mart-1-antigen and Carcinoma-in-Situ

Actinic keratosis (AK) and squamous cell carcinoma in-situ (SCCIS) within or near melanoma in situ (MIS) can complicate diagnosis due to overlapping clinical and microscopic features. This study aimed to describe basilar melanocyte density and pagetoid spread in AK and SCCIS for improved diagnostic accuracy.. A total of 22 AK and 22 SCCIS biopsies containing a margin of uninvolved epidermis were immunostained with MART-1 (melanoma antigen recognized by T-cells 1). The basilar melanocyte:keratinocyte ratio and the number and distribution of pagetoid melanocytes were compared in AK, SCCIS, and uninvolved epidermis. An in-vitro human skin model was created to assess the impact of keratinocyte atypia on melanocyte distribution.. The median basilar melanocyte:keratinocyte ratio in SCCIS (1:11.49) was lower than in uninvolved epidermis (1:5.59, P = 0.0011), and the ratio in AK (1:6.94) was similar to uninvolved epidermis (P = 0.987). Pagetoid melanocytes were absent in perilesional skin but common in AK (21/22, P < 0.0001) and SCCIS (22/22, P < 0.0001). Pagetoid melanocytes at or above the mid-spinous layer were more common in SCCIS (21/22) vs AK (7/22, P < 0.0001). Pagetoid melanocytes were present in the in-vitro skin model made with neoplastic but not normal keratinocytes.. Pagetoid melanocytes in AK and SCCIS should be interpreted with caution to avoid overdiagnosis of MIS.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Diagnostic Errors; Female; Humans; Keratinocytes; Keratosis, Actinic; Male; MART-1 Antigen; Melanocytes; Melanoma; Middle Aged; Skin Neoplasms

Mohs micrographic surgery (MMS) with frozen section immunohistochemistry is a treatment option for malignant melanoma in situ (MMIS) and lentigo maligna melanoma (LMM). Melan-A is a cytoplasmic melanocyte immunostain useful on frozen sections but may lack specificity. Microphthalmia transcription factor (MITF) is a more specific nuclear melanocyte immunostain less frequently used in MMS.. To quantify melanocyte density in chronic sun-damaged skin (CSDS), negative margin, and tumor from patients undergoing MMS for MMIS and LMM using MITF and melan-A.. Sixteen patients with MMIS or LMM had frozen sections from CSDS, negative margin, and 12 tumor samples, stained with MITF and melan-A. Melanocyte counts were performed.. Chronic sun-damaged skin mean melanocyte count (MMC) for MITF and melan-A was 9.8 and 13.7, respectively, (p < .001). Negative margin MMC for MITF and melan-A was 8.84 and 14.06, respectively, (p < .001). Tumor MMC for MITF and melan-A was 63.5 and 62.4, respectively.. Although both MITF and melan-A facilitate the identification of tumor during MMS for MMIS and LMM, the apparent melanocyte density on tumor-free CSDS appears higher with melan-A than MITF. Microphthalmia transcription factor provides a crisp outline of melanocyte nuclei and is a useful alternative stain to melan-A for MMS of melanoma.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma in Situ; Cell Count; Female; Frozen Sections; Humans; Hutchinson's Melanotic Freckle; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Melanoma; Microphthalmia-Associated Transcription Factor; Middle Aged; Mohs Surgery; Skin Neoplasms

Mohs micrographic surgery (MMS) with melanoma antigen recognized by T-cell (MART-1) immunostaining is an effective treatment of cutaneous melanoma.. To determine the efficacy of MMS with MART-1 immunostain in the management of invasive and in situ melanoma.. A retrospective cohort study evaluated 2,114 melanomas in 1,982 patients excised using MMS and MART-1 immunostain. The margins required for excision were calculated based on Breslow thickness, location, and size. Survival and local recurrence rates were calculated and compared with those of historical controls.. The mean follow-up period was 3.73 years. Local recurrence was identified in 0.49% (7/1,419) of primary melanomas. Approximately 82% of melanomas were excised with ≤6-mm margins. The surgical margin was significantly related to tumor location and size but not to Breslow thickness. The five-year Kaplan-Meier local recurrence and disease-specific survival rates were 0.59 ± 0.30 and 98.53 ± 0.42, respectively. Mohs micrographic surgery with MART-1 immunostain achieved lower local recurrence rates and equivalent or higher Kaplan-Meier survival rates than conventional wide local excision.. Mohs micrographic surgery with MART-1 immunostain is an effective treatment of melanoma as evidenced by low local recurrence rates. It offers the advantage of more tissue-conserving margins than those recommended for conventional excision.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Child; Female; Humans; Male; MART-1 Antigen; Melanoma; Middle Aged; Mohs Surgery; Neoplasm Invasiveness; Retrospective Studies; Skin Neoplasms; Survival Rate; Treatment Outcome

The MART1-verified Ki-67 proliferation index is a valuable aid to distinguish melanomas from nevi. Because such indices are quantifiable by image analysis, they may provide a novel automated diagnostic aid. This study aimed to validate the diagnostic performance of automated dermal Ki-67 indices and to explore the diagnostic capability of epidermal Ki-67 in lesions both with and without a dermal component. In addition, we investigated the automated indices' ability to predict sentinel lymph node (SLN) status. Paraffin-embedded tissues from 84 primary cutaneous melanomas (35 with SLN biopsy), 22 melanoma in situ, and 270 nevi were included consecutively. Whole slide images were captured from Ki-67/MART1 double stains, and image analysis computed Ki-67 indices for epidermis and dermis. In lesions with a dermal component, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% confidence interval [CI], 0.72-0.86) for dermal indices. By excluding lesions with few melanocytic cells, this area increased to 0.93 (95% CI, 0.88-0.98). A simultaneous analysis of epidermis and dermis yielded an ROC area of 0.94 (95% CI, 0.91-0.96) for lesions with a dermal component and 0.98 (95% CI, 0.97-1.0) for lesions with a considerable dermal component. For all lesions, the ROC area of the simultaneous analysis was 0.89 (95% CI, 0.85-0.92). SLN-positive patients generally had a higher index than SLN-negative patients (P ≤ .003). Conclusively, an automated diagnostic aid seems feasible in melanocytic pathology. The dermal Ki-67 index was inferior to a combined epidermal and dermal index in diagnosis but valuable for predicting the SLN status of our melanoma patients.

Topics: Area Under Curve; Automation; Biomarkers, Tumor; Carcinoma in Situ; Female; Humans; Image Interpretation, Computer-Assisted; Immunohistochemistry; Ki-67 Antigen; Male; MART-1 Antigen; Melanoma; Melanoma, Cutaneous Malignant; Middle Aged; Mitotic Index; Nevus, Pigmented; ROC Curve; Sentinel Lymph Node Biopsy; Skin Neoplasms

Topics: Aged; Biomarkers, Tumor; Carcinoma in Situ; Cell Proliferation; Humans; Hutchinson's Melanotic Freckle; Immunohistochemistry; Male; MART-1 Antigen; Melanoma; S100 Proteins; Skin Neoplasms

Evaluation of cutaneous pigmented lesions can be diagnostically challenging and represents an activity often supplemented by immunohistochemistry. Immunohistochemical studies typically employ 3,3'-diaminobenzidine (DAB) resulting in brown staining of both melanocytes and melanin. Difficulty may thus arise in distinguishing different cell types in heavily melanized lesions. Azure blue counterstaining has been used in conjunction with melanoma antigen recognized by T-cells (MART-1) to differentiate melanocytes from melanin by highlighting the latter blue-green. Microphthalmia transcription factor (MiTF) represents an alternative immunomarker that shows nuclear reactivity, which facilitates ease of interpretation.. Twenty examples of solar lentigo and melanoma in situ (MIS) were independently evaluated utilizing MiTF and MART-1/Azure blue for melanocyte quantification. Melanocyte counts were averaged over five high-power fields (×400) to obtain a mean melanocytic count.. There was no significant difference in the mean melanocytic count between MART-1/Azure blue and MiTF as assessed in the solar lentigo group and as assessed independently in the MIS group. MiTF nuclear staining facilitated interpretation and required less laboratory preparation, as an additional counterstain was not necessary.. MiTF is as effective as MART-1/Azure blue in identifying melanocytes in the context of solar lentigo or MIS. On the basis of our results, we favor expanding the use of MiTF as an immunohistochemical marker, as it provides an efficient alternative to MART-1 with Azure blue counterstaining in the evaluation of cutaneous pigmented lesions.

Topics: Azure Stains; Biomarkers, Tumor; Carcinoma in Situ; Diagnosis, Differential; Humans; Immunohistochemistry; Lentigo; MART-1 Antigen; Melanoma; Microphthalmia-Associated Transcription Factor; Skin Neoplasms

Pigmented actinic keratosis is one of the simulators of early melanoma in situ from severely sun-damaged skin. Close scrutiny of the hematoxylin and eosin stained section does not always allow an unequivocal diagnosis, because it is sometimes difficult to distinguish pigmented keratinocytes from melanocytes. Immunohistochemical stains, such as S-100 and HMB-45, are used routinely to address this problem. Melan-A, also known as MART-1, is an additional melanocytic marker and has proved to be useful in identifying metastatic tumors of melanocytic origin. The usefulness of this marker to discriminate pigmented actinic keratosis from early melanoma in situ, however, has not yet been a subject of investigation. In this study we evaluated Melan-A expression in ten unequivocal cases of pigmented actinic keratosis and compared the staining pattern with that of S-100, HMB-45, and tyrosinase. In all ten cases the number of cells highlighted with Melan-A was by far larger than those labeled with S-100, HMB-45, and tyrosinase. Four cases showed clusters of Melan-A positive cells being suggestive of melanocytic nests. Even areas of normal skin adjacent to the actinic keratosis featured prominent staining of Melan-A, but only inconsistent labeling of intraepidermal melanocytes with S-100, HMB-45, and tyrosinase. We therefore believe that Melan-A is a more sensitive marker for intraepidermal melanocytes than S-100, HMB-45, and tyrosinase. In addition there may be expression of Melan-A in keratinocytes and nonmelanocytic cells. To avoid an erroneous diagnosis of malignant melanoma one should therefore interpret results obtained from Melan-A stained slides carefully and in the context with other melanocytic markers.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma in Situ; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratosis; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; S100 Proteins; Skin Neoplasms; Sunlight

Melanocytic lesions with lichenoid regression may mimic a benign lichenoid keratosis (BLK) histologically. A total of 336 BLKs were reviewed and deeper sections obtained to determine the frequency of this phenomenon. Two cases (0.6%) showed at least 1 melanocytic nest or junctional multinucleated melanocyte (starburst melanocyte) on deeper sections confirmed by MART-1 immunostaining. Both of these cases demonstrated solar elastosis, and 1 case had an effaced rete ridge pattern. Not included in the histological study are 5 additional cases in which the initial slide showed only lichenoid dermatitis, but deeper sections obtained before to the initial sign-out revealed a melanocytic proliferation. These 5 cases would have been signed out as "consistent with BLK" if deeper sections had not been obtained. Fluorescent in situ hybridization (FISH) was performed on 3 cases; in each case, the melanocytes demonstrated a loss of chromosome 9p21 DNA copy number. The finding of nests of genetically altered melanocytes on severely sun-damaged skin strongly suggests that these cases represent lichenoid regression of melanoma in situ. Pathologists should approach a diagnosis of BLK cautiously in the setting of severely sun-damaged skin.

Topics: Aged; Antigens, Neoplasm; Carcinoma in Situ; Chromosomes, Human, Pair 9; Diagnosis, Differential; DNA; Gene Dosage; Giant Cells; Humans; Hyperplasia; In Situ Hybridization, Fluorescence; Lichen Planus; MART-1 Antigen; Melanocytes; Melanosis; Middle Aged; Neoplasm Proteins; Precancerous Conditions; Skin Neoplasms; Sunlight