Histopathologic PD-L1 Tumor Expression and Prognostic Significance in Nonmelanoma Skin Cancers: A Systematic Review.

ABSTRACT: PD-L1 and PD-1 inhibitors are being increasingly used to treat a variety of nonmelanoma skin cancers (NMSCs). This systematic review summarizes PD-L1 expression in NMSCs and determines its use for prognosis using targeted immunotherapy. A primary search of peer-reviewed English-language medical literature was conducted for studies on PD-L1 tumor expression in biopsied or excised NMSCs. Fifty-nine articles met criteria for inclusion. PD-L1 expression in advanced NMSCs ranged from 22%-89% for basal cell carcinomas, 42%-50% for Merkel cell carcinomas, and 26%-100% for squamous cell carcinomas. Study limitations included clone heterogeneity across studies, complicating comparison of PD-L1 expression. Differences were also noted in the selection of tumor reactivity threshold. We conclude that there is insufficient evidence to determine the prognostic significance of PD-L1 expression in NMSCs as a whole, but this remains a promising area. More investigation into the role of tumor PD-L1 as a biomarker for predicting clinical response to PD-L1 and PD-1 inhibitors in NMSCs is needed.

Epidermal expression of eotaxins and thymic stromal lymphopoietin in eosinophil rich dermatoses.

Eosinophils are seen in a number of dermatologic conditions. While the extent of their function in these diseases remains to be fully elucidated, pathogenic activity in bullous pemphigoid suggests a more significant role than previously thought. Several dermatoses have a fairly characteristic histologic morphology of eosinophil infiltration. We hypothesized that epidermal expression of eotaxins and TSLP would differ by disease, perhaps explaining the different histologic morphologies. We performed a retrospective study of eosinophil rich dermatoses to perform immunohistochemistry. We collected 49 specimens composed of bullous pemphigoid (n = 15), atopic dermatitis (n = 12), drug rash (n = 8), arthropod assault (n = 5), and non-bullous pemphigoid eosinophilic spongiosis (n = 5). We used lichen planus (n = 4) as a control for lymphocyte-mediated inflammation. TSLP was diffusely expressed in all epidermal samples, whereas eotaxins demonstrated a weaker staining. Eotaxins and TSLP demonstrated a gradient between basal and spinous keratinocytes. The correlation between overall basal keratinocyte and spinous keratinocyte staining of eotaxins and TSLP with the number of eosinophils demonstrated a significant correlation between eotaxin-1 (R = 0.404, P = 0.004), eotaxin-2 (R = 0.576, P < 0.001), and eotaxin-3 (R = 0.512, P < 0.001), but not TSLP (R = 0.164, P = 0.251). These remained significant after correcting for multiple comparisons. While we were unable to detect significant differences in epidermal expression of eotaxins and TSLP in various eosinophil rich dermatoses, we identified a significant correlation of spinous keratinocyte eotaxin staining with tissue eosinophilia. Our identification of a correlation of spinous keratinocyte eotaxin staining with tissue eosinophilia may provide insight into local eosinophil chemotaxis.

Matrical carcinoma with melanocytic hyperplasia mimicking nodular melanoma in an elderly Mexican male.

Matrical carcinoma with melanocytic hyperplasia (MCMH), previously referred to as malignant melanocytic matricoma, is a rare variant of the uncommon pilomatrical carcinoma, occurring most often on the head/neck and upper backs of middle-aged men. Nodular lesions may resemble pigmented basal cell carcinoma or melanoma clinically. We present a case of MCMH in a Hispanic patient with history of melanoma. Histopathological clues to appropriate diagnosis include basaloid cells, numerous atypical mitotic figures, matrical differentiation, shadow cells, strong diffuse nuclear and cytoplasmic expression of ß-catenin, and interspersed pigmented dendritic melanocytes.

Keratosis pilaris rubra with mucin deposition.

Keratosis pilaris (KP) is a benign cutaneous disorder characterized by folliculocentric hyperkeratotic papules most often occurring on the proximal extremities. Erythema is usually limited to perifollicular skin, but when keratosis pilaris presents on a background of confluent erythema, the term keratosis pilaris rubra (KPR) is used. The histological findings associated with KP have not been well described in the literature. Herein, we present a case of a 14-year-old male with a 7-year history of erythema and follicular-based papules over his bilateral cheeks, consistent with KPR. Histological examination revealed abundant mucin, keratotic follicular plugging, and periadnexal lymphocytosis. Our novel finding of abundant dermal mucin expands the histopathologic description of KPR.

Diffuse cutaneous mastocytosis: Case report and literature review.

A 6-month-old boy was referred to our burn unit with a recurrent bullous dermatitis, fever, and emesis, originally diagnosed as staphylococcal scalded skin syndrome (SSSS) at an outside hospital. Infectious workup was negative and shave biopsy revealed a dense, diffuse dermal infiltrate of mast cells, consistent with diffuse cutaneous bullous mastocytosis-a rare variant of cutaneous mastocytosis. Treatment included a prolonged course of corticosteroids and antihistamines. Recognition of this rare form of mastocytosis is important, as it can be easily mistaken for other pediatric bullous diseases and is associated with life-threatening complications including vasodilation, anaphylactic shock, gastrointestinal bleeding, and death.

Myoepithelioma of Soft Tissue With Both Squamous and Adipocytic Metaplasia.

Soft tissue, or cutaneous, myoepitheliomas are rare tumors arising solely from a myoepithelial origin. These neoplasms are typically associated with uncertain differentiation and can contain cellular morphologies that include spindle, plasmacytoid, epithelioid, or clear cell forms. Soft tissue myoepitheliomas are commonly found on the lower limbs and in the pelvic girdle but can occur throughout the body. A small minority display heterogenous differentiation, typically osseous or cartilaginous in nature. Squamous and adipocytic cell types are much rarer. We report the case of myoepithelioma of soft tissue with both squamous and adipocytic metaplasia. In the largest myoepithelioma series of 101 soft tissue myoepitheliomas, there were only 2 cases of squamous metaplasia and 1 case of adipocytic metaplasia. Our case displays the unique occurrence of 2 rare histologic findings occurring simultaneously within an already uncommon neoplasm.

Nuclear and cytoplasmic features in the diagnosis of Clark's nevi.

BACKGROUND: Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions. METHODS: This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity. RESULTS: Clark's nevi showed a significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas. CONCLUSION: Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.

Distinguishing Neurofibroma From Desmoplastic Melanoma: The Value of p53.

Distinguishing desmoplastic melanomas (DMs) from neurofibromas (NFs) can be histologically challenging in some cases. To date, a reliable marker to differentiate the 2 entities has remained elusive. S100 subtyping and CD34 fingerprinting have been proposed, but controversy remains as to their reliability. Missense mutations in TP53 are often found in DMs, resulting in a dominant negative effect and paradoxical accumulation of the tumor suppressor protein p53. We hypothesized that p53 may be expressed differentially in DMs, making it a valuable tool in differentiating DMs from NFs. Using immunohistochemistry, we compared p53 protein expression in 20 DMs and 20 NFs retrieved from our tissue archives and stained with p53 antibody (Monoclonal, DO-7). Patients with DM included 18 men and 2 women (age, 36 to 95 y; mean, 70.5 y; median, 70 y). Fifteen (15/20) tumors occurred in head and neck area; 2 (2/20) on the trunk; and 3 (3/20) on the extremities. Patients with NF included 12 men and 8 women (age, 47 to 85 y; mean, 65.2 y; median, 69.5 y). Eleven (11/20) tumors occurred on the trunk, 6 (6/20) on the extremities, and 3 (3/20) on the head and neck area. A total of 19/20 (95%) DMs were positive for p53. DM Histo-scores ranged from 0 to 300 (mean, 203; median, 260). Nuclear accumulation of p53 was seen in all 19 positive DMs. None of the 20 NFs were positive for p53 (2-tailed t test P-value <0.0001). Detection of p53 by immunohistochemistry can help to distinguish DMs from NFs.