Role of ß-catenin expression in paediatric mesenchymal lesions: a tissue microarray-based immunohistochemical study.

Beta-catenin is a major protein in the Wnt signalling pathway. Although it has been studied in various types of carcinoma, little is known about its expression in mesenchymal tumours. In this study 41 specimens of a variety of mesenchymal childhood tumours were compared to 24 samples of the corresponding adult tumours to assess the diagnostic value of nuclear ß-catenin expression using tissue microarray-based immunohistochemistry. Similar to adult sarcoma and fibromatosis, ß-catenin was not expressed in the majority of childhood sarcomas, and its nuclear translocation was detected in paediatric fibromatosis; non-negligible levels of nuclear staining in other tumour types demonstrate Wnt pathway activation in mesenchymal neoplasms of childhood and adolescence.

C-kit protein expression in Wilms' tumour: an immunohistochemical study.

AIM: The use of a non-toxic tyrosine kinase receptor inhibitor, Imatinib Mesylate (IM), has become an ever-more common therapeutic alternative in some Kit (CD117) over-expressing neoplasms. As the treatment eligibility for these drugs hinges on CD117 expression, Kit immunostaining has recently been widely examined in various tumours. There are only limited data in the literature on the expression of c-kit expression in Wilms' Tumour. We examined CD117 expression in Wilms' tumour in order to correlate this marker with clinico-pathological data and to clarify its prognostic impact. METHODS: This study included 40 cases of Wilms' tumour. Sections from paraffin-embedded tumour samples were immunostained by standard ABC technique using c-kit polyclonal antibody with antigen retrieval. RESULTS AND CONCLUSIONS: In the case of C-kit positive examples, the staining was focal, with patch distribution. On univariate analysis, significantly higher c-kit expression was observed in neoplasms in a more advanced stage of development than those in a less advanced stage (p=0.0055). In addition, over-expression of this marker was significantly correlated with the death of patients (p=0.0294) and recurrences of disease (p=0.0118). Moreover, all our Wilms' tumour anaplastic subtypes showed over-expression of c-kit and this was significantly higher than in favourable histology examples (p=0.0182). The results of multivariate analysis, instead, did not reveal any correlation of c-kit expression and prognosis. In our opinion these results could be due to the number of cases considered which is not particularly high. However, it seems likely that c-kit expression could be a secondary event related to tumour progression and could be influenced by chemotherapy and unfavourable histology.

Anaplastic large cell lymphomas: a study of 75 pediatric patients.

In this article, we describe the morphologic and immunophenotypic features of 75 cases of pediatric anaplastic large cell lymphoma (ALCL). According to the World Health Organization classification, 49 cases were common subtype ALCL, and respectively, 3, 6, and 17 cases were small cell, lymphohistiocytic, or mixed histologic variants. Anaplastic lymphoma kinase positivity was detected in 90.7% of the tumors and, using a panel of 9 T-cell surface markers, 88% could be assigned to the T-cell lineage. A molecular analysis for the T-cell receptor gamma (TCR- gamma) and the heavy chain of the immunoglobulin H rearrangements was performed on 6/9 ALCLs with a null immunophenotype, and a TCR clonal pattern was detected in 5/6 cases. In addition, 94.1% were immunoreactive for 1 or more cytotoxic proteins (Tia1, granzyme B, or perforin), and 15% expressed CD56. Clusterin, CD83, and Pax5, respectively, expressed in 91.3%, 1.7%, and 0% of the ALCLs, were useful biomarkers for the differential diagnosis with Hodgkin's lymphomas.

Effect of Helicobacter pylori infection on gastric cell proliferation and genomic instability in a paediatric population of southern Italy.

BACKGROUND: The incidence of gastric cancer is high in areas with a high prevalence of Helicobacter pylori infection. Cell transformation and tumour progression occur over a long period of time and markers of genomic instability usually precede morphological changes. AIM: To evaluate the effect of Helicobacter pylori infection on cell proliferation, DNA status and oncogene expression in children. PATIENTS AND METHODS: Morphometric and immunohistochemical techniques were used to analyse DNA content, p53 and c-myc oncogene expression and cell proliferation on gastric biopsies of 53 children (27 Helicobacter pylori-negative and 26 Helicobacter pylori-positive). RESULTS: Gastric mucosa was normal in 11% of Helicobacter pylori-positive and in 33% of Helicobacter pylori-negative subjects. Most children had chronic non-atrophic gastritis regardless of Helicobacter pylori infection, and only a minority of children affected by Helicobacter pylori had mild atrophic gastritis. Cell proliferation was significantly higher in children with Helicobacter pylori-positive gastritis than in those with Helicobacter pylori-negative gastritis. No metaplasia, dysplasia, p53 overexpression or altered DNA content was found in any child. Interestingly, 46% of children with and 29% without Helicobacter pylori infection had c-myc overexpression closely related to the cell proliferation rate. CONCLUSION: Helicobacter pylori infection in children may coexist with a normal gastric mucosa, and it is not associated with genomic instability markers in cases of chronic gastritis.

Metastasis to the male breast from carcinoma of the urinary bladder.

We report a case of male breast metastasis from a urothelial carcinoma. Only two cases of this type of metastasis have been previously reported, and these were in the female breast. Clinical examination showed a progressive swelling of the left mammary region, with periareolar skin infiltration. Both mammography and ultrasound showed a rounded mass. Only histological examination with immunohistochemical staining permitted the correct diagnosis to be made. A particular feature of the present case is the absence of contralateral gynaecomastia, normally seen in cases of metastatic tumour to the breast from prostatic carcinoma.

Epithelioid hemangioendothelioma of the larynx.

Epithelioid hemangioendothelioma is an uncommon vascular tumor of the soft tissues. Several reports have described this tumor in visceral locations such as liver, lung, and brain. To the best of our knowledge this is the first report of an immunohistochemical and ultrastructural study of a primary epithelioid hemangioendothelioma occurring in the larynx. Difficulties concerning the differential diagnosis and clinical problems arising from surgical therapy in the laryngeal area are also discussed.

Symplastic leiomyoma of the scrotum. A case report.

Mesenchimal tumors of the scrotum are rare lesions. Here, we describe a case of symplastic leiomyoma of the scrotum, in a 49-year old man. This is the third case reported in the world literature. Grossly, the lesion is a white-gray nodule, with fasciculated pattern, on sectioning. Histologically, the neoplasm is formed by whorling bundles of fusiform cells, which have atypical nuclei, with occasional cytoplasmatic inclusions. Mitoses are absent. The muscolar nature of the lesion is demonstrated by positivity for Masson-trichrome stain and for actin and desmine antigens.

Prognostic evaluation of HPV-associated precancerous and microinvasive carcinoma of the oral cavity: combined use of nucleolar organiser regions (AgNOR) and proliferating cell nuclear antigen (PCNA).

Nucleolar Organiser Regions (NORs) and Proliferating Cell Nuclear Antigen (PCNA) were investigated on routine paraffin embedded histologic sections of 30 oral biopsy specimens (six cases of leukoplakia with low-degree of dysplasia, nine cases of leukoplakia with moderate-degree of dysplasia, nine cases of leukoplakia with severe-degree of dysplasia, six cases of squamous microinvasive carcinomas), tested for HPV-DNA by in situ hybridisation (ISH). The absolute number of NORs per nucleus and the percentage of nuclear positivity for PCNA were found to be different in each group of pathology, with further diversity due to the presence or absence of HPV-DNA. In the major part of HPV-positive lesions, the AgNOR number and percentage of cells positive for PCNA were found to be generally lower than in corresponding negative forms. Conversely, a few cases of HPV+ lesions showed significantly higher values both of AgNOR and PCNA, if compared to the other cases of HPV+ and HPV- lesions. These data suggested that high values of AgNOR and PCNA, in moderate and high grade oral dysplasia, could represent an "alarm signal" of a worse prognosis, and then a possible indication for a strict clinical management and/or a stronger treatment of some HPV-associated preneoplastic lesions.

Fibronectin, laminin, type IV collagen distribution, and myofibroblastic stromal reaction in aggressive and nonaggressive basal cell carcinoma.

The stromal myofibroblastic reaction and extracellular matrix in a series of 19 morphologically and clinically aggressive basal cell carcinomas (BCC) were examined by an immunohistochemical staining panel for myofibroblastic markers (vimentin, actin, and desmin), for basement membrane components (laminin and type IV collagen), and for fibronectin. Results were compared with a series of 19 nonaggressive BCC. The aggressive BCC showed discontinuous staining for laminin and type IV collagen, a marked myofibroblastic response, and increased stromal fibronectin. Conversely, the nonaggressive BCC showed a continuous basement membrane and a total lack of staining for fibronectin and myofibroblastic markers in all but three cases. This report suggests that a combined analysis of extracellular matrix components and myofibroblastic markers may be useful for evaluating the clinical behavior including the metastatic capability of aggressive BCC.

Smooth muscle tumors of the breast: clinicopathologic features of two cases.

Two cases of smooth muscle tumor of the breast with high tendency to local relapses are reported. The common cytohistologic feature of these infrequent neoplasms is interfacing bundles with spindle-shaped cells showing eosinophilic cytoplasm and blunt-ended nuclei. In estimating the prognosis of these lesions, the mitotic index must be evaluated together with evidence of necrosis and hypercellularity. The present cases suggest that, in the absence of the ancillary features, a mitotic rate of 1-3 x 10 HPF might define a "grey zone" in the spectrum of lesions between leiomyomas and leiomyosarcomas: the smooth muscle tumors of indeterminate prognosis (low risk lesions).

Primary rhabdoid tumour of the skin in a 14-month-old child.

We report on a primary cutaneous rhabdoid tumour in a 14-month-old child, to the best of our knowledge, the second case in the literature. The tumour showed a multipolypoid gross appearance and classical histological features. The neoplastic cells were positive for keratin and vimentin and most were positive for proliferating cell nuclear antigen. The ultrastructural examination revealed typical intracytoplasmic aggregates of intermediate filaments. The tumour showed a very aggressive course, and the child died 5 months after the diagnosis of cerebral metastasis.

p53 protein in aggressive and non-aggressive basal cell carcinoma.

Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm, with a generally favorable clinical behavior. Sometimes, indeed, it recurs after therapy and/or metastasizes. As point mutations in the coding sequence of the p53 tumor suppressor gene have been implicated in the progression of many human tumors, we studied the expression of p53 protein on this neoplasia. We tested immunohistochemically the positivity for p53 protein (NCL-p53-CM1, YLEM) on 19 cases of morphologically "non aggressive" BCC (BCC1) and on 19 "aggressive" BCC (BCC2), all with one or more relapses and 3 with distant metastases also. Results were related to clinico-pathological and follow-up data. All but one BCC2 were found positive for p53 protein. Conversely, only 2 cases of BCC1 exhibited low immunoreactivity for p53 protein, with high statistical differences between the two groups. No correlation was found between the immunoreactivity, age of patients, and site of the lesions. The availability of immunohistochemistry and the relatively easy interpretation of the results make screening for p53 protein a possibly useful tool in the prognostic evaluation of BCC.

Adenosquamous carcinoma of the colon. Case report of an unusual type.

Primary adenosquamous carcinoma of the colon is a rare entity. Its prevalent site of origin is at the level of the proximal portion of the large bowel. The tumor presents in young patients and follows a highly aggressive course. We present an extremely unusual case of adenosquamous carcinoma in which the classical mucinous and signet-ring cell adenocarcinoma was associated with the squamous component. The prognosis of this rare neoplasm is very poor.

Blue nevus of the uterine cervix.

A case of blue naevus of the endocervix is reported with immunohistochemical and ultrastructural findings. The dendritic melanin-containing cells are analogous to the blue naevi cells of the skin. Electron microscopy showed melanosomes in dendritic cells but no cells with melanin-producing Schwann cells features were observed. Histogenetic hypotheses are discussed.

Tricholemmal carcinoma: a study of seven cases.

Seven cases of tricholemmal carcinoma (TLC), a rarely recognized cutaneous adnexal neoplasm of external hair sheath origin, are described. Most occurred on sun-exposed skin; five involved the head and neck, one the right leg, and one the right thigh. TLC had a generally short history and all were treated by local excision. The lesions had an exophytic (3 cases) or polypoid (4 cases) gross appearance. Histologically, TLC exhibited a sharply circumscribed, lobular epithelial proliferation in continuity with the epidermis. A cytologic hallmark of these tumors was the presence of large cells with PAS-reactive, diastase-sensitive, clear or pale eosinophilic cytoplasm. High mitotic rate was a constant feature. Four tumors were infiltrative, with pushing borders, whereas three were intraepithelial. One case showed acantholysis. Immunocytochemistry revealed positivity for prekeratin and negativity for CEA and EMA, supporting the trichogenic origin of these tumors. Ultrastructural examination gave clear indication of epithelial origin for the cells but did not verify hair follicular differentiation. Despite locally aggressive growth, the clinical course of TLC appeared indolent. Moreover, there are no cases with metastases reported in the literature.

Intracystic papillary carcinoma of the male breast. A case report (histochemical, immunohistochemical and ultrastructural study).

We report a case of intracystic papillary carcinoma of the male breast in a 70-year-old male Caucasian. Grossly, the tumor was a cystic lesion measuring 6 cm in diameter. It contained hemorrhagic fluid and a mural nodule with filiform projections. PAS stain with and without digestion revealed small clumps of diastase-resistant material in the cytoplasm of the neoplastic cells. Grimelius stain was positive. Immunoperoxidase stains were negative for neuron-specific enolase, S100 protein, cromogranin and synaptophysin and were positive for carcinoembryonic antigen and epithelial membrane antigen. On ultrastructural examination the neoplastic cells showed membrane-bound, dense-core secretory granules. We believe that this neoplasm, despite negative neuroendocrine markers, is a variant of mammary adenocarcinoma with endocrine differentiation, partly because of the positive Grimelius stain and partly because of the presence of electron-dense granules, which according to some authors represent lactational differentiation.

Multicystic mesothelial proliferation. Immunohistochemical, ultrastructural and DNA analysis of five cases.

We investigated the clinicopathological findings in five cases of multicystic mesothelial proliferation (MMP). All masses consisted of multiloculated cysts attached to pelvic organs and sometimes growing into the upper abdominal cavity. The cystic spaces were lined by flattened or cuboidal cells. The stroma showed fibrosis, oedema and chronic inflammation. Immunohistochemistry revealed strong positive staining for cytokeratin and epithelial membrane antigen, and focal positivity for vimentin and carcinoembryonic antigen. The endothelial markers were negative. Electron microscopy showed abundant surface microvilli and well-developed basal lamina. DNA analysis identified euploid cell populations in all cases. All but one case had a previous history of abdominal surgery. Despite the worrying appearance the clinical outcome was favourable in all cases; there was one recurrence. Clinical and pathological data support the hypothesis that MMP represent a reactive mesothelial proliferation and not a neoplastic process.

Ovarian serous tumor with mural nodules of carcinomatous derivation (sarcomatoid carcinoma): report of a case.

An ovarian serous cystic tumor of low malignant potential with solid mural sarcoma-like nodules is reported. This tumor metastasized to the ileal wall. The nodules in the ovary and in the ileal wall were made up of highly malignant cells with admixed osteoclast-like multinucleate giant cells. Immunohistochemical reactions demonstrated the epithelial differentiation of the tumor. We propose that the term "sarcomatoid carcinoma" of the ovary should be adopted for these lesions.

Multiple hereditary trichoepithelioma and cylindroma (Brooke-Spiegler syndrome).

Three cases of trichoepithelioma associated with cylindroma (Brooke-Spiegler syndrome) in the same family are reported. Three generations were affected. The syndrome usually beginning at puberty is inherited as an irregular autosomal dominant trait.