John G. Zampella

Long Interspersed Element-1 Protein Expression Is a Hallmark of Many Human Cancers

Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen.

Diagnostic utility of 5-hydroxymethylcytosine immunohistochemistry in melanocytic proliferations

Decreased hydroxymethylated cytosine (5‐hydroxymethycytosine, 5‐hmC) is reported to correlate with melanocyte dysplasia. The purpose of this study was to assess the diagnostic utility of this observation. 5‐hmC immunohistochemistry was performed on tissue microarrays containing 171‐melanocytic lesions from two different institutions. An immunohistochemical staining score representing the percentage and intensity of nuclear staining was assigned. The performance characteristics of 5‐hmC immunohistochemistry for discriminating between a nevus and melanoma were determined. Additional cases of melanoma arising in a nevus (n = 8), nodal nevi (n = 5) and melanoma micrometastases to a lymph node (n = 6) were also assessed. Pronounced 5‐hmC loss was observed in melanomas when compared with nevi (mean ± standard deviation = 6.71 ± 11.78 and 55.19 ± 23.66, respectively, p < 0.0001). While the mean immunohistochemical staining score values for melanocytic nevi and melanoma were distinct, there was considerable variability in immunohistochemical staining score within a single diagnostic category. The sensitivity and specificity of this assay for nevus vs. melanoma is 92.74 and 97.78%, respectively. Distinct biphasic staining patterns were observed in cases of melanoma arising in association with a nevus. Relative changes of 5‐hmC expression within a single lesion may be more informative than absolute values when using 5‐hmC as a diagnostic adjunct.

Translocation junctions in TCF3-PBX1 acute lymphoblastic leukemia/lymphoma cluster near transposable elements

BackgroundHematolymphoid neoplasms frequently harbor recurrent genetic abnormalities. Some of the most well recognized lesions are chromosomal translocations, and many of these are known to play pivotal roles in pathogenesis. In lymphoid malignancies, some translocations result from erroneous V(D)J-type events. However, other translocation junctions appear randomly positioned and their underlying mechanisms are not understood.ResultsWe tested the hypothesis that genomic repeats, including both simple tandem and interspersed repeats, are involved in chromosomal translocations arising in hematopoietic malignancies. Using a database of translocation junctions and RepeatMasker annotations of the reference genome assembly, we measured the proximity of translocation sites to their nearest repeat. We examined 1,174 translocation breakpoints from 10 classifications of hematolymphoid neoplasms. We measured significance using Student’s t-test, and we determined a false discovery rate using a random permutation statistics technique.ConclusionsMost translocations showed no propensity to involve genomic repeats. However, translocation junctions at the transcription factor 3 (TCF3)/E2A immunoglobulin enhancer binding factors E12/E47 (E2A) locus clustered within, or in proximity to, transposable element sequences. Nearly half of reported TCF3 translocations involve a MER20 DNA transposon. Based on this observation, we propose this sequence is important for the oncogenesis of TCF3-PBX1 acute lymphoblastic leukemia.

Racial differences in mycosis fungoides: a retrospective study with a focus on eosinophilia.

BACKGROUND Mycosis fungoides (MF) is often associated with eosinophilia and portends a poorer prognosis. MF is more common in blacks and follows a more aggressive course compared with whites. OBJECTIVE We further elucidate racial differences between blacks and whites with MF, focusing on blood eosinophilia. METHODS The records of 345 patients with MF were reviewed for demographic, clinical, and pathologic data and evaluated by analysis of variance. RESULTS The average age at diagnosis for blacks was 45 years and was 55 years for white patients (P < .001). In the cohorts of patients with and without blood eosinophilia, the average maximum blood eosinophil count had a greater range in blacks. Independent of race, blood eosinophilia was predictive of more advanced disease (P < .0001), increased number of treatment types (P < .002), and less responsiveness to treatment (P < .0006). LIMITATIONS This was a retrospective study at a single institution. CONCLUSIONS These differences observed in eosinophil values may highlight disparities in MF diagnosis or a difference in pathophysiology between races.

Management of hidradenitis suppurativa in pregnancy

&NA; Hidradenitis suppurativa is a debilitating inflammatory skin disease with a chronic course and often disappointing response to treatment. Though a minority of persons (20%) reports symptom remission during pregnancy, the vast majority experiences no relief (72%), and few experience clinical deterioration (8%). Disease flares are also observed post‐partum. The pathophysiological basis for pregnancy‐associated fluctuations in clinical status is currently unknown. Because most women with HS require ongoing management throughout pregnancy, it is important to evaluate the suitability and safety of current treatment options for pregnant women. The following review will outline current management strategies for HS and their compatibility with pregnancy and lactation.

Racial differences in the use of extracorporeal photopheresis for mycosis fungoides

Abstract Background: Extracorporeal photopheresis (ECP) is an effective treatment option for mycosis fungoides (MF) and associated with few systemic side effects. Objective: We sought to investigate whether there were differences in rates of ECP use between African-American and Caucasian patients with stage III/IV MF. Methods: We conducted a retrospective review of all patients treated for MF at the Johns Hopkins Hospital main campus outpatient clinic between 1999 and 2011. Results: We identified 65 patients with stage III or IV disease, 20 African-American and 45 Caucasian. Only 7 of 20 African-American patients (35%) compared with 30 of 45 (66%) of Caucasian patients were treated with ECP (p = 0.029). In addition, ECP was discussed as an option for 45% of African-Americans compared to 82% of Caucasians (p = 0.007). When discussed as an option, African-Americans and Caucasians had identical rates of ECP use (78% vs 81%, p = 0.841). Conclusions: Differences in rates of ECP use exist among African-American patients when compared to their Caucasian counterparts and may be related to how often ECP is offered as a treatment option. Improving physician awareness of the factors that influence treatment decision making may help diminish discrepancies in treatment regimens among patients with MF.

Madura foot caused by Gordonia terrae misdiagnosed as Nocardia

Actinomycetomas are soft tissue bacterial infections that are in the differential for unusual masses of the extremities. Typical infectious agents include Actinomyces and Nocardia and are treated with long‐term antibiotics. We report a rare case of Gordonia actinomycetoma that was misdiagnosed as Nocardia and subsequently required surgical excision in addition to antibiotic therapy.

Interleukin-31 receptor and pruritus associated with primary localized cutaneous amyloidosis.

odeficiency-associated lymphoproliferative disorders. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al., eds), 4th edn. Lyon: International Agency for Research on Cancer, 2008; 350. 4 Curry JL, Prieto VG, Jones DM et al. Transient iatrogenic immunodeficiency-related B-cell lymphoproliferative disorder of the skin in a patient with mycosis fungoides/S ezary syndrome. J Cutan Pathol 2011; 38:295–7. 5 Rausch T, Cairoli A, Benhattar J et al. EBV cutaneous B-cell lymphoproliferation of the leg in an elderly patient with mycosis fungoides and methotrexate treatment. APMIS 2013; 121:79–84. 6 Koens L, Senff NJ, Vermeer MH et al. Methotrexate-associated Bcell lymphoproliferative disorders presenting in the skin: a clinicopathologic and immunophenotypical study of 10 cases. Am J Surg Pathol 2014; 38:999–1006. 7 Dojcinov SD, Venkataraman G, Raffeld M et al. EBV positive mucocutaneous ulcer – a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010; 34:405–17. 8 Salloum E, Cooper DL, Howe G et al. Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases. J Clin Oncol 1996; 14:1943–9. 9 Kim YH, Tavallaee M, Sundram U et al. Phase II investigatorinitiated study of brentuximab vedotin in mycosis fungoides and S ezary syndrome with variable CD30 expression level: a multi-institution collaborative project. J Clin Oncol 2015; 33:3750–8. 10 Novelli M, Merlino C, Ponti R et al. Epstein-Barr virus in cutaneous T-cell lymphomas: evaluation of the viral presence and significance in skin and peripheral blood. J Invest Dermatol 2009; 129:1556–61.

Considering the impact of pregnancy on the natural history of hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic and debilitating inflammatory skin disease that disproportionately affects women of childbearing age. Yet, little has been written about the impact of pregnancy on the natural history of HS. It has been postulated that apocrine-gland activity diminishes in pregnancy, accounting for symptom remission. This article is protected by copyright. All rights reserved.

Tinea in Tots: Cases and Literature Review of Oral Antifungal Treatment of Tinea Capitis in Children under 2 Years of Age

Tinea capitis is a fungal infection classically affecting children at ages 3-7 years and rarely has been reported in children less than 2 years of age. The most common etiologic agents in the US are Trichophyton tonsurans and Microsporum canis. Pathogens vary and country of origin should be considered when investigating the causative organism. Occasionally, Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton violaceum, and Trichophyton Sudanese can trigger outbreaks of tinea capitis that are indistinguishable from T tonsurans and are associated with immigrants from the Mediterranean, Eastern Europe, and Central Asia. Other commonly identified dermatophytes associated with tinea capitis outside of North America include T tonsurans, T mentagrophytes, and Microsporum audouinii. In general, black children have a higher incidence of tinea capitis compared with other racial groups. Specific data on tinea capitis in the 0to 2-year age group are lacking because of the low reported prevalence of tinea capitis at this age. However, tinea capitis in infants has been recognized since the 1950s. Clinical findings for tinea capitis in infants are similar to older children and include alopecia, scaling/flaking, and lymphadenopathy. However, these findings likely are confused with more common conditions such as seborrhea or eczema leading to misdiagnosis and mistreatment. Management using topical agents, although posing less drugrelated risk, is less effective for tinea capitis, and oral antifungal therapy is the standard. In infants, use of systemic drugs has been off-label with no Food and Drug Administrationapproved agents or treatment guidelines for this age group. Tinea capitis in infants likely is misdiagnosed and underreported. We present cases of infants with tinea capitis who were treated successfully with systemic agents, review the literature, and provide recommendations on the treatment of tinea capitis in children younger than 2 years of age.