Theta and gamma rhythmic coding through two spike output modes in the hippocampus during spatial navigation.

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice. We found that spike bursts are preferentially linked to cellular and network theta rhythms (3-12 Hz) and encode an animal's position via theta phase precession, particularly as animals are entering a place field. In contrast, single spikes exhibit additional coupling to gamma rhythms (30-100 Hz), particularly as animals leave a place field. Biophysical modeling suggests that intracellular properties alone are sufficient to explain the observed input frequency-dependent spike coding. Thus, hippocampal neurons regulate the generation of bursts and single spikes according to frequency-specific network and intracellular dynamics, suggesting that these spiking modes perform distinct computations to support spatial behavior.

Blepharochalasis: something to cry about.

Blepharochalasis is a rare disorder of unknown etiology defined by loose, atrophic periorbital skin following recurrent episodes of eyelid edema. Characteristic histopathology shows complete absence of elastic fibers. The current case progressed after multiple episodes of crying, which may be related to matrix metalloproteinase dysregulation. This case offers further insights into the possible pathogenesis of blepharochalasis, paving the way for more targeted, disease-modifying therapies.

Altered Morphology and Immunohistochemical Characteristics in Metastatic Malignant Melanoma After Therapy With Vemurafenib.

Metastatic melanoma is traditionally diagnosed using classic morphologic features in addition to immunohistochemical studies. The authors report a case of metastatic malignant melanoma where both morphology and immunohistochemistry were altered after treatment. This 51-year-old patient presented with metastatic melanoma to the brain and axilla. Initially, both metastases showed classic morphology and diffuse staining with the pan-melanoma antibody cocktail. This cocktail is a combination of 3 antibodies commonly used to diagnose melanocytic neoplasms: Melan-A (MART-1), tyrosinase, and HMB-45. In combination, the cocktail is highly sensitive for detecting melanocytic neoplasms and is commonly used to diagnose metastatic melanoma. Her tumor was positive for the BRAF 1799T>A (V600E) mutation, and she was treated with BRAF inhibitor therapy (vemurafenib). However, the axillary tumor recurred after treatment with vemurafenib. The recurrent tumor showed a markedly different morphology and complete loss of staining with the pan-melanoma antibody cocktail. This loss of staining accompanied by the change in morphology was an observation not previously documented after therapy with vemurafenib. This case demonstrates a potential pitfall in the diagnosis of metastatic or recurrent malignant melanoma.

Poorly differentiated carcinoma arising in the setting of erythema ab igne.

Erythema ab igne (EAI) is a reticulated, erythematous, or hyperpigmented dermatosis that is caused by chronic exposure to infrared radiation. Chronic lesions of EAI have significant potential for malignant transformation. We report a case of poorly differentiated carcinoma arising within a patch of long-standing EAI on the lower extremity of a 92-year-old female. This case highlights the importance of recognizing EAI early and counseling patients to avoid further exposure to the offending infrared source to reduce the risk of malignant transformation. EAI has been associated with several different types of cutaneous neoplasms including the Merkel cell carcinoma, squamous cell carcinoma, and cutaneous marginal zone lymphoma.

Refractory Hailey-Hailey disease successfully treated with sandpaper dermabrasion.

A 53-year-old woman presented with a 20-year history of pruritic dermatitis on the groin, axillae, inframammary folds, posterior aspect of the neck, and popliteal fossae. She was referred to our clinic by an outside facility after results from a punch biopsy diagnosed Hailey-Hailey disease (HHD). The patient had previously attempted treatment with many traditional noninvasive options with no success. Topical treatment modalities included corticosteroids, immunomodulators, antifungals, retinoids, and antibiotic preparations. Intralesional corticosteroids, as well as botulinum toxin and carbon dioxide laser, were also unsuccessful. Failed systemic treatment modalities included antibiotics, antihistamines, prednisone, azathioprine, mycophenolate mofetil, acitretin, isotretinoin, adalimumab, and etanercept. Of note, cyclosporine was successful in clearing the cutaneous involvement in our patient, but elevation ofcreatinine and exacerbated hypertension precluded continued use. The decision was made to treat the patient by dermabrasion with sandpaper. The patient was prepped in a sterile fashion, and a field block with 1% lidocaine with epinephrine was performed. This was followed by abrasion down to the superficial dermis with 3M Sandblaster fine sandpaper (3M, St. Paul, MN) and hyfrecation between rounds ofdermabrasion. The treated areas were then covered with petrolatum and sterile gauze, and antibiotics and pain medication were prescribed. This treatment was initially performed on the patient's posterior aspect of the neck and later to the bilateral popliteal fossae and axillae. Three months post-treatment, desirable functional and cosmetic results of the treated areas had been achieved (Figure 1 and Figure 2). While no recurrence of clinically active HHD has been seen in the dermabraded areas of the neck and popliteal fossae, the patient continues to have active disease in the axillae despite sandpaper dermabrasion. To quantify our results, we performed two biopsies in the dermabraded sites of the popliteal fossae as healing occurred: a shave biopsy from an obviously active area, and a punch biopsy from a peripheral inactive border. The biopsy from the active area showed diffuse epidermal acantholysis similar to that seen in untreated HHD, while the healing periphery showed only scattered acantholytic areas and a sparse perivascular infiltrate-a marked improvement from the untreated areas.

Epidermolytic hyperkeratosis and congenital platelike osteoma cutis in a child.

Epidermolytic hyperkeratosis is a rare congenital ichthyosis. Platelike osteoma cutis also is a rare diagnosis and is associated with abnormal ossification of cutaneous or subcutaneous tissue. A 17-month-old Hispanic girl presented with a plate of subcutaneous bone since birth as well as considerable scaling and hyperkeratosis centered around the joints. Histologic examination confirmed the diagnosis of both epidermolytic hyperkeratosis and osteoma cutis. Although there have been some cases of epidermolytic hyperkeratosis with other dermatologic conditions, we report a rare case of epidermolytic hyperkeratosis and platelike osteoma cutis.

Retrospective study of intraepidermal nerve fiber distribution in biopsies of patients with nummular eczema.

BACKGROUND: Nummular eczema is a chronic inflammatory condition characterized by pruritus and histologically characterized by spongiosis. The etiology is unknown, and the lesions frequently arise spontaneously. Neuropeptides contribute to mediating and maintaining eczematous conditions. Previous research indicates that the number of immunoreactive nerve fibers is increased in pruritic skin lesions. OBJECTIVE: We sought to determine if the number of immunoreactive nerve fibers is increased in nummular eczema, as in other inflammatory pruritic conditions. METHODS: Protein gene product 9.5 (PGP 9.5) was assessed by immunohistochemistry in 22 biopsies of nummular eczema and was compared with immunohistochemical expression of 8 skin biopsies uninvolved by nummular eczema. RESULTS: Nerve fiber distribution using PGP 9.5 stain showed that there was significantly reduced PGP9.5 stain amount in the epidermis of patients with nummular eczema compared with their respective healthy control (P = 0.0054). However, no statistical difference was seen in the papillary dermis. CONCLUSION: Pruritus of nummular eczema is not associated with an increase of epidermal nerve fiber density and sprouting.

The role of sirolimus in the prevention of cutaneous squamous cell carcinoma in organ transplant recipients.

Skin cancers are common in organ transplant recipients (OTRs). In this review, we discuss the epidemiology of and risk factors for cutaneous neoplasms, particularly squamous cell carcinoma (SCC) in OTRs. The pathogenesis of SCC is reviewed, as well as the potential mechanisms for tumor progression and metastasis associated with two commonly used immunosuppressive medications: tacrolimus and cyclosporine. Finally, we discuss the mechanism of action and potential preventative use of sirolimus, a member of a newer class of immunosuppressants, the mammalian target of rapamycin inhibitors. The authors have indicated no significant interest with commercial supporters.

Abnormal aquaporin-3 protein expression in hyperproliferative skin disorders.

Non-melanoma skin cancers (NMSCs) and psoriasis represent common hyperproliferative skin disorders, with approximately one million new NMSC diagnoses each year in the United States alone and a psoriasis prevalence of about 2% worldwide. We recently demonstrated that the glycerol channel, aquaporin-3 (AQP3) and the enzyme phospholipase D2 (PLD2) interact functionally in epidermal keratinocytes of the skin to inhibit their proliferation. However, others have suggested that AQP3 is pro-proliferative in keratinocytes and is upregulated in the NMSC, squamous cell carcinoma (SCC). To evaluate the AQP3/PLD2 signaling module in skin diseases, we determined their levels in SCC, basal cell carcinoma (BCC) and psoriasis as compared to normal epidermis. Skin biopsies with the appropriate diagnoses (10 normal, 5 SCC, 13 BCC and 10 plaque psoriasis samples) were obtained from the pathology archives and examined by immunohistochemistry using antibodies recognizing AQP3 and PLD2. In normal epidermis AQP3, an integral membrane protein, was localized mainly to the plasma membrane and PLD2 to the cell periphery, particularly in suprabasal layers. In BCC, AQP3 and PLD2 levels were reduced as compared to the normal-appearing overlying epidermis. In SCC, AQP3 staining was "patchy," with areas of reduced AQP3 immunoreactivity exhibiting positivity for Ki67, a marker of proliferation. PLD2 staining was unchanged in SCC. In psoriasis, AQP3 staining was usually observed in the cytoplasm rather than in the membrane. Also, in the majority of psoriatic samples, PLD2 showed weak immunoreactivity or aberrant localization. These results suggest that abnormalities in the AQP3/PLD2 signaling module correlate with hyperproliferation in psoriasis and the NMSCs.

Pseudolymphomatous and lichenoid reaction to a red tattoo: a case report.

A pseudolymphomatous reaction is an unusual immune response that can be caused by a tattoo, most commonly by red ink. We present the case of a 40-year-old woman with discolored and pruritic plaques in the areas of red ink tattooed on her right ankle that developed shortly after tattoo application. The patient had 2 other tattoos with red ink for more than 20 years without any disfigurement. Histopathology, immunohistochemistry, and polymerase chain reaction analysis from biopsy of the affected area showed polyclonal pseudolymphomatous and lichenoid reaction, confirming the diagnosis of pseudolymphoma secondary to a tattoo. Total excision of the lesion was performed.

Adjunctive radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion.

Perineural invasion is a feature associated with significantly poorer outcomes when present in cutaneous squamous cell carcinoma (CSCC). The incidence of this subset of CSCC continues to rise in the US, as does the confusion surrounding exactly how it should be managed. While management typically involves excision, considerable debate exists as to the appropriate use of adjuvant radiotherapy (ART) in addition to excision. This article reviews the current relevant evidence for the use of ART.