Atypical fibroxanthoma of the scalp following hair transplantation in a 35-year-old male.

Atypical fibroxanthoma (AFX) is an uncommon spindle cell neoplasm of the elderly. This case report presents an atypical case of AFX of the scalp 8 years after hair transplantation in a 35-year-old male patient. Possible synergistic effects of previous sun exposure radiation to the scalp, together with the thermal and radiation injury of carbon dioxide (CO(2)) laser, might explain the mechanisms of the development of AFX at such an early age. To the best of our knowledge, this case report is the first description in the medical literature of development of skin malignancy on a hair-transplanted scalp.

Computerised analysis of liver texture with correlation to needle biopsy.

AIM: To assist in tissue characterisation for the non-invasive diagnosis of diffuse fatty liver infiltration by providing quantitative indices of ultrasonic (US) backscatter with correlation to histology. METHODS AND MATERIALS: US images from patients referred to US-guided liver needle biopsy (LNB) for persistently elevated liver enzymes or serologically positive markers for viral hepatitis were recorded. The histopathological reports were reviewed. Steatosis, inflammation and degree of fibrosis were scored from 0 (normal) to 3 (severe). Patients with level 3 steatosis without inflammation or fibrosis were selected. US images from twenty-four healthy subjects served as control. Four textural indices were calculated for a selected ROI corresponding to the biopsy site. Sensitivity and specificity of discrimination between the two groups were evaluated. RESULTS: Fatty and healthy livers formed two distinct clusters. However, in all parametric subspaces there was a slight overlap between the groups with a few numbers of cases located across the dichotomy line.The sensitivity for all the indices was high (90 - 100 %). The specificity for each of the indices was moderate. The co-occurrence local homogeneity index yielded the highest specificity (88.5 %), with a sensitivity equivalent to two of the other indices (90 %). CONCLUSIONS: Highly accurate "ultrasonic biopsy" may be obtained for severe fatty liver. The described indices can serve as a tool in US computer- aided diagnosis (CAD) of diffuse parenchymal liver disease, in particular for severe steatosis of the liver.

Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

MIB-1 monoclonal antibody to determine proliferative activity of Ki-67 antigen as an adjunct to the histopathologic differential diagnosis of Spitz nevi.

BACKGROUND: The histopathologic differential diagnosis of Spitz nevus (SN) from malignant melanoma (MM) may be difficult. OBJECTIVE: Our purpose was to determine the staining pattern and usefulness of MIB-1 antibody, which recognizes Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, as an adjunct to the histopathologic differential diagnosis of SN. METHODS: Twenty-five compound SNs, 27 MMs, and 26 compound nondysplastic melanocytic nevi (MNs) were immunostained with the MIB-1 antibody. RESULTS: The mean counts of MIB-1--stained tumor cells of the epidermal and dermal components, both alone and together, were significantly lower in SNs and MNs than in MMs (P <.0001). The dermal counts showed the best discriminating power. In addition, the mean dermal/epidermal count ratios for MIB-1 in SNs and MNs (0.25 and 0.23, respectively) were significantly lower than the corresponding ratio (0.94) in MMs (P <.0001). CONCLUSION: MIB-1-stained tumor cell counts, especially of the dermal component, and dermal/epidermal MIB-1 count ratios may be helpful as an adjunct to the histopathologic differential diagnosis of SN.

[Autochthonous subcutaneous dirofilariasis in Israel].

BACKGROUND: Canine dirofilariasis has been recognized for over 300 years, but human dirofilariasis has received relatively little attention. Sporadic cases of human dirofilariasis have been reported in Israel. Dogs, cats and foxes are the reservoir, mosquitoes of the genera Culex and Aedes are the vectors and humans are the accidental hosts. CASE REPORT: We present a case of human dirofilariasis (Dirofilaria repens) in a young Israeli patient. The thickness of the multilayered cuticle of the worm, the size of the body and the form and numbers of the longitudinal ridges on its surface are used in the histological diagnosis of the parasite. CONCLUSIONS: Since our patient had never been abroad, this case must be considered an autochthonous infection. Furthermore, since the reservoir and the vectors are abundant in Israel, the potential for human infection exists, but probably this pathology is underdiagnosed in primary care practice.

Localized amyloidosis in nasopharyngeal carcinoma diagnosed by fine needle aspiration and electron microscopy. A case report.

BACKGROUND: The association of amyloidosis and tumors is well known, but only rarely has it been found in the nasopharynx. Moreover, only a single case of tumor-associated amyloidosis in the nasopharynx has been diagnosed by exfoliative cytology and reported in the English-language literature. We describe a case of localized amyloidosis in metastatic nasopharyngeal carcinoma diagnosed by fine needle aspiration and confirmed by histology and electron microscopy. CASE: Bilateral neck enlargement appeared six months before consultation in a 57-year-old man. Both masses were resected, and during exploration of the nasopharynx, several blind biopsies were taken. Smears from the fine needle aspirate showed malignant epithelial cells, consistent with metastatic carcinoma, and Congo red stain showed the presence of amyloid. Histologic examination of the resected cervical masses and nasopharyngeal biopsies confirmed the diagnosis of nasopharyngeal carcinoma, nonkeratinizing variant with amyloid, and metastases in two lymph nodes. Electron microscopic examination of a lymph node showed extracellular, ribbon-like amyloid deposits as well as masses of amorphous amyloid, apparently intracellular. CONCLUSION: The origin of this form of amyloidosis is unclear in this patient since he had no other known etiologic factors for the condition. Increased awareness of the potential association of these two conditions and the use of fine needle aspiration may reveal a higher frequency than hitherto reported.

Primary malignant melanoma of the anterior mediastinum in a child.

Primary malignant melanoma of the mediastinum is extremely rare. We report a case not previously reported of primary malignant melanoma located in the mediastinum in a 11-year-old boy. The tumor could not be completely resected as a result of extensive invasion of the large blood vessels. Histologically, the tumor was heavily pigmented and composed of vague fascicles of spindle cells intermingled with epithelioid cells. Immunohistochemical analysis showed vimentin, S-100 protein, Melan-A, and HMB-45 immunoreactivity in most of the tumor cells. Nearly 50% of the tumor cells were also positive for p53. It is suggested that primary malignant melanoma of the anterior mediastinum may have a histogenetic relationship to the recently described aggregates of nevus cells in the thymus or mediastinal lymph nodes.

The diagnostic value of power Doppler measurements in the endometrium of women with postmenopausal bleeding.

OBJECTIVE: The objective was to evaluate the accuracy of blood flow measurements by power Doppler in endometrial vessels in women with postmenopausal bleeding (PMB). METHODS: Sixty consecutive patients with PMB participated in the study. Endometrial thickness and power Doppler measurements of small vessels in the endometrium and subendometrial tissue were performed prior to dilatation and curettage. Correlation between Doppler indices, endometrial thickness (by transvaginal sonography), and histopathologic examination was performed. A Student t test was used for statistical analysis with P < 0.05 as the level of significance. RESULTS: Fourteen positive cases were found: 11 endometrial cancers, 1 sarcoma, 1 simple hyperplasia, and 1 complex hyperplasia with atypia. Measurements of endometrial thickness using a cutoff point of 5 mm revealed a sensitivity of 78% and specificity of 45.6% (P > 0.05, NS) for detecting endometrial pathology. Power Doppler measurements (pulsatility index cutoff point = 1.0) revealed a sensitivity of 85. 7% and specificity of 89% (P = 0.001) for detecting endometrial pathology. CONCLUSIONS: The noninvasive methods for endometrial evaluation are not sensitive enough to exclude endometrial pathology. When invasive methods could not be performed, the combination of transvaginal sonography and power Doppler imaging provided the best results. When both modalities are negative, the probability of cancer is less than 5%.

Xanthogranulomatous appendicitis--an incidental finding of localized pathology.

The clinical, histopathological, and electron microscopic features of an unusual case of xanthogranulomatous appendicitis are reported. The patient, a 37-year-old female, presented with typical signs of acute appendicitis and the appendix appeared slightly dilated at laparatomy. The histopathological sections showed numerous xanthoma cells mixed with inspissated fecaliths. Electron microscopy disclosed the presence of xanthoma cells filled with electron-lucent lipid droplets of variable size. The ultrastructural characteristics of these cells enabled the distinction of two types of lipid-laden histiocytes, in relationship to the size of the lipid droplets. Since the lipid droplets were seen also in cells other than histiocytes, it appears that these changes are secondary to a common mechanism, comprising factors such as obstruction, hemorrhage, inflammation, and local hypoxia.

Selective loss of the transforming growth factor-beta apoptotic signaling pathway in mutant NRP-154 rat prostatic epithelial cells.

Retroviral insertional mutagenesis was used to select mutant NRP-154 rat prostate carcinoma cells resistant to transforming growth factor (TGF)-beta-induced cell death. Similar to the parental cells, a mutant clone, M-NRP1, expressed TGF-beta receptors and was still responsive to induction both of direct target genes by TGF-beta and of apoptosis by staurosporine or okadaic acid. In contrast, indicators of cell growth, strongly suppressed by TGF-beta in the parental cells, were unaffected in M-NRP1 cells. M-NRP1 cells overexpress the antiapoptotic protein, Bcl-xL, and show dysregulated expression and localization of a protein related to a novel human septin, ARTS (designation of apoptotic response to TGF-beta signals), cloned by homology to an exonic sequence flanked by the viral long terminal repeats in M-NRP1 cells and shown to make cells competent to undergo apoptosis in response to TGF-beta. We propose that ARTS might operate within the same apoptotic pathway as Bcl-xL and that M-NRP1 cells could serve as a useful model for characterization of this pathway.

A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif.

Here we describe a protein product of the human septin H5/PNUTL2/CDCrel2b gene, which we call ARTS (for apoptosis-related protein in the TGF-beta signalling pathway). ARTS is expressed in many cells and acts to enhance cell death induced by TGF-beta or, to a lesser extent, by other apoptotic agents. Unlike related septin gene products, ARTS is localized to mitochondria and translocates to the nucleus when apoptosis occurs. Mutation of the P-loop of ARTS abrogates its competence to activate caspase 3 and to induce apoptosis. Taken together, these observations expand the functional attributes of septins previously described as having roles in cytokinesis and cellular morphogenesis.

Ovarian dysplasia in prophylactic oophorectomy specimens: cytogenetic and morphometric correlations.

BACKGROUND: Ovarian dysplasia, a potential precursor to ovarian carcinoma, has been described in ovarian tissue obtained by prophylactic oophorectomy and also adjacent to ovarian carcinoma. Women with a family history of ovarian carcinoma, especially those of Jewish Ashkenazi descent, often test positive for BRCA mutant genes. Prophylactically removed ovaries, generally described as normal on macroscopic examination, can exhibit a "preneoplastic phenotype" and unsuspected neoplasm. METHODS: Histologic slides of ovarian tissue from 54 Ashkenazi Jewish women were reviewed. All had a family history of ovarian carcinoma and all were tested for BRCA mutations. Forty-four women tested positive. Thirty-one women underwent prophylactic oophorectomy and 23 underwent oophorectomy for ovarian carcinoma. Normal, dysplastic, and ovarian carcinoma epithelial cells were analyzed morphometrically combining nuclear area measurements with chromatin texture assessment using a novel method based on the computation of autocorrelation coefficients and a derived parameter (Beta). Discriminant analysis between classificatory algorithms was used to obtain results. RESULTS: Ovarian dysplasia was identified in 77.6% of the prophylactic oophorectomy specimens. An unsuspected ovarian carcinoma was diagnosed in one prophylactic oophorectomy specimen. Of 10 women who underwent prophylactic oophorectomy and were negative for BRCA mutations, three had ovarian dysplasia. The average nuclear measurements of the dysplastic cells were similar to those published previously. The new autocorrelation-based method evaluating nuclear texture, as revealed by tridimensional surface plots, demonstrated high discriminatory potential. Discriminant analysis based on nuclear area and nuclear texture information resulted in the correct classification of nearly all the cases in the three diagnostic categories. CONCLUSIONS: Ovaries removed by prophylactic oophorectomy examined in their entirety often reveal ovarian dysplasia and occasionally ovarian carcinoma. The new morphometric method used was highly discriminatory in the evaluation of nuclear texture. Ovarian dysplasia in women with risk factors for ovarian carcinoma is significant in early ovarian carcinogenesis.

Tissue-specific p53 expression in the nervous system.

P53 is a transcription factor that has been found to be expressed in association with cell proliferation and apoptosis. Previously, bacterial chloramphenicol acetyl transferase (CAT) enzymatic expression was predominantly found in the testes of p53 promoter driven-CAT transgenic mice. In the current study, we extended this study to survey p53 expression across both the central and peripheral nervous systems of the same strain of transgenic mice as well as their parental strain. High levels of p53 promoter driven-CAT activity was observed in the cerebellum, hippocampus, hypothalamus, pons, thalamus and upper cerebral spine. Furthermore, we consistently found unexpectedly high levels of p53 promoter-driven CAT expression in the eyes. These observations were reinforced by p53 protein analysis using a p53 pan ELISA assay. Immunohistochemical studies confirmed and further defined p53 expression in several regions of the nervous system. Significantly, p53 promoter-driven CAT expression was visualized in the Ammon horn of the hippocampus, in the Purkinje cells of the cerebellum and in the cornea as well as in the retina of the eye. Furthermore, strong p53 protein expression was found in the cornea of the parental mouse strain. p53 ELISA demonstrated a profile of p53 protein concentration, which correlate well with the high p53 promoter-driven CAT activities observed in the cerebellum, hindbrain, hypothalamus, thalamus, hippocampus, whole eyes as well as with the low CAT activities observed in the cortex and spinal cord. In both of these assays considerable p53 promoter activity and p53 protein levels were found in post-mitotic non-dividing cells.

Evaluation of muscle capillary basement membrane in inflammatory myopathy. A morphometric ultrastructural study.

The capillary basement membranes from 16 skeletal muscle biopsies from patients with a clinical and histological diagnosis of inflammatory myopathy and from six controls were analysed ultrastructurally and morphometrically. Resin sections from 244 endomysial capillaries were examined by light microscope, and the results were correlated with findings seen in electron micrographs of these capillaries. The ultrastructural morphometric measurements and the statistical analysis showed that the capillary basement membrane was thick and multilaminated in 87% specimens affected by inflammatory myopathy. No thick or multilaminated basement membrane was observed in controls. In inflammatory myopathy the endomysial space next to the capillaries contained an increased amount of collagen fibrils and showed signs of a chronic reparative process. It is suggested that the thick multilaminated basement membrane in inflammatory myopathy represents an advanced stage of vascular regeneration.

Apoptosis, Fas and Fas-ligand expression in melanocytic tumors.

Impaired regulation of apoptosis is known to be associated with the development of various forms of cancer. Fas binding to its ligand, Fas ligand (Fas-L), has been shown to trigger apoptosis in various cell types. Fas-L is expressed by melanoma cells and has been suggested to play a role in melanoma escape from immune surveillance. In the present study, we assessed apoptotic activity and examined Fas and Fas-L expression in malignant melanomas, Spitz nevi and ordinary melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling. Apoptotic activity was found to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi demonstrated significant levels of apoptosis in the deep parts of the tumor. Fas was found to be expressed by all Spitz nevi, most melanocytic nevi and approximately half of the malignant melanoma specimens. Fas expression was also significantly more pronounced in Spitz nevus cells as compared with the two other tumors. The anti-Fas-L antibody was found to stain all three melanocytic tumors. Staining was shown to be stronger and more frequent in melanoma cells as compared to the nevus cells. Using the Spearman test, no significant correlation between Fas-L expression in melanoma cells and apoptosis in MM-infiltrating mononuclear cells was found, suggesting that Fas-L expression in melanoma cells may not be instrumental in their ability to escape immune mechanisms of defense. In contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may reflect and possibly contribute to their benign nature.

Immunophenotyping and T-cell receptor gamma gene rearrangement analysis as an adjunct to the histopathologic diagnosis of mycosis fungoides.

BACKGROUND: The histopathologic diagnosis of mycosis fungoides (MF) may be difficult. OBJECTIVE: Our purpose was to evaluate the role of immunophenotyping and T-cell receptor (TCR) gene rearrangement studies as an adjunct to the histopathologic diagnosis of MF. METHODS: Immunohistochemical studies with antibodies to CD4, CD5, CD7, and CD8 and TCR gamma gene rearrangement analysis with a polymerase chain reaction were performed on fresh-frozen material of patients with "classic" histology of MF, "inconclusive" histology, and benign inflammatory dermatoses. RESULTS: Clonal TCR gamma gene rearrangements were found in 11 of 16 (69%) of classic MF cases, in 3 of 19 (16%) of inconclusive cases, and in none of the 12 inflammatory dermatoses cases (P < .05 and P < .001, respectively). Only the mean CD7 counts were statistically significantly different between these 3 groups (MF < inconclusive < inflammatory). CONCLUSION: Inconclusive histology is probably a heterogeneous group in which CD7 counts and TCR gamma gene rearrangement studies might help to differentiate the MF cases from the benign cases.

C-fos protein expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.

The expression of c-fos protein was studied in formalin-fixed, paraffin-embedded sections of 11 compound Spitz nevi (SNs), 16 ordinary compound melanocytic nevi (MNs), and 17 malignant melanomas (MMs) using monoclonal antibody MAB1283 and an immunoperoxidase technique. Eleven (100%) SNs, 15 (94%) MNs, and 16 (94%) MMs showed positive reactions in some of the tumor cells (p = nonsignificant). In the majority of the tumors the staining was located in nuclei and graded as moderate to strong in intensity. The percentages of positively stained cells did not differentiate the three types of tumor, although they were higher in the melanocytic nevi. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Positive staining for c-fos was also frequently found in the normal skin constituents within and adjacent to the melanocytic tumors. In conclusion, the pattern of expression of c-fos in routinely processed specimens does not differentiate between SNs, MNs, and MMs.