Multifocal pleomorphic dermal sarcoma and the role of inflammation and immunosuppression in a lung transplant patient: a case report.

BACKGROUND: Pleomorphic dermal sarcoma is the cutaneous variant of undifferentiated pleomorphic sarcoma. It is a rare malignancy of unclear histogenesis; it is a diagnosis of exclusion that requires extensive use of immunohistochemistry to rule out other malignancies. Pleomorphic dermal sarcoma typically presents as a solitary tumor in sun-exposed areas and may have unpredictable clinical behavior, with some tumors associated with metastasis and death. CASE PRESENTATION: We present an unusual case of multifocal pleomorphic dermal sarcoma arising in the areas of alpha-1-antitrypsin deficiency panniculitis in a lung transplant patient. Our patient was a 58-year-old white woman whose initial presentation was consistent with alpha-1-antitrypsin deficiency panniculitis. She then developed extensive multifocal, bleeding, and ulcerated nodules in the areas of the panniculitis. A skin biopsy was consistent with a diagnosis of pleomorphic dermal sarcoma. Her immunosuppressive regimen was decreased, and she was treated with liposomal doxorubicin 40 mg/m2 every 3 weeks with some initial improvement in the size of her tumors. However, soon after beginning therapy, she developed pneumonia and septic shock and ultimately died from multi-organ failure. CONCLUSIONS: We hypothesize that chronic, multifocal inflammation in the skin in the setting of immunosuppression led to simultaneous, malignant transformation in numerous skin lesions. We discuss the challenges of diagnosing pleomorphic dermal sarcoma, therapeutic options, and stress the need for multidisciplinary management of these cases.

Ethics of clinical trials in dermatology.

The ethics of clinical trials have been the subject of numerous previous publications and mandates that are used by institutional review boards on an everyday basis. The protection of human rights and the sanctity of informed consent are critical components of clinical research monitored by human subjects investigation committees throughout our profession. In this contribution, the everyday conflicts of interest that can compromise clinical research in dermatology are presented in a case format. Of utmost importance, the primary interest of the investigating dermatologist should always be the patient at hand and those who could benefit from the research. Navigating the turbulence created by finances, academia, and corporate America is critical. By presenting several case scenarios within the relatively rare disease arena of cutaneous T-cell lymphoma, these conflicts can be appreciated. Consequently, understanding these influences in one disease setting permits generalizations to be applied to any dermatologic clinical research.

Menus for managing patients with cutaneous T-cell lymphoma.

In the management of patients with cutaneous T-cell lymphoma (CTCL), there are numerous distinct therapy options. Each of these therapies is discussed in terms of when to use it, what factors limit the success of the treatment, and what to expect. A menu is defined as a list of items from which to choose. The treatments for CTCL are presented in various menus where they are options for a particular goal in a particular setting of CTCL. The best recognized clinical scenarios of CTCL are those recognized by the staging system: limited patch plaque (T1), disseminated patch plaque (T2), erythroderma (T4), and tumor (T3). Each phase of the disease will have the menu of therapy options presented for a given goal of management.

Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer.

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

Innovative therapy of cutaneous T-cell lymphoma: beyond psoralen and ultraviolet light and nitrogen mustard.

Cutaneous T-cell lymphoma is a malignancy of skin-homing T cells. This unique population of lymphocytes requires alternative therapies to those used in nodal lymphomas. Although phototherapy and nitrogen mustard have been standard treatments for decades, newer therapies have been arriving with increased frequency. Moreover, some therapies, currently used to treat other diseases, have been used with good effect. These innovative therapies are discussed, with review of current data and examples of how these therapies may be used today.

A rectangular dermatosis of the left back.

BACKGROUND: Cardioversion and defibrillation have become widely used techniques aimed at restoring normal sinus rhythm in patients with cardiac arrhythmias. Following the procedure, cutaneous lesions are often seen at the site of the electrodes, but little has been reported regarding the evolution of such lesions over time. OBSERVATIONS: Two patients presented with unusual, well-defined rectangular eruptions on the left back, and both reported a history of having undergone electrical cardioversion or defibrillation several years previously. The histologic characteristics of each lesion were distinct, and the management was symptomatic, with most of the relief coming from the recognition that the eruption was actually a self-limited manifestation of cardioversion and defibrillation. CONCLUSIONS: The clinical cases and corresponding histologic findings represent possible long-term sequelae of electrical cardioversion or defibrillation. They are presented in order to enhance the diagnostic acumen of dermatologists and to avoid potential misdiagnosis.

Primary cutaneous T-cell lymphoma localized to the lower leg: a distinct, locally aggressive cutaneous T-cell lymphoma.

BACKGROUND: Distinct categories of skin lymphoma with preferential site localization and unique clinical behavior, including leg-type primary cutaneous diffuse large B-cell lymphoma, have recently been described. Although these entities are rare, they exhibit reproducible clinicopathologic features, and their recognition may allow more appropriate treatment protocols. OBSERVATIONS: We describe the distinctive clinicopathologic features that were observed in 3 patients with an unusual variant of primary cutaneous T-cell lymphoma. All cases originated on the legs of elderly patients and exhibited a locally aggressive clinical behavior with relatively rapid relapses after radiotherapy and resistance to other therapies. Histologically, dense dermal-centered infiltrates of atypical, variably sized mature helper T cells were identified. One patient died of progressive disease. CONCLUSIONS: Rare cases of primary cutaneous lymphomas do not necessarily fit current criteria for a standard diagnostic category but may represent unique clinicopathologic entities, such as primary cutaneous T-cell lymphoma localized to the lower leg. It is important to be able to identify these unusual lymphoma variants for prognosis and adequate treatment. The aggressive nature of lymphomas preferentially localized on the lower extremities may not be restricted to B-cell or cytotoxic neoplasms.

Cutaneous T-cell lymphoma in skin of color.

Over the past three decades, there has been a marked increase in the incidence of cutaneous T-cell lymphoma (CTCL), with significant differences in the rates of CTCL by race and ethnicity. The overall incidence of CTCL has been shown to be higher among blacks than among whites and other racial groups. In addition, CTCL is thought to follow a more aggressive course in black patients. This article highlights the differences in clinical appearance and response to therapy, and discusses the differential diagnosis of CTCL in skin of color in an attempt to ensure earlier diagnosis and better outcomes for these patients.

A distinct entity in the spectrum of the CD30+ cutaneous lymphoproliferative diseases: oligolesional nodules with pseudoepitheliomatous hyperplasia followed by spontaneous resolution.

Pseudoepitheliomatous hyperplasia (PEH) in biopsies of CD30+ anaplastic large-cell lymphoma (ALCL) is present infrequently and is of unknown prognostic value and significance. Our goal was to review the clinicopathologic features of cases of ALCL with PEH, study their course, and review the literature on the subject. Biopsy specimens of all cases of CD30+ lymphoproliferative disorders (59) were retrieved from the files of Yale Dermatopathology Laboratory over a 17-year period and reviewed. We identified 4 cases of ALCL (7%) exhibiting prominent PEH. All 4 patients presented with 1 or 2 nodules. In 2 patients, the lesions spontaneously regressed within a few months after initial diagnosis. One patient chose to have an excision in which only a small number of CD30+ cells were present. We were unable to obtain follow-up for the fourth patient. In the spectrum of CD30+ lymphoproliferative disorders, cases of ALCL with PEH are infrequent. In addition to the 4 cases described here, in our review of the literature we found 35 cases of ALCL with PEH. Most of these patients present with 1 or a few lesions. In the majority of these cases, the lesions started showing evidence of clinical spontaneous regression and even complete resolution within a few months of initial diagnosis. The clinicopathologic correlation between ALCL and PEH has not been emphasized. Because most of these cases follow a relatively benign clinical course, we recommend a more conservative approach in the clinical management of these patients.

Strategies for treating cutaneous T-cell lymphoma: part 1: remission.

In this article, the management of cutaneous T-cell lymphoma will be presented in terms of the strategies that guide treatment. With the strategies and goals in mind, treatment options to achieve a measurable goal will be presented. The treatments presented in this article are those utilized to reliably achieve a remission. If remission is not achieved, a patient's management plan must be changed. The landmarks that help guide the therapy plan will be discussed.

A case of disseminate and recurrent infundibulofolliculitis responsive to treatment with topical steroids.

Disseminate and recurrent infundibulofolliculitis (DRIF) is an uncommon pruritic follicular eruption of unknown etiology that is predominantly seen in black men. This condition tends to affect the trunk and upper extremities and is usually unresponsive to local and systemic treatment. Recently, several investigators have reported successful treatment with isotretinoin. Herein, we report a case of a patient with disseminate and recurrent infundibulofolliculitis who was successfully treated with potent topical corticosteroids.

'Coral reef' psoriasis: a marker of resistance to topical treatment.

Psoriasis plaques that have very thick adherent scale (so-called coral reef or rupioid psoriasis) tend to be resistant to topical treatment. We present a case of coral reef psoriasis that responded to topical clobetasol 0.05% spray without concomitant use of moisturizers or keratolytic agents. We propose that coral reef psoriasis is resistant to topical corticosteroids because of poor adherence to treatment, not because of poor penetration of applied agents.

FDG-PET/CT for the evaluation of response to therapy of cutaneous T-cell lymphoma to vorinostat (suberoylanilide hydroxamic acid, SAHA) in a phase II trial.

INTRODUCTION: Harnessing the power of molecular imaging in particular positron emission tomography (PET) to assess response to therapy in early clinical trials has the potential to yield crucial data on efficacy and streamline drug development. Vorinostat (also known as SAHA, suberoylanilide hydroxamic acid) is a histone deacetylase (HDAC) inhibitor which alters gene transcription to inhibit proliferation and promote apoptosis. METHODS: In a phase II trial of vorinostat for cutaneous T cell lymphoma (CTCL), 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET/computed tomography (CT) was performed on patients with both cutaneous and nodal disease. FDG-PET/CT fuses the power of metabolic imaging from FDG-PET with the anatomic detail of CT. Scans were conducted on subjects pre-therapy and during therapy. RESULTS: Changes in the values of FDG uptake and measurements of nodal dimensions and thickness of cutaneous lesions were tabulated. FDG-PET/CT provided an objective measure of the response (or lack thereof) of both cutaneous and nodal disease to therapy with vorinostat. The results of this study are encouraging for the potential utility of FDG-PET/CT in future trials with HDAC inhibitors for other diseases and for CTCL with other therapies. CONCLUSION: Further study will be required to determine the prognostic value of the initial PET/CT scan and response on follow-up scans.

Bilateral dialysis-associated steal syndrome.

Dialysis-associated steal syndrome (DASS) is an uncommon complication of arteriovenous fistula formation, but can have dire consequences. This entity is likely to be seen more commonly in the future as the number of patients with end stage renal disease increases. We present the unique case of a patient with end stage renal disease who developed bilateral DASS after presenting with a painful skin lesion.

FDG-PET/CT in the evaluation of cutaneous T-cell lymphoma.

This comprehensive case series illustrates the findings on 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) positron-emission tomography/computed tomography (PET/CT) of patients with varying stages of cutaneous T-cell lymphoma (CTCL). Patients were imaged with full-body scanning using a General Electric Discovery ST 16-slice PET/CT machine. Patients were assessed by PET/CT for cutaneous, nodal, and solid organ FDG uptake, indicative of highly metabolically active (i.e., putatively malignant cells) disease, and comparisons were made to CT data alone and to the physical examination. Several key observations strongly suggested that information afforded by PET/CT scan may be valuable. Various cutaneous lesions, from thin subtle plaques to thick tumors, were revealed and corresponded accurately to the cutaneous examination. In the case of subcutaneous lesions, PET/CT outperformed physical exam. CT also provided the depth/thickness of lesions. The differing levels of FDG uptake in enlarged nodes found within an individual patient as well as among different patients may potentially distinguish reactive from malignant adenopathy. Additionally, lymph nodes that did not meet staging size criteria (e.g., were not > 1 cm) revealed increased metabolic activity and, therefore, could be targeted for subsequent monitoring or biopsy. In addition, PET/CT identified visceral involvement in cases with advanced disease. In summary, PET/CT can provide physiologic and anatomic information on the wide diversity of external and internal lesions in CTCL and, therefore, may have great potential for improving the staging and monitoring of response to therapy of cutaneous, nodal, and visceral disease.

Persistent agmination of lymphomatoid papulosis: an equivalent of limited plaque mycosis fungoides type of cutaneous T-cell lymphoma.

BACKGROUND: Lymphomatoid papulosis (LyP) is a self-healing eruption in the spectrum of CD30+ lymphoproliferative disorders. The most common lymphoproliferative disorder associated with LyP is the most common form of cutaneous T-cell lymphoma: mycosis fungoides. OBJECTIVE: We sought to describe a distinct entity on the spectrum of CD30+ lymphoproliferative disorders. RESULTS: Seven patients presented with similar findings. Within a well-circumscribed area, the size and location of a patch of mycosis fungoides, these patients had continual eruptions of papulonodules that were histologically typical of LyP. The localized areas of involvement were treated as oligolesional mycosis fungoides and long-standing remissions occurred even after years of experiencing continuous localized eruptions. The clinical and histologic findings are reviewed and presented in a way to further the identification of patients with this entity. LIMITATIONS: This distinct entity is only defined by 7 patients. CONCLUSION: The agmination of LyP-like papulonodules confined to a discrete circumscribed area is a distinct clinical subset within the spectrum of CD30+ lymphoproliferative disorders. The behavior of this entity is that of a progressive lymphoma that warrants therapy.