Dilation of Multiple Eccrine Ducts as a Highly Specific Marker for Cicatricial Alopecia Background: Eccrine duct dilation (EDD) was recently described to occur more frequently in cicatricial alopecias than noncicatricial alopecias. Because single EDD can be useful in the evaluation of alopecias, we aimed to determine whether dilation of multiple eccrine duct units, or “multiple eccrine duct dilation (MEDD),” could more specifically discriminate between cicatricial and noncicatricial alopecias. Methods: We retrospectively evaluated 611 scalp biopsies (342 cicatricial alopecias and 269 noncicatricial alopecias). Results: Among cicatricial alopecias, MEDD was found in 21% (25/118) of central centrifugal cicatricial alopecia, 26% (29/109) of lichen planopilaris, 13% (10/73) of discoid lupus erythematosus, 31% (5/16) of acne keloidalis nuchae, and 26% (7/26) of folliculitis decalvans. In noncicatricial alopecias, MEDD was found in 1% (1/102) of androgenetic alopecia, 0.7% (1/150) of alopecia areata, and 0% (0/17) of telogen effluvium. In cicatricial alopecias, MEDD occurred in a significantly higher frequency (22%; 76/342) compared with noncicatricial alopecias (0.7%; 2/269) (P-value <0.0001). The presence of MEDD correlated with a diagnosis of cicatricial alopecia with 22% sensitivity and 99% specificity. MEDD also occurred more frequently in cases with moderate to severe inflammation and fibroplasia, suggesting that EDD is a reactive change secondary to the scarring processes. Conclusion: The presence of MEDD on scalp biopsies may be a highly specific marker of cicatricial alopecia and can aid in rendering a more accurate diagnosis. MEDD without other definitive histopathologic features of cicatricial alopecia may compel pathologists to pursue additional workup and/or raise the possibility that a cicatricial alopecia cannot be entirely excluded.

Epithelioid Fibrous Histiocytoma: A Concise Review Abstract: Epithelioid fibrous histiocytoma (EFH) is a rare lesion believed to arise from dermal microvascular unit fibroblasts and dendritic histiocytes. EFH has long been considered a morphologic variant of benign fibrous histiocytoma (dermatofibroma), with prominent epithelioid cytomorphology that can mimic both vascular and melanocytic neoplasms. The molecular basis for the relationship between EFH and benign fibrous histiocytoma has remained largely unknown, with some authors suggesting that EFH represents an entity that is biologically distinct from benign fibrous histiocytoma. Recent molecular studies have identified the presence of recurrent anaplastic lymphoma kinase (ALK) gene rearrangements, a phenomenon that has not been described in benign fibrous histiocytoma. These new molecular findings highlight the uniqueness of this rare tumor and may prove useful as a diagnostic tool for differentiation from other histologic mimics.

“Personalized Excision” of Malignant Melanoma—Need for a Paradigm Shift in the Beginning Era of Personalized Medicine Abstract: The premises on which guidelines for the excision of primary cutaneous melanoma are based are illogical and fail to take into account peculiarities of the individual lesion. The horizontal margins of excision continue to be adjusted to the vertical thickness of the neoplasm, and recommended clinical margins do not reflect the histopathologic borders of melanoma. Micrographically controlled surgery has become accepted for acral melanomas and melanomas of the face and neck but not for melanomas on the trunk, arms, and legs, although the latter tend to be more sharply confined. Extending margins of excision for the purpose of removing inapparent metastases is fallacious because the latter are rare, their localization cannot be foretold, and satellite metastases are usually associated with distant metastases, so that patients do not profit from early removal of cutaneous lesions. The only meaningful objective of excision is complete removal of the primary melanoma. The success of excision must be controlled histopathologically. Because of limitations of the method, a histopathologic safety margin should be observed that must depend on the characteristics of the individual lesion. In sharply confined melanomas, a histopathologic margin of at least 1 mm is sufficient. In the case of poor demarcation, with solitary atypical melanocytes extending far beyond the bulk of the lesion, a broader histopathologic safety margin is advisable. Special caution should be exercised in the presence of regression and for desmoplastic melanomas, acral melanomas, and melanomas on the face and scalp. Instead of wide and deep excisions with standardized margins, “personalized excisions” are required for primary cutaneous melanoma. The concept of clinical safety margins is a relic of former times that has no place in modern medicine.

Dermatological Implications of Galectin-3 in Circulation: An Evaluation From the Perspective of Patients With Differential Manifestations of Post–Kala-Azar Dermal Leishmaniasis Abstract: Galectin-3, a β-galactoside–binding lectin, has been implicated in vast repertoire of inflammatory and immunomodulatory processes including skin diseases. However, galectin-3 has not been comprehensively studied in infectious diseases. This study emphasizes on fascinating aspects of galectin-3 expression in dermal infection by studying post–kala-azar dermal leishmaniasis (PKDL), an intracellular infection caused by Leishmania donovani. Indian PKDL is a well-recognized parasitic dermatosis, with a high risk of anthroponotic transmission of L. donovani in causing leishmaniasis. This study aims to investigate the levels of galectin-3 and galectin-3–binding site expression in circulation of different forms of Indian patients with PKDL. Thirty-seven confirmed untreated PKDL patients, comprising 20 polymorphic and 17 macular PKDL manifestations, were evaluated for the levels of sera galectin-3 with respect to 28 age- and sex-matched healthy controls from endemic areas. Result shows a significant increment (P < 0.001) in circulatory galectin-3 levels in PKDL variants as compared to healthy controls. In addition, there were heightened levels of galectin-3 and galectin-3–binding sites on cellular infiltrates on lesional sites. Furthermore, there was a positive correlation between frequencies of mononuclear cells and galectin-3 during microcirculation in lesions. Data were well corroborated with positive correlation of IL-10 and IFN-γ with sera galectin-3 levels. Moreover, flow cytometry demonstrated the enhanced expression levels of the galectin-3–binding site in circulation in patients with PKDL as compared to healthy controls. Taken together, elevated levels of galectin-3 reflect its involvement in PKDL pathogenesis.

FARP1 Facilitates Cell Proliferation Through Modulating MAPK Signaling Pathway in Cutaneous Melanoma Purpose: The purpose of our study was to investigate the biological functions of FARP1 gene in cutaneous melanoma. Methods: The mRNA expression level of FARP1 in cutaneous melanoma was analyzed based on the data obtained from ONCOMINE and The Cancer Genome Atlas database. Kaplan–Meier analysis was conducted to explore the association between FARP1 expression and the overall survival time of patients with cutaneous melanoma. The mRNA expression of FARP1 in melanoma cells was determined by qRT-PCR. A-375 cell line with silenced FARP1 was constructed to explore its biological functions. Cell proliferation, migration, and invasion abilities were determined by CCK8 assay, wound-healing assay, and transwell assays, respectively. Western blot was performed to explore the protein expression of FARP1, pMEK, MEK, pERK, and ERK. Results: Our results showed that the expression level of FARP1 was upregulated in cutaneous melanoma tissues and cells. Kaplan–Meier analysis revealed that high expression of FARP1 is predictive of shorter overall survival time in patients with cutaneous melanoma. Through CCK8 assay, we found that knockdown of FARP1 in A-375 cells exhibited dramatically inhibitory effect on cell proliferation. The results of wound-healing and transwell assays revealed that the motility of A-375 cells was notably suppressed after silencing FARP1. Moreover, the relative expression levels of pMEK/MEK and pERK/ERK decreased remarkably in A-375 cells following being transfected with si-FARP1. Conclusions: Our present results preliminary proofed that FARP1 possibly acts as a promoter in cutaneous melanoma development and possesses the potential to be a therapeutic target in patients with cutaneous melanoma.

Histopathological and Immunohistochemical Characteristics of Measles Exanthema: A Study of a Series of 13 Adult Cases and Review of the Literature Abstract: Despite available vaccination, measles is one of the leading causes of death among young children in developing countries. In clinical practice, the spectrum of differential diagnoses of morbilliform exanthemas associated with fever is wide, and it can be hard to differentiate from other infectious eruptions, especially in adults or in atypical courses in immunocompromised patients. The goal of our study was to identify characteristic histomorphological and immunohistochemical patterns of measles exanthema through the study of 13 skin biopsy specimens obtained from 13 patients with this disease and a review of cases in the literature. Histopathological features of measles exanthema are quite distinctive and characterized by a combination of multinucleated keratinocytes, and individual and clustered necrotic keratinocytes in the epidermis with pronounced folliculosebaceous as well as acrosyringeal involvement. Immunohistochemical staining of skin biopsies with anti-measles virus (MeV) nucleoprotein and anti-MeV phosphoprotein can be of great value in confirming the diagnosis of measles. Both methods can serve as quick additional diagnostic tools for prompt implementation of quarantine measures and for providing medical assistance, even in patients in whom the clinician did not consider measles as a differential diagnosis of the rash due to the rarity of the disease in a putatively vaccinated community.

Highlighting a Potential Pitfall: Positive: Treponema pallidum: Immunohistochemical Stain in a Patient Without Syphilis Abstract: The Treponema pallidum antibody immunohistochemical (IHC) stain has improved our ability to detect the organism histologically. We present a case of a man with genital condyloma acuminatum with a positive T. pallidum IHC stain but negative T. pallidum serologies and no syphilitic symptoms. It has been shown that the T. pallidum antibody IHC can cross-react, staining other spirochetes, including Borrelia burgdorferi and the Brachyspira family of intestinal spirochetes. Because of the proximity of our patient's lesions to the anus, and the persistently negative T. pallidum serologies, we believe nontreponemal spirochetes colonized the condyloma, giving a false-positive T. pallidum IHC. This cross-reactivity is a potential diagnostic pitfall and is important for the dermatopathologist to recognize, thereby avoiding false diagnosis of syphilis.

Epstein–Barr Virus–Induced Cutaneous Diffuse Large B-Cell Lymphoma in a Patient With Angioimmunoblastic T-Cell Lymphoma Abstract: Cutaneous manifestations of Epstein–Barr virus (EBV)-driven B-cell lymphoid proliferations occur rarely as a result of severe immunodeficiency. To date, only a few cases of extranodal EBV-associated B-cell lymphomas arising in patients with angioimmunoblastic T-cell lymphoma (AITL) have been reported, and less common is a cutaneous presentation. AITL is a rare aggressive tumor that carries a poor prognosis and prompt diagnosis, and recognition of EBV-associated diffuse B-cell lymphoma is essential in these patients to instigate the correct treatment.

Superficial Nodular Fasciitis With Atypical Presentations: Report of 3 Cases and Review of Recent Molecular Genetics Abstract: Nodular fasciitis is a benign proliferation of fibroblasts/myofibroblasts that can be mistaken for an aggressive neoplasm because of its spectrum of appearances and anatomical locations, rapid growth, infiltrative growth pattern, and high mitotic rate. The presence of fusions involving USP6 gene in most cases provides a useful tool for diagnostic confirmation. Nodular fasciitis is often deep, in association with fascia, but less commonly, it arises superficially and can be biopsied by dermatologists. We present herein 3 such cases with confirmed USP6 rearrangement by fluorescence in situ hybridization (FISH) in which the diagnosis of nodular fasciitis was not initially obvious because of atypical morphologic and clinical features. These cases illustrate that in cutaneous myofibroblastic proliferations, nodular fasciitis should be given consideration even when encountered in unusual locations.

An Unusual Presentation of Pyemotes ventricosus Dermatitis Presenting With Umbilicated Papules Mimicking Poxvirus Infection Pyemotes ventricosus mites are an uncommon cause of pruritic dermatitis seen most commonly in occupational exposure, prominently found in professionals such as farmers, landscapers, and factory workers who work with grains, wheat, dried beans, or grasses. The clinical description of the rash has typically been described as papular, erythematous, with a central vesicular lesion. We describe a case of Pyemotes dermatitis with an atypical clinical presentation. A 30-year-old man presented with pruritic, umbilicated papules, which involved his right lateral trunk and upper thigh leading to the submitted clinical impression of molloscum contagiosum. A biopsy of the skin was taken, and fragments of arthropod consistent with P. ventricosus were identified within umbilicated indentations of skin. The patient subsequently admitted to the onset of the rash immediately after carrying bales of straw while supporting each bale with his right side. The possibility of Pyemotes dermatitis mimicking a poxvirus–like eruption should be considered when encountering an unusual umbilicated papular eruption in the appropriate patient with occupational exposure.