Malignant Melanocytic Lesions Research Articles

Step-wise expression of melanoma-associated antigens in tumor progression

Selection of monoclonal antibodies for differential reactivity with benign and malignant melanocytic lesions has led to the identification of molecules which may be involved in the development of metastases. Based on the observed alterations in the antigenic profile we propose a scheme representing the tumor progression of melanocytes to metastatic melanoma.

Ultrastructural Study of Melanocytic Lesions in Albino Guinea Pigs Induced with 7,12-Dimethyl-Benzanthracene

We studied the fine structure of benign, premalignant and malignant melanocytic lesions induced in Dunkin-Hartley guinea pigs by means of topical application of 7,12-dimethyl-benzanthracene (DMBA). The most noteworthy characteristics of the atypical melanocytes (melanocytic dysplasia and melanomas) were the variable morphology and structure, and, in particular, the aberrant character of the melanosomes. The melanocytes presented irregularity of nuclear outlines with frequent lobulation. The heterochromatin was usually found in thick clumps reinforcing the nuclear membrane, and the nucleoli were usually multiple. The melanosomes were ellipsoidal and spherical with a pattern that was lamellar, concentric, incomplete, and even microgranular and microvesicular. The melanization was usually in thick, irregular clumps. Melanosome complexes were always present.

Molecular profile, tissue distribution and prognostic evaluation of a human melanoma-carcinoma antigen recognized by the murine monoclonal antibody B1.1.

Using the murine monoclonal antibody (MoAb) B1.1 we have analyzed the immunochemical profile and the tissue distribution of a human melanoma associated antigen (MAA) carrying an epitope shared by the 180 kd CEA. Results of this study have demonstrated that the epitope expressed by the MAA is carried by a distinct set of molecules of 110-140 kd. Similarly to the 180 kd CEA molecules synthesized by carcinomas, the expression of the melanoma associated CEA like components (MA-CEA) is upregulated by IFN-alpha. The tissue distribution of MA-CEA is not restricted to malignant primary and metastatic melanocytic lesions but is found also at low levels in 64% of benign nevi. No circulating CEA was found in patients bearing widespread metastatic disease of MA-CEA positive lesions. Preliminary clinical evaluation of stage I melanoma patients bearing MoAb B1.1 positive lesions has not shown a significative prognostic association of this phenotypic marker with clinical course of the disease.

Nucleolar organizer region associated proteins in benign and malignant cutaneous melanocytic lesions

Nucleolar organizer region associated proteins in benign and malignant cutaneous melanocytic lesions

Nuclear Parameters in the Superficial and Deep Portion of Melanocytic Lesions: A Morphometrical Investigation

Morphometric techniques in diagnostic pathology of pigmented skin lesions are not yet well established. The so-called maturation of melanocytes (nevus cells) with progressive descent into the dermis is one important criterion to differentiate benign from malignant melanocytic lesions in conventional histology. We therefore examined morphometrically the nuclear parameters of melanocytes (nevus cells) in the superficial and deep portion of 120 pigmented skin tumors (40 cases each of malignant melanoma. Spitz's nevus and benign dermal nevus) with special emphasis on the "maturation to the depth". A "maturation parameter" (MP) was assessed in each individual case, calculating the ratio of the nuclear area in the deep portion and in the superficial portion. The mean values of MP were 0.720 +/- 0.11 for dermal nevi, 0.725 +/- 0.10 for Spitz's nevi and 1.125 +/- 0.11 for malignant melanoma. The difference between malignant melanoma and both groups of benign nevi was statistically significant (p less than or equal to 0.01). The efficiency of the maturation parameter was 0.95 for the distinction of dermal nevi and malignant melanomas, and 0.97 for the distinction of Spitz's nevi and malignant melanoma. Measurements of the superficial portion only revealed comparatively low efficiency values (0.70 and 0.56, respectively). Our results indicate that morphometric evaluations of the nuclear area of melanocytes (nevus cells) in the deep portion of the infiltrate are more discriminative than those in the superficial portions. The establishment of the MP allows a better differentiation between benign and malignant melanocytic lesions and therefore morphometric methods may obviously be a helpful tool in the diagnosis of melanocytic skin tumors.

New Primary Malignant Melanoma, Epidermotropism and Indian-File Arrangement of Metastatic Tumor Cells in a Case with Intransit Metastases of Acral Type of Malignant Melanoma

Multiple malignant melanocytic lesions developed on a localized area of the thigh in an 80-year-old woman 3 years after excision of a primary malignant melanoma on the left second toe and dissection of left inguinal lymph nodes. Biopsy specimens obtained from 2 small pigmented macules revealed the histologic features of new primary lesions, simulating that of the primary lesion on the toe; no tumor cells were found within vessel lumina. A brown-black papule neighboring one of the macules histologically resembled compound type of melanocytic nevus, but the tumor cells compressed thinned epidermis with focal epidermotropism. Other papules, whose color ranged from light brown to reddish brown, showed metastatic tumor cells only in the dermis. In 3 of them, individual tumor cells were lined up along the collagen bundles, showing an 'Indian-file' arrangement. Such a combination of various histologic features in a case of intransit metastases of acral type of melanoma has not been reported in the literature.

Recombinant gamma-interferon induces changes in expression and shedding of antigens associated with normal human melanocytes, nevus cells, and primary and metastatic melanoma cells.

Recombinant gamma-interferon (rIFN-gamma) induced or augmented the expression of HLA-DR class II antigens on melanocytes isolated from newborn foreskin, from congenital, common acquired, and dysplastic nevi, and from primary and metastatic melanoma. The stimulatory effect of rIFN-gamma on HLA-DR antigen expression was suppressed by the addition of the phorbol ester TPA or its analog PDBu to the culture medium. Whereas rIFN-gamma did not significantly alter the expression of melanoma-associated, non-class II antigens on melanoma cells, there was a marked decrease in the expression of antigens associated with nevus cells. In addition, rIFN-gamma stimulated shedding of antigens. Increased antigen shedding was most apparent for an intracytoplasmic melanoma-associated protein of 80kd, followed by the ganglioside GD2 and by an alkali labile ganglioside. The simultaneous stimulation of class II antigen expression and shedding of melanoma-associated antigens as well as suppression of nevus-associated antigen expression could play an important role in the host immune response to premalignant and malignant melanocytic lesions.

Pigmented melanocytic lesions of the conjunctiva — a new approach to their classification

We report a series of 23 malignant melanomas and 24 cases of benign and premalignant lesions of the conjunctiva and propose a new classification of non-nevoid pigmented benign, premalignant and malignant melanocytic lesions. The question of prognostic features in conjunctival melanoma is briefly discussed.

Neurone specific enolase and S100 protein as possible prognostic indicators in melanoma*

Fourteen cases of primary melanoma and 25 of their subsequent metastases were stained for Neurone Specific Enolase (NSE) and S100 protein. Intensity of staining for NSE and S100 protein broadly corresponded in 11 of the primary lesions and was disparate in three. Staining intensity for NSE or S100 was independent of tumour thickness. Primary lesions showing marked or moderate staining for NSE and S100 protein took a shorter time to metastasize than those showing slight or no staining. Assessment of staining intensity for NSE and S100 thus identified prognostic categories corresponding to disease free interval obtained by division according to tumour thickness. Staining intensity for S100 protein appears to give a clearer indication as to expectation of disease free interval. Staining intensity in individual cases showed an increase both for NSE and S100 protein between primary and metastatic lesions. The data presented are not sufficient to assign statistical significance but may lead to the incorporation of functional studies into the pathological assessment of malignant melanocytic lesions. The simultaneous occurrence of a functional neuronal and Schwann cell marker in melanoma is discussed.

Use of NK1 C3 monoclonal antibody in the assessment of benign and malignant melanocytic lesions.

The monoclonal antibody NK1 C3, synthesised by the Netherlands Cancer Institute, has been used to assess its value in the diagnosis of melanocytic lesions. The antigen recognised by this antibody is not denatured by formalin fixation, with the result that the antibody can be used for retrospective studies on conventionally processed material. Positive results were obtained in primary melanoma (18/18), secondary melanoma (21/21), junctional and compound naevi (32/32), intradermal naevi (9/12), congenital naevi (3/3), so called dysplastic naevi (13/13), blue naevi (5/5), and Spitz tumours (3/14). Non-melanocytic tumours were tested for comparison. The results showed relative but not complete specificity of the antibody for melanocytic tumours, with positive results only in breast and prostate tumours (2/6 and 2/5 respectively). Negative results were obtained with basal and squamous cell carcinoma, appendage tumours, neural tumours, and apudomas. The staining pattern of NK1 C3 was compared with that of antibodies to S100 protein and to neurone specific enolase. Compared with S100 protein NK1 C3 gave stronger staining of a higher percentage of cells in the 12 specimens in which a direct comparison was made. Antibody raised against neurone specific enolase in sheep gave very poor results with heavy background staining. We suggest that NK1 C3 is a useful addition to the battery of monoclonal antibodies of value to the diagnostic histopathologist.

Fluorescein Angiographic Patterns of Iris Melanocytic Tumors

Iris fluorescein angiography was performed on 23 patients with primary iris melanocytic tumors. Four angiographic patterns were identified, the first three of which were considered to be usually indicative of a benign lesion, based on clinical duration and follow-up, biopsy specimens, and stable patterns on repeated angiography. (1) Eleven moderately to heavily pigmented placoid lesions were angiographically silent, in that they failed to display either a tumor-associated vasculature or diffuse leakage. (2) Seven generally nonpigmented lesions demonstrated a quasi-geometric filigree vascular network, approximating the caliber of the normal radial vasculature. These tumor-associated vessels fluoresced early and in synchrony with the appearance of dye in the radial vasculature from which they probably were derived, but they diffusely and confluently leaked fluorescein in the late phases of the angiogram. (3) Three brown or variably pigmented lesions manifested a mixed angiographic pattern, combining features of groups 1 and 2. (4) The final angiographic pattern was comprised of two pathologically proved mixed spindle-epithelioid cell melanomas, each of which in part or in toto showed diffuse and eventually confluent fluorescence emanating from ill-defined vascular foci. One of these two lesions additionally exhibited a large area that was perfused late by irregular leashes of vessels. The ability to distinguish benign from malignant melanocytic lesions of the iris can be greatly enhanced by iris fluorescein angiography.

Clinical and Pathological Correlation of Malignant Melanoma

We have attempted to review virtually all forms of cutaneous and mucocutaneous melanomas. Superficial spreading, lentigo maligna and nodular melanomas have been more thoroughly investigated and documented in previous studies. Lentigo maligna melanoma appears to have a longer duration and better prognosis than SSM or NM. The overall prognosis probably correlates better with the anatomic level and thickness of invasion than with type (Clark et al. 1975, Breslow 1970, 1975). It appears that certain pitfalls exist in either method of assessing prognosis, and it is recommended that both methods be applied in evaluating a malignant melanocytic lesion when feasible. With regard to in situ melanoma or Level I melanoma, it is our experience that such lesions can achieve a 100% cure rate when completely excised. Hence, we prefer to call such lesions severely atypical melanocytic hyperplasia, and thus avoid labeling these patients with a malignant diagnosis. The most difficult histologic challenge in diagnosing a lesion of malignant melanoma is the Spitz nevus. The pathologist should never be biased by the age of the patient, for a serious mistake can arise. We have seen a case of nodular melanoma in a 13-year-old girl diagnosed as Spitz nevus only to be followed by a lymph node metastasis years later. Other examples of histologic differential diagnoses of malignant melanomas include, for example, halo nevus, soft tissue sarcoma, squamous cell carcinoma with spindle cell proliferation, Paget's disease of metastatic carcinoma, (for example, from the breast). Therefore, the approach to the diagnosis of malignant melanoma necessitates an evaluation of both clinical and pathological features. Histologic study must encompass both the pattern of growth and cellular cytologic detail for successful interpretation.