Interstitial mycosis fungoides, a variant of mycosis fungoides resembling granuloma annulare and inflammatory morphea *

Interstitial mycosis fungoides (IMF) is a rare variant of mycosis fungoides that resembles the interstitial form of granuloma annulare and inflammatory morphea. IMF has received little attention in the literature. Methods:   Clinical, histological, immunophenotypical, and genotypical findings of five cases of IMF were reviewed. The histological and immunophenotypical findings were compared with those of eight cases of interstitial granuloma annulare and six cases of inflammatory morphea. Results:   Five patients with IMF presented with non-indurated, erythematous macules; ill-defined erythematous plaques with slight scale; and nodules on the trunk and proximal limbs. Two of five patients had a prior diagnosis of mycosis fungoides. Skin biopsies revealed a striking dermal interstitial infiltrate of lymphocytes with rare histiocytes that resembled the interstitial form of granuloma annulare or inflammatory morphea. Epidermotropic lymphocytes were present at least focally in all cases. A band-like lymphocytic infiltrate was observed in two of five cases. In contrast, many plasma cells and histiocytes were observed in cases of inflammatory morphea and interstitial granuloma annulare, respectively. With Movat-pentachrome stains, increased dermal mucin deposition was observed in two of five IMF cases, in all cases of interstitial granuloma annulare, and in one of six cases of inflammatory morphea. There was focal loss of elastic fibers in all cases of inflammatory morphea. Immunohistochemical studies of IMF highlighted a dominant population of T cells (CD3+) in the dermis and epidermis. In contrast, moderate numbers of B cells (CD20+) were admixed with T cells and plasma cells in inflammatory morphea. Almost equal numbers of histiocytes (CD68+) and T cells comprised the infiltrate of interstitial granuloma annulare. In two of five IMF cases, a clonal T-cell population was detected by PCR T-cell gamma gene rearrangement analysis. Conclusion:   Mycosis fungoides occasionally presents as an interstitial lymphocytic infiltrate that mimics granuloma annulare and inflammatory morphea. Hematoxylin & eosin (H&E) findings alone can sometimes distinguish the three disorders. Immunophenotyping and genotyping may be helpful in difficult cases. Su LD, Kim YH, LeBoit PE, Swetter SM, Kohler S. Interstitial mycosis fungoides, a variant of mycosis fungoides resembling granuloma annulare and inflammatory morphea. J Cutan Pathol 2002; 29: 135–141. © Blackwell Munksgaard 2002.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72026/1/j.1600-0560.2002.290302.x.pd

Case Series of Fertility Treatment in HIV-Discordant Couples (Male Positive, Female Negative): The Ontario Experience

The success of combination antiretroviral therapies for the treatment of human immunodeficiency virus (HIV) has resulted in prolonged life expectancy (over 40 years from diagnosis) and an improved quality of life for people living with HIV. The risk of vertical HIV transmission during pregnancy has been reduced to less than 1%. As a result of these breakthroughs and as many of these individuals are of reproductive age, fertility issues are becoming increasingly important for this population. One population in which conception planning and reduction of horizontal HIV transmission warrants further research is HIV-discordant couples where the male partner is HIV-positive and the female partner is HIV-negative. Sperm washing is a technique carried out in a fertility clinic that separates HIV from the seminal fluid. Although sperm washing followed by intrauterine insemination significantly reduces the risk of horizontal HIV transmission, there has been limited access to the procedure in North America. Furthermore, little is known about the conception decision-making experiences of HIV-discordant couples who might benefit from sperm washing. Chart reviews and semi-structured interviews were completed with 12 HIV-discordant couples in Ontario, Canada. Couples were recruited through HIV clinics and one fertility clinic that offered sperm washing. Participants identified a number of factors that affected their decision-making around pregnancy planning. Access to sperm washing and other fertility services was an issue (cost, travel and few clinics). Participants identified a lack of information on the procedure (availability, safety). Sources of support (social networks, healthcare providers) were unevenly distributed, especially among those who did not disclose their HIV status to friends and family. Finally, the stigmatisation of HIV continues to have a negative affect on HIV-discordant couples and their intentions to conceive. Access to sperm washing and fertility service is significantly limited for this population and is accompanied with a number of challenges

Operational Risk: Stepping Beyond Bow-Ties

Abstract This paper presents the Multiple Physical Barrier (MPB) approach to operational (or process) risk that was developed by Argonne National Laboratory with the help of key collaborators from the upstream oil and gas industry. This approach begins with a comparison to the “bow-tie” technique that is commonly used in the industry for identifying operational (or process) risk. Bow-ties identify a variety of different types of barriers and help communicate safety principles that link causal factors and subsequent actions to a specific event – such as a loss of well control event. Bow-tie barriers commonly include equipment, processes, plans, methods, and sometimes people, with their know-how and experience. However, by narrowing the focus to physical barriers (e.g. the source of operational risk) as is consistent with the NORSOK D-010 Standard, and by developing “success paths” that enable each barrier to perform its “safety function,” the MPB approach is demonstrated to step further toward a systematic approach to operational risk management. Additionally, this approach can be seen to help guide operational process design as well as lifecycle management. To demonstrate the versatility of the MPB approach, several applications have been selected that highlight how operational risk can be systematically identified and communicated in different offshore applications: Drilling, including an operational risk comparison between conventional drilling and Managed Pressure Drilling; Completions, installing and de-installing production packers, a barrier that highlights the life-cycle aspect of the MPB approach; and Coiled Tubing Workovers, a risk based design diagram for ensuring that barriers are in place to ensure a successful operation. By making a clear distinction between physical barriers and success path components (including human actions, processes, and plans), the MPB approach adds systematic clarification for understanding and characterizing risks in a direct manner. The MPB approach also enables the identification of chains of causality and builds important steps toward enabling risk quantification. As such, the MPB approach provides a direct and systematic approach for assessing and communicating risk, as well as helping operations to be successful.</jats:p

Large-cell transformation following detection of minimal residual disease in cutaneous T-cell lymphoma: molecular and in situ analysis of a single neoplastic T-cell clone expressing the identical T-cell receptor.

PURPOSE One of the unique characteristics of cutaneous T-cell lymphoma (CTCL) is its ability to undergo cytologic transformation in which the malignant T cells develop the morphologic appearance of a large-cell lymphoma. Reported to occur in up to 20% of advanced cases, large-cell transformation (LCT) is associated with an aggressive clinical course. Little is known about the risk factors or the molecular mechanisms of LCT. Before current immunohistochemical and molecular techniques, it was not possible to determine if LCT represented changes of the initial neoplastic T-cell clone or, in fact, was a distinct second malignancy. The goal of this study was to define the clonal evolution of LCT in CTCL. PATIENTS AND METHODS Polymerase chain reaction (PCR) amplification of T-cell receptor-beta (TCR-beta) gene rearrangements and immunohistochemistry with monoclonal antibodies to TCR-V beta regions were used as markers of T-cell clonality to analyze the skin and peripheral blood of a patient with CTCL and LCT. RESULTS We first detected the presence of minimal residual disease (MRD) in a CTCL patient with a complete clinical response to biologic response modifiers (BRMs). When clinical relapse occurred and demonstrated LCT, TCR-beta-PCR and in situ immunohistochemistry with a specific TCR-V beta monoclonal antibody identified a single neoplastic T-cell clone that expressed the identical TCR as the original clone. CONCLUSION Our results confirm a common clonal origin for CTCL and LCT. We also provide evidence of MRD in CTCL by molecular analysis, implying that residual malignant cells maintain a potential for clinical relapse and possibly LCT. The role of MRD detection remains to be defined in the clinical assessment of CTCL. LCT in CTCL provides a unique model to investigate the molecular events that underlie terminal-stage tumor progression. </jats:sec