mart-1-antigen and Melanosis

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

Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma.. To report our experience of initial evaluation and follow-up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM).. We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining.. Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern.. In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non-invasive monitoring of foci of melanocytic hyperplasia.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Dermoscopy; Diagnosis, Differential; Female; Humans; MART-1 Antigen; Melanoma; Melanosis; Microscopy, Confocal; Middle Aged; Retrospective Studies; Skin; Vulvar Neoplasms

Treatment of mixed melasma remains challenging. Promising results have been achieved with low-fluence 1064-nm Q-switched Nd-YAG laser; however, multiple sessions are necessary with occurrence of complications especially in dark skin types. So, combination methods may be recommended.. To compare efficacy of Q-switched Nd-YAG laser alone or with modified Jessner's peel in mixed melasma in dark skin.. Nineteen patients with mixed melasma received 6 sessions of laser on left side of face and alternating laser and modified Jessner on right side. Evaluation was carried out clinically through modified melasma area and severity index at 1 month after last session. Using histopathological, immunohistochemical, and computerized morphometric analysis, objective evaluation of melanin particle surface area and MART-1-positive cells was performed for pre- and post-treated skin biopsies.. There was significant clinical improvement on both sides of face (P < .001), without significant difference (P > .05). At the sixth laser session on left side of face, ill-defined mottled hypopigmentation was observed in 21.05% of patients. Histopathologically, melanin particle surface area and number of MART-1-positive cells (total, epidermal, and dermal) were significantly decreased after two treatment modalities (P < .001), without significant difference in their reduction percentage between both sides of face (P > .05).. Low-fluence Q-switched Nd-YAG laser alone and with modified Jessner's peel are equally effective regimens for mixed melasma clinically, histopathologically, and immunohistochemically. However, combined method is preferred, especially in dark skin, for obtaining better cosmetic result with fewer side effects of multiple laser sessions and decreasing cost rate of laser.

Topics: Adult; Biopsy; Chemexfoliation; Combined Modality Therapy; Female; Humans; Hypopigmentation; Lasers, Solid-State; MART-1 Antigen; Melanosis; Middle Aged; Severity of Illness Index; Skin; Skin Pigmentation; Treatment Outcome

Tranexamic acid (TXA), a plasmin inhibitor, is an antifibrinolytic drug widely used to prevent and treat hemorrhage. We evaluated the effects of oral TXA clinically and immunohistopathologically in patients of refractory melasma. To evaluate the efficacy of oral TXA in patients with refractory melasma and correlate histopathological and immunohistochemical changes in pretreatment and post-treatment skin biopsies in patients willing to undergo biopsy. Thirty patients with refractory melasma were treated with oral TXA 500 mg twice daily along with a sunscreen and followed up. Modified MASI score (MMASI) and melasma quality of life (MELASQOL) were noted at baseline and after treatment. In patients willing to undergo skin biopsy, a 2 mm punch biopsy was obtained for histopathology and immunohistochemistry examination both before and after treatment with TXA. Clinical, histopathological, and immunohistochemical parameters were compared and correlated. Clinical improvement in melasma correlated in a perfect linear relationship with quality of life, decrease in epidermal pigmentation and decrease in Melan A staining on immunohistochemistry. Based on our observations, TXA can be said to have an inhibitory action on melanin synthesis and melanocyte proliferation. Future studies are required to further characterize the effects of TXA on the histopathology and immunohistochemistry of melasma, to standardize dosing schedule, duration of treatment and long term outcome, of which there are no definitive guidelines at present.

Topics: Administration, Oral; Adult; Antifibrinolytic Agents; Female; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanosis; Quality of Life; Retreatment; Severity of Illness Index; Sunscreening Agents; Tranexamic Acid

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

To study the clinicopathologic features and differential diagnosis of cutaneous regressing/regressed melanoma.. Histopathologic evaluation and immunohistochemical study by EnVision method were performed in 8 cases of cutaneous regressing/regressed melanoma. The clinical presentation, treatment and follow-up data were analyzed.. The age of the patients ranged from 40 to 69 years (mean 58 years). The male-to-female ratio was 3: 1. Tumors were located on the back (4 cases), sole of the foot (2 cases), ventral aspect of the toes (1 case), and the forearm (1 case). Clinically, 6 patients presented with progressive black mole of the skin, followed by subsequent focal hypopigmentation, even scarring. Two patients presented with multiple foci of dark-brown pigmentation. Microscopically, 3 cases were completely regressed malignant melanoma. Tumoral melanosis was found in 1 of 3 cases. The other 5 cases were melanoma with severe regression. The extent of regression ranged from 75% to 90%. The Breslow depth of the tumors ranged from 0.5 to 1.0 mm. Immunohistochemically, both metastatic and primary tumor cells were diffusely positive for S-100, HMB45 and Melan A, while melanophages were positive for CD68. Follow-up data were available in 8 patients, ranging from 8 to 27 months. Five patients were alive with no evidence of disease, 1 patient was alive with stable disease and 2 patients died of metastatic melanoma.. Correlation between clinical presentation and pathologic features is important for diagnosis of cutaneous regressing/regressed melanoma. Thin melanoma with extensive regression ( ≥ 75%) should not been regarded as low metastatic risk and wide excision combined with sentinel lymph node biopsy is recommended.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Back; Female; Follow-Up Studies; Foot; Humans; Lymphatic Metastasis; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Melanoma, Cutaneous Malignant; Melanosis; Middle Aged; S100 Proteins; Sentinel Lymph Node Biopsy; Skin Neoplasms; Toes; Treatment Outcome

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

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 authors investigated the expression of S100A1, S100A6, S100B, MelanA, and CEA in conjunctival naevi, primary acquired melanosis (PAM), conjunctival melanoma, and uveal melanoma in order to assess their potential usefulness in the pathological differential diagnosis of these entities.. Paraffin embedded sections of 18 conjunctival naevi, 14 PAM, 16 conjunctival melanomas, and 20 uveal melanomas were immunostained for S100A1, S100A6, S100B, MelanA, and CEA, and expression was scored semiquantitatively.. Expression of S100A1 differed significantly between conjunctival naevi and conjunctival melanoma, with percentages of positive cells of 30.6% and 71.4%, respectively. Conjunctival melanomas had high average scores for S100A1 and S100B (71.4%, 62.9%, respectively), while uveal melanomas also had high S100A1 but low S100B scores (88.5%, 18.5%, respectively). MelanA was highly variable; naevi and uveal melanoma had higher average scores than conjunctival melanoma. CEA was hardly detectable in all four groups.. S100A1 seems to be a possible candidate to differentiate conjunctival naevi from conjunctival melanoma. S100B seems to differentiate between uveal melanoma and conjunctival melanoma. However, the study size was small and therefore the data have to be confirmed by others.

Topics: Antigens, Neoplasm; Biomarkers; Carcinoembryonic Antigen; Cell Cycle Proteins; Conjunctival Diseases; Conjunctival Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma; Melanosis; Neoplasm Proteins; Nerve Growth Factors; Nevus; S100 Calcium Binding Protein A6; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Uveal Neoplasms

This paper describes the first documented case of mucoepidermoid carcinoma (MEC) with melanin pigmentation manifested in the palate. Histopathological sections showed a neoplasm composed of epidermoid, mucous-producing and intermediate cells. Numerous large cells contained dark pigmented materials. Fontana Masson staining revealed dendritic melanocytes and melanin granules. HMB-45, Melan A and S-100 protein were all positive for melanocytes. Histopathological examination was not typical for malignant melanoma; the lesion was diagnosed as a low-grade MEC with melanin pigmentation.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Dendritic Cells; Diagnosis, Differential; Female; Humans; Immunohistochemistry; MART-1 Antigen; Melanins; Melanocytes; Melanoma; Melanoma-Specific Antigens; Melanosis; Neoplasm Proteins; Palatal Neoplasms; S100 Proteins; Salivary Glands, Minor

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