Primary cutaneous extraskeletal osteosarcoma of the pretibial leg: A case report and summary of the literature.

Primary cutaneous extraskeletal osteosarcoma is a rare tumor, with fewer than 30 known cases worldwide. We report the case of a 60-year-old female who presented with a solitary right pretibial nodule of 3 mm. She had no known comorbidities, trauma to the area, or prior malignancy. The biopsy specimen showed abundant mineralized osteoid, in which pleomorphic and spindled cells with anaplastic features were embedded. The osteoid matrix in this case contained overtly malignant cells, with frequent mitotic figures, as well as multinucleated giant cells. Immunohistochemistry and imaging led to the conclusion that this nodule represented a primary cutaneous extraskeletal osteosarcoma. The previously reported cases are variable in location, size, gross appearance, and clinical course. The prognosis of osteosarcoma is typically poor, with aggressive behavior; this, however, may be less severe in these strictly cutaneous tumors, though additional follow-up would be beneficial to determine long-term outcomes for the known cases. Ultimately, despite the fact that this is an extremely rare entity, primary cutaneous extraskeletal osteosarcomas should be considered when relevant.

Identifying Toll-like receptor expression in cutaneous sarcoidosis.

Toll-like receptors (TLRs) are known to be expressed in the skin. Antigenic stimulation of TLRs in the skin has been implicated in several inflammatory dermatologic diseases including psoriasis, syphilis, atopic dermatitis, and cutaneous T-cell lymphoma. However, the expression of TLRs in cutaneous sarcoidosis has not yet been defined. Expression of TLRs 1-9 was examined in cutaneous sarcoid by immunohistochemical staining. It was found that TLRs 5 and 6 stained most intensely in both the granulomas and epidermis of the sarcoid cases. TLRs 2, 3, 4, 7, and 8 stained more intensely compared with normal skin. All sarcoidosis cases showed an increased level of staining compared with the control. The nuclear factor-kappa B activation pathway was confirmed by staining for p65. All cases strongly stained for p65 in the granulomas and varied in staining intensity in the epidermis. The identified TLR expression in cutaneous sarcoidosis indicates that a bacterial antigen could be an etiologic agent of the disease. Future studies that clearly define the etiology of sarcoid will lead to better therapies and a better prognosis for affected patients.

Next-generation sequencing in dermatology.

Over the past decade, Next-Generation Sequencing (NGS) has advanced our understanding, diagnosis, and management of several areas within dermatology. NGS has emerged as a powerful tool for diagnosing genetic diseases of the skin, improving upon traditional PCR-based techniques limited by significant genetic heterogeneity associated with these disorders. Epidermolysis bullosa and ichthyosis are two of the most extensively studied genetic diseases of the skin, with a well-characterized spectrum of genetic changes occurring in these conditions. NGS has also played a critical role in expanding the mutational landscape of cutaneous squamous cell carcinoma, enhancing our understanding of its molecular pathogenesis. Similarly, genetic testing has greatly benefited melanoma diagnosis and treatment, primarily due to the high prevalence of BRAF hot spot mutations and other well-characterized genetic alterations. Additionally, NGS provides a valuable tool for measuring tumor mutational burden, which can aid in management of melanoma. Lastly, NGS demonstrates promise in improving the sensitivity of diagnosing cutaneous T-cell lymphoma. This article provides a comprehensive summary of NGS applications in the diagnosis and management of genodermatoses, cutaneous squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma, highlighting the impact of NGS on the field of dermatology.

Mapping Toll-like receptor activity in different stages of cutaneous T-cell lymphoma.

It is known that human keratinocytes (KCs) express Toll-like receptors (TLRs). However, published reports conflict regarding TLR expression in cutaneous T-cell lymphoma patient's KCs. To define the pattern of expression and detect any differences of TLRs 1-9 and p65 expression in epidermal KCs, tumor infiltrate, and endothelial cell types using immunohistochemical stains on fixed and paraffin-embedded sections of mycosis fungoides (MF) in patch, plaque, and nodular stages. MF cases showed no change in pattern of TLRs expressed through different stages but increased epidermal staining of TLRs 2, 3, 4, 5, 6, and 8 with higher scores associated with more aggressive stages. Endothelial cell staining was increased for TLR 4 and 6. Tumor infiltrate staining was strongest with TLRs 5 and 7. Individual cases with disease progression showed increased intensity of TLRs 4, 5, and 6 staining in the epidermis, tumor infiltrate, and endothelial cell. p65 verified nuclear factor kappa B activation of the TLR pathway with trace staining of the epidermis and 1-2+ staining of tumor infiltrate. MF cases showed increased epidermal expression of TLRs and increased endothelial cell staining compared with controls. TLR expression may be driven by antigenic stimulation and may play a role in the activation of neoplastic T cells in the skin. Further definition of TLR patterns may refine the use of TLR modifiers for treatment.

Melanoma developing in a nevoid melanocytoma with myxoid changes: a case report.

Nevoid and myxoid melanoma are rare variants of melanoma; association of the two is a unique finding. Nevoid melanoma is characterized by morphologic resemblance to a nevus, whereas myxoid melanoma demonstrates a basophilic mucinous matrix. We present an atypical case of a melanoma progressing from a nevoid melanocytoma with myxoid changes. A 78-year-old female presented with a pigmented growth on her right thigh. Biopsy demonstrated a biphenotypic melanocytic proliferation composed of a nodule showing epithelioid melanocytes with enlarged nuclei, prominent nucleoli, lack of maturation, and abundant amphophilic cytoplasm with a rare mitotic figure. These findings were suggestive of melanoma along with a nevoid dermal component and myxoid stroma. FISH testing revealed a homozygous loss of 9p21 in the atypical component. SNP-microarray from the nevoid component demonstrated three abnormalities including a gain of whole chromosome 8, as well as loss of a copy of nearly an entire chromosome 9 and 16q most consistent with a melanocytoma.

Multicenter, prospective feasibility study of Nano-Pulse Stimulation™ technology for the treatment of both nodular and superficial low-risk basal cell carcinoma.

Background: Nano-Pulse Stimulation™ (NPS™) therapy is a new, non-thermal bioelectric modality that applies ultrashort pulses of electric energy to trigger regulated cell death (RCD) in treated tissues. Instead of initiating necrosis by heating or freezing, NPS therapy permeabilizes intracellular organelles to activate the cell's own self-destruct pathway of programmed or regulated cell death. Unlike cryotherapeutic procedures that can both damage structural tissues and diffuse into the periphery beyond the margins of the lesion, NPS therapy only affects cells within the treated zone leaving surrounding tissue and acellular components unaffected. Methods: In this study we treated 37 basal cell carcinoma lesions on 30 subjects (NCT04918381). The treated lesions were photographed on 3-, 7-, 14-, 30- and 60-days after treatment. All subjects then underwent surgical excision for histological examination of the treated tissue. Results: 92% of the BCC lesions (34 of 37) showed complete histological clearance of BCC. Histologic analysis of the 3 cases where residual BCC was noted indicated that full energy coverage was not achieved, which could be remedied with an improved treatment guide to standardize and optimize the CellFX® procedure based on NPS technology. Conclusion: The CellFX procedure was shown to be safe and effective for the treatment of low-risk nodular and superficial BCC lesions.

Comparison of SOX-10, HMB-45, and Melan-A in Benign Melanocytic Lesions.

PURPOSE: Different immunohistochemical stains are used in dermatopathology to stain melanocytes and diagnose benign and malignant melanocytic lesions. METHODS: SOX-10, HMB-45, and Melan-A immunohistochemical stains were used to assess 32 biopsy specimens with a histologic diagnosis of lentigo. The total number of melanocytes stained with each immunohistochemical stain was counted and an average count was obtained from two readings. RESULTS: Analysis of the data revealed a significant difference in staining melanocytes between these three immunostains (p=0.0010, ANOVA). SOX-10 stained 0.195 more melanocytes than HMB-45 (p=0.0026). Similarly, Melan-A stained 0.195 more melanocytes than HMB-45 (p=0.0011). However, the difference between SOX-10 and Melan-A was not statistically significant (p=0.9810). CONCLUSION: SOX-10 and Melan-A immunostaining stain more melanocytes than HMB-45. No significant difference was noted between Melan-A and SOX-10.

WT1 marker is not sufficient for distinguishing between melanoma and melanocytic nevi.

BACKGROUND: The heterogeneous histological features of melanoma may often overlap with melanocytic nevi. For this reason, pathologists have sought after immunohistochemistry to assist with difficult cases. Recently, Wilms' tumor 1 protein (WT1) has been suggested to differentiate between melanoma and melanocytic nevi. OBJECTIVE: Our objective was to determine whether immunohistochemistry analysis of WT1 expression is a reliable tool in differentiating cutaneous melanoma from melanocytic nevi. METHODS: Forty-five melanoma and 43 melanocytic nevi were immunostained with anti-WT1 monoclonal antibody (clone 6F-H2). RESULTS: Forty of the 45 cutaneous melanoma (89%) and 22 of the 43 melanocytic nevi (51%) stained (> 10% cells) for WT1. The highest sensitivity for WT1 was expressed by nodular melanoma (19/20), superficial spreading melanoma (8/10) and Spitz nevi (9/11). At the threshold of above 75% WT1-stained cells, the specificity for melanoma was 95% but the sensitivity was only 31%. At the threshold of 10%, the sensitivity increased to 89% but the specificity decreased to only 49%. Finally, at the threshold of 25% and 50%, the sensitivity and specificity were 71%, 61% and 64%, 77%, respectively. CONCLUSIONS: Our data suggest that melanoma is associated with increased WT1 expression. However, as a single immunostaining marker, WT1 is not sufficient for distinguishing melanoma from melanocytic nevi.

Blueberry muffin rash secondary to hereditary spherocytosis.

The term blueberry muffin rash is used to describe the clinical presentation of dermal extramedullary hematopoiesis. The common culprits of this rash include a TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes) infection or hematologic dyscrasia. Association of this rash with hereditary spherocytosis is extremely rare. We present a unique case of a neonate born with a blueberry muffin rash secondary to hereditary spherocytosis.

Traction folliculitis: an underreported entity.

Traction folliculitis is a component of traction alopecia syndrome and has received minimal attention in primary source medical literature. The popularity of hairstyles that produce hair traction and the knowledge that early intervention improves prognosis amplify the importance of recognizing this entity. Traction folliculitis presents as perifollicular erythema and pustules on the scalp in areas where hairstyles produce traction on the hair shaft. In addition to the traction, concurrent hair care practices may play a facilitatory role in the development of traction folliculitis. Treatment involves immediate removal of traction on hair and temporary alteration of the facilitatory hair care practices. In more severe cases, topical or systemic antibacterial therapy and, occasionally, topical corticosteroid therapy may be necessary. Failure to discontinue traction-producing hairstyles can lead to traction alopecia and irreversible hair loss. Cultural considerations often are paramount in hairstyle choices and hair care practices that cause predisposition to traction disorders. Thus, culturally competent counseling requires understanding the significance of the hairstyle and hair care practices to the patient (or caregivers), discussing the recommendations in a culturally sensitive manner, and negotiating mutually acceptable alternative practices.

Extensive lichenoid drug eruption due to glyburide: a case report and review of the literature.

Lichenoid reactions to sulfonylurea drugs have been reported, albeit infrequently. To our knowledge, this is the first case of a generalized lichenoid dermatitis likely induced by the third-generation sulfonylurea hypoglycemic drug glyburide.

A survey of self-reported skin disease in the elderly African-American population.

BACKGROUND: In the USA, the geriatric population, almost 12% of which will be comprised of African-Americans, is expected to exceed 88 million by 2050. Data on dermatologic conditions in elderly African-Americans are deficient. OBJECTIVES: This study aimed to identify prevalences of self-reported skin disease and skin-related concerns in elderly African-Americans, and to assess participants' perceptions of skin disease and awareness of skin cancer. METHODS: Elderly African-Americans were recruited into a cross-sectional study and asked to complete a 17-item questionnaire. RESULTS: A total of 101 participants aged 60-91 years (median age: 71 years) completed the questionnaire. The majority (75.2%) of the subjects were female. The most common self-reported skin diseases were eczema/dermatitis (28.7%), fungal skin infections (16.8%), alopecia (6.9%), viral skin infections (4.9%), and urticaria (4.9%). The most common skin concerns were dry skin/pruritus (40.6%), moles (27.7%), hair loss (25.7%), skin discoloration (20.8%), and wrinkles (15.8%). Overall, 40.6% of participants reported concern about skin cancer, and 75.2% reported examining their skin regularly. However, 34.7% did not believe that people with darker skin types should be concerned about skin cancer. CONCLUSIONS: This study provides an important overview of the most common self-reported skin conditions in elderly African-Americans. Substantial age-related differences in the frequencies of skin disorders were apparent. It is important to include the elderly population within campaigns to educate minority group members on skin cancer.

Granuloma faciale: distribution of the lesions and review of the literature.

Granuloma faciale (GF) is an uncommon inflammatory condition characterized by reddish brown papules and plaques that usually involve the facial area. Extrafacial lesions are rare. Histologically, the lesions are marked by leukocytoclastic vasculitis and extensive fibrin deposition. There are a variety of treatment options available for GF.

Rad6 is a Potential Early Marker of Melanoma Development.

Melanoma is the leading cause of death from skin cancer in industrialized countries. Several melanoma-related biomarkers and signaling pathways have been identified; however, their relevance to melanoma development/progression or to clinical outcome remains to be established. Aberrant activation of Wnt/ß-catenin pathway is implicated in various cancers including melanoma. We have previously demonstrated Rad6, an ubiquitin-conjugating enzyme, as an important mediator of ß-catenin stability in breast cancer cells. Similar to breast cancer, ß-catenin-activating mutations are rare in melanomas, and since ß-catenin signaling is implicated in melanoma, we examined the relationship between ß-catenin levels/activity and expression of ß-catenin transcriptional targets Rad6 and microphthalmia-associated transcription factor-M (Mitf-M) in melanoma cell models, and expression of Rad6, ß-catenin, and Melan-A in nevi and cutaneous melanoma tissue specimens. Our data show that Rad6 is only weakly expressed in normal human melanocytes but is overexpressed in melanoma lines. Unlike Mitf-M, Rad6 overexpression in melanoma lines is positively associated with high molecular weight ß-catenin protein levels and ß-catenin transcriptional activity. Double-immunofluorescence staining of Rad6 and Melan-A in melanoma tissue microarray showed that histological diagnosis of melanoma is significantly associated with Rad6/Melan-A dual positivity in the melanoma group compared to the nevi group (P=.0029). In contrast to strong ß-catenin expression in normal and tumor areas of superficial spreading malignant melanoma (SSMM), Rad6 expression is undetectable in normal areas and Rad6 expression increases coincide with increased Melan-A in the transformed regions of SSMM. These data suggest a role for Rad6 in melanoma pathogenesis and that Rad6 expression status may serve as an early marker for melanoma development.

Melanoma Development and Progression Are Associated with Rad6 Upregulation and ß -Catenin Relocation to the Cell Membrane.

We have previously demonstrated that Rad6 and ß -catenin enhance each other's expression through a positive feedback loop to promote breast cancer development/progression. While ß -catenin has been implicated in melanoma pathogenesis, Rad6 function has not been investigated. Here, we examined the relationship between Rad6 and ß -catenin in melanoma development and progression. Eighty-eight cutaneous tumors, 30 nevi, 29 primary melanoma, and 29 metastatic melanomas, were immunostained with anti- ß -catenin and anti-Rad6 antibodies. Strong expression of Rad6 was observed in only 27% of nevi as compared to 100% of primary and 96% of metastatic melanomas. ß -Catenin was strongly expressed in 97% of primary and 93% of metastatic melanomas, and unlike Rad6, in 93% of nevi. None of the tumors expressed nuclear ß -catenin. ß -Catenin was exclusively localized on the cell membrane of 55% of primary, 62% of metastatic melanomas, and only 10% of nevi. Cytoplasmic ß -catenin was detected in 90% of nevi, 17% of primary, and 8% of metastatic melanoma, whereas 28% of primary and 30% of metastatic melanomas exhibited ß -catenin at both locations. These data suggest that melanoma development and progression are associated with Rad6 upregulation and membranous redistribution of ß -catenin and that ß -catenin and Rad6 play independent roles in melanoma development.

Use of Ber-EP4 and Epithelial Specific Antigen to Differentiate Clinical Simulators of Basal Cell Carcinoma.

EpCam is a transmembrane epithelial adhesion molecule present on all non-squamous epithelial cells. It is often overexpressed in certain carcinomas, such as breast and colon, and in dermatology, eg, basal cell carcinoma (BCC). Various monoclonal antibodies have been used to detect EpCam, including BerEP4 and epithelial specific antigen. We compared anti-EpCam clones, BerEP4, and epithelial specific antigen clone VU-1D9. One hundred and twelve lesions were stained with both antibodies. All basal cell carcinomas stained uniformly and strongly positive with both antibodies. Diffuse positive staining was also seen in all trichoepitheliomas and merkel cell carcinomas. Focal positive staining was seen in squamous cell carcinoma and benign sebaceous neoplasms. Clone VU-1D9 was more likely to produce focal positive staining as compared to BerEP4. This focal positive staining of sebaceous neoplasms and squamous cell carcinomas is a potential diagnostic pitfall.