orally (75 mg/day for a week, 50 mg/day for a month, 25 mg/day for six months, i.e. up to now), which proved to be effective in improving porokeratosis lesions and preventing the occurrence of other squamous cell carcinomas.

The cases of 5 patients with cerebral gliosarcomas examined by computed tomography are reported and the correlations among the computed tomographic (CT) findings, the surgical and histological aspects, and the prognosis are discussed. In some patients, these tumors appear on CT scan as intracerebral lesions, with large necrotic areas and peripheral contrast enhancement; this CT aspect, similar to that of glioblastomas, corresponds to a diffusely infiltrating growth of the tumor and the prevalence of a gliomatous component. In other patients, the tumor appears on the CT scan as a hyperdense mass with well-defined margins and homogenous contrast enhancement; this CT finding, which may mimic that of a meningioma, corresponds to a rather well-demarcated surgical aspect and the prevalence of sarcomatous component. In our series, we have also noticed a more prolonged survival in a patient with a CT aspect that suggested a meningioma and prevalence of the sarcomatous component.

Neuroendocrine (Merkel-cell) carcinoma of the skin, a neoplasm usually found in elderly individuals, is often locally aggressive and has the potential to metastasize to lymph nodes and cause death. Microscopically the neoplasm is a small-cell carcinoma that involves primarily the dermis. We report a case of such a neoplasm in a 61-year-old female, stressing the possible contribution of fine needle aspiration cytology in the recognition of this neoplasm and its differentiation from other small-cell neoplasms that may involve the skin.

Remembering an observed case of intestinal invagination from Meckel's diverticle the A. describe the most important anatomical and anatomo-surgical characteristics of the diverticle of Meckel, laying particular stress on the variation in form; position and size with reference to the part they have in surgical operations. The operation tecnique of transportation of the diverticle in its various pathologic cases is also a point treated in this work; the principle methods of ablation are brought up to date with synthetic iconography.