The following communication summarizes the proceedings of a one-day International Workshop focusing on the histology of benign melanocytic nevi. Areas of controversy identified in 6 focus sessions were the nomenclature and relationships among common nevi including nevi with halo reactions, traumatized nevi, "dysplastic" nevi, and nevi from particular anatomic sites; developmental biology and frequency of malignant transformation associated with congenital nevi; the characterization and biologic nature of atypical spitzoid neoplasms; the basic definition of particular melanocytic cellular phenotypes, and the nomenclature and biologic nature of many candidate blue nevi, combined nevi, and other controversial lesions such as deep penetrating nevus and pigmented epithelioid melanocytoma. Concentrated data collection and follow-up, molecular characterization, and future consensus Workshops may facilitate the resolution of some of these problems. The Group recommended the description of ambiguous or "borderline" lesions as tumors with indeterminate or uncertain biologic/malignant potential. The participants also advised that such lesions at a minimum should be managed by complete excision with clear surgical margins.

In melanoma patients, examination of tissue sections stained for immunohistochemical markers as an adjunct to examination of haematoxylin and eosin (H&E)-stained sections has been shown to increase the detection rate of micrometastatic disease in sentinel lymph nodes (SLNs). However, immunohistochemical stains are not routinely performed on completion regional lymph node dissection (CLND) specimens in most centres and it is not known whether their use would increase the detection of micrometastatic disease in these specimens. This study was performed to determine whether the application of immunohistochemical stains for S100 and HMB45 (in addition to H&E stains) increases the detection of micrometastatic disease in CLND specimens of melanoma patients and whether their use would be cost-effective in routine pathological practice. Forty-nine CLND specimens from patients with a prior positive SLN biopsy were examined by performing H&E stains and immunohistochemical stains for S100 protein and HMB-45 on each node, and the detection rate of melanoma metastases using H&E-stained sections was compared with that using immunohistochemically stained sections. The number of nodes in the CLND specimens ranged from 4 to 37 (median 14, mean 14.7). Nodal deposits of melanoma cells were detected in 12 of 49 cases (24%). Among these 12 positive cases, the mean number of positive nodes per CLND specimen was 2.2 (range, 1-14). The total number of positive nodes in the 12 CLND specimens was 27, accounting for 3.8% of the 720 nodes removed in the study group of 49 cases. Melanoma cells in all 27 positive nodes were identified both on the H&E-stained slides and the slides stained immunohistochemically for S100. The melanoma cells were positive for HMB45 in 24 of the 27 lymph nodes that contained metastatic melanoma (the metastatic melanoma cells were negative for HMB45 in three positive nodes from one specimen). No further positive lymph nodes were detected with the immunostains that had not been identified on the H&E-stained sections. This study suggests that the use of immunostains does not increase the detection rate of metastatic melanoma in CLND specimens, and that their routine use would not be cost-effective. We therefore recommend only H&E staining on sections of all lymph nodes in CLND specimens from melanoma patients.

The aim of the present study was to determine whether micromorphometric features of positive sentinel lymph nodes (SLNs) from patients with melanoma are useful for predicting further nodal involvement in completion lymph node dissection (CLND) specimens. Of 986 patients with melanoma undergoing SLN biopsy between March 1992 and February 2001, 175 (17.7%) had at least 1 positive SLN and 140 had subsequent CLND specimens available for review. Further nodal involvement in CLND specimens was present in 24 (17.1%) of 140 patients. Of 8 micromorphometric features of the SLNs that were assessed, the presence of metastases in CLND specimens was correlated significantly with a tumor penetrative depth (maximum distance of melanoma cells from the inner margin of the SLN capsule) of more than 2 mm (P < .05), a deposit size of more than 10 mm2 (P < .01), the presence of melanoma cells in perinodal lymphatic vessels (P < .01), and the effacement of nodal architecture by metastatic melanoma cells (P < .05). Our results indicate that some morphologic features of melanoma metastases in SLNs predict the likelihood of further nodal involvement in CLND specimens.

It is well recognized that the pathologic diagnosis of melanocytic tumors can sometimes be difficult. For some atypical melanocytic tumors that do not display clear-cut features of malignancy, it may be difficult or impossible to exclude a diagnosis of melanoma; this includes those showing some resemblance to Spitz nevi, blue nevi, deep penetrating nevi, and possible nevoid melanomas. When there is uncertainty about whether a primary melanocytic tumor is a nevus or a melanoma, we recommend that a second opinion be sought from one or more experienced colleagues. If diagnostic uncertainty persists, the evidence for or against the various differential diagnostic considerations should be presented in the pathology report and a "most likely" or "favored" diagnosis given. Molecular testing of the primary tumor by using techniques such as comparative genomic hybridization or fluorescence in situ hybridization may assist in establishing a diagnosis of melanoma if multiple chromosomal aberrations are identified. However, these tests require further independent validation and are not widely available at present. Complete excision of the lesion is probably mandatory, but plans for further management should be formulated on a case-by-case basis. While the safest course of action will usually be to manage the tumor as if it were a melanoma (taking into account the tumor's thickness and other prognostic variables), this may not always be appropriate, particularly if it is located in a cosmetically sensitive site such as the face. In some cases, it may be appropriate for the surgical oncologist to convey the diagnostic uncertainty to patients and to present them with management choices so that they can decide whether they wish to be managed aggressively (as for a melanoma) or conservatively. While a sentinel lymph node biopsy may be recommended on the basis of the primary tumor characteristics, the clinical significance of lymph node involvement for these tumors is not yet clear, and it may not have the same prognostic implications as nodal involvement from an unequivocal "conventional" melanoma.

These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of EOC and have potential application in the early detection of disease.

Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT-PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC.

Metastases from head and neck melanomas can occur in any SN demonstrated by lymphoscintigraphy. SNs in discordant as well as predicted node fields should be removed and examined to optimize the accuracy of staging.

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.03.115 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12663739 Challenging and Unusual Cases CASE 4. MALIGNANT MESOTHELIOMA PRESENTING AS AN ANTERIOR MEDIASTINAL MASS C. FeatherstonexC. FeatherstoneSearch for articles by this author , R. ScolyerxR. ScolyerSearch for articles by this author , G. HrubyxG. HrubySearch for articles by this author , M. TinxM. TinSearch for articles by this author , E.J. WillsxE.J. WillsSearch for articles by this author , P.N. HendelxP.N. HendelSearch for articles by this author Show More Royal Prince Alfred Hospital and Concord Repatriation General Hospital, Sydney, Australia https://doi.org/10.1200/JCO.2003.03.115 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology

We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the ultimate goal of fruitfully driving both preclinical and clinical research on anticancer targeted therapy. In the light of its theoretical nature, the prediction performance of this model must be validated before it can be implemented in the clinical setting.