BACKGROUND: Benign lichenoid keratosis (BLK) is a cutaneous lesion that can clinically mimic malignancy and may represent regression of a pre-existing lesion. BLK may show epidermal pseudo-nests prompting evaluation for a melanocytic lesion. False positivity of MART-1/Melan-A immunostaining in pseudonests has been showed; however, the value of SRY-related HMG-box 10 (SOX10) staining in BLK with features suspicious for a melanocytic proliferation has not been previously reported.
METHODS: Twenty-one cases of BLK from 2015 to 2020 were identified. Slides were reviewed and SOX10 immunohistochemistry was performed on each case. Subsequently, Melan-A immunohistochemical staining was performed on all cases.
RESULTS: In 10 cases (47.6%), unexpected SOX10 staining was seen in rare to numerous small, single cells in the epidermis above the basal cell layer. No malignancy was identified. Of the 10 cases, 8 (80%) showed suprabasal SOX10 staining did not show similar suprabasal Melan-A staining; 2 (20%) cases showed scattered suprabasal cells positive for Melan-A.
CONCLUSIONS: SOX10 immunostaining in BLK can highlight scattered cells in the epidermis (not easily noticeable on routine stain). Performing SOX10 immunostain alone on BLK can prompt a misdiagnosis of a melanocytic lesion and should be done with caution.

UNASSIGNED: To evaluate the efficacy and tolerability of needling/microneedling as an adjunct to NB-UVB phototherapy in the treatment of stable refractory patches of acral vitiligo, based upon clinical and immunohistochemical assessment of melanocyte count and distribution in response to needling/microneedling.
UNASSIGNED: Twenty patients with stable acral vitiligo (≥2 patches) were enrolled. One of the two index patches was randomized to receive needling or microneedling in conjunction with NB-UVB. Patients received phototherapy sessions 3 times weekly, while needling was carried out on biweekly basis for 6 months. Assessment was done clinically using point counting method, VESTA, and global patients\' satisfaction, and immunohistochemically by quantitative assessment of melanocyte count by Melan-A.
UNASSIGNED: No statistically significant difference was observed between NB-UVB monotherapy and either of the combined therapy regimens as regards the mean percentage change in vitiligo surface area (p = .451), mean change in absolute melanocyte count from baseline (p = .589), and mean VESTA (p = .916). Patches subjected to adjuvant microneedling/needling were afflicted by koebnerization in 50% and 20% of cases, respectively.
UNASSIGNED: Neither microneedling nor needling appear to confer an added therapeutic value to NB-UVB phototherapy in the treatment of stable acral vitiligo. Moreover, both carry the risk of koebnerization.

Adoptive cell transfer (ACT) of tumor-specific T lymphocytes represents a relevant therapeutic strategy to treat metastatic melanoma patients. Ideal T-cells should combine tumor specificity and reactivity with survival in vivo, while avoiding autoimmune side effects. Here we report results from a Phase I/II clinical trial (NCT02424916, performed between 2015 and 2018) in which 6 metastatic HLA-A2 melanoma patients received autologous antigen-specific T-cells produced from PBMC, after peptide stimulation in vitro, followed by sorting with HLA-peptide multimers and amplification. Each patient received a combination of Melan-A and MELOE-1 polyclonal specific T-cells, whose specificity and anti-tumor reactivity were checked prior to injection, with subcutaneous IL-2. Transferred T-cells were also characterized in terms of functional avidity, diversity and phenotype and their blood persistence was evaluated. An increase in specific T-cells was detected in the blood of all patients at day 1 and progressively disappeared from day 7 onwards. No serious adverse events occurred after this ACT. Clinically, five patients progressed and one patient experienced a partial response following therapy. Melan-A and MELOE-1 specific T-cells infused to this patient were diverse, of high avidity, with a high proportion of T lymphocytes co-expressing PD-1 and TIGIT but few other exhaustion markers. In conclusion, we demonstrated the feasibility and safety of ACT with multimer-sorted Melan-A and MELOE-1 specific T cells to metastatic melanoma patients. The clinical efficacy of such therapeutic strategy could be further enhanced by the selection of highly reactive T-cells, based on PD-1 and TIGIT co-expression, and a combination with ICI, such as anti-PD-1.

BACKGROUND: NB-UVB phototherapy is still an effective treatment in vitiligo but requires more than 1 year for its completion. Topical 5-flurouracil could improve the proliferation and migration of melanocytes. Laser-assisted dermabrasion results in stimulation of the inactive melanocytes present at the outer root sheath of the lower portion of the hair follicle, which migrates upward until they reach the surface of the skin.
OBJECTIVE: To evaluate the effect of Er:YAG laser skin ablation followed by topical 5-flurouracil on the outcome of NB-UVB phototherapy as a short term technique in resistant and stable vitiligo.
METHODS: The current study included 40 patients suffering from bilateral stable vitiligo resistant to NB-UVB. For each patient, one side of the body subjected to 4 months NB-UVB sessions (control side). While the other side of the body subjected to one session of Er:YAG laser ablation combined with topical 5% 5-flurouracil application under occlusion followed by NB-UVB sessions for 4 months after complete re-epithelization. Outcomes were evaluated objectively based on standard digital photographs, histopathological examination, patient satisfaction, and adverse effects.
RESULTS: There was a statistically significant improvement in the repigmentation in laser side compared with control side. Histopathological examination revealed expression of prominent melanin pigmentation, with marked expression for Melan-A in laser side, whereas these findings were negative in control side.
CONCLUSIONS: Er:YAG laser ablation, followed by 5FU application before NB-UVB phototherapy for vitiligo, is a safe and tolerable technique that improves the outcome of short-term NB-UVB therapy and is expected to increase patient compliance.

Amelanotic malignant melanoma (AMM) is rare in the oral region. The present study examined the clinical features of this tumor in an attempt to establish diagnostic criteria. The expression of three melanocytic differentiation markers, HMB-45, S-100 and Melan-A, was also measured in primary oral AMMs in order to determine whether the markers could be used to diagnose primary oral AMMs and to find out which marker was the most sensitive. It may be particularly difficult to correctly diagnose AMM that lacks a radial growth phase without immunohistochemical assistance. In the present study, mixtures of polygonal and spindle cells at different ratios were observed in the tumors with and without a radial growth phase. Immunohistochemistry was used to examine the HMB-45, S-100 and Melan-A expression in the formalin-fixed paraffin-embedded specimens of primary oral AMMs. Comparison of staining intensities (SIs) and labeling indices (LIs) of the markers was also performed. The immunostaining results revealed that the SI of Melan-A was significantly higher than that of S-100 (P=0.0011). HMB-45, S-100 and Melan-A also exhibited high positive rates and LIs in AMMs and, therefore, may be good markers for the immunohistochemical diagnosis of primary oral AMMs. Furthermore, Melan-A may be a more sensitive marker than S-100 and HMB-45, as it has a higher SI.

Anorectal malignant melanomas (AMMs) are aggressive neoplasms, which account for less than 1% of all anorectal tumors. Anorectal malignant melanomas are notorious for their diversity of histologic features and mimic a number of other tumors. Aberrant expression of immunohistochemical stains such as cytokeratins and CD117 (c-kit) further increases the risk of misdiagnosis. Aim of our study was to describe the common as well as unusual architectural and cytologic features that create difficulty in diagnosis. We also discussed the role of immunohistochemical stains in diagnosis of AMMs. We retrieved and reviewed 61 cases of anal melanoma diagnosed in our institution between January 2005 and May 2014. Epithelioid cell type was observed in 57 (93.4%) cases, spindle cells in 35 (57.4%) cases, pleomorphic in 12 (19.7%) cases, and lymphoma-like in 2 (3.3%) cases. Cytoplasmic clearing was observed in 16.4% and nuclear pseudoinclusions in 9.8% cases. Twenty-one point three percent cases were completely amelanotic, and 36.1% showed focal melanin pigment. Average mitotic count was 2 mitoses/high-power fields. Nesting pattern was seen in 24.6%, pseudoalveolar pattern in 11.5%, and peritheliomatous/pseudopapillary pattern in 5% cases. Positive expression of vimentin, S-100, HMB-45, and Melan A was seen in 100%, 100%, 94.4%, and 93.3% cases, respectively. Cytokeratins were positive in 9% and CD117 (c-kit) in 20% of cases in which they were performed. In conclusion, AMMs should be considered in the differential of any malignant tumor of anorectal region without obvious glandular and squamoid differentiation. The knowledge of amelanotic nature, unusual histologic features, and aberrant immunohistochemical expression is helpful in avoiding misdiagnosis.

BACKGROUND: A few series addressing the cutaneous side effects related to imatinib in the skin have been published, but only one described scarce histopathologic information in seven patients.
OBJECTIVE: To characterize these lesions and compare the number of melanocytes between hypopigmented lesions and normal appearing skin.
METHODS: We retrieved clinical data of the patients and performed 24 skin biopsies (13 from hypopigmented skin and 11 from normal-appearing skin) within a cohort of 41 patients with chronic myeloid leukemia treated with imatinib. We classified the biopsies into three patterns.
RESULTS: About 45% of patients presented with periocular hypopigmentation. Perifollicular fibrosis was observed in hypopigmented skin biopsies (76.9%) and in normal-appearing skin (45.5%). Epidermal melanin, as determined with Masson-Fontana staining, and melanocyte number, as evaluated with MiTF, Melan A and c-kit immunostains, were lower in hypopigmented skin.
CONCLUSIONS: Histopathologic study of hypopigmented macules demonstrates the presence of melanin with a statistically significant decrease in the number of melanocytes. Therefore, these findings differ from vitiligo, as melanocytes are present. Three histopathological patterns may be found, namely (a) perifollicular fibrosis, (b) lichen planopilaris-like and (c) apparently normal skin. One of the most striking histopathologic finding consisted of the presence of perifollicular fibrosis in both hypopigmented lesions and apparently normal skin.

BACKGROUND: Although angiomyolipoma (AML) is a relatively rare entity, it is the most common benign mesenchymal neoplasm of the kidney.
OBJECTIVE: To highlight the clinicopathological characteristics of AML and to assess the role of Human Melanoma Black-45 (HMB-45), Melan-A, smooth muscle actin (SMA), S-100 and cytokeratin in its diagnosis.
METHODS: The study included 15 cases of AML. Clinical and radiological data were retrieved from the archival files and all cases were subjected to a histopathological evaluation as well as immunohistochemical staining for HMB-45, Melan-A, SMA, S-100, and cytokeratin.
RESULTS: AML was more common in females (female:male = 4:1), the mean age was 53.9 ± 6.45 years. 60% of patients were symptomatic while the remaining 40% were asymptomatic. A statistically significant relationship was found between size of the tumor and the presence of the symptoms (P = 0.02). Patients with tumor size less than 4 cm were asymptomatic, while those with tumor size larger than 4 cm had different symptoms. Thirteen cases were classic AML, while 2 cases were epithelioid AML. Classic AML demonstrated admixture of fatty tissue, thick-walled blood vessels, and smooth muscle, while epithelioid AML was composed mainly of epithelioid cells and contained no fat. HMB-45 was positive in all cases of AML (100%), Melan-A was positive in 13/15 (87%) while SMA was positive in 11/15 (73%) of AML with variable staining intensity. All cases of AML were negative for S-100 and cytokeratin.
CONCLUSIONS: AMLs have characteristic clinicopathological and immunohistochemical features and their recognition is crucial for proper diagnosis and treatment.