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.

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.

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.

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.

Defining early mycosis fungoides.

This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma.

Primary cutaneous B-cell lymphoma treated with radiotherapy: a comparison of the European Organization for Research and Treatment of Cancer and the WHO classification systems.

PURPOSE: To determine the relationship between the WHO and European Organization for Research and Treatment of Cancer (EORTC) pathologic classifications for primary cutaneous B-cell lymphoma (CBCL) and the implication of this relationship on initial treatment. PATIENTS AND METHODS: Patients with primary CBCL treated with radiotherapy were identified retrospectively. Initial biopsy specimens were reviewed by two dermatopathologists and classified according to the EORTC and WHO systems. Primary outcomes were recurrence-free and overall survival. RESULTS: Thirty-four patients were identified; initial biopsy specimens were adequate for classification in 32 patients. Four different composite histopathologic subtypes of lymphoma were identified: 53% (17 of 32) follicle center cell by EORTC and diffuse large B-cell by WHO (FCC/DLB), 25% (eight of 32) follicle center cell by EORTC and follicular by WHO (FCC/Fol), 13% (four of 32) marginal zone by EORTC and WHO (MZ/MZ), and 9% (three of 32) large B-cell of the leg by EORTC and diffuse large B-cell by WHO (Leg/DLB). Five-year relapse-free survival ranged from 62% to 73% for FCC/DLB, FCC/Fol, and MZ/MZ but was 33% for Leg/DLB (P =.6). Five-year overall survival was 100% for FCC/DLB, FCC/Fol, and MZ/MZ but was 67% for Leg/DLB (P =.07). At 5 years, 21% of all patients had developed extracutaneous disease. CONCLUSION: Two-thirds of primary cutaneous FCC lymphomas by EORTC criteria satisfy WHO criteria for DLB lymphoma. Unlike DLB lymphoma presenting in nodal or noncutaneous sites, these lesions are associated with an indolent course and may be treated with local radiotherapy alone.

Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with denileukin diftitox (ONTAK).

Cutaneous T-cell lymphoma (CTCL) can be associated with painful, pruritic, disfiguring lesions. As part of a multicenter, randomized phase III trial in patients with heavily pretreated advanced and/or recurrent CTCL, the effects of an interleukin-2 receptor-targeted fusion protein, denileukin diftitox (DAB389IL-2, ONTAK), on patient-rated overall quality of life (QOL), skin appearance, and pruritus severity were evaluated. A total of 71 patients with stage IB-IVA CTCL received intravenous denileukin diftitox 9 microg/kg/day or 18 microg/kg/day over 15-60 minutes for 5 consecutive days on an outpatient basis; cycles were planned for every 21 days for a total of 8 cycles over 6 months. Prior to each treatment cycle, patients were evaluated for disease response and were asked to self-rate their overall QOL via the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, skin appearance (7-point scale), and pruritus severity (10-cm visual analogue scale). Composite FACT-G and most individual subscale scores (physical, social/family, emotional, and functional well being) in documented responders (n = 21) gradually increased during the study period, generally reaching statistical significance (P < 0.05) by cycle 3, and were significantly (P < or = 0.041) higher than the scores of nonresponders at endpoint. Additionally for responders, assessments of skin severity and pruritus severity showed significant (P < or = 0.05) improvements at study endpoint compared with baseline. Adverse transfusion-related events (eg, hypersensitivity reactions, flu-like syndrome) were common during cycles 1 and 2, and vascular-leak syndrome occurred in 25% of patients. Denileukin diftitox was not associated with any clinically significant myelosuppression. Heavily pretreated patients with advanced and/or recurrent CTCL who responded to denileukin diftitox therapy showed significant improvements in self-rated overall QOL, skin appearance, and pruritus severity.