The classification of melanoma: time for a further revision?

The current classification of cutaneous melanoma was developed in 1972 and revised in 1982. Since that time new concepts and terminology have evolved that require consideration of a further revision. This paper reviews some of the concepts that will form part of that process.

Demonstration of cytoplasmic tyrosinase mRNA in tissue-cultured cells by reverse transcription (RT) in situ polymerase chain reaction (PCR) and RT PCR in situ hybridization.

To evaluate the specificity and applicability to the study of human tumor cells of the reverse transcription (RT) in situ PCR and RT polymerase chain reaction (PCR) in situ hybridization techniques, we examined five melanoma cell lines and five nonmelanoma lines for tyrosinase mRNA using primers specific for tyrosinase. Each procedural step was optimized and minutely controlled, and results from the in situ techniques and solution-phase RT-PCR were compared. All melanoma lines showed a specific pattern of perinuclear cytoplasmic reaction not seen in nonmelanoma lines.

Nodal nevi and cutaneous melanomas.

Nevocytes in melanoma-draining lymph nodes can be mistaken for melanoma metastases and may possibly transform to melanoma. During the development of a new technique for managing high-risk primary melanomas, selective lymph node dissection, we examined 4,821 nodes from 208 melanoma patients by light microscopy and immunohistochemistry. Nodal nevi were identified in 49 of 226 lymphadenectomy specimens (22%), a frequency considerably higher than previously recorded (5-6%).

Imitation of Escherichia coli aspartate receptor signaling in engineered dimers of the cytoplasmic domain.

Transmembrane signaling by bacterial chemotaxis receptors appears to require a conformational change within a receptor dimer. Dimers were engineered of the cytoplasmic domain of the Escherichia coli aspartate receptor that stimulated the kinase CheA in vitro. The folding free energy of the leucine-zipper dimerization domain was harnessed to twist the dimer interface of the receptor, which markedly affected the extent of CheA activation.

Tumor vascularity is not a prognostic factor for malignant melanoma of the skin.

Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic site.

Selective expression of PNA-binding glycoconjugates by invasive human melanomas: a new marker of metastatic potential.

Alterations of cell-surface glycoconjugates have been associated with invasiveness and metastatic capacity in a number of experimental and human tumors (bladder and colon cancer). We have recently shown that human melanoma cells from variants selected for high metastatic potential in an animal model bind the lectin peanut agglutinin (PNA), and that human melanoma cell populations enriched for PNA binding cells generated a higher frequency of metastases when xenografted into immune suppressed neonatal rats. We have therefore sought cells binding PNA in biopsied human melanocytic tumors and compared frequencies of PNA binding by cells from benign nevi, early and late primary melanomas, and metastatic melanomas.

Application of multistage Markov modeling to malignant melanoma progression.

Background: A fundamental research goal in clinical melanoma studies is to understand the natural history of melanoma and its relationship with prognostic factors. The current understanding of melanoma progression and the relationship of risk factors is based on two-stage modeling.

Methods: The authors propose a multistage Markov model for melanoma progression.

Pathology of the lymph nodes in patients with malignant melanoma.

The poor survival rate for patients with regional lymph node metastases of malignant melanoma reflects the strong association between lymph node and subsequent visceral metastases. The authors discuss clinical considerations, pathologic risk factors, selective lymphadenectomy, examination of lymph node dissections, difficulties of diagnosis, and prognosis.

Studies of monoclonal antibody BL2-10D1 as a marker for the detection of the urothelial origin of tumors.

Background: In previous studies, the authors demonstrated the value of the monoclonal antibody (MoAb) BL2-10D1 in identifying malignant transitional cells. In this study, the authors evaluate the possible diagnostic value of a murine MoAb, BL2-10D1, raised against human bladder cancer in the determination of the urothelial origin of metastases in a series of 29 patients with metastatic bladder or prostatic carcinoma.

Methods: Using an immunoperoxidase method, BL2-10D1 and anti-prostate-specific antigen (anti-PSA) reactivity were studied, using histologic sections from 18 pelvic lymph nodes and 4 other anatomic sites invaded by transitional cell cancer, and from 7 pelvic lymph nodes containing prostatic cancer.

S-100 protein remains a practical marker for melanocytic and other tumours.

S-100 protein, extracted from bovine brain, is the first described of the modern generation of marker molecules for melanocytic tumours. Despite the observation that many different types of cells express S-100 protein, detection of the molecule in tumour cells in appropriate clinical and pathological circumstances is a widely used and effective adjunct to the determination that a tumour is melanocytic. Antibodies to S-100 protein are best deployed as part of a package that includes antibodies to other melanoma-associated epitopes (HMB-45, NKI-C3/Beteb), cytokeratins and common leukocyte antigen.

Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck.

Purpose: We developed intraoperative lymphatic mapping with selective lymphadenectomy (SLND) to identify micrometastatic spread of cutaneous melanoma to regional lymph nodes. This study was undertaken to assess the sensitivity and specificity of our technique in patients with clinical stage I (CS-I) melanoma of the head or neck.

Patients And Methods: Seventy-two CS-I melanoma patients underwent intraoperative lymphatic mapping of primary cutaneous melanomas located on the head, neck, or upper chest/back draining to the neck.

Dobutamine thallium-201 tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or vasodilator pharmacologic stress testing.

Objectives: The aim of this study was to assess the feasibility, safety and diagnostic accuracy of a high dose dobutamine infusion in conjunction with thallium-201 single-photon emission computed tomography in 144 patients (72 men and 72 women with a mean age of 65 +/- 10 years) unable to perform exercise or pharmacologic vasodilator stress testing.

Background: Dobutamine increases myocardial oxygen consumption by increasing heart rate, contractility and arterial blood pressure. In addition, it causes myocardial blood flow heterogeneity and thus may be a useful stress for noninvasive detection of coronary artery disease.

Multivariate analysis of the relationship between survival and the microstage of primary melanoma by Clark level and Breslow thickness.

Background: The American Joint Committee on Cancer (AJCC) uses both Breslow thickness and Clark level in its staging system for malignant melanoma. Stage I corresponds to Breslow thicknesses less than 1.5 mm and Clark levels II and III.

Frequency and distribution of occult micrometastases in lymph nodes of patients with non-small-cell lung carcinoma.

Background: Accurate assessment of the presence and absence of tumor in the regional lymph nodes is critical in assessment of prognosis for patients with lung cancer. Development of sensitive immunohistochemical techniques and specific monoclonal antibodies has increased our capacity, in melanoma and breast cancer, to detect small groups of tumor cells or even single tumor cells in lymph nodes that appear to be tumor free in conventionally stained sections.

Purpose: This retrospective study was designed to assess whether use of a polyclonal antikeratin reagent in immunohistochemical analysis offers any advantage over conventional histopathology in detection of regional lymph node metastases in non-small-cell lung cancer.

Variations in the distribution, frequency, and phenotype of Langerhans cells during the evolution of malignant melanoma of the skin.

We examined the frequency, distribution, and immunophenotype (S-100 protein, CD1) of epidermal Langerhans cells (LC) in the epidermis overlying primary melanoma, and dermal dendritic cells (DC) in the dermis deep to melanoma, and in adjacent normal skin. There is a substantial reduction in S-100+ LC and a lesser decline in CD1+ LC in the epidermis over melanoma. There is a simultaneous increase in the frequency of cells expressing these phenotypes in the dermis deep to tumor.

The histology and differential diagnosis of Spitz nevus.

We attempted to identify features by which Spitz nevi (SN) and melanomas that resemble SN may be distinguished, by examining the light microscopic features of 43 SN, using a multifactorial protocol. The data confirm that SN evolve in a manner similar to melanocytic nevi, with well-defined junctional, compound, and intradermal phases. Because of their growth kinetics most SN are excised at the compound stage, the most readily identifiable stage of evolution.

Nevi, other than dysplastic and Spitz nevi.

Cutaneous nevi are common lesions that develop by proliferation of melanocyte-derived cells. The majority develop as junction nevi from melanocytes at the epidermo-dermal junction. Cells from this proliferation pass into the underlying dermis forming compound nevi.

Pathological evaluation of the regional lymph nodes in malignant melanoma.

The clinical implications of lymph node metastasis in patients with malignant melanoma remain serious. Five-year survival rate for clinical stage II disease is between 36% and 50% compared with more than a 80% 5-year survival rate for stage I melanoma. The purpose of this article is to review the known clinical and pathological risk factors for the development of lymph node metastasis in melanoma, to consider the prognostic significance of metastasis once it has occurred, and to discuss the histopathology and differential diagnosis of metastatic melanoma in lymph nodes.

Intratumoral interleukin-2 immunotherapy: activation of tumor-infiltrating and splenic lymphocytes in vivo.

Direct intratumoral injection of interleukin-2 (IL-2) was evaluated in a murine model. Balb/c mice received 5 x 10(4) Line 1 alveolar carcinoma cells (L1C2) by subcutaneous injection. On the third day following tumor implantation, mice received injections of IL-2 (5 x 10(3)-5 x 10(4) units) or diluent twice daily, either by i.