Yann Charli-Joseph

Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus.

Abstract:Neutrophilic dermatoses have long been known to be associated with autoinmune systemic diseases. Recently, a small number of cases of a disorder distinct from Sweet syndrome or bullous lupus erythematosus (LE) have been described as specifically related to systemic LE under diverse terms, including nonbullous neutrophilic dermatosis, nonbullous neutrophilic LE, and Sweet-like neutrophilic dermatosis. We describe 7 patients that developed urticarial lesions in the context of a known or concurrently diagnosed autoimmune connective tissue disease. Of a total of 7 patients, 6 were afflicted by systemic LE and 1 by rheumatoid arthritis and secondary Sjögren syndrome. Histological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, vacuolar alteration along the dermal-edidermal junction, and no vasculitis. Most patients had active systemic disease at the time of the cutaneous eruption. Skin lesions resolved rapidly after the administration of immunomodulating agents. In conclusion, we provide additional evidence of the existence of a recently defined nonbullous neutrophilic dermatosis in the context of autoimmune connective tissue diseases and propose the term autoimmunity-related neutrophilic dermatosis as an appropriate designation. Furthermore, we believe that this entity should prompt physicians to screen the presence of an active systemic disorder in afflicted patients.

Primary cutaneous perivascular epithelioid cell tumor: A clinicopathological and molecular reappraisal

BACKGROUND Perivascular epithelioid cell tumor (PEComa) is a rare neoplasm of uncertain histogenesis with a mixed myomelanocytic immunophenotype, rarely arising in the skin (primary cutaneous PEComa [pcPEComa]). OBJECTIVE We analyzed the clinicopathological features of 8 pcPEComas, assayed for DNA copy number changes and for initiating mutations common in melanocytic neoplasms. METHODS pcPEComas were evaluated using immunohistochemistry, comparative genomic hybridization, and DNA sequencing. RESULTS pcPEComas were erythematous nodules, mostly in the lower extremities of women (5/8), composed of large pale-staining epithelioid cells. The patients age range was 26 to 67 (mean 46) years. The percentages of tumors staining positively were as follows: micro-ophthalmia-associated transcription factor, NKI/C3, bcl-1, E-cadherin, and cathepsin K (100%); HMB-45, 4E-binding protein 1, and CD68 (88%); smooth muscle actin and muscle-specific actin (40%); S100 (38%); calponin (20%); desmin (13%); and melan-A, SOX10, and keratin (0%). No chromosomal copy number changes or initiating mutations were identified. LIMITATIONS Small sample size is a limitation. CONCLUSIONS pcPEComas have a different molecular signature than extracutaneous tumors and are unrelated to tuberous sclerosis. However, the common expression of 4E-binding protein 1 points to a role of the mTOR pathway in their pathogenesis. Because pcPEComas are diagnostically challenging, we propose that micro-ophthalmia-associated transcription factor, NKIC3, smooth muscle actin, desmin, bcl-1, cathepsin K, and 4E-binding protein 1 can be used when evaluating a possible pcPEComa.

Amicrobial pustulosis of the folds associated with autoimmune disorders: systemic lupus erythematosus case series and first report on the association with autoimmune hepatitis.

Amicrobial pustulosis of the folds (APF) associated with autoimmune disorders is an infrequent entity characterized by the recurrent appearance of follicular and nonfollicular sterile pustules in the context of autoimmune disease. Most reports on APF suggest systemic lupus erythematosus (SLE) as the major immunological associated disorder but the association with autoimmune hepatitis (AH) has not been previously documented. We describe the clinical and histological characteristics of 5 patients with APF: 4 with SLE and 1 with AH. As APF is an exclusion diagnosis, in order to establish an opportune diagnosis and treatment, physicians should be aware of patients with any autoimmune disease who develop a pustular dermatosis for which cultures and stains are negative. We propose the inclusion of anti-liver kidney microsome antibodies in the minor criteria for APF diagnosis.

SOX-10 expression in cutaneous myoepitheliomas and mixed tumors.

SOX‐10 expression can be demonstrated by immunohistochemistry in salivary gland myoepitheliomas, but its expression in cutaneous myoepitheliomas and in cutaneous mixed tumors with prominent myoepithelial cells has not been studied.

Are corticosteroids and immunosuppressors an efficacious treatment for bullous lupus erythematosus with systemic manifestations

Auteur(s) : Monica Fernandez-Sanchez1, Yann Charli-Joseph1, Marcela Saeb-Lima2, Linda Garcia-Hidalgo1, Rocio Orozco-Topete1 1Dermatology 2Pathology Dept, Instituto Nacional de Ciencias Medicas y Nutricion “Salvador Zubiran”, Distrito Federal 14000, Mexico Bullous systemic lupus erythematosus (SLE) is an autoantibody-mediated blistering skin disease occurring in patients with SLE, in isolation or in conjunction with systemic manifestations of lupus. It has an acute onset with a rapidly expanding [...]

Cutaneous Spindle-Cell B-Cell Lymphomas: Most are Neoplasms of Follicular Center Cell Origin.

Cutaneous lymphomas of both B cells and less commonly T cells can exceptionally exhibit spindle-cell morphology. Less than 30 spindle-cell B-cell lymphomas of the skin have been described, mostly before the adoption of detailed immunohistochemistry, and thus initially interpreted as variants of diffuse large B-cell lymphoma (DLBCL). Furthermore, some authors suggest that cutaneous spindle-cell B-cell lymphomas (cSCBCLs) may behave more aggressively than their conventional morphologic counterparts and may thus merit more aggressive treatment. Herein we describe the largest case series of cSCBCL analyzed to date to characterize their clinicopathologic and immunohistochemical features and clarify their subtype according to the current WHO/EORTC classification scheme. Twenty-four cSCBCLs arose in 18 male and 6 female individuals with a mean age of 55 years, mostly on the head (12/24), trunk (8/24), and lower extremities (4/24). Histopathologic features were similar for all cases. Neoplasms involved the entire dermis and focally the subcutis. The neoplastic infiltrates comprised a mixture of medium-sized, visually prominent spindled cells (15%; up to 85% of the infiltrate) arranged in a fascicular pattern around nodular aggregates and admixed in a random manner between centrocyte/centroblast-like cells within these nodular collections. Immunohistochemical support for a follicular center cell origin was present in 22/24 cases, 1 was consistent with DLBCL-leg type and 1 defied precise classification, best fitting with intermediate-grade DLBCL-other. Our findings reinforce the concept that most cSCBCLs are variants of low-grade B-cell lymphomas of follicle center cell origin and not intermediate-grade variants of DLBCL.

DNA copy number changes in tumors within the spectrum of cellular, atypical, and metastasizing fibrous histiocytoma

BACKGROUND Cutaneous fibrous histiocytoma (FH) is a common mesenchymal neoplasm. Metastasis is rare, disproportionately occurring among the aneurysmal, cellular, atypical, and deep variants. OBJECTIVE We determined whether DNA copy number changes occurred in atypical FH (AFH), and whether they were similar to those in metastasizing FH (MetFH) and benign cellular FH (CFH). METHODS Five primary tumors of MetFH were evaluated by array-based comparative genomic hybridization analysis, with tissue from local recurrences and lung metastases in 2 and 2 patients, respectively. Seven indolent AFH and 5 CFH were identified for comparison. RESULTS Substantial differences between the groups were found both in the frequency of chromosomal aberrations (higher among MetFH and absent or solitary in CFH) and array-based comparative genomic hybridization profiles (frequent gains of 7 and 8q and losses of Xq in MetFH; recurrent losses of chromosomes 9 and 22 in AFH; isolated loss of 5q and gain in chromosome 20 in 2 CFH). Fatal MetFH cases (2 of 5 cases) exhibited the highest rate of chromosomal aberrations. LIMITATIONS This study included a small sample size with a short-term follow-up. CONCLUSIONS Benign CFH, indolent AFH, and MetFH represent distinct biological entities within the spectrum of FH; array-based comparative genomic hybridization may be a tool in recognizing FH cases with metastatic potential and increasingly aggressive behavior.

Approach to cutaneous lymphoid infiltrates: When to consider lymphoma?

Cutaneous lymphoid infiltrates (CLIs) are common in routine dermatopathology. However, differentiating a reactive CLI from a malignant lymphocytic infiltrate is often a significant challenge since many inflammatory dermatoses can clinically and/or histopathologically mimic cutaneous lymphomas, coined pseudolymphomas. We conducted a literature review from 1966 to July 1, 2015, at PubMed.gov using the search terms: Cutaneous lymphoma, cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia, simulants/mimics/imitators of cutaneous lymphomas, and cutaneous lymphoid infiltrates. The diagnostic approach to CLIs and the most common differential imitators of lymphoma is discussed herein based on six predominant morphologic and immunophenotypic, histopathologic patterns: (1) Superficial dermal T-cell infiltrates (2) superficial and deep dermal perivascular and/or nodular natural killer/T-cell infiltrates (3) pan-dermal diffuse T-cell infiltrates (4) panniculitic T-cell infiltrates (5) small cell predominant B-cell infiltrates, and (6) large-cell predominant B-cell infiltrates. Since no single histopathological feature is sufficient to discern between a benign and a malignant CLI, the overall balance of clinical, histopathological, immunophenotypic, and molecular features should be considered carefully to establish a diagnosis. Despite advances in ancillary studies such as immunohistochemistry and molecular clonality, these studies often display specificity and sensitivity limitations. Therefore, proper clinicopathological correlation still remains the gold standard for the precise diagnosis of CLIs.

Nasal-type extranodal natural killer/T-cell lymphoma presenting as genital ulcers

carcinoma. The degree of cellularity, atypia of the cells, mitotic rate, and evidence of vascular or lymphatic invasion can be useful but not definitive. Various markers have been used to ascertain the identity of these tumors, including ER, PR, S-100, cytokeratins, carcinoembryonic antigen, alphalactalbumin, HMFG-1 and -2 (human milk fat globulins), MUC1, MUC2, EMA (epithelial membrane antigen), myoepithelial markers such as p63 and smooth muscle actin, podoplanin, GCDFP 15, epidermal growth factor receptor, and E-cadherin, but none is perfect. A recent report demonstrated that a panel of p63, CK5, CK14, CK17, and mammaglobin had 100% sensitivity and 91% specificity in distinguishing these two. However, it included only 23 cases and has not been confirmed by others. Clinically, cutaneous metastases usually develop rapidly, over a course of weeks to months, and there are frequently multiple lesions. Also, although in majority of the cases, a primary tumor can be found in metastases of breast cancer, there have been cases of metastases without a primary tumor. In conclusion, more research is required to further differentiate these entities, and long-term follow-up is essential in the care of these patients.

Paraneoplastic acanthosis nigricans paralleling disease course in a patient with mycosis fungoides

ejd.2013.2232 Auteur(s) : Yann Charli-Joseph1 YannVincent.CharliJoseph@ucsf.edu, Kim Chong2, Weiyun Z. Ai3, Philip E. Leboit1,2, Laura B Pincus1,2 1 Department of Pathology, 2 Department of Dermatology, 3 Department of Medicine, Division of Hematology and Oncology, University of California San Francisco. 1701 Divisadero Street, Suite 280, San Francisco, California, 94115, USA Acanthosis nigricans (AN) is a dermatosis characterized by hyperpigmented, thickened plaques, characteristically on the intertriginous [...]