mart-1-antigen and Nevus--Pigmented

The presence or absence of metastasis in sentinel lymph nodes often drives melanoma staging, prognosis, and treatment. However, distinguishing between metastatic melanoma cells and clusters of benign melanocytic nevus cells is not always straightforward. When morphologic hematoxylin and eosin interpretation alone is not sufficient, additional hematoxylin and eosin sections and immunohistochemical (IHC) studies may be beneficial. This review and small cases series of 3 diagnostically challenging melanocytic sentinel lymph node cases highlights the IHC approach to evaluate intraparenchymal nodal melanocytic nevi, coexistent metastatic melanoma with adjacent melanocytic nevi cells, and nodal blue nevi. In challenging cases, cytological morphology of the melanocytes, location within the lymph node, and IHC studies may assist in diagnosis. If these tools yield conflicting results, expert opinion is recommended.

Topics: Aged; Diagnosis, Differential; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Ki-67 Antigen; Lymphatic Metastasis; Male; MART-1 Antigen; Melanocytes; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasms, Multiple Primary; Nevus, Pigmented; Sentinel Lymph Node; Skin Neoplasms; SOXE Transcription Factors

Whereas the pigmented (melanotic) variant of diffuse neurofibroma (DNF) with positivity for melanocytic markers is well recognized, expression of melanocytic markers in nonpigmented DNF has not been systematically studied. We analyzed 28 unselected consecutive DNFs for expression of melanocytic markers, including melan A, microphthalmia transcription factor (MITF), and HMB-45 antigen. For comparison, we also analyzed 40 localized skin neurofibromas and 7 intraneural neurofibromas. One case of nonpigmented DNF was analyzed by electron microscopy. Of the 28 DNFs studied by immunohistochemistry, 3 were pigmented and 25 nonpigmented. The 3 pigmented DNFs and 9 of 25 (36%) nonpigmented DNFs expressed melan A, MITF, and HMB-45 antigen. These markers were expressed either focally or more diffusely, typically in a minority of the lesional cells, and usually both in the dermal and subcutaneous portion of the DNF. Melan A was expressed in the largest number of the lesional cells (up to 50%), whereas only a small fraction of the melan A-positive cells (from 5% to 10% in most cases) also expressed HMB-45 antigen. None of the 47 non-DNFs expressed these markers. Ultrastructurally, melanosomes were present in some cells in nonpigmented DNF that expressed the melanocytic markers. Twenty-three of 28 (82%) DNFs, including 10 of 12 (83%) DNFs with melanocytic differentiation, were associated with neurofibromatosis type 1. Expression of melanocytic markers, including melan A, HMB-45 antigen, and MITF in DNF is a potential pitfall in differential diagnosis with melanocytic lesions that may clinically or histopathologically resemble DNF, in particular congenital melanocytic nevus with neurotization and neurofibroma-like melanoma.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Cell Differentiation; Diagnosis, Differential; Diagnostic Errors; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Microscopy, Electron; Middle Aged; Neurofibromatoses; Nevus, Pigmented; Predictive Value of Tests; Prognosis; Skin Neoplasms; Slovenia; Texas; Young Adult

Melanocytic nevi existing in lymph nodes create a diagnostic challenge by mimicking metastases. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) stain can differentiate one from another. FLI-1 IHC expression has been shown in malignant melanoma with variable sensitivity while melanocytic nevi were reported to be negative. We hypothesized that FLI-1/Melan-A dual IHC staining may be used in the distinction of metastatic melanoma from nodal nevi and can be an alternative and/or complementary to PRAME. In this study, we examined 13 lymph nodes with metastatic melanoma and 13 lymph nodes with benign deposits. We stained all of the lymph nodes with FLI-1, FLI-1/Melan-A dual, and PRAME IHC stains. In addition, we stained paired skin samples of the metastatic lymph nodes with FLI-1 and PRAME. In primary cutaneous melanomas, 11 of 13 were positive for FLI-1 and PRAME expression (85%). Malignant cells in 12 and 13 lymph nodes showed positive expression of PRAME and FLI-1, respectively. Only one case with a nevic cell deposit was weakly positive for FLI-1 and the remaining benign cases were negative for both FLI-1 and PRAME. Our results show that FLI-1/Melan-A dual stain is as sensitive and specific as PRAME in distinguishing lymph nodes with metastatic melanoma from nodal nevi. Further studies with larger case numbers are needed to support our significant results.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Coloring Agents; Humans; Lymphatic Metastasis; MART-1 Antigen; Melanoma; Melanoma, Cutaneous Malignant; Nevus; Nevus, Pigmented; Proto-Oncogene Protein c-fli-1; Retrospective Studies; Sentinel Lymph Node Biopsy; Skin Neoplasms

Divided nevus with verrucous hyperplasia will always recur after surgery but non-verrucous divided eyelid nevus rarely recur. This study analyzed the differential expression of Ki-67, S100, Melan A and HMB45 and identified the correlation between the clinical and histopathological features of verrucous and non-verrucous divided eyelid nevus.. This study included 29 patients, of whom 8 patients had verrucous divided nevus. Immunohistochemistry labeling was used to assess the expression of Ki-67, S100, Melan A and HMB45 after excision. The difference between verrucous and non-verrucous divided eyelid nevus was analyzed.. The patients' ages ranged from 2 to 59 years, with a mean age of 19 years. The lesion size ranged from 1.5 to 2.0 cm in diameter and invaded the eyelid margins and the posterior lamella of the eyelids. Immunohistochemistry labeling showed strong positivity for approximately 98.5% of S100 and positive staining for approximately 27.6% of Ki-67, 72.4% of Melan A and 6.8% of HMB45. However, Ki-67 was significantly upregulated in verrucous divided nevus of the eyelids compared with non-verrucous divided nevus, with approximately 38.8% upregulation in verrucous and 18.3% upregulation in non-verrucous nevus.. This study correlated the clinic-pathologic features of verrucous divided eyelid nevus by means of statistically analyzing the varied clinical features and pathological impressions. The significant over-expression of S100 may be used as an indicator of divided nevus of the eyelids, and the over-expressed Ki-67 may contribute to the recurrence of verrucous divided nevus. High expression of HMB45 and Melan A may represent malignant transformation.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Child; Child, Preschool; Eyelid Neoplasms; Eyelids; Humans; Ki-67 Antigen; MART-1 Antigen; Middle Aged; Nevus; Nevus, Pigmented; Skin Neoplasms; Young Adult

Blue naevi are uncommon dermal melanocytic neoplasms characterised by GNAQ/GNA11 mutations, which very rarely progress to melanoma. Such melanomas also often have BAP1 mutations, and lack genetic events associated with conventional melanoma. Exceptionally, blue naevi arise in extracutaneous locations; one melanoma arising in this setting has been reported. We report the clinicopathological, immunohistochemical and molecular genetic features of two cases of melanoma arising in extracutaneous blue naevus.. Both arose in males, aged 25 and 63 years, with no history of other melanocytic lesions, and presented as large, painful intra-abdominal masses. The tumours were dark-brown/black, multilobulated, involved small intestinal mesentery and consisted of a predominantly fascicular and spindled, but occasionally nested and epithelioid, proliferation of variably pigmented, relatively monotonous cells with pale cytoplasm and ovoid nuclei with mild to moderate atypia. Mitotic activity was variable but generally low. Both cases showed areas of conventional and cellular blue naevus. Recurrent tumour in one case showed predominantly epithelioid morphology and greater cytological atypia and mitotic activity. One case expressed Melan-A, SOX10 and CD117, with absent expression of S100 protein and DOG1; the other expressed Melan-A, HMB45 and S100 protein. Next-generation sequencing identified GNAQ and BAP1 mutations in one case and GNA11 mutation in the other. Both patients developed widespread metastatic disease.. Exceptionally rare, aggressive melanomas arising in extracutaneous blue naevi should be distinguished from metastatic melanoma, gastrointestinal stromal tumour and malignant melanotic nerve sheath tumour, especially given the significant therapeutic and prognostic differences between these different entities.

Topics: Adult; Biomarkers, Tumor; Diagnosis, Differential; Gastrointestinal Neoplasms; Genetic Markers; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Melanoma; Middle Aged; Neoplasm Metastasis; Nevus, Blue; Nevus, Pigmented; Oncogenes; Prognosis; S100 Proteins; Skin Neoplasms; Tumor Suppressor Proteins; Ubiquitin Thiolesterase

The use of immunohistochemical (IHC) stains in dermatopathology is commonplace; however, little is known regarding utilization trends in melanoma diagnosis. Current Medicare local coverage determinations (LCDs) state that most pigmented lesions, including melanoma, can be diagnosed using H&E alone.. Histopathology reports for all biopsy-proven melanomas excised between January 1, 2017 and June 30, 2018, at a single dermatology clinic, were identified with the following parameters abstracted: laboratory/dermatopathologist rendering the diagnosis, whether IHC was performed, type/number of stains utilized, presence/depth of invasion, and melanoma subtype. The association of characteristics with IHC utilization was evaluated using χ. Three hundred and fifty six eligible melanomas were identified. IHC was employed in 228 (64%) of the diagnoses. Invasive melanoma was diagnosed in 199 cases (55.9%) while 157 (44.1%) were identified as melanoma in situ (MIS). Of the 228 that utilized IHC, 117 were performed on invasive melanoma (58.8%) and 111 were performed on MIS (70.7%).. Our findings suggest a higher IHC usage for the diagnosis of melanoma than previously reported. Existing LCDs regarding IHC utilization in melanoma do not reflect the current state of practice. Further investigation regarding IHC utilization and the development of appropriate-use criteria for melanoma IHC is necessary.

Topics: Biopsy; Female; Humans; Immunohistochemistry; Male; MART-1 Antigen; Medicare; Melanoma; Neoplasm Invasiveness; Nevus, Pigmented; Retrospective Studies; Skin Neoplasms; SOXE Transcription Factors; United States

To implement a double-staining technique to identify the most sensitive and specific combinations of melanoma antigen recognized by T cells (Melan-A), microphthalmia-associated transcription factor (MITF), human melanoma black 45 (HMB45), and Ki67 aiming to assist in the diagnosis of atypical melanocytic conjunctival lesions that are more prone to malignant progression.. Eight specimens of conjunctival melanoma and of primary acquired melanosis with moderate to severe atypia were double-immunostained with a combination of a cytoplasmic marker (anti-Melan-A or anti-HMB45), and a nuclear marker (anti-MITF or anti-Ki67). Eight specimens of normal conjunctiva and of conjunctival nevi served as controls. The specimens were processed using 3,3-diaminobenzidine substrate for nuclear stains and the fast-red substrate for cytoplasmic stains. Each slide was analyzed by light microscopy and provided a percent scale and a 0 to 4+ score for each nuclear and cytoplasmic component.. Melan-A and MITF were strongly positive markers for all melanocytic cells, whereas Ki67 and HMB45 provided a variable response for identifying potentially proliferative or aggressive cells. HMB45 and MITF proved to be the best combination for differentiating between atypical and benign lesions on a percent scale and a 0 to 4+ scale (p = 0.0004), with the 3 other combinations providing mainly confirmatory diagnostic information (p < 0.05).. Our study used an immunohistochemical double-staining approach to differentiate between atypical and benign melanocytic lesions of the conjunctiva. Our findings should aid in a more complete immunohistopathological diagnosis of conjunctival melanocytic lesions, particularly in diagnostically difficult cases.

Topics: Biomarkers, Tumor; Conjunctival Neoplasms; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Ki-67 Antigen; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Melanosis; Microphthalmia-Associated Transcription Factor; Middle Aged; Nevus, Pigmented; Retrospective Studies; Staining and Labeling

Distinguishing benign nodal nevus from metastatic melanoma can be diagnostically challenging, with important clinical consequences. Recently, the loss of epigenetic marker, 5-hydroxymethylcytosine (5-hmC) expression by immunohistochemistry has been found in melanomas and atypical melanocytic neoplasms.. About 41 metastatic melanomas and 20 nodal nevi were retrieved. Nuclear 5-hmC (brown) and cytoplasmic Melan-A Red (red) double immunohistochemical staining was performed.. Total or partial loss of nuclear expression of 5-hmC was noted in 40/41 metastatic melanomas; these tumor cells were strongly positive for Melan-A Red, except in one case of desmoplastic melanoma. All cases of nodal nevus showed uniformly retained nuclear expression of 5-hmC accompanied by strong Melan-A Red cytoplasmic staining. In two cases containing both nodal nevus and metastatic melanoma, all tumor cells were positive for Melan-A Red, but a nuclear expression of 5-hmC was selectively absent only in the melanoma tumor cells.. Dual 5-hmC/Melan-A Red immunohistochemistry is highly specific in distinguishing nodal nevus from metastatic melanoma. Our protocol for brown and red chromogens used in this study provides excellent color contrast and is easy to interpret. Furthermore, this dual staining method allows the preservation of limited tumor tissue, which could be used for potential molecular studies.

Topics: 5-Methylcytosine; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Lymphatic Metastasis; MART-1 Antigen; Melanoma; Melanoma, Cutaneous Malignant; Nevus, Pigmented; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Skin Neoplasms; Staining and Labeling

Topics: Animals; Antineoplastic Agents; Cell Proliferation; Child; Child, Preschool; Female; GTP Phosphohydrolases; Humans; Infant; Injections, Intradermal; Injections, Intralesional; Male; MART-1 Antigen; Melanocytes; Membrane Proteins; Mice; Mitogen-Activated Protein Kinase Kinases; Nevus, Pigmented; Proto-Oncogene Proteins c-akt; Signal Transduction; Skin; Skin Neoplasms; SOXE Transcription Factors; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

A promising arsenal of targeted and immunotherapy treatments for metastatic melanoma has emerged over the last decade. With these therapies, we now face new mechanisms of tumor-acquired resistance. We report here a patient whose metastatic melanoma underwent dedifferentiation as a resistance mechanism to adoptive T-cell transfer therapy (ACT) to the MART1 antigen, a phenomenon that had been observed only in mouse studies to date. After an initial period of tumor regression, the patient presented in relapse with tumors lacking melanocytic antigens (MART1, gp100) and expressing an inflammation-induced neural crest marker (NGFR). We demonstrate using human melanoma cell lines that this resistance phenotype can be induced

Topics: Cell Dedifferentiation; Cell Line, Tumor; Coculture Techniques; Drug Resistance, Neoplasm; Humans; Immunotherapy, Adoptive; Male; MART-1 Antigen; Melanoma; Middle Aged; Neoplasm Metastasis; Nerve Tissue Proteins; Nevus, Pigmented; Receptors, Chimeric Antigen; Receptors, Nerve Growth Factor; Recurrence

Conjunctival melanocytic lesions encompass a group of clinically diverse, benign to malignant, neoplasms that may contain overlapping histopathological features, making definitive diagnosis challenging in some cases. In this series, we compared multiple immunohistochemical (IHC) markers in 11 conjunctival nevi, 10 primary acquired melanosis (PAM) lesions, and 11 conjunctival melanomas. Immunostains included the melanocytic markers HMB-45 and Melan-A, as well as the proliferative marker Ki-67. Loss of beta-catenin expression has been associated with more aggressive clinical disease in cutaneous melanoma, but its status in conjunctival melanocytic lesions is not known, therefore we incorporated beta-catenin immunohistochemical staining in our study. In this series, conjunctival melanomas had a higher Ki-67 proliferative index and HMB-45 immunoreactivity than did PAM lesions and conjunctival nevi (P<0.001). Melan-A was highly expressed in all 3 groups. Beta-catenin was more strongly expressed in melanomas and nevi than in PAM (P<0.001). There was high inter-grader reliability (Kappa=0.53). Overall, IHC labeling of HMB-45 and Ki-67 is increased in conjunctival melanomas compared to PAM or conjunctival nevi. Beta-catenin, an IHC marker previously unstudied in conjunctival melanocytic lesions, is not preferentially expressed in benign lesions and may play a different role in conjunctival atypia than it does in cutaneous melanoma.

Topics: beta Catenin; Cell Proliferation; Conjunctival Neoplasms; Gene Expression Profiling; Genetic Markers; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Ki-67 Antigen; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Melanoma, Cutaneous Malignant; Nevus, Pigmented; Skin Neoplasms

To review the diagnostic categories of a group of conditions referred to as "primary acquired melanosis.". Literature review on the subject and proposal of an alternative diagnostic schema with histopathologic and immunohistochemical illustrations.. Standard hematoxylin-eosin-stained sections and immunohistochemical stains for MART-1, HMB-45, microphthalmia-associated transcription factor (MiTF), and Ki-67 for calculating the proliferation index are illustrated.. "Melanosis" is an inadequate and misleading term because it does not distinguish between conjunctival intraepithelial melanin overproduction ("hyperpigmentation") and intraepithelial melanocytic proliferation. It is recommended that "intraepithelial melanocytic proliferation" be adopted for histopathologic diagnosis. Atypical proliferations are characterized either by bloated dendritic melanocytes with enlarged cell components (dendrites, cell bodies, and nuclei) or by epithelioid melanocytes without dendrites. Atypical polygonal or epithelioid pagetoid cells may reach higher levels of the epithelium beyond the basal layer. Immunohistochemistry defines the degree of melanocytic proliferation or the cellular shape (dendritic or nondendritic) (MART-1, HMB-45) or identifies the melanocytic nuclei (MiTF). Intraepithelial melanocytic proliferation without atypia represents increased numbers of normal-appearing dendritic melanocytes (hyperplasia or early neoplasia) that generally remain confined to the basal/basement membrane region. Intraepithelial nonproliferative melanocytic pigmentation signifies the usually small number of conjunctival basal dendritic melanocytes that synthesize increased amounts of melanin that is transferred to surrounding keratinocytes.. All pre- and postoperative biopsies of flat conjunctival melanocytic disorders should be evaluated immunohistochemically if there is any question regarding atypicality. This should lead to a clearer microscopic descriptive diagnosis that is predicated on an analysis of the participating cell types and their architectural patterns. This approach is conducive to a better appreciation of features indicating when to intervene therapeutically. An accurate early diagnosis should forestall unnecessary later surgery.

Topics: Biomarkers; Conjunctival Diseases; Conjunctival Neoplasms; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Ki-67 Antigen; MART-1 Antigen; Melanoma-Specific Antigens; Melanosis; Microphthalmia-Associated Transcription Factor; Nevus, Pigmented; Terminology as Topic

Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Dermis; Dermoscopy; Female; Humans; MART-1 Antigen; Middle Aged; Neoplasms, Multiple Primary; Nevus, Pigmented; Nose Neoplasms; Skin Neoplasms

Acquired melanocytic nevi (AMN) have been reported to undergo morphological and dermoscopic changes following exposure to narrow-band ultraviolet B (NB-UVB) radiation.. To study the morphological, dermoscopic and immunohistochemical changes in AMN following NB-UVB radiation.. Suberythemogenic NB-UVB sessions were delivered to 40 patients with AMN. For each patient, a minimum of 2 nevi were selected. One nevus was surgically removed from each patient prior to sessions as control; for the other nevus, dermoscopic images were captured before and after NB-UVB sessions. The images were evaluated for changes. At the end, another nevus was surgically removed for immunohistochemical assessment of Ki-67 and melan-A.. Our study showed a statistically significant increase in the size of AMN following NB-UVB radiation. Benign dermoscopic changes were observed. Statistically significant positive correlations were found between some dermoscopic findings and the total cumulative dose of NB-UVB. Immunohistochemical analysis did not show any significant change in the exposed AMN.. AMN irradiated with repeated suberythemogenic doses of NB-UVB showed benign morphological and dermoscopic changes, and this was confirmed by our immunohistochemical study.

Topics: Adult; Dermoscopy; Dose-Response Relationship, Radiation; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Male; MART-1 Antigen; Middle Aged; Nevus, Pigmented; Severity of Illness Index; Skin; Skin Neoplasms; Ultraviolet Therapy

The presence of Melan-A positive dermal cells in excisions for melanoma in situ represents a frequent conundrum for pathologists. These cells may represent superficially invasive melanoma, benign, incidental, dermal nevi or non-specific staining of dermal melanophages. Occasionally, rare, Melan-A positive dermal cells are present which do not clearly correspond to the above three categories. Our objective was to further characterize these Melan-A positive dermal cells. To do this, immunoperoxidase staining for Melan-A and SOX-10 was performed on 188-cutaneous excisions, including examples of melanoma in situ, atypical junctional melanocytic hyperplasia and non-melanocytic tumors. These were evaluated for the presence of Melan-A and SOX-10 positive dermal cells. Dermal cells, positive for both markers, were identified in 17% of the excisions. The cells were present in 10% of cases from the melanocytic group and 31% of the cases from the non-melanocytic group. These cells did not exhibit cytologic atypia and resembled neither the co-existing neoplasm nor melanophages. We conclude that positivity of these rare Melan-A positive cells for SOX-10 argues that they represent true melanocytes and not non-specific staining. The absence of cytologic atypia in these cells and their presence in excisions of non-melanocytic neoplasms argues that they are benign, reactive, dermal melanocytes.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Melanoma; Melanoma, Cutaneous Malignant; Nevus, Pigmented; Skin Neoplasms; SOXE Transcription Factors

Topics: Biomarkers, Tumor; Ciliary Body; Eye Banks; Eye Enucleation; Humans; Ki-67 Antigen; Limbus Corneae; Male; MART-1 Antigen; Middle Aged; Neoplasm Invasiveness; Nevus, Pigmented; S100 Proteins; Tissue Donors; Uveal Neoplasms

Benign melanocytic rests are a frequent finding in superficial lymph nodes removed during sentinel lymph node biopsies for melanoma. Whereas the histopathology of these deposits is well understood, very little is known regarding melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi.. We analyzed lymph nodes removed from the drainage basin of giant congenital melanocytic nevi in three patients who had developed melanoma within their giant congenital nevi.. Two of three patients showed widespread, capsular and parenchymal melanocytic deposits in multiple nodes (9 of 11 nodes in one patient and 6 of 8 in the other). Melanocytes were small, non-mitotically active and resembled those in the associated giant congenital melanocytic nevus. Melanocytes were arranged singly and in small nests ∼0.05 mm in diameter, with some larger sheets up to 1 mm. Nodal melanocytes stained for Melan A and S100 on immunohistochemical evaluation, but showed negative or minimal HMB-45 reactivity.. Evaluation of lymph nodes in the setting of giant congenital melanocytic nevi is complicated by the presence of often numerous, parenchymal melanocytic nevic deposits. Bland cytology and minimal or absent HMB-45 staining may be helpful in differentiating these nodal melanocytic nevi from metastatic melanoma. We term this phenomena large congenital nodal nevus.

Topics: Adolescent; Aged; Biomarkers, Tumor; Follow-Up Studies; gp100 Melanoma Antigen; Humans; Lymph Nodes; Male; MART-1 Antigen; Melanocytes; Melanoma; Melanoma-Specific Antigens; Middle Aged; Nevus, Pigmented; S100 Proteins; Sentinel Lymph Node Biopsy; Skin Neoplasms

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

Melanocytic nevi can undergo clinical and histopathologic changes during pregnancy, as well as after various forms of surgical and nonsurgical trauma. We report the case of a 9-month postpartum 29-year-old female who presented to her dermatologist with a clinically worrisome nevus. This nevus had been treated with liquid nitrogen by her primary care physician 6 months prior to presentation. Histopathologic evaluation revealed a crowded proliferation of atypical melanocytes at the dermal-epidermal junction overlying a scar. The dermal component contained scattered mitotic figures. A combined MART-1, tyrosinase and Ki-67 immunohistochemical study showed foci of increased melanocytic proliferation. These atypical features were interpreted as associated with both the prior cryotherapy, as well as her recent pregnancy. Knowledge of the clinical context in evaluating difficult melanocytic lesions is essential.

Topics: Adult; Cryotherapy; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Ki-67 Antigen; MART-1 Antigen; Melanocytes; Melanoma-Specific Antigens; Nevus, Pigmented; Nitrogen; Pregnancy; Skin Neoplasms

Neural differentiation by melanocytic nevi represents a well-recognized phenomenon, and melanocytic nevi with perineurial differentiation have been reported recently. We reported a case of a congenital melanocytic nevus with histopathologic features of hybrid schwannoma/perineurioma. The patient was a 36-year-old male who presented with a black tumor on his arm since birth. Histopathology showed a congenital melanocytic nevus in the superficial dermis, but more strikingly, in continuity with the melanocytic nevus, there was a well-circumscribed but unencapsulated nodule in the deep dermis. The nodule was composed of cellular and myxoid areas with storiform, laminated or whorled growth patterns. The cellular area was mainly composed of proliferation of plump spindle, oval or epithelioid cells. The myxoid area was mainly composed of proliferation of slender spindle cells with mucin deposition. Immunohistochemical stains showed that the cellular area was positive for S100 and CD34, weakly positive for EMA, negative for Glut-1 and collagen IV, the myxoid area was positive for S100, negative for CD34, strongly positive for EMA and focally positive for Glut-1 and collagen IV. Our results show that congenital melanocytic nevi may show neural differentiation with histopathologic features of hybrid schwannoma/perineurioma.

Topics: Adult; Biomarkers, Tumor; Humans; Male; MART-1 Antigen; Neoplasms, Multiple Primary; Nerve Sheath Neoplasms; Neurilemmoma; Nevus, Pigmented; S100 Proteins; Skin Neoplasms

Intraocular melanocytoma is a rare naevus variant that can be located at the optic disc or within the uvea, and belongs to the group of non-epithelial-associated melanocytic lesions. We wanted to gain an understanding of the role of GNAQ, GNA11 and BRAF V600E in the pathogenesis of uveal melanocytoma and in cases of transformation to uveal melanoma and also to perform a differential immunohistochemical study comparing melanocytoma with uveal melanoma.. Two patients were identified with melanocytoma, one of which had transformed to melanoma. In the latter case, the melanocytoma exhibited an immunophenotype that featured nuclear p27 and no HMB45 staining, with very low Cyclin D1 expression compared with the melanoma that featured little nuclear but more cytoplasmic p27 positivity, much higher Cyclin D1 expression and HMB45 positivity. The melanocytomas were negative for CD68 allowing distinction from melanophages. Both melanocytomas and the melanoma harboured mutations in GNAQ, with no mutations of GNA11 or BRAF V600E.. GNAQ mutations are present in uveal melanocytomas and in a case of transformation to melanoma, implicating GNAQ-dependent mitogen activation signals, in the pathogenesis of uveal melanocytoma. This assists in explaining why a proportion of uveal melanocytoma can transform to uveal melanoma, known to harbour high-frequency GNAQ mutations at exon 5, codon 209.

Topics: Adolescent; Adult; Cell Transformation, Neoplastic; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 8; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p27; gp100 Melanoma Antigen; GTP-Binding Protein alpha Subunits; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Mutation; Nevus, Pigmented; Polymerase Chain Reaction; Proto-Oncogene Proteins B-raf; Retrospective Studies; Uveal Neoplasms

Melanocytic nevus rests in lymph nodes are a known diagnostic challenge, especially in patients with a history of melanoma. Reticulin and NM23 have been studied in this context. The pattern of reticulin staining in melanomas surrounds groups/nests of melanocytes but individual cells in benign nevi. NM23, a metastasis-suppressor gene, has an association with metastatic potential in melanomas and some carcinomas. Twenty-eight cases (14 cases of metastatic melanoma to lymph nodes and 14 cases of lymph node nevus rests, all confirmed with Melan-A staining) were stained with reticulin and NM23. The pattern of reticulin staining was reported as surrounding groups if staining was noted in approximately 5-10 melanocytes in greater than 50% of the lesion but was otherwise reported as surrounding individual melanocytes. Cytoplasmic staining was considered to represent reactivity for NM23. Reticulin staining around groups of melanocytes was identified in all 14 cases of metastatic melanoma. Regarding nodal nevus rest cases, 12 of 14 cases (86%) demonstrated staining around individual melanocytes, whereas in 2 cases, reticulin surrounded melanocytic groups. NM23 staining was equivocal in all cases. Reticulin staining reliably invests groups of melanocytes in cases of metastatic melanoma, whereas in nodal nevus rests, it predominantly surrounds individual melanocytes. NM23 demonstrated no discriminatory value in this analysis. In cases in which a collection of melanocytes is present within a lymph node, reticulin deposition around individual melanocytes supports a diagnosis of lymph nodal nevus rest.

Topics: Aged; Biomarkers, Tumor; Biopsy; Female; Humans; Immunohistochemistry; Lymph Nodes; Lymphatic Metastasis; Male; MART-1 Antigen; Melanocytes; Melanoma; Nevus, Pigmented; NM23 Nucleoside Diphosphate Kinases; Reticulin; Skin Neoplasms; United States

Topics: Adolescent; Biomarkers, Tumor; Biopsy; Cell Transformation, Neoplastic; Conjunctival Neoplasms; gp100 Melanoma Antigen; Humans; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Nevus, Pigmented; S100 Proteins

Previous studies have reported that repeated solar and artificial UVB (280-320 nm) and UVA (320-400 nm) exposures can modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes in AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least three AMN on the trunk were enrolled in the present study and randomized into two groups to receive equally effective doses of narrow-band (NB)-UVB or UVA1. Three exposures per week were delivered for a total of 4 weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and underwent histological and immunohistochemical assessment of melanocyte/melanogenesis-related proteins (MART-1, tyrosinase, HMB-45), cell cycle activation markers (Ki-67, topoisomerase IIalpha, p53, Cdk2) and transcription factors (microphthalmia-associated transcription factor, STAT3). Nevi that were exposed to NB-UVB or UVA1 also showed statistically significant increase in size and changes in their dermoscopic features, including overall darkening, increased pigment network expression, formation of branched streaks, and increased number and size of brown globules and dots. AMN that had been covered with opaque tape or sunscreen did not show changes in size or dermoscopic features following UVA1 or NB-UVB exposure. Histological and immunohistochemical analysis did not show any significant change in exposed AMN in comparison with AMN shielded with an opaque adhesive tape or covered with the sunscreen.

Topics: Adult; Aged; Antigens, Neoplasm; Cyclin-Dependent Kinase 2; Dermoscopy; DNA Topoisomerases, Type II; DNA-Binding Proteins; Female; gp100 Melanoma Antigen; Histological Techniques; Humans; Immunohistochemistry; Ki-67 Antigen; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Middle Aged; Monophenol Monooxygenase; Nevus, Pigmented; Skin; STAT3 Transcription Factor; Tumor Suppressor Protein p53; Ultraviolet Rays

The aim of this study was to assess the importance of immunohistochemical markers in the diagnosis of pigmented conjunctival lesions. Due to the difficulty of making an exact clinical diagnosis, the suspicion of malignancy requires the removal of the lesion and performing a histopathology study in which immunohistochemical markers may help to determine the nature of the lesion.. A case is presented of a 25 year-old woman with a pigmented lesion in the caruncle. It appeared recently and was growing fast with increasing pigmentation. Due to a suspicion of malignancy, the total lesion was removed. The microscopic study revealed cellular alterations which suggested malignancy. However, after carrying out immunohistochemical markers the diagnosis was conjunctival compound nevus.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Conjunctival Neoplasms; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Nevus, Pigmented; Young Adult

Neurotized melanocytic nevi and neurofibromas are common, benign cutaneous neoplasms. Usually they are histologically distinct from each other; however, neurotized melanocytic nevi and neurofibromas can be clinically and histologically similar.. To determine whether Melan-A (MART-1) immunohistochemical stain is sufficient to differentiate neurotized melanocytic nevi from neurofibromas.. Forty-nine consecutive specimens of melanocytic nevi with neurotization and 49 specimens of neurofibromas were selected. We used antibodies against Melan-A, S100, and neurofilament protein.. All of the melanocytic nevi showed Melan-A staining within the neurotized areas, with most of the areas staining strongly positive, whereas all the neurofibromas were completely absent of Melan-A stain. All of the nevi, including the neurotized areas, stained strongly and diffusely for S100, whereas all the neurofibromas showed a distinctive, sharp, wavy pattern of S100 staining. Neurofilament protein showed scattered staining of both melanocytic nevi and neurofibromas.. Our data indicate that Melan-A immunohistochemical staining is helpful in differentiating neurotized melanocytic nevi from neurofibromas when distinction on histomorphology alone is difficult.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Male; MART-1 Antigen; Middle Aged; Neurofibroma; Nevus, Pigmented; Skin Neoplasms

A 7-year-old Caucasian girl presented with a pigmented lesion on the left bulbar conjunctiva that increased in size from 1 mm to 4 mm over a 12-month period. She underwent excision biopsy and reconstruction of the ocular surface with amniotic membrane graft. Histopathology showed the naevus was composed of somewhat swollen naevus cells with clear cytoplasm and central nucleus. These vacuolated naevus cells were approximately 40 µm in diameter. Over 90% of the cells in the naevus were composed of these swollen cells. Immunohistochemical staining was positive for S100 and Melan-A. This case illustrates that balloon cells may be observed in conjunctival naevi at a previously unreported pre-pubescent age. Awareness of ballon cell naevus is important to avoid clinical and histological pitfalls in diagnosis.

Topics: Biomarkers, Tumor; Child; Conjunctival Neoplasms; Female; Humans; MART-1 Antigen; Melanocytes; Nevus, Pigmented; Ophthalmologic Surgical Procedures; S100 Proteins

To evaluate the role of immunohistochemical methods in the diagnosis of benign and malignant conjunctival melanocytic proliferations.. Retrospective immunohistopathologic study.. Paraffin-embedded tissue sections from 20 conjunctival nevi and 15 invasive melanomas were immunoreacted with antibodies against cellular antigens S-100 protein, MART-1, HMB-45, CD-45, and Ki-67 nuclear proliferation protein.. All nevi immunostained moderately to strongly for S-100 protein and MART-1. Results for HMB-45 were negative in the middle and lower subepithelial portions of 18 of 20 lesions; it was usually only weakly positive within the superficial junctional zone. Only 1 melanoma did not stain positively for S-100; MART-1 and HMB-45 were positive in all lesions at some level of intensity. Ki-67 positivity was restricted to the junctional zone of nevi and was diffuse in melanomas. The mean Ki-67 proliferation indices were 1.89% for the nevi and 17.3% for the melanomas. CD-45 can help to highlight lymphocytes that immunostain with Ki-67. Melanomas in situ and atypical primary acquired melanoses had more than twice the Ki-67 proliferation counts of intraepithelial junctional nevocytes (P < .001) and more intense HMB-45 cytoplasmic staining than junctional zone nevocytes.. S-100 and MART-1 were not useful in separating benign from malignant lesions. Results for nevus cells beneath the junctional zone were overwhelmingly negative for HMB-45 and Ki-67. Two nevi and all melanomatous nodules were positive for HMB-45 (P < .001). A higher Ki-67 proliferation index convincingly separated melanomas from nevi (P < .001). Immunostaining for HMB-45 and Ki-67 are valuable adjuncts to careful histopathologic evaluation in assessing benign and malignant conjunctival melanocytic tumors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Child; Conjunctival Neoplasms; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Leukocyte Common Antigens; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Nevus, Pigmented; Retrospective Studies; S100 Proteins; Young Adult

Recent studies indicate that WT1 and Bcl2 protein are detected in melanocytic lesions of the skin. We examined, for the first time, WT1 and Bcl2 expression in a variety of conjunctival melanocytic lesions to evaluate their diagnostic utility compared with other melanocytic markers.. Protein expression and localization of WT1 and Bcl2 were studied by means of immunolabeling and semiquantification in 123 conjunctival melanocytic lesions (71 benign nevi, 21 atypical nevi, 11 primary acquired melanosis, and 20 malignant melanomas). Ancillary immunohistochemical studies were performed with Bcl2, S100, HMB45, and Melan A antibodies.. WT1 showed a graded increase in expression in lesions with increasing atypia. Higher mean numbers of WT1-positive cells correlated with increasing atypia in melanocytes. In all cases, Bcl2 expression was positive and more robust than was S100, HMB45, or Melan A expression. WT1 and HMB45 frequently showed diffuse and strong staining in atypical nevi, primary acquired melanosis with atypia, and malignant melanomas compared with benign lesions.. Bcl2 is a highly sensitive immunohistochemical marker for melanocytic tumors of the conjunctiva; HMB45 and WT1 staining distinguishes benign from malignant lesions.. Our results show that HMB45 and WT1 immunolabeling is helpful in the evaluation of conjunctival melanocytic lesions. Accordingly, we recommend the development of an immunohistochemical panel to classify these lesions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Child; Child, Preschool; Conjunctival Diseases; Conjunctival Neoplasms; Dysplastic Nevus Syndrome; Female; Humans; Immunoenzyme Techniques; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Melanosis; Middle Aged; Neoplasm Proteins; Nevus, Pigmented; Proto-Oncogene Proteins c-bcl-2; S100 Proteins; WT1 Proteins; Young Adult

To evaluate with immunohistochemical methods 5 atypical melanocytic conjunctival lesions.. This was a retrospective clinicoimmunopathologic study. Routine histochemical staining was performed with multiparametric immunohistochemical analysis with monoclonal antibodies immunoreacted on paraffin sections to identify the following cell antigens: S-100, MART-1, HMB-45, CD45, CD68, CD1a, lysozyme, and Ki-67 (nuclear proliferation protein).. A unique granular cell nevus contained periodic acid-Schiff-positive, diastase-resistant granules and immunoreacted with monoclonal antibodies against S-100 protein and melanocytic-associated antigens MART-1 and HMB-45. Results for CD45, CD1a, CD68, and lysozyme immunostaining of the granular cells were negative. Two epithelioid cell (clonal or inverted) nevi exhibited an identical immunohistochemical profile. Only the balloon cell nevus was MART-1-positive and HMB-45-negative. The granular cell and blue nevi immunoreacted negligibly with Ki-67 (approximately 1% of cells).. S100 and MART-1 reliably immunostained all nevocytic morphologic variants. HMB-45 immunoreactivity of the granular, epithelioid/clonal, and blue nevi did not indicate a more active or proliferative lesion but instead suggested abnormal melanogenesis. Ki-67 was the most valuable immunohistochemical adjunct to morphology for the diagnosis of these benign variant conjunctival nevi, because melanomas display a much higher proliferation index (>10% nuclear positivity among all cells counted) than the current nevi (approximately 1%).

Topics: Adult; Antigens, CD; Antigens, Neoplasm; Biomarkers, Tumor; Conjunctival Neoplasms; Female; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Muramidase; Neoplasm Proteins; Nevus, Blue; Nevus, Pigmented; Retrospective Studies; S100 Proteins; Young Adult

Unlike in common melanocytic naevi, an acquired leukoderma (halo) surrounding a congenital melanocytic naevus is a rare phenomenon. A 6-year-old boy developed a depigmentation around a congenital melanocytic naevus on the right thigh. Simultaneously, segmental vitiligo appeared on the thigh, lower abdomen and buttock of the same side with sharp midline demarcation. Examination for associated autoimmune diseases proved negative. The simultaneous occurrence of a halo phenomenon around a congenital melanocytic naevus and segmental vitiligo, as well as identical histological and immunohistological findings in both pigmented lesions, suggest shared immunological mechanisms.

Topics: Antigens, Neoplasm; Child; Dermis; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Neoplasm Proteins; Nevus, Pigmented; Skin Neoplasms; Skin Pigmentation; T-Lymphocytes, Cytotoxic; Vitiligo

Smooth muscle hamartoma (SMH) is a rare benign congenital or acquired lesion sometimes associated with Becker's nevus (Becker's melanosis). We report an unusual lesion with combined features of SMH and melanocytic nevus. The patient is a 49-year-old male with a history of a changing 'mole' on the left upper back. Clinical examination showed a solitary 1.2-cm nodule with central gray pigmentation. Histological examination showed a relatively well-circumscribed intradermal lesion. The superficial portion of the lesion consisted of melanocytes with nevoid morphology. The melanocytes had congenital pattern of distribution. Lesional melanocytes acquired a spindled morphology in the deeper dermis. The base of the lesion consisted of intersecting smooth muscle fascicles focally admixed with spindled melanocytes. The melanocytic component strongly expressed melanoma antigen recognized by T-cells-1 (MART-1) and HMB-45. The smooth muscle component was strongly positive for smooth muscle actin and h-caldesmon. Neither components showed significant cytological atypia or mitotic activity. Unlike a recently reported case of SMH combined with a melanocytic nevus and basal cell carcinoma, the current lesion did not occur in association with a Becker's nevus.

Topics: Actins; Antigens, Neoplasm; Calmodulin-Binding Proteins; Hamartoma; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Muscle, Smooth; Neoplasm Proteins; Nevus, Pigmented

Becker nevus (BN) is a unilateral, hairy, pigmented cutaneous hamartoma that frequently appears in adolescence. Several features of BN suggest that increased androgen sensitivity plays a role in its pathogenesis. There have been only a few studies of histopathologic and immunohistochemical characteristics of BN, and the etiopathogenesis has not been fully established.. Two-millimeter punch biopsies were taken from lesional and perilesional normal skin of 30 patients diagnosed as having BN. Fifteen skin samples each of lentigo and café au lait spots were used as controls. The sections were stained with hematoxylin-eosin, Fontana-Masson, antibodies to NKI/beteb, MART-1 (Melanoma Antigen Recognized by T cells), S-100 protein and androgen receptor (AR).. Histopathologic features of BN showed frequent acanthosis, papillomatosis, keratotic plugging, irregular rete ridge elongation and flattening in the epidermis. Especially, the shape of the rete ridges in BN had a relatively characteristic appearance, which was the fusion of more than two adjacent rete ridges. Melanocyte counts were significantly increased in BN skin. The extent of AR expression was significantly higher in the epidermis of BN.. Our study indicates that there may be an association between AR and BN, but additional studies will be required to evaluate this further.

Topics: Adolescent; Adult; Antigens, Neoplasm; Child; Child, Preschool; Female; Humans; Image Interpretation, Computer-Assisted; Immunohistochemistry; Infant; Male; MART-1 Antigen; Melanins; Melanocytes; Neoplasm Proteins; Nevus, Pigmented; Receptors, Androgen; S100 Proteins; Skin Neoplasms

Balloon cell nevi and balloon cell changes in nevi have rarely been reported in the literature. We describe a compound nevus showing focal balloon cell changes in a 20-year-old man. The melanocytic nature of the balloon cells is confirmed by an immunohistochemical study. The findings are compared with those in balloon cell melanomas.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; MART-1 Antigen; Melanocytes; Neoplasm Proteins; Nevus, Pigmented; S100 Proteins; Skin Neoplasms

A brown cornea is relatively rare. We report a case of progressive brown corneal pigmentation in a patient with a primary acquired melanosis of the conjunctiva. Later the patient developed an iris melanoma.. Case report with clinico-pathological correlation and discussion of possible mechanisms of particle clearance of the cornea.. A 36-year-old female developed a corneal stromal pigmentation adjacent to a pigmented conjunctival lesion of the left eye. The corneal pigmentation had progressed through 8 years. The conjunctival lesion was surgically removed, and proved histopathologically to be a compound nevus with slight atypia and an acquired melanosis. Despite surgery the corneal pigmentation increased, and visual acuity dropped in the diseased eye. A perforating keratoplasty was performed, and two small pigmented iris nodules were now noted. Three years after grafting, growth of the two iris tumours was obvious. In addition, pigmentation of the trabecular meshwork and large, pigmented endothelial precipitates were observed. The corneal pigmentation also increased. The eye was enucleated. Histopathologic evaluation demonstrated a marked accumulation of melanophages on the endothelium of the graft. The host cornea contained pigmented cells in the mid-stroma. The iris contained two melanomas.. The brown pigmentation of the cornea was due to pigment granules from the iris tumours liberated to the anterior chamber. The pigment was transported into the cornea through the endothelium and accumulated in melanophages between corneal lamellas. The pigment subsequently cleared via the corneal limbus in a process resembling clearance of corneal haemochromatosis.

Topics: Adult; Antigens, Neoplasm; Conjunctival Neoplasms; Corneal Diseases; Corneal Stroma; Eye Enucleation; Female; Humans; Iris Neoplasms; Keratoplasty, Penetrating; MART-1 Antigen; Melanocytes; Melanoma; Melanoma-Specific Antigens; Melanosis; Neoplasm Proteins; Nevus, Pigmented; S100 Proteins

The balloon cell nevus is an uncommon variant of melanocytic nevi in which the majority of the proliferation consists of cells demonstrating peculiarly large clear, foamy, or finely vacuolated cytoplasm. The vacuolated cells represent altered nevus cells and upon immunoperoxidase evaluation react positively with several melanocytic markers. Complete excision results in cure. This report describes the second balloon cell nevus of the oral mucosa documented in the English-language literature.

Topics: Adult; Antigens, Neoplasm; Female; Humans; Immunoenzyme Techniques; MART-1 Antigen; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; Nevus, Pigmented; S100 Proteins

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; Neoplasms, Multiple Primary; Nevus, Pigmented; S100 Proteins; Skin Neoplasms

Pigment synthesizing melanoma (so-called animal type melanoma) (PSM) is a rare histopathological variant of melanoma so termed because of prominent melanin production and its similarity to a variant of melanoma seen in grey horses. The aim of this study was to report the clinicopathological characteristics of 14 cases of animal type melanoma.. Six patients were female and eight were male with ages ranging from 5 to 52 years (mean 31 years, median 39 years). The head and neck represented the most common site. The clinical diagnosis was of melanoma in seven cases, blue naevus in three cases, benign naevus in three cases and a pigmented basal cell carcinoma in one case. The histological diagnosis of PSM was predicated on the basis of an asymmetrical, predominantly intradermal tumour formed of deeply pigmented, round or short, spindle-shaped dendritic melanocytes with some degree of hyperchromatism and a single nucleolus. Cytological atypia was always present but was not pronounced. A prominent population of macrophages was invariably present. Four tumours were compound and 10 tumours were predominantly intradermal. The mitotic count was usually low, ranging from 1 to 5 per 10 high-power fields (mean 2). Perineural and lymphovascular invasion was not seen. The Breslow thickness ranged from 1.1 to 7.5 mm (mean 3.3 mm). Follow-up was available in 13 patients. The median follow-up period was 5 years. Six patients had no recurrence, three had local recurrence in the form of satellite nodules adjacent to the scar, four had spread to the regional lymph nodes and one patient had distant metastases to the liver. There were no deaths.. This study demonstrates that PSM is a distinctive, possible low-grade variant of melanoma usually lacking the histological features predictive of aggressive behaviour seen in ordinary melanoma. It should be managed in the same way as other melanomas with wide local excision.

Topics: Adolescent; Adult; Antigens, Neoplasm; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Neoplasm Recurrence, Local; Nevus, Blue; Nevus, Pigmented; S100 Proteins; Skin Neoplasms

Topics: Adolescent; Antigens, Neoplasm; Diagnosis, Differential; Epithelioid Cells; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Melanoma; Neoplasm Proteins; Nevus, Blue; Nevus, Pigmented; S100 Proteins; Sentinel Lymph Node Biopsy; Shoulder; Skin Neoplasms

Unusual or atypical melanocytic nevi can be confused with malignant melanoma. Two patients are presented here with a rare variant of melanocytic nevus. Both were men. One was 39 years old and sought medical attention after trauma of a "congenital mole". The other was 24 years old and presented with a history of a slowly growing lesion, which had been known since childhood. In both patients, the lesion occurred on the buttock. They were dermal and superficial subcutaneous nodules measuring 1.5 and 2.3 cm in greatest dimension, respectively. The tumors were composed of densely cellular fascicles of melanocytes arranged in a lobulated growth pattern. Rare nests of small epithelioid melanocytes were also seen. No melanin pigment was seen on hematoxylin and eosin-stained sections. Focal minimal pigment was noted by Fontana-Masson stain in one case. Involvement of numerous peripheral nerve trunks by fusiform melanocytes was a prominent feature. Rare mitotic figures were seen in melanocytes [1-2 mitoses per 50 high-power fields (HPF)]. The MIB-1 labeling index was low (less than 5% of the lesional cell population was immunopositive). Both tumors were excised with negative surgical margins. One patient underwent sentinel lymph node biopsy because there was controversy regarding the biologic potential of the lesion. No melanocytic tumor deposits were found in the lymph nodes. On clinical follow up of 11 years and 18 months after complete excision, both patients are alive and well with no evidence of recurrence. We regard these lesions as congenital monophasic and pauci-melanotic variants of cellular blue nevus. The nevi are presented here to enhance our knowledge of the morphologic spectrum of melanocytic tumors and to help avoid confusion with malignant melanoma.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Cell Division; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Male; MART-1 Antigen; Neoplasm Proteins; Nevus, Blue; Nevus, Pigmented; S100 Proteins; Skin Neoplasms

Two cases of compound melanocytic nevi with granular cell changes were studied. Histological examination revealed compound melanocytic nevi with a portion of the dermal component exhibiting a sheet like proliferation of nevoid cells with granular cytoplasm. Immunohistochemically, both populations of cells stained positive for S-100 and Melan-A. However, HMB-45 was positive only for the nevus cells with granular cytoplasm. We believe this represents granular cytoplasmic changes of nevus cells and does not denote malignant transformation.

Topics: Adolescent; Antigens, Neoplasm; Biomarkers, Tumor; Female; Granular Cell Tumor; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; Nevus, Pigmented; S100 Proteins; Skin Neoplasms

Biphenotypical nevi or nevi with phenotypical heterogeneity consist of phenotypically different cell populations in a pattern other than that observed in classical combined nevi or in various maturation stages of banal nevocellular nevi. Besides several well-known entities such as deep penetrating nevi and plexiform spindle cell nevi, this category of pigment cell lesions also harbors fewer delineated lesions such as nevi with atypical dermal nodules (N-ADN) and nevi with a focal atypical epithelioid cell component (N-FAECC). Their worrisome histology may result in a wrong diagnosis of malignancy. In order to discriminate them from malignant melanoma and to shed light on their histogenesis, we analyzed the immunophenotypical profile of 33 N-FAECC, 6 N-ADN, and 10 giant congenital nevi removed shortly after birth, using antibodies directed to S100 protein, gp100, tyrosinase, NKI-C3, Melan-A and Mib-1. In N-FAECC and N-ADN, the large polygonal cells expressed gp100, S100 protein and Melan-A, and reacted with monoclonal antibody NKI-C3. In addition, there was intense tyrosinase expression but no Mib-1 immunoreactivity. Unexpectedly, we observed similar single or clustered, large epithelioid cells in three out of ten giant congenital nevi; these cells showed a similar phenotype to those observed in N-ADN and N-FAECC. Our histological and immunohistochemical data suggest that N-FAECC and N-ADN may reflect different stages of the same disorder. Moreover, their resemblance to the large polygonal cells in congenital nevi may suggest that the histogenesis of N-ADN and N-FAECC may be related to the persistence and expansion of large epithelioid cells in congenital nevi shortly after birth.

Topics: Antigens, Neoplasm; Diagnosis, Differential; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Infant, Newborn; MART-1 Antigen; Membrane Glycoproteins; Monophenol Monooxygenase; Neoplasm Proteins; Nevus; Nevus, Epithelioid and Spindle Cell; Nevus, Pigmented; Phenotype; S100 Proteins; Skin Neoplasms

Features of peripheral nerve sheath differentiation such as neuroid cords, nerve corpuscles, fascicle-like structures, and, exceptionally, palisading have been reported in melanocytic nevi. We report an intradermal melanocytic nevus with prominent Verocay-like bodies. The upper portion of the neoplasm was composed of typical round intradermal nevus cells, many of which were pigmented. Within the deeper portion, there was a nonpigmented spindle cell proliferation with prominent Verocay bodies, simulating a neurilemmoma. Typical nevus nests merged with neurilemmoma-like areas. The entire lesion stained positively for S-100 and Mart-1 proteins and negatively for HMB-45 stain. Diffuse Mart-1 positivity excluded a collision of a melanocytic lesion with a neurilemmoma. The histopathologic features of this nevus further support a close relation between nevus cells and Schwann cells.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Inclusion Bodies; Male; MART-1 Antigen; Neoplasm Proteins; Nevus, Pigmented; S100 Proteins; Schwann Cells; Skin Neoplasms

Recurrent melanocytic lesions may histologically resemble malignant melanoma.. We evaluated the original nevi (ON) and recurrent nevi (RN) of 15 patients by routine histology and immunohistochemistry (IHC), examining expression of S-100 protein, gp100 (with HMB-45), MART-1, tyrosinase, and the Ki-67 proliferation marker.. Compared with ON, RN had a dermal scar, a significantly greater number of melanophages, and a greater extent of cellular atypia including prominent nucleoli and larger cell size. Architecturally, RN showed significantly less symmetry than ON; however, the percentage of junctional cohesive nests, the presence of suprabasal spread, and the degree of confluence were similar between ON and RN. Both ON and RN showed a decrease in expression of gp100 and tyrosinase with increasing depth ("maturation gradient") and low proliferative activity in both the junctional (4.6% for ON vs. 4.13% for RN) and the dermal components (0.93% for ON vs. 1.45% for RN).. RN exhibit a dermal scar, a greater number of melanophages, cytologic atypia, and asymmetry than ON, features that may raise concern about the possibility of malignant melanoma. However, the area with the irregular architectural pattern is restricted to the epidermis and dermis immediately above the scar. In addition, IHC helps to distinguish RN from malignant melanoma; specifically, RN demonstrate an immunohistochemical "maturation pattern" (with HMB-45 and anti-tyrosinase) and a low proliferative index (with Ki-67).

Topics: Adolescent; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Child; Female; Fluorescent Antibody Technique, Indirect; gp100 Melanoma Antigen; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Male; MART-1 Antigen; Melanocytes; Melanoma-Specific Antigens; Membrane Glycoproteins; Monophenol Monooxygenase; Neoplasm Proteins; Neoplasm Recurrence, Local; Nevus, Pigmented; S100 Proteins; Skin Neoplasms

The histopathologic differential diagnosis of Spitz nevus (SN) from malignant melanoma (MM) may be difficult.. We attempted to elucidate the pattern of expression of a newly recognized melanocyte-specific melanosomal protein MART-1 in routinely processed specimens of SNs, MMs, and ordinary melanocytic nevi (MNs) and to see whether it can help to differentiate between them.. Twenty SN, 22 MM, and 27 ordinary MN were immunostained with anti-MART-1 monoclonal antibody (clone A103).. All SNs, MNs, and MMs demonstrated cytoplasmic staining for MART-1 in some of their tumor cells, of which 17 of 20 (85%) and 24 of 27 (89%) of SN and MN, respectively, demonstrated positive stainings in more than half of their tumor cells, as compared with only 10 of 22 (45%) of the MM (P <.05). The majority of lesions in all 3 types of tumors showed a homogeneous mode of staining, although MM tended to show a more heterogeneous pattern. A consistent pattern of stratification of staining with progressive descent into the dermis was not demonstrated in these tumors.. MART-1 does not differentiate between SN, MM, and ordinary MN in a consistent pattern, but it may be used as a marker for these tumors.

Topics: Antigens, Neoplasm; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma; Neoplasm Proteins; Nevus, Epithelioid and Spindle Cell; Nevus, Pigmented; Skin Neoplasms

Histiocytic tumors can be confused with melanocytic nevi and malignant melanoma and vice versa. To explore the use of immunohistochemistry for this diagnostic problem, we examined the expression of S-100 protein, gp100 (the antigen recognized by HMB-45), tyrosinase (T311), Melan-A (A103), Factor XIIIa (FXIIIa), and CD68 in 10 juvenile xanthogranulomas (JXGs), five epithelioid histiocytomas (EHs), and 15 melanocytic nevi composed of large epithelioid cells. All epithelioid melanocytic nevi were immunoreactive for Melan-A, tyrosinase, and S-100 protein in most melanocytes. Four nevi were completely negative with HMB-45. Nine nevi had only a minor HMB-45-positive component in the superficial dermis. Two nevi were diffusely HMB-45-positive. Melanocytes in all nevi were completely negative for FXIIIa. Thirteen nevi were completely negative for CD68. Two nevi contained rare cells with weak staining for CD68. All 15 histiocytic proliferations were completely negative for Melan-A, tyrosinase, and gp100. They lacked expression of S-100 protein or had at most 10% immunopositive cells. In JXGs, most cells were strongly reactive for CD68, although only a few were positive for FXIIIa. In EHs, 40% to 60% of cells were immunoreactive for FXIIIa, and only 20% to 30% were positive for CD68. Our results demonstrate that Melan-A and tyrosinase are sensitive and specific markers to distinguish epithelioid melanocytic nevi from epithelioid histiocytic tumors.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Histiocytoma, Benign Fibrous; Humans; MART-1 Antigen; Melanoma-Specific Antigens; Monophenol Monooxygenase; Neoplasm Proteins; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Xanthogranuloma, Juvenile

We stained benign melanocytic nevi and malignant melanoma with antibodies to melanoma antigen recognized by T cells (Mart-1) to determine if this was useful in differentiating benign from malignant melanocytic neoplasms. Forty-five primary malignant melanomas and 71 benign melanocytic nevi were stained with antibodies to Mart-1. Two cases of malignant melanoma metastatic to lymph node and three cutaneous metastases of malignant melanoma were also stained. The degree of staining was graded into diffuse positive staining, focal positive staining, and negative staining. Thirty-six of 45 primary malignant melanomas stained diffusely positive with antibodies to Mart-1. This included three of five desmoplastic malignant melanomas that showed positive staining. Four melanomas showed faint or focal positive staining. One of two metastases to lymph node showed strong positive staining and one showed no staining. All three cutaneous metastases showed diffuse positive staining. Sixty-one of 71 melanocytic nevi showed no staining or faint staining with antibodies to Mart-1. Ten of 71 melanocytic nevi showed strong positive staining. The majority of these were congenital nevi. Staining with antibodies to Mart-1 antigen was a useful marker of malignant melanoma. However, staining may also be seen in benign melanocytic neoplasms. The presence or absence of staining for Mart-1 antigen cannot be used to differentiate benign melanocytic nevi from malignant melanocytic tumors.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Lymphatic Metastasis; MART-1 Antigen; Melanoma; Neoplasm Proteins; Nevus, Pigmented; Skin Neoplasms

Typically, melanocytic nevi "mature" (i.e., exhibit a morphologic shift to smaller or spindle cells with progressive depth in the dermis). In contrast, most malignant melanomas (conventional MMs) lack maturation, and are composed of large pleomorphic cells throughout. The authors describe a series of melanomas with paradoxical maturation mimicking the pattern of nevi. Seventeen primary invasive melanomas with paradoxical maturation (IMPs), two epidermotropic metastatic melanomas with maturation (EMMMs), 13 compound nevi (CN), and 14 conventional MMs without apparent maturation were analyzed by histologic, cytomorphometric, and immunohistochemical techniques. With increasing dermal depth, both CN and IMPs had smaller nuclear and cellular areas, and decreased expression of Ki-67, glycoprotein (gp)100 (with HMB-45), and tyrosinase. IMPs had significant differences from conventional MMs; namely, smaller nuclear and cytoplasmic areas (deep), and decreased expression of Ki-67 (superficial and deep), gp100 (deep), and tyrosinase (deep). IMPs also had notable differences from CN: namely, larger nuclear and cellular areas, more confluence, more mitotic figures, increased Ki-67 and gp100 expression in both the superficial and deep portions, and more melanin (deep). The two EMMMs exhibited histologic and immunohistochemical features similar to the primary IMPs. IMP, because of its mimicry of nevus, can present a diagnostic hazard. The authors propose histologic, morphometric, and immunohistochemical criteria that facilitate recognition and accurate diagnosis of this unusual variant of melanoma.

Topics: Adolescent; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Cell Differentiation; Child; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Ki-67 Antigen; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Membrane Glycoproteins; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; Nevus, Intradermal; Nevus, Pigmented; Skin Neoplasms

The Melan-A (MART1) gene encodes an antigen recognized by cytotoxic T cells. Although its expression in metastatic melanoma has been documented in the literature by several investigators, little is known about its distribution in primary melanomas and benign melanocytic nevi. In this study, we evaluated Melan-A expression immunohistochemically on sections from paraffin-embedded material of 50 benign nevi and 40 primary cutaneous melanomas using the monoclonal antibody A103. To evaluate a potential role of A103 in the differential diagnosis of melanocytic from nonmelanocytic tumors, we also analyzed a number of benign and malignant peripheral nerve sheath tumors, fibrohistiocytic tumors, and leiomyosarcomas. Immunoreactivity with A103 was present in all "nonneurotized" nevi and in all nondesmoplastic primary melanomas, both in the intraepidermal and the dermal component. Only two nevi that underwent prominent neurotization showed no staining with A103. Although all melanomas with epithelioid cells tended to be strongly positive with A103, only 4 of 13 spindle cell and desmoplastic melanomas (all positive with anti-S-100 and negative with HMB-45) were immunoreactive with A103 (two focally, two diffusely). None of the nonmelanocytic lesions expressed Melan-A. Our results confirm that Melan-A protein is broadly expressed in the majority of benign and malignant melanocytic lesions and suggest that A103 can be helpful diagnostically, not only for metastatic tumors, but also for primary skin lesions. Its use in distinguishing between melanocytic and peripheral nerve sheath tumors, however, is limited because of the low or absent expression of Melan-A in nevi that underwent neurotization and spindle cell and desmoplastic melanomas.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma; Neoplasm Proteins; Nevus, Pigmented; Skin Neoplasms

Monoclonal antibody (MAb) A103 specifically detects Melan A/MART-1 protein expression. Melan A/MART-1-derived peptides are recognized by CD8+ T-cells and are used in immunotherapy. We examined formalin-fixed paraffin-embedded tissue from 57 melanomas (34 primary, 23 metastatic) and 39 control cases (junctional, dermal, compound, Spitz, Reed and balloon-cell naevi) using the alkaline phosphatase and anti-alkaline phosphatase immunochemical method after antigen retrieval. Immunoreactivity was rated as low, medium or high, and staining pattern as homogeneous or heterogeneous. Staining with MAb A103 showed a sensitivity of 88% for melanoma, with a very high specificity for melanocytic cells. Immunopositivity decreased along with clinical stage, with stage I showing 100%, stage II 88%, stage III 90% and stage IV 75% immunoreactivity. Staining changed from an exclusively homogeneous pattern in the early clinical stages to a more heterogeneous pattern in the later stages. Melanocytic control tissues consisting of naevi of different subtypes all showed weak to moderate homogeneous immunoreactivity, with polarity towards the epidermis. Analysis of short-term melanoma cell cultures using reverse transcription-polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA) demonstrated mRNA expression in only one third of the originally immunopositive tumours, suggesting rapid mRNA expression loss in culture. MAb A103 allows the detection of melanoma-associated Melan A/MART-1 protein expression in routine archival tissue and thus enables the profiling of melanomas suited for immunotherapy approaches involving Melan A/MART-1 derived epitopes.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Enzyme-Linked Immunosorbent Assay; Fixatives; Formaldehyde; Humans; Immunoenzyme Techniques; MART-1 Antigen; Melanoma; Neoplasm Proteins; Neoplasm Staging; Nevus, Pigmented; Paraffin Embedding; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Skin Neoplasms; Tissue Fixation; Tumor Cells, Cultured

Twenty-eight primary and 29 metastatic melanoma lesions and 18 pigmented nevi lesions were analyzed by using the immunoperoxidase reaction with anti-MART-1 and anti-gp100 monoclonal antibodies (mAbs). The MART-1 was expressed in 28, 29, and 18, and gp100 was expressed in 27, 28, and eight of these lesions, respectively. Intensity and percentage of stained cells with anti-MART-1 mAb were stronger and higher than those with anti-gp100 mAb. MART-1 was expressed homogeneously in primary melanoma and pigmented nevi, whereas it was heterogeneously expressed in metastatic melanoma lesions. The level of expression of MART-1 in primary melanoma lesions did not correlate with any clinicopathologic parameters. These results suggest that anti-MART-1 mAb is a useful tool for immunohistochemical analysis of melanocytic lesions and also is useful for patients' selection and monitoring of antigen-loss variants in clinical trials with the MART-1-based immunotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Female; gp100 Melanoma Antigen; HLA-A2 Antigen; Humans; Immunoenzyme Techniques; Male; MART-1 Antigen; Melanoma; Membrane Glycoproteins; Middle Aged; Neoplasm Metastasis; Neoplasm Proteins; Nevus, Pigmented