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1.
Am J Dermatopathol ; 35(6): 663-5, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23563253

ABSTRACT

Herpes virus infections presenting as folliculitis are uncommon. We describe a 48-year-old white man with a distant history of a childhood gastric lymphoma and renal cell carcinoma presenting with an itchy eruption. He was concerned about recurrence. A punch biopsy revealed interface dermatitis with a dense atypical superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate with occasional eosinophils extending to the subcutis, with destruction of vessel walls. It was composed of predominantly CD3-positive lymphocytes with scattered CD56-positive cells and CD20-positive cells, concerning for lymphoma. A T-cell gene rearrangement study was negative. Deeper sections uncovered multinucleated giant keratinocytes in the follicular epithelium of 1 hair follicle, consistent with herpes folliculitis. Cutaneous herpes infections can exhibit several variable clinical and histopathological features. Knowledge of alternative presentations of herpes infections, histological clues to the presence of herpes infections, and careful clinicopathological correlation are necessary to differentiate herpes infections from cutaneous lymphomas and other inflammatory dermatoses.


Subject(s)
Folliculitis/diagnosis , Herpesviridae Infections/diagnosis , Lymphoma/diagnosis , Skin Neoplasms/diagnosis , Skin/pathology , Biopsy , Diagnosis, Differential , Folliculitis/immunology , Folliculitis/pathology , Folliculitis/virology , Herpesviridae Infections/complications , Herpesviridae Infections/immunology , Herpesviridae Infections/pathology , Herpesviridae Infections/virology , Humans , Immunohistochemistry , Lymphoma/genetics , Lymphoma/immunology , Lymphoma/pathology , Male , Middle Aged , Predictive Value of Tests , Skin/immunology , Skin/virology , Skin Neoplasms/genetics , Skin Neoplasms/immunology , Skin Neoplasms/pathology
2.
Leuk Lymphoma ; 54(2): 284-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22839723

ABSTRACT

Patients with cutaneous T-cell lymphoma (CTCL) frequently experience severe pruritus that can significantly impact their quality of life. Romidepsin is approved by the US Food and Drug Administration (FDA) for the treatment of patients with CTCL who have received at least one prior systemic therapy, with a reported objective response rate of 34%. In a phase 2 study of romidepsin in patients with CTCL (GPI-04-0001), clinically meaningful reduction in pruritus (CMRP) was evaluated as an indicator of clinical benefit by using a patient-assessed visual analog scale. To determine the effect of romidepsin alone, confounding pruritus treatments including steroids and antihistamines were prohibited. At baseline, 76% of patients reported moderate-to-severe pruritus; 43% of these patients experienced CMRP, including 11 who did not achieve an objective response. Median time to CMRP was 1.8 months, and median duration of CMRP was 5.6 months. Study results suggest that the clinical benefit of romidepsin may extend beyond objective responses.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Depsipeptides/therapeutic use , Lymphoma, T-Cell, Cutaneous/complications , Lymphoma, T-Cell, Cutaneous/drug therapy , Pruritus/etiology , Aged , Antibiotics, Antineoplastic/administration & dosage , Depsipeptides/administration & dosage , Female , Humans , Lymphoma, T-Cell, Cutaneous/pathology , Male , Middle Aged , Neoplasm Staging , Pruritus/diagnosis , Treatment Outcome
5.
J Clin Oncol ; 29(18): 2598-607, 2011 Jun 20.
Article in English | MEDLINE | ID: mdl-21576639

ABSTRACT

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.


Subject(s)
Clinical Trials as Topic/standards , Mycosis Fungoides/drug therapy , Neoplasm Staging/standards , Outcome Assessment, Health Care/standards , Sezary Syndrome/drug therapy , Skin Neoplasms/drug therapy , Clinical Trials as Topic/methods , Humans , Lymph Nodes/pathology , Mycosis Fungoides/blood , Mycosis Fungoides/classification , Mycosis Fungoides/pathology , Mycosis Fungoides/psychology , Neoplasm Staging/methods , Quality of Life , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/standards , Research Design , Severity of Illness Index , Sezary Syndrome/blood , Sezary Syndrome/classification , Sezary Syndrome/pathology , Sezary Syndrome/psychology , Skin/pathology , Skin Neoplasms/blood , Skin Neoplasms/classification , Skin Neoplasms/pathology , Skin Neoplasms/psychology , Treatment Outcome , Tumor Burden , Viscera/pathology
7.
J Am Acad Dermatol ; 64(2): 352-404, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21145619

ABSTRACT

Sézary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine. Finally, guidelines for the treatment of SS and suggestions for adjuvant treatment are noted.


Subject(s)
Sezary Syndrome/pathology , Sezary Syndrome/therapy , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Alkylating Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Combined Modality Therapy , Drug Therapy, Combination , Evidence-Based Medicine , Histone Deacetylase Inhibitors/therapeutic use , Humans , Immunologic Factors/therapeutic use , Methotrexate/therapeutic use , Mycosis Fungoides/pathology , Mycosis Fungoides/therapy , Quality of Life , Retinoids/therapeutic use , Sezary Syndrome/immunology , Skin Neoplasms/immunology
8.
Pediatr Dermatol ; 28(5): 568-9, 2011.
Article in English | MEDLINE | ID: mdl-21073512

ABSTRACT

Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant spindle-cell tumor usually presenting in adulthood. The epidemiology of DFSP has recently been reviewed, and there have been 152 reported cases of DFSP in patients below the age of sixteen. We present the case of a DFSP arising in a young patient with Shwachman-Diamond syndrome (SDS).


Subject(s)
Bone Marrow Diseases/complications , Carcinoma/etiology , Dermatofibrosarcoma/etiology , Exocrine Pancreatic Insufficiency/complications , Lipomatosis/complications , Skin Neoplasms/etiology , Biopsy , Carcinoma/pathology , Carcinoma/surgery , Female , Humans , Shwachman-Diamond Syndrome , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Young Adult
9.
Pediatr Dermatol ; 27(6): 607-13, 2010.
Article in English | MEDLINE | ID: mdl-21138468

ABSTRACT

Mycosis fungoides (MF) is rare in children and adolescents. This study was aimed to determine the clinicoepidemiologic features of juvenile onset (≤18 yrs) MF in Kuwait. Thirty-six children and adolescents (≤18 yrs) with MF registered in a referral photobiology unit for cutaneous lymphomas between July 1991 and June 2009 were included in this study. Children and adolescents were observed to constitute 16.6% of the total number of patients with MF, with 97% of patients of Arab ethnicity. The age-adjusted incidence rate of MF in children and adolescents among the total population was 0.29/100,000 persons/year. Among 36 Arab children and adolescents, boys outnumbered girls by 1.25:1. Mean and median age at onset of disease was 9 years, and age at diagnosis was 13 years. Patch stage disease was the most common clinical variant (75%) with 56% with pure hypopigmented MF-variant. The majority of patients (75%) had stage IB (TNM and B staging) disease. The study highlights a high prevalence and incidence of juvenile MF in Kuwait with a predominantly hypopigmented presentation.


Subject(s)
Mycosis Fungoides/epidemiology , Mycosis Fungoides/pathology , Skin Neoplasms/epidemiology , Skin Neoplasms/pathology , Adolescent , Age Distribution , Age of Onset , Biopsy , Child , Child, Preschool , Female , Humans , Incidence , Kuwait/epidemiology , Male , Registries/statistics & numerical data , Sex Distribution
10.
Int J Dermatol ; 49(12): 1393-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21155090

ABSTRACT

BACKGROUND: Mycosis fungoides (MF) is an indolent, most common type of cutaneous T-cell lymphoma (CTCL) with an average estimated incidence of 0.5 cases per 100,000 persons per year in the western world. Although various clinical and epidemiological features are well delineated in the western population, the data is scarce from our region. OBJECTIVES: To study the clinicoepidemiological features of MF from Kuwait. SETTING: A referral photobiology unit for cutaneous lymphomas in a national dermatology department in collaboration with three other dermatology departments in Kuwait and Kuwait cancer center. PATIENTS AND METHODS: One hundred and ninety-three cases of MF registered between July 1991 and June 2006 were included for this study. RESULTS: Eighty-six percent of our MF cases were of Arab ethnicity. Males outnumbered the females by 2:1 ratio. Mean age at diagnosis was 35.20 ± 14.37 years, and 16% of the patients were diagnosed by the age 20 years. The annual incidence rate (IR) of MF in Kuwait was observed to be 0.43 cases per 100,000 persons with a significantly higher IR among Arabs as compared to non-Arab Asians (RR = 4.4; 95% CI = 2.9-6.6). A successive rise in the IR of MF was noticed with the advancing age. The annual IR among males was more or less comparable to that of females. Skin patches were the most prevalent skin lesions (67%) at diagnosis, and 22% of the patients had a pure hypopigmented variant. Patients with hypopigmented MF were observed to have younger mean age at diagnosis (27.60 ± 12.42 years) as compared to other MF cases (38.14 ± 14.37 years) (P = 0.000). Ninety-two percent of the patients had the early stage (IA, IB, and IIA) of disease. CONCLUSIONS: Our patients with MF were observed to have a relatively younger age at diagnosis, with a high proportion of patients diagnosed by the age 20 years. Arabs were observed to have a higher annual IR of MF as compared to non-Arab Asians. Hypopigmented MF is prevalent in our population. The study highlights the ethnic and/or regional variations in the clinicoepidemiological characteristics of MF.


Subject(s)
Arabs , Asian People , Mycosis Fungoides/diagnosis , Mycosis Fungoides/ethnology , Skin Neoplasms/diagnosis , Skin Neoplasms/ethnology , Adult , Age Factors , Female , Humans , Incidence , Kuwait/epidemiology , Male , Middle Aged , Neoplasm Staging , Young Adult
11.
J Clin Oncol ; 28(29): 4485-91, 2010 Oct 10.
Article in English | MEDLINE | ID: mdl-20697094

ABSTRACT

PURPOSE: The primary objective of this study was to confirm the efficacy of romidepsin in patients with treatment refractory cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: This international, pivotal, single-arm, open-label, phase II study was conducted in patients with stage IB to IVA CTCL who had received one or more prior systemic therapies. Patients received romidepsin as an intravenous infusion at a dose of 14 mg/m(2) on days 1, 8, and 15 every 28 days. Response was determined by a composite assessment of total tumor burden including cutaneous disease, lymph node involvement, and blood (Sézary cells). RESULTS: Ninety-six patients were enrolled and received one or more doses of romidepsin. Most patients (71%) had advanced stage disease (≥ IIB). The response rate was 34% (primary end point), including six patients with complete response (CR). Twenty-six of 68 patients (38%) with advanced disease achieved a response, including five CRs. The median time to response was 2 months, and the median duration of response was 15 months. A clinically meaningful improvement in pruritus was observed in 28 (43%) of 65 patients, including patients who did not achieve an objective response. Median duration of reduction in pruritus was 6 months. Drug-related adverse events were generally mild and consisted mainly of GI disturbances and asthenic conditions. Nonspecific, reversible ECG changes were noted in some patients. CONCLUSION: Romidepsin has significant and sustainable single-agent activity (including improvement in pruritus) and an acceptable safety profile, making it an important therapeutic option for treatment refractory CTCL.


Subject(s)
Depsipeptides/therapeutic use , Lymphoma, T-Cell, Cutaneous/drug therapy , Skin Neoplasms/drug therapy , Skin/drug effects , Aged , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Asthenia/chemically induced , Depsipeptides/administration & dosage , Depsipeptides/adverse effects , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Nausea/chemically induced , Neoplasm Staging , Prospective Studies , Skin/pathology , Treatment Outcome , Vomiting/chemically induced
12.
Stem Cells ; 28(10): 1728-40, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20715179

ABSTRACT

The development of methods to achieve efficient reprogramming of human cells while avoiding the permanent presence of reprogramming transgenes represents a critical step toward the use of induced pluripotent stem cells (iPSC) for clinical purposes, such as disease modeling or reconstituting therapies. Although several methods exist for generating iPSC free of reprogramming transgenes from mouse cells or neonatal normal human tissues, a sufficiently efficient reprogramming system is still needed to achieve the widespread derivation of disease-specific iPSC from humans with inherited or degenerative diseases. Here, we report the use of a humanized version of a single lentiviral "stem cell cassette" vector to accomplish efficient reprogramming of normal or diseased skin fibroblasts obtained from humans of virtually any age. Simultaneous transfer of either three or four reprogramming factors into human target cells using this single vector allows derivation of human iPSC containing a single excisable viral integration that on removal generates human iPSC free of integrated transgenes. As a proof of principle, here we apply this strategy to generate >100 lung disease-specific iPSC lines from individuals with a variety of diseases affecting the epithelial, endothelial, or interstitial compartments of the lung, including cystic fibrosis, α-1 antitrypsin deficiency-related emphysema, scleroderma, and sickle-cell disease. Moreover, we demonstrate that human iPSC generated with this approach have the ability to robustly differentiate into definitive endoderm in vitro, the developmental precursor tissue of lung epithelia.


Subject(s)
Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Cell Differentiation/genetics , Cell Differentiation/physiology , Cells, Cultured , Cellular Reprogramming/genetics , Cellular Reprogramming/physiology , Endoderm/cytology , Fibroblasts/cytology , Fibroblasts/metabolism , Flow Cytometry , Genetic Vectors/genetics , Humans , Lentivirus/genetics , Reverse Transcriptase Polymerase Chain Reaction
14.
Am J Dermatopathol ; 32(5): 505-8, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20489572

ABSTRACT

Mucoepidermoid carcinoma (MEC), an invasive malignant neoplasm composed of mucus-secreting, epidermoid, and intermediate cells in varying proportions, is the commonest malignant salivary gland neoplasm in adults. Cutaneous metastases from the same, although not entirely common, has been previously reported but are typically confined to dermis. In this report, we present a case of MEC presenting as a cutaneous metastasis. A histologic feature unique to this case was epidermotropism, previously not noted in either metastatic or primary MEC.


Subject(s)
Carcinoma, Mucoepidermoid/secondary , Epidermis/pathology , Salivary Gland Neoplasms/pathology , Skin Neoplasms/secondary , Adrenal Gland Neoplasms/secondary , Biopsy , Cerebellar Neoplasms/secondary , Diagnosis, Differential , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Male , Middle Aged
15.
J Am Acad Dermatol ; 63(1): 63-70, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20226565

ABSTRACT

BACKGROUND: Passing tanning bed legislation restricting underage use has remained challenging. OBJECTIVE: We sought to determine the resources required to pass tanning bed legislation restricting use to children and identify key barriers to its passage. METHODS: A total of 15 states sought to pass tanning bed legislation in 2006; in-depth surveys were completed with advocates in 10 states and legislators in 5 states. RESULTS: Advocates sought advice from the sponsoring legislator or legislators (n = 9), held discussions with other organizations (n = 8), and used a lobbyist (n = 5). The 3 major barriers were strong lobbying efforts by the tanning bed industry (n = 10), proceedings after the bill was filed (n = 5), and obtaining support from other organizations (n = 4). For legislators, the most significant barrier was making colleagues aware of the health effects of tanning bed use. LIMITATIONS: Five of 10 legislators and 10 of 15 advocates responded to the survey. CONCLUSION: Barriers to passage of tanning bed legislation can potentially be surmounted with advice to advocates and coordinated efforts by multiple organizations.


Subject(s)
Beauty Culture/legislation & jurisprudence , Legislation as Topic , Sunbathing/legislation & jurisprudence , Adolescent , Data Collection , Humans , Public Opinion , United States
16.
J Cutan Pathol ; 37(10): 1088-91, 2010 Oct.
Article in English | MEDLINE | ID: mdl-19638066

ABSTRACT

Anaplastic Kaposi sarcoma (KS) is an uncommon histologic phenotype of Kaposi's and one that is typically associated with a locally aggressive clinical course. We report a case of a 53-year-old human immunodeficiency virus-positive male, on highly active antiretroviral therapy 1 month prior to admission, who presented with fever, cough, respiratory distress, multiple skin lesions and cervical and inguinal lymphadenopathy not responding to multiple antibiotics. Microscopic examination of punch biopsies from the forehead and chest revealed a spindled cell neoplasm with marked cytologic atypia and scattered mitoses, features consistent with a diagnosis of anaplastic KS and confirmed by immunohistochemistry with HHV-8. Biopsy of an involved lymph node also revealed involvement by KS. Despite aggressive clinical treatment, the patient rapidly deteriorated and expired 1 week after the diagnosis of anaplastic KS was rendered. Our case underscores the aggressive clinical course of this uncommon histologic variant of KS and its recalcitrant clinical behavior.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Sarcoma, Kaposi/pathology , Skin Neoplasms/pathology , Fatal Outcome , Herpesvirus 8, Human , Humans , Immunohistochemistry , Male , Middle Aged , Phenotype , Sarcoma, Kaposi/virology , Skin Neoplasms/virology
18.
J Am Acad Dermatol ; 61(4): 677.e1-14, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19751883

ABSTRACT

Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.


Subject(s)
Genetic Counseling , Genetic Testing , Melanoma/genetics , Patient Selection , Skin Neoplasms/genetics , Humans
19.
J Cutan Pathol ; 36(12): 1303-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19519875

ABSTRACT

Epidermal growth factor receptor inhibitors (EGFRIs) are new anticancer agents that act by inhibiting EGFR signaling transduction pathways, thus decreasing tumor growth. In more than 30 countries, EGFRIs are currently used in the treatment of a number of solid tumors, and other indications are being sought. In the United States, select EGFRIs have been approved in certain patients with non-small cell lung cancer, metastatic colorectal carcinoma, and advanced squamous cell carcinoma of the head and neck. Various cutaneous side effects of EGFRIs have been reported, including acneiform eruptions, chronic paronychia, xerosis, a seborrheic dermatitis-like eruption, changes in hair texture, and nonscarring alopecia. We present a 60-year-old woman with non-small cell lung cancer who developed a persistent generalized itchy eruption and progressive nonscarring alopecia shortly after initiation of erlotinib (Tarceva). Scalp biopsy showed near-equal number of anagen and catagen/telogen hair follicles, and a superficial and deep perivascular lymphoplasmocytic infiltration. These changes are typical of the nonscarring alopecia induced by EGFRIs. Because it is likely that EGFRIs will be increasingly used, dermatopathologists are likely to see more reactions from these agents. Familiarity with their side effects is essential to accurate diagnosis and effective patient management.


Subject(s)
Alopecia/chemically induced , Alopecia/pathology , Antineoplastic Agents/adverse effects , Enzyme Inhibitors/adverse effects , Quinazolines/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride , Female , Humans , Inflammation/chemically induced , Inflammation/pathology , Lung Neoplasms/drug therapy , Middle Aged
20.
Cancer ; 115(6): 1318-27, 2009 Mar 15.
Article in English | MEDLINE | ID: mdl-19189368

ABSTRACT

BACKGROUND: Worldwide, the incidence of thick melanoma has not declined, and the nodular melanoma (NM) subtype accounts for nearly 40% of newly diagnosed thick melanoma. To assess differences between patients with thin (or=2.01 mm) nodular melanoma, the authors evaluated factors such as demographics, melanoma detection patterns, tumor visibility, and physician screening for NM alone and compared clinical presentation and anatomic location of NM with superficial spreading melanoma (SSM). METHODS: The authors used data from a large population-based study of Queensland (Australia) residents diagnosed with melanoma. Queensland residents aged 20 to 75 years with histologically confirmed first primary invasive cutaneous melanoma were eligible for the study, and all questionnaires were conducted by telephone (response rate, 77.9%). RESULTS: During this 4-year period, 369 patients with nodular melanoma were interviewed, of whom 56.7% were diagnosed with tumors 2.00 mm). CONCLUSIONS: Awareness of factors related to earlier detection of potentially fatal nodular melanomas, including the benefits of a physician examination, should be useful in enhancing public and professional education strategies. Particular awareness of clinical warning signs associated with thin nodular melanoma should allow for more prompt diagnosis and treatment of this subtype.


Subject(s)
Melanoma/pathology , Skin Neoplasms/pathology , Adult , Aged , Early Detection of Cancer , Female , Health Surveys , Humans , Male , Melanoma/diagnosis , Middle Aged , Physical Examination , Queensland/epidemiology , Registries , Skin Neoplasms/diagnosis , Surveys and Questionnaires
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