text:
- Vitamin B complex
- Vitamin B5 (pantothenic acid) promotes skin renewal by acting on the germinative layer in the dermis and the epidermis. Thus it stimulates hair follicle growth. Moreover, due to its excellent moisturising properties, vitamin B5 prevents drying and makes the hair shiny and manageable.
- Vitamin B8 (biotin) has a stimulating effect on the hair follicle, together with demonstrated action against seborrhoea.
- Vitamin B6 (pyridoxine) is essential to protein and amino acid metabolism, particularly sulfurated amino acids (cystine and methionine).
- Vitamin B12 promotes methionine synthesis and activates keratin synthesis.
- Zinc is essential to keratin synthesis, acting synergetically with vitamin B6. Zinc also inhibits 5-alpha reductase, an enzyme present in the hair bulb and the sebaceous gland and which is responsible for the transformation of testosterone into its active derivative, dihydrotestosterone. Alopecia may be related to an excess of dihydrotestosterone in the hair follicle. Thus, a zinc deficiency is more often than not accompanied by hair loss, nail deterioration and skin dryness.
- Sulfurated amino acids
- Methionine is a precursor and activator of keratin synthesis.
- Cystine helps to increase hair diameter and stimulates regrowth in cases of hair loss with no pathological cause.
2 capsules in the morning to be taken with a large glass of water.
Founded in 1980 in Carros, near Nice in France, by Dr. Max Rombi, Arkopharma is a pharmaceutical laboratory specialised in the area of phytotherapy, natural medicine and dietary supplements. By offering a global approach to health and well-being, ARKOPHARMA Pharmaceutical Laboratories meets consumers' needs. It offers natural medicines intended for treatment and prevention, increases consumption oriented towards family self-medication, and also offers healthcare professionals new possibilities for prescriptions.
For more than 30 years, ARKOPHARMA Laboratories has been dedicated to new "healthy medicines" based on natural products. It has been a period marked by the search for a healthier life and for essential values; phytotherapy and dietary supplements are favoured by an ever expanding number of consumers around the world.
Arkopharma is a pharmaceutical laboratory specialised in the area of phytotherapy, natural medicine and dietary supplements. Arkopharma means 30 years of taking care of your health! For more than 30 years, Arkopharma Laboratories has been dedicated to new "healthy medicines" based on natural products.
Copyright Arkopharma
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text:
Youth Venture, Inc.
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1700 North Moore Street Arlington VA 22209 USA
Youth venture assists young
Marketing and message- encouraging young people to take their own community service initiatives and persuading both young people and adults to redefine the youth years as a time of responsibility.
program implementation- includes product development, fellowship/ network support and online/mobile strategies to encourage young americans to start their own venture and help the broader society become effectively supportive.
partner/venture support- provides wide support and small seed grants to support the venturers.
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Iclusig registration conditions and product labeling may vary by country.
Iclusig® (ponatinib) is approved in the U.S. and EU.
Iclusig (ponatinib) is approved in the U.S. for:
These indications are based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.
Limitations of use:
Iclusig is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase CML (5.6).
Iclusig is approved in Europe as an orphan medicinal product for two indications:
Full European prescribing information (PDF)
Full U.S. prescribing information and Medication Guide (PDF)
WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY
See full prescribing information for complete boxed warning
Vascular Occlusion: Arterial and venous thrombosis and occlusions, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures have occurred in at least 27% of Iclusig-treated patients from the phase 1 and phase 2 trials. Iclusig can also cause recurrent or multi-site vascular occlusion. Overall, 20% of Iclusig-treated patients experienced an arterial occlusion and thrombosis event of any grade. Fatal and life-threatening vascular occlusion has occurred within 2 weeks of starting Iclusig treatment and in patients treated with average daily dose intensities as low as 15 mg per day. The median time to onset of the first vascular occlusion event was 5 months. Patients with and without cardiovascular risk factors have experienced vascular occlusion although these events were more frequent with increasing age and in patients with prior history of ischemia, hypertension, diabetes, or hyperlipidemia. Interrupt or stop Iclusig immediately in patients who develop vascular occlusion events.
Heart Failure: Fatal and serious heart failure or left ventricular dysfunction occurred in 5% of Iclusig treated patients (22/449). Eight percent of patients (35/449) experienced any grade of heart failure or left ventricular dysfunction. Monitor patients for signs or symptoms consistent with heart failure and treat as clinically indicated, including interruption of Iclusig. Consider discontinuation of Iclusig in patients who develop serious heart failure.
Hepatotoxicity: Iclusig can cause hepatotoxicity, including liver failure and death. Fulminant hepatic failure leading to death occurred in an Iclusig-treated patient within one week of starting Iclusig. Two additional fatal cases of acute liver failure also occurred. The fatal cases occurred in patients with blast phase CML (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Severe hepatotoxicity occurred in all disease cohorts. Iclusig treatment may result in elevation in ALT, AST, or both. Monitor liver function tests at baseline, then at least monthly or as clinically indicated. Interrupt, reduce or discontinue Iclusig as clinically indicated.
Hypertension: Treatment-emergent hypertension (defined as systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg on at least one occasion) occurred in 67% of patients (300/449). Eight patients treated with Iclusig (2%) experienced treatment-emergent symptomatic hypertension as a serious adverse reaction, including one patient (<1%) with hypertensive crisis. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. In 131 patients with Stage 1 hypertension at baseline, 61% (80/131) developed Stage 2 hypertension. Monitor and manage blood pressure elevations during Iclusig use and treat hypertension to normalize blood pressure. Interrupt, dose reduce, or stop Iclusig if hypertension is not medically controlled. In the event of significant worsening, labile or treatment-resistant hypertension, interrupt treatment and consider evaluating for renal artery stenosis.
Pancreatitis: Clinical pancreatitis occurred in 6% (28/449) of patients (5% Grade 3) treated with Iclusig. Pancreatitis resulted in discontinuation or treatment interruption in 6% of patients (25/449). The incidence of treatment-emergent lipase elevation was 41%. Check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse. Dose interruption or reduction may be required. In cases where lipase elevations are accompanied by abdominal symptoms, interrupt treatment with Iclusig and evaluate patients for pancreatitis. Do not consider restarting Iclusig until patients have complete resolution of symptoms and lipase levels are less than 1.5 x ULN.
Increased Toxicity in Newly Diagnosed Chronic Phase CML: In a prospective randomized clinical trial in the first line treatment of newly diagnosed patients with chronic phase (CP) CML, single agent Iclusig 45 mg once-daily increased the risk of serious adverse reactions 2-fold compared to singe agent imatinib 400 mg once-daily. The median exposure to treatment was less than 6 months. The trial was halted for safety in October 2013. Arterial and venous thrombosis and occlusions occurred at least twice as frequently in the Iclusig arm compared to the imatinib arm. Compared to imatinib-treated patients, Iclusig-treated patients exhibited a greater incidence of myelosuppression, pancreatitis, hepatotoxicity, cardiac failure, hypertension and skin and subcutaneous tissue disorders. Iclusig is not indicated and is not recommended for the treatment of patients with newly diagnosed CP CML.
Neuropathy: Peripheral and cranial neuropathy have occurred in Iclusig-treated patients. Overall, 13% (59/449) of Iclusig-treated patients experienced a peripheral neuropathy event of any grade (2%, grade 3/4). In clinical trials, the most common peripheral neuropathies reported were peripheral neuropathy (4%, 18/449), paresthesia (4%, 17/449), hypoesthesia (2%, 11/449), and hyperesthesia (1%, 5/449). Cranial neuropathy developed in 1% (6/449) of Iclusig-treated patients (<1% grade 3/4).
Of the patients who developed neuropathy, 31% (20/65) developed neuropathy during the first month of treatment. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness. Consider interrupting Iclusig and evaluate if neuropathy is suspected.
Ocular Toxicity: Serious ocular toxicities leading to blindness or blurred vision have occurred in Iclusig-treated patients. Retinal toxicities including macular edema, retinal vein occlusion, and retinal hemorrhage occurred in 3% of Iclusig-treated patients. Conjunctival or corneal irritation, dry eye, or eye pain occurred in 13% of patients. Visual blurring occurred in 6% of the patients. Other ocular toxicities include cataracts, glaucoma, iritis, iridocyclitis, and ulcerative keratitis. Conduct comprehensive eye exams at baseline and periodically during treatment.
Hemorrhage: Serious bleeding events, including fatalities, occurred in 5% (22/449) of patients treated with Iclusig. Hemorrhagic events occurred in 24% of patients. The incidence of serious bleeding events was higher in patients with accelerated phase CML (AP-CML), BP-CML, and Ph+ ALL. Most hemorrhagic events, but not all occurred in patients with grade 4 thrombocytopenia. Interrupt Iclusig for serious or severe hemorrhage and evaluate.
Fluid Retention: Serious fluid retention events occurred in 3% (13/449) of patients treated with Iclusig. One instance of brain edema was fatal. In total, fluid retention occurred in 23% of the patients. The most common fluid retention events were peripheral edema (16%), pleural effusion (7%), and pericardial effusion (3%). Monitor patients for fluid retention and manage patients as clinically indicated. Interrupt, reduce, or discontinue Iclusig as clinically indicated.
Cardiac Arrhythmias: Symptomatic bradyarrhythmias that led to a requirement for pacemaker implantation occurred in 1% (3/449) of Iclusig-treated patients. Advise patients to report signs and symptoms suggestive of slow heart rate (fainting, dizziness, or chest pain). Supraventricular tachyarrhythmias occurred in 5% (25/449) of Iclusig-treated patients. Atrial fibrillation was the most common supraventricular tachyarrhythmia and occurred in 20 patients. For 13 patients, the event led to hospitalization. Advise patients to report signs and symptoms of rapid heart rate (palpitations, dizziness). Interrupt Iclusig and evaluate.
Myelosuppression: Severe (grade 3 or 4) myelosuppression occurred in 48% (215/449) of patients treated with Iclusig. The incidence of these events was greater in patients with AP-CML, BP-CML and Ph+ ALL than in patients with CP-CML. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated, and adjust the dose as recommended.
Tumor Lysis Syndrome: Two patients (<1%) with advanced disease (AP-CML, BP-CML, or Ph+ ALL) treated with Iclusig developed serious tumor lysis syndrome. Hyperuricemia occurred in 7% (30/449) of patients overall; the majority had CP-CML (19 patients). Due to the potential for tumor lysis syndrome in patients with advanced disease, ensure adequate hydration and treat high uric acid levels prior to initiating therapy with Iclusig.
Compromised Wound Healing and Gastrointestinal Perforation: Since Iclusig may compromise wound healing, interrupt Iclusig for at least 1 week prior to major surgery. Serious gastrointestinal perforation (fistula) occurred in one patient 38 days post-cholecystectomy.
Embryo-Fetal Toxicity: Iclusig can cause fetal harm. If Iclusig is used during pregnancy, or if the patient becomes pregnant while taking Iclusig, the patient should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking Iclusig.
Most common non-hematologic adverse reactions: (≥20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia.
Please see accompanying full Prescribing Information for Iclusig
PB/0416/0083/US May 2016


text:
Erin Brockovich Film Plot Summary
A selection of articles related to erin brockovich film plot summary.
Original articles from our library related to the Erin Brockovich Film Plot Summary. See Table of Contents for further available material (downloadable resources) on Erin Brockovich Film Plot Summary.
- Mabon / The Autumnal Equinox
- Mabon is a Sabbat of celebration for the abundance of the harvest; a time meant for us to give thanks through song, dance and feasts. This is a time of balance, when day and night are equal once again; a time of meditation and introspection; a time to slow...
Holidays >> Mabon
- Erin
- Irish. One of the Three Queens of the Tuatha De Danann, daughters of the Dagda, who asked that Ireland be named after them....
Deities & Heros >> Celtic, Welsh, Irish & Brittish
- Samhain - October 31st
- The Celtic year is divided into halves, marked by the two great Fire Festivals of Samhain and Beltaine. The period from Samhain to Beltaine is called "an Ghrian beag" or the "lessor Sun", and the period from Beltaine to Samhain is called &q...
Holidays >> Samhain
- Serious Cleansing Ritual
- This cleansing ritual has been modified from one that I performed for a dear friend who was having trouble dispelling negativity possibly sent from a former romantic acquaintance. This is not a ritual to perform for just anybody - the performer actually...
Paganism & Wicca >> Spells
- Survivalists' Guide for the New Millennium: Summary
- As we enter into the new millennium, the dreams of a fading era carry us all to an uncertain destination. The modern age has in no way resolved the human crisis, which is not significantly different except in terms of scale and severity, than the tragedies...
Philosophy >> Survivalists Guide for the New Millennium
- A Treatise on Astral Projection
- There are certain aspects of the astral dimension and the projection process that are very complicated. Much of it is misunderstood and it can all be very confusing at times. This series of articles attempts to shed a little light on the subject, and...
Parapsychology >> Astral Projection
- Bringing it Down to Earth: A Fractal Approach
- 'Clouds are not spheres, mountains are not cones, coastlines are not circles, and bark is not smooth, nor does lightning travel in a straight line.' B. Mandelbrot W e want to think about the future - it's our nature. Unlike other creatures, humans possess an...
Mystic Sciences >> Astrology
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Suggested Pdf Resources
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- The Story. After sustaining a neck injury in a car accident,. Erin Brockovich retains attorney Ed Masry to represent her in a personal injury suit.
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- Erin Brockovich is a 2000 biographical film directed by Steven Soderbergh and written by Susannah Grant. The film is a dramatization of the true story of Erin ...
- en.wikipedia.org
- Erin Brockovich - Summary - Awesome Stories
- Jun 15, 2015 In this story behind the movie, meet the real Erin Brockovich and Ed Masry. Take a virtual trip to Hinkley to see the compressor station (and the ...
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- Erin Brockovich | My Story
- The story and eventual film helped make the "Erin Brockovich" a household name. Over time, Erin realized that she could use her notoriety to spread positive ...
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The following bibliography has been generated by bringing together all references provided by our content partners. There may be duplication.
- Higo, Shun'ichi, Paul Callomon, and Yoshihiro Goto. 1999. Catalogue and Bibliography of the Marine Shell-bearing Mollusca of Japan: Gastropoda, Bivalvia, Polyplacophora, Scaphopoda. 749
- Metaxas A, Kelly NE, 2010. Do Larval Supply and Recruitment Vary among Chemosynthetic Environments of the Deep Sea?. PLoS ONE 5(7): e11646. doi:10.1371/journal.pone.0011646
- Myers, P., R. Espinosa, C. S. Parr, T. Jones, G. S. Hammond, and T. A. Dewey. 2006. The Animal Diversity Web (online). Accessed February 16, 2011 at http://animaldiversity.org. http://www.animaldiversity.org
- Syst. Nat., ed. 10, 734.
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20 years of experience
New Brunswick, NJ 08901 Phone number & directions
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Anu Venkat:
View the full profile to get information on:
- Qualifications
- What's important to you
View full profile
Patient Reviews
The overall average patient rating of Dr. Anu Venkat is Below Average.
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Diabetic Nerve Pain Patient Education Read our patient education guide and understand diabetic nerve pain and symptoms and treatments for nerve damage.Before Visiting Dr. Venkat Learn More
Specialties & Research
Dr. Anu Venkat, MD is board certified in Pediatrics, Neurodevelopmental Disabilities, and Neurology with Special Qualifications in Child Neurology.
- She has special expertise in 14 areas:
- Amenorrhea
- Colonoscopy
- Contraception
- Cryosurgery
- Cysts
- Endometriosis
- Epilepsy
- Genital Warts
- Hysterectomy (Uterus)
- Menopause
- Polycystic Ovary Syndrome (PCOS)
- Pre-Eclampsia
- Urinary Tract Infections (UTI)
- Uterine Cervical Dysplasia
Education & Awards
Dr. Venkat graduated from Coimbatore Medical College.
Dr. Venkat has 10 hospital affiliations:
- Virtua Memorial Hospital Of Burlington County
- Saint Peter's University Hospital
- Spanish
- Polish
- Tamil
- Russian
- Korean
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- Additional Information
- Dr. Anu Venkat MD is a female Pediatrician, has 20 years of experience and practices in Pediatrics, Neurodevelopmental Disabilities, and Neurology with Special Qualifications in Child Neurology.
- Where does Dr. Anu Venkat practice?
- Dr. Anu Venkat has 1 office location.
Dr. Anu Venkat practices Pediatrics, Neurodevelopmental Disabilities, and Neurology with Special Qualifications in Child Neurology near New Brunswick, NJ.
See New Brunswick Pediatricians and New Brunswick Neurologists.


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realmagick.com The shrine of knowledge.
Astigmatism A Simple Eye Test
A selection of articles related to astigmatism a simple eye test.
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- Psychic Protection - Barriers
- Introduction: The countermeasures given in these short articles are extremely basic. They only contain the bare bones of what is necessary to use them. To understand the principles behind these countermeasures, please get a copy of 'Practical Psychic Self-Defe...
Psychic Abilities >> Psychic Protection
- A Few Simple Stretches
- Here are a few simple Yoga stretches for those days when life gets you in the neck, in the back, in the shoulder or for the dreaded internetitis rigor mortis. Always work within your comfort level, it is meant to relax and stretch the muscles not to force...
Body Mysteries >> Yoga
- Survivalists' Guide for the New Millennium: Chapter 6
- AS THE WORM TURNS Health and well being are part of the natural birthright of the human being. With all of its organs intact, the right diet, exercise and mental focus, a human body can overcome any disease. Even so, the effects of living in this...
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- Serveral Simple But Useful Meditations
- MEDITATIONS Before you start any kind of meditation, here are a few tips: Pick a place where you will not be disturbed. If you want, you may put on some relaxing music or nature sounds to keep you from possible distractions. Get into an upright position...
Mind >> Meditation
- A Simple Cleansing Meditation
- Make sure that you have a comfortable chair where you can sit with your feet firmly flat on the ground. Loosen any tight clothing and rest your hands in your lap. Relax and breathe deeply and rhythmically. In. Out. Each time you breathe in, envision yourself...
Mind >> Meditation
- Love and Clarity
- Literally any state of mind may be created or enhanced within. It is commonly assumed that our thoughts and feelings are difficult, if not impossible, to change at will. But this is not so. The meditator soon realizes that it is they who are primarily...
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- A Treatise on Astral Projection, Part 4: More Rope Techniques
- ROPE is a very effective projection technique, but it still has to be learned to be effective. I would like to elaborate on a couple of points about the technique, inspired by the feedback I have received so far. There is NO visualization required - AT ALL -...
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- Thailand's Universal Eye Screening in Action
- Thailand's new nationally-approved program for testing and treating children with vision impairment exemplifies the shift in the global health agenda from the Millennium Development Goals (MDGs) to the Sustainable Development Goals (SDGs). ...
- Newly launched mobile eye-test device could lead to prescription virtual
- In July, the startup launched Blink, an on-demand refractive test service in New York, where employees bring the Netra device to people's homes. In India, EyeNetra has launched Nayantara, a similar program to provide low-cost eye tests to the poor and ...
- Eating This Daily May Decrease Glaucoma Risk
- 14, 2016 (HealthDay News) -- Eating green leafy vegetables daily may decrease the risk of glaucoma -- a serious eye disease -- by 20 percent or more over many years, a new study suggests. "We found those consuming the most green leafy vegetables had ...
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Mimics of Cutaneous LymphomaReport of the 2011 Society for Hematopathology/European Association for Haematopathology Workshop
The Society for Hematopathology and European Association for Haematopathology workshop, from October 27 to 29, 2011, in Los Angeles, CA, exhibited many exemplary skin biopsy specimens with interesting inflammatory changes mimicking features of cutaneous lymphoma. This article reviews features observed in cutaneous lymphoid hyperplasia, cutaneous drug reactions, lupus-associated panniculitis, pityriasis lichenoides, hypereosinophilic syndrome, histiocytic necrotizing lymphadenitis, traumatic ulcerative granuloma with stromal eosinophils, and pigmented purpuric dermatosis, as well as a brief review of the pertinent literature and discussion of submitted conference cases. For the pathologist, it is important to be aware of diagnostic pitfalls as well as the limitations of ancillary testing (eg, clonality studies). Finally, correlation with total clinical information, good communication with clinical colleagues, close clinical follow-up with rebiopsy, and prudent use of laboratory studies are vital and will likely offer the best path toward a correct diagnosis.
- Lymphoma
- Cutaneous
- Mimic
- Pseudolymphoma
- Histopathology
- Immunohistochemistry
The Society for Hematopathology and European Association for Hematopathology (SH/EAHP) Workshop convened at the Ritz-Carlton Hotel, Marina del Rey, CA, from October 27 to 29, 2011, and featured world-renowned experts in the fields of hematopathology, dermatopathology, and dermatology. Attendees were encouraged to submit difficult or interesting cases, of which 200 cases were selected by the expert panel and presented at the meeting. Cases submitted were of the following types: cutaneous B-cell lymphomas, mycosis fungoides (MF), nonmycosis fungoides, cutaneous T-cell lymphomas, other lymphohistiocytic malignancies of the skin, and reactive lymphoproliferations of the skin mimicking cutaneous lymphomas (as discussed in this article).
Although still relatively rare, skin is second only in frequency to the gastrointestinal tract as the most common extranodal non-Hodgkin primary lymphoma site.1,2 There exists considerable histopathologic overlap between the features of B-cell and T-cell lymphoma and many of the inflammatory dermatoses. Therefore, distinguishing "reactive" histologic patterns from those of lymphoma is often very difficult. This article discusses several of the important mimics of cutaneous lymphoma as observed and highlighted within the 2011 SH/EAHP Workshop, their possible causes, and distinguishing clinical and histopathologic features, as well as submitted cases and a brief review of the current literature.
Cutaneous Lymphoid Hyperplasia
Cutaneous lymphoid hyperplasia (CLH; aka lymphocytoma cutis, lymphoadenoma benign cutis, and pseudolymphoma) is most commonly assigned to those cases lacking a sufficient array of accepted malignant findings.3 CLH is believed to be the result of some often unknown, outward cause (eg, tattoo, vaccination, arthropod bite/sting, drug, or infection).4,5 Of note, 1 submitted workshop case showed the finding of reactive lymphoid hyperplasia following treatment with leeches (hirudotherapy)—a very uncommon but nonetheless reported phenomenon.6
Clinically, cases of CLH typically exhibit a range of findings that may mimic those seen in cutaneous lymphoma. Cases may present as nodules, plaques, or papules and are most often identified on the head, neck, trunk, and extremities.7 Indeed, submitted cases labeled as CLH, reactive lymphoid hyperplasia, or atypical lymphoid proliferation by the expert panel revealed a similar body distribution, with the majority of cases identified in 1 or 2 body sites, including head and neck, extremities, and trunk. One submitted case showed lesions in all 3 regions. As expected, a range of clinical presentations was reported, including single nodules, plaques, multiple pruritic papules, or a rash-like presentation. Of note, 2 cases submitted as likely "reactive" lymphoid infiltrates, but subsequently labeled malignant by the expert panel, were described as more deep-seated masslike lesions at initial presentation.
Histologically, CLH is typically described as lymphocyte predominant (both B and T cells) with a nodular or diffuse pattern within the dermis, often with accompanying conspicuous inflammatory cells (including histiocytes, eosinophils, and plasma cells).7 Additional features include an obvious grenz zone separating uninvolved epidermis from underlying inflammation, lymphoid follicles with or without a well-formed mantle zone, associated tingible-body macrophages, a wedge shape to the inflammatory infiltrate, sharp circumscription of lymphoid aggregates, and a "pushing" border.8 Of note, however, some features classically suggestive of malignancy, including "epidermotropism" of lymphocytes and a more diffuse or "bottom-heavy" infiltrate, may also be observed in some cases of CLH Image 1.8,9
The majority of submitted workshop cases ultimately labeled as CLH, reactive lymphoid hyperplasia, or atypical lymphoid hyperplasia/proliferation showed many common findings of CLH, including a well-defined inflammatory infiltrate, an obvious grenz zone, and a polymorphous infiltrate. Of note, 1 case submitted as "florid cutaneous lymphoid infiltrate—favor reactive" and subsequently labeled by the expert panel as "primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma" revealed a combination of "benign" features, including sparing of epidermis and adnexa by a vaguely nodular infiltrate of predominantly small- to medium-sized lymphocytes admixed with conspicuous eosinophils. Similarly, another submitted case initially called "atypical lymphoid hyperplasia" and subsequently labeled by the expert panel as "cutaneous lymphoid hyperplasia with progression to primary cutaneous follicle center lymphoma" showed a dense but fairly well-delineated lymphoid infiltrate with lymphoid follicles and a well-developed grenz zone, without epidermotropism or observed infiltration of the follicular epithelium. Therefore, changes historically suggestive of benignity may also be seen in cases of low-grade or evolving lymphoid malignancy.8 Indeed, additional ancillary studies are most often required to arrive at the best diagnosis.
Immunohistochemistry typically reveals a predominance of CD3+ T lymphocytes and a subpopulation of associated CD20+ B lymphocytes. In cases with well-defined germinal centers, expected central zones of CD20+ B cells with surrounding CD3+ T cells are seen.7 Well-formed germinal centers retain cells with positive staining for BCL6 and CD10.10 CD68 will highlight associated tingible-body macrophages, and S-100 and/or CD1a will highlight well-dispersed dendritic cells. Associated plasma cells should not exhibit either κ or λ light chain restriction, and coexpression of CD20 and CD43 by constituent B cells is not expected.9,11 Similarly, coexpression of BCL2 by germinal center cells is not seen.8 Immunostaining for CD21 to highlight follicular dendritic meshworks in B-cell nodules may be useful in detecting aberrant patterns (eg, colonization or disruption).
Of note, CD7 may exhibit moderate loss despite other features of overall benignity.11 Submitted workshop cases ultimately labeled as CLH by the expert panel showed similar benign staining patterns to those described earlier. Of note, 1 submitted case showed a somewhat peculiar pattern of predominantly CD8+ T cells on a middle-aged man's ear for 6 months that simulated CD8+ cutaneous T-cell lymphoma; however, the lesion abated following biopsy without recurrence and was considered a form of rare "indolent CD8-positive lymphoproliferative disorder of the ear."12 (Note: this disorder is summarized in "Nonmycosis Fungoides Cutaneous T-Cell Lymphomas," by Quintanilla-Martinez et al,13 in this issue of the journal.)
Molecular testing to evaluate lymphocyte clonality has become fairly routine and may offer additional useful information. However, clonality may also be seen in a small subset of CLH cases.7,10,14 Although not diagnostic of malignancy, demonstration of clonality has been correlated with evolution to lymphoma.14 Of the submitted cases, most did not undergo molecular analysis or reveal a polyclonal population of constituent lymphocytes. Interestingly, 2 cases submitted initially as "likely reactive" and subsequently labeled as "primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma" and "CLH with progression to primary follicle center cell lymphoma" showed clonal lymphocyte populations per T-cell gene rearrangement studies.
Submitted cases ultimately labeled by the expert panel as "atypical lymphoid hyperplasia" or "atypical lymphoid proliferation" showed findings suggestive of evolving malignancy, including dense superficial and deep lymphoid infiltrates of small- to intermediate-sized lymphocytes with some atypia, as well as a positive T-cell gene rearrangement in 1 case. However, other supporting features of malignancy, including aberrant immunostaining patterns or systemic findings, were not apparent. In cases of uncertain malignancy, an overall air of caution was advised. In such cases, close clinical follow-up and rebiopsy are typically recommended. Of note, 1 submitted case was thought likely due to the patient's longstanding phenytoin therapy, a well-known cause of cutaneous drug reactions (further discussion to follow).
Cutaneous Drug Reactions
Cutaneous drug reactions are some of the most common inflammatory reactions observed in skin, with 10% to 20% of patients seen in the hospital setting and greater than 7% of the community outpatient population affected.15 Adverse reactions to drugs include a range of clinical manifestations, including photosensitivity, urticarial reactions, morbilliform or diffuse rashes, and even marked erythroderma. Drug reactions may mimic the findings of cutaneous T-cell and B-cell lymphoma both clinically and histopathologically (termed pseudolymphoma) and, therefore, careful examination and correlation of all pertinent diagnostic and clinical information are paramount.16
The morbilliform or exanthematous type of drug reaction is the most common clinically reported drug-related eruption (>50%).17–19 More prototypical histopathologic clues include (1) conspicuous eosinophils, (2) associated plasma cells (within some reactions), (3) associated necrotic keratinocytes/dyskeratosis, (4) urticarial-type dermal edema with mast cells, (5) extravasated erythrocytes, and (6) associated "activated" lymphocytes, which may appear cytologically atypical. Importantly, the array of histologic patterns observed with drug reactions is large and may mimic literally any inflammatory dermatosis—for example, pustular, eczéma-tous, vesiculobullous, vasculitic, lichenoid, lymphomatous, and sclerodermoid (as reviewed in Justiniano et al17 and Ramdial and Naidoo20).
One workshop case submitted as a possible drug or transfusion reaction, and subsequently labeled by the expert panel as "reactive CD30+ lymphoid proliferation associated with marrow reconstitution," showed several key findings typically observed with the morbilliform-type drug reaction, including conspicuous eosinophils and associated, overlying epidermal acanthosis and spongiosis.21 In fact, polyclonal infiltrates of enlarged CD30+ activated lymphocytes may be seen in a range of inflammatory or reactive conditions, including drug eruptions, arthropod bite reactions, and viral infections.22,23 The presence of increased numbers of CD30+ lymphocytes should raise suspicion for the possibility of CD30+ lymphoproliferative disease (including the clinically benign variant lymphomatoid papulosis [LyP]). Although discussion of this group of diseases extends somewhat beyond the scope of this review, it is important to note that a diagnosis of LyP is typically accompanied by a fairly characteristic clinical picture of recurrent, regressing papules and nodules, often in crops, that often become necrotic and scar.24 In addition, use of fascin immunohistochemistry has been shown to be more often positive in CD30 lymphoproliferative disease with a tendency to evolve to lymphoma (LyP type C) vs more indolent forms of the disease (LyP types A and B), which may add additional useful diagnostic information in difficult cases.25
The lichenoid drug eruption, in which a lymphocytic infiltrate is observed within a fairly dense, band-like configuration in superficial dermal tissues and involving overlying epidermis, is common and may raise suspicion for lymphoma. In addition, mild epidermal spongiosis with parakeratosis, exocytosis of lymphocytes, dermal edema, and extravasated erythrocytes may be seen (as reviewed in Justiniano et al17 and Ramdial and Naidoo20). Close examination of the superficial papillary dermis may show incontinent melanin pigment or even melanophages—the result of melanin release from damaged basilar keratinocytes. Associated dermal blood vessels may show perivascular lymphocytic inflammation with intramural lymphocytes and endothelial swelling (so-called lymphocytic vasculitis).26
As a result of the many similar histopathologic features, the lichenoid drug eruption is most apt to mimic cutaneous T-cell lymphoma/MF and prompt additional special studies, including immunohistochemistry, which often reveals a T-cell–rich superficial infiltrate. CD4+ T-helper lymphocytes with atypical cytomorphology may be seen within the overlying epidermis and may mimic the epidermotropism characteristic of MF. In addition, the CD4 to CD8 ratio (CD4:CD8) may be elevated, and loss of immunostaining for pan–T-cell marker CD7 may also be seen. To further confound matters, increased numbers of enlarged and activated CD30+ lymphocytes—occasionally in great numbers—may be seen in some cases27 (and as reviewed in Ploysangam et al28).
Conventional wisdom has suggested that benign inflammatory conditions are composed of polyclonal aggregates of "reactive" lymphocytes. However, study in recent years has shown that clonal populations of lymphocytes (both B cell and T cell) may be demonstrated via gene rearrangement studies within cutaneous drug reactions. Debate persists as to whether the finding of clonality is an indicator of evolving lymphoid malignancy or a sort of "reactive lymphomatoid dermatitis," as postulated by Magro and colleagues.27 One difficult submitted case showed a dense lichenoid infiltrate with epidermotropism, associated spongiosis, and a somewhat mixed infiltrate (T cell > B cell, with admixed plasma cells and histiocytes), possibly due to an ingested or topical drug administration. The positive T-cell gene rearrangement study in this case, however, is of unknown significance, and the expert panel prudently labeled this lesion as an "atypical lymphoid proliferation" Image 2.
Indeed, pseudolymphoma may be caused by administering certain types of drugs, classically antiepileptic drugs such as phenytoin and carbamazepine (as reviewed by Harris et al29).30 Other causative drugs include valproate, atenolol, griseofulvin, imatinib, angiotensin-converting enzyme (ACE) inhibitors, allopurinol, cyclosporine, levofloxacin, antihistamines, and analgesics.31,32 Antidepressant drugs are especially associated with pseudolymphoma and may mimic B-cell lymphoma. In particular, fluoxetine may be associated with clonal B-cell lymphoid proliferations, and atypical lymphoid hyperplasia may progress to frank marginal zone lymphoma. Fluoxetine and other antidepressants may exert marked immune dysregulating effects, including a reduction in T-cell proliferation. This suppressive effect on T-cell function may lead to overresponsiveness of B cells to unknown antigens, which in turn may foster antigenically responding B-cell clones, possibly a critical event in B-cell lymphomagenesis.33,34 Interestingly, 2 submitted cases dramatically illustrated a "lymphomatoid reaction" and "benign lymphoid hyperplasia," most likely secondary to ongoing sertraline (Zoloft) therapy (Image 2). Ultimately, the diagnosis of drug-associated pseudolymphoma is established based on the resolution of skin lesions with cessation of drug therapy, which may take weeks or even months.27,31,33
Finally, an inflammatory disorder may occur with reexposure following prior sensitization to a particular allergen. Rarely, contact dermatitis may simulate MF histologically (so-called lymphomatoid contact dermatitis).35,36 As these lesions progress, psoriasiform change, often with spongiosis, dermal fibrosis, overlying scale crust, hyperkeratosis, and parakeratosis, may be seen. Most cases result from contact with chemicals or metals, such as nickel or gold.37,38 However, numerous offending agents have been reported that may produce lymphomatoid reactions, including such diverse items as resin in treated leather, constituents of ophthalmic preparations, ingredients in baby wipes, emulsifiers in shampoo, teak wood, and the striker portion of matchboxes.35,39–42 Gene rearrangement studies often reveal a polyclonal population of lymphocytes; however, rare clonal T-cell gene rearrangements have been reported.31 Although long thought to be less frequent than irritant contact dermatitis, with use of better clinical studies (including more sensitive patch testing), an increasing prevalence of allergic contact dermatitis has been suggested.43
Lupus-Associated Panniculitis
Lupus-associated panniculitis (LEP) is a rare variant form of lupus erythematosus, which affects predominantly middle-aged female patients (ages 30–60 years). Lesions consist primarily of plaques, typically observed on the upper trunk, face, and buttocks44 (reviewed by Crowson and Magro45). Considerable overlap exists between the clinical presentation and susceptible patient populations of both LEP and subcutaneous panniculitis-like T-cell lymphoma (SPCTL), including the distribution and clinical appearance of lesions.46,47
Histopathologically, LEP typically shows a dense lobular infiltrate of lymphocytes, admixed with plasma cells and histiocytes, with thickened adjoining fibrous septa and hyalinized fat necrosis. Although some disagreement persists as to specific criteria used to diagnosis LEP, the findings of lymphocytic nuclear dust within the associated plasmalymphocytic infiltrate of involved fatty lobules, in addition to well-formed lymphoid follicles with germinal centers, are considered by some to be clues for the diagnosis of LEP (as reviewed by Crowson and Magro45 and Requena and Sanchez Yus48). Of note, so-called rimming of adipocytes by lymphocytes—classically known as a distinguishing feature of SPCTL—may also be observed in cases of LEP; however, in contrast to only atypical lymphocytes in cases of SPCTL, Massone et al47 observed adipocyte "rimming" in cases of LEP by lymphocytes, plasma cells, and histiocytes Image 3.47 However, Crowson and Magro45 warn that cases of LEP may show significant lymphocyte atypia, making distinction between LEP and SPCTL often very difficult. Associated interface dermatitis (characteristic of lupus) may be seen and offer additional supporting evidence of benignity; however, this finding may be absent in up to 50% of cases.47,49
Submitted cases subsequently labeled by the expert panel as consistent with LEP showed a range of findings, including the features of LEP as described above (Image 3). Of note, 1 submitted case showed extension of marked lobular inflammation into surrounding fibrous septa (deemed "mixed lobular and septal panniculitis"), which may be observed in established cases.47 Similarly, although 1 patient was known to have Epstein-Barr virus (EBV)–positive diffuse large B-cell lymphoma, the expert panel concluded that the somewhat disparate findings observed in the subcutaneous biopsy specimen (including a mixture of T lymphocytes and histiocytes, rimming of adipocytes by T cells, and virtual absence of associated B cells) were most suggestive of a reactive panniculitis, likely due to the patient's ongoing EBV infection.
Immunohistochemical analysis is required when attempting to discern LEP from SPCTL. As in SPCTL, lymphocytes observed in LEP are typically CD8+; however, the number and extent of CD8+ T cells seen in LEP are typically not as great as in cases of SPCTL.47 Staining for pan–T-cell markers CD5 and CD7 is observed and may be somewhat diminished.44 CD20 will highlight small clusters or scattered B cells.46,50 Ki-67 (MIB-1) may assess the degree of constituent lymphocyte proliferation, with higher rates (often exceeding >50% of cells) considered additional evidence for lymphoma.51 Molecular studies may be employed to discern tumor cell clonality; however, LEP cases may exhibit clonal lymphoid populations in a minority of cases, and this result should be interpreted with caution.44 Submitted workshop cases showed a T-lymphocyte–predominant infiltrate without evidence of clonality. Some cases showed typical CD8-predominant T-cell infiltrates, whereas others showed a CD4+ T-lymphocyte–predominant inflammatory response, perhaps due to the proposed EBV reaction or the mixed nature of the observed, ongoing panniculitis.
Finally, because of the considerable clinical and histopathologic overlap between LEP and SPCTL, studies by Magro and colleagues44,52 support the notion that a continuum exists between these entities, with "atypical" variants and premalignant dyscrasias. In fact, a growing number of reported cases closely mimicking LEP, but ultimately demonstrating a malignant course, further highlight the likelihood of this proposition.51,53 With that said, it is important to note that the coexistence of SPCTL and LEP has been reported as well.54
Pityriasis Lichenoides
Pityriasis lichenoides (PL) is an uncommon, self-limited dermatosis of disputed histogenesis with a spectrum of clinical and histopathologic findings. Pityriasis lichenoides et varioliformis acuta (PLEVA) is an acute disorder with characteristic hemorrhagic papules that resolve to leave variably shaped scars. Pityriasis lichenoides chronica (PLC) is a subacute or chronic disorder characterized by small, scaly, red-brown maculopapules (as reviewed by Fernandes et al55). The distinction between PLEVA and PLC is not always clear-cut, and a continuum of findings with some degree of overlap is often observed.
PL exhibits a predilection for male patients in the second and third decades of life (although cases in children may also be seen). Crops of lesions, which vary in number, are most commonly identified on the trunk and/or flexor surfaces of the proximal extremities. The duration of disease is typically weeks to months and may recur.56–58 Rare cases of PL will progress to lymphoma, and MF is the most common lymphoproliferative disorder to occur in association with PLEVA/PLC.59
The cause of PL is unknown. However, cell-mediated and/or immune complex–mediated causes are postulated, possibly related to viral or other infections. Proposed associations include EBV, parvovirus B19, toxoplasma, Streptococcus, Staphylococcus, herpes viruses, and HIV infections, among others (as reviewed by Fernandes et al55). A relationship of PL to LyP has been proposed but remains somewhat controversial; however, these entities are more than likely pathogenically distinct.60 In fact, Kempf et al61 recently described what they believe to be a variant of PLEVA with a prominent CD30+ cell component. Some experts still believe, however, that PLEVA/PLC and LyP reside within a similar spectrum of often clonal T-cell lymphoproliferative disorders.62,63
The histologic changes of PLEVA include those of interface dermatitis, with basal vacuolar degeneration and a sparse to moderately dense lymphocyte-predominant, superficial, and, typically, deep perivascular inflammatory infiltrate.56–58,64 Scattered necrotic keratinocytes within the epidermis, not seen in direct association with atypical lymphocytes, are considered by some to be a feature that distinguishes inflammatory "reactive" dermatoses from lymphoproliferative disorders.57 Both PLEVA and PLC may show scattered, enlarged atypical lymphocytes within the inflammatory infiltrate. Although cases of PLC typically exhibit less overall inflammation than PLEVA, a greater degree of lymphocyte atypia, as well as epidermotropism and Pautrier-like pseudo-abscesses, may be observed—all changes that mimic the findings of MF.58 Of note, 1 submitted case showed histopathologic findings of MF, including apparent epidermotropism of lymphocytes. Close examination, however, revealed additional histologic features that supported an inflammatory etiology, including rare necrotic keratinocytes, associated spongiosis, orthokeratosis/hyperkeratosis, parakeratosis with intracorneal neutrophils, and an overall lack of atypia among the epidermotropic lymphocytes Image 4.
Immunohistochemistry often reveals a T-cell–predominant dermal inflammatory infiltrate. Of note, a majority of CD8+ T-suppressor/cytotoxic cells are seen in cases of PLEVA, whereas CD4+ T-helper cells predominate in cases of PLC, particularly in those cases with progression to MF.57 In addition, loss of CD7 by the large majority of T cells—a fairly characteristic feature of MF—may be observed in cases of PL.57 Scattered, enlarged CD30+ lymphoid cells may be seen as well and may further raise suspicion for CD30+ lymphoproliferative disorder.60 One submitted workshop case showed a superficial and deep dermal lymphohistiocytic infiltrate, including some enlarged CD30+ lymphocytes within areas of crusting, ulceration, and marked reactive epidermal changes. T cells in this case were CD8 predominant with some aberrant loss of CD5 immunoreactivity. Of note, the most unusual finding in this case was the T-cell receptor γ positivity. Although the possibility of lymphoid malignancy was entertained, the pathologists in this case assessed all available clinical and pathologic information to arrive at the most prudent diagnosis of PLEVA.65 Moreover, a diagnosis of LyP was considered for this case and is perhaps the most likely diagnosis.
Monoclonal populations of T cells may be observed in both PLEVA and PLC.57,58,63,66,67 Observed monoclonality of constituent lymphocytes has been reported to be greater in cases of PLEVA vs PLC (approximately 60% vs 10%, respectively).67 A subsequent study by Magro et al57 examining only cases of PLC, however, found the number of clonal proliferations closer to that described for PLEVA (approximately 52%). Regardless of relative frequency, this fairly consistent finding of clonality within both PLEVA and PLC has led Magro and colleagues58 to include PL within the classification of "T-cell dyscrasias."
Hypereosinophilic Syndrome
Hypereosinophilic syndrome (HES) is a somewhat peculiar entity and is reported to have associations with lymphoma and leukemia (as reviewed by Weller and Bubley68). However, the most damaging sequelae most often arise from blood and end-organ damage—heart, lung, central nervous system, and skin—all secondary to marked eosinophilia and subsequent release of eosinophilic granules (as reviewed by Gleich and Leiferman69).
Myeloproliferative and lymphocytic variants of HES have been described. In addition to end-organ damage caused by peripheral eosinophilia, myeloproliferative and lymphocytic variants both share the possibility of developing myelogenous (myeloid leukemia, "chronic myelogenous leukemia-like disease," or eosinophilic sarcoma) or lymphoid malignancy (peripheral T-cell lymphoma), respectively.70
Skin may be affected in up to 50% of HES cases and typically manifests as urticarial or erythematous papules, nodules, or plaques. Histologically, lesions show a superficial or deep mixed inflammatory infiltrate, as well as a prominent population of eosinophils without vasculitis (as reviewed by Weller and Bubley68). Of note, clonal populations of constituent T lymphocytes (either CD4 or CD8 predominant) and a reduction in expression of CD2, CD5, and CD7 have been documented in cases of HES, with a subset of these patients ultimately diagnosed with T-cell lymphoma.71 One submitted workshop case showed similar histopathologic features, with small and large atypical lymphocytes Image 5. Although flow cytometry, fluorescent in situ hybridization, and cytogenetic analyses were all negative, a positive T-cell gene rearrangement study revealed evidence of T-cell clonality. This case was submitted and confirmed by the expert panel as the lymphocytic variant of HES.
Kikuchi-Fujimoto Disease
Kikuchi-Fujimoto disease (KFD; aka histiocytic necrotizing lymphadenitis) is a benign, self-limited, fairly acute disease of unknown etiology that most commonly affects women of Asian descent. Patients typically present with cervical lymphadenopathy, local tenderness, fever, and sweats, and cutaneous involvement has been described (as reviewed by Bosch et al72). Although considered idiopathic, several causes have been suggested, including neoplasia and infection (HIV, human herpesvirus 8, cytomegalovirus, Giardia, and hepatitis C, among others).73,74 Awareness of this rare disease is important because of its propensity to mimic malignant lymphoma clinically.
Characteristic histopathologic features of KFD include effacement of normal lymph node architecture, large areas of paracortical necrosis, and associated karyorrhectic debris. A range of cell types is seen, including small and large lymphocytes, histiocytes, and plasmacytoid dendritic cells. Immunoblasts are also identified, which may appear atypical. Neutrophils are not seen and plasma cells are typically scarce (as reviewed by Bosch et al72). Cutaneous lesions may show changes of interface dermatitis (erythema multiforme or lupus-like) or more nonspecific inflammatory changes with underlying perivascular lymphocyte-predominant inflammation.75,76 Similar to what is observed within an affected lymph node, abundant karyorrhectic debris may also be identified.77 Immunohistochemical analysis typically shows a majority of CD3/CD8+ T lymphocytes.78 Associated histiocytes express CD68, myeloperoxidase (MPO), and CD123.79 Plasmacytoid dendritic cells express CD123, CD4, and CD68 but are generally negative for MPO.80,81
Submitted cases nicely demonstrated the typical cutaneous changes of KFD consistent with lymphocyte-predominant interface dermatitis (mimicking the changes of lupus) with associated enlarged and atypical-appearing lymphocytes Image 6. Immunohistochemical staining of skin revealed a T-cell–predominant infiltrate with numerous CD68+ histiocytes. Subsequent lymph node biopsy specimens showed changes most consistent with KFD, including a CD8-predominant T-cell infiltrate with numerous CD68+ histiocytes. The expert panel concurred with changes associated with KFD.
Traumatic Ulcerative Granuloma With Stromal Eosinophils
Traumatic ulcerative granuloma with stromal eosinophils (TUGSE) is a rare benign condition of the oral mucosa that may mimic CD30+ lymphoproliferative disease. Histologically, TUGSE lesions exhibit a mixed inflammatory infiltrate that may extend deeply into underlying tissues, including numerous eosinophils, associated histiocytes, and plasma cells, as well as a variable population of enlarged lymphoid cells. A key immunohistochemical finding is often positive staining for CD30 within enlarged lymphoid cells, which typically raises concerns for the possibility of anaplastic large-cell lymphoma.82 In fact, subsequent molecular studies often demonstrate a clonal proliferation, which may further confound the diagnosis or lead to an erroneous "confirmation" of malignancy.82,83 Submitted cases ultimately labeled consistent with TUGSE by the expert panel shared similar clinical and histopathologic features, including quickly growing oral mucosal lesions with a population of enlarged lymphoid cells in a background of mixed inflammation, including histiocytes, plasma cells, and numerous eosinophils Image 7. Of note, 1 submitted case showed a clonal T-cell gene rearrangement by polymerase chain reaction (PCR).
Pigmented Purpuric Dermatosis
Finally, pigmented purpuric dermatosis (PPD) is considered by the authors as worthwhile because of the increasing evidence linking this group of disorders to cutaneous lymphoma. There are a number of known and proposed causes for the various forms of PPD. Various systemic diseases, including rheumatoid arthritis, liver disease, lupus erythematosus, lymphoid malignancy, and hyperlipidemia, have all been associated with PPD. Drugs, including nonsteroidal anti-inflammatory drugs, lipid-lowering medications, and interferon, are known common causes of PPD (as reviewed by Sardana et al84). In addition, several drug classes, including calcium channel blockers, ACE inhibitors, lipid-lowering agents, β-blockers, antihistamines, and antidepressants, may produce a histologically atypical pigmented purpura with T-cell clonality.85
Despite the many described clinical variants, all forms of PPD share similar histopathologic changes. Perivascular lymphocytic inflammation, extravasated erythrocytes, and characteristic (but variable) hemosiderin pigment are identified, either lying free or within associated macrophages or dendritic-appearing histiocytes. Variant-specific changes, including obvious neutrophils within the inflammatory infiltrate and obvious associated spongiosis (itching purpura), an overall predominant lichenoid pattern within the superficial dermal inflammatory infiltrate (Gougerot and Blum), or a thin grenz zone separating uninvolved epidermis from dermal inflammation (lichen aureus), may help to distinguish borderline cases or those with limited clinical history histopathologically (as reviewed by Sardana et al84) Image 8.
Obvious overlap exists between cutaneous T-cell lymphoma and the changes observed within PPD. MF, in fact, may even present clinically with purpuric lesions.86–88 The histopathologic findings observed within PPD may mimic more classical features of MF, including epidermotropism, pseudoPautrier abscesses, and "lining up" of lymphocytes along the dermal-epidermal junction, as well as obvious irregularity of nuclear membrane contours of associated lymphocytes.86,88,89
In such borderline cases, immunohistochemical studies may offer additional helpful information. A CD8-predominant lymphocytic infiltrate, although positive in a subset (approximately 20%) of early MF cases, is commonly considered an indicator of benignity.88 However, immunostaining may be of only limited use, as cases of PPD may share a profile similar to that of MF, including a CD4-predominant population of constituent lymphocytes.84,88 Diminution of staining for CD7, a common finding in cases of MF, may also be seen in cases of PPD; however, this finding was less marked when compared with those cases demonstrating other supportive features of MF, such as monoclonality.88
As expected, PPD may also exhibit monoclonality of constituent lymphocytes.86 A study by Crowson et al85 demonstrated a drug-related cause for cases of "atypical pigmented purpura," some of which demonstrated clonality. Similarly, in a study of 23 cases of lichen aureus, although one half demonstrated a monoclonal gene restriction, no cases progressed to lymphoma in 5 years.90
A follow-up study by Magro et al88 showed that 21 of 43 patients with PPD had clonally restricted molecular profiles via PCR analysis. Eight of these patients progressed to cutaneous T-cell lymphoma, each of whom was known to have taken a drug previously implicated as a trigger for PPD or drug-induced reversible T-cell dyscrasia. Although not a reliable marker of malignancy, the finding of clonality within lymphocytes, in conjunction with associated atypia of constituent lymphocytes—including "cerebriform" nuclear contours—was more commonly identified within cases of MF by Magro et al. Similarly, cases exhibiting clonality were CD4 predominant (vs CD8) and showed marked loss (often >90%) of CD7 in comparison to cases of polyclonal PPD.
A growing number of experts believe that PPD truly represents a form of T-cell dyscrasia that falls within the spectrum of cutaneous T-cell lymphoma.85,86,88,91 Therefore, extreme caution is advised when examining a purpuric eruption, particularly those in which no known cause is suspected clinically or when the clinical presentation is atypical and concerning.
Caution must be taken when faced with an atypical lymphocytic infiltrate in a cutaneous biopsy specimen. Drug reactions are fairly commonplace—perhaps even underreported—and ingestion of drugs and chemicals may cause a wide range of both benign and atypical skin disorders. Numerous pathologic entities show many overlapping features with lymphoma, and familiarity with these entities is vital. When in doubt, good communication with clinical colleagues, including a comprehensive past medical history, description of the clinical presentation, and a thorough review of the patient's current and past drug regimen, is invaluable. Overreliance on pathologic studies, in contrast, may offer somewhat misleading clues and, therefore, all ancillary information should be interpreted within the overall clinical context of each case. In particular, observed clonality within lesional lymphocytes should not be considered as unequivocal evidence of malignancy. In fact, use of positive serial gene studies at separate anatomic sites has been used as additional evidence of malignancy with a fairly high sensitivity in 1 study.92 This, too, suggests that negative gene studies separated anatomically and temporally would likely offer additional evidence of a reactive lymphoid process. With that said, it remains important that all diagnostic information be evaluated and used within the overall individual clinical context. When in doubt, the dermatopathologist or hematopathologist is well advised to show a measure of restraint. Often, close clinical follow-up with rebiopsy will reveal natural involution of lesions and resolution of clinical symptoms/signs.
Upon completion of this activity you will be able to:
identify benign mimics of lymphoma in skin.
understand key histopathologic findings of benign lymphoma mimics in skin.
understand what ancillary studies are used in the diagnosis of skin lymphohistiocytic proliferations.
The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.
The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.
Questions appear on p 553. Exam is located at www.ascp.org/ajcpcme.
- © American Society for Clinical Pathology


text:
Varian said that xoma plans on collecting results for all poc's before they decide which indication to pursue, if any. clearly, xoma is following the lead of anakinra carved through the mountainous terrains in search of an indication they will work on. For example, in regards acne vulgaris:
"The TNF-a inhibitor infliximab and anakinra are investigational drugs in these severe forms and show promising effects"
Maybe the question is what if one or more of the poc's shows enough promise to continue? What should xoma do? Will xoma really put a promising indication on the backburner when they are so starved for revenue?
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On the 11/07/2012 audio varian estimated poc #3 would be announced in 4-6 weeks which puts the announcement between 12/5 and 12/19, so within the next 2 weeks we should find out what the mystery is.
Did you hear in the same audio Varian mentioned aceon had sales of $150M outside the u.s.? Varian also said that it is a relatively new product which is showing good sales growth.
Xoma should get aceon combination approval (assuming 12 months review period) by the beginning of 2014. Xoma has enough cash to get through 2014. Xoma should muster more cash [than present aceon figures) all through 2014.
In the same audio, Varian estimates tests of xmeta, and xmets should be complete with higher animals in 12-18 months which puts us at the latest of mid 2014. xmetd should also be ready for beginning trials by mid 2014. Hopefully, xoma can auction license/development agreements before the end of 2014.


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|Gamma irradiation
|Gasos d'efecte hivernacle -- Aspectes ambientals
|Genètica microbiana
|Genetic engineering
|Greenhouse gases -- Environmental aspects
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|Heavy metals
|Heavy metals -- Absorption and adsorption
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|Hortalisses -- Malalties i plagues
|Interdisciplinarietat en l'ensenyament
|Interdisciplinary approach in education
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Campground, RV Park & Resort Insurance
|The Resort & Campground Insurance Program has been specifically designed for thousands of recreational businesses throughout the United States. Our comprehensive campground insurance program gives you the ability to combine broad property, liability, commercial auto, bonds, workers compensation and umbrella coverage with low preferred rates.
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|Allen Financial Insurance Group © Copyright 2007, 2016


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Fixed PriceDelivery by April 4, 2014
I need a power MTA expert for my Email Marketer Tool.
I already have following things:
Email Marketing Script
High Configured Linux Dedicated Account with CentOS6
10 Whitelisted Fresh PIs
Root SSH Access
I also have a copy of Power MTA 3.5 and 4.
I need a person who is an expert in Configuring Power MTA in any Linux Dedicated Server.
Your Duty for this job is:
1. Configure the Power MTA in my servers that works in all domain that is hosted
2. Setup the 10 IP rotation
3. Setting up Feedback loop
You will work with us full-time in setting up PMTA on many servers for us on daily bases, about 1 server per day, apply with a FLAT RATE how much you will charge us MONTHLY for this work and support, we will consider the lowest bidders from India, Pakistan, Philippines and the rest of the world, so don't bid too high and be fair.
at the starting of your quote you need to add the word " LLADAERI " in reverse so I see that how many geniune bidder or freelance are available for this job.
About the Client
Thornhill 05:41 AM
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Total Spent
118 Hires, 6 Active
Avg Hourly Rate Paid
11,331 Hours


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The Earth and Environmental Sciences Area has several world-class instrumentation, analytical, and simulation resources that support and augment many research programs within the Area. Many of these resources are also available to collaborators, Berkeley scientists, and visiting researchers. A few of these resources are widely used to support cross-Division research.
Berkeley Synchrotron Infrared Structural Biology Program
The Berkeley Synchrotron Infrared Structural Biology Program is uniquely located on the roof blocks of the Advanced Light Source linac and beamline test facility and has the capability to advance the imaging of living microbes with space available for the biological equipment necessary to grow and prepare living specimens immediately next to the Fourier transform infrared microscopes.
Center for Computational Geoscience
The Center for Computational Geoscience maintains a state-of-the-art computing environment in support of various seismological and geophysical research programs, in particular the development of new methods for imaging the subsurface and its processes, and methods for visualizing results.
Center for Isotope Geochemistry
The Center for Isotope Geochemistry (CIG) is a joint-institution research center, with labs both at LBNL and UC Berkeley. This state-of-the-art analytical facility has the capabilities to measure the concentrations and isotopic compositions of elements in rocks, minerals, and fluids in the earth's crust, atmosphere, and oceans.
Geosciences Measurement Facility
The Geosciences Measurement Facility has an extensive inventory of commercial and world-unique equipment, as well as a staff that can support a variety of laboratory and field research activities. Engineers and technicians develop novel instrumentation and field methods, carry out field experiments, and perform project management associated with subsurface, terrestrial, atmosphere, and ocean-based projects.
Rock Dynamics and Imaging Lab
The Rock Dynamics and Imaging Lab consists of facilities for preparing samples and conducting geomechanical, hydrological, and geophysical tests on geological materials under elevated temperature and pressure. It also includes and X-ray CT imaging facility with core-scale multiphysics experimental capability. Ultra-high resolution synchrotron computed tomographic imaging and nanometer-scale imaging capability using the focused-ion-beam milling/SEM imaging technique are linked to the Rock Dynamics and Imaging Lab through partnerships with the ALS and Materials Sciences Division, respectively.


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Professors' Guide(TM) to Getting Good Grades in CollegeThe Professors' Guide to Getting Good Grades in College is the first book to reveal the insider secrets about how professors really grade. The book offers high-value, practical tips about how to succeed at each of the five "grade-bearing" moments of the semester: (1) The Start (2) The Class (3) The Exam (4) The Paper and (5) The Last Month of the Semester. Fast-paced, entertaining, and easy-to
The Secrets of College SuccessHeading off to college? Or perhaps already there? This book's just for you. Winner of the 2010 USA Book News Award for best book in the college category, The Secrets of College Success combines easy-to-follow tips that really work with insider information that few professors are willing to reveal. The over 800 tips in this book will show you how to: Pick courses and choose a major Manage your
The Secrets of Picking a College (and Getting In!)Two award-winning professors, a former admissions officer at a major university (now a counselor at a prestigious high school), and a gifted high school senior (now in the throes of the college admissions process himself) team up to offer you over 600 tips, techniques, and strategies to help you get in to the college of your choice. Comprehensive, yet easy-to-read, this book will teach you: How
The Story of Innovation and Customer ChoiceThe foremost authority on innovation and growth presents a path-breaking book every company needs to transform innovation from a game of chance to one in which they develop products and services customers not only want to buy, but are willing to pay premium prices for.How do companies know how to grow? How can they create products that they are sure customers want to buy? Can innovation be more
The Better Approach to Breakthrough Ideas"[The Coynes'] logical thinking exercises will help readers to maximize their ideation skills, both by systematically exploring every possible nook and cranny of an issue to find new ideas, and by systematically evaluating and honing the results." —Publishers WeeklyFrom business strategists (and brothers) Shawn and Kevin Coyne comes a breakthrough approach to developing better ideas.
The Magic of Believing: Believe in Yourself and The Universe Is Forced to Believe in You* Do you find yourself on the edge of succeeding at something and then all of a sudden everything falls apart? (it's called self-sabotage and it kills millions of dreams everyday. Learn how to blast away self-sabotage forever)* Have you struggled for years with the knowledge that you have at least as much on the ball as many others who have succeeded, but you're still mired in mediocre results?*
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7 Steps to Becoming a Network Marketing ProfessionalOver twenty years ago at a company convention, Eric Worre had an aha moment that changed his life forever. At that event he made the decision to Go Pro and become a Network Marketing expert. Since that time, he has focused on developing the skills to do just that. In doing so, Eric has touched and been touched by hundreds of thousands of people around the world. Now he shares his wisdom in a
The Unique Sales System Proven Successful by the World's Best CompaniesThe Book that Sparked A Selling Revolution In 1985 one book changed sales and marketing forever. Rejecting manipulative tactics and emphasizing "process," Strategic Selling presented the idea of selling as a joint venture and introduced the decade's most influential concept, Win-Win. The response to Win-Win was immediate. And it helped turn the small company that created Strategic Selling, Miller
$11.99Why trying to be the best … competing like crazy … makes you mediocreEvery few years a book—through a combination of the author's unique voice, storytelling ability, wit, and insight—simply breaks the mold. Bill Bryson's A Walk in the Woods is one example. Richard Feynman's "Surely You're Joking, Mr. Feynman!" is another. Now comes Youngme Moon's Different, a book for "people who don't read
Perfect Phrases for Performance Reviews 2/ETHE RIGHT PHRASE FOR EVERY SITUATION . . . EVERY TIME The ability to craft an employee review that is meaningful and change-driven is what separates average supervisors from great managers. How often, though, have you struggled to find the most appropriate words for your needs? This completely revised and updated second edition of Perfect Phrases for Performance Reviews provides hundreds of ready


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First off, let me apologize for using that word in the title; we've all heard enough about the NBA lockout to last us a lifetime.
Nothing gets me going more than rich people arguing over money. Neither side is right yet the dollars are blinding both to the obvious. Their ongoing bickering has cost the fans, the neglected kid in this bitter married-couple argument, their first month of games and likely the first week or two of December to boot.
But, believe it or not, there are some who will benefit from the lockout-shortened season we might end up with.


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Attention A T users. To access the menus on this page please perform the following steps. 1. Please switch auto forms mode to off. 2. Hit enter to expand a main menu option (Health, Benefits, etc). 3. To enter and activate the submenu links, hit the down arrow. You will now be able to tab or arrow up or down through the submenu options to access/activate the submenu links.
Contact Us
VA » Locations » Veterans Health Administration » VISN 16: South Central VA Health Care Network » Gulf Coast Veterans Health Care System
Gulf Coast Veterans Health Care System
Gulf Coast Veterans Health Care System (GCVHCS) consists of a VHA hospital facility in Biloxi, Mississippi. GCVHCS also has Community Based Outpatient Clinics in Mobile, Alabama; and Pensacola, Eglin Air Force Base and Panama City, Florida, serving the four counties along the Alabama Gulf Coast, seven counties along the Mississippi Gulf Coast, and seven counties in Northwest Florida.GCVHCS is a tertiary care facility classified at Clinical Referral Level 1c. It is a teaching hospital, providing a full range of patient care services with state-of-the-art technology, education, and research. Comprehensive health care is provided through primary care, medicine, surgery, psychiatry, psychology, neurology, oncology, dentistry, geriatrics, extended care, and physical medicine and rehabilitation. GCVHCS is a part of Veterans Integrated Service Network 16, which includes facilities in Alexandria, New Orleans, and Shreveport, LA; Houston, TX; Oklahoma City and Muskogee, OK; Little Rock and Fayetteville, AR; and Jackson, MS.The GCVHCS is privileged to serve more than 60,000 veterans. Additionally, it provides support to readjustment counseling centers and VA National Cemeteries along the Gulf Coast.
Keesler Air Force Base
Louisiana State University
Tulane University
University of South Alabama
Outpatient Substance Abuse Treatment
Post Traumatic Stress Disorder Treatment (PTSD)
Day Treatment
Pain Management
Spinal Cord Injury Program
Women Veterans Program
Visual Impaired Services Team (VIST)
Homemaker/Home Health Aid (HHHA) Program
Respite Care
Home Based Primary Care
Telephone Advice Program (TAP)
Veterans Industries Program
Graduate Training Program


text:
Design some Business Cards
This project received 22 bids from talented freelancers with an average bid price of $15 AUD / hour.Get free quotes for a project like this
Skills Required
Project Budget$8 - $15 AUD / hour
Total Bids22
Project Description
I am looking for someone to design business cards for our company. Must use the logo attached and would like to have it on a black background. Looking for something different and attention grabbing. Colour must be on the front and back. Looking for this design to be completed today and must see 2 or 3 different designs to choose from. Please show previous designs in your bid.
Thank you
Looking to make some money?
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realmagick.com The shrine of knowledge.
Mount Shasta Geology
A selection of articles related to mount shasta geology.
Original articles from our library related to the Mount Shasta Geology. See Table of Contents for further available material (downloadable resources) on Mount Shasta Geology.
- King James Bible: Exodus, Chapter 19
- Chapter 19 19:1 In the third month, when the children of Israel were gone forth out of the land of Egypt, the same day came they into the wilderness of Sinai. 19:2 For they were departed from Rephidim, and were come to the desert of Sinai, and had pitched in...
Old Testament >> Exodus
- King James Bible: Exodus, Chapter 24
- Chapter 24 24:1 And he said unto Moses, Come up unto the LORD, thou, and Aaron, Nadab, and Abihu, and seventy of the elders of Israel; and worship ye afar off. 24:2 And Moses alone shall come near the LORD: but they shall not come nigh; neither shall the...
Old Testament >> Exodus
- King James Bible: Exodus, Chapter 34
- Chapter 34 34:1 And the LORD said unto Moses, Hew thee two tables of stone like unto the first: and I will write upon these tables the words that were in the first tables, which thou brakest. 34:2 And be ready in the morning, and come up in the morning unto...
Old Testament >> Exodus
- King James Bible: Numbers, Chapter 20
- Chapter 20 20:1 Then came the children of Israel, even the whole congregation, into the desert of Zin in the first month: and the people abode in Kadesh; and Miriam died there, and was buried there. 20:2 And there was no water for the congregation: and they...
Old Testament >> Numbers
- King James Bible: Deuteronomy, Chapter 9
- Chapter 9 9:1 Hear, O Israel: Thou art to pass over Jordan this day, to go in to possess nations greater and mightier than thyself, cities great and fenced up to heaven, 9:2 A people great and tall, the children of the Anakims, whom thou knowest, and of whom...
Old Testament >> Deuteronomy
- King James Bible: Genesis, Chapter 31
- Chapter 31 31:1 And he heard the words of Laban's sons, saying, Jacob hath taken away all that was our father's; and of that which was our father's hath he gotten all this glory. 31:2 And Jacob beheld the countenance of Laban, and, behold, it was not toward...
Old Testament >> Genesis
- King James Bible: Numbers, Chapter 33
- Chapter 33 33:1 These are the journeys of the children of Israel, which went forth out of the land of Egypt with their armies under the hand of Moses and Aaron. 33:2 And Moses wrote their goings out according to their journeys by the commandment of the LORD:...
Old Testament >> Numbers
Mount Shasta Geology is described in multiple online sources, as addition to our editors' articles, see section below for printable documents, Mount Shasta Geology books and related discussion.
Suggested Pdf Resources
- Introduction to the Geology of the Mount Shasta Region
- Geology Papers. Introduction to the Geology of the Mount Shasta Region by Dr. William Hirt (hirt@siskiyous.
- www.siskiyous.edu
- Mount Shasta Fact Sheet - College of the Siskiyous
- Mount Shasta for the first time is struck by the beauty and majesty of this .... 1862 California Geological Survey, J. D.
- www.siskiyous.edu
- Geology and Ground- Water Features of Shasta Valley, Siskiyou
- Geology and ground-water features of Shasta Valley, Siskiyou. County, Calif. ....
- pubs.usgs.gov
- Gigantic debris avalanche of Pleistocene age from ancestral Mount
- Mount Shasta Volcano, California, and. Debris-Avalanche Hazard Zonation. By DWIGHT R.
- pubs.usgs.gov
- Geology of Northern California Geolo - Cengage Learning
- terrain, Mt. Shasta is the largest volcano in northern California and symbolizes the dynamic geologic processes that have shaped a spectacular landscape.
- www.cengage.com
Suggested News Resources
- Northern California road collapses
- The California Department of Transportation says more than 500 feet of roadway slid off State Route 3 in Northern California, approximately 14 miles west of I-5, between Mt. Shasta and Redding, California.
- Celebrate climate change
- It is one of what the United States Geological Survey identifies as California's four most active volcanoes that includes Mt. Shasta, Mt. Lassen, and Medicine Lake.
- Shasta Historical Society's unique footage of Mt. Lassen eruption goes viral
- The public can now view the c.1917 Mt. Lassen Eruption on the Society's YouTube channel The Shasta Historical Society has been working to digitize its collection, including film reels of unknown content.
- Mount St. Helens Has Nothing on Its Little-Known Neighbors
- Most people, when asked what area in the Cascade Range has spit the most lava and ash out over the past 5,000 years, would answer Mount St. Helens.
- Silvio Calabi: Chrysler's flagship 300 swaggers on
- Periodically, the Passenger-in-Chief gets ticked off at me: Men are so lucky! You go gray and pick up a few wrinkles, and everyone just thinks you look more distinguished!
Great care has been taken to prepare the information on this page. Elements of the content come from factual and lexical knowledge databases, realmagick.com library and third-party sources. We appreciate your suggestions and comments on further improvements of the site.
Mount Shasta Geology Topics
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Mushroom Sauce
17 Oct 2009
This mushroom sauce recipe is an easy homemade sauce recipe. Prepared with canned mushroom soup and sour cream along with added mushrooms, this is a cooked sauce recipe. Sherried lightly, it has a mild yet unique flavor to it.
|Canned mushroom soup
|10 3⁄4 Ounce, undiluted (1 Can)
|Sour cream
|8 Ounce (1 Carton, Use Any Commercial Brand)
|Canned sliced mushrooms
|4 Ounce, drained (1 Can)
|Dry sherry
|1⁄3 Cup (5.33 tbs)
Combine all ingredients; cook over medium heat, stirring occasionally, until thoroughly heated
Rate It
Nutrition Rank
Nutrition Facts
Serving size: Complete recipe
Calories 772 Calories from Fat 551
% Daily Value*
Total Fat 63 g96.5%
Saturated Fat 30.3 g151.5%
Trans Fat 0 g
Cholesterol 117.9 mg39.3%
Sodium 2675.1 mg111.5%
Total Carbohydrates 40 g13.2%
Dietary Fiber 0 g
Sugars 12.4 g
Protein 10 g19.2%
Vitamin A 27.9% Vitamin C 3.4%
Calcium 28.6% Iron 20.9%
*Based on a 2000 Calorie diet
Mushroom Sauce Recipe