Nonmelanocytic Tumors Research Articles

Immunohistochemical detection of melanoma-associated antigens on formalin-fixed, paraffin-embedded canine tumors.

Seven monoclonal antibodies (Moabs), recognizing melanoma-associated antigens in human tissues, were evaluated for their ability to immunohistochemically stain formalin-fixed, paraffin-embedded canine melanomas. Only 2 Moabs, designated human melanosome-specific antigen (HMSA)-1 and HMSA-5, stained routinely processed canine melanomas, staining 21/35 (60%) and 24/35 (69%), respectively. Twenty-nine of 35 (83%) melanomas tested were stained if results of the 2 Moabs were combined. Monoclonal antibody HMSA-1 also stained neoplastic cells of 10/35 (29%) tumors of nonmelanocytic origin and some neurons and salivary gland epithelial cells in normal canine tissues. However, Moab HMSA-1 staining in the nonmelanocytic tumors, consisting of small, discrete periodic acid-Schiff-positive cytoplasmic droplets, was readily distinguishable from the diffusely granular, cytoplasmic staining of melanocytic tumors. In addition to melanomas, Moab HMSA-5 stained melanocytes and some melanin-containing tumor cells of a pigmented basal cell tumor and melanocytes in normal canine skin. Monoclonal antibodies HMSA-1 and HMSA-5 immunohistochemically identified the majority of canine melanomas, had limited and distinguishable staining in normal tissues and nonmelanocytic tumors, and therefore may be a useful adjunct for the diagnosis of canine melanoma in formalin-fixed, paraffin-embedded tissues.

HMB‐45 in non‐melanocytic tumours

HMB‐45 in non‐melanocytic tumours

Non-Melanocytic Tumors of the Skin

Non-Melanocytic Tumors of the Skin

Non-Melanocytic Tumors of the Skin and Melanocytic Tumors of the Skin

Non-Melanocytic Tumors of the Skin and Melanocytic Tumors of the Skin

Atlas of tumor pathology third series: Non-melanocytic tumors of the skin (fascicle 1); Melanocytic tumors of the skin fascicle (2). D. E. Elder and G. F. Murphy. AFIP. Washington, DC, 1990. No. of pages: 278 and 216. Price: each £45. ISSN: 0160 6344

Atlas of tumor pathology third series: Non-melanocytic tumors of the skin (fascicle 1); Melanocytic tumors of the skin fascicle (2). D. E. Elder and G. F. Murphy. AFIP. Washington, DC, 1990. No. of pages: 278 and 216. Price: each £45. ISSN: 0160 6344

Immunohistochemical characterization of atypical fibroxanthoma and dermatofibrosarcoma protuberans.

Atypical fibroxanthoma (AFX) and dermatofibrosarcoma protuberans (DFSP) have generated undue interest regarding their histogenesis, biological behavior, and differentiation from other forms of spindle cell tumors of the skin, including spindle cell squamous carcinomas and desmoplastic melanomas. To identify characteristic immunophenotypes, 12 AFXs and 15 DFSPs were examined with a panel of antibodies against cytokeratin; vimentin; desmin; proteolytic enzymes (alpha-1-antitrypsin and alpha-1-antichymotrypsin); melanoma-associated antigens defined by HMB-45, HMB-50, and NKI/C3; muscle-specific actin (HHF-35); and S-100 protein. The staining patterns of these two tumors were nearly identical. All cases tested negative for cytokeratin, desmin, and S-100 protein and strongly positive for vimentin. Six (50%) AFXs and 12 (80%) DFSPs tested focally positive for muscle-specific actin. None of the cases were reactive with melanoma antibodies HMB-45 and HMB-50; NKI/C3 strongly stained 26 of 27 tumors. Compared to HMB-45 and HMB-50, NKI/C3 cross-reacted with nonmelanocytic neoplasms. Two AFXs stained for alpha-1-antitrypsin and alpha-1-antichymotrypsin. This study confirms (1) the immunophenotypic similarity of AFX and DFSP, (2) the presence of myofibroblastic differentiation in both tumors, as reflected by HHF-35 staining, and (3) that AFX and DFSP are easily distinguished from spindle cell squamous carcinoma and desmoplastic melanoma by the absence of cytokeratin, HMB-45, and HMB-50 staining.

Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase

The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors.

HMB-45 recognizes stimulated melanocytes.

A monoclonal antibody (HMB-45) was previously reported to bind to melanoma cells, and the junctional component of nevus cells, but not to normal adult melanocytes. We have tested HMB-45 binding in several conditions under which melanocyte stimulation might be expected in adults, i.e. 3 simple lentigines, 2 solar lentigines, 7 recent surgical scars (from re-excision of non-melanocytic tumors), 2 surgical scars from re-excisions of melanomas (after complete primary excisions), 9 hemangiomas from non-sun-exposed skin, 1 basal cell carcinoma, 1 acute ecchymosis, 1 keloid, and 1 dermatofibroma. Positive controls included 6 malignant melanomas and 1 fetal skin sample. Melanocytes were strongly positively stained overlying hemangiomas, within or near recent surgical scars of melanocytic and non-melanocytic tumor re-excisions, near basal cell carcinoma, and in fetal skin. Melanocytes either were not stained or were stained only focally for trace amounts in the normal skin near the new margins of the wide re-excision specimens for melanoma, i.e., at a distance from the scar, in the simple lentigines and in the fibrotic lesions. Thus, HMB-45 is staining an antigen which appears in adult melanocytes during stimulation and in fetal skin, as well as in melanomas. This stimulation is associated with conditions that would have increased vascularity, suggesting a melanocyte response to a plasma factor, or other endothelial cell derived factor. HMB-45 would not be a useful marker for residual melanoma cells in melanoma re-excision specimens.

An experience of malignant melanoma

The diagnosis of malignant melanoma involves its differentiation from many benign and malignant non-melanocytic tumours as well as from benign melanocytic lesions. Frequently knowledge of the clinical history and the site of the tumour is very valuable. The diagnostic value of many microscopic features 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.

Detection of S-100 protein as an aid to the identification of melanocytic tumors.

We sought S-100 protein in sections prepared from formalin-fixed paraffin-embedded tumor and normal tissues by an immunoperoxidase technique with a rabbit anti-bovine S-100 protein antiserum as first antibody and aminoethyl carbazole as developer. S-100 protein was demonstrated in 56 of 56 cutaneous melanomas, regardless of their primary or metastatic status, and in 35 of 35 nevocytic nevi. The amount of S-100 protein was independent of the degree of melanization of the tumors. Only 1 of 51 non-neural non-melanocytic tumors tested contained S-100 protein. The technique is valuable in confirming the melanocytic nature of primary or metastatic tumors and in detecting small foci of metastatic melanoma in lymph nodes and other tissues. It also seems applicable to research on melanocytic anomalies.

S100 PROTEIN: A MARKER FOR HUMAN MALIGNANT MELANOMAS?

S100 protein is a nervous-system-specific cytoplasmic protein which is also present in human malignant melanoma cell lines. To test for its tumour specificity, biopsy specimens from normal tissue and a wide variety of tumours were tested for S100 by complement fixation and immunofluorescence tests. S100 was present in all of thirteen samples of malignant melanoma tissue and absent from nineteen samples of non-melanocytic tumours, and from normal skin and normal lymph nodes. S100 levels did not correlate with tyrosinase activity in the tissues examined. Detection and measurement of S100 protein may help distinguish poorly differentiated amelanotic malignant melanoma from tumours of obscure histological origin; they may also aid the detection of micrometastatic disease in the lymph nodes and other tissues of melanoma patients.

Frozen section diagnosis of suspected melanoma of the skin

Due to the frequency of malignant melanoma in Queensland urgent frozen section diagnosis of pigmented skin lesions suspected of melanoma has become a routine procedure, second only to breast lumps in frequency. Review of the Department's experience shows 329 pigmented skin lesions from 316 patients were diagnosed by urgent cryostat section. There were 3 main groups of lesions—about one half were malignant melanomas and about one quarter each were naevi and non-melanocytic lesions. Histological error occurred in 4 cases (1.2%) and in 2 cases of combined naevi resulted in unnecessary surgery. The recognition of the combined naevus is important in avoiding error as 11 tumours in the series were combined naevi. Seven were combined Spitz (juvenile melanoma) and common naevi at the junctional, compound or intradermal stage and 4 were combined blue or cellular blue and common naevi. The error rate of 1.2% is acceptable when compared with published rates of frozen section diagnoses on a wider range of tissues. The diagnosis was withheld in 19 lesions (5.8%) which on paraffin section were predominantly melanomas. The causes were superficial levels of tumour, heavy lymphocytic infiltration, partial tumour regression and unusual cell shape and arrangement in the melanomas. In all 3 groups most of the lesions were less than 15mm diam. and were flat. Nearly 40% of the melanomas were Level I or II. The majority of the naevi were compound naevi. The non-melanocytic tumours were mainly pigmented basal cell carcinomas and basal cell papillomas. As a result of the frozen section report, further treatment was performed in 83 (52%) of the malignant melanoma cases. It is concluded that cryostat section diagnosis of malignant melanoma in experienced hands is reliable and is of considerable value to the surgeon.

Frozen section diagnosis of suspected malignant melanoma of the skin.

From 316 patients admitted to hospital, 329 pigmented skin lesions suspected of malignant melanoma were diagnosed by urgent frozen sections prepared in the cryostat. There were three groups: about one-half were malignant melanomas, and about one-quarter each were nevi and nonmelanocytic tumors, predominantly pigmented basal cell carcinomas and basal cell papillomas. Histologic error occurred in 4 cases (1.2%), and in 2 cases of combined nevi resulted in unnecessary surgery. The recognition of combined nevi is important in avoiding error; histologic guides are mentioned. The error rate is acceptable when compared with published rates of frozen section diagnoses on a wider range of tissues. The diagnosis was withheld in 19 lesions (5.8%); the causes were superficial level of the tumor, heavy lymphocytic infiltration, partial tumor regression, and unusual cell shape and arrangement in the melanomas. In the three groups the majority of lesions was less than 15 mm maximum diameter, and had no measurable height. Nearly 40% of the melanomas were Level I and II. Most of the nevi were compound, but an important group were combined nevi. Surgical excision was apparently excessive in 16 (5%) lesions. It is concluded that frozen section diagnosis of malignant melanoma in experienced hands is reliable and is of considerable value to the surgeon.