Subungual melanoma. Features of clinic, diagnostics and treatment.

Subungual melanoma (SM) is a rare tumor and is 3-5% of all malignant skin melanoma. There was analyzed database of the Population-based Cancer Registry of the N.N.Petrov Research Institute of Oncology of St. Petersburg, the first in Russia, including information on more than 2,500 patients with malignant melanoma, of which for the period from 1986 to 2014 there were selected cases of acral lentiginous melanoma - 85 patients (3.4%). This group included 40 patients with SM (1.6%). More than half of patients were referred to a specialist in a year since the appearance of the first symptoms of the disease. Distribution of SM patients by Stages was as follows: 30% (n = 12) cases of the disease were identified in the Stage I, 40% (n = 16) - in the Stage II, 25% (n = 10) - in the Stage III and 5% (n = 2) - in the Stage IV. The most commonly misdiagnosed cases were considered as inflammation, fungal or other lesions of the nail phalanx. Histologically SM patients met all morphological types of melanoma. Over half of patients had Clark IV and V levels of invasion. The mean value of tumor by Breslow thickness was 5.5 mm. All patients with SM underwent radical surgery in the following volumes: 75% (30 cases) - amputation at the middle level (n = 16) and basic (n = 14) phalanges; 20% (8 cases) - disarticulation at the level of the proximal interphalangeal (n = 6) and metatarsusphalanx (n = 2) joints; 5% (n = 2) - resection metacarpal and metatarsal. Inguinal-femoral lymphadenectomy was performed in 8 patients with metastatic lesion of regional lymph nodes.

[Acral lentiginous melanoma: the current state of the problem].

This review is aimed at the analysis the current state of acral lentiginous melanoma. This tumor has rather aggressive course and is the main cause of death in skin cancer patients. In Russia the incidence of melanoma during the period 2000-2010 increased from 3.18 to 3.95 cases per 100000 of population. The average annual growth rate was 1.99% and the total growth rate was 21.81%. Although skin melanoma is a visual tumor, more than one third of patients visit oncologists at advanced stages of the disease. Primary melanoma with localizations on the skin of fingers, interdigital spaces, soles, palms and nail plates is especially difficult for early diagnostics.

[COMPARATIVE EVALUATION OF SURGICAL APPROACHES TO TREATMENT OF PATIENTS WITH SKIN MELANOMA].

In recent years there has been rapid growth in the incidence of melanoma. Due to the large number of patients with various pigmented lesions, suspicious for melanoma, requiring differential diagnosis there is an actual problem of excisional biopsy in this group of patients. This review extensively covered approaches to radical surgical treatment of patients with skin melanoma. There are described in detail results of the studies of foreign experts regarding the influence of excisional and incisional biopsy on overall and disease-free survival rates of patients. On a large representative material (1126 patients) there are widely reflected the results of our studies to assess the effect of different surgical approaches to treatment of patients with skin melanoma. At present the authors can not recommend to perform excisional biopsy of patients with primary skin melanoma in oncological practice. Obviously for a final resolution of this problem it is necessary to conduct a multicenter randomized trial.

[Reasons of non-radical surgery for patients with primary skin melanoma].

It was found that up to now a significant number of patients with primary skin melanoma continued to have non-radical surgery. Based on the analysis of clinical and morphological data on 288 of these patients it was revealed that most non-radical treatment was performed for patients who had had primary skin melanoma of linear dimensions of 1 cm and a pink color. It was proved that patients with tumors of the skin should first be examined by the oncologist. A lack of knowledge of semiotics of primary skin melanoma was revealed among doctors. Widely used diagnostic biopsy of the primary tumor with subsequent cytology is recommended.

[The detection of early regional metastases in patients with skin melanoma by dopplerography].

Color Doppler mapping (CDM) of the regional lymph nodes was performed in 152 patients with primary skin melanoma without clinically determined regional and distant metastases. The patients were divided into 2 groups. The first group included 52 patients in whom biopsy was fulfilled after sonography and CDM of the regional lymph nodes. The second group (control) included 100 patients. After sonography and CDM biopsy of the lymph nodes was not fulfilled. Using CDM of the regional lymph nodes in the preoperative period allowed unjustified lymphadenectomies in patients with skin melanoma to be avoided. An algorithm of preoperative diagnosis of the degree of regional spreading of skin melanoma was developed which will give better results of treatment. The method of color Doppler mapping was first used for the detection of micrometastases of the tumor in the regional lymph system.

[Potential of detection of early regional metastases in patients with primary skin melanoma].

Diagnostic procedures for skin melanoma in regional lymph nodes were compared in 250 patients. Doppler effect examination and sentinel biopsy were carried out in 60 patients with primary skin melanoma and clinically intact lymph nodes. Identical examination and regional lymphadenectomy were used in 80 patients with clinically detectable metastases to regional lymph nodes. The same procedures were performed in 110 healthy controls. Histological findings fully confirmed Doppler effect evidence. Regional lymphadenectomy was indicated only in patients with verified Doppler effect-related metastatic lesions to the lymph nodes.

[Pre- and early natal exposure to geomagnetic field as risk for melanoma and basal cell skin tumors].

Histories of 173 male and female patients with melanoma and basal cell skin tumors (BCST) were followed to elucidate the influence of pre- and early natal exposure to geomagnetic field (GMF) on future incidence of cancer. A positive correlation was established between exposure to GMF during critical months of prenatal period, on the one hand, and melanoma detection, on the other. However, a similar correlation involving BCST was inverse which suggests a difference in the etiologies. Tumor regression coefficients which link total Ki-indices for critical months of pre- and early natal exposure with tumor detection time are presented.

Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors: miscellaneous tumors.

BACKGROUND: The use of genetically modified autologous tumor cells appears to be a promising approach for cancer therapy. A phase I/II trial was undertaken to define the feasibility, safety and antitumor effects of the autologous vaccine prepared by transferring tag7/PGRP-S gene into malignant melanoma and renal cell carcinoma cells. PATIENTS AND METHODS: Twenty-one patients (17 with disseminated malignant melanoma and four with metastatic renal cell carcinoma) were enrolled in this study. Cytoreduction was performed in all cases prior to therapy. Autologous tumor cells were transfected with the tag7/PGRP-S gene, irradiated and injected intradermally every 3 weeks. RESULTS: Vaccinations were well tolerated by all patients, without clinically significant signs of toxicity. Delayed-type hypersensitivity was observed in 48% of cases. Antitumor immune response was observed in 95% of patients. There were no complete or partial responses; however, a minor response was achieved in one patient with renal cell carcinoma. The stabilization of neoplastic disease was observed in eight patients (seven with malignant melanoma and one with renal cell carcinoma). Median time to tumor progression was 3 months. CONCLUSIONS: The approach suggested here appears to be well tolerated and produces a number of durable clinical effects. Further studies are required to determine whether promising effects on immune activation will result in an actual clinical benefit for patients with malignant melanoma and renal cell carcinoma.

[Phase I-II trial of gene therapy with tag-7 modified autologous tumor cells in patients with metastatic solid tumors]. / I-II faza klinicheskoi otsenki éffektivnosti genoterapii na osnove autologichnykh opukholevykh kletok, modifitsirovannykh genom TAG7 u bol'nykh s disseminirovannymi solidnymi opukholiami.

A prospective (phase I-II) trial was undertaken to study the efficacy and toxicity of gene therapy with tag 70-modified autologous tumor cells in 32 patients with metastatic renal cell carcinoma (RC) (5) and melanoma (MBL) (27) treated at the Institute's Clinic (2001-2003). Resected material was reduced to cell culture, which was transfected with tag 70 gene and devitalized by irradiation. Immune blotting was used for gene expression. Clinical and immunological effectiveness was evaluated in 22 patients (MBL--17 and RC--5) who received 1-6 injections (3 on the average). Full course of vaccination was given to 8 (MBL--6 and RC--2). No complete or partial response was reported while least regression (50%) was registered in a case of RC metastatic to the lung. According to CT and ultrasound evidence, stabilization was achieved in 5 (23.8%) (MBL--4 and RC--1). Relapse-free period was 6.5+/-3.5 months beginning from the start of treatment. The vaccine was well tolerated while DHT reaction was observed in 47.6% (10 out of 17) of primary immunized patients. A trend of increased content of T- and B-cells in peripheral blood and intensified functional activity was established.

[An improved procedure for autologous gene-modified cancer vaccine preparation for active specific immunotherapy of disseminated solid tumors]. / Usovershenstvovanie metoda prigotovleniia autologichnykh modifitsirovannykh protivoopukholevykh vaktsin dlia aktivnoi spetsificheskoi immunoterapii bol'nykh s disseminirovannymi solidnymi opukholiami.

Resected material was used from 108 patients with disseminated skin melanoma and 47 patients suffering metastasized renal tumors to test procedures of tumor cell culture preparation and to search the best parameters. Gene tag 7 transfer, liposome delivery and electroporation were employed to stimulate immunogenic tumor cells. The transfer results were evaluated by expression of beta-galactosidase and EGFP genes whose products were detected microscopically. Transfer efficiency was boosted by 30% due to selecting suitable parameters of tumor cell modification. Maximum effectiveness was attained by individualized choice of the parameters. Yet, undoubtedly, the best way of cell isolation was mechanical fragmentation of tumor. To speed up cell production, DMEM/F12 medium should be recommended. It should contain cattle embryonic serum (20%), conditioned medium of cultured fibroblasts of human embryonic lungs (20%), transferin, insulin and selenium (standard dose).

[Influence of growth rates of local recurrences and in-transit metastases on survival of patients with cutaneous melanoma]. / Vliianie kineticheskikh kharakteristik mestnykh retsidivov i tranzitnykh metastazov na vyzhivaemost' bol'nykh melanomoi kozhi.

The growth rates of local recurrences and in-transit metastases of skin melanoma were assessed in 271 patients. Median growth rate in the course of chemotherapy was 0.02 a day--1 which corresponded to a doubling time of 34.7 days. Median survival time for patients with local recurrences and in-transit metastases was 22.6 months, 12-month survival--70.1%, 5-year--19.6% and 10-year--9.9%. Growth rate appeared to be the most significant prognostic factor; similarly important were tumor volume, relapse-free interval, tumor mitotic rate, site and number of recurrences. The following additional characteristics of tumor growth rate have been suggested: maximum growth rate and doubling time limit, to assess the rates of secondary tumor focus development.

[Ulrasound diagnosis of melanoma metastasis into the gallbladder]. / Ul'trazvukovaia diagnostika metastazov melanomy v zhelchnyi puzyr'.

A clinico-ultrasound description of presentation of melanoma metastases to the gallbladder in 8 patients is discussed. Secondary lesions to the bladder presented as exophytic outgrowths extending from the bladder wall into the lumen. Echo generated by the lesions was of medium intensity and low intensity around the edge of the elastic wall. They revealed dopplergaphic signs of blood flow. Complex application of echo- and dopplergraphy offered a means of differential diagnosis of metastatic lesions and other pathologies of the gallbladder presenting as exophytic outgrowths in the bladder wall in melanoma patients.

[Clinical diagnosis of primary melanoma of the skin]. / Klinicheskaia diagnostika pervichnykh melanom kozhi.

Procedures for early diagnosis of primary skin melanoma have been developed on the basis of the data available on 1.500 cases. Symptoms of malignant transformation of long-term pigmented nevi have been analyzed. The problems involved in screening primary skin melanoma and differential diagnosis have been studied.

[Prophylactic lymph node excision in cutaneous melanomas of the lower limbs]. / Profilakticheskie limfadenéktomii pri melanomakh kozhi nizhnikh konechnostei.

An analysis of 67 cases of skin melanoma of feet and legs aggravated by the risk of regional metastatic spreading established a significant improvement in five-year survival (over 30%) in patients who had undergone prophylactic lymphadenectomy. Indications for preventive surgery are suggested and rationale of its extent is discussed.

[RLadiolymphography with 113mIn-chloride in the diagnosis of the lymphogenic metastases of skin melanomas]. / Radiolimfografiia 113mIn-khloridom v diagnostike limfogennykh metastazov melanom kozhi.

One hundred and thirty indirect lymphoscintigraphies (74 lower and 56 upper ones) using 113mIn-chloride were performed in 121 cases of skin melanoma. Metastatic involvement of lymph nodes was characterized by either increased or decreased accumulation of the radionuclide. The overall accuracy of the procedure was 0.85 for the inguinal, 0.82--iliac and 0.75--for the axillary lymph nodes.