Cellular neurothekeoma: Report of two cases with unusual immunohistochemical features.

Cellular neurothekeoma (CNT) is a dermal lesion with still unknown histogenesis, characterized by immunohistochemical staining for NKI/C3, NSE, MiTF, CD10 and CD68, whereas S100 protein, desmin and cytokeratins are negative. Particularly, in several studies NKI/C3 has been reported as a strong marker of CNT. We describe herein the clinical, histopathological and immunohistochemical features of two cases morphologically consistent with myxoid CNT, one of which showing some atypical features, both characterized by negative immunohistochemical staining for NKI/C3. Our findings stress the importance of morphology in diagnosing CNT and underline the fact that NKI/C3 can fail to stain cases belonging to the "neurothekeoma family." In selected cases of CNT, an expanded immunohistochemical panel is mandatory to differentiate this tumor from other dermal lesions.

Primary Pediatric Cutaneous T-Cell Lymphoproliferative Disorders: 3 New Cases.

Primary cutaneous lymphoproliferative disorders are a composite group of diseases with considerable differences in histopathologic, immunophenotypic, and clinical features. They are exceedingly rare in children and in the literature only few cases are reported with extremely different therapeutic approaches. Because of the rarity of cutaneous lymphomas we consider crucial to increase the knowledge of these diseases providing every single case. We present 3 pediatric cases of primary cutaneous T-cell lymphomas occurred to our center with different features and therapeutic approach.

Impact of Dermoscopy and Reflectance Confocal Microscopy on the Histopathologic Diagnosis of Lentigo Maligna/Lentigo Maligna Melanoma.

BACKGROUND: Equivocal pigmented lesions of the head are usually biopsied to avoid inappropriate treatment. Clinical approach has evolved from simple visual examination to sophisticated techniques for selecting the biopsy sites. OBJECTIVE: This study aimed to retrospectively evaluate the efficiency of dermoscopy (DE) and reflectance confocal microscopy (RCM) in sampling a histopathologically representative focus of lentigo maligna/lentigo maligna melanoma. METHODS: Punch biopsies and surgical excisions of 72 patients, 37 men and 35 women (median age 70.6 years, range 39-90 years), affected by lentigo maligna/lentigo maligna melanoma of the head, sent from a single dermatology clinic, were reviewed for the presence of 5 histopathologic criteria: atypical junctional melanocytes, increased junctional melanocytes, follicular colonization, pagetoid spread and melanocytic junctional nests, plus other minor features. Forty-two patients were biopsied under DE and 30 under RCM guidance. RESULTS: Accuracy of the 2 techniques in sampling a representative tissue overlapped in most cases, although RCM selected sites to biopsy with more histopathologic criteria, in particular pagetoid spread and melanocytic nests. Interestingly, with RCM, inflammation and melanophages were observed more in biopsy than in excision. False positive cases were not registered. CONCLUSION: Compared with the sampling at naked eye, our results show that DE and RCM help selecting the most appropriate areas for biopsies, thus allowing not only more robust histopathologic diagnoses, but also a more accurate microstaging of tumor.

Annular Lichenoid Dermatitis (of Youth): Report of a Case With Lichen Planus-Like Features.

Annular lichenoid dermatitis of youth (ALDY), a dermatosis with peculiar clinical and pathological features, represents still a debated entity, given its similarity, among others, with mycosis fungoides. A case of ALDY in a 50-year-old male patient is reported. Clinically, the patient presented an oval scleroderma-like plaque on the right flank. Histology and immunohistochemistry showed the classic appearance described in ALDY. T-cell receptor rearrangement was absent. Interestingly, a focus consistent with lichen planus was observed. The lesion resolved with topical steroids and at a follow-up of 24 months no recurrence has been registered. The case described herein supports the hypothesis that ALDY is a reactive lichenoid dermatosis, closely related to lichen planus.

Comparative Analysis of PRAME Expression in 127 Acral and Nail Melanocytic Lesions.

PRAME (PReferentially expressed Antigen in MElanoma), a cancer testis antigen expressed in low levels in gonadal, endometrial, and adrenal gland tissues, has been recently considered a valuable tool in the differential diagnosis between benign and malignant melanocytic lesions. The aim of the current study is to perform PRAME immunostaining on a large series of benign and malignant acral lesions to evaluate the reproducibility of data reported in the literature and to validate PRAME as an affordable tool in the differential diagnosis between benign and malignant acral melanocytic tumors. Immunohistochemical analysis for PRAME was performed in 127 benign and malignant acral and nail melanocytic lesions. To better correlate PRAME expression with the nature (benign vs. malignant) of the lesions, we categorized PRAME tumor cells percentage positivity and intensity in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Adopting an arbitrary PRAME expression score of < 5 versus ≥5 resulted in a correct identification of 82.5% of benign and 87.1% of malignant lesions. PRAME immunohistochemistry demonstrated good sensitivity and specificity in the diagnosis of acral melanocytic lesions, however, in line with the previous literature, we identified a subset of challenging cases such as acral Spitz nevi, in situ melanomas, and small, thin, invasive melanomas in which PRAME did not correlate with morphologic features. This suggests that PRAME can be a valid tool to be incorporated in a diagnostic clinicopathologic algorithm, subject to morphologic characteristics.

Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy.

AIMS: Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well-documented complication in the setting of breast-conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation-induced AVL and angiosarcomas (AS). METHODS AND RESULTS: Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon. CONCLUSIONS: The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation-associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.

BRAFp.V600E, p.V600K, and p.V600R Mutations in Malignant Melanoma: Do They Also Differ in Immunohistochemical Assessment and Clinical Features?

INTRODUCTION: Although the detection of BRAF p.V600E mutation by immunohistochemistry was clearly described in melanoma, discordant evidences were reported for the detection of p.V600K and p.V600R mutations. The aim of the study was to evaluate the efficacy of BRAFp.V600E, p.V600K, and p.V600R detection by immunohistochemistry in melanoma. MATERIALS AND METHODS: Immunohistochemistry with VE1 antibody was performed on 18 tissue samples of metastatic melanomas with known BRAF mutational status. RESULTS: The concordance rate of immunohistochemistry was 100% for p.V600E mutation. In contrast, the 7 p.V600K-mutated melanomas were scored as negative. p.V600K-mutated melanomas were significantly associated with older age, male sex, and worst clinical outcome. CONCLUSIONS: Immunohistochemistry could efficaciously be adopted as a first step for the detection of BRAFp.V600E mutation in the initial selection of patients with advanced melanomas as candidates for BRAF inhibitors. It should be followed by molecular techniques in p.V600E-negative melanomas, for the specific search of p.V600K and other non-p.V600E BRAF mutations.

Can noninvasive imaging tools potentially predict the risk of ulceration in invasive melanomas showing blue and black colors?

The aim of this study was to evaluate the reflectance microscopy and histopathologic correlates of dermoscopic blue and black color (BB) in a series of melanomas. We searched our database for dermoscopic images of histopathologically diagnosed pigmented nodular melanomas (pNM), superficial spreading melanomas with a nodular component (SSM+Nod), and melanoma metastasis (METs). All cases were assessed for the presence of dermoscopic BB. Confocal microscopy findings were then compared with those of histopathology. A total of 17 BB-positive tumors including eight pNMs, five SSM+Nod, and four METs were included in the study. We identified two different dermoscopic patterns associated with black color, namely, large black blotches and irregular black dots/globules, which corresponded to two different confocal and histopathologic findings. Black blotches resulted from a total filling of the epidermis by an upward migration of melanocyte nests and pagetoid melanocytes as single cells and clusters, whereas black dots/globules also corresponded to the upward migration of melanocyte nests in the epidermis and pagetoid spread, but with sparing of intervening areas of epidermis. Interestingly, two pNM and two METs showing black color lacked any epidermal involvement and, instead, they were characterized by upward-bulging dermal masses of atypical melanocytes covered by an highly attenuated epidermis. In both cases, black color corresponded to pigment-containing melanocytes in close proximity to the surface of the skin. Our study suggests that black color results not only from epidermal melanin but also from a dense dermal proliferation of pigmented melanocytes under a thinned epidermis. It seems reasonable to suggest that a bulging proliferation of dermal melanocytes beneath a thin epidermal layer could precede ulceration. As ulceration is a very significant prognostic factor, speculation arising from this study that dermoscopic black color may in some cases indicate incipient ulceration is worthy of further study.

In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases.

We describe two algorithms to diagnose basal cell carcinomas (BCCs) and melanomas (MMs) using in vivo reflectance confocal microscopy (RCM). A total of 710 consecutive cutaneous lesions excised to exclude malignancy (216 MMs, 266 nevi, 119 BCCs, 67 pigmented facial macules, and 42 other skin tumors) were imaged by RCM. RCM features were correlated with pathology diagnosis to develop diagnostic algorithms. The diagnostic accuracy of the BCC algorithm defined on multivariate analysis of the training set (50%) and tested on the remaining cases was 100% sensitivity, 88.5% specificity. Positive features were polarized elongated features, telangiectasia and convoluted vessels, basaloid nodules, and epidermal shadowing corresponding to horizontal clefting. Negative features were non-visible papillae, disarrangement of the epidermal layer, and cerebriform nests. Multivariate discriminant analysis on the training set (excluding the BCCs) identified seven independently significant features for MM diagnosis. The diagnostic accuracy of the MM algorithm on the test set was 87.6% sensitivity, 70.8% specificity. The four invasive MMs that were misdiagnosed by RCM were all of nevoid subtype. RCM is a highly accurate non-invasive technique for BCC diagnosis. Good diagnostic accuracy was achieved also for MM diagnosis, although rare variants of melanocytic tumors may limit the strict application of the algorithm.

"Connective tissue nevus" and a serendipitous S-100 discovery.

Although desmoplastic melanoma is classically described as an indurated nodule on the head of an elderly patient associated with the histologic changes of an atypical intraepidermal melanocytic lesion accompanied by abnormal dermal spindled cells and rounded lymphoid infiltrates, it is capable of presenting in a variety of clinical and pathologic guises. Herein, a case with unusual clinical and histologic attributes is reported, which was initially misdiagnosed as a connective tissue nevus.

Verruca vulgaris with CD30-positive lymphoid infiltrate: a case report.

Expression of CD30 has been reported in reactive lymphoid cells that accompany some cutaneous viral infections. It is interpreted as a marker of lymphocyte activation in response to the infecting virus. We report on a case of viral wart presenting with an inflammatory infiltrate with numerous CD30+ atypical lymphoid cells. These cells comprised approximately 10% of the reactive cell population and showed a T-helper phenotype. Infection by human papillomavirus should be included among the causes of cutaneous CD30+ reactive lymphoid infiltrates.