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PubMed1991

Cutaneous glomus tumor. A comparative immunohistochemical study with pseudoangiomatous intradermal melanocytic nevi.

Glomus tumor of the skin and subcutis is an uncommon neoplasm in which the histologic features can be mimicked by other dermal lesions of diverse types. The cell of origin is thought by most to be the pericyte, which has some of the ultrastructural features of smooth muscle. We examined six glomus tumors with a panel of antibodies including the myogenic markers, muscle-specific actin (HHF-35), and desmin; all tumors were immunoreactive for muscle-specific actin, but only two expressed desmin. Half of these tumors expressed the endothelial determinant, factor VIII-related antigen. Pseudoangiomatous melanocytic nevi stimulating glomus tumors were consistently immunoreactive for S-100 protein, which was not expressed by glomus tumors.

Actins↗

PubMed1983

The value of S-100 immunostaining as a diagnostic tool in human malignant melanomas. A comparative study using S-100 and neuron-specific enolase antibodies.

The brain proteins S-100 and neuron-specific enolase have been reported by separate groups to be present in human malignant melanomas. There is no systematic study comparing the occurrence of these proteins in the same tumour specimens. We have examined 33 primary malignant melanomas, including 5 which were amelanotic, and 25 metastatic melanomas using immunohistochemical methods with specific, non-cross-reacting antibodies to S-100 and NSE. We found S-100 immunoreactivity to be present in all cases but one, whereas NSE immunoreaction was very weak and patchy, and present in only 6 cases. S-100 immunoreactivity was not demonstrated in 40 control tumours, either primary or metastatic in skin, including basal- and squamous-cell carcinomas, spindle-cell sarcomas, lymphomas and Merkel cell tumours. All intradermal (n = 4) and compound (n = 1) naevi were positive for S-100, 2 blue naevi showing much less reaction. NSE immunoreactivity was detected in Merkel cell tumours (n = 8), undifferentiated (n = 2) and small cell (n = 1) carcinomas, and all melanocytic naevi. It is suggested therefore that antibody to S-100 is the reagent of choice for demonstration of melanocytic tumours, and may be especially valuable in the diagnosis of amelanotic melanoma or metastatic tumours of doubtful origin where melanoma is suspected.

Fluorescent Antibody Technique↗

PubMed2002

Cerebriform intradermal naevus (a rare form of secondary cutis verticis gyrata).

BACKGROUND: Acquired cerebriform intradermal naevus (CIN) is a rare form of pseudo cutis verticis gyrata. CASE REPORT: A case of acquired CIN of the scalp in a 46-year-old male patient is presented. The clinical and histopathological presentations of CIN are described and the therapeutic possibilities are discussed. CONCLUSIONS: In each individual case the physician must decide whether to do surgery or follow a wait-and-see policy. There is little risk of malignant change of CIN, and surgical excision of such lesions often involves evident mutilation.

Diagnosis, Differential↗

PubMed1995

bcl-2 expression in melanocytic nevi. Insights into the biology of dermal maturation.

BACKGROUND AND DESIGN: Recently, a new category of oncogenes has been discovered that regulate programmed cell death. The bcl-2 oncogene has been found to inhibit cellular death without affecting cellular proliferation. In the skin, bcl-2 expression is limited to cells along the basal cell layer. However, we also noticed that resting melanocytes appeared to express bcl-2. We examined the expression of bcl-2 and its possible role in the biology of benign melanocytic proliferations. Routine paraffin sections of formalin-fixed tissue were labeled with anti-bcl-2 monoclonal antibody, and expression of bcl-2 was detected by a biotin-avidin-immunoperoxidase procedure. RESULTS: We examined 13 congenital, 11 acquired, and six atypical or dysplastic nevi for expression of bcl-2. Expression of bcl-2 was observed in 11 of 13 congenital nevi. All 11 acquired nevi and 6 nevi with architectural disarray and cytologic atypia expressed bcl-2. Both junctional and intradermal melanocytes expressed bcl-2 in a perinuclear and cytoplasmic pattern. Within neurotized areas, bcl-2 became significantly weaker and totally absent. CONCLUSIONS: In mature tissues, bcl-2 expression is quite limited. It appears to be restricted to pluripotential stem cells that serve as a reservoir for tissue that is constantly undergoing renewal, such as the hematopoietic cells and the intestinal mucosa. In the skin, bcl-2 expression has been previously reported to be limited to the epidermal basal cell layer and proliferation zones. Our results indicate that resting melanocytes and melanocytic nevi regularly express bcl-2.

Aging↗

PubMed1986

Measuring S100 protein and neurone specific enolase in melanocytic tumours using video image analysis.

Using a computed video image analysis system, the staining intensity for both neurone specific enolase (NSE) and S100 protein was measured in sections from 19 malignant melanomas and 16 benign melanocytic lesions. The results of this study confirm previous reports that NSE and S100 protein are useful markers for malignant melanoma. NSE staining intensity in the cases of malignant melanoma was significantly higher than that in benign naevi (p = 0.011). Intensity of staining for S100 protein was not significantly higher in the malignant melanomas. There was, however, a significant S100 gradient when comparing superficial and deep intradermal portions of these tumours (p = 0.003). This feature was not seen in benign naevi. The greatest intensity of S100 protein staining was found in the deeper portions of the malignant melanomas. This gradient difference was not seen with staining for NSE. Although it seems that the overall intensity of staining for NSE is more effective in differentiating between benign and malignant lesions, the difference in staining intensity between the superficial and deep portions of the tumour may be the better indicator of adverse behaviour in lesions in which the diagnosis of malignancy is uncertain.

Humans↗

PubMed1984

Immunoperoxidase staining for Ia-like antigens in paraffin-embedded tissues from human melanoma and lung carcinoma.

The human Ia-like antigens that are predominantly expressed by cells associated with immunologic function has been considered as a diagnostic marker of malignant transformation of some nonlymphoid tissues. Immunoperoxidase staining of formalin-fixed and paraffin-embedded tissue sections with a monoclonal antibody to Ia-like antigens was chosen for assessment of the value of this marker for diagnosis in surgical pathology. Monoclonal antibody LK8D3 developed against a human melanoma cell line bearing Ia-like antigens was found to react in serologic and immunochemical studies with an antigenic determinant of Ia-like antigens that was relatively stable to formalin fixation and paraffin embedding. Avidin-biotin complex peroxidase staining of formalin-paraffin sections with LK8D3 showed focal expression of Ia-like antigens in 3 of 12 melanomas, whereas all 8 cases of intradermal nevi were negative. Immunoperoxidase staining of formalin-paraffin sections of lung carcinomas with antibody LK8D3 was related to the histologic subtype of tumors. Thus, squamous cell carcinomas showed only very focal staining for Ia-like antigens in 5/9 cases, while widespread and intense Ia-like immunoreactivity was seen in 3/5 cases of lung adenocarcinomas, including two bronchioalveolar carcinomas. The presence of Ia-like antigens in lung adenocarcinoma may not be entirely associated with malignant transformation, because normal alveolar lining cells were stained with the antibody.

Adenocarcinoma↗

PubMed1989

Type VII collagen antibody LH 7.2 identifies basement membrane characteristics of thin malignant melanomas.

A monoclonal antibody (LH 7.2) to the carboxy terminal of type VII collagen has been used in an indirect immunoperoxidase method on frozen sections of biopsies of benign compound and intradermal cellular naevi, dysplastic naevi, and malignant melanomas, to label the epidermal basement membrane. Benign intradermal naevi had an intact membrane with the dermal naevus cell component lying beneath it. Compound naevi showed proliferating junctional nests of naevus cells pushing through the membrane towards the dermis beneath. In contrast, dysplastic naevi and melanomas showed a progressive displacement of the membrane downwards. Thin lesions were confined above the membrane. With increasing tumour thickness, discontinuities in the membrane were seen and foci of invasive growth through the line of the membrane were identified. These studies suggest that the good prognosis of thin melanomas is associated with confinement of the tumour within an expanded epidermis above the basement membrane.

Antibodies, Monoclonal↗

PubMed1995

Expression of the antigen recognized by mAb GB36 in normal skin and in skin tumours.

GB36, a mouse monoclonal antibody (mAb) raised against an epithelial antigen of the human trophoblast, reacts with the epithelial basement membrane of chorionic villi; it does not react with the invasive extravillous cytotrophoblast. Expression and characterization of the antigen of GB36 (designated GBA36) were investigated in normal keratinocytes by immunoprecipitation, immunofluorescence and immunoelectron microscopic studies. Immunoprecipitation experiments demonstrated that the proteins identified on keratinocytes by mAb GB36 and a rat mAb anti-integrin alpha 6 (GoH3) were the same. Using immunofluorescence and immunoelectron microscopic methods, GBA36 was localized on the cell membrane facing the epithelial basal lamina of basal keratinocytes. GBA36 distribution in benign and malignant skin tumours was evaluated by immunostaining methods (immunofluorescence and immunoperoxidase). Analysis of tumours revealed that whereas benign epithelial tumours and intradermal naevi displayed high levels of GBA36, the expression of this antigen decreased progressively in spinocellular and basal cell carcinomas, and in cutaneous melanomas in relation to invasiveness. During cell transformation, GBA36 undergoes quantitative alterations, and expression is down-regulated. Although the functional relevance of these changes remains unknown, the correlation of decreased GBA36 expression with tumour progression may indicate a role for altered integrin expression in tissue invasion by human skin carcinoma and melanoma.

Adult↗

PubMed2005

Histological features used in the diagnosis of melanoma are frequently found in benign melanocytic naevi.

AIMS: The histological features used in the diagnosis of melanoma may be present in benign naevi, but quantitative data are not available. The aim of this study was to establish the real prevalence of such features in naevi. METHODS: Ten dermatopathologists, from nine Italian institutions, studied a series of naevi. Eleven histological parameters currently used in melanoma diagnosis were analysed: asymmetry, poor circumscription, predominance of single melanocytes, irregular confluent nests, suprabasal melanocytes, hair follicle involvement, absence of maturation, cytological atypia, dermal lymphocytic infiltrate, mitoses, and necrosis. RESULTS: Ninety one naevi were examined: 22 junctional, 59 compound, and 10 intradermal. None of the studied parameters was seen in 22 of the benign naevi studied. One or more investigated features were found in 69 naevi. Poor circumscription was found in 49 cases, single melanocytic predominating in 42, asymmetry in 41, irregular confluent nests in 16, cytological atypia in 14, suprabasal melanocytes in seven, and hair follicle involvement in seven; absence of maturation, mitoses and necrosis were not found. CONCLUSIONS: The histological features used for the histological diagnosis of melanoma are often present in benign melanocytic naevi. This suggests a critical, non-mechanical use of them in melanoma diagnosis.

Adult↗

PubMed2003

[Sentinel lymph nodes in cutaneous melanoma: the experience in the Florence area].

In the period 1997-2001, 466 sentinel lymph nodes from 342 lymphatic basins in 322 melanoma patients were examined at the Health Unit of Florence. The lymphatic mapping was performed through pre-operative lymphoscintigraphy using technetium-labelled nano-colloid, intradermal injections of vital blue dye and intra-operative gamma-probe. The examined patients were 182 females and 140 males. Sentinel lymph node was one in 65.2% of cases; two sentinel lymph nodes were detected in 27% of cases and more than 2 sentinel nodes were detected in 7.8% of cases. Melanoma metastases in one or more sentinel lymph nodes were found in 61/322 patients (18.9%). Lymphatic basins resulted to be involved by melanoma metastases were 64/342 (18.7%); sentinel lymph nodes containing metastatic melanoma deposits were 73/466 (15.6%). No metastasis was found in patients with melanoma thickness < or = 1 mm. One or more positive sentinel lymph nodes were found in 7.5% of patients with melanoma thickness > 1.00 and < or = 1.50 mm, in 27.7% of patients with melanoma > 1.50 and < or = 3.00 mm, in 38.2% of patients with melanoma > 3.00 and < or = 4.00, and in 60.7% of patients with melanoma > 4.00 mm. Frozen section analysis of sentinel lymph nodes, performed in 59/61 patients with nodal metastases, detected nodal involvement in 21 patients (35.6%). Metastases were identified by routine hematoxylin-eosin staining in 57/64 positive lymphatic basins; in 7 cases (11%) metastases were detected by immunohistochemical stainings (S100 and HMB-45). A nodal nevus was found in 3/466 sentinel lymph nodes (0.6%). Our data are analyzed and compared to previously data of the literature. The value of frozen section analysis and the major problems in the diagnosis of melanoma micrometastases in sentinel lymph nodes are discussed. The importance of the sentinel node biopsy for the detection of occult metastases and for the correct staging of melanoma patients are stressed, according to the new TNM melanoma classification.

Adolescent↗

PubMed1980

Intradermal nevi of the eyelid.

Intradermal nevi of the eyelid may be found on the eyelid margin, but occasionally occur on the eyelid skin. Excision of the tumor is performed to substantiate the diagnosis and to improve cosmesis. If the tumor involves the skin alone, an elliptical resection of tumor is recommended. If the tumor appears on the eyelid margin only, it is sliced off parallel with the lid margin. This provides a simple technique to obtain a specimen for diagnosis. It spares the cilia, requires no sutures, and provides a good cosmetic result. If the tumor involves eyelid margin and skin simultaneously, a combination of the elliptical excision and slicing technique is used. When the tumor is more extensive, a full-thickness pentagonal resection of the eyelid with or without canthotomy and cantholysis is performed.

Eyelid Neoplasms↗

PubMed2000

The pathologist's role in sentinel lymph node evaluation.

Patients with high-risk (thick, deeply invasive) primary melanoma were, in the past, managed by wide local excision and elective node dissection or wide local excision alone, with subsequent lymphadenectomy if the regional nodes developed clinically detectable metastases. We recently developed a more logical approach called selective lymph node dissection. To be effective, this requires close collaboration of surgeons, pathologists, and nuclear medicine physicians. The draining lymph node basin is identified preoperatively by lymphoscintigraphy. During surgery, a marker dye (isosulfan blue) and radioactive technetium labeled albumin are injected intradermally around the primary melanoma and the afferent lymphatics are followed up to the first lymph nodes of the ipsilateral regional nodal basin. The surgeon excises the blue-colored and maximally radioactive sentinel nodes and the pathologist critically evaluates these for the presence of a metastatic tumor. If the sentinel nodes are tumor free, no further nodal dissection is undertaken; if a tumor is present, a complete dissection of the nodal basin is performed. We have examined 1,119 sentinel lymph nodes from 669 patients treated by selective lymph node dissection. We identified melanoma cells in sentinel nodes from 126 patients (17.8%). A single node contained tumors in 67% of patients, 2 nodes were positive in 25%, and the remaining 12% of patients had three tumor-containing nodes. Melanoma cells were dispersed singly or in variably sized groups, usually in the peripheral nodal sinus. In around 40% of patients, immunohistochemistry is required to identify minute numbers of tumor cells. With experience, pathologists identify tumors in hematoxylin and eosin (H&E) preparations in an increasing proportion of lymph nodes. Tumor cells are more frequent in the sentinel nodes of patients with primary tumors of deeper Clark level and greater Breslow thickness. Tumor cells must be discriminated from capsular nevus cells, interdigitating dendritic leukocytes, macrophages, and intranodal neural tissues.

Humans↗

PubMed1989

An assessment of the value of Ag NOR staining in the identification of dysplastic and other borderline melanocytic naevi.

One hundred and six melanocytic lesions were studied to determine the value of the so called Ag NOR technique in differentiating dysplastic naevi, Spitz naevi and spindle cell naevi of Reed from malignant melanoma and from 'banal' compound or intradermal naevi. In 79 cases Ag NOR counts were possible. The banal naevi (36) had a mean count of 1.54, (SD 0.3), and the unequivocally malignant superficial spreading melanomas (13), lentigo maligna melanomas (4) and secondary melanomas (4) had a mean count overall of 3.9 (SD 1.59). For dysplastic naevi (16) the mean Ag NOR count was 1.63 (SD 0.36) and for Spitz and spindle cell naevi (in toto 6) the figure was 1.72 (SD 0.55). The difference in Ag NOR counts between all types of naevi and all types of melanoma was highly statistically significant, but there was no difference between banal naevi and dysplastic, Spitz, and spindle cell naevi. Correlation of Ag NOR counts between three independent observers was good. This technique may, therefore, be a useful adjunct in separating true melanoma from borderline melanocytic naevi.

Antigens, Nuclear↗

PubMed2002

Evaluation of melanocytic neoplasms: application of a pan-melanoma antibody cocktail.

Incidence of malignant melanoma (MM) is rising rapidly throughout the Western world, and the number of melanocytic lesions removed for histological assessment has increased. MM can present with a myriad of histological appearances that make diagnosis problematic, particularly when dealing with metastatic deposits. Immunohistochemical diagnosis relies on a panel of antibodies comprising polyclonal S100 protein and the monoclonal antibodies HMB 45, MART-1, tyrosinase and, to a lesser extent, NKIC3. Confirmation of problematic cases relies on the use of polyclonal S100 protein, as its sensitivity has yet to be matched by any monoclonal antibody. The introduction of a potentially valuable pan-melanoma cocktail, composed of HMB 45, MART-1 and tyrosinase, is examined in 50 primary cutaneous malignant melanomas, five desmoplastic malignant melanomas (DMM), 35 benign naevi, 20 metastatic malignant melanomas, 10 basal cell carcinomas (BCC) and 10 squamous cell carcinomas (SCC) and compared to individual immunolabelling with S100 protein, HMB 45, MART-1 and tyrosinase. All BCCs and SCCs were negative with all antibodies. S100 protein, MART-1, tyrosinase and the pan-melanoma cocktail were positive for all cases of benign naevi. HMB 45 labelled all junctional and compound naevi, five of the eight intradermal naevi and five of the seven blue naevi. All 50 primary cutaneous MMs were positive with S100 protein, 49/50 with the pan-melanoma cocktail and tyrosinase, 47/50 with MART-1 and 46/50 with HMB 45. Of the five cases of DMM, all were positive with S100 protein and three of the five were positive with HMB 45, MART-1, tyrosinase and the pan-melanoma cocktail. In the case of metastatic MM, all 20 cases were positive with S100 protein, the pan-melanoma cocktail and tyrosinase. MART-1 was positive in 19/20 cases and HMB 45 in 17/20 cases. The pan-melanoma cocktail showed a high sensitivity for all forms of MM and should be considered a complementary marker to polyclonal S100 protein. Results confirmed that currently there is no alternative antibody available to match the sensitivity of polyclonal S100 protein for immunolabelling DMM.

Antibodies, Monoclonal↗

PubMed2004

The T1796A mutation of the BRAF gene is absent in Spitz nevi.

BACKGROUND: BRAF, a serine/threonine kinase, is a component of the retrovirus-associated sequence (RAS)-RAF-extracellular-regulated protein kinase (ERK)-MAP kinase signal transduction pathway mediating signals from RAS to ERK. The T1796A single point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage of malignant melanomas and benign melanocytic lesions such as congenital nevi, compound nevi, intradermal nevi and dysplastic nevi. The T1796A mutation has been shown to promote cell proliferation. METHODS: We screened 21 Spitz nevi and six spitzoid malignant melanomas for the presence of the T1796A BRAF mutation. RESULTS: The T1796A BRAF mutation could not be detected in any of the 21 Spitz nevi but was present in two of the six spitzoid malignant melanomas. CONCLUSIONS: Our results, in conjunction with data from a previous investigation, suggest that the melanocytic proliferation of Spitz nevi might be induced by components of the RAS-RAF-ERK-MAP kinase pathway different from BRAF, possibly combined with other genetic aberrations. The lack of the T1796A BRAF mutation might be of practical importance in distinguishing Spitz nevi from other melanocytic lesions simulating Spitz nevi as a part of a future complex diagnostic assay.

Base Sequence↗

PubMed1982

The histogenesis of malignant melanoma in relation to pre-existing pigmented lesions.

One hundred and twenty-nine cases of malignant melanoma seen at Bangour General Hospital over an eleven year period were reviewed clinically and histologically. In 51 patients (39.5%) there was a history of pre-existing pigmented lesion at the site of the melanoma. In 14 cases (10.8%) histology confirmed traces of a benign melanocytic naevus. The relationships between naevus cells and malignant melanocytes are described. The patterns most frequently observed were those of intradermal naevus cells in the deeper part of an invasive melanoma and of a compound naevus undergoing malignant change in its junctional component. From these histological observations a histogenetic sequence of events is postulated. In the 37 patients with a positive history of a preceding pigmented lesion but no histological traces of a naevus, the percentage incidence of Lentigo Maligna (LM) and Superficial Spreading Melanoma (SSM), as compared with the 78 patients with a negative clinical history, was significantly higher than the incidence of nodular melanoma (NM). Although LM and SSM are thought to have separate histogenesis and aetiology, they share an important clinical and histological factor, i.e. in both, the radial growth phase is preceded by a, more or less, prolonged stage of intraepidermal horizontal growth. It is postulated that this pre-existing lesion of atypical melanocytic proliferation rather than a hypothetical benign naevus is in most cases the precursor of an invasive melanoma.

Adolescent↗

PubMed1984

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.

Antibodies, Monoclonal↗

PubMed1996

Diagnostic impact of nuclear DNA content and proliferative activity in benign and malignant melanocytic lesions.

Nuclear DNA content was assessed, using image cytometry, in adult melanocytes in normal skin and in 20 intradermal naevi, 60 junction naevi, 107 compound naevi, 61 dysplastic naevi, 17 melanomas in situ and 101 primary malignant melanomas. Proliferation was estimated using mitotic counting and immunohistochemical staining by anti-Ki-67 (clone MIB1) monoclonal antibodies. All normal adult melanocytes; and intradermal naevi (97% junction naevi, 98% compound naevi, 66% dysplastic naevi) were diploid. Thirty-four percent of the dysplastic naevi, 88% of the melanomas in situ and 96% of the malignant melanomas were clearly aneuploid. Proliferation, as assessed by mitotic counting and MI81 index, was significantly higher in aneuploid invasive malignant melanomas than in aneuploid dysplastic naevi (P<0.0001). The results indicate that histomorphologically defined entities of melanocytic lesions are characterized by typical DNA distribution patterns. Distinct aneuploidy combined with high proliferation rates generally seem to be well correlated to an increased malignancy potential of the lesion. In dysplastic naevi, the clonic expansion of aneuploid naevus cells may be limited by host defence mechanisms. Thus, DNA aneuploidy seems to indicate increased risk of malignant transformation, but has to be combined with other data, such as proliferation, in order to differentiate more precisely between different melanocytic lesions.

Adult↗