Cutaneous Atypical Fibroxanthoma With Osteoclast-Like Giant Cell: A Rare but Diagnostic Pitfall.

BACKGROUND: Atypical fibroxanthoma (AFX) is a dermal-based, low-grade neoplasm with no specific lineage of differentiation. The occurrence of AFX with osteoclast-like giant cells is exceptionally rare. Less than 20 cases have been reported in the literature. CASE PRESENTATION: A 77-year-old man with a medical history of multiple basal and squamous cell carcinomas of the skin, presented with a progressively growing erythematous nodule on the sun-damaged right central parietal scalp. A shave biopsy showed a dermal spindle cell proliferation accompanied by numerous osteoclast-like multinucleated giant cells and predominant atypical mitotic figures. The immunohistochemical staining showed a diffuse positive staining for CD68 and SMA, patchy staining for CD10, and negative staining for SOX-10, pan-cytokeratin, CK5/6, S100, CD34, and desmin. The tumor was completely excised with negative margins. A subsequent follow-up over a period of 13 months showed no recurrence. CONCLUSION: Distinguishing AFX with osteoclast-like giant cells from both malignant and benign skin lesions with osteoclast-like giant cells is crucial. Although AFX tumors display worrisome malignant histologic features, most cases have a favorable prognosis with a local recurrence rate below 5% and exceedingly rare metastasis.

Subacute cutaneous lupus erythematosus presenting in twins.

Subacute cutaneous lupus erythematosus is a clinically distinct form of cutaneous lupus erythematosus, with age of onset typically in the second to fifth decades. Eleven cases have been reported in childhood, and we present the first known case of subacute cutaneous lupus erythematosus in identical twins. Although flares are typically photo-induced, we present an annular eruption typical of subacute cutaneous lupus erythematosus with concurrent pinworm infestation, with recurrence of disease with cutaneous larva migrans. The patient's identical twin had a similar eruption with pinworm infection. This case highlights the possibility of parasitic infestation as a trigger for subacute cutaneous lupus erythematosus in genetically susceptible individuals.

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

PURPOSE: Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers. METHODS: The study was conducted in 11 healthy men aged 47-57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug. RESULTS: The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported. CONCLUSION: The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

A case of self-healing juvenile cutaneous mucinosis.

IMPORTANCE: Self-healing juvenile cutaneous mucinosis is a very rare, self-limiting disease characterized by the abrupt onset of asymptomatic papules and nodules located primarily on the face and periarticular regions of a juvenile patient. There have been less than 20 cases reported since it was first described in 1973. OBSERVATIONS: Most cases have been reported in children 15 years and younger. Herein we present a case affecting a 17-year-old. To our knowledge, this the oldest reported patient with this condition in the USA. CONCLUSIONS AND RELEVANCE: Despite the rarity of this disease, it is important to keep SHJCM on the differential in pediatric patients presenting with proliferating papules and nodules. Knowledge of this entity may prevent unnecessary diagnostic testing and aggressive treatment in the pediatric population with this self-limited disease.

Shave biopsy is a safe and accurate method for the initial evaluation of melanoma.

BACKGROUND: Shave biopsy of cutaneous lesions is simple, efficient, and commonly used clinically. However, this technique has been criticized for its potential to hamper accurate diagnosis and microstaging of melanoma, thereby complicating treatment decision-making. STUDY DESIGN: We retrospectively analyzed a consecutive series of patients referred to the University of Florida Shands Cancer Center or to the Moffitt Cancer Center for treatment of primary cutaneous melanoma, initially diagnosed on shave biopsy to have Breslow depth < 2 mm, to determine the accuracy of shave biopsy in T-staging and the potential impact on definitive surgical treatment and outcomes. RESULTS: Six hundred patients undergoing shave biopsy were diagnosed with melanoma from extremity (42%), trunk (37%), and head or neck (21%). Mean (± SEM) Breslow thickness was 0.73 ± 0.02 mm; 6.2% of lesions were ulcerated. At the time of wide excision, residual melanoma was found in 133 (22%), resulting in T-stage upstaging for 18 patients (3%). Recommendations for additional wide excision or sentinel lymph node biopsy changed in 12 of 600 (2%) and 8 of 600 patients (1.3%), respectively. Locoregional recurrence occurred in 10 (1.7%) patients and distant recurrence in 4 (0.7%) patients. CONCLUSIONS: These data challenge the surgical dogma that full-thickness excisional biopsy of suspicious cutaneous lesions is the only method that can lead to accurate diagnosis. Data obtained on shave biopsy of melanoma are reliable and accurate in the overwhelming majority of cases (97%). The use of shave biopsy does not complicate or compromise management of the overwhelming majority of patients with malignant melanoma.

Naloxone as part of a prolonged release oxycodone/naloxone combination reduces oxycodone-induced slowing of gastrointestinal transit in healthy volunteers.

OBJECTIVES: This exploratory study in healthy volunteers investigated the effect of single doses of oxycodone on gastrointestinal (GI) transit time and the degree to which a single dose of naloxone reverses the oxycodone-induced effect. METHODS: Fifteen healthy male volunteers received: oxycodone 10 and2 0 mg, oxycodone/naloxone 10/5 and 20/10 mg (all as prolonged release tablets) and placebo. Each dose was radiolabelled and administered with a capsule containing radiolabelled resin (surrogate for GI contents). RESULTS: Scintigraphic analysis showed that 20 mg oxycodone significantly increased colon arrival time (mean 7.19 vs 5.15 h for placebo, p = 0.0159). Mean colon arrival time for oxycodone/naloxone 20/10 mg (5.16 h) was similar to placebo, although the difference between oxycodone/naloxone 20/10 mg versus oxycodone 20 mg was not significant (p = 0.0653). Colonic geometric centre analysis showed a significant increase in mean time for the resin to reach the colon following oxycodone 10 and 20 mg compared with placebo (increases of 5.3 and 8.8 h). There was no significant effect of naloxone at the lower dose; however, oxycodone/naloxone 20/10 mg significantly reduced mean colonic transit time by 2.1 h (p = 0.0376). CONCLUSION: A single dose of oxycodone 20 mg significantly prolonged GI transit time but this effect was reduced by co-administration of naloxone.

Mycophenolate mofetil in dermatology.

UNLABELLED: Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA), a medication used to treat psoriasis in the 1970s until side effects and the concern of carcinogenesis led to its discontinuation. The prodrug, MMF, emerged decades later in the transplant field. Dermatologists have since used MMF off-label to treat various inflammatory skin conditions, with most research concentrating on its use in psoriasis, autoimmune blistering disorders, dermatitides, and connective tissue disorders. The appeal of MMF is predicated upon its lymphocyte specificity and consequent decreased toxicity profile. These attributes may make it a preferable treatment option. Its use in the field of dermatology is currently limited by a lack of randomized controlled trials, potential unknown side effects, and cost of treatment. In reviewing both current literature and our own clinic records, MMF appears to be a promising therapeutic option for the treatment of cutaneous inflammatory diseases. LEARNING OBJECTIVE: After completing this learning activity, participants should be able to summarize the history and pharmacology of mycophenolate mofetil as an immunosuppressant; recognize its potential role in the treatment of dermatologic conditions, including general dosing guidelines, use in pregnancy and pediatrics, and potential adverse effects; and identify future considerations and developing areas of research regarding the use of mycophenolate mofetil in dermatology.

Phase I clinical trial of repeat dose terameprocol vaginal ointment in healthy female volunteers.

OBJECTIVES: This safety study of terameprocol (also called M4N, EM-1421) daily vaginal application in healthy women explores its potential application as a microbicide in interrupting human immunodeficiency virus sexual transmission and additional interruption of human papillomavirus and herpes simplex virus transmission. METHODS: A double-blind placebo controlled phase I repeat dose tolerability and pharmacokinetic, crossover study of 90 mg terameprocol (2% w/w ointment) administered intravaginally for 7 consecutive days in healthy female subjects. The pharmacokinetics after administration was examined on days 1 and 7 of dosing. Subjects underwent vaginal examination following the 6-hour pharmacokinetic sample on day 7 of each study period. RESULTS: Recruitment started January 2006 and ended May 2006, and 14 subjects completed the study. Median age was 24 years. No treatment-related serious adverse events were reported, and there were a total of 17 treatment-emergent adverse events (AE) reported by 11 participants. The most common AE was headache. Terameprocol was not detectable in serum in pharmacokinetic samples. CONCLUSIONS: Terameprocol was well tolerated at a 90 mg dose (2% wt/wt) administered vaginally daily for 7 days. No serious adverse events occurred and any AEs were mild. The excellent safety profile supports future clinical trial to evaluate the application of intravaginal terameprocol in women.

Pilot study of nasal morphine-chitosan for the relief of breakthrough pain in patients with cancer.

Breakthrough pain in patients with cancer is common, often unpredictable, and can rapidly become severe. Treatment using the oral administration of opioids is not optimal due to the slow onset of pain relief. Nasal administration of analgesics potentially offers more rapid pain relief. This study investigates the tolerability and efficacy of a novel morphine-chitosan formulation. Twenty episodes of breakthrough pain were observed in 14 patients with cancer who received 5-80 mg of nasal morphine-chitosan. Nasal symptoms, sedation, giddiness, nausea, and other volunteered symptoms, along with pain scores (pain intensity and pain relief), were recorded at baseline and at regular intervals up to 4 hours after administration, together with an overall satisfaction rating. The formulation was acceptable to patients, generally well tolerated, and had an onset of pain relief 5 minutes after dosing. This formulation warrants further study.