Symptomatic perineural and intraneural invasion of the trigeminal nerve and subsequent abducens Nerve palsy by cutaneous squamous cell carcinoma.

A 74-year-old woman who presented initially with trigeminal neuralgia of the left forehead and scalp was later found to have a poorly differentiated squamous cell carcinoma (SCC) with large-nerve perineural and intraneural invasion of the left supraorbital nerve. Negative histopathologic margins were achieved in three stages of permanent fixed tissue en face processing and the final defect was repaired with a large rotation flap. Approximately one month after repair, the patient presented with new-onset diplopia and was found to have a complete left cranial nerve VI palsy suspicious for continued disease spread. MRI confirmed perineural spread along the ophthalmic branch of the trigeminal nerve through the superior orbital fissure into the cavernous sinus. She was subsequently treated with radiation therapy (66Gy in 33 fractions). The involvement of two distinct cranial nerves by perineural invasion is uncommon and has mostly been described involving branches of the trigeminal and facial nerves. This case highlights the rare presentation of perineural invasion involving both the trigeminal nerve and the abducens nerve. Anatomically, this clinical presentation can be explained by the retrograde perineural spread along the ophthalmic branch of the trigeminal nerve through the supraorbital fossa into the cavernous sinus where these two nerves are in close proximity.

Bedside Diagnostics for Infections: A Guide for Dermatologists.

In dermatology, there are many bedside diagnostic tests that may aid in more rapid diagnosis and early initiation of appropriate therapy. When performed correctly, these bedside diagnostic tests can provide both sensitive and specific results. We discuss bedside diagnostic tests, such as the Tzanck smear, potassium hydroxide (KOH) preparation, and mineral oil preparation, with a specific focus on their use in diagnosing infectious dermatoses.

Basomelanocytic Neoplasms: A Report of Two Similar Tumors With Divergent Treatments.

Basomelanocytic neoplasms are tumors consisting of elements of both basal cell carcinoma and melanoma. These tumors are exceedingly rare and present a unique challenge as to how the melanoma component should be classified. Due to the paucity of cases, there are no clear-cut evidence-based guidelines as to how these tumors should be staged and which treatment options provide the optimal outcome. We present 2 separate patients with similar cases of colonizing basomelanocytic tumors that were treated in drastically different ways, highlighting the differing approaches to treatment. We discuss theses treatment modalities and the challenges inherent to diagnosing and treating basomelanocytic neoplasms.

Cutaneous nontuberculous mycobacteria infections: A retrospective case series of 78 patients from the Texas Gulf Coast region.

BACKGROUND: The incidence of cutaneous nontuberculous mycobacteria (NTM) infections is increasing. These infections are a diagnostic and therapeutic challenge. OBJECTIVE: We investigated the clinical features, diagnosis, and management of cutaneous NTM infections. METHODS: A retrospective case series studied 78 patients from a Gulf Coast tertiary referral center diagnosed with cutaneous NTM infection by culture or stain of a skin biopsy specimen. RESULTS: A history of trauma, procedure, or environmental exposure was common. The mean time between the initial evaluation and diagnosis was 12 weeks. Only 15% of acid-fast bacillus-positive cultures had a positive acid-fast bacillus smear, and only 43% of those accompanied by skin biopsy specimen had a positive Fite stain. Immunosuppressed patients were more likely to have a positive Fite stain. Treatment included surgery and multiple antibiotics. Immunosuppressed patients and Mycobacterium abscessus group infections were more likely to have persistent disease. LIMITATIONS: M chelonae and M abscessus isolates were indistinguishable and therefore were reported together. Five cases were not confirmed by culture. CONCLUSIONS: Even with clinical suspicion, the diagnosis of NTM infection can be difficult. Results of acid-fast bacillus smears and special stains are frequently negative. Antibiotic resistance is common. Multidrug treatment is often required, and surgical therapy may be needed.

Chronic myelomonocytic leukemia masquerading as cutaneous indeterminate dendritic cell tumor: Expanding the spectrum of skin lesions in chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a hematopoietic stem cell neoplasm exhibiting both myelodysplastic and myeloproliferative features. Cutaneous involvement by CMML is critical to recognize as it typically is a harbinger of disease progression and an increased incidence of transformation to acute myeloid leukemia. Cutaneous lesions of CMML exhibit heterogeneous histopathologic features that can be challenging to recognize as CMML. We describe a 67-year-old man with a 3-year history of CMML who had been managed on single-agent azacitidine with stable disease before developing splenomegaly and acute onset skin lesions. Examination of these skin lesions revealed a dense infiltrate of histiocytic cells morphologically resembling Langerhans type cells (lacking frank histopathologic atypia), and with the immunophenotype of an indeterminate cell histiocytosis (S100+ CD1a+ and langerin-). Given the history of CMML, next-generation sequencing studies were performed on the skin biopsy. These revealed a KRAS (p.G12R) mutation identical to that seen in the CMML 3 years prior, establishing a clonal relationship between the 2 processes. This case expands the spectrum for and underscores the protean nature of cutaneous involvement by CMML and underscores the importance of heightened vigilance when evaluating skin lesions of CMML patients.

Immune Cell Targets of Infection at the Tick-Skin Interface during Powassan Virus Transmission.

Powassan virus (POWV) is a tick-borne flavivirus that can result in a severe neuroinvasive disease with 50% of survivors displaying long-term neurological sequelae. Human POWV cases have been documented in Canada, the United States, and Russia. Although the number of reported POWV human cases has increased in the past fifteen years, POWV remains one of the less studied human pathogenic flaviviruses. Ixodes ticks are the vectors for POWV, and the virus is transmitted to a host's skin very early during the tick feeding process. Central to the successful transmission of a tick-borne pathogen are complex interactions between the host immune response and early tick-mediated immunomodulation, all of which initially occur at the skin interface. In our prior work, we examined the cutaneous immune gene expression during the early stages of POWV-infected Ixodes scapularis feeding. The present study serves to further investigate the skin interface by identifying early cell targets of infection at the POWV-infected tick feeding site. An in vivo infection model consisting of POWV-infected ticks feeding on mice for short durations was used in this study. Skin biopsies from the tick feeding sites were harvested at various early time points, enabling us to examine the skin histopathology and detect POWV viral antigen in immune cells present at the tick feeding site. The histopathology from the present study demonstrates that neutrophil and mononuclear cell infiltrates are recruited earlier to the feeding site of a POWV-infected tick versus an uninfected tick. This is the first report demonstrating that macrophages and fibroblasts contain POWV antigens, which suggests that they are early cellular targets of infection at the tick feeding site. These data provide key insights towards defining the complex interactions between the host immune response and early tick-mediated immunomodulation.

An Unusual Cutaneous Manifestation in a Patient with Murine Typhus.

Murine typhus is a flea-borne febrile illness caused by Rickettsia typhi. Although often accompanied by rash, an inoculation lesion has not been observed as it is with many tick- and mite-transmitted rickettsioses. We describe a patient with murine typhus and an unusual cutaneous manifestation at the site of rickettsial inoculation.

Dual S-100-AE1/3 Immunohistochemistry to Detect Perineural Invasion in Nonmelanoma Skin Cancers.

Background. Perineural invasion (PNI) is an adverse prognostic histologic finding and increases the risk of local recurrence and metastasis. Objective. We aimed to determine if dual immunohistochemical (IHC) staining with S-100 and AE1/3 would increase the detection of PNI on nonmelanoma skin cancers (NMSCs). Methods. We collected 45 specimens of NMSCs in which there was clinical suspicion for PNI. Two dermatopathologists independently reviewed the tumors for the unequivocal presence of PNI. Results. Unequivocal PNI was present on 10 of the 45 tumors by H&E staining and on 15 of the 45 tumors by IHC staining. Large nerves (>0.1 mm) were involved in 3 of 10 H&E-stained cases and 3 of 15 IHC-stained cases, with 2 of the 4 cases demonstrating large nerve involvement with both staining methods. Of the 8 cases of PNI detected only on IHC, 7 were small nerves (≤0.1 mm). Limitations. All cases were selected because they were clinically suspicious for PNI, and this may be considered selection bias. Conclusions. PNI detection may be increased using dual S-100 and AE1/3 staining, but the majority of additional cases detected were small nerves. The clinical significance, given the small size of the involved nerves, is unclear.

Omalizumab as a desensitizing agent and treatment in mastocytosis: a review of the literature and case report.

Patients with all forms of mastocytosis can experience urticaria, abdominal cramps, nausea, diarrhea, or hypotension due to release of mediators by mast cells. Patients with mastocytosis and Hymenoptera venom allergy can develop severe adverse reactions to Hymenoptera stings. In addition, patients with mastocytosis and on venom immunotherapy are at high risk for incomplete protection and fatal reactions. Recent literature has reported the use of omalizumab as an adjunctive treatment in patients with mastocytosis, used for both symptom improvement and to dampen adverse effects caused by venom immunotherapy. This article reviews the literature regarding omalizumab use in the treatment of mastocytosis and for protection against the adverse effects during venom immunotherapy. In addition, we report the case of a patient at high risk and with cutaneous mastocytosis, whose symptoms improved with concomitant administration of omalizumab and venom immunotherapy.

Incorporating resident research into the dermatology residency program.

Programmatic changes for the dermatology residency program at The University of Texas Medical Branch were first introduced in 2005, with the faculty goal incorporating formal dermatology research projects into the 3-year postgraduate training period. This curriculum initially developed as a recommendation for voluntary scholarly project activity by residents, but it evolved into a program requirement for all residents in 2009. Departmental support for this activity includes assignment of a faculty mentor with similar interest about the research topic, financial support from the department for needed supplies, materials, and statistical consultation with the Office of Biostatistics for study design and data analysis, a 2-week elective that provides protected time from clinical activities for the purpose of preparing research for publication and submission to a peer-reviewed medical journal, and a departmental award in recognition for the best resident scholarly project each year. Since the inception of this program, five classes have graduated a total of 16 residents. Ten residents submitted their research studies for peer review and published their scholarly projects in seven dermatology journals through the current academic year. These articles included three prospective investigations, three surveys, one article related to dermatology education, one retrospective chart review, one case series, and one article about dermatopathology. An additional article from a 2012 graduate about dermatology education has also been submitted to a journal. This new program for residents was adapted from our historically successful Dermatology Honors Research Program for medical students at The University of Texas Medical Branch. Our experience with this academic initiative to promote dermatology research by residents is outlined. It is recommended that additional residency programs should consider adopting similar research programs to enrich resident education.

Severe serum sickness after H1N1 influenza vaccination.

In this study, the case of a 48-year-old man with severe serum sickness reaction in response to H1N1 influenza immunization is reported. He presented with renal failure and several of the classic signs reported in early descriptions of serum sickness by Clemens von Pirquet and Bela Schick including lymphadenopathy, urticarial skin eruption and facial edema. Serum immunologic studies and tissue histology/immunohistochemistry assisted in firmly establishing the diagnosis in this case. With appropriate therapy, the patient's rash, edema and lymphadenopathy resolved and normal renal function returned. This first reported case of severe serum sickness to H1N1 vaccine is particularly important in light of the Centers for Disease Control and Prevention's recommendation for universal vaccination against influenza, including H1N1, in patients 6 months and older. With increasing numbers of patients receiving this vaccine, even rare adverse reactions may be experienced by numerous individuals. It is imperative that clinicians remain vigilant about possible reactions and quickly institute appropriate therapy.

Porcine xenograft biosynthetic wound dressings for the management of postoperative Mohs wounds.

Cadaveric allografts and a large variety of other biologic dressings have been reported as being useful for the postoperative management of Mohs micrographic surgery (MMS) wounds. Although the use of porcine xenografts for the immediate postoperative management of these wounds is known, their use has not been detailed in the dermatology literature. A case series of 15 consecutive Mohs micrographic surgery patients (mean age = 74.9 years, range = 49 to 89 years) with wounds initially managed with porcine xenografts is described. Porcine xenografts were useful in a variety of clinical settings following MMS. These included: (1) wound management when tumor margins were indeterminate pending additional dermatopathology studies and (2) wound management when there are issues such as through and through nasal defects involving the mucosa, large wound depth, exposed cartilage and or bone, or patient medical comorbidities that delay or prevent plans for immediate wound reconstruction. Future controlled studies of biologic dressings are needed to determine which options are best for micrographic surgery wounds. Comparisons should also include the traditional option of second intention healing without biologic dressings.

The imbalanced expression of matrix metalloproteinases in nephrogenic systemic fibrosis.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) occurs in patients with renal dysfunction and gadolinium exposure. Although little is known about the pathogenesis of this disease, increased expression of transforming growth factor-beta has been recently demonstrated. Other fibrosing conditions have been shown to express an imbalance in matrix metalloproteinase (MMP) expression and their corresponding inhibitors. Myofibroblast differentiation, in which cells often express alpha-smooth muscle actin and achieve the ability to contract, is also a hallmark of fibrosis. OBJECTIVE: We theorized that NSF may overexpress tissue inhibitor of metalloproteinase-1 (TIMP-1), while simultaneously showing decreased expression of MMP-1. As a secondary aim, we sought to evaluate the presence of smooth muscle actin in our samples. METHODS: We applied immunohistochemistry to 16 skin biopsies from 10 patients with NSF using antibodies to TIMP-1, MMP-1, MMP-2, MMP-9, and alpha-smooth muscle actin. Samples from normal skin, scar, keloid and scleroderma were stained for comparison. RESULTS: TIMP-1 was strongly expressed in all NSF specimens compared to normal skin. MMP-1 expression was nearly absent in all tested samples. In all 16 NSF cases, the dermal spindle cells did not stain for alpha-smooth muscle actin. MMP-2 and MMP-9 expression was variable but was increased compared to normal skin. LIMITATIONS: The expression is semiquantitative and based on immunohistochemistry and unconfirmed by other techniques. CONCLUSIONS: In NSF, TIMP-1 is strongly expressed and MMP-1 is nearly absent, characteristic of the MMP imbalances seen in other fibrosing processes. Using smooth muscle actin immunohistochemistry, there was no evidence of myofibroblast differentiation.