IL-17 Expression in the Perifollicular Fibrosis in Biopsies From Lichen Planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia for which therapy is often ineffective and there is no cure. OBJECTIVES: Looking for a new targetable molecule in the treatment of LPP, we sought to verify whether IL-17 expression is increased in scalp biopsies from patients with active scalp lesions of LPP. METHODS: Horizontal sections of hematoxylin and eosin-stained slides from 40 scalp biopsies of active LPP were retrospectively collected and stained with the monoclonal antibody against IL-17 (Abcam, Cambridge, MA; ab79056, dilution 1:100). Twenty biopsies from patients with chronic telogen effluvium served as controls because of their morphological resemblance to the normal scalp. Statistical analysis was performed using IBM SPSS Statistics for Windows (IBM Corporation, Armonk, NY). RESULTS: The main finding was the positive cytoplasmic expression of IL-17 in the perifollicular fibrosis of the affected follicles in LPP which was statistically significant compared with the controls ( P < 0.0001). The labeled cells were identified as fibroblasts based on their spindle shape and fascicular concentric arrangement in tight perifollicular distribution. Although most of the LPP specimens (n = 35; 87.5%) also revealed cytoplasmic IL-17 expression in the lichenoid inflammatory infiltrate, the results were not statistically significant ( P = 0.1351). CONCLUSION: Our immunohistochemistry results show that blocking the IL-17 inflammatory pathway may interfere with the progression of the perifollicular fibrosis and inflammation in LPP.

Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta.

Prurigo nodularis (PN) is a chronic skin dermatosis with hyperkeratotic and intensely pruritic nodules. Managing PN-associated itch is difficult because its aetiology is still unknown. This study aimed to investigate the correlation between itch intensity in PN and the expression of a pruritogenic cytokine interleukin (IL)-31, its receptor complex components IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMRß), and oncostatin M (OSM), which is a ligand of OSMR ß, through immunofluorescence staining examination. Itch intensity in PN was closely correlated with the number of dermal IL-31(+) cells (Spearman's r = 0.551, p < 0.05), dermal IL-31RA(+) cells (r = 0.475, p < 0.05) and dermal OSM(+) cells (r = 0.505, p < 0.05). In addition, the number of dermal OSMRß (+) cells was increased in PN (t test, p < 0.05), despite not being correlated with itch intensity (Spearman's r = 0.375, p > 0.05). Major cellular sources of dermal IL-31 were T cells (27.0% of total IL-31-expressing cells) and macrophages (35.0%), while those of OSM were mainly T cells (49.8%) and mast cells (26.8%). IL-31RA-expressing dermal cells were mostly mast cells (49.3%) and macrophages (36.6%), and OSMRß was mainly expressed by macrophages (51.8%) in the dermis. These findings indicate that IL-31 (mainly from macrophages and T cells) and OSM (principally from T cells and mast cells) stimulate dermal cells expressing IL-31RA and OSMRß (e.g. macrophages), which may further promote itch and inflammation in PN. This complex dermal milieu of cell/cytokine/receptor network can be a therapeutic target for PN-associated itch.

Cutaneous Presentation of T-Cell Prolymphocytic Leukemia Mimicking Dermatomyositis.

ABSTRACT: T-cell prolymphocytic leukemia (TPLL) is a rare form of leukemia by T lymphocytes at a post-thymic intermediate stage of development with an α/ß immunophenotype. Facial involvement is common in TPLL and displays significant heterogeneity of the lesions' description and location. TPLL also contains a wide array of histology findings, cell cytology, and molecular studies. Here, we describe a TPLL patient who presented with an ill-defined erythematous patch involving the right axilla progressing to the left axilla, upper back, and face that resembled dermatomyositis. The diagnosis of TPLL was established using flow cytometry of bone marrow and peripheral blood, and histopathology of the involved skin. Dermatologists should be aware of these unique features.

KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis.

Kaposi's sarcoma (KS) herpesvirus (KSHV) causes KS, an angiogenic AIDS-associated spindle-cell neoplasm, by activating host oncogenic signaling cascades through autocrine and paracrine mechanisms. Tyrosine kinase receptor (RTK) proteomic arrays, identified PDGF receptor-alpha (PDGFRA) as the predominantly-activated RTK in KSHV-induced mouse KS-tumors. We show that: 1) KSHV lytic replication and the vGPCR can activate PDGFRA through upregulation of its ligands PDGFA/B, which increase c-myc, VEGF and KSHV gene expression in infected cells 2) KSHV infected spindle cells of most AIDS-KS lesions display robust phospho-PDGFRA staining 3) blocking PDGFRA-signaling with N-acetyl-cysteine, RTK-inhibitors Imatinib and Sunitinib, or dominant-negative PDGFRA inhibits tumorigenesis 4) PDGFRA D842V activating-mutation confers resistance to Imatinib in mouse-KS tumorigenesis. Our data show that KSHV usurps sarcomagenic PDGFRA signaling to drive KS. This and the fact that PDGFRA drives non-viral sarcomas highlights the importance for KSHV-induced ligand-mediated activation of PDGFRA in KS sarcomagenesis and shows that this oncogenic axis could be successfully blocked to impede KS tumor growth.

Multidrug resistant gastrointestinal stromal tumor with multiple metastases to the skin and subcutaneous soft tissue: A case report and review of literature.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms which account for less than 1% of all gastrointestinal malignancies. Of all the extra-abdominal metastases of GIST, superficial soft tissue metastases are the rarest. Previous reports have found success with sunitinib in imatinib-resistant GIST, but we report a certain wild-type KIT mutation GIST with cutaneous and subcutaneous metastasis that was unresponsive to multiple tyrosine kinase inhibitor (TKI) treatments. This case illustrates that knowing the specific type of KIT mutations may uncover resistance of certain GIST's to TKIs, necessitating more targeted and alternative therapy.

Lichenoid drug eruption after treatment with ixekizumab for plaque psoriasis.

Lichen Planus (LP), the prototype of lichenoid dermatoses, is an idiopathic, T cell-mediated, autoimmune, inflammatory disease. It may affect the skin, hair, nails, and mucous membranes. Many clinical variants of LP have been described, including lichenoid drug eruption or drug induced LP, associated with a myriad of culprit medications. We describe a 63-year-old woman with longstanding psoriasis effectively controlled with ixekizumab, who developed lichenoid drug eruption . Her lichen planus lesions improved after treatment discontinuation and the patient was started on an IL23 inhibitor to treat her psoriasis through an alternative mechanism of action. Our report adds to the literature and provides insight into the complex pathophysiology of lichen planus.

Carcinosarcoma of the hand.

Carcinosarcomas are rare malignant tumors derived of both epithelial and mesenchymal elements. Herein, we report an elderly man originally diagnosed with a squamous cell carcinoma of the hand. Upon excision, the tumor was found to be a more aggressive carcinosarcoma. Immunohistochemical stains revealed that the sarcoma component of the lesion was vimentin positive, whereas the primary carcinoma tumor cells were positive for p63 and CK903. Both components were negative for CD34 and D2-40. This tumor was found to have angiolymphatic invasion and eventually metastasized to the axillary lymph nodes and lungs.

Scanning the Immunopathogenesis of Psoriasis.

Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells. Among these key cytokines lie therapeutic targets for currently approved antipsoriatic therapies. This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic model of psoriasis.

Ocrelizumab-induced psoriasiform dermatitis in a patient with multiple sclerosis.

Multiple Sclerosis (MS) is a chronic autoimmune disease that presents with a wide variety of sensory and motor deficiencies. New medications targeting B cells have been approved to treat MS, but the side effect profile has not been widely explored. Herein, we report a case of drug-induced psoriasiform dermatitis following ocrelizumab treatment. Physicians should be cognizant of this possible side effect in patients receiving treatment for MS.

Clear Cell Acanthoma on the Areola.

Clear cell acanthoma (CCA) is a rare, benign cutaneous condition most often seen on the lower extremities. Lesions are of variable morphology and have been described as polypoid, pigmented, giant, and cystic lesions. Although no racial or gender predilection has been reported, CCA on the breast is a very rare finding that has been observed mainly in young Korean women. Herein, we describe a case of CCA of the areola in an elderly woman with metastatic renal cell carcinoma. Physical exam revealed a pink plaque with central erosions on the left areola. Given the concern for cutaneous metastasis, excisional biopsy was performed, which showed pale glycogenated epithelium consistent with CCA. No evidence of recurrence or new lesions was observed after 6 months of follow-up. Our case exemplifies that clinicians should consider CCA in the differential diagnosis for a new eczematous lesion involving the breast, even in the setting of malignancy.

Nodular cutaneous amyloidoma of the extremity secondary to chronic granulomatous inflammation in setting of sarcoidosis.

Soft tissue amyloidoma is a rare condition that presents primarily in the abdomen and/or mediastinum and more uncommonly on the extremities. Soft tissue amyloidomas on the extremities have been associated with chronic inflammation, particularly when accompanied by AA-type amyloid deposition as seen in local trauma, surgery, hypertension and diabetes. To our knowledge, this is the first reported case of nodular cutaneous amyloidoma in the setting of systemic and cutaneous sarcoidosis. A 65-year-old woman presented with an asymptomatic subcutaneous nodule above her left lateral malleolus. Histopathology of the lesion showed an inconspicuous epidermis with amorphous eosinophilic material deposited in masses within the entire dermis. Congo red and crystal violet stains were positive. Based on the clinical and pathologic findings she was diagnosed with nodular cutaneous amyloidoma. We hypothesize that this process developed secondary to the chronic granulomatous inflammation of sarcoidosis.

Connective Tissue Nevi: A Review of the Literature.

Connective tissue nevi (CTN) are hamartomas of the dermis, with the 3 main components being collagen, elastin, and proteoglycans. Each subtype can present as a solitary lesion or multiple lesions. They could present as part of systemic diseases or inherited disorders. This article provides a comprehensive literature review of the different types of CTN, their clinical presentations, associations, and treatment options. Treatment options for 56 lesions were reviewed. Fifty-two percent of lesions were present in males, and the age range at the time of presentation was wide (1.6-80 years). Management varied according to CTN subtypes. Most lesions (14) received topical or intralesional treatment with corticosteroids, followed by surgical removal of lesions (12), whereas the remaining lesions were clinically monitored.

Primary cutaneous diffuse large B-cell lymphoma presenting as chronic non-healing ulcer.

Primary cutaneous diffuse large B-cell lymphoma is an uncommon and aggressive lymphoproliferative disorder with a rapid growth rate and dismal prognosis. We present the case of a 91-year-old female with an unusual manifestation of primary cutaneous diffuse large B-cell lymphoma, mimicking other more prevalent diseases like chronic non-healing venous ulceration. Dermatopathologic evaluation rendered the correct diagnosis. A discussion of this rare presentation is important for clinician consideration to prevent misdiagnosis and prolongation of proper management in patients with chronic non-healing leg ulcers.

Autochthonous borderline tuberculoid leprosy in a man from Florida.

Leprosy (Hansen's disease) is a chronic contagious granulomatous disease principally affecting the skin and peripheral nervous system, caused by Mycobacterium leprae. In this report, we present a case of autochthonous leprosy in a man from Florida as the first human case reported from this region. Authors believe dermatologists need to be aware of the possibility of autochthonous transmission of leprosy in the Eastern-Southern United States, and should consider leprosy in any patient with atypical skin lesions, even when a history of contact with armadillo is missing.

Matrical Carcinoma With Melanocytic Proliferation and Prominent Squamoid Whorls.

Matrical carcinoma (pilomatrix carcinoma) is a rare follicular low-grade malignancy with matrical differentiation. A pigmented variant with admixed dendritic melanocytes is exceedingly rare with only 7 cases reported in the literature. The diagnosis of malignancy can be difficult to establish. The authors report a case of a 79-year-old woman with a matrical carcinoma who presented with an ulcerated nodule on the posterior right leg, measuring 2.2 cm in greatest dimension. The excisional biopsy showed irregularly shaped dermal and subcutaneous nodules ranging in size from 0.1 to 0.5 cm. The nodules were composed of aggregates of large atypical basaloid cells, with multiple, sometimes atypical, mitoses, admixed with ghost cells, and central necrosis en masse. In addition, the neoplasm was characterized by focal marked melanocytic proliferation and multiple whorls of pink eosinophilic material reminiscent of keratin pearls (squamoid whorls). The basaloid cells were positive for beta-catenin both in the nuclei and the cytoplasm and negative for BerEp4. S100, Melan-A, and HMB45 highlighted the melanocytic dendritic cells. Pan-cytokeratin was negative in the ghost cells and focally positive in the squamoid whorls. Squamoid whorls seem to be a significant feature of matrical carcinoma.

Adalimumab treatment leads to reduction of tissue tumor necrosis factor-alpha correlated with venous leg ulcer improvement: a pilot study.

Venous leg ulcers (VLUs) have higher tumor necrosis factor-α (TNF-α) levels compared with normal skin. Refractory VLUs of long duration have higher TNF-α levels compared with VLUs of shorter duration. As up to 75% of VLUs fail to heal with standard care, we sought to evaluate the role of anti-TNF-α therapy for patients with refractory VLUs. Evaluable data were obtained in four of five subjects with recalcitrant VLUs treated with 80 mg of subcutaneous adalimumab at week 0 and with 40 mg at week 2 along with compression therapy and were followed-up for 6 weeks. Wound biopsies taken at weeks 0 and 4 were stained with anti-TNF-α antibodies. Average 4-week percent wound size reduction was 20.5% ± 6.4%. Two patients had wound size reduction more than 25%, and their percent wound size reduction correlated to percent TNF-α staining score reductions (P = 0.02, R(2) = 0.999). VLU TNF-α level decrease 4 weeks post-adalimumab treatment correlated with wound healing.